Placental genetic variations in vitamin D metabolism and birthweight.

INTRODUCTION: Vitamin D has pleiotropic functions that regulate fetal growth and development. We investigated associations of common placental genetic variations in vitamin D metabolism with birthweight. METHODS: The study was conducted among participants (506 maternal-infant pairs) of a pregnancy cohort study. Data were collected using interviewer-administered questionnaires and post-delivery medical record abstraction. DNA, extracted from placental samples collected at delivery, was genotyped for eight single nucleotide polymorphisms (SNPs) in five vitamin D metabolism genes (CUBN, LRP2, VDR, GC, and CYP2R1). Linear and logistic regression models were used to evaluate associations of SNPs with birthweight and risk of low birthweight, respectively. Effect modification of associations by infant sex was examined using stratified analyses and interaction terms in regression models. RESULTS: Mean (standard-deviation) birthweight among all, male, and female infants was 3482.1 (549.9), 3544.6 (579.0) and 3419.2 (512.5) grams, respectively. Each copy of the minor allele of rs2282679 (GC) was associated with a 68.6 g (95%CI:3.1134.7 g) increase in birthweight overall. Sex-specific associations were observed for SNP rs4667591 (LRP2) (p-value for interaction \u3c 0.001). Each copy of the minor allele of rs4667591 was associated with a 124.7 g (95%CI:20.1229.0 g) increase in birthweight among female infants, and a suggested 81.6 g decrease in birthweight among male infants (95%CI:-183.7,20.5 g). DISCUSSION: Our study identified overall and sex-specific associations between placental genetic variations in vitamin D metabolism and birthweight. If confirmed by larger replication studies, observed associations may provide insight into mechanistic underpinnings of the relationships between placental vitamin D metabolism and birth size

Walking for Health During Pregnancy: A Literature Review and Considerations for Future Research

Walking is the most commonly chosen type of physical activity (PA) during pregnancy and provides several health benefits to both mother and child. National initiatives have promoted the importance of walking in general, but little emphasis is directed toward pregnant women, the majority of whom are insufficiently active. Pregnant women face a variety of dynamic barriers to a physically active lifestyle, some of which are more commonly experienced during specific times throughout the pregnancy experience. Walking is unique in that it appears resistant to a number of these barriers that limit other types of PA participation, and it can be meaningfully integrated into some transportation and occupational activities when leisure-time options are unavailable. Preliminary intervention work suggests that walking programs can be effectively adopted into a typical pregnancy lifestyle. However, a great deal of work remains to administer successful pregnancy walking interventions, including developing and using validated methods of PA and walking assessment. This narrative review discusses the unique advantages of walking during pregnancy, provides recommendations for future intervention work, and outlines the need for pregnancy-focused community walking initiatives.Standard search procedures were followed to determine sources from the literature specific to walking during pregnancy for use in each section of this review

Maternal periconceptional physical activity, sedentary behavior, and offspring growth

