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The adipocyte hormone, leptin, is secreted in proportion to adipose mass and is implicated in the regulation of energy balance via its central actions on food intake and sympathetic nervous system activity. The placenta was also shown recently to be a possible source of leptin in pregnant women, raising the possibility that the normal relationship between leptin and adiposity may be altered in pre-eclampsia. We therefore sought to assess the extent to which maternal second trimester serum leptin concentrations differed for women who would subsequently develop pre-eclampsia and those who would remain normotensive. This nested case-control study population comprised 38 women with pregnancy-induced hypertension and proteinuria (pre-eclampsia) and 192 normotensive women. Multiple least-squares regression procedures were used to assess the independent relationship between leptin concentrations and risk of pre-eclampsia. Serum leptin concentrations, measured by radioimmunoassay, were highly correlated with maternal pre-pregnancy and second trimester body mass index (r = 0.71 and r = 0.74 respectively; P < 0.001 for both) among normotensive women, and to a lesser extent among women who developed pre-eclampsia (r = 0.29 and r = 0.42; P = 0.09 and 0.02 respectively). Among women with a pre-pregnancy body mass index of < or = 25 kg/m2, pre-eclampsia cases compared with controls had higher mean second trimester leptin concentrations after adjustment for confounding factors. In contrast, pre-eclampsia cases had lower mean leptin concentrations than controls for those women with a pre-pregnancy body mass index above 25 kg/m2. Other factors in addition to the level of adiposity may therefore influence serum leptin concentrations in pre-eclamptic pregnant women. Our results suggest the possibility that leptin, like several other placentally derived substances (e.g. steroid hormones, eicosanoids and cytokines), may be involved in the pathogenesis of pre-eclampsia. Further work is needed to confirm our findings and to assess the metabolic importance and determinants of leptin concentrations in uncomplicated and pre-eclamptic pregnancies.

OBJECTIVE: This study was undertaken to evaluate a group B streptococcal protocol in a large community hospital that combined treatment of high-risk patients with rapid screening of low-risk patients. STUDY DESIGN: In a prospective cohort study from 1994 through 1996 laboring patients in a level III community hospital were considered to be at high risk for neonatal group B streptococcal transmission if they were at <37 weeks' gestation, if they had rupture of membranes >12 hours, if they were known carriers of group B streptococci, if they had a temperature > or =100 degrees F, if the gestation was complicated by fetal growth restriction or was a multiple gestation, or if they had a previous neonate infected with group B streptococci. High-risk patients were treated intravenously with antibiotics during labor. Low-risk patients were screened for group B streptococcal antigen by means of a rapid optical immunoassay. Patients with positive screening results were treated. Neonatal morbidity and mortality were evaluated. RESULTS: Two of 9932 infants delivered had group B streptococcal sepsis diagnosed. In the 2 previous years without a protocol 9 cases of neonatal group B streptococcal sepsis had been diagnosed in 8188 deliveries (P =.0287 by Fisher exact test). The 2 cases of group B streptococcal sepsis during the protocol were as follows: 1 infant born to a high-risk mother with delay in treatment and 1 infant born to a low-risk mother with negative results of both culture and rapid screen during labor. During the previous period 7 infected infants had been born to high-risk mothers and 2 had been born to low-risk mothers. The maternal group B streptococcal carriage rate during the study was 18%. Group B streptococcal rapid optical immunoassay sensitivity was 81%. Elapsed time from screening to treatment was < or =2(1/2) hours for 93% of patients. No maternal anaphylaxis, no increase in bacterial neonatal sepsis caused by organisms other than group B streptococci, and no protocol-related group B streptococcal antibiotic resistance were noted. CONCLUSION: Successful implementation and maintenance of a protocol combining treatment of high-risk patients with rapid screening of low-risk patients during labor reduced neonatal group B streptococcal sepsis. [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: The objective was to ascertain the practices and opinions of US maternal-fetal medicine specialists regarding termination of pregnancy as a management option following late diagnosis of lethal fetal anomalies., Study Design: We conducted a cross-sectional mail survey of all US members of the Society of Maternal Fetal Medicine to ascertain how they manage pregnancies diagnosed with lethal fetal anomalies after 24 weeks of gestation. We analyzed the proportion of respondents that discuss termination of pregnancy as a management option, barriers to offering or accessing late termination services, and respondents' opinions about what anomalies are lethal and when pregnancy termination should be permitted., Results: The response rate was 41% (869/2119). Nearly all (93%) respondents discuss delivery near term or when complications arise, while 75% discuss the option of termination of pregnancy soon after the diagnosis of lethal fetal anomalies. Only 52% of the physicians indicated that their patients could obtain termination of pregnancy after 24 weeks at their affiliated medical centers or through providers within 50 miles. Real or perceived legal restrictions represented the most common reason for lack of local services. The proportion of respondents that felt strongly or very strongly that termination of pregnancy should be allowed was 76% for lethal anomalies and 58% for anomalies likely to result in significant long-term impairment., Conclusion: Although limited by a modest response rate, our study found that physicians do not consistently discuss immediate termination of pregnancy as an option following late diagnosis of lethal fetal anomalies, and they face numerous barriers to providing these services., Implications: This national survey supports the need for improved services for pregnant women who desire later termination of pregnancy following diagnosis of serious fetal anomalies. Helpful efforts might include educating physicians about the laws and regulations governing late termination of pregnancy, forging more consistent standards of care, and improving collaboration between MFM specialists and family planning providers to enhance access to care., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Objective: Our goal was to lower unplanned primary cesarean deliveries by reducing elective inductions., Study Design: To implement and sustain an induction management program, a committee of care providers reviewed induction rates. "Elective" and other categories were defined. An induction consent form was drafted. Consent compliance, induction rates, hours in labor and delivery and mode of delivery were evaluated. Outcomes were compared with historical data from 2 years earlier., Results: A total of 10,166 nulliparas and 9869 multiparas attempted vaginal deliveries. Elective inductions decreased significantly, from 4.3% to 0.8% in nulliparas and from 13% to 9.5% in multiparas. A longer time to delivery was seen for both nulliparas (5.2 hours) and multiparas (4 hours) with elective inductions. Unplanned primary cesarean delivery rates are significantly lower in spontaneously laboring women, compared with those induced., Conclusion: A program aimed at reducing elective inductions was successfully implemented and sustained.

