Large-for-gestational age and stillbirth: is there a role for antenatal testing?

OBJECTIVE: To investigate the association between large-for-gestational-age (LGA) pregnancy and stillbirth to determine if the LGA fetus may benefit from antenatal testing with non-stress test or biophysical profile. METHODS: This was a retrospective cohort study of singleton pregnancies that were ongoing at 24 weeks' gestation and that had undergone routine second-trimester anatomy ultrasound examination, during the period 1990 to 2009. Pregnancies complicated by fetal anomaly or aneuploidy, those with missing birth weight information and those that were small-for-gestational age were excluded. Appropriate-for-gestational age (AGA) and LGA were defined as birth weight between the 10th and 90th percentiles and > 90th percentile, respectively, according to the Alexander growth standard. The incidence of stillbirth was calculated as the number of stillbirths per 10 000 ongoing pregnancies. Adjusted odds ratios (aOR) with 95% CI for stillbirth in LGA compared with AGA pregnancies were estimated using logistic regression analysis, controlling for pre-existing and gestational diabetes. The incidence and aOR for stillbirth were estimated at 4-week intervals from ≥ 24 to ≥ 40 weeks' gestation. RESULTS: Of 52 749 pregnancies ongoing at 24 weeks, 46 205 (87.6%) were AGA and 6544 (12.4%) were LGA at delivery. The incidence of stillbirth in LGA pregnancies was significantly higher than that in AGA pregnancies from 36 weeks' gestation (26/10 000 vs 7/10 000; aOR, 3.10; 95% CI, 1.68-5.70). When women with diabetes were excluded in stratified analysis, pregnancies complicated by LGA continued to be at increased risk for stillbirth ≥ 36 weeks (18/10 000 vs 7/10 000; OR, 2.63; 95% CI, 1.27-5.43). CONCLUSION: Pregnancies complicated by LGA are at significantly increased risk for stillbirth at or beyond 36 weeks, independent of maternal diabetes status, and may benefit from antenatal testing. Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd.

Early versus 6-12 week postpartum glucose tolerance testing for women with gestational diabetes.

OBJECTIVE: The objective of this study is to estimate the accuracy of early oral glucose tolerance testing (GTT), to predict impaired glucose tolerance. STUDY DESIGN: This was a prospective cohort study. Women received an early 75 g 2 h GTT between postpartum days 2-4 and again 6-12 weeks postpartum. The ability of the early GTT to accurately detect impaired glucose tolerance and diabetes was assessed by calculating sensitivity, specificity, positive predictive value (PPV) and negative predictive values (NPVs). The routine 6-12-week postpartum GTT was considered the gold standard. RESULTS: The early GTT was completed by 100% of subjects, whereas only 31 of 58 (53%) women returned to complete the 6-12-week postpartum GTT. The early GTT had modest sensitivity for impaired glucose tolerance (62.5%) and overt diabetes (50%). However, it had excellent specificity (100%), PPV (100%) and NPV (96.7%) for diabetes. The NPV for impaired glucose tolerance with the early GTT was 80%. CONCLUSION: Rates of 6-12 week postpartum GTT completion among patients with gestational diabetes is poor. Appropriate postpartum management may improve by using the early GTT as a screening test.

Group versus traditional prenatal care in low-risk women delivering at term: a retrospective cohort study.

OBJECTIVE: Group prenatal care (GC) models are receiving increasing attention as a means of preventing preterm birth; yet, there are limited data on whether group care improves perinatal outcomes in women who deliver at term. The purpose of this study was to evaluate our institutional experience with GC over the past decade and test the hypothesis that GC, compared with traditional individual care (TC), improves perinatal outcomes in women who deliver at term. STUDY DESIGN: We performed a retrospective cohort study of women delivering at term who participated in GC compared with TC. A group of 207 GC patients who delivered at term from 2004 to 2014 were matched in a 1:2 ratio to 414 patients with term singleton pregnancies who delivered at our institution during the same period by delivery year, maternal age, race and insurance status. The primary outcome was low birth weight (<2500 g). Secondary outcomes included early term birth (37.0 to 38 6/7 weeks), 5 min APGAR score <7, special care nursery admission, neonatal intensive care unit (NICU) admission, neonatal demise, cesarean section and number of prenatal visits. Outcomes were compared between the two groups using univariable statistics. RESULTS: Baseline characteristics were similar between the two matched groups. GC was associated with a significant reduction in low birth weight infants compared with TC (11.1% vs 19.6%; relative risk (RR) 0.57; 95% confidence interval (CI) 0.37 to 0.87). Patients in GC were significantly less likely than controls to require cesarean delivery, have low 5 min APGAR scores and need higher-level neonatal care (NICU: 1.5% vs 6.5%; RR 0.22; 95% CI 0.07 to 0.72). There were no significant differences in rates of early term birth and neonatal demise. CONCLUSIONS: Low-risk women participating in GC and delivering at term had a lower risk of low birth weight and other adverse perinatal outcomes compared with women in TC. This suggests GC is a promising alternative to individual prenatal care to improve perinatal outcomes in addition to preterm birth.

