Fredric D. Frigoletto

The risks of lowering the cesarean-delivery rate.

In 1995, the rate of cesarean delivery in the United States was 21 percent.1 The goal of Healthy People 2000, a project of the Department of Health and Human Services, is to reduce this rate to 15 ...

Sonographic scoring index for prenatal detection of chromosomal abnormalities.

Current indications for cytogenetic evaluation leave the majority of Down syndrome fetuses undetected. Using advanced maternal age and low maternal serum alpha‐fetoprotein (AFP) levels as criteria, only 40% of fetuses with Down syndrome (trisomy 21) are identified (positive predictive value, 0.4% to 1%). We evaluate the sonographically detectable physical features of second trimester fetuses to determine whether these features are more sensitive and specific than maternal age for detecting fetuses with abnormal karyotypes. From March 1, 1990, to September 1, 1991, more than 5,000 fetuses between 14 and 20 weeks of development were referred for genetic amniocentesis because of advanced maternal age or abnormal AFP levels. Forty‐three of these 5,000 fetuses were later found to have autosomal trisomies by karyotype (32 with trisomy 21, nine with trisomy 18, and two with trisomy 13). A sample of 588 consecutive normal fetuses from the total of more than 5,000 amniocenteses performed during this period of time was used as our control group for statistical analysis. The sonographic features of these 588 normal second trimester fetuses and the 43 trisomic fetuses recorded prospectively prior to knowledge of the karyotype were evaluated statistically. The femur and humerus lengths, nuchal fold, renal pelvic dimension, and major structural defects were compared in the normal and trisomic fetuses. On the basis of our results, a weighted sonographic score was developed to optimize the detection of fetuses at risk for aneuploidy. Using our previously published formulas and criteria for a short femur and humerus, 17/32 (53%) fetuses with Down syndrome and 23/588 (3.9%) of the normal fetuses were identified. Twenty two of 32 Down syndrome fetuses (69%) and 2/588 (0.34%) of normals had a nuchal fold > or = 6 mm, and 11 of 32 Down syndrome fetuses and all those with trisomies 18 and 13 had a major anomaly detected sonographically. The following scoring system was developed for the detection of aneuploidy: nuchal fold = 2, major structural defect = 2, and short femur, short humerus, and pyelectasis = 1 each. Selecting fetuses with a score of > or = 2 would identify 26/32 (81%) Down syndrome fetuses, and 9/9 (100%) and 2/2 (100%) fetuses with trisomies 18 and 13 respectively, but only 26/588 (4.4%) of the normal fetuses. Using the sonographic score of 2 results in a positive predictive value for a 1/250 risk group of 6.87% for identifying Down syndrome fetuses and 7.25% for all three trisomies.(ABSTRACT TRUNCATED AT 400 WORDS)

Association of epidural analgesia with cesarean delivery in nulliparas.

Objective To evaluate whether epidural analgesia during the first stage of labor is associated with an increased risk of cesarean delivery. Methods The association of epidural analgesia and cesarean delivery was examined in a retrospective study of 1733 low-risk, term nulliparas with singleton infants in vertex presentations, in which labor began spontaneously. To evaluate the effect of epidural analgesia on cesarean deliveries, independent of other factors influencing the use of epidural analgesia, we used propensity scores to create five subgroups (quintiles) of women who, based on characteristics discernible at admission, appeared equally likely to receive epidural analgesia. Multivariate logistic regression analysis was used to control for confounding. Results Overall, the cesarean rate among women receiving epidural analgesia was 17% (168 of 991), compared with 4% (30 of 742) among those who did not receive epidural analgesia. An increased cesarean rate among women receiving epidural analgesia was present in all propensity quintiles. In an adjusted logistic regression analysis, women receiving epidural analgesia were 3.7 times more likely to undergo a cesarean (95% confidence interval 2.4, 5.7). The greatest increase in cesarean risk was noted when epidural analgesia was administered earlier in labor, but there was a more than twofold increase regardless of the dilation and station at administration of epidural analgesia. Conclusions Epidural analgesia may increase substantially the risk of cesarean delivery. Although the causal nature of this association remains open to debate, prenatal care providers should routinely discuss the risks and benefits of epidural analgesia with women during their pregnancies so that they can make informed decisions about the use of pain relief during labor.

