The Fecal Fermentation Profile of Twins and Infants with Opioid Exposure Dawson Brown-Ezell Michelle Johnson PhD, RD, LDN W. Andrew Clark PhD, RD Amy Wahlquist, PhD Introduction: The gut microbiome is believed to have a significant impact on health throughout the lifespan, and the influence of infant nutrition and other environmental factors are of particular interest in its development. The aim of this research project was to learn more about the microbiome and short chain fatty acid (SCFA) composition of toddlers of differing weights, considering birth history, environment, and diet. In East Tennessee, opioid misuse is a growing issue, and a number of participants in this study were exposed in utero. We also hoped to identify related effects on infant’s SCFA composition. Finally, it has been concluded that twins share a variety of traits, but much about their microbiome is unknown. With several pairs of twins in the sample, we aimed to identify any associations with SCFAs in this group. Methods: With informed consent, the child’s history was obtained, including age, birth length and weight, delivery type (C-section or vaginal), and feeding method (breast, bottle fed, or both). The child’s current weight, height, and BMI %ile were determined. Caregivers completed the 90-question Block Questionnaire for Ages 2-7 Kids food frequency questionnaire, and results were analyzed by Berkeley Analytics Inc (dba NutritionQuest). Participant-provided stool samples were freeze-dried and ground, and SCFAs were extracted and analyzed by content and concentration. Data analysis was generated using SAS software, Version 9.4 of the SAS System, Copyright © 2013 SAS Institute Inc. Results: Nine SCFAs were measured in duplicate, and the concentrations averaged. Statistical analysis included comparisons of SCFAs related to factors including weight status, infant feeding modality, twin status, and intrauterine drug exposure, and significance determined with a p value < 0.05. Results did not identify significant differences in individual SCFA concentrations between obese and non-obese toddlers, however concentrations of isobutyrate, isovaleric acid, and octanoic acid were greater in toddlers who were formula fed as infants versus toddlers who were breastfed, and those fed a combination of breastmilk, and formula. Analysis further revealed a higher mean concentration of caproic and propionic acid in twin subjects. Of particular interest, toddlers with a history of opioid exposure had higher mean concentrations of isovaleric and octanoic acids, but less isocaproic acid when compared to those who were not drug exposed. Further analysis will help determine if these findings may be related to nutrient intake, in particular dietary fiber intake.

Introduction: The gut microbiome is believed to have a significant impact on health throughout the lifespan, and the influence of infant nutrition and other environmental factors are of particular interest in its development. The aim of this research project was to learn more about the microbiome and short chain fatty acid (SCFA) composition of toddlers of differing weights, considering birth history, environment, and diet. In East Tennessee, opioid misuse is a growing issue, and a number of participants in this study were exposed in utero. We also hoped to identify related effects on infant’s SCFA composition. Finally, it is known that twins share a variety of traits, but much about their microbiome is unknown. With several pairs of twins in the sample, we aimed to identify any associations with SCFAs in this group. Methods: With informed consent, the child’s history was obtained, including age, birth length and weight, delivery type (C-section or vaginal), and feeding method (breast, bottle fed, or both). The child’s current weight, height, and BMI percentile were determined. Caregivers completed a 90-question Block Questionnaire for Ages 2-7 Kids food frequency questionnaire, and results were analyzed by Berkeley Analytics Inc (dba NutritionQuest). Participant-provided stool samples were freeze-dried and ground, and SCFAs were extracted and analyzed by content area % and concentration ppm. Data analysis was generated using SAS software, Version 9.4 of the SAS System, Copyright © 2013 SAS Institute Inc. Results: Nine SCFAs were measured in duplicate, and the concentrations averaged. Statistical analysis included comparisons of SCFAs related to factors including weight status, infant feeding modality, twin status, and intrauterine drug exposure, and significance determined with a p value < 0.05. Results did not identify significant differences in individual SCFA concentrations between obese and non-obese toddlers, however concentrations of isobutyrate, isovaleric acid, and octanoic acid were greater in toddlers who were formula fed as infants versus toddlers who were breastfed, and those fed a combination of breastmilk, and formula. Analysis further revealed a higher mean concentration of caproic and propionic acid in twin subjects. Of particular interest, toddlers with a history of opioid exposure had higher mean concentrations of isovaleric and octanoic acids, but less isocaproic acid when compared to those who were not drug exposed. Further analysis will help determine if these findings may be related to nutrient intake, in particular dietary fiber intake.

