Sunni Mumford

National Institutes of Health | NIH

Study question: To what extent are self-reported diagnoses of food allergies associated with fecundability, the per-cycle probability of conception? Summary answer: Fecundability was not appreciably associated with self-reported food allergy diagnoses, number of food allergies, age at first diagnosis, or time since last allergic reaction. What...

Children born via cesarean delivery have a higher risk of metabolic, immunological, and neurodevelopmental disorders compared to those born via vaginal delivery, although mechanisms remain unclear. We conducted a meta-analysis of epigenome-wide association studies to examine the associations between delivery mode and blood DNA methylation at birth...

Low maternal vitamin D concentrations during pregnancy have been associated with a range of offspring health outcomes. DNA methylation is one mechanism by which the maternal vitamin D status during pregnancy could impact offspring’s health in later life. We aimed to evaluate whether maternal vitamin D insufficiency during pregnancy was conditionall...

Purpose To identify sleep dimensions (characteristics) that co-occur in premenopausal women. The second aim was to examine associations between multiple dimensions of sleep and a set of demographic, lifestyle, and health correlates. The overarching goal was to uncover patterns of poor-sleep correlates that might inform interventions to improve slee...

Context Dyslipidemia is common, and resultant endothelial dysfunction may impact reproductive outcomes. No prospective study has examined the effect of preconception lipid parameters in both female and male partners or their interaction on live birth. Objective To determine whether live birth is associated with preconception lipids in both partner...

Background: Accumulating evidence shows that peri-conceptional and in-utero exposures have lifetime health impacts for mothers and their offspring. Objectives: We conducted a Follow-Up Study of the Effects of Aspirin in Gestation and Reproduction (EAGeR) trial with two objectives. First, we determined if women who enrolled at the Utah site (N =...

Worldwide trends to delay childbearing have increased parental ages at birth. Older parental age may harm offspring health, but mechanisms remain unclear. Alterations in offspring DNA methylation (DNAm) patterns could play a role as aging has been associated with methylation changes in gametes of older individuals. We meta‐analyzed epigenome‐wide a...

(Abstracted from Lancet 2023;402:1857–1865 Weight gain during pregnancy that exceeds the recommendations updated by the National Academy of Medicine (NAM) in 2009 has been associated with greater postpartum weight retention. One systematic review of 9 studies found an association between excessive weight gain during pregnancy and postpartum weight...

It is presently not known whether endogenous neuroactive steroid hormone trajectories across the menstrual cycle are distinguishable in women with premenstrual dysphoric disorder (PMDD). To improve the rigor in this area of research, we implemented a validated study methodology, involving blood sample collection at 8 key menstrual cycle timepoints,...

Context Patients with polycystic ovary syndrome (PCOS) are at high risk of depression, anxiety, and metabolic syndrome (MetSyn), a key predictor of cardiovascular disease. The impact of depression and/or anxiety on MetSyn is unknown in this population. Objective To compare the risk of developing MetSyn in patients with PCOS with and without a hist...

Menopause marks the cessation of fertility and the transition to post-reproductive years. Nearly 1M US women experience menopause annually, but despite the significant impact it has on their physical and mental health, menopause has been insufficiently studied. Oxytocin is a neurohormone that regulates emotionality, social behaviors, and fundamenta...

Context Along the menstrual cycle, associations between inconsistent sleep duration and levels of metabolic biomarkers are uncertain and could involve fluctuations in estrogen concentrations. Objective To examine associations between patterns of sleep duration and metabolic biomarkers across 2 menstrual cycles within a cohort of premenopausal wome...

Objective To compare neonatal outcomes in pregnancies resulting from embryos that have undergone preimplantation genetic testing (PGT) biopsy compared with no biopsy in both fresh and frozen embryo transfers (ETs) and determine whether findings are mediated by multiple births. Design Retrospective cohort study. Setting Society of Assisted Reprodu...

