Benign Neonatal Shudders, Shivers, Jitteriness, Or Tremors

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Benign Neonatal Shudders, Shivers, Jitteriness,Millicent Collins, MD, Michal Young, or MD Tremors: Early Signs of Vitamin D Deficiencyabstract

Jitteriness and tremors in the newborn period typically precipitate an extensive, invasive, and expensive search for the etiology. Vitamin D deficiency has not been historically included in the differential of tremors. We report a shivering, jittery newborn who was subjected to a battery of testing, with the only biochemical abnormality being vitamin D deficiency. A second case had chin tremors and vitamin D deficiency. Review of our patients suggests that shudders, shivers, jitteriness, or tremors may be the earliest sign of vitamin D deficiency in the newborn. Neonates who present with these signs should be investigated for vitamin D deficiency.

Department of Pediatrics, Howard University College of Shudders, shivers, jitteriness, sepsis, seizure, or neurologic Medicine and Hospital, Washington, District of Columbia and tremors are terms used to disorder. Vitamin D deficiency has Dr Collins provided 1 case report, drafted the describe excessive movements in not been historically included in initial manuscript, and reviewed and revised the neonates. These terms, although the differential of such movements; manuscript: Dr Young conceptualized this case report, provided 1 case report, and reviewed used interchangeably, are defined however, vitamin D deficiency is the manuscript; and both authors approved the variably, depending on the author. common in pregnant women (5% to final manuscript as submitted and agree to be Jittery is a term used to describe 50%) and in breastfed infants (10% accountable for all aspects of the work. a series of recurrent tremors in to 56%), despite the widespread use DOI: https://doi.org/10.1542/peds.2016-0719 of prenatal vitamins, because these infants. Tremors are involuntary, ≥ Accepted for publication Jan 19, 2017 rhythmic, oscillatory movements may be inadequate to maintain normal 2 Address correspondence to Millicent Collins, of equal amplitude. Tremors are vitamin D levels ( 32 ng/mL). We MD, Department of Pediatrics, Howard University described as fine or coarse. A fine report 2 jittery newborns with the Hospital, 2041 Georgia Ave, NW, Washington, DC tremor is of high frequency (>6 only biochemical abnormality being 20060. E-mail: [email protected] cycles per second) and low amplitude vitamin D deficiency. Review of our PEDIATRICS (ISSN Numbers: Print, 0031-4005; Online, (<3 cm). Coarse tremors are of low patients suggests that shudders, 1098-4275). frequency (>6 cycles per1 second) and shivers, jitteriness, or tremors may be Copyright © 2017 by the American Academy of high amplitude (>3 cm). Shudders among the earliest signs of vitamin D Pediatrics ’ and shivers have a more colloquial deficiency in the newborn. FINANCIAL DISCLOSURE: The authors have usage. Meriam-Webster s dictionary Case 1 indicated they have no financial relationships describes a shudder as the act of relevant to this article to disclose. trembling convulsively or shaking Past History FUNDING: No external funding. because of fear or cold. A shiver is ’ POTENTIAL CONFLICT OF INTEREST: The authors described as a momentary trembling have indicated they have no potential conflicts of movement. Regardless of the term LB s mother (G2, P1) presented for interest to disclose. used, if repetitive and recurrent, a prenatal visit in her ninth month of such movements in the newborn pregnancy. She had no complications To cite: Collins M and Young M. Benign Neonatal period typically precipitate a search during this pregnancy, but complained Shudders, Shivers, Jitteriness, or Tremors: Early for the etiology among possibilities, that the prenatal vitamins had Signs of Vitamin D Deficiency. Pediatrics. 