Cord Blood Sex Hormones Concentration: Relation to Birth Weight and Pregnancy Complications
AbstractObjectives: Umbilical cord blood can be taken at birth and largely gives indication of fetal and maternal conditions. The aim of the study was to investigate the relation between sex hormones in cord blood and birth weight of newborns and pregnancy complications.
Materials and methods: Fifty cord blood samples were collected from newborns at labor room of Baghdad Teaching Hospital between May and October 2018. Blood was withdrawn from their mothers for lead analysis. Five milliliters (ml) of cord blood was taken, 3 ml was used for testosterone and estradiol analysis (using enzyme-linked immunosorbent assay) and 2 ml for lead measurement by lead care analyzer. Newborns weight and head circumference were measured. Delivered women were divided into 4 groups: Women with normal pregnancy, women with preeclampsia, diabetic women and polycystic ovary syndrome (PCOS) women.
Results: There was no significant difference in age between women in all groups (p˃0.05). Birth weights, estradiol, and testosterone were significantly different between groups. Estradiol was higher in cord blood of newborns of PCOS women (p˂0.05) than others. Testosterone was higher in cord blood of babies of PCOS and preeclampsia women compared to those of diabetes (p˂0.05). There were no significant differences between male and female neonates regarding cord estradiol (3596.27±1934.69, 3714.57±1581.47 pg/ml respectively), and testosterone (393.18±87.14, 361.43±102.14 ng/ml respectively) (p˃0.05). Maternal lead levels correlated positively with cord lead (r=0.905, p˂0.05), which correlated negatively with head circumference (r=-0.766, p˂0.05). Birth weight correlated negatively with estradiol (r=-0.295), but positively with testosterone (r=0.006) (p˃0.05).
Conclusion: Cord blood estradiol and testosterone levels do not differ between males and females. Estradiol was high in cord blood of PCOS mothers. Testosterone was high in cord blood of PCOS and preeclampsia mothers. The increase in cord lead causes decrease in babies head circumference.
2. Paskova A, Parizek A, Hill M, Velíková M, Kubátová J, Duskova M, et al. Steroid metabolome in the umbilical cord: is it necessary to differentiate between arterial and venous blood?. Physiol Res. 2014;63:115-126.
3. StefanoLuisi FR, GiovanniCentini FS, Petraglia F. Human placenta as a source of neuroendocrine factors. Biol Neonate. 2001;79:150-156.
4. Cohen-Bendahan CC, Van Goozen SH, Buitelaar JK, Cohen-Kettenis PT. Maternal serum steroid levels are unrelated to fetal sex: a study in twin pregnancies. Twin Res Hum Genet. 2005;8:173-177.
5. Sloboda DM, Hickey M, Hart R. Reproduction in females: the role of the early life environment. Hum Reprod Update. 2010;17:210-227.
6. Hill M, Pařízek A, Kancheva R, Dušková M, Velíková M, Kříž L, et al. Steroid metabolome in plasma from the umbilical artery, umbilical vein, maternal cubital vein and in amniotic fluid in normal and preterm labor. J Steroid Biochem Mol Biol. 2010;121:594-610.
7. Keelan JA, Mattes E, Tan H, Dinan A, Newnham JP, Whitehouse AJ, et al. Androgen concentrations in umbilical cord blood and their association with maternal, fetal and obstetric factors. PLoS One. 2012;7:e42827.
8. Ahamed M, Siddiqui MK. Low level lead exposure and oxidative stress: current opinions. Clin Chim Acta. 2007;383:57-64.
9. Stella CL, Sibai BM. Preeclampsia: diagnosis and management of the atypical presentation. J Matern Fetal Neonatal Med. 2006;19:381-386.
10. Wang R, Mol BW. The Rotterdam criteria for polycystic ovary syndrome: evidence-based criteria?. Hum Reprod. 2017;32:261-264.
11. Tunon K, Eik‐Nes SH, Grøttum P, Von Düring V, Kahn JA. Gestational age in pregnancies conceived after in vitro fertilization: a comparison between age assessed from oocyte retrieval, crown‐rump length and biparietal diameter. Ultrasound Obstet Gynecol. 2000;15(1):41-46.
