Lakshmi D. Katikaneni

THE IMPACT OF PRENATAL DRUG EXPOSURE ON THE NEONATE

Several social or recreational drugs singly or together have demonstrated effects on the fetus and neonate, with those effects extending into adulthood. The use of recreational drugs during pregnancy remains a major health problem, with adverse effects including higher rates of fetal distress and demise, lower Apgar scores, growth retardation, and adverse neurodevelopmental outcome. Ethanol has the most profound effects, with physical stigmata of the drug seen in one third of exposed infants. In children without the affected physical appearance, profound neurodevelopmental sequelae have been demonstrated. Other drugs, such as cocaine, heroin, amphetamines, and nicotine, have been associated with impaired fetal growth and acute withdrawal during the neonatal period. Subsequently, these infants and children have an increased risk for altered neurodevelopment and long-term health status. Long-term follow-up and assessment are essential. The risk of neonatal withdrawal or abstinence syndrome is greatest with narcotic drugs but has been found to occur in neonates following exposure to cocaine, nicotine, and amphetamines. Early treatment with tincture of opium, paregoric, or phenobarbital is crucial. Assessment of the overall health status of the infant should include growth parameters, signs and symptoms of infection (especially hepatitis, syphilis, and immunodeficiency viruses), and neurobehavioral function. Such assessments should not be limited to the newborn period, as neurodevelopmental sequelae may not be manifest until later in infancy and childhood. In addition, evaluation of the social milieu is warranted because of the increased risk for neglect and abuse of drug-exposed infants and children. Early intervention, maternal drug rehabilitation treatment, and parenting classes are frequently prescribed, but their efficacy is variable. Further investigations should study the potential benefits of these recommendations.

The use of hypothermia: a role in the treatment of neonatal asphyxia?

Perinatal asphyxia remains one of the most devastating neurologic processes. Although the understanding of the pathophysiology after perinatal asphyxia is extensive, there are few therapeutic interventions available to prevent or even mitigate the devastating process that unfolds after injury. The search for a safe and efficacious therapy has prompted scientists and clinicians to consider various promising therapies. One such therapy is therapeutic hypothermia. On the basis of adult, pediatric, and animal research, there is increasing evidence to suggest that therapeutic hypothermia may be an effective intervention to lessen the secondary neuronal injury that ensues after a hypoxic-ischemic insult. In this article the historic and modern-day uses of therapeutic hypothermia are first reviewed. The pathophysiology of neonatal asphyxia is examined next, with emphasis on the changes that occur when therapeutic hypothermia is implemented. Potential side-effects of the therapy in the neonate and the debate over systemic vs selective hypothermia are discussed. Lastly, although hypothermia as a potential treatment modality for neonates with hypoxic-ischemic encephalopathy is supported by numerous studies, the need for well-designed multicenter trials with detailed patient entry criteria and therapeutic conditions is emphasized.

Caretaker Perception of Child Vulnerability Predicts Behavior Problems in NICU Graduates

This study explores parental perception of child vulnerability (PPCV) and parent overprotection (POP) and their relationship to neonatal medical problems, child development and behavior. Participants included 90 lower income parents of NICU graduates ages 22–81 months consecutively enrolled at a high-risk neonatal developmental follow-up clinic. Parents completed the Child Vulnerability Scale (CVS), the Parent Protection Scale (PPS) and the Child Behavior Checklist (CBCL) regarding their children. Step-wise regression analysis revealed the CVS as the sole predictor of child behavior, accounting for 13% of the variance in the CBCL Total T-score (R2 = .13,

Infant screening : The usefulness of the Bayley Infant Neurodevelopmental Screener and the Clinical Adaptive Test/Clinical Linguistic Auditory Milestone Scale

be = .86, p < .006). Neonatal medical problems, Child DQ, and most parental demographic variables did not correlate with CVS or PPS scores. A significant correlation between CVS and the separation subscale of the PPS was noted (r = .31, p < .01). We conclude that NICU graduates perceived vulnerable by their caretakers have significant behavioral difficulties compared to those perceived as not vulnerable. Future research should address early parental antecedents of PPCV, the persistence of PPCV, and its effects on behavioral outcomes.

Neonatal Hair Analysis for Benzoylecgonine: A Sensitive and Semiquantitative Biological Marker for Chronic Gestational Cocaine Exposure

&NA; We assessed the usefulness of the Bayley Infant Neurodevelopmental Screener (BINS) and the Clinical Adaptive Test/Clinical Linguistic Auditory Milestone Scale (CAT/CLAMS) for screening high‐risk infant populations in a sample of 78 infants followed after premature birth and/or perinatal insults. Both measures were highly correlated with the Bayley Scales of Infant Development‐II, but sensitivity and specificity analyses revealed disparities related to the tests administered and the cutoffs used. The BINS had optimal sensitivity (true positives) of 90% when referral was made for a BINS score of high or moderate. The CAT/CLAMS had excellent specificity (true negatives) of 95% to 98% but poor sensitivity (5%‐36%). Until the cutoff issue can be clarified, clinicians should be cautious in using the CAT/CLAMS as the primary screening instrument in settings in which early identification of infants with developmental problems is the main goal.

