Perinatal cocaine and methamphetamine exposure: maternal and neonatal correlates

Maternal and neonatal growth, behavior, and physiologic organization were evaluated in 104 mother-infant pairs with positive results of urine toxicology screens. ANOVA comparison of cocaine, methamphetamine, and cocaine plus methamphetamine groups revealed no significant differences in perinatal variables. The Finnegan withdrawal scoring scheme demonstrated that all three groups of infants had altered neonatal behavioral patterns, characterized by abnormal sleep patterns, poor feeding, tremors, and hypertonia. Infants exposed to cocaine or methamphetamine or both were combined and compared with both narcotic-exposed and drug-free mother-infant pairs matched for known maternal risk factors. All drug-exposed groups had significantly higher rates of prematurity and intrauterine growth retardation and smaller head circumferences than did the drug-free comparison group. A significantly higher rate of placental hemorrhage occurred in the cocaine plus methamphetamine group. Stepwise multiple regression analysis assessed the independent contribution of maternal factors; cocaine or methamphetamine was adversely, negatively associated with gestational age, birth weight, length, and occipitofrontal circumference. The increased rate of prematurity, intrauterine growth retardation, and perinatal complications associated with perinatal exposure to cocaine or methamphetamine was greater than that predicted by coexisting risk factors and was consistent with the pharmacologic properties of these drugs.     

Cocaine and development: mechanisms of fetal toxicity and neonatal consequences of prenatal cocaine exposure.

As cocaine use during pregnancy has become increasingly recognized, there also has been increased concern about the toxic and teratogenic properties of cocaine on the fetus. A significant literature exists describing the adverse fetal and neonatal outcomes associated with in utero cocaine exposure. However, specific causality by cocaine on outcome in the human is difficult to ascertain because of multiple confounding variables associated with substance abuse including social factors and polydrug use as well as difficulty in confirming timing, dose and frequency of cocaine exposure. Most literature suggests that prenatal cocaine exposure is associated with developmental risk to the fetus. What is currently unknown is the extent of risk, the additive and/or synergistic factors contributing to cocaine's toxicity and the reversibility of the injury. In this paper we review the pharmacologic properties of cocaine as related to a model of mechanisms for developmental injury secondary to cocaine exposure and the published literature on the adverse fetal and neonatal outcomes associated with cocaine use during pregnancy. Specific attention has been focused on the structural, neurobehavioral and respiratory control teratogenesis.     

Neurobehavioral sequelae of fetal cocaine exposure

The number of infants born to cocaine-using mothers has continued to rise during the past 5 years. Maternal cocaine use during pregnancy is associated with medical and life-style characteristics detrimental to fetal and infant development. Cocaine exposure has been independently linked to growth retardation and impaired fetal oxygenation even when polydrug use and other confounding factors are considered. Neurologic and neurobehavioral abnormalities noted in the immediate neonatal period have also been associated with fetal cocaine exposure. The direct and indirect toxic effects of cocaine, per se, have not yet been independently linked to specific behavioral outcomes because of small sample sizes, confounding factors, and lack of long-term follow-up. The impoverished environments and increased risk for out-of-family placement of cocaine-exposed infants are known independent correlates of negative developmental outcomes. Poor maternal nutrition, lack of prenatal care, and other health and life-style factors related to maternal cocaine use during pregnancy also appear to be factors mediating the developmental problems of cocaine-exposed infants. The cocaine-using mother often uses other drugs, particularly alcohol, independently known to be linked to growth and behavioral impairments similar to those proposed for cocaine-exposed infants. Accounting for these multiple confounding variables in studies of the specific effects of cocaine on neurobehavioral outcome may be scientifically appropriate, but in clinical practice these factors cannot be "isolated," and their statistical consideration in studies does not diminish clinical risk. Finally, currently available studies of behavioral outcome have restricted their samples to term infants. It is possible that preterm infants may be less affected by prenatal cocaine exposure because of decreased exposure. However, because epidemiologic studies suggest that prematurity is a sequelae of maternal cocaine use, restriction of samples to term or appropriately sized infants may underestimate the spectrum of morbidity associated with cocaine exposure. We believe that maternal cocaine use during pregnancy is a "marker" variable for early impairments in infant growth and behavioral functioning that have long-term implications for later developmental outcome, especially for learning disabilities and behavioral disorders. Critically assessing the independent contribution of cocaine to negative developmental outcome and determining whether early neonatal abnormalities are permanent or modifiable may allow clinical intervention and improved social policy. Assessing the independent effects of cocaine on child developmental outcome will require carefully designed, long-term, longitudinal, population-based studies with samples large enough to allow multivariate data analyses and statistical control of confounding medical and social variables.     

