Holly Loudon

Diversified Microbiota of Meconium Is Affected by Maternal Diabetes Status

Objectives This study was aimed to assess the diversity of the meconium microbiome and determine if the bacterial community is affected by maternal diabetes status. Methods The first intestinal discharge (meconium) was collected from 23 newborns stratified by maternal diabetes status: 4 mothers had pre-gestational type 2 diabetes mellitus (DM) including one mother with dizygotic twins, 5 developed gestational diabetes mellitus (GDM) and 13 had no diabetes. The meconium microbiome was profiled using multi-barcode 16S rRNA sequencing followed by taxonomic assignment and diversity analysis. Results All meconium samples were not sterile and contained diversified microbiota. Compared with adult feces, the meconium showed a lower species diversity, higher sample-to-sample variation, and enrichment of Proteobacteria and reduction of Bacteroidetes. Among the meconium samples, the taxonomy analyses suggested that the overall bacterial content significantly differed by maternal diabetes status, with the microbiome of the DM group showing higher alpha-diversity than that of no-diabetes or GDM groups. No global difference was found between babies delivered vaginally versus via Cesarean-section. Regression analysis showed that the most robust predictor for the meconium microbiota composition was the maternal diabetes status that preceded pregnancy. Specifically, Bacteroidetes (phyla) and Parabacteriodes (genus) were enriched in the meconium in the DM group compared to the no-diabetes group. Conclusions Our study provides evidence that meconium contains diversified microbiota and is not affected by the mode of delivery. It also suggests that the meconium microbiome of infants born to mothers with DM is enriched for the same bacterial taxa as those reported in the fecal microbiome of adult DM patients.

Exposure to Gestational Diabetes Mellitus and Low Socioeconomic Status: Effects on Neurocognitive Development and Risk of Attention-Deficit/Hyperactivity Disorder in Offspring

OBJECTIVE To examine the independent and synergistic effects of gestational diabetes mellitus (GDM) and low socioeconomic status (SES) on neurodevelopment and attention-deficit/hyperactivity disorder (ADHD) outcomes. DESIGN Cohort study. SETTING Flushing, New York. PARTICIPANTS A total of 212 preschool children as a part of the ongoing cohort study. MAIN EXPOSURES Gestational diabetes mellitus and low SES. MAIN OUTCOME MEASURES Primary outcomes are ADHD diagnosis based on Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition) criteria at age 6 years and several well-validated measures of neurobehavioral outcomes, cognitive functioning, ADHD symptoms, and temperament at age 4 years. Secondary outcomes are parent and teacher reports of behavioral and emotional problems at age 6 years. Neurobehavioral measures in relation to GDM and low SES were examined using generalized estimating equations and multivariate logistic regression analyses. RESULTS Both maternal GDM and low SES were associated with an approximately 2-fold increased risk for ADHD at age 6 years. However, the risk by GDM was greater among lower SES families than among higher SES families. Children exposed to both GDM and low SES demonstrated compromised neurobehavioral functioning, including lower IQ, poorer language, and impoverished behavioral and emotional functioning. A test of additive interaction found that the risk for ADHD increased over 14-fold (P = .006) when children were exposed to both GDM and low SES. Neither children exposed to maternal GDM alone nor those exposed to low SES alone had a notable increased risk for ADHD. CONCLUSIONS Maternal GDM and low SES, especially in combination, heighten the risk for childhood ADHD. Long-term prevention efforts should be directed at mothers with GDM to avoid suboptimal neurobehavioral development and mitigate the risk for ADHD among their offspring.

Global Methylation in the Placenta and Umbilical Cord Blood From Pregnancies With Maternal Gestational Diabetes, Preeclampsia, and Obesity

Emerging evidence indicates that maternal medical risk during pregnancy, such as gestational diabetes mellitus (GDM), preeclampsia, and obesity, predisposes the offspring to suboptimal development. However, the underlying biological/epigenetic mechanism in utero is still unknown. The current pilot study (N = 50) compared the levels of global methylation in the placenta and umbilical cord blood among women with and without each risk condition (GDM, preeclampsia, and obesity) and explored whether the levels of global methylation were associated with fetal/infant growth. Results show that global methylation levels in the placenta were lower in patients with gestational diabetes (P = .003) and preeclampsia (P = .05) but higher with obesity (P = .01). Suggestive negative associations were found between global methylation level in the placenta and infant body length and head circumference. While preliminary, it is possible that the placenta tissue, but not umbilical cord blood, may be epigenetically programmed by maternal GDM, preeclampsia, and obesity to carry out its own specific functions that influence fetal growth.

