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The North American site in the INTERGROWTH-21st Project was North Seattle, Washington State, USA. The majority of the data were collected from within Seattle City, which has approximately 12 300 births per year. The sample for the Newborn Cross- Sectional Study (NCSS) was drawn from two hospitals ( Swedish Medical Center and the University of Washington) covering almost 80% of deliveries within the target population. The Fetal Growth Longitudinal Study (FGLS) sample was recruited from several antenatal clinics serving the University of Washington Medical Center and Providence Everett Medical Center. Special activities to encourage participation and raise awareness of the studies included furnishing the recruitment sites with fliers designed by the Project Coordinating Unit, and presenting the studies to clinical staff to encourage providers to refer appropriate patients. One of the major challenges at this site was the low recruitment rate in the early phase of the FGLS because of the high rates of smoking, maternal age >35 years and body mass index >30 years. This was remedied by the inclusion of other ancillary clinics, as well as increased advertising among the general public. [ABSTRACT FROM AUTHOR]

Purpose: Although literature suggests that physical activity may reduce preeclampsia risk, most prior studies have relied on retrospective exposure assessment. We aimed to assess prospectively the relation between recreational physical activity before and during pregnancy and risk of preeclampsia. Methods: We used data from a 1996-2003 cohort study of 2241 pregnant western Washington State residents. During structured interviews conducted at 15 wk of gestation, on average, women reported recreational activities during the year before pregnancy and during the previous 7 d. Preeclampsia diagnosis was established for 111 women using medical record data and standard guidelines. Results: Recreational activity in the year before pregnancy was nonstatistically significantly associated with reduced preeclampsia risk (adjusted odds ratio [OR] for any vs none 0.55, 95% confidence interval [CI] 0.30-1.02). Any activity during early pregnancy was not strongly associated with preeclampsia risk (adjusted OR = 1.07, 95% CI = 0.67-1.69). Compared with women who reported no recreational activity before or during early pregnancy, risk was nonsignificantly lower among those who were active only before pregnancy (OR = 0.73, 95% CI = 0.30-1.77) and during both periods (OR = 0.76, 95% CI = 0.34-1.73). Those who were active only in early pregnancy had nonsignificantly increased preeclampsia risk (OR = 2.03, 95% CI = 0.71-5.81). Conclusion: These results corroborate previous case-control studies suggesting that prepregnancy recreational activity reduces preeclampsia risk. The absence of an association with early-pregnancy recreational activity in this cohort may be due to misclassification of usual early-pregnancy activity. [ABSTRACT FROM AUTHOR]

Increasing prevalence of overweight and obesity motivated this prospective examination of gestational diabetes mellitus in relation to self-reported adult height, weight, and weight fluctuation. Gestational diabetes was assessed by use of medical records in 1,644 women enrolled in Seattle and Tacoma, Washington, between 1996 and 2002. After adjustment, risk was inversely related to height and directly related to pregravid body mass index (p(trend) < 0.001). The relation with body mass index at age 18 years was J shaped, with higher risk among lean women (adjusted relative risk (RR) = 1.79, 95% confidence interval (CI): 1.01, 2.84) and obese women (RR = 4.53, 95% CI: 1.25, 16.43) versus normal-weight women. Weight gain between age 18 years and the study pregnancy was associated with increased risk independently of body mass index at 18 years and other confounders (>/=10-kg gain vs. <2.5-kg change: RR = 3.43, 95% CI: 1.60, 7.37). Weight cycling (loss and regain of >/=6.8 kg) was not associated after adjustment for body mass index at 18 years and adult weight change (>/=3 vs. zero cycles: RR = 1.23, 95% CI: 0.56, 2.73). Cycling was nonsignificantly related among women who gained 10 kg or more during adulthood (>/=3 vs. zero cycles: RR = 2.04, 95% CI: 0.83, 5.02). Efforts to prevent obesity and weight gain among young women may reduce gestational diabetes risk. [ABSTRACT FROM AUTHOR]

