COMPARISON OF NEONATAL OUTCOMES IN MATERNAL USERS AND NON-USERS OF HERBAL SUPPLEMENTS
A Thesis
Presented in Partial Fulfillment of the Requirements for
the Degree Master of Science in the Graduate
School of The Ohio State University
By
Holly A Larson, B.S.
*****
The Ohio State University 2008
Master‟s Examination Committee:
Dr. Maureen Geraghty, Advisor Approved by
Annette Haban Bartz ______
Dr. Christopher A. Taylor Advisor Graduate Program in Allied Medical Professions
COMPARISON OF NEONATAL OUTCOMES IN MATERNAL USERS AND NON-USERS OF HERBAL SUPPLEMENTS
By
Holly A. Larson, M.S.
The Ohio State University, 2008
Dr. Maureen Geraghty, Advisor
This pilot study was a retrospective chart review. The purposes of this study were to describe the prevalence herbal supplement use, to identify characteristics linked to increased herbal supplement use and, to identify adverse outcomes linked to herbal supplement use.
Rate of use in the study sample of 2136 charts was 1.1% and identified 17 supplements. The most common supplements identified were teas. Characteristics of the neonates and controls were analyzed as appropriate and revealed no statistical significance. Characteristics of the mothers also revealed no statistical difference. There was a statistically significant difference between herbal users and herbal non-users and the trimester prenatal care began. Neonatal outcomes were statistically different on two measures. Further study is needed to be able to make recommendations regarding safety and efficacy of herbal supplements as well as to be able to better understand motives for choosing to use them.
ii
Dedicated to the Mama and the Daddy Bears
iii ACKNOWLEDGMENTS
I would like to express my heartfelt gratitude to my advisor, Dr. Maureen
Geraghty. Her genuine interest in me and my learning experience is the backbone of my academic success at The Ohio State University. She set the bar high but provided the counsel and support to be victorious. Thank you.
I wish to enthusiastically thank my research team at Nationwide Children‟s
Hospital. Annette Haban-Bartz, Joyce Brezny, Nancy Ryan-Wenger, Robin Catlett and
Darcy Harmon were all my teachers, coaches and team members. Thank you for your willingness to teach, your support and your many hours contributed to this project.
Many thanks to Dr. Chris Taylor for his numerous “technology consults”, his aid and guidance in writing of chapter three and support throughout the entire process.
Thank you to Mariel Viggers for countless hours of data entry assistance and moral support. Thanks to Anne Arlinghaus for helping edit and polish the entire document, even though she was in Nigeria.
Finally, thank you to my friends and family for supporting me on this learning journey. Thank you for your strength and encouragement and for helping celebrate as this project comes to a close.
Thank you.
iv VITA
August 17,1984 ...... Born – Cincinnati, Ohio
2006...... B.S. Dietetics, Ohio University
2006-2007 ...... Dietetic Internship The Ohio State University
FIELD OF STUDY
Major Field: Allied Medical Professions
v TABLE OF CONTENTS
Page Abstract ...... ii
Dedication ...... iii
Acknowledgments...... iv
Vita ...... v
List of Tables ...... ix
Chapters:
1. Introduction ...... 1 Background of the Problem ...... 1 Significance of the Problem ...... 2 Objectives ...... 3 Research Approach ...... 4 Definition of Terms...... 4 Abbreviations ...... 8 2. Review of Literature ...... 9 Herbal Supplement Use in the United States and Worldwide ...... 11 Herbal supplement use in pregnancy ...... 13 Patient Disclosure of Herbal Supplement Use ...... 15 Increased disclosure in acute situation ...... 16 Risks and Safety of Herbal Supplement Use ...... 21 Attitudes Regarding Risk ...... 23 Sources of Information for Herbal Supplement Use ...... 23 Midwives...... 24 Healthcare practitioners and physicians ...... 25 Friends and family ...... 26 Health food store ...... 26 Internet, self-education, television ...... 27 Common Herbal Supplements Used During Pregnancy; use, safety ...... 30 Aloe ...... 30 Anise ...... 30 Black cohosh ...... 31
vi Page Blessed thistle herb ...... 31 Blue cohosh ...... 31 Castor ...... 32 Chamomile, German ...... 33 Coriander...... 33 Cranberry ...... 33 Echinacea ...... 34 Evening primrose oil ...... 35 Fennel ...... 35 Fenugreek ...... 35 Garlic...... 36 Ginger ...... 36 Ginkgo biloba...... 37 Ginseng, American ...... 38 Ginseng, Panax ...... 38 Ginseng, Siberian ...... 39 Goldenseal...... 39 Green Tea ...... 40 Juniper ...... 41 Kava kava...... 42 Lemongrass ...... 42 Lemon verbena...... 43 Marshmallow root ...... 43 Mother‟s Milk Tea ...... 44 Nettle (Stinging)...... 44 Noni juice (morinda) ...... 45 Omega-3 fatty acids ...... 46 Papaya ...... 46 Peppermint ...... 46 Red Raspberry ...... 47 Spearmint ...... 47 St. John‟s Wort...... 48
3. Materials and Methods ...... 56 Transport Team Logistics ...... 56 Transport Log Data Collection ...... 57 Identification of Matched Controls ...... 58 Data Analysis ...... 60 Study Limitations ...... 60 Page
4. Comparison of Neonatal Outcomes in Maternal Users and Non-Users of Herbal Supplements ...... 61 Abstract ...... 61 Introduction ...... 63 Methods...... 64 Data Analysis ...... 66 Results ...... 66 Discussion ...... 71 Conclusions and Applications ...... 71
5. Discussion and Conclusion ...... 74
References ...... 79
Appendix A: Transport Log ...... 88 Appendix B: Ohio Region IV County Demographics ...... 93
viii LIST OF TABLES
Table Page
2.1 Identified concerns with herbal use in pregnancy ...... 17
2.2 Selected herbal supplements used in pregnancy ...... 28
2.3 Possible herb-drug and herb-food interactions ...... 49
3.1 Statistical procedures ...... 59
4.1 Non-vitamin, non-mineral supplement reported ...... 67
4.2 Characteristics of the neonates and matched controls ...... 68
4.3 Reason for neonate‟s referral to Nationwide Children‟s Hospital ...... 69
4.4 Characteristics of the mothers ...... 69
4.5 Comparison of month prenatal care began ...... 70
4.6 Statistically significant neonatal outcomes ...... 71
4.7 Comparison of Chem 7 by herbal users and herbal non-users...... 71
5.1 Frequencies of estimated gestational ages ...... 76
5.2 Example format for herbal supplement use in pregnancy health history ...... 78
ix CHAPTER 1
INTRODUCTION
Background of the Problem
Herbal supplements have been used around the world for thousands of years.1-3
Herbal supplements are used to treat illness and as part of a general wellness program.1,4-6
The herbs selected and their forms (ie tincture, tablet, tea, powder, etc) have varied over time with changes in the field of medicine and fluctuations in public acceptance. For example, herbal supplement use decreased in the 1920s as the medical model, an approach to medicine now popular in western society, prevailed.1 The medical model describes a set of procedures in which all doctors are trained. This set includes complaint, history, examination, ancillary tests if needed, diagnosis, treatment, and prognosis with and without treatment. Herbal supplements later increased after the thalidomide tragedy, where from 1956 to 1962, approximately 10,000 children were born with severe malformities due to their mothers ingesting thalidomide during their pregnancy to ameliorate morning sickness. Herbal remedies were also sought after at the onset of the
HIV/AIDS epidemic.7
The trend of herbal supplement use worldwide has been on the rise for the past five decades.7,8 This has been illustrated by both national and local surveys in the U.S. and is generally estimated to be around 20%.4,9 Several characteristics linked to increased herbal supplement use have also been identified.8-13 However, potential 1 differences in herbal supplement use by specific populations, such as African Americans, the uninsured, the Amish or cancer patients, are less well understood.12,14-16 A wide range in herbal supplement use is reported depending on the tools and sampling techniques used and the language in which the surveys are conducted.4,11,12,15-20 Glover et al21 assessed herbal supplement use by three measuring tools and found that reported use varied widely by tool. Specifically, estimates of herbal use by pregnant women, and the reasons for doing so, are much less understood.5,22-27 Of the studies investigating herbal supplement use in pregnancy, some exclude those women with a neonate in the intensive care unit, ignoring and underreporting possible complications of taking herbal supplements.28,29 This opportunity for study, especially in the intensive care unit, is evidenced by the wide ranges of estimates in the current literature.28
Significance of the Problem
Despite evidence to the contrary, most herbal supplement users report doing so because they perceive the herbs to be safe, benign alternatives to over-the-counter and prescription pharmaceuticals.5,23,26,30 Utah Senator Orrin Hatch captured the view of the general public in an address to the Senate in 1993, saying that herbal remedies “have been on the market for centuries…most of these have been on the market for 4,000 years, and the real issue is risk. And there is not much risk in any of these products.3”. Despite being used for centuries, clinical investigations of herbal supplement active components, species, possible interactions with other herbs and drugs, efficacy and safety are in their infancy. In particular, the safety of using most herbal supplements during pregnancy is unknown.2,31-35 Herbal supplements may contain very similar chemical components to their tested and regulated prescription pharmaceutical counterpart.6,24,36,37
2 Unlike pharmaceuticals, herbal supplements are not well regulated in the United
States.38 Whereas pharmaceuticals must be tested to demonstrate safety and efficacy before being placed on the market, herbal supplements are first put on the market and later pulled if evidence of danger has been reported. Independent tests of herbal supplements have demonstrated enormous variations on contents, labeling recommendations and contaminants.36,39,40
Lack of disclosure by herbal supplement users to their healthcare professionals is a contributing predicament.14,17,18 The literature has reported that the majority of herbal supplement users do not tell their physicians or other healthcare professionals.41 Failure to disclose may be due to the beliefs of herbal supplement users that there is no risk involved with herbal supplement use, language barriers, physicians not posing the questions to the patient, or by reasons not yet understood. Further, when a patient does disclose herbal supplement use, the majority of physicians surveyed felt incapable of adequately addressing their questions and concerns.23,39,41,42
Herbal supplement users can obtain information, reliable or not, from a plethora of sources. The internet, friends, family, midwives, cultural traditions, physicians, herbalists and health food stores all may influence herbal supplement decisions.26,43-46
However, these recommendations may not be based on clinical evidence and may recommend a potentially dangerous supplement or supplement combination.47
Objectives
The purpose of this study was to better understand herbal supplement use by pregnant women and how to most accurately capture this information. Specifically, the researchers aimed to:
3 1. determine the rate of herbal supplement use during pregnancy in a sample of women whose neonates were transported from a delivering hospital to Nationwide Children‟s Hospital?
2. identify differences in herbal supplement use by mother‟s age, marital status, medications taken during pregnancy, tobacco use?
3. assess whether use of herbal supplements by the mother during pregnancy changed neonatal outcomes?
Research Approach
This was a retrospective pilot study of existing patient records. The majority of data was collected from the Transport Log, a four page document completed by a transport team before a neonate is transported from the outside hospital to Nationwide
Children‟s Hospital. This document contains information regarding the mother‟s and infant‟s medical history, herbal supplement use, race, age and other variables.
For each herbal supplement user subject identified in the records, two matched controls were also identified for comparison. Neonates were matched for gestational age, gender, race, gravida and parity in this case-control pilot study. Matched Controls were identified by a nurse transport clinician using the Nationwide Children‟s Hospital NICU medical records from the same time frame from which the positive response “herbal use” mothers were identified. See Appendix A for Transport Log.
These data were entered into SPSS, analyzed and be used to answer the following research questions;
1) What was the prevalence of herbal supplement use in pregnancy in this population?
2) What factors were associated with herbal supplement use?
4
3) What relationships existed between herbal supplement use and the subsequent conditions or medical diagnosis of the mother and neonate?
Definition of Terms
Allopathy - the method of treating disease by the use of agents that produce effects different from those of the disease treated
Apgar Score - simple and repeatable method to quickly and summarily assess the health of newborn children immediately after childbirth based on five criteria with a score from
0 to 10; developed in 1952
Ballard Score - a set of procedures developed by Dr. Jeanne L Ballard, MD to determine
Gestational Age through neuromuscular and physical assessment of a newborn fetus
Bishop‟s Score - is a pre-labor scoring system to assist in predicting whether induction of labor will be required
Carminative - is a medicinal drug with antispasmodic activity that is used against cramps of the digestive tract in combination with flatulence; often mixtures of essential oils and herbal spices with a tradition in folk medicine for this use (ex: ginger)
Cathartic - a substance which accelerates defecation; purging
Complementary and Alternative Medicine (CAM) - a group of diverse medical and health care systems, practices, and products that are not presently considered to be part of conventional medicine. Conventional medicine is medicine as practiced by holders of
M.D. (medical doctor) or D.O. (doctor of osteopathy) degrees and by their allied health professionals, such as physical therapists, psychologists, and registered nurses.48
Congenital Malformation - A physical defect present in a baby at birth, irrespective of whether the defect is caused by a genetic factor or by prenatal events that are not genetic.
5 In a malformation, the development of a structure is arrested, delayed, or misdirected early in embryonic life and the effect is permanent
Delivering Hospital – the location of neonate‟s birth
Embryonic Period – time period from the second to the eighth week of pregnancy.25
Emmenagogue – increasing blood to uterus and pelvic area; stimulating menstruation, abortion
Galactagogues – agents that increase milk production.49
Generally Recognized as Safe (GRAS) - United States of America Food and Drug
Administration (FDA) designation that a chemical or substance added to food is considered safe by experts, and so is exempted from the usual Federal Food, Drug, and
Cosmetic Act (FFDCA) food additive tolerance requirements.
Herbal Supplement – (definition varies) products made from botanicals that are used to maintain or improve health.48; crude drugs of vegetable origin utilized for the treatment of disease states, often of a chronic nature, or to attain or to maintain a condition of improved health.8
Hyperemesis - Hyperemesis gravidarum (HG) is a severe form of nausea and vomiting in pregnancy; generally described as unrelenting, excessive pregnancy-related nausea and/or vomiting that prevents adequate intake of food and fluids; typically associated with:
* loss of greater than 5% of pre-pregnancy body weight (usually over 10%)
* dehydration and production of ketones
* nutritional deficiencies
* metabolic imbalances (hyperemesis.org)
Labor – 1 or more contractions every 5 minutes with cervical dilation of 4cm or more.50
6 Meconium - the first stool of an infant, composed of materials ingested during the time the infant spends in the uterus
Medical Model - approach to illness which is dominant in Western medicine; aims to find medical treatments for diagnosed symptoms and syndromes and treats the human body as a very complex mechanism
Mother‟s Cordial – traditional herbal preparation used during labor that contains black cohosh, squaw vine, raspberry, blue cohosh and false unicorn.34
Oxytoxic - Hastening or facilitating childbirth, especially by stimulating contractions of the uterus
Tachycardia - a form of cardiac arrhythmia which refers to a rapid beating of the heart; by convention the term refers to heart rates of 120-160 beats per minute in the pediatric patient
Tincture – An alcoholic extraction of an herb
7 Abbreviations
CAM - Complementary and Alternative Medicine
CNM - Certified Nurse Midwife
DSHEA - Dietary Supplements Health and Education Act
FDA - Food and Drug Administration
GRAS - Generally Recognized As Safe
IV - Intravenous
LM - Licensed Midwives
NICU - Neonatal Intensive Care Unit
NIH - National Institute of Health
NCCAM - National Center for Complementary and Alternative Medicine
NVP - Nausea and Vomiting of Pregnancy
OTC - Over-the-counter (refers to medications)
PNC - Prenatal Care
RDD - Recommended Daily Dose
SES - Socioeconomic status
SJW - St. John‟s Wort
TCM - Traditional Chinese Medicine
UTI - Urinary Tract Infection
8 CHAPTER 2
REVIEW OF LITERATURE
Herbal supplement use in the United States and worldwide
Complementary and Alternative Medicine (CAM), is defined by the National
Center for Complementary and Alternative Medicine (NCCAM) of the National Institute of Health as;
“a group of diverse medical and health care systems, practices, and products that are not presently considered to be part of conventional medicine. Conventional medicine is medicine as practiced by holders of M.D. (medical doctor) or D.O. (doctor of osteopathy) degrees and by their allied health professionals, such as physical therapists, psychologists, and registered nurses”.48
Complementary medicine is those practices used concurrently with conventional medicine, while alternative medicines are those used in place of conventional medicine.
