Effect of COVID-19 vaccination and booster on maternal-fetal outcomes: a retrospective cohort study.

BACKGROUND: COVID-19 in pregnant people increases the risk for poor maternal-fetal outcomes. However, COVID-19 vaccination hesitancy remains due to concerns over the vaccine's potential effects on maternal-fetal outcomes. Here we examine the impact of COVID-19 vaccination and boosters on maternal SARS-CoV-2 infections and birth outcomes. METHODS: This was a retrospective multicentre cohort study on the impact of COVID-19 vaccination on maternal-fetal outcomes for people who delivered (n=106 428) at Providence St Joseph Health across seven western US states from Jan 26, 2021 to Oct 26, 2022. Cohorts were defined by vaccination status at delivery: vaccinated (n=35 926; two or more doses of mRNA-1273 Moderna or BNT162b2 Pfizer-BioNTech), unvaccinated (n=55 878), unvaccinated propensity score matched (n=16 771), boosted (n=10 927; three or more doses), vaccinated unboosted (n=13 243; two doses only), and vaccinated unboosted with propensity score matching (n=4414). We built supervised machine learning classification models, which we used to determine which people were more likely to be vaccinated or boosted at delivery. The primary outcome was maternal SARS-CoV-2 infection. COVID-19 vaccination status at delivery, COVID-19-related health care, preterm birth, stillbirth, and very low birthweight were evaluated as secondary outcomes. FINDINGS: Vaccinated people were more likely to conceive later in the pandemic, have commercial insurance, be older, live in areas with lower household composition vulnerability, and have a higher BMI than unvaccinated people. Boosted people were more likely to have more days since receiving the second COVID-19 vaccine dose, conceive earlier in the pandemic, have commercial insurance, be older, and live in areas with lower household composition vulnerability than vaccinated unboosted people. Vaccinated pregnant people had lower rates of COVID-19 during pregnancy (4·0%) compared with unvaccinated matched people (5·3%; p<0·0001). COVID-19 rates were even lower in boosted people (3·2%) compared with vaccinated unboosted matched people (5·6%; p<0·0001). Vaccinated people were also less likely to have a preterm birth (7·9%; p<0·0001), stillbirth (0·3%; p<0·0002), or very low birthweight neonate (1·0%; p<0·0001) compared with unvaccinated matched people (preterm birth 9·4%; stillbirth 0·6%; very low birthweight 1·5%). Boosted people were less likely to have a stillbirth (0·3%; p<0·025) and have no differences in rates of preterm birth (7·6%; p=0·090) or very low birthweight neonates (0·8%; p=0·092) compared with vaccinated unboosted matched people (stillbirth 0·5%; preterm birth 8·4%; very low birthweight 1·1%). INTERPRETATION: COVID-19 vaccination protects against adverse maternal-fetal outcomes, with booster doses conferring additional protection. Pregnant people should be high priority for vaccination and stay up to date with their COVID-19 vaccination schedule. FUNDING: National Institute for Child Health & Human Development and the William O and K Carole Ellison Foundation.

Adoption of a National Prophylactic Anticoagulation Guideline for Hospitalized Pregnant Women With COVID-19: Retrospective Cohort Study.

