Diabetes Care Volume 43, Supplement 1, January 2020 S183

14. Management of in American Diabetes Association : Standards of Medical Care in Diabetesd2020 Diabetes Care 2020;43(Suppl. 1):S183–S192 | https://doi.org/10.2337/dc20-S014 4 AAEETO IBTSI PREGNANCY IN DIABETES OF MANAGEMENT 14.

The American Diabetes Association (ADA) “Standards of Medical Care in Diabetes” includes the ADA’s current clinical practice recommendations and is intended to provide the components of diabetes care, general treatment goals and guidelines, and tools to evaluate quality of care. Members of the ADA Professional Practice Committee, a multidisciplinary expert committee (https://doi.org/10.2337/dc20-SPPC), are responsible for updating the Standards of Care annually, or more frequently as warranted. For a detailed description of ADA standards, statements, and reports, as well as the evidence- grading system for ADA’s clinical practice recommendations, please refer to the Standards of Care Introduction (https://doi.org/10.2337/dc20-SINT). Readers who wish to comment on the Standards of Care are invited to do so at professional.diabetes.org/SOC.

DIABETES IN PREGNANCY The prevalence of diabetes in pregnancy has been increasing in the U.S. in parallel with the worldwide epidemic of obesity. Not only is the prevalence of and increasing in women of reproductive age, but there is also a dramatic increase in the reported rates of mellitus. Diabetes confers significantly greater maternal and fetal risk largely related to the degree of but also related to chronic complications and comorbidities of diabetes. In general, specific risks of diabetes in pregnancy include spontaneous , fetal anomalies, preeclampsia, fetal demise, macrosomia, neonatal hypo- glycemia, hyperbilirubinemia, and neonatal respiratory distress syndrome, among others. In addition, diabetes in pregnancy may increase the risk of obesity, hypertension, and type 2 diabetes in offspring later in life (1,2).

PRECONCEPTION COUNSELING

Recommendations 14.1 Starting at puberty and continuing in all women with diabetes and re- productive potential, preconception counseling should be incorporated into routine diabetes care. A 14.2 should be discussed, and effective contraception (with consid- eration of long-acting, reversible contraception) should be prescribed and used Suggested citation: American Diabetes Associa- until a woman’s treatment regimen and A1C are optimized for pregnancy. A tion. 14. Management of diabetes in pregnancy: 14.3 Preconception counseling should address the importance of achieving Standards of Medical Care in Diabetesd2020. levels as close to normal as is safely possible, ideally Diabetes Care 2020;43(Suppl. 1):S183-S192 A1C ,6.5% (48 mmol/mol), to reduce the risk of congenital anomalies, © 2019 by the American Diabetes Association. preeclampsia, macrosomia, and other complications. B Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. More infor- All women of childbearing age with diabetes should be informed about the mation is available at http://www.diabetesjournals importance of achieving and maintaining as near euglycemia as safely possible prior .org/content/license. S184 Management of Diabetes in Pregnancy Diabetes Care Volume 43, Supplement 1, January 2020

to conception and throughout preg- additional details on elements of pre- multidisciplinary clinic including nancy. Observational studies show an conception care (15,17). Counseling an endocrinologist, maternal-fetal increased risk of diabetic embryopathy, on the specificrisksofobesityinpreg- medicine specialist, registered di- especially anencephaly, microcephaly, nancy and lifestyle interventions to etitian nutritionist, and diabetes congenital heart disease, renal anoma- prevent and treat obesity, including educator, when available. B lies, and caudal regression, directly pro- referral to a registered dietitian nutri- 14.5 In addition to focused attention portional to elevations in A1C during the tionist (RD/RDN), is recommended when on achieving glycemic targets A, first 10 weeks of pregnancy (3). Although indicated. standard preconception care observational studies are confounded Diabetes-specific counseling should should be augmented with ex- by the association between elevated include an explanation of the risks to tra focus on nutrition, diabetes periconceptional A1C and other poor mother and related to pregnancy education, and screening for di- self-care behavior, the quantity and con- and the ways to reduce risk including abetes comorbidities and com- sistency of data are convincing and sup- glycemic goal setting, lifestyle manage- plications. E port the recommendation to optimize ment, and medical nutrition therapy. The 14.6 Women with preexisting type 1 glycemia prior to conception, given most important diabetes-specific com- or type 2 diabetes who are that organogenesis occurs primarily ponent of preconception care is the planning pregnancy or who at 5–8 weeks of gestation, with an attainment of glycemic goals prior to have become pregnant should A1C ,6.5% (48 mmol/mol) being as- conception. Diabetes-specifictesting be counseled on the risk of de- sociated with the lowest risk of con- should include