Recent rise in rates of opiate replacement therapy among pregnant women have resulted in increasing number of infants requiring treatment for neonatal abstinence syndrome. Short- and long-term developmental outcomes associated with prenatal opiate exposure are discussed, including symptoms and severity of neonatal abstinence syndrome (NAS), and early cognitive and motor delays. Maternal and infant risk factors are discussed, and include patterns of maternal substance use during pregnancy, genetic risk, polysubstance exposure pharmacologic treatment for NAS and breastfeeding. The importance of characterizing corollary environmental risk factors is also considered.

Background and Objectives There is significant variability in severity of neonatal abstinence syndrome (NAS) due to in-utero opioid exposure. Our previous study identified single nucleotide polymorphisms (SNPs) in the prepronociceptin (PNOC) and catechol-O-methyltransferase (COMT) genes that were associated with differences in NAS outcomes. This study looks at the same SNPs in PNOC and COMT in an independent cohort in an attempt to replicate previous findings. Methods For the replication cohort, full-term opioid-exposed newborns and their mothers (n=113 pairs) were studied. A DNA sample was obtained and genotyped for 5 SNPs in the PNOC and COMT genes. The association of each SNP with NAS outcomes (length of hospitalization, need for pharmacologic treatment, and total opioid days) was evaluated, with an experiment-wise significance level set at α<0.003 and point-wise level of α<0.05.. SNP associations in a combined cohort of n=199 pairs (replication cohort plus 86 pairs previously reported), were also examined. Results In the replication cohort, mothers with the COMT rs4680 G allele had infants with a reduced risk for treatment with 2 medications for NAS (adjusted OR=0.5, p=0.04), meeting point-wise significance. In the combined cohort, infants with the PNOC rs4732636 A allele had a reduced need for medication treatment (adjusted OR 2.0, p=0.04); mothers with the PNOC rs351776 A allele had infants who were treated more often with 2 medications (adjusted OR 2.3, p=0.004) with longer hospitalization by 3.3 days (p=0.01). Mothers with the COMT rs740603 A allele had infants who were less often treated with any medication (adjusted OR 0.5, p=0.02). Though all SNP associations all met point wise and clinical significance, they did not meet the experiment-wise significance threshold. Conclusions and Scientific Significance We found differences in NAS outcomes depending on PNOC and COMT SNP genotype. Further testing in a larger sample is warranted. This has important implications for prenatal prediction and personalized treatment regimens for infants with NAS.

Objective: Standardized developmental screening tools are important for the evaluation and management of developmental disorders in children with congenital heart disease (CHD). However, psychometric properties and clinical utility of screening tools, such as the Ages and Stages Questionnaires, Third Edition (ASQ-3), have not been examined for the CHD population. We hypothesized the ASQ-3 would be clinically useful for this population. Study Design: ASQ-3 developmental classifications for 163 children with CHD at 6, 12, 24 and/or 36 months of age were compared to those obtained from concurrent developmental testing with the Bayley Scales of Infant and Toddler Development, Third Edition. Results: When ASQ-3 screening failure was defined as ≥ 1 standard deviations below the normative mean, specificity (≥81.9%) and negative predictive value (≥ 81.0%) were high across ASQ-3 areas. Sensitivity was high for gross motor (79.6%), increased with age for communication (35.7%−100%), and generally decreased with age for problem solving (73.1%−50.0%). When ASQ-3 screening failure was defined as ≥ 2 standard deviations below the normative mean, specificity (≥93.6%) and positive predictive value (≥74.5%) were generally high across ASQ-3 areas, but sensitivity was low (31.1%) to fair (62.8%). The ASQ-3 improved accuracy in predicting delays over clinical risk factors alone. Conclusions: The ASQ-3 appears to be a clinically useful tool for screening development in children with CHD, although utility varied based on developmental area and time point. Clinicians are encouraged to refer children scoring ≥ 1 standard deviation below the normative mean on any ASQ-3 area for formal developmental evaluation.

Learning Health Networks (LHN) improve the well‐being of populations by aligning clinical care specialists, technology experts, patients and patient advocates, and other thought leaders for continuous improvement and seamless care delivery. A novel LHN focused on pediatric transplantation, the Starzl Network for Excellence in Pediatric Transplantation (SNEPT), convened its inaugural meeting in September 2018. Clinical care team representatives, patients, and patient families/advocates partnered to take part in educational sessions, pain point exercises, and project identification workshops. Participants discussed the global impact of transplant from both a population and individual perspective, identifying challenges and opportunities where the Starzl Network could work to improve outcomes at scale across a variety of transplant‐related conditions.

Use and abuse of prescription opioids and concomitant increase in Neonatal Abstinence Syndrome (NAS), a condition that may lead to protracted pharmacological treatment in more than 60% of infants, has tripled since 2000. This study assessed neurobehavioral development using the NICU Network Neurobehavioral Scale in six-week old infants with prenatal methadone exposure who did (NAS+; n=23) or did not (NAS−; n=16) require pharmacological treatment for NAS severity determined by Finnegan Scale. An unexposed, demographically similar group of infants matched for age served as comparison (COMP; n=21). NAS+, but not NAS− group, had significantly lower scores on the regulation (p<.01) and quality of movement (p<.01) summary scales than the COMP group. The NAS+ and NAS− groups had higher scores on the stress-abstinence scale than the COMP group (p<.05). NAS diagnosis (NAS+) was associated with poorer regulation and quality of movement at six weeks of age compared to infants without prenatal methadone exposure from the same demographic.