BACKGROUND: Both COVID-19 and pregnancy are associated with hypercoagulability. Due to the increased risk for thrombosis, the United States National Institute of Health's recommendation for prophylactic anticoagulant use for pregnant patients has expanded from patients hospitalized for severe COVID-19 manifestation to all patients hospitalized for the manifestation of COVID-19 (no guideline: before December 26, 2020; first update: December 27, 2022; second update: February 24, 2022-present). However, no study has evaluated this recommendation. OBJECTIVE: The objective of this study was to characterize prophylactic anticoagulant use among hospitalized pregnant people with COVID-19 from March 20, 2020, to October 19, 2022. METHODS: This was a retrospective cohort study in large US health care systems across 7 states. The cohort of interest was pregnant patients who were hospitalized with COVID-19, without previous coagulopathy or contraindication to anticoagulants (n=2767). The treatment group consisted of patients prescribed prophylactic dose anticoagulation between 2 days before and 14 days after COVID-19 treatment onset (n=191). The control group was patients with no anticoagulant exposure between 14 days before and 60 days after COVID-19 treatment onset (n=2534). We ascertained the use of prophylactic anticoagulants with attention to the updates in guidelines and emerging SARS-CoV-2 variants. We propensity score matched the treatment and control group 1:1 on the most important features contributing to the prophylactic anticoagulant administration status classification. Outcome measures included coagulopathy, bleeding, COVID-19-related complications, and maternal-fetal health outcomes. Additionally, the inpatient anticoagulant administration rate was validated in a nationwide population from Truveta, a collective of 700 hospitals across the United States. RESULTS: The overall administration rate of prophylactic anticoagulants was 7% (191/2725). It was lowest after the second guideline update (no guideline: 27/262, 10%; first update: 145/1663, 8.72%; second update: 19/811, 2.3%; P<.001) and during the omicron-dominant period (Wild type: 45/549, 8.2%; Alpha: 18/129, 14%; Delta: 81/507, 16%; and Omicron: 47/1551, 3%; P<.001). Models developed on retrospective data showed that the variable most associated with the administration of inpatient prophylactic anticoagulant was comorbidities prior to SARS-CoV-2 infection. The patients who were administered prophylactic anticoagulant were also more likely to receive supplementary oxygen (57/191, 30% vs 9/188, 5%; P<.001). There was no statistical difference in a new diagnosis of coagulopathy, bleeding, or maternal-fetal health outcomes between those who received treatment and the matched control group. CONCLUSIONS: Most hospitalized pregnant patients with COVID-19 did not receive prophylactic anticoagulants across health care systems as recommended by guidelines. Guideline-recommended treatment was administered more frequently to patients with greater COVID-19 illness severity. Given the low rate of administration and differences between treated and untreated cohorts, efficacy could not be assessed.

A hybrid educational approach to service learning: impact on student attitudes and readiness in working with medically underserved communities.

Medical students engage with medically underserved communities (MUC) and vulnerable populations but often lack preparation to advocate appropriately for these communities. While preclinical programs with an experiential community component effectively increase knowledge about serving MUC, the pandemic limited clinical opportunities in community settings for learners. We examined the impact of a streamlined, hybrid service learning curriculum on first-year medical student attitudes towards MUC and their readiness and interest in addressing health barriers faced by this population. The redesigned curriculum for the student-led program required participants to attend nine virtual seminars led by faculty and community members with expertise serving MUC. Students partnered with one of three community agencies to organize service projects and gain exposure to the life experiences of MUC using virtual and in-person approaches. Of the fifteen first year medical students who participated in the program, positive attitudes were sustained across all scales using the Medical Student Attitudes Toward the Underserved (MSATU) questionnaire after one year. A majority (≥50%) of students reported a large increase in their knowledge of the health challenges faced by underserved populations after each didactic session. Despite the mostly virtual nature of community partnerships, students reported increased confidence in their ability to direct MUC patients to local resources (p < 0.01). The program also had a positive impact on student interest in working with medically underserved patients in the future, with 71% of participants indicating a significant impact on their interest in working in a medically underserved area. Our redesigned elective curriculum provided participants with foundational knowledge to advocate appropriately for underserved populations and demonstrated the efficacy of virtual approaches for community service and service learning. Our findings suggest hybrid and virtual experiential learning opportunities are a viable and non-inferior curricular approach to teaching health equity and community health.

The effect of COVID-19 vaccination and booster on maternal-fetal outcomes: a retrospective multicenter cohort study.