Purpose: We studied the relation between maternal history of asthma and preterm delivery.Methods: The 312 preterm delivery cases, studied in aggregate, and in subgroups (spontaneous preterm labor, preterm premature rupture of membranes, medically induced preterm delivery), were compared with 424 randomly selected women who delivered at term. Maternal medical records provided information on maternal lifetime asthma status, pregnancy outcome, and sociodemographic characteristics. Using multivariate logistic regression, we derived maximum likelihood estimates of adjusted odds ratios (OR) and 95% confidence intervals (CI).Results: Maternal history of asthma was associated with an increased risk of preterm delivery overall (OR = 2.37; 95% CI 1.15-4.88). Analyses of preterm delivery sub-groups indicated that maternal history of asthma was associated with at least a doubling in risk of spontaneous preterm labor (OR = 2.35; 95% CI 0.84-6.58) and medically induced preterm delivery (OR = 2.69; 95% CI 1.11-6.53), though only the latter approached statistical significance. There was some evidence of a modest association between maternal asthma and risk of preterm premature rupture of membranes (OR = 1.63; 95% CI 0.50-5.33).Conclusions: These results support the hypothesis that maternal asthma is associated with an increased risk of preterm labor and delivery. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To evaluate the association between maternal reproductive history and preterm delivery. METHODS: The 312 preterm delivery cases, studied in aggregate, and in subgroups (spontaneous preterm labor, preterm premature rupture of membranes, medically induced preterm delivery, moderate preterm delivery [gestational age at delivery 34-36 weeks], and very preterm delivery [gestational age at delivery <34 weeks]), were compared with 424 randomly selected women who delivered at term. Maternal medical records provided information on maternal reproductive history, pregnancy outcome, as well as sociodemographic characteristics. Using multivariate logistic regression, we derived maximum likelihood estimates of adjusted odds ratios (OR) and 95% confidence intervals (CI). RESULTS: A history of 2+ miscarriages was (OR = 2.2; 95% CI 1.2-3.9), but a history of 2+ prior induced abortions (OR = 1.2; 95% CI 0.7-2.0) was not, associated with preterm delivery in the index pregnancy. Analyses of preterm delivery subgroups indicated that a history of 2+ miscarriages was associated with an increased risk of spontaneous preterm labor (OR = 2.6; 95% CI 1.2-2.8), preterm premature rupture of membrane (OR = 1.8; 95% 0.7-4.4), and medically induced preterm delivery (OR = 1.9; 95% CI 0.8-4.2), though only the former approached statistical significance. Excess risk of preterm delivery was associated with maternal prior history of delivering a stillborn infant (OR = 10.7), a prior history of delivering a newborn that later died during the neonatal period (OR = 3.2), and a prior history of having a pregnancy complicated by spontaneous preterm delivery (OR = 6.0). Generally these associations were evident for each subgroup of preterm delivery, though inferences were often hindered by our relatively small sample size. CONCLUSIONS: These results support the hypothesis that maternal adverse reproductive history is associated with an increased risk of preterm labor and delivery. [ABSTRACT FROM AUTHOR]

Syndesmotic fixation remains a controversial topic, however most authors recommend fixation of the disrupted syndesmotic complex in unstable ankle fractures. There is no clear reference for the angle of syndesmotic fixation, historically 30° has been cited but recently refuted, with new and current literature. It is common practice to place 2 points of transyndesmotic fixation one with fixation placed at around 2 cm above the ankle joint and the second point approximately 3.5 cm above the plafond. Our hypothesis is that the ideal angle of transyndesmotic fixation is less than 30° and that the ideal angle changes when you move proximal from the 2-cm level to 3.5-cm level. This is based on cross-sectional anatomy as seen on weightbearing computerized tomography imaging. It is imperative to achieve adequate reduction of the syndesmosis to prevent instability and a malaligned ankle joint, as this can result in refractory pain and early onset of degenerative changes. We reviewed 50 weightbearing computerized tomography scans of the foot and ankle to identify what we call the adjusted syndesmotic fixation angle. Our review found adjusted syndesmotic fixation angle to be 19.7° with ranges of (8°-31°) at 2 cm and 24.8° with ranges of (14°-38°) at 3.5 cm above the tibial plafond. These values were statistically significant when compared to historically cited 30°. Our research concludes that the historically cited 30° angle is frequently not the ideal angle for syndesmotic fixation and actually is less., (Copyright © 2020 the American College of Foot and Ankle Surgeons. Published by Elsevier Inc. All rights reserved.)

