Measurement of androgen and estrogen concentrations in cord blood: Accuracy, biological interpretation, and applications to understanding human behavioral development

Frontiers in Endocrinology

Volumn 5, Issue MAY, 2014, Pages

  Hollier, Lauren P ^a,b   Keelan, Jeffrey A ^c   Hickey, Martha ^d   Maybery, Murray T ^b   Whitehouse, Andrew J O ^a  

^a UNIVERSITY OF WESTERN AUSTRALIA   (Australia)

^b UNIVERSITY OF WESTERN AUSTRALIA   (Australia)

^c UNIVERSITY OF WESTERN AUSTRALIA   (Australia)

^d UNIVERSITY OF MELBOURNE   (Australia)

Author keywords

Androgens; Cord blood; Estrogens; Human development; Prenatal

Indexed keywords

ANDROGEN BLOOD LEVEL; AUTISM; BEHAVIOR; COGNITION; EMOTION; ESTROGEN BLOOD LEVEL; EXTRAVERSION; FETUS CIRCULATION; GESTATIONAL AGE; HUMAN; HUMAN DEVELOPMENT; LANGUAGE DEVELOPMENT; MASS SPECTROMETRY; MEASUREMENT ACCURACY; MUSCLE STRENGTH; PRENATAL EXPOSURE; RADIOIMMUNOASSAY; REVIEW; SOLVENT EXTRACTION; UMBILICAL CORD BLOOD;

EID: 84905508570     PISSN: None     EISSN: 16642392     Source Type: Journal    
DOI: 10.3389/fendo.2014.00064     Document Type: Review

References (86)