Background: COVID-19 infection in pregnant people has previously been shown to increase the risk for poor maternal-fetal outcomes. Despite this, there has been a lag in COVID-19 vaccination in pregnant people due to concerns over the potential effects of the vaccine on maternal-fetal outcomes. Here we examine the impact of COVID-19 vaccination and booster on maternal COVID-19 breakthrough infections and birth outcomes. Methods: This was a retrospective multicenter cohort study on the impact of COVID-19 vaccination on maternal-fetal outcomes for people that delivered (n=86,833) at Providence St. Joseph Health across Alaska, California, Montana, Oregon, New Mexico, Texas, and Washington from January 26, 2021 through July 11, 2022. Cohorts were defined by vaccination status at time of delivery: unvaccinated (n=48,492), unvaccinated propensity score matched (n=26,790), vaccinated (n=26,792; two doses of mRNA-1273 Moderna or BNT162b2 Pfizer-BioNTech), and/or boosted (n=7,616). The primary outcome was maternal COVID-19 infection. COVID-19 vaccination status at delivery, COVID-19 infection-related health care, preterm birth (PTB), stillbirth, very low birth weight (VLBW), and small for gestational age (SGA) were evaluated as secondary outcomes. Findings: Vaccinated pregnant people were significantly less likely to have a maternal COVID-19 infection than unvaccinated matched (p<0.0001) pregnant people. During a maternal COVID-19 infection, vaccinated pregnant people had similar rates of hospitalization (p=0.23), but lower rates of supplemental oxygen (p<0.05) or vasopressor (p<0.05) use than those in an unvaccinated matched cohort. Compared to an unvaccinated matched cohort, vaccinated people had significantly lower stillbirth rate (p<0.01) as well as no difference in rate of PTB (p=0.35), SGA (p=0.79), or rate of VLBW (>1,500 g; 0.31). Vaccinated people who were boosted had significantly lower rates of maternal COVID-19 infections (p<0.0001), COVID-19 related hospitalization (p<0.05), PTB (p<0.05), stillbirth (p<0.01), SGA (p<0.05), and VLBW (p<0.01), compared to vaccinated people that did not receive a third booster dose five months after completing the initial vaccination series. Interpretation: COVID-19 vaccination protects against adverse maternal-fetal outcomes with booster doses conferring additional protection against COVID-19 infection. It is therefore important for pregnant people to have high priority status for vaccination, and for them to stay current with their COVID-19 vaccination schedule. Funding: This study was funded by the National Institute for Child Health & Human Development and the William O. and K. Carole Ellison Foundation.

The effect of maternal SARS-CoV-2 infection timing on birth outcomes: a retrospective multicentre cohort study.

BACKGROUND: The impact of maternal SARS-CoV-2 infection remains unclear. In this study, we evaluated the risk of maternal SARS-CoV-2 infection on birth outcomes and how this is modulated by the pregnancy trimester in which the infection occurs. We also developed models to predict gestational age at delivery for people following a SARS-CoV-2 infection during pregnancy. METHODS: We did a retrospective cohort study of the impact of maternal SARS-CoV-2 infection on birth outcomes. We used clinical data from Providence St Joseph Health electronic health records for pregnant people who delivered in the USA at the Providence, Swedish, or Kadlec sites in Alaska, California, Montana, Oregon, or Washington. The SARS-CoV-2 positive cohort included people who had a positive SARS-CoV-2 PCR-based test during pregnancy, subdivided by trimester of infection. No one in this cohort had been vaccinated for COVID-19 at time of infection. The SARS-CoV-2 negative cohort were people with at least one negative SARS-CoV-2 PCR-based test and no positive tests during pregnancy. Cohorts were matched on common covariates impacting birth outcomes, and univariate and multivariate analysis were done to investigate risk factors and predict outcomes. The primary outcome was gestational age at delivery with annotation of preterm birth classification. We trained multiple supervised learning models on 24 features of the SARS-CoV-2 positive cohort to evaluate performance and feature importance for each model and discuss the impact of SARS-CoV-2 infection on gestational age at delivery. FINDINGS: Between March 5, 2020, and July 4, 2021, 73 666 pregnant people delivered, 18 335 of whom had at least one SARS-CoV-2 test during pregnancy before Feb 14, 2021. We observed 882 people infected with SARS-CoV-2 during their pregnancy (first trimester n=85; second trimester n=226; and third trimester n=571) and 19 769 people who have never tested positive for SARS-CoV-2 and received at least one negative SARS-CoV-2 test during their pregnancy. SARS-CoV-2 infection indicated an increased risk of preterm delivery (p<0·05) and stillbirth (p<0·05), accounted for primarily by first and second trimester SARS-CoV-2 infections. Gestational age at SARS-CoV-2 infection was correlated with gestational age at delivery (p<0·01) and had the greatest impact on predicting gestational age at delivery. The people in this study had mild or moderate SARS-CoV-2 infections and acute COVID-19 severity was not correlated with gestational age at delivery (p=0·31). INTERPRETATION: These results suggest that pregnant people would benefit from increased monitoring and enhanced prenatal care after first or second trimester SARS-CoV-2 infection, regardless of acute COVID-19 severity. FUNDING: US National Institutes of Health.