Herbal supplements, “products made from botanicals that are used to maintain or improve health”, are one category of CAM, under the domain of “biologically based therapies”.48 Herbal supplements and remedies have been used for thousands of years.1-3
Their use in the U.S. declined in the early 20th century as the number of physicians increased and the medical model took hold with the general public.1 The use of herbal supplements began to regain popularity in the HIV epidemic; patients sought alternatives to the conventional medicines with which they were unsatisfied.1,7 Today, increasingly more people are incorporating CAM, especially herbal supplements into their 9 personalized health and wellness plan, despite limited evidence to verify safety or efficacy.1,4-6 CAM is also common among those with chronic illness, a condition not easily treated with conventional medicine or a condition that may be subject to stigma, such as mental illness.7 The line distinguishing between CAM and conventional medicines continues to blur as more conventional practitioners incorporate CAM into their practice.5,19,51
Herbal supplement use is the second most common used CAM therapy among women, after spiritual healing or prayer.19 Use of herbal supplements is found among every age bracket, every culture, every race and ethnicity, in both men and women, and in children, adults and the elderly.42 Herbal use has been reported in an infant as young as
1 week old; supplements used included aloe, chamomile, garlic and peppermint.52 Herbal supplement use may be found in as many as 1 in 10 children.42 Reported use of herbal supplements is rising, but more precise scope of use is little understood.16-19
Investigations of the U.S. population in general do not adequately address influences of culture, race and ethnicity.15,16 Community acceptance of herbal supplements is rising; so too is its availability.6,27
The World Health Organization states that “80% of the world population covers their need of drugs through herbal drugs”.28 In Italy, studies of herbal supplement use have estimated herbal supplement use at 47%.41 The most common choices were aloe, blueberry, dandelion, Echinacea and thyme.41 Rachel Westfall found that 50% of women surveyed in Canada were using ginger in some form during their pregnancy in contrast to other studies indicating use at 7%, 12% and 6.7%.53 In a 2001 study by Nordeng and
Havnen in Norway,36% of women surveyed were using herbal supplements during
10 pregnancy, with an average of 1.7 products per woman.28 Forster et al29 demonstrated 36% of women used herbal supplements in Australia during their pregnancy using a survey translated into five languages. The most common choices were raspberry, ginger and chamomile.
Current estimates for herbal supplements use for the U.S. population is 20%, almost doubling estimates of use of 12% in 1997.4,9 However, estimates vary widely based on survey population, the exact phrasing of the herbal supplement definition and survey instrument used and in what language the survey is conducted.4,11,15,21,52 The
California Health Interview Survey (CHIS) is conducted in English, Spanish, Mandarin,
Cantonese or Korean, the National Comparative Minority Health Care Survey is conducted in six languages, whereas the National Health Interview Survey (NHIS) is conducted only in English and Spanish.4,11,12,15 Glover et al21 assessed herbal supplement use by three measuring tools and found that reported use varied widely by tool. The
Hispanic population‟s estimated use of herbal supplements range as high as 80% and
Asian American use is estimated to be 25%. Estimates for the population in general increase to 42% if the question is phrased to incorporate use in the past 12 months vs. current use.9,15,54,55 The most common herbal supplements taken by Hispanics in Los
Angeles are mint, chamomile, cactus, aloe vera, rue, arnica and cat‟s claw.54 Grenigen et al14 surveyed CAM use by a small sample of Amish and reported 43% of the sample were using herbal supplements.
In Ohio, Martin et al8 investigated CAM therapy use and found that of the 329 participants not within a clinical setting,40% reported using herbal therapy with an average of 2.3 herbs per person. The most common choices were garlic, ginseng, ginkgo
11 biloba, SJW and echinacea.8 These herbs were used to improve general wellbeing, to treat colds, to improve memory or metabolism and for other reasons.8 Fifteen percent of herbal users reported giving herbal supplement to a child in their care.8 See appendix B for demographic data on the counties served by Nationwide Children‟s Hospital
Transport Team.
Several factors have been associated with herbal supplement use patterns in the
United States. These include being uninsured, female, middle age, having greater than a high-school education and use of prescription or OTC medications.8-13,17,18 Typical use by specific ethnic or racial groups is less well understood.12,15,16 In contrast to studies of the general population, race and ethnicity influences herbal supplement use and lead to differing patterns.12,15,16 Even to specify “Asian Americans” is to generalize the patterns of 25 ethnic groups, many countries, languages, cultures, access to health care, acculturation and immigration patterns and is an oversimplification of a complex group of people.11,15 Hsiao et al15,16 found only white and African-American women are more likely to use herbal supplements whereas this is not the case in American Indian, Asian or
Latino groups. High self-perceived health status is reported in the literature as both positively and negatively correlated with increased herbal supplement use.15,17,19 These factors are not universally corroborated.8,9,13,15-17
Herbal supplement use may be related to treatment of a specific condition, such as chest or head cold, depression,.17 arthritis or menopause, or, they may be a part of a general wellness problem.15,18 The literature reports that most herbal supplements are being used concurrently with prescription or OTC drugs.6,9,13,15,18 Only the minority of herbal supplement users are reporting herbal use to investigators; a scant 34% reported
12 disclosure of herbal use to their conventional medical professional.17,18 Most people who use herbal supplement plan to continue to doing so.23
Herbal supplement use in pregnancy
The prevalence of herbal medicine use by women during pregnancy is largely unknown; estimates range from 4 to 45%.5,22-27 Refuerzo et a10l, in an urban study largely of African American women found 4.1% of the 418 patients interviewed used herbal or alternative medicines during their pregnancy. However, Glover et al21 surveyed mostly white women in a rural population and found herbal supplements were used by 45% of the subjects. Because women are the main consumers of herbal medicine and that herbs are perceived to be natural, therefore safe, it can be assumed that a significant number of women are using herbal medicine during their pregnancy, delivery or lactation.5,23,26,30
Like the general population, most herbal supplement users during pregnancy are doing so concurrently with OTCs and prescription drugs.6,10,21,24 Some herbs used during pregnancy include chamomile, Echinacea, ginseng, aloe, cranberry, valerian, lemon balm, sage, ginger, red raspberry leaf, peppermint.6,23,24 The most common of these herbal supplement may be ginger, which is taken for nausea and vomiting.45,56
Women use herbal medicine during pregnancy for many reasons. The most common of which is nausea and vomiting, but also includes hyperemesis, foot edema, relaxation, low back pain, labor facilitation, mood enhancement and prevention or reduction of perineal trauma.5,23,45,51 Morning sickness is extremely common, affecting nearly 80% of women, and may have a significant negative impact on women‟s quality of life, relationships with their partner and family and lead to reduced work efficiency.5,45,53,56,57 The thalidomide tragedy has made women extremely cautious about
13 selecting treatment to their nausea and vomiting, and may have increased interest in
“natural” remedies.56,57
Hyperemesis, severe nausea and vomiting leading to electrolyte imbalance and dehydration, affects an estimated 1% of women during pregnancy and requires medical intervention.5,56 The challenge to treating morning sickness in any degree of severity, is that nausea and vomiting is most prevalent during the embryonic period, the period of development in which the fetus is most at risk for spontaneous abortion, birth defect or other chemical injury.5,25 Further, the mother may not even be aware of being pregnant at this time. Herbal medicines are selected over conventional pharmaceuticals due to the perception of being safer for both the mother and the fetus.5,6,23,24
The four main factors for women‟s satisfaction with their childbirth experience are the amount of support received, relationship quality with caregiver, personal expectations and their involvement in the decision making.58 CAM, including herbal medicines may align well with these factors and be appealing for use in preparation for and during delivery.58
Similar to use in pregnancy, women are self-medicating with herbal supplements during breastfeeding due to their belief that the herbal products are safer than prescribed or over-the-counter medications (OTC).21,49 One herb that is used during this time is fenugreek. 2 Fenugreek is believed to increase breast milk production, although there are no clinical trials to support safety or efficaty. 2 The majority of medications taken by a breastfeeding mother enter the milk supply; herbal products are believed to mirror pharmaceuticals, but evidence is lacking.49 Increased caution should be given to premature, medically unstable or newborn babies whose liver have not yet developed
14 their full metabolic capacity.49
Patient disclosure of herbal supplement use
Patient disclosure of herbal supplement use is affected by many factors. Recent studies of the U.S. population indicate that only one-third of herbal supplement users are disclosing this information to their doctors and other healthcare professionals.14,17,18 Due to the common perception that herbal supplements are benign, many herbal supplement users do not feel it is important to disclose their herbal supplementation to their healthcare professionals and physicians.41,52 Patients may not disclose herbal supplement use due to narrow-mindedness on the part of their physician or to assumed disinterest.7
Women are more likely to disclose herbal supplement use to their physician, as are older adults and those with a poorer health status, as measured by self-assessed health status and increased hospitalization. Perhaps the biggest barrier to patient disclosure is related to physician and other healthcare professionals not asking about herbal supplement use.15,55
Minorities, including African Americans, Asian Americans, the Amish and non- citizens are less likely to disclose their herbal supplement use to their physician and other healthcare professionals.13-15 Asian American disclosure of herbal supplement use may be as low as 16%.15 The Hispanic population, found to be heavy consumers of herbal supplements, is less likely than the general U.S. population to disclose use to their physician. The underlying principle for the higher use in this population is not well understood at this time.15,52,55 Potential barriers to disclosure for the Hispanic population include language, less rapport with the physician and not being as likely to be encouraged to participate in their healthcare decision making.55 Another barrier is not knowing the
15 English word for an herbal supplement, even if they feel comfortable communicating in
English. If healthcare professionals were able to better understand the reasons for using herbal supplements in general, they may be better able to facilitate dialogue with their patients individually.59
Increased disclosure in acute situation
It has been noticed anecdotally, that in an acute situation, such as when a neonate must be admitted to an emergency room, that the mother may disclose information to healthcare professionals not previously divulged.60 The hope of the mother is that the information may help her baby.
There are many potential adverse effects associated with herbal supplement use.
Some of these have been reported anecdotally and others have been reported from clinical trials. A summary of these potential adverse events are summarized in the following table.
16 Herb Potential adverse Additional Reports from the effects related to potential problems literature specific to usage identified for specific to the pregnant the general pregnancy/neonatal population population period Aloe Possible Anecdotal reports of hypoglycemia; Proven aloe latex inducing potassium depletion spontaneous abortion when taken orally in 2,62 large amounts. Possible renal failure when taken orally in large amounts 2,61 N,D Aniseed * Topically, anise in combination with other herbs can cause localized pruritus 2 Black Question of possible Possible teratogenic; Cohosh liver damage, seizures possible and kidney damage 2,35 abortifacient 2 N,D Blessed Allergy, for those with Thistle * allergies to ragweed and marigold and GI irritation 2 Blue Cohosh Possible coronary Possible teratogenic; artery constriction, Probable Myocardial infarction, abortifactient 2,64 profound congestive heart failure and cardio-shock, seizures and kidney damage 2,63 D Caster Oil Probable fluid and Probable Increased Meconium electrolyte imbalance, abortifactient and staining; Report that particularly with may induce preterm castor oil may cause potassium when used labor/delivery; may amniotic fluid embolism for greater than one delay rupture of and cardio pulmonary week. NOTE: membranes 2,65 arrest 2,66 Chewing castor seeds can be poisonous 2 N,V,D Continued Table 2.1: Identified concerns with herbal use in pregnancy 17 Table 2.1 Continued Herb Potential adverse Additional Reports from the effects related to potential problems literature specific to usage identified for specific to the pregnant the general pregnancy/neonatal population population period Chamomile German variety: Possible estrogenic (German) Possible increase effects that could bleeding time; possible affect pregnancy 2 2,61 allergic reaction N,V,C,D
(Roman) Roman variety: Possible possible allergic abortifacient 61 reaction 2,61 Coriander * One case report of diarrhea, stomach pain and depression following 7 days of coriander extract 2 Cranberry D 2 Echinacea Possible allergic reactions 2,67 N,V,C,D Evening Possible prolonged Reports of delayed Primrose bleeding time 2,68 progression of labor and prolonged rupture of membranes 2 Fennel fruit * allergic reaction, photodermatitis 2 Fenugreek * D, dyspepsia, uterine stimulating misdiagnosis of maple- effects 2 69 syrup disease, 2 Garlic Proven prolonged bleeding time 2,61 N,V,D Ginger Possible prolonged Might affect fetal sex bleeding time 61,61 hormones (preliminary D evidence) 2 Ginkgo N,V,C,D 2 Intrauterine growth retardation reported with use in rats 33 Continues Table 2.1: Identified concerns with herbal use in pregnancy
18 Table 2.1 Continued
Herb Potential adverse Additional Reports from the effects related to potential problems literature specific to usage identified for specific to the pregnant the general pregnancy/neonatal population population period Ginseng Possible prolonged Possible teratogenic (American, bleeding time; Possible effects 2,67 Panax, Siberian) 2,67 hypoglycemia
Goldenseal Possible hypoglycemia Probable that Several reports of 2,67 berberine in the Kernicterus in newborn Goldenseal is infants exposed to thought to cross the goldenseal. Particularly placenta and then it a concern in preterm replaces the bilirubin infants 2 from the albumin which causes hyperbilirubinemia in infants 2 Green Tea N,V,C,D 38 , insomnia Caffeine content 2 Antifolate activity of 2 catechin compounds found in tea may increase risk of spina bifida 2,70 Juniper Kidney irritation 2 Juniper oil taken orally can cause spontaneous abortion 2 71
Kava kava Hepatoxicity 2 Loss of uterine tone 71 Lemongrass Uterine stimulating * effects 2
Lemon Kidney irritation 2 verbena * Continued Table 2.1: Identified concerns with herbal use in pregnancy
19
Table 2.1 Continued
Herb Potential adverse Additional Reports from the effects related to potential problems literature specific to usage identified for specific to the pregnant the general pregnancy/neonatal population population period Marshmallow Hypoglycemia 2,72 root * Mother‟s Fennel fruit, aniseed fruit, coriander fruit, fenugreek seed, blessed thistle, Milk Tea spearmint leaf, lemongrass leaf, verbena leaf, marshmallow root
Nettle Gastrointestinal discomfort, sweating 2 Noni Juice Hepatoxicity 2
Omega-3 weight gain, fatty acids anticoagulant 2,73-76 Papaya Esophageal perforation Spontaneous enzyme abortion 2 Peppermint Possible allergic reactions; possibly affects sex hormones (preliminary evidence) 2,61 N,V,C,D Raspberry Possible estrogenic effects that could affect pregnancy, 2,43 St. John‟s Insomnia, anxiety, Intrauterine growth Wort photosensitivity 2 retardation reported N,D with use in rats 34 Spearmint * None reported 2 Stinging N,V,D, rash 2 Possible uterine- nettle stimulating effects 2 Ingredient in Mother‟s Milk Tea 77; N= nausea, V = vomiting, D = diarrhea, C = constipation
Table 2.1 Identified concerns with herbal use in pregnancy
20 With countless identified and unidentified potential chemical compounds found in herbal supplements, and a documented wide variation in active ingredients, as well as the high potential for interactions with prescription and OTC medications, it is a daunting task for the healthcare professional to make judgments of safety for their patients wishing to use herbal supplements.6,24,36,37 The evidence for use during pregnancy, labor and delivery and lactation is even smaller.2,6,37 Many changes occur in the body during pregnancy, including physiologic and pharmacokenitic .10 These changes may alter dosing, efficacy and safety of any drugs; prescription, OTC or herbal. The majority of pharmaceutical studies exclude women, especially pregnant women.22 At the time a new drug is approved for testing in humans, it may have only been tested in male animals and cells. This gives the physician the individual responsibility to judge how a women‟s metabolism may differ from a male‟s metabolism, and, how a pregnant women‟s may change dosing needs further.
