European Journal of Nutrition

, Volume 58, Issue 2, pp 681–687 | Cite as

Consumption of soy-based infant formula is not associated with early onset of puberty

  • Tali SinaiEmail author
  • Shely Ben-Avraham
  • Inbal Guelmann-Mizrahi
  • Michael R. Goldberg
  • Larisa Naugolni
  • Galia Askapa
  • Yitzhak Katz
  • Marianna Rachmiel
Original Contribution



The use of soy products is common in young children with cow milk allergy (CMA). The aim was to examine prospectively the association between infantile consumption of soy-based formula, growth parameters and early pubertal signs, in comparison to cow milk-based formula.


A nested case–control study was conducted, selected from a cohort of infants prospectively followed from birth until the age of 3 years for eating habits and the development of IgE-mediated CMA. Infants who consumed only soy-based formula were included in the soy group. The control group was randomly selected from those without IgE-CMA and not receiving soy formula. Study participants were reevaluated between ages 7.8 and 10.5 years by an interview, nutritional intake by 3 days diaries, and height, weight, and pubertal signs by physical examination.


The soy-fed group included 29 participants (17 males), median age 8.92 years IQR (8.21, 9.42). The control group included 60 participants (27 males), median age 8.99 years IQR (8.35, 9.42). The groups had comparable height and BMI z scores (− 0.17 ± 1.08 versus − 0.16 ± 1.01, p = 0.96, and 0.67 ± 1.01 versus 0.53 ± 1.02, p = 0.56, for soy and control groups, respectively). Four (three males and one female) from the soy-group (13.8%) and eight females from the control-group (13.3%) had early pubertal signs (p = 0.95). No association was detected between puberty and infantile nutrition, after controlling for BMI and family data. No association with puberty or differences between groups were found in current daily consumption of soy, micronutrients, energy, carbohydrates, fat, and protein.


This is the first prospective, physical examination-based study, demonstrating no association between infantile soy-based formula consumption and growth and puberty parameters.


Growth Children BMI Prospective Cow milk allergy Nutritional intake 



The authors would like to thank Dr. Aliza Stark for her help in manuscript editing and Dr. Tomer Ziv for the statistical analysis.

Compliance with ethical standards

Conflict of interest

There are no reported conflicts of interest for any of the authors.

Source of funding

Michael R. Goldberg is supported by a Kamea grant from the Ministry of Health, Israel. No honorarium, grant, or other form of payment was given to produce the manuscript.

Research registration

Website: ID Number: NCT02908971.