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 (β = 0.137, 95% CI: 0.004-0.270) and higher circulating miR-146b-5p (β = 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 (β = 0.431, 95% CI: 0.089-0.772) in women carrying female offspring, and lower circulating miR-146b-5p (β = -0.285, 95% CI: -0.528 to -0.043) and miR-517-5p (β = -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.

The treatment of Jones fractures has been controversial in terms of nonoperative versus operative management, given the high incidence of nonunion secondary to the delicate blood supply to the proximal fifth metatarsal. We report a retrospective review of a patient cohort treated with an early weightbearing protocol after operative intramedullary fixation in acute Jones fractures. Thirty-one consecutive patients with an acute Jones fracture underwent operative fixation with a single intramedullary solid screw. The postoperative protocol consisted of immediate weightbearing in a controlled ankle motion boot for 2 weeks with a gradual transition to regular shoes at 2 weeks postoperative. At 2 weeks, the patients were allowed to perform low-impact activities such as walking, swimming, biking, or elliptical training. Patients were allowed to return to all activities, as tolerated, regardless of radiographic healing, at 6 weeks postoperatively. Serial postoperative radiographs were taken at 2-week intervals to determine radiographic union. Our patient population consisted of 24 males (77.42%) and 7 females (22.58%), with a mean average age of 37.5 ± 12.59 years and mean average body mass index of 25.7 ± 2.32 kg/m 2 . Fracture union was observed in all 31 patients (100%) at a mean average of 5.7 ± 1.47 (range 4 to 10) weeks. Two (6.5%) patients required hardware removal, with one (3.2%) experiencing sural neuritis. This review of patients undergoing early weightbearing after operative fixation of an acute Jones fracture demonstrated a satisfactory incidence of union compared with traditional postoperative protocols at a mean follow-up duration of 18.58 ± 5.66 months., (Copyright © 2017 The American College of Foot and Ankle Surgeons. Published by Elsevier Inc. All rights reserved.)

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 2 ) 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 (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.

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/m 2 ) or lean (ppBMI<25kg/m 2 ) 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 (β=0.260/p=0.028) and -21-3p (β=0.316/p=0.005) levels were positively associated with GDM. MiR-146b-5p (β=0.266/p=0.068) and miR-517-5p (β=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., (Published by Elsevier B.V.)

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.

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., (© The Author(s) 2017. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

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 (β = -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., (Copyright © 2017 Elsevier Inc. All rights reserved.)

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.

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.

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 β-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., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

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 (β = 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 (β = 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.

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.

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.

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.

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.

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., (© The Author 2011. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved.)

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., (Copyright © 2011 Mosby, Inc. All rights reserved.)

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.

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.

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.

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.