BACKGROUND AND OBJECTIVES: Research on in utero opioid exposure impacts has focused on Neonatal Opioid Withdrawal Syndrome (NOWS). However, possible impacts on fetal growth and newborn wellbeing have emerged, with inconsistencies likely driven by methodological issues. Our goal was to compare birth outcomes between newborns with prenatal opioid exposure and a matched control group. METHODS: Participants were identified manual review of electronic medical records of all deliveries over five years within a regional health system (6 delivery hospitals across 2 states). From over 18,000 births, 300 with prenatal opioid exposure and 300 control newborns matched on exposure, medical, and background factors were included. Additional factors were statistically controlled. Outcomes included pregnancy/delivery complications, newborn size, and newborn health complications. RESULTS: Compared to biochemically verified controls, exposed newborns had higher rates of fetal growth restriction, weighed less, had decreased length and head circumference, and had higher rates of respiratory distress, sepsis, and jaundice. No significant differences in gestational length, Apgar scores, or neonatal hypoglycemia were found. Adjusted regression analyses revealed that compared to controls, those exposed had an average 150 g decrease in birth weight, a two-fold increased risk for IUGR (OR = 2.09), a nearly three-fold (OR = 2.80) increased risk for jaundice, a more than seven-fold (OR = 7.40) increased risk for respiratory distress, and a thirty-fold (OR = 30.47) increased risk for sepsis. CONCLUSIONS: Results suggest significant pregnancy and newborn outcomes beyond NOWS following pregnancy opioid use, informing clinical screening and treatment decisions to enhance health and wellbeing in pregnancy, during the neonatal period, and beyond.

Background and objectives: Research on in utero opioid exposure impacts has focused on Neonatal Opioid Withdrawal Syndrome (NOWS). However, possible impacts on fetal growth and newborn wellbeing have emerged, with inconsistencies likely driven by methodological issues. Our goal was to compare birth outcomes between newborns with prenatal opioid exposure and a matched control group. Methods: Participants were identified via manual review of electronic medical records of all deliveries over five years within a regional health system (6 delivery hospitals across 2 states). From over 18,000 births, 300 with prenatal opioid exposure and 300 control newborns matched on exposure, medical, and background factors were included. Additional factors were statistically controlled. Outcomes included pregnancy/delivery complications, newborn size, and newborn health complications. Results: Compared to biochemically verified controls, exposed newborns had higher rates of fetal growth restriction, weighed less, had decreased length and head circumference, and had higher rates of respiratory distress, sepsis, and jaundice. No significant differences in gestational length, Apgar scores, or neonatal hypoglycemia were found. Adjusted regression analyses revealed that compared to controls, those exposed had an average 150 g decrease in birth weight, a two-fold increased risk for IUGR (OR = 2.09), a nearly three-fold (OR = 2.80) increased risk for jaundice, a more than seven-fold (OR = 7.40) increased risk for respiratory distress, and a thirty-fold (OR = 30.47) increased risk for sepsis. Conclusions: Results suggest significant pregnancy and newborn outcomes beyond NOWS following pregnancy opioid use, informing clinical screening and treatment decisions to enhance health and wellbeing in pregnancy, during the neonatal period, and beyond.

No description available.

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.

Background: Opioid maintenance therapy has been advocated by American College of Obstetrics and Gynecology (ACOG) along with American Society of Addiction Medicine (ASAM) for opioid use disorder in pregnancy. Marijuana use has been increasing with legalization of marijuana in many states along with reported benefit of antiemetic effect in pregnancy. Both have been independently implicated in adverse neonatal outcome but they haven't been studied for concurrent use in pregnancy. Objective: Objective of the study was to look in to the use of opioid and marijuana in pregnancy related with neonatal outcomes; birth weight, Apgar scores,low birth weight, preterm birth along with social determinant of opioid and marijuana use in pregnancy. Design/Methods: A retrospective chart review from July 2011 to June 2016 of all births from 6 delivery hospitals in South-Central Appalachia was conducted to determine pregnancy and neonatal outcomes of pregnancies exposed to any form of opioid and positive urine drug screen (UDS) for marijuana(THC) at the time of delivery. Inclusion criteria were UDS positive for THC at delivery and exposure to opioid during pregnancy.18730 births were identified during the study period, 2638 pregnancy were opioid exposed, and 2375 pregnancies met the inclusion criteria were included for analysis with 108 pregnancies positive for THC in UDS at the time of delivery. Maternal characteristics, delivery and perinatal outcome were studied. Student t-test and Chi-Square test were used for group comparison for presence and absence of marijuana. Logistic regression was done for significant confounding variables like parity, maternal status, tobacco, and benzodiazepine to find aOR for marijuana exposure for NAS diagnosis, premature birth, and low birth weight (LBW). Results: Among opioid using women, marijuana positive women were more likely to be unmarried, nulliparous, and use tobacco and benzodiazepines. Infants born to the marijuana users were likely to be of earlier gestational age (3 days), lower birth weight, and preterm; with preterm birth and low birth weight (mean difference = 265 gms) increased two fold even after controlling for parity, marital status, tobacco and benzodiazepine use with aOR of 2.35 (1.30-4.23) and 2.02 (1.18-3.47) respectively. Conclusion(s): In view of ACOG and ASAM guidelines for continuing opioid for opioid use disorder during pregnancy, finding of increased prematurity along with LBW carries significance of advocating counseling against use of marijuana in pregnancy exposed to opioids.

No description available.

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.