This work aimed to study clinical and neonatal outcomes of embryos derived from frozen compared to fresh donor oocytes in gestational carrier cycles. This is a retrospective cohort study using the Society for Assisted Reproductive Technology Clinic Outcome Reporting System database between 2014 and 2015, comprising of 1284 fresh transfer cycles to...

Background: Phthalates are endocrine-disrupting chemicals linked to adverse pregnancy outcomes. Despite the sensitivity of female reproductive processes to oxidation-reduction reaction stress and endocrine disruption, evidence for the impact of women's phthalate exposure on the ability to establish and maintain pregnancy has been inconclusive. Ob...

Maternal educational attainment (MEA) shapes offspring health through multiple potential pathways. Differential DNA methylation may provide a mechanistic understanding of these long-term associations. We aimed to quantify the associations of MEA with offspring DNA methylation levels at birth, in childhood and in adolescence. Using 37 studies from h...

Research suggests that polycystic ovary syndrome (PCOS) traits (e.g., hyperandrogenism) may create a suboptimal intrauterine environment and induce epigenetic modifications. Therefore, we assessed the associations of PCOS traits with neonatal DNA methylation (DNAm) using two independent cohorts. DNAm was measured in both cohorts using the Infinium...

STUDY QUESTION Are there significant associations existing between parental age differences and adverse perinatal outcomes? SUMMARY ANSWER Large differences in parental age are associated with adverse perinatal outcomes, particularly with older mothers paired with younger fathers. WHAT IS KNOWN ALREADY The association between advanced maternal ag...

Background Multifetal gestation could be associated with higher long‐term maternal mortality because it increases the risk of pregnancy complications such as preeclampsia and preterm birth, which are in turn linked to postpartum cardiovascular risk. Objectives We examined whether spontaneously conceived multifetal versus singleton gestation was as...

Twin gestations have greater nutritional demands than singleton gestations, yet dietary intakes of women with twin gestations have not been well described. In a prospective, multi-site US study of 148 women with dichorionic twin gestations (2012–2013), we examined longitudinal changes in diet across pregnancy. Women completed a food frequency quest...

Objective To study the clinical and neonatal outcomes of embryos derived from frozen oocytes relative to fresh oocytes in both autologous and donor oocyte cycles after fresh embryo transfer (ET). Design This is a retrospective cohort study using the Society for Assisted Reproductive Technology Clinic Outcome Reporting System database between 2014...

Background The metabolic changes that ultimately lead to gestational diabetes mellitus (GDM) likely begin before pregnancy. Cannabis use might increase the risk of GDM by increasing appetite or promoting fat deposition and adipogenesis. Objectives We aimed to assess the association between preconception cannabis use and GDM incidence. Methods We...

Complex diseases have multifactorial etiologies making actionable diagnostic biomarkers difficult to identify. Diagnostic research must expand beyond single or a handful of genetic or epigenetic targets for complex disease and explore a broader system of biological pathways. With the objective to develop a diagnostic tool designed to analyze a comp...

Background: The PrePARED consortium creates a novel resource for addressing preconception health by merging cohorts. We describe our data harmonization methods and results. Methods: Individual-level data from 12 prospective studies were pooled. The crosswalk-cataloging-harmonization procedure was used. The index pregnancy was defined as the firs...

Introduction: Prenatal exposure to stress has been associated with poor pregnancy outcomes, yet evidence linking stress and placental size is limited. Asthma is associated with worse pregnancy outcomes and women with asthma may be more susceptible to stress. Using the asthma-enriched B-WELL-Mom cohort, we examined the association between perceived...

Background: While redox stress likely plays an important role in reproductive health, the utility of peripheral biomarkers of oxidative stress, such as isoprostanes, during the periconception period remains underexplored. We evaluated the relationship between isoprostanes during preconception and gestational week 4 and women's reproductive health...

Variability in sleep duration and cardiovascular health have been infrequently investigated, particularly among reproductive-age women. We examined these associations across the menstrual cycle among a cohort of 250 healthy premenopausal women, aged 18-44y. The BioCycle study had collected cardiovascular biomarkers (serum high- and low-density lipo...