Physical activity and epigenetic biomarkers in maternal blood during pregnancy.

AIM: Investigate associations of leisure time physical activity (LTPA) with DNA methylation and miRNAs during pregnancy. Patients & methods: LTPA, candidate DNA methylation and circulating miRNAs were measured (average 15 weeks gestation) in pregnant women (n = 92). RESULTS: Each additional hour of prepregnancy LTPA duration was associated with hypermethylation in C1orf212 (ß = 0.137, 95% CI: 0.004-0.270) and higher circulating miR-146b-5p (ß = 0.084, 95% CI: 0.017-0.151). Each additional metabolic equivalent hour of early-pregnancy LTPA energy expenditure was associated with higher circulating miR-21-3p (ß = 0.431, 95% CI: 0.089-0.772) in women carrying female offspring, and lower circulating miR-146b-5p (ß = -0.285, 95% CI: -0.528 to -0.043) and miR-517-5p (ß = -0.406, 95% CI: -0.736 to -0.076) in women carrying male offspring. CONCLUSION: Our findings suggest that LTPA may influence maternal epigenetic biomarkers, possibly in an offspring sex-specific manner.

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/m2) and prepregnancy LTPA. 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 (ß = 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.

Risk of glucose intolerance and gestational diabetes mellitus in relation to maternal habitual snoring during early pregnancy.

BACKGROUND: Obstructive sleep apnea (OSA) or habitual snoring is known to be associated with impaired glucose tolerance and type 2 diabetes among both men and non-pregnant women. We examined the association of habitual snoring during early pregnancy with risk of impaired glucose tolerance (IGT) and gestational diabetes mellitus (GDM). METHODS: A cohort of 1,579 women was interviewed during early pregnancy. We collected information about snoring frequency during early pregnancy. Results from screening and diagnostic tests for IGT and GDM were abstracted from medical records. Multivariate logistic regression models were fitted to estimate odds ratios (OR) and 95% confidence intervals (95% CI) of IGT and GDM associated with snoring in early pregnancy. RESULTS: Overall, women who snored "most or all of the time" had a 2.1-fold increased odds of IGT (OR 2.10; 95% CI 1.31-3.35) and a 2.5-fold increased odds of GDM (OR 2.50; 95% CI 1.34-4.67) as compared with women who never snored. Compared with lean women (pre-pregnancy body mass index (BMI) <25 kg/m2) who did not snore, lean snorers had a 2-fold increased odds of GDM (OR = 1.99, 95% CI: 1.07-3.68). The odds of GDM risk was particularly elevated among overweight women (BMI ≥ 25 kg/m2) who snored (OR = 5.01; 95% CI 2.71-9.26). However, there was no evidence of an interaction between overweight and snoring with GDM risk (p-value = 0.144). CONCLUSIONS: These findings, if confirmed, may have important implications for tailoring prenatal care for overweight pregnant women, and /or those with a history of habitual snoring in early pregnancy.

Circulating early- and mid-pregnancy microRNAs and risk of gestational diabetes.

AIMS: Epigenetic regulators, including microRNAs (miRNAs), are implicated in type 2 diabetes, but evidence linking circulating miRNAs in pregnancy and risk of gestational diabetes (GDM) is sparse. Potential modifiers, including pre-pregnancy overweight/obesity and offspring sex, are unexamined. We hypothesized that circulating levels of early-mid-pregnancy (range 7-23weeks of gestation) candidate miRNAs are related to subsequent development of GDM. We also hypothesized that miRNA-GDM associations might vary by pre-pregnancy body-mass index (ppBMI) or offspring sex. METHODS: In a case-control analysis (36GDM cases/80 controls) from the Omega study, a prospective cohort study of pregnancy complications, we measured early-mid-pregnancy plasma levels of 10miRNAs chosen for potential roles in pregnancy course and complications (miR-126-3p, -155-5p, -21-3p, -146b-5p, -210-3p, -222-3p, -223-3p, -517-5p, -518a-3p, and 29a-3p) using qRT-PCR. Logistic regression models adjusted for gestational age at blood draw (GA) were fit to compare circulating miRNAs between cases and controls. We repeated analyses among overweight/obese (ppBMI≥25kg/m2) or lean (ppBMI<25kg/m2) women, and women with male or female offspring separately. RESULTS: Mean age was 34.3years (cases) and 32.9years (controls). GA-adjusted miR-155-5p (ß=0.260/p=0.028) and -21-3p (ß=0.316/p=0.005) levels were positively associated with GDM. MiR-146b-5p (ß=0.266/p=0.068) and miR-517-5p (ß=0.196/p=0.074) were borderline. Associations of miR-21-3p and miR-210-3p with GDM were observed among overweight/obese but not lean women. Associations of six miRNAs (miR-155-5p, -21-3p, -146b-5p, -223-3p, -517-5p, and -29a-3p) with GDM were present only among women carrying male fetuses (all p<0.05). CONCLUSIONS: Circulating early-mid-pregnancy miRNAs are associated with GDM, particularly among women who are overweight/obese pre-pregnancy or pregnant with male offspring. This area has potential to clarify mechanisms underlying GDM pathogenesis and identify at-risk mothers earlier in pregnancy.

