Second trimester total human chorionic gonadotropin, alpha-fetoprotein and unconjugated estriol in predicting pregnancy complications other than fetal aneuploidy Koraljka Duric, Snjezana Skrablin, Josko Lesin, Drzislav Kalafatic, Ivan Kuvacic, Ernest Suchanek * Department of Obstetrics and Gynecology, Zagreb University School of Medicine, Petrova 13, 10 000 Zagreb, Croatia Received 1 June 2002; received in revised form 27 December 2002; accepted 3 January 2003 Abstract Objective: To assess the value of alpha-fetoprotein (AFP), total human chorionic gonadotropin (ThCG) and unconjugated estriol in predicting certain complications of pregnancy other than fetal aneuploidy. Study design: Among 2384 women that underwent biochemical screening between 15 and 22 weeks of gestation, pregnancy outcome was evaluated in 677 women under 35 years of age according to serum marker levels by using cut-off points discriminative for Down syndrome or neural tube defect (NTD). Results: High alpha-fetoprotein levels (MoM  2:0) were found to be significantly more frequent (P < 0:05) in cases of fetal growth restriction (odds ratio ¼ 2:7), miscarriage (odds ratio ¼ 4:4) and intrauterine fetal death (odds ratio ¼ 5:8). High chorionic gonadotropin levels (MoM  2:02) were associated with intrauterine growth restriction (odds ratio ¼ 2:1; P < 0:05), miscarriage (odds ratio ¼ 4; P < 0:01), preterm birth (odds ratio ¼ 2:5; P < 0:05), and intrauterine fetal death (odds ratio ¼ 4:2; P < 0:01). Among pregnancies with intrauterine growth restriction and threatening preterm delivery, low unconjugated estriol levels (MoM  0:74) were significantly more frequent (odds ratio ¼ 2:2; P < 0:05 and odds ratio ¼ 2:6; P < 0:01, respectively). Conclusion: All three markers predictive for fetal trisomy 21 shown to be associated with various pregnancy complications in euploid pregnancies. # 2003 Elsevier Science Ireland Ltd. All rights reserved. Keywords: Alpha-fetoprotein; Human chorionic gonadotropin; Unconjugated estriol; Pregnancy outcome 1. Introduction Biochemical screening for Down syndrome by means of the triple-marker test (alpha-fetoprotein ðAFPÞþ human chorionic gonadotropin þ unconjugated estriol) has been successfully used in antenatal care for more than 10 years. Although different biochemical [1–3] and ultrasound [4] markers changed non-invasive approach to Down syndrome diagnosis, triple-marker test is still in clinical practice due to improvements even today [5]. Because of the origin and sites of metabolism, chorionic gonadotropin, alpha-fetoprotein and estriol are markers of the feto-placental unit during pregnancy. Its function can be changed even if fetus has normal karyotype. Since the introduction of triple-marker test in screening for Down syndrome [6], a lot of work has been done to evaluate implications of atypical alpha-feto- protein, chorionic gonadotropin and unconjugated estriol levels on adverse pregnancy outcome [7–13]. Still, there appear to be conflicting data as to the association of bio- chemical markers and pregnancy complications, and some papers have seriously questioned the usefulness of such tests [8,13]. Study design specificities and variations of marker levels in different populations could be the explanation for such controversies. That is why we analyzed the relationship between pregnancy outcome and abnormal maternal second trimester biochemistry in a relatively homogeneous popula- tion of Croatia and after having set our own population standards for all three markers [14]. 2. Materials and methods During the 1996–1998 period, 2384 pregnant women were enrolled in the antenatal care program—1707 of them due to age (35 years or older) and 677 women younger than 35 on their own request, or when indicated by a history of fetal aneuploidy. Blood samples were obtained between 15 European Journal of Obstetrics & Gynecology and Reproductive Biology 110 (2003) 12–15 * Corresponding author. Fax: þ385-1-4633-512. E-mail address: suchaneksuchanek@netscape.net (E. Suchanek). 0301-2115/$ – see front matter # 2003 Elsevier Science Ireland Ltd. All rights reserved. doi:10.1016/S0301-2115(03)00081-2