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Research Letter |

Association of Breastfeeding With Higher Serum Inhibin B Level at Adolescence FREE

Alfred Bernard, PhD1; Marc Nickmilder, PhD1
[+] Author Affiliations
1Unit of Toxicology and Applied Pharmacology, Catholic University of Louvain, Brussels, Belgium
JAMA Pediatr. 2013;167(9):869-870. doi:10.1001/jamapediatrics.2013.95.
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Published online

Breastfeeding has a number of beneficial effects on child growth and development.1 Surprisingly, however, very few data exist about the possible influence of breastfeeding on the development of the male reproductive system, which is known to be particularly vulnerable to hormone dysregulation. A recent study2 in young adults found no association between breastfeeding and male fertility but most subjects examined in this study had been exposed to maternal smoking during pregnancy, which is an important risk and confounding factor.3 Herein, we report observations among school-aged adolescents showing for the first time, to our knowledge, a beneficial effect of breastfeeding on testes development.

The ethics committee of the Faculty of Medicine of the Catholic University approved the study, which was conducted with the assent of all adolescents and the informed consent of their parents. Study participants were secondary school–aged male adolescents (participation rate, 72%) who were examined in a cross-sectional study evaluating the impact of environmental stressors on adolescent health.4 Of 361 recruited subjects, we excluded 108 subjects with no information about breastfeeding duration and another 55 subjects who were smokers or who had been exposed to maternal smoking during pregnancy. Because there were only 6 subjects who had been exclusively breastfed, we could only study the influence of the total breastfeeding duration. To consolidate our study, we measured inhibin B with 2 different methods: the Oxford Bio-Innovation (OBI) enzyme-linked immunosorbent assay and the Diagnostic System Laboratories (DSL) enzyme-linked immunosorbent assay. Other hormones were measured by the Immulite assay. We used stepwise regression analyses to assess the influence of breastfeeding while adjusting for potential confounders. When age and time of blood sampling were not retained, they were forced in the models. After adjustment for model covariates, we stratified subjects according to breastfeeding duration and compared inhibin B levels by analysis of variance and the Bonferroni-Dunn post hoc test. Continuous variables were normalized by cubic root (inhibin B and testosterone levels) or log transformation. The threshold for statistical significance was a 2-sided α level of .05.

As shown in the Table, adolescents who had been breastfed as infants were well matched with those who were not with respect to age, birth weight, body mass index, and time of blood sampling. While there were no significant differences in gonadotropin and testosterone levels, inhibin B measured by the OBI or DSL method was significantly higher in breastfed adolescents than in their peers. Multiple regression analyses confirmed this increase of inhibin B associated with breastfeeding, whether testing follicle-stimulating hormone or not among predictors (all P < .02). The Figure shows that the covariate-adjusted concentrations of OBI and DSL inhibin B increased dose dependently with the duration of breastfeeding. Associations were the strongest with the DSL inhibin B concentration, with a median increase up to 25% in the group breastfed for more than 4 months. A similar increase was seen in the prevalences of high values of OBI and DSL inhibin B (>90th percentile of values in controls) that were 3 times higher when breastfeeding duration exceeded 4 months (no follicle-stimulating hormone adjustment, P for trend = .08 and .05; follicle-stimulating hormone adjustment, P for trend = .02 and .003, respectively)

Table Graphic Jump LocationTable.  Characteristics and Reproductive Hormone Levels of Study Participants
Place holder to copy figure label and caption
Figure.
Serum Inhibin B Levels in School-Aged Adolescents According to the Total Duration of Breastfeeding

The middle horizontal bars represent the median values; the upper and lower limits of the boxes, the interquartile range; and the whiskers, the 10th and 90th percentiles. Inhibin B level was adjusted for age, time of blood sampling, and the cumulative attendance at indoor chlorinated pools before the age of 10 years. The group of breastfed adolescents was dichotomized at the median split of breastfeeding duration. P values represent the Bonferroni-adjusted P values for the comparison of breastfed groups (n = 61 in each group) with the nonbreastfed group (n = 76). DSL indicates Diagnostic System Laboratories; FSH, follicle-stimulating hormone; and OBI, Oxford Bio-Innovation.