Thesis (Ph.D.)--University of Washington, 2017-06Background: Current guidelines recommend regular moderate/vigorous physical activity before and during pregnancy to reduce pregnancy complications. However, the recommendations do not include light physical activity or address fetal and postnatal growth. While reductions in sedentary behavior, in addition to regular moderate/vigorous physical activity, have been recommended for the general population, little is known about the effect of maternal sedentary behavior before and during pregnancy on offspring in utero or postnatal growth. In addition, consequences of long-term patterns of preconception physical activity during young adulthood, offspring sex-specific differences in associations, as well as potential mechanisms of observed associations have not been adequately investigated. Objectives: The specific aims of this dissertation project were to investigate associations of 1) maternal pre-pregnancy and early pregnancy light physical activity and sedentary behavior with measures of offspring birth size, 2) maternal early pregnancy moderate/vigorous physical activity and sedentary behavior with offspring growth at 12 months of age, 3) trajectories of maternal preconception moderate/vigorous physical activity and sedentary time during adolescence and young adulthood with offspring birthweight, and 4) maternal pre-pregnancy and early pregnancy moderate/vigorous physical activity and epigenetic regulation in maternal peripheral blood. Methods: Aim 1 was addressed using data from participants (N=3,687) of the Omega study, a pregnancy cohort study based in Seattle, WA. Aim 2 was addressed using data from participants (N=40,638) of the Danish National Birth Cohort (DNBC). Aim 3 was addressed using data from participants (N=1,408) of the National Longitudinal Study of Adolescent to Adult Health (Add Health). Aim 4 was addressed using data and specimens collected from a subset (N=92) of Omega study participants. I used self-reported leisure time physical activity and sedentary behavior before and during pregnancy, information on offspring birth size and offspring weight at 12 months from medical records (Omega study) or maternal report (DNBC and Add Health), and epigenetic biomarkers (DNA methylation and microRNA expression) in peripheral blood (Aim 4), as well as information on relevant covariates in regression (linear and logistic) models and group-based trajectory analyses (Aim 3) to examine associations. Offspring sex-specific associations were evaluated using interaction terms and stratified analyses. Results: Leisure time walking in the year before pregnancy and in early pregnancy were positively associated (0.8 kg/m3 comparing the highest tertile to no walking (95% CI: 0.2, 1.4 and 0.2, 1.3, respectively)) with greater offspring ponderal index at birth (Aim 1). Moderate/vigorous leisure time physical activity in early pregnancy was inversely associated (0.01 kg per hour per week (95% CI: -0.02, -0.001)) with offspring weight at 12 months old among males, but not females (Aim 2). Early pregnancy leisure time sedentary behavior was also inversely associated (0.09 kg comparing 5+ hours per day to 0-1 hours per day (95% CI: -0.17, -0.003)) with offspring weight at 12 months old (Aim 2). I identified sex-specific associations of a pattern of preconception moderate/vigorous physical activity characterized by high physical activity at age 15 years followed by decreasing physical activity by age 22 years compared to a pattern of low then decreasing physical activity from ages 15-22 years with 90g (95% CI: -4, 184) greater birthweight and 1.7 (95% CI: 0.9, 3.1) times greater odds of large-for-gestational age among female offspring, but not male offspring (Aim 3). I did not observe associations of pre-pregnancy or early pregnancy yoga practice with offspring birth size (Aim 1) or associations of maternal pre-pregnancy or early pregnancy sedentary behavior with offspring birth size (Aim 1 and 3). Each additional hour per week of pre-pregnancy and early pregnancy moderate/vigorous physical activity were associated with peripheral blood DNA methylation in C1orf212 and circulating miR-146b expression (Aim 4). Conclusions: Our results support associations of maternal physical activity with offspring birth size, postnatal growth, and maternal epigenetic regulation. Our results also support associations of maternal sedentary behavior with offspring postnatal growth. Several of these associations were sex-specific. Future research in this area, conducted in diverse populations and using objective measurement to capture accurate measures of time spent in these behaviors across multiple domains, will facilitate adoption of effective interventions to promote physical activity among reproductive age and pregnant women and improve maternal and fetal health outcomes

Antepartum and intrapartum stillbirth rates across gestation: a cross-sectional study using the revised foetal death reporting system in the U.S.

