Maternal telehealth: innovations and Hawai'i perspectives.

Access to maternal-fetal medicine (MFM) subspecialty services is a critical part of a healthcare system that optimizes pregnancy outcomes for women with complex medical and obstetrical disorders. Healthcare services in the State of Hawai'i consist of a complicated patchwork of independently run community health clinics and hospital systems which are difficult for many pregnant patients to navigate. Maternal telehealth services have been identified as a solution to increase access to subspecialty prenatal services for women in rural communities or neighboring islands, especially during the COVID-19 pandemic. Telehealth innovations have been rapidly developing in the areas of remote ultrasound, hypertension management, diabetes management, and fetal monitoring. This report describes how telehealth innovations are being introduced by MFM specialists to optimize care for a unique population of high-risk patients in a remote area of the world such as Hawai'i, as well as review currently available telemedicine technologies and future innovations.

Integrating Mobile and Portable Technologies With In-Person and Telehealth Care to Increase Perinatal Healthcare Equity for the Unstably Housed.

Pregnant people living in rural areas are at an increased risk of experiencing poor perinatal outcomes due, in part, to the need to travel long distances to see a perinatal care provider. Telehealth care has been used successfully to increase access to perinatal care but requires patients to have access to broadband Internet access and devices capable of establishing secure connections so they can participate in their care. This places an additional burden on unstably housed pregnant persons who may not have access to the required technology. The Midwifery Integrated Home Visitation Program was developed to bridge this digital divide by bringing perinatal care services to the unstably housed at their desired location of care. The included case studies outline how telehealth and portable technology were used to address the medical and nonmedical needs of unstably housed pregnant people. They also outline how bridging the digital divide by combining in-person perinatal care with mobile technology, portable technology, and telehealth care has the potential to decrease unnecessary emergency department care and ambulance use while facilitating the receipt of appropriate care and thus potentially preventing poor perinatal outcomes.

Diet quality predicts hypertensive disorders of pregnancy in Asian and Pacific Islander Cohort.

Background: There is limited data on diet quality during pregnancy and its impact on hypertensive disorders of pregnancy (HDP). Aim: Examine the association with diet quality and development of HDP in an Asian and Pacific Islander Cohort Methods: Pregnant women from the 4 largest ethnic groups in Hawai'i were recruited for participation. Participants completed a food frequency questionnaire during each trimester. Adherence to three diet quality indices (DQIs) were scored-The Healthy Eating Index (HEI), The Alternate Mediterranean Diet score (aMED), and the Dietary approaches to Stop Hypertension (DASH) score. Mean scores were compared among those who did and did not develop HDP. Logistic Regression models were used to examine the association between diet quality and HDP accounting for confounders (age, parity, obesity, ethnicity, gestational weight gain). Results: Among 55 participants with complete follow-up, there was a high incidence of HDP (23%). There was no significant change of DQIs over time. Non-Hispanic White participants had higher DQIs than Filipinas, Japanese, or Native Hawaiians (not statistically significant). Across gestation, participants who did not have HDP had better diet quality than those who did. Logistic regression showed that HEI and DASH indices are predictive of HDP development, with the high DASH diet score having the greatest reduced odds. Every point higher of DASH diet score portended approximately 30% reduced odds of developing HDP. Conclusions: The DASH diet had the strongest association with reduced odds of HDP, but better diet quality in any of the indices was also predictive.

Adherence to Mediterranean diet impacts gastrointestinal microbial diversity throughout pregnancy.

