Abstract
Aim:
The aim of this study was to evaluate the predictive value of α-fetoprotein in maternal serum (MS-AFP) as a marker for diverse pregnancy outcomes.
Methods:
The study was based on pregnancy and delivery data from 5520 women between 1999 and 2014 at University Hospital of Zurich (UHZ). Inclusion criteria: both MS-AFP and pregnancy outcome were known for the same pregnancy. Pregnancy outcomes and characteristics such as fetal malformation, intrauterine fetal death (IUFD) and intrauterine growth retardation as well as maternal age, weight before pregnancy, gestational age (GA) at delivery, newborn weight, length and head circumference were analyzed with respect to the MS-AFP value. MS-AFP value was categorized into three groups: elevated MS-AFP>2.5 multiples of the median (MoM), normal 0.5–2.49 MoM and decreased <0.5 MoM.
Results:
Newborn weight (g) and length (cm) were significantly lower in the elevated MS-AFP (P<0.001) group, and infants had 1 week lower GA at delivery (P<0.05). In the group of elevated MS-AFP (n=46), 26.1% of pregnancies were significantly related to adverse pregnancy outcomes, such as fetal malformations, fetuses small for gestational age (SGA) and IUFD. Adverse pregnancy outcomes of 5.6% were registered in the group of normal MS-AFP and 7.3% in the group of low MS-AFP (P<0.05).
Conclusion:
MS-AFP level in the second trimester is still an important indicator of fetal surface malformations; however, ultrasound still outweighs as a screening method. Nevertheless, pregnant women with elevated MS-AFP values and with no sonographically detected fetal malformations should additionally receive the third trimester ultrasound examination to exclude other possible complications of pregnancy.
Author’s statement
Conflict of interest: Authors state no conflict of interest.
Material and methods: Informed consent: Informed consent has been obtained from all individuals included in this study.
Ethical approval: The research related to human subject use has complied with all the relevant national regulations, and institutional policies, and is in accordance with the tenets of the Helsinki Declaration, and has been approved by the authors’ institutional review board or equivalent committee.
References
[1] Canick JA, Kellner LH, Bombard AT. Prenatal screening for open neural tube defects. Clin Lab Med. 2003;23:385–94.10.1016/S0272-2712(03)00032-5Search in Google Scholar PubMed
[2] David Gitlin MB. Serum a-fetoprotein, albumin, and yG-globulin in the human conceptus. J Clin Invest. 1966;45:1826–38.10.1172/JCI105486Search in Google Scholar
[3] Mizejewski GJ. Alpha-fetoprotein structure and function: relevance to isoforms, epitopes, and conformational variants. Exp Biol Med (Maywood). 2001;226:377–408.10.1177/153537020122600503Search in Google Scholar PubMed
[4] Gitlin D, Perricelli A, Gitlin GM. Synthesis of -fetoprotein by liver, yolk sac, and gastrointestinal tract of the human concept. Cancer Res. 1972;35:979–82.Search in Google Scholar
[5] Mizejewski GJ. Levels of alpha-fetoprotein during pregnancy and early infancy in normal and disease states. Obstet Gynecol Surv. 2003;58:804–26.10.1097/01.OGX.0000099770.97668.18Search in Google Scholar PubMed
[6] Mizejewski GJ. Physiology of alpha-fetoprotein as a biomarker for perinatal distress: relevance to adverse pregnancy outcome. Exp Biol Med (Maywood). 2007;232:993–1004.10.3181/0612-MR-291Search in Google Scholar PubMed
[7] Christensen RL, Rea MR, Kessler G, Crane JP, Valdes R Jr. Implementation of a screening program for diagnosing open neural tube defects: selection, evaluation, and utilization of alpha-fetoprotein methodology. Clin Chem. 1986;32:1812–7.10.1093/clinchem/32.10.1812Search in Google Scholar PubMed
[8] Bredaki FE, Sciorio C, Wright A, Wright D, Nicolaides KH. Serum alpha-fetoprotein in the three trimesters of pregnancy: effects of maternal characteristics and medical history. Ultrasound Obstet Gynecol. 2015;46:34–41.10.1002/uog.14809Search in Google Scholar PubMed
[9] Bredaki FE, Wright D, Akolekar R, Cruz G, Nicolaides KH. Maternal serum alpha-fetoprotein in normal pregnancy at 11–13 weeks’ gestation. Fetal Diagn Ther. 2011;30:274–9.10.1159/000330200Search in Google Scholar PubMed
[10] Crandall BF, Robinson L, Grau P. Risks associated with an elevated maternal serum a-fetoprotein level. Am J Obstet Gynecol. 1991;165:581–6.10.1016/0002-9378(91)90289-4Search in Google Scholar