Background: Substantial epidemiological evidence documents diverse health benefits, including reduced risks of hypertension, associated with diets high in fiber. Few studies, however, have investigated the extent to which dietary fiber intake in early pregnancy is associated with reductions in preeclampsia risk. We assessed the relationship between maternal dietary fiber intake in early pregnancy and risk of preeclampsia. We also evaluated cross-sectional associations of maternal early pregnancy plasma lipid and lipoprotein concentrations with fiber intake., Methods: The study population comprised 1,538 pregnant Washington State residents. A 121-item food frequency questionnaire (FFQ) was used to assess maternal dietary intake, 3 months before and during early pregnancy; and generalized linear regression procedures were used to derive relative risk (RR) and 95% confidence intervals (CIs)., Results: Dietary total fiber intake was associated with reduced preeclampsia risk. After adjusting for confounders, the RR of preeclampsia for women in the highest (> or =21.2 g/day) vs. the lowest quartile (<11.9 g/day) was 0.28 (95% CI = 0.11-0.75). We observed associations of similar magnitude when the highest vs. the lowest quartiles of water-soluble fiber (RR = 0.30; 95% CI = 0.11-0.86) and insoluble fiber (RR = 0.35; 95% CI = 0.14-0.87) were evaluated. Mean triglyceride concentrations were lower (-11.9 mg/dl, P = 0.02) and high-density lipoprotein cholesterol concentrations were higher (+2.63 mg/dl, P = 0.09) for women in the highest quartile vs. those in the lowest quartile., Conclusions: These findings of reduced preeclampsia risk with higher total fiber intake corroborate an earlier report; and expand the literature by providing evidence, which suggests that dietary fiber may attenuate pregnancy-associated dyslipidemia, an important clinical characteristic of preeclampsia.

Background: Migraine, a common chronic-intermittent disorder of idiopathic origin characterized by severe debilitating headaches and autonomic nervous system dysfunction, and preeclampsia, a hypertensive disorder of pregnancy, share many common epidemiological and pathophysiological characteristics. Both conditions are associated with higher subsequent risk of ischemic stroke. Moreover, endothelial dysfunction, platelet activation, hyper-coagulation, and inflammation are common to both disorders. We assessed the risk for preeclampsia in relation to the maternal history of migraine before and during pregnancy in Peruvian women., Methods: Cases consisted of 339 women with preeclampsia, and controls were 337 normotensive women. During in-person interviews conducted at delivery, women were asked whether they had physician-diagnosed migraines, and they were asked questions that allowed for headaches and migraines to be classified according to criteria established by the International Headache Society (IHS). Logistic regression procedures were used to calculate odds ratios (ORs) and 95% confidence intervals (CIs)., Results: A history of any headache before or during pregnancy was associated with a 2.4-fold increased risk for preeclampsia (OR = 2.4; 95% CI 1.7-3.3). Women classified as having migraines that began prior to pregnancy had a 3.5-fold increased risk for preeclampsia (95% CI 1.9-6.4) as compared with those who reported no migraines. Women with migraines during pregnancy had a fourfold increased risk of preeclampsia (OR = 4.0, 95% CI 1.9-8.2) compared with non-migraineurs., Conclusions: Our findings are consistent with previous reports and we have extended them to the Peruvian population. Prospective cohort studies, however, are needed to more rigorously evaluate the extent to which migraines and/or its treatments are associated with the occurrence of preeclampsia.

Background: Coffee consumption has been associated with a decreased risk of type 2 diabetes mellitus. We examined the relationship between coffee consumption and the risk of gestational diabetes mellitus [GDM]., Methods: In this prospective study, 1744 non-diabetic pregnant women were questioned during early gestation about their coffee consumption. We studied the association of coffee consumption before and during pregnancy, and the subsequent risk of GDM. Generalised, linear models were fitted to estimate risk ratios and 95% confidence intervals., Results: Women who reported moderate pre-pregnancy caffeinated coffee intake had a significantly reduced risk of GDM (adjusted RR 0.50; 95% CI 0.29-0.85) compared with non-consumers. No risk reduction was associated with decaffeinated coffee intake., Conclusions: Moderate pre-pregnancy caffeinated coffee consumption may have a protective association with GDM. Prospective studies, including a wider range of consumption habits, are necessary.