BACKGROUND: Consumption of a diet with high adherence to a Mediterranean diet pattern (MDP) has been associated with a favorable gastrointestinal tract (GIT) microbiome. A healthy GIT microbiome in pregnancy, as defined by increased alpha diversity, is associated with lower chance of adverse perinatal outcomes. This study aimed to evaluate the impact of adherence to an MDP on GIT microbial diversity longitudinally throughout pregnancy. METHODS: Adherence to MDP was scored by the Alternate Mediterranean (aMED) Diet Quality Score, after being applied to a validated Food Frequency Questionnaire. Association of aMED Scores with GIT alpha diversity profiles were compared linearly and across time using a linear mixed model, including covariates of age, body mass index (BMI), ethnicity, and parity. RESULTS: Forty-one participants of Filipino, Japanese, Native Hawaiian, and Non-Hispanic White descent provided dietary information and microbiome samples during each trimester of pregnancy. Alpha diversity profiles changed over gestation, with decreased microbial diversity in the third trimester. aMED scores positively correlated with Chao1 Index and Observed Species Number (r = 0.244, p = 0.017, and r = 0.233, p = 0.023, respectively). The strongest association was detected in the third trimester (Chao 1: r = 0.43, p = 0.020, Observed Species Number: r = 0.41, p = 0.026). Participants with higher aMED scores had higher relative abundance of Acidaminoacaeae at the family level (p = 0.0169), as well as higher abundance of several species known to increase production of short chain fatty acids within the GIT. CONCLUSIONS: Adherence to MDP pattern is associated with increased maternal GIT microbial diversity, and promotes the abundance of bacteria that produce short chain fatty acids. Increased consumption of fruits, vegetables and legumes with low red meat consumption were key components driving this association. The effect of nutrition however, was less of an effect than pregnancy itself. Further studies are needed to determine if adherence to a Mediterranean diet translates not only into microbial health, but also into reduced risk of adverse pregnancy outcomes.

Racial/Ethnic Representation in United States and Australian Obstetric Research.

OBJECTIVE: To describe racial/ethnic representation in United States (US) and Australian obstetric research, represented by the Maternal-Fetal Medicine Units Network (MFMU) and Australian Research Centre for Health of Women and Babies (ARCH) trials. METHODS: MFMU studies were identified through PubMed and ARCH studies through their online publication listing from 2011 to 2016. Observational and randomized cohorts and primary and secondary data analyses were included. Studies with race-based enrollment were excluded. Racial/ethnic representation was expressed as the mean racial/ethnic percentages of the studies (i.e.,: studies weighted equally regardless of sample size). Racial/ethnic percentages in MFMU studies were compared to US registered births and ARCH compared to Australian census ancestry data. RESULTS: 38 MFMU studies included 580,282 women. Racial/ethnic representation (% [SD]) included White 41.7 [12.3], Hispanic 28.1 [15.4], Black 26.2 [12.3], Asian 3.6 [2.3], and American Indian/Alaskan Native (AI/AN) 0.2 [0.02]. No studies reported Native Hawaiian/other Pacific Islanders (NHOPI) separately. Comparatively, registered US births (%) were White 75.7, Hispanic 28.1, Black 16.1, Asian/Pacific Islander 7.1, and AI/AN 1.1, which differed from the MFMU (P = 0.02). 20 ARCH studies included 51,873 women. The most reported groups were White 76.5 [17.4], Asian 15.2 [14.8], and Aboriginal/Torres Strait Islander 13.9 [30.5], compared to census numbers of White 88.7, Asian 9.4, and Aboriginal/Torres Strait Islander 2.8 (P < 0.01). Two ARCH studies reported African ethnicity. CONCLUSION: There is racial diversity in studies by MFMU and ARCH, with opportunities to increase enrollment and enhanced reporting of Asian, AI/AN, and NHOPI races in MFMU studies and Black race in ARCH studies.

Effects of repeat prenatal corticosteroids given to women at risk of preterm birth: An individual participant data meta-analysis.

