The maternal lifestyle study: effects of substance exposure during pregnancy on neurodevelopmental outcome in 1-month-old infants.

OBJECTIVE This was a prospective longitudinal multisite study of the effects of prenatal cocaine and/or opiate exposure on neurodevelopmental outcome in term and preterm infants at 1 month of age. METHODS The sample included 658 exposed and 730 comparison infants matched on race, gender, and gestational age (11.7% born <33 weeks' gestational age). Mothers were recruited at 4 urban university-based centers and were mostly black and on public assistance. Exposure was determined by meconium assay and self-report with alcohol, marijuana, and tobacco present in both groups. At 1 month corrected age, infants were tested by masked examiners with the NICU Network Neurobehavioral Scale and acoustical cry analysis. Exposed and comparison groups were compared adjusting for covariates (alcohol, marijuana, tobacco, birth weight, social class, and site). Separate analyses were conducted for level of cocaine exposure. RESULTS On the NICU Network Neurobehavioral Scale, cocaine exposure was related to lower arousal, poorer quality of movement and self-regulation, higher excitability, more hypertonia, and more nonoptimal reflexes with most effects maintained after adjustment for covariates. Some effects were associated with heavy cocaine exposure, and effects were also found for opiates, alcohol, marijuana, and birth weight. Acoustic cry characteristics that reflect reactivity, respiratory, and neural control of the cry sound were also compromised by prenatal drug exposure, including cocaine, opiates, alcohol, and marijuana and by birth weight. Fewer cry effects remained after adjustment for covariates. CONCLUSIONS Cocaine effects are subtle and can be detected when studied in the context of polydrug use and level of cocaine exposure. Effects of other drugs even at low thresholds can also be observed in the context of a polydrug model. The ability to detect these drug effects requires a large sample and neurobehavioral tests that are differentially sensitive to drug effects. Long-term follow-up is necessary to determine whether these differences develop into clinically significant deficits.

[1]  B. Zuckerman,et al.  Growth, development, and behavior in early childhood following prenatal cocaine exposure: a systematic review. , 2001, JAMA.

[2]  A. Salvator,et al.  Neurobehavioral outcomes of cocaine-exposed infants. , 2000, Neurotoxicology and teratology.

[3]  J. Jacobson,et al.  Validity of maternal report of prenatal alcohol, cocaine, and smoking in relation to neurobehavioral outcome. , 2002, Pediatrics.

[4]  P. Fernhoff,et al.  Neonatal neurobehavioral characteristics as correlates of maternal alcohol use during gestation. , 1985, Alcoholism, clinical and experimental research.

[5]  N. Day,et al.  The effect of prenatal alcohol, marijuana, and tobacco exposure on neonatal behavior , 1989 .

[6]  A. Salvator,et al.  Cognitive and Motor Outcomes of Cocaine-Exposed Infants , 2002 .

[7]  M. Bornstein,et al.  The problem of prenatal cocaine exposure. A rush to judgment. , 1992, JAMA.

[8]  M. Strauss,et al.  Behavioural concomitants of prenatal addiction to narcotics. , 1976, The Journal of pediatrics.

[9]  H. Barr,et al.  Maternal alcohol use and neonatal habituation assessed with the Brazelton scale. , 1983, Child development.

[10]  K. Standley,et al.  Clinical uses of the Brazelton Neonatal Scale. , 1974, Pediatrics.

[11]  L. Allen,et al.  Pregnancy outcome in North American women. II. Effects of diet, cigarette smoking, stress, and weight gain on placentas, and on neonatal physical and behavioral characteristics. , 1982, The American journal of clinical nutrition.

[12]  A. Falek,et al.  Persistence over the first month of neurobehavioral differences in infants exposed to alcohol prenatally , 1987 .

[13]  L. Wright,et al.  The Maternal Lifestyle Study: drug exposure during pregnancy and short-term maternal outcomes. , 2002, American journal of obstetrics and gynecology.

[14]  M. Black,et al.  Prenatal drug exposure: neurodevelopmental outcome and parenting environment. , 1993, Journal of pediatric psychology.