Objective: To quantify the associations between asthma characteristics and the risk of preeclampsia., Study Design: In this case-control study, asthma history among 286 preeclampsia cases and 470 normotensive controls in Seattle was assessed by postpartum interview and medical record abstraction. OR and 95% CI were estimated using logistic regression. The sample size was adequate to detect unadjusted asthma history with ORs of > or =1.6 at a power of 80%., Results: After adjustment, women with a history of prepregnancy asthma diagnosis were not at increased preeclampsia risk (OR 0.94, 95% CI 0.58-1.52). Women experiencing asthma symptoms during pregnancy were more likely than pregnant nonasthmatics to have preeclampsia (OR 2.20, 95% CI 0.79-6.10). Those with long-term pre-pregnancy asthma and symptoms during pregnancy were at particularly increased risk (OR 9.09, 95% CI 1.02-81.6). Point estimates were generally higher after restriction to women withfull-term deliveries., Conclusion: This analysis suggests that asthmatics, particularly those who are symptomatic during pregnancy, may be at higher risk of developing preeclampsia.

The objective of this study was to determine if early pregnancy maternal plasma lipid concentrations are elevated in women who later developed gestational diabetes mellitus (GDM) as compared with women who do not. Women, recruited prior to 16 weeks gestation, were followed until delivery. Maternal plasma lipid concentrations were measured in samples collected at 13 weeks gestation on average. Generalized linear models were used to estimate relative risks (RR) and 95% confidence intervals (95% CI). 5.5% of the cohort (47/851) developed GDM. Elevated triglyceride (TG) was positively associated with GDM risk (p for trend <0.001). After adjusting for maternal pre-pregnancy adiposity and other confounders, women with TG concentrations > or =137 mg/dl experienced a 3.5-fold increased risk of GDM (95% CI: 1.1-10.5) as compared with women who had concentrations <96 mg/dl. We noted a linear component of trend in risk of GDM with increasing plasma TG. Each 20mg/dl increase in TG was associated with a 10% increase in GDM risk (RR=1.1; 95% CI: 1.0-1.3). Associations between GDM risk and plasma concentrations of other lipids (i.e., total cholesterol, high-density lipoprotein, and low-density lipoprotein) were not evident. Larger prospective studies are needed to confirm our findings and to identify modifiable determinants of pregnancy-associated dyslipidemia.

Preeclampsia and diabetes are complications of pregnancy that contribute to maternal and perinatal mortality worldwide. Results emerging from molecular studies of placentae may elucidate etiologically important genomic alterations. Appropriate application of real time reverse transcription (RT) PCR in comparative gene expression studies requires endogenous housekeeping genes to normalize between sample variations. Ideal housekeeping genes must have stable tissue expression, but few have been specifically studied in the placenta. We sought to identify candidate control genes by analyzing seven functionally distinct housekeeping genes (B2M, GAPDH, HMBS, HPRT, SDHA, TBP, YWHAZ) for their expression stability and level in the placenta. mRNA isolated from 20 placentae was analyzed for gene expression using RT-PCR. Expression stability (M) was assessed using normalization strategies previously used for other tissues. TBP and SDHA were the most stable, with an average expression stability of M = 0.43, followed by YWHAZ (M = 0.44) > HPRT (M = 0.53) > HMBS (M = 0.57) > GAPDH (M = 0.61) > B2M (M = 0.69). The genes tested ranged in abundance, with an approximately 300-fold increase from the lowest (HMBS) to the highest (B2M). By using TBP, SDHA and YWHAZ, with greater expression stability than those housekeeping genes commonly used in placenta studies, gene expression profile comparisons will have more sensitivity and specificity.

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.

Objective: The purpose of this study was to assess the contribution of the individual physician to the probability of cesarean delivery among nulliparous women who undergo elective induction., Study Design: A cohort study compared spontaneous labor and elective induction for all term, singleton, and cephalic nulliparous gestations over 2 years (1999-2000) at a large metropolitan hospital (n = 3215). Bivariate analysis was used to identify significant variables that were related to cesarean delivery. Logistic regression analysis was used to calculate the adjusted risk of cesarean delivery and to assess the independent effect of individual physician practice on cesarean delivery. Physician effect was evaluated in terms of its relative contribution to the explanatory power of the logistic regression model to predict cesarean delivery., Results: The adjusted odds ratio for cesarean delivery with elective induction was 1.78 (95% CI, 1.39, 2.27). Using forward stepwise regression, the individual physician was a significant independent risk factor in the model with an R square statistic increase from 0.194 to 0.249 when the physician statistic was added to the final model., Conclusion: Nulliparous women are at a significant increased risk of cesarean delivery if elective induction is performed. The individual physician has a contributing effect to this increased risk.