BACKGROUND: Infants born preterm compared with infants born at term are at an increased risk of dying and of serious morbidities in early life, and those who survive have higher rates of neurological impairments. It remains unclear whether exposure to repeat courses of prenatal corticosteroids can reduce these risks. This individual participant data (IPD) meta-analysis (MA) assessed whether repeat prenatal corticosteroid treatment given to women at ongoing risk of preterm birth in order to benefit their infants is modified by participant or treatment factors. METHODS AND FINDINGS: Trials were eligible for inclusion if they randomised women considered at risk of preterm birth who had already received an initial, single course of prenatal corticosteroid seven or more days previously and in which corticosteroids were compared with either placebo or no placebo. The primary outcomes for the infants were serious outcome, use of respiratory support, and birth weight z-scores; for the children, they were death or any neurosensory disability; and for the women, maternal sepsis. Studies were identified using the Cochrane Pregnancy and Childbirth search strategy. Date of last search was 20 January 2015. IPD were sought from investigators with eligible trials. Risk of bias was assessed using criteria from the Cochrane Collaboration. IPD were analysed using a one-stage approach. Eleven trials, conducted between 2002 and 2010, were identified as eligible, with five trials being from the United States, two from Canada, and one each from Australia and New Zealand, Finland, India, and the United Kingdom. All 11 trials were included, with 4,857 women and 5,915 infants contributing data. The mean gestational age at trial entry for the trials was between 27.4 weeks and 30.2 weeks. There was no significant difference in the proportion of infants with a serious outcome (relative risk [RR] 0.92, 95% confidence interval [CI] 0.82 to 1.04, 5,893 infants, 11 trials, p = 0.33 for heterogeneity). There was a reduction in the use of respiratory support in infants exposed to repeat prenatal corticosteroids compared with infants not exposed (RR 0.91, 95% CI 0.85 to 0.97, 5,791 infants, 10 trials, p = 0.64 for heterogeneity). The number needed to treat (NNT) to benefit was 21 (95% CI 14 to 41) women/fetus to prevent one infant from needing respiratory support. Birth weight z-scores were lower in the repeat corticosteroid group (mean difference -0.12, 95%CI -0.18 to -0.06, 5,902 infants, 11 trials, p = 0.80 for heterogeneity). No statistically significant differences were seen for any of the primary outcomes for the child (death or any neurosensory disability) or for the woman (maternal sepsis). The treatment effect varied little by reason the woman was considered to be at risk of preterm birth, the number of fetuses in utero, the gestational age when first trial treatment course was given, or the time prior to birth that the last dose was given. Infants exposed to between 2-5 courses of repeat corticosteroids showed a reduction in both serious outcome and the use of respiratory support compared with infants exposed to only a single repeat course. However, increasing numbers of repeat courses of corticosteroids were associated with larger reductions in birth z-scores for weight, length, and head circumference. Not all trials could provide data for all of the prespecified subgroups, so this limited the power to detect differences because event rates are low for some important maternal, infant, and childhood outcomes. CONCLUSIONS: In this study, we found that repeat prenatal corticosteroids given to women at ongoing risk of preterm birth after an initial course reduced the likelihood of their infant needing respiratory support after birth and led to neonatal benefits. Body size measures at birth were lower in infants exposed to repeat prenatal corticosteroids. Our findings suggest that to provide clinical benefit with the least effect on growth, the number of repeat treatment courses should be limited to a maximum of three and the total dose to between 24 mg and 48 mg.

Management of Hepatitis B Infection in Pregnancy.

In many parts of the world, perinatal transmission is the most common route of infection for hepatitis B virus. In the United States, sexual contact is the most common source of hepatitis B virus infection. As a result, it is essential that women's health care providers become aware of the recommended strategies used to identify women infected with hepatitis B and to subsequently reduce perinatal transmission, particularly now that immigration and globalization is more common and reproductive science makes pregnancy more possible for women with liver disease. This article reviews evidence-based strategies for management of hepatitis B infection during pregnancy.

Trachelectomy during pregnancy: what has experience taught us?

The treatment of early stage cervical malignancy in a pregnant patient remains a challenge. We report the successful application of a vaginal radical trachelectomy (VRT) during pregnancy to treat a patient diagnosed with early stage cervical cancer and subsequently review the published work. A 22-year-old female diagnosed at the gestational age of 17 weeks with International Federation of Gynecology and Obstetrics stage IB1 squamous cell cervical carcinoma was treated with VRT at 19(+5) weeks. At 36 weeks, the patient underwent a scheduled cesarean section. A healthy male infant was delivered with a weight of 2795 g. After 13 months of follow-up, the patient is doing well with no evidence of recurrent disease.

Temporal Investigation of the Maternal Origins of Fetal Gut Microbiota.

