Is There an Association of Being Breastfed as an Infant and Fertility Status as an Adult?

Abstract

Background:

Breastfeeding has many short-term and long-term health benefits for infants. Short-term benefits include protection against childhood infections and mortality in low-income countries. The adult long-term effects usually emphasized are a reduction of excess weight and type 2 diabetes. However, there is a lack of available data on the impact of having been breastfed on adult fertility. Indeed, infertility probably has a multifactorial origin, including an environmental origin. The aim of this study was to investigate whether having been breastfed could be associated with unexplained infertility.

Materials and Methods:

This research is an ancillary study of the case–control study ALIFERT, for which both fertile and infertile couples were recruited. Breastfeeding statuses, collected from childhood health records, were compared among fertile and infertile individuals. Anthropometrics parameters were also used for analysis.

Results:

About 65.6% of infertile women and 63.3% of fertile women were breastfed, and 69% of infertile men and 67.4% of fertile men were breastfed. There was no statistically significant difference between fertile and infertile groups. Nevertheless, infertile women who were not breastfed had a significantly higher body mass index than those who were breastfed (25.8 kg/m² vs. 23.2 kg/m²).

Conclusion:

In our study, we did not observe any association between having been breastfed and fertility in adulthood. However, we observed that, in infertile women, having not been breastfed may influence weight in adulthood. Trial registration: NCT01093378 ALIFERT. Registered: March 25, 2010.

Introduction

Several studies have reported that breastfeeding has many short- and long-term health benefits to infants. In 2001, World Health Organization (WHO) gave some worldwide recommendations on breastfeeding. Specifically, it encouraged exclusive breastfeeding until the age of 6 months.¹ More evidence based on a systematic literature review published in 2007 confirmed these recommendations.² These observations published by the WHO were recently confirmed in a meta-analysis published in The Lancet.³ The short-term benefits highlighted were a protection against childhood infection such as diarrhea and respiratory infections. Forty-six studies conducted in low-income countries showed that breastfeeding is associated with a 68% reduction in malocclusions.⁴ A reduction of the risk of death in high-income countries was also highlighted.⁵

Long-term effects of breastfeeding were associated with a 13% reduction in adults becoming overweight or obese and a 35% reduction in the incidence of type 2 diabetes in adulthood.³ Having been breastfed was also associated with increased performance in intelligence tests during childhood and adolescence, with a 3- to 4-point increase in intelligence quotient (IQ) points.⁶

Given the manifest health benefits of breastfeeding, we wondered about the possibility of an association between having been breastfed and fertility in adulthood. To our knowledge, there is no published research on this particular aspect of breastfeeding.

Few animal studies have been published about the influence of newborns overfeeding or underfeeding on their reproductive functions. Castellano demonstrated the influence of changes in early postnatal feeding on the timing of puberty and development of the hypothalamic kisspeptin system involved in the reproductive function.⁷ These results have been confirmed by Caron's study.⁸ They showed that neonatally undernourished and overnourished women display perturbed development of neural projections from the arcuate nucleus to the preoptic region with adverse consequences on neural projection of kisspeptin and puberty onset.

These experiments underline the importance of early nutrition in the development of the reproductive system. Similarly, having been breastfed has largely been described as protective against several illnesses; thus, in this article, we intended to evaluate if it may impact fertility in adulthood. To answer to this question, we compared the breastfeeding status of both fertile and infertile couples.

Materials and Methods

Couple recruitment

Data from patients recruited for the ALIFERT case–control study were analyzed.⁹ The purpose of the ALIFERT study was to evaluate the link between unexplained infertility and the patient's nutritional behavior. Unexplained infertility is defined by a lack of diagnosis for couples that have failed to conceive after 1 year of unprotected sexual intercourse. Standard investigation protocol of unexplained infertility is somewhat limited and mainly involves normal ovulation and tubal assessment for women, as well as normal semen analysis for men.

Couples were recruited from September 2009 to December 2013 from four fertility centers in France (Jean Verdier Hospital in Bondy, Cochin Hospital in Paris, North Hospital in Saint Etienne, and Polyclinic Navarre in Pau).

The inclusion criteria for the infertile groups were as follows: individuals who had experienced >12 months of unexplained infertility; female or male age between 18 and 38, or 18 and 45 years, respectively; and individuals being in possession of childhood health records.