While prescription drugs are regulated by the federal government and contain purified, stable, tested compounds.22 Herbal supplements are not regulated by the federal government nor do they contain verified amounts of a single compound.24,38,42 This regulation scheme falls under the Dietary Supplement Health and Education Act of
1994.38,42 This act stipulates that manufacturers of herbal supplement are required to ensure, but not demonstrate safety or efficacy of their herbal products prior to being placed on the market.42,47 “FDA's post-marketing responsibilities include monitoring safety, e.g. voluntary dietary supplement adverse event reporting, and product information, such as labeling, claims, package inserts, and accompanying literature.38”.
The FDA is only required to take action if a product already on the market has been
21 found to be unsafe. In June of this year,2007, the FDA strengthened regulations for herbal supplements.38 In a press release, the Commissioner of Food and Drugs Andrew C. von Eschenbach, M.D. 38 stated that “by the end of the year, industry will be required to report all serious dietary supplement related adverse events to the FDA”. In light of these vague acts, and the laws being only recently strengthened, it is clear why there is an enormous difference in contents and quality of herbal products found on the market.36,38-
40,42
Standardized herb preparations that have been independently verified must be used in many additional clinical trials to establish safety, proper dose and efficacy before clear recommendations can be made.36 These studies cannot simply include a short term assessment of congenital birth defects at birth, but also a long term assessment of possible subtle effects that may only be apparent as the neonate ages.6 The Teratology
Society has recommended to the FDA that “dietary supplements should not be labeled for use in pregnancy unless they have been shown safe by standard scientific methods”.37
Enormous discrepancies exist between ingredient claim of the bottle and what is independently verified.36,39,40 In a study of Echinacea preparations, Gilroy et al40 found that 10% of supplements contained no measurable Echinacea at all and only 31% of the labels matched the content. It is rare that a specific dose is universally recommended for a particular herbal supplement for treatment of a particular condition.36,40
Recommendations for a single herb vary widely between brands. For example, Harvey
Schwertner et al36 found that recommendations for ginger supplementation found on the product bottle varied from 250 mg to 4.77 g per day.
Manufacturers are not required to disclose adverse events associated with use of
22 their herbal supplements, either to any health agency or to the federal government.9
Current reports come largely from consumers, emergency departments and poison control centers.30,37 As few as one-fourth of consumers who experienced an adverse event believed to be related to a supplement that they took reported the event to a health authority and less than ten percent complained to the manufacturer.9
Attitudes regarding risk
Herbal supplement users have a high perception of safety of the products that they choose.23,28,42,45,56 Less than 20% of users believe that their herbal supplement practices carry potential risk1,23 The overwhelming belief is that herbal supplements carry far less risk than prescription medications.28,45,56 Most herbal supplement users are unable to identify a potential side effect or drug interaction.28,42 Howell et al55, in a study of 620
Hispanic persons in Indiana found that one third of study participants “believed that some herbs could interact with prescriptions and that herbs were not safe to use during pregnancy”.
Sources of information for herbal supplement use
Herbal supplement use in the general population, as well as in pregnancy, is largely self directed and unsupervised by a physician or healthcare professional.56 The most common cited source for herbal supplement advice is from friends and family, and may be the sole criteria for a decision to use herbal supplements.52,54,56 However, advice for using herbal supplements can come from any source. Hollyer et al56 found that only
21.6% of CAM users did so after consultation with a CAM practitioner. Race and ethnicity are strong influences on health-seeking behavior.16,54
In a world with easily accessible technology, too few clinical studies and too little
23 evidence, anyone can claim to be an expert.52 Women using herbal supplements are obtaining advice from friends, family, midwives, health food stores, the internet, books, magazines, doctors, naturopaths, herbalists and advertisements.26,43-46 An herbal supplement user or advocate may simply base their recommendations on historical use.3,6
Current herbal usage patterns in the U.S.A. do not necessarily mirror traditional medicines such as Chinese Medicine.6 Herbal supplement users tend to be self-care- based in their decisions to treat.4,9 In 2002, 95% of herbal supplement users were self- care-based whereas in 1995, 85% of users were self-care based.4
Midwives
Several studies have found that midwives are likely to recommend herbal supplements for women during pregnancy, labor and lactation.44-46,50 McFarlin et al44 conducted a national survey of Certified Nurse Midwives (CNMs) in the U.S. to investigate use of herbal supplement use to stimulate labor. Close to half of the CNMs who returned the survey did not report herbal supplement use, citing lack of scientific data to support efficacy and safety. The half who did report use of herbal supplements during labor reported black and blue cohosh, castor, red raspberry leaf and evening primrose oil. The doses of these herbal supplements were quite varied. For example, the dose of castor oil recommended ranged from 5 to 120 ml. A survey of U.S. midwives found that 45% of them were using black cohosh, as part of a traditional preparation of
“mother‟s cordial” to facilitate labor.34 Bayles 45 surveyed LMs and CNMs in Texas regarding CAM and herbal supplement use and found that 90% of the practitioners used, recommended or referred their clients to use herbal supplements. Herbal supplements
24 were in the top three recommendations for 7 out of the 13 clinical indications, such as back pain, headache and nausea. The two most common herbs recommendations were mint and ginger. Similarly, in North Carolina, Alliare et al26 surveyed CNMs and found that 73% were recommending herbal therapy including ginger, peppermint, raspberry and chamomile. In this study, most midwives stated that they were recommending herbal therapy because of patient preference.
Nurses and midwives have the greatest potential for educating women before, during and after pregnancy but minimal evidence from which to draw conclusions.6 Not only do CNMs give herbal supplement information to the women they are helping in childbirth; they are sharing information with one another. CNMs have reported other
CNMs as their primary source of herbal supplement information, not scientific studies or a specific medical reference.78 Herbal supplement articles in nursing and midwifery journals are mainly dated post 1995, suggesting that discussion of this increasing phenomenon is relatively recent.6
Healthcare practitioners and physicians
Patients are increasingly asking their primary care physician for advice on herbal supplement use but most physicians surveyed do not feel they are adequately prepared to provide such advice.23,39,41,42 Conversely, Chao et al59 report 14% of women herbal supplement users do so at the recommendation of their physician.
Friends and family
25 Friends and family are a substantial influence on the health care choices that people make, and herbal supplements are no exception.54,59 Family can be the single most influential factor for choosing to use herbal supplements.56,59 In the Hispanic population, the majority of information and recommendations regarding herbal supplement use is from friends and family.54,55,59 In a survey of WIC participants, the vast majority of information upon which herbal supplements users were basing their decisions were from family (78.9%) and friends (32.9%).52
Health food store
After family and friends, many women may believe their local health food store is the best source for herbal supplement advice.23 In Ohio, the second most common source of information about herbal supplements is the health food store.8 Patrons of health food stores seek advice from the employees often, despite the fact that the employees may have little to no training to prepare them to give credible advice.47 Buckner et al47 posed as pregnant women and asked health food store employees, over the phone, for advice for their nausea and vomiting of pregnancy (NVP). The most common recommendations included ginger in multiple forms, mint and red raspberry. Of all the recommendations from this study, most were benign, but a small percentage was not safe for pregnant women to be consuming (black cohosh, aloe and bilberry) and several were incorrect.
The sheer volume of herbal supplements available in health food stores can also make it difficult to find appropriate supplements for pregnancy. Selecting an herbal
26 supplement to purchase may be a daunting task because of the enormous number of brands and products.39 In a study of the top ten herbs sold in the U.S., Garrard et al39 found 880 different single ingredient products by 241 brands.
Internet, self-education, television
Many people are influenced to use herbal supplements by advertisements on the television or radio. For Hispanics in Los Angeles, the television is the second most common source for herbal supplement information.54 As many as 43% of herbal supplement users did so because of these kinds of ads that portray OTCs and prescription drugs as more dangerous than „natural‟ cures.41,59 In Ohio, the most common source of information about herbal supplements is magazines.8
It is possible to purchase many herbal supplements over the internet.37 On these sites, it is possible to find many illegal health claims that consumers believe have been verified by the FDA.37
Herbal supplements are widely available, poorly regulated by the FDA and understudied in the scientific literature. Didactic and continuing education programs for healthcare professionals must incorporate the fundamentals of herbal supplements, their uses, safety and efficacy and interactions, such that health care professionals are able to confidently provide counsel to their patients and clients. Educational materials are also needed for the general public such that they are able to evaluate the merit of the advice given to them by the sources they use the most; friends, family and the internet.
27 Herb Reported reason for use during pregnancy Aloe topically as an antibacterial and antifungal and orally for constipation 2,67 Aniseed to increase lactation and to facilitate birth 2 Black cohosh to induce labor 2,35,67,79
Blessed thistle To stimulate milk flow 2
Blue cohosh to induce labor 2,67,79
Caster Oil to prevent pre-eclampsia, to induce and to shorten labor, to prevent post-date deliveries 2 Chamomile (also for calming effect 2,67 called Manzanilla) Coriander to augment lactation; general use for nausea, diarrhea and antiflatulent 2 Cranberry General use for urinary tract infection prevention 2 Echinacea as an immunostimulant 2,6,67,80
Evening primrose to prevent pre-eclampsia, induce labor; stimulate labor, and to prevent post-date deliveries 2,67 Fennel fruit to facilitate labor and to increase lactation2 Fenugreek promoting lactation 2
Garlic as a antihyperlipidemic, antihypertensive and antifungal 2,67 Ginger as an anti-emetic .2,56,57,63,67,81-83
Continues
Table 2.2: Selected herbal supplements used in pregnancy
28 Ginkgo general use for memory loss, dementia, mood disturbances, concentration and PMS 2 Ginseng to enhance memory 16,38 Green tea general use for cognitive performance, vomiting, diarrhea, headache and others 2 Goldenseal as an immunostimulant; as an antibacterial and antifungal agent 38 Juniper general use for UTI 2
Kava kava general use for calming effect 2
Lemongrass general use for vomiting, abdominal pain, fever, common cold, exhaustion 2 Lemon verbena general use for digestive disorders (38}
Omega-3 fatty general use for hypercholesterolemia, acids depression and multiple sclerosis 2 Marshmallow root general use for respiratory tract infection, cough and UTI 2
Mother‟s milk tea “to promote healthy lactation” 77 Nettle general use for UTI and allergic rhinitis 2
Noni juice preparation for childbirth 2
Papaya enzyme general use for digestive aid 2
Peppermint as an anti-emetic, to decrease gas production and for calming effect.16,38 Raspberry to increase uterine tone and alleviate nausea 16,38,46 St. John‟s Wort general use for depression
Spearmint Generally used for digestive disorders, sore throat, cramps, nausea 2
Table 2.2: Selected herbal supplements used in pregnancy
29 The following pages are brief summaries of the herbal supplements identified by this and other studies as being used during pregnancy. For each supplement, the reasons for use are identified, possible drug or herbal interactions, safety and efficacy and any clinical trials. For most herbal supplements there is insufficient evidence to rate safety or efficacy for use in pregnancy. 2
Aloe:
Topically, aloe is used to treat minor cuts, burns, osteoarthritis and inflammation.2
Orally, aloe is used for bowel upset, including inflammatory bowel disease, constipation and ulcers, for fever, inflammation and as a general tonic. Oral use during pregnancy or lactation may be harmful to the fetus; aloe inducing abortion has been reported anecdotally. 62 Orally, aloe may interact with digoxin, antidiabetes drugs, diuretics, sevofluane and stimulant laxatives.Topically, aloe is considered safe during pregnancy.2,47
Anise
Anise, a separate species from star anise, is used medicinally to treat dyspepsia, flatulence, to stimulate the appetite, as a diuretic and as an expectorant. Anise is also used to increase lactation and to facilitate birth. 2 Topically, anise is used to treat lice and scabies. In foods and in manufacturing, anise is used as a flavoring; it has a flavor similar to licorice. In food amounts, anise has GRAS status in the U.S. The GRAS status applies in pregnancy and lactation, however there is yet insufficient evidence to rate medicinal amounts of anise. Anise may interact with contraceptive drugs and tamoxifen. There are no known food or herbal interactions.
30 Black cohosh:
Black cohosh, a distinct species from blue cohosh, is used orally to induce labor.2,35 Black cohosh is used alone, or as part of a “mother‟s cordial”; a preparation of five herbs.35 If used during pregnancy, black cohosh may increase risk of miscarriage and has been used as an abortifacient, with the highest risk during the first trimester. There is additional concern that black cohosh may have an emmenagogue effect. Due to some reports of decreased liver function in patients using black cohosh, liver function should be monitored.2 Safety of black cohosh during labor has only been verified observationally, not clinically. It is not recommenced to use black cohosh during lactation. Black cohosh may interact with cicplatin and hepatoxic drugs.
Blessed thistle
Blessed thistle, a separate species from milk thistle, is used medicinally for loss of appetite, diarrhea. Blessed thistle is also used orally for promoting lactation, and for treating colds and fever. Topically, blessed thistle is used as a poultice for boils, wounds, and ulcers. In manufacturing, blessed thistle is used as a flavoring in alcoholic beverages.
2 Blessed thistle has GRAS status for amount commonly found in food. However, it is likely unsafe for use in pregnancy and there is insufficient evidence to rate safety or efficacy for use in lactation; avoid using. Blessed thistle may interact with antacids, H2- pump blockers and proton pump inhibitors. Blessed thistle is also known as holy thistle and spotted thistle.
Blue cohosh:
Like black cohosh, blue cohosh is also used orally in pregnancy to induce labor and has been used for centuries.2,27,63 Blue cohosh is pharmacologically similar to
31 nicotine and leads to blood pressure increases.44 Blue cohosh has several chemical components that can be teratogenic and can cause congenital defects in newborns and life-threatening toxicity.2 Case reports of infants suffering seizure, stroke and renal failure have been linked to blue cohosh. Less severe possible complications include nausea, meconium stained fluid and transient fetal tachycardia.27 In a 1998 case report by Jones and Lawson, one women‟s neonate was admitted to the intensive care unit shortly after spontaneous vaginal birth due to acute myocardial infarction.63 The mother had taken three times the dose of blue cohosh recommended by her midwife three times per day for the three weeks prior to birth. The neonate was intubated for three weeks.2 At age two years, the child exhibits cardiomegaly.63
Castor:
Anecdotal reports of castor use date to ancient Egypt.50 Orally, castor seeds are used to treat constipation and to prevent conception. Castor oil is used orally to stimulate labor and to stimulate breast milk.2 Whole seeds, which contain the poison ricin, are not considered safe orally because as few as one to six seeds have been found lethal in adults when chewed. Use of oil at term to stimulate labor has been shown to be effective and is possibly safe but should occur under the care of a clinician.2,50 Gary et al50 found castor effective within 24 hours for stimulating active labor. However, all women in the study ingesting the 60ml dose of castor experienced nausea. “There is one case of amniotic fluid embolism and cardiopulmonary arrest within one hour of ingestion of 30mL of castor oil at full-term pregnancy”.2 Oral use of castor oil during lactation and before the fetus is full term is not recommended. Castor oil may interact with diuretic drugs.
32 Chamomile, German:
In pregnancy, German chamomile is mainly used orally to sooth restlessness and insomnia.2 It is also used topically for hemorrhoids, ulcers and bacterial skin diseases and as an inhalant for irritation of the respiratory tract. In general, German chamomile is considered safe for use in amounts found in foods. However, for pregnant or lactating women, there is insufficient evidence available. One case study reports a women‟s neonate‟s fatal reaction following a chamomile extract enema.84 Within an hour of the enema, the women underwent emergency cesarean. The neonate was born severely asphyxiated and with an Apgar score of 0 and died the following day. German chamomile may interact with benzodiazepines, CNS depressants, contraceptive drugs, estrogens, tamoxifen and warfarin.2
Coriander
Coriander, also known as cilantro, is used for loss of appetite, nausea, vomiting, and diarrhea, to treat hernia, hemorrhoids and toothache and to augment lactation. In foods, coriander is a spice and is used both for flavoring and to prevent food poisoning. 2
The seeds and leaves of the coriander plant are used. There are no known herbal, drug or food interactions.