In utero colonization or deposition of beneficial microorganisms and their by-products likely occurs through various mechanisms, such as hematogenous spread or ascension from the reproductive tract. With high-throughput sequencing techniques, the identification of microbial components in first-pass neonatal meconium has been achieved. While these components are low-biomass and often not abundant enough to culture, the presence of microbial DNA signatures may promote fetal immune tolerance or epigenetic regulation prior to birth. The aim of this study was to investigate the maternal source of the neonatal first-pass meconium microbiome. Maternal vaginal and anal samples collected from twenty-one maternal-infant dyad pairs were compared via principal component analysis to first-pass neonatal meconium microbial compositions. Results demonstrated the greatest degree of similarity between the maternal gut microbiome in the second and third trimesters and vaginal microbiome samples across pregnancy, suggesting that the maternal gut microbiota may translocate to the fetal gut during pregnancy. This study sheds light on the origin and timing of the potential transfer of maternal microbial species to offspring in utero.

A Patient Interview-Based Needs Assessment and Evaluation of Experiences with Periviable Pregnancies.

Given the complex ethical and emotional nature of births during the periviable period for both health care providers and families, this investigation sought to identify strategies for improved counseling of pregnant patients facing preterm birth at the cusp of viability at a tertiary care center in Hawai'i. As part of a larger quality improvement project on periviability counseling, 10 patients were interviewed during either individual or small focus groups using a progression of hypothetical scenarios. Interviews were analyzed independently by 3 investigators to identify themes of patient experience and potential areas for improvement when counseling patients who are carrying periviable pregnancies. Several common themes emerged from the interviews. Patients expressed the desire for more information throughout the process delivered in a jargon-free manner with unified messaging from the medical teams, and emotional support. These findings add to a limited body of literature which addresses patient perceptions of interactions with health care providers in the face of uncertainty, particularly in a Pacific Islander population. The authors recommend increasing provider training and developing a more structured process to counsel pregnant women facing periviable pregnancy loss to improve the patient experience.

Epigenetic Changes in the HTR8 and 3A-sub E placental Cell Lines Exposed to Bisphenol A and Benzyl Butyl Phthalate.

OBJECTIVE: Bisphenol A and phthalate are known endocrine disruptors and capable of inducing epigenetic changes in the human population. However, their impact on the placenta is less well studied. Our objective was to measure the effect of exposure to bisphenol A and benzyl butyl phthalate in first-trimester HTR8-SVneo and third-trimester 3A-sub E trophoblast cells by profiling the DNA methylation pattern of the imprinting control region of the IGF2 (insulin-like growth factor) and H19 genes. METHODS: Human placental HTR8-SVneo and 3A-sub E cell lines were treated with two sub-lethal concentrations of bisphenol A and benzyl butyl phthalate. Demethylating agent, 5-azacytidine, was used as a positive control. Cells were harvested on post-treatment days 1 and 4. The methylation profile of six CpG dinucleotide sites, part of the CTCF 6 binding site of the IGF2/H19 imprinting control region, was determined by pyrosequencing. RESULTS: In the first-trimester HTR8-SVneo cell line, we observed a significant increased methylation of the CpG sites 3, 4 when treated with a high concentration of bisphenol A or benzyl butyl phthalate while increased methylation at site 6 for both high and low dose treatment on day 4. Demethylation of the CpG sites 1, 4, and 6 was observed when treated with 5-azacytidine on day 4. In the third-trimester 3A-sub E cell line, no significant changes in the methylation profile were observed under any treatment conditions. CONCLUSIONS: The results of this study demonstrate the capability of epigenetic changes in human placenta cells induced by bisphenol A and benzyl butyl phthalate. The observed methylation changes only in the first-trimester HTR8-SVneo cells phthalate may reflect a window of epigenetic susceptibility related to these environmental toxicants.

Effects of Dietary Quality on Vaginal Microbiome Composition Throughout Pregnancy in a Multi-Ethnic Cohort.