Prenatal visit utilization and outcomes in pregnant women with type II and gestational diabetes.

OBJECTIVE: To investigate the association between the number of prenatal visits (PNVs) and pregnancy outcomes in women with gestational diabetes (GDM) and Type 2 diabetes mellitus (DM). STUDY DESIGN: A 4-year prospective cohort study of women with GDM and DM and was conducted. Patients ⩾75th percentile for number of PNVs were compared with those ⩽25th percentile. The primary outcomes were large for gestational age (LGA) with birth weight >90% and neonatal intensive care unit (NICU) admission for >24 h. Secondary neonatal outcomes included severe LGA (>95%), shoulder dystocia, hyperbilirubinemia requiring phototherapy, neonatal hypoglycemia, low 5 min APGAR score (<7) and preterm birth (prior to 37 weeks). Secondary maternal outcomes included mean third trimester fasting blood glucose, hemoglobin A1c (Hgb A1c) in labor, preeclampsia, gestational weight gain over Institute of Medicine recommendations, mode of delivery and maternal readmission within 30 days. Logistic regression was used to adjust for maternal race, nulliparity and body mass index. RESULTS: Of the 305 women, 4 were excluded for unknown number of PNVs. Among the 301 included, the average number of visits was 12. Rates of LGA were similar between the high (28%) compared with low (18%) utilization groups (adjusted odds ratio (aOR) 1.69; 95% confidence interval (CI) 0.81-3.54). The high utilization group was 85% less likely to deliver an infant requiring NICU admission (aOR 0.15; 95% CI 0.04-0.53) and 59% less likely to have a preterm birth (aOR 0.41; 95% CI 0.21-0.80). A time-to-event analysis to account for the fact that patients who delivered earlier had fewer weeks to experience PNVs showed that the risk for NICU admission was still significantly lower in the high PNV utilization group (hazard ratio 0.15; 95% CI 0.04-0.51) after adjusting for confounders in a Cox proportional hazard model. The mean Hgb A1c at the time of delivery was significantly better in the high (6.4%) compared with low (6.9%) utilization groups (P=0.01). There were no differences in other maternal outcomes based on prenatal care utilization. CONCLUSIONS: Diabetic women with high PNV utilization have better glycemic control in the 3 months prior to delivery and are significantly less likely to deliver preterm infants or infants requiring NICU admission. There may be innovative ways to provide prenatal care for GDM and DM to optimize maternal and neonatal outcomes.

Diagnostic ability of elevated 1-h glucose challenge test.

OBJECTIVE: To determine whether a threshold of a 1-h glucose challenge test (GCT) eliminates the need for a 3-h glucose tolerance test (GTT). STUDY DESIGN: A retrospective cohort of patients undergoing GTT after GCT was ⩾140 mg dl(-1). Gestational diabetes mellitus (GDM) was diagnosed using National Diabetes Data Group (NDDG) and Carpenter-Coustan (CC) criteria. Sensitivity, specificity and predictive values were calculated for 1-h GCT values of 160 to 220 mg dl(-1). RESULT: Of 6218 patients, 988 (15.9%) had an elevated GCT and 753 (12.1%) underwent a GTT. In all, 165 (2.7%) were diagnosed with GDM using NDDG criteria, and 250 (4.0%) by CC criteria. The positive predictive value of a 1-h of GCT ⩾200 mg dl(-1) for GDM was 68.6% by NDDG and 80.0% for GDM by CC criteria. CONCLUSION: Although the predictive value of an elevated 1-h ⩽200 mg dl(-1) for GDM was high, 1 in 3 to 1 in 5 women would be overdiagnosed with GDM if the 3-h GTT was omitted.

