Bronchopulmonary Dysplasia: Comparison Between the Two Most Used Diagnostic Criteria.

Objectives: To compare the Shennan's and the consensus definition of Bronchopulmonary Dysplasia (BPD) from the National Institutes of Health (NIH) workshop and analyze specific risk factors associated with each definition. Study design: Retrospective analysis of records of 274 infants admitted to a level IV intensive care unit. Infants were classified as having BPD or no BPD by both definitions. Differences in incidence and risk factors were analyzed. Statistical methods included descriptive statistics, comparative tests, and marginal logistic regression modeling. Results: The estimated difference in prevalence was 32% [95% CI: (26%, 37%), (p < 0.0001)] between both criteria. The prevalence of BPD was 80% higher based on the NIH criteria [RR = 1.80; 95% CI: (1.58, 2.06)]. Infants with no BPD by the Shennan definition were breathing room air with or without positive or continuous pressure support and were most likely to be discharged home on oxygen [OR = 4.47, 95% CI: (1.20, 16.61), p = 0.03]. Gestational age, birth weight, and 1-min Apgar score predicted BPD by both definitions. Chorioamnionitis increased the risk of BPD by the Shennan definition but was associated with lower risk by the NIH criteria. IUGR was associated with BPD by the Shennan definition and with severe BPD by the NIH criteria. Conclusion: Compared to the Shennan's definition, the NIH consensus identified 80% more infants with BPD and is a better predictor of oxygen requirement at discharge. Until a new better criteria is develop, the NIH consensus definition should be used across centers.

Prenatal Opioid Exposure and Intermittent Hypoxemia in Preterm Infants: A Retrospective Assessment.

INTRODUCTION: Intermittent hypoxemia (IH) is defined as episodic drops in oxygen saturation (SpO2). Preterm infants are at increased risk for IH due to their immature respiratory control/apnea of prematurity. The clinical relevance of IH is a relatively new observation with rising evidence linking IH to neonatal morbidities and long-term impairment. Hence, assessing factors that influence IH in preterm infants is imperative. Given the epidemic of opioid misuse in the USA, there is an urgent need to understand the impact of prenatal opioid exposure on neonatal outcomes. Hence, we wanted to assess the relationship between isolated prenatal opioid exposure and IH in preterm infants. METHODS: In order to accurately calculate IH, SpO2 data were prospectively collected using high-resolution pulse oximeters during the first 8 weeks of life in preterm infants less than 30 weeks gestational age. Data related to prenatal opioid misuse were retrospectively collected from medical charts. Infants with tobacco or poly-drug exposure were excluded. The primary outcome measure is percent time spent with SpO2 below 80% (%time-SpO2 < 80). The secondary outcome measure is the number of severe IH events/week with SpO2 less than 80% (IH-SpO2 < 80). RESULTS: A total of 82 infants with isolated opioid exposure (n = 14) or who were unexposed (n = 68) were included. There were no significant differences in baseline characteristics between opioid exposed and unexposed groups. There was a statistically significant increase of 0.23 (95% CI: 0.03, 0.43, p = 0.03) in mean of the square root of %time-SpO2 < 80. The number of IH-SpO2 < 80 events was higher in the opioid exposed group (mean difference = 2.95, 95% CI: -0.35, 6.25, p-value = 0.08), although statistical significance was not quite attained. CONCLUSION: This study shows that preterm infants prenatally exposed to opioids have increased IH measures compared to unexposed infants. Interestingly, the increased IH in the opioid exposed group persists beyond the immediate postnatal period.

Genes and environment in neonatal intraventricular hemorrhage.

Emerging data suggest intraventricular hemorrhage (IVH) of the preterm neonate is a complex disorder with contributions from both the environment and the genome. Environmental analyses suggest factors mediating both cerebral blood flow and angiogenesis contribute to IVH, while candidate gene studies report variants in angiogenesis, inflammation, and vascular pathways. Gene-by-environment interactions demonstrate the interaction between the environment and the genome, and a non-replicated genome-wide association study suggests that both environmental and genetic factors contribute to the risk for severe IVH in very low-birth weight preterm neonates.