Sonographically estimated fetal weights: Accuracy and limitation

To determine the accuracy of our ultrasonographically predicted birth weights we studied 1301 women delivered of infants within a week of an obstetric ultrasonogram to compare the ultrasonographically predicted birth weights with the actual birth weights. The fetuses varied from 700 to 5800 gm and were consecutive singleton fetuses in vertex presentations delivered at a single institution. Overall 74% of the infants had birth weights within 10% of the ultrasonographic estimates and 42% had birth weights within 5% of the ultrasonographic estimates. The presence of oligohydramnios or polyhydramnios made no difference in the percent errors. The sensitivity for identifying a fetus with macrosomia (birth weight greater than 4000 gm) with an estimated weight of greater than or equal to 4000 gm was 65%. The specificity or percent of fetuses correctly identified ultrasonographically as not macrosomic was 90%. If fetuses predicted by ultrasonography to be greater than 3800 gm were included, the sensitivity for the prediction of macrosomia rises to 82% but the specificity would be 79%. There appears to be a fixed limitation to obtaining estimated fetal weights by ultrasonography, even in large series, because these data reaffirm the success and limitations of other methods used to estimate fetal weight previously reported in the literature.

Prenatal diagnosis of hemoglobinopathies. A review of 15 cases.

We attempted prenatal diagnosis of hemoglobinopathies in 15 cases--11 for beta-thalassemia and four for sickle-cell disease. Fetoscopy was used in seven cases, and placental aspiration in eight. One premature labor, with fetal loss, followed placental aspiration. Globin synthesis was assessed by incubation of samples with 3H-leucine and chain separation on carboxymethylcellulose columns. Homozygous disease was predicted in two pregnancies, which were interrupted, and the diagnosis confirmed. In one case homozygosity was suspected. A repeat test was advised but not accepted. The fetus had thalassemia trait. One pregnancy was interrupted despite our prediction of thalassemia trait. Eight pregnancies went to term. Seven predictions that the infants would not have homozygous disease were confirmed. One prediction of sickle trait proved to be sickle-cell disease. Although prenatal diagnosis of hemoglobinopathies is feasible, the present frequency of fetal loss and diagnostic error indicates need for improvement.

HUMERAL SHORTENING IN SECOND-TRIMESTER FETUSES WITH DOWN SYNDROME

Individuals with Down syndrome have abnormally short long bones. Sonography has previously revealed slightly shortened femurs and thickened nuchal folds in affected second-trimester fetuses. Humeral and femoral lengths and nuchal folds were evaluated in 400 normal second-trimester controls and in 24 consecutive Down syndrome fetuses (14-20 weeks) undergoing amniocentesis for advanced maternal age or low maternal serum alpha-fetoprotein (MSAFP). Using the 400 normal control fetuses undergoing amniocentesis, the relationship between humeral length and biparietal diameter (BPD) was: Expected humeral length = -7.9404 + 0.8492 x BPD. A ratio of measured-to-expected humeral length of less than 0.90 identified 12 of 24 fetuses (50%) with Down syndrome and 25 of 400 normals (6.25%). Twelve of the 24 Down syndrome fetuses had a nuchal fold measuring 6 mm or larger. Combining nuchal fold findings with these humeral length criteria identified 18 of 24 affected fetuses (75%) without appreciable change in specificity, yielding a positive predictive value of 4.6% for women with a risk of one in 250 (age 35) of having a Down syndrome fetus. For women with risks of one in 500 and one in 1000 of having an affected fetus based on maternal age, a shortened humerus or thickened nuchal fold yielded positive predictive values of 2.3 and 1.2%, respectively.

