Maternal Cocaine Research Articles

Maternal cocaine alters eupneic ventilation but not gasping of neonatal rats

In severe hypoxia, normal eupneic respiration is replaced by gasping. Gasping provides for `autoresuscitation' such that, if air is available, normal breathing returns. As maternal use of cocaine may increase the incidence of the Sudden Infant Death Syndrome (SIDS), prenatal exposure to cocaine was hypothesized to result in a failure of gasping in the newborn. Cocaine was administered daily to pregnant rats. In the newborn, no impairment of gasping as a mechanism of autoresuscitation was detected. However, on the first and second days after birth, ventilation in hypoxia was less in newborns having exposure to cocaine than in the control rats. Maternal use of cocaine may retard the development of the ventilatory control system. However, gasping mechanisms are not included in this retardation.

INTERVENING WITH PRENATAL CRACK COCAINE USERS

Nurses in primary care, maternal child health, and community health practice settings are in a unique position to intervene with clients who are prenatal crack cocaine users. Clinical assessment is considered in both the context of the pregnancy and the crack cocaine use. A synthesis model of intervention related to both the pregnancy and the drug use are outlined to support a healthy baby and a healthy recovery.

The impact of maternal cocaine use on neonates in socioeconomic disadvantaged population.

Maternal cocaine use has emerged as a major public health concern because the number of users has markedly increased in 1990s and the impact on neonates is severe. The problem of maternal cocaine use is especially important in socioeconomic disadvantaged population since they are more likely to be victims of this drug use. Social support programs including drug education are utmost important and should be offered to all socioeconomic disadvantage pregnant women to prevent and control maternal cocaine use.

The association between maternal cocaine use and placenta previa

Objective: Our aim was to determine whether maternal cocaine exposure is a risk factor for placenta previa. Study Design: In this case-control study, cases of placenta previa confirmed at delivery (ascertained by International Classification of Diseases, ninth revision, Clinical Modification, code-based search, N = 40) were compared with a random sample of patients without placenta previa ( N = 80) in a ratio of two controls per case. Data on antecedent maternal cocaine use, as well as other potential risk factors for placenta previa, were obtained from a review of the prenatal chart and the hospital record. Categorization of cocaine use was based on either patient self-report or urine toxicologic testing, or both. Multiple logistic regression was performed to assess the association between cocaine and placenta previa while we controlled for other variables. Results: After the effects of other variables were adjusted for, maternal cocaine use was an independent risk factor for placenta previa (adjusted odds ratio = 4.39, 95% confidence interval 1.17 to 16.4). Other significant risk factors included a history of cesarean section and prior elective abortion. Conclusion: These results suggest that cocaine use, as well as prior cesarean section, prior elective abortion, and parity, are associated with placenta previa.

Assessing the relationship between maternal cocaine use and abruptio placentae

Abruptio placentae during pregnancy can result in significant morbidity and mortality to both mother and infant. A comprehensive literature search of publications from 1966 to April 1995 identified 11 studies on the association between maternal cocaine use and abruptio placentae. Their results were combined in a meta-analysis. The pooled odds ratio for abruptio placentae and maternal cocaine use was 3.92 (95% confidence interval 2.77-5.46). The strength and consistency of the association, its biological plausibility and the results of experimental studies in animals all suggest that cocaine use during pregnancy causes abruptio placentae.

Predictive factors for neonatal morbidity in neonates with an umbilical arterial cord pH less than 7.00

Objective: Fewer than 50% of neonates with an umbilical arterial pH <7.00 have neonatal complications. Our objective was to identify clinical predictive factors for adverse outcomes in this group of neonates. Study Design: In this case-control study both cases and controls had an umbilical arterial cord pH <7.00. Cases were defined as those neonates who had seizures, grade 3 to 4 intraventricular hemorrhage, gastrointestinal dysfunction, respiratory distress syndrome requiring intubation, sepsis, or death. Controls had an umbilical arterial cord pH <7.00 and no complications. A multivariable prediction model was created, with variables having an association with adverse outcome by bivariate analyses, attempting to predict which neonates in this umbilical arterial pH range are at greatest risk for adverse outcomes. Results: We identified 73 of 10,705 neonates born between July 1992 and October 1996 with an umbilical arterial cord pH <7.00. Thirty-five neonates met our case definition, and the remaining 38 composed the control group. Cases had significantly lower arterial pH values and 1- and 5-minute Apgar scores, greater arterial base deficit values, and a higher incidence of abruptio placentae and maternal cocaine use. More cases were delivered before 34 weeks. There were three neonatal deaths, two cases of grade 3 or 4 intraventricular hemorrhage, five cases of gastrointestinal dysfunction, and four cases of neonatal seizures. In our predictive model for adverse neonatal outcome, an arterial base deficit ≥16 mmol/L and a 5-minute Apgar score <7 had a sensitivity and a specificity of 79% and 80.8%, respectively. Conclusion: Neonatal morbidity in neonates with an umbilical arterial cord pH <7.00 can be predicted by a high arterial base deficit value and low 5-minute Apgar score.