Objectives: We investigated the relationship between maternal plasma free insulinlike growth factor-1 (IGF-1) and insulinlike growth factor-binding protein-1 (IGFBP-1) concentrations and risk of preeclampsia., Design and Methods: Maternal blood samples were collected at 13 weeks' gestation on average. From the cohort, we selected 53 women who developed preeclampsia and 477 who remained normotensive. Free IGF-1 and IGFBP-1 concentrations were measured using immunoassays. Logistic regression procedures were used to calculate odds ratios (OR) and 95% confidence intervals (95% CI)., Results: Women who developed preeclampsia had 18% and 27% lower concentrations of free IGF-1 and IGFBP-1, respectively, than controls (P < 0.05). There was a 57% reduced risk of preeclampsia among women with free IGF-1 concentrations of >or= 0.81 ng/mL (OR = 0.43, 95% CI 0.23-0.83) and a 43% reduced risk among women with IGFBP-1 concentrations of >or= 72.36 ng/mL (OR = 0.53, 95% CI 0.23-1.21)., Conclusions: Alterations of free IGF-1 and IGFBP-1 concentrations in maternal plasma during early pregnancy are associated with risk of preeclampsia. These associations may help to further elucidate the pathologic processes of preeclampsia.

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.

Background: We investigated the relationship between early pregnancy plasma lipid concentrations and risk of preeclampsia., Methods: In a prospective cohort study, maternal blood samples were collected at an average of 13 weeks gestation. From the cohort, we selected 57 women who developed preeclampsia and 510 who remained normotensive and served as control subjects. Plasma lipid concentrations were measured enzymatically by standardized assays. Logistic regression procedures were used to calculate adjusted odds ratios (OR) and 95% confidence intervals (CI)., Results: Women who subsequently developed preeclampsia had 10.4%, 13.6%, and 15.5% higher concentrations of LDL cholesterol, triglycerides, and LDL/HDL ratios, respectively, than did control subjects (P <.05). The HDL cholesterol concentrations were 7.0% lower in women with preeclampsia than in control subjects (P <.05). After adjustment, there was a 3.60-fold increase in risk of preeclampsia among women with total cholesterol >205 mg/dL (95% CI 1.23 to 10.51) and a 4.15-fold increase in the risk of preeclampsia among women with triglyceride levels >133 mg/dL (95% CI 1.50 to 11.49). A linear increase in preeclampsia risk was observed with increasing tertiles of LDL cholesterol, triglyceride concentrations, and LDL/HDL ratio (all P <.05 for trend)., Conclusion: Early pregnancy dyslipidemia is associated with an increased risk of preeclampsia. This association may be significant in understanding the pathologic processes of preeclampsia and may help in developing strategies for prevention or early diagnosis of the disorder.

Low plasma adiponectin has been identified as a risk factor for type 2 diabetes. Our objective was to determine the extent to which low maternal plasma adiponectin is predictive of gestational diabetes mellitus (GDM), a condition that is biochemically and epidemiologically similar to type 2 diabetes. We used a prospective, nested case-control study design to compare maternal plasma adiponectin concentrations in 41 cases with 70 controls. Subjects were selected from a population of 968 women who provided blood samples in early pregnancy. Plasma adiponectin was determined using an ELISA. Adiponectin concentrations were statistically significantly lower in women with GDM than controls (4.4 vs. 8.1 micro g/ml, P < 0.001). Approximately 73% of women with GDM, compared with 33% of controls, had adiponectin concentrations less than 6.4 micro g/ml. After adjusting for confounding, women with adiponectin concentrations less than 6.4 micro g/ml experienced a 4.6-fold increased risk of GDM, as compared with those with higher concentrations (95% confidence interval, 1.8-11.6). Our findings are consistent with other reports suggesting an association between hypoadiponectemia and risk of type 2 diabetes. Our findings extend the literature to include GDM. Studies designed to examine the effect of dietary and pharmacological mediators of adiponectin concentrations in pregnant and nonpregnant subjects are warranted.