The fertile couples were healthy volunteers recruited nearby these hospitals. The inclusion criteria for the fertile group were as follows: female or male age between 18 and 38, or 18 to 45 years, respectively, individuals who were the biological parent of a child under 2 years of age, spontaneously conceived in <12 months, and in possession of their childhood health records.

Data collection

To avoid reporting bias, only childhood health records completed by doctors were accepted as viable records of a participant's breastfeeding status. Each participant had his or her weight and height measured by the same trained investigator, using the same calibrated devices. The body mass index (BMI) of each participant was calculated as the weight in kilograms divided by the square of height in meters.

All participants gave their written informed consent. The ALIFERT study was approved by an ethics committee. (National biomedical research ID no. P071224; ethics committee approval [“Comité de Protection des Personnes”] ID no. AOM 2009-A00256–51; NEudra CT ID no. 08180; ClinicalTrials.gov ID no. NCT01093378).

Statistical analysis

Data were summarized using means and standard deviations. Statistical differences were analyzed using unpaired Student's t test for the quantitative data; and the chi-squared test for the qualitative data. p < 0.05 was considered significant.

Results

A total of 93 infertile women, 98 fertile women, 87 infertile men and 95 fertile men were included in this ancillary study. All participants were born at term (gestational age was between 37 and 41 weeks of amenorrhea).

Age, BMI, and breastfeeding status of the participants are given in Table 1. Fertile and infertile men had comparable ages, whereas fertile women were slightly older than the infertile women. The BMI of infertile men and women was significantly higher than fertile participants.

Table 1.

Age, Body Mass Index and Breastfeeding Status of the Fertile and Infertile Women and Men

	Infertile women	Fertile women	Infertile men	Fertile men
Total	93	98	87	95
Age	30.9 ± 4.25^*	32.1 ± 3.18^*	33.1 ± 5.19	34.3 ± 3.85
BMI (kg/m²)	24.1 ± 4.77^**	21.9 ± 3.02^**	26.3 ± 4.17^**	23.9 ± 2.64^**
Breastfeeding (%)	61 (65.6)	62 (63.3)	60 (68.9)	64 (67.3)

Data are given as mean ± standard deviation. Significant differences are given in bold italic.

p = 0.02, ^**p < 0.001.

BMI, body mass index.

About 65.6% of infertile women and 63.3% of fertile women had been breastfed and 69% of infertile men and 67.4% of fertile men had been breastfed. The difference was not statistically significant between groups (respectively, p = 0.764 and p = 0.874).

We examined more specifically the BMI according to the different groups. We observed that infertile women who had not been breastfed had a significantly higher BMI than those who had been breastfed (25.8 ± 5.55 kg/m² vs. 23.2 ± 4.13 kg/m², p = 0.018). We did not observe such differences in the other groups (Table 2).

Table 2.

Body Mass Index of Infertile and Fertile Women and Men

	Infertile women		Fertile women		Infertile men		Fertile men
	Breastfed	Not breastfed	Breastfed	Not breastfed	Breastfed	Not breastfed	Breastfed	Not breastfed
Total	61	32	62	36	60	27	64	31
Weight (kg)	63.4 ± 11.8^*	71 ± 16^*	60.2 ± 7.8	58.8 ± 6.8	83.5 ± 15.4	83.9 ± 17.2	75.8 ± 9.3	77.1 ± 11.5
Height (m)	1.65 ± 0.06	1.66 ± 0.05	1.66 ± 0.04	1.65 ± 0.05	1.78 ± 0.07	1.79 ± 0.06	1.79 ± 0.06	1.77 ± 0.07
BMI (kg/m2)	23.2 ± 4.1^**	25.8 ± 5.5^**	21.8 ± 2.7	22 ± 3.6	26.4 ± 3.9	26.2 ± 4.7	23.6 ± 2.4	24.6 ± 2.9

Data are given as mean ± standard deviation. Significant differences are given in bold italic.

p = 0.012, ^**p = 0.018.

Discussion

We did not observe any association between unexplained infertility in adulthood and having been breastfed in the neonate period, neither for women or men. Nevertheless, interestingly, among the infertile group, we noted that the nonbreastfed women had significantly higher BMI than those who had been breastfed, with a shift toward the overweight BMI category.