Number of prenatal visits and pregnancy outcomes in low-risk women.

OBJECTIVE: We investigated the association between number of prenatal visits (PNV) and pregnancy outcomes. STUDY DESIGN: A retrospective cohort of 12 092 consecutive, uncomplicated term births was included. Exclusion criteria included unknown or third trimester pregnancy dating, pre-existing medical conditions and common pregnancy complications. Patients with ⩽10 PNV were compared with those with >10. The primary outcome was a neonatal composite including neonatal intensive-care unit admission, low APGAR score (<7), low umbilical cord pH (<7.10) and neonatal demise. Secondary outcomes included components of the composite as well as vaginal delivery, induction and cesarean delivery. Logistic regression was used to adjust for potential confounders. RESULT: Of 7256 patients in the cohort meeting inclusion criteria, 30% (N=2163) had >10 PNV and the remaining 70% (N=5093) had ⩽10, respectively. There was no difference in the neonatal composite between the two groups. However, women with>10 PNV were more likely to undergo induction of labor and cesarean delivery. CONCLUSION: Low-risk women with ⩾10 PNV had higher rates of pregnancy interventions without improvement in neonatal outcomes.

Stillbirth and the small fetus: use of a sex-specific versus a non-sex-specific growth standard.

OBJECTIVE: To determine if the use of a sex-specific standard to define small-for-gestational age (SGA) will improve prediction of stillbirth. STUDY DESIGN: We performed a retrospective cohort study of singleton pregnancies excluding anomalies, aneuploidy, undocumented fetal sex or birthweight. SGA was defined as birthweight <10th percentile by the non-sex-specific and sex-specific Alexander standards. The association between SGA and stillbirth using these standards was assessed using logistic regression. RESULT: Among 57,170 pregnancies meeting inclusion criteria, 319 (0.6%) pregnancies were complicated by stillbirth. The area under the receiver operating characteristic curve for the prediction of stillbirth was greater for the sex-specific compared to the non-sex-specific standard (0.83 vs 0.72, P<0.001). CONCLUSION: Our findings suggest adoption of a sex-specific standard for diagnosis of SGA as it is more discriminative in identifying the SGA fetus at risk for stillbirth.

Timing of elective delivery in gastroschisis: a decision and cost-effectiveness analysis.

OBJECTIVE: To determine the most cost-effective timing of delivery in pregnancies complicated by gastroschisis, using a decision-analytic model. METHODS: We created a decision-analytic model to compare planned delivery at 35, 36, 37, 38 and 39 weeks' gestation. Outcomes considered were stillbirth, death within 1 year of birth and respiratory distress syndrome (RDS). Probability estimates of events (stillbirth, complex gastroschisis and RDS for each gestational age at delivery and risk of death with simple and complex gastroschisis), utilities and costs assigned to the outcomes were obtained from the published literature. Cost analysis was assessed from a societal perspective, using a willingness-to-pay threshold of $100,000 per surviving infant. Outcomes and costs were considered throughout 1 year of postnatal life. Multiway sensitivity analysis was performed to address uncertainties in baseline assumptions. RESULTS: In the base-case analysis, delivery at 38 weeks' gestation was the most cost-effective strategy. Planned delivery at 35 weeks was associated with the fewest stillbirths and deaths within 1 year of delivery, owing largely to a lower ongoing risk of stillbirth. In Monte Carlo simulation when every variable was varied over its entire range, delivery at 38 weeks was cost-effective compared to delivery at 39 weeks in 76% of trials and delivery at 37 weeks was cost-effective in 69% of trials. Delivery at 38 weeks resulted in three additional cases of RDS for every 100 stillbirths or deaths within 1 year that were prevented. CONCLUSIONS: For pregnancies complicated by gastroschisis, the most cost-effective timing of delivery is at 38 weeks. Few additional cases of RDS are caused for every one stillbirth or death within 1 year that was prevented with delivery at 37-38 weeks compared with at 39 weeks.

Loop electrosurgical excision procedure and risk of vaginal infections during pregnancy: an observational study.