Reactivity and regulation of motor responses in cocaine-exposed infants.

UNLABELLED: Effects of prenatal exposure to cocaine on the reactivity and regulation of the motor system of 825 four-month-old infants enrolled in the Maternal Lifestyle Study were examined. Videotaped assessments of 338 cocaine-exposed (CE) infants and 487 non-exposed comparison infants were coded by examiners masked to exposure status. Exposure status was determined by meconium assay and maternal self-report of prenatal cocaine use. Infants were presented with a series of 17 visual, auditory and tactile stimuli for 30-s each. Intensity and latency of limb movement responses on a subset of items were analyzed to test the following hypotheses: CE infants are more active in general; CE infants exhibit increased movement levels for a larger proportion of time in response to stimulation; the motor systems of CE infants are more reactive to stimulation (e.g., shorter latencies to respond); and CE infants are poorer regulators of the motor system. RESULTS: CE infants were not more active in general and data do not indicate a more highly reactive motor system. However, CE infants exhibited increased movement levels for a larger proportion of time in response to stimulation. Additional analysis of movement exhibited during three tactile items found increased movement lability in CE infants and different patterns of responding, suggesting that the effects of prenatal cocaine exposure on the motor system may vary by context. Covariate effects for tobacco, alcohol, and marijuana are also reported.

Consequences of prenatal substance use.

BACKGROUND: Prenatal substance use is a major public health problem and a social morbidity, with consequences on the drug user and the offspring. OBJECTIVE: This review focuses on the child and adolescent outcomes following in utero drug exposure. METHODS: Studies on the effects of specific substances, legal and illegal; i.e., tobacco or nicotine, alcohol, marijuana, cocaine, opiates, and methamphetamine were evaluated and analyzed. RESULTS: In general, manifestations of prenatal exposure to legal and illegal substances include varying deficits in birth anthropometric measurements, mild-to-moderate transient neurobehavioral alterations in infancy and long-term behavioral problems noted from early childhood to adolescence. Severity of expression of behavioral problems is influenced by environmental factors. Further, behavioral alterations following in utero drug exposure often exist with mental health co-morbidities. CONCLUSION: Because of the long-term consequences of prenatal drug exposure on child and adolescent mental health, health providers need to promote substance use prevention, screen for exposure effects and provide or refer affected youths for intervention services. Preventive measures and treatment should consider other factors that may further increase the risk of psychopathology in the exposed children.

Neurobehavioral disinhibition predicts initiation of substance use in children with prenatal cocaine exposure.

BACKGROUND: In previous work we (Fisher et al., 2011) examined the emergence of neurobehavioral disinhibition (ND) in adolescents with prenatal substance exposure. We computed ND factor scores at three age points (8/9, 11 and 13/14 years) and found that both prenatal substance exposure and early adversity predicted ND. The purpose of the current study was to determine the association between these ND scores and initiation of substance use between ages 8 and 16 in this cohort as early initiation of substance use has been related to later substance use disorders. Our hypothesis was that prenatal cocaine exposure predisposes the child to ND, which, in turn, is associated with initiation of substance use by age 16. METHODS: We studied 386 cocaine exposed and 517 unexposed children followed since birth in a longitudinal study. Five dichotomous variables were computed based on the subject's report of substance use: alcohol only; tobacco only; marijuana only; illicit substances and any substance. RESULTS: Cox proportional hazard regression showed that the 8/9 year ND score was related to initiation of alcohol, tobacco, illicit and any substance use but not marijuana use. The trajectory of ND across the three age periods was related to substance use initiation in all five substance use categories. Prenatal cocaine exposure, although initially related to tobacco, marijuana and illicit substance initiation, was no longer significant with ND scores in the models. CONCLUSION: Prenatal drug exposure appears to be a risk pathway to ND, which by 8/9 years portends substance use initiation.