2017;140(2): such as hypoglycemia, hypocalcemia, made her sick throughout her entire e20160719 ’ hypothermia, hyperthyroidism, pregnancy. She did not drink milk. hypomagnesemia, drug withdrawal, LB s mother was a dark-skinned Downloaded from www.aappublications.org/news by guest on September 27, 2021 PEDIATRICS Volume 140, number 2, August 2017:e20160719 CASE REPORT TABLE 1 Results of Comprehensive Metabolic Panel in Case 1 Result Normal Range native of Barbados and had lived for ° 15 years in Washington, DC, which is Sodium, mEq/L 138 135–148 Potassium, mEq/L 5.2 3.5–5.3 located at latitude 38 N. There were ’ Chloride, mEq/L 105 95–111 no cultural or religious reasons that HCO2-, mEq/L 24 25–32 would limit the mother s exposure Glucose, mg/dL 116 70–115 to the sun. She had successfully Serum urea nitrogen, mg/dL 6 6–25 breastfed her first child for 1 year Creatinine, mg/dL 0.4 0.7–1.4 Calcium, mg/dL 10.7 8.5–10.6 while in Barbados. Birth History Phosphorus, mg/dL 6.5 2.5–4.5 Magnesium, mg/dL 2.7 1.7–2.5 Total bilirubin, mg/dL 1.8 0.2–1.2 Aspartate amino transferase, U/L 28 0–50 LB was born via normal spontaneous Alanine amino transferase, U/L 11 0–55 vaginal delivery at term in the Alkaline phosphatase, U/L 430 30–165 month of August. Birth weight was Total protein, g/dL 6.1 6–8.5 Albumin, g/dL 3.9 3.2 5.5 7 pounds, 2.2 ounces, length 20.5 – inches, head circumference 35 cm. He was in the nursery for 3 days, had TABLE 2 Results of Complete Blood Count in Case 1 mild jaundice (bilirubin 8.1), and White blood cell 11.5 × 103/μL was totally breastfed. His mother Red blood cell 4.14 × 106/μL expressed no difficulties relevant to Hemoglobin, g/dL 14.5 Hematocrit, % 41.3 breastfeeding. Mean corpuscular volume, fL 99.7 Postnatal Visits Mean corpuscular hemoglobin, pg 35.1 Mean corpuscular hemoglobin concentration, g/dL 35.2 Red blood cell distribution width, % 15.6 3 At age 6 days, on the initial Platelet count 339 × 10 /μL ’ Neutrophil, % 14.6 ambulatory newborn visit, the “ Lymphocyte, % 66.5 mother s only concern was that LB ” Monocyte, % 14.3 seemed to shiver a lot like he was Eosinophil, % 2.8 cold. She noted that she lived in Basophil, % 1.9 a basement apartment where her husband and her other child (age 2 TABLE 3 Results of Urine Drug Screen in Case 1 years) often felt cold and sometimes Drug Result shivered. The pediatrician counseled the mother about dressing an infant Amphetamine Negative Barbiturates Negative for a cool, damp environment. Just Cocaine Negative before leaving the office, the mother Methadone Negative remembered that she had seen Opiates Negative the tremors in the nursery but on Benzodiazepines Negative questioning the staff about it, she Marijuana Negative Propoxyphene Negative had been told that it was normal. Phencyclidine Negative The mother assured the pediatrician that she was continuing to take her prenatal vitamins. During the physical examination, no tremors or she continued to feel his movements. ‍3 for results. Urinalysis and thyroid shaking were noted. Because of the severity of his shaking, function were normal. At the age of 12 days, LB was brought he was sent to the emergency by his mother for a follow-up department for evaluation. Vital signs Consultation with the neurology visit. She noted that the tremors remained normal for age. LB was department was obtained. The were worse. Indeed, on physical afebrile and continued to be alert and neurologist noted that the head and examination, the infant would interactive. Laboratory studies were body were shaking rhythmically at periodically shiver as if cold. Even done. These included complete blood intervals lasting 2.0 to 2.5 minutes. his head would shake. However, he count, comprehensive metabolic Shaking was not related to crying or remained alert and appropriately panel, magnesium, phosphorus, nasal regurgitation. Other segments responsive. Mother would wrap him urine for toxicology, urinalysis, and of developmental and behavior tightly, noting that while wrapped thyroid function. See Tables 1, 2, and evaluation were appropriate. On Downloaded from www.aappublications.org/news by guest on September 27, 2021 e2 Collins and Young – ’ 4 7 physical examination, the infant Within 2 weeks, after starting life. ‍ ‍ Isolated tremors presenting was noted to have normal sutures treatment, LB s tremors had within the first few days from birth and normal neonatal reflexes with subsided completely. are generally considered benign excellent Moro and traction. The Case 2 or physiologic, and generally7 infant fixated and briefly followed. disappear within days. However, Good head control was noted. when tremors persist, and/or Asymmetrical tonic neck reflex was Baby Boy VR was delivered via exacerbate, more serious diagnoses negative. Landau, grasp, Galant, normal spontaneous vaginal delivery are often considered. These include support, and March reflexes were in the month of October, to a 20-year- seizures, neurologic