Background: Pregnancy complications are associated with increased risk of development of cardiometabolic diseases and earlier mortality. However, much of the previous research has been limited to White pregnant women. We aimed to investigate pregnancy complications in association with total and cause-specific mortality in a racially diverse cohort...

Background: Randomized trials in pregnancy are extremely challenging, and observational studies are often the only option to evaluate medication safety during pregnancy. However, such studies are often susceptible to immortal time bias if treatment initiation occurs after time zero of follow-up. We describe how emulating a sequence of target trial...

Background Premenstrual symptoms, including food cravings, are often a regular complaint among menstruating women. However, existing evidence regarding the biological mechanisms by which these food cravings occur remains unclear. Inflammation may play an essential role in the occurence of these food cravings before menstruation. Purpose The purpos...

Shorter gestational age (GA) is a risk factor of developmental delay. GA is usually estimated clinically from last menstrual period and ultrasound. DNA methylation (DNAm) estimates GA using sets of cytosine-guanine-sites coupled with a clock algorithm. Therefore, DNAm estimated GA may better reflect biological maturation. A DNAm GA greater than cli...

Background: Maternal adaptations may vary by foetal sex. Whether male infants influence long-term mortality in mothers remains uncertain. Objective: The objective of the study was to examine whether male infants increase the risk of maternal mortality. Methods: This study included pregnant women enrolled at 12 US sites from 1959 to 1966 in the Coll...

Objective: Determine relations between preconception adiposity and human offspring sex and sex ratio. Methods: Within a prospective preconception cohort nested within a randomized controlled trial based at 4 U.S. clinical sites, logistic regression estimated odds ratios (ORs) and 95% confidence intervals (CIs) for male:female sex ratio and log-i...

Salivary steroid immunoassays are widely used in psychoneuroendocrinological studies of menstrual cycle phase, puberty, and menopause. Though manufacturers advertise their assays as suitable, they have not been rigorously validated for these purposes. We collated data from eight menstrual cycle studies across >1,200 female participants and >9,500 t...

Background Diet is increasingly recognized as an important determinant of human fertility, with most research focused on specific nutrients or food groups. However, there has been limited assessment of the effect of dietary patterns on fertility. Objectives We evaluated the association between 4 dietary patterns [the alternative Mediterranean Diet...

Objective: To examine whether semen parameters are associated with live birth among couples seeking infertility treatment after accounting for semen parameter variability. Design: Folic Acid and Zinc Supplementation Trial (FAZST) prospective cohort. Setting: Four US reproductive endocrinology and infertility care study centers, 2013-2017. Pat...

Context Ovarian stimulation (OS) increases pregnancy rates but can cause multiple folliculogenesis and multiple pregnancy. Objective To determine whether the probability of pregnancy differs in OS cycles with mono- versus multi-folliculogenesis in women with unexplained infertility (UI). Design Secondary analysis of a multi-center, randomized con...

Objective To determine the cost-effectiveness of planned oocyte cryopreservation (OC) as a strategy for delayed childbearing to achieve 1 or 2 live births (LB) compared with in vitro fertilization (IVF) and preimplantation genetic testing for aneuploidy (PGT-A) at advanced reproductive age. Design Decision tree model with sensitivity analyses usin...

STUDY QUESTION What is the association between perceived stress during peri-conception and early pregnancy and pregnancy loss among women who have experienced a prior pregnancy loss? SUMMARY ANSWER Daily perceived stress above the median is associated with over a 2-fold risk of early pregnancy loss among women who have experienced a prior loss. W...

Introduction We have recently shown that sperm epigenetic age (SEA), a surrogate measure of biological aging in sperm, is associated with couples’ time-to-pregnancy (TTP). Advanced SEA was also observed among smokers, suggesting its susceptibility to environmental exposures. Therefore, we assessed the association between urinary phthalate metabolit...