Abstract Background There is a renewed call to address preventable foetal deaths in high-income countries, especially where progress has been slow. The Centers for Disease Control and Prevention released publicly, for the first time, the initiating cause and estimated timing of foetal deaths in 2014. The objective of this study is to describe risk and characteristics of antepartum versus intrapartum stillbirths in the U.S., and frequency of pathological examination to determine cause. Methods We conducted a cross-sectional study of singleton births (24–43 weeks) using 2014 U.S. Fetal Death and Natality data available from the National Center for Health Statistics. The primary outcome was timing of death (antepartum (n = 6200), intrapartum (n = 453), and unknown (n = 5403)). Risk factors of interest included maternal sociodemographic, behavioural, medical and obstetric factors, along with foetal sex. We estimated gestational week-specific stillbirth hazard, risk factors for intrapartum versus antepartum stillbirth using multivariable log-binomial regression models, conditional probabilities of intrapartum and antepartum stillbirth at each gestational week, and frequency of pathological examination by timing of death. Results The gestational age-specific stillbirth hazard was approximately 2 per 10,000 foetus-weeks among preterm gestations and > 3 per 10,000 foetus-weeks among term gestations. Both antepartum and intrapartum stillbirth risk increased in late-term and post-term gestations. The risk of intrapartum versus antepartum stillbirth was higher among those without a prior live birth, relative to those with at least one prior live birth (RR 1.32; 95% CI 1.08–1.61) and those with gestational hypertension, relative to those with no report of gestational hypertension (RR 1.47; 95% CI 1.09–1.96), and lower among Black, relative to white, individuals (RR 0.70; 95% CI 0.55–0.89). Pathological examination was not performed/planned in 25% of known antepartum stillbirths and 29% of known intrapartum stillbirths. Conclusion These findings suggest greater stillbirth risk in the late-term and post-term periods. Primiparous mothers had greater risk of intrapartum than antepartum still birth, suggesting the need for intrapartum interventions for primiparous mothers in this phase of pregnancy to prevent some intrapartum foetal deaths. Efforts are needed to improve understanding, prevention and investigation of foetal deaths as well as improve stillbirth data quality and completeness in the United States

Lifestyle-related education and counseling resource utilization and cardiovascular biomarkers in midlife women with low physical activity

Health plan-based resources are promising avenues for decreasing cardiovascular disease risk. This study examined associations of lifestyle-related resource utilization within a healthcare delivery system and cardiovascular biomarkers among midlife women with low physical activity. Midlife women (45-55 years old) with <10 min/week of reported physical activity at a primary care visit within a large integrated healthcare delivery system in Northern California in 2015 (n = 55,393) were identified. Within this cohort, subsequent lifestyle-related health education and individual coaching resource utilization, and the next recorded physical activity, weight, systolic blood pressure, plasma glucose, HDL and LDL cholesterol measures up to 2 years after the index primary care visit were identified from electronic health records. We used a multilevel linear model to estimate associations. About 3% (n = 1587) of our cohort had ≥1 lifestyle-related resource encounter; 0.3% (n = 178) had ≥ 4 encounters. Participation in ≥4 lifestyle-related resource encounters (compared to none) was associated with 51 more minutes/week of physical activity (95% CI: 33,69) at the next clinical measurement in all women, 6.2 kg lower weight (95% CI: −7.0,-5.5) at the next measurement in women with obesity, and 8–10 mg/dL lower plasma glucose (95% CI: −30,14 and −23,2, respectively) at the next measurement in women with diabetes or prediabetes. Our results support the sustained utilization of health plan-based lifestyle-related resources for improving physical activity, weight, and plasma glucose in high-risk midlife women. Given the observed low utilization, health system-wide efforts may be warranted to increase utilization of lifestyle-related resources in this population

Maternal sedentary behavior during pre-pregnancy and early pregnancy and mean offspring birth size: a cohort study

