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.

Timing of and outcomes after selective termination of anomalous fetuses in dichorionic twin pregnancies.

OBJECTIVE: The objective of this article is to determine if selective termination (ST) of an anomalous dichorionic twin at early gestational age (GA) is associated with a decreased risk of fetal loss and prematurity. METHOD: All patients who had ST for dichorionic twin pregnancies from 2004 through 2010 at Mount Sinai Medical Center were included. Data were collected via chart review and patient interview. Two case-control analyses were carried out: first, cases were nonviable deliveries, and controls were live births; and second, cases were live births <37 weeks' GA, and controls were live births ≥37 weeks' GA. Univariable and then multivariable analyses identified characteristics associated with pregnancy loss and prematurity. RESULTS: Among 80 participants, there were four (5%) fetal losses and 15 (19%) premature births. GA at ST was the only characteristic associated with pregnancy loss in multivariable exact logistic regression [OR = 1.43, 95% CI (1.03, 2.26), P = 0.03]. GA at ST was the only characteristic associated with premature delivery in multivariable exact logistic regression [OR = 1.18, 95% CI (1.02, 1.37), P = 0.03]. CONCLUSION: This study suggests that ST performed earlier in pregnancy is associated with decreased fetal loss and prematurity.

8p23.1 duplication syndrome; common, confirmed, and novel features in six further patients.

The 8p23.1 duplication syndrome is a relatively rare genomic condition that has been confirmed with molecular cytogenetic methods in only 11 probands and five family members. Here, we describe another prenatal and five postnatal patients with de novo 8p23.1 duplications analyzed with oligonucleotide array comparative genomic hybridization (oaCGH). Of the common features, mild or moderate developmental delays and/or learning difficulties have been found in 11/12 postnatal probands, a variable degree of mild dysmorphism in 8/12 and congenital heart disease (CHD) in 4/5 prenatal and 3/12 postnatal probands. Behavioral problems, cleft lip and/or palate, macrocephaly, and seizures were confirmed as additional features among the new patients, and novel features included neonatal respiratory distress, attention deficit hyperactivity disorder (ADHD), ocular anomalies, balance problems, hypotonia, and hydrocele. The core duplication of 3.68 Mb contains 31 genes and microRNAs of which only GATA4, TNKS, SOX7, and XKR6 are likely to be dosage sensitive genes and MIR124-1 and MIR598 have been implicated in neurocognitive phenotypes. A combination of the duplication of GATA4, SOX7, and related genes may account for the variable penetrance of CHD. Two of the duplications were maternal and intrachromosomal in origin with maternal heterozygosity for the common inversion between the repeats in 8p23.1. These additional patients and the absence of the 8p23.1 duplications in published controls, indicate that the 8p23.1 duplication syndrome may now be considered a pathogenic copy number variation (pCNV) with an estimated population prevalence of 1 in 58,000.

Influence of maternal BMI on genetic sonography in the FaSTER trial.

OBJECTIVE: We sought to evaluate the influence of maternal body mass index (BMI) on sonographic detection employing data from the FaSTER trial. METHOD: Unselected singleton pregnancies underwent detailed genetic sonogram to evaluate for structural fetal anomalies and soft markers for aneuploidy. BMI (kg/m(2)) were calculated from reported initial visit values. Sensitivity, specificity, false positive and false negative rates (FPR and FNR), likelihood ratio, detection rates, and a missed diagnosis rate (MDR: FNR + marker recorded as 'missing'/N) were calculated. RESULTS: Eight thousand five hundred and fifty-five patients with complete BMI information had detailed genetic sonography. A lower sensitivity with an elevated FNR and MDR was observed in obese women for multiple aneuploid markers (e.g. > or =2 markers 32% sensitivity with 68% FNR among BMI <25 vs 22% and 78% among BMI >30). Similarly, the detection rate for cardiac anomalies among women at BMI <25 was higher (21.6%) at a significantly lower FPR (78.4%; 95% CI 77.3-79.5%) in comparison to obese women (8.3% with FPR 91.7%; 95% CI 90.1-93.2%). In a logistic regression model, maternal obesity significantly decreased the likelihood of sonographic detection of common anomalies (adjusted OR 0.7; 95% CI 0.6-0.9; p = 0.001). CONCLUSION: The performance of second trimester genetic sonography is influenced by obesity, with a significantly higher MDR for multiple minor markers and lower likelihood for detecting common anomalies.