Assessing the relationship between maternal cocaine use and abruptio placentae

Assessing the relationship between maternal cocaine use and abruptio placentae

Maternal cocaine use and low birth weight newborns: a meta‐analysis

Many epidemiological studies published on the association between maternal cocaine/crack use and birth weight have either lacked precision or failed to control for major confounding, predominantly by tobacco smoking. Meta-analysis enables a single summary measure of effect to be calculated by combining data from any number of individual studies, thus enhancing statistical power. We undertook a number of meta-analyses using only studies that had adjusted for tobacco smoking to estimate more precisely the effect of maternal cocaine use on birth weight. A meta-analysis of five studies presenting data for 'any' prenatal cocaine exposure, adjusted for tobacco smoking but unadjusted for gestational age, produced a pooled relative risk estimate from a fixed effects analysis of 2.15 (95% CI 1.75-2.64). However, there was substantial heterogeneity among studies (p < 0.001), and the relative risk from a random effects analysis was smaller (1.65) with a confidence interval that included unity (95% CI 0.94-2.83). Addition of a further study adjusted for gestational age had minimal effect on the pooled estimate: the fixed effects relative risk was 2.14 (1.77-2.60) and the random effects estimate 1.77 (1.15-2.71). When data on more intense prenatal exposure were analysed, the fixed and random effects analysis produced the same pooled estimate of the relative risk of 4.42 (2.24-8.71), suggesting that more frequent cocaine exposure was associated with a higher relative risk for low birth weight. Data from studies on mean reduction in birth weight produced a pooled estimate of 112 g (95% CI 62-161 g). The current study suggests that maternal cocaine use causes low birth weight, and that the effect is greater with heavier use. However, despite the adjustment for tobacco and the adjustment by some studies for other confounders such as race, maternal age, gravidity and socio-economic status, it could be argued that other life-style factors not controlled for may account for the observed effects. While this argument is not supported by some other types of study, the issue of residual confounding can only be finally addressed by analytical studies which adequately control for important variables.

Relationship of prenatal cocaine exposure and maternal postpartum psychological distress to child developmental outcome.

Maternal cocaine use during pregnancy can affect the infant directly through toxic effects or indirectly through cocaine's influence on maternal psychological status. We followed 160 cocaine exposed and 56 nonexposed infants and their mothers identified at birth through interview and/or urine screen. Although cocaine exposure defined the groups, infant exposure to alcohol, marijuana, and tobacco was allowed to vary. Infants were 99% African American and poor. All mothers completed the Brief Symptom Inventory (BSI) and infants were given the Bayley Scales of Mental (MDI) and Motor (PDI) Development at a mean corrected age of 17 +/- 8 months. Both MDIs (94 +/- 17 vs. 103 +/- 16) and PDIs (101 +/- 16 vs. 108 +/- 12) were lower for cocaine exposed infants. Psychological distress was greater in cocaine using mothers. Hierarchical multiple regression was used to assess the relative effects of gestational age, maternal psychological distress, and cocaine and polydrug exposure on infant outcomes. Both psychological distress and cocaine and alcohol exposure predicted lower MDIs after controlling for prematurity. Neither psychological distress nor alcohol exposure predicted motor outcome, while cocaine had a significant effect. Tobacco and marijuana exposure were unrelated to outcome. These findings provide further support for direct effects of cocaine and alcohol on infant development as well as highlight the need for studies to document maternal psychological factors, which may increase child risk for poorer outcomes.

Ecgonine methyl ester, a major cocaine metabolite, causes cerebral vasodilation in neonatal sheep.

