Telemedicine Consultation to Assess Neonatal Encephalopathy in Rural Community Hospitals

We studied the feasibility of tele consults in community hospitals for neonatal encephalopathy evaluation.https://knowledgeconnection.mainehealth.org/lambrew-retreat-2021/1048/thumbnail.jp

Identification of PKD1L1 Gene Variants in Children with the Biliary Atresia Splenic Malformation Syndrome

Biliary atresia (BA) is the most common cause of end‐stage liver disease in children and the primary indication for pediatric liver transplantation, yet underlying etiologies remain unknown. Approximately 10% of infants affected by BA exhibit various laterality defects (heterotaxy) including splenic abnormalities and complex cardiac malformations — a distinctive subgroup commonly referred to as the biliary atresia splenic malformation (BASM) syndrome. We hypothesized that genetic factors linking laterality features with the etiopathogenesis of BA in BASM patients could be identified through whole exome sequencing (WES) of an affected cohort. DNA specimens from 67 BASM subjects, including 58 patient‐parent trios, from the NIDDK‐supported Childhood Liver Disease Research Network (ChiLDReN) underwent WES. Candidate gene variants derived from a pre‐specified set of 2,016 genes associated with ciliary dysgenesis and/or dysfunction or cholestasis were prioritized according to pathogenicity, population frequency, and mode of inheritance. Five BASM subjects harbored rare and potentially deleterious bi‐allelic variants in polycystin 1‐like 1, PKD1L1, a gene associated with ciliary calcium signaling and embryonic laterality determination in fish, mice and humans. Heterozygous PKD1L1 variants were found in 3 additional subjects. Immunohistochemical analysis of liver from the one BASM subject available revealed decreased PKD1L1 expression in bile duct epithelium when compared to normal livers and livers affected by other non‐cholestatic diseases. Conclusion WES identified bi‐allelic and heterozygous PKD1L1 variants of interest in 8 BASM subjects from the ChiLDReN dataset. The dual roles for PKD1L1 in laterality determination and ciliary function suggest that PKD1L1 is a new, biologically plausible, cholangiocyte‐expressed candidate gene for the BASM syndrome

Stability of the vaginal, oral, and gut microbiota across pregnancy among African American women: the effect of socioeconomic status and antibiotic exposure

Objective A growing body of research has investigated the human microbiota and pregnancy outcomes, especially preterm birth. Most studies of the prenatal microbiota have focused on the vagina, with fewer investigating other body sites during pregnancy. Although pregnancy involves profound hormonal, immunological and metabolic changes, few studies have investigated either shifts in microbiota composition across pregnancy at different body sites or variation in composition at any site that may be explained by maternal characteristics. The purpose of this study was to investigate: (1) the stability of the vaginal, oral, and gut microbiota from early (8–14 weeks) through later (24–30 weeks) pregnancy among African American women according to measures of socioeconomic status, accounting for prenatal antibiotic use; (2) whether measures of socioeconomic status are associated with changes in microbiota composition over pregnancy; and (3) whether exposure to prenatal antibiotics mediate any observed associations between measures of socioeconomic status and stability of the vaginal, oral, and gut microbiota across pregnancy. Methods We used paired vaginal, oral, or gut samples available for 16S rRNA gene sequencing from two time points in pregnancy (8–14 and 24–30 weeks) to compare within-woman changes in measures of alpha diversity (Shannon and Chao1) and beta-diversity (Bray–Curtis dissimilarity) among pregnant African American women (n = 110). Multivariable linear regression was used to examine the effect of level of education and prenatal health insurance as explanatory variables for changes in diversity, considering antibiotic exposure as a mediator, adjusting for age, obstetrical history, and weeks between sampling. Results For the oral and gut microbiota, there were no significant associations between measures of socioeconomic status or prenatal antibiotic use and change in Shannon or Chao1 diversity. For the vaginal microbiota, low level of education (high school or less) was associated with an increase in Shannon and Chao1 diversity over pregnancy, with minimal attenuation when controlling for prenatal antibiotic use. Conversely, for within-woman Bray–Curtis dissimilarity for early compared to later pregnancy, low level of education and prenatal antibiotics were associated with greater dissimilarity for the oral and gut sites, with minimal attenuation when controlling for prenatal antibiotics, and no difference in dissimilarity for the vaginal site. Conclusions Measures of maternal socioeconomic status are variably associated with changes in diversity across pregnancy for the vaginal, oral, and gut microbiota, with minimal attenuation by prenatal antibiotic exposure. Studies that evaluate stability of the microbiota across pregnancy in association with health outcomes themselves associated with socioeconomic status (such as preterm birth) should incorporate measures of socioeconomic status to avoid finding spurious relationships

Association of medication-assisted treatment and short acting opioids with newborn head circumference and birth weight

OBJECTIVE: We compared the association of methadone, buprenorphine, and short-acting opioid exposure with newborn head circumference (HC) and birth weight (BW), and evaluated gestational age (GA) as a mediator. STUDY DESIGN: We included newborns born 2013-2018 identified by neonatal abstinence syndrome diagnosis code (N = 572) and birthday-matched unexposed controls (N = 571). Linear regressions of opioid exposure with HC and BW controlled for tobacco, marijuana, cocaine, gabapentin, cesarean section, Medicaid, and newborn sex, with mediation analysis by GA. RESULT: Methadone was associated with 0.81 cm lower HC (95% CI = -1.22, -0.40) and 0.23 kg lower BW (95% CI = -0.35, -0.10) with approximately 24% and 41% mediated by GA, respectively. Buprenorphine and short acting opioids were not associated with HC or BW. CONCLUSION: Methadone exposed newborns have smaller HC and lower BW not fully attributable to younger GA, suggesting a direct effect of methadone on intrauterine growth. Exploration of potential developmental consequences of this is urgently needed