Preconceptional folate supplementation and the risk of spontaneous preterm birth: a cohort study.

BACKGROUND: Low plasma folate concentrations in pregnancy are associated with preterm birth. Here we show an association between preconceptional folate supplementation and the risk of spontaneous preterm birth. METHODS AND FINDINGS: In a cohort of 34,480 low-risk singleton pregnancies enrolled in a study of aneuploidy risk, preconceptional folate supplementation was prospectively recorded in the first trimester of pregnancy. Duration of pregnancy was estimated based on first trimester ultrasound examination. Natural length of pregnancy was defined as gestational age at delivery in pregnancies with no medical or obstetrical complications that may have constituted an indication for delivery. Spontaneous preterm birth was defined as duration of pregnancy between 20 and 37 wk without those complications. The association between preconceptional folate supplementation and the risk of spontaneous preterm birth was evaluated using survival analysis. Comparing to no supplementation, preconceptional folate supplementation for 1 y or longer was associated with a 70% decrease in the risk of spontaneous preterm delivery between 20 and 28 wk (41 [0.27%] versus 4 [0.04%] spontaneous preterm births, respectively; HR 0.22, 95% confidence interval [CI] 0.08-0.61, p = 0.004) and a 50% decrease in the risk of spontaneous preterm delivery between 28 and 32 wk (58 [0.38%] versus 12 [0.18%] preterm birth, respectively; HR 0.45, 95% CI 0.24-0.83, p = 0.010). Adjustment for maternal characteristics age, race, body mass index, education, marital status, smoking, parity, and history of prior preterm birth did not have a material effect on the association between folate supplementation for 1 y or longer and spontaneous preterm birth between 20 and 28, and 28 to 32 wk (adjusted HR 0.31, 95% CI 0.11-0.90, p = 0.031 and 0.53, 0.28-0.99, p = 0.046, respectively). Preconceptional folate supplementation was not significantly associated with the risk of spontaneous preterm birth beyond 32 wk. The association between shorter duration (<1 y) of preconceptional folate supplementation and the risk of spontaneous preterm birth was not significant after adjustment for maternal characteristics. However, the risk of spontaneous preterm birth decreased with the duration of preconceptional folate supplementation (test for trend of survivor functions, p = 0.01) and was the lowest in women who used folate supplementation for 1 y or longer. There was also no significant association with other complications of pregnancy studied after adjustment for maternal characteristics. CONCLUSIONS: Preconceptional folate supplementation is associated with a 50%-70% reduction in the incidence of early spontaneous preterm birth. The risk of early spontaneous preterm birth is inversely proportional to the duration of preconceptional folate supplementation. Preconceptional folate supplementation was specifically related to early spontaneous preterm birth and not associated with other complications of pregnancy.

Contemporary outcomes with the latest 1000 cases of multifetal pregnancy reduction (MPR).

OBJECTIVE: This study was undertaken to report on the outcome of multifetal pregnancy reduction in the most up-to-date largest single center experience with this procedure, and compare the outcome to the first 1000 cases performed at the same institution. STUDY DESIGN: 1000 consecutive cases of multifetal pregnancy reduction performed at the Mount Sinai Medical Center between the years 1999-2006 were identified. Pregnancy outcomes were retrieved from a large database as well as chart review. Differences in means and proportions were evaluated by analysis of variance, chi-square, Cochran-Armitage test for trend or 2-tailed Fisher exact test as appropriate. RESULTS: Outcomes were available on 841 cases, for a follow-up rate of 84.1%; 95.2% of patients delivered after 24 weeks, for a complete loss rate of 4.7%. There was a significant trend toward decreasing loss rates with decreasing starting numbers. Mean gestational age at delivery was later, and birthweights greater, for reduction to singletons vs twins. CONCLUSION: Loss rates after multifetal pregnancy reduction have remained stable at 4.7%. The lowest loss rate occurred in the patients reducing from twins to a singleton (2.1%). Reduction to a singleton was also associated with higher birthweights and lower rates of preterm deliveries.

Chorionic villus sampling and the risk of adverse outcome in patients undergoing multifetal pregnancy reduction.