Neural Dysfunction in Postpartum Depression: An fMRI Pilot Study

INTRODUCTION With approximately 4 million births each year in the United States, an estimated 760,000 women annually suffer from a clinically significant postpartum depressive illness. Yet even though the relationship between psychiatric disorders and the postpartum period has been documented since the time of Hippocrates, fewer than half of all these cases are recognized. OBJECTIVE Because postpartum depression (PPD), the most common complication of childbearing, remains poorly characterized, and its etiology remains unclear, we attempted to address a critical gap in the mechanistic understanding of PPD by probing its systems-level neuropathophysiology, in the context of a specific neurobiological model of fronto-limbic-striatal function. METHODS Using emotionally valenced word probes, with linguistic semantic specificity within an integrated functional magnetic resonance imaging (fMRI) protocol, we investigated emotional processing, behavioral regulation, and their interaction (functions of clinical relevance to PPD), in the context of fronto-limbic-striatal function. RESULTS We observed attenuated activity in posterior orbitofrontal cortex for negative versus neutral stimuli with greater PPD symptomatology, increased amygdala activity in response to negative words in those without PPD symptomotology, and attenuated striatum activation to positive word conditions with greater PPD symptomotology. CONCLUSION Identifying the functional neuroanatomical profile of brain systems involved in the regulation of emotion and behavior in the postpartum period will not only assist in determining whether the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition psychiatric diagnostic specifier of PPD has an associated, unique, functional neuroanatomical profile, but a neurobiological characterization in relation to asymptomatic (postpartum non-depressed) control subjects, will also increase our understanding of the affective disorder spectrum, shed additional light on the possible mechanism(s) responsible for PPD and provide a necessary foundation for the development of more targeted, biologically based diagnostic and therapeutic strategies for PPD.

The neural processing of negative emotion postpartum: a preliminary study of amygdala function in postpartum depression

While contemporary diagnostic nosology characterizes postpartum depression (PPD) as a specifier of a major depressive disorder (MDD), this classification continues to be questioned. Functional magnetic resonance imaging (fMRI) holds the promise of helping to characterize the neuroanatomical dysfunction associated with dysregulated emotion after childbirth. Twenty postpartum women underwent fMRI in the presence of emotionally valenced stimuli. The observation of relative amygdala non-responsivity in subjects demonstrating greater depression symptomotology stands in contrast to imaging studies of MDD and provides insight into possible phenotypic differences of PPD.

Epigenome-wide cross-tissue predictive modeling and comparison of cord blood and placental methylation in a birth cohort.

AIM We compared predictive modeling approaches to estimate placental methylation using cord blood methylation. MATERIALS & METHODS We performed locus-specific methylation prediction using both linear regression and support vector machine models with 174 matched pairs of 450k arrays. RESULTS At most CpG sites, both approaches gave poor predictions in spite of a misleading improvement in array-wide correlation. CpG islands and gene promoters, but not enhancers, were the genomic contexts where the correlation between measured and predicted placental methylation levels achieved higher values. We provide a list of 714 sites where both models achieved an R2 ≥0.75. CONCLUSION The present study indicates the need for caution in interpreting cross-tissue predictions. Few methylation sites can be predicted between cord blood and placenta.

Association Between Senior Obstetrician Supervision of Resident Deliveries and Mode of Delivery

