Second trimester total human chorionic gonadotropin, alpha-fetoprotein and unconjugated estriol in predicting pregnancy complications other than fetal aneuploidy

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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=2.7), miscarriage (odds ratio=4.4) and intrauterine fetal death (odds ratio=5.8). High chorionic gonadotropin levels (MoM≥2.02) were associated with intrauterine growth restriction (odds ratio=2.1; P<0.05), miscarriage (odds ratio=4; P<0.01), preterm birth (odds ratio=2.5; P<0.05), and intrauterine fetal death (odds ratio=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=2.2; P<0.05 and odds ratio=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.

Introduction

Biochemical screening for Down syndrome by means of the triple-marker test (alpha-fetoprotein(AFP)+human chorionic gonadotropin+unconjugated estriol) has been successfully used in antenatal care for more than 10 years. Although different biochemical [1], [2], [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-fetoprotein, chorionic gonadotropin and unconjugated estriol levels on adverse pregnancy outcome [7], [8], [9], [10], [11], [12], [13]. Still, there appear to be conflicting data as to the association of biochemical 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 population of Croatia and after having set our own population standards for all three markers [14].

Section snippets

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 and 22 weeks of gestation and fetal biparietal diameter was ultrasonographically measured for gestational dating. Previous Down syndrome was reported in 63 (2.6%) women. Prenatal karyotyping was performed in all women

Results

Relative risks for the occurrence of various pregnancy complications in euploid gestations according to biochemical marker results are shown in Table 1. There were 40 euploid pregnancies with high alpha-fetoprotein levels, considered borderline positive for NTD. Among them, gestations with IUGR (odds ratio=2.7), spontaneous abortion (odds ratio=4.4), and intrauterine fetal death (odds ratio=5.8) were significantly more frequent (P<0.05). Total human chorionic gonadotropin (ThCG) levels equal or

Discussion

Biochemical markers of Down syndrome in maternal circulation are of fetal/placental origin and not directly related to chromosome 21. By means of main step through screening for Down syndrome (transformation of individual marker level to MoM value) we screen in general for all disorders of their synthesis and metabolism in fetal and placental tissues. During this study, atypical concentrations of alpha-fetoprotein, chorionic gonadotropin and unconjugated estriol were observed in relation to

Acknowledgements

This study was in part supported by a research grant no.108-250 from the Scientific Research Funds of the Ministry of Science of Croatia.

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