Objective: The purpose of this study was to determine the extent to which, if at all, maternal weight at birth is related to dyslipidemia during early pregnancy, which is a risk factor for preeclampsia., Study Design: This hospital-based prospective cohort study included 1000 women who initiated prenatal care before 16 weeks of gestation. Participants provided information about their birth weight and other sociodemographic and reproductive covariates. Plasma triglyceride, high-density lipoprotein cholesterol, and total cholesterol concentrations were measured at approximately 13 weeks of gestation. beta coefficients and standard errors were estimated by multiple linear regression; odds ratios and 95% confidence intervals were estimated by logistic regression., Results: Maternal birth weight was correlated negatively with triglycerides (r =-0.12; P =.001) and was correlated positively with high-density lipoprotein cholesterol (r =0.08; p =.02) but not statistically significantly related with total cholesterol (r =-0.004; P=.91). After adjusting for potential confounders, women who weighed <2500 g at birth had higher triglyceride and total cholesterol concentrations (beta=23.4 mg/dL [P<.001]; beta =2.6 mg/dL [P =.585], respectively) and lower high-density lipoprotein cholesterol concentrations (beta =-3.2 mg/dL; P=.105), when compared with women who weighed 3000 to 3499 g at birth. Women who were born small (<2500 g) and became overweight (body mass index, >or=25 kg/m(2)) in adulthood had less favorable lipid profiles than their counterparts who weighed >or=2500 g at birth and remained lean (body mass index, <25 kg/m(2))., Conclusion: Our findings suggest that factors that are related to growth in utero may help to predict the subsequent risk of altered lipid metabolism during pregnancy, which may, in turn, be causally related to the occurrence of preeclampsia.

Physical activity has been associated with a reduced risk of gestational diabetes mellitus, but inferences have been hampered by recall and selection bias. The authors examined the relation between recreational physical activity before and during pregnancy and risk of gestational diabetes mellitus in a prospective cohort study. In 1996-2000, 909 normotensive, nondiabetic women in Seattle and Tacoma, Washington, were questioned during early gestation about physical activity performed during the year before and 7 days prior to the interview during pregnancy. Compared with inactive women, women who participated in any physical activity during the year before experienced a 56% risk reduction (relative risk (RR) = 0.44, 95% confidence interval (CI): 0.21, 0.91). Women spending >/=4.2 hours/week engaged in physical activity experienced a 76% reduction in gestational diabetes mellitus risk (RR = 0.24, 95% CI: 0.10, 0.64), and those expending >/=21.1 metabolic equivalent-hours/week experienced a 74% reduction (RR = 0.26, 95% CI: 0.10, 0.65) compared with inactive women. Physical activity during pregnancy was also associated with reductions in gestational diabetes mellitus risk. Women who engaged in physical activity during both time periods experienced a 69% reduced risk (RR = 0.31, 95% CI: 0.12, 0.79). Findings suggest that efforts to increase maternal physical activity may contribute to substantial reductions in gestational diabetes mellitus risk.

Objective: To examine whether low maternal dietary intake of vitamin C and low maternal plasma ascorbic acid (AA) concentrations are associated with an increased risk of gestational diabetes mellitus (GDM)., Methods: Cases were 67 women with GDM meeting National Diabetes Data Group criteria. Controls were 260 women without such a diagnosis. Maternal dietary vitamin C consumption during the periconceptional period and during pregnancy was assessed using a 121-item, semiquantitative food frequency questionnaire. Maternal plasma AA concentrations were determined using automated enzymatic procedures on specimens collected during the intrapartum period., Results: Mean maternal daily consumption of vitamin C and plasma AA concentrations were 10% and 31% lower, respectively, among GDM cases as compared with controls (130.7 +/- 10.2 vs. 145 +/- 4.9 mg/d, P = .190; 36 +/- 2.0 vs. 53 +/- 1.0 micromol/L, P <.001). After controlling for maternal age, race, prepregnancy adiposity, family history of type 2 diabetes, energy intake and income, women reporting low daily vitamin C intake (< 70 mg/d), as compared with the other women, experienced a 3.7-fold increased risk of GDM (odds ratio [OR] = 3.7, 95% confidence interval [CI] 1.7-8.2). There was a linear relation in risk of GDM with decreasing concentrations of plasma AA (P for linear trend <.001). After adjusting for confounders, women in the lowest quartile (< 42.6 micromol/L), as compared with women in the highest quartile (> 63.3 micromol/L), experienced > 12-fold increased risk of GDM (OR = 12.8, 95% CI 3.5-46.2)., Conclusion: Low maternal dietary vitamin C intake and low plasma AA concentrations are associated with an increased risk of GDM. Large, prospective, cohort studies are needed to further evaluate the potential beneficial role of vitamin C and other antioxidants in the prevention of impaired glucose tolerance in pregnancy.

Objectives: To investigate correlations between sonographic soft markers and biochemical markers (human chorionic gonadotrophin, alpha-fetoprotein, and estriol) for Down syndrome in the second trimester of pregnancy., Methods: A total of 2183 women with apparently normal singleton fetuses who underwent second-trimester sonography (14-22 weeks) and maternal serum biochemical testing (triple test) were identified. Seven sonographic markers were recorded: nuchal fold thickness, humerus length, femur length, renal pyelectasis, hyperechoic bowel, echogenic intracardiac focus, and choroid plexus cysts., Results: Weak negative but statistically significant correlations were observed between human chorionic gonadotropin (multiples of the median) and both femur length (multiples of the median; Spearman p = -0.073; P < .01) and humerus length (multiples of the median; Spearman p = -0.083; P < .01). No other correlations significant at the 1% level were observed between femur length (multiples of the median) or humerus length (multiples of the median) and the biochemical markers. There were no significant correlations between nuchal fold thickness and any of the 3 biochemical markers. At the 5% (P < .05) level, the median human chorionic gonadotropin level (multiples of the median) was lower when an echogenic intracardiac focus was detected. Hyperechoic bowel also tended to be associated with higher median human chorionic gonadotropin (multiples of the median) and alpha-fetoprotein (multiples of the median) levels (P < .05)., Conclusions: We found that sonographic and biochemical markers for trisomy 21 are largely independent in unaffected pregnancies. For accurate risk estimation, correlations in both affected and unaffected pregnancies need to be considered. No or minimal correlation between sonographic markers and serum screening tests indicates that they can be used as independent modifiers of the maternal age-specific risk for Down syndrome.

