Faculty Bibliography

OBJECTIVE:To estimate the usefulness of absent nasal bone by ultrasound in the prenatal detection of second-trimester fetuses with trisomy 21. METHODS:This was a matched case-control study of sonograms from January 1, 1997 to April 30, 2002. Genetic sonograms and facial profile pictures of all fetuses that were subsequently proven to have trisomy 21 were reviewed (study group). A control group was identified during the same study period by using a 4-to-1 ratio matching for gestational age at the time of the ultrasound examination. The sensitivity and specificity of absent fetal nasal bone for trisomy 21 were determined, and overlap with other ultrasound aneuploidy markers was assessed. RESULTS:Forty fetuses were identified with trisomy 21; in 29 (72.5%) a facial profile had been obtained. Of the 160 controls, 102 (64%) had facial profiles documented. Of the 29 fetuses with trisomy 21 with facial profile available, 12 had absent nasal bone (sensitivity 41%). None of the 102 control fetuses with facial profiles available had absent nasal bone (specificity 100%). The sensitivity of genetic ultrasound was increased from 83% (24 of 29) to 90% (26 of 29) by adding absent nasal bone to the other ultrasound aneuploidy markers. CONCLUSION/CONCLUSIONS:In the second trimester of pregnancy, absent nasal bone has a sensitivity of 41% and a specificity of 100% in detecting fetal trisomy 21. Absent fetal nasal bone may be added to the list of ultrasound aneuploidy markers evaluated during a genetic sonogram.

Much information has been published regarding the use of second-trimester genetic sonography for the prenatal detection of Down syndrome by examining multiple aneuploidy markers. Among high-risk mothers (advanced maternal age, abnormal triple screen, or both), while many undoubtedly will choose to have invasive testing as a first option, others will instead use the information derived from genetic sonography to obtain an adjusted risk for Down syndrome to guide their decision about genetic amniocentesis. Accordingly, it is imperative that these patients have accurate and detailed counseling regarding their degree of risk reduction when the genetic sonogram is normal. This article reviews the use of second trimester genetic sonography in reducing the need for amniocentesis in the high-risk patient. At our institution, in high-risk patients when the genetic ultrasound is normal, the amniocentesis rate has been only 3%. We have found that genetic sonography is a patient-driven service, and that the information obtained at the time of ultrasound is an important component of the patient's decision of whether or not to proceed with invasive testing.

OBJECTIVE:This study was undertaken to determine whether intrapartum fevers at term are associated with markers of acute inflammation in maternal, fetal, and placental compartments. STUDY DESIGN/METHODS:Term cases with intrapartum fever (temperature >/=100.4 degrees F) were recruited with gestational age-matched controls. Maternal serum and umbilical vein blood were collected and assayed for interleukin-6 (IL-6) levels. Placentas were examined for histologic chorioamnionitis. Demographic and clinical data were collected and compared between cases and controls. RESULTS:Forty-seven case-control pairs were analyzed. Maternal IL-6 levels were higher in cases than in controls (median of 145 pg/mL vs 42 pg/mL, P <.0001). Umbilical vein IL-6 levels also were higher in cases than controls (median 9 pg/mL vs 3.5 pg/mL, P =.01), but more than half of levels in cases were below 11 pg/mL. Only 31.1% of febrile cases had moderate or severe histologic chorioamnionitis. Multivariable logistic regression identified maternal serum IL-6 levels, nulliparity, and number of vaginal examinations as the major predictors of intrapartum fever at term. CONCLUSION/CONCLUSIONS:The maternal inflammatory response as measured by maternal serum IL-6 levels is a strong marker for term intrapartum fever. The much weaker association of fetal and placental inflammatory responses suggest a smaller than expected contribution of intra-amniotic inflammation to term intrapartum fevers.