Sex-specific associations of maternal birthweight with offspring birthweight in the Omega study.

PURPOSE: We investigated nonlinear and offspring sex-specific associations of maternal birthweight (BW) with offspring BW among participants of the Omega study, a pregnancy cohort. METHODS: Maternal BW was modeled as a continuous variable, linear spline and binary variable indicating low birthweight (LBW; <2500 vs. ≥2500 grams). Offspring BW was modeled as a continuous and binary variable in regression models. Nonlinearity was assessed using likelihood ratio tests (LRTs) in marginal linear spline models. RESULTS: For every 100-gram increase of maternal BW, offspring BW increased by 22.29 (95% CI: 17.57, 27.02) or 23.41 (95% CI: 6.87, 39.96) grams among mothers with normal BW or born macrosomic, respectively, but not among LBW mothers (ß = -8.61 grams; 95% CI: -22.88, 5.65; LRT P-value = .0005). For every 100-gram increase in maternal BW, BW of male offspring increased 23.47 (95% CI: 16.75, 30.19) or 25.21 (95% CI: 4.35, 46.07) grams among mothers with normal BW or born macrosomic, respectively, whereas it decreased 31.39 grams (95% CI: -51.63, -11.15) among LBW mothers (LRT P-value < .0001). Corresponding increases in BW of female offspring (16-22 grams) did not differ among mothers with LBW, normal BW or macrosomia (LRT P-value = .9163). CONCLUSIONS: Maternal and offspring BW associations are evident among normal BW and macrosomic mothers. These associations differ by offspring sex.

Healthy Lifestyle During Early Pregnancy and Risk of Gestational Diabetes Mellitus.

Previous studies have found associations between individual healthy behaviors and reduced risk of gestational diabetes mellitus (GDM); however, the association of composite healthy lifestyle during pregnancy with GDM has not been examined. Participants in the Omega Study (n = 3,005), a pregnancy cohort study conducted in Washington State (1996-2008), reported information on diet, physical activity, smoking, and stress during early pregnancy. Lifestyle components were dichotomized into healthy/unhealthy and then combined into a total lifestyle score (range, 0-4). Regression models were used to determine relative risk of GDM (n = 140 cases) in relation to healthy lifestyle. Twenty percent of participants had a healthy diet, 66% were physically active, 95% were nonsmokers, and 55% had low stress. Each 1-point increase in lifestyle score was associated with a 21% lower risk of GDM (95% confidence interval: 0.65, 0.96) after adjustment for age, race, and nulliparity. Adjustment for prepregnancy body mass index, prepregnancy physical activity, and prepregnancy smoking attenuated the associations slightly. Associations were similar in normal-weight and overweight/obese women. In this study, a composite measure of healthy lifestyle during early pregnancy was associated with substantially lower GDM risk. Public health messaging and interventions promoting multiple aspects of a healthy lifestyle during early pregnancy should be considered for GDM prevention.

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 < 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.

Maternal Early Pregnancy Serum Metabolomics Profile and Abnormal Vaginal Bleeding as Predictors of Placental Abruption: A Prospective Study.

