Background: Prenatal exposure to organophosphate (OP) insecticides, a widely-used class of pesticides, may be associated with decreased gestational age and lower birthweight. Single nucleotide polymorphisms in paroxanase (PON1) enzyme genotypes may modify the relationships between OP exposure and perinatal outcomes. Objectives: To examine the relationship of prenatal OP insecticide exposure, measured using urinary dialkyl phosphate (DAP) metabolite concentrations, with gestational age and birthweight. Methods: We measured the concentrations of six nonspecific DAP metabolites of OP insecticides in two maternal spot urine samples collected in a prospective birth cohort. We performed multivariable regression to examine associations between the sum of six DAP concentrations (ΣDAP) with gestational age and birthweight. We also examined whether these associations differed according to infant PON1192 and PON1108 genotypes. Results: Among 306 mother/infant dyads, a 10-fold increase in ΣDAP concentrations was associated with a decrease in covariate-adjusted gestational age (-0.5 weeks; 95% confidence interval [CI]:-0.8,-0.1), and birthweight (-151g; CI:-287,-16); the decrements in birthweight were attenuated after adjusting for gestational age. The relationship between ΣDAP concentrations and gestational age was stronger for white (-0.7 weeks, CI:-1.1,-0.3) than black (-0.1 weeks, 95% CI:-0.9, 0.6) newborns. In contrast, there was a greater decrease in birthweight with increasing urinary ΣDAP concentrations for black (-188g, CI:-395, 19) than white (-118g, CI:-296, 60) newborns. Decrements in birthweight and gestational age associated with ΣDAP concentrations were greatest among infants with PON192QR and PON108CT genotypes. Conclusions: Prenatal urinary ΣDAP concentrations were associated with shortened gestation and reduced birthweight in this cohort, but the effects differed by race/ethnicity and PON1192/108 genotypes.

OBJECTIVES: To compare 18- to 22-month cognitive scores and neurodevelopmental impairment (NDI) in 2 time periods using the National Institute of Child Health and Human Development's Neonatal Research Network assessment of extremely low birth weight infants with the Bayley Scales of Infant Development, Second Edition (Bayley II) in 2006-2007 (period 1) and using the Bayley Scales of Infant and Toddler Development, Third Edition (Bayley III), with separate cognitive and language scores, in 2008-2011 (period 2). STUDY DESIGN: Scores were compared with bivariate analysis, and regression analyses were run to identify differences in NDI rates. RESULTS: Mean Bayley III cognitive scores were 11 points higher than mean Bayley II cognitive scores. The NDI rate was reduced by 70%(from 43% in period 1 to 13% in period 2; P <.0001). Multivariate analyses revealed that Bayley III contributed to a decreased risk of NDI by 5 definitions: cognitive score <70 and <85, cognitive or language score <70; cognitive or motor score <70, and cognitive, language, or motor score <70 (P <.001). CONCLUSION: Whether the Bayley III is overestimating cognitive performance or whether it is a more valid assessment of emerging cognitive skills than the Bayley II is uncertain. Because the Bayley III identifies significantly fewer children with disability, it is recommended that all extremely low birth weight infants be offered early intervention services at the time of discharge from the neonatal intensive care unit, and that Bayley scores be interpreted with caution.

OBJECTIVE:Examine the prevalence, patterns, and persistence of parent-reported sleep problems during the first 3 years of life.METHODS:Three hundred fifty-nine mother/child pairs participated in a prospective birth cohort study. Sleep questionnaires were administered to mothers when children were 6, 12, 24, and 36 months old. Sleep variables included parent response to a nonspecific query about the presence/absence of a sleep problem and 8 specific sleep outcome domains: sleep onset latency, sleep maintenance, 24-hour sleep duration, daytime sleep/naps, sleep location, restlessness/vocalization, nightmares/night terrors, and snoring.RESULTS:Prevalence of a parent-reported sleep problem was 10% at all assessment intervals. Night wakings and shorter sleep duration were associated with a parent-reported sleep problem during infancy and early toddlerhood (6-24 months), whereas nightmares and restless sleep emerged as associations with report of a sleep problem in later developmental periods (24-36 months). Prolonged sleep latency was associated with parent report of a sleep problem throughout the study period. In contrast, napping, sleep location, and snoring were not associated with parent-reported sleep problems. Twenty-one percent of children with sleep problems in infancy (compared with 6% of those without) had sleep problems in the third year of life.CONCLUSIONS:Ten percent of children are reported to have a sleep problem at any given point during early childhood, and these problems persist in a significant minority of children throughout early development. Parent response to a single-item nonspecific sleep query may overlook relevant sleep behaviors and symptoms associated with clinical morbidity.