1. Collaer ML, Hines M. Human behavioral sex differences: a role for gonadal hormones during early development? Psychol Bull (1995) 118(1):55-107. doi:10.1037/0033-2909.118.1.55
2. Finegan J-A, Bartleman B, Wong P. A window for the study of prenatal sex hormone influences on postnatal development. J Genet Psychol (1989) 150(1):101-12. doi:10.1080/00221325.1989.9914580
3. Ngun TC, Ghahramani N, Sánchez FJ, Bocklandt S, Vilain E. The genetics of sex differences in brain and behavior. Front Neuroendocrinol (2011) 32(2):224-46. doi:10.1016/j.yfrne.2010.10.001
4. Bettencourt B, Miller N. Gender differences in aggression as a function of provocation: a meta-analysis. Psychol Bull (1996) 119(3):422. doi:10.1037/0033-2909.119.3.422
5. McIntyre MH, Barrett ES, McDermott R, Johnson DDP, Cowden J, Rosen SP. Finger length ratio (2D:4D) and sex differences in aggression during a simulated war game. Pers Individ Dif (2007) 42(4):755-64. doi:10.1016/j.paid.2006.08.009
6. Hines M. Brain Gender. New York: Oxford University Press (2004).
7. Collaer ML, Nelson JD. Large visuospatial sex difference in line judgment: possible role of attentional factors. Brain Cogn (2002) 49(1):1-12. doi:10.1006/brcg.2001.1321
8. Voyer D, Voyer S, Bryden MP. Magnitude of sex differences in spatial abilities: a meta-analysis and consideration of critical variables. Psychol Bull (1995) 117(2):250. doi:10.1037/0033-2909.117.2.250
9. Herlitz A, Airaksinen E, Nordström E. Sex differences in episodic memory: the impact of verbal and visuospatial ability. Neuropsychology (1999) 13(4):590. doi:10.1037/0894-4105.13.4.590
10. Lewin C, Wolgers G, Herlitz A. Sex differences favoring women in verbal but not in visuospatial episodic memory. Neuropsychology (2001) 15(2):165. doi:10.1037/0894-4105.15.2.165
11. Sherwin BB. Estrogen and cognitive functioning in women. Endocr Rev (2003) 24(2):133-51. doi:10.1210/er.2001-0016
12. Zambrano E, Guzmán C, Rodríguez-González GL, Durand-Carbajal M, Nathanielsz PW. Fetal programming of sexual development and reproductive function. Mol Cell Endocrinol (2014) 382(1):538-49. doi:10.1016/j.mce.2013.09.008
13. Dean A, Sharpe RM. Anogenital distance or digit length ratio as measures of fetal androgen exposure: relationship to male reproductive development and its disorders. J Clin Endocrinol Metab (2013) 98(6):2230-8. doi:10.1210/jc.2012-4057
14. Knickmeyer RC, Woolson S, Hamer RM, Konneker T, Gilmore JH. 2D:4D ratios in the first 2 years of life: stability and relation to testosterone exposure and sensitivity. Horm Behav (2011) 60(3):256-63. doi:10.1016/j.yhbeh.2011.05.009
15. Nagami M, McDonough P, Ellegood J, Mahesh V. Maternal and amniotic fluid steroids throughout human pregnancy. Am J Obstet Gynecol (1979) 134:674-80.
16. van de Beek C, Thijssen JHH, Cohen-Kettenis PT, van Goozen SHM, 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(5):663-9. doi:10.1016/j.yhbeh.2004.06.010
17. Kuijper EAM, Ket JCF, Caanen MR, Lambalk CB. Reproductive hormone concentrations in pregnancy and neonates: a systematic review. Reprod Biomed Online (2013) 27(1):33-63. doi:10.1016/j.rbmo.2013.03.009
18. Albrecht ED, Pepe GJ. Placental steroid hormone biosynthesis in primate pregnancy. Endocr Rev (1990) 11(1):124-50. doi:10.1210/edrv-11-1-124
19. Pašková A, Parízek A, Hill M, Velíková M, Kubátová J, Dušková M, et al. Steroid metabolome in the umbilical cord: is it necessary to differentiate between arterial and venous blood? Physiol Res (2014) 63(1):115-26.
20. Reis FM, Florio P, Cobellis L, Luisi S, Severi FM, Bocchi C, et al. Human placenta as a source of neuroendocrine factors. Biol Neonate (2001) 79(3-4):150-6. doi:10.1159/000047083
21. Ishimoto H, Jaffe RB. Development and function of the human fetal adrenal cortex: a key component in the feto-placental unit. Endocr Rev (2011) 32(3):317-55. doi:10.1210/er.2010-0001
22. Keelan JA, Mattes E, Tan H, Dinan A, Newnham JP, Whitehouse AJO, et al. Androgen concentrations in umbilical cord blood and their association with maternal, fetal and obstetric factors. PLoS One (2012) 7(8):e42827. doi:10.1371/journal.pone.0042827
23. Cohen-Bendahan CCC, van Goozen SHM, Buitelaar JK, Cohen-Kettenis PT. Maternal serum steroid levels are unrelated to fetal sex: a study in twin pregnancies. Twin Res Hum Genet (2005) 8:173-7. doi:10.1375/twin.8.2.173
