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Acute Neonatal Effects of Cocaine Exposure During Pregnancy

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Acute Neonatal Effects of Cocaine Exposure During Pregnancy ARTICLE Acute Neonatal Effects of Cocaine Exposure During Pregnancy Charles R. Bauer, MD; John C. Langer, MSc; Seetha Shankaran, MD; Henrietta S. Bada, MD; Barry Lester, PhD; Linda L. Wright, MD; Heidi Krause-Steinrauf, MS; Vincent L. Smeriglio, PhD; Loretta P. Finnegan, MD; Penelope L. Maza, PhD; Joel Verter, PhD Objective: To identify associations between cocaine ex- (2.44; 1.06-5.66), irritability (1.81; 1.18-2.80), exces- posure during pregnancy and medical conditions in new- sive suck (3.58; 1.63-7.88), hyperalertness (7.78; 1.72- born infants from birth through hospital discharge. 35.06), and autonomic instability (2.64; 1.17-5.95). No differences were detected in organ systems by ultra- Design: Multisite, prospective, randomized study. sound examination. Exposed infants had more infec- tions (3.09; 1.76-5.45), including hepatitis (13.46; 7.46- Setting: Brown University, University of Miami, Uni- 24.29), syphilis (8.84; 3.74-20.88), and human versity of Tennessee (Memphis), and Wayne State Uni- immunodeficiency virus exposure (12.37; 2.20-69.51); versity. were less often breastfed (0.26; 0.15-0.44); had more child protective services referrals (48.92; 28.77-83.20); and were Subjects: A total of 717 cocaine-exposed infants and 7442 more often not living with their biological mother (18.70; nonexposed infants. 10.53-33.20). Main Outcome Measures: Results of physical exami- Conclusions: Central and autonomic nervous system nation and conditions observed during hospitalization. symptoms were more frequent in the exposed cohort and persisted in an adjusted analysis. They were usually tran- Results: Cocaine-exposed infants were about 1.2 weeks sient and may be a true cocaine effect. Abnormal ana- younger, weighed 536 g less, measured 2.6 cm shorter, tomic outcomes previously reported were not con- and had head circumference 1.5 cm smaller than non- firmed. Increased infections, particularly sexually exposed infants (all PϽ.001). Results did not confirm pre- transmitted diseases, pose a serious public health chal- viously reported abnormalities. Central and autonomic lenge. Exposure increased involvement of child protec- nervous system symptoms were more frequent in the ex- tive services and out-of-home placement. posed group: jittery/tremors (adjusted odds ratio, 2.17; 99% confidence interval, 1.44-3.29), high-pitched cry Arch Pediatr Adolesc Med. 2005;159:824-834 RUG USE BY PREGNANT lar hemorrhage,14,15 various neurologic im- women remains a perva- pairments,16,17 genitourinary tract and re- sive problem in American nal anomalies,18-20 gastrointestinal tract society. In 2002, 3% of all defects,21,22 limb deformities,23 and respira- pregnant women aged 15 tory insufficiency including sudden infant to 44 years exposed their fetus to 1 or more death syndrome.24-27 A differential effect of D1 illicit drugs. Attempts to isolate effects drug exposure on preterm vs term infants attributable to a specific drug exposure, such has been suggested.28 More recent studies as cocaine, have often been confounded by and systematic reviews have emphasized po- the use of multiple drugs and limited ac- tential effects on long-term neurodevelop- cess to large varied populations. Drug abus- ment, behavior, and learning29-33 while both ers are mobile, difficult to track over time, the acute and chronic impacts of cocaine on and often noncompliant.2,3 From the mid- growth remain.32,34,35 How race, sex, drug 1980s into the early 1990s, a number of re- dose, sociodemographics, and other impor- ports raised concerns about the potential tant modifying variables impact ultimate out- teratogenic impact of fetal cocaine expo- come has recently been considered.36,37 Well- sure during pregnancy. These observa- designed, prospective studies that fail to tions included congenital anomalies,4,5 identify significant drug effects, ie, nega- growth retardation,6-8 microcephaly,9,10 cen- tive studies, may be published less often and Author Affiliations are listed at tral nervous system infarction,11 seizures,12 therefore not referenced.38 This may result the end of this article. cortical atrophy and cysts,13 intraventricu- in a biased overreporting of less signifi- (REPRINTED) ARCH PEDIATR ADOLESC MED/ VOL 159, SEP 2005 WWW.ARCHPEDIATRICS.COM 824 ©2005 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 09/28/2021 cant observations, as occurred in the early years of the crack and cocaine epidemic. 19 079 (100%) The Maternal Lifestyle Study (see page 833 for a list of Mother/Infant Dyads Screened institutions and investigators) was conceived and de- 2091 (11.0%) Noneligible signed as a large multisite, prospective, randomized study, 195 (9.3%) Unlikely to Survive whose objective was to confirm or negate the null hypoth- 67 (3.2%) Multiple Gestation 79 (3.8%) Outborn esis that fetal cocaine exposure during pregnancy has no 1690 (80.8%) Maternal Age <18 y impact on acute maternal and infant medical outcomes, 18 (0.9%) Mother Institutionalized or on long-term neurodevelopmental infant outcomes. 