A1C, creatinine, and uri- velopment and/or progression genital anomalies (3–6). nary albumin-to-creatinine ratio. Special of . Dilated There are opportunities to educate all attention should be paid to the review of eye examinations should occur women and adolescents of reproductive the medication list for potentially harm- ideally before pregnancy or in age with diabetes about the risks of ful drugs (i.e., ACE inhibitors [18], angio- the first trimester, and then unplanned and about im- tensin receptor blockers [18], and statins patients should be monitored provedmaternalandfetaloutcomeswith [19,20]). A referral for a comprehensive every trimester and for 1 year pregnancy planning (7). Effective pre- eye exam is recommended. Women with postpartum as indicated by the conception counseling could avert sub- preexisting diabetic retinopathy will need degree of retinopathy and as stantial health and associated cost close monitoring during pregnancy to as- recommended by the eye care burdens in offspring (8). Family planning sess for progression of retinopathy and provider. B should be discussed, including the ben- provide treatment if indicated (21). The efits of long-acting, reversable contra- use of aspirin (81–150 mg) can be consid- The importance of preconception care ception, and effective contraception ered preconception as it is recommended for all women is highlighted by the should be prescribed and used until a for all pregnant women with diabetes (if no American College of Obstetricians and woman is prepared and ready to become contraindication) by 16 weeks of gesta- Gynecologists (ACOG) committee opin- pregnant (9–13). tion to reduce the risk of preeclampsia. ion 762, Prepregnancy Counseling (15). To minimize the occurrence of com- Please see PREECLAMPSIA AND ASPIRIN for more A key point is the need to incorporate plications, beginning at the onset of information. a question about a woman’s plans for puberty or at diagnosis, all girls and Several studies have shown improved pregnancy into routine primary and gy- women with diabetes of childbearing outcomes when necologic care. The preconception care potential should receive education about care has been delivered from preconcep- 1) the risks of malformations associated of women with diabetes should include tion through pregnancy by a multidisci- with unplanned pregnancies and even the standard screenings and care recom- plinary group focused on improved mild hyperglycemia and 2)theuseofef- mended for all women planning preg- glycemic control (22–25). One study fective contraception at all times when nancy (15). Prescription of prenatal showed that care of preexisting diabetes preventing a pregnancy. Preconception vitamins (with at least 400 mg of folic in clinics that included diabetes and m counseling using developmentally ap- acid and 150 g of potassium iodide [16]) obstetric specialists improved care propriate educational tools enables is recommended prior to conception. (25). However, there is no consensus adolescent girls to make well-informed Review and counseling on the use of on the structure of multidisciplinary decisions (7). Preconception counseling nicotine products, alcohol, and recrea- team care for diabetes and pregnancy, resources tailored for adolescents are tional drugs, including marijuana, is and there is a lack of evidence on the available at no cost through the American important. Standard care includes impact on outcomes of various methods Diabetes Association (ADA) (14). screening for sexually transmitted dis- of health care delivery (26). eases and thyroid disease, recommended Preconception Care vaccinations, routine genetic screen- GLYCEMIC TARGETS IN ing, a careful review of all prescription PREGNANCY Recommendations and nonprescription medications and 14.4 Women with preexisting diabe- Recommendations supplements used, and a review of travel tes who are planning a preg- 14.7 Fasting and postprandial self- history and plans with special attention nancy should ideally be managed monitoring of glucose to areas known to have Zika virus, as beginning in preconception in a are recommended in both outlined by ACOG. See Table 14.1 for care.diabetesjournals.org Management of Diabetes in Pregnancy S185

Table 14.1—Checklist for preconception care for women with diabetes (15,17) Preconception education should include: ☐ Comprehensive nutrition assessment and recommendations for: c Overweight/obesity or underweight c Meal planning c Correction of dietary nutritional deficiencies c Caffeine intake c Safe food preparation technique ☐ Lifestyle recommendations for: c Regular moderate exercise c Avoidance of hyperthermia (hot tubs) c Adequate sleep ☐ Comprehensive diabetes self-management education ☐ Counseling on diabetes in pregnancy per current standards, including: natural history of resistance in pregnancy and postpartum; preconception glycemic targets; avoidance of DKA/severe hyperglycemia; avoidance of severe ; progression of retinopathy; PCOS (if applicable); fertility in patients with diabetes; genetics of diabetes; risks to pregnancy including , still birth, congenital malformations, macrosomia, preterm labor and delivery, hypertensive disorders in