OBJECTIVE: The objective of the study was to determine whether patients undergoing chorionic villus sampling (CVS) prior to MPR are at increased risk for adverse outcome compared to those who did not. STUDY DESIGN: We retrospectively identified multifetal pregnancy reduction (MPR) patients from an established database. Maternal demographic data were collected. Outcomes including complete pregnancy loss prior to 24 weeks' gestation, gestational age at delivery, and birthweight were analyzed. RESULTS: There was no significant difference in pregnancy loss between the 2 groups (CVS [4%] vs no CVS [7%], P = .098). When stratified by finishing number, there was a significantly lower loss rate in the singleton CVS group (2% vs 9%, P = .025) and no significant difference in reduced twins. There was no significant difference in the average gestational age of delivery or birthweight. CONCLUSION: CVS prior to MPR does not increase the risk of pregnancy loss. Our data suggest that CVS prior to singleton reduction may decrease the risk of adverse outcome.

Prediction of patient-specific risk for fetal loss using maternal characteristics and first- and second-trimester maternal serum Down syndrome markers.

OBJECTIVE: To develop and evaluate a method of estimating patient-specific risk for fetal loss by combining maternal characteristics with serum markers. STUDY DESIGN: Data were obtained on 36,014 women from the FaSTER trial. Separate likelihood ratios were estimated for significant maternal characteristics and serum markers. Patient-specific risk was calculated by multiplying the incidence of fetal loss by the likelihood ratios for each maternal characteristic and for different serum marker combinations. RESULTS: Three hundred eighteen women had fetal loss < 24 weeks (early) and 103 > 24 weeks (late). Clinical characteristics evaluated included maternal age, body mass index, race, parity, threatened abortion, previous preterm delivery, and previous early loss. Serum markers studied as possible predictors of early loss included first-trimester pregnancy-associated plasma protein A and second-trimester alpha-fetoprotein, and unconjugated estriol. A risk assessment for early loss based on all of these factors yielded a 46% detection rate, for a fixed 10% false-positive rate, 39% for 5% and 28% for 1%. The only significant marker for late loss was inhibin A. The detection rate was 27% for a fixed 10% false-positive rate and only increased slightly when clinical characteristics were added to the model. CONCLUSION: Patient-specific risk assessment for early fetal loss using serum markers, with or without maternal characteristics, has a moderately high detection. Patient-specific risk assessment for late fetal loss has low detection rates.

Nuchal translucency and the risk of congenital heart disease.

OBJECTIVE: To estimate whether nuchal translucency assessment is a useful screening tool for major congenital heart disease (CHD) in the absence of aneuploidy. METHODS: Unselected patients with singleton pregnancies at 10(3/7) to 13(6/7) weeks of gestation were recruited at 15 U.S. centers to undergo nuchal translucency sonography. Screening characteristics of nuchal translucency in the detection of major CHD were determined using different cutoffs (2.0 or more multiples of the median [MoM], 2.5 or more MoM, 3.0 or more MoM). RESULTS: A total of 34,266 euploid fetuses with cardiac outcome data were available for analysis. There were 224 cases of CHD (incidence 6.5 per 1,000), of which 52 (23.2%) were major (incidence 1.5 per 1,000). The incidence of major CHD increased with increasing nuchal translucency: 14.1 per 1,000, 33.5 per 1,000, and 49.5 per 1,000 at 2.0 or more MoM, 2.5 or more MoM, and 3.0 or more MoM cutoffs, respectively. Sensitivity, specificity, and positive predictive values were 15.4%, 98.4%, and 1.4% at 2.0 or more MoM; 13.5%, 99.4%, and 3.3% at 2.5 or more MoM; and 9.6%, 99.7%, and 5.0% at 3.0 or more MoM. Nuchal translucency of 2.5 or more MoM (99th percentile) had a likelihood ratio (95% confidence interval) of 22.5 (11.4-45.5) for major CHD. Based on our data, for every 100 patients referred for fetal echocardiography with a nuchal translucency of 99th percentile or more, three will have a major cardiac anomaly. CONCLUSION: Nuchal translucency sonography in the first trimester lacks the characteristics of a good screening tool for major CHD in a large unselected population. However, nuchal translucency of 2.5 or more MoM (99th percentile or more) should be considered an indication for fetal echocardiography. LEVEL OF EVIDENCE: II.

The contribution of birth defects to preterm birth and low birth weight.