Serial pediatric symptom checklist screening in children with prenatal drug exposure.

OBJECTIVE: To examine screening results obtained by serial annual behavioral assessment of children with prenatal drug exposure. METHOD: The Maternal Lifestyle Study enrolled children with prenatal cocaine exposure (PCE) at birth for longitudinal assessments of developmental, behavioral, and health outcomes. At 8, 9, 10, 11, and 12 years of age, caregivers rated participants on the Pediatric Symptom Checklist (PSC). Serial PSC results were compared with an established broad-based behavioral measure at 9, 11, and 13 years. PSC results were analyzed for 1081 children who had at least 2 annual screens during the 5-year time span. Most subjects (87%) had 4 or more annual screens rated by the same caregiver (80%). PSC scores (and Positive screens) over time were compared at different time points for those with and without PCE. Covariates, including demographic factors and exposures to certain other substances, were controlled. RESULTS: Children with PCE had significantly higher scores overall, with more Positive screens for behavior problems than children without PCE. Children with PCE had more externalizing behavior problems. Children exposed to tobacco prenatally and postnatally also showed higher PSC scores. Over time, PSC scores differed slightly from the 8-year scores, without clear directional trend. Earlier PSC results predicted later behavioral outcomes. CONCLUSION: Findings of increased total PSC scores and Positive PSC screens for behavioral concerns in this group of children with prenatal substance exposure support the growing body of evidence that additional attention to identification of mental health problems may be warranted in this high-risk group.

Preadolescent behavior problems after prenatal cocaine exposure: Relationship between teacher and caretaker ratings (Maternal Lifestyle Study).

BACKGROUND: We previously reported an association between prenatal cocaine exposure (PCE) and childhood behavior problems as observed by the parent or caretaker. However, these behavior problems may not manifest in a structured environment, such as a school setting. OBJECTIVE: We determined whether there is an association between PCE and school behavior problems and whether ratings of behavior problems from the teacher differ from those noted by the parent or caretaker. METHODS: The Maternal Lifestyle Study, a multicenter study, enrolled 1388 children with and without PCE at one month of age for longitudinal assessment. Teachers masked to prenatal drug exposure status completed the Teacher Report Form (TRF/6-18) when children were 7, 9, and 11 years old. We also administered the Child Behavior Checklist-parent report (CBCL) to the parent/caretaker at same ages and then at 13 years. We performed latent growth curve modeling to determine whether high PCE will predict externalizing, internalizing, total behavior, and attention problems at 7 years of age and whether changes in problems' scores over time differ between those exposed and non-exposed from both teacher and parent report. Besides levels of PCE as predictors, we controlled for the following covariates, namely: site, child characteristics (gender and other prenatal drug exposures), family level influences (maternal age, depression and psychological symptomatology, continuing drug use, exposure to domestic violence, home environment, and socioeconomic status), and community level factors (neighborhood and community violence). RESULTS: The mean behavior problem T scores from the teacher report were significantly higher than ratings by the parent or caretaker. Latent growth curve modeling revealed a significant relationship between intercepts of problem T scores from teacher and parent ratings; i.e., children that were rated poorly by teachers were also rated poorly by their parent/caretaker or vice versa. After controlling for covariates, we found high PCE to be a significant predictor of higher externalizing behavior problem T scores from both parent and teacher report at 7 years (p=0.034 and p=0.021, respectively) in comparison to non-PCE children. These differences in scores from either teacher or caregiver were stable through subsequent years or did not change significantly over time. Boys had higher T scores than girls on internalizing and total problems by caretaker report; they also had significantly higher T scores for internalizing, total, and attention problems by teacher ratings; the difference was marginally significant for externalizing behavior (p=0.070). Caretaker postnatal use of tobacco, depression, and community violence were significant predictors of all behavior problems rated by parent/caretaker, while lower scores on the home environment predicted all behavior outcomes by the teacher report. CONCLUSIONS: Children with high PCE are likely to manifest externalizing behavior problems; their behavior problem scores at 7 years from either report of teacher or parent remained higher than scores of non-exposed children on subsequent years. Screening and identification of behavior problems at earlier ages could make possible initiation of intervention, while considering the likely effects of other confounders.