pregnancy, etc. ☐ Supplementation c Folic acid supplement (400 mg routine) c Appropriate use of over-the-counter medications and supplements Medical assessment and plan should include: ☐ General evaluation of overall health ☐ Evaluation of diabetes and its comorbidities and complications, including: DKA/severe hyperglycemia; severe hypoglycemia/ hypoglycemic unawareness; barriers to care; comorbidities such as hyperlipidemia, hypertension, NAFLD, PCOS, and thyroid dysfunction; complications such as macrovascular disease, nephropathy, neuropathy (including autonomic bowel and bladder dysfunction), and retinopathy ☐ Evaluation of obstetric/gynecologic history, including history of: cesarean section, congenital malformations or fetal loss, current methods of contraception, hypertensive disorders of pregnancy, postpartum hemorrhage, preterm delivery, previous macrosomia, Rh incompatibility, and thrombotic events (DVT/PE) ☐ Review of current medications and appropriateness during pregnancy Screening should include: ☐ Diabetescomplicationsandcomorbidities,including: comprehensivefootexam;comprehensiveophthalmologicexam;ECGinwomenstartingat age 35 years who have cardiac signs/symptoms or risk factors, and if abnormal, further evaluation; lipid panel; serum creatinine; TSH; and urine protein-to-creatinine ratio ☐ Anemia ☐ Genetic carrier status (based on history): c Cystic fibrosis c Sickle cell anemia c Tay-Sachs disease c Thalassemia c Others if indicated ☐ Infectious disease c Neisseria gonorrhea/Chlamydia trachomatis c Hepatitis C c HIV c Pap smear c Syphilis Immunizations should include: ☐ Rubella ☐ Varicella ☐ Hepatitis B ☐ Influenza ☐ Others if indicated Preconception plan should include: ☐ Nutrition and medication plan to achieve glycemic targets prior to conception, including appropriate implementation of monitoring, continuous glucose monitoring, and pump technology ☐ Contraceptive plan to prevent pregnancy until glycemic targets are achieved ☐ Management plan for general health, gynecologic concerns, comorbid conditions, or complications, if present, including: hypertension, nephropathy, retinopathy; Rh incompatibility; and thyroid dysfunction DKA, ; DVT/PE, deep vein thrombosis/pulmonary ; ECG, electrocardiogram; NAFLD, nonalcoholic fatty liver disease; PCOS, polycystic ovary syndrome; TSH, thyroid-stimulating hormone. S186 Management of Diabetes in Pregnancy Diabetes Care Volume 43, Supplement 1, January 2020

diabetogenic placental hormones. In pa- c Fasting glucose ,95 mg/dL (5.3 gestational diabetes mellitus tients with preexisting diabetes, glycemic mmol/L) and either and preexisting diabetes in targets are usually achieved through a com- c One-hour postprandial glucose ,140 pregnancy to achieve optimal bination of insulin administration and med- mg/dL (7.8 mmol/L) or glucose levels. Glucose targets ical nutrition therapy. Because glycemic c Two-hour postprandial glucose ,120 are fasting plasma glucose ,95 targets in pregnancy are stricter than in mg/dL (6.7 mmol/L) mg/dL (5.3 mmol/L) and either nonpregnant individuals, it is important 1-h postprandial glucose ,140 that women with diabetes eat consistent These values represent optimal control if mg/dL(7.8mmol/L)or2-hpost- amounts of carbohydrates to match with they can be achieved safely. In practice, prandial glucose ,120 mg/dL insulin dosage and to avoid hyperglycemia it may be challenging for women with (6.7 mmol/L). Some women or hypoglycemia. Referral to a registered type 1 diabetes to achieve these with preexisting diabetes should dietitian nutritionist is important in order targets without hypoglycemia, particu- also test blood glucose prepran- to establish a food plan and insulin-to- larly women with a history of recurrent dially. B carbohydrate ratio and to determine hypoglycemia or hypoglycemia unaware- 14.8 Due to increased red blood cell weight gain goals. ness. If women cannot achieve these turnover, A1C is slightly lower targets without significant hypoglyce- in normal pregnancy than in mia, the ADA suggests less-stringent normal nonpregnant women. Insulin Physiology Given that early pregnancy is a time of targets based on clinical experience and Ideally, the A1C target in preg- enhanced insulin sensitivity and lower glu- individualization of care. nancy is ,6% (42 mmol/mol) if cose levels, many women with type 1 di- this can be achieved without abetes will have lower insulin requirements significant hypoglycemia, but A1C in Pregnancy and increased risk for hypoglycemia (27). The In studies of women without preexisting the target may be relaxed to situation rapidly reverses by approximately diabetes, increasing A1C levels within the ,7%(53mmol/mol)ifnecessary 16weeksasinsulinresistance increases normal range are associated with ad- to prevent hypoglycemia. B exponentially during the second and early verse outcomes (33). In the Hyperglyce- 14.9 When used in addition to pre- thirdtrimestersto2–3 times the preprandial mia and Adverse Pregnancy Outcome and postprandial self-monitoring requirement. The insulin requirement levels (HAPO) study, increasing levels of glyce- of blood glucose, continuous off toward the end of the third trimester mia were also associated