OBJECTIVE: To investigate the risk for preterm birth associated with vaginal infections in pregnancies after a loop electrosurgical excision procedure (LEEP), compared with women with no prior LEEP. DESIGN: Multicentre retrospective cohort study. SETTING: USA. POPULATION: Women with LEEP between 1996 and 2006 were compared with two unexposed groups who had cervical biopsy or Pap test, without any other cervical procedure, in the same calendar year. METHODS: The first pregnancy progressing beyond 20 weeks of gestation in women with prior LEEP was compared with pregnancy in women without LEEP. Stratified analysis according to the presence or the absence of vaginal infection during pregnancy was used to investigate whether the risk for preterm birth differed according to the presence or the absence of infection. The interaction between LEEP and vaginal infection was investigated using multivariable logistic regression with interaction terms, as well as the Mantel-Haenszel test for homogeneity. MAIN OUTCOME MEASURES: Spontaneous preterm birth (<37 and <34 weeks of gestation). RESULTS: Of 1727 patients who met the inclusion criteria, 34.4% (n = 598) underwent LEEP prior to an index pregnancy. There was no increased risk for vaginal infections among women with LEEP compared with women without LEEP. Chlamydia infection and LEEP demonstrated significant interaction, suggesting that the presence of chlamydia infection in women with a history of LEEP augments the risk for preterm birth, compared with women with no history of LEEP. CONCLUSIONS: Vaginal infections during pregnancy in women with a history of LEEP may be associated with an increased risk for preterm birth, compared with women with no history of LEEP.

Gestational weight gain in insulin-resistant pregnancies.

OBJECTIVE: To examine the Institute of Medicine (IOM) guidelines for gestational weight gain (GWG) in insulin-resistant pregnancy. STUDY DESIGN: Secondary analysis of a prospective cohort of 435 women with type 2 or gestational diabetes from 2006 to 2010. The exposure was categorized as GWG less than, within or greater than the IOM recommendations for body mass index. The maternal outcome was a composite of preeclampsia, eclampsia, third- to fourth-degree laceration, readmission or wound infection. The neonatal outcome was a composite of preterm delivery, level 3 nursery admission, oxygen requirement >6 h, shoulder dystocia, 5-min Apgar3, umbilical cord arterial pH<7.1 or base excess <-12. Secondary outcomes were cesarean delivery (CD), macrosomia and small for gestational age (SGA). RESULT: Incidence of the maternal outcome did not differ with GWG (P=0.15). Women gaining more than recommended had an increased risk of CD (relative risk (RR) 1.31, 95% confidence interval (CI) 1.01 to 1.69) and the neonatal outcome (RR 1.40, 95% CI 1.01 to 1.95) compared with women gaining within the IOM recommendations. Women gaining less than recommended had an increased risk of SGA (RR 3.29, 95% CI 1.09 to 9.91) without a decrease in the risk of the maternal outcome (RR 0.93, 95% CI 0.49 to 1.78) or CD (RR 0.74, 95% CI 0.40 to 1.37) compared with women gaining within the IOM recommendations. CONCLUSION: Women with insulin resistance should be advised to gain within the current IOM guidelines.

First-trimester serum soluble fms-like tyrosine kinase-1, free vascular endothelial growth factor, placental growth factor and uterine artery Doppler in preeclampsia.

OBJECTIVE: To compare the first-trimester serum concentrations of soluble fms-like tyrosine kinase-1 (sFlt-1), free vascular endothelial growth factor (free-VEGF), placental growth factor (PlGF), and uterine artery pulsatility index (PI) in women who later developed preeclampsia (PE). STUDY DESIGN: Prospectively collected maternal serum samples were evaluated for sFlt-1, free VEGF, and PlGF levels in 63 cases who later developed PE compared with 252 unaffected controls. Serum levels of these angiogenic factors were measured using Quantikine immunoassays. Both univariate and multivariate analyses were used to evaluate the association between angiogenic factors and PE. The relationship between the angiogenic factors and mean maternal uterine artery PI was also evaluated. RESULT: Maternal serum sFlt-1 levels were not significantly different between the cases and controls. Mean free-VEGF levels were significantly higher in women destined to develop PE compared with the controls (P=0.04), and mean PlGF levels were significantly lower in women who later developed PE (P=0.01). There was no significant correlation between maternal mean uterine artery PI and angiogenic factors evaluated. Receiver-operating characteristic curves revealed that none of the factors were clinically useful for prediction in the first trimester of PE. CONCLUSION: Despite some significant differences in the first-trimester serum levels of angiogenic factors, our models suggest that these factors are not clinically useful for prediction in women who later developed PE.

