Skip to main content
SpringerLink
Log in

US assessment of estrogen-responsive organ growth among healthy term infants: piloting methods for assessing estrogenic activity

  • Original Article
  • Published:
Pediatric Radiology Aims and scope Submit manuscript

Abstract

Background

A mother’s circulating estrogen increases over the third trimester, producing physiological effects on her newborn that wane postnatally. Estrogenization might be prolonged in newborns exposed to exogenous estrogens, such as isoflavones in soy formula.

Objective

We evaluated ultrasonography for monitoring growth of multiple estrogen-responsive organs in healthy infants and developed organ-growth trajectories.

Materials and methods

We studied 38 boys (61 visits) from birth to age 6 months and 41 girls (96 visits) from birth to age 1 year using a partly cross-sectional, partly longitudinal design. We measured uterus and ovaries in girls, testes and prostate in boys, and kidneys, breasts, thymus, and thyroid in all children. We imaged all organs from the body surface in one session of < 1 h.

Results

Uterine volume decreased from birth (P < 0.0001), whereas ovarian volume increased sharply until age 2 months and then decreased (P < 0.001). Testicular volume increased with age (P < 0.0001), but prostatic volume showed minimal age trend. Breast bud diameter showed no age trend in girls but declined from birth in boys (P = 0.03).

Conclusion

US examination of multiple estrogen-responsive organs in infants in a single session is feasible and yields volume estimates useful for assessing potential endocrine disruptor effects on organ growth.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8

Similar content being viewed by others

References

  1. Rogan WJ, Ragan NB (2007) Some evidence of effects of environmental chemicals on the endocrine system in children. Int J Hyg Environ Health 210:659–667

    Article  PubMed  CAS  Google Scholar 

  2. Rozman KK, Bhatia J, Calafat AM et al (2006) NTP-CERHR expert panel report on the reproductive and developmental toxicity of genistein. Birth Defects Res B Dev Reprod Toxicol 77:485–638

    Article  PubMed  CAS  Google Scholar 

  3. Rozman KK, Bhatia J, Calafat AM et al (2006) NTP-CERHR expert panel report on the reproductive and developmental toxicity of soy formula. Birth Defects Res B Dev Reprod Toxicol 77:280–397

    Article  PubMed  CAS  Google Scholar 

  4. Arbuckle TE, Hauser R, Swan SH et al (2008) Meeting report: measuring endocrine-sensitive endpoints within the first years of life. Environ Health Perspect 116:948–951

    Article  PubMed  Google Scholar 

  5. Bernbaum JC, Umbach DM, Ragan NB et al (2008) Pilot studies of estrogen-related physical findings in infants. Environ Health Perspect 116:416–420

    Article  PubMed  Google Scholar 

  6. Borgert CJ, LaKind JS, Witorsch RJ (2003) A critical review of methods for comparing estrogenic activity of endogenous and exogenous chemicals in human milk and infant formula. Environ Health Perspect 111:1020–1036

    Article  PubMed  CAS  Google Scholar 

  7. American Academy of Pediatrics Committee on Nutrition (1998) Soy protein-based formulas: recommendations for use in infant feeding. Pediatrics 101:148–153

    Article  Google Scholar 

  8. Setchell KD, Zimmer-Nechemias L, Cai J et al (1997) Exposure of infants to phytoestrogens from soy-based infant formula. Lancet 350:23–27

    Article  PubMed  CAS  Google Scholar 

  9. Setchell KD, Zimmer-Nechemias L, Cai J et al (1998) Isoflavone content of infant formulas and the metabolic fate of these phytoestrogens in early life. Am J Clin Nutr 68:1453S–1461S

    PubMed  CAS  Google Scholar 

  10. Barnes S (2004) Soy isoflavones—phytoestrogens and what else? J Nutr 134:1225S–1228S

    PubMed  Google Scholar 

  11. Schmidt IM, Damgaard IN, Boisen KA et al (2004) Increased kidney growth in formula-fed versus breast-fed healthy infants. Pediatr Nephrol 19:1137–1144

    PubMed  Google Scholar 

  12. Hasselbalch H, Jeppesen DL, Engelmann MD et al (1996) Decreased thymus size in formula-fed infants compared with breastfed infants. Acta Paediatr 85:1029–1032

    Article  PubMed  CAS  Google Scholar 

  13. Jeppesen DL, Hasselbalch H, Nielsen SD et al (2003) Thymic size in preterm neonates: a sonographic study. Acta Paediatr 92:817–822

    Article  PubMed  CAS  Google Scholar 

  14. Jeppesen D, Hasselbalch H, Ersboll AK et al (2003) Thymic size in uninfected infants born to HIV-positive mothers and fed with pasteurized human milk. Acta Paediatr 92:679–683

    Article  PubMed  CAS  Google Scholar 

  15. Aaby P, Marx C, Trautner S et al (2002) Thymus size at birth is associated with infant mortality: a community study from Guinea-Bissau. Acta Paediatr 91:698–703

    Article  PubMed  CAS  Google Scholar 

  16. Cohen HL, Shapiro MA, Mandel FS et al (1993) Normal ovaries in neonates and infants: a sonographic study of 77 patients 1 day to 24 months old. AJR 160:583–586

    PubMed  CAS  Google Scholar 

  17. Hasselbalch H, Nielsen MB, Jeppesen D et al (1996) Sonographic measurement of the thymus in infants. Eur Radiol 6:700–703