Cranberry:
Cranberry is used for the prevention and treatment of bladder and urinary tract infections (UTIs) and is considered possibly effective in juice form.2,85 The current evidence for encapsulated cranberry is not reliable.2 Optimal dose of cranberry is not known.85 When faced with a UTI, a pregnant woman may first turn to cranberry juice before an antibiotic.23 Although the woman may feel she is decreasing risk of harm to
33 herself and her fetus, she may be doing the opposite if the UTI is not controlled and leads to other complications. Pregnant women are at higher risk for UTIs because of changes in their immune function; this fact places pregnant women with a UTI at a greater need for treatment to prevent further complications.85 While considered likely safe by the Natural
Medicines Comprehensive Database, there is insufficient evidence for therapeutic use during pregnancy and lactation.2 Cranberry may interact with Warfarin (Coumadin).2
Echinacea
There are nine species of Echinacea; only three of which are generally used.40,80
Historically, Echinacea was used by Native Americans to treat many conditions including bites, infection and joint pain.49,80Today, Echinacea is one of the most common herbal supplements used in the U.S., representing 10% of the U.S. herbal supplement market.2,9,40,47,49Amounts of active compounds in echinacea are not consistant; mature, two-year old plants have 10 to 100 times the active compounds as young plants.40
Echinacea has exhibited anti-viral, antibacterial and antifungal properties.49,80 Since the early twentieth century, Echinacea has been commonly used orally for the treatment and for the prevention of the common cold and upper respiratory infections.2,24,40,80 Orally,
Echinacea is also used as a general immunostimulant for several other conditions.
Echinacea may be safe for use in pregnancy and lactation, but further studies are needed to make more concrete recommendations.2 In one study, Echinacea was not found to increase risk of major malformations.80 In addition, an expert panel in Germany judged
Echinacea to be safe for use in pregnancy and lactation if appropriate doses are followed.
Echinacea may interact with caffeine, immunosuppresants and midazolam.2,80
34 Evening Primrose Oil
Evening primrose oil (EPO) is extracted from the seed of Oenothera biennis .2,44 It has been widely studied in Europe and is used to treat a variety of conditions including
PMS, acne, menopause, eczema, rheumatoid arthritis and others.44 In labor, EPO is used to stimulate cervical ripening, but it is not recommended for use due to increase risk of complications including delayed rupture of membranes, oxytocin augmentation and vacuum extraction.2,44 EPO is recommended as a dietary supplement to increase the total fat content of breast milk.44 EPO is possibly safe for use during lactation. 2 EPO may interact with anesthesia, anticoagulants and phenothiazines.
Fennel
Fennel is used during pregnancy to facilitate birth and after birth to increase lactation. Fennel is also used to treat upper respiratory tract infections, backache, bedwetting and dyspepsia. 2 In foods and in manufacturing, fennel oil is used as a flavoring agent. Fennel has GRAS status in the U.S., but is possibly unsafe when used in medicinal amounts for long term. In pregnancy and lactation, there is insufficient evidence to rate safety or efficacy. Fennel can cause allergic reactions affecting the skin and photodermatitis. Fennel can interact with ciprofloxacin, contraceptive drugs, estrogens and tamoxifen. There are no known food or herbal interactions.
Fenugreek
Fenugreek is used both as a spice in cooking as well as in traditional medicine.49,86 In Traditional Chinese Medicine, fenugreek is used in pregnancy to stimulate milk production and has been found to be efficacious in doubling milk production without report of negative effects. Fenugreek may interact with warfarin,
35 anticoagulant medications and antidiabetes drugs.2,49,86 There is concern that fenugreek may increase risk of bleeding in women taking anti-inflammatory medications, such as aspirin.86 Furthermore, there is concern for use in pregnancy due to potential oxytocic and uterine stimulant activity.2 Fenugreek, used in foods to imitate maple syrup, has been linked to false diagnosis of maple syrup disease when the mother consumed fenugreek prior to delivery.
Garlic
Garlic is used in the treatment of many conditions including hypertension, hyperlipidemia, fungal infection and coronary heart disease.2,49 Garlic is also used to stimulate the immune system, as a diuretic and to increase circulation.2 For the general population as well as for pregnant women, garlic is considered likely safe when used orally and in the amounts found in foods. In oral therapeutic doses, garlic may act as an abortifacient. Garlic used topically or during lactation may pose a threat to the mother or neonate; it has been found in breast milk.49 Garlic may interact with warfarin, contraceptive drugs and isoniazid.2
Ginger
Ginger has a significant history in medicine, dating back to the 1500s in Chinese,
Japanese, and Indian medicine.57,83,87 Several active compounds have been identified in ginger, including 6-gingerol,6-shogaol,8-gingerol and 10-gingerol, but there may be more.36 Concentrations of these compounds and recommended doses vary widely between available supplements, anywhere from .5 to 2g per day.36,82 Ginger is quite common today, largely as a carminative for nausea, including motion sickness, morning
36 sickness and post-surgical nausea.2,27 Westfall found that 50% of women surveyed in
Canada were using ginger in some form during their pregnancy in contrast to other studies indicating use at 7%, 12% and 6.7%.53
Ginger does appear to be efficacious for nausea and vomiting; one small study of ginger syrup equivalent to 1g ginger per day indicated decreased nausea as compared to placebo.30,57,82,88 However, ginger may not be more effective than pyridoxine (vitamin B6) and sometimes exacerbates, not mediates nausea.27,30 Ginger does not appear to increase risk for major malformations, but further studies are recommended.30,57,87 However, there is some evidence that ginger may affect fetal sex hormones.2 Of particular concern during labor and delivery, ginger may increase bleeding risk by inhibiting platelet aggregation.6,27,53,83 Use of ginger is cautioned against by midwives and herbalists if the women exhibit any signs of impending miscarriage such as uterine cramping or bleeding.53 Due to insufficient reliable evidence, it is not recommended to use amounts greater that what is found in food during lactation.2,30,83 Ginger may interact with anticoagulant drugs, antidiabetes drugs, antacids, calcium channel blockers, and Warfarin
(Coumadin).2,83
Ginkgo biloba
The ginkgo biloba tree is the world‟s oldest tree and has been used medicinally for thousands of years in TCM.33 The first standardized extract was available in 1975.33
Ginkgo biloba leaf is used orally for the treatment of dementia, memory loss, poor circulation, vertigo, poor concentration, and headache.2,27,33 Ginkgo is not considered safe during pregnancy due to potential labor-inducing hormonal effects and increased bleeding time during labor and delivery.2,33 There is insufficient evidence to support use
37 in lactation; it is not reported as safe or as toxic.2,33 Ginkgo may interact with Alprazolam
(Xanax), anticoagulants, anticonvulsants, Antidiabetes drugs, Fluoxetine (Prozac),
Ibuprofen, Omeprazone (Prilosec), Trazodone, Warfarin (Coumadin) and Buspirone.2
Ginkgo may interact with SJW.33
Ginseng
Ginseng has been used medicinally for over two thousand years.2 In contrast to
American recommendations to use as a stimulant, ginseng is used in Traditional Chinese
Medicine as a sedative and to enhance both physical and mental performance.2,49
Although potentially used for similar conditions, American ginseng is a different species from both Siberian ginseng and Panax ginseng and must be investigated separately.2 All three types of ginseng are in the Araliaceae family and have estrogenic properties.2,24 It is not known if ginseng transfers to breast milk.49
Ginseng, American:
American ginseng is used orally to increase resistance to environmental and emotional stress, as a stimulant, for treating insomnia and to stimulate the appetite.2,49
One active component of American ginseng may be teratogenic. Therefore, it is not recommended to use during pregnancy or lactation.2 American ginseng may interact with antidiabetes drugs, monoamine oxide inhibitors and Warfarin (Coumadin).
Ginseng, Panax:
Panax ginseng is used to generally increase wellbeing, adaptation to stress and stimulate immune function.2 Panax ginseng is also used for memory, concentration, anxiety and chronic fatigue syndrome. Panax ginseng, like American ginseng, has the potential to be teratogenic and is not recommended for use during pregnancy or lactation.
38 Panax ginseng may interact with anticoagulants, antidiabetes drugs, furosemides, immunosuppresants, insulin, monoamine oxidase inhibitors (MAOIs), stimulant drugs and warfarin.
Ginseng, Siberian:
Like Panax and American ginseng, Siberian ginseng is used orally as an adaptogen to help the user better tolerate environmental stress.2 It is used as an immune stimulant, for prevention of colds and the flu and to normalize blood pressure. Siberian ginseng may interact with anticoagulant drugs, antidiabetes drugs, CNS depressants and digoxin. Silk vine, a common adulteration of Siberian ginseng, has been reported to have caused androgenization of a fetus following maternal use.
Goldenseal:
Goldenseal is used, often in combination with Echinacea, for the treatment of upper respiratory infections.2,83 There are few clinical studies of berberine salts, the main active ingredient, and even fewer on goldenseal itself.83 Use during pregnancy is not recommended for fear of premature induction of labor. There is also evidence of the berberine salts crossing the placenta, placing the fetus at risk.2 There are several fatal case reports of goldenseal causing kernicterus, brain damage due to excessive jaundice.Use during lactation may also place the infant at risk. Goldenseal may interact with cyclosporine and digoxin.
39 Green Tea:
Green tea as a beverage is used for a wide variety of reasons including nausea, vomiting, diarrhea, osteoporosis, solid tumor cancers, headache, to reduce the risk for cancer, genital warts, Crohn‟s disease, cardiovascular disease, chronic fatigue syndrome, kidney stones and skin damage.2 Topically, green tea is used to treat sun burnt skin or as a compress for headaches or to sooth tired or irritated eyes. In Asian cultures, green tea may be consumed daily and is an important part of the culture. It is likely safe when consumed as a beverage in moderate amounts or when used topically. Green tea extract is possibly safe and has been used safely in a trial lasting six months. Concern is warranted in excessive doses due to the significant amount of caffeine found in green tea.
In pregnancy, green tea is possibly safe when consumed in moderate doses; caffeine can cross the placenta, but is not considered to be a teratogen.2 Concentrations of caffeine in the neonate‟s blood are close to that of the mother. Current recommendations are for mothers to not consume above 200mg of caffeine, which is equivalent to approximately 2 cups of green tea. Kohkhar et al70 found the caffeine content in various green teas to range from 11.5 to 19.5 mg/g of dry tea.
Other than caffeine, there is concern in pregnancy due to catechins; catechins is the collective name for the polyphenols found in the tea and include epigallocatechin gallate (EGCG), epigallocatechin (EGC), epicatechin gallate (ECG) and epicatechin (EG).
Catechins are present in the highest concentrations in green tea (16-30%), over black tea
(3-10%) or oolong tea (8-20%).70 These compounds can cause antifolate activity due to
40 their inhibition of the enzyme dihydrofolate reductase. This is the enzyme responsible for converting folic acid to its active form. There is preliminary evidence for green tea consumption increasing risk of spina bifida.2
In lactation, green tea is considered possibly safe in moderate amounts; breast milk concentrations of caffeine are approximately half of the blood concentrations.2
Adverse reactions reported for green tea are usually associated with large amounts of tea
(5-6 liters) or consumption of green tea extract in pill form. These reactions include nausea, vomiting, diarrhea, insomnia, and hepatotoxicity.
Green tea can interact with many herbs and drugs. These include bitter orange, creatine, ephedra (Ma Huang), hepatotoxic herbs and drugs, iron, adenoside, alcohol, amphetamines, anticoagulant drugs, cimetidine, clozapine, contraceptive drugs, estrogens,
MAOIs, pentobarbital and warfarin.2 Green tea appears to reduce the absorption of non- heme iron from foods due to the flavonoid content; this is especially pertinent in pregnancy.2,89,90 The inhibitory effects of tea on iron absorption are diminished when the tea is consumed between meals rather than with meals.90
Juniper
Oil from juniper berry, a tree native to Europe, Asia and North America, is used orally for dyspepsia, UTIs, bladder stones and snake bite. 2 Juniper berry is used as a condiment in foods and is a flavor component of gin. Juniper has GRAS status in the U.S. when used orally in the amounts commonly found in foods. However, it is ranked by the
Natural Medicines Comprehensive Database as likely unsafe in excessive amounts or for long-term as use increases risk of kidney damage. Juniper is most often taken medicinally as a tea prepared with crushed juniper berries and boiling water or as a tincture with a 1:5
41 ratio of juniper oil to alcohol. Juniper is unsafe for use during pregnancy as it can increase uterine tone and risk spontaneous abortion. Evidence for use during lactation is lacking; avoid using. Cade oil, distilled from juniper wood, had different properties to juniper oil from the berries and should be evaluated separately.
Kava kava
Kava beverage has been drunk for social and ritual purposes in the South Pacific for thousands of years.2 Kava with discovered by Captain Cook who named the plant
“intoxicating pepper”. Kava kava is used orally mainly to lower anxiety and to induce sleep but also for UTIs, chronic fatigue syndrome and the common cold.2,49 Kava has been shown to cause hepatotoxicity and liver failure, even with normal, short-term doses.2 Kava has been banned in several countries, including Canada, Switzerland and
Germany. It is not considered safe for use in pregnancy or lactation. Kava may interact with alprazolam, CNS depressants, hepatotoxic drugs, levodopa, and alcohol.
Lemongrass
Orally, lemongrass is used to treat stomachache, hypertension, vomiting, cough, common cold and exhaustion. 2 Lemongrass and lemongrass essential oil are used topically to treat headache, abdominal pain and muscle pain. In foods and in manufacturing, lemongrass is used as a flavoring agent, commonly in teas. Lemongrass has GRAS status and is considered safe when consumed in food amounts. Lemongrass is possibly safe when used medicinally topically or orally for short term, two weeks or less.
Lemongrass is likely unsafe for oral use during pregnancy due to its uterine stimulating
42 effects. There is insufficient evidence to rate use during lactation therefore it is recommended to avoid until further study is conducted. There are no known food, herbal or drug interactions.
Lemon verbena
The leaves and flowering tops of the lemon verbena are used orally for fever, digestive disorders, insomnia, varicose veins, chills and constipation. 2 The essential oils from the leaves are also used. Lemon verbena has GRAS status in the U.S. for the amounts commonly found in foods and possibly safe when used appropriately and orally for medicinal amounts. There is insufficient evidence to rate safety for used in pregnancy or lactation. The essential oils of the lemon verbena may cause kidney irritation. There are no known food, herbal or drug interactions. Lemon verbena and verbena are separate listings in the NMCD.
Marshmallow root
Orally, the leaf and root of the marshmallow plant, Althaea officinalis, are used for respiratory tract inflammation, cough, peptic ulcers, diarrhea, urinary tract infection and constipation.2,72 Topically, marshmallow leaf is used to sooth insect bites, abscesses and chapped skin. Marshmallow is used in foods and beverages as a flavoring agent.2 In
Germany, marshmallow root and leaf are licensed as standard medicinal teas.72
Marshmallow has GRAS status in the U.S. for use in foods and is possibly safe when applied topically. There is insufficient evidence to rate safety for use in pregnancy or lactation.2,72 Marshmallow is a separate species from mallow flower or mallow leaf,
Malva sylvestris.2 Confectionary marshmallows were once made from the Althaea officinalis plant; now they primarily contain sugar.72
43 In theory, marshmallow may interfere with the absorption of oral medications.72
There are reports of marshmallow causing hypoglycemia; caution is warranted in those with diabetes.2,72
Mother‟s Milk Tea
Sold by Traditional Medicinals, Mother‟s Milk Tea is used to “promote healthy lactation” and is a blend of nine ingredients; bitter fennel fruit, aniseed fruit, coriander fruit, fenugreek seed, blessed thistle herb), spearmint leaf, West Indian lemongrass leaf, lemon verbena leaf and marshmallow root.77 Literature for these herbs and supplements are reviewed individually.