Objective:We sought to determine the incidence of necrotizing enterocolitis (NEC) and spontaneous intestinal perforation (SIP) in surviving extremely low-birth-weight (ELBW,<1000 g birth weight) infants and to establish the impact of NEC on outcomes by hospital discharge and at 18 to 22 months adjusted age in a large, contemporary, population-based practice.Study Design:Hospital outcome data for all ELBW infants born in the greater Cincinnati region from 1998 to 2009 were extracted from the National Institute of Child Health Neonatal Research Network Database. Neurodevelopmental outcome at 18 to 22 months was assessed using Bayley Scales of Infant Development-II scores for Mental Developmental Index and Psychomotor Developmental Index. Multivariable logistic regression was used and adjusted odds ratios reported to control for confounders.Result:From 1998 to 2009, ELBW infants accounted for 0.5% of the 352 176 live-born infants in greater Cincinnati. The incidence of NEC was 12%, with a 50% case-fatality rate. Death before discharge, morbid complications of prematurity and neurodevelopmental impairment were all increased among infants diagnosed with NEC. Infants with surgical NEC and SIP had a higher incidence of death, but long-term neurodevelopmental outcomes were not different comparing surviving ELBW infants with medical NEC, surgical NEC and SIP.Conclusion:Although ELBW infants comprise a very small proportion of live-born infants, those who develop NEC and SIP are at an increased risk for death, morbid complications of prematurity and neurodevelopmental impairment. No significant differences in neurodevelopmental outcomes were observed between the medical and surgical NEC and SIP groups.Journal of Perinatology advance online publication, 8 December 2011; doi:10.1038/jp.2011.176.

OBJECTIVES To estimate the impact of gestational and childhood bisphenol A (BPA) exposures on behavior and executive function at 3 years of age and to determine whether child gender modified those associations. METHODS We used a prospective birth cohort of 244 mothers and their 3-year-old children from the greater Cincinnati, Ohio, area. We characterized gestational and childhood BPA exposures by using the mean BPA concentrations in maternal (16 and 26 weeks of gestation and birth) and child (1, 2, and 3 years of age) urine samples, respectively. Behavior and executive function were measured by using the Behavior Assessment System for Children 2 (BASC-2) and the Behavior Rating Inventory of Executive Function-Preschool (BRIEF-P). RESULTS BPA was detected in >97% of the gestational (median: 2.0 μg/L) and childhood (median: 4.1 μg/L) urine samples. With adjustment for confounders, each 10-fold increase in gestational BPA concentrations was associated with more anxious and depressed behavior on the BASC-2 and poorer emotional control and inhibition on the BRIEF-P. The magnitude of the gestational BPA associations differed according to child gender; BASC-2 and BRIEF-P scores increased 9 to 12 points among girls, but changes were null or negative among boys. Associations between childhood BPA exposure and neurobehavior were largely null and not modified by child gender. CONCLUSIONS In this study, gestational BPA exposure affected behavioral and emotional regulation domains at 3 years of age, especially among girls. Clinicians may advise concerned patients to reduce their exposure to certain consumer products, but the benefits of such reductions are unclear.

OBJECTIVE To examine the association of prenatal exposure to bisphenol A and select common phthalates with infant neurobehavior measured at 5 weeks. METHODS We compared the concentration of maternal urinary metabolites of bisphenol A and phthalates at two distinct time points in pregnancy (16w, 26w) with scores on the NICU Network Neurobehavioral Scale (NNNS) at 5 weeks of age in a cohort of 350 mother/infant pairs. RESULTS Prenatal exposure to BPA was not significantly associated with neurobehavioral outcomes at 5 weeks. Significant associations between prenatal exposure to measured phthalates and infant neurobehavioral outcomes differed by type of phthalate and were only seen with exposure measured at 26 weeks. Higher total di-butyl phthalate (DBP) metabolites at 26w were associated with improved behavioral organization evidenced by decreased arousal (p=.04), increased self-regulation (p=.052), and decreased handling (p=.02). In males, higher total di-2-ethylhexyl phthalate (DEHP) metabolites at 26w were associated with more nonoptimal reflexes (p=.02). CONCLUSION The association between prenatal phthalate exposure and infant neurobehavior differed by type of phthalate and was evident only with exposure measured at 26w. Prenatal exposure to DBP was associated with improved behavioral organization in 5-week-old infants. Prenatal exposure to DEHP was associated with nonoptimal reflexes in male infants. There was no evidence of an association between prenatal BPA exposure and infant neurobehavior.

