Placentas delivered by pre-pregnant obese women have reduced abundance and diversity in the microbiome.

Maternal pre-pregnancy obesity may have an impact on both maternal and fetal health. We examined the microbiome recovered from placentas in a multi-ethnic maternal pre-pregnant obesity cohort, through an optimized microbiome protocol to enrich low bacterial biomass samples. We found that the microbiomes recovered from the placentas of obese pre-pregnant mothers are less abundant and less diverse when compared to those from mothers of normal pre-pregnancy weight. Microbiome richness also decreases from the maternal side to the fetal side, demonstrating heterogeneity by geolocation within the placenta. In summary, our study shows that the microbiomes recovered from the placentas are associated with pre-pregnancy obesity. IMPORTANCE: Maternal pre-pregnancy obesity may have an impact on both maternal and fetal health. The placenta is an important organ at the interface of the mother and fetus, and supplies nutrients to the fetus. We report that the microbiomes enriched from the placentas of obese pre-pregnant mothers are less abundant and less diverse when compared to those from mothers of normal pre-pregnancy weight. More over, the microbiomes also vary by geolocation within the placenta.

Prepregnant Obesity of Mothers in a Multiethnic Cohort Is Associated with Cord Blood Metabolomic Changes in Offspring.

Maternal obesity has become a growing global health concern that may predispose the offspring to medical conditions later in life. However, the metabolic link between maternal prepregnant obesity and healthy offspring has not yet been fully elucidated. In this study, we conducted a case-control study using a coupled untargeted and targeted metabolomic approach from the newborn cord blood metabolomes associated with a matched maternal prepregnant obesity cohort of 28 cases and 29 controls. The subjects were recruited from multiethnic populations in Hawaii, including rarely reported Native Hawaiian and other Pacific Islanders (NHPI). We found that maternal obesity was the most important factor contributing to differences in cord blood metabolomics. Using an elastic net regularization-based logistic regression model, we identified 29 metabolites as potential early-life biomarkers manifesting intrauterine effect of maternal obesity, with accuracy as high as 0.947 after adjusting for clinical confounding (maternal and paternal age, ethnicity, parity, and gravidity). We validated the model results in a subsequent set of samples (N = 30) with an accuracy of 0.822. Among the metabolites, six metabolites (galactonic acid, butenylcarnitine, 2-hydroxy-3-methylbutyric acid, phosphatidylcholine diacyl C40:3, 1,5-anhydrosorbitol, and phosphatidylcholine acyl-alkyl 40:3) were individually and significantly different between the maternal obese and normal-weight groups. Interestingly, hydroxy-3-methylbutyric acid showed significantly higher levels in cord blood from the NHPI group compared to that from Asian and Caucasian groups. In summary, significant associations were observed between maternal prepregnant obesity and offspring metabolomic alternation at birth, revealing the intergenerational impact of maternal obesity.

Multi-omics Analysis of Umbilical Cord Hematopoietic Stem Cells from a Multi-ethnic Cohort of Hawaii Reveals the Transgenerational Effect of Maternal Pre-Pregnancy Obesity.

Background: Maternal obesity is a health concern that may predispose newborns to a high risk of medical problems later in life. To understand the transgenerational effect of maternal obesity, we conducted a multi-omics study, using DNA methylation and gene expression in the CD34+/CD38-/Lin- umbilical cord blood hematopoietic stem cells (uHSCs) and metabolomics of the cord blood, all from a multi-ethnic cohort (n=72) from Kapiolani Medical Center for Women and Children in Honolulu, Hawaii (collected between 2016 and 2018). Results: Differential methylation (DM) analysis unveiled a global hypermethylation pattern in the maternal pre-pregnancy obese group (BH adjusted p<0.05), after adjusting for major clinical confounders. Comprehensive functional analysis showed hypermethylation in promoters of genes involved in cell cycle, protein synthesis, immune signaling, and lipid metabolism. Utilizing Shannon entropy on uHSCs methylation, we discerned notably higher quiescence of uHSCs impacted by maternal obesity. Additionally, the integration of multi-omics data-including methylation, gene expression, and metabolomics-provided further evidence of dysfunctions in adipogenesis, erythropoietin production, cell differentiation, and DNA repair, aligning with the findings at the epigenetic level. Furthermore, the CpG sites associated with maternal obesity from these pathways also predicted highly accurately (average AUC = 0.8687) between cancer vs. normal tissues in 14 cancer types in The Cancer Genome Atlas (TCGA). Conclusions: This study revealed the significant correlation between pre-pregnancy maternal obesity and multi-omics level molecular changes in the uHSCs of offspring, particularly in DNA methylation. Moreover, these maternal obesity epigenetic markers in uHSCs may predispose offspring to higher cancer risks.

A review of omics approaches to study preeclampsia.

Preeclampsia is a medical condition affecting 5-10% of pregnancies. It has serious effects on the health of the pregnant mother and developing fetus. While possible causes of preeclampsia are speculated, there is no consensus on its etiology. The advancement of big data and high-throughput technologies enables to study preeclampsia at the new and systematic level. In this review, we first highlight the recent progress made in the field of preeclampsia research using various omics technology platforms, including epigenetics, genome-wide association studies (GWAS), transcriptomics, proteomics and metabolomics. Next, we integrate the results in individual omic level studies, and show that despite the lack of coherent biomarkers in all omics studies, inhibin is a potential preeclamptic biomarker supported by GWAS, transcriptomics and DNA methylation evidence. Using network analysis on the biomarkers of all the literature reviewed here, we identify four striking sub-networks with clear biological functions supported by previous molecular-biology and clinical observations. In summary, omics integration approach offers the promise to understand molecular mechanisms in preeclampsia.

Shingles in Pregnancy: An Elusive Case of Left Upper Quadrant Abdominal Pain.

Pregnancy can complicate the presentation and workup of abdominal pain. A healthy 21-year-old gravida-3 para-1 woman at 34 weeks of gestation presented for severe pain localized to her abdominal left upper quadrant (LUQ. Physical exam was unremarkable except for localized pain on palpation, and she was discharged with acetaminophen and cyclobenzaprine for presumed musculoskeletal pain. The next day, she returned for worsening pain. An extensive workup including labs, electrocardiogram, chest x-ray, and abdominal computed tomography was unremarkable, and she was discharged with hydrocodone/acetaminophen. Later that evening, after two discharges, the patient presented for increased pain with new onset of vesicles in her left T6 dermatome. She was diagnosed with shingles, started on valacyclovir and gabapentin, and eventually went on to deliver a healthy infant. Shingles classically presents as excruciating pain followed by the eruption of vesicles. This case is important because it reviews the significance of shingles in pregnancy and is one of the first reports to extensively discuss the differential and workup of LUQ abdominal pain in pregnancy. Abdominal pain is a relatively common complaint during pregnancy, and a methodical approach should be taken when evaluating LUQ in pregnancy. Shingles could be considered in the differential diagnosis of pain of unclear origin.