AN ASSOCIATION BETWEEN ELEVATED LEVELS OF HUMAN CHORIONIC-GONADOTROPIN IN THE MIDTRIMESTER AND ADVERSE PREGNANCY OUTCOME

OBJECTIVE: Unexplained elevations in maternal serum alpha-fetoprotein in the midtrimester are associated with adverse pregnancy outcome. Recently it has also been suggested that elevations of maternal serum human chorionic gonadotropin in the second trimester may be associated with adverse pregnancy outcome. STUDY DESIGN: We conducted a cohort study of 460 women at Swedish Medical Center, Seattle, Washington, between Jan. 1, 1990, and Aug. 15, 1991, inclusive. Entry criteria for the cohort included (1) triple screen analysis (maternal serum alpha-fetoprotein, human chorionic gonadotropin, unconjugated estriol) between 15 and 18 weeks' gestation, (2) a risk for Down syndrome of more than one in 195 on the basis of triple screen analysis, (3) study group human chorionic gonadotropin greater-than-or-equal-to 2 multiples of the median and referent group less-than-or-equal-to 2 multiples of the median, alpha-fetoprotein less-than-or-equal-to 2 multiples of the median, unconjugated estriol greater-than-or-equal-to 0.5 multiples of the median, and (4) chromosomally normal single gestation without anomalies. Cumulative incidence risk ratios were estimated for each pregnancy outcome as a measure of the relative association with elevated human chorionic gonadotropin (greater-than-or-equal-to 2.0 multiples of the median) and adverse pregnancy outcome: low birth weight, less-than-or-equal-to 2500 gm; preterm delivery, <37 weeks' gestation; and small for gestational age, less-than-or-equal-to 10th percentile. The Mantel extension test was used to evaluate any apparent linear trend in risk between level of human chorionic gonadotropin and adverse pregnancy outcome. RESULTS: Elevated human chorionic gonadotropin levels were associated with an increased risk for low birth weight (relative risk = 4.0), preterm delivery (relative risk = 2.8), and small for gestational age (relative risk = 1.8). The risk for each adverse outcome increased with increasing levels of human chorionic gonadotropin. CONCLUSIONS: Elevations of human chorionic gonadotropin in the midtrimester appear to be associated with adverse pregnancy outcome. The magnitude of the risk correlates with the level of human chorionic gonadotropin. This risk appears to be independent of the risk for adverse pregnancy outcome associated with unexplained elevations of maternal serum alpha-fetoprotein.