Objective: To evaluate the potential clinical use of maternal serum free beta-human chorionic gonadotropin (beta-hCG) and uterine artery Doppler investigation to screen for placenta-related adverse outcome in pregnancies at positive risk for Down's syndrome at 15-18 weeks.
Design: A cohort of 329 consecutive pregnant women with a singleton viable pregnancy and a positive risk for Down's syndrome was retrospectively investigated. This group was obtained from an unselected population of 3952 women attending the same hospital over a 2-year period. Using the results of this first analysis, we selected a group of 26 women with unexplained high levels of free beta-hCG and followed them prospectively with monthly ultrasound and uterine artery Doppler examinations.
Results: In the retrospective cohort, risk ratios stratified for maternal serum beta-hCG multiple of the median (MoM) values indicated that the highest incidence of adverse pregnancy outcome was in those women with values of > or = 5.0. In the prospective study, pregnancy outcome was complicated by uteroplacental disorders in eight cases. Analysis of the Doppler investigation indicated that, in women with a very high level of hCG, an abnormally high uterine artery pulsatility index (PI) had lower sensitivity and negative predictive value than early diastolic notch, whereas the specificity and positive predictive value were higher for a high uterine artery PI.
Conclusions: These findings suggest an association between a high level of maternal serum beta-hCG at 15-18 weeks, the presence of an early diastolic notch in the uterine artery flow velocity waveform and adverse pregnancy outcome due to abnormal development of the uteroplacental circulation. Young women with an unexplained high beta-hCG level would benefit, apart from detailed sonography of the fetus and/or karyotyping, from uterine Doppler investigation and counselling about the follow-up and management of placenta-related pregnancy disorders.