Background: Neonatal Abstinence Syndrome (NAS), a manifestation of the widespread opioid epidemic, has plagued our country, and particularly the region of Northeast Tennessee, for quite some time now. One question among many that seems to baffle almost everyone involved in research on the topic at hand is that why do only 35-40% of opioid exposed pregnancies result in NAS requiring medication while sparing the rest. Is there some discriminatory factor other than in utero opioid exposure involved? Thus, in light of this knowledge, we wanted to investigate whether birth weight at the time of delivery can influence the development of NAS; that is, are neonates of a low birth weight or high birth weight (with respect to gestational age thresholds) more likely to develop NAS. Methods: Therefore, we conducted a retrospective chart analysis of all deliveries within the Mountain States Health Alliance System over a 5 years period between July 1, 2011- June 30, 2016 at all 5 delivery sites in Northeast Tennessee and Southwest Virginia (N=18,728). Out of this sample size, we identified 2,392 at-term newborns as positive for prenatal opioid exposure, and then we stratified them into 2 categories: birth weight ≤3.5kg (proxy for low or average birth weight with respect to gestational age thresholds) and birth weight ≥3.5kg (proxy for high birth weight with respect to gestational age thresholds). Thereafter, we ran SPSS statistical analyses involving chi square, t tests, and logistic regression to assess whether one birth weight group was more likely to have a higher incidence rate of NAS compared to the other birth weight group. Results: We found that even after controlling for significant confounders such as marital status, race, and pregnancy smoking, benzodiazepine, and marijuana use, infants who were in the low to average birth weight group (≤3.5kg in this study) were almost twice as likely (statistically significant adjusted odds ratio of 1.95) to develop NAS compared to infants who were in the high birth weight group (≥3.5kg in this study). Our study helps shed some important light on the discriminatory factors for NAS development, with birth weight being a significantly associated clinical factor as we now know. Discussion & Implications: Unfortunately, the mechanism for the transport of opioids across the placenta is complicated, and poorly understood. There may be more ‘unbound or free opioids’ available in infants of low to average birth weight (with respect to gestational age thresholds) compared to infants of high birth weight (with respect to gestational age thresholds) resulting in a higher incidence of NAS in the former population. It is more of a speculation rather than a conclusion to explain the results of our study. However, being equipped with this knowledge that opioid exposed neonates of low to average birth weight (with respect to gestational age thresholds) have a higher risk of developing NAS will allow physicians to identify infants with a higher risk for NAS early, and this will subsequently lead to better outcomes and reduced severity in cases of NAS.

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Prenatal opioid exposure has been studied in relation to infants' medical outcomes. However, large gaps exist in the literature supporting early identification of atypical neurobehavior and motor development of infants with prenatal opioid exposure. The purpose of the study was to investigate whether prenatal opioid exposure has a negative influence on a newborn infant’s neurobehavior and motor development to aid in the early identification of potential delays. Using a prospective quasi experimental design, infants motor development using the Test of Infant Motor Performance (TIMP) and neurobehavior using the NICU Neonatal Network Scale (NNNS) was assessed on 58 infants in a hospital setting. Even after statistically controlling for covariates both the TIMP and the six out of twelve subscales of the NNNS: attention, handling, self-regulation, arousal, excitability, and stress were significantly different between the two groups of infants. Infants’ TIMP z-scores were significantly correlated with the NNNS subscales of attention, handing, self-regulation, arousal, excitability, hypertonicity, non-optimal reflexes, and stress. The findings highlight the similarities between the two groups and the outcome measures used for early identification of infants at-risk for delays following prenatal opioid exposure. The neonatal outcomes described here, including growth deficits, motor delays and altered neurobehavior are critical given their association with longer-term health and developmental impacts.