Objectives: We investigated the relationship between selected maternal erythrocyte omega-3 and omega-6 polyunsaturated fatty acids (PUFA) and plasma lipids in early pregnancy and reported habitual fish consumption during the periconceptional period., Design and Methods: This cohort study included 923 pregnant women who reported periconceptional dietary habits and provided a blood sample before 20 weeks of gestation. PUFA was determined by gas chromatography and plasma lipids by standard enzymatic methods. Differences in erythrocyte PUFA and plasma lipid concentrations were estimated using linear regression., Results: Mean erythrocyte eicosapentanoic acid and other PUFA content (%/total) were positively associated with frequency of self-reported fish consumption. Arachidonic acid was inversely related with frequent fish consumption (p trend <0.001). Women who consumed fish >twice/week had lower plasma triglyceride (-11.5 mg/dl) and higher HDL-cholesterol (+2.8 mg/dl) concentrations than women consuming fish

Background: Physical activity has been associated with decreased risk of gestational diabetes mellitus. Expanding on 2 previously published analyses of absolute exertion measures (time spent and energy expended), we assessed the relation between perceived exertion during usual prepregnancy recreational physical activity and gestational diabetes., Methods: We analyzed data from a Washington State 1998-2002 case-control study (216 cases, 472 controls) and a 1996-2002 prospective cohort study (897 participants) separately. We used logistic regression models to derive odds ratios (ORs) and 95% confidence intervals (CIs)., Results: Among case-control participants, risk of gestational diabetes was markedly lower for women who reported very strenuous to maximal exertion in usual activity during the year before pregnancy versus those who reported negligible or minimal exertion (adjusted OR = 0.19; CI = 0.15-0.50). There was a direct inverse relation between perceived exertion and risk of gestational diabetes. This relation was also evident among the subset of participants who did not meet physical activity guidelines in the year before pregnancy. Similarly, the OR among cohort participants reporting very strenuous to maximal exertion was 0.57 (0.24-1.37) versus those reporting negligible to moderate exertion., Conclusions: These results suggest that risk of gestational diabetes is inversely related to the exertion perceived during recreational physical activity in the year before pregnancy. Perceived exertion may be a valuable addition to behavior and fitness measures in assessing relations between physical activity and pregnancy-related health outcomes.

Purpose: Studies have shown that absolute intensity of physical activity is associated with reduced risk of preeclampsia. This analysis was performed to examine whether relative intensity may also be related to preeclampsia risk., Methods: Using data from a case-control study conducted from 1998 to 2002, the authors assessed the relation between perceived exertion (i.e., relative intensity) during usual recreational physical activity in the year before pregnancy and risk of preeclampsia. In a structured interview conducted during postpartum hospitalization, 244 preeclampsia cases and 470 normotensive controls provided details on their recreational physical activities in the year before pregnancy., Results: Participants who reported feeling very strenuous to maximal exertion during usual prepregnancy physical activity were 78% less likely to have developed preeclampsia than those who reported negligible or minimal exertion (adjusted odds ratio 0.22, 95% confidence interval 0.11-0.44). A significant trend was noted of decreased preeclampsia risk with increased perceived exertion (P < 0.001). This association was independent of prepregnancy adiposity, and was also apparent among the subset of participants who did not meet physical activity guidelines in the year before pregnancy., Conclusions: In this study, relative intensity of recreational physical activity performed during the year before pregnancy was associated with a decreased risk of preeclampsia.

Bisdioxopiperazines are inhibitors of topoisomerase II trapping this protein as a closed clamp on DNA with concomitant inhibition of its ATPase activity. Here, we analyse the effects of N-terminal mutations identified in bisdioxopiperazine-resistant cells on ATP hydrolysis by this enzyme. We present data consistent with bisdioxopiperazine resistance arising by two different mechanisms; one involving reduced stability of the N-terminal clamp (the N-gate) and one involving reduced affinity for bisdioxopiperazines. Vanadate is a general inhibitor of type P ATPases and has recently been demonstrated to lock topoisomerase II as a salt-stable closed clamp on DNA analogous to the bisdioxopiperazines. We show that a R162K mutation in human topoisomerase II alpha renders this enzyme highly resistant towards vanadate while having little effect on bisdioxopiperazine sensitivity. The implications of these findings for the mechanism of action of bisdioxopiperazines versus vanadate with topoisomerase II are discussed.

