Detection of microbial invasion of the amniotic cavity by analysis of cervicovaginal proteins in women with preterm labor and intact membranes.

OBJECTIVE: Microbial invasion of the amniotic cavity (MIAC) is common in early preterm labor and is associated with maternal and neonatal infectious morbidity. MIAC is usually occult and is reliably detected only with amniocentesis. We sought to develop a noninvasive test to predict MIAC based on protein biomarkers in cervicovaginal fluid (CVF) in a cohort of women with preterm labor (phase 1) and to validate the test in an independent cohort (phase 2). STUDY DESIGN: This was a prospective study of women with preterm labor who had amniocentesis to screen for MIAC. MIAC was defined by positive culture and/or 16S ribosomal DNA results. Nine candidate CVF proteins were analyzed by enzyme-linked immunosorbent assay. Logistic regression was used to identify combinations of up to 3 proteins that could accurately classify the phase 1 cohort (N = 108) into those with or without MIAC. The best models, selected by area under the curve (AUC) of the receiver operating characteristic curve in phase 1, included various combinations of interleukin (IL)-6, chemokine (C-X-C motif) ligand 1 (CXCL1), alpha fetoprotein, and insulin-like growth factor binding protein-1. Model performance was then tested in the phase 2 cohort (N = 306). RESULTS: MIAC was present in 15% of cases in phase 1 and 9% in phase 2. A 3-marker CVF model using IL-6 plus CXCL1 plus insulin-like growth factor binding protein-1 had AUC 0.87 in phase 1 and 0.78 in phase 2. Two-marker models using IL-6 plus CXCL1 or alpha fetoprotein plus CXCL1 performed similarly in phase 2 (AUC 0.78 and 0.75, respectively), but were not superior to CVF IL-6 alone (AUC 0.80). A cutoff value of CVF IL-6 ≥463 pg/mL (which had 81% sensitivity in phase 1) predicted MIAC in phase 2 with sensitivity 79%, specificity 78%, positive predictive value 38%, and negative predictive value 97%. CONCLUSION: High levels of IL-6 in CVF are strongly associated with MIAC. If developed into a bedside test or rapid laboratory assay, cervicovaginal IL-6 might be useful in selecting patients in whom the probability of MIAC is high enough to warrant amniocentesis or transfer to a higher level of care. Such a test might also guide selection of potential subjects for treatment trials.

Removal versus retention of cerclage in preterm premature rupture of membranes: a randomized controlled trial.

OBJECTIVE: The decision of whether to retain or remove a previously placed cervical cerclage in women who subsequently rupture fetal membranes in a premature gestation is controversial and all studies to date are retrospective. We performed a multicenter randomized controlled trial of removal vs retention of cerclage in these patients to determine whether leaving the cerclage in place prolonged gestation and/or increased the risk of maternal or fetal infection. STUDY DESIGN: A prospective randomized multicenter trial of 27 hospitals was performed. Patients included were those with cerclage placement at ≤23 weeks 6 days in singleton or twin pregnancies, with subsequent spontaneous rupture of membranes between 22 weeks 0 days and 32 weeks 6 days. Patients were randomized to retention or removal of cerclage. Patients were then expectantly managed and delivered only for evidence of labor, chorioamnionitis, fetal distress, or other medical or obstetrical indications. Management after 34 weeks was at the clinician's discretion. RESULTS: The initial sample size calculation determined that a total of 142 patients should be included but after a second interim analysis, futility calculations determined that the conditional power for showing statistical significance after randomizing 142 patients for the primary outcome of prolonging pregnancy was 22.8%. Thus the study was terminated after a total of 56 subjects were randomized with complete data available for analysis, 32 to removal and 24 to retention of cerclage. There was no statistical significance in primary outcome of prolonging pregnancy by 1 week comparing the 2 groups (removal 18/32, 56.3%; retention 11/24, 45.8%) P = .59; or chorioamnionitis (removal 8/32, 25.0%; retention 10/24, 41.7%) P = .25, respectively. There was no statistical difference in composite neonatal outcomes (removal 16/33, 50%; retention 17/30, 56%), fetal/neonatal death (removal 4/33, 12%; retention 5/30, 16%); or gestational age at delivery (removal mean 200 days; retention mean 198 days). CONCLUSION: Statistically significant differences were not seen in prolongation of latency, infection, or composite neonatal outcomes. However, there was a numerical trend in the direction of less infectious morbidity, with immediate removal of cerclage. These findings may not have met statistical significance if the original sample size of 142 was obtained, however they provide valuable data suggesting that there may be no advantage to retaining a cerclage after preterm premature rupture of membranes and a possibility of increased infection with cerclage retention.