12. Janssen PA, Thiessen P, Klein MC, Whitfield MF, MacNab YC, Cullis-Kuhl SC. Standards for the measurement of birth weight, length and head circumference at term in neonates of European, Chinese and South Asian ancestry. Open Med. 2007;1:e74-e88.
13. Mercer JS, Vohr BR, Erickson-Owens DA, Padbury JF, Oh W. Seven-month developmental outcomes of very low birth weight infants enrolled in a randomized controlled trial of delayed versus immediate cord clamping. J Perinatol. 2010;30:11-16.
14. Lindley AA, Benson JE, Grimes C, Cole III TM, Herman AA. The relationship in neonates between clinically measured head circumference and brain volume estimated from head CT-scans. Early Hum Dev. 1999;56:17-29.
15. AL-OMARY HL, ALAWAD ZM, HUSSEI SY. Lymphocyte Apoptosis in Third Trimester of Pregnancy. J Clin Diagn Res. 2018;12:CC05-CC08.
16. Touger L, Looker HC, Krakoff J, Lindsay RS, Cook V, Knowler WC. Early growth in offspring of diabetic mothers. Diabetes Care. 2005;28:585-589.
17. Morgan K, Rahman M, Atkinson M, Zhou SM, Hill R, Khanom A, et al. Association of diabetes in pregnancy with child weight at birth, age 12 months and 5 years–a population-based electronic cohort study. PLoS One. 2013;8:e79803.
18. Kamana KC, Shakya S, Zhang H. Gestational diabetes mellitus and macrosomia: a literature review. Ann Nutr Metab. 2015;66:14-20.
19. Daan NM, Koster MP, Steegers-Theunissen RP, Eijkemans MJ, Fauser BC. Endocrine and cardiometabolic cord blood characteristics of offspring born to mothers with and without polycystic ovary syndrome. Fertil Steril. 2017;107:261-268.
20. Xita N, Tsatsoulis A. Fetal programming of polycystic ovary syndrome by androgen excess: evidence from experimental, clinical, and genetic association studies. J Clin Endocrinol Metab. 2006;91:1660-1666.
21. Barry JA, Kay AR, Navaratnarajah R, Iqbal S, Bamfo JE, David AL, et al. Umbilical vein testosterone in female infants born to mothers with polycystic ovary syndrome is elevated to male levels. J Obstet Gynaecol. 2010;30:444-446.
22. Mehrabian F, Kelishadi R. Comparison of the metabolic parameters and androgen level of umbilical cord blood in newborns of mothers with polycystic ovary syndrome and controls. J Res Med Sci. 2012;17:207-211.
23. Maliqueo M, Lara HE, Sánchez F, Echiburú B, Crisosto N, Sir-Petermann T. Placental steroidogenesis in pregnant women with polycystic ovary syndrome. Eur J Obstet Gynecol Reprod Biol. 2013;166:151-155.
24. Anderson H, Fogel N, Grebe SK, Singh RJ, Taylor RL, Dunaif A. Infants of women with polycystic ovary syndrome have lower cord blood androstenedione and estradiol levels. J Clin Endocrinol Metab. 2010;95:2180-2186.
25. Steegers-Theunissen RP, Verheijden-Paulissen JJ, van Uitert EM, Wildhagen MF, Exalto N, Koning AH, et al. Cohort profile: the Rotterdam periconceptional cohort (predict study). Int J Epidemiol. 2016;45:374-381.
26. Chinnathambi V, Balakrishnan M, Ramadoss J, Yallampalli C, Sathishkumar K. Testosterone alters maternal vascular adaptations: role of the endothelial NO system. Hypertension. 2013;61: 647–654.
27. Troisi R, Potischman N, Roberts J, Ness R, Crombleholme W, Lykins D, et al. Maternal serum oestrogen and androgen concentrations in preeclamptic and uncomplicated pregnancies. Int J Epidemiol. 2003;32:455-460.
28. Rohrmann S, Sutcliffe CG, Bienstock JL, Monsegue D, Akereyeni F, Bradwin G, et al. Racial variation in sex steroid hormones and the insulin-like growth factor axis in umbilical cord blood of male neonates. Cancer Epidemiol Biomarkers Prev. 2009;18:1484-1491.
