Sabrina D. Craigo

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 patients 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. LEVEL OF EVIDENCE: II-2

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

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

Fetal growth in early pregnancy and risk of delivering low birth weight infant: prospective cohort study

Objective To determine if first trimester fetal growth is associated with birth weight, duration of pregnancy, and the risk of delivering a small for gestational age infant. Design Prospective cohort study of 38 033 pregnancies between 1999 and 2003. Setting 15 centres representing major regions of the United States. Participants 976 women from the original cohort who conceived as the result of assisted reproductive technology, had a first trimester ultrasound measurement of fetal crown-rump length, and delivered live singleton infants without evidence of chromosomal or congenital abnormalities. First trimester growth was expressed as the difference between the observed and expected size of the fetus, expressed as equivalence to days of gestational age. Main outcome measures Birth weight, duration of pregnancy, and risk of delivering a small for gestational age infant. Results For each one day increase in the observed size of the fetus, birth weight increased by 28.2 (95% confidence interval 14.6 to 41.2) g. The association was substantially attenuated by adjustment for duration of pregnancy (adjusted coefficient 17.1 (6.6 to 27.5) g). Further adjustments for maternal characteristics and complications of pregnancy did not have a significant effect. The risk of delivering a small for gestational age infant decreased with increasing size in the first trimester (odds ratio for a one day increase 0.87, 0.81 to 0.94). The association was not materially affected by adjustment for maternal characteristics or complications of pregnancy. Conclusion Variation in birth weight may be determined, at least in part, by fetal growth in the first 12 weeks after conception through effects on timing of delivery and fetal growth velocity.

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. Level of Evidence: II-2

First-trimester septated cystic hygroma: prevalence, natural history, and pediatric outcome.

Objective: To estimate prevalence, natural history, and outcome of septated cystic hygroma in the first trimester in the general obstetric population, and to differentiate this finding from simple increased nuchal translucency. Methods: Patients at 10.3–13.6 weeks of gestation underwent nuchal translucency sonography as part of a multicenter clinical trial. Septated cystic hygroma cases were offered chorionic villi sampling for karyotype, and targeted fetal anatomical and cardiac evaluations. Survivors were followed up for fetal and long-term pediatric outcome (median 25 months, range 12–50 months). Cases of septated cystic hygroma were also compared with cases of simple increased nuchal translucency. Results: There were 134 cases of cystic hygroma (2 lost to follow-up) among 38,167 screened patients (1 in 285). Chromosomal abnormalities were diagnosed in 67 (51%), including 25 trisomy-21, 19 Turner syndrome, 13 trisomy-18, and 10 others. Major structural fetal malformations (primarily cardiac and skeletal) were diagnosed in 22 of the remaining 65 cases (34%). There were 5 cases (8%) of fetal death and 15 cases of elective pregnancy termination without evidence of abnormality. One of 23 (4%) normal survivors was diagnosed with cerebral palsy and developmental delay. Overall, survival with normal pediatric outcome was confirmed in 17% of cases (22 of 132). Compared with simple increased nuchal translucency, cystic hygroma has 5-fold, 12-fold, and 6-fold increased risk of aneuploidy, cardiac malformation, and perinatal death, respectively. Conclusion: First-trimester cystic hygroma was a frequent finding in a general obstetric screening program. It has the strongest prenatal association with aneuploidy described to date, with significantly worse outcome compared with simple increased nuchal translucency. Most pregnancies with normal evaluation at the completion of the second trimester resulted in a healthy infant with a normal pediatric outcome. Level of Evidence: II-2

Preconceptional Folate Supplementation and the Risk of Spontaneous Preterm Birth: A Cohort Study

In an analysis of a cohort of pregnant women, Radek Bukowski and colleagues describe an association between taking folic acid supplements and a reduction in the risk of preterm birth.

Use of array comparative genomic hybridization for prenatal diagnosis of fetuses with sonographic anomalies and normal metaphase karyotype

To prospectively study the addition of array comparative genomic hybridization (CGH) to the prenatal evaluation of fetal structural anomalies.