Amniotic fluid infection, inflammation, and colonization in preterm labor with intact membranes.

OBJECTIVE: The purpose of this study was to compare intraamniotic inflammation vs microbial invasion of the amniotic cavity (MIAC) as predictors of adverse outcome in preterm labor with intact membranes. STUDY DESIGN: Interleukin-6 (IL-6) was measured in prospectively collected amniotic fluid from 305 women with preterm labor. MIAC was defined by amniotic fluid culture and/or detection of microbial 16S ribosomal DNA. Cases were categorized into 5 groups: infection (MIAC; IL-6, ≥11.3 ng/mL); severe inflammation (no MIAC; IL-6, ≥11.3 ng/mL); mild inflammation (no MIAC; IL-6, 2.6-11.2 ng/mL); colonization (MIAC; IL-6, <2.6 ng/mL); negative (no MIAC; IL-6, <2.6 ng/mL). RESULTS: The infection (n = 27) and severe inflammation (n = 36) groups had similar latency (median, <1 day and 2 days, respectively) and similar rates of composite perinatal morbidity and mortality (81% and 72%, respectively). The colonization (n = 4) and negative (n = 195) groups had similar outcomes (median latency, 23.5 and 25 days; composite morbidity and mortality rates, 21% and 25%, respectively). The mild inflammation (n = 47) groups had outcomes that were intermediate to the severe inflammation and negative groups (median latency, 7 days; composite morbidity and mortality rates, 53%). In logistic regression adjusting for gestational age at enrollment, IL-6 ≥11.3 and 2.6-11.2 ng/mL, but not MIAC, were associated significantly with composite morbidity and mortality rates (odds ratio [OR], 4.9; 95% confidence interval [CI], 2.2-11.2, OR, 3.1; 95% CI, 1.5-6.4, and OR, 1.8; 95% CI, 0.6-5.5, respectively). CONCLUSION: We confirmed previous reports that intraamniotic inflammation is associated with adverse perinatal outcomes whether or not intraamniotic microbes are detected. Colonization without inflammation appears relatively benign. Intraamniotic inflammation is not simply present or absent but also has degrees of severity that correlate with adverse outcomes. We propose the designation amniotic inflammatory response syndrome to denote the adverse outcomes that are associated with intraamniotic inflammation.

Reduction of elective inductions in a large community hospital.

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.

Recurrent bilateral pneumothorax.

A 71-year-old male with a history of coronary artery bypass surgery 7 years ago underwent a transthoracic needle aspiration biopsy of a pulmonary nodule in the right lung. Three hours later, the patient complained of dyspnea and left sided thoracic pain. The chest x-ray showed bilateral apical pneumothoraces. A second chest x-ray two hours later showed an increase in pneumothorax size on the left side. An intercostal drainage tube (size 24 French) was inserted into the fourth intercostal space on the X side and continuous suction was applied with 20 cm H2O. One day later, the chest x-ray revealed resolution on both sides with only minimal residual bilateral pneumothoraces. There was no air leak and hence the chest tube was removed. Histology revealed a non small cell lung cancer and a lobectomy was performed. At the second postoperative day a chylothorax was diagnosed because of elevated triglycerides. Parenteral nutrition was begun and the quantity of drained effusion diminished. Nine days after successful lobectomy the patient accidentally removed the chest tube and bilateral pneumothoraces were seen in the x-ray again.

Maternal thyroid hypofunction and pregnancy outcome.

