Decreased First-trimester Maternal Serum Free-β Subunit Human Chorionic Gonadotropin and Preterm Birth in Twin Gestations

ABSTRACT

We investigated whether abnormal concentrations of first-trimester free-β subunit human chorionic gonadotropin (fßhCG) and pregnancy-associated plasma protein A (PAPP-A) are associated with preterm delivery in twin gestations. This was a hospital-based, retrospective study of 70 twin gestations between 11¹/₇ and 13⁶/₇ weeks' gestation undergoing first-trimester screening. Free βhCG and PAPP-A multiples of the median were determined by our laboratory standards. Odds ratios (ORs) were estimated that compared the prevalence of very preterm (< 32 weeks), preterm (≥ 32 and < 37 weeks), and term birth (≥ 37 weeks) between the lower and higher percentile groups for each analyte. FßhCG levels ≤ 25th percentile were associated with very preterm birth < 32 weeks' gestation (OR 5.10; 95% confidence interval [CI]: 1.19 to 21.95), but not with preterm birth ≥ 32 and < 37 weeks' gestation (OR 0.50; 95% CI: 0.16 to 1.61). PAPP-A was not associated with very preterm (OR 2.95; 95% CI: 0.69 to 12.60) or preterm birth (OR 0.71; 95% CI: 0.23 to 2.21). Low first-trimester fßhCG was a strong predictor for very preterm birth in twin gestations. Low first-trimester PAPP-A was associated with a trend in increased risk of very preterm birth.

Free βhCG - PAPP-A - preterm labor - preterm birth - twin gestation

REFERENCES

• 1 Gabbe S. Obstetrics: Normal and Problem Pregnancies. 5th ed. Philadelphia; Churchill Livingstone 2007
• 2 Goldenberg R L, Iams J D, Miodovnik M et al.. The preterm prediction study: risk factors in twin gestations. National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network.  Am J Obstet Gynecol. 1996;  175(4 Pt 1) 1047-1053
• 3 Dugoff L, Hobbins J C, Malone F D 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
• 4 Ong C Y, Liao A W, Spencer K, Munim S, Nicolaides K H. First trimester maternal serum free beta human chorionic gonadotrophin and pregnancy associated plasma protein A as predictors of pregnancy complications.  BJOG. 2000;  107 1265-1270
• 5 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
• 6 Krantz D, Goetzl L, Simpson J L et al.. 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
• 7 Spencer K, Cowans N J, Molina F, Kagan K O, Nicolaides K H. First-trimester ultrasound and biochemical markers of aneuploidy and the prediction of preterm or early preterm delivery.  Ultrasound Obstet Gynecol. 2008;  31 147-152
• 8 Ticconi C, Piccione E, Belmonte A, Rao Ch V. HCG—A new kid on the block in prematurity prevention.  J Matern Fetal Neonatal Med. 2006;  19 687-692
• 9 Lawrence J B, Oxvig C, Overgaard M T 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
• 10 Irwin J C, Suen L F, Martina N A, Mark S P, Giudice L C. Role of the IGF system in trophoblast invasion and pre-eclampsia.  Hum Reprod. 1999;  14(Suppl 2) 90-96
• 11 van Kleffens M, Groffen C, Lindenbergh-Kortleve D J et al.. The IGF system during fetal-placental development of the mouse.  Mol Cell Endocrinol. 1998;  140 129-135
• 12 Kwik M, Morris J. Association between first trimester maternal serum pregnancy associated plasma protein-A and adverse pregnancy outcome.  Aust N Z J Obstet Gynaecol. 2003;  43 438-442
• 13 Smith G C, Stenhouse E J, Crossley J A et al.. 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
• 14 Spencer K. Screening for trisomy 21 in twin pregnancies in the first trimester using free beta-hCG and PAPP-A, combined with fetal nuchal translucency thickness.  Prenat Diagn. 2000;  20 91-95
• 15 Lockwood C J, Kuczynski E. Risk stratification and pathological mechanisms in preterm delivery.  Paediatr Perinat Epidemiol. 2001;  15(Suppl 2) 78-89
• 16 Rouse D J, Caritis S N, Peaceman A M et al.. A trial of 17 alpha-hydroxyprogesterone caproate to prevent prematurity in twins.  N Engl J Med. 2007;  357 454-461
• 17 Fonseca E B, Celik E, Parra M, Singh M, Nicolaides K H. Progesterone and the risk of preterm birth among women with a short cervix.  N Engl J Med. 2007;  357 462-469