[15]  H. Breiter,et al.  Functional Magnetic Resonance Imaging of Brain Reward Circuitry in the Human , 1999, Annals of the New York Academy of Sciences.

[16]  P. Fried,et al.  Neonatal behavioural correlates of prenatal exposure to marihuana, cigarettes and alcohol in a low risk population. , 1987, Neurotoxicology and teratology.

[17]  D. Leon.  Failed or misleading adjustment for confounding , 1993, The Lancet.

[18]  L. Lagasse,et al.  Studies of cocaine-exposed human infants. , 1996, NIDA research monograph.

[19]  I. Chasnoff,et al.  Polydrug- and methadone-addicted newborns: a continuum of impairment? , 1982, Pediatrics.

[20]  Jing Liu,et al.  Smoking during pregnancy and newborn neurobehavior. , 2003, Pediatrics.

[21]  C. Bauer,et al.  Perinatal effects of prenatal drug exposure. Neonatal aspects. , 1999, Clinics in perinatology.

[22]  B. Lester,et al.  Effects of in utero substance exposure on infant neurobehavior. , 1996, Pediatrics.

[23]  L. Lagasse,et al.  Neurobehavioral effects of treatment for opiate withdrawal , 2004, Archives of Disease in Childhood - Fetal and Neonatal Edition.

[24]  S. Curtin,et al.  Births: preliminary data for 1999. , 2000, National vital statistics reports : from the Centers for Disease Control and Prevention, National Center for Health Statistics, National Vital Statistics System.

[25]  K I Bolla,et al.  The neuropsychiatry of chronic cocaine abuse. , 1998, The Journal of neuropsychiatry and clinical neurosciences.

[26]  N. Day,et al.  Studies of Prenatal Cocaine Exposure: Assessing the Influence of Extraneous Variables , 1999 .

[27]  M. Behnke,et al.  Birth outcome from a prospective, matched study of prenatal crack/cocaine use: I. Interactive and dose effects on health and growth. , 1998, Pediatrics.

[28]  R. J. Valentine,et al.  Nonocclusive mesenteric ischemia in renal patients: recognition and prevention of intestinal gangrene. , 1990, American journal of kidney diseases : the official journal of the National Kidney Foundation.

[29]  M Peucker,et al.  Neurobehavioral syndromes in cocaine-exposed newborn infants. , 1991, Child development.

[30]  Audra Lewis,et al.  Maternal Cocaine Use and Infant Behavior , 2002 .

[31]  M. Behnke,et al.  Birth outcome from a prospective, matched study of prenatal crack/cocaine use: II. Interactive and dose effects on neurobehavioral assessment. , 1998, Pediatrics.

[32]  L. Wright,et al.  Immunoassay and GC-MS procedures for the analysis of drugs of abuse in meconium. , 1999, Journal of analytical toxicology.

[33]  L. Wright,et al.  The Maternal Lifestyle Study: drug use by meconium toxicology and maternal self-report. , 2001, Pediatrics.

[34]  T. Field,et al.  Cocaine-exposed preterm neonates show behavioral and hormonal differences. , 1996, Pediatrics.

[35]  C. Storrs,et al.  Alcohol consumption in pregnancy. How much is safe? , 1982, Archives of disease in childhood.

[36]  B. Lester,et al.  The effects of prenatal cocaine exposure and child outcome , 1994 .

[37]  B. Lester.  The Maternal Lifestyles Study a , 1998, Annals of the New York Academy of Sciences.

[38]  B. Lester,et al.  Effects of marijuana use during pregnancy on newborn cry. , 1989, Child development.

[39]  W N Tavolga,et al.  Variations in birth cries of newborn infants from narcotic-addicted and normal mothers. , 1971, American journal of obstetrics and gynecology.

[40]  B. Lester,et al.  The effects of maternal alcohol consumption and cigarette smoking during pregnancy on acoustic cry analysis. , 1996, Child development.

[41]  T. Slotkin.  Fetal nicotine or cocaine exposure: which one is worse? , 1998, The Journal of pharmacology and experimental therapeutics.

[42]  B. Lester,et al.  Analysis of cry features in newborns with differential fetal growth. , 1981, Child development.

