Prognostic significance of unexplained elevated amniotic fluid alpha-fetoprotein.

OBJECTIVE: To compare the prognostic values of unexplained elevated amniotic fluid alpha-fetoprotein (AF AFP > or = 2.0 multiples of the median [MoM]) and unexplained elevated maternal serum alpha-fetoprotein (MSAFP > or = 2.5 MoM). METHODS: We accessed a data base containing the results of MSAFP screening tests, genetic amniocenteses, and pregnancy outcome data on all women undergoing second-trimester genetic amniocentesis from October 1988 through August 1994. After excluding all patients whose elevated AFP levels had any identifiable cause (positive AF acetylcholinesterase, AF blood contamination, fetal malformation or aneuploidy, multiple gestation, etc), 5743 cases were analyzed. Relative risks (RR) for selected pregnancy complications were determined. RESULTS: Elevated MSAFP, with any AF AFP, was associated with fetal growth restriction (RR 2.5, 95% confidence interval [CI] 1.4-4.4), stillbirth (RR 3.5, 95% CI 1.4-8.3), preeclampsia (RR 2.8, 95% CI 1.1-7.0), and preterm delivery (RR 2.8, 95% CI 2.3-3.4). Elevated AF AFP, with any MSAFP, was associated with preeclampsia (RR 4.4, 95% CI 2.0-10.0) and preterm delivery (RR 1.7, 95% CI 1.3-2.4). Elevation of both AF AFP and MSAFP was associated with preterm delivery (RR 4.0, 95% CI 2.8-5.7). When elevated AF AFP was found in association with a normal MSAFP, the RR to develop preeclampsia was 4.6 (95% CI 1.9-11.2). CONCLUSION: Maternal serum alpha-fetoprotein is a better predictor of late pregnancy complications than AF AFP. However, unexplained elevated AF AFP appears to be especially predictive of preeclampsia.

Ultrasound findings and multiple marker screening in trisomy 18.

OBJECTIVE: To compare detection of trisomy 18 in the second trimester by ultrasound and multiple-marker testing. METHODS: A computerized genetics database was used to identify fetuses of 14-22 weeks' gestation who had comprehensive ultrasound examinations, multiple-marker screening tests (alpha-fetoprotein [AFP]), hCG, unconjugated estriol [E3], and trisomy 18 karyotype. A positive trisomy 18 screen was defined as AFP up to 0.75 multiples of the median (MoM), hCG up to 0.55 MoM, and unconjugated E3 up to 0.60 MoM. A risk of at least 1:190 defined a positive Down syndrome screen. Ultrasound abnormalities were diagnosed prospectively and were confirmed later by retrospective review of sonographic images. RESULTS: From 1988-1997, 30 trisomy 18 fetuses who had comprehensive ultrasounds and multiple-marker testing were identified. Twenty-one (70%) had abnormalities detected by ultrasound, of which the most common isolated finding was choroid plexus cyst. Eleven fetuses (37%) had positive trisomy 18 screens, and two had positive Down syndrome screens, for a total of 13 of 30 (43%) fetuses with positive multiple-marker screening tests. CONCLUSION: We found that ultrasound was more likely to be abnormal than multiple-marker screening tests in fetuses with trisomy 18 (70%) (95% confidence interval [CI] 54, 86 versus 43% CI 25, 61). However, combining the two testing methods yielded the highest detection rate (80% [CI 66%, 94%]).

Delay in delivery: influence of gestational age and the duration of delay on perinatal outcome.

The potential benefits to be gained in neonatal survival and freedom from serious morbidity by delaying delivery at various gestational ages was explored by examining the results of studies of neonatal mortality and subsequent morbidity published from 1978 and 1984. The major benefits were found to occur between 24 and 27 weeks' gestational age. In general, little benefit was found in delaying delivery after 34 weeks' gestational age.

Risk factors for fetal death in white, black, and Hispanic women. Collaborative Group on Preterm Birth Prevention.