Maternal cocaine abuse has been associated with fetal and neonatal neurologic abnormalities, including hemorrhagic cerebral infarctions, but the mechanisms for cocaine's cerebral effects are unknown. We previously showed that acute cocaine injection causes cerebral vasodilation in cats and immature sheep; others have shown that cocaine causes cerebral vasoconstriction in piglets and in pressurized neonatal sheep arteries. Although methodologic and species differences may explain these conflicting results, we tested another possibility; that is, that ecgonine methyl ester (EME), a major cocaine metabolite in sheep, causes cerebral vasodilation and may account, in part, for cocaine's vascular effects. We studied the cerebral effects of a single i.v. injection of EME (2.5 mg/kg) in eight chronically catheterized, unanesthetized neonatal sheep (4 +/- 2 d old). We measured cerebral hemisphere blood flow (CBF) using radiolabeled microspheres, mean arterial pressure, heart rate, and arteriovenous oxygen content, and we calculated cerebral oxygen consumption (CMRo2) and cerebrovascular resistance at baseline and 0.5, 2, 5, and 60 min after EME injection. EME injection had no systemic effects, including no changes in mean arterial pressure, heart rate, or arterial blood gases. Within 0.5 min of injection, EME caused a 21% decrease in cerebrovascular resistance, which remained decreased for 60 min. CBF increased by 20% at 0.5, 2, and 5 min. Blood flow to brain regions other than the cerebral hemispheres paralleled changes in CBF, with cerebellar flow remaining increased at 60 min. There was no change in CMRo2. There was a small, but physiologically insignificant, decrease in arterial oxygen content. We conclude that EME causes cerebral vasodilation in neonatal sheep and may account, in part, for cocaine's cerebral vascular effects.

Cocaine administration in pregnant rabbits alters cortical structure and function in their progeny in the absence of maternal seizures.

Previous studies have reported that cocaine exposure in utero results in structural and functional alterations in the development of the anterior cingulate cortex (ACC). In the present study, the effects of maternal cocaine dosage and of cocaine-elicited maternal seizures on the progeny were studied. The incidence of maternal generalized tonic clonic seizures (GTCSs) elicited by cocaine was recorded. No GTCSs were elicited in pregnant rabbits by doses of 2 or 3 mg/kg of cocaine, but GTCSs were sometimes elicited by the highest dose (4 mg/kg per injection). We analyzed the offspring of cocaine-exposed and control animals using three assays of ACC development: (i) the structure of apical dendrites of pyramidal neurons, (ii) the distribution of a calcium binding protein (parvalbumin) in the dendrites of GABAergic neurons, and (iii) coupling of D1-like receptors and their G proteins. In all progeny of rabbits exposed to 3 or 4 mg/kg of cocaine during pregnancy, there was a significant change in the structure of apical dendrites, a significant increase in the number of dendrites of GABAergic neurons which were parvalbumin immunoreactive, and a significant reduction in D1/G protein coupling. In assays of apical dendrites, the effects on offspring of rabbits given 2 mg/kg cocaine were as pronounced as in offspring of rabbits given 3 or 4 mg/kg, but the effects on parvalbumin immunoreactivity and D1/G protein coupling were reduced at this low dose. Thus, previous findings of ACC developmental abnormalities in offspring of rabbits given a dose of 4 mg/kg were replicated, the effects were shown to be dose-related and to be independent of maternal seizures. A mechanism by which dysfunction of the D1 receptor system could mediate cocaine-associated changes in all three parameters of ACC structure and function is discussed.

Cigarette smoking and maternal-child HIV transmission.

We investigated the association of cigarette smoking with maternal-child HIV transmission, adjusting for illicit drug use, maternal clinical status, and delivery factors. Vital statistics birth data were linked to the New York State Medicaid HIV/AIDS Research Database for HIV-infected women delivering a liveborn singleton from 1988 through 1990. Follow-up of these children was accomplished by Medicaid data > or = 2 years after birth, and their HIV status was ascertained by a clinically based classification. The adjusted relative risk or hazard (RH) of transmission for maternal factors was determined from Cox models. The overall transmission was 24.5% for the 901 maternal-child pairs. Smokers comprised 40% of women with data on smoking (n = 768); their transmission rate was 31% versus 22% for nonsmokers (p = 0.02). In the entire cohort, the adjusted RH of transmission for smokers was 1.45 (95% confidence interval [CI] 1.07-1.96); among women with advanced HIV, the adjusted RH was even higher (RH = 1.71; 95% CI 1.14-2.58). Users of cocaine (15% of the cohort) or of mixed or unspecified illicit drugs (28%) had higher transmission rates in unadjusted analysis (33%, p = 0.06 and 31%, p = 0.06 respectively); after adjustment for smoking and other maternal factors, neither cocaine (RH = 1.04 (95% CI 0.66-1.63)) nor mixed nor unspecified drug use (RH = 1.13 (95% CI = 0.75-1.70)) was significantly associated with transmission. Our data document an association of cigarette smoking during pregnancy with an increased risk of maternal-child HIV transmission that can be added to the growing list of complications caused by cigarette smoking.

