The association between maternal serum alpha-fetoprotein and preterm birth, small for gestational age infants, preeclampsia, and placental complications.

OBJECTIVE: To determine whether high levels of serum alpha-fetoprotein (AFP) predict increased risk of adverse pregnancy outcomes, including preterm birth (before 37 weeks), preterm birth occurring at or before 28 weeks, small for gestational age (SGA) infant, preeclampsia, and placental abnormalities, and to determine whether low levels of serum AFP predict increased or decreased risk of these outcomes. METHODS: Using the mother's first name, last name, and zip code, we linked the records of 51,008 women who participated in the California Alpha-Fetoprotein Screening Program between June 15, 1986, and October 31, 1987, with California birth certificates for singleton infants born in 1987. The accuracy of the data linkage was confirmed by manually examining complete names, mother's ethnicity, and mother's age for a sample of 500 of the mother-infant linkages. Blood samples were obtained at 15-19 weeks. RESULTS: A strong gradient of increasing risk of preterm birth with increasing levels of serum AFP was observed (test for trend, P < .01). Among women with high levels of serum AFP (at least 2.5 multiples of the median [MoM]), 24.3% had preterm births, compared with 3.8% of women with low levels of serum AFP (0.81 MoM or less), odds ratio 8.7, 95% confidence interval 7.1-10.7). This gradient persisted when preterm infants of 28 weeks or less were examined separately. Similar gradients were observed for the risk of preeclampsia and placental abnormalities. There was a weaker U-shaped relation between serum AFP level and the risk of an SGA infant. CONCLUSION: Low levels of second-trimester maternal serum AFP are associated with a very low risk of preterm birth, preeclampsia, and placental complications. High levels of serum AFP are strongly associated with preterm birth, preeclampsia, and placental abnormalities. There is a modest association between AFP levels (both low and high) and SGA birth.

Fetal karyotyping for chromosome abnormalities after an unexplained elevated maternal serum alpha-fetoprotein screening.

OBJECTIVE: To study the chromosome abnormality rate among women with elevated levels of maternal serum alpha-fetoprotein (MSAFP) and the types of chromosome abnormalities in this population, and to compare this rate with reports in the literature and the rate observed in the general population. METHODS: We studied 8097 women who chose to undergo amniocentesis and fetal karyotyping after having an elevated MSAFP test of 2.5 multiples of the median (MOM) or higher. All abnormal karyotypes were reviewed and grouped according to whether the elevated MSAFP value could be explained by a ventral wall or neural tube defect. RESULTS: The overall chromosome abnormality rate was 13.83 per 1000 amniocenteses. The rate in the "unexplained" group was 10.92 per 1000 amniocenteses. Just over half (53%) of the abnormal karyotypes were autosomal anomalies, and 47% were sex chromosome abnormalities. The autosomal aneuploidies observed most frequently were triploidy and trisomy 13. The sex chromosome abnormalities observed most frequently were the XXY and XYY karyotypes. CONCLUSION: Women who have unexplained elevated MSAFP values of 2.5 MOM or greater have a twofold increase in the rate of chromosome abnormalities in their fetuses compared with the general population (P < or = .001). This rate is consistent with other studies that used a 2.5 MOM cutoff. Studies that used a 2.0 MOM cutoff have reported chromosome abnormality rates that do not vary from general population estimates.

Reducing the need for amniocentesis in women 35 years of age or older with serum markers for screening.