Breastfeeding has many beneficial and protective effects on the short- and long-term health of individuals, as evidenced by the recommendations of the WHO on breastfeeding.^3,6,10 Several studies have shown that long-term health programming mechanisms are established during the prenatal and first years of life.¹¹ This concept is well-known as the “first 1000 days” of life (including gestation and the first 2 years of life), a period of vulnerability in human development.^12,13

In the ALIFERT cohort, we had previously reported that an increased birth weight was a risk factor for unexplained infertility both in men¹⁴ and women,¹⁵ suggesting a link between prenatal period and fertility in adulthood. In this study, we aimed to examine the potential impact of early postnatal period on fertility at adulthood. An association between having been breastfed and fertility was not highlighted; but we observed a link between having been breastfed and female weight in the infertile subgroup.

Studies have indicated that nutrient imbalance in early life influences the risk of obesity later in life,^16,17 suggesting that obesity may result from “developmental programming.” Breastfed newborns have a better regulation of the amount of milk ingested¹⁸ and they are significantly lighter at 9 months of age.¹⁹ Some reports highlighted an association between having been breastfed and a relative protection against obesity later in life. Higher plasma-insulin concentrations in bottle-fed compared with breastfed infants could stimulate fat deposition and lead to an early development of adipocytes.²⁰ Although the origin of obesity is complex and multifactorial, rapid weight gain in early childhood has been clearly identified as a risk factor for the development of subsequent obesity and metabolic dysfunction.²¹ Thus, breastfeeding is known to have a protective effect on the early rebound of adiposity in children, which is known to have deleterious effects on the onset of puberty and increases the risk of long-term obesity.^22,23 Pubertal timing is an indicative marker for the neuroendocrine system, which regulates the development of reproductive system. A recent large-scale study showed that early pubertal timing was associated with a lower sperm concentration and negatively associated with estrogen levels.²⁴ Both testicular somatic cells and germ cells are sources of estrogen in mammals. Exposure of testis to extra-estrogen contributes to lower sperm concentration.²⁵ Pubertal timing can therefore be used as an indicative marker for hormone levels in adult men, and consequently for their fertility.

Overweight and obesity are known risk factors of infertility in both men²⁶ and women.²⁷ We assume that the lack of protective breastfeeding in early life, combined with an unhealthy lifestyle in adulthood, could lead to obesity and therefore, by extension, could contribute to infertility. An accumulation of risk factors could be envisaged, reinforcing our hypothesis that unexplained infertility origin is multifactorial and may have a developmental origin (pre- and postnatal). Studies have shown that infertile individuals are in poorer health than fertile individuals,^28,29 and would have been more susceptible to unfavorable fetal or neonatal programming. These hypotheses underline a possible indirect impact of having been breastfed on the reproductive functions in adulthood.

A direct effect of having been breastfed on fertility in adulthood may also be considered. Thus, leptin is present in breast milk³⁰ and plays a critical role in the long-term protection against obesity and metabolic disorders.³¹ Leptin is also an essential factor for brain development and neural projection.³² A lack of leptin intake during the neonatal period could have consequences on the development of the reproductive axis^7,8,33 and, therefore, have consequences on fertility in adulthood. Another theory is the potential role of epigenetics mechanisms through early postnatal nutrition in the developmental programming. Leptin may play a critical role in the DNA methylation patterns establishment and the response to dietary conditions in later life.³⁴ Furthermore, miRNAs are present in high concentration in breast milk³⁵ and could influence individual development.

The strengths of the study are the recruitment of two comparable groups of fertile and infertile couples. The assessments on breastfeeding status were registered from health book completed by a medical staff, to limit bias owing to declarative information. However, our study had some limitations, such as the lack of information concerning the duration of breastfeeding and the type of breastfeeding (exclusive or not). In some meta-analyses, the duration of exclusive breastfeeding is a protective factor for obesity in adulthood.^36,37 The duration of breastfeeding may also have an impact on the age at which adiposity rebound occurs.^38,39 We recognize that the limited sample size of the groups may decrease the accuracy of our study. Consequently, further studies are needed for meaningful conclusions; in particular, studies that take into account breastfeeding characteristics such as its duration and the type of breastfeeding (exclusive or not). It should be noted that animal studies could be useful in obtaining quick answers.