Cerebral blood flow regulation in neonatal rabbits is altered by chronic cocaine administration

Maternal cocaine abuse has several deleterious effects in the newborn, including perinatal asphyxia, hypoxia, and hypercapnia. We hypothesized that chronic cocaine exposure during development may alter cerebral blood flow (CBF) regulation. We studied 16 neonatal rabbits that had received cocaine (20 mg/kg, i.p. b.i.d.) or saline since birth. Changes in CBF were measured by laser doppler flowmetry before (baseline), and during hypercapnia (FiCO 2 = 7.5%), hypoxia (FiO 2 = 12%), and asphyxia (apnea for 1 min). During hypercapnia, CBF increased less in cocaine than in control animals (28 + 3% vs. 69 ± 10%, P < 0.05). During hypoxia, CBF increased similarly in both groups. During reventilation after asphyxia, CBF increased more in cocaine than in control animals (391 + 52% vs. 225 ± 43%, P < 0.05). Chronic cocaine exposure during brain development appears to alter CBF regulation to hypercapnia and asphyxia, which may put the drug exposed newborn at risk for neurologic injury around birth.

Prenatal cocaine exposure and mother-infant interaction: implications for occupational therapy intervention.

The literature from multiple disciplines on in utero cocaine exposure and mother-infant interaction and attachment was examined for possible relationships and implications for occupational therapists. Maternal cocaine use and neurobehavioral deficits in neonates prenatally exposed to cocaine may result in interactional difficulties between mother and infant. Knowledge of child development, sensory regulation, and infant cues will enable therapists to assist the mother in creating positive interactive experiences between herself and her child.

Maternal Cocaine Treatment Alters Dynorphin and Enkephalin mRNA Expression in Brains of Fetal Rhesus Macaques

Cocaine exposure in utero is known to cause a variety of behavioral and motor deficits that may be attributable to alterations in the dopamine neurocircuitry. To ascertain cocaine effects in the fetus, we developed a nonhuman primate model in which pregnant monkeys were administered cocaine from day 20 through day 60 or 70 of gestation. Fetuses from these pregnancies develop a repertoire of neural deficiencies, including decreased mRNA expression of tyrosine hydroxylase in the midbrain and increased mRNA expression of dopamine receptor subtypes in the rostral forebrain. Presently, we studied the effects of maternal cocaine treatment on the mRNA expression of the endogenous opioids preprodynorphin (PPD) and preproenkephalin (PPE) in fetal monkey brains. Fetuses exposed to saline (0.9%) or cocaine (3 mg/kg) were delivered by Caesarean section, the fetal brains were dissected, and tissue RNA was extracted and quantified using ribonuclease protection assay analysis. The opioid peptides PPD and PPE were expressed in the fetal monkey brain by day 60, and even higher levels were found in day 70 fetuses. Maternal exposure to cocaine increased gene expression of PPD and PPE in the fetus at both day 60 and day 70 of gestation. Dynorphin mRNA levels were significantly elevated in the striatum, whereas enkephalin mRNA was elevated in both the frontal cortex and the striatal area of fetuses whose mothers received cocaine. Changes in the expression of these opioid peptides in presumed dopamine target neurons, which mediate motivation and reward, as well as motor control, provide further evidence for profound consequences of in utero cocaine exposure on the developing dopamine neurocircuitry.

The association between maternal cocaine use and placenta previa

The association between maternal cocaine use and placenta previa

Vascular disruption birth defects and history of prenatal cocaine exposure: a case control study.

To test the hypothesis that prenatal cocaine exposure is associated with a 3-fold increased risk for vascular disruption among malformations. A retrospective case-control study was based upon >68,000 delivery records at Hutzel Hospital for a 9-year period. Ascertainment was based upon ICD-9 codes for limb defects, abdominal wall defects, and facial clefts. Transverse limb defects and gastroschisis were defined as cases, and nondisruption anomalies served as controls. Statistical analysis for history of maternal cocaine use reported during pregnancy was performed by chi(2) analysis and the odds ratio determined. A total of 190 cases of limb anomalies, abdominal wall defects, and cleft lips were identified after exclusion criteria. Statistical analysis was performed on the 119 cases informative for maternal cocaine use during pregnancy. Seven of 34 vascular disruption cases had cocaine exposure reported versus 12 of 85 other malformations controls. The odds ratio for cocaine exposure and vascular disruption is 1.58 (95% confidence interval = 0.55-4.47). The putative association of prenatal cocaine exposure and vascular disruption birth defects remains unresolved, but the attributable risk is very likely less than the 3-fold odds ratio previously reported.