with worsen- glucose monitoring can help with placental aging. A rapid reduction ing outcomes (34). Observational studies to achieve A1C targets in dia- in insulin requirements can indicate the in preexisting diabetes and pregnancy betes and pregnancy. B development of placental insufficiency show the lowest rates of adverse fetal 14.10 When used in addition to self- (28). In women with normal pancreatic outcomes in association with A1C ,6– monitoring of blood glucose function, insulin production is sufficient 6.5% (42–48 mmol/mol) early in gesta- targeting traditional pre- and to meet the challenge of this physiolog- tion (4–6,35). Clinical trials have not postprandial targets, continu- ical and to maintain evaluated the risks and benefits of ous glucose monitoring can normal glucose levels. However, in achieving these targets, and treatment reduce macrosomia and neo- women with diabetes, hyperglycemia goals should account for the risk of natal hypoglycemia in preg- occurs if treatment is not adjusted ap- maternal hypoglycemia in setting an nancy complicated by type 1 propriately. individualized target of ,6% (42 diabetes. B mmol/mol) to ,7% (53 mmol/mol). Due 14.11 Continuous glucose monitor- to physiological increases in red blood ing metrics should not be Glucose Monitoring Reflecting this physiology, fasting and cell turnover, A1C levels fall during nor- used as a substitute for self- postprandial monitoring of blood glucose mal pregnancy (36,37). Additionally, as monitoring of blood glucose to is recommended to achieve metabolic A1C represents an integrated measure achieve optimal pre- and post- control in pregnant womenwith diabetes. of glucose, it may not fully capture post- prandial glycemic targets. E Preprandial testing is also recommended prandial hyperglycemia, which drives 14.12 Commonly used estimated A1C when using insulin pumps or basal-bolus macrosomia. Thus, although A1C may and glucose management indi- therapy so that premeal rapid-acting in- be useful, it should be used as a second- catorcalculations should notbe sulindosagecanbeadjusted.Postprandial ary measure of glycemic control in preg- used in pregnancy as estimates monitoring is associated with better gly- nancy, after self-monitoring of blood of A1C. C cemiccontrolandlowerriskofpreeclamp- glucose. sia (29–31). There are no adequately In the second and third trimesters, Pregnancy in women with normal glu- powered randomized trials comparing A1C ,6% (42 mmol/mol) has the lowest cose metabolism is characterized by fast- different fasting and postmeal glycemic risk of large-for-gestational-age in- ing levels of blood glucose that are targets in diabetes in pregnancy. fants (35,38,39), preterm delivery (40), lower than in the nonpregnant state Similar to the targets recommended and preeclampsia (1,41). Taking all of due to insulin-independent glucose up- by ACOG (the same as for GDM; de- this into account, a target of ,6% take by the fetus and and by scribed below) (32), the ADA-recommended (42 mmol/mol) is optimal during preg- mild postprandial hyperglycemia and targets for women with type 1 or type 2 nancy if it can be achieved without carbohydrate intolerance as a result of diabetes are as follows: significant hypoglycemia. The A1C target care.diabetesjournals.org Management of Diabetes in Pregnancy S187

in a given patient should be achieved between the woman and an RD/RDN fa- medications lack long-term without hypoglycemia, which, in addition miliar with the management of GDM safety data. to the usual adverse sequelae, may in- (50,51). The food plan should provide 14.15 Metformin, when used to treat crease the risk of low (42). adequate calorie intake to promote polycystic ovary syndrome and Given the alteration in red blood cell fetal/neonatal and maternal health, induce ovulation, should be kinetics during pregnancy and physiolog- achieve glycemic goals, and promote discontinued by the end of ical changes in glycemic parameters, A1C weight gain according to 2009 Institute the first trimester. A levels may need to be monitored more of Medicine recommendations (52). frequently than usual (e.g., monthly). There is no definitive research that GDM is characterized by increased risk identifies a specific optimal calorie intake Continuous Glucose Monitoring in of macrosomia and birth complications for women with GDM or suggests that Pregnancy and an increased risk of maternal type 2 their calorie needs are different from CONCEPTT (Continuous Glucose Moni- diabetes after pregnancy. The associa- those of pregnant women without toring in Pregnant Women With Type 1 tion of macrosomia and birth complica- GDM. The food plan should be based Diabetes Trial) was a randomized con- tions with oral on a nutrition assessment with guidance trolled trial of continuous glucose mon- (OGTT) results is continuous with no from the Dietary Reference Intakes fl itoring (CGM) in addition to standard clear in ection points (34). In other (DRI). The DRI for all pregnant women care, including optimization of pre- words, risks increase with progressive recommends a minimum of 175 g of and postprandial glucose targets versus hyperglycemia. Therefore, all women carbohydrate, a minimum