Objective: We measured maternal plasma leptin concentrations in 55 women with pre-eclampsia and 487 normotensive women to determine whether elevated leptin concentrations were associated with the occurrence of pre-eclampsia., Methods: Maternal blood samples were collected at 13 weeks' gestation, on average. Plasma leptin concentrations were determined using immunoassay. Logistic regression procedures were used to calculate odds ratios (OR) and 95% confidence intervals (95% CI)., Results: Leptin concentrations were 78% higher in cases than control subjects (median 34.6 vs. 19.5 ng/ml; p < 0.001). Relative to women with leptin concentrations of < 27.4 ng/ml, those with elevated leptin concentrations (> or = 27.4 ng/ml) experienced a 2.3-fold increased risk of pre-eclampsia (OR 2.3; 95% CI 1.1-4.6). We observed evidence of a strong linear component of trend in risk of pre-eclampsia with increasing maternal plasma leptin concentration. Each 10-ng/ml increase in leptin concentration was associated with a 30% increase in pre-eclampsia risk (OR 1.3; 95% CI 1.1-1.5). Overweight women with elevated leptin concentrations experienced the highest risk of pre-eclampsia (OR 6.4; 95% CI 3.1-13.2) as compared with lean women with no leptin elevations., Conclusion: Elevated plasma leptin concentration and maternal overweight status appear to be independently associated with an increased risk of pre-eclampsia.

Background: We measured C-reactive protein (CRP), a clinical marker of systemic inflammation, in maternal serum collected at 13 weeks gestation on average, to determine whether elevations precede the clinical manifestation of preeclampsia., Methods: Using a prospective, nested, case-control study design we measured CRP concentrations using a competitive immunoassay in 60 women who developed preeclampsia and in 506 women who remained normotensive throughout pregnancy. Logistic regression procedures were used to calculate odds ratio (OR) and 95% CI. Because maternal serum CRP is highly correlated with maternal prepregnancy body mass index (BMI), all analyses were repeated after stratification by maternal prepregnancy overweight status (BMI <25 v > or =25 kg/m(2))., Results: Overall, the risk of preeclampsia increased across successively higher tertiles of CRP (OR = 1.0, 1.6, and 3.5, with the lowest tertile as the referent group; P <.001 for trend). After adjusting for parity and first-degree family history of chronic hypertension, the OR in the highest tertile was 3.2 (95% CI = 1.5 to 6.7). Further adjustment for BMI greatly attenuated this association (OR = 1.8, 95% CI = 0.8 to 4.1). Elevated CRP concentrations (> or =4.9 mg/L) were associated with a 2.5-fold increased risk of preeclampsia (95% CI = 1.1 to 5.5) in lean women. No similar association was observed among overweight women., Conclusions: Elevated CRP is highly correlated with prepregnancy adiposity and appears to be an independent predictor of preeclampsia in lean women. Further work is needed to identify modifiable risk factors for systemic inflammation in early pregnancy and to explore further the extent to which CRP and prepregnancy adiposity independently and jointly contribute to preeclampsia risk.

Objective: To perform a case-control study to assess the extent to which women with a positive parental history of type 2 diabetes and/or chronic hypertension experienced an increased risk of developing gestational diabetes mellitus (GDM)., Study Design: Participants (133 GDM cases and 373 controls) provided information on first-degree family history of the 2 conditions and other covariates of interest in interviews. Logistic regression procedures were used to derive odds ratios and 95% confidence intervals adjusted for confounding by maternal age, race/ethnicity and prepregnancy adiposity., Results: As compared with women with no parental history of diabetes, women with a maternal-only (odds ratio = 2.0), paternal-only (odds ratio = 2.3) or both maternal and paternal history of diabetes (odds ratio = 3.8) experienced a statistically significant increased risk of GDM. The odds ratio for women with a positive parental history of diabetes and hypertension was 2.6 (95% confidence interval, 1.3-5.3). Women with a diabetic sibling had an 8.4-fold increased risk of GDM (95% confidence interval, 2.1-33.4). First-degree family history of chronic hypertension was predictive of GDM risk but only when hypertension was associated with a diagnosis of diabetes., Conclusion: Our results are consistent with the thesis that family history of diabetes (alone or when associated with hypertension) reflects genetic and behavioral factors whereby women may be predisposed to an increased GDM risk.

