Faculty Bibliography

OBJECTIVE:To estimate the effect of specific maternal-fetal high-risk conditions on the risk and timing of fetal death. METHODS:This study examined 10,614,679 non-anomalous singleton pregnancies delivering at or beyond 24 weeks' gestation, derived from the U.S. linked birth/infant death data sets, 1995-1997. Fetal death rates for pregnancies at low risk were compared with pregnancies complicated by chronic hypertension, gestational hypertensive disorders, diabetes, small for gestational age infants, and abruption. Adjusted relative risks as well as population-attributable risks for fetal death were derived by gestational age for each high-risk condition compared with low-risk pregnancies. RESULTS:The fetal death rate for low-risk pregnancies was 1.6 per 1000 births. Adjusted relative risk for fetal death was 9.2 (95% confidence interval [CI] 8.8, 9.7) for abruption, 7.0 (95% CI 6.8, 7.2) for small for gestational age infants, 1.4 (95% CI 1.3, 1.5) for gestational hypertensive disorders, 2.7 (95% CI 2.4, 3.0) for chronic hypertension, and 2.5 (95% CI 2.3, 2.7) for diabetes. Fetal death rates were lowest between 38 and 41 weeks. The fetal death rate (per 1000 births) for these high-risk conditions was 61.4, 9.6, 3.5, 7.6, and 3.9, respectively. Almost two thirds of fetal deaths were attributable to the pregnancy complications examined. CONCLUSION/CONCLUSIONS:High-risk conditions in pregnancy are associated with an increased risk for fetal death, particularly in the third trimester. Delivery should be considered at 38 weeks, but no later than 41 weeks, for these pregnancies.

As genetic research and technology continues to expand, carrier testing for an increasing number of single gene disorders is becoming available. Tay-Sachs disease and cystic fibrosis are two common recessive conditions with large-scale health implications. Tay-Sachs disease was the first genetic disorder for which community-based screening efforts were utilized and has provided a foundation for the development of other screening programs. Cystic fibrosis testing, on the other hand, has additional complexities and the implementation of population-based screening has been under debate. The many issues (technical, educational, social, psychological and economical) which must be considered as preconceptional and prenatal genetic screening is incorporated into clinical practice are discussed here in the context of Tay-Sachs disease and cystic fibrosis.

OBJECTIVE:Our purpose was to evaluate the association between birth weight (BW) and fetal death (FD) among pregnant nondiabetic and diabetic patients. STUDY DESIGN/METHODS:This was a retrospective cohort study using data for singleton births delivered between 1995 and 1997 in the United States (n = 10, 733, 983). Analysis was restricted to births that occurred at > or =20 completed weeks. FD rates among nondiabetic and diabetic patients (n = 271, 691) were determined for different 250-g BW categories. Adjusted relative risk (RR) and 95% CI for FD among diabetic compared with nondiabetic patients were derived through multivariable logistic regression models after potential confounders were controlled. RESULTS:Overall FD rates for nondiabetic and diabetic patients were 4.0 and 5.9 per 1,000 births, respectively, with adjusted RR of 2.0 (95% CI 1.8-2.2). Maternal diabetes was associated with increased FD rate for all BW categories after 1250 g. CONCLUSION/CONCLUSIONS:The FD rate is increased when birth weight is > or =4250 g in nondiabetic patients and > or =4000 g in diabetic patients.

OBJECTIVE:The purpose of this study was to determine the association between prenatal care in the United States and the neonatal death rate in the presence and absence of antenatal high-risk conditions. STUDY DESIGN/METHODS:Data were derived from the national perinatal mortality data sets for the years 1995 through 1997, which were provided by the National Center for Health Statistics. Analyses were restricted to singleton live births that occurred after 23 completed weeks of gestation. Multivariable logistic regression analyses were used to adjust for the presence or absence of various antenatal high-risk conditions, maternal age, gestational age at delivery, and birth weight. RESULTS:Of 10,530,608 singleton live births, 18,339 (1.7/1000 births) resulted in neonatal death. Neonatal death rates (per 1000 live births) were higher for African American infants compared with white infants in the presence (2.7 vs 1.5, respectively) and absence (10.7 vs 7.9, respectively) of prenatal care. Lack of prenatal care was associated with an increase in neonatal deaths, which was greater for infants born at > or =36 weeks of gestation (relative risk, 2.1; 95% CI, 1.8, 2.4). Lack of prenatal care was also associated with increased neonatal death rates in the presence of preterm premature rupture of the membranes (relative risk, 1.3; 95% CI, 1.1, 1.5), placenta previa (relative risk, 1.9; 95% CI, 1.2, 2.9), fetal growth restriction (relative risk, 1.7; 95% CI, 1.2, 1.6), and postterm pregnancy (relative risk, 1.4; 95% CI, 1.0, 2.9). CONCLUSION/CONCLUSIONS:In the United States, prenatal care is associated with fewer neonatal deaths in black and white infants. This beneficial effect was more pronounced for births that occurred at > or =36 weeks of gestation and in the presence of preterm premature rupture of the membranes, placenta previa, fetal growth restriction, and postterm pregnancy.