BACKGROUND & OBJECTIVE: Placental abruption, an ischemic placental disorder, complicates about 1 in 100 pregnancies, and is an important cause of maternal and perinatal morbidity and mortality worldwide. Metabolomics holds promise for improving the phenotyping, prediction and understanding of pathophysiologic mechanisms of complex clinical disorders including abruption. We sought to evaluate maternal early pregnancy pre-diagnostic serum metabolic profiles and abnormal vaginal bleeding as predictors of abruption later in pregnancy. METHODS: Maternal serum was collected in early pregnancy (mean 16 weeks, range 15 to 22 weeks) from 51 abruption cases and 51 controls. Quantitative targeted metabolic profiles of serum were acquired using electrospray ionization liquid chromatography-mass spectrometry (ESI-LC-MS/MS) and the Absolute IDQ® p180 kit. Maternal sociodemographic characteristics and reproductive history were abstracted from medical records. Stepwise logistic regression models were developed to evaluate the extent to which metabolites aid in the prediction of abruption. We evaluated the predictive performance of the set of selected metabolites using a receiver operating characteristics (ROC) curve analysis and area under the curve (AUC). RESULTS: Early pregnancy vaginal bleeding, dodecanoylcarnitine/dodecenoylcarnitine (C12 / C12:1), and phosphatidylcholine acyl-alkyl C 38:1 (PC ae C38:1) strongly predict abruption risk. The AUC for these metabolites alone was 0.68, for early pregnancy vaginal bleeding alone was 0.65, and combined the AUC improved to 0.75 with the addition of quantitative metabolite data (P = 0.003). CONCLUSION: Metabolomic profiles of early pregnancy maternal serum samples in addition to the clinical symptom, vaginal bleeding, may serve as important markers for the prediction of abruption. Larger studies are necessary to corroborate and validate these findings in other cohorts.

Leisure Time Physical Activity and Gestational Diabetes Mellitus in the Omega Study.

PURPOSE: Findings of studies investigating associations of leisure time physical activity (LTPA) with gestational diabetes mellitus (GDM) risk have been inconsistent. We investigated associations of LTPA with GDM and whether these associations differ by prepregnancy overweight/obese status or gestational weight gain category. METHODS: Participants (N = 3209) of the Omega study, a pregnancy cohort study in Washington State (1996-2008), reported LTPA duration (h·wk) and energy expenditure (MET·h·wk) in the year before pregnancy and in early pregnancy. Diagnoses of GDM were abstracted from medical records. Poisson regression models were used to determine relative risks of GDM across tertiles of prepregnancy or early pregnancy LTPA duration and energy expenditure. Stratified analyses and interaction terms were used to assess effect modification by prepregnancy overweight/obese status (BMI ≥25 kg·m) or gestational weight gain category (adequate or excessive). RESULTS: Each tertile increase in prepregnancy LTPA duration or energy expenditure was associated with 15% (95% CI = 0.72-1.00) and 19% (95% CI = 0.69-0.96) lower risk of GDM, respectively. Each tertile increase in early pregnancy LTPA duration or energy expenditure was associated with 16% (95% CI = 0.72-0.97) and 17% (95% CI = 0.72-0.95) lower risk of GDM, respectively. LTPA during both prepregnancy and early pregnancy was associated with a 46% reduced risk of GDM (95% CI = 0.32-0.89) compared with inactivity during both periods. LTPA-GDM associations were similar by prepregnancy BMI and gestational weight gain. CONCLUSION: Our results support a role for the promotion of physical activity before and during pregnancy in the prevention of GDM.

Sleep disturbances among pregnant women with history of migraines: A cross-sectional study.

BACKGROUND: Migraine is associated with sleep disturbances in men and non-pregnant women. However, relatively little is known about sleep disturbances among pregnant migraineurs. We investigated sleep disturbances among pregnant women with and without history of migraine. METHODS: This cross-sectional study was conducted among 1324 women who were recruited during early pregnancy. Migraine diagnoses were based on the International Classification of Headache Disorders-II criteria. The Pittsburgh Sleep Quality Index (PSQI) questionnaire was used to evaluate sleep-related characteristics including sleep duration, sleep quality, excessive daytime sleepiness, and other sleep traits. Multivariable logistic regression procedures were used to estimate adjusted odds ratios (AORs) and 95% confidence intervals (CIs). RESULTS: Migraineurs were more likely than non-migraineurs to report short sleep duration (<6.5 hours) (AOR = 1.47, 95% CI 1.07-2.02), poor sleep quality (PSQI>5) (AOR = 1.73, 95% CI 1.35-2.23), and daytime dysfunction due to sleepiness (AOR = 1.51, 95% CI 1.12-2.02). Migraineurs were also more likely than non-migraineurs to report taking sleep medication during pregnancy (AOR = 1.71, 95% CI 1.20-2.42). Associations were generally similar for migraine with or without aura. The odds of sleep disturbances were particularly elevated among pre-pregnancy overweight migraineurs. CONCLUSION: Migraine headache and sleep disturbances are common comorbid conditions among pregnant women.