Graphic Jump Location

Serum inhibin B is a marker of the Sertoli cell number that determines testis size and sperm production in adults. Sertoli cells develop during fetal and neonatal life and also at puberty when their number is definitively set. Our study suggests that breastfeeding is important for neonatal testes development because the inhibin B increase associated with breastfeeding was of the same magnitude as the proportion of Sertoli cells formed during the first year of life.5

Corresponding Author: Alfred Bernard, PhD, Unit of Toxicology and Applied Pharmacology, Catholic University of Louvain, 30.54 Clos Chapelle-aux-Champs, B-1200, Brussels 1200, Belgium (alfred.bernard@uclouvain.be).

Published Online: July 8, 2013. doi:10.1001/jamapediatrics.2013.95.

Author Contributions: Drs Bernard and Nickmilder had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.

Study concept and design: Bernard.

Acquisition of data: All authors.

Analysis and interpretation of data: All authors.

Drafting of the manuscript: Bernard.

Critical revision of the manuscript for important intellectual content: All authors.

Statistical analysis: All authors.

Obtained funding: All authors.

Administrative, technical, and material support: All authors.

Study supervision: Bernard.

Conflict of Interest Disclosures: None reported.

Correction: This article was corrected online September 2, 2013, for a typographical error in the Methods section.

Section on Breastfeeding.  Breastfeeding and the use of human milk. Pediatrics. 2012;129(3):e827-e841.
PubMed   |  Link to Article
Laustsen  JM, Jensen  MS, Thulstrup  AM,  et al.  Does breastfeeding influence future sperm quality and reproductive hormones? Int J Androl. 2011;34(2):165-172.
PubMed   |  Link to Article
Ramlau-Hansen  CH, Thulstrup  AM, Aggerholm  AS, Jensen  MS, Toft  G, Bonde  JP.  Is smoking a risk factor for decreased semen quality? a cross-sectional analysis. Hum Reprod. 2007;22(1):188-196.
PubMed   |  Link to Article
Nickmilder  M, Bernard  A.  Associations between testicular hormones at adolescence and attendance at chlorinated swimming pools during childhood. Int J Androl. 2011;34(5, pt 2):e446-e458.
PubMed   |  Link to Article
Sharpe  RM, McKinnell  C, Kivlin  C, Fisher  JS.  Proliferation and functional maturation of Sertoli cells, and their relevance to disorders of testis function in adulthood. Reproduction. 2003;125(6):769-784.
PubMed   |  Link to Article

Figures

Place holder to copy figure label and caption
Figure.
Serum Inhibin B Levels in School-Aged Adolescents According to the Total Duration of Breastfeeding

The middle horizontal bars represent the median values; the upper and lower limits of the boxes, the interquartile range; and the whiskers, the 10th and 90th percentiles. Inhibin B level was adjusted for age, time of blood sampling, and the cumulative attendance at indoor chlorinated pools before the age of 10 years. The group of breastfed adolescents was dichotomized at the median split of breastfeeding duration. P values represent the Bonferroni-adjusted P values for the comparison of breastfed groups (n = 61 in each group) with the nonbreastfed group (n = 76). DSL indicates Diagnostic System Laboratories; FSH, follicle-stimulating hormone; and OBI, Oxford Bio-Innovation.

Graphic Jump Location

Tables

Table Graphic Jump LocationTable.  Characteristics and Reproductive Hormone Levels of Study Participants

References

Section on Breastfeeding.  Breastfeeding and the use of human milk. Pediatrics. 2012;129(3):e827-e841.
PubMed   |  Link to Article
Laustsen  JM, Jensen  MS, Thulstrup  AM,  et al.  Does breastfeeding influence future sperm quality and reproductive hormones? Int J Androl. 2011;34(2):165-172.
PubMed   |  Link to Article
Ramlau-Hansen  CH, Thulstrup  AM, Aggerholm  AS, Jensen  MS, Toft  G, Bonde  JP.  Is smoking a risk factor for decreased semen quality? a cross-sectional analysis. Hum Reprod. 2007;22(1):188-196.
PubMed   |  Link to Article
Nickmilder  M, Bernard  A.  Associations between testicular hormones at adolescence and attendance at chlorinated swimming pools during childhood. Int J Androl. 2011;34(5, pt 2):e446-e458.
PubMed   |  Link to Article
Sharpe  RM, McKinnell  C, Kivlin  C, Fisher  JS.  Proliferation and functional maturation of Sertoli cells, and their relevance to disorders of testis function in adulthood. Reproduction. 2003;125(6):769-784.
PubMed   |  Link to Article

Correspondence

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