    Article  PubMed  CAS  Google Scholar 

  18. Ingram S, Hollman AS, Azmy AF (1994) Ultrasound evaluation of the paediatric prostate. Br J Urol 74:601–603

    Article  PubMed  CAS  Google Scholar 

  19. Khadilkar VV, Khadilkar AV, Kinare AS et al (2006) Ovarian and uterine ultrasonography in healthy girls between birth to 18 years. Indian Pediatr 43:625–630

    PubMed  CAS  Google Scholar 

  20. Kuijper EA, van Kooten J, Verbeke JI et al (2008) Ultrasonographically measured testicular volumes in 0- to 6-year-old boys. Hum Reprod 23:792–796

    Article  PubMed  CAS  Google Scholar 

  21. Perry RJ, Hollman AS, Wood AM et al (2002) Ultrasound of the thyroid gland in the newborn: normative data. Arch Dis Child Fetal Neonatal Ed 87:F209–F211

    Article  PubMed  CAS  Google Scholar 

  22. Schmidt IM, Main KM, Damgaard IN et al (2004) Kidney growth in 717 healthy children aged 0–18 months: a longitudinal cohort study. Pediatr Nephrol 19:992–1003

    PubMed  Google Scholar 

  23. Soyupak SK, Narli N, Yapicioglu H et al (2002) Sonographic measurements of the liver, spleen and kidney dimensions in the healthy term and preterm newborns. Eur J Radiol 43:73–78

    Article  PubMed  Google Scholar 

  24. Stettler N (2007) Nature and strength of epidemiological evidence for origins of childhood and adulthood obesity in the first year of life. Int J Obes (Lond) 31:1035–1043

    Article  CAS  Google Scholar 

  25. Ostrom KM, Cordle CT, Schaller JP et al (2002) Immune status of infants fed soy-based formulas with or without added nucleotides for 1 year. Part 1: vaccine responses, and morbidity. J Pediatr Gastroenterol Nutr 34:137–144

    Article  PubMed  CAS  Google Scholar 

  26. Zerin JM, Blane CE (1994) Sonographic assessment of renal length in children: a reappraisal. Pediatr Radiol 24:101–106

    Article  PubMed  CAS  Google Scholar 

  27. Cao Y, Calafat AM, Doerge DR et al (2009) Isoflavones in urine, saliva, and blood of infants: data from a pilot study on the estrogenic activity of soy formula. J Expo Sci Environ Epidemiol 19:223–234

    Article  PubMed  CAS  Google Scholar 

  28. Haber HP, Mayer EI (1994) Ultrasound evaluation of uterine and ovarian size from birth to puberty. Pediatr Radiol 24:11–13

    Article  PubMed  CAS  Google Scholar 

  29. Cnaan A, Laird NM, Slasor P (1997) Using the general linear mixed model to analyse unbalanced repeated measures and longitudinal data. Stat Med 16:2349–2380

    Article  PubMed  CAS  Google Scholar 

  30. Winter JS, Hughes IA, Reyes FI et al (1976) Pituitary-gonadal relations in infancy: 2. Patterns of serum gonadal steroid concentrations in man from birth to 2 years of age. J Clin Endocrinol Metab 42:679–686

    Article  PubMed  CAS  Google Scholar 

  31. Hasselbalch H, Jeppesen DL, Ersboll AK et al (1997) Thymus size evaluated by sonography: a longitudinal study on infants during the first year of life. Acta Radiol 38:222–227

    PubMed  CAS  Google Scholar 

  32. Gilchrist JM, Moore MB, Andres A et al (2010) Ultrasonographic patterns of reproductive organs in infants fed soy formula: comparisons to infants fed breast milk and milk formula. J Pediatr 156:215–220

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgements

This research was supported by the Intramural Research Program of the NIH, National Institute of Environmental Health Sciences (NIEHS). RHNN was an NIEHS Intramural Postdoctoral Fellow at the time of this work. The authors appreciate study coordination and analysis assistance of Janet Archer and Holly Schmidt-Davis; clinical contributions of Jane Share, Kathy Howard, Julie Hart, and Deirdre Ellard; recruitment assistance by Drs. Joanne Cox and Lise Johnson; imaging supervision at BWH by Dr. Carol Benson, and imaging by all participating sonologists at BWH and Children’s Hospital Boston.

Author information

Authors and Affiliations

  1. Division of Epidemiology & Community Health, University of Minnesota, Minneapolis, MN, USA

    Ruby H. N. Nguyen

  2. Epidemiology Branch, National Institute of Environmental Health Sciences, NIH, Research Triangle Park, NC, USA

    Ruby H. N. Nguyen & Walter J. Rogan

  3. Biostatistics Branch, National Institute of Environmental Health Sciences, NIH, P. O. Box 12233, Research Triangle Park, NC, 27709-2233, USA

    David M. Umbach

  4. Department of Newborn Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA

    Richard B. Parad

  5. Division of Newborn Medicine, Children’s Hospital Boston, Harvard Medical School, Boston, MA, USA

    Richard B. Parad

  6. Social and Scientific Systems Inc., Durham, NC, USA

    Berrit Stroehla

  7. Department of Radiology, Children’s Hospital Boston, Harvard Medical School, Boston, MA, USA

    Judy A. Estroff

Authors
  1. Ruby H. N. Nguyen
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. David M. Umbach
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Richard B. Parad
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Berrit Stroehla
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Walter J. Rogan
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Judy A. Estroff
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to David M. Umbach.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Nguyen, R.H.N., Umbach, D.M., Parad, R.B. et al. US assessment of estrogen-responsive organ growth among healthy term infants: piloting methods for assessing estrogenic activity. Pediatr Radiol 41, 633–642 (2011). https://doi.org/10.1007/s00247-010-1895-0

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00247-010-1895-0

Keywords

Search

Navigation