Sleep problems in children with prenatal substance exposure: the Maternal Lifestyle study.

OBJECTIVE: To examine the associations between sleep problems and prenatal exposure to cocaine, opiates, marijuana, alcohol, and nicotine in children aged 1 month to 12 years. DESIGN: Sleep data were collected by maternal report in a prospective longitudinal follow-up of children participating in the Maternal Lifestyle multisite study. SETTING: Hospital-based research centers in Providence, Rhode Island; Miami, Florida; Detroit, Michigan; and Memphis, Tennessee. PARTICIPANTS: There were 808 participants, 374 exposed to cocaine and/or opiates, and 434 comparison subjects. MAIN EXPOSURE: Prenatal cocaine, opiate, marijuana, alcohol, and/or nicotine exposure. OUTCOME MEASURE: Sleep problems in early, middle, and/or late childhood, assessed as composites of maternal report items. RESULTS: Of the 5 substances, prenatal nicotine exposure was the only unique predictor of sleep problems (B = 0.074, R(2) change = 0.008, P = .01), with adjustment for covariates, including socioeconomic status, marital status, physical abuse, prenatal medical care, and postnatal cigarette smoke exposure. CONCLUSIONS: Prenatal exposure to nicotine was positively associated with children's sleep problems persisting throughout the first 12 years of life. Targeting of this group of children for educational and behavioral efforts to prevent and treat sleep problems is merited given that good sleep may serve as a protective factor for other developmental outcomes.

Small for gestational age and higher birth weight predict childhood obesity in preterm infants.

We sought to determine the association between small for gestational age (SGA), birth weight, and childhood obesity within preterm polysubstance exposed children. We sampled 312 preterm children with 11-year body mass index (BMI; age- and sex-specific) data from the Maternal Lifestyle Study (51% girls, 21.5% SGA, 46% prenatal cocaine, and 55% tobacco exposed). Multinomial regression analyzed the association between 11-year obesity (OBE) and overweight (OW) and SGA, birth weight, first-year growth velocity, diet, and physical activity variables. Overall, 24% were OBE (BMI for age ≥95th percentile) and 16.7% were OW (BMI ≥85th and <95th percentiles). In adjusted analyses, SGA was associated with OW (odds ratio [OR] = 3.4, confidence interval [CI] 1.5 to 7.5). Higher birth weight was associated with OBE (OR = 1.8, CI 1.3 to 2.4) and OW (OR = 1.4, CI 1.1 to 2.0). Growth velocity was associated with OBE (OR = 2.7, CI 1.8 to 4.0) and OW (OR = 1.6, CI 1.1 to 2.4). Low exercise was associated with OBE (OR = 2.1, CI 1.0 to 4.4) and OW (OR = 2.1, CI 1.0 to 4.5). There was no effect of substance exposure on obesity outcomes. Many (41%) of these high-risk preterm 11-year-olds were obese/overweight. Multiple growth-related processes may be involved in obesity risk for preterm children, including fetal programming as indicated by the SGA effect.

Prenatal cocaine exposure related to cortisol stress reactivity in 11-year-old children.