85 (4.1%) Mother With Psychosis Access to a large, multisite population was possible through the National Institute of Child Health and Hu- 16 988 (89.0%) Mothers Eligible for Enrollment man Development Neonatal Research Network, which, at the time the study was initiated, consisted of 12 major uni- 5177 (30.5%) Nonenrolled versity research centers. The feasibility of successfully study- 8 (0.2%) Reason Unknown ing multicultural, multiethnic, sociodemographically var- 2664 (51.5%) Mother Refused Consent 1361 (26.3%) Mother Unavailable ied populations with widespread use of drugs had been 1124 (21.7%) Language Problem previously documented at several of the network partici- 20 (0.4%) Sibling in a Research pating centers.39-41 Four of the 12 network sites were se- Study lected by competitive peer review to participate in the Ma- 11 811 (69.5%) ternal Lifestyle Study. A wide range of acute medical Mothers Consenting and Enrolled outcomes in cocaine-exposed and nonexposed infants, in- cluding sociodemographic circumstances and polydrug use, 3184 (27.0%) Exposure Indeterminate were assessed in infants recruited at these sites. Acute ma- 3014 (94.7%) Meconium Not Available or Amount Inadequate ternal pregnancy outcomes in these cohorts have already 170 (5.3%) No GC/MS Confirmation 42 been reported. This report presents identified associa- or Consent Withdrawn tions between cocaine exposure during pregnancy and medical conditions in the newborn infant from birth 8627 (73.0%) through hospital discharge or death. Mothers Consenting With Known Exposure 1072 (12.4%) 113 (1.3%) 7442 (86.3%) METHODS Cocaine Opiates Nonexposed (Only and Uncertain Recruitment and screening occurred during a 2-year period at Cocaine) 4 centers: Brown University, Providence, RI; the University of Miami, Miami, Fla; the University of Tennessee, Memphis; and 717 (66.9%) 92 (8.6%) 263 (24.5%) Wayne State University, Detroit, Mich. Informed maternal con- Cocaine Cocaine and Cocaine, sent and institutional review board approval were required for Only Opiates Uncertain participation. Reasons for noneligibility and nonenrollment are Opiates listed in Figure 1. Mothers who consented were more likely to be black (50.5% vs 46.5%), to be unmarried (62.3% vs 56.5%), Figure 1. Screening, enrollment, exclusions, eligibility, consent, and and to have a history of drug use (13.0% vs 9.3%). Mothers who exposure identification. GC/MS indicates gas chromatography–mass identified themselves as white consented equally often (44.4% spectroscopy. vs 44.9%) while those who responded that they were of “other” race consented at lower rates (5.1% vs 8.6%). Differences in preterm delivery rate, abruptio placentae, prenatal care, and use Cocaine exposure was defined by maternal admission of co- of Medicaid between those who consented and those who did caine use at any time during this pregnancy or a positive enzyme- not were small. All low-birth-weight infants (Ͻ1500 g) were multiplied immunoassay technique (EMIT) screen for cocaine screened. Maternal and infant charts were reviewed to iden- metabolites in the infant’s meconium, confirmed by gas chro- tify obvious protocol exclusions. Informed consent was usu- matography–mass spectroscopy, coupled with a negative EMIT ally obtained before or within 24 hours of delivery. screen for opiates. All analyses were performed by a central labo- Initial screening included the mother’s labor and delivery ratory (El Sohly Laboratories Inc, Oxford, Miss)43 after in- record, the newborn admission record, and a meconium sample. formed consent was obtained. A history of cocaine use re- A detailed drug use questionnaire that addressed the mother’s corded in the medical record was not sufficient to qualify as use of nicotine, alcohol, marijuana, cocaine, opiates, and other exposed. Mothers who denied use, but in whom the infant’s me- illicit drugs was given by research staff trained and certified in conium EMIT screen was positive and gas chromatography– the reliable administration of all the study interviews. A De- mass spectroscopy analysis was not available, were excluded.44 partment of Health and Human Services Certificate of Confi- A nonexposure designation required both a maternal denial of dentiality allowed for strict confidentiality regarding all drug use and a negative result of meconium screening. There were use information, including the 2 states (Florida and Rhode Is- 3183 infants of consenting mothers whose exposure could not land) that had mandatory reporting statutes. The certificate did be determined primarily because of lack of gas chromatography– not, however, circumvent required reporting of child abuse, mass spectroscopy confirmation. This included 2760 in whom sexual abuse, or neglect. meconium was unavailable, 254 in whom the quantity of me- Although recruitment addressed exposure to cocaine and/or conium collected was insufficient for any analysis, and 169 with opiates, all analyses presented herein are limited to the cocaine- a positive EMIT screen but who had insufficient amounts of me- only and the non–cocaine-exposed cohorts.
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