First-Trimester Prediction of Birth Weight

Abstract

Objectives To determine whether the parameters used in first-trimester screening for aneuploidies contribute significantly to the prediction of birth weight.

Methods In this retrospective cohort study (n = 4110), nuchal translucency (NT), free β-chorionic gonadotropin (fβ-hCG), and pregnancy-associated plasma protein-A (PAPP-A) blood concentrations were measured between 11 + 0 and 13 + 6 weeks. Multiple pregnancies, chromosomal anomalies, major fetal defects, and deliveries before 24 weeks were excluded.

Results NT (0.95 versus 0.98 multiples of the expected median [MoM], p < 0.001) and PAPP-A (0.93 versus 1.06 MoM, p = 0.005) were significantly lower in small-for-gestational-age (SGA) newborns (<10th percentile) than the unaffected group, but not fβ-hCG (0.89 versus 0.93 MoM, p = 0.113). NT was significantly higher (1.03 versus 0.98 MoM, p < 0.001) in the large-for-gestational-age (LGA) group (>90th percentile) compared with the unaffected group, and biomarkers did not differ. After controlling for gestational age, maternal weight, smoking status, ethnicity, and fetal sex, first-trimester markers contributed to the prediction of birth weight in a multiple linear model but did not significantly improved the prediction of SGA and LGA compared with maternal characteristics alone.

Conclusions Parameters used in first-trimester screening for aneuploidies contribute to the prediction of birth weight but their clinical utility to detect women at risk of SGA or LGA baby is limited.

Keywords

birth weight - first-trimester screening - pregnancy-associated plasma protein A - free β-human chorionic gonadotropin - nuchal translucency - small for gestational age - large for gestational age