OBJECTIVE: To estimate whether maternal thyroid hypofunction is associated with complications. METHODS: A total of 10,990 patients had first- and second-trimester serum assayed for thyroid-stimulating hormone (TSH), free thyroxine (freeT4), and antithyroglobulin and antithyroid peroxidase antibodies. Thyroid hypofunction was defined as 1) subclinical hypothyroidism: TSH levels above the 97.5th percentile and free T4 between the 2.5th and 97.5th percentiles or 2) hypothyroxinemia: TSH between the 2.5th and 97.5th percentiles and free T4 below the 2.5th percentile. Adverse outcomes were evaluated. Patients with thyroid hypofunction were compared with euthyroid patients (TSH and free T4 between the 2.5th and 97.5th percentiles). Patients with and without antibodies were compared. Multivariable logistic regression analysis adjusted for confounders was used. RESULTS: Subclinical hypothyroidism was documented in 2.2% (240 of 10,990) in the first and 2.2% (243 of 10,990) in the second trimester. Hypothyroxinemia was documented in 2.1% (232 of 10,990) in the first and 2.3% (247 of 10,990) in the second trimester. Subclinical hypothyroidism was not associated with adverse outcomes. In the first trimester, hypothyroxinemia was associated with preterm labor (adjusted odds ratio [aOR] 1.62; 95% confidence interval [CI] 1.00-2.62) and macrosomia (aOR 1.97; 95% CI 1.37-2.83). In the second trimester, it was associated with gestational diabetes (aOR 1.7; 95% CI 1.02-2.84). Fifteen percent (1,585 of 10,990) in the first and 14% (1,491 of 10,990) in the second trimester had antithyroid antibodies. When both antibodies were positive in either trimester, there was an increased risk for preterm premature rupture of membranes (P=.002 and P<.001, respectively). CONCLUSION: Maternal thyroid hypofunction is not associated with a consistent pattern of adverse outcomes. LEVEL OF EVIDENCE: II.

Pregnancy loss rates after midtrimester amniocentesis.

OBJECTIVE: The purpose of this study was to quantify the contemporary procedure-related loss rate after midtrimester amniocentesis using a database generated from patients who were recruited to the First And Second Trimester Evaluation of Risk for Aneuploidy trial. METHODS: A total of 35,003 unselected patients from the general population with viable singleton pregnancies were enrolled in the First And Second Trimester Evaluation of Risk for Aneuploidy trial between 10 3/7 and 13 6/7 weeks gestation and followed up prospectively for complete pregnancy outcome information. Patients who either did (study group, n=3,096) or did not (control group, n=31,907) undergo midtrimester amniocentesis were identified from the database. The rate of fetal loss less than 24 weeks of gestation was compared between the two groups, and multiple logistic regression analysis was used to adjust for potential confounders. RESULTS: The spontaneous fetal loss rate less than 24 weeks of gestation in the study group was 1.0% and was not statistically different from the background 0.94% rate seen in the control group (P=.74, 95% confidence interval -0.26%, 0.49%). The procedure-related loss rate after amniocentesis was 0.06% (1.0% minus the background rate of 0.94%). Women undergoing amniocentesis were 1.1 times more likely to have a spontaneous loss (95% confidence interval 0.7-1.5). CONCLUSION: The procedure-related fetal loss rate after midtrimester amniocentesis performed on patients in a contemporary prospective clinical trial was 0.06%. There was no significant difference in loss rates between those undergoing amniocentesis and those not undergoing amniocentesis. LEVEL OF EVIDENCE: II-2.

Maternal asthma and risk of preeclampsia: a case-control study.

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.

Assisted reproductive technology and pregnancy outcome.

OBJECTIVE: To determine whether the use of assisted reproductive technology (ART) is associated with an increase in chromosomal abnormalities, fetal malformations, or adverse pregnancy outcomes. METHODS: A prospective database from a large multicenter investigation of singleton pregnancies, the First And Second Trimester Evaluation of Risk trial, was examined. Subjects were divided into 3 groups: no ART use, use of ovulation induction (with or without intrauterine insemination), and use of in vitro fertilization (IVF). Multivariate logistic regression analysis was used to assess association between ART and adverse pregnancy outcomes (significance of differences was accepted at P < .05). RESULTS: A total of 36,062 pregnancies were analyzed: 34,286 (95.1%) were spontaneously conceived, 1,222 (3.4%) used ovulation induction, and 554 (1.5%) used IVF. There was no association between ART and fetal growth restriction, aneuploidy, or fetal anomalies after adjustment for age, race, marital status, years of education, prior preterm delivery, prior fetal anomaly, body mass index, smoking history, and bleeding in the current pregnancy. Ovulation induction was associated with a statistically significant increase in placental abruption, fetal loss after 24 weeks, and gestational diabetes after adjustment. Use of IVF was associated with a statistically significant increase in preeclampsia, gestational hypertension, placental abruption, placenta previa, and risk of cesarean delivery. CONCLUSION: Patients who undergo IVF are at increased risk for several adverse pregnancy outcomes. Although many of these risks are not seen in patients undergoing ovulation induction, several adverse pregnancy outcomes are still increased in this group. There was no increased incidence of fetal chromosomal or structural abnormalities in the women who used any type of ART compared with the women who conceived spontaneously. LEVEL OF EVIDENCE: II-2.