OBJECTIVE Ultraprocessed foods (UPFs) have been linked with obesity and cardiometabolic diseases in the general population but are understudied in pregnancy. We examined associations of UPF intake with gestational weight gain (GWG), glycemic, and blood pressure outcomes in pregnancy. RESEARCH DESIGN AND METHODS Pregnant women (n = 1,948) in a pros...

Study question: Is sperm epigenetic aging (SEA) associated with probability of pregnancy among couples in the general population? Summary answer: We observed a 17% lower cumulative probability at 12 months for couples with male partners in the older compared to the younger SEA categories. What is known already: The strong relation between chro...

Salivary steroid immunoassays are widely used in psychoneuroendocrinology to investigate the psychological effects of menstrual cycle phase. Though manufacturers advertise their assays as suitable, they have not been rigorously validated for this purpose. We collated data from eight studies across more than 1,200 women and more than 9,500 time poin...

Background Maternal prenatal stress is associated with physiologic and adverse mental health outcomes in the offspring, but the underlying biologic mechanisms are unknown. We examined the associations of maternal perceived stress, including preconception exposure, with DNA methylation (DNAm) alterations in the cord blood buffy coats of 358 singleto...

Background Complex diseases have multifactorial etiologies making clinically actionable diagnostic markers difficult to identify. Novel tools with higher diagnostic yield and utility in driving personalized care are needed. Methods We utilized Illumina methylation array data from 2612 samples to assess DNA methylation patterns in 19 distinct cell...

Pregnancy loss is a common reproductive complication but its association with long-term mortality and whether this varies by maternal race/ethnicity is not well understood. A racially diverse cohort of pregnant women enrolled in the Collaborative Perinatal Project (CPP) from 1959-1966 was used for this study. CPP records were linked to the National...

Objective To examine the relationship of preconception hemoglobin A1c, a marker of cumulative exposure to glucose over the preceding 2-3 months, with time to pregnancy (TTP), pregnancy loss, and live birth among fecund women without diagnosed diabetes or other medical diseases. Design A secondary analysis of a prospective cohort of women participa...

Background: Caffeine is the most frequently used psychoactive substance in the U.S. and more than 90% of reproductive-age women report some level of intake daily. Despite biological plausibility, previous studies on caffeine and fecundability report conflicting results. Importantly, prior studies measured caffeine exposure exclusively by self-repo...

Systematic reviews and meta-analyses are essential for drawing conclusions regarding etiologic associations between exposures or interventions and health outcomes. Observational studies comprise a substantive source of the evidence base. One major threat to their validity is residual confounding, which may occur when component studies adjust for di...

Introduction Adverse pregnancy outcomes such as preterm delivery and preeclampsia are associated with a higher maternal risk for subsequent cardiovascular disease (CVD) and all-cause mortality. While such pregnancy conditions are related to abnormal placentation, little research has investigated whether pathologic placental measures could serve as...

Importance Women are recommended to limit caffeine consumption to less than 200 mg per day based on risks to fetal health. Impacts of caffeine on maternal health remain unclear. Objective To determine whether caffeinated-beverage intake and plasma caffeine and paraxanthine are associated with cardiometabolic complications in pregnancy (ie, gestati...

Background: Epigenetic mechanisms may underlie associations between maternal caffeine consumption and adverse childhood metabolic outcomes. However, limited studies have examined neonate DNA methylation (DNAm) patterns in the context of preconception or prenatal exposure to caffeine metabolites. Objective: We examined preconception and pregnancy...

PurposeTo examine associations between objectively measured sleep duration and sleep timing with odds of completion of an in vitro fertilization (IVF) cycle.Methods This prospective cohort study enrolled 48 women undergoing IVF at a large tertiary medical center between 2015 and 2017. Sleep was assessed by wrist-worn actigraphy, 1–2 weeks prior to...

Objective To determine if 6-month folic acid (5 mg) and zinc (30 mg) supplementation impacts sperm DNA methylation patterns. Design A multicenter, double-blind, block randomized, placebo-controlled trial titled “The Folic Acid and Zinc Supplementation Trial (FAZST).” Setting Infertility care centers. Patient(s) Male partners (18 years and older)...