OBJECTIVE: To document the relation between stillbirth and various demographic, obstetric, and medical risk factors. METHODS: We analyzed the risk factors and medical origins of 403 stillbirths. The population studied included 34,350 births occurring during the March of Dimes Preterm Birth Prevention Trial. All births occurring in five perinatal centers from 1982-1986 were included in the analysis. Stillbirth was defined as those infants born at 20 weeks' gestation or later whose Apgar score was 0 at 1 and 5 minutes. RESULTS: Stillbirth occurred in 1.2% of all births. Fifty-one percent occurred before 28 weeks and only 18% were at term. Blacks had a greater risk of stillbirth when compared to other women. Prior preterm delivery yielded nearly a two-fold increase in the risk of stillbirth. Preeclampsia, chronic hypertension, and class A or class B-R diabetes were not associated with an increased risk of stillbirth. Other medical factors (hemoglobinopathies, Rh sensitization) resulted in a greater than sixfold increase in the rate of stillbirth, and congenital anomalies resulted in a fivefold increase. Abruption was associated with a 12-fold increase in the risk of stillbirth; nearly 14% of all stillbirths were associated with abruption. CONCLUSION: Eighty-two percent of all stillbirths occurred before term, and more than 50% occurred before 28 weeks. The majority of stillbirths were not explained by medical complications, but instead were often associated with other risk factors related to preterm birth. Further investigations are needed to understand the complex etiology of stillbirth.

Unexplained elevation in maternal serum alpha-fetoprotein and subsequent fetal loss.

OBJECTIVE: To examine the frequency and timing of fetal death and its association with maternal serum alpha-fetoprotein (MSAFP) levels. METHODS: Pregnancy outcomes were evaluated in 6927 predominantly middle-class women (83% white, 17% black) who had second-trimester MSAFP determinations performed in our laboratory. All cases of multiple gestation, preexisting fetal death, and fetal malformation were excluded. RESULTS: The overall fetal death rate was 13 per 1000 (n = 90). Black women had a higher fetal death rate than white women (35.6 per 1000 versus 8.4 per 1000; P < .001). One hundred forty-eight women (2.1%) had an adjusted MSAFP multiples of the median (MoM) value of at least 2.5, which was not explained by multiple gestation, congenital anomaly, or preexisting fetal death. As the MSAFP increased, the fetal death rate increased (MoM less than 2.0, 11 per 1000; MoM 2-2.49, 29 per 1000; MoM 2.5 or greater, 95 per 1000; P < .001). Despite the increased risk of fetal death in the elevated MSAFP group, most fetal deaths (84%) occurred in women with levels below 2.5 MoM. Furthermore, the timing of fetal loss was significantly different between the group less than 2.5 MoM and the group at or above 2.5 MoM. Fetal death occurred at or after 26 weeks in 45% of the women with normal MSAFP, compared with only 14% of women with high MSAFP (at least 2.5 MoM) (P = .023). CONCLUSIONS: Women with unexplained elevations in MSAFP are at increased risk for fetal loss, with most of the losses occurring in the second trimester. Because many of these fetal deaths occur at gestational ages when the neonatal survival is very low, it is unlikely that antepartum fetal surveillance aimed at early delivery would substantially increase fetal salvage.

Second-trimester cystic hygroma: prognosis of septated and nonseptated lesions.

OBJECTIVE: To compare karyotypic, ultrasonographic, and prognostic features of septated cystic hygromas and nonseptated cystic hygromas in second-trimester fetuses. METHODS: A computerized ultrasound data base was used to identify fetuses diagnosed with cystic hygromas at 14-22 weeks' gestation. Photographs from the initial ultrasound were reviewed retrospectively for hygroma type (septated or nonseptated) and any abnormal structural findings. Fetal karyotypes were obtained from amniotic fluid, aspiration of hygroma pouches, or fetal tissue culture. Pregnancy outcome information was obtained from hospital charts and physician office records. Ultrasound findings were then compared with fetal karyotype results and pregnancy outcome data. RESULTS: From 1990 to 1995, 61 fetuses with cystic hygromas were identified. Karyotypes were obtained in 55 fetuses, and pregnancy outcome was available for 59. Abnormal karyotype was present in 42 of 55 fetuses (76%). The most common chromosomal abnormality in septated hygromas was the 45,X karyotype. Trisomy 21 was the most common chromosomal abnormality in nonseptated hygromas. Compared with fetuses with nonseptated cystic hygromas, those with septated cystic hygromas were more likely to be aneuploid (33 of 39 [85%] versus nine of 16 [56%]; P = .03), more likely to develop hydrops (27 of 45 [60%] versus three of 16 [19%]; P = .005), and less likely to be live-born (one of 44 [2%] versus four of 15 [27%]; P = .01). CONCLUSIONS: Fetuses with septated cystic hygromas are more likely to be aneuploid and to develop hydrops, and thus are less likely to be survive than fetuses with nonseptated hygromas.