Customized growth charts for twin gestations to optimize identification of small-for-gestational age fetuses at risk of intrauterine fetal death.

OBJECTIVE: Customized growth charts developed for singleton pregnancies have been shown to be more effective than population-based ones at identifying small-for-gestational age (SGA) fetuses at risk for intrauterine fetal death (IUFD). We sought to compare the association between SGA and IUFD in twins using customized growth charts designed for twin gestations compared to those designed for singletons. METHODS: This was a retrospective cohort study using a database including singleton and twin pregnancies undergoing ultrasound examination between 16 and 20 weeks' gestation. After excluding preterm births < 34 weeks, congenital anomalies and stillbirths, we identified 51, 150 singleton births. Coefficients for significant physiological and pathological variables affecting birth weight for singletons were derived using backward stepwise multiple regression. The same process was repeated for twin births (1608 pairs), also adjusting for chorionicity. Customized growth charts for each pregnancy were derived using these two regression models for optimal birth weight at term and a proportionality equation. The association between SGA < 10(th) percentile, defined using the twin and singleton-customized charts, and IUFD were compared. Statistical analysis, including calculation of adjusted odds ratios (OR) for IUFD and screening accuracy using each chart, was performed. RESULTS: The derived coefficients for optimal birth weight for twins were different from those for singletons, with lower constants and root mean square error (3422 and 288.9, respectively, in twins vs 3543 and 416 in singletons). Among 3786 twin infants, IUFD was seen in 123 (3.2%). The numbers of fetuses identified as SGA were 575 (15.2%) and 504 (13.3%) by the singleton and twin charts, respectively. Fetuses classified as SGA by the twin-specific customized charts were at a significantly increased risk for IUFD (adjusted OR, 2.3 (95% CI, 1.4-3.5)), whereas those classified as SGA by the singleton-customized charts were not (adjusted OR, 1.2 (95% CI, 0.7-2.0)). CONCLUSION: Customized charts designed specifically for twins are more effective at identifying twin pregnancies at risk for IUFD than are those derived using singleton birth data.

Screening for fetal growth disorders by clinical exam in the era of obesity.

OBJECTIVE: To evaluate the performance of clinical estimation of fetal weight as a screening test for fetal growth disorders and then to estimate the effect of maternal body mass index (BMI) on its screening efficiency. STUDY DESIGN: This was a retrospective cohort study of patients referred for third trimester ultrasound for the indication of 'size unequal to dates'. Patients with medical co-morbidities that may alter their a priori risk for fetal growth disorders were excluded. The incidence of fetal growth disorders as well as amniotic fluid disturbances was determined for each group and then compared across maternal BMI categories of <25 kg m(-2), 25-30 kg m(-2), ≥ 30 kg m(-2) and ≥ 40 kg m(-2). To evaluate the accuracy of clinical estimation of fetal weight in predicting fetal growth disorders, the sensitivity, specificity, positive predictive value, negative predictive value, likelihood ratios, as well as number needed to scan (NNS) was calculated and compared across BMI categories. RESULT: Of 51366 patients, 1623 were referred for the indication of size>dates and 1543 for the indication of size90th percentile and 13.5 and 96.7% for predicting BW<10th percentile. The NNS to detect one neonate with a BW<10th percentile ranged from 5 to 19, whereas the NNS to detect one neonate with a BW>90th percentile ranged from 6 to 13 across BMI categories. CONCLUSION: Overall, clinical estimation of fetal weight yields a low detection rate of fetal growth abnormalities; however, its screening efficiency is not adversely impacted by maternal BMI.

First trimester serum analytes, maternal characteristics and ultrasound markers to predict pregnancies at risk for preterm birth.