Study question: Is preconception leukocyte telomere length associated with fecundability, pregnancy loss and live birth among women attempting natural conception with a history of 1-2 prior pregnancy losses? Summary answer: Preconception leukocyte telomere length is not associated with fecundability, pregnancy loss or live birth. What is known...

Objectives Maternal diet prior to and during pregnancy has been related to child health across the lifespan; however, mechanisms remain unclear. Gestational age acceleration (GAA), a measure of epigenetic aging relative to clinically estimated gestational age (GA), has emerged as a potential biomarker predictive of childhood BMI and atopic diseases...

Objectives Prior research has suggested that epigenetic mechanisms may underly associations between maternal caffeine intake and adverse childhood metabolic outcomes. We examined preconception and early pregnancy maternal caffeine exposure with DNA methylation (DNAm) patterns in the cord blood of 378 neonates. Methods DNAm was profiled by the Infi...

Background Cadmium is an endocrine disrupting chemical that affects the hypothalamic-pituitary-gonadal axis. Though evidence suggests its potential role in altering androgen synthesis and metabolic pathways that are characteristic of polycystic ovary syndrome (PCOS), its relation in healthy women of reproductive age is largely unknown. As women wit...

Evolutionary theory suggests that some animal species may experience shifts in their offspring sex ratio in response to maternal health and environmental conditions, and in some unfavorable conditions, females may be less likely to bear sons. Experimental data in both animals and humans indicate that maternal inflammation may disproportionately imp...

STUDY QUESTION Are insufficient 25-hydroxyvitamin D (25(OH)D) concentrations, and other markers of vitamin D metabolism, associated with premenstrual symptoms in healthy women with regular menstrual cycles? SUMMARY ANSWER 25(OH)D insufficiency was associated with specific physical premenstrual symptoms, while no associations were observed with psy...

Background Research has established that maternal diet influences fetal growth and preterm birth, but most studies only evaluate single nutrients. Relations between dietary patterns and neonatal outcomes are understudied. Objective We evaluated associations of neonatal outcomes with maternal diet patterns derived using 3 a priori diet scores [Alte...

Context Diets high in plant-based protein have gained popularity due to increasing health concerns regarding consumption of animal products. Though links between intakes of certain protein-rich foods and reproductive disorders have been suggested, the relationship of overall animal and vegetable proteins with reproductive hormones among reproductiv...

Background It has been suggested that premenstrual syndrome (PMS) may derive from either elevated oxidative stress or reduced antioxidant vitamin levels in the body; however, these relationships have been minimally studied in a large cohort of healthy women. Our objective was to estimate the association between serum concentrations of antioxidant v...

Background: A previous large randomized trial indicated that preconception-initiated low-dose aspirin (LDA) therapy did not have a positive effect on pregnancy outcomes. However, this trial was subject to nonadherence, which was not taken into account by the intention-to-treat approach. Objective: To estimate per protocol effects of preconceptio...

Study question: Is cannabis use assessed via urinary metabolites and self-report during preconception associated with fecundability, live birth and pregnancy loss? Summary answer: Preconception cannabis use was associated with reduced fecundability among women with a history of pregnancy loss attempting pregnancy despite an increased frequency o...

Objective: To characterize variation in circulating vascular endothelial growth factor (VEGF) and its receptor, soluble fms-like tyrosine kinase-1 (sFLT-1), across the menstrual cycle in normal ovulating women in relation to reproductive hormones to identify the utility of VEGF and sFLT-1 as peripheral biomarkers of endometrial remodeling. Method...

Objective To prospectively investigate the association of selective serotonin reuptake inhibitor (SSRI) exposure through critical windows of pregnancy establishment with fecundability and pregnancy loss. Design Prospective cohort study using longitudinal urine measurements of common SSRIs while women are actively trying to conceive. Setting Four...