Hostname: page-component-cd9895bd7-hc48f Total loading time: 0 Render date: 2024-12-25T13:59:32.841Z Has data issue: false hasContentIssue false
  • English
  • Français

Fetal sex differences in human chorionic gonadotropin fluctuate by maternal race, age, weight and by gestational age

Published online by Cambridge University Press:  05 August 2015

J. J. Adibi ,
M. K. Lee ,
S. Saha ,
W. J. Boscardin ,
A. Apfel  and
R. J. Currier
J. J. Adibi*
Affiliation:
Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, USA Department of Obstetrics, Gynecology and Reproductive Sciences, University of Pittsburgh, Pittsburgh, PA, USA
M. K. Lee
Affiliation:
Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, USA
S. Saha
Affiliation:
California Department of Public Health, Genetic Disease Screening Program, Program Development and Evaluation, Richmond, CA, USA
W. J. Boscardin
Affiliation:
Statistical Analysis Core, UCSF Pepper Center, University of California, San Francisco, CA, USA
A. Apfel
Affiliation:
Bioinformatics Core, Clinical Translation and Science Institute, University of Pittsburgh, Pittsburgh, PA, USA
R. J. Currier
Affiliation:
California Department of Public Health, Genetic Disease Screening Program, Program Development and Evaluation, Richmond, CA, USA
*
*Address for correspondence: J. J. Adibi, Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, 130 Desoto Street, Parran Hall 516 Pittsburgh, PA 15261, USA. (Email [email protected])
Get access Rights & Permissions [Opens in a new window]

Abstract

Circulating levels of the placental glycoprotein hormone human chorionic gonadotropin (hCG) are higher in women carrying female v. male fetuses; yet, the significance of this difference with respect to maternal factors, environmental exposures and neonatal outcomes is unknown. As a first step in evaluating the biologic and clinical significance of sex differences in hCG, we conducted a population-level analysis to assess its stability across subgroups. Subjects were women carrying singleton pregnancies who participated in prenatal and newborn screening programs in CA from 2009 to 2012 (1.1 million serum samples). hCG was measured in the first and second trimesters and fetal sex was determined from the neonatal record. Multivariate linear models were used to estimate hCG means in women carrying female and male fetuses. We report fluctuations in the ratios of female to male hCG by maternal factors and by gestational age. hCG was higher in the case of a female fetus by 11 and 8% in the first and second trimesters, respectively (P<0.0001). There were small (1–5%) fluctuations in the sex difference by maternal race, weight and age. The female-to-male ratio in hCG decreased from 17 to 2% in the first trimester, and then increased from 2 to 19% in the second trimester (P<0.0001). We demonstrate within a well enumerated, diverse US population that the sex difference in hCG overall is stable. Small fluctuations within population subgroups may be relevant to environmental and physiologic effects on the placenta and can be probed further using these types of data.

Keywords

placental hormonespregnancysexual dimorphism
Type
Original Article
Information
Journal of Developmental Origins of Health and Disease , Volume 6 , Issue 6 , December 2015 , pp. 493 - 500
Check for updates
Copyright
© Cambridge University Press and the International Society for Developmental Origins of Health and Disease 2015 