[11] Roig MD, Sabrià J, Valls C, Borràs M, Miró E, Ponce J, et al. The use of biochemical markers in prenatal diagnosis of intrauterine growth retardation: insulin-like growth factor I, Leptin, and alpha-fetoprotein. Eur J Obstet Gynecol Reprod Biol. 2005;120:27–32.10.1016/j.ejogrb.2004.07.028Search in Google Scholar PubMed
[12] Audibert F, Benchimol Y, Benattar C, Champagne C, Frydman R, et al. Prediction of preeclampsia or intrauterine growth restriction by second trimester serum screening and uterine Doppler velocimetry. Fetal Diagn Ther. 2005;20:48–53.10.1159/000081369Search in Google Scholar PubMed
[13] Beta J, Bredaki FE, Rodriguez Calvo J, Akolekar R, Nicolaides KH. Maternal serum alpha-fetoprotein at 11–13 weeks’ gestation in spontaneous early preterm delivery. Fetal Diagn Ther. 2011;30:88–93.10.1159/000324352Search in Google Scholar PubMed
[14] Bredaki FE, Mataliotakis M, Wright A, Wright D, Nicolaides KH, et al. Maternal serum alpha fetoprotein at 12, 22, 32 weeks’ gestation in screening for preeclampsia. Ultrasound Obstet Gynecol. 2016;47:466–71.10.1002/uog.15818Search in Google Scholar PubMed
[15] Androutsopoulos G, Gkogkos P, Decavalas G. Mid-trimester maternal serum HCG and alpha fetal protein levels: clinical significance and prediction of adverse pregnancy outcome. Int J Endocrinol Metab. 2013;11:102–6.10.5812/ijem.5014Search in Google Scholar PubMed
[16] Tancrède S, Bujold E, Giguère Y, Renald MH, Girouard J, Forest JC. Mid-trimester maternal serum AFP and hCG as markers of preterm and term adverse pregnancy outcomes. J Obstet Gynaecol Can. 2015;37:111–6.10.1016/S1701-2163(15)30331-5Search in Google Scholar PubMed
[17] Wei Yuan LC. Andres Lopez Bernal, Is elevated maternal serum alpha-fetoprotein in the second trimester of pregnancy associated with increased preterm birth risk? A systematic review and meta-analysis. Eur J Obstet Gynecol Reprod Biol. 2009;145:57–64.10.1016/j.ejogrb.2009.04.017Search in Google Scholar
[18] Roman A, Desai N, Krantz D, Liu HP, Rosner J, Vohra N, et al. Maternal serum analytes as predictors of IUGR with different degrees of placental vascular dysfunction. Prenat Diagn. 2014;34:692–8.10.1002/pd.4369Search in Google Scholar PubMed
[19] Wilson RD; SOGC Genetics Committee, Wilson RD, Audibert F, Brock JA, Campagnolo C, Carroll J, et al. Prenatal screening, diagnosis, and pregnancy management of fetal neural tube defects. J Obstet Gynaecol Can. 2014;36:927–39.10.1016/S1701-2163(15)30444-8Search in Google Scholar PubMed
[20] National Institute for Clinical Excellence. Antenatal care for uncomplicated pregnancies. NICE clinical guidelines. Updated edition. London, 2008.Search in Google Scholar
[21] Driscoll DA, Gross SJ. Screening for fetal aneuploidy and neural tube defects. Genet Med. 2009;11:818–21.10.1097/GIM.0b013e3181bb267bSearch in Google Scholar PubMed
[22] Yaron Y, Cherry M, Kramer RL, O’Brien JE, Hallak M, Johnson MP. Second-trimester maternal serum marker screening: maternal serum alpha-fetoprotein, beta-human chorionic gonadotropin, estriol, and their various combinations as predictors of pregnancy outcome. Am J Obstet Gynecol. 1999;181:968–74.10.1016/S0002-9378(99)70334-0Search in Google Scholar PubMed
[23] Poon LC, Lesmes C, Gallo DM, Akolekar R, Nicolaides KH. Prediction of small-for-gestational-age neonates: screening by biophysical and biochemical markers at 19–24 weeks. Ultrasound Obstet Gynecol. 2015;46:437–45.10.1002/uog.14904Search in Google Scholar PubMed
[24] Lesmes C, Gallo DM, Gonzalez R, Poon LC, Nicolaides KH. Prediction of small-for-gestational-age neonates: screening by maternal serum biochemical markers at 19–24 weeks. Ultrasound Obstet Gynecol. 2015;46:341–9.10.1002/uog.14899Search in Google Scholar PubMed
[25] Bartha JL, Illanes S, González-Bugatto F, Abdel-Fattah SA, Mizejewski GJ, Soothill PW. Maternal serum transformed alpha-fetoprotein levels in women with intrauterine growth retardation. Fetal Diagn Ther. 2007;22:294–8.10.1159/000100794Search in Google Scholar PubMed
[26] Sharony R, Dayan D, Kidron D, Manor M, Berkovitz A, Biron-Shental T, et al. Is the ratio of maternal serum to amniotic fluid AFP superior to serum levels as a predictor of pregnancy complications? Arch Gynecol Obstet. 2016;293:767–70.10.1007/s00404-015-3905-9Search in Google Scholar PubMed
[27] Dugoff L; Society for Maternal-Fetal Medicine. First- and second-trimester maternal serum markers for aneuploidy and adverse obstetric outcomes. Obstet Gynecol. 2010;115:1052–61.10.1097/AOG.0b013e3181da93daSearch in Google Scholar PubMed
©2017 Walter de Gruyter GmbH, Berlin/Boston