Objective: We examined the influence of maternal birth weight on the risk of the development of preeclampsia, a likely precursor to adult chronic disease., Study Design: This hospital-based case-control study included 181 preeclampsia cases and 349 control subjects. Participants provided information about their birth weight and other covariates that included medical and reproductive history, prepregnancy weight, and adult height. Odds ratios and 95% CIs were estimated by logistic regression., Results: The risk of preeclampsia decreased as maternal birth weight increased (P=.01). After an adjustment was made for confounders, data showed that women with a low birth weight (<2500 g) had a 2.3-fold increased risk of experiencing preeclampsia (95% CI, 1.0-5.3) as compared with women who weighed 2500 to 2999 g at birth. Conversely, women with a birth weight of >/=4000 g appeared to have a nonstatistically significant, but >50%, reduction in the risk of experiencing preeclampsia (95% CI, 0.2-1.2). This relationship differed for lean and overweight women (body mass index, <25 kg/m(2) vs >/=25 kg/m(2)). Among lean women, those who were low birth weight had a near doubling in risk of the development of preeclampsia (odds ratio, 1.9; 95% CI, 0.8-4.6), although this association did not reach statistical significance. However, among overweight women, those women who weighed <2500 g at birth had an almost 4-fold increased risk of experiencing preeclampsia (odds ratio, 3.8; 95% CI, 1.1-13.8)., Conclusion: These results confirm two earlier reports and expand the literature by showing that women who are small at birth and who become overweight as adults are at particularly high risk of the development of preeclampsia.

Objective: To examine the effect of abortion type, number and timing on risk of preeclampsia in subsequent pregnancies., Study Design: We conducted a hospital-based, case-control study in Seattle and Tacoma, Washington, between 1998 and 2001. Preeclampsia cases (n = 199) and controls (n = 383) provided detailed information regarding their pregnancy histories and other covariates, such as prepregnancy weight and adult height. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated by logistic regression., Results: Multiparous women, both with a history of abortion and without, experienced decreases of 60% (adjusted OR = 0.40, 95% CI .23-.71) and 71% (adjusted OR = .29, 95% CI .16-.53), respectively, in risk of preeclampsia when compared to nulliparous women with no history of abortion. Type (spontaneous and/or induced), number and timing of prior abortion did not appear to influence the risk of preeclampsia among nulliparous women., Conclusion: These results confirm the work of others that multiparous women, both with and without a history of abortion, have a reduced risk of preeclampsia. However, much work remains with respect to exploring mechanistic hypotheses offering biologic explanations and examining possible confounding factors of this association, such as change in paternity and interpregnancy interval.

Objective: Despite the well-documented benefits of a physically active lifestyle, over 25% of American adults report that they never engage in regular recreational physical activity. Little is known about the determinants of physical activity among pregnant women. We investigated the predictors of physical activity in 386 normotensive pregnant women., Methods: Participants provided information about the type, frequency and duration of each physical activity performed during the first 20 weeks of pregnancy. We calculated odd ratios (OR) for active compared with inactive women using logistic regression models., Results: Approximately 61% of women reported participating in some regular physical activity during pregnancy. Walking, swimming, gardening and jogging were the most common activities. Physical activity as an adolescent (OR 4.0) and during the year before pregnancy (OR 48.9) were the strongest predictors of physical activity in pregnancy. Active women who continued to exercise during pregnancy decreased the average intensity of their exercise and the weekly duration of exercise compared with the year before pregnancy. Nulliparas were twice as likely to engage in physical activity as compared with multiparas. Education and income were positively related with physical activity. Non-White women were 40-60% less likely to engage in physical activity as compared with White women. Smokers were also less likely to engage in physical activity. High protein intake was positively associated with physical activity, while the opposite was true for high carbohydrate intake., Conclusions: The identification of determinants of physical activity in pregnancy has important implications for developing strategies aimed at promoting a physically active lifestyle among young women.

The potential benefits and risks of physical activity before and during pregnancy are not well studied. We studied the relation between recreational physical activity and the risk of preeclampsia in a case-control study of 201 preeclamptic and 383 normotensive pregnant women. Participants provided information about the type, intensity, frequency, and duration of physical activity performed during the first 20 weeks of pregnancy and during the year before pregnancy. Women who engaged in any regular physical activity during early pregnancy, compared with inactive women, experienced a 35% reduced risk of preeclampsia (odds ratio, 0.65; 95% confidence interval [CI], 0.43 to 0.99). Compared with inactive women, those engaged in light or moderate activities (ie, activities with metabolic-equivalent scores <6) experienced a 24% reduced risk of preeclampsia (95% CI, 0.48 to 1.20). The corresponding reduction for women participating in vigorous activities (metabolic equivalent scores > or =6) was 54% (95% CI, 0.27 to 0.79). Brisk walking (average walking pace > or =3 mi/h), when compared with no walking at all, was associated with a 30% to 33% reduction in preeclampsia risk. Stair climbing was inversely associated with the risk of preeclampsia (P for trend=0.039). Recreational physical activity performed during the year before pregnancy was associated with similar reductions in preeclampsia risk. These data suggest that regular physical activity, particularly when performed during the year before pregnancy and during early pregnancy, is associated with a reduced risk of preeclampsia.

Objective: The purpose of this study was to assess the contribution of physician management to the probability of cesarean delivery., Study Design: A prospective cohort study was performed of all live births who weighed > or =500 g for a 2-year period (1999-2000) at a large metropolitan hospital (n = 10,027 births). Factors that were associated significantly with cesarean delivery at one time excluded cases in which cesarean delivery was a necessary or probable outcome. In the planned vaginal delivery sample (n = 7940 births), a risk-adjusted logistic regression model was used to assess the prediction of cesarean delivery. To test for the effect of physician-management physician, we used the subset of physicians with > or =45 deliveries in the 2-year time period (n = 6563 deliveries)., Results: When physician-management physician data were added to the use of forward stepwise regression, entry order was abnormal position, nulliparity, birth weight of >4000 g, and physician. The model's predictive ability improved from 43.8% to 50.2%., Conclusion: Physician management adds a significant independent effect to the cesarean delivery risk model.