  1. 1.
    Messina M, Messina V (2010) The role of soy in vegetarian diets. Nutrients 2:855–888. CrossRefGoogle Scholar
  2. 2.
    Rossen LM, Simon AE, Herrick KA (2016) Types of infant formulas consumed in the United States. Clin Pediatr (Phila) 55:278–285. CrossRefGoogle Scholar
  3. 3.
    Vandenplas Y, De Greef E, Devreker T (2014) Treatment of cow’s milk protein allergy. Pediatr Gastroenterol Hepatol Nutr 17:1–5. CrossRefGoogle Scholar
  4. 4.
    Patisaul HB, Jefferson W (2010) The pros and cons of phytoestrogens. Front Neuroendocrinol 31:400–419. CrossRefGoogle Scholar
  5. 5.
    Setchell KD, Zimmer-Nechemias L, Cai J, Heubi JE (1997) Exposure of infants to phyto-oestrogens from soy-based infant formula. Lancet 350:23–27. CrossRefGoogle Scholar
  6. 6.
    Biro FM, Greenspan LC, Galvez MP (2012) Puberty in girls of the 21st century. J Pediatr Adolesc Gynecol 25:289–294. CrossRefGoogle Scholar
  7. 7.
    Carel JC, Lahlou N, Roger M, Chaussain JL (2004) Precocious puberty and statural growth. Hum Reprod Update 10:135–147. CrossRefGoogle Scholar
  8. 8.
    Downing J, Bellis MA (2009) Early pubertal onset and its relationship with sexual risk taking, substance use and anti-social behaviour: a preliminary cross-sectional study. BMC Public Health 9:446. CrossRefGoogle Scholar
  9. 9.
    Prentice P, Viner R (2013) Pubertal timing and adult obesity and cardiometabolic risk in women and men: a systematic review and meta-analysis. Int J Obes (Lond) 37:1036–1043. CrossRefGoogle Scholar
  10. 10.
    Collaborative Group on Hormonal Factors in Breast Cancer (2012) Menarche, menopause, and breast cancer risk: individual participant meta-analysis, including 118 964 women with breast cancer from 117 epidemiological studies. Lancet Oncol 13:1141–1151. CrossRefGoogle Scholar
  11. 11.
    Strom BL, Schinnar R, Ziegler EE et al (2001) Exposure to soy-based formula in infancy and endocrinological and reproductive outcomes in young adulthood. JAMA 286:807–814CrossRefGoogle Scholar
  12. 12.
    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. CrossRefGoogle Scholar
  13. 13.
    Segovia-Siapco G, Pribis P, Messina M, Oda K, Sabaté J (2014) Is soy intake related to age at onset of menarche? A cross-sectional study among adolescents with a wide range of soy food consumption. Nutr J 13:54. CrossRefGoogle Scholar
  14. 14.
    Cheng G, Remer T, Prinz-Langenohl R, Blaszkewicz M, Degen GH, Buyken AE (2010) Relation of isoflavones and fiber intake in childhood to the timing of puberty. Am J Clin Nutr 92:556–564. CrossRefGoogle Scholar
  15. 15.
    Giampietro PG, Bruno G, Furcolo G et al (2004) Soy protein formulas in children: no hormonal effects in long-term feeding. J Pediatr Endocrinol Metab 17:191–196CrossRefGoogle Scholar
  16. 16.
    Andres A, Moore MB, Linam LE, Casey PH, Cleves MA, Badger TM (2015) Compared with feeding infants breast milk or cow-milk formula, soy formula feeding does not affect subsequent reproductive organ size at 5 years of age. J Nutr 145:871–875. CrossRefGoogle Scholar
  17. 17.
    Freni-Titulaer LW, Cordero JF, Haddock L, Lebrón G, Martínez R, Mills JL (1986) Premature thelarche in Puerto Rico. A search for environmental factors. Am J Dis Child 140:1263–1267CrossRefGoogle Scholar
  18. 18.
    Zung A, Glaser T, Kerem Z, Zadik Z (2008) Breast development in the first 2 years of life: an association with soy-based infant formulas. J Pediatr Gastroenterol Nutr 46:191–195. CrossRefGoogle Scholar
  19. 19.
    Kim J, Kim S, Huh K, Kim Y, Joung H, Park M (2011) High serum isoflavone concentrations are associated with the risk of precocious puberty in Korean girls. Clin Endocrinol (Oxf) 75:831–835. CrossRefGoogle Scholar
  20. 20.
    Adgent MA, Daniels JL, Rogan WJ et al (2012) Early-life soy exposure and age at menarche. Paediatr Perinat Epidemiol 26:163–175. CrossRefGoogle Scholar
  21. 21.
    Katz Y, Rajuan N, Goldberg MR et al (2010) Early exposure to cow’s milk protein is protective against IgE-mediated cow’s milk protein allergy. J Allergy Clin Immunol 126:77–82. CrossRefGoogle Scholar
  22. 22.
    Kuczmarski RJ, Ogden CL, Grummer-Strawn LM et al (2000) CDC growth charts: United States. Adv Data 314:1–27Google Scholar
  23. 23.
    Marshall WA, Tanner JM (1969) Variations in pattern of pubertal changes in girls. Arch Dis Child 44:291–303CrossRefGoogle Scholar
  24. 24.
    Marshall WA, Tanner JM (1970) Variations in the pattern of pubertal changes in boys. Arch Dis Child 45:13–23CrossRefGoogle Scholar
  25. 25.
    Tzameret [computer program] (2010) Version 2. Jerusalem: Israeli Ministry of HealthGoogle Scholar
  26. 26.
    National Agricultural Library, United States Department of Agriculture United States: Food and Nutrition Information Center. DRI tables and application reports; Available at: Accessed 22 Nov 2017
  27. 27.
    Biro FM, Galvez MP, Greenspan LC et al (2010) Pubertal assessment method and baseline characteristics in a mixed longitudinal study of girls. Pediatrics 126:e583–e590. CrossRefGoogle Scholar
  28. 28.
    Garibaldi L, Chemaitilly W (2015) Disorders of pubertal development. In: Kliegman RM, Stanton BF,, Schor NF, Behrman RE, eds. Nelson textbook of pediatrics St. Geme JW, 20th edn. Elsevier, Philadelphia, pp 2656–2662Google Scholar
  29. 29.
    Wohlfahrt-Veje C, Mouritsen A, Hagen CP et al (2016) Pubertal onset in boys and girls is influenced by pubertal timing of both parents. J Clin Endocrinol Metab 101:2667–2674. CrossRefGoogle Scholar
  30. 30.
    Sloboda DM, Hart R, Doherty DA, Pennell CE, Hickey M (2007) Age at menarche: influences of prenatal and postnatal growth. J Clin Endocrinol Metab 92:46–50. CrossRefGoogle Scholar
  31. 31.
    Kaplowitz PB (2008) Link between body fat and the timing of puberty. Pediatrics 121:S208–S217. CrossRefGoogle Scholar
  32. 32.
    Kale A, Deardorff J, Lahiff M et al (2015) Breastfeeding versus formula-feeding and girls’ pubertal development. Matern Child Health J 19:519–27. .CrossRefGoogle Scholar
  33. 33.
    Villamor E, Jansen EC (2016) Nutritional determinants of the timing of puberty. Annu Rev Public Health 37:33–46. CrossRefGoogle Scholar
  34. 34.
    Bacil EDA, Mazzardo O, Rech CR, Legnani RF, dos de Campos SW (2015) Physical activity and biological maturation: a systematic review. Revista Paulista de Pediatria 33:114–121. CrossRefGoogle Scholar
  35. 35.
    Baranowski T (2013) 24-h recall and diet record methods. In: Willett W (ed) Nutritional epidemiology, 3rd edn. Oxford University Press, New York, pp 49–69Google Scholar
  36. 36.
    Ministry of Health. Mabat Youth- First Israeli National Health and Nutrition Survey. Available at: Accessed 22 Nov 2017
  37. 37.
    Vandenplas Y, Castrellon PG, Rivas R et al (2014) Safety of soya-based infant formulas in children. Br J Nutr 111:1340–1360. CrossRefGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  1. 1.School of Nutritional Sciences, Institute of Biochemistry, Food Science and NutritionThe Hebrew University of JerusalemRehovotIsrael
  2. 2.Pediatric Endocrinology UnitAssaf-Harofeh Medical CenterZerifinIsrael
  3. 3.Allergy and Immunology InstituteAssaf-Harofeh Medical CenterZerifinIsrael
  4. 4.Sackler Faculty of MedicineTel Aviv UniversityTel AvivIsrael

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