Objective: We examined the relationship between migraines and preeclampsia risk., Study Design: Cases were 244 women with preeclampsia and controls were 470 normotensive women. Women were asked if a physician had ever told them that they had migraines. Odds ratios (OR) and 95% confidence intervals (CI) were calculated., Results: A history of migraines was associated with a 1.8-fold increased risk of preeclampsia (95% CI 1.1-2.7). Women who were 30+ years old when diagnosed with migraines had the highest risk (OR 2.8, 95% CI 0.8-9.0). The migraine-preeclampsia association appeared to be modified by pre-pregnancy overweight status (p = 0.06). Overweight migrainous women, compared with lean nonmigrainous women, had a 12-fold increased preeclampsia risk (95% CI 5.9-25.7)., Conclusion: Our findings are consistent with reports from six of eight previous studies on the topic. Nevertheless, prospective cohort studies are needed to further evaluate the extent to which migraines and/or its treatments are associated with preeclampsia risk.

Type II DNA topoisomerases catalyze changes in DNA topology and use nucleotide binding and hydrolysis to control conformational changes required for the enzyme reaction. We examined the ATP hydrolysis activity of a bisdioxopiperazine-resistant mutant of human topoisomerase II alpha with phenylalanine substituted for tyrosine at residue 50 in the ATP hydrolysis domain of the enzyme. This substitution reduced the DNA-dependent ATP hydrolysis activity of the mutant protein without affecting the relaxation activity of the enzyme. A similar but stronger effect was seen when the homologous mutation (Tyr28 --> Phe) was introduced in yeast Top2. The ATPase activities of human TOP2alpha(Tyr50 --> Phe) and yeast Top2(Tyr28 --> Phe) were resistant to both bisdioxopiperazines and the ATPase inhibitor sodium orthovanadate. Like bisdioxopiperazines, vanadate traps the enzyme in a salt-stable closed conformation termed the closed clamp, which can be detected in the presence of circular DNA substrates. Consistent with the vanadate-resistant ATPase activity, salt-stable closed clamps were not detected in reactions containing the yeast or human mutant protein, vanadate, and ATP. Similarly, ADP trapped wild-type topoisomerase II as a closed clamp, but could not trap either the human or yeast mutant enzymes. Our results demonstrate that bisdioxopiperazine-resistant mutants exhibit a difference in the stability of the closed clamp formed by the enzyme and that this difference in stability may lead to a loss of DNA-stimulated ATPase. We suggest that the DNA-stimulated ATPase of topoisomerase II is intimately connected with steps that occur while the N-terminal domain of the enzyme is dimerized.

Objective: To determine the extent to which, if at all, maternal pre-pregnancy adiposity and other anthropometric factors are related to risk of cesarean delivery., Methods: This hospital-based prospective cohort study included 738 nulliparous women who initiated prenatal care prior to 16 weeks gestation. Participants provided information about their pre-pregnancy weight and height and other sociodemographic and reproductive covariates. Labor and delivery characteristics were obtained from maternal and infant medical records. Risk ratios (RR) and 95% CI were estimated by fitting generalized linear models., Results: The proportion of cesarean deliveries in this population was 26%. Women who were overweight (BMI 25.00-29.99 kg/m2) were twice as likely to deliver their infants by cesarean section as lean women (BMI<20.00 kg/m2) (RR=2.09; 95% CI 1.27-3.42). Obese women (BMI>or=30.00 kg/m2) experienced a three-fold increase in risk of cesarean delivery when compared with this referent group (RR=3.05; 95% CI 1.80-5.18). The joint association between maternal pre-pregnancy overweight status and short stature was additive. When compared with tall (height>or=1.63 m), lean women, short (<1.63 m), overweight (BMI>or=25.00 kg/m2) women were nearly three times as likely to have a cesarean delivery (RR=2.79; 95% CI 1.72-4.52)., Conclusion: Our findings suggest that nulliparous women who are overweight or obese prior to pregnancy, and particularly those who are also short, have an increased risk of delivering their infants by cesarean section.

