Stephen R. Carr

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

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

First- and second-trimester evaluation of risk for Down syndrome

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 &bgr;-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 (

Lipid Tolerance Testing in Pregnancy

719,675 compared with

High Risk Pregnancy: Management Options

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.

Treatment of Antenatal Myasthenia Gravis

Objective— Macrosomia in the infant of the well-controlled diabetic mother suggests that a substrate other than glucose may influence fetal growth. We hypothesized that GDM alters lipid homeostasis during pregnancy. Our objective was to determine if an LTT could assist in identification of lipid abnormalities in the GDM individual. Research Designs and Methods— The LTT consisted of bolus infusion of 1.0 mg/kg 10% Intralipid (Cutter Vitrum, Berkeley, CA) followed by measurements of plasma glucose, insulin, glycerol, total triglycerides, and triglyceride fatty acids (18:1 and 18:2), total FFAs, and total phospholipids for 30 min before and 90 min after the bolus. The study groups were composed of 8 nonpregnant, nondiabetic subjects, 8 pregnant, nondiabetic subjects, 8 GDM patients receiving insulin, and 8 GDM patients who were diet controlled. Results— Plasma glucose and plasma insulin concentrations did not change significantly after the bolus. No significant difference was noted in the K2 for glycerol of the nonpregnant, nondiabetic group compared with the pregnant groups. The K2 for total triglycerides, plasma triglyceride 18:1, and plasma triglyceride 18:2 indicated increased rates of disappearance of these substrates for the nonpregnant nondiabetic group compared with all pregnant groups. No significant differences were observed among the pregnant groups for any of these parameters. Conclusions— Pregnancy may be associated with a decreased rate of triglyceride lipolysis compared with nonpregnancy. No differences in lipid metabolism were noted among normal pregnant and relatively well-controlled GDM patients.

The unpredictable character of congenital cystic lung lesions

I do not envy editors of medical texts. The pace at which new information accrues is rapid and ever increasing. Pity the person who has to bring together information from so many sources in a manner sufficiently timely that it is not outdated by the time it is published. The editors of this weighty book (more than 1300 pages) have found a way to circumvent the problem of information being outdated by publication time— instead of giving minute detail for each pregnancy complication (detail that will undoubtedly change), they concentrate on an approach to management. Authors supply enough information to provide an understanding of our current state of knowledge about a particular pregnancy problem and to construct a paradigm for evaluation and treatment. The particular details concerning a disease state may change, but the paradigm, if well constructed, is more durable over time. This type of presentation helps to construct

Pregnancy loss rates after midtrimester amniocentesis: the faster trial

Maternal myasthenia gravis has been associated with the presence of neonatal myasthenia and sometimes fatal congenital anomalies. As a result, antenatal therapy directed at fetal sequelae may be indicated. We present the case of a pregnant myasthenic woman whose two previous pregnancies had ended in neonatal deaths from fetal deformations that were presumably due to maternal myasthenia. Serial plasmaphereses and oral prednisone therapy were used in an attempt to depress maternal anti-acetylcholine receptor antibody titers. As anti-acetylcholine receptor antibody titers fell, fetal breathing movements became apparent by ultrasound, and as these titers rose, no fetal breathing movements were apparent. Our patient delivered an infant with transient neonatal myasthenia but normal pulmonary development and no deformations. We suggest that the therapy given may have improved the outcome of this pregnancy compared with her two previous pregnancies.