OBJECTIVE: Determine the association between prenatal cocaine exposure and postnatal environmental adversity on salivary cortisol stress reactivity in school-aged children. STUDY DESIGN: Subjects included 743 11-year-old children (n = 320 cocaine-exposed; 423 comparison) followed since birth in a longitudinal prospective multisite study. Saliva samples were collected to measure cortisol at baseline and after a standardized procedure to induce psychological stress. Children were divided into those who showed an increase in cortisol from baseline to post stress and those who showed a decrease or blunted cortisol response. Covariates measured included site, birthweight, maternal pre and postnatal use of alcohol, tobacco or marijuana, social class, changes in caretakers, maternal depression and psychological symptoms, domestic and community violence, child abuse, and quality of the home. RESULTS: With adjustment for confounding variables, cortisol reactivity to stress was more likely to be blunted in children with prenatal cocaine exposure. Children exposed to cocaine and who experienced domestic violence showed the strongest effects. CONCLUSIONS: The combination of prenatal cocaine exposure and an adverse postnatal environment could downregulate the hypothalamic-pituitary-adrenal axis resulting in the blunted cortisol response to stress possibly increasing risk for later psychopathology and adult disease.

Primary immunization of premature infants with gestational age <35 weeks: cardiorespiratory complications and C-reactive protein responses associated with administration of single and multiple separate vaccines simultaneously.

OBJECTIVE: To determine the incidence of cardiorespiratory events and abnormal C-reactive protein (CRP) level associated with administration of a single vaccine or multiple separate vaccines simultaneously. STUDY DESIGN: Prospective observational study on 239 preterm infants at > or =2 months of age in the neonatal intensive care unit (NICU). Each infant received either a single vaccine or multiple vaccines on one day. CRP levels and cardiorespiratory manifestations were monitored for 3 days following immunization. RESULTS: Abnormal elevation of CRP level occurred in 85% of infants administered multiple vaccines and up to 70% of those given a single vaccine. Overall, 16% of infants had vaccine-associated cardiorespiratory events within 48 hours postimmunization. In logistic regression analysis, abnormal CRP values were associated with multiple vaccines (OR, 15.77; 95% CI 5.10-48.77) and severe intraventricular hemorrhage (IVH) (OR, 2.28; 95% CI 1.02-5.13). Cardiorespiratory events were associated marginally with receipt of multiple injections (OR, 3.62; 95% CI 0.99-13.25) and significantly with gastroesophageal reflux (GER) (OR, 4.76; 95% CI 1.22-18.52). CONCLUSION: CRP level is expected to be elevated in the 48 hours following immunization. In a minority of infants immunized, cardiorespiratory events were associated with presumed need for intervention. Underlying medical conditions and possibly multiple injections are associated with cardiorespiratory events. Precautionary monitoring following immunizations is warranted.

Impact of maternal substance use during pregnancy on childhood outcome.

The impact of maternal substance abuse is reflected in the 2002-2003 National Survey on Drug Use and Health. Among pregnant women in the 15-44 age group, 4.3%, 18% and 9.8% used illicit drugs, tobacco and alcohol, respectively. Maternal pregnancy complications following substance use include increases in sexually transmitted disorders, placental abruption and HIV-positive status. Effects on the neonate include a decrease in growth parameters and increases in central nervous system and autonomic nervous system signs and in referrals to child protective agencies. In childhood, behavioral and cognitive effects are seen after prenatal cocaine exposure; tobacco and alcohol have separate and specific effects. The ongoing use of alcohol and tobacco by the caretaker affects childhood behavior. Therefore, efforts should be made to prevent and treat behavioral problems as well as to limit the onset of drug use by adolescent children born to women who use drugs during pregnancy.

Impact of prenatal cocaine exposure on child behavior problems through school age.