INTRODUCTION: Markers of placental dysfunction are used for risk prediction of adverse obstetric outcomes including preeclampsia and growth restriction. Although medically indicated preterm birth is often distinguished from spontaneous preterm birth, we hypothesize that similar placental dysfunction may underlay all preterm birth. We aimed to investigate whether first trimester placental protein 13 (PP-13), pregnancy associated plasma protein A (PAPP-A) and uterine artery pulsatility index, with maternal characteristics could be used to predict all preterm birth. METHODS: Prospective cohort study of singleton gestations between 11 and 14 weeks who underwent serum measurement of PP-13, PAPP-A, and measurement of uterine artery Doppler pulsatility index. Primary outcomes were preterm birth (PTB) at less than 37 and 33 weeks. Analysis performed both including and excluding preeclampsia to assess the utility of the predictors for all types of preterm birth. Predictive models assembled using logistic regression with each predictor alone and in combination, along with maternal characteristics. Predictive utility of models was assessed using receiver operating curve (ROC) analysis and sensitivities for fixed false positive values. RESULTS: Of 471 women, PTB occurred in 12.5% and early PTB (<33 weeks) occurred in 4.7%. PP-13 was decreased in PTB <37 weeks. PAPP-A was decreased in a dose-response pattern for PTB at <37 weeks and <33 weeks. Uterine artery pulsatility index was increased in early PTB. All patterns of predictors remained the same whether patients with preeclampsia were excluded or included suggesting predictive utility for all causes of PTB. Predictive models all demonstrated good predictive ability with ROC ≥ 0.90. CONCLUSIONS: PP-13, PAPP-A, and uterine artery Doppler pulsatility index obtained in the first trimester are good predictors of all types of preterm birth, both indicated and spontaneous. Models including first trimester markers combined with maternal characteristics demonstrated good predictive ability and could be investigated for application of targeted prophylactic strategies.

Prediction of intrauterine fetal death in small-for-gestational-age fetuses: impact of including ultrasound biometry in customized models.

OBJECTIVE: Customized growth charts derived from maternal demographic characteristics alone have been shown to improve the prediction of pregnancy complications compared to population growth curves. We sought to estimate the impact of adding ultrasound biometric parameters to the customized chart for the prediction of intrauterine fetal death (IUFD). METHODS: A retrospective cohort study was undertaken using an ultrasound database including singleton pregnancies followed between 16 and 20 weeks' gestation. After exclusion of preterm births, congenital anomalies, multifetal pregnancies and stillbirths (excluded only from derivation samples), we identified 59 016 births, divided into derivation (34 832) and validation (24 184) samples. Coefficients for significant physiological and pathological variables affecting fetal growth were derived using backward stepwise multiple regression (Cust-chart). The same process was repeated including second-trimester biometric parameters: biparietal diameter, head circumference, femur length and abdominal circumference in the regression models (Cust-plus-USS-chart). The association between small-for-gestational age < 10(th) centile (SGA) pregnancies, defined using the two customized charts or our population-based growth chart (Pop-chart) and IUFD, were compared. Statistical analyses including OR, 95% CI and screening accuracy using each chart were performed. RESULTS: The derived coefficients for fetal growth are comparable to those of previously published series. Of 24 184 pregnancies in the validation sample, IUFD was seen in 169 (0.7%). The pregnancies identified as SGA were: 2482 (10.26%), 2499 (10.33%) and 2634 (10.89%) using the Cust-chart, Cust-plus-USS-chart and Pop-chart, respectively. The OR (95% CI) for the association between SGA defined by the three charts and IUFD was: 7.0 (4.5-11), 6.5 (4.2-10.2) and 2.4 (1.6-3.6) according to the Cust-chart, Cust-plus-USS-chart and Pop-chart, respectively. Screening efficiency for IUFD using both customized charts was similar, with both demonstrating a higher sensitivity compared with the Pop-chart. CONCLUSIONS: Customized charts are more efficient in identifying pregnancies at risk for IUFD compared with population-based charts. However, adding second-trimester ultrasound biometric parameters to the customized model does not improve the prediction of IUFD compared with using maternal characteristics only.

Effect of maternal weight on postterm delivery.