of 71 g of standard care for pregnant women with should be tested as outlined in Sec- protein, and 28 g of fiber. The diet should “ fi type 1 diabetes. It demonstrated the tion 2 Classi cation and Diagnosis of not be high in saturated fat. As is true ” value of CGM in pregnancy complicated Diabetes (https://doi.org/10.2337/dc20- for all nutrition therapy in patients with by type 1 diabetes by showing a mild S002). Although there is some heteroge- diabetes, the amount and type of car- improvement in A1C without an increase neity, many randomized controlled trials bohydrate will impact glucose levels. in hypoglycemia and reductions in large- (RCTs) suggest that the risk of GDM may be Simple carbohydrates will result in higher for-gestational-age births, length of stay, reduced by diet, exercise, and lifestyle postmeal excursions. and neonatal hypoglycemia (43). An ob- counseling, particularly when interven- Pharmacologic Therapy servational cohort study that evaluated tions are started during the first or early Treatment of GDM with lifestyle and the glycemic variables reported using in the second trimester (46–48). insulin has been demonstrated to im- CGM and their association with large- Lifestyle Management prove perinatal outcomes in two large for-gestational-age births found that After diagnosis, treatment starts with randomized studies as summarized in a mean glucose had a greater association medical nutrition therapy, physical ac- U.S. Preventive Services Task Force re- than time in range, time below range, or tivity, and weight management depend- view (53). Insulin is the first-line agent time above range (44). Using the CGM- ing on pregestational weight, as outlined recommended for treatment of GDM in reported mean glucose is superior to the in the section below on preexisting type 2 the U.S. While individual RCTs support use of estimated A1C, glucose manage- diabetes, and glucose monitoring aiming limited efficacy of metformin (54,55) and ment indicator, and other calculations for the targets recommended by the Fifth glyburide (56) in reducing glucose levels to estimate A1C given the changes to International Workshop-Conference on for the treatment of GDM, these agents A1C that occur in pregnancy (45). Gestational Diabetes Mellitus (48): are not recommended as first-line treat- ment for GDM because they are known to MANAGEMENT OF GESTATIONAL c Fasting glucose ,95 mg/dL (5.3 cross the placenta and data on long-term DIABETES MELLITUS mmol/L) and either safety for offspring is of some concern Recommendations c One-hour postprandial glucose ,140 (32). Furthermore, glyburide and met- 14.13 Lifestyle behavior change is an mg/dL (7.8 mmol/L) or formin failed to provide adequate glyce- essential component of man- c Two-hour postprandial glucose ,120 mic control in separate randomized agement of gestational diabe- mg/dL (6.7 mmol/L) controlled trials, failing in 23% and tes mellitus and may suffice for 25–28% of women with GDM, respec- the treatment of many women. Depending on the population, studies tively (57,58). Insulinshouldbeaddedifneeded suggest that 70–85% of women diag- to achieve glycemic targets. A nosed with GDM under Carpenter- Sulfonylureas Sulfonylureas are known to cross the 14.14 Insulin is the preferred medi- Coustan can control GDM with lifestyle placenta and have been associated cation for treating hyperglyce- modification alone; it is anticipated with increased neonatal hypoglycemia. mia in gestational diabetes that this proportion will be even higher Concentrations of glyburide in umbilical mellitus. Metformin and gly- if the lower International Association of cord plasma are approximately 50–70% buride should not be used as Diabetes and Pregnancy Study Groups of maternal levels (57,58). Glyburide first-line agents, as both cross (49) diagnostic thresholds are used. was associated with a higher rate of the placenta to the fetus. A neonatal hypoglycemia and macrosomia Other oral and noninsulin Medical Nutrition Therapy Medical nutrition therapy for GDM is an than insulin or metformin in a 2015 meta- injectable glucose-lowering individualized nutrition plan developed analysis and systematic review (59). S188 Management of Diabetes in Pregnancy Diabetes Care Volume 43, Supplement 1, January 2020

More recently, glyburide failed to be cost, language barriers, comprehension, While many providers prefer insulin found noninferior to insulin based on a or cultural influences, may not be able to pumps in pregnancy, it is not clear that composite outcome of neonatal hypogly- use insulin safely or effectively in preg- they are superior to multiple daily cemia, macrosomia, and hyperbilirubine- nancy. Oral agents may be an alternative injections (88–90). Closed-loop technol- mia (60). Long-term safety data for in these women after a discussion of ogy that is U.S. Food and Drug Admin- offspring exposed to glyburide are not the known risks and the need for more istration approved outside of pregnancy available (60). long-term safety data in offspring. How- can only target a glucose of 120 mg/dL at Metformin ever, due to the potential for growth this time, which is likely to be too high for Metformin was associated with a