24. 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(4):347-55. doi:10.1023/A:1023934518975
25. 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(5):452-6.
26. Hickey M, Sloboda DM, Atkinson HC, Doherty DA, Franks S, Norman RJ, et al. The relationship between maternal and umbilical cord androgen levels and polycystic ovary syndrome in adolescence: a prospective cohort study. J Clin Endocrinol Metab (2009) 94(10):3714-20. doi:10.1210/jc.2009-0544
27. Sloboda DM, Hickey M, Hart R. Reproduction in females: the role of the early life environment. Hum Reprod Update (2011) 17(2):210-27. doi:10.1093/humupd/dmq048
28. Hickey M, Hart R, Keelan JA. The relationship between umbilical cord estrogens and perinatal characteristics. Cancer Epidemiol Biomarkers Prev (2014). doi:10.1158/1055-9965.EPI-13-1321
29. Smith LM, Cloak CC, Poland RE, Torday J, Ross MG. Prenatal nicotine increases testosterone levels in the fetus and female offspring. Nicotine Tob Res (2003) 5(3):369-74. doi:10.1080/146222031000094196
30. Varvarigou AA, Liatsis SG, Vassilakos P, Decavalas G, Beratis NG. Effect of maternal smoking on cord blood estriol, placental lactogen, chorionic gonadotropin, FSH, LH, and cortisol. J Perinat Med (2009) 37(4):364-9. doi:10.1515/JPM.2009.028
31. Pardridge WM. Serum bioavailability of sex steroid hormones. Clin Endocrinol Metab (1986) 15(2):259-78. doi:10.1016/S0300-595X(86)80024-X
32. Herruzo AJ, Mozas J, Alarcón JL, López JM, Molina R, Molto L, et al. Sex differences in serum hormone levels in umbilical vein blood. Int J Gynecol Obstet (1993) 41(1):37-41. doi:10.1016/0020-7292(93)90152-M
33. Maccoby EE, Doering CH, Jacklin CN, Kraemer H. Concentrations of sex hormones in umbilical-cord blood: their relation to sex and birth order of infants. Child Dev (1979) 50(3):632-42. doi:10.2307/1128928
34. Beek C, Goozen SM, Buitelaar J, Cohen-Kettenis P. Prenatal sex hormones (maternal and amniotic fluid) and gender-related play behavior in 13-month-old infants. Arch Sex Behav (2009) 38(1):6-15. doi:10.1007/s10508-007-9291-z
35. Hill M, Pašková A, Kanceva R, Velíková M, Kubátová J, Kancheva L, et al. Steroid profiling in pregnancy: a focus on the human fetus. J Steroid Biochem Mol Biol (2014) 139(0):201-22. doi:10.1016/j.jsbmb.2013.03.008
36. 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(5):2180-6. doi:10.1210/jc.2009-2651
37. 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(5):287-94. doi:10.1159/000244074
38. Balthazart J. Minireview: hormones and human sexual orientation. Endocrinology (2011) 152(8):2937-47. doi:10.1210/en.2011-0277
39. Sathishkumar K, Elkins R, Yallampalli U, Balakrishnan M, Yallampalli C. Fetal programming of adult hypertension in female rat offspring exposed to androgens in utero. Early Hum Dev (2011) 87(6):407-14. doi:10.1016/j.earlhumdev.2011.03.001
40. Clifton VL, Bisits A, Zarzycki PK. Characterization of human fetal cord blood steroid profiles in relation to fetal sex and mode of delivery using temperature-dependent inclusion chromatography and principal component analysis (PCA). J Chromatogr B Analyt Technol Biomed Life Sci (2007) 855(2):249-54. doi:10.1016/j.jchromb.2007.05.041
41. 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(3-5):594-610. doi:10.1016/j.jsbmb.2009.10.012
42. Dawood MY, Saxena BB. Testosterone and dihydrotestosterone in maternal and cord blood and in amniotic fluid. Am J Obstet Gynecol (1977) 129(1):37-42.
43. Gemer O, Sevillia J, Zalis J, Segal S. Umbilical cord androgens in infants of diabetic mothers. Arch Gynecol Obstet (1997) 259(3):139-41. doi:10.1007/BF02505322
44. Hickey M, Doherty DA, Hart R, Norman RJ, Mattes E, Atkinson HC, et al. Maternal and umbilical cord androgen concentrations do not predict digit ratio (2D:4D) in girls: a prospective cohort study. Psychoneuroendocrinology (2010) 35(8):1235-44. doi:10.1016/j.psyneuen.2010.02.013
45. Laatikainen TJ, Pelkonen JM, Pesonen AK. Steroid concentrations in placenta and fetal membranes at elective caesarean section and after spontaneous labour. Placenta (1982) 3(3):319-24. doi:10.1016/S0143-4004(82)80008-8