Effects of prenatal cocaine exposure on the developing hippocampus: intrinsic and synaptic physiology.

A variety of neurological complications has been reported in infants exposed to cocaine during gestation. In the present study, intrinsic cell properties of hippocampal neurons from CA1, CA3, and dentate gyrus regions were measured and compared in tissue from neonatal rats exposed to saline or cocaine in utero. Synaptic properties of the CA1 pyramidal cell region were analyzed at postnatal day (P) 20 with the use of extracellular and intracellular recording techniques. In vitro intracellular recordings (n = 223) obtained at P10, P15 and P20 in tissue from cocaine- and saline-exposed animals revealed no differences in standard cell properties such as resting membrane potential, input resistance, time constant, and action potential amplitude or duration. Hippocampal slices from cocaine-exposed animals exhibited a marked reduction of spike frequency adaptation for all three types of principal hippocampal neurons (e.g., CA1, CA3, and granule cells). The amplitudes of afterhyperpolarizations following a spike train were also decreased in CA1 and CA3 cells in tissue from cocaine-exposed animals. Extracellular and intracellular recordings in the CA1 pyramidal cell region at P20 were obtained to assess and compare synaptic function in tissue from cocaine- and saline-exposed animals. In hippocampal slices from cocaine-exposed animals, synaptic responses in the CA1 region were characterized by multiple population spike activity and reduced inhibitory postsynaptic potentials. The reduction in fast inhibitory postsynaptic potential conductance was not associated with a change in reversal potential. These results suggest that gestational cocaine exposure induces significant changes in intrinsic and synaptic electrophysiological properties of hippocampal neurons in the developing animal. The cell and synaptic features are consistent with an increase in hippocampal excitability, which may contribute to the neurobehavioral deficits and epileptogenic predisposition reported in this infant population. As such, this in utero drug exposure model may provide a useful system in which to elucidate and study the basic cellular mechanisms underlying neurological complications associated with maternal cocaine abuse.

Cocaine concentrations in fetal C57BL/6 mouse brain relative to maternal brain and plasma.

Cocaine concentrations in maternal plasma and brain and fetal brain of mice were evaluated as a model for fetal brain exposure during maternal cocaine use. On days 12-18 of gestation, mice (C57BL/6; N = 5-7/group) received SC cocaine-HCI: 20 or 40 mg/kg. Maternal plasma and brain (accumbens and caudate nuclei removed), and fetal brain were collected at 0.5, 1, and 2 h following the last injection. Analysis was by GC-MS. Brain cocaine levels in the dams declined from 9.6 to 3.4 and 20.9 to 12.5 micrograms/g [corrected] during the 0.5-1-h period after the low and high doses, respectively, and were 7.5-14.3 times greater than plasma levels. The corresponding fetal brain concentrations changed from 1.6 to 1.3 and 2.9 to 3.4 micrograms/g [corrected]. By 2 h, brain cocaine concentrations in dams declined to approximately 10% of their 0.5-h values, with a slower drug decay occurring in fetal brain. Maternal plasma cocaine concentrations correlated with those of maternal brain (r = 0.94, p < 0.01) and fetal brain (r = 0.69, p < 0.01). The present results indicate that cocaine accumulates to a lesser extent in fetal brain than in maternal brain of C57BL/6 mice; however, the duration of exposure appears to be more sustained in the fetus, a phenomenon that may have toxicological implications for human in utero cocaine exposure.

A murine model of prenatal cocaine exposure: Effects on the mother and the fetus

To develop and characterize a murine model for investigating the long-term effects of prenatal cocaine exposure, the present study established the route of drug administration and the doses to be used for pregnant C57BL/6 mice. Comparison of the effects of a high dose of cocaine (60 mg/kg) when gavaged or injected subcutaneously (SC) established patterns of pathology characteristic of administration route but no dominating logic for selecting one over the other route for prenatal studies; however, because of the fourfold greater brain levels, with no evidence of greater pathology, the SC route was selected. When injected daily during gestation days 12–18, the period of prenatal development of dopamine systems, cocaine at doses producing plasma concentrations consistent with its stimulatory effects reduced food ingestion and weight gains during pregnancy and fetal body and brain weights at term. The extent of these reductions was comparable to reports on babies exposed to cocaine prenatally. Furthermore, the present study suggests that maternal undernutrition is not a likely mediator of these perinatal effects and that differences in the amount of cocaine exposure may cause the contrasting effects of maternal cocaine noted in the human literature.