abnormality, normal. Cranial nerves II to XII were old, dark-skinned African American hypoglycemia, hypocalcemia, normal. Motor evaluation revealed primigravida, after an uncomplicated hypomagnesemia, hyperthyroidism, mild increase in tone of the lower pregnancy in Washington, DC. drug7 withdrawal, and sepsis. Leone extremities recurring periodically. Apgar scores were 9 and 9 at 1 and et al followed 84 low-risk infants Spontaneous movements also were 5 minutes, respectively. Mother in Rome, Italy, with persistence of noted. Evaluation of reflexes revealed had fair prenatal care beginning tremors after the first week. Initial mild hyperreflexia of all extremities: at the fifth month of pregnancy. evaluation was done to exclude the ankle clonus 4 to 5 beats sustained She took prenatal vitamins during previously mentioned more serious ’ over 7 to 8 repetitions. Tremors were her pregnancy. After delivery, the diagnoses but did not include alkaline present at rest and in absence of infant s examination was remarkable phosphatase or vitamin D levels. No ’ excitation also involving the head and only for occasional shudder of the mention was made of feeding and were not exaggerated or precipitated infant s chin. Glucose screening was nutrition, making the role of vitamin by crying or movement. It was also normal. Vitamin D level was done D indeterminable in this study. They confirmed that tremulous muscular and the level was 17 ng/mL. The concluded that neonatal tremors activity continued regardless of infant was being formula fed. He was can have a variable evolution and swaddling. Other clinical features of started on vitamin D at 800 IU daily. resolution. All infants were7 healthy the tremors (frequency, distribution, He was referred to his pediatrician at the age of 24 months7 . Relative to amplitude, duration) were not for follow-up care. No further etiology, Leone et al proposed the measured numerically. Computed information was available for this possibility of transient immaturity, tomography of the brain was infant. defects at the level of supraspinal normal. EEG was recommended but organization, and circulating Discussion 7 the mother did not return at the catecholamines, all of which indicate appointed time. the need for additional study, but dietary considerations are obviously The classification of neonatal The initial workup revealed a absent. tremors is not as clearly defined tremulous infant with laboratory as the case for childhood and adult studies that were all within Our patients initially exhibited μ tremors. Additional terms, such as normal limits, except for alkaline tremors within the first 2 days of life. shudders, shivers, or jitteriness, are “ ” phosphatase of 430 m. This was Case 1 presented in the office at the often applied. These terms seem followed up with studies on mother age of 6 days with shivers that had to be used interchangeably with and infant for 25 hydroxy vitamin D. been noted in the nursery and again – tremors. Tremors may be defined as Results for infant: 6 ng/mL (normal at the age of 12 days with obvious an involuntary, rhythmic, periodic, 30 100). Studies were not available worsening. Most descriptions mechanical oscillation of a body for the mother at the same time. 1,3 4 of physiologic tremors do not part. ‍ Riehl and Mink described ’ indicate that worsening should be shuddering as brief episodes of The infant was recalled to start expected. In addition, the infant s shivering-like movements of the vitamin D at 800 IU daily. When the 5 mother was breastfeeding, she was head, shoulders, and arms. Basheer mother was told the results, she not supplementing with formula, defines jitteriness as tremor of admitted that she had not taken and she was not taking prenatal variable amplitude and frequency, any prenatal vitamins ever. She was vitamins, hence her breast milk was involving the jaw and extremities. successfully breastfeeding her infant a limited source of vitamin D. The and was not supplementing with workup was negative for the more ’ Neonatal tremors in otherwise formula. She was not giving vitamins healthy newborns have largely common causes of tremors but with to the infant. Mother s vitamin D was laboratory studies compatible with – been assumed to be a benign not available until day 65 of life: 22.5 neonatal characteristic that resolves vitamin D deficiency. Notable in case ng/mL (normal = 30 100). spontaneously