46. Lagiou P, Samoli E, Okulicz W, Xu B, Lagiou A, Lipworth L, et al. Maternal and cord blood hormone levels in the United States and china and the intrauterine origin of breast cancer. Ann Oncol (2011) 22(5):1102-8. doi:10.1093/annonc/mdq565
47. Mathur RS, Landgrebe S, Moody LO, Powell S, Williamson HO. Plasma steroid concentrations in maternal and umbilical circulation after spontaneous onset of labor. J Clin Endocrinol Metab (1980) 51(6):1235-8. doi:10.1210/jcem-51-6-1235
48. Nagata C, Iwasa S, Shiraki M, Sahashi Y, Shimizu H. Association of maternal fat and alcohol intake with maternal and umbilical hormone levels and birth weight. Cancer Sci (2007) 98(6):869-73. doi:10.1111/j.1349-7006.2007.00464.x
49. 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 Prevent (2009) 18(5):1484-91. doi:10.1158/1055-9965.EPI-08-0817
50. Savarese T, Strohsnitter W, Low H, Liu Q, Baik I, Okulicz W, et al. Correlation of umbilical cord blood hormones and growth factors with stem cell potential: implications for the prenatal origin of breast cancer hypothesis. Breast Cancer Res (2007) 9(3):1-10. doi:10.1186/bcr1674
51. Simmons D. Interrelation between umbilical cord serum sex hormones, sex hormone-binding globulin, insulin-like growth factor i, and insulin in neonates from normal pregnancies and pregnancies complicated by diabetes. J Clin Endocrinol Metab (1995) 80(7):2217-21. doi:10.1210/jc.80.7.2217
52. Troisi R, Hoover RN, Thadhani R, Hsieh CC, Sluss P, Ballard-Barbash R, et al. Maternal, prenatal and perinatal characteristics and first trimester maternal serum hormone concentrations. Br J Cancer (2008) 99(7):1161-4. doi:10.1038/sj.bjc.6604639
53. Troisi R, Lagiou P, Trichopoulos D, Xu B, Chie L, Stanczyk FZ, et al. Cord serum estrogens, androgens, insulin-like growth factor-i, and insulin-like growth factor binding protein-3 in Chinese and U.S. Caucasian neonates. Cancer Epidemiol Biomarkers Prev (2008) 17(1):224-31. doi:10.1158/1055-9965.EPI-07-0536
54. Troisi R, Potischman N, Johnson CN, Roberts JM, Lykins D, Harger G, et al. Estrogen and androgen concentrations are not lower in the umbilical cord serum of pre-eclamptic pregnancies. Cancer Epidemiol Biomarkers Prev (2003) 12(11):1268-70.
55. Troisi R, Potischman N, Roberts JM, Ness R, Crombleholme W, Lykins D, et al. Maternal serum oestrogen and androgen concentrations in preeclamptic and uncomplicated pregnancies. Int J Epidemiol (2003) 32(3):455-60. doi:10.1093/ije/dyg094
56. Rosner W, Auchus RJ, Azziz R, Sluss PM, Raff H. Utility, limitations, and pitfalls in measuring testosterone: an endocrine society position statement. J Clin Endocrinol Metab (2007) 92(2):405-13. doi:10.1210/jc.2006-1864
57. Stanczyk FZ. Measurement of androgens in women. Paper Presented at the Seminars in Reproductive Medicine. New York (2006).
58. Demers LM. Androgen deficiency in women; role of accurate testosterone measurements. Maturitas (2010) 67(1):39-45. doi:10.1016/j.maturitas.2010.04.019
59. Stanczyk FZ, Cho MM, Endres DB, Morrison JL, Patel S, Paulson RJ. Limitations of direct estradiol and testosterone immunoassay kits. Steroids (2003) 68(14):1173-8. doi:10.1016/j.steroids.2003.08.012
60. 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(1):e197-201. doi:10.1542/peds.2010-2127
61. Soldin OP, Guo T, Weiderpass E, Tractenberg RE, Hilakivi-Clarke L, Soldin SJ. Steroid hormone levels in pregnancy and 1 year postpartum using isotope dilution tandem mass spectrometry. Fertil Steril (2005) 84(3):701-10. doi:10.1016/j.fertnstert.2005.02.045
62. Stanczyk FZ, Clarke NJ. Advantages and challenges of mass spectrometry assays for steroid hormones. J Steroid Biochem Mol Biol (2010) 121(3-5):491-5. doi:10.1016/j.jsbmb.2010.05.001
63. Vicente FB, Smith FA, Sierra R, Wang S. Measurement of serum testosterone using high-performance liquid chromatography/tandem mass spectrometry. Clin Chem Lab Med (2006) 44:70. doi:10.1515/CCLM.2006.014
64. Jacklin CN, Maccoby EE, Doering CH. Neonatal sex-steroid hormones and timidity in 6-18-month-old boys and girls. Dev Psychobiol (1983) 16(3):163-8. doi:10.1002/dev.420160302
65. Jacklin CN, Maccoby EE, Doering CH, King DR. Neonatal sex-steroid hormones and muscular strength of boys and girls in the first three years. Dev Psychobiol (1984) 17(3):301-10. doi:10.1002/dev.420170309