OBJECTIVE: To assess the impact of birth defects on preterm birth and low birth weight. METHODS: Data from a large, prospective multi-center trial, the First and Second Trimester Evaluation of Risk (FASTER) Trial, were examined. All live births at more than 24 weeks of gestation with data on outcome and confounders were divided into two comparison groups: 1) those with a chromosomal or structural abnormality (birth defect) and 2) those with no abnormality detected in chromosomes or anatomy. Propensity scores were used to balance the groups, account for confounding, and reduce the bias of a large number of potential confounding factors in the assessment of the impact of a birth defect on outcome. Multiple logistic regression analysis was applied. RESULTS: A singleton liveborn infant with a birth defect was 2.7 times more likely to be delivered preterm before 37 weeks of gestation (95% confidence interval [CI] 2.3-3.2), 7.0 times more likely to be delivered preterm before 34 weeks (95% CI 5.5-8.9), and 11.5 times more likely to be delivered very preterm before 32 weeks (95% CI 8.7-15.2). A singleton liveborn with a birth defect was 3.6 times more likely to have low birth weight at less than 2,500 g (95% CI 3.0-4.3) and 11.3 times more likely to be very low birth weight at less than 1,500 g (95% CI 8.5-15.1). CONCLUSION: Birth defects are associated with preterm birth and low birth weight after controlling for multiple confounding factors, including shared risk factors and pregnancy complications, using propensity scoring adjustment in multivariable regression analysis. The independent effects of risk factors on perinatal outcomes such as preterm birth and low birth weight, usually complicated by numerous confounding factors, may benefit from the application of this methodology, which can be used to minimize bias and account for confounding. Furthermore, this suggests that clinical and public health interventions aimed at preventing birth defects may have added benefits in preventing preterm birth and low birth weight. LEVEL OF EVIDENCE: II.

Evolving trends in 2000 cases of multifetal pregnancy reduction: a single-center experience.

OBJECTIVE: The purpose of this study was to examine changes in multifetal pregnancy reduction (MPR) procedures in 2000 cases and to evaluate evolving trends within the last 1000 MPRs. STUDY DESIGN: Two thousand patients who underwent MPR were identified. Data were collected from a computerized database. Comparisons were made between the first 1000 patients (group 1) and the second 1000 patients (group 2). In addition, changing trends within group 2 were also analyzed. Differences in proportions were evaluated by chi-square test and Fisher's exact test, as appropriate. RESULTS: There was a significant difference in the starting and finishing number of fetuses and a significant increase in the use of chorionic villus sampling before MPR in group 2 vs group 1 (43.7% vs 1.5%; P < .0001). The incidence of monochorionicity was significantly higher in group 2 (5.7%), compared with group 1 (2.1%; P < .001). CONCLUSION: Recent trends in MPR demonstrates significant increases in overall reductions to a singleton fetus, the use of chorionic villus sampling, and the presence of monochorionicity.

The effect of low body mass index on the development of gestational hypertension and preeclampsia.

OBJECTIVES: To evaluate the relationship between low maternal body mass index (BMI) as calculated in the first trimester and the risk of preeclampsia and gestational hypertension. METHODS: Patients enrolled in the First And Second Trimester Evaluation of Risk for aneuploidy (FASTER) trial were grouped into three weight categories: low BMI (BMI <19.8 kg/m2), normal BMI (BMI 19.8 - 26 kg/m2), and overweight BMI (26.1 - 29 kg/m2). The incidences of gestational hypertension and preeclampsia were ascertained for each group. Tests for differences in crude incidence proportions were performed using Chi-square tests. Multiple logistic regression was used to adjust for maternal age, race, parity, obesity, use of assisted reproductive technology (ART), in vitro fertilization (IVF), gestational diabetes, pre-gestational diabetes, cocaine use, and smoking. RESULTS: The proportion of patients having gestational hypertension in the low BMI group was 2.0% compared to 3.2% for normal BMI and 6.0% for overweight BMI (p < 0.0001). Women with low BMI were also less likely to develop preeclampsia, 1.1% vs. 1.9% for normal BMI and 2.8% for overweight BMI (p < 0.0001). CONCLUSIONS: We found that women with low BMI in the first trimester were significantly less likely to develop gestational hypertension or preeclampsia than women with a normal BMI.

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.

Is misoprostol safe for labor induction in twin gestations?