after a few months of 1 are several risk factors exhibited Downloaded from www.aappublications.org/news by guest on September 27, 2021 PEDIATRICS Volume 140, number 2, August 2017 e3 ° by the mother: (1) dark skin, lived in latitude 38 N during their tremors in otherwise healthy (2) refusal to take prenatal vitamins, pregnancies. Although the infants newborns, has largely been regarded (3) distaste for milk and milk were born during the late summer/ as a physiologic condition without products, (4) breastfeeding without early fall, outdoor activities were the need for treatment. In this study, taking prenatal vitamins, and (5) 8,9 likely limited in the third trimester healthy Japanese neonates were location in a low-sunlight latitude. ‍ of pregnancy. Considering that both checked for craniotabes at 5 to 7 As the infant in case 1 was being mothers had dark skin, maternal days as part of routine discharge. breastfed without supplementation production of vitamin D could be Twenty-two percent were found13 to and the mother was not taking expected to be low. have craniotabes. Yorifuji et al did prenatal vitamins, the tremors were not address the presence or absence Currently, the American Academy worsening. Improvement was not of abnormal movements, specifically, of Pediatrics recommends noted until the infant was receiving jitteriness, tremors, shivers, or exclusive breastfeeding of infants. supplemental vitamin D. Had the shudders, in their study population. The Academy also recommends infant been fed formula that contains On recheck at 1 month, craniotabes “ ” that, while doing so, vitamin D vitamin D, it is possible that an persisted in approximately one- supplementation of these infants apparent spontaneous resolution third. Laboratory evaluation of should start soon after delivery. may have been ultimately noted after these infants showed statistically Recognizing the reality that mothers 4 to 6 weeks. significant elevations in serum may not be adherent in taking alkaline phosphatase with slightly Case 2 exhibited chin tremors and the prenatal vitamins or supplementing more than one-third having 25 OH only pertinent abnormality was low infants, practitioners who care for vitamin D <10 ng/mL. Early evidence vitamin D. In case 2, vitamin D levels children should equally advocate the of vitamin D deficiency was detected were drawn because the authors importance of supplementing vitamin in both the Japanese patients and had noted the tremors of case 1 and D for these infants. our patients within the first week of were curious as to what the vitamin The degree of hypovitaminosis life. More research will be needed D levels might reveal with this D appears related to variable to determine if one precedes the symptomatology. We were surprised symptomatology. Case 1 had a low other or perhaps both may present to get this finding. Attempts to locate vitamin D level and significant simultaneously as early signs of this dyad failed, as the mother did clinical manifestations. This level is in vitamin D deficiency. not keep the appointment with the the range in which an infant without community physician. Attempts to Conclusions supplementation and without locate her through the Medicaid sufficient sun exposure can develop managed care insurer also failed; clinical signs of rickets. The infant either she had changed insurers or Benign newborn tremors may not in case 2 had chin tremors with a moved out of the area. We included always be benign. The assumption higher vitamin D level of 17 ng/mL this case because of the surprised that neonatal tremors, in the and much milder symptoms, but still association with these subtle otherwise asymptomatic healthy- recognizable as abnormal. symptoms. Further studies will be appearing neonate, are benign, may needed to clarify this association Clinical manifestations of vitamin be incorrect. Neonatal tremors may more fully. Formula feeding would D deficiency are related to calcium be among the earliest clinical signs of address this deficiency over time. and bone metabolism. It has been vitamin D deficiency. Consequently, However, as we are encouraging recognized that low calcium can vitamin D deficiency should be mothers to make a healthier feeding cause general neuromuscular considered in the workup of tremors in the term neonate who has no other choice by breastfeeding their infants, excitability but the mechanism12 of this physicians