Significance of a false-positive trisomy 18 multiple-marker screening test.

OBJECTIVE: To determine if a false-positive trisomy 18 multiple-marker screening test (all three analytes low: maternal serum alpha-fetoprotein [AFP] at most 0.75 multiples of the median [MoM], unconjugated estriol at most 0.60 MoM, and hCG at most 0.55 MoM) indicates increased risk for obstetric complications or is related to maternal weight. METHODS: We accessed our genetic database to obtain multiple-marker screening test results, fetal karyotypes, and pregnancy outcomes from all patients with a normal multiple-marker screening test (n = 3900) and from all patients with a positive trisomy 18 screening test (n = 103) seen in the prenatal diagnosis clinic from 1992 to 1996. During this period, only maternal serum AFP was adjusted for maternal weight. RESULTS: A positive trisomy 18 screen identified five of 12 trisomy 18 fetuses. Women with a false-positive trisomy 18 screen were heavier (175.6 +/- 43.8 lb versus 159.9 +/- 37.9 lb, P < .001) and younger (29.7 +/- 6.5 years versus 32.3 +/- 6.5 years, P < .001) than women with a normal multiple-marker screening test, but were not at increased risk for pregnancy complications. Weight-adjusting all three analytes reduced the false-positive trisomy 18 screen rate by 42% (from 1.9% to 1.1%) but did not change the trisomy 18 detection rate. CONCLUSION: A false-positive trisomy 18 screening test does not indicate increased risk to develop pregnancy complications and may be related to inadequate correction for increased maternal weight.

Pregnancy outcomes following sonographic nonvisualization of the fetal stomach.

OBJECTIVE: To review pregnancy outcomes when two or more ultrasound scans persistently fail to visualize the fetal stomach. METHODS: A computerized ultrasound database was used to identify all fetuses in which two or more serial ultrasound examinations failed to visualize the fetal stomach. Sonographic images were reviewed retrospectively, with the reviewer blinded to outcome data, to confirm persistent nonvisualization. Pregnancy outcome data were obtained from hospital charts and physicians' office records. Fetal karyotypes, when performed, were obtained from amniotic fluid (AF) culture. The ultrasound findings then were compared with fetal karyotype results and pregnancy outcome data. RESULTS: Of 35,569 ultrasound scans performed during 1991-1996, 26 fetuses (0.07%) with persistently nonvisualized stomachs were identified. Structural defects were detected in 17 fetuses (65%), most often involving the cardiothoracic (n = 5), genitourinary (n = 4), and central nervous systems (n = 4). Karyotypes were obtained in 12 fetuses, and four of them were abnormal. Only five of 17 fetuses (29%) with a structural defect survived. In nine of 26 fetuses (35%) with persistently nonvisualized stomachs, no structural defect was identified. Each of these nine fetuses had abnormal AF volume in its surrounding sac, and the overall perinatal survival in fetuses without a structural defect was only 50%. CONCLUSION: Fetuses with persistently nonvisualized stomachs have an increased incidence of structural defects and AF abnormalities and are more likely to have a poor outcome. A detailed ultrasound examination and fetal karyotype analysis should be performed to evaluate fetuses with persistently nonvisualized stomachs.