Background: A limited amount of literature suggests that plasma leptin concentrations are reduced with habitual physical activity in men and non-pregnant women. We investigated the relationship between maternal physical activity and plasma leptin during early pregnancy., Methods: The study population included 879 normotensive, non-diabetic pregnant women who reported physical activity type, frequency, and duration in early pregnancy. Plasma leptin, measured in blood samples collected <16 weeks gestation, were determined using enzyme immunoassays. Weekly duration (h/week) and energy expended on recreational physical activity [metabolic equivalent score (MET)-h/week] were categorized by tertiles among active women. Physical activity intensity was categorized as none, moderate (<6 MET) and vigorous (> or =6 MET). Differences in leptin concentrations across categories were estimated using linear regression procedures., Results: Mean leptin was 5.8 ng/ml lower among active versus inactive women (P=0.001). Mean leptin was lower among women in the highest levels (>12.8 h/week) of time performing physical activity (-8.1 ng/ml, P<0.001) and energy expenditure (>70.4 MET-h/week) (-8.3 ng/ml, P=0.001) compared with inactive women. Leptin was inversely associated with the intensity of physical activity., Conclusions: Our findings are consistent with other reports suggesting an independent inverse relationship between habitual physical activity and leptin concentrations. Our findings extend the literature to include pregnant women.

Despite the maternal and infant morbidity associated with gestational diabetes mellitus (GDM), few modifiable risk factors have been identified. We explored the relation between recreational physical activity performed during the year before and during the first 20 weeks of pregnancy and the risk of GDM. 155 GDM cases and 386 normotensive, non-diabetic pregnant controls provided information about the type, intensity, frequency, and duration of physical activity performed during these time periods. Women who participated in any recreational physical activity during the first 20 weeks of pregnancy, as compared with inactive women, experienced a 48% reduction in risk of GDM (odds ratio [OR] = 0.52; 95% confidence interval [CI] 0.33-0.80). The number of hours spent performing recreational activities and the energy expended were related to a decrease in GDM risk. No clear patterns related to distance walked and pace of walking emerged. Daily stair climbing, when compared with no stair climbing, was associated with a 49-78% reduction in GDM risk (P for trend <0.011). Recreational physical activity performed during the year before the index pregnancy was also associated with statistically significant reductions in GDM risk, but women who engaged in physical activity during both time periods experienced the greatest reduction in risk (OR = 0.40; 95% CI 0.23-0.68). These data suggest that recreational physical activity performed before and/or during pregnancy is associated with a reduced risk of GDM.

Low-grade systemic inflammation is associated with an increased risk of type 2 diabetes mellitus. Limited available data suggest inflammatory factors are predictive of gestational diabetes (GDM), a condition that is biochemically similar to type 2 diabetes. We examined the association between C-reactive protein (CRP) and GDM risk. Women were recruited before 16 weeks gestation and were followed until delivery. Maternal serum CRP (collected at 13 weeks' gestation, on average) was measured by a competitive immunoassay. We used generalised linear models to derive estimates of relative risks and 95% confidence intervals [CI]. Approximately 4.5% of the cohort (38 of 851) developed GDM. Elevated CRP was positively associated with GDM risk (P for trend = 0.007). After adjusting for maternal prepregnancy body mass index (BMI), family history of type 2 diabetes and nulliparity, women with CRP in the highest tertile experienced a 3.5-fold increased risk of GDM [95% CI 1.2, 9.8] as compared with those in the lowest tertile. The association between CRP and GDM was evident when analyses were restricted to lean women (BMI < 25 kg/m(2)). Lean women with CRP > or = 5.3 mg/L experienced a 3.7-fold increased risk of GDM [95% CI 1.6, 8.7] as compared with women with CRP < 5.3 mg/L. Systemic inflammation is associated with an increased risk of GDM, and the association is independent of maternal prepregnancy adiposity.