29. Caanen MR, Kuijper EA, Hompes PG, Kushnir MM, Rockwood AL, Meikle WA, et al. Mass spectrometry methods measured androgen and estrogen concentrations during pregnancy and in newborns of mothers with polycystic ovary syndrome. Eur J Endocrinol. 2016;174:25-32.
30. Kallen CB. Steroid hormone synthesis in pregnancy. Obstet Gynecol Clin. 2004;31:795-816.
31. Troisi R, Potischman N, Roberts J, Siiteri P, Daftary A, Sims C, et al. Associations of maternal and umbilical cord hormone concentrations with maternal, gestational and neonatal factors (United States). Cancer Causes Control. 2003;14:347-355.
32. Troisi R, Potischman N, Roberts JM, Harger G, Markovic N, Cole B, et al. Correlation of serum hormone concentrations in maternal and umbilical cord samples. Cancer Epidemiol Biomarkers Prev. 2003;12:452-456.
33. Hickey M, Hart R, Keelan JA. The relationship between umbilical cord estrogens and perinatal characteristics: implications for early life origins of reproductive cancers. Cancer Epidemiol Biomarkers Prev. 2014; cebp-1321.
34. Hill M, Pašková A, Kančeva R, Velikova M, Kubatova J, Kancheva L, et al. Steroid profiling in pregnancy: a focus on the human fetus. J Steroid Biochem Mol Biol. 2014;139:201-222.
35. Simmons D, France JT, Keelan JA, Song L, Knox BS. Sex differences in umbilical cord serum levels of inhibin, testosterone, oestradiol dehydroepiandrosterone sulphate, and sex hormone-binding globulin in human term neonates. Neonatology. 1994;65:287-294.
36. van de Beek C, Thijssen JH, Cohen-Kettenis PT, van Goozen SH, Buitelaar JK. Relationships between sex hormones assessed in amniotic fluid, and maternal and umbilical cord serum: what is the best source of information to investigate the effects of fetal hormonal exposure?. Horm Behav. 2004;46:663-669.
37. Krogh C, Cohen AS, Basit S, Hougaard DM, Biggar RJ, Wohlfahrt J, et al. Testosterone levels in umbilical-cord blood and risk of pyloric stenosis. Pediatrics. 2011;127:e197-201.
38. Reddy YS, Aparna Y, Ramalaksmi BA, Kumar BD. Lead and trace element levels in placenta, maternal and cord blood: A cross‐sectional pilot study. J Obstet Gynaecol Res. 2014;40:2184-2190.
39. Akbari-Nassaji N, Sabeti F, Ziaei KT, Fakharzadeh L, Nazari Z, Cheraghian B, et al. Lead level in umbilical cord blood and its effects on newborns anthropometry. J Clin Diagn Res. 2017;11:SC01-SC04.
40. Falcon M, Vinas P, Luna A. Placental lead and outcome of pregnancy. Toxicology. 2003;185:59-66.
41. West WL, Knight EM, Edwards CH, Manning M, Spurlock B, James H, et al. Maternal low level lead and pregnancy outcomes. J Nutr. 1994;124: 981S–986S.
42. Nagata C, Iwasa S, Shiraki M, Shimizu H. Estrogen and α-fetoprotein levels in maternal and umbilical cord blood samples in relation to birth weight. Cancer Epidemiol Biomarkers Prev. 2006;15:1469-1472.
43. Lagiou P, Samoli E, Hsieh CC, Lagiou A, Xu B, Yu GP, et al. Maternal and cord blood hormones in relation to birth size. Eur J Epidemiol. 2014;29:343-351.
44. Hollier LP, Keelan JA, Hickey M, Maybery MT, Whitehouse AJ. Measurement of androgen and estrogen concentrations in cord blood: accuracy, biological interpretation, and applications to understanding human behavioral development. Front Endocrinol. 2014;5:64.
45. Zlotkin SH, Casselman CW. Percentile estimates of reference values for total protein and albumin in sera of premature infants (less than 37 weeks of gestation). Clin Chem. 1987;33:411-413.