OBJECTIVE:To determine whether the presence of labor affects infant mortality among small-for-gestational-age (SGA) infants. METHODS:Data were derived from the United States national linked birth/infant death data sets for 1995-97. Singleton SGA live births in cephalic presentation delivered at 24-42 weeks' gestation were included. Mortality rates for SGA infants exposed and unexposed to labor were compared, and relative risks (RR) were derived using multivariable logistic regression models, after adjusting for potential confounding factors. RESULTS:Of 986 405 SGA infants, 87.4% were exposed to labor. Infants exposed to labor at 24-31 weeks had greater risks of dying during the early neonatal period (RR 1.79-1.86). Decreased risks of late and postneonatal death were observed at all gestational ages in the presence of labor. CONCLUSIONS:Exposure to labor is associated with an increased risk of early neonatal death among SGA infants, especially at gestational ages below 32 weeks. Future randomized trials are warranted to determine the optimal obstetric management of these high-risk infants.

OBJECTIVE:The purpose of this study was to determine the incidence of trisomy 18 in women who are <35 years old and who have sonographically detected isolated choroid plexus cyst. STUDY DESIGN/METHODS:A meta-analysis of prospective trials that were published in the English language between 1990 and 2000 was performed. Each trial met the following inclusion criteria: (1) prospective trial, (2) total population screened during the study period reported, (3) maternal age (either numeric or descriptive) reported, and (4) pregnancy/neonatal outcomes reported. An isolated choroid plexus cyst for the purpose of this study was defined as absence of sonographically detected structural abnormalities and normal serum analyte screens, if reported. RESULTS:Eight trials met the criteria and were used for analysis. A total of 106,732 women were screened through articles that were published between 1990 and 2000. The total number of fetuses with choroid plexus cysts that were identified in second-trimester scans were 1,235 (incidence, 1.2%). The incidence of isolated choroid plexus cysts in women who were <35 years old was 1.0% (n = 1,017 women). There were no cases of trisomy 18 in women with isolated choroid plexus cyst who were <35 years old. Four structural abnormalities were noted on postnatal examination; all four neonates had normal karyotypes. CONCLUSION/CONCLUSIONS:There is no evidence that detection of isolated choroid plexus cyst in women who are <35 years of age increases the risk of trisomy 18. Therefore, amniocentesis is not warranted because of the inherent risk of pregnancy loss that is associated with the procedure. Better algorithms are needed to screen women who have a low risk for trisomy 18.

This study was undertaken to examine the relationship between paternal and maternal age differences and adverse perinatal outcomes in the United States. Data were obtained on singleton pregnancies delivering at >or=20 weeks gestation in the United States in 1995-97 from the National Center for Health Statistics data sets. Adverse perinatal outcomes that were evaluated included fetal death rate (>or=20 weeks), preterm delivery <37 weeks and small-for-gestational-age (SGA) births (birthweight <10th centile for gestational age and corrected for sex). Age difference was defined as paternal minus maternal age. The analysis included 8995274 pregnancies (11.3% blacks, 88.7% whites). An increase in fetal death rate, preterm delivery and SGA births was noted among white women who were older than their male partners. For black mothers older than their partners, there was an increase in fetal death rate when the women were <20 years old, but a decrease in fetal death rate when >35 years old. Neither rates of preterm delivery nor SGA births were increased much for black women with varying parental age differences. This demonstrates that race and maternal age both contribute to the effects of parental age difference on adverse perinatal outcomes.