Nettle (Stinging)
Orally, stinging nettle is used for urinary disorders including nocturia, dysuria, irritable bladder, rheumatoid and osteoarthritis, urinary tract infection (UTI), internal bleeding, poor circulation, allergies, asthma, wound healing and as a general tonic.2
Stinging nettle can be taken as a juice, tea, a tincture, by eating the stewed leaves.91,92
Stinging nettle has been used in trials lasting six months; it is possibly safe when used orally and appropriately.2 The active component in stinging nettle has not yet been identified.92 Topically, stinging nettle is used for oily hair and hair loss and for muscle aches and pains. Stinging nettle leaves are also eaten as a green vegetable; steaming destroys the stinging hairs.2,91 In manufacturing, extracts from stinging nettle are used in hair and skin products.2 There is insufficient evidence to rate the effectiveness of stinging nettle for any indication. Orally, stinging nettle can cause gastrointestinal upset and topically, stinging nettle can cause rash. As a leafy green vegetable, stinging nettle can
44 increase risk for clotting for those taking anticoagulants such as warfarin.2,92 In pregnancy, stinging nettle is likely unsafe due to possible abortifacient and uterine- stimulating effects.2
Noni Juice
Noni juice, is extracted from the fruit of an evergreen native to the Pacific Islands,
Southeast Asia, Australia and India. Noni juice is the common reference for the juice from the morinda tree fruit. 2 The usable parts from the morinda tree include the fruit, juice from the fruit, leaves, flower, roots, seeds and bark; the juice is the most popular form used in the U.S. 2,93 Noni juice gained rapid popularity after several health claims related to blood pressure, depression, digestion and others. 93 Uses for the noni juice and other morinda products are many but in brief include orally for colic, hepatosis, constipation, nausea, cancer, gastric ulcers, headache and in preparation for childbirth.
Topical uses include joint ache, anti-aging skin treatment, burns, sores and for stingray wounds. In research studies, morinda has exhibited antibacterial and antiviral activity.
There is also preliminary data to suggest anticancer activity. 2
Morinda is possibly safe when consumed as food but is possibly unsafe when used medicinally. There are case reports of noni juice causing hepatoxicity; two cases reported spontaneous recovery after ceasing noni consumption, one case required liver transplantation. 93 Noni juice is possibly unsafe for use during pregnancy as it is historically used as an abortifacient. There is insufficient evidence to rate safety during lactation; avoid using. 2
45 Omega-3 fatty acids
Omega-3 fatty acids are essential fats that our bodies cannot make. Any fatty acid available to the fetus is through placental transfer of acids of those consumed by the mother. 74Omega-3 fatty acids, a natural component of English walnut, fish, flaxseed, and safflower oils, is used therapeutically for hypercholesterolemia, hypertension, rheumatoid arthritis, multiple sclerosis, depression and migraine headache. 2 In pregnancy and lactation, omega-3 fatty acids are likely safe for those amounts commonly found in foods.
However, there is insufficient evidence to rate safety for therapeutic amounts. There is growing evidence that supports use of moderate doses of omega-3 fatty acids due to increased birth weights and prolonged pregnancy. 75 However, in doses greater than 3 grams per day, there is concern regarding the anticoagulant properties of fish oil. 2 There are no known food, drug or herbal interactions. 2
Papaya enzyme (papain)
Papaya enzymes are used orally as a digestive aid and to decrease swelling following injury. 2 Papain is used topically to treat wounds, sores and ulcers. In manufacturing, papain is a component of meat tenderizers. Papaya is likely unsafe for use during pregnancy as it may be both teratogenic and embryotoxic. There are no known drug interactions, but those who are allergic to figs or kiwi may also be allergic to papaya.
Peppermint
Peppermint is used orally for morning sickness, the common cold, IBS and tension headache.2 It is used topically for headache, inflammation and infections. Used orally, peppermint is Generally Recognized as Safe in the U.S. in the amounts commonly found in foods. In pregnancy, amounts found in food are considered likely safe. For
46 therapeutic doses, there is insufficient evidence for safety for use in pregnancy or lactation. Peppermint may interact with antacids, cyclosporine, H2-Blockers and proton pump inhibitors.
Red raspberry
The earliest record of red raspberry leaf dates back to 1597 in “The Herbal” or “A
General History of Plants” in Europe.2,44 The leaves of red raspberry are harvested just before the flowers bloom.44 Red raspberry is used orally in pregnancy for morning sickness, prevention of miscarriage, reduction of labor pains and for facilitating labor and delivery.2,43,44 Red raspberry is typically taken as a tea, tincture or tablet.43 Red raspberry is likely safe for use in pregnancy in amounts found naturally in foods, but, red raspberry may not be safe when used in therapeutic doses.2 Some believe that the uterus will become more toned if raspberry is consumed regularly throughout the pregnancy.6,43 In a randomized controlled trial by Simpson et al43, it was found that the second stage of labor, not the first, was shortened by use of raspberry leaf tablet from week 32 until delivery.
The concern that raspberry may increase risk for preterm labor was not validated by this study. Red raspberry has no known interactions with drugs.2
Spearmint
Spearmint is used orally for digestive disorders including indigestion, nausea, diarrhea, and flatulence, as well as for IBS, cramps and headache. Spearmint is used topically for arthritis and to sooth local nerve and muscle pain. 2 Spearmint is used in foods, beverages and in manufacturing (example: toothpaste) as a flavoring agent.
47 Spearmint is GRAS in the U.S. for both spearmint leaves and oil. There is insufficient evidence to rate the safety of spearmint for use in pregnancy or lactation; avoid medicinal use. There are no known food, drug or herbal interactions.
St. John‟s Wort
St. John‟s Wort (SJW) is so named for blooming near the birthday of John the
Baptist.2,34 Its use in recorded history dates back to Hippocrates and was originally for treatment against demonic possession.2,34,94 St. John‟s Wort is primarily used for mental health concerns such as depression and anxiety, but is also used for heart palpitations, obsessive compulsive disorder (OCD) and attention-deficit hyperactivity disorder
(ADHD).2,49,94 Depression occurs in almost 10% of pregnant women and they may use
SJW as a natural remedy.34 At this time, SJW is not recommended for use during pregnancy or lactation.2 In one case study, hypericin has been found in breast milk but has not been reported to have caused adverse reactions for the infant nor was the constituent measurable in the infant‟s plasma2,32,34,51} Another study that lasted for two years found no higher risk in the 33 women using SJW as compared to 101 controls.94 In clinical trials, SJW is usually standardized for hypericin content, though it contains at least nine other active compounds including hyperforin.2,32,94 SJW has been shown to increase uterine tone and risk for photodermatitis.34 While it appears SJW is well tolerated by most individuals, SJW may interact with many conventional medications, briefly including Alprazolam, antidepressants, carbamazepine, selective serotonin reuptake inhibitors (SSRIs), barbiturates and contraceptive drugs and warfarin2,34 SJW may interact with Ginkgo biloba.33
48 A summary of possible herb-drug, herb-food and herb-herb interactions is presented in the following table;
Herb Possible Drug Interaction.2 Aloe Antidiabetic Drugs: may lower blood glucose levels (moderate) Digoxin: overuse of aloe may increase risk of toxicity (moderate) Diuretic: overuse of aloe may compound potassium loss that is diuretic induced (moderate) Stimulant Laxative: use with aloe may increase fluid and electrolyte loss (moderate) Aniseed Contraceptive drugs: may interfere (moderate) Tamoxifen: may interfere (moderate) No known food or herbal interactions Black Cohosh Cisplatin: may decrease cytotoxic effect on breast cancer cells in animal model (moderate) Hepatotoxic Drugs: may lead to liver failure (moderate) No known food interactions Blessed Antacids: blessed thistle may decrease effectiveness of (minor) Thistle H2-Blockers: may decrease effectiveness (minor) Proton pump inhibitors: may decrease effectiveness (minor) Blue Cohosh Antidiabetes: may increase blood glucose levels (moderate) Antihypertensive drugs: may increase blood pressure, decreasing drug effectiveness (moderate) Nicotine: may increase effects of nicotine (moderate) No known food interactions Caster Oil Diuretic Drugs: may compound diuretic-induced potassium loss (moderate) No known food interactions Chamomile Benzodiazepines: may cause additional side effects (moderate) (German) CNS Depressants: may cause additional sedative side effects (moderate) Contraceptive Drugs: may interfere (moderate) Estrogens: may interfere with hormone replacement therapy (moderate) Tamoxifen: may interfere (moderate) Warfarin: may increase risk of bleeding (moderate) No known food interactions Continues
Table 2.3: Possible herb-drug and herb-food interactions
49 Table 2.3 Continued
Coriander No known food, drug or herbal interactions Cranberry No known food interactions Echinacea Caffeine: May increase plasma caffeine concentrations (moderate) Immunosuppressants: may interfere (moderate) Midazolam: may increase hepatic clearance (minor) No known food interactions Evening Anesthesia: may lead to seizure (moderate) Primrose Anticoagulant: may increase effect (major) Phenothiazine: may increase risk of seizure (moderate) No known food interactions Fennel Ciprofloxacin: may reduce effectiveness (moderate) Contraceptive drugs: may interfere (moderate) Estrogens: may interfere with hormone replacement therapy (moderate) Tamoxifen: may decrease antiestrogenic effect (moderate) No known herbal or food interactions Fenugreek Anticoagulant: fenugreek may have additive effect (moderate) Antidiabetes: may reduce blood sugar further (moderate) Warfarin: may have additive effect (moderate) Patients with allergy to Fabaceae plants (soy, peanuts, green peas) may also be allergic to fenugreek Fenugreek may interact with anticoagulant herbs and increase risk of bleeding Garlic Anticoagulant: enhancement of coumadin as measured by INR. Possible enhancement of other anticoagulant drugs as well (moderate) Contraceptive: supplements, especially those containing allicin may decrease contraceptive effectiveness (moderate). Cyclosporine: may decrease effectiveness (moderate) Isoniazid: reduces blood levels; possibly blocking intestinal absorption (major) NNRTI‟s: preparations containing allicin may decrease plasma concentration of NNRTI‟s; preparations with alliin and allinase may not affect NNRTI activity (major) No known food interactions Ginger Anticoagulant: may increase risk of bleeding (moderate) Antidiabetic: may increase insulin levels (minor) Calcium Channel Blockers: may have additive effect (minor) Continues Table 2.3: Possible herb-drug and herb-food interactions
50 Table 2.3 Continued
Ginkgo Alprazolam: may decrease effectiveness; possibly by decreasing absorption (major) Anticoagulant: increase risk of bleeding (major) Anticonvulsants: Ginkotoxin may cause seizure; toxin more concentrated in seeds than in leaves and leaf extract (moderate) Antidiabetes: may alter insulin secretion and affect blood glucose levels (moderate) Buspirone: use in combination with ginkgo, fluoxetine, St. John‟s wort, melatonin and buspirone may lead to hypomania. Use of ginkgo alone or only with buspirone can cause hypomania is unknown (moderate) Ibuprofen: may lead to spontaneous, severe bleeding (major) Omeprazole: may decrease effectiveness (minor) Trazadone: may cause coma in combination with ginkgo (moderate) No known food interactions Ginseng American Cisplatin: may decrease cytotoxic effect on breast cancer cells in animal model (moderate) Antidiabetes: may lower blood glucose (moderate) Monoamine Oxidase Inhibitors (MAOIs): may interfere (moderate) Warfarin: can decrease effectiveness (major) Panax Alcohol: increase alcohol clearance (moderate) Anticoagulant: may decrease platelet aggregation (moderate) Antidiabetes: may enhance blood glucose lowering effects Caffeine: may have an added stimulant effect (moderate) Furosemide: may contribute to diuretic resistance (moderate) Immunosuppressant: may interfere with therapy (moderate) Insulin: may increase hypoglycemic effect of insulin(moderate) Monoamine Oxidase Inhibitors (MAOIs): may interfere (moderate) Warfarin: may decrease effectiveness (major)
Continues
Table 2.3: Possible herb-drug and herb-food interactions
51
Table 2.3: Continued
Ginseng Siberian Alcohol: may have additional sedative effect (moderate) (continued) Anticoagulant: may increase risk of bleeding (moderate) Antidiabetic: hypoglycemic activity (moderate) CNS depressant: may have additional sedative effects (moderate) Digoxin: may increase drug blood levels (moderate) No known food interactions Goldenseal Cyclosporine: may decrease metabolism and blood levels of cyclosporine (moderate) Digoxin: moderately increases peak levels (moderate) No known food interactions Green tea Adenosine: caffeine in green tea may inhibit adenosine at the cellular level (moderate) Amphetamines: may increase risk of additive effects (major) Anticoagulants: may increase risk of bleeding (moderate) Antidiabetes drugs: man interfere with blood glucose control (minor) Cimetidine: (moderate) Clozapine: may increase effects (moderate) Contraceptive drugs: oral contraceptives may decrease caffeine clearance (moderate) Dipyridamole: (moderate) Fluconazole: may decrease caffeine clearance (minor) Warfarin: may decrease effects of warfarin (moderate) Green tea may decrease iron absorption from plant sources Milk seems to reduce some benefits of green tea Green tea may interact with bitter orange, creatine, Ma Huang, folic acid, hepatotoxic herbs and iron Juniper Antidiabetes Drugs: may increase effect of these drugs No known food or supplement interaction Continues
Table 2.3: Possible herb-drug and herb-food interactions
52 Table 2.3 Continued
Kava kava Alprazolam: (major) CNS Depressants: (major) Hepatotoxic drugs: increased risk of liver damage (moderate) Levodopa: increased effectiveness (moderate) Concomitant use with alcohol can increase risk of negative side effects such as drowsiness and hepatotoxicicity Concomitant use with other potentially hepatotoxic herbs may increase risk of liver damage Lemongrass No known food, drug or herbal interactions Lemon No known food, drug or herbal interactions Verbena Omega-3 No known food, drug or herbal interactions fatty acids
Marshmallow Antidiabetes drugs: may interfere (moderate) root No known food interactions Marshmallow may interfere with absorption with other drugs or herbal supplements Nettle Antidiabetes drugs: may interfere (moderate) Antihypertentive drugs: may further lower blood pressure (moderate) CNS Depressants: may have additive effect (moderate) Warfarin: decrease effects (moderate) No known food interactions May interact with other anticoagulant herbal supplements Noni Juice ACE Inhibitors: high potassium content of noni may increase risk of hyperkalemia when taken with ACE inhibitors Hepatoxic drugs: taking noni with drugs that are hepatotoxic may further increase risk of liver damage Potassium sparing diuretics: may increase risk of hyperkalemia Warfarin: may decrease effectiveness of warfarin Noni may increase risk of hepatotoxicity when combined with drugs already believed to be hepatoxic such as red yeast and kava No known food interactions Continues
Table 2.3: Possible herb-drug and herb-food interactions
53 Table 2.3 Continued
Omega-3 No known food, drug or herbal interactions Fatty Acid Papaya No known drug interactions enzyme Those with allergies to kiwi or fig may also be allergic to papaya (papain) enzymes May interact with other anticoagulant herbal supplements Peppermint Antacids: may cause dissolution of peppermint capsules prematurally; dose separately by a minimum of two hours (minor) Cyclosporine: inhibit metabolism and increase levels (moderate) Red No known drug interactions Raspberry No known food interactions St. John’s Triptans: increase risk of serotonin syndrome (moderate) Wort Alprazolam (Xanax): decrease effects (major) Aminolevulinic Acid: may cause synergistic phototoxicity (major) Amitriptyline (Elavil): increased clearance and lowered serum concentrations (major) Antidepressants: increase adverse side effects (major) Barbiturates: can decrease barbiturate-induced sleep time (major) Clopidrogrel (Plavix): decreased activity (moderate) Contraceptive drugs: may lead to unplanned pregnancy (major) Cyclosporine: decreased plasma levels (major) Digoxin: reduced serum levels (major) Fenfluramine: can increase the risk of serotonergic side effects (major) Fexofenadine (Allegra): increased plasma concentrations (moderate) Imatinib (Gleevec): decreased plasma concentrations (major) Irinotecan (Camptosar): decrease serum concentrations (major) Meperidine (Demerol): might cause additive serotonergic effects and increase the risk of serotonin syndrome (major)
Continues
Table 2.3: Possible herb-drug and herb-food interactions
54 Table 2.3 Continued
Monoamine Oxidase Inhibitors (MAOIs): might cause additive adverse effects (moderate) Narcotic drugs: can increase narcotic-induced sleep time (major) Nefazodone (Serzone): associated with serotonergic side effects (major) Non-Nucleoside Reverse Transcriptase Inhiboitors (NNRTIs): decrease serum levels (major) Nortriptylene (Pamelor, Aventyl): can reduce serum concentrations (major) Paroxetine (Paxil): might increase the risk of adverse effects and serotonin syndrome-like symptoms (major) Pentazocine (Talwin): concurrent use with pentazocine might cause additive serotonergic effects and increase the risk of serotonin syndrome (major) Phenobarbital (Luminal): may increase the metabolism of phenobarbital, resulting in loss of seizure control (major) Phenprocoumon: appears to increase the metabolism of phenprocoumon (major) Phenytoin (Dilantin): may increase the metabolism of phenytoin, resulting in the loss of seizure control (major) Photosensitivity: might increase the possibility of photosensitivity reaction (major) Protease Inhibitors: can reduce serum concentrations (major) Reserpine: can antagonize the effects (major) Sertraline (Zoloft): can cause serotonergic side effects, including dizziness, nausea, vomiting, epigastric pain, headache, anxiety, confusion, and feelings of restlessness and irritability (major) Simvastatin (Zocor): can reduce plasma concentrations of the simvastatin metabolite (moderate) Tacrolimus (Prograf, Protopic): can increase serum levels (major) Tramadol (Ultram): concurrent use with tramadol might cause additive serotonergic effects and increase the risk of serotonin syndrome (major) Warfarin (Coumadin): can decrease the therapeutic effects of warfarin (major) Spearmint No known food, drug or herbal interactions
Table 2.3: Possible herb-drug and herb-food interactions
55 CHAPTER 3
MATERIALS AND METHODS
This pilot study was a retrospective clinical chart review of transport log data investigating the medical outcomes in neonates presenting to the Neonatal Intensive Care
Unit (NICU) whose mothers consumed herbal supplements during pregnancy, compared to neonates whose mothers did not ingest herbal supplements. These data were entered into SPSS, analyzed and were used to answer the following research questions;
1. What was the rate of herbal supplement use during pregnancy in a sample of women whose neonates were transported from a delivering hospital to Nationwide Children‟s Hospital?