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

1. Bremme, K, Lagerström, M, Andersson, O, Johansson, S, Eneroth, P. Influences of maternal smoking and fetal sex on maternal serum oestriol, prolactin, hCG, and hPI levels. Arch Gynecol Obstet. 1990; 247, 95–103.Google Scholar
2. Clements, JA, Reyes, FI, Winter, JS, Faiman, C. Studies on human sexual development. III. Fetal pituitary and serum, and amniotic fluid concentrations of LH, CG, and FSH. J Clin Endocrinol Metab. 1976; 42, 9–19.Google Scholar
3. Cowans, NJ, Stamatopoulou, A, Maiz, N, Spencer, K, Nicolaides, KH. The impact of fetal gender on first trimester nuchal translucency and maternal serum free beta-hCG and PAPP-A MoM in normal and trisomy 21 pregnancies. Prenat Diagn. 2009; 29, 578–581.Google Scholar
4. Steier, JA, Myking, OL, Bergsjo, PB. Correlation between fetal sex and human chorionic gonadotropin in peripheral maternal blood and amniotic fluid in second and third trimester normal pregnancies. Acta obstetricia et gynecologica Scandinavica. 1999; 78, 367–371.Google Scholar
5. Yaron, Y, Lehavi, O, Orr-Urtreger, A, et al. Maternal serum HCG is higher in the presence of a female fetus as early as week 3 post-fertilization. Hum Reprod. 2002; 17, 485–489.CrossRefGoogle Scholar
6. Kauppila, A, Huhtaniemi, I, Ylikorkala, O. Raised serum human chorionic gonadotrophin concentrations in hyperemesis gravidarum. Br Med J. 1979; 1, 1670–1671.Google Scholar
7. Huhtaniemi, IT, Korenbrot, CC, Jaffe, RB. HCG binding and stimulation of testosterone biosynthesis in the human fetal testis. J Clin Endocrinol Metab. 1977; 44, 963–967.Google Scholar
8. Scott, HM, Mason, JI, Sharpe, RM. Steroidogenesis in the fetal testis and its susceptibility to disruption by exogenous compounds. Endocr Rev. 2009; 30, 883–925.Google Scholar
9. Huhtaniemi, IT, Korenbrot, CC, Jaffe, RB. Content of chorionic gonadotropin in human fetal tissues. J Clin Endocrinol Metab. 1978; 46, 994–997.CrossRefGoogle ScholarPubMed
10. Berndt, S, Blacher, S, Munaut, C, et al. Hyperglycosylated human chorionic gonadotropin stimulates angiogenesis through TGF-β receptor activation. FASEB J. 2013; 27, 1309–1321.Google Scholar
11. Hatzirodos, N, Bayne, RA, Irving-Rodgers, HF, et al. Linkage of regulators of TGF-β activity in the fetal ovary to polycystic ovary syndrome. FASEB J. 2011; 25, 2256–2265.Google Scholar
12. Ridano, ME, Racca, AC, Flores-Martín, J, et al. Chlorpyrifos modifies the expression of genes involved in human placental function. Reprod Toxicol. 2012; 33, 331–338.Google Scholar
13. Honkisz, E, Zieba-Przybylska, D, Wojtowicz, AK. The effect of triclosan on hormone secretion and viability of human choriocarcinoma JEG-3 cells. Reprod Toxicol. 2012; 34, 385–392.Google Scholar
14. Fowler, PA, Bhattacharya, S, Gromoll, J, Monteiro, A, O’Shaughnessy, PJ. Maternal smoking and developmental changes in luteinizing hormone (LH) and the LH receptor in the fetal testis. J Clin Endocrinol Metab. 2009; 94, 4688–4695.CrossRefGoogle ScholarPubMed
15. Catalano, RA, Saxton, KB, Bruckner, TA, et al. Hormonal evidence supports the theory of selection in utero. Am J Hum Biol. 2012; 24, 526–532.Google Scholar
16. Lewis, RM, Demmelmair, H, Gaillard, R, et al. The placental exposome: placental determinants of fetal adiposity and postnatal body composition. Ann Nutr Metab. 2013; 63, 208–215.Google Scholar
17. Jukic, AMZ, Weinberg, CR, Baird, DD, Wilcox, AJ. The association of maternal factors with delayed implantation and the initial rise of urinary human chorionic gonadotrophin. Hum Reprod. 2011; 26, 920–926.CrossRefGoogle ScholarPubMed
18. Brock, DJ, Sutcliffe, RG. Alpha-fetoprotein in the antenatal diagnosis of anencephaly and spina bifida. Lancet. 1972; 2, 197–199.CrossRefGoogle ScholarPubMed
19. Jelliffe-Pawlowski, LL, Shaw, GM, Currier, RJ, et al. Association of early-preterm birth with abnormal levels of routinely collected first- and second-trimester biomarkers. YMOB. 2013; 208, 492.e491–492.e411.Google Scholar