Pregnancy outcome following genetic amniocentesis at 11-14 versus 16-19 weeks' gestation.

OBJECTIVE: To compare pregnancy complications in women having genetic amniocentesis at 11-14 weeks versus those undergoing amniocentesis at 16-19 weeks' gestation. METHODS: A genetics data base was used to identify patients retrospectively, those who had genetic amniocenteses by three experienced operators during a 4-year period. The study group consisted of women who had amniocenteses at 11-14 weeks' gestation. For each study patient (early amniocentesis), two controls (amniocentesis at 16-19 weeks) were identified and matched for maternal age, race, and the number of prior spontaneous abortions. An immediate post-procedure complication was defined as any vaginal bleeding, rupture of membranes, or fetal loss occurring up to 30 days after the amniocentesis. A later complication was defined as any fetal death longer than 30 days after the amniocentesis, any preterm delivery, any infant weighing less than the tenth percentile for gestational age, and any neonatal death. Immediate and later complications were compared between the study and control groups. RESULTS. The study group consisted of 314 patients who were matched to 628 controls. Women who had a genetic amniocentesis performed at 11-14 weeks were significantly more likely to have post-procedure amniotic fluid leakage (2.9 versus 0.2%), post-procedure vaginal bleeding (1.9 versus 0.2%), and a fetal loss within 30 days of the amniocentesis (2.2 versus 0.2%) than women undergoing genetic amniocentesis at 16-19 weeks' gestation. Four of the seven patients (57%) with a fetal loss within 30 days of an early amniocentesis had procedure-related complications, such as amniotic fluid leakage, bleeding, and infection, that caused the pregnancy to be lost. No differences were noted between the two groups in the number of preterm deliveries, later fetal deaths, neonatal deaths, or newborns weighing less than the tenth percentile for gestational age. CONCLUSION: Genetic amniocentesis at 11-14 weeks is associated with more post-procedure complications and a higher fetal loss rate within 30 days of the procedure than a genetic amniocentesis performed at 16-19 weeks' gestation.

Toxemia of pregnancy masquerading as idiopathic thrombocytopenic purpura.

A case of toxemia misdiagnosed as idiopathic thrombocytopenic purpura is presented. An unusual temporal relationship between the fall in platelets and the appearance of hypertension was the cause of the confusion. A rise in platelets following glucocorticoid administration is discussed.

Association of extrauterine fetal death with failure of prostaglandin E2 suppositories.

The use of prostaglandin E2 vaginal suppositories is an effective method of uterine evacuation for patients with intrauterine fetal demise. Advanced extrauterine gestation, because of its rarity, is usually not a primary consideration for patients presenting with fetal death. This report presents 4 such cases and strongly suggests that, when this drug is used for the treatment of fetal death, failure to induce contractions and to effect uterine evacuation within a reasonable time should prompt the consideration of extrauterine pregnancy.

Effect of labor on the postpartum bladder.

Urodynamic investigations were performed on 20 patients at 48 hours and at four weeks after delivery to assess the effect of modern obstetric practice on the postpartum bladder. Although there were significant differences in some values over this period, the mean urodynamic measurements on both occasions were within normal limits. It is concluded that the current management of labor does not predispose women to bladder hypotonia, the chief factors responsible being avoidance of prolonged labor and early catheterization after delivery.

Anthropometric assessment of body size differences of full-term male and female infants.

OBJECTIVE: To determine gender-specific differences in anthropometric characteristics of full-term male and female infants. METHODS: Twelve hundred five term newborn infants were examined. All measures of length and skinfold thickness were performed in a standardized manner. RESULTS: After adjusting for confounding variables by regression analysis, we found that nearly all length and circumference measurements were significantly smaller in female infants than in male infants but that subcutaneous fat deposition in female infants was significantly increased. However, there was no difference in the ponderal index between male and female newborns, indicating that this measure does not correlate with newborn fat deposition across the sexes. CONCLUSIONS: Despite being shorter and having smaller circumferences, female infants have more subcutaneous fat than male infants. The ponderal index is not useful as a measure of fatness when the sexes are compared. We speculate that the greater subcutaneous fat deposition in female infants may be related to their better neonatal outcomes.

