Christine H. Comstock

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.

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.

The ultrasonographic appearance of ovarian ectopic pregnancies.

OBJECTIVE: To evaluate the ultrasonographic findings of ovarian ectopic pregnancies. METHODS: The ultrasonographic reports, videotapes, medical records, and operative summaries were reviewed for all women with a confirmed diagnosis of an ovarian ectopic pregnancy. Examinations were personally conducted by a physician who was either a radiologist-obstetrician or an obstetrician-maternal-fetal medicine specialist RESULTS: Six cases were identified in the 13-year period studied. Menstrual ages ranged from 6 to 9 2/7 weeks. Most (5/6) patients had abdominal pain, with 3 demonstrating it before or at 7 weeks gestation. A wide echogenic ring with an internal echolucent area was seen in 5 of 6 patients; 1 of these also contained a yolk sac, and in another, fetal heart motion could be seen. The echogenic ring seemed to be on the surface of the ovary or within the substance of the ovary in all 5 patients. The echogenicity of the ring was greater than that of the ovary in the 5 patients in whom it was identified. At surgery, the ovarian pregnancies had the appearance of a hemorrhagic ovarian cyst in all 6 patients. In the patient in whom no echogenic ring was seen the pregnancy had ruptured. All 6 cases were biopsy proven. CONCLUSION: Ovarian pregnancies usually appeared on or within the ovary as a cyst with a wide echogenic outside ring. A yolk sac or embryo was less commonly seen. The appearance of the contents lagged in comparison with the gestational age. Early abdominal pain was common. LEVEL OF EVIDENCE: III

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

The Early Sonographic Appearance of Placenta Accreta

Objective. To determine whether any sonographic findings in the first trimester predict placenta accreta. Methods. Patients who had a diagnosis of placenta accreta, increta, or percreta by clinical course or pathologic examination of the uterus and who had had a sonographic examination at 10 weeks or earlier were included in this study. Results. Seven patients met the study criteria. In 6 of these, who had had at least 1 previous cesarean delivery, the gestational sac was located in the lower uterine segment at the time of the early scan. Two of these pregnancies failed shortly after the early scan, and the patients underwent dilation and curettage, at which time severe bleeding necessitated a hysterectomy. The other 4 continued to term but had sonographic findings typical of placenta accreta during subsequent scans. In the seventh patient (who had had no previous cesarean deliveries), the gestational sac was located in the uterine fundus. Conclusions. In a patient with a previous cesarean delivery, a sac lying in the lower uterine segment on a scan at 10 weeks or earlier suggests the possibility of placenta accreta.

Early access to prenatal care: implications for racial disparity in perinatal mortality.

OBJECTIVE: To investigate racial disparities in perinatal mortality in women with early access to prenatal care. METHODS: A prospectively collected database from a large, multicenter investigation of singleton pregnancies, the FASTER trial, was queried. Patients were recruited from an unselected obstetric population between 1999 and 2002. A total of 35,529 pregnancies with early access to prenatal care were reviewed for this analysis. The timing of perinatal loss was assessed. The following intervals were evaluated: fetal demise at less than 24 weeks of gestation, fetal demise at 24 or more weeks of gestation, and neonatal demise. Perinatal mortality was defined as the sum of these three intervals. RESULTS: The study population was 5% black, 22% Hispanic, 68% white, and 5% other. All minority races experienced higher rates of intrauterine growth restriction, preeclampsia, preterm premature rupture of membranes, gestational diabetes, placenta previa, preterm birth, very-preterm birth, cesarean delivery, light vaginal bleeding, and heavy vaginal bleeding compared with the white population. Overall perinatal mortality was 13 per 1,000 (471/35,529). The adjusted odds ratios (95% confidence intervals) for perinatal mortality (utilizing the white population as the referent race) were: black 3.5 (2.5–4.9), Hispanic 1.5 (1.2–2.1), and other 1.9 (1.3–2.8). CONCLUSION: Racial disparities in perinatal mortality persist in contemporary obstetric practice despite early access to prenatal care. LEVEL OF EVIDENCE: II-2