The effects of prenatal alcohol and marijuana exposure: disturbances in neonatal sleep cycling and arousal

Neonatal EEG and sleep findings are presented from a longitudinal study of the effects of maternal alcohol and marijuana use during pregnancy. Infant outcome has been examined relative to the trimester(s) of pregnancy during which use occurred. Disturbances in sleep cycling, motility, and arousals were noted that were both substance and trimester specific. Alcohol consumed during the first trimester of pregnancy was associated with disruptions in sleep and arousal, whereas marijuana use affected sleep and motility regardless of the trimester in which it was used. Although these findings are preliminary and based on a small sample of women exhibiting only moderate substance use during pregnancy, they do suggest that specific neurophysiological systems may be differentially affected by prenatal alcohol or marijuana exposure even in the absence of morphological abnormalities.     

Prenatal cocaine exposure and fetal vascular disruption

The question of the potential teratogenicity of cocaine has been raised by the increasing frequency of its abuse in the United States. In previous studies, an increased incidence has been documented of spontaneous abortion, placental abruption, prematurity, intrauterine growth retardation, and neurologic deficits in the infants of women who abused cocaine. More recently, it has been suggested in studies that fetal vascular disruption accompanying maternal cocaine abuse may lead to cavitary central nervous system lesions and genitourinary anomalies. In this article, 10 children born of women who abused cocaine are described, 9 of whom have congenital limb reduction defects and/or intestinal atresia or infarction. The spectrum of anomalies associated with embryonic and fetal vascular disruption accompanying maternal cocaine abuse is thus enlarged. The specific risk for congenital anomalies accompanying maternal cocaine abuse during an individual pregnancy is unknown. However, data from these patients and the available literature suggest that counseling pregnant women concerning cocaine use should incorporate warnings about the possibility of associated embryonic or fetal vascular disruption.     

Measurement of gestational cocaine exposure: sensitivity of infants' hair, meconium, and urine.

We studied the sensitivity of testing the newborn infant's hair, meconium, and urine in detecting gestational cocaine exposure. The infants were born to 59 women who were interviewed to determine their use of cocaine during pregnancy and whose hair was analyzed for the presence of cocaine. Regression analysis was used to evaluate the relationship between cocaine in newborn hair and in maternal hair. Radioimmunoassay of infants' hair and gas chromatography-mass spectrometry of meconium were more sensitive than immunoassay of urine (p less than 0.02), which failed to identify 60% of cocaine-exposed infants. The quantity of benzoylecgonine in the newborn infant's hair correlated best with the proximal-segment maternal hair, representing the last 12 weeks of antepartum hair growth (R = less than R less than 0.83). Approximately half (52%) of the variation in infants' hair was explained by variation in the proximal maternal hair segment. Correlation (R = 0.77) and explained variation (59%) improved slightly when premature infants (n = 9) were excluded. We conclude that analysis of the newborn infant's hair by radioimmunoassay or of meconium by gas chromatography-mass spectrometry is more sensitive than analysis by immunoassay of urine, and can detect fetal cocaine exposure that occurred during the last two trimesters of pregnancy.     

