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.

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.

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.

Risk of gestational diabetes mellitus in relation to maternal egg and cholesterol intake.

Higher egg and cholesterol intakes are associated with increased risk of type 2 diabetes mellitus. However, their association with gestational diabetes mellitus (GDM) has not been evaluated. The authors assessed such associations in both a prospective cohort study (1996-2008; 3,158 participants) and a case-control study (1998-2002; 185 cases, 411 controls). A food frequency questionnaire was used to assess maternal diet. Multivariable models were used to derive relative risks and 95% confidence intervals. Compared with no egg consumption, adjusted relative risks for GDM were 0.94, 1.01, 1.12, 1.54, and 2.52 for consumption of ≤1, 2-3, 4-6, 7-9, and ≥10 eggs/week, respectively (P for trend=0.008). Women with high egg consumption (≥7/week) had a 1.77-fold increased risk compared with women with lower consumption (95% confidence interval (CI): 1.19, 2.63). The relative risk for the highest quartile of cholesterol intake (≥294 mg/day) versus the lowest (<151 mg/day) was 2.35 (95% CI: 1.35, 4.09). In the case-control study, the adjusted odds ratio for consuming ≥7 eggs/week versus <7 eggs/week was 2.65 (95% CI: 1.48, 4.72), and the odds of GDM increased with increasing cholesterol intake (P for trend=0.021). In conclusion, high egg and cholesterol intakes before and during pregnancy are associated with increased risk of GDM.

Global maternal early pregnancy peripheral blood mRNA and miRNA expression profiles according to plasma 25-hydroxyvitamin D concentrations.

OBJECTIVE: We investigated associations of early pregnancy maternal vitamin D concentrations with differential gene expression and post-transcription regulation. METHOD: Plasma 25-hydroxyvitamin D (25[OH]D) was measured among participants of a nested case-control study. Participants with low (<25.5 ng/ml) and high (≥31.7 ng/ml) 25[OH]D were identified among controls. Peripheral blood messenger RNA (mRNA) (N = 21) and microRNA (miRNA) (N = 13) expression studies were conducted among participants with low and high 25[OH]D concentrations. Differential expression between low/high groups were evaluated using Student's t-test, fold change, and SAM comparisons. We further investigated functions and functional relationships of differentially expressed mRNAs and targets of differentially expressed miRNAs. RESULTS: Three hundred and five genes (299 upregulated and 6 downregulated) and 11 miRNAs (10 downregulated and 1 upregulated) were differentially expressed among participants with low 25[OH]D compared with those who had high 25[OH]D. Genes that participate in a wide range of cellular functions, including organ and system development (e.g. angiogenesis), inflammation and metabolic processes (e.g. carbohydrate/lipid metabolism), as well as miRNAs that target these genes were differentially expressed among women with low 25[OH]D compared with those with high 25[OH]D. CONCLUSION: Early pregnancy plasma 25[OH]D concentrations are associated with maternal peripheral blood gene expression and post-transcription regulation.

Placental microRNA expression in pregnancies complicated by preeclampsia.

OBJECTIVE: The role of posttranscription regulation in preeclampsia is largely unknown. We investigated preeclampsia-related placental microRNA (miRNA) expression using microarray and confirmatory quantitative real-time polymerase chain reaction experiments. STUDY DESIGN: Placental expressions of characterized and novel miRNAs (1295 probes) were measured in samples collected from 20 preeclampsia cases and 20 controls. Differential expression was evaluated using Student t test and fold change analyses. In pathway analysis, we examined functions/functional relationships of targets of differentially expressed miRNAs. RESULTS: Eight miRNAs were differentially expressed (1 up-regulated and 7 down-regulated) among preeclampsia cases compared with controls. These included previously identified candidates (miR-210, miR-1, and a miRNA in the 14q32.31 cluster region) and others that are novel (miR-584 and miR-34c-5p). These miRNAs target genes that participate in organ/system development (cardiovascular and reproductive system), immunologic dysfunction, cell adhesion, cell cycle, and signaling. CONCLUSION: Expression of miRNAs that target genes in diverse pathophysiological processes is altered in the setting of preeclampsia.

Risk of placental abruption in relation to migraines and headaches.

BACKGROUND: Migraine, a common chronic-intermittent disorder of idiopathic origin characterized by severe debilitating headaches and autonomic nervous system dysfunction, and placental abruption, the premature separation of the placenta, share many common pathophysiological characteristics. Moreover, endothelial dysfunction, platelet activation, hypercoagulation, and inflammation are common to both disorders. We assessed risk of placental abruption in relation to maternal history of migraine before and during pregnancy in Peruvian women. METHODS: Cases were 375 women with pregnancies complicated by placental abruption, and controls were 368 women without an abruption. During in-person interviews conducted following delivery, women were asked if they had physician-diagnosed migraine, and they were asked questions that allowed headaches and migraine to be classified according to criteria established by the International Headache Society. Logistic regression procedures were used to calculate odds ratios (aOR) and 95% confidence intervals (CI) adjusted for confounders. RESULTS: Overall, a lifetime history of any headaches or migraine was associated with an increased odds of placental abruption (aOR = 1.60; 95% CI 1.16-2.20). A lifetime history of migraine was associated with a 2.14-fold increased odds of placental abruption (aOR = 2.14; 95% CI 1.22-3.75). The odds of placental abruption was 2.11 (95% CI 1.00-4.45) for migraineurs without aura; and 1.59 (95% 0.70-3.62) for migraineurs with aura. A lifetime history of tension-type headache was also increased with placental abruption (aOR = 1.61; 95% CI 1.01-2.57). CONCLUSIONS: This study adds placental abruption to a growing list of pregnancy complications associated with maternal headache/migraine disorders. Nevertheless, prospective cohort studies are needed to more rigorously evaluate the extent to which migraines and/or its treatments are associated with the occurrence of placental abruption.