In a case-control study of 190 preeclamptic patients and 373 control subjects, we assessed maternal family history of chronic hypertension and type 2 diabetes in relation to preeclampsia risk. Participants provided information on first-degree family history of the 2 conditions and other covariates during postpartum interviews. Logistic regression was used to estimate odds ratios and 95% confidence intervals adjusted for confounding by age, race, and obesity. Compared with women with no parental history of hypertension, women with maternal only (odds ratio=1.9), paternal only (odds ratio=1.8), or both maternal and paternal history of hypertension (odds ratio=2.6) had a statistically significant increased risk of preeclampsia. The odds ratio for women with at least one hypertensive parent and a hypertensive sibling was 4.7 (95% confidence interval, 1.9 to 11.6). Both maternal only (odds ratio=2.1; 95% confidence interval, 0.9 to 4.6) and paternal only (odds ratio=1.9; 95% confidence interval, 1.0 to 3.2) history of diabetes was associated with an increased risk of preeclampsia. Women with a diabetic sibling had a 4.7-fold increased risk of preeclampsia (95% confidence interval, 1.1 to 19.8). For women with at least one hypertensive parent and at least one diabetic parent, relative to those with parents with neither diagnosis, the odds ratio for preeclampsia was 3.2 (95% confidence interval, 1.6 to 6.2). Our results are consistent with the thesis that family history of hypertension and diabetes reflects genetic and behavioral factors whereby women may be predisposed to an increased preeclampsia risk.

Objective: We examined the effect of pre-eclampsia on fetal growth in a cohort of pregnant women delivering singleton infants., Methods: Analyses were restricted to 155 women with pre-eclampsia and 5570 normotensive women. Logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (CI) after adjusting for confounders. We estimated ORs for very low birth weight (VLBW; < 1500 g), low birth weight (LBW; < 2500 g), and small for gestational age (SGA; weight < or = 10th centile by each gestational age, race, sex and parity strata) in relation to maternal pre-eclampsia status., Results: After adjusting for maternal age, race, smoking, Medicaid status and gestational age, the OR for VLBW was 30.7 (95% CI 7.0-134.9). Pre-eclampsia was associated with a 3.8-fold increased risk of LBW (95% CI 1.9-7.5). Women with pre-eclampsia were 3.6 times more likely to deliver an SGA newborn as compared with normotensive women (95% CI 2.3-5.7). Advanced maternal age, African-American race, parity or smoking status did not modify the associations of pre-eclampsia with LBW and SGA., Conclusions: Our results are consistent with other reports that have documented a strong relationship between pre-eclampsia and restricted fetal growth. Further, our results expand the literature by documenting a particularly strong association between pre-eclampsia and VLBW. However, our findings regarding the relationship between pre-eclampsia and fetal growth may be confounded by unmeasured factors including maternal weight prior to pregnancy and pregnancy weight gain.

Background: Oxidative stress plays an important role in the pathophysiology of preeclampsia., Methods: In a case-control study of 109 women with preeclampsia and 259 controls, maternal dietary and plasma vitamin C in relation to preeclampsia risk were assessed. Dietary intake during the periconceptional period and pregnancy was ascertained using a semiquantitative food frequency questionnaire. Logistic regression procedures were used to derive odds ratios (OR) and 95% confidence intervals (CI). Plasma ascorbic acid was determined using automated enzymatic procedures., Results: After adjusting for maternal age, parity, prepregnancy body mass index, and energy intake, women who consumed <85 mg of vitamin C daily (below the recommended dietary allowance), as compared with others, experienced a doubling in preeclampsia risk (OR = 2.1; 95% CI = 1.1-3.9). The OR for extreme quartiles of plasma ascorbic acid (<42.5 vs > or = 63.3 micromol/liter) was 2.3 (95% CI = 1.1-4.6). Compared with women in the highest quartile, those with plasma ascorbic acid <34.6 micromol/liter (lowest decile) experienced a 3.8-fold increased risk of preeclampsia (95% CI = 1.7-8.8)., Conclusions: Our results, if confirmed, would suggest that current public health efforts to increase intake of fruits and vegetables rich in vitamin C and other antioxidants may reduce the risk of preeclampsia.