BACKGROUND: As maternal age advances, the risk of fetal Down's syndrome increases. Pregnant women 35 years of age or older are routinely offered amniocentesis because of this risk. Recently, maternal serum markers have been reported to be useful in screening for Down's syndrome, primarily in younger women. We therefore investigated whether offering amniocentesis only to selected women 35 years of age or older who were identified by screening measurements in serum might prove a useful alternative to the current practice. METHODS: We studied 5385 women with singleton pregnancies who were 35 years of age or older and were undergoing routine amniocentesis. Along with information about the pregnancy, we obtained a serum sample for measurement of alpha-fetoprotein, unconjugated estriol, and human chorionic gonadotropin. Individual estimates of the risk of Down's syndrome in the fetus were calculated for each pregnancy before the karyotype was known. RESULTS: If amniocentesis had been reserved for the women calculated to have a risk greater than 1 in 200 of having a fetus with Down's syndrome, 48 of the 54 cases of Down's syndrome (89 percent) would have been identified, 25 percent of the unaffected pregnancies would also have been identified as being at high risk for Down's syndrome (false positives). Seven of 15 fetuses (47 percent) with other trisomies, 11 of 25 (44 percent) with sex aneuploidy, and 1 of 9 (11 percent) with miscellaneous chromosomal abnormalities would also have been detected. In practice, such screening would have made 75 percent of the amniocentesis unnecessary, along with a proportion of the amniocentesis-associated fetal losses. If the cutoff for the risk of Down's syndrome were set higher than 1 in 200, both the rate of detection and the false positive rate would be lower. Conversely, these rates would be higher if the cutoff were set lower. CONCLUSIONS: Prenatal screening of serum to generate individual estimates of the risk of Down's syndrome in the fetus can provide a basis for decision making in the cases of women 35 years of age or older, as it does in younger pregnant women, and is an alternative to current testing practices.

Alpha-fetoprotein: a biomarker for pregnancy outcome.

Beginning in 1977, numerous studies have reported an association between high levels of maternal serum alpha-fetoprotein, measured in early pregnancy, and low birthweight and perinatal death. It has been suggested, however, that these findings may be explained by bias. We reviewed 21 studies and found that they were unanimous in reporting this association and that the association cannot be explained by any of the proposed biases. Comparing women whose alpha-fetoprotein levels were 2.5 times the median or more with all other women, the highest relative risk of fetal death was 21.0, with a 95% confidence interval of 8.4-52.2, and the lowest relative risk of fetal death was 4.4, with a 95% confidence interval of 2.8-7.0. For low birthweight (< 2,500 grams), the highest relative risk was 6.4 (95% confidence interval = 3.1-13.1) and the lowest relative risk was 1.9 (95% confidence interval = 1.5-2.5).

Second-trimester maternal serum alpha-fetoprotein levels and the risk of subsequent fetal death.

BACKGROUND: The finding of an elevated level of maternal serum alpha-fetoprotein during the second trimester of pregnancy may indicate that the fetus has died or is about to die. It is uncertain, however, whether the finding is associated with an increased risk of fetal death later in gestation independent of known causes of elevation, such as the presence of neural-tube defects or multiple gestation. METHODS: To address this question, we performed a case-control study of 612 women whose pregnancies ended in fetal death and 2501 women who gave birth to live infants, using reports from California vital statistics for 1987. All the women had signleton pregnancies and alpha-fetoprotein screening in the second trimester. RESULTS: Women with elevated levels of serum alpha-fetoprotein in the second trimester of pregnancy had an increased risk of fetal death, and the risk was increased until term. Women with the highest levels of serum alpha-fetoprotein--greater than or equal to 3.0 times the median value--had a very high risk of fetal death (odds ratio, 10.4; 95 percent confidence interval, 4.9 to 22.0) as compared with women who had normal levels of alpha-fetoprotein. Maternal serum alpha-fetoprotein levels that were 2.0 to 2.9 times the median were also associated with an elevated risk of fetal death (odds ratio, 2.4; 95 percent confidence interval, 1.7 to 3.4). Elevated levels of alpha-fetoprotein were especially likely to be associated with fetal death in cases in which maternal hypertension or placental infarction was also present. CONCLUSIONs. An unexplained elevated level of maternal serum alpha-fetoprotein in the second trimester of pregnancy is associated with an increased risk of subsequent fetal death, up to four to five months after alpha-fetoprotein screening.