OBJECTIVE: We examined the trajectory of childhood behavior problems after prenatal cocaine exposure. METHODS: The Maternal Lifestyle Study, a longitudinal cohort study, enrolled children between 1993 and 1995 at 4 centers. Prenatal cocaine exposure was determined from mothers who admitted use and/or meconium results. Exposed children were matched with a group of nonexposed children within site and by gestational age, gender, race, and ethnicity. The study began at the 1-month corrected age with a total of 1388 children enrolled. A total of 1056 were assessed for internalizing, externalizing, and total behavior problems at ages 3, 5, and 7 years using the Child Behavior Checklist. Longitudinal hierarchical linear models were used to determine the effect of prenatal cocaine exposure on behavior problem trajectories while controlling for other prenatal exposures; time-varying covariates, including ongoing caregiver use of legal and illegal substances; demographic factors; family violence; and caregiver psychological distress. RESULTS: High prenatal cocaine exposure was associated with the trajectory of internalizing, externalizing, and total behavior problems; these effects were independent of and less than the significant combined effect of prenatal and postnatal tobacco and alcohol exposures. Caregiver depression and family violence had independent negative influence on all behavior outcomes. CONCLUSIONS: Prenatal cocaine exposure has a negative impact on the trajectories of childhood behavior outcomes. When they co-occur with prenatal cocaine exposure, prenatal and postnatal tobacco and alcohol exposures have added negative effects on behavior outcomes.

Low birth weight and preterm births: etiologic fraction attributable to prenatal drug exposure.

OBJECTIVES: To determine the factors that would increase the likelihood of outcomes: low birth weight (LBW), preterm births and intrauterine growth restriction (IUGR). STUDY DESIGN: Secondary data analysis from a multi-center study. Risk factors for each outcome were derived from logistic regression models. Odds ratios (OR), 95% confidence intervals, and population-attributable risk proportions (PAR%) were estimated. RESULTS: Prenatal cocaine exposure increased the likelihood of LBW (OR: 3.59), prematurity (OR: 1.25), and IUGR (OR: 2.24). Tobacco, but not marijuana, significantly influenced these outcomes. Alcohol had an effect on LBW and IUGR. Etiologic fractions (PAR%) attributable to tobacco for LBW, prematurity, and IUGR were 5.57, 3.66, and 13.79%, respectively. With additional drug exposure including cocaine, estimated summary PAR% increased to 7.20% (LBW), 5.68% (prematurity), and 17.96% (IUGR). CONCLUSION: Disease burden for each outcome increases with each added drug exposure; however, etiologic fraction attributable to tobacco is greater than for cocaine.

Predictors of motor development in children prenatally exposed to cocaine.

The current study examined the pattern of motor development across the first 18 months of life in infants with in utero exposure to cocaine to determine how prenatal drug effects and level of exposure relates to motor development. Motor development was examined at 1, 4, 12, and 18 months of age (corrected for prematurity). Infants were divided into cocaine exposed (n=392) and comparison (n=776) groups. Exposure status was determined by meconium assay and maternal self-report with alcohol, marijuana, tobacco, and opiates present in both groups. Motor skills were assessed at 1 month using the NICU Network Neurobehavioral Scale (NNNS), at 4 months using the posture and fine motor assessment of infants (PFMAI), at 12 months using the Bayley Scales of Infant Development-Second Edition (BSID-II), and at 18 months using the Peabody Developmental Motor Scales (PDMS). Examiners masked to exposure status performed all assessments. Motor scores were converted to standard (z) scores, and hierarchical linear modeling (HLM) was used to examine the change in motor skills from 1 to 18 months of age. Infants with exposure to cocaine showed low motor skills at their initial status of 1 month but displayed significant increases over time. Both higher and lower levels of tobacco use related to poorer motor performance on average. Heavy cocaine use related to poorer motor performance as compared to no use, but there were no effects of level of cocaine use on change in motor skills.

Brain-type natriuretic peptide in the diagnosis and management of persistent pulmonary hypertension of the newborn.