2. What were the differences in herbal supplement use by mother‟s age, marital status, medications taken during pregnancy, tobacco use?
3. Did use of herbal supplements by the mother during pregnancy change neonatal outcomes?
The Nationwide Children‟s Hospital Institutional Review Board approved this study. See appendix A for Transport Log.
Transport Team Logistics
All neonates are transported to Nationwide Children‟s Hospital via the
Nationwide Children‟s Hospital Transport Team. This Team is comprised of Nurses,
Respiratory Therapists and Paramedics who transport critically ill neonates from 56 delivering hospitals to one of the Nationwide Children‟s Hospital Managed Nurseries.
The Transport Team serves, but does not limit their services to, the 33 counties in Central and Southern Ohio in Perinatal Region IV. See appendix B for county demographics of
Neonatal Region IV. Infants may also be transported from other Ohio regions, as well as contiguous states such as Kentucky and West Virginia. The Transport Team Leader, a
Registered Nurse (RN) is designated to be the team leader when the Transport Team is dispatched.
Transport Log Data Collection
The Transport Team Leader is responsible for completion of the Transport Log.
Instructions for interviewing the mother as well as how to complete the Transport Log are part of the training for becoming a team leader.
In preparation for transportation of a neonate, the Transport Log is completed.
This task is accomplished by reference to prenatal records from the referring hospital and an interview of the mother prior to transport to Nationwide Children‟s, unless prohibited by emergent circumstances of the neonate. As able, the neonate is stable prior to transport as defined by heart rate from 60 to 80 BPM, a secure airway and intravenous (IV) access.
Information collected on the transport log includes birth information, maternal history, medications and herbal supplements ingested during pregnancy, mother‟s complication/illnesses during pregnancy, family history, labor and delivery, relevant lab work including CBC and Chem 7. A physical assessment of the neonate is then performed by the transport team. This assessment includes the following systems: Head,
Eyes, Ears, Nose and Throat (HEENT), neurological, cardiovascular, respiratory, gastrointestinal, genitourinary, musculoskeletal, and integumentary. The completed
57 transport log becomes a part of the medical record once the team returns to Nationwide
Children‟s Hospital while a copy is kept with the Transport Team Office.
These Transport Logs are available from the medical record as well as the
Transport Team office. Transport logs from February 2006, when the herbal history question was added to the chart, through February 2008 were utilized.
Identification of Matched Controls
Neonates and controls were matched for gestational age, gender, race, gravida and parity in this case-control pilot study. It was attempted to match the neonates on socioeconomic status (SES) as well, but this proved to be too many variables and made the matching process impossible. Matched Controls were identified by the Transport
Office secretary using the Nationwide Children‟s Hospital neonatal intensive care unit
(NICU) medical records from the same time frame from which the positive response
“herbal use” mothers were identified.
58 Research Question Data from transport log to be used Statistical Transport log section: procedure(s) Specific question 1. Herbal Complications/Illness: Frequency supplement Herbal supplements distributions prevalence 2. Factors Infant: associated Birth weight T-Test: continuous with herbal Estimated Gestational Age variables such as supplement Ballard score age, gravida and use Race parity Sex Maternal Hx: Chi Square: all Age categorical Marital status variables such as Gravida/para race, SES, infant Complications/Illness: weight, sex, etc. Smokes/Alcohol/Drugs Blood pressure Diabetes Medications taken during pregnancy Family Hx: Each question 3. Herbal Delivery: Frequency supplement Apgar scores (x3) distributions: use and Ballard score events, complications complications, Labwork: medications and Chem 7 RN assessments
RN Assessment: T-Test: for all Each assessment box continuous variables such Apgar scores and lab work
Table 3.1: Statistical procedures
59 Data Analysis
All data acquired from the Transport Log for positive response herbal users were entered into SPSS V15.0.1 (Statistical Program for Social Sciences, SPSS, Inc. Chicago,
Ill.) along with all Transport Log data from the matched controls. Differences between the two groups (herbal supplement users and matched controls) were compared as appropriate in terms of frequencies, Chi-square analyses, and t-tests.
Study Limitations
There are several limitations associated with this pilot study. The Transport Log question related to herbal supplement use is not clearly stated; no further details regarding type of herb, duration, trimester of ingestion, or dose are available. There is also no ability to assess intention for taking an herbal supplement. This sample of women may not be a accurate representation of all women in Ohio.
60 CHAPTER 4
COMPARISON OF NEONATAL OUTCOMES IN MATERNAL USERS
AND NON-USERS OF HERBAL SUPPLEMENTS
Abstract
Objective
The primary purposes of this chart review study were; 1) to describe the prevalence of non-vitamin, non-mineral supplementation disclosure by mothers with neonates being transferred to Nationwide Children‟s Hospital (NCH) and 2) to identify characteristics linked to increased herbal supplement use and 3) to identify adverse outcomes linked to herbal supplement use.
Design
This pilot study was a retrospective clinical chart review of transport log data. The researchers investigated the medical outcomes in neonates presenting to the Neonatal
Intensive Care Unit (NICU) whose mothers consumed herbal supplements during pregnancy, compared to neonates whose mothers did not ingest herbal supplements.
Neonates and controls were matched for estimated gestational age, gender, race, gravida and parity. Data from transport logs for neonates of mothers reporting supplement use as well as two matched controls per neonate were identified and entered into SPSS V15.0.1
(Statistical Program for Social Sciences, SPSS, Inc. Chicago, Ill.) for statistical analysis.
61 Subjects
Subjects of this study were neonates being transported to Nationwide Children‟s
Hospital Neonatal Intensive Care Unit (NICU) for care not available at their delivering hospital or due to lack of bed space.
Main outcome measures
Frequencies, T-tests and χ2 analyses were used to investigate herbal supplement prevalence, neonatal characteristics (weight, age in days and size for gestational age
[SGA], etc), maternal characteristics (mothers‟ age, language spoken, prenatal care, medical history and marital status) and differences in neonatal assessment outcomes,
(neonates‟ reason for referral, Apgar scores and Chem 7).
Results
Rate of use in the study sample of 2136 charts was 1.1%. This study identified 17 supplements and included teas (green and red raspberry), juice (noni), herbal vitamins, papaya enzyme and fish oil as well as nettle, echinacea, juniper, marshmallow root and thistle. The most common supplements identified were red raspberry leaf tea (n=5), green tea (n=4), cranberry supplement (n=2) and fish oil (n=2). Six additional positive responses on the transport log were identified that did not meet the non-vitamin, non- mineral criteria. These included chromium, folic acid, B vitamins and magnesium.
Characteristics of the neonates and controls were analyzed as appropriate using χ2 analysis and t-tests and revealed no statistical significance (p ≥ 0.05). These characteristics included age (days), mean birth weight, size for gestational age, race and gender as well as reason for referral to Nationwide Children‟s Hospital. Characteristics of the mothers also revealed no statistical difference for age, gravida, para, cigarette,
62 vitamin or iron use during pregnancy, prenatal care, maternal medical history (including diabetes mellitus) marital status or language spoken. There was no reported use of alcohol in this study. There was a statistically significant difference between herbal users and herbal non-users and the trimester prenatal care began (PNC); significantly more non-herbal users began their PNC in the second trimester (p = .05).
Neonatal patients had significantly lower 1st Apgar score and chloride level from the Chem 7 blood than control.
Introduction
Herbal supplements have been used around the world for thousands of years.1-3
Herbal supplements are used to treat illness and as part of a general wellness program.1,4-6
Despite being used for centuries, clinical investigations of herbal supplement active components, species, possible interactions with other herbs and drugs, efficacy and safety are in their infancy. In particular, the safety of using most herbal supplements during pregnancy is unknown.2,31-35
The trend of herbal supplement use worldwide has been on the rise for the past five decades.7,8 This has been illustrated by both national and local surveys in the U.S. and is generally estimated to be around 20%.4,9 Herbal supplement use in pregnancy increased after the thalidomide tragedy, where from 1956 to 1962, approximately 10,000 children were born with severe malformities due to their mothers ingesting thalidomide during their pregnancy to ameliorate morning sickness. 7 Several characteristics linked to increased herbal supplement use have also been identified.8-13 However, potential differences in herbal supplement use by specific populations are less well understood.12,14-16
63 A wide range in herbal supplement use has been reported. These estimates vary depending on the survey tools and sampling techniques used and the language in which the surveys are conducted.4,11,12,15-20 Specifically, estimates of herbal use by pregnant women, and the reasons for doing so, are much less understood.5,22-27 Of the studies investigating herbal supplement use in pregnancy, some exclude those women with a neonate in the intensive care unit, now assessing or underreporting possible complications of taking herbal supplements.28,29 This opportunity for study, especially in the intensive care unit, is evidenced by the wide ranges of estimates in the current literature.28
Methods
Data for this study were obtained via clinical chart review. Transport logs were completed by the transport team in preparation of neonatal transport from outside hospital to Nationwide Children‟s Hospital. The Transport Log is part of the patient permanent record. All data on charts were collected on the Transport Log prior to this study period.
The question regarding herbal supplement use has been a component of the
Transport Log for approximately two years. More than two-thousand charts were completed in this time frame. All transport logs from this time period were reviewed for inclusion in this study.
Each of the more than two-thousand paper chart was individually reviewed by hand to assess herbal supplement use. Each Transport Log with a positive response to the herbal supplement question was photocopied, assigned a subject number and all identifying information was blacked out. All subjects with positive response to herbal supplement use were reviewed; those who met definition criteria of non-vitamin, non-
64 mineral were included in the data analysis. Those subjects with a vitamin or mineral supplement listed were excluded from data analysis but are referred to in the final discussion. If the subject mentioned both an herbal supplement and a vitamin or mineral supplement, the subject was included in data analysis with the herbal supplement, but the vitamin or mineral supplement was excluded. The master list of subject numbers and hospital identification numbers were kept confidential, as specified by the IRB.
The matching variables of gestational age, race, gravida and para were collected for each subject and organized in a Microsoft Excel spreadsheet. These criteria were entered into the two electronic charting systems currently in place at Nationwide
Children‟s Hospital. The electronic charting systems were used to access a list of possible matches for the study subjects based on these matching criteria. This large group of charts was again reviewed by hand to locate the two control matches for each subject.
Transport Logs for matches were also photocopied, assigned a study identification number and identifying information was blacked out.
During the matching process, it was the goal to match neonates (subjects) and controls on exact gravida and para of the mother. However, the medical histories of the mothers revealed that several of our subjects had unusually high numbers of pregnancies and births (example: eleven pregnancies, eight births). For the majority of our subjects, we were able to match these variables exactly. However, for a few, we had to instead match on the basis of this being the mother‟s first or subsequent pregnancy (uniparous versus multiparous)
Every item on the transport log for each patient was entered into SPSS to create a comprehensive database available for analysis. Once all data were entered, the data were
65 organized and refined. Further data variables were created from the original data to allow for more detailed analysis. For example, each individual nursing assessment was analyzed as well as the sum of nursing assessments not within normal limits. The
Nationwide Children‟s Hospital Institutional Review Board approved this study.
Data Analysis
All data acquired from the Transport Log for positive response herbal users were entered into SPSS V15.0.1 (Statistical Program for Social Sciences, SPSS, Inc. Chicago,
Ill.) along with all Transport Log data from the matched controls. Differences between the two groups (herbal supplement users and matched controls) were compared using frequencies, Chi-square analyses, and t-tests.
Results
The results of this study are reported here and answer the three research questions included in the proposal. The results include descriptive data of our sample and results of statistical comparisons of the herbal supplement users and herbal supplement non-users.
Prevalence
In our sample of 2136 transport logs, the rate of supplement use was1.1%
(=24/2136). There were 30 positive responses. However, six of those responses to the herbal use question did not meet the research criteria of non-vitamin, non-mineral supplement (example: chromium).
The non-vitamin, non-mineral supplements identified by this study are listed here in Table 4.1 and include their frequency of use. The most common herbal supplements reported were teas; red raspberry, green and herbal tea, not otherwise specified.
66
Supplement Frequency Estimated Gestational Age Red Raspberry Leaf Tea 5 40,42,42,37,40 Green Tea 4 39,35,38,40 Fish Oil 2 35,33 Papaya Enzyme 2 31,31 Cranberry Supplement 2 32,32 Echinacea 1 36 Ginger 1 36, Herbal Tea 1 36 Herbal Vitamins 1 39 Juniper 1 33 Marshmallow Root 1 38 Mother Tea 1 39 Nettle 1 37, Noni Juice 1 40, Omega-3's 1 40, Peppermint Tea 1 26, Thistle 1 38
Table 4.1: Non-vitamin, non-mineral supplements reported
Characteristics of the sample
The characteristics of our study subjects and their matched controls, as measured by age in days, their mean birth weight and their size for gestational age are described in the following table. None of these characteristics vary significantly between groups
(p = .05).