Abstract Background Sedentary behavior is associated with adverse health outcomes in the general population. Whether sedentary behavior during pregnancy is associated with newborn outcomes, such as birth size, is not established, and previous studies have been inconsistent. While previous research suggests that male and female fetuses respond differently to maternal behaviors, such as physical activity, the role of infant sex in sedentary behavior-birth size associations has not been examined. Methods Participants in the Omega study, a cohort in Washington State (1996–2008), reported leisure time sedentary behavior (non-work time spent sitting), light intensity physical activity, and moderate/vigorous leisure time physical activity duration in the year before pregnancy (N = 1373) and in early pregnancy (N = 1535, mean 15 weeks). Offspring birth size was abstracted from delivery records. Non-parametric calibration weighting was used to assign adjustment weight (matching the distribution of sociodemographic and medical characteristics of the full cohort (N = 4128)) to participants with available sedentary behavior data. Weighted linear regression models were used to estimate mean differences in offspring birthweight, head circumference, and ponderal index (birthweight/length3) associated with leisure time sedentary behavior. Regression models were run overall and stratified by offspring sex. Isotemporal substitution modeling was used to determine mean differences in birthweight associated with replacing sedentary behavior with light or moderate/vigorous physical activity. Results On average, women spent 2.3 and 2.6 h/day in leisure time sedentary behavior during pre- and early pregnancy, respectively. There were no associations of pre-pregnancy leisure time sedentary behavior with mean birthweight, head circumference, or ponderal index (adjusted β = − 12, 95% CI: -28, 4.1; β = 0.0, 95% CI: -0.04, 0.1; and β = 0.1, 95% CI: -0.2, 0.4, respectively). Early pregnancy sedentary behavior was not associated with mean birth size. Associations of sedentary behavior with mean birth size did not differ by offspring sex. Replacing sedentary time with light or moderate/vigorous physical activity was not associated with mean birthweight. Conclusions We did not observe associations of maternal sedentary behavior during pre- or early pregnancy with mean offspring birth size. Pre-pregnancy and early pregnancy sedentary behavior may have important adverse effects on maternal health, but our results do not support associations with mean offspring birth size

Maternal healthy lifestyle during early pregnancy and offspring birthweight: differences by offspring sex.

PURPOSE: Individual maternal lifestyle factors during pregnancy have been associated with offspring birthweight; however, associations of combined lifestyle factors with birthweight and potential differences by offspring sex have not been examined. MATERIALS AND METHODS: Participants (N = 2924) were identified from a pregnancy cohort in Washington state. Lifestyle factors during early pregnancy were dichotomized based on Alternate Healthy Eating Index score ≥62, leisure time physical activity (LTPA) ≥ 150 min/week, not smoking during pregnancy and Perceived Stress Scale score ≤3, then combined into a lifestyle score (0-4). Regression models were run overall and stratified by offspring sex, prepregnancy overweight/obese (BMI ≥25 kg/m RESULTS: Overall, 20% of participants had healthy diet, 95% were nonsmokers, 55% had low stress levels, and 66% were physically active. Lifestyle score was not associated with birthweight (β = 3.3 g; 95% CI: -14.5, 21.0); however, associations differed by offspring sex (p = .009). For each unit increase in lifestyle score, there was a suggested 22.4 g higher birthweight (95% CI: -2.7, 47.6) among males and 14.6 g lower birthweight (95% CI: -39.9, 10.7) among females. Prepregnancy BMI and LTPA did not modify associations. CONCLUSIONS: Healthy lifestyle score in early pregnancy may be associated with greater birthweight among male offspring, but lower birthweight among female offspring

Healthy preconception and early-pregnancy lifestyle and risk of preterm birth: a prospective cohort study.

BackgroundPreterm birth (PTB) remains a leading cause of neonatal mortality and long-term morbidity. Individual factors have been linked to PTB risk. The impact of a healthy lifestyle, with multiple modifiable prenatal factors, remains unknown.ObjectivesWe aimed to examine the associations of preconceptional and early-pregnancy low-risk modifiable factors (individually and in combination) with PTB risk.MethodsThis prospective cohort study included 2449 women with singleton pregnancies in the Pregnancy Environment and Lifestyle Study. PTB was defined as ultrasound-confirmed obstetric estimate-based gestational age at delivery &lt;37 wk. A set of low-risk modifiable factors were identified: healthy weight (prepregnancy BMI: 18.5-24.9 kg/m2) based on clinical measurements and high-quality diet (Alternate Healthy Eating Index-Pregnancy score ≥75th percentile) and low-to-moderate stress during early pregnancy (Perceived Stress Scale score &lt;75th percentile) assessed at gestational weeks 10-13. Poisson regression estimated adjusted relative risk (aRR) of PTB in association with individual and combined low-risk modifiable prenatal factors, adjusting for sociodemographic, clinical, and other prenatal factors.ResultsOne hundred and sixty women (6.5%) delivered preterm. Risk of PTB was lower among women who had a healthy weight (aRR: 0.58; 95% CI: 0.39, 0.86), high-quality diet (aRR: 0.68; 95% CI: 0.39, 0.99), and low-to-moderate stress (aRR: 0.60; 95% CI: 0.41, 0.88). Women with 1, 2, or 3 low-risk modifiable prenatal factors compared with none had a 38% (aRR: 0.72; 95% CI: 0.45, 1.16), 51% (aRR: 0.49; 95% CI: 0.29, 0.84), or 70% (aRR: 0.30; 95% CI: 0.13, 0.70) lower PTB risk, respectively. Associations of having ≥1 low-risk factor with PTB risk were more pronounced for medically indicated than for spontaneous PTB and for late than for early or moderate PTB. Associations also varied by race or ethnicity, although with overlapping 95% CIs.ConclusionsA healthy prenatal lifestyle with multiple low-risk modifiable factors was associated with lower risk of PTB. Our findings may inform multicomponent preconceptional or early-pregnancy prevention strategies to mitigate PTB risk