Background: Vaginal Lactobacillus predominance is associated with improved vaginal health and reduced pregnancy complications. Little is known about how dietary quality may improve vaginal microbial composition or about dietary interventions that may promote Lactobacillus abundance. To understand the host factors affecting vaginal microbiota during pregnancy in a multi-ethnic cohort in Hawai`i. We hypothesize that better diet quality improves vaginal microbial composition, as represented by Lactobacillus abundance and depletion of anaerobic organisms. Methods: We compared comprehensive diet quality, as measured by the Healthy Eating Index-2015 (HEI-2015), to taxonomic classifications of bacteria present within the vagina. Participants of the four predominant ethnic groups in Hawai'i (Japanese, Filipino, Non-Hispanic White and Native Hawaiian) completed Quantitative Food Frequency Questionnaires (QFFQs) and collected vaginal swabs during each trimester. 16s rRNA amplicon sequencing (V2-V9 regions) was performed on vaginal samples. HEI-2015 scores and macro- and micronutrient intake were compared with the predominant species present using the Mann-Whitney-U test, PERMANOVA, and the Pearson correlation coefficient. A mixed-effects logistics regression model was used to predict the depletion of Lactobacillus species while accounting for confounding demographic factors. Results: Matched, longitudinal data for 40 participants demonstrated three predominant Lactobacillus species: L. crispatus, L. iners, and L. gasseri, with another subset of samples with anaerobic abundance. (Primarily, Atopobium vaginae, Prevotella, and Gardnerella vaginalis.) Non-Hispanic White participants had lower amounts of Lactobacillus iners compared to other racial and ethnic groups. HEI scores correlated with the chao index and observed species number primarily in the first trimester (r = 0.25, p < 0.05). Greater carbohydrate intake was associated with a higher abundance of L. crispatus, while lower carbohydrate intake trended towards more L. iners (0.056) and anaerobic species. Conclusions: Increased carbohydrate consumption and improved diet quality may be associated with beneficial vaginal microbial composition in pregnancy.

Impact of Maternal Mediterranean-Type Diet Adherence on Microbiota Composition and Epigenetic Programming of Offspring.

Understanding how maternal diet affects in utero neonatal gut microbiota and epigenetic regulation may provide insight into disease origins and long-term health. The impact of Mediterranean diet pattern adherence (MDA) on fetal gut microbiome and epigenetic regulation was assessed in 33 pregnant women. Participants completed a validated food frequency questionnaire in each trimester of pregnancy; the alternate Mediterranean diet (aMED) score was applied. Umbilical cord blood, placental tissue, and neonatal meconium were collected from offspring. DNA methylation patterns were probed using the Illumnia EPICarray Methylation Chip in parturients with high versus low MDA. Meconium microbial abundance in the first 24 h after birth was identified using 16s rRNA sequencing and compared among neonates born to mothers with high and low aMED scores. Twenty-one mothers were classified as low MDA and 12 as high MDA. Pasteurellaceae and Bacteroidaceae trended towards greater abundance in the high-MDA group, as well as other short-chain fatty acid-producing species. Several differentially methylated regions varied between groups and overlapped gene regions including NCK2, SNED1, MTERF4, TNXB, HLA-DPB, BAG6, and LMO3. We identified a beneficial effect of adherence to a Mediterranean diet on fetal in utero development. This highlights the importance of dietary counseling for mothers and can be used as a guide for future studies of meconium and immuno-epigenetic modulation.

Temporal trends in microplastic accumulation in placentas from pregnancies in Hawai'i.

Microplastics are created for commercial use, are shed from textiles, or result from the breakdown of larger plastic items. Recent reports have shown that microplastics accumulate in human tissues and may have adverse health consequences. Currently, there are no standardized environmental monitoring systems to track microplastic accumulation within human tissues. Using Raman spectroscopy, we investigated the temporal exposures to plastic pollution in Hawai'i and noted a significant increase in the accumulation of microplastics in discarded placentas over the past 15 years, with changes in the size and chemical composition of the polymers. These findings provide a rare insight into the vulnerability and sensitivity of Pacific Island residents to plastic pollution and illustrate how discarded human tissues can be used as an innovative environmental plastic pollution monitoring system.

Neonatal Hypoxic Ischemic Encephalopathy and Planned Home Birth.

