Abstract:  Objective · To evaluate the association between the abnormal maternal serum markers of alpha fetoprotein (AFP), human chorionic gonadotrophin (hCG) and unconjugated estriol (uE3) in the second trimester screening and the adverse obstetric outcomes other than trisomy 21 (T21), trisomy 18 (T18) and open neural tube defects (ONTD), and to provide local data for supporting evidence based clinical managements.  Methods · A retrospective cohort study was performed in the women who received second trimester maternal serum screening in the International Peace Maternal and Child Health Hospital between 2012 and 2014, with naturally conceived singleton pregnancies. Obstetric outcomes were followed up by searching electronic medical records within the hospital. Abnormal level of marker was defined as a MOM value ≥ 99th (P99) or  ≤?1st percentile (P1) of the overall screened population. Incidence of an adverse obstetric outcome was compared between the groups with abnormal markers and the control with all markers in normal.  Results · ① A total of 25 616 pregnancies were included in this study, in which 4 526 were identified as having various adverse obstetric outcomes. Among them 4 143 pregnancies were with isolated and 383 pregnancies were with co-occurring two or more adverse outcomes. ② When compared to pregnancies with normal levels of all three serum markers, pregnancies with decreased AFP or decreased hCG did not show associations with any adverse obstetric outcomes. However, pregnancies with increased AFP, increased hCG or decreased uE3 were at increased risk for a variety of abnormal pregnancy outcome. In 18 pregnancies with an outcome of fetal chromosomal abnormalities other than T21 and T18, 9 presented with either increased AFP, increased hCG or decreased uE3, with relative risk ratios of 13.33、35.00 and 59.00, respectively. ③ The performance of those markers tended to be improved in a subset of adverse obstetric outcomes, including low birth weight <P3, fetal loss prior to 28 weeks, and preeclampsia onset before 34 weeks. Compared to the conditions with a broad definition, relative risk ratios increased 1.5-15 folders in these narrowly defined more severe forms.  Conclusion · Pregnancies with abnormal serum markers should receive close attention. For women in particular with increased AFP, increased hCG or decreased uE3, invasive prenatal diagnosis for a comprehensive examination of fetal chromosomal abnormalities is strongly suggested. Even in the absence of positive diagnostic result, managements of increased frequency of antenatal visits and ultrasound surveillance should still be offered, in order to achieve an earlier or improved detection of adverse obstetric outcomes, especially of those with severe clinical manifestations such as early fetal loss, small for gestational age infant, and early onset preeclampsia.

Key words: adverse obstetric outcomes, second trimester maternal screening, alpha fetoprotein, human chorionic gonadotrophin, unconjugated estriol