Sonographic detection of fetuses with trisomies 13 and 18: Accuracy and limitations

Nine fetuses having trisomy 13 and 15 fetuses with trisomy 18 were diagnosed by cytogenetic studies and also underwent a sonogram between 15 and 40 weeks. All nine fetuses with trisomy 13 had been prospectively identified as having sonographic findings suggestive of trisomy 13. Twelve of the 15 fetuses with trisomy 18 had sonographic abnormalities compatible with trisomy 18. Findings included abnormalities of the face and head, extremities, and diaphragmatic hernia. This report examines criteria for the ultrasound diagnosis of trisomies 13 and 18 and describes the accuracy of prenatal sonography for these diagnoses.

Sonographic diagnosis of Down syndrome in the second trimester

We report a sonographic sign consisting of increased skin or soft tissue thickening at the back of the fetal neck during the second trimester, which correlates well with the diagnosis of Down syndrome. Eight hundred consecutive sonograms were performed in conjunction with genetic amniocentesis where four fetuses had trisomy 21 (Down syndrome) by karyotype. Two or 50% had sonographic findings consistent with Down syndrome. Recently we described a retrospective series where 904 sonograms were performed at the time of amniocentesis and seven fetuses had trisomy 21 on cytogenetic analysis. The abnormal sonographic finding at the back of the neck was present in three of those seven cases. Combining these series, 1704 fetuses were examined and 11 cases of Down syndrome were diagnosed cytogenetically. Five of the 11 or 45% had an abnormal sonogram suggestive of Down syndrome. Two of these were patients undergoing sonography for ascertainment of dates at 16 weeks and submitted to amniocentesis solely on the basis of this sonographic finding.

Spontaneous preterm birth: A case-control study

Information on demographic characteristics, life-style, and reproductive, prenatal, and medical history was obtained from the prenatal records of 140 women with a preterm delivery (cases) and 280 women with a term delivery (controls) matched by age. Compared with controls, a greater proportion of cases were nonwhite, never married, and educated less than 12 years. When logistic regression was used to control for confounding variables, a number of risk factors were found to be associated with an increased risk for preterm delivery: a history of a prior preterm delivery (relative risk, 3.5; confidence interval, 1.6 to 7.8), smoking during the pregnancy (p value test of trends, 0.005), and a prepregnancy weight less than 61.5 kg (relative risk, 2.0; 95% confidence interval, 1.2 to 3.2). Seven (5%) cases and none of the controls indicated a history of maternal diethylstilbestrol exposure (p less than 0.001). A history of prior induced abortion was associated with a modest increase in risk for a spontaneous preterm delivery (relative risk, 1.6; confidence interval, 0.9 to 2.7), and this risk increased with increasing numbers of induced abortions (p value for chi 2 test of trend, 0.02).

Absence of Need for Amniocentesis in Patients with Elevated Levels of Maternal Serum Alpha-Fetoprotein and Normal Ultrasonographic Examinations

Abstract Background. Recent improvements in the accuracy of sonographic diagnosis of neural-tube and ventral-wall defects have raised a question about the wisdom of routinely offering amniocentesis to women who have elevated levels of maternal serum alpha-fetoprotein with a structurally normal fetus as determined by ultrasonography. Methods. We reviewed the ultrasound findings in 51 consecutive fetuses with spina bifida, encephalocele, gastroschisis, or omphalocele that were delivered or aborted at a single hospital, to estimate the sensitivity of ultrasonography for these diagnoses. In all cases, the mothers had undergone prenatal sonography at one facility between 16 and 24 weeks after the last menstrual period. We used these data to calculate the probability of an affected fetus in a woman with a given level of maternal serum alpha-fetoprotein and a normal sonogram. Results. These four types of anomalies were correctly identified in all 51 cases, yielding a sensitivity of 100 percent (95 percent confid...