Early pregnancy urinary biomarkers of fatty acid and carbohydrate metabolism in pregnancies complicated by gestational diabetes.

AIMS: Alterations in organic acid biomarkers from fatty acid and carbohydrate metabolism have been documented in type 2 diabetes patients. However, their association with gestational diabetes mellitus (GDM) is largely unknown. METHODS: Participants were 25 GDM cases and 25 non-GDM controls. Biomarkers of fatty acid (adipate, suberate and ethylmalonate) and carbohydrate (pyruvate, l-lactate and ß-hydroxybutyrate) metabolism were measured in maternal urine samples collected in early pregnancy (17 weeks) using liquid chromatography-mass spectrometry methods. Logistic regression were used to calculate odds ratios (OR) and 95% confidence intervals (CI). RESULTS: GDM cases and controls differed in median urinary concentrations of ethylmalonate (3.0 vs. 2.3µg/mg creatinine), pyruvate (7.4 vs. 2.1µg/mg creatinine), and adipate (4.6 vs. 7.3µg/mg creatinine) (all p-values <0.05). Women in the highest tertile for ethylmalonate or pyruvate concentrations had 11.4-fold (95%CI 1.10-117.48) and 3.27-fold (95%CI 0.72-14.79) increased risk of GDM compared with women in the lowest tertile for ethylmalonate and pyruvate concentrations, respectively. Women in the highest tertile for adipate concentrations, compared with women in the lowest tertile, had an 86% reduction in GDM risk (95%CI 0.02-0.97). CONCLUSIONS: These preliminary findings underscore the importance of altered fatty acid and carbohydrate metabolism in the pathogenesis of GDM.

Sleep duration and plasma leptin concentrations in early pregnancy among lean and overweight/obese women: a cross sectional study.

BACKGROUND: Early-pregnancy short sleep duration is predictive of gestational diabetes and preeclampsia; mechanisms for these associations are unknown. Leptin, an adipocyte-derived peptide involved in regulating food intake and energy expenditure, may play a role in these observed associations. Given inconsistent reports linking short sleep duration with leptin, and absence of studies among pregnant women, we examined the association of maternal sleep duration with plasma leptin in early pregnancy. METHODS: This cross-sectional study included 830 pregnant women. Plasma leptin was measured in samples collected around 13 weeks gestation. Sleep duration was categorized as: ≤5, 6, 7-8 (reference), and ≥9 hours. Differences in leptin concentrations across categories were estimated using linear regression. Analyses were completed for lean and overweight/obese women. RESULTS: Overall, women with long sleep duration had elevated plasma leptin (p-value = 0.04). However, leptin concentrations were not statistically significantly elevated in women with a short sleep duration. There was no association of leptin with sleep duration among lean women. Among overweight/obese women, a U-shaped relation between leptin and sleep duration was observed: Mean leptin was elevated (ß = 21.96 ng/ml, P < 0.001) among women reporting ≤5 hour of sleep compared with reference group; and women reporting ≥9 hours of sleep also had elevated leptin (ß = 4.29 ng/ml, P = 0.09). CONCLUSIONS: Short sleep duration, and to a lesser extent long sleep duration, were associated with elevated leptin among overweight/obese women. These data add some evidence to help understand mechanistic relationships of sleep duration with pregnancy complications.

The prevalence and correlates of habitual snoring during pregnancy.