OBJECTIVE High-risk infant follow-up programs have the potential to act as multipurpose clinics by providing continuity of clinical care, education of health care trainees and facilitating outcome data research. Currently there are no nationally representative data on high-risk infant follow-up practices in the United States. The objective of this study is to collect information about the composition of high-risk infant follow-up programs associated with academic centers in the United States, with respect to their structure, function, funding resources and developmental assessment practices, and to identify the barriers to establishment of such programs. STUDY DESIGN Staff neonatologists, follow-up program directors and division directors of 170 Neonatal Intensive Care Units (NICU) associated with pediatric residency programs were invited to participate in an anonymous online survey from October 2009 to January 2010. RESULT The overall response rate was 84%. Ninety three percent of the respondents have a follow-up program associated with their NICU. Birth weight, gestational age and critical illness in the NICU were the major criteria for follow-up care. Management of nutrition and neurodevelopmental assessments was the most common service provided. Over 70% have health care trainees in the clinic. About 75% of the respondents have the neurodevelopmental outcome data available. Most of the respondents reported multiple funding sources. Lack of personnel and funding were the most common causes for not having a follow-up program. CONCLUSION High-risk infant follow-up programs associated with academic centers in the United States are functioning as multidisciplinary programs providing clinical care, trainee education and facilitating outcomes research.

CONTEXT Most of the U.S. population is exposed to the high-production-volume chemical bisphenol A (BPA), but targetable sources of exposure remain to be determined. Animal studies and one human study suggest that BPA is a neurotoxicant. CASE PRESENTATION A mother in the Health Outcomes and Measures of the Environment (HOME) Study, a prospective birth cohort examining prenatal and postnatal environmental toxicants and childhood health outcomes, had a urinary BPA concentration of 583 µg/g creatinine at 27 weeks of pregnancy, which was the highest concentration observed in this cohort (median, 2.0 µg/g creatinine) and the general population. We used prenatal questionnaire data and a follow-up interview to identify potential sources of exposure that included daily plastic use and consumption of canned beverages and foods. Her male infant had a normal newborn neurobehavioral assessment but presented with abnormalities at the 1-month examination that prompted physician referral. Subsequently, the child had normal neurobehavioral testing results at annual evaluations from 1 to 5 years of age. DISCUSSION Investigations into sources of high gestational urinary BPA concentrations provide an opportunity to identify potential targets for reduction of BPA exposure. This case highlights a potential link between gestational BPA exposure and transient neurobehavioral changes that is hypothesis generating and can serve to alert researchers to potential areas for examination in future studies. RELEVANCE TO CLINICAL PRACTICE It is important to educate health care practitioners regarding potential sources of BPA exposure and anticipatory guidance on minimization of exposures during vulnerable periods of development.

OBJECTIVE To assess the effect of examination time on newborn neurobehavioral examinations administered within 48 hours of delivery and to identify the earliest appropriate time for performing the assessment. METHODS We analyzed data from neurobehavioral examinations on 324 newborns using the NICU Network Neurobehavioral Scale (NNNS). Trends over examination time and cumulative percentage within published normal ranges were analyzed to identify the earliest appropriate time for administering the examination. Ordinal logistic regression and multivariate regression were used for testing and defining the earliest appropriate time for administering the examination without being influenced by acute effects of labor and delivery while controlling for several potential confounding factors. RESULTS The arousal, excitability, lethargy, quality-of-movement, hypotonicity, and nonoptimal-reflexes scales were sensitive to timing of the examination. Results of ordinal logistic regression showed that 20 hours after delivery seemed to be the earliest appropriate time for administering newborn NNNS examinations. The proportion of NNNS scores within the normal range increased with time significantly when the examination was made less than 20 hours after delivery (n = 148)(odds ratio: 1.12 [95% confidence interval: 1.02-1.23]), but there was no longer significant association with time of examination after 20 hours (n = 176)(odds ratio: 1.04 [95% confidence interval: 0.99-1.09]). This result was confirmed by multivariate regression. CONCLUSIONS We recommend 20 hours after delivery as the earliest appropriate time for administering newborn NNNS examinations to obtain results reflecting outcomes that are a representative assessment of newborn neurobehavior and not contaminated by acute effects of labor and delivery.