• References

• 1 Spencer K, Cowans NJ, Avgidou K, Molina F, Nicolaides KH. First-trimester biochemical markers of aneuploidy and the prediction of small-for-gestational age fetuses. Ultrasound Obstet Gynecol 2008; 31: 15-19
• 2 Poon LC, Karagiannis G, Staboulidou I, Shafiei A, Nicolaides KH. Reference range of birth weight with gestation and first-trimester prediction of small-for-gestation neonates. Prenat Diagn 2011; 31: 58-65
• 3 Goetzinger KR, Singla A, Gerkowicz S, Dicke JM, Gray DL, Odibo AO. The efficiency of first-trimester serum analytes and maternal characteristics in predicting fetal growth disorders. Am J Obstet Gynecol 2009; 201: 412 , e1–e6
• 4 Plasencia W, González Dávila E, Tetilla V, Padrón Pérez E, García Hernández JA, González González NL. First-trimester screening for large-for-gestational-age infants. Ultrasound Obstet Gynecol 2012; 39: 389-395
• 5 Montanari L, Alfei A, Albonico G , et al. The impact of first-trimester serum free beta-human chorionic gonadotropin and pregnancy-associated plasma protein A on the diagnosis of fetal growth restriction and small for gestational age infant. Fetal Diagn Ther 2009; 25: 130-135
• 6 Kagan KO, Wright D, Baker A, Sahota D, Nicolaides KH. Screening for trisomy 21 by maternal age, fetal nuchal translucency thickness, free beta-human chorionic gonadotropin and pregnancy-associated plasma protein-A. Ultrasound Obstet Gynecol 2008; 31: 618-624
• 7 Pedersen JF, Sørensen S, Ruge S. Human placental lactogen and pregnancy-associated plasma protein A in first trimester and subsequent fetal growth. Acta Obstet Gynecol Scand 1995; 74: 505-508
• 8 Canini S, Prefumo F, Pastorino D , et al. Association between birth weight and first-trimester free beta-human chorionic gonadotropin and pregnancy-associated plasma protein A. Fertil Steril 2008; 89: 174-178
• 9 Leung TY, Sahota DS, Chan LW , et al. Prediction of birth weight by fetal crown-rump length and maternal serum levels of pregnancy-associated plasma protein-A in the first trimester. Ultrasound Obstet Gynecol 2008; 31: 10-14
• 10 Tul N, Pusenjak S, Osredkar J, Spencer K, Novak-Antolic Z. Predicting complications of pregnancy with first-trimester maternal serum free-betahCG, PAPP-A and inhibin-A. Prenat Diagn 2003; 23: 990-996
• 11 Dugoff L, Hobbins JC, Malone FD , et al. First-trimester maternal serum PAPP-A and free-beta subunit human chorionic gonadotropin concentrations and nuchal translucency are associated with obstetric complications: a population-based screening study (the FASTER Trial). Am J Obstet Gynecol 2004; 191: 1446-1451
• 12 Krantz D, Goetzl L, Simpson JL , et al; First Trimester Maternal Serum Biochemistry and Fetal Nuchal Translucency Screening (BUN) Study Group. Association of extreme first-trimester free human chorionic gonadotropin-beta, pregnancy-associated plasma protein A, and nuchal translucency with intrauterine growth restriction and other adverse pregnancy outcomes. Am J Obstet Gynecol 2004; 191: 1452-1458
• 13 Boldt HB, Conover CA. Pregnancy-associated plasma protein-A (PAPP-A): a local regulator of IGF bioavailability through cleavage of IGFBPs. Growth Horm IGF Res 2007; 17: 10-18
• 14 Lawrence JB, Oxvig C, Overgaard MT , et al. The insulin-like growth factor (IGF)-dependent IGF binding protein-4 protease secreted by human fibroblasts is pregnancy-associated plasma protein-A. Proc Natl Acad Sci U S A 1999; 96: 3149-3153
• 15 Fox H. Effect of hypoxia on trophoblast in organ culture. A morphologic and autoradiographic study. Am J Obstet Gynecol 1970; 107: 1058-1064
• 16 Kelekci S, Yilmaz B, Savan K, Sonmez S. Can increased nuchal translucency in the first trimester of pregnancy predict gestational diabetes mellitus. J Obstet Gynaecol 2005; 25: 579-582
• 17 Cowans NJ, Spencer K. First-trimester ADAM12 and PAPP-A as markers for intrauterine fetal growth restriction through their roles in the insulin-like growth factor system. Prenat Diagn 2007; 27: 264-271
• 18 Pihl K, Sørensen TL, Nørgaard-Pedersen B , et al. First-trimester combined screening for Down syndrome: prediction of low birth weight, small for gestational age and pre-term delivery in a cohort of non-selected women. Prenat Diagn 2008; 28: 247-253
• 19 Kuc S, Wortelboer EJ, Koster MP, de Valk HW, Schielen PC, Visser GH. Prediction of macrosomia at birth in type-1 and 2 diabetic pregnancies with biomarkers of early placentation. BJOG 2011; 118: 748-754
• 20 Hadlock FP, Shah YP, Kanon DJ, Lindsey JV. Fetal crown-rump length: reevaluation of relation to menstrual age (5–18 weeks) with high-resolution real-time US. Radiology 1992; 182: 501-505
• 21 Kramer MS, Platt RW, Wen SW , et al; Fetal/Infant Health Study Group of the Canadian Perinatal Surveillance System. A new and improved population-based Canadian reference for birth weight for gestational age. Pediatrics 2001; 108: E35
• 22 Poon LC, Karagiannis G, Stratieva V, Syngelaki A, Nicolaides KH. First-trimester prediction of macrosomia. Fetal Diagn Ther 2011; 29: 139-147
• 23 Leung TY, Chan LW, Leung TN, Fung TY, Sahota DS, Lau TK. First-trimester maternal serum levels of placental hormones are independent predictors of second-trimester fetal growth parameters. Ultrasound Obstet Gynecol 2006; 27: 156-161
• 24 Pihl K, Larsen T, Krebs L, Christiansen M. First trimester maternal serum PAPP-A, beta-hCG and ADAM12 in prediction of small-for-gestational-age fetuses. Prenat Diagn 2008; 28: 1131-1135
• 25 Morssink LP, Kornman LH, Hallahan TW , et al. Maternal serum levels of free beta-hCG and PAPP-A in the first trimester of pregnancy are not associated with subsequent fetal growth retardation or preterm delivery. Prenat Diagn 1998; 18: 147-152
• 26 Ong CYT, Liao AW, Spencer K, Munim S, Nicolaides KH. First trimester maternal serum free β human chorionic gonadotrophin and pregnancy associated plasma protein A as predictors of pregnancy complications. BJOG 2000; 107: 1265-1270
• 27 Smith GC, Stenhouse EJ, Crossley JA, Aitken DA, Cameron AD, Connor JM. Early pregnancy levels of pregnancy-associated plasma protein a and the risk of intrauterine growth restriction, premature birth, preeclampsia, and stillbirth. J Clin Endocrinol Metab 2002; 87: 1762-1767
• 28 Yaron Y, Ochshorn Y, Heifetz S, Lehavi O, Sapir Y, Orr-Urtreger A. First trimester maternal serum free human chorionic gonadotropin as a predictor of adverse pregnancy outcome. Fetal Diagn Ther 2002; 17: 352-356
• 29 Smith GC, Smith MF, McNay MB, Fleming JE. First-trimester growth and the risk of low birth weight. N Engl J Med 1998; 339: 1817-1822
• 30 Burton GJ, Hempstock J, Jauniaux E. Nutrition of the human fetus during the first trimester—a review. Placenta 2001; 22 (Suppl A) S70-S77
• 31 Brausewetter F, Jehle PM, Jung MF , et al. Microvascular permeability is increased in both types of diabetes and correlates differentially with serum levels of insulin-like growth factor I (IGF-I) and vascular endothelial growth factor (VEGF). Horm Metab Res 2001; 33: 713-720
• 32 Haak MC, Bartelings MM, Jackson DG, Webb S, van Vugt JM, Gittenberger-de Groot AC. Increased nuchal translucency is associated with jugular lymphatic distension. Hum Reprod 2002; 17: 1086-1092
• 33 de Mooij YM, Bartelings MM, Twisk JWR , et al. Altered jugular vein and ductus venosus flow velocities in fetuses with increased nuchal translucency and distended jugular lymphatic sacs. Am J Obstet Gynecol 2010; 202: 566 , e1–e8
• 34 Smith GCS. First trimester origins of fetal growth impairment. Semin Perinatol 2004; 28: 41-50
• 35 Dickey RP, Gasser RF. Ultrasound evidence for variability in the size and development of normal human embryos before the tenth post-insemination week after assisted reproductive technologies. Hum Reprod 1993; 8: 331-337
• 36 Ericsson A, Säljö K, Sjöstrand E , et al. Brief hyperglycaemia in the early pregnant rat increases fetal weight at term by stimulating placental growth and affecting placental nutrient transport. J Physiol 2007; 581 (Pt 3) 1323-1332