Faculty Bibliography

Varicella infection in the first trimester has been associated with a constellation of congenital abnormalities. The incidence of the congenital varicella syndrome is unknown, although it has been reported to be as high as 9%. In a prospective study performed between 1986-1990, 40 patients were identified who had first-trimester varicella infection. Pregnant patients were referred from physicians in the perinatal regional network after developing the classical picture of varicella infection. Targeted fetal ultrasound examinations were performed between 16-20 weeks' gestation in all cases and neonatal outcome was determined. Of the 40 patients, three had first-trimester losses and another underwent an elective termination of pregnancy after counseling. Of the remaining 36 women, one had fetal omphalocele. Thirty-five pregnancies continued until term, and no infant had features of the congenital varicella syndrome at birth. Other than the case of omphalocele, no major congenital anomalies were identified. This study, the largest series of patients with first-trimester varicella infection, showed an incidence of congenital varicella syndrome of 0% and an incidence of congenital anomalies of 3% (range 0-8% at 95% confidence level).

Microscopic features of placentas from 539 consecutive preterm deliveries and 214 term deliveries were compared. The presence of either umbilical or chorionic vasculitis was identified in 38% of the cases at 22 to 28 weeks' gestation, in 32% of the cases at 29 to 32 weeks' gestation, in 13% of the cases at 33 to 36 weeks' gestation, and in 10% of the cases at term (p less than 0.0001). Decidual vascular abnormality was present in 70% of the cases at 22 to 28 weeks' gestation, in 35% of the cases at 29 to 32 weeks, in 29% of the cases at 33 to 36 weeks, and in 15% of the cases at term (p less than 0.0001). Chronic villitis was significantly more frequent in preterm deliveries without umbilical vasculitis than in those cases with umbilical vasculitis (17% vs 8%, p less than 0.05). Our data indicate that the placental lesions of umbilical-chorionic vasculitis, decidual vascular abnormality, and chronic villitis are related to preterm birth. Umbilical-chorionic vasculitis reflects acute ascending bacterial infection. Decidual vascular abnormality has been associated with maternal autoimmune or alloimmune disorders. Chronic villitis may indicate either congenital viral infection or maternal-fetal immunopathologic conditions. Both decidual vascular abnormality and chronic villitis may reflect the activation of inflammatory mechanisms capable of leading to preterm delivery

A recent report by FitzSimmons et al. demonstrated a greater frequency of upper- versus lower-extremity shortening in autopsies of second-trimester fetuses with trisomy 21. We undertook this study to determine whether this upper-limb shortening could be detected by prenatal ultrasonography in the second trimester and therefore identify fetuses at risk for trisomy 21. A retrospective review of all prenatal sonograms preceding genetic amniocentesis was conducted. Between 1987 and 1990 11 consecutive fetuses between 15 and 22 weeks' gestation with trisomy 21 were identified by genetic amniocentesis. Femur and humerus lengths were plotted on growth curves created from 1470 normal patients between 12 and 26 weeks. Gestational age was confirmed by last menstrual period and biparietal diameter. In fetuses with trisomy 21, seven of 11 humeri were less than 5th percentile, for a sensitivity of 64%, whereas only two of 11 femurs were less than 5th percentile, for a sensitivity of 18%. Biparietal diameter/femur length and biparietal diameter/humerus length ratios were also tested to predict Down syndrome. In only 2 of 11 cases was the biparietal diameter/femur length ratio greater than 95th percentile, whereas the biparietal diameter/humerus length ratio was greater than 95th percentile in 7 of 11. Since all seven were identified by shortened humerus alone, we conclude that humerus length versus gestational age is the simplest and most effective screen. The positive predictive value of an abnormally short humerus length in detecting Down syndrome was 6.8% in our population where the prevalence of Down syndrome was 1 of 173. The present study supports the observations of FitzSimmons et al. that shortened humerus length has a greater sensitivity than femur length in cases of trisomy 21. We conclude that in fetuses at risk for trisomy 21 humerus length should be determined, because it may, if shortened, aid in the prenatal diagnosis.

