Maternal serum markers levels in consecutive pregnancies: a possible genetic predisposition to abnormal levels.

The study comprised 2,361 women, each with two consecutive normal uncomplicated pregnancies screened at 15-20 weeks gestation for maternal serum alpha-fetoprotein levels (AFP). In 1,816 of these women, maternal serum human chorionic gonadotropin (hCG) levels were tested as well. The proportion of women who had a second high AFP level (> or = 2.0 MOM) in their subsequent pregnancy was 6.5-fold higher as compared with the proportion of women who had normal levels of AFP in their first tested pregnancy. The relative chance of having a second positive result of a low level of AFP (AFP < or = 0.5 MOM) in subsequent pregnancies was 3.8-fold higher. The relative chances of having a second positive result of high or low levels of hCG were 3.9- and 2.2-fold higher, respectively. It is concluded that there is a predisposition for abnormal levels of serum markers that is influenced by genetic and/or environmental factors. Therefore it is suggested that the individual's risk of having a Down syndrome baby, or other adverse pregnancy outcome that is derived from the serum markers' levels, should be adjusted taking into account unexplained high or low levels in previous pregnancies. A screening policy is suggested which is designed to yield a lower false-positive rate without affecting the detection rate of abnormal pregnancies. More data are needed before an accurate adjustment based on previous results can be made.

The association between unexplained second-trimester maternal serum hCG elevation and pregnancy complications.

OBJECTIVE: We conducted this cohort analytic study to determine whether women with unexplained elevations of maternal serum hCG at 16-20 weeks' gestation are at increased risk for pregnancy complications and adverse perinatal outcomes. METHODS: The inclusion criteria were a singleton gestation, a confirmed gestational age, and an hCG level greater than 2.5 multiples of the median (MOM). The exclusion criteria were fetal anomalies, an abnormal karyotype, and a maternal serum alpha-fetoprotein (MSAFP) level greater than 2.5 MOM. A group of randomly selected women with normal hCG and MSAFP levels served as controls. RESULTS: Of the 6011 women screened, 284 (4.7%) had an unexplained elevated hCG level. Patients with elevated levels of hCG had a significantly higher risk for hypertension (odds ratio 4.4; 95% confidence interval [CI] 1.9-10) and fetal growth restriction (odds ratio 2.8; 95% CI 1-7). Women with hCG levels greater than 4 MOM also had an increased risk of preterm delivery (odds ratio 3.3; 95% CI 1.3-8.2). CONCLUSION: Pregnancies with unexplained elevated hCG levels should be regarded as high-risk pregnancies and managed accordingly.

Alpha-fetoprotein in the early neonatal period--a large study and review of the literature.

BACKGROUND: Alpha-fetoprotein (AFP) is a glycoprotein molecule, which has similarity to albumin and is produced by the fetal liver. Its biological role is unclear and factors that may influence its concentrations in neonates are only partially identified. However, it has an important role as a diagnostic marker, especially in certain tumors and liver diseases of childhood. Its normal reference values in newborns have not been well defined. METHODS: Serum AFP concentrations were measured and characterized in 260 term and near-term newborns [gestational age (GA)> or =34 weeks, birthweight (BW)> or =1700 g] at birth [umbilical cord (UC) blood] and upon discharge from the nursery at 60+/-24 h of life (venous sample). RESULTS: Due to the nonnormal distribution of AFP levels, it is useful to relate to reference interval for AFP concentrations at birth that was 15.7-146.5 microg/ml, based on 95% confidence interval (CI). The median value of 48.3 microg/ml is also a useful reference. However, mean AFP concentrations at birth that were 61.6+/-44.8 microg/ml are less informative due to the large standard deviation (S.D.). Upon discharge, AFP concentrations dropped to 9.7-111.9 microg/ml (95% CI) with a median of 34.2 microg/ml. A significant negative correlation was found between AFP serum levels and gestational age and to a lesser extent with birthweight. No significant differences were found between males and females. CONCLUSIONS: Normal reference intervals for AFP in term and near-term newborns have been defined, but need to be addressed with caution due to the wide range of normal values. AFP levels at birth decrease as gestation advances and the newborn weighs more.

Unconjugated estriol as maternal serum marker for the detection of Down syndrome pregnancies.

The effectiveness of unconjugated estriol (uE3) as a serum marker for the detection of Down syndrome (DS) during the 2nd trimester of pregnancy was evaluated. A population of 18,764 normal singleton pregnancies was screened for alpha-feto-protein and human chorionic gonadotropin. In 9,311 women, uE3 was added. Using a risk of 1:250 at term as a cutoff value, the false-positive rates were 4.1 and 4.3% without and with uE3, respectively. The detection rates in 47 DS serum samples, some of which were studied retrospectively, were 66% without uE3 and 57% with uE3. In 12 of 25 younger women and in 19 of 22 older women, DS was detected without uE3. The uE3 contributed to the detection of 4 additional DS pregnancies (1 in the young and 3 in older women). On the other hand, 8 DS pregnancies (3 in younger women and 5 in older women) escaped detection. In our sample the addition of uE3 lowered the detection rate of DS pregnancies with only a small and insignificant effect on the false-positive rate. Our results call for special caution in the addition of markers for risk calculations. We suggest that pregnancies with a calculated risk of > 1:250 following maternal serum alpha-fetoprotein and human chorionic gonadotropin markers tests should be regarded as high-risk pregnancies, even in cases in whom the addition of uE3 lowers the risk beneath the cutoff value.

Very low maternal serum unconjugated estriol and prenatal diagnosis of steroid sulfatase deficiency.

Twenty-four women out of 7,875 pregnant women who enrolled in a prenatal screening program showed extremely low levels of unconjugated estriol (< 0.15 MOM). In 19 cases, intrauterine fetal death was reported. In 1 case anencephalus was detected. In the remaining 4 cases apparently normal healthy babies (1 female and 3 males) were born following uneventful pregnancies. Physical examination of the 3 boys at 4-6 weeks revealed mild ichthyosis compatible with the X-linked type. Two of them had a positive family history of X-linked ichthyosis. The examination of the girl did not reveal any significant findings. In both cases in which amniocentesis was performed, low levels of steroid sulfatase and arylsulfatase C were found. The prevalence of X-linked ichthyosis in this study is higher than previously reported, i.e. 1:1,300 males. Our results suggest that the prenatal screening program for neural tube defects and for Down's syndrome is useful for the prenatal detection of X-linked ichthyosis as well. These results are in accordance with two recent reports. The implications regarding genetic counseling are discussed.

The role of umbilical cord alpha fetoprotein as a screening tool for neonatal hyperbilirubinemia.

Our aim was to test whether alpha fetoprotein (AFP) might serve as a marker of hepatic immaturity sufficient to predict an increased risk for neonatal hyperbilirubinemia (NHB) in term babies. We checked umbilical cord AFP (UC AFP) levels in 174 healthy full-term infants (male/female ratio 1.26:1) at birth. Bilirubin levels were measured upon discharge from the nursery on day 3 of life (mean, 57 +/- 10 hours of life). Mean UC AFP was 60.2 +/- 45.9 mg/L. UC AFP levels were linearly correlated with subsequent bilirubin levels, and significantly higher bilirubin levels were found in neonates whose UC AFP levels were 100 mg/L or more. Although statistically significant correlation between UC AFP and subsequent NHB exists, UC AFP cannot currently be recommended for use in clinical practice because of its inability to serve as a screening tool for significant NHB in the individual newborn.