OBJECTIVE: To evaluate whether abnormal umbilical cord insertion (UCI) into the placenta is a risk factor for birth weight discordancy in twin gestations.METHODS: Pathology records of all liveborn twins delivered between January 1993 and June 1996 were reviewed. The information collected included gestational age at delivery, birth weight, gross placental pathology, and placental UCI-velamentous, marginal, or disc. Discordancy in birth weight was defined as an intrapair difference of at least 20%. Analyses were stratified on placental chorionicity. Odds ratios and 95% confidence intervals for birth weight discordancy were calculated based on the presence of an abnormal (velamentous or marginal) placental UCI relative to normal (disc) UCI on both placentae, after adjusting for potential confounders. RESULTS: There were 447 twin pairs identified. Dichorionic diamniotic placentation was present in 358 pairs (80.1%), monochorionic diamniotic in 84 (18.8%), and monochorionic monoamniotic in five (1.1%). There was a 13-fold increase in the risk of birth weight discordancy in monochorionic diamniotic twins in the presence of a velamentous UCI (odds ratio 13.5, 95% confidence interval 1.4, 138.4), with a rate of birth weight discordancy of 46%. This relationship was not demonstrated in dichorionic diamniotic twins (odds ratio 1.0, 95% confidence interval 0.3, 3.5). CONCLUSION: Birth weight discordancy in twins is a different entity depending on chorionicity. The substantial increase in birth weight discordancy in monochorionic diamniotic twins that accompanies velamentous UCI underscores the need for prenatal detection and increased surveillance in these twins

OBJECTIVE: The objective of this study was to determine whether there are any indication-specific variations in risk reduction for fetal Down syndrome after a normal genetic sonogram. STUDY DESIGN: A second-trimester genetic sonogram was offered to all pregnant women who were at increased risk for fetal Down syndrome (>/=1:274) because of either advanced maternal age (>/=35 years), an abnormal triple screen, or both. Outcome information included the results of genetic amniocentesis (if performed), the results of pediatric assessment, and follow-up after birth. Normal genetic sonography was defined as the absence of all ultrasound aneuploidy markers. RESULTS: The overall prevalence of fetal Down syndrome in the tested population was 1.41% (53/3,753 pregnancies); however, in the presence of normal genetic sonography, the overall prevalence of fetal Down syndrome was 0.21% (7/3,291 pregnancies). The overall risk reduction for fetal Down syndrome in the presence of normal genetic sonography was 6.64-fold (95% CI, 3.01-14.62); the overall negative likelihood ratio was 0.15 (95% CI, 0.07-0.33). In the presence of normal genetic sonography, the risk for fetal Down syndrome was reduced by 83% in patients with advanced maternal age, 88% in patients with abnormal triple screen, 89% in patients with abnormal triple screen who were <35 years old, and 84% in patients who had both abnormal triple screen and advanced maternal age. CONCLUSION: There were no significant variations in the risk reduction for fetal Down syndrome in the presence of normal genetic sonography. Regardless of the indication for testing, the likelihood for fetal Down syndrome was reduced by 83% to 89%. This information will be useful in counseling pregnant women who are at high risk for fetal Down syndrome and who prefer to undergo genetic sonography before deciding about genetic amniocentesis

OBJECTIVE: To estimate the value of second-trimester genetic sonography in detecting fetal Down syndrome in patients with advanced maternal age (at least 35 years) and normal triple screen. METHODS: Since July 1999, a prospective collection and recording of all individual triple screen risks for fetal Down syndrome was initiated for all patients with advanced maternal age presenting in our ultrasound unit for second-trimester genetic sonography. Genetic sonography evaluated the presence or absence of multiple aneuploidy markers. Outcome information included the results of genetic amniocentesis, if performed, and the results of pediatric assessment and follow-up after birth. RESULTS: By June 2001, 959 patients with advanced maternal age and normal triple screen were identified. Outcome information was obtained in 768 patients. The median risk for fetal Down syndrome based on maternal age was 1:213 (range 1:37-1:274). The median risk for fetal Down syndrome based on triple screen results was 1:1069 (range 1:275-1:40,000). A total of 673 patients had normal genetic sonography, and none (0%) had Down syndrome; 95 had one or more aneuploidy markers present, and four (4.2%) had fetuses with Down syndrome. The triple screen risks for these four fetuses ranged from 1:319 to 1:833. CONCLUSION: This study suggests that patients with advanced maternal age and normal genetic sonography carried very little risk for Down syndrome. The use of genetic sonography may increase the detection rate of fetal Down syndrome in this group of pregnant women