A Web-Based mHealth Intervention With Telephone Support to Increase Physical Activity Among Pregnant Patients With Overweight or Obesity: Feasibility Randomized Controlled Trial.

BackgroundPregnant patients with overweight or obesity are at high risk for perinatal complications. Excess gestational weight gain (GWG) further exacerbates this risk. Mobile health (mHealth) lifestyle interventions that leverage technology to facilitate self-monitoring and provide just-in-time feedback may motivate behavior change to reduce excess GWG, reduce intervention costs, and increase scalability by improving access.ObjectiveThis study aimed to test the acceptability and feasibility of a pilot mHealth lifestyle intervention for pregnant patients with overweight or obesity to promote moderate intensity physical activity (PA), encourage guideline-concordant GWG, and inform the design of a larger pragmatic cluster randomized controlled trial.MethodsWe conducted a mixed methods acceptability and feasibility randomized controlled trial among pregnant patients with a prepregnancy BMI of 25 to 40 kg/m2. Patients with singletons at 8 to 15 weeks of gestation who were aged ≥21 years and had Wi-Fi access were recruited via email from 2 clinics within Kaiser Permanente Northern California and randomized to receive usual prenatal care or an mHealth lifestyle intervention. Participants in the intervention arm received wireless scales, access to an intervention website, activity trackers to receive automated feedback on weight gain and activity goals, and monthly calls from a lifestyle coach. Surveys and focus groups with intervention participants assessed intervention satisfaction and ways to improve the intervention. PA outcomes were self-assessed using the Pregnancy Physical Activity Questionnaire, and GWG was assessed using electronic health record data for both arms.ResultsOverall, 33 patients were randomly assigned to the intervention arm, and 35 patients were randomly assigned to the usual care arm. All participants in the intervention arm weighed themselves at least once a week, compared with 20% (7/35) of the participants in the usual care arm. Participants in the intervention arm wore the activity tracker 6.4 days per week and weighed themselves 5.3 times per week, and 88% (29/33) of them rated the program "good to excellent." Focus groups found that participants desired more nutrition-related support to help them manage GWG and would have preferred an app instead of a website. Participants in the intervention arm had a 23.46 metabolic equivalent of task hours greater change in total PA per week and a 247.2-minute greater change in moderate intensity PA per week in unadjusted models, but these effects were attenuated in adjusted models (change in total PA: 15.55 metabolic equivalent of task hours per week; change in moderate intensity PA: 199.6 minutes per week). We found no difference in total GWG (mean difference 1.14 kg) compared with usual care.ConclusionsThe pilot mHealth lifestyle intervention was feasible, highly acceptable, and promoted self-monitoring. Refined interventions are needed to effectively affect PA and GWG among pregnant patients with overweight or obesity.Trial registrationClinicalTrials.gov NCT03936283; https://clinicaltrials.gov/ct2/show/NCT03936283