lower restriction or acidosis in the setting optimal nocturnal control in pregnancy. fi fi risk of neonatal hypoglycemia and less of placental insuf ciency, metformin However, given potential bene ts, on- maternal weight gain than insulin in should not be used in women with hy- going work is being done in this area. systematic reviews (59,61,62,65). How- pertension, preeclampsia, or at risk for intrauterine growth restriction (78,79). Type 1 Diabetes ever, metformin readily crosses the pla- Women with type 1 diabetes have an centa, resulting in umbilical cord blood Insulin increased risk of hypoglycemia in the first levels of metformin as high or higher than Insulin use should follow the guidelines trimester and, like all women, have al- simultaneous maternal levels (66,67). In below. Both multiple daily insulin injec- tered counterregulatory response in the Metformin in Gestational Diabetes: tions and continuous subcutaneous in- pregnancy that may decrease hypogly- The Offspring Follow-Up (MiG TOFU) sulin infusion are reasonable delivery cemia awareness. Education for patients study’s analyses of 7- to 9-year-old off- strategies, and neither has been shown and family members about the preven- spring, the 9-year-old offspring exposed to be superior to the other during preg- tion, recognition, and treatment of hy- to metformin in the Auckland cohort for nancy (80). poglycemia is important before, during, the treatment of GDM were heavier and and after pregnancy to help to prevent had a higher waist-to-height ratio and MANAGEMENT OF PREEXISTING and manage the risks of hypoglycemia. waist circumference than those exposed TYPE 1 DIABETES AND TYPE Insulin resistance drops rapidly with de- to insulin (68). This was not found in the 2 DIABETES IN PREGNANCY livery of the placenta. Adelaide cohort. In two RCTs of metfor- Insulin Use Pregnancy is a ketogenic state, and min use in pregnancy for polycystic ovary women with type 1 diabetes, and to a Recommendations syndrome, follow-up of 4-year-old off- lesser extent those with type 2 diabetes, 14.16 Insulin is the preferred agent spring demonstrated higher BMI and are at risk for diabetic ketoacidosis (DKA) for management of both type 1 increased obesity in the offspring ex- at lower blood glucose levels than in the diabetes and type 2 diabetes in posed to metformin (69,70). A follow-up nonpregnant state. Women with type 1 pregnancy. E – diabetes should be prescribed ketone study at 5 10 years showed that the 14.17 Either multiple daily injections strips and receive education on diabetic offspring had higher BMI, weight-to- or technology ketoacidosis prevention and detection. height ratios, waist circumferences, can be used in pregnancy com- DKA carries a high risk of . and a borderline increase in fat mass plicated by type 1 diabetes. C (70,71). Metformin is being studied in Women in DKA who are unable to eat often require 10% dextrose with an in- two ongoing trials in type 2 diabetes The physiology of pregnancy necessi- sulin drip to adequately meet the higher (Metformin in Women with Type 2 Di- tates frequent titration of insulin to carbohydrate demands of the placenta abetes in Pregnancy Trial [MiTY] [72] and match changing requirements and and fetus in the third trimester in order to Medical Optimization of Management of underscores the importance of daily resolve their ketosis. Type 2 Diabetes Complicating Pregnancy and frequent self-monitoring of blood Retinopathy is a special concern in [MOMPOD] [73]), but long-term off- glucose. Due to the complexity of insulin pregnancy. Rapid implementation of eu- spring data will not be available for management in pregnancy, referral to a glycemia in the setting of retinopathy is some time. A recent meta-analysis con- specialized center offering team-based associated with worsening of retinopa- cluded that metformin exposure resulted care (with team members including thy (21). in smaller neonates with acceleration of maternal-fetal medicine specialist, en- postnatal growth resulting in higher BMI docrinologist, or other provider experi- Type 2 Diabetes in childhood (68,69). enced in managing pregnancy in women Type 2 diabetes is often associated with Randomized, double-blind, controlled with preexisting diabetes, dietitian, obesity. Recommended weight gain dur- trials comparing metformin with other nurse, and social worker, as needed) ing pregnancy for overweight women is therapies for ovulation induction in is recommended if this resource is 15–25lband forobese womenis10–20lb women with polycystic ovary syndrome available. (52). There is no adequate data on op- have not demonstrated benefit in pre- None of the currently available human timal weight gain versus weight mainte- venting spontaneous abortion or GDM insulin preparations have been demon- nance in women with a BMI .35 kg/m2. (74), and there is no evidence-based strated to cross the placenta (80–86). A Glycemic control is often easier to need to continue metformin in such recent Cochrane systematic review was achieve in women with type 2 diabetes patients (75–77). not able to recommend any specific in- than in those with type 1 diabetes but There are some women with GDM sulin regimen over another for the treat- can require much higher doses of insulin, requiring medical therapy who, due to ment of diabetes in pregnancy (87). sometimes necessitating concentrated care.diabetesjournals.org Management of Diabetes in Pregnancy S189