OBJECTIVE: Examine the effect of prepregnancy weight and maternal gestational weight gain on postterm delivery rates. STUDY DESIGN: This was a retrospective cohort study of term, singleton births (N=375 003). We performed multivariable analyses of the association between postterm pregnancy and both prepregnancy body mass index (BMI) and maternal weight gain. RESULT: Prolonged or postterm delivery (41 or 42 weeks) was increasingly common with increasing prepregnancy weight (P<0.001) and increasing maternal weight gain (P<0.001). Underweight women were 10% less likely to deliver postterm than normal weight women who gain within the recommendations (adjusted odds ratio 0.90 (95% confidence interval 0.83, 0.97)). Overweight women who gain within or above recommendations were also at increased risk of a 41-week delivery. Finally, obese women were at increased risk of a 41-week delivery with increasing risk with increasing weight (below, within and above recommendations adjusted odds ratios 1.19, 1.21, and 1.27, respectively). CONCLUSION: Elevated prepregnancy weight and maternal weight gain both increase the risk of a postterm delivery. Although most women do not receive preconceptional care, restricting weight gain to the within the recommended range can reduce the risk of postterm pregnancy in normal, overweight and obese women.

First-trimester serum analytes, biophysical tests and the association with pathological morphometry in the placenta of pregnancies with preeclampsia and fetal growth restriction.

OBJECTIVE: We test the hypothesis that first-trimester serum analytes, 4-D power Doppler placental vascular indices and uterine artery Doppler (UAD) predicts abnormal placental morphometry in pregnancies with preeclampsia (PE) and fetal growth restriction (FGR). STUDY DESIGN: Maternal serum analytes (PAPP-A, hCG, ADAM12s, and PP13), bilateral UADs, and placental vascular indices were measured at 11-14 weeks in a nested-case control study within a prospective cohort of women followed from the first-trimester to delivery. Vascularization index (VI), flow index (FI), and vascularization flow index (VFI) were obtained from 4-D power Doppler histograms. Serum analytes were measured using immunofluorometric assays and values converted to multiples of the median (MoM) for gestational age. Morphometric analysis was performed on placentas from pregnancies complicated by PE (n = 13), gestational hypertension (HBP, n = 7) and FGR (defined as fetal weight <10th percentile with abnormal umbilical artery Doppler: n = 7); and 20 uncomplicated pregnancies. Two pregnancies had both FGR and PE. Each placenta was weighed and random samples taken, and fixed in formalin within 1 h of delivery. Hematoxylin & Eosin stained slides were analyzed by design-based stereology to quantify linear dimensions, surface areas and volumes of placental components. Paired t-test and ANOVA with adjustments for multiple comparisons were used. RESULTS: The surface areas of terminal and intermediate villi as well as the volume of terminal villi were significantly smaller in placentas from pregnancies complicated by FGR and PE. Compared with the control group the mean PAPP-A (MoM) was lower in the pregnancies with abnormal placenta morphometry (1.1 ± 0.5 versus 0.7 ± 0.5, P = 0.03). The morphometric indices were lower in those pregnancies with low PAPP-A and IUGR compared with preeclampsia. CONCLUSION: First-trimester PAPP-A levels are associated with abnormal placental morphometry at delivery in pregnancies with PE and IUGR. These findings may explain the association between adverse pregnancy outcomes and first-trimester PAPP-A.

Association of early-onset pre-eclampsia in first pregnancy with normotensive second pregnancy outcomes: a population-based study.

OBJECTIVE: To evaluate pregnancy outcomes in normotensive second pregnancy following pre-eclampsia in first pregnancy. DESIGN: Population-based retrospective cohort study. SETTING: State of Missouri in the USA. SAMPLE: White European origin or African-American women who delivered their first two non-anomalous singleton pregnancies between 20 and 44 weeks of gestation in Missouri, USA, 1989-2005, without chronic hypertension, renal disease or diabetes mellitus (n = 12 835). METHODS: Pre-eclampsia or delivery at 34 weeks of gestation or less in first pregnancy was defined as early-onset pre-eclampsia, whereas late-onset pre-eclampsia was defined as pre-eclampsia with delivery after 34 weeks of gestation. Multivariate regression models were fitted to estimate the crude and adjusted odds ratios and 95% confidence intervals. MAIN OUTCOME MEASURES: Preterm delivery, large and small-for-gestational-age infant, Apgar scores at 5 minutes, fetal death, caesarean section, placental abruption. RESULTS: Women with early-onset pre-eclampsia in first pregnancy were more likely to be younger, African-American, recipients of Medicaid, unmarried and smokers. Despite a second normotensive pregnancy, women with early-onset pre-eclampsia in their first pregnancy had greater odds of a small-for-gestational-age infant, preterm birth, fetal death, caesarean section and placental abruption in the second pregnancy, relative to women with late-onset pre-eclampsia, after controlling for confounders. Moreover, maternal ethnic origin modified the association between early-onset pre-eclampsia in the first pregnancy and preterm births in the second pregnancy. Having a history of early-onset pre-eclampsia reduces the odds of having a large-for-gestational-age infant in the second pregnancy. CONCLUSION: A history of early-onset pre-eclampsia is associated with increased odds of adverse pregnancy outcomes despite a normotensive second pregnancy.