In conclusion, in our study, we did not observe any association between having been breastfed and fertility in adulthood. However, an association was observed between having not been breastfed and a high BMI in the subgroup of infertile women, suggesting that not being breastfed could constitute a factor contributing to the onset of infertility. Nevertheless, infertility may be multifactorial. Although further studies are needed to fully understand this phenomenon, breastfeeding should continue to be encouraged.

Availability of Data and Materials

Data are the property of the Public Assistance—Paris Hospitals (Assistance Publique—Hôpitaux de Paris [AP-HP]) that does not authorize as a promoter the sharing of data without a contract. Consultation by the editorial board or interested researchers may nevertheless be considered.

Ethics approval and consent to participate

The ethics committee (“Comité de Protection des Personnes”) approved the study. ALIFERT study (national biomedical research P071224/AOM 08180:NEudra CT 2009-A00256–51/clinical trials NCT01093378). All the participants signed a written informed consent.

CPP Ile de France, Numéro de dossier: 2012-nov-13076.

Footnotes

Authors' Contributions

C.D., C.F. participated in the study conception and design, in patient's recruitment, data acquisition, interpretation and analysis, and drafting of the article. P.T. participated in study design, performed statistical analysis, and participated in drafting of the article. S.C. and N.S. participated in study conception and design, in patient recruitment and critical revisions of the article for intellectual content. R.L. participated in study conception and design, interpretation of data, critical revision of the manuscript for intellectual content and supervised the study. The collaborators of the ALIFERT collaborative group participated in study design and were involved in patients' recruitment. All authors read and approved the final article.

Acknowledgments

The authors acknowledge the Alifert Collaborative Group: Isabelle Aknin: Unité́ fonctionnelle de biologie de la reproduction, histology—embryologie—cytogénétique, hôpital Nord, Saint-Étienne, France; Isabelle Cedrin-Durnerin: Service de Médecine de la Reproduction, Hôpital Jean Verdier, APHP, Bondy, France; Steven Cens, Centre d'AMP de PAU, Polyclinique de Navarre, Pau, France; Serge Hercberg: EREN, INSERM U557; INRA; CNAM; Université Paris 13, CRNH IdF, 93017 Bobigny, France; Claude Uthurriague, Centre d'AMP de PAU, Polyclinique de Navarre, Pau; Jean-Philippe Wolf: Service d'Histologie-Embryologie-Biologie de la Reproduction, Hôpital Cochin, APHP, Paris, France. The authors acknowledge all the participants involved in the study. The authors thank Clinical Research Unit Paris-centre coordinator Christelle Auger and CRA Deborah Rechard.

Disclosure Statement

No competing financial interests exist.

Funding Information

Financial support: this study was supported by French national biomedical research P071224 ALIFERT.

References

World Health

Assembly 54

. Global Strategy for Infant and Young Child Feeding: The Optimal Duration of Exclusive

Breastfeeding

. Annex: Expert consultation on the optimal duration of exclusive breastfeeding: conclusions and recommendations (Geneva, 28 to 30 March 2001). Published online 2001. https://apps.who.int/iris/handle/10665/78801 (accessed December 6, 2019).

Horta

, World Health

Organization

, Department of Child and Adolescent Health and

Development

. Evidence on the Long-Term Effects of Breastfeeding. WHO, 2007.

Victora

, Bahl

, Barros

AJD

, et al. Breastfeeding in the 21st century: Epidemiology, mechanisms, and lifelong effect. Lancet, 2016; 387:475–490.

Peres

, Cascaes

, Nascimento

, et al. Effect of breastfeeding on malocclusions: A systematic review and meta-analysis. Acta Paediatr, 2015; 104:54–61.

, Chung

, Raman

, et al. Breastfeeding and maternal and infant health outcomes in developed countries. Evid Rep Technol Assess (Full Rep), 2007; 153:1–186.

Horta

, Loret de Mola

, Victora

. Breastfeeding and intelligence: A systematic review and meta-analysis. Acta Paediatr, 2015; 104:14–19.

Castellano

, Bentsen

, Sánchez-Garrido

, et al. Early metabolic programming of puberty onset: Impact of changes in postnatal feeding and rearing conditions on the timing of puberty