Dose-response effect of fetal cocaine exposure on newborn neurologic function

BACKGROUND: Studies of fetal cocaine exposure and newborn neurologic function have obtained conflicting results. Although some studies identify abnormalities, others find no differences between cocaine-exposed and cocaine-unexposed infants. To determine the effects of prenatal cocaine exposure on intrauterine growth and neurologic function in infants, we prospectively evaluated 253 infants shortly after birth. METHODS: Women who delivered a live singleton >36 weeks by dates were eligible for enrollment. Maternal exclusionary criteria were known parenteral drug use, alcoholism, and acquired immunodeficiency syndrome; infant exclusionary criteria were Apgar scores 相似文献   

Cocaine use during pregnancy: prevalence and correlates

Cocaine use during pregnancy was assessed by interviews and urine assays obtained prenatally and immediately postpartum from 679 urban women enrolled in prenatal care. Of these, 17% were found to have used cocaine at least once during pregnancy. Eight percent had urine assays positive for cocaine metabolites using the enzyme-mediated immunoassay technique with a cut-off of 300 ng/mL of benzoylecgonine. Of the cocaine users, 24% denied use at the time of the interview and were identified solely by urine assay. Cocaine users were significantly (P less than .01) less likely than nonusers to be married, Hispanic, or black born outside of the United States and were less well nourished. Users reported significantly (P less than .01) more sexually transmitted diseases, prior low birth weight infants, spontaneous and elective abortions, and greater use of alcohol, cigarettes, marijuana, opiates, and other illicit drugs during pregnancy. Because cocaine use is correlated with many potential risk factors, large sample sizes and multivariate statistical techniques are needed to determine whether cocaine use during pregnancy poses an independent risk for adverse neonatal outcomes.     

Maternal cocaine use during pregnancy: effect on the newborn infant

The newborn infants of 56 mothers who used cocaine were prospectively studied in to determine the effects of cocaine. There were no differences with respect to maternal preeclampsia or cesarean section rate. Meconium-stained amniotic fluid was increased (10 of 56 cases [17.8%]) compared with the control group (3 of 56 cases [5.3%]) (X2 = 4.2, P less than .05). Fetal distress recorded with fetal monitoring and Apgar scores at 1 and 5 minutes were similar. The weight, length, and head circumference growth curves of the infants born to cocaine-using mothers were shifted below the 25th percentile. Microcephaly was present in 12 of 56 (21.4%) infants whose mothers used cocaine during pregnancy (X2 = 5.96, P less than .01), and 15 of 56 (26.7%) had intrauterine growth retardation (X2 = 9.53, P less than .01) compared with the control infants (2 of 5 [3.5%] and 3 of 56 [5.3%], respectively). There was no increase in teratogenicity. Neither narcotic withdrawal symptoms nor illness could distinguish the infants born of cocaine-using mothers from the control infants. In conclusion, cocaine use during pregnancy results in newborn infants with growth retardation and microcephaly.     

Fetal origin of childhood disease: intrauterine growth restriction in term infants and risk for hypertension at 6 years of age

OBJECTIVE: To examine the association between intrauterine growth restriction (IUGR) status at birth among full-term infants, exposure to substance use during pregnancy, and risk of hypertension at 6 years of age. DESIGN: Prospective evaluation of high-risk children. SETTING: Four centers of the National Institute of Child Health and Human Development Neonatal Research Network. PARTICIPANTS: One thousand three hundred eighty-eight infants (600 cocaine exposed, 781 nonexposed, and 7 indeterminate, matched by gestational age, race, and sex), were enrolled at these sites. Nine hundred fifty children (415 exposed, 535 nonexposed) were followed up for 6 years.Intervention Right arm blood pressure was measured using the Dinamap portable adult/pediatric monitor with appropriate cuff size.Main Outcome Measure Blood pressure levels. Hypertension was defined as either systolic or diastolic blood pressure higher than the 95th percentile for sex, age, and height. RESULTS: Eight hundred ninety-one children had blood pressure data at 6 years of age: 516 were born at full term; 144 (28%) of the 516 children had a diagnosis of IUGR at birth. At 6 years of age, 93 (19%) of 516 children had hypertension. Of 144 children with IUGR, 35 (24%) had hypertension as compared with 58 (16%) of 372 children without IUGR (P<.05). Twenty percent of cocaine-exposed children had hypertension as compared with 16% of nonexposed children (P = .20). Intrauterine growth restriction status at birth was significantly associated with hypertension (relative risk, 1.8 [95% confidence interval, 1.2-2.7]) when multivariable Poisson regression analysis was performed adjusting for site; maternal race, education, and tobacco, marijuana, alcohol, and cocaine use during pregnancy; and child's current body mass index (calculated as weight in kilograms divided by height in meters squared). CONCLUSION: In term infants, IUGR is linked to risk of hypertension in early childhood, which may be a marker for adult cardiovascular disease.     

