Hyperglycosylated human chorionic gonadotrophin (hCG-h), produced by the placental trophoblast cells, is involved in placental development in early pregnancy. Decreased second trimester urine hCG-h is associated with later preeclampsia, which may be a sign of impaired trophoblastic invasion preceding symptoms of the disease.To study whether maternal second trimester serum hCG-h concentrations predict later development of preeclampsia.Fifty-five women with subsequent preeclampsia, 21 women with gestational hypertension, 30 normotensive women with small-for-gestational-age (SGA) infants and 83 controls with uneventful pregnancies were included in the study. Their serum hCG and hCG-h concentrations were analyzed by fluoroimmunoassay at 14–17weeks of gestation. The proportion of hCG-h of total hCG (%hCG-h) was calculated and converted to multiples of the median (MoMs) of the controls. MoMs of the groups were compared by Mann–Whitney U test. Pearson’s correlation was used to analyze correlations between clinical characteristics and serum marker concentrations. The results are given as medians with 95% confidence intervals (95% CI). A two-tailed P<0.05 was considered significant.The concentrations of hCG-h and %hCG-h decreased with advancing gestational weeks in women with subsequent preeclampsia (r=−0.289, p=0.032 and r=−0.464, p<0.001), but not in women in the other groups. There was a tendency towards lower concentrations of hCG-h and %hCG-h in women with subsequent preeclampsia than in controls. The median MoMs of %hCG-h were 0.89 (95% CI,0.79–1.00) in women with subsequent preeclampsia and 1.00 (0.91–1.11) in controls. The corresponding values for women with subsequent gestational hypertension were 1.00 (0.86–1.16), for those with subsequent SGA infants they were 1.09 (0.89–1.23). The difference between preeclampsia and the other groups together was significant (p=0.029).Earlier studies suggest that decreased urine hCG-h concentrations reflect changes in placental function that precede the development of preeclampsia. At 14–17weeks of gestation, the serum concentrations of hCG-h showed moderate validity to predict later development of preeclampsia. Further studies on the utility of hCG-h for prediction of subsequent preeclampsia are warranted.