20. Taché, V, Baer, RJ, Currier, RJ, et al. Population-based biomarker screening and the development of severe preeclampsia in California. Am J Obstet Gynecol. 2014; 211, 377.e1–377.e8.CrossRefGoogle ScholarPubMed
21. Blumenfeld, YJ, Baer, RJ, Druzin, ML, et al. Association between maternal characteristics, abnormal serum aneuploidy analytes, and placental abruption. Am J Obstet Gynecol. 2014; 211, 144e1–144e9.Google Scholar
22. Chedane, C, Puissant, H, Weil, D, Rouleau, S, Coutant, R. Association between altered placental human chorionic gonadotrophin (hCG) production and the occurrence of cryptorchidism: a retrospective study. BMC Pediatr. 2014; 14, 191.CrossRefGoogle ScholarPubMed
23. Wald, NJ, Cuckle, H, Brock, JH, et al.. Maternal serum-alpha-fetoprotein measurement in antenatal screening for anencephaly and spina bifida in early pregnancy. Report of U.K. collaborative study on alpha-fetoprotein in relation to neural-tube defects. Lancet. 1977; 1, 1323–1332.Google Scholar
24. Wald, NJ, Rodeck, C, Hackshaw, AK, et al.. First and second trimester antenatal screening for Down’s syndrome: the results of the Serum, Urine and Ultrasound Screening Study (SURUSS). J Med Screen. 2003; 10, 56–104.Google Scholar
25. Miron, P, Côté, YP, Lambert, J. Effect of maternal smoking on prenatal screening for Down syndrome and trisomy 18 in the first trimester of pregnancy. Prenat Diagn. 2008; 28, 180–185.Google Scholar
26. Spencer, K, Cicero, S, Atzei, A, Otigbah, C, Nicolaides, KH. The influence of maternal insulin-dependent diabetes on fetal nuchal translucency thickness and first-trimester maternal serum biochemical markers of aneuploidy. Prenat Diagn. 2005; 25, 927–929.Google Scholar
27. Spencer, K, Heath, V, El-Sheikhah, A, Ong, CY, Nicolaides, KH. Ethnicity and the need for correction of biochemical and ultrasound markers of chromosomal anomalies in the first trimester: a study of Oriental, Asian and Afro-Caribbean populations. Prenat Diagn. 2005; 25, 365–369.Google Scholar
28. Lambert-Messerlian, G, Dugoff, L, Vidaver, J, et al. First- and second-trimester Down syndrome screening markers in pregnancies achieved through assisted reproductive technologies (ART): a FASTER trial study. Prenat Diagn. 2006; 26, 672–678.Google Scholar
29. Feuchtbaum, L, Carter, J, Dowray, S, Currier, RJ, Lorey, F. Birth prevalence of disorders detectable through newborn screening by race/ethnicity. Genet Med. 2012; 14, 937–945.Google Scholar
30. Stumpf, DA, Cranford, RE, Elias, S, et al. The infant with anencephaly. The Medical Task Force on Anencephaly. N Engl J Med. 1990; 322, 669–674.Google Scholar
31. Sabol, BA, de Sam Lazaro, S, Salati, J, et al. Racial and ethnic differences in pregnancy outcomes in women with chronic hypertension. Obstet Gynecol. 2014; 123(Suppl. 1), 168S–169S.Google Scholar
32. Carlsen, F, Grytten, J, Eskild, A. Changes in fetal and neonatal mortality during 40 years by offspring sex: a national registry-based study in Norway. BMC Pregnancy Childbirth. 2013; 13, 101.Google Scholar
33. Cooperstock, M, Campbell, J. Excess males in preterm birth: interactions with gestational age, race, and multiple birth. Obst Gynecol. 1996; 88, 189–193.Google Scholar
34. Becerra, TA, von Ehrenstein, OS, Heck, JE, et al. Autism spectrum disorders and race, ethnicity, and nativity: a population-based study. Pediatrics. 2014; 134, e63–e71.Google Scholar
35. Lorusso, L, Bacchini, F. A reconsideration of the role of self-identified races in epidemiology and biomedical research. Stud Hist Philos Biol Biomed Sci. 2015; 52, 1–9.Google Scholar
36. Ahmed, AT, Quinn, VP, Caan, B, et al.. Generational status and duration of residence predict diabetes prevalence among Latinos: the California Men’s Health Study. BMC Public Health. 2009; 9, 392.Google Scholar
37. Donnenfeld, AE, Icke, KV, Pargas, C, Dowman, C. Biochemical screening for aneuploidy in ovum donor pregnancies. Am J Obstet Gynecol. 2002; 187, 1222–1225.Google Scholar
38. Hussa, RO. Biosynthesis of human chorionic gonadotropin. Endocr Rev. 1980; 1, 268–294.Google Scholar