Association between Alpha-fetoprotein Levels during the Second Trimester of Pregnancy and the Incidence of Low Birth Weight Infants at Sunpasitthiprasong Hospital
Article Sidebar
Main Article Content
Abstract
Objectives: To evaluate the association between maternal serum alpha-fetoprotein (MSAFP) levels during the second trimester and low birth weight (LBW) incidence, at Sunpasitthiprasong Hospital.
Materials and Methods: This retrospective cohort study included 1,937 pregnant women who underwent chromosomal abnormality screening between June 2021 and May 2025. Data from medical records included maternal baseline characteristics, antenatal history, quadruple test results, and delivery outcomes. Univariable and multivariable analyses were performed using logistic regression. Predictive performance of MSAFP for LBW was assessed by receiver operating characteristic curve analysis.
Results: The mean age of pregnant women was 28.5 ± 5.4 years. Birthweight less than 2,500 grams was observed in 10.9% of infants. The quadruple test was positive in 7.4% of cases. The median MSAFP levels were 34.36 ng/mL (interquartile range, IQR 26.94, 45.30), converting to 1.01 multiple of median (MoM) (IQR 0.83, 1.28). MSAFP levels were significantly higher in the LBW group compared to the non-LBW group (median 37.33 vs 34.12 ng/mL). In multivariable analysis, MSAFP in ng/mL, MoM, and > 2.0 MoM was significantly associated with LBW (adjusted odds ratios 1.01, 1.34, and 2.52 respectively). However, serum AFP demonstrated low predictive performance for LBW (area under the curve = 0.566).
Conclusion: MSAFP levels were significantly correlated with LBW, with higher levels observed in pregnancies with LBW. However, its predictive performance was low, limiting clinical utility. Elevated MSAFP may indicate risk to LBW but should be evaluated alongside other maternal and biochemical factors for effective risk assessment.
Article Details
This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.
References
World Health Organization. Newborns with low birth weight [Internet]. 2019 [cited 2025 Feb 20]. Available from: https://www.who.int/data/nutrition/nlis/info/low-birth-weight
Blencowe H, Krasevec J, de Onis M, Black RE, AnX, Stevens GA, et al. National, regional, and worldwide estimates of low birthweight in 2015, with trends from 2000: a systematic analysis. Lancet Global Health 2019;7:e849–e860.
Office of Policy and Strategy, Ministry of Public Health. Number and percentage of live newborns weighing less than 2,500 grams, classified by province, 2020. [Internet]. 2021 [cited 2025 Feb 20]. Available from: https://spd.moph.go.th/wp-content/uploads/2022/11/Hstatistic64.pdf
Goldenberg RL, Culhane JF. Low birth weight in the United States. Am J Clin Nutr 2007;85:584–90.
Vachirasrisoontra C, Anansakunwat W, Suthantikorn C, Prichakas P. Second trimester prenatal screening for Down syndrome in Thai pregnant women using alpha-fetoprotein and free beta-hCG. Thai J Obstet Gynaecol 2017;15:69-77.
Waller DK, Lustig LS, Cunningham GC, Feuchtbaum LB, Hook EB. The association between maternal serum alpha-fetoprotein and preterm birth, small for gestational age infants, preeclampsia, and placental complications. Obstet Gynecol 1996;88:816–22.
Krause TG, Christens P, Wohlfahrt J, Lei U, Westergaard T, Pedersen BN, et al. Second-trimester maternal serum alpha-fetoprotein and risk of adverse pregnancy outcome. Obstet Gynecol 2001;97:277-82.
Dugoff L, Hobbins JC, Malone FD, Vidaver J, Sullivan L, Canick JA, et al. Quad screen as a predictor of adverse pregnancy outcome. Obstet Gynecol 2005;106:260–7.
Puntachai P, Wanapirak C, Sirichotiyakul S, Tongprasert F, Srisupundit K, Luewan S, et al. Associations between pregnancy outcomes and unexplained high and low maternal serum alpha-fetoprotein levels. Arch Gynecol Obstet 2015;292: 81-5.
Fleiss JL, Levin B, Paik MC. Statistical methods for rates and proportions. 3rd ed. New York: John Wiley&Sons;2003:76.
Burton GJ, Jauniaux E. Pathophysiology of placental-derived fetal growth restriction. Am J Obstet Gynecol 2015;218:S745-61.
Ciemmy JG, Szmyt K, Kuszerska A, Rzepka R, Kaisenberg CV, Kocylowski R. Fetal and placental causes of elevated serum alpha-fetoprotein levels in pregnant women. J Clin Med 2024;13:466.
Zahra S, Sampurana MTA, Aditiawarman. The role of maternal serum alpha-fetoprotein in preterm birth: A literature review. WJARR 2023;18:738–41.