OBJECTIVE:A multicenter study was undertaken to evaluate the diagnostic efficacy of a genetic sonogram. METHODS:Eight centers provided data on 176 pregnancies complicated by fetal Down syndrome. One hundred thirty-four pregnancies were considered high risk because of advanced maternal age (> 35 years), and 42 were considered high risk for having "abnormal" triple-screen results (risk > 1:250). Each center provided fetal biometric data, information regarding the presence or absence of major structural abnormalities, and between 3 and 6 additional ultrasonographic markers for trisomy 21. The heterogeneity of our 8 independent "sensitivity estimates" was evaluated by Poisson regression, and a single combined estimate of the sensitivity was calculated. RESULTS:Of the total 176 cases of trisomy 21, 125 fetuses (71.0%) had either an abnormal long bone length (femur length, humerus length, or both), a major structural abnormality, or a Down syndrome marker. The combined diagnostic sensitivity was 71.6%, with a range of 63.6% (7 of 11) to 80% (8 of 10). Five centers had sensitivity estimates falling between 64% and 76%. The sensitivity of individual markers varied between 3% (sandal gap) and 46.5% (nuchal skin fold thickness). A condensed regimen of nuchal skin fold thickness, femur length, and a standard anatomic survey would screen in 56.8% of fetuses with Down syndrome. CONCLUSIONS:This 8-center study that included many fetuses with Down syndrome validates the concept that the genetic sonogram can be used to better adjust the Down syndrome risk for high-risk patients.

OBJECTIVE:The purpose of this study was to compare risk factor profiles for placenta previa between singleton and twin live births. STUDY DESIGN/METHODS:This cohort study was based on United States natality data files (1989 through 1998) and comprised 37,956,020 singleton births and 961,578 twin births. Women who were diagnosed with placenta previa were included only if they were delivered by cesarean delivery. Risk factors for placenta previa that were examined included sociodemographic (age, gravidity, education, marital status, and race), behavioral (prenatal care, smoking, and alcohol use), previous preterm birth, and medical and obstetric factors. Effect modification between maternal age and gravidity and the dose-response relationship with number of cigarettes smoked/day on placenta previa risk were also evaluated. RESULTS:The rate of placenta previa was 40% higher among twin births (3.9 per 1,000 live births, n = 3,793 births) than among singleton births (2.8 per 1,000 live births, n = 104,754 births). Comparison of risk factors for placenta previa between the singleton and twin births revealed fairly similar risk factor profiles. Compared with primigravid women <20 years old, the risk for placenta previa increased by advancing age and by increasing number of pregnancies among both singleton and twin births. The number of cigarettes smoked per day also showed a dose-response trend for placenta previa risk in the two groups. CONCLUSION/CONCLUSIONS:The increased rate of placenta previa among twin births underscores the need to monitor carefully such pregnancies with heightened suspicion and awareness for the development of this condition.

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.

OBJECTIVE:This study was undertaken to determine the association, if any, between prenatal care and postneonatal death in the presence and absence of high-risk pregnancy conditions. STUDY DESIGN/METHODS:Data were derived from the national linked birth/infant death data set for the years 1995 to 1997 provided by the National Center for Health Statistics. Analyses were restricted to singleton live births that occurred after 23 completed weeks of gestation. Multiple births, congenital malformations, chromosomal abnormalities, missing data on gestational age, and birth weight less than 500 g were excluded. Multivariable logistic regression analyses were used to adjust for various antenatal high-risk conditions, maternal age, gravidity, gestational age at delivery, birth weight, maternal education, marital status, smoking, and alcohol use. Postneonatal death rate was defined as the number of deaths between 28 and 365 days of life per 1,000 neonatal survivors. RESULTS:For 10,512,269 singleton live births analyzed, 21,962 (2.1 per 1,000) resulted in postneonatal death. Postneonatal death rates were higher for African American women than white women in the presence (3.8 vs 1.7 per 1,000) and absence (11.2 vs 5.3 per 1,000) of prenatal care. Lack of prenatal care was associated with increased relative risk (RR) for postneonatal death, 1.8-fold in African American women and 1.6-fold in white women. Lack of prenatal care was associated with increased postneonatal death rates to a similar degree for the individual high-risk pregnancy conditions for both African American and white women. Lack of prenatal care was associated with increased postneonatal death rates, especially in the presence of postterm pregnancy (RR 2.3, 95% CI 1.6, 3.1), pregnancy-induced hypertension (RR 2.2, 95% CI 1.5, 3.4), intrapartum fever (RR 2.1, 95% CI 1.2, 3.5), and small-for-gestational-age infant (RR 1.6, 95% CI 1.3, 2.0). CONCLUSION/CONCLUSIONS:Lack of prenatal care should be considered as a high-risk factor for postneonatal death for both African American and white women, especially if the pregnancy has been complicated by postdates, pregnancy-induced hypertension, intrapartum fever or small-for-gestational-age infant.

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.