OBJECTIVE: The diagnosis of persistent pulmonary hypertension (PPHN) can often be difficult to make, especially in a clinical setting in which pediatric echocardiography is not readily available. A noninvasive test that could differentiate PPHN from other cardiorespiratory disease would be very useful in the early management of the disease, because it would allow rapid identification of those infants at greatest risk of requiring the services of a level 3 nursery. Brain-type natriuretic peptide (BNP) is an endogenous peptide hormone secreted by the cardiac ventricles in response to increased wall stress and related ventricular filling pressures. The purpose of this study was to determine if BNP levels are elevated in newborns with PPHN and therefore may be used as a marker for differentiating PPHN from other forms of respiratory disease during the early newborn period. METHOD: We used a prospective cohort design with 3 groups. One group was diagnosed with PPHN by clinical and echocardiographic criteria (PPHN group: n = 15). The second group had been diagnosed with respiratory disease; however, PPHN had been ruled out by having no evidence of elevated pulmonary pressure by echocardiography (RD group: n = 17). The third group had no respiratory disease and was breathing room air (RA group: n = 15). BNP levels were measured with a point-of-care fluorescence immunoassay at various time intervals between birth and 150 hours of life. RESULTS: There were no differences between groups for birth weight, gestational age, gender, race, Apgar scores at 1 minute, or age at time of initial blood sampling. Initial BNP levels (pg/mL) were elevated in the PPHN group relative to both the RA and RD groups (median [25%, 75%]: PPHN group = 1610 [1128, 1745]; RD group = 132 [76, 327]; RA group = 248 [127, 395]). There was no difference in the initial BNP level between the RA and RD groups. BNP levels remained elevated in the PPHN group over both groups for the first 4 days of life. BNP levels correlated with the gradient of the tricuspid regurgitation jet and with the ratio of tricuspid regurgitation jet gradient to mean blood pressure. BNP levels were not affected by administration of dopamine or dobutamine. BNP weakly correlated with the oxygenation index but not with the alveolar-arterial oxygenation gradient. CONCLUSIONS: Our findings indicate that BNP levels are elevated in infants with PPHN but not in infants with other forms of respiratory distress not associated with PPHN. Elevated BNP levels in term or near-term infants with respiratory distress should increase the suspicion of PPHN. Serial determination may also be helpful in monitoring the clinical course of such infants.

Chronic prenatal exposure to cocaine alters cerebrovascular responses in newborn pigs.

Maternal cocaine abuse may increase the incidence of perinatal asphyxia. In nonexposed asphyxiated neonates, decreased cerebrospinal fluid (CSF) cAMP concentrations are associated with poor neurological outcome. On the other hand, cocaine increases central nervous system (CNS) cAMP. Therefore, we hypothesized that in utero cocaine exposure may increase brain cAMP and thereby preserve cerebrovascular responses to cAMP-dependent stimuli following asphyxia. Pregnant pigs received either cocaine (1 mg/kg, i.v.) twice weekly during the last trimester or normal saline vehicle (sham-control) and were allowed to deliver vaginally at term. Cranial windows were implanted in the newborn pigs within the first week of life and used to collect CSF for cAMP determinations and to assess changes in pial arteriolar diameters (PAD). In the first part of the study, pial arteriolar responses to different vasodilator and vasoconstrictor stimuli were evaluated in piglets prior to asphyxia (n = 20). In newborn pigs exposed to cocaine, cerebrovascular responses to hypercapnia and norepinephrine were significantly exaggerated compared to controls. Then, piglets were randomly selected for the second part of the study that involved prolonged asphyxia (n = 12). In cocaine-exposed but not sham-control piglets, CSF cAMP increased markedly during asphyxia. In the sham piglets, but not the cocaine-exposed piglets, CSF cAMP fell progressively below the baseline during recovery. Cerebrovascular reactivity to cAMP-dependent stimuli (hypercapnia and isoproterenol) was preserved during recovery from asphyxia in the cocaine-exposed piglets but significantly attenuated in the sham controls. We conclude that piglets with chronic prenatal exposure to cocaine show exaggerated cerebrovascular responses to vasogenic stimuli and preserved cAMP-dependent cerebral vasoreactivity following asphyxia.