Iron deficiency anemia, cigarette smoking and risk of abruptio placentae.

AIM: A higher frequency of abruptio placentae among anemic patients has been documented in some, but not all previously published studies. Altered feto-placental angiogenesis during early pregnancy in anemic women may partially explain this increased risk. The present study assesses the iron deficiency anemia-abruptio placentae association in pregnant women from the Pacific Northwest. METHODS: A retrospective case-control study of 145 abruptio placentae cases and 1710 control subjects was conducted. The diagnosis of abruptio placentae was based on routine clinical examination performed by attending physicians. Iron deficiency anemia was assessed in early pregnancy and defined as hemoglobin level <10 g/dL or by physician diagnosis. Information on maternal sociodemographic characteristics, cigarette smoking status during pregnancy and reproductive history was abstracted from medical records. Logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (CI) after adjusting for confounders. RESULTS: Eleven percent of abruptio placentae cases and 3.3% of controls were diagnosed with iron deficiency anemia. Maternal iron deficiency anemia in early pregnancy was associated with a 3.60-fold increased risk of abruptio placentae (95% CI 2.01-6.04). After adjusting for maternal age, gravidity, smoking during pregnancy, Medicaid payment status, and pre-gestational hypertension, the association was attenuated but remained statistically significant (adjusted OR = 2.40; 95% CI 1.22-4.73). Maternal smoking during pregnancy was associated with a 2.40-fold increased risk of abruptio placentae (95% CI 1.19-3.52). The iron deficiency anemia-abruptio placentae association was not modified by maternal smoking. CONCLUSION: Our results support the hypothesis that maternal iron deficiency anemia is associated with an increased risk of abruptio placentae.

Preeclampsia risk in relation to maternal mood and anxiety disorders diagnosed before or during early pregnancy.

BACKGROUND: Mood and anxiety disorders are common, debilitating psychiatric illnesses that disproportionally affect women of childbearing age. Relatively few studies have evaluated the extent to which, if at all, maternal mood and anxiety disorders are risk factors for preeclampsia, and results from available studies are inconsistent. We examined the risk of preeclampsia in relation to maternal medical history of mood and anxiety disorders. METHODS: We used data from a cohort study of 2,601 pregnant women. Maternal pregestational and early pregnancy (before completion of 20 weeks gestation) psychiatric diagnoses were ascertained from medical records. Generalized linear regression procedures were used to derive relative risk (RR) estimates and 95% confidence intervals (CIs). RESULTS: A positive history of maternal mood or anxiety disorder was associated with a 2.12-fold increased risk of preeclampsia after adjustment for age, race/ethnicity, and pre-pregnancy body mass index (95% CI 1.02-4.45). The risk of preeclampsia appeared to be more strongly related with maternal mood or anxiety disorders first diagnosed during the index pregnancy (adjusted RR = 3.64; 95% CI 1.13-11.68). The corresponding RR for maternal mood and anxiety disorders diagnosed before pregnancy was 1.73 (95% CI 0.71-4.20). CONCLUSIONS: Maternal mood and anxiety disorders are associated with increased preeclampsia risk. These observations must be explored in larger pharmacoepidemiological studies that allow precise evaluations of independent and joint effects of maternal psychopathologies and the use of psychotropic medications on preeclampsia risk.

Global placental gene expression in gestational diabetes mellitus.

OBJECTIVE: Gestational diabetes mellitus (GDM) is thought to modify the pattern of placental transcriptome. In a microarray study and a confirmatory quantitative real-time reverse transcription-polymerase chain reaction study, we investigated global placental gene expression in GDM. STUDY DESIGN: Ribonucleic acid was extracted from placental samples collected from 19 GDM cases and 21 controls. Oligonucleotide probes representing 22,000 genes were used to measure gene expression. Differential gene expression was evaluated using the Student t test, fold change assessment, and significance analysis of microarrays. Path analysis was used to assess functions and functional relationships of differentially expressed genes. RESULTS: Sixty-six genes participating in cell functions involving cell activation, immune response, organ development, and regulation of cell death were differentially expressed in GDM placentas. These genes include previously described candidate genes (eg, LEP, CEBPA, and MIF), genes with related functions (eg, ADFP), and novel genes (eg, AQP3). CONCLUSION: Expression of genes responsible for diverse biologic processes are modified in GDM.