Prenatal exposure to alcohol: effect on infant growth and morphologic characteristics

In this prospective study of alcohol and other substance use during pregnancy, a cohort of 650 women was interviewed at each trimester of pregnancy. Data are presented concerning the status of 595 live singleton births. A relationship was demonstrated between prenatal maternal alcohol use and growth and morphologic abnormalities in the offspring. Low birth weight, decreased head circumference and length, and an increased rate of fetal alcohol effects were all found to be significantly correlated with exposure to alcohol during the first 2 months of the first trimester.     

Effect of maternal heroin addiction on 67 liveborn neonates. Withdrawal symptoms, small body size, and small head circumference were frequent findings.

It is apparent that maternal addiction affects the fetus and causes serious problems in the neonatal period. Whether intrauterine exposure to heroin has far-reaching, long-term residual effects remains to be determined. We believe that prospective studies are indicated in order to evaluate the incidence of small head circumference, the pattern of intrauterine growth retardation, and the correlation of these findings with later neurologic and behavioral development.     

Cocaine/polydrug use in pregnancy: two-year follow-up.

The impact of cocaine on pregnancy and neonatal outcome has been well documented over the past few years, but little information regarding long-term outcome of the passively exposed infants has been available. In the present study, the 2-year growth and developmental outcome for three groups of infants is presented: group 1 infants exposed to cocaine and usually marijuana and/or alcohol (n = 106), group 2 infants exposed to marijuana and/or alcohol but no cocaine (n = 45), and group 3 infants exposed to no drugs during pregnancy. All three groups were similar in racial and demographic characteristics and received prenatal care through a comprehensive drug treatment and follow-up program for addicted pregnant women and their infants. The group 1 infants demonstrated significant decreases in birth weight, length, and head circumference, but by a year of age had caught up in mean length and weight compared with control infants. The group 2 infants exhibited only decreased head circumference at birth. Head size in the two drug-exposed groups remained significantly smaller than in control infants through 2 years of age. On the Bayley Scales of Infant Development, mean developmental scores of the two groups of drug-exposed infants did not vary significantly from the control group, although an increased proportion of group 1 and 2 infants scored greater than two standard deviations below the standardized mean score on both the Mental Developmental Index and the Psychomotor Developmental Index compared with the control infants. Cocaine exposure was found to be the single best predictor of head circumference.(ABSTRACT TRUNCATED AT 250 WORDS)     

Analysis of facial shape in children gestationally exposed to marijuana, alcohol, and/or cocaine.

The association between fetal marijuana and/or alcohol exposure and facial features resembling fetal alcohol syndrome was investigated in a sample of 80 children. Standardized lateral and frontal facial photographs were taken of 40 children, 5 to 7 years of age, whose mothers reported frequent use of marijuana during the first trimester of pregnancy and 40 children whose mothers reported no use of marijuana during pregnancy. The marijuana-exposed and unexposed children were group-matched on alcohol exposure prior to and during pregnancy, sex, race, and age at the time of assessment. The photographs were assessed clinically by a study staff dysmorphologist and morphometrically by computerized landmark analysis. Fetal alcohol syndrome-like facial features were not associated with prenatal marijuana exposure in this study sample. No consistent patterns of facial features were identified among the marijuana-exposed group. Maternal consumption of two or more ounces of alcohol per day, on average, in early gestation was found to be associated with fetal alcohol syndrome-like facial features identified both clinically and morphometrically. Cocaine use reported by 13 of the 80 women was independently associated with mild facial dysmorphic features of hypertelorism and midfacial flattening. The results demonstrate the usefulness of this diagnostic technique for quantifying anomalies apparently unique to fetal alcohol syndrome and for targeting clusters of anomalies in new conditions for future evaluation.     