PURPOSE: Mounting evidence implicate habitual snoring, a prominent symptom of sleep-disordered breathing, as an important risk factor for adverse pregnancy outcomes including preeclampsia and gestational diabetes. Little, however, is known about the determinants of habitual snoring among pregnant women. We sought to assess its prevalence and to identify maternal characteristics associated with habitual snoring during pregnancy. METHODS: Pregnant women (N = 1,303) receiving prenatal care provided information about habitual snoring before and during pregnancy in in-person interviews completed in early pregnancy. We calculated adjusted odds ratios (aOR) and 95 % confidence intervals (95 % CI) from multivariable models designed to identify factors associated with snoring during pregnancy. RESULTS: Approximately 7.3 % of pregnant women reported habitual snoring during early pregnancy. The odds of habitual snoring during pregnancy was strongly related with maternal reports of habitual snoring prior to the index pregnancy (aOR = 24.32; 95 % CI, 14.30-41.51). Advanced maternal age (≥35 years) (aOR = 2.02; 95 % CI, 1.11-3.68), history of pregestational diabetes (aOR = 3.61; 95 % CI, 1.07-12.2), history of mood and anxiety disorders (aOR = 1.81; 95 % CI, 1.02-3.20), and prepregnancy overweight (25-29.9 kg/m(2)) (aOR = 2.31; 95 % CI, 1.41-3.77) and obesity (≥30 kg/m(2)) (aOR = 2.81; 95 % CI, 1.44-5.48) status were statistically significant risk factors for habitual snoring during pregnancy. In addition, maternal smoking during pregnancy (aOR = 2.70; 95 % CI, 1.17-6.26) was associated with habitual snoring during pregnancy. CONCLUSIONS: Identification of risk factors for habitual snoring during pregnancy has important implications for developing strategies aimed at reducing the prevalence of sleep-disordered breathing, promoting improved sleep hygiene and improved pregnancy outcomes among reproductive-age women.

Migraine-asthma comorbidity and risk of hypertensive disorders of pregnancy.

BACKGROUND: To evaluate the association of migraine and asthma and to estimate the risk of hypertensive disorders of pregnancy in relation to maternal comorbid migraine and asthma. METHODS: Reproductive age women (N = 3.731) were interviewed during early pregnancy. At the time of interview, we ascertained participants' migraine and asthma status. From medical records, we collected information to allow the diagnosis of pregnancy-induced hypertension (PIH) and preeclampsia. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using logistic regression procedures. RESULTS: After adjusting for confounders, migraineurs had 1.38-fold increased odds of asthma as compared with nonmigraineurs (95% CI 1.09-1.38). The odds of hypertensive disorders of pregnancy were highest among women with comorbid migraine-asthma. The ORs for PIH preeclampsia and the two disorders combined were 2.53 (95% CI 1.39-4.61), 3.53 (95% CI 1.51-8.24), and 2.64 (95% CI 1.56-4.47), respectively, for women with comorbid migraine-asthma as compared with those who had neither disorder. CONCLUSION: These findings confirm prior reports and extend the literature by documenting particularly high odds of pregnancy-induced hypertension and preeclampsia among women with comorbid migraine-asthma. Increased knowledge about the prevalence and sequelae of comorbidities during pregnancy may lead to improved symptom management and perinatal outcomes.

Differential Expression of HrtA1 and ADAM12 in Placentas from Preeclamptic and Normotensive Pregnancies.

BACKGROUND: High temperature requirement factor A 1 (HtrA1) and a disintegrin and metalloproteinase 12 (ADAM12), which play roles in placental implantation and placental growth, have been implicated in the pathogenesis of preeclampsia. METHODS: We investigated relative mRNA expression of both genes in placental tissues from women with preeclampsia (N=18) (average gestational age 36 weeks) and an equal number of women with normotensive pregnancies (average gestational age 39 weeks). Real-time polymerase chain reaction was used to measure mRNA extracted from term placental biopsies. Differential gene expression was evaluated using Student's T-test and fold change analyses. RESULTS: Statistically significant increases in placental HtRA1 (1.69-fold, p=0.030) and ADAM12 (1.48-fold, p=0.010) mRNA expression were observed among preeclamptic cases as compared with normotensive controls. HtrA1 expression was correlated with maternal age (p-value <0.01) among preeclampsia cases. CONCLUSION: Increases in HtRA1 and ADAM12 placental gene expression in placentas from preeclamptic pregnancies are consistent with some earlier reports of altered serum protein concentrations in preeclamptic pregnancies. This adds to the literature suggesting that defects in placentation (e.g. involving trophoblast invasion) are of etiologic importance in preeclampsia.