67
Herbal supplement Non-herbal users supplement users Age (mean)±SD 2.2 ± 5.5 4.51 ± 13.5 (days) Mean birth (mean)±SD 2.81 kg ± 0.93 2.83 kg ± 0.91 weight Size for Small 0 5 (11.9) gestational Appropriate 20 (83.3) 32 (76.2) age: n (%) Large 4 (16.7) 5 (11.9) Caucasian 19 (79.2) 33 (76.7) Race of African American 2 (8.3) 7 (16.3) neonate: Hispanic 0 1 (2.3) n (%) Chinese American 1 (4.2) 0 Biracial 2 (8.3) 2 (4.7) Male 12 (50) 20 (43.5) Gender Female 12 (50) 26 (56.5)
Table 4.2: Characteristics of the neonates and matched controls
The reason that the neonate was referred to Nationwide Children‟s Hospital was recorded on the Transport Log, see table 4.2 for complete results. The most common reasons for transport were respiratory distress syndrome (RDS), bowel obstruction, lack of bed space and diaphragmatic hernia.RDS is a common problem in premature neonates and so this finding is not surprising here.
The characteristics of the mothers are summarized in the following table. None of the characteristics analyzed were statistically significant (p = .05). Alcohol use was not reported during pregnancy. There was no significant difference for use of prenatal vitamins, iron supplements or any other medication, including prescription or over the counter (p = .05). Whereas other studies have found increased use of herbal supplements by those people also using OTC or prescription drugs, the results of this study do not 68 confirm these data. All analyses for maternal history of various conditions were not significant, including history of diabetes mellitus (p = .05).
Reason Herbal User Herbal Non-User Respiratory distress syndrome (RDS) 9 14 Bowel obstruction 0 4 Bed Space 0 3 Diaphragmatic Hernia 2 1 Testicular Torsion 0 2 Neurological Evaluation 2 0 Preterm Delivery 1 2 Possible Hypoplastic 0 2 Cleft lip/palate 0 2 Feeding Evaluation 1 1 Seizure 1 1 Other 7 14
Table 4.3: Reason for neonate‟s referral to Nationwide Children‟s Hospital
Herbal Users Herbal Non-Users Age 27.7 ± 7.5 26.1 ± 6.7 Gravida 2.7 ± 2.2 2.7 ± 2.2 Para 2.0 ± 1.3 2.1 ± 1.5 Smoked during Yes 3 (12.5%) 11 (32.4%) pregnancy No 21 (87.5%) 23 (67.6%) Drug use during Yes 1 (4.2 %) 1 (3.4 %) pregnancy No 23 (95.8 %) 33 (96.6%) Prenatal Care Yes 21 (91.3 %) 34 (97.1 %) No 2 (8.7%) 1 (2.9%) Marital Status Single 6 (26.1%) 12 (31.6) Married 17 (73.9%) 26 (68.4) Language Spoken English 20 (90.9%) 40 (97.6%) Spanish 0 1 (2.4%) Chinese 1 (4.5%) 0 Dutch 1 (4.5%) 0
Table 4.4: Characteristics of the mothers 69 There was a statistically significant difference between herbal users and herbal non-users and the trimester prenatal care began (PNC); significantly more non-herbal users began their PNC in the second trimester (p = .05).
Herbal User Herbal Non-User Prenatal care began 1st 18 (100%) 22 (71%) trimester Prenatal care began 2nd 0 9 (29%) trimester
Table 4.5: Comparison of month prenatal care began
Neonatal outcome measures
For the purposes of this study, neonatal outcomes were analyzed by several variables located on the transport record. These variables included the individual eight nurse assessments which were not within normal limits, sum of nurse assessments not within normal limits, reason for cesarean section, amniotic fluid color and Apgar scores.
Analysis of the nursing assessments and of total number of nursing assessments that were abnormal bore no statistical difference. Reason for cesarean section or amniotic fluid color also showed no statistical significance nor did Ballard scores (p = .05). However, analysis of the Apgar scores revealed that the herbal users have a significantly lower 1st
Apgar score than herbal non-users. The 2nd and 3rd Apgar scores were not statistically different. See table 4.6 for statistically significant results in neonatal outcomes.
70
Herbal Users Herbal Non-Users st n = 24 n = 41 1 Apgar Score a a 5.88 ± 2.9 6.63 ± 2.4
n = 24 n = 41 2nd Apgar Score 7.8 ± 2.1 7.9 ± 1.6
rd n = 4 n = 4 3 Apgar Score 6 ± 2.4 6 ± 1.4 No 19 (79.2%) No 22 (71.0 %) Preterm Labor Yes 5 (20.8%) Yes 9 (29.0%) a 1st apgar scores statistically significant (p = .05)
Table 4.6: Statistically significant neonatal outcomes
Neonatal outcomes were also assessed by comparing mean values for the Chem 7 blood analysis. The Chem 7 includes sodium, carbon dioxide levels and others. Chloride values were statistically significantly different; the other six values were not.
Herbal User Herbal Non-User Sodium 137.5 ± 4.5 128.6 ± 38.6 Chloride 105.7 ± 4.9 a 109 ± 9 a Potassium 4.9 ± 0.7 4.1 ± 1.2 Carbon Dioxide 21 ± 4.9 23.4 ± 21.3 Blood Urea Nitrogen 14.9 ± 6.6 10.2 ± 6.4 Blood Glucose 97.3 ± 41 104.9 ± 100.7 Creatine 1.3 ± 0.6 10.2 ± 30.8 a Chloride statistically significant (p = .05)
Table 4.7: Comparison of Chem 7 by herbal users and herbal non-users
Discussion
The prevalence of herbal medicine use by women during pregnancy is largely unknown; estimates range from 4 to 45%.5,22-27 This is the first known study to investigate herbal supplement use during pregnancy in Ohio. This study reported an
71 herbal supplement use prevalence of 1.1%, which is less than current estimates for use in pregnancy or for the general population. The sample size for this study too small to identify characteristics linked to increased supplement use identified by other studies.
The ability to extrapolate these data to all pregnant Ohio women is limited due to the small sample size and the unique data collection circumstances of having a neonate in need of critical care; critically ill neonates are not an adequate representation of all Ohio neonates. However, any measure taken to describe and critically analyze herbal supplement use is an asset to healthcare professionals.
Several of the positive responses to the herbal supplement usage question were not true herbal supplements as assessed by the definition of “non-vitamin, non-mineral”.
This illustrates the education gap for both healthcare professionals as well as the general public. The most fundamental aspect of discussing herbal supplement use, safety and efficacy is the definition. The author would recommend amending the Transport Log question to include several examples of substances that are appropriate responses for the question, and collect further data to include brand, dose, reason for taking supplement, history of herbal supplement usage and source(s) of information about the supplement(s).
The majority of the comparisons of maternal characteristics, neonatal characteristics and neonatal outcome measures were not statistically significant. This illustrates the great challenge to healthcare professionals to further investigate herbal supplement usage patterns and identify more reliable methods for assessing and predicting herbal supplement usage.
72 Conclusions and Applications
It is the charge of healthcare professionals to gather the best clinical evidence regarding our patients and clients and to review the current literature to create the most comprehensive care plans. To give the best care, it is best practice to specifically question every single patient and client about their use of herbal supplements and incorporate possible drug-herb interactions, safety, efficacy and the manufacturing practices of the selected brand into the recommendations we make for our patients and clients.
73 CHAPTER 5
DISCUSSION, CONCLUSIONS AND RECOMMENDATIONS
The purpose of this study was to describe the herbal supplement use in pregnancy in a high risk population in Ohio, to search the data for any characteristics of the mother that increase the likelihood of their using herbal supplements and to see if any of the herbal supplements placed the neonate at higher risk than their matched control. This study contributed to the limited knowledge base currently available about herbal supplements.
Conclusions
While it is an important step above general practice to have a question on the medical history form to question the mother about herbal supplement use, the question is not ideal in format. Bearing in mind that this history is completed in a stressful situation where time is of the essence, the author suggests that the form have a question that includes examples of common herbal supplements and supplement forms to spark the memory of a mother whose mind is likely focused on the health of their baby rather than on the questionnaire at hand. The question could be stated “at any time during your pregnancy or labor, did you consume any herbal supplements such as ginger tablets, raspberry tea, castor oil or black cohosh”? If they mother answers yes or maybe, this could be flagged for a later time when a thorough history of supplement use could be
74 obtained. It is a weakness of this study that no information regarding dose of herbal supplement, length of use during pregnancy, use during labor or believed benefit of use could be obtained.
After data analysis, several conclusions can be drawn. In our sample, reported herbal supplement use was 1.1%. This may be the first time that the herbal supplement use in pregnancy has been described for women in Ohio. However, the applicability of this rate to populations outside of our sample are limited due to the unique circumstances under which these data are collected and a knowledge gap observed in which the exact definition of herbal supplement was not clear. Due to the retrospective nature of this study, it is also unclear the intension for use of the herbal supplement. The most common herbal supplements reported in this study were teas; however, it is unclear if the teas were medicinal purposes, for comfort, to satisfy a craving or for any other purpose.
Many of the subjects of this study were delivered preterm. Many herbal supplements in pregnancy are intended for use in preparation for delivery. It is possible that this study would have captured more herbal supplements had these pregnancies gone full term. Table 5.1 lists the estimated gestational ages of the subjects in this study.
Discussion
For healthcare professionals, no single field has claimed herbal supplement knowledge, research and recommendations as their own. In this situation, there are both positive and negative aspects. All healthcare professionals share responsibility for reviewing literature and educating themselves and reviewing all available data to best answer to their patients‟ and clients‟ questions and needs. Unfortunately, no single profession is singly responsible for the push to further research or to better incorporate
75 Frequency Percent Cumulative Percent 26.00 1 1.4 1.5 26.50 1 1.4 3.0 27.50 1 1.4 4.5 31.00 6 8.6 13.6 31.50 2 2.9 16.7 32.00 3 4.3 21.2 33.00 5 7.1 28.8 34.00 1 1.4 30.3 34.50 1 1.4 31.8 35.00 5 7.1 39.4 36.00 5 7.1 47.0 36.40 1 1.4 48.5 36.50 1 1.4 50.0 37.00 1 1.4 51.5 38.00 6 8.6 60.6 38.50 1 1.4 62.1 39.00 10 14.3 77.3 39.50 1 1.4 78.8 40.00 9 12.9 92.4 40.30 1 1.4 93.9 40.50 1 1.4 95.5 41.00 1 1.4 97.0 42.00 2 2.9 100.0 Total 66 94.3
Table 5.1: Frequencies of estimated gestational ages
these materials into core curriculum. Dietitians, midwives and pharmacists may have the strongest foundations, but this is far from adequate and somewhat irrelevant when the general public is questioning health food store professionals, their friends, family, doctors, nurses and the internet. There is opportunity here for dietitians to become experts and to expand the literature.
76 Recommendations
There are enormous gaps in the clinical studies to date. In the review of literature for this study, there was insufficient evidence to rate safety or efficacy of most herbal supplements for use in the general population, let alone for use during pregnancy, labor or lactation. People are going to choose herbal supplements if they are perceived to be efficacious and safe; it is the duty of the healthcare professionals to advance the research such that we can make concrete recommendations. Natural does not equal safe.
It would be advantageous for further research to have a standardized transport log for transport units across the nation. This would allow for consistent data collection and a much larger data set for use in future studies. For the most thorough patient history, a detailed question set would ask the patient to describe the herbal supplements used, reason for use, the duration and dose, brand name, sources of information and form of supplement. While it may not be realistic to complete all of this information prior to transport, it may be feasible to complete that part of the patient history at a later time. The situation in which most neonates are being transported is critical and time is valuable; the transport team makes every effort to use their time effectively. In this situation, it may be most effective to complete herbal supplement use histories once the mother and neonate are transported to Nationwide Children‟s Hopsital. At this point, the mother may be able to better focus on the health history rather than the status of her baby.
Example question: At any time during your pregnancy, labor or while breastfeeding did you, or are you currently taking herbal supplements? Examples of herbal supplements are ginger tablets, green tea, garlic, ginseng, aloe and nettle.
77
Herb Reason Dose & Brand Provider Frequency Example Ginger nausea 1g bid CVS Pharmacist 1st trimester 2nd trimester 3rd trimester labor and delivery Lactation
Table 5.2: Example format for herbal supplement use in pregnancy health history
This study is an important step in the attempts to better describe herbal supplement use during pregnancy. Review of literature has uncovered large gaps in the literature and considerably more research is warranted.
78 Reference List
(1) Born D, Barron ML. Herb use in pregnancy: what nurses should know. MCN Am J Matern Child Nurs. 2005;30:201-206.
(2) The Natural Medicines Comprehensive Database. Jellin, J. M. http://www.naturaldatabase.com/ . 2007. 11-14-2007.
(3) Hurley H. Diet Supplements and Safety: Some Disquieting Data. The New York Times. January 16, 2007.
(4) Tindle HA, Davis RB, Phillips RS, Eisenberg DM. Trends in use of complementary and alternative medicine by US adults: 1997-2002. Altern Ther Health Med. 2005;11:42-49.
(5) Wilkinson JM. What do we know about herbal morning sickness treatments? A literature survey. Midwifery. 2000;16:224-228.
(6) McKenna L, McIntyre M. What over-the-counter preparations are pregnant women taking? A literature review. J Adv Nurs. 2006;56:636-645.
(7) Cauffield JS. The psychosocial aspects of complementary and alternative medicine. Pharmacotherapy. 2000;20:1289-1294.
(8) Martin KJ, Jordan TR, Vassar AD, White DB. Herbal and nonherbal alternative medicine use in Northwest Ohio. Ann Pharmacother. 2002;36:1862-1869.
(9) Timbo BB, Ross MP, McCarthy PV, Lin CT. Dietary supplements in a national survey: Prevalence of use and reports of adverse events. J Am Diet Assoc. 2006;106:1966-1974.
(10) Refuerzo JS, Blackwell SC, Sokol RJ et al. Use of over-the-counter medications and herbal remedies in pregnancy. Am J Perinatol. 2005;22:321-324.
79 (11) Hsiao AF, Wong MD, Goldstein MS, Becerra LS, Cheng EM, Wenger NS. Complementary and alternative medicine use among Asian-American subgroups: prevalence, predictors, and lack of relationship to acculturation and access to conventional health care. J Altern Complement Med. 2006;12:1003-1010.
(12) Mackenzie ER, Taylor L, Bloom BS, Hufford DJ, Johnson JC. Ethnic minority use of complementary and alternative medicine (CAM): a national probability survey of CAM utilizers. Altern Ther Health Med. 2003;9:50-56.
(13) Kennedy J, Wang C, Wu C. Patient Disclosure about Herb and Supplement Use among Adults in the US. eCAM. 2007.
(14) von G, V, Showalter AL, Gil KM, Frasure HE, Hopkins MP, Jenison EL. Complementary and alternative medicine use in the Amish. Complement Ther Med. 2001;9:232-233.
(15) Mehta DH, Phillips RS, Davis RB, McCarthy EP. Use of complementary and alternative therapies by Asian Americans. Results from the National Health Interview Survey. J Gen Intern Med. 2007;22:762-767.
(16) Hsiao AF, Wong MD, Goldstein MS et al. Variation in complementary and alternative medicine (CAM) use across racial/ethnic groups and the development of ethnic-specific measures of CAM use. J Altern Complement Med. 2006;12:281-290.
(17) Gardiner P, Graham R, Legedza AT, Ahn AC, Eisenberg DM, Phillips RS. Factors associated with herbal therapy use by adults in the United States. Altern Ther Health Med. 2007;13:22-29.
(18) Kennedy J. Herb and supplement use in the US adult population. Clin Ther. 2005;27:1847-1858.
(19) Upchurch DM, Chyu L. Use of complementary and alternative medicine among American women. Womens Health Issues. 2005;15:5-13.
(20) Murphy P. Alternative therapies for nausea and vomiting of pregnancy. Obstet Gynecol. 1998;91:149-155.
80 (21) Glover DD, Amonkar M, Rybeck BF, Tracy TS. Prescription, over-the-counter, and herbal medicine use in a rural, obstetric population. Am J Obstet Gynecol. 2003;188:1039-1045.