OBJECTIVE In December 2012, the Mount Sinai Hospital implemented a program to have senior obstetricians (more than 20 years of experience) supervise residents on labor and delivery during the daytime. The objective of this study was to estimate the association of resident supervision by senior obstetricians with mode of delivery. METHODS This was a retrospective cohort study of all resident deliveries at Mount Sinai from July 2011 to June 2015. We included all patients with live, term, singleton, vertex fetuses. We compared delivery outcomes between patients delivered before December 2012 and patients delivered December 2012 and later using logistic regression analysis to control for age, body mass index, parity, induction, and prior cesarean delivery. During the study period there were no other specific departmental initiatives to increase forceps deliveries aside from having six obstetricians with significant experience in operative deliveries supervise and teach residents on labor and delivery. RESULTS There were 5,201 live, term, singleton, vertex deliveries under the care of residents, 1,919 (36.9%) before December 2012 and 3,282 (63.1%) December 2012 or later. The rate of forceps deliveries significantly increased from 0.6% to 2.6% (adjusted odds ratio [OR] 8.44, 95% confidence interval [CI] 3.1-23.1), and the rate of cesarean deliveries significantly decreased from 27.3% to 24.5% (adjusted OR 0.68, 95% CI 0.55-0.83). There were no statistically significant differences in the rates of third- or fourth-degree lacerations or 5-minute Apgar scores less than 7. Among nulliparous women, the forceps rate increased from 1.0% to 3.4% (adjusted OR 4.87, 95% CI 1.74-13.63) and the cesarean delivery rate decreased from 25.6% to 22.7% (adjusted OR 0.69, 95% CI 0.53-0.89). The increase in forceps deliveries and the decrease in cesarean deliveries were seen only in daytime hours (7 AM to 7 PM), that is, the shift that was covered by senior obstetricians. CONCLUSION Having senior obstetricians supervise resident deliveries is significantly associated with an increased rate of forceps deliveries and a decreased rate of cesarean deliveries.

Abstract B60: Racial/ethnic differences in pregnant women's knowledge of the relationship between breast cancer risk and breastfeeding

Objectives: Breastfeeding reduces the risk of breast cancer, particularly triple negative breast cancer. Yet black women, who are at greater risk of developing triple negative breast cancer, are the least likely racial group to breastfeed. Little is known about black women9s knowledge of the link between breast cancer and breastfeeding. Given the link between BC and breastfeeding, among other benefits to breastfeeding, it is critical to understand why black women are the least likely racial group to breastfeed. The current study was designed to describe pregnant women9s knowledge of the breastfeeding and breast cancer link and other psychosocial variables among three racial/ethnic groups (black, white and Hispanic). It is hypothesized that pregnant black women will have lower knowledge about the benefits of breastfeeding, including knowledge about the link between breastfeeding and breast cancer than either white or Hispanic women. It is further hypothesized that, compared to other racial groups, black women will have lower intentions to breastfeed, poorer attitudes toward breastfeeding, lower self-efficacy, and lower levels of social influence/support to breastfeed. Methods: This research study was Institutional Review Board-approved and conducted in accordance with prevailing ethical principles. Pregnant women 18 years or older (N=93; 48.4% black; 28.0% Hispanic) were recruited during a prenatal visit at the OB/GYN practice of an urban hospital. The practice primarily serves underinsured women. The one-time, anonymous self-report survey was comprised of questions that captured each participant9s socio-demographic information such as age, race/ethnicity, education level and income as well as their breastfeeding knowledge, intentions, attitudes, and social influences (i.e., baby9s father, maternal/paternal grandmother opinion and preference for infant feeding). Results: Less than 40% of both black and white women were aware of the relationship between breastfeeding and breast cancer risk reduction, in comparison to 64.7% of Hispanic women. The opinions of the baby9s father and their doctor about breastfeeding were regarded the most important to black women. Contrary to our hypotheses, all women reported high intentions to breastfeed but most women indicated that they intended to breastfeed for less than 12 months. Black women also had the highest levels of positive breastfeeding attitudes and self-efficacy. Conclusions: The benefits of breastfeeding for long-term maternal health such as reduced risk of BC, including triple negative breast cancer in black women, have been documented in the literature; yet black women are least likely to breastfeed. The current study demonstrates that women have low knowledge about the link between BC and breastfeeding, particularly black and white women. These findings support the need for targeted interventions educating black women about the protective benefits of breastfeeding, particularly breast health, as a strategy to reduce their incidence and mortality of breast cancer. Despite our hypotheses, black women had higher rates of self-efficacy, breastfeeding attitudes, breastfeed intent, and medical mistrust. Future research efforts need to further explore why black women have the lowest breastfeeding rates, yet high rates of intentions, self-efficacy and attitudes about breastfeeding. Citation Format: Jamilia Sly, Sarah Miller, Rhoda Sperling, Fahimeh Sasan, Holly Loudon, Elizabeth Howell, Lina Jandorf. Racial/ethnic differences in pregnant women9s knowledge of the relationship between breast cancer risk and breastfeeding. [abstract]. In: Proceedings of the Eighth AACR Conference on The Science of Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; Nov 13-16, 2015; Atlanta, GA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2016;25(3 Suppl):Abstract nr B60.