Drug use among adolescent mothers: profile of risk

Adolescent pregnancy and adolescent drug use are important clinical and public health problems. Yet, few studies have systematically investigated the patterns of substance use among pregnant and parenting adolescents. Because adverse outcomes are not found uniformly for all adolescent mothers, use of illicit drugs may be a key factor in determining which mothers and their infants will have poor outcomes. In this study, the patterns of drug use are described and differences in the demographic and psychosocial profile among 253 pregnant adolescents are investigated. Results obtained from interviews and urine assay for marijuana and cocaine indicate that lifetime use was 84% for alcohol, 62% for marijuana, and 23% for cocaine, whereas use in the past year was 40% for marijuana and 17% for cocaine. Compared with nonusers, pregnant adolescent drug users were more likely to be North American black, have a history of elective abortion and venereal disease, report more negative life events and violence during pregnancy, and receive more support from the father of the baby who was more likely to use marijuana and cocaine (P less than .01). Furthermore, according to logistic regression analysis results after controlling for age and ethnicity, adolescents who used illicit substances in the past year were three times more likely to have a male partner who used marijuana or cocaine and were two times more likely to have a history of venereal disease compared with nonusers. The findings suggest that drug use, whether as a mechanism or a marker, is associated with social and medical characteristics that are likely to contribute to negative outcomes among adolescent mothers and their infants.(ABSTRACT TRUNCATED AT 250 WORDS)     

Stimulants: How big is the problem and what are the effects of prenatal exposure?

Globally, cocaine use increased by 7%–18.2 million people in 2016 or 0.4% of the world population aged 15–64. In 2016, over 34 million (0.7%) people aged 15–64 used amphetamines and a further 0.4% used MDMA (Ecstasy). Women of child bearing age worldwide are increasingly using and becoming dependent on stimulants; and are, in turn, more vulnerable to sexually transmitted diseases, sexual violence, unplanned pregnancies and mental health problems. Stimulant use during pregnancy increases obstetric complications for the mother, increases the rate of preterm birth and decreases birth weight, length and head circumference for the exposed infant. No consistent signs of neonatal abstinence syndrome requiring pharmacological treatment have been identified for cocaine or methamphetamine, however, infants exposed to one or both drugs exhibit disorganized neurobehaviour at birth. Increased efforts worldwide are needed to determine the extent of maternal stimulant use and to prevent or identify and treat substance use early during pregnancy.     

Maternal and fetal influences on blood pressure.

To study maternal and fetal influences on blood pressure in childhood 405 children aged 4 years who were born and still resident in the Salisbury health district were visited at home for blood pressure and growth measurements. Information on the pregnancy, delivery, and baby was abstracted from the routine obstetric notes. Similar to recent findings in adults, the child's systolic pressure was inversely related to birth weight and positively related to placental weight. Systolic pressure at 4 years increased by 1.2 mm Hg for every SD decrease in the ratio of head circumference to length at birth, and by 1.1 mm Hg for every SD decrease in ponderal index at birth. Mothers whose haemoglobin concentrations fell below 100g/l during pregnancy had children whose systolic pressures were on average 2.9 mm Hg higher than the children of mothers with higher haemoglobin concentrations. Patterns of placental weight, birth weight, head circumference, and length that are associated with high blood pressure in adults are also associated with higher blood pressure in 4 year old children. Identification of the intrauterine influences that lead to these patterns of fetal growth could lead to the primary prevention of hypertension.     