Background: Antioxidants, particularly vitamin C (ascorbic acid), have the capacity to influence glucose tolerance. Modification of diet could reduce the likelihood of developing gestational diabetes mellitus., Methods: In a prospective cohort study of pregnant women, we studied the association of maternal plasma ascorbic acid concentrations, measured at an average of 13 weeks' gestation, with subsequent risk of gestational diabetes. Maternal plasma ascorbic acid concentrations were determined using automated enzymatic procedures. Dietary vitamin C intake during the periconceptional period and early pregnancy was ascertained using a semiquantitative food frequency questionnaire. We fitted generalized linear models to derive estimates of relative risks and 95% confidence intervals (CIs)., Results: Approximately 4% (n = 33) of 755 women who completed pregnancy developed gestational diabetes mellitus. Plasma ascorbic acid concentrations were inversely associated with the risk of gestational diabetes (P for trend = 0.023). After adjusting for maternal age, race, prepregnancy adiposity, parity, family history of type 2 diabetes, and household income, women with plasma ascorbic acid <55.9 micromol/L (lowest quartile) experienced a 3.1-fold increased risk of gestational diabetes (95% CI = 1.0 - 9.7) compared with women whose concentrations were > or = 74.6 micromol/L (upper quartile). Women who consumed <70 mg vitamin C daily experienced a 1.8-fold increased risk of gestational diabetes compared with women who consumed higher amounts (95% CI = 0.8 - 4.4)., Conclusions: If confirmed, our results raise the possibility that current efforts to encourage populations to consume diets rich in antioxidants, including vitamin C, could reduce the occurrence of gestational diabetes mellitus.

The authors examined the relation between recreational physical activity and plasma lipid concentrations in early pregnancy. Between 1996 and 2000, 925 normotensive, nondiabetic pregnant women in Washington State were interviewed at approximately 13 weeks' gestation regarding type, frequency, and duration of physical activity during the previous 7 days. Plasma triglyceride, total cholesterol, and high density lipoprotein cholesterol concentrations were measured in contemporaneous blood samples. After adjustment, mean triglyceride concentration was 12.7 mg/dl lower in women performing any physical activity versus none (95% confidence interval (CI): -22.7, -2.6). Mean triglyceride concentration was lower in women in the highest tertiles of time performing physical activity (-23.6 mg/dl, 95% CI: -34.9, -12.2), energy expenditure (-23.6 mg/dl, 95% CI: -35.1, -12.2), and peak intensity (-18.1 mg/dl, 95% CI: -29.5, -6.8) versus inactive women. Reductions in mean total cholesterol were also observed for women with the highest levels of time performing physical activity, energy expenditure, and peak intensity. Linear relations were observed across levels of physical activity measures for triglyceride and total cholesterol. No association was found between physical activity and high density lipoprotein cholesterol. These data suggest that habitual physical activity may attenuate pregnancy-associated dyslipidemia.

We have developed a gene switch based on the human transcription factor peroxisome proliferator-activated receptor gamma (PPARgamma) and its activation by rosiglitazone. However, ectopic expression of PPARgamma has been demonstrated to convert myogenic cells into adipocyte-like cells and, more generally, may interfere with the physiology of the target tissue. Consequently we modified the DNA-binding specificity of PPARgamma, resulting in a transcription factor that we named PPAR*. We demonstrated by histological and molecular assessment of cell phenotype that the overexpression of PPAR* did not alter the myogenic differentiation program of G8 myoblasts. We showed that PPAR* does not transactivate promoters containing PPARgamma-responsive elements but transactivates promoters containing PPAR*-responsive elements that are at least 80% identical to a 20-bp consensus. We improved the rosiglitazone-dependent gene switch by tuning PPAR* expression with a scaffold/matrix attachment region and by expressing both PPAR* and the reporter gene under the control of PPAR*-responsive elements. Treatment of cultured murine muscle cells (myotubes) with rosiglitazone induced reporter gene expression from assay background up to the level attained by a CMV I/E promoter-enhancer. These results indicate the potential of the PPAR* gene switch for use in gene therapy applications.