need to be aware of paradox remains elusive. However, indicators of pathology. Additional vitamin D levels in the face of this early vitamin D deficiency may occur study is needed to solidify this feeding choice. Further, the maternal apparent relationship. ’ with a normal calcium. Perhaps, vitamin D deficiency is important in the early stages of vitamin D References to this mother s subsequent health, deficiency, neuronal excitability is as vitamin D deficiency has been elicited by changes at the level of 1. Armentrout DC, Caple J. The jittery 10,11 newborn. J Pediatr Health Care. associated with hypertension. ‍ intracellular calcium and cannot be 2001;15(3):147–149 ° ’ detected by current testing methods. It is well known that above the 13 2. Mulligan ML, Felton SK, Riek AE, Bernal- latitude of 37 N, an individual s skin Yorifuji et al suggest that the Mizrachi C. Implications of vitamin D makes lesser amounts of vitamin earliest sign of vitamin D deficiency D from the sun. Both mothers had is craniotabes. Craniotabes, like Downloaded from www.aappublications.org/news by guest on September 27, 2021 e4 Collins and Young deficiency in pregnancy and lactation. 7. leone D, Brogna C, Ricci D, et al. 11. Reeves IV, Bamji ZD, Rosario GB, Am J Obstet Gynecol. 2010;202(5):429. Development of clinical signs in low Lewis KM, Young MA, Washington e1–429.e9 risk term born infants with neonatal KN. Vitamin D deficiency in pregnant 3. Habib-ur -Rehman. Diagnosis and hyperexcitability. Early Hum Dev. women of ethnic minority: a potential management of tremor. Arch Intern 2013;89(2):65–68 contributor to preeclampsia. J Perinatol. 2014;34(10): Med. 2000;160(16):2438–2444 8. Dawodu A, Wagner CL. Mother-child vitamin D deficiency: an international 767–773 4. Riehl JA, Mink JW. Shuddering attacks. perspective. Arch Dis Child. 12. Han P, Trinidad BJ, Shi J. Hypocalcemia- J Pediatr Neurol. 2010;8:25–27 2007;92(9):737–740 induced seizure: demystifying the 5. Basheer SN. Neonatal jitters. J Pediatr 9. Williams AF. Vitamin D in pregnancy: an calcium paradox. ASN Neuro. 2015; Neurol. 2010;8:5–6 old problem still to be solved? Arch Dis 7(2) 6. Fernandez-Alvarez E. Polymorphic, Child. 2007;92(9):740–741 13. Yorifuji J, Yorifuji T, Tachibana K, et al. benign, nonepileptic, paroxysmal, 10. Forman JP, Scott JB, Ng K, et al. Effect Craniotabes in normal newborns: the infantile movements (Fejerman of vitamin D supplementation on blood earliest sign of subclinical vitamin D condition). J Pediatr Neurol. pressure in blacks. Hypertension. deficiency. J Clin Endocrinol Metab. 2015;13(04):231–236 2013;61(4):779–785 2008;93(5):1784–1788

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Updated Information & including high resolution figures, can be found at: Services http://pediatrics.aappublications.org/content/early/2017/07/24/peds.2 016-0719 References This article cites 13 articles, 2 of which you can access for free at: http://pediatrics.aappublications.org/content/early/2017/07/24/peds.2 016-0719#BIBL Subspecialty Collections This article, along with others on similar topics, appears in the following collection(s): Fetus/Newborn Infant http://www.aappublications.org/cgi/collection/fetus:newborn_infant_ sub Permissions & Licensing Information about reproducing this article in parts (figures, tables) or in its entirety can be found online at: http://www.aappublications.org/site/misc/Permissions.xhtml Reprints Information about ordering reprints can be found online: http://www.aappublications.org/site/misc/reprints.xhtml

Downloaded from www.aappublications.org/news by guest on September 27, 2021 Benign Neonatal Shudders, Shivers, Jitteriness, or Tremors: Early Signs of Vitamin D Deficiency Millicent Collins and Michal Young Pediatrics originally published online July 26, 2017;

The online version of this article, along with updated information and services, is located on the World Wide Web at: http://pediatrics.aappublications.org/content/early/2017/07/24/peds.2016-0719

Pediatrics is the official journal of the American Academy of Pediatrics. A monthly publication, it has been published continuously since 1948. Pediatrics is owned, published, and trademarked by the American Academy of Pediatrics, 345 Park Avenue, Itasca, Illinois, 60143. Copyright © 2017 by the American Academy of Pediatrics. All rights reserved. Print ISSN: 1073-0397.

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