Effect of prenatal alcohol exposure on growth and morphology of offspring at 8 months of age

In this prospective study of alcohol and other substance use during pregnancy, a cohort of women was interviewed at each trimester of pregnancy and when the offspring were 8 months of age. Data are presented concerning the outcome for 461 infants. A significant relationship was found between alcohol use during pregnancy and the growth and morphology of the offspring at the 8-month follow-up observation. Alcohol use during the second and third trimesters of pregnancy and continuous use of alcohol throughout pregnancy were significantly related to lower weight, length, and head circumference in the exposed infants at the follow-up observation. A significant increase in the risk of minor physical anomalies and fetal alcohol effects was also predicted by prenatal alcohol exposure.     

Maternal and paternal recreational drug use and sudden infant death syndrome.

OBJECTIVE: To determine whether maternal or paternal use of cocaine, opiates, or marijuana during conception and pregnancy and postnatally increases the risk of sudden infant death syndrome (SIDS) during the first year of the infant's life. This is an important issue and may prove useful in further decreasing the rate of SIDS. METHODS: A case-control study was conducted consisting of 239 infants who died of SIDS in southern California between 1989 and 1992, and 239 healthy infants who were matched on the basis of birth hospital, date of birth, age, and sex. Specific drug use at the period of conception, during pregnancy and breastfeeding, and in the presence or vicinity of the infant was ascertained by telephone for the white, African American, Hispanic, Asian American, and Pacific Islander case and control fathers and mothers. RESULTS: Maternal recreational drug use during pregnancy was not associated with the risk of SIDS after adjusting for maternal smoking during pregnancy (adjusted odds ratio [OR] = 2.0; 95% confidence interval [CI], 0.6-6.5). There were statistically significant differences between case and control fathers' use of marijuana during conception (OR = 2.2; 95% CI, 1.2-4.2; P =.01), during pregnancy (OR = 2.0; 95% CI, 1.0-4.1; P =.05), and postnatally (OR = 2.8; 95% CI, 1.1-7.3; P =.04) and the risk of SIDS, while adjusting for paternal smoking and alcohol use. CONCLUSIONS: There was no association between maternal recreational drug use and SIDS. Paternal marijuana use during the periods of conception and pregnancy and postnatally were significantly associated with SIDS. The role of paternal psychoactive drug use, especially the relationship between marijuana and SIDS, is an understudied area; however, before any definitive role for the father can be confirmed, these findings should be investigated and replicated in future studies.     

Difference in ponderal growth and body composition among pregnant vs. never-pregnant adolescents varies by birth outcomes

Recently, we showed that following pregnancy and 6 months of lactation, adolescents cease linear growth and have reduced fat and lean mass in rural Bangladesh. Here, we examined whether these changes varied by pregnancy outcomes such as fetal loss, low birthweight (LBW) and neonatal mortality. Anthropometric measurements were taken among 12–19‐year‐old primigravidae (n = 229) in early pregnancy and at 6 months post‐partum. Never‐pregnant adolescents (n = 456) matched on age and time since menarche were also measured at the same time. Change in anthropometry among pregnant vs. never‐pregnant adolescents was compared by pregnancy outcome adjusting for confounders using mixed effects regression models. Pregnant girls, irrespective of birth outcome, did not gain in stature, while never‐pregnant girls increased in height by 0.36 ± 0.04 cm year^?1 (P < 0.05). Body mass index, mid‐upper arm circumference (MUAC) and % body fat among pregnant adolescents whose infants survived the neonatal period had decreased at 6 months post‐partum, whereas those who experienced a fetal loss or neonatal death did not change in any of the measurements. Consequently, the difference in change in ponderal size and body composition measures between pregnant and never‐pregnant girls was higher among those whose neonates survived vs. those who experienced a fetal loss/neonatal death (BMI: ?0.64 ± 0.11 vs. 0.01 ± 0.16 kg m^?2 year^?1; MUAC: ?0.96 ± 0.12 vs. ?0.35 ± 0.17 cm year^?1, both P < 0.05). LBW and preterm birth did not have a similar effect modification. Linear growth ceased among pregnant girls regardless of birth outcome. Maternal weight loss and depletion of fat and lean mass at 6 months post‐partum were more pronounced when the infants survived through the neonatal period.