Black-white differences in newborn anthropometric measurements.

The mean birth weight of black infants is consistently less than that of white infants. In 1518 low-income multiparous women, the mean difference in singleton births was 171 g, of which 38 g was partitioned to preterm births and another 35 g reflected lower gestational ages in term births. A series of regression analyses were used to determine the effect of black race on various newborn measurements in 1205 term newborns, adjusting for other known risk factors. In this model, black race accounted for a mean decrease of 148 g in weight and 0.52 cm in length. There were also significant decreases in mean head (0.44 cm), chest (0.66 cm), and abdominal (0.56 cm) circumferences. Arm and leg lengths were not different, but black arm circumferences (0.14 cm) were significantly larger. Triceps and thigh skin fold measurements were not statistically different, but black subscapular skin fold values were significantly smaller (0.17 mm). The ponderal index in blacks was significantly less than in whites. These data suggest that in this population, intrinsic and/or extrinsic factors associated with race account for most smaller black newborn measurements and for much of the racial difference in birth weight.

Etiologies of preterm birth in an indigent population: is prevention a logical expectation?

To assess the expectations of preterm birth prevention, we determined the causes of preterm birth in a population of indigent women. We studied 13,119 singleton births in a predominantly black, indigent population occurring between November 1982 and April 1986 to identify the proportion of preterm births that may have been prevented using current treatment modalities. Forty-four percent of the preterm births occurred at 35 to 36 weeks' gestational age, a time when most practitioners do not attempt tocolysis. Of the remainder, 17% occurred before 35 weeks but were indicated for maternal medical or obstetric complications, and another 17% occurred before 35 weeks but followed spontaneous premature rupture of the membranes. Therefore, of the 1445 preterm births, we calculated that only 336 (23.2%) were theoretically preventable. A fourth of these presented at less than 3 cm cervical dilatation and were treated appropriately with tocolytics, but delivered anyway. Therefore, most of the potentially preventable births occurred in the group that presented with cervical dilatation of more than 3 cm. We conclude that improving the preterm birth rate significantly below current levels may be difficult to achieve.

Maternal serum alpha 2-macroglobulin and fetal growth retardation.

Maternal serum alpha 2-macroglobulin levels were measured twice, at approximately 18 and 30 weeks' gestation, in 289 pregnant women who later delivered at or after 37 weeks. Levels were elevated as early as 18 weeks' gestation in women destined to have a growth-retarded infant, and this elevation persisted through 30 weeks' gestational age. Furthermore, levels were higher in white women than black, in smokers than in non-smokers, and in thin than in heavier women. When the effect of alpha 2-macroglobulin on birth weight was evaluated in a multiple regression analysis adjusting for gestational age, race, body size, smoking, fetal sex, and a history of a low birth weight infant, high alpha 2-macroglobulin levels were associated with a statistically significant decrease in birth weight. The effect was greater in women who smoked. This relationship did not appear to be associated with differences in serum zinc or hematocrit levels.

The effect of cigarette smoking on neonatal anthropometric measurements.

OBJECTIVE: To estimate the effect of maternal cigarette smoking on birth weight, crown-heel length, and ten other neonatal anthropometric measurements. METHODS: Data are from a cohort study on risk factors for fetal growth retardation (FGR) in multiparous women conducted from December 1985 through October 1988. Information on smoking status was collected four times during pregnancy. Data analysis included 1205 singleton infants of women delivering at term. Neonatal anthropometric measurements were obtained within 48 hours of birth, including birth weight, crown-heel length, ponderal index, head and abdominal circumferences, arm length and circumference, femur length and thigh circumference, and triceps, thigh, and subscapular skinfold measurements. Analysis of covariance models were used to assess the independent effect of smoking on each neonatal measurement. RESULTS: Neonates born to women who reported smoking during the first trimester had a 0.6-1.9% reduction in most neonatal anthropometric measurements, resulting in an overall reduction of birth weight of 130 g (4%). Neonates born to women who continued to smoke throughout pregnancy had an average adjusted reduction in birth weight of 189 g (5.9%), compared with a 55 g (1.7%) reduction for neonates born to women who stopped smoking after the first trimester. For women who continued to smoke throughout pregnancy, an increased number of cigarettes smoked was associated with increased reductions in birth weight and neonatal chest and abdominal circumferences. For women who stopped smoking after the first trimester, stopping was a better predictor of neonatal anthropometric measurements than the number of cigarettes smoked early in pregnancy. CONCLUSIONS: Except for the ponderal index, all neonatal anthropometric measurements studied showed some negative effect of maternal cigarette smoking. Head circumference is the measurement least reduced. Smoking cessation is a better predictor of infant size than the number of cigarettes smoked in the first trimester.