Mizejewski G. Physiology of alpha-fetoprotein as a biomarker for perinatal distress: relevance to adverse pregnancy outcome. Exp Biol Med (Maywood) 2007;232:993-1004.
Dai X, Zhang H, Wu B, ning W, Chen Y, Chen Y. Correlation between elevated maternal serum alpha-fetoprotein and ischemic placental disease: a retrospective cohort study. Clin Exp Hypertens 2023;45:2175848.
Yu MY, Xi L, Zhang JX, zhang SC. Possible connection between elevated serum α-fetoprotein and placental necrosis during pregnancy: A case report and review of literature. World J Clin Cases 2018;6:675–8.
Williams MA, Hickok DE, Zingheim RW, Luthy DA, Kimelman J, Nyberg DA, et al. Elevated maternal serum alpha-fetoprotein levels and midtrimester placental abnormalities in relation to subsequent adverse pregnancy outcomes. Am J Obstet Gynecol 1992;167:1032-7.
Chandra S, Scott H, Dodds L, Watts C, Blight C, Den Hof MV. Unexplained elevated maternal serum alpha-fetoprotein and/or human chorionic gonadotropin and the risk of adverse outcomes. Am J Obstet Gynecol 2003;189:775-81.
Butler E, Dashe J, Ramus RM. Association between maternal serum alpha-fetoprotein and adverse outcomes in pregnancies with placenta previa. Obstet Gynecol 2001;97:35-8.
Buckland CM, Thom H, Campbell AG. Maternal serum alpha-fetoprotein levels in low birth weight singleton pregnancies. J Perinat Med 1984;12: 127-32.
Basbug D, Basbug A, Gulerman C. Is unexplained elevated maternal serum alpha-fetoprotein still important predictor for adverse pregnancy outcome? Ginekol Pol 2017;88:325-30.
Ozdemir S, Sahin O, Acar Z, Demir GZ, Ermin E, Aydin A. Prediction of pregnancy complications with maternal biochemical markers used in Down syndrome screening. Cureus 2022;14:e23115.
Allen R, Marleen S, Velauthar L, Harrington K, Aquilina J. The relationship between second trimester alpha fetoprotein levels and adverse pregnancy outcome. Open J Obstet Gynecol 2013;3:262-6.
Buckland CM, Thom H, Campbell AG. Maternal serum alpha-fetoprotein levels in low birth weight singleton pregnancies. J Perinat Med 1984;12:127-32.
Bartkute K, Balsyte D, Wisser J, Kurmanavicius J. Pregnancy outcomes regarding maternal serum AFP value in second trimester screening. J Perinant Med 2017;45:817-20.
Karya U, Kumari S, Rani A, Singh S. Clinical significance of unexplained elevated maternal serum alpha feto-protein in second trimester of pregnancy. Int J Reprod Contracept Obstet Gynecol 2018;7: 2245-50.
ACOG. Indications for outpatient antenatal fetal surveillance [Internet]. 2019 [cited 2025 Oct 23]. Available from: https://www.acog.org/clinical/clinical-guidance/committee-opinion/articles/2021/06/indications-for-outpatient-antenatal-fetal-surveillance
Boonpaim R, Wanapirak C, Sirichotiyakul S, Sekararithi R, Traisrisilp K, Tongsong T. Quad test for fetal aneuploidy screening as a predictor of small-for-gestational age fetuses: a population-based study. BMC Pregnancy Childbirth 2020;20:621.
American College of Obstetricians and Gynecologists (ACOG). Weight gain during pregnancy. Committee opinion No.548. Obstet Gynecol 2013;121:210-2.
Goldstein RF, Abell SK, Ranasinha S, Boyle JA, Black MH, Li N, et al. Association of gestational weight gain with maternal and infant outcomes: a systematic review and meta-analysis. JAMA 2017;317:2207-25.
Ruax X, Chen K, Li Z, Wei J, Chen Y, Zou Q, et al. The impact of maternal health and lifestyle on low birth weight: a prospective cohort study. Italian J Pediatr 2025;51:217.
Khalaf SA, Bodunde E, Maher GM, O’Reilly E, McCarthy FP, O’Shaughnessy MM, et al. Chronic kidney disease and adverse pregnancy outcomes: a systematic review and meta-analysis. Am J Obstet Gynecol 2022;226:656-70.
Arabzadeh H, Doosti-Irani A, Kamkari S, Farhadian M, Elyasi E, Mohammadi Y. The maternal factors associated with infant low birth weight: an umbrella review. BMC Pregnancy Childbirth 2024;24:316.
Nazir P. Gestational weight gain and estimated fetal growth in different trimesters among Saudi women. Pak J Med Sci 2025;41:3088–94.
Shaohua Y, Bin Z, Mei L, Jingfei Z, Pingping Q, Yanping H, et al. Maternal risk factors and neonatal outcomes associated with low birth weight. Front Genet 2022;28:1019321.
