Faculty Bibliography

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

OBJECTIVE: To investigate the differences in costs and outcomes of Down syndrome screening using data from the First and Second Trimester Evaluation of Risk (FASTER) Trial. METHODS: Seven possible screening options for Down syndrome were compared: 1) Triple Screen-maternal serum alpha fetoprotein, estriol, and hCG; 2) Quad-maternal serum alpha fetoprotein, estriol, hCG, and Inhibin A; 3) Combined First-nuchal translucency, pregnancy-associated plasma protein A (PAPP-A), free beta-hCG; 4) Integrated-nuchal translucency, PAPP-A, plus Quad; 5) Serum Integrated-PAPP-A, plus Quad; 6) Stepwise Sequential-Combined First plus Quad with results given after each test; and 7) Contingent Sequential-Combined First and only those with risk between 1:30 and 1:1,500 have Quad screen. The detection rates for each option were used given a 5% false-positive rate except for Contingent Sequential with a 4.3% false-positive rate. Outcomes included societal costs of each screening regimen (screening tests, amniocentesis, management of complications, and cost of care of Down syndrome live births), Down syndrome fetuses identified and born, the associated quality-adjusted life years, and the incremental cost-utility ratio. RESULTS: Based on the screening results derived from the 38,033 women evaluated in the FASTER trial, the Contingent Sequential screen dominated (lower costs with better outcomes) all other screens. For example, the Contingent Sequential cost 32.3 million dollars whereas the other screens ranged from 32.8 to 37.5 million dollars. The Sequential strategy led to the identification of the most Down syndrome fetuses of all of the screens, but at a higher cost per Down syndrome case diagnosed ($719,675 compared with $690,427) as compared with the Contingent Sequential. Because of the lower overall false-positive rate leading to fewer procedure-related miscarriages, the Contingent Sequential resulted in the highest quality-adjusted life years as well. The Contingent Sequential remained the most cost-effective option throughout sensitivity analysis of inputs, including amniocentesis rate after positive screen, rate of therapeutic abortion after Down syndrome diagnosis, and rate of procedure-related miscarriages. CONCLUSION: Analysis of this actual data from the FASTER Trial demonstrates that the Contingent Sequential test is the most cost-effective. This information can help shape future policy regarding Down syndrome screening

Sexual size dimorphism is thought to contribute to the greater mortality and morbidity of men compared with women. However, the timing of onset of sexual size dimorphism remains uncertain. The authors determined whether human fetuses exhibit sexual size dimorphism in the first trimester of pregnancy. Using a prospective cohort study, conducted in 1999-2002 in the United States, they identified 27,655 women who conceived spontaneously and 1,008 whose conception was assisted by in vitro fertilization or intrauterine insemination and for whom a first-trimester measurement of fetal crown-rump length was available. First-trimester size was expressed as the difference between the observed and expected size of the fetus, expressed as equivalence to days of gestational age. The authors evaluated the association between fetal sex, first-trimester size, and birth weight. Eight to 12 weeks after conception, males were larger than females (mean difference: assisted conception = 0.4 days, 95% confidence interval (CI): 0.1, 0.7, p = 0.008; spontaneous conception = 0.3 days, 95% CI: 0.2, 0.4, p < 0.00001). The size discrepancy remained significant at birth (mean birth weight difference: assisted conception = 90 g, 95% CI: 22, 159, p = 0.009; spontaneous conception = 120 g, 95% CI: 107, 132, p < 0.00001). These data demonstrate that human fetuses exhibit sexual size dimorphism in the first trimester of pregnancy

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

PURPOSE OF REVIEW: Developments in ultrasound in general, but even more so in three-dimensional ultrasound, parallel the growth in computing power and speed of computer technology. It is not surprising, therefore, that three-dimensional ultrasound technology is constantly evolving at a fast pace. The purpose of this article is to provide enhanced diagnostic capabilities for the obstetrical and gynecologic provider. RECENT FINDINGS: The most recent advances in three-dimensional ultrasound have to do with two main features. First, an increasingly fast acquisition speed, enabling quick sequences of fast moving organs such as the heart to be captured. Second, the increasing number of different display modalities, making understanding and analysis of normal anatomy and pathology easier for clinicians. SUMMARY: This article highlights a selected number of clinical situations in which three-dimensional ultrasound meaningfully enhances the contribution of this fast evolving diagnostic imaging tool

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

Ultrasound examination of the fetal central nervous system (CNS) distinguishes itself from the sonographic evaluation of all other organs or organ systems because during the course of pregnancy, the CNS (mainly the fetal brain) undergoes significant changes, in size and in the shape of its different anatomic regions, which follow a well-defined timeline and can be recognized sonographically. The developmental milestones of the CNS from the time of its first sonographic detection to term can, and should, be taken into consideration when a fetal neurosonogram is performed. This article describes a systematic approach to the evaluation of the fetal brain by discussing the differential diagnosis of two important sonographic findings, namely ventriculomegaly and an enlarged posterior fossa, and by touching on other important brain abnormalities