Congenital central nervous system (CNS) malformations are relatively rare conditions present in fetuses that may result in intrauterine fetal deaths (IUFDs). We report a case of a 42-year-old female who presented at 29 weeks gestation with lack of a fetal heart beat likely due to a congenital malformation resulting in IUFD. This case report and literature review provides a better understanding of the encephalocele as a harbinger for IUFD.
OBJECTIVE: Assess placental opioid metabolism (POM) of methadone and buprenorphine to predict treatment for severe neonatal abstinence syndrome (NAS). STUDY DESIGN: Multi-center prospective observational cohort study (July 2016 to December 2017). Eligible pregnant women: ! 18 years old, on methadone or buprenorphine, delivering a non-anomalous live-born singleton infant ! 34 weeks. Severe NAS was defined by Finnegan scoring: 3 consecutive scores !8 or sum of 3 consecutive scores !24 occurring 72 hours after birth. QPCR-derived placental aromatase mRNA levels (PmRNA) were compared to reference genes-actin, glyceraldehyde-3-phosphate dehydrogenase and glucuronidase beta. PmRNA and aromatase gene single nucleotide polymorphisms (SNPs: rs749292, rs727479, rs93606) were compared to Finnegan scores. SNPs assessed POM. Finnegan scores were compared to umbilical cord (UC) drugs and their metabolites. Data analysis: descriptive, parametric, non-parametric statistics, survival curves. Significance was set to p <0.05 to detect a large difference (cohen¼1) in PmRNA. RESULTS: 38 patients were included. 36/38 (95%) were Caucasian and mean delivery was at 38.5 AE 1.6 weeks. 29/38 (76%) and 9/38 (24%) used methadone and buprenorphine respectively. Severe NAS was present in 19/38 (50%) of infants, 16/19 (84%) used methadone and 3/19 (16%) used buprenorphine (p ¼0.02). There was no difference in maternal methadone or buprenorphine dose, UC methadone, UC buprenorphine and metabolites levels (EDDP, norbuprenorphine) (p>0.05) between groups. PmRNA were lower in severe NAS. However, only significant for the aromatase/Actin expression (severe NAS 0.52AE 0.34 vs. non-severe NAS 0.76AE0.36, p¼0.04). Mean UC EDDP/methadone ratio was significantly higher (0.68 vs 0.36, p ¼0.03) in infants meeting criteria for severe NAS vs those not meeting criteria; not so for norbuprenorphine/ buprenorphine ratios (2.44 vs.1.41, p¼0.59). SNP genotypes did not predict severe NAS (p >0.05), but sample size was underpowered. PmRNA were weakly to moderately correlated with UC methadone, buprenorphine and their metabolites (r ¼0.4-0.8). CONCLUSION: Maternal dose and umbilical cord levels of methadone and buprenorphine were not significantly different in neonates with or without severe NAS. However, PmRNA are lower and UC EDDP/ methadone ratios higher in severe NAS. Additional investigation of PmRNA and SNP analysis is needed to assess placental opioid metabolism to predict severe NAS.
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