66. Jacklin CN, Wilcox KT, Maccoby EE. Neonatal sex-steroid hormones and cognitive abilities at six years. Dev Psychobiol (1988) 21(6):567-74. doi:10.1002/dev.420210607
67. Hollier LP, Mattes E, Maybery MT, Keelan JA, Hickey M, Whitehouse AJO. The association between perinatal testosterone concentration and early vocabulary development: a prospective cohort study. Biol Psychol (2013) 92(2):212-5. doi:10.1016/j.biopsycho.2012.10.016
68. Whitehouse AJO, Mattes E, Maybery M, Dissanayake C, Sawyer M, Jones R, et al. Perinatal testosterone exposure and autistic-like traits in the general population: a longitudinal pregnancy-cohort study. J Neurodev Disord (2012) 4(1):25. doi:10.1186/1866-1955-4-25
69. Farrant BM, Mattes E, Keelan JA, Hickey M, Whitehouse AJO. Fetal testosterone, socio-emotional engagement and language development. Infant Child Dev (2013) 22(2):119-32. doi:10.1002/icd.1771
70. Whitehouse AJO, Mattes E, Maybery MT, Sawyer MG, Jacoby P, Keelan JA, et al. Sex-specific associations between umbilical cord blood testosterone levels and language delay in early childhood. J Child Psychol Psychiatry (2012) 53(7):726-34. doi:10.1111/j.1469-7610.2011.02523.x
71. Robinson M, Whitehouse AJO, Jacoby P, Mattes E, Sawyer MG, Keelan JA, et al. Umbilical cord blood testosterone and childhood internalizing and externalizing behavior: a prospective study. PLoS One (2013) 8(4):e59991. doi:10.1371/journal.pone.0059991
72. Rescorla L. The language development survey: a screening tool for delayed language in toddlers. J Speech Hear Disord (1989) 54(4):587-99.
73. Berglund EVA, Eriksson M, Westerlund M. Communicative skills in relation to gender, birth order, childcare and socioeconomic status in 18-month-old children. Scand J Psychol (2005) 46(6):485-91. doi:10.1111/j.1467-9450.2005.00480.x
74. Feldman HM, Dollaghan CA, Campbell TF, Kurs-Lasky M, Janosky JE, Paradise JL. Measurement properties of the Macarthur communicative development inventories at ages one and two years. Child Dev (2000) 71(2):310-22. doi:10.1111/1467-8624.00146
75. Zubrick SR, Taylor CL, Rice ML, Slegers DW. Late language emergence at 24 months: an epidemiological study of prevalence, predictors, and covariates. J Speech Lang Hear Res (2007) 50(6):1562-92. doi:10.1044/1092-4388(2007/106)
76. Squires J, Bricker D, Potter A. Infant/Child Monitoring Questionnaires Procedures Manual. Eugene: University of Oregon (1990).
77. Knickmeyer RC, Baron-Cohen S, Raggatt P, Taylor K. Foetal testosterone, social relationships, and restricted interests in children. J Child Psychol Psychiatry (2005) 46(2):198-210. doi:10.1111/j.1469-7610.2004.00349.x
78. Fullard W, McDevitt SC, Carey WB. Assessing temperament in one-to three-year-old children. J Pediat Psychol (1984) 9(2):205-17. doi:10.1093/jpepsy/9.2.205
79. Dunn LM, Dunn LM. Peabody Picture and Vocabulary Test. 4th ed. Bloomington: Pearson (2007).
80. Baron-Cohen S, Wheelwright S, Skinner R, Martin J, Clubley E. The autism-spectrum quotient (aq): evidence from Asperger syndrome/high-functioning autism, males and females, scientists and mathematicians. J Autism Dev Disord (2001) 31(1):5-17. doi:10.1023/A:1005653411471
81. Auyeung B, Taylor K, Hackett G, Baron-Cohen S. Foetal testosterone and autistic traits in 18 to 24-month-old children. Mol Autism (2010) 1(1):11. doi:10.1186/2040-2392-1-11
82. Lutchmaya S, Baron-Cohen S, Raggatt P. Foetal testosterone and eye contact in 12-month-old human infants. Infant Behav Dev (2002) 25(3):327-35. doi:10.1016/S0163-6383(02)00094-2
83. Auyeung B, Baron-Cohen S, Ashwin E, Knickmeyer R, Taylor K, Hackett G. Fetal testosterone and autistic traits. Br J Psychol (2009) 100:1-22. doi:10.1348/000712608X311731
84. Achenbach TM. Manual for the Child Behaviour Checklist/4-18. Burlington: University of Vermont (1991).
85. Achenbach TM, Edelbrock C, Howell CT. Empirically based assessment of the behavioral/emotional problems of 2- and 3-year-old children. J Abnorm Child Psychol (1987) 15(4):629-50. doi:10.1007/BF00917246
86. Roselli CE, Estill CT, Stadelman HL, Meaker M, Stormshak F. Separate critical periods exist for testosterone-induced differentiation of the brain and genitals in sheep. Endocrinology (2011) 152(6):2409-15. doi:10.1210/en.2010-1445