insulin formulations. As in type 1 diabe- at conception and avoided in requirements for the initial tes, insulin requirements drop dramati- sexually active women of child- few days postpartum. C cally after delivery. bearing age who are not using 14.22 A contraceptive plan should be The risk for associated hypertension reliable contraception. B discussed and implemented and other comorbidities may be as high with all women with diabetes or higher with type 2 diabetes as with of reproductive potential. C type 1 diabetes, even if diabetes is better In normal pregnancy, blood pressure is 14.23 Screen women with a recent controlled and of shorter apparent du- lower than in the nonpregnant state. In a history of gestational diabetes ration, with pregnancy loss appearing to pregnancy complicated by diabetes and mellitus at 4–12 weeks post- be more prevalent in the third trimester chronic hypertension, a target goal blood , partum, using the 75-g oral in women with type 2 diabetes compared pressure of 135/85 mmHg is reason- glucosetolerancetestandclin- with the first trimester in women with able (98,99). Blood pressure targets ically appropriate nonpreg- type 1 diabetes (91,92). lower than 120/80 mmHg may be as- sociated with impaired fetal growth, nancy diagnostic criteria. B especially in the setting of placental in- 14.24 Women with a history of ges- PREECLAMPSIA AND ASPIRIN sufficiency. In a 2015 study targeting tational diabetes mellitus found Recommendation diastolic blood pressure of 100 mmHg to have should re- 14.18 Women with type 1 or type 2 versus 85 mmHg in pregnant women, ceive intensive lifestyle inter- diabetes should be prescribed only 6% of whom had GDM at enroll- ventions and/or metformin to low-dose aspirin 60–150 mg/ ment, there was no difference in preg- prevent diabetes. A day (usual dose 81 mg/day) by nancy loss, neonatal care, or other 14.25 Womenwithahistoryofgesta- the end of the first trimester neonatal outcomes, although women tional diabetes mellitus should in order to lower the risk of in the less intensive treatment group have lifelong screening for the preeclampsia. A had a higher rate of uncontrolled hyper- development of type 2 diabetes tension (100). or prediabetes at least every Diabetes in pregnancy is associated with During pregnancy, treatment with 3 years. B an increased risk of preeclampsia (93). ACE inhibitors and angiotensin receptor 14.26 Women with a history of ges- Based upon the results of clinical trials blockers is contraindicated because tational diabetes mellitus should and meta-analyses (94), the U.S. Preven- they may cause fetal renal dysplasia, seek preconception screen- tive Services Task Force recommends the , pulmonary hypoplasia, ing for diabetes and precon- use of low-dose aspirin (81 mg/day) as a and intrauterine growth restriction (18). ception care to identify and treat preventive medication at 12 weeks of Antihypertensive drugs known to be hyperglycemia and prevent con- gestation in women who are at high risk effective and safe in pregnancy include genital malformations. E for preeclampsia (95). A cost-benefit methyldopa, nifedipine, labetalol, diltia- 14.27 should in- analysis has concluded that this approach zem, clonidine, and prazosin. Atenolol is clude psychosocial assessment would reduce morbidity, save lives, and not recommended, but other b-blockers and support for self-care. E lower health care costs (96). However, may be used, if necessary. Chronic di- uretic use during pregnancy is not rec- more study is needed to assess the long- Gestational Diabetes Mellitus term effects of prenatal aspirin exposure ommended as it has been associated with restricted maternal plasma volume, Initial Testing on offspring (97). Because GDM often represents previ- which may reduce uteroplacental perfu- ously undiagnosed prediabetes, type 2 sion (101). On the basis of available PREGNANCY AND DRUG diabetes, maturity-onset diabetes of the evidence, statins should also be avoided CONSIDERATIONS young, or even developing type 1 di- in pregnancy (102). abetes, women with GDM should be Recommendations See PREGNANCY AND ANTIHYPERTENSIVE MEDI- tested for persistent diabetes or predi- 14.19 In pregnant patients with di- CATIONS in Section 10 “Cardiovascular Dis- abetes at 4–12 weeks postpartum with a abetes and hypertension or ease and Risk Management” (https://doi 75-g OGTT using nonpregnancy criteria significant , a consis- .org/10.2337/dc20-s010) for more infor- as outlined in Section 2 “Classification tent blood pressure .135/85 mation on managing blood pressure in and Diagnosis of Diabetes” (https://doi mmHg should be treated in pregnancy. the interest of optimizing long- .org/10.2334/dc20-S002). term maternal health. Blood POSTPARTUM CARE Postpartum Follow-up pressure targets should range The OGTT is recommended over A1C at no lower than 120/80 mmHg, Recommendations 4–12 weeks postpartum because A1C as lower blood pressure tar- 14.21 Insulin resistance decreases may be persistently impacted (lowered) gets may impair fetal growth. C dramatically immediately post- by the increased red blood cell turnover 14.20 Potentially harmful medications partum, and insulin require- related to pregnancy, by blood loss at in pregnancy (i.e., ACE inhibi- ments need to be evaluated delivery, or by the preceding 3-month tors, angiotensin receptor block- and adjusted as they are often glucose profile. The OGTT is more sen- ers, statins) should be stopped roughly half the prepregnancy sitive at detecting glucose intolerance, S190 Management of Diabetes in Pregnancy Diabetes Care Volume 43, Supplement 1, January 2020