OBJECTIVE: To compare the safety and efficacy of intravaginal misoprostol to oxytocin for the induction of labor in twin gestations. METHODS: All twin gestations that underwent induction of labor with misoprostol or oxytocin during a 4-year period were identified from the Mount Sinai obstetrical database. Only twins > or = 34 weeks with a vertex presenting twin A were included. Labor and delivery characteristics, maternal complications and neonatal outcomes were compared between the two groups. RESULTS: Of 134 patients with twins, 57 initially received misoprostol and 77 received oxytocin. These groups had similar demographics, but women who received misoprostol had less cervical dilation (0.8 vs. 2.2 cm, p < 0.0001) and were less likely to be multiparous (19% vs. 44%, p = 0.003). There was a shorter length of induction to delivery (7.8 hours vs. 15.1 hours, p = 0.001) and a trend toward a lower cesarean section rate (16.9% vs. 31.6%, p = 0.06) in the oxytocin-only group. There were no cases of uterine rupture or maternal mortality in this series. There were no significant differences in neonatal outcomes between the two groups, but the sample size was underpowered to detect significant differences between the groups. CONCLUSIONS: Misoprostol and oxytocin both appear to be safe and efficacious for use in inductions of labor in twins in this limited retrospective investigation. The safety of these agents with regard to neonatal outcomes should be confirmed by larger studies.

Circulating Cell-Free DNA to Determine the Fetal RHD Status in All Three Trimesters of Pregnancy.

OBJECTIVE: To estimate the accuracy of a new assay to determine the fetal RHD status using circulating cell-free DNA. METHODS: This was a prospective, observational study. Maternal blood samples were collected in each trimester of pregnancy in 520 nonalloimmunized RhD-negative patients. Plasma samples were analyzed for circulating cell-free DNA using the SensiGENE RHD test, which used primers for exons 4 and 7 as previously described and incorporated a new primer design for exon 5 of the RHD gene. Neonatal serology for RhD typing using cord blood at birth was undertaken and results were stored in a separate clinical database. After unblinding the data, results of the DNA analysis were compared with the neonatal serology. RESULTS: Inconclusive results secondary to the presence of the RHD pseudogene or an RHD variant were noted in 5.6%, 5.7%, and 6.1% of the first-, second-, and third-trimester samples, respectively. The incidence of false-positive rates for RhD (an RhD-negative fetus with an RHD-positive result) was 1.54% (95% confidence interval [CI] 0.42-5.44%), 1.53% (CI 0.42-5.40%), and 0.82% (CI 0.04-4.50%), respectively. There was only one false-negative diagnosis (an RhD-positive fetus with an RHD-negative result), which occurred in the first trimester (0.32%; 95% CI 0.08-1.78%). Genotyping for mismatches across repeated samples revealed that this error was related to mislabeling of samples from two patients collected on the same day at one of the collection sites. Overall test results were in agreement across all three trimesters (P>.99). CONCLUSION: Circulating cell-free DNA can accurately predict the fetal RhD status in all three trimesters of pregnancy.

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.

Impact of maternal age on obstetric outcome.

OBJECTIVE: To estimate the effect of maternal age on obstetric outcomes. METHODS: A prospective database from a multicenter investigation of singletons, the FASTER trial, was studied. Subjects were divided into 3 age groups: 1) less than 35 years, 2) 35-39 years, and 3) 40 years and older. Multivariable logistic regression analysis was used to assess the effect of age on outcomes after adjusting for race, parity, body mass index, education, marital status, smoking, medical history, use of assisted conception, and patient's study site. RESULTS: A total of 36,056 women with complete data were available: 28,398 (79%) less than 35 years of age; 6,294 (17%) 35-39 years; and 1,364 (4%) 40 years and older. Increasing age was significantly associated with miscarriage (adjusted odds ratio [adjOR]2.0 and 2.4 for ages 35-39 years and age 40 years and older, respectively), chromosomal abnormalities (adjOR 4.0 and 9.9), congenital anomalies (adjOR 1.4 and 1.7), gestational diabetes (adjOR 1.8 and 2.4), placenta previa (adjOR 1.8 and 2.8), and cesarean delivery (adjOR 1.6 and 2.0). Patients aged 35-39 years were at increased risk for macrosomia (adjOR 1.4). Increased risk for abruption (adjOR 2.3), preterm delivery (adjOR 1.4), low birth weight (adjOR 1.6), and perinatal mortality (adjOR 2.2) was noted in women aged 40 years and older. CONCLUSION: Increasing maternal age is independently associated with specific adverse pregnancy outcomes. Increasing age is a continuum rather than a threshold effect.

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.

Invasive procedures in multifetal pregnancies.

This review discusses the various invasive techniques currently performed in multiple pregnancies.

Maternal complications of multifetal pregnancy.

This article reviews the common maternal complications encountered in multifetal gestations.