[43]  T. Field,et al.  Perinatal cocaine effects on neonatal stress behavior and performance on the Brazelton Scale. , 1991, Pediatrics.

[44]  L. Lagasse,et al.  Effects of in Utero Exposure to Cocaine and/or Opiates on Infants' Reaching Behavior , 1998, Annals of the New York Academy of Sciences.

[45]  A. Sandler,et al.  Developing language skills of cocaine-exposed infants. , 2001 .

[46]  H L Golub,et al.  The infant cry: what can it tell us? , 1996, Current problems in pediatrics.

[47]  H. Wilcox,et al.  Prenatal drug exposure and child outcome. Past, present, future. , 1999, Clinics in perinatology.

[48]  G. Richardson,et al.  The effects of prenatal cocaine use on neonatal neurobehavioral status. , 1996, Neurotoxicology and teratology.

[49]  B. Zuckerman,et al.  Growth, Development, and Behavior in Early Childhood Following Prenatal Cocaine Exposure , 2001 .

[50]  B. Zuckerman,et al.  "Crack kids": not broken. , 1992, Pediatrics.

[51]  J. Jacobson,et al.  Methodological issues in human behavioral teratology , 1990 .

[52]  K J Rothman,et al.  No Adjustments Are Needed for Multiple Comparisons , 1990, Epidemiology.

[53]  D. Saxton,et al.  The behaviour of infants whose mothers smoke in pregnancy. , 1978, Early human development.

[54]  P. Fried.  Marihuana use by pregnant women and effects on offspring: an update. , 1982, Neurobehavioral toxicology and teratology.

[55]  T. Brazelton,et al.  Neonatal Behavioral Assessment Scale , 1973 .

[56]  B. Lester.  The Maternal Lifestyles Study. , 1998, Annals of the New York Academy of Sciences.

[57]  H L Golub,et al.  Effects of in utero cocaine exposure on newborn acoustical cry characteristics. , 1992, Pediatrics.

[58]  Cora Lee Wetherington,et al.  Behavioral Studies of Drug-Exposed Offspring: Methodological Issues in Human and Animal Research : (NIDA Research Monograph ; 164) , 1996 .

[59]  L. Lagasse,et al.  Interpreting research on prenatal substance exposure in the context of multiple confounding factors. , 1999, Clinics in perinatology.

[60]  John A. Harvey,et al.  COCAINE: EFFECTS ON THE DEVELOPING BRAIN , 1998 .

[61]  B. Lester.  Prenatal drug exposure and child outcome , 1999 .

[62]  B. Lester,et al.  Buprenorphine treatment of pregnant opioid--dependent women: maternal and neonatal outcomes. , 2001, Drug and alcohol dependence.

[63]  R. Jeremy,et al.  Behavior of neonates exposed in utero to methadone as assessed on the Brazelton scale , 1985 .

[64]  R J Sokol,et al.  New evidence for neurobehavioral effects of in utero cocaine exposure. , 1996, The Journal of pediatrics.

[65]  S. Hans,et al.  The relations among cry characteristics, demographic variables, and developmental test scores in infants prenatally exposed to methadone , 1990 .

[66]  B. Zuckerman,et al.  Late dose-response effects of prenatal cocaine exposure on newborn neurobehavioral performance. , 1996, Pediatrics.

[67]  A. Falek,et al.  Effects of cocaine and alcohol use in pregnancy on neonatal growth and neurobehavioral status. , 1992, Neurotoxicology and teratology.

[68]  D. A. Kenny,et al.  The moderator-mediator variable distinction in social psychological research: conceptual, strategic, and statistical considerations. , 1986, Journal of personality and social psychology.

[69]  L. Lagasse,et al.  Cocaine Exposure and Children: The Meaning of Subtle Effects , 1998, Science.

[70]  J. Jacobson,et al.  Effects of prenatal exposure to alcohol, smoking, and illicit drugs on postpartum somatic growth. , 1994, Alcoholism, clinical and experimental research.

[71]  R. Little,et al.  Behavioral correlates of prenatal alcohol exposure: a four-year follow-up study. , 1981, Neurobehavioral toxicology and teratology.