including both prediabetes and diabetes. following 1–2 weeks. In women taking pregnancy outcome in 933 women with type 1 Women of reproductive age with pre- insulin, particular attention should be diabetes. Diabetes Care 2009;32:1046–1048 diabetes may develop type 2 diabetes by directed to hypoglycemia prevention in 5. Nielsen GL, Møller M, Sørensen HT. HbA1c in early diabetic pregnancy and pregnancy out- the time of their next pregnancy and will the setting of and erratic comes: a Danish population-based cohort study need preconception evaluation. Because sleep and eating schedules (111). of 573 pregnancies in women with type 1 di- GDM is associated with an increased abetes. Diabetes Care 2006;29:2612–2616 lifetime maternal risk for diabetes esti- Lactation 6. Suhonen L, Hiilesmaa V, Teramo K. Glycaemic mated at 50–70% after 15–25 years control during early pregnancy and fetal In light of the immediate nutritional and malformations in women with type I diabetes (103,104), women should also be tested immunological benefits of breastfeeding mellitus. Diabetologia 2000;43:79–82 every 1–3 years thereafter if the 4– for the baby, all women including those 7. Charron-Prochownik D, Sereika SM, Becker D, 12 weeks postpartum 75-g OGTT is with diabetes should be supported in et al. Long-term effects of the booster-enhanced normal. Ongoing evaluation may be attempts to breastfeed. Breastfeeding READY-Girls preconception counseling program performedwithanyrecommendedgly- on intentions and behaviors for family planning may also confer longer-term metabolic in teens with diabetes. Diabetes Care 2013;36: cemic test (e.g., annual A1C, annual benefits to both mother (112) and off- 3870–3874 fasting plasma glucose, or triennial spring (113) However, lactation can 8. Peterson C, Grosse SD, Li R, et al. Preventable 75-g OGTT using nonpregnant thresh- increase the risk of overnight hypogly- health and cost burden of adverse birth outcomes olds). cemia, and insulin dosing may need to associated with pregestational diabetes in the United States. Am J Obstet Gynecol 2015;212: be adjusted. 74.e1–74.e9 Gestational Diabetes Mellitus and 9. Britton LE, Hussey JM, Berry DC, Crandell JL, Type 2 Diabetes Contraception Brooks JL, Bryant AG. Contraceptive use among Women with a history of GDM have a A major barrier to effective preconcep- women with prediabetes and diabetes in a US greatly increased risk of conversion to tion care is the fact that the majority of national sample. J Womens Health 2019;64:36–45 type 2 diabetes over time (103). In the pregnancies are unplanned. Planning prospective Nurses’ Health Study II (NHS 10. Morris JR, Tepper NK. Description and com- pregnancy is critical in women with pre- parison of postpartum use of effective contra- II), subsequent diabetes risk after a his- existing diabetes due to the need for ception among women with and without diabetes. fi tory of GDM was signi cantly lower in preconception glycemic control to pre- Contraception. 1 September 2019 [Epub ahead women who followed healthy eating vent congenital malformations and re- of print]. DOI: 10.1016/j.contraception.2019 .08.008 patterns (105). Adjusting for BMI mod- duce the risk of other complications. erately, but not completely, attenuated 11. Goldstuck ND, Steyn PS. The intrauterine Therefore, all women with diabetes of device in women with diabetes mellitus type I this association. Interpregnancy or post- childbearing potential should have family and II: a systematic review. ISRN Obstet Gynecol partum weight gain is associated with planning options reviewed at regular 2013. Accessed 3 October 2019. Available increased risk of adverse pregnancy out- intervals to make sure that effective from https://www.ncbi.nlm.nih.gov/pmc/articles/ PMC3874344/ comes in subsequent pregnancies (106) contraception is implemented and main- and earlier progression to type 2 diabe- 12. Wu JP, Moniz MH, Ursu AN. Long-acting tained. This applies to women in the reversible contraception-highly efficacious, safe, tes. immediate . Women and underutilized. JAMA 2018;320:397–398 Both metformin and intensive lifestyle with diabetes have the same contracep- 13. ACOG Practice Bulletin No. 201: Pregesta- intervention prevent or delay progres- tion options and recommendations as tional Diabetes Mellitus. Obstet Gynecol 2018; 132:e228–e248 sion to diabetes in women with predia- those without diabetes. Long-acting, re- betes and a history of GDM. Of women 14. Charron-Prochownik D, Downs J. 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