(22) Mattison D, Zajicek A. Gaps in knowledge in treating pregnant women. Gend Med. 2006;3:169-182.
(23) Nordeng H, Havnen GC. Use of herbal drugs in pregnancy: a survey among 400 Norwegian women. Pharmacoepidemiol Drug Saf. 2004;13:371-380.
(24) Kuczkowski KM. Labor analgesia for the parturient with herbal medicines use: what does an obstetrician need to know? Arch Gynecol Obstet. 2006;274:233-239.
(25) Chuang CH, Doyle P, Wang JD, Chang PJ, Lai JN, Chen PC. Herbal medicines used during the first trimester and major congenital malformations: an analysis of data from a pregnancy cohort study. Drug Saf. 2006;29:537-548.
(26) Allaire AD, Moos MK, Wells SR. Complementary and alternative medicine in pregnancy: a survey of North Carolina certified nurse-midwives. Obstet Gynecol. 2000;95:19-23.
(27) Tiran D. The use of herbs by pregnant and childbearing women: a risk-benefit assessment. Complement Ther Nurs Midwifery. 2003;9:176-181.
(28) Nordeng H, Havnen GC. Impact of socio-demographic factors, knowledge and attitude on the use of herbal drugs in pregnancy. Acta Obstet Gynecol Scand. 2005;84:26-33.
(29) Forster DA, Denning A, Wills G, Bolger M, McCarthy E. Herbal medicine use during pregnancy in a group of Australian women. BMC Pregnancy Childbirth. 2006;6:21.
(30) Smith C, Crowther C, Willson K, Hotham N, McMillian V. A randomized controlled trial of ginger to treat nausea and vomiting in pregnancy. Obstet Gynecol. 2004;103:639-645.
81 (31) Klier CM, Schmid-Siegel B, Schafer MR et al. St. John's wort (Hypericum perforatum) and breastfeeding: plasma and breast milk concentrations of hyperforin for 5 mothers and 2 infants. J Clin Psychiatry. 2006;67:305-309.
(32) Klier CM, Schafer MR, Schmid-Siegel B, Lenz G, Mannel M. St. John's wort (Hypericum perforatum)--is it safe during breastfeeding? Pharmacopsychiatry. 2002;35:29-30.
(33) Dugoua JJ, Mills E, Perri D, Koren G. Safety and efficacy of ginkgo (Ginkgo biloba) during pregnancy and lactation. Can J Clin Pharmacol. 2006;13:e277- e284.
(34) Dugoua JJ, Mills E, Perri D, Koren G. Safety and efficacy of St. John's wort (hypericum) during pregnancy and lactation. Can J Clin Pharmacol. 2006;13:e268-e276.
(35) Dugoua JJ, Seely D, Perri D, Koren G, Mills E. Safety and efficacy of black cohosh (Cimicifuga racemosa) during pregnancy and lactation. Can J Clin Pharmacol. 2006;13:e257-e261.
(36) Schwertner HA, Rios DC, Pascoe JE. Variation in concentration and labeling of ginger root dietary supplements. Obstet Gynecol. 2006;107:1337-1343.
(37) Marcus DM, Snodgrass WR. Do no harm: avoidance of herbal medicines during pregnancy. Obstet Gynecol. 2005;105:1119-1122.
(38) The U.S. Food and Drug Administration. http://www.cfsan.fda.gov . 11-6-0007. 11-23-2007.
(39) Garrard J, Harms S, Eberly LE, Matiak A. Variations in product choices of frequently purchased herbs: caveat emptor. Arch Intern Med. 2003;163:2290- 2295.
(40) Gilroy CM, Steiner JF, Byers T, Shapiro H, Georgian W. Echinacea and truth in labeling. Arch Intern Med. 2003;163:699-704.
(41) Zaffani S, Cuzzolin L, Benoni G. Herbal products: behaviors and beliefs among Italian women. Pharmacoepidemiol Drug Saf. 2006;15:354-359. 82 (42) Lanski SL, Greenwald M, Perkins A, Simon HK. Herbal therapy use in a pediatric emergency department population: expect the unexpected. Pediatrics. 2003;111:981-985.
(43) Simpson M, Parsons M, Greenwood J, Wade K. Raspberry leaf in pregnancy: its safety and efficacy in labor. J Midwifery Womens Health. 2001;46:51-59.
(44) McFarlin BL, Gibson MH, O'Rear J, Harman P. A national survey of herbal preparation use by nurse-midwives for labor stimulation. Review of the literature and recommendations for practice. J Nurse Midwifery. 1999;44:205-216.
(45) Bayles BP. Herbal and other complementary medicine use by Texas midwives. J Midwifery Womens Health. 2007;52:473-478.
(46) Tenore JL. Methods for cervical ripening and induction of labor. Am Fam Physician. 2003;67:2123-2128.
(47) Buckner KD, Chavez ML, Raney EC, Stoehr JD. Health food stores' recommendations for nausea and migraines during pregnancy. Ann Pharmacother. 2005;39:274-279.
(48) The National Center for Complementary and Alternative Medicine. http://nccam.nih.gov/ . 2007. 8-10-2007.
(49) Conover E, Buehler BA. Use of herbal agents by breastfeeding women may affect infants. Pediatr Ann. 2004;33:235-240.
(50) Garry D, Figueroa R, Guillaume J, Cucco V. Use of castor oil in pregnancies at term. Altern Ther Health Med. 2000;6:77-79.
(51) Anderson FW, Johnson CT. Complementary and alternative medicine in obstetrics. Int J Gynaecol Obstet. 2005;91:116-124.
(52) Lohse B, Stotts JL, Priebe JR. Survey of herbal use by Kansas and Wisconsin WIC participants reveals moderate, appropriate use and identifies herbal education needs. J Am Diet Assoc. 2006;106:227-237.
83 (53) Westfall RE. Use of anti-emetic herbs in pregnancy: women's choices, and the question of safety and efficacy. Complement Ther Nurs Midwifery. 2004;10:30-36.
(54) Mikhail N, Wali S, Ziment I. Use of alternative medicine among Hispanics. J Altern Complement Med. 2004;10:851-859.
(55) Howell L, Kochhar K, Saywell R, Jr. et al. Use of herbal remedies by Hispanic patients: do they inform their physician? J Am Board Fam Med. 2006;19:566-578.
(56) Hollyer T, Boon H, Georgousis A, Smith M, Einarson A. The use of CAM by women suffering from nausea and vomiting during pregnancy. BMC Complement Altern Med. 2002;2:5.
(57) Chandra K, Einarson A, Koren G. Taking ginger for nausea and vomiting during pregnancy. Can Fam Physician. 2002;48:1441-1442.
(58) Huntley AL, Coon JT, Ernst E. Complementary and alternative medicine for labor pain: a systematic review. Am J Obstet Gynecol. 2004;191:36-44.
(59) Chao MT, Wade C, Kronenberg F, Kalmuss D, Cushman LF. Women's reasons for complementary and alternative medicine use: racial/ethnic differences. J Altern Complement Med. 2006;12:719-720.
(60) Brezny, J. Personal communication. 8-17-2007.
(61) National Center for Complimentary and Alternative Medicine. and National Institutes of Health. Herbs at a Glance. http://nccam.nih.gov/health/herbsataglance.htm . 2008. 4-13-2007. Ref Type: Electronic Citation
(62) Wichtl MW. Herbal Drugs and Phytopharmaceuticals. 1994.
(63) Jones TK, Lawson BM. Profound neonatal congestive heart failure caused by maternal consumption of blue cohosh herbal medication. J Pediatr. 1998;132:550-552.
84 (64) Finkel RS, Zarlengo KM. Blue cohosh and perinatal stroke. N Engl J Med. 2004;351:302-303.
(65) McFarlin BL, Gibson MH, O'Rear J, Harman P. A national survey of herbal preparation use by nurse-midwives for labor stimulation. Review of the literature and recommendations for practice. J Nurse Midwifery. 1999;44:205-216.
(66) Mitri F, Hofmeyr GJ, van Gelderen CJ. Meconium during labour--self-medication and other associations. S Afr Med J. 1987;71:431-433.
(67) Sarubin-Fragakis A, Thomson C. The health professional's guide to popular dietary supplements. 3rd ed ed. Chicago, Ill: American Dietetic Association; 2007.
(68) Dove D, Johnson P. Oral evening primrose oil: its effect on length of pregnancy and selected intrapartum outcomes in low-risk nulliparous women. J Nurse Midwifery. 1999;44:320-324.
(69) Abdo MS, al-Kafawi AA. Experimental studies on the effect of Trigonella foenum-graecum. Planta Med. 1969;17:14-18.
(70) Khokhar S, Magnusdottir SG. Total phenol, catechin, and caffeine contents of teas commonly consumed in the United kingdom. J Agric Food Chem. 2002;50:565-570.
(71) Brinker F. Herb Contraindications and Drug Interactions. 2nd ed. 1998.
(72) Basch E, Ulbricht C, Hammerness P, Vora M. Marshmallow (Althaea officinalis L.) monograph. J Herb Pharmacother. 2003;3:71-81.
(73) van EM, Hornstra G, van der Wal MF, Vrijkotte TG, Bonsel GJ. Maternal n-3, n- 6, and trans fatty acid profile early in pregnancy and term birth weight: a prospective cohort study. Am J Clin Nutr. 2008;87:887-895.
(74) Innis SM, Friesen RW. Essential n-3 fatty acids in pregnant women and early visual acuity maturation in term infants. Am J Clin Nutr. 2008;87:548-557.
85 (75) Church MW, Jen KL, Dowhan LM, Adams BR, Hotra JW. Excess and deficient omega-3 fatty acid during pregnancy and lactation cause impaired neural transmission in rat pups. Neurotoxicol Teratol. 2008;30:107-117.
(76) Cetin I, Koletzko B. Long-chain omega-3 fatty acid supply in pregnancy and lactation. Curr Opin Clin Nutr Metab Care. 2008;11:297-302.
(77) The Vitamin Shoppe. http://www.vitaminshoppe.com/store/en/browse/sku_detail.jsp?id=TT- 1017&source=FGTT-1017&ci_src=14110944&ci_sku=TT-1017 . 2008. 3-19- 2008.
(78) Ernst E, Schmidt K. Health risks over the Internet: advice offered by "medical herbalists" to a pregnant woman. Wien Med Wochenschr. 2002;152:190-192.
(79) Gunn TR, Wright IM. The use of black and blue cohosh in labour. N Z Med J. 1996;109:410-411.
(80) Perri D, Dugoua JJ, Mills E, Koren G. Safety and efficacy of echinacea (Echinacea angustafolia, e. purpurea and e. pallida) during pregnancy and lactation. Can J Clin Pharmacol. 2006;13:e262-e267.
(81) Oates-Whitehead R. Nausea and vomiting in early pregnancy. Clin Evid. 2004;1840-1852.
(82) Keating A, Chez RA. Ginger syrup as an antiemetic in early pregnancy. Altern Ther Health Med. 2002;8:89-91.
(83) Medline Plus. http://www.nlm.nih.gov/medlineplus/ . Date Accessed: 11-17-2007.
(84) Jensen-Jarolim E, Reider N, Fritsch R, Breiteneder H. Fatal outcome of anaphylaxis to camomile-containing enema during labor: a case study. J Allergy Clin Immunol. 1998;102:1041-1042.
(85) Jepson RG, Mihaljevic L, Craig J. Cranberries for preventing urinary tract infections. Cochrane Database Syst Rev. 2004;CD001321.
86 (86) Tiran D. The use of fenugreek for breast feeding women. Complement Ther Nurs Midwifery. 2003;9:155-156.
(87) Portnoi G, Chng LA, Karimi-Tabesh L, Koren G, Tan MP, Einarson A. Prospective comparative study of the safety and effectiveness of ginger for the treatment of nausea and vomiting in pregnancy. Am J Obstet Gynecol. 2003;189:1374-1377.
(88) Vutyavanich T, Kraisarin T, Ruangsri R. Ginger for nausea and vomiting in pregnancy: randomized, double-masked, placebo-controlled trial. Obstet Gynecol. 2001;97:577-582.
(89) Merhav H, Amitai Y, Palti H, Godfrey S. Tea drinking and microcytic anemia in infants. Am J Clin Nutr. 1985;41:1210-1213.
(90) Zijp IM, Korver O, Tijburg LB. Effect of tea and other dietary factors on iron absorption. Crit Rev Food Sci Nutr. 2000;40:371-398.
(91) Urtica dioica; Urtica urens (Nettle) - monograph. Altern Med Rev. 2007;12:280- 284.
(92) Chrubasik JE, Roufogalis BD, Wagner H, Chrubasik SA. A comprehensive review on nettle effect and efficacy profiles, Part I: herba urticae. Phytomedicine. 2007;14:423-435.
(93) Potterat O, Hamburger M. Morinda citrifolia (Noni) fruit--phytochemistry, pharmacology, safety. Planta Med. 2007;73:191-199.
(94) Charrois TL, Sadler C, Vohra S. Complementary, holistic, and integrative medicine: St. John's wort. Pediatr Rev. 2007;28:69-72.
87
APPENDIX A
Transport Log
88
89
90
91
92
APPENDIX B
County Data
93
# #
Rate
Teen Teen Birth
Race (%) Race
Hospitals
Poverty Birth Rate # Physicia ns
County < percent
African
Hispanic
American
Caucasion Total Total Minority Athens 93.4 2.4 1 7.3 14 10.1 16.9 130 2 Belmont 94.8 3.5 0.5 5.6 11.7 10.1 40.8 84 3 Delaware 94.2 2.5 0.9 6.4 2.9 16.7 15.2 506 1 Fairfield 95.1 2.6 1 5.5 4.5 12.9 28.2 239 1 Fayette 95.7 2.1 1 4.8 7.7 13.5 59.6 23 1 Franklin 75.5 17.6 2.3 25.6 8.2 15.7 46.7 3,683 10 Gallia 94.9 2.6 0.4 5.3 13.5 12 46.3 104 1 Guernsey 95.9 1.6 0.6 4.3 12.9 11.8 41.6 65 1 Harrison 96.6 2 0.2 3.5 11 11.6 45.5 6 1 Hocking 97.7 1.1 0.3 2.5 10.3 13.2 64.2 23 1 Jackson 97.3 1 1.2 3.6 13.6 13.5 74.1 28 2 Jefferson 92.6 5.7 0.8 7.9 11.4 9.1 30.3 104 2 Knox 97.4 0.8 0.4 2.8 7.4 13.1 27.9 72 1 Lawrence 96.1 2.4 0.5 4.2 15.1 11.6 58.4 49 0 Licking 95.5 2.2 0.6 4.9 5.5 13.8 38.6 192 1 Madison 91.5 6 0.7 8.7 6.2 12.3 42.6 52 1 Marion 92.4 5.4 1.3 8.2 7.4 11.9 50 103 1 Meigs 97.3 0.6 0.6 3 14.3 13.1 70.4 4 1 Monroe 98.5 0.1 0.5 1.7 11 10.8 39.9 6 0 Morrow 98.8 0.2 0.6 1.7 6.6 13.5 31.9 13 1 Noble 92.6 5.6 0.8 7.9 8.3 10.9 22.8 3 0 Pickaway 92.2 5.7 0.8 8.3 7.6 10.2 42.6 39 1 Pike 96.3 0.8 0.5 4 15.1 13.8 72.4 27 1 Ross 92 5.7 0.8 8.5 9.1 12 46.1 137 1 Scioto 94.7 2.6 0.6 5.5 15.2 12.4 63.5 139 1 Union 95.5 2.4 0.7 4.8 3.6 13.8 30.1 40 1 Vinton 97.9 0.1 0.6 2.5 15.1 12.6 51.2 0 0 Washington 97.1 0.8 0.4 3.2 8.6 11.3 33.7 112 2 Wyandot 97.8 0 1.9 2.8 3.8 12.5 34.5 14 1 Athens 93.4 2.4 1 7.3 14 10.1 16.9 130 2
94