Vaginal birth after caesarean for women with three or more prior caesareans: assessing safety and success.

OBJECTIVE: To estimate the rate of success and risk of maternal morbidities in women with three or more prior caesareans who attempt vaginal birth after caesarean (VBAC). DESIGN: Retrospective cohort design. SETTING: Multicentre, from 1996 to 2000, including 17 tertiary and community delivery centres in north-eastern USA. POPULATION: A total of 25 005 women who had had at least one prior caesarean delivery. METHODS: Women who attempted VBAC with three or more prior caesareans were compared with those who attempted after one and two prior caesareans. Univariable and stratified analyses were used to select factors for multivariable analyses for maternal morbidity. Maternal characteristics were compared using a Student's t test, Mann-Whitney U test, chi-square test or Fisher's exact test, as appropriate. MAIN OUTCOME MEASURES: The primary outcome was composite maternal morbidity, defined as at least one of the following: uterine rupture, bladder or bowel injury, or uterine artery laceration. Secondary outcomes were VBAC success, blood transfusion and fever. RESULTS: Of 25 005 women, 860 had three or more prior caesarean deliveries: 89 attempted VBAC and 771 elected for repeat caesarean. Of the 89 who attempted VBAC, there were no cases of composite maternal morbidity. They were also as likely to have a successful VBAC as women with one prior caesarean (79.8% versus 75.5%, adjusted OR 1.4, 95% CI 0.81-2.41, P = 0.22). CONCLUSION: Women with three or more prior caesareans who attempt VBAC have similar rates of success and risk for maternal morbidity as those with one prior caesarean, and as those delivered by elective repeat caesarean.

Validation of placental vascular sonobiopsy for obtaining representative placental vascular indices by three-dimensional power Doppler ultrasonography.

OBJECTIVE: Placental vascular sonobiopsy has been proposed for obtaining a representative sample of the placental vascular tree when evaluation of the whole placenta is not feasible. We tested the hypothesis that placental vascular indices from sonobiopsy correlate well with those from the entire placenta. METHODS: Three-dimensional power Doppler ultrasound examinations were performed in 120 singleton pregnancies at 11-14 weeks' gestation. The VOCAL program was used to calculate placental vascularization index (VI), flow index (FI) and vascularization flow index (VFI) from stored images of each placenta by whole placenta evaluation and placenta vascular sonobiopsy. The mean of each index from four spherical sonobiopsies were compared to those from evaluation of the entire placenta for their degree of correlation and agreement. RESULTS: The mean VI and VFI from the two techniques were similar (13.9 [95% CI 12.3-15.8] versus 14.3 [95% CI 12.1-17.0], p = 0.62 and 6.1 [95% CI 5.2-7.1] versus 6.1 [95% CI 5.0-7.4], p = 0.93, respectively) and significantly correlated (Pearson's r = 0.70 [95% CI 0.60-0.78, p < 0.001] and r = 0.69 [95% CI 0.58-0.77, p < 0.001], respectively). The mean FI from the two techniques were significantly different (44.5 [95% CI 42.9-46.1] versus 41.3 [95% CI 39.6-43.0], p = 0.001), but correlated (r = 0.59 [95% CI 0.46-0.70, p < 0.001]). CONCLUSION: Our findings suggest that placenta vascular indices from sonobiopsy have a good correlation with those from evaluation of the entire placenta. Sonobiopsy may be a valid alternative for evaluation of the placental vascular tree when visualization of the entire placenta is not feasible. Measurements of VI and VFI appear to be more reliable than FI in sonobiopsy specimen.