Objective: The aim of the present study was to assess possible correlations between ultrasound findings and maternal serum biochemical ('triple test') markers among fetuses with trisomy 21 in the second trimester of pregnancy., Methods: The study was a retrospective cohort study of 72 pregnancies affected by trisomy 21 who had a second trimester ultrasound and biochemical screen performed at a single center between 1990 and 1999. The biochemical screen consisted of alpha-fetoprotein (AFP), total beta human chorionic gonadotrophin (hCG) and estriol (uE(3)). Marker levels were expressed in multiples of the median (MoM). The ultrasound findings assessed were major structural anomalies, short humerus length, short femur length, increased nuchal fold thickness (NF), hyperechoic bowel, echogenic intracardiac focus (EIF), ventriculomegaly, choroid plexus cysts and renal pyelectasis., Results: Second trimester maternal serum biochemical markers and ultrasound findings appeared to be largely independent of each other. However, some significant correlations were observed. Estriol was significantly lower when a fetal cystic hygroma was detected on ultrasound compared to those with no cystic hygroma (0.40 vs. 0.70 MoM, p<0.05). The median hCG level was significantly lower in those pregnancies with a normal second trimester fetal ultrasound compared to those with positive ultrasound findings (2.07 vs. 2.87 MoM, p<0.05). Median hCG levels were also significantly higher in those cases with NF> or =5 mm as compared to those with NF<5 mm (2.99 vs. 2.49 MoM, p<0.05). This difference persisted after exclusion of the five cases with cystic hygromas (2.99 vs. 2.49 MoM, p<0.05). A significant positive correlation was observed between log(10) hCG and log(10) NF MoM (Spearman's rho=0.252, p<0.05). NF was significantly greater among fetuses with an identifiable cardiac defect compared with those without a detectable cardiac defect (median of 7.0 mm vs. 3.8 mm, p<0.01). This difference persisted when expressed as multiples of the median (2.8 vs. 1.3 MoM, p<0.01)., Conclusion: Second trimester ultrasound and biochemical markers are largely independent in fetuses with trisomy 21, however significant correlations between the two were observed in the present series. These may be important in screening protocols that combine second trimester ultrasound and biochemical markers., (Copyright 2002 John Wiley & Sons, Ltd.)

Objective: To determine whether sonographic "markers" are associated with fetal Down syndrome during the second trimester and to estimate the degree of risk of individual markers using likelihood ratios., Methods: Second-trimester (14-20 weeks) sonographic findings in 186 fetuses with trisomy 21 were compared with a control group of 8728 consecutive control fetuses. Six markers were evaluated: nuchal thickening, hyperechoic bowel, shortened femur, shortened humerus, echogenic intracardiac focus, and renal pyelectasis., Results: Major or structural abnormalities were observed in 31 fetuses with trisomy 21 (16.7%) and 53 control fetuses (0.6%) (P< .001). Some type of sonographic finding (major abnormality, minor marker, or both) was observed in 68.8% of fetuses with trisomy 21 compared with 13.6% of control fetuses (P < .001). An isolated minor or "soft" marker was the only sonographic finding in 42 (22.6%) of 186 fetuses with trisomy 21 compared with 987 (11.3%) of 8728 control fetuses (P < .001). Nuchal thickening (P < .001; likelihood ratio, 11) and hyperechoic bowel (P < .001; likelihood ratio, 6.7) showed the strongest association with trisomy 21 as isolated markers, followed by shortened humerus (likelihood ratio, 5.1), echogenic intracardiac focus (likelihood ratio, 1.8), shortened femur (likelihood ratio, 1.5), and pyelectasis (likelihood ratio, 1.5). Echogenic intracardiac focus was the single most common isolated marker in both affected fetuses (7.1%) and control fetuses (3.9%) but carried a low risk (P= .046; likelihood ratio, 1.8)., Conclusions: A single soft marker is commonly encountered during the second trimester among fetuses with trisomy 21. The risk of fetal Down syndrome, reflected by likelihood ratios, was determined for 6 individual markers. This information can be combined with the a priori risk to estimate the individual patient risk for fetal Down syndrome.

Preeclampsia is characterized by diffuse vascular endothelial dysfunction. Tumor necrosis factor-alpha (TNF-alpha), which plays a key role in the cytokine network responsible for immunoregulation, is also known to contribute to endothelial dysfunction and other metabolic disturbances noted in preeclampsia. Results from cross-sectional studies and one longitudinal study indicate that TNF-alpha (or its soluble receptor, sTNFp55) is increased in the peripheral circulation and amniotic fluid of women with preeclampsia as compared with normotensive women. Between December 1993 and August 1994, prediagnostic sTNFp55 concentrations (a marker of excessive TNF-alpha release) were measured in 35 women with preeclampsia and 222 normotensive women to determine whether elevations precede the clinical manifestation of the disorder. Logistic regression procedures were used to calculate maximum likelihood estimates of odds ratios and 95% confidence intervals. Mean second trimester (15-22 weeks' gestation) serum sTNFp55 concentrations, measured by enzyme-linked immunosorbent assay, were 14.4% higher in preeclamptic women than in normotensive controls (716.6 pg/ml (standard deviation 193.6) vs. 626.4 pg/ml (standard deviation 158.0); p = 0.003). The relative risk of preeclampsia increased across successively higher quintiles of sTNFp55 (odds ratios were 1.0, 1.3, 2.1, and 3.7, with the lowest quintile used as the referent; p for trend = 0.007). After adjustment for maternal age, adiposity, and parity, the relative risk between extreme quintiles was 3.3 (95% confidence interval 0.8-13.4). These findings indicate that the level of TNF-alpha in maternal circulation is increased prior to the clinical manifestation of the disorder, and they are consistent with the hypothesized role of cytokines in mediating endothelial dysfunction and the pathogenesis of preeclampsia. Further work is needed to identify modifiable risk factors for the excessive synthesis and release of TNF-alpha in pregnancy, and to assess whether lowering of TNF-alpha concentrations in pregnancy alters the incidence and severity of preeclampsia.