Racial/ethnic standards for fetal growth: The NICHD Fetal Growth Studies

OBJECTIVE Fetal growth is associated with long-term health yet no appropriate standards exist for the early identification of undergrown or overgrown fetuses. We sought to develop contemporary fetal growth standards for 4 self-identified US racial/ethnic groups. STUDY DESIGN We recruited for prospective follow-up 2334 healthy women with low-risk, singleton pregnancies from 12 community and perinatal centers from July 2009 through January 2013. The cohort comprised: 614 (26%) non-Hispanic whites, 611 (26%) non-Hispanic blacks, 649 (28%) Hispanics, and 460 (20%) Asians. Women were screened at 8w0d to 13w6d for maternal health status associated with presumably normal fetal growth (aged 18-40 years; body mass index 19.0-29.9 kg/m(2); healthy lifestyles and living conditions; low-risk medical and obstetrical history); 92% of recruited women completed the protocol. Women were randomized among 4 ultrasonography schedules for longitudinal fetal measurement using the Voluson E8 (GE Healthcare, Milwaukee, WI). In-person interviews and anthropometric assessments were conducted at each visit; medical records were abstracted. The fetuses of 1737 (74%) women continued to be low risk (uncomplicated pregnancy, absent anomalies) at birth, and their measurements were included in the standards. Racial/ethnic-specific fetal growth curves were estimated using linear mixed models with cubic splines. Estimated fetal weight (EFW) and biometric parameter percentiles (5th, 50th, 95th) were determined for each gestational week and comparisons made by race/ethnicity, with and without adjustment for maternal and sociodemographic factors. RESULTS EFW differed significantly by race/ethnicity >20 weeks. Specifically at 39 weeks, the 5th, 50th, and 95th percentiles were 2790, 3505, and 4402 g for white; 2633, 3336, and 4226 g for Hispanic; 2621, 3270, and 4078 g for Asian; and 2622, 3260, and 4053 g for black women (adjusted global P < .001). For individual parameters, racial/ethnic differences by order of detection were: humerus and femur lengths (10 weeks), abdominal circumference (16 weeks), head circumference (21 weeks), and biparietal diameter (27 weeks). The study-derived standard based solely on the white group erroneously classifies as much as 15% of non-white fetuses as growth restricted (EFW <5th percentile). CONCLUSION Significant differences in fetal growth were found among the 4 groups. Racial/ethnic-specific standards improve the precision in evaluating fetal growth.

Role of second-trimester genetic sonography after Down syndrome screening.

OBJECTIVE: To estimate the effectiveness of second-trimester genetic sonography in modifying Down syndrome screening test results. METHODS: The First and Second Trimester Evaluation of Risk (FASTER) aneuploidy screening trial participants were studied from 13 centers where a 15- to 23-week genetic sonogram was performed in the same center. Midtrimester Down syndrome risks were estimated for five screening test policies: first-trimester combined, second-trimester quadruple, and testing sequentially by integrated, stepwise, or contingent protocols. The maternal age-specific risk and the screening test risk were modified using likelihood ratios derived from the ultrasound findings. Separate likelihood ratios were obtained for the presence or absence of at least one major fetal structural malformation and for each “soft” sonographic marker statistically significant at the P<.005 level. Detection and false-positive rate were calculated for the genetic sonogram alone and for each test before and after risk modification. RESULTS: A total of 7,842 pregnancies were studied, including 59 with Down syndrome. Major malformations and 8 of the 18 soft markers evaluated were highly significant. The detection rate for a 5% false-positive rate for the genetic sonogram alone was 69%; the detection rate increased from 81% to 90% with the combined test, from 81% to 90% with the quadruple test, from 93% to 98% with the integrated test, from 97% to 98% with the stepwise test, and from 95% to 97% with the contingent test. The stepwise and contingent use of the genetic sonogram after first-trimester screening both yielded a 90% detection rate. CONCLUSION: Genetic sonography can increase detection rates substantially for combined and quadruple tests and more modestly for sequential protocols. Substituting sonography for quadruple markers in sequential screening was not useful. LEVEL OF EVIDENCE: II