INTRODUCTION: As planned home births increase, emerging evidence on the perinatal outcomes of newborns who were planned hospital births versus planned home births has been inconsistent, and a growing number of states have attempted to legislate community births. We sought to determine whether an association exists between neonatal hypoxic ischemic encephalopathy (HIE), a complication of ischemic birth injury, and planned location of birth. METHODS: A case-control study design was used to compare data from neonates with HIE obtained from electronic health records at Kapiolani Medical Center for Women and Children in Honolulu, Hawaii, with data from neonates without HIE obtained from Hawaii state birth certificate data. A penalized backward stepwise logistic regression was performed to control for confounders. RESULTS: We included 164 neonates with HIE and 656 neonates in the control group. The odds of having been a planned home birth were 2.77 times higher in neonates with HIE compared with those without HIE (95% CI, 1.05-6.87). After adjusting for insurance, mode of birth, meconium fluid, maternal hypertension, and chorioamnionitis, neonates with HIE were still more likely to have been a planned home birth compared with those without HIE (odds ratio, 11.56; 95% CI, 1.37-118.77). DISCUSSION: Neonates with HIE were more likely to have been a planned home birth compared with neonates without HIE.

Urine drug screening on labor and delivery.

BACKGROUND: Substance use including opioids, methamphetamines, benzodiazepines, and barbiturates during pregnancy is harmful for the pregnant person and the fetus. Routine screening using validated questionnaires is recommended, but often biologic sampling is done instead. There is often bias in urine drug screening on labor and delivery units. OBJECTIVE: This study aimed to compare characteristics of people who did and did not receive urine drug screening during labor and delivery and to examine the relationship of maternal results to neonatal results. STUDY DESIGN: This was a retrospective chart review examining all people in 2017 who delivered in the labor and delivery unit at our institution. We collected urine drug screening result information, maternal demographic data, follow-up after positive maternal tests, and neonatal test results. Individual characteristics and obstetrical outcomes were analyzed. RESULTS: Of 6265 deliveries, 297 urine drug screening tests were ordered. People who were tested identified most commonly as Native Hawaiian or Pacific Islander (P<.0001). The most common indications for ordering tests were a history of substance use and insufficient prenatal care (P<.0001). People who tested positive were more likely to self-identify as White (P=.03) and have history of substance use (P<.0001). Among the positive test results, 24 (24%) were caused by a provider-ordered medication. Self-identification as Native Hawaiian or Pacific Islander was not predictive of a positive result. Of the tested people, 36% (108/297) had a positive result on preliminary testing, and 33% (98/295) on confirmatory testing. CONCLUSION: Native Hawaiians and Pacific Islanders were more likely to undergo testing, whereas White people were more likely to have a positive result. Maternal results were not reliable for predicting neonatal drug test results and vice versa. With rising rates of substance use disorders in the pregnant and reproductive-age population, standardized unbiased race-neutral guidelines for urine drug screening should be implemented using laboratory test results that include preliminary and reflex confirmatory results.

Demonstration of all-or-none loss of imprinting in mRNA expression in single cells.

Loss of imprinting (LOI) is the reactivation of the silenced allele of an imprinted gene, leading to perturbation of monoallelic expression. We tested the hypothesis that LOI of PLAGL1, a representative maternally imprinted gene, occurs through an all-or-none process leading to a mixture of fully imprinted and nonimprinted cells. Herein using a quantitative RT-PCR-based experimental approach, we measured LOI at the single cell level in human trophoblasts and demonstrated a broad distribution of LOI among cells exhibiting LOI, with the mean centered at approximately 100% LOI. There was a significant (P < 0.01) increase in expression after 2 days of 5-aza-2'-deoxycytidine (AZA) treatment and a significant (P < 0.01) increase in LOI after both 1 and 2 days of AZA treatment, while the distribution remained broad and centered at approximately 100% LOI. We propose a transcriptional pulsing model to show that the broadness of the distribution reflects the stochastic nature of expression between the two alleles in each cell. The mean of the distribution of LOI in the cells is consistent with our hypothesis that LOI occurs by an all-or-none process. All-or-none LOI could lead to a second distinct cell population that may have a selective advantage, leading to variation of LOI in normal tissues, such as the placenta, or in neoplastic cells.

Genetic risk factors associated with gestational diabetes in a multi-ethnic population.