The relationship between peak-systolic/end-diastolic ratio of the umbilical artery waveform and fetal biometry was studied in 127 uncomplicated pregnancies with established dates between 20 and 40 weeks' gestation. At each ultrasonographic examination fetal biometry included measurement of the biparietal diameter, head circumference, abdominal circumference, and femur length. The peak-systolic/end-diastolic ratio was measured by either a continuous or a pulsed-wave method. There were significant linear negative correlations between all the biometric parameters, as well as between the ultrasonographically estimated fetal weight and peak-systolic/end-diastolic ratio. Of the individual ultrasonographic parameters the femur length (for gestations less than 30 weeks) and the abdominal circumference (for gestations greater than or equal to 30 weeks) were found to be best correlated with the peak-systolic/end-diastolic ratio. Regression curves, including the 10th and the 90th percentile, were developed between each biometric parameter (biparietal diameter, head circumference, abdominal circumference, and femur length), as well as between estimated fetal weight and peak-systolic/end-diastolic ratio. The estimated fetal weight nomogram had the best sensitivity (48%) in predicting intrauterine growth retardation. These nomograms should prove most useful in assessing downstream placental vascular resistance in high-risk patients with unknown dates.

In a prospective study of 62 patients undergoing cesarean section before the onset of labor a fetal biophysical profile assessment was performed within 3 hours before the cesarean section. The presence or absence of the individual fetal biophysical activities (fetal heart rate reactivity, fetal breathing movements, fetal body movements, and fetal tone) were correlated with umbilical cord blood gas and acid-base measurements (artery and vein). Fetuses with nonreactive nonstress test results or the absence of breathing had significantly lower cord artery pH, PO2 bicarbonate, and base excess measurements but not a significantly different PCO2 level as compared with fetuses that had these activities present. Fetuses with the absence of movements or tone had lower pH, PO2 bicarbonate, and base excess levels and higher PCO2 levels as compared with fetuses with the presence of movements or tone, respectively. These blood gas and acid-base differences were observed in both umbilical cord artery and vein. Subsequent analysis of the blood gas and acid-base measurements of the fetuses with compromised biophysical activities revealed that there are different levels of acidemia, hypoxemia, and hypercapnia at which the individual biophysical activities are compromised. These data suggest that the first manifestations of fetal hypoxemia and acidemia are nonreactive nonstress test results and loss of fetal breathing; in advanced acidemia, hypoxemia, and hypercapnia fetal movements and fetal tone are compromised.

In a prospective study of 162 patients, measurements of the transverse cerebellar diameter (TCD) and abdominal circumference (AC) were obtained between 15-38 weeks' gestation. A ratio between the TCD and AC was calculated after each examination. This ratio remained constant during gestation. The mean ratio was 13.7% (fifth and 95th percentiles of 11.9 and 15.9%, respectively); the median ratio was 13.6%. Forty-two patients had repeat measurements and the ratio did not change. This ratio is gestational age-independent; however, further investigation is needed to determine its application in the assessment of fetal growth abnormalities.

The relationship between cord blood gases and infection outcome was determined in 53 consecutive patients with preterm premature rupture of the membranes who were delivered because of abnormal fetal biophysical assessment. Measures of infection outcome included the presence of clinical amnionitis, possible neonatal sepsis, and neonatal sepsis. Fetal acidosis at birth, as defined by cord arterial pH less than 7.20, was found in six fetuses; five of these developed neonatal sepsis and the other was born to a mother who had intrapartum clinical amnionitis. The mean cord blood pH (artery and vein) of fetuses with neonatal sepsis was significantly less than in fetuses with possible neonatal sepsis or no sepsis; however, two thirds (10 of 15) of the neonates with sepsis had normal acid-base status at birth. These data suggest that the fetal biophysical assessment becomes abnormal before the development of fetal acidosis. The possible mechanisms by which fetal infection diminishes fetal biophysical activities prior to the development of acidosis are discussed