Sonographic measurements and ratios in fetuses with Down syndrome.

Ultrasound measurements of 15 fetuses with trisomy 21 detected during the 17th week of gestation were matched retrospectively to those of 45 normal controls. We compared nine standard ultrasound measurements of the fetal head, abdomen, and femur in these two groups. The fetuses with trisomy 21 had significantly shorter mean femur lengths, narrower occipitofrontal diameters, and increased biparietal diameter (BPD)/femur length and abdominal circumference/femur length ratios. An increased BPD/femur length ratio was the ultrasound finding that best predicted a fetus with Down syndrome. A BPD/femur length ratio of 1.80 or higher was 40% sensitive and 97.8% specific in predicting Down syndrome, and had a false-positive rate of only 2.2%. An increased second-trimester BPD/femur length ratio measured by ultrasound may prove beneficial as an additional screening test for Down syndrome.

The Alabama preterm birth prevention project.

A preterm birth prevention program consisting of risk scoring, intensive weekly observation including cervical examinations, and detailed education about preterm labor signs and symptoms was tested in a predominantly black, indigent population. One thousand high-risk women were randomized to treatment or control groups. Although more preterm labor was diagnosed and treated in the treatment group, there were no significant differences between the groups with respect to mean birth weight or gestational age, spontaneous preterm delivery rates, or low or very low birth weight rates. The rates of respiratory distress syndrome and fetal and neonatal mortality, although greater in the treatment group, were not statistically different. However, the treatment-group infants had significantly more intracranial hemorrhages and spent more days on ventilators. At this institution, the preterm birth prevention program was not effective.

The relationships among psychosocial profile, maternal size, and smoking in predicting fetal growth retardation.

OBJECTIVE: We explored the relationships among measures of psychosocial well-being, maternal size, and smoking in predicting infant size at birth. METHODS: Participants in this population-based cohort study were drawn from public health prenatal clinics in Jefferson County, Alabama during 1985-1988. Para 1 and 2 women were screened for 11 risk factors for low birth weight, including small stature, a previous low birth weight infant, and smoking. RESULTS: Poor scores on five of six psychosocial scales, as well as on a combined profile, were associated with a significantly higher relative risk of fetal growth retardation (FGR) only in thinner women, defined as having a body mass index less than the median (relative risk [RR] 2.11, 95% confidence interval [CI] 1.47, 3.04). A significant association between the psychosocial profile and birth weight was demonstrated for thin women in a multivariate analysis adjusting for gestational age, race, infant sex, and smoking (P = .0003). The relationship remained significant when hypertension, alcohol and drug use, and weight gain were added to the model (P = .003). In women with a body mass index above the median, a poor psychosocial profile showed little association with FGR (RR 1.20, 95% CI 0.73, 1.98) and did not have a significant association with birth weight. A poor profile had a greater association with FGR in non-smokers (RR 2.04, 95% CI 1.29, 3.22) than in smokers (RR 1.4, 95% CI 0.95, 2.06). CONCLUSIONS: Greater pre-pregnancy weight for height appears to protect against the adverse effects of a poor psychosocial profile in a population of poor, primarily black women. In thinner women, both smoking and a poor psychosocial profile were associated with a substantially increased rate of FGR, indicating a subgroup of women who may receive greater benefits from intervention programs.