AIMS: Genome-wide association studies have shown an increased risk of type-2-diabetes (T2DM) in patients who carry single nucleotide polymorphisms in several genes. We investigated whether the same gene loci confer a risk for gestational diabetes mellitus (GDM) in women from Hawaii, and in particular, Pacific Islander and Filipino populations. METHODS: Blood was collected from 291 women with GDM and 734 matched non-diabetic controls (Pacific Islanders: 71 GDM, 197 non-diabetic controls; Filipinos: 162 GDM, 395 controls; Japanese: 58 GDM, 142 controls). Maternal DNA was used to genotype and show allele frequencies of 25 different SNPs mapped to 18 different loci. RESULTS: After adjusting for age, BMI, parity and gravidity by multivariable logistic regression, several SNPs showed significant associations with GDM and were ethnicity specific. In particular, SNPs rs1113132 (EXT2), rs1111875 (HHEX), rs2237892 (KCNQ1), rs2237895 (KCNQ1), rs10830963 (MTNR1B) and rs13266634 (SLC30A8) showed significant associations with GDM in Filipinos. For Japanese, SNPs rs4402960 (IGFBP2) and rs2237892 (KCNQ1) were significantly associated with GDM. For Pacific Islanders, SNPs rs10830963 (MTNR1B) and rs13266634 (SLC30A8) showed significant associations with GDM. Individually, none of the SNPs showed a consistent association with GDM across all three investigated ethnicities. CONCLUSION: Several SNPs associated with T2DM are found to confer increased risk for GDM in a multiethnic cohort in Hawaii.

Intrauterine Growth Restriction Is Associated with Unique Features of the Reproductive Microbiome.

Intrauterine growth restriction (IUGR) is an obstetrical complication with an increased risk of perinatal mortality and morbidity. The uterus, once considered to be a sterile environment, has now been described in recent microbiome studies to harbor diverse commensal placenta microbiota, as well as potentially pathogenic flora known to cause infection. Therefore, in this pilot study, we tested whether IUGR was associated with changes to the reproductive microbiome. The reproductive microbiome was surveyed using 16S sequencing (20 IUGR, 20 controls). Alpha and beta diversity were compared, and differential taxa features associated with IUGR were identified. Microbial screening of the placenta demonstrated a diverse range of flora predominantly including Proteobacteria, Fusobacteria, Firmicutes, and Bacteroidetes. Neither alpha- nor beta-diversity was significantly different by IUGR status. However, at the taxa level, IUGR patients had significantly higher prevalence of Neisseriaceae, mucosal ß-hemolytic bacteria known to uptake iron-bound host proteins including hemoglobin. Moreover, the increase in anaerobic bacteria such as Desulfovibrio reflects the emergence of a hypoxic environment in the IUGR placenta. Further analysis of the reproductive microbiome of IUGR samples showed lower levels of H202-producing Bifidobacterium and Lactobacillus that switch from respiration to fermentation, a less energetic metabolic process, when oxygen levels decrease. Source tracking analysis showed that the placental microbial contents were predominantly contributed from an oral source, as compared to a gut or vaginal source. Our results suggest that the reproductive microbiome profiles may, in the future, constitute potential biomarkers for fetal health during pregnancy, while Neisseriaceae may constitute promising therapeutic targets for IUGR treatment.

Genomic loss of imprinting in first-trimester human placenta.

OBJECTIVE: The purpose of this study was to investigate imprinting patterns in first-trimester human placentas. STUDY DESIGN: Using samples of 17 first-trimester and 14 term placentas from uncomplicated pregnancies, we assessed loss of imprinting (LOI) at the RNA level in a panel of 14 genes that are known to be imprinted in the placenta with the use of a quantitative allele-specific reverse transcriptase polymerase chain reaction analysis of those genes that contained readout single nucleotide polymorphisms in their transcripts. RESULTS: There is significant LOI (ie, biallelic expression) in all 14 genes in first-trimester placentas. LOI was more variable and generally at lower levels at term. Although there is little difference in gene expression, the level of LOI is higher in the first-trimester placentas, compared with term placentas. CONCLUSION: Genomic imprinting appears to be a dynamic maturational process across gestation in human placenta. In contrast with prevailing theories, epigenetic imprints may continue to evolve past 12 weeks of gestation.