Quad screen as a predictor of adverse pregnancy outcome.

OBJECTIVE: To estimate the effect of second-trimester levels of maternal serum alpha-fetoprotein (AFP), human chorionic gonadotrophin (hCG), unconjugated estriol (uE3), and inhibin A (the quad screen) on obstetric complications by using a large, prospectively collected database (the FASTER database). METHODS: The FASTER trial was a multicenter study that evaluated first- and second-trimester screening programs for aneuploidy in women with singleton pregnancies. As part of this trial, patients had a quad screen drawn at 15-18 6/7 weeks. We analyzed the data to identify associations between the quad screen markers and preterm birth, intrauterine growth restriction, preeclampsia, and fetal loss. Our analysis was performed by evaluating the performance characteristics of quad screen markers individually and in combination. Crude and adjusted effects were estimated by multivariable logistic regression analysis. Patients with fetal anomalies were excluded from the analysis. RESULTS: We analyzed data from 33,145 pregnancies. We identified numerous associations between the markers and the adverse outcomes. There was a relatively low, but often significant, risk of having an adverse pregnancy complication if a patient had a single abnormal marker. However, the risk of having an adverse outcome increased significantly if a patient had 2 or more abnormal markers. The sensitivity and positive predictive values using combinations of markers is relatively low, although superior to using individual markers. CONCLUSION: These data suggest that components of the quad screen may prove useful in predicting adverse obstetric outcomes. We also showed that the total number and specific combinations of abnormal markers are most useful in predicting the risk of adverse perinatal outcome.

Early pregnancy lipid concentrations and the risk of gestational diabetes mellitus.

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.

Risk of preeclampsia in relation to maternal history of migraine headaches.

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.

Late termination of pregnancy for lethal fetal anomalies: a national survey of maternal-fetal medicine specialists.

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.

Plasma adiponectin concentrations in early pregnancy and subsequent risk of gestational diabetes mellitus.

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.

Maternal asthma and risk of preterm delivery.

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.

A prospective study of maternal serum C-reactive protein concentrations and risk of preeclampsia.

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.

Maternal plasma lipid concentrations in early pregnancy and risk of preeclampsia.

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.

Increased maternal plasma leptin in early pregnancy and risk of gestational diabetes mellitus.

OBJECTIVE: Emerging evidence suggests that leptin, an adipocyte-derived hormone, may have independent direct effects on both insulin secretion and action, in addition to its well documented effects on appetite and energy expenditure. Some, but not all, previously published studies suggest that maternal leptin concentrations may be increased in pregnancies complicated by gestational diabetes mellitus (GDM). We examined the association between plasma leptin concentration and GDM risk. METHODS: Women were recruited before 16 weeks of gestation and were followed up until delivery. Maternal plasma leptin concentrations (collected at 13 weeks of gestation) were measured by using immunoassay. We used generalized linear models to estimate relative risks and 95% confidence intervals. RESULTS: GDM developed in 5.7% of the cohort (47 of 823). Elevated leptin concentrations were positively associated with GDM risk (P for trend <.001). After adjusting for maternal prepregnancy adiposity and other confounders, women with leptin concentrations of 31.0 ng/mL or higher experienced a 4.7-fold increased risk of GDM (95% confidence interval 1.2, 18.0) as compared with women who had concentrations of 14.3 ng/mL or lower. We noted a strong linear component of trend in risk of GDM with increasing maternal plasma leptin concentration. Each 10-ng/mL increase in the leptin concentration was associated with a 20% increase in GDM risk (relative risk 1.2; 95% confidence interval 1.0, 1.3). CONCLUSIONS: Hyperleptinemia, independent of maternal adiposity, in early pregnancy appears to be predictive of an increased risk of GDM later in pregnancy. Additional larger prospective cohort studies are needed to confirm and more precisely assess the etiologic importance of hyperleptinemia in pregnancy. LEVEL OF EVIDENCE: II-2

Maternal plasma concentrations of insulinlike growth factor-1 and insulinlike growth factor-binding protein-1 in early pregnancy and subsequent risk of preeclampsia.

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.

Familial aggregation of type 2 diabetes and chronic hypertension in women with gestational diabetes mellitus.

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.