Ultrasound assessment of intrauterine growth restriction: relationship to neonatal body composition

Hair analysis for the major metabolite of cocaine, benzoylecgonine (BZE) was performed in a cohort of 251 predominantly African-American newborns utilizing a modified radioimmunoassay (RIA) (Abuscreen Roche Laboratories, Nutley, N.J., USA). Maternal drug intake was confirmed by positive urine drug screen for cocaine metabolites at the time of delivery. The BZE concentrations reported here are the composites of both the parent compound cocaine (hydrolyzed to BZE) and the native BZE metabolized by the patient and deposited in the hair follicle. Hair analysis as an indicator for gestational cocaine exposure had a sensitivity of 88%, specificity of 100%, positive predictive value of 100%, and negative predictive value of 85%. The range of BZE was 99–23,300 ng/g of hair, with 79% having hair BZE levels <5,000 ng/g of hair. The BZE RIA was confirmed by gas chromatography and mass spectrometry (GC/MS). Of the 18 mother/infant pairs tested, the hair BZE ratio (maternal to neonatal) varied from 0.5 to 8.9 in 13 pairs. In spite of maternal high hair BZE levels, 5 newborns had no evidence of hair BZE, stressing the importance of the placental role for the cocaine transfer to the fetus. After controlling for gestational age, higher BZE levels significantly correlated with smaller head circumference (p < 0.03) and birth weight (p < 0.01).

Customized versus population-based growth curves: Prediction of low body fat percent at term corrected gestational age following preterm birth

OBJECTIVE The objective of the study was to compare prenatal ultrasound parameters for intrauterine growth restriction (IUGR) with newborn percent body fat (%BF). STUDY DESIGN This was a prospective study of 87 pregnancies followed with ultrasound. Subjects were categorized into 3 groups: estimated fetal weight (EFW) less than the 10th percentile, abdominal circumference (AC) less than the fifth percentile, and normal biometry. Neonatal %BF by air displacement plethysmography was compared between each group using multivariable analyses. RESULTS The %BF in the EFW less than the 10th percentile group (5.1 ± 2.9%) was significantly lower than either AC less than the fifth percentile (9.5 ± 3.3%) or normal groups (11.6 ± 5.6%). EFW less than the 10th percentile best predicted %BF by regression model. Neonatal morbidity was not significantly higher in the EFW less than the 10th percentile group. CONCLUSION Newborn %BF was significantly lower in infants with EFW less than the 10th percentile compared with AC less than the fifth percentile, an intermediate finding. An AC less than the fifth percentile on ultrasound does not reflect the same severity of IUGR as EFW less than the 10th percentile.

Vitamin D insufficiency in neonatal hypoxic-ischemic encephalopathy

Objective: Compare customized versus population-based growth curves for identification of small-for-gestational-age (SGA) and body fat percent (BF%) among preterm infants. Methods: Prospective cohort study of 204 preterm infants classified as SGA or appropriate-for-gestational-age (AGA) by population-based and customized growth curves. BF% was determined by air-displacement plethysmography. Differences between groups were compared using bivariable and multivariable linear and logistic regression analyses. Results: Customized curves reclassified 30% of the preterm infants as SGA. SGA infants identified by customized method only had significantly lower BF% (13.8 ± 6.0) than the AGA (16.2 ± 6.3, p = 0.02) infants and similar to the SGA infants classified by both methods (14.6 ± 6.7, p = 0.51). Customized growth curves were a significant predictor of BF% (p = 0.02), whereas population-based growth curves were not a significant independent predictor of BF% (p = 0.50) at term corrected gestational age. Conclusion: Customized growth potential improves the differentiation of SGA infants and low BF% compared with a standard population-based growth curve among a cohort of preterm infants.

Humoral Immunity to Candida albicans (Anti-Candida Antibody Titers) in Premature Infants

Background:Vitamin D has neuroprotective and immunomodulatory properties, and deficiency is associated with worse stroke outcomes. Little is known about effects of hypoxia–ischemia or hypothermia treatment on vitamin D status in neonates with hypoxic–ischemic encephalopathy (HIE). We hypothesized vitamin D metabolism would be dysregulated in neonatal HIE altering specific cytokines involved in Th17 activation, which might be mitigated by hypothermia.Methods:We analyzed short-term relationships between 25(OH) and 1,25(OH)2 vitamin D, vitamin D binding protein, and cytokines related to Th17 function in serum samples from a multicenter randomized controlled trial of hypothermia 33 °C for 48 h after HIE birth vs. normothermia in 50 infants with moderate to severe HIE.Results:Insufficiency of 25(OH) vitamin D was observed after birth in 70% of infants, with further decline over the first 72 h, regardless of treatment. 25(OH) vitamin D positively correlated with anti-inflammatory cytokine IL-17E in all HIE infants. However, Th17 cytokine suppressor IL-27 was significantly increased by hypothermia, negating the IL-27 correlation with vitamin D observed in normothermic HIE infants.Conclusion:Serum 25(OH) vitamin D insufficiency is present in the majority of term HIE neonates and is related to lower circulating anti-inflammatory IL-17E. Hypothermia does not mitigate vitamin D deficiency in HIE.

Neonatal hair benzoylegonine (BZE) levels: A predictor for neurodevelopment (ND) at 3 years in children exposed to cocaine in utero (CECU)

ABSTRACT: Although the role of humoral and cell mediated immunity in neonatal defense against Candida infections is not precisely defined, one of the contributing immunologic factors may be a lack of decreased specific passive humoral immunity. Thus, serum samples from the umbilical veins of 98 term gestation and 105 premature neonates (majority <33 wk gestation) and their mothers (n = 100) were tested for the presence of hemagglutinating antibodies to commercially available Candida antigen. The titers of Candida antibodies (mean log2 ± SEM) were significantly higher in 11 term neonates (4.73 ± 0.69) of mothers with high antibody titers (5.18 ± 0.40, <0.001) as contrasted with 87 normal term (2.38 ± 0.15) and 105 premature (2.87 ± 0.15) infants with normal mothers (1.96 ± 0.13 and 3.31 ± 0.26, respectively). Contrary to our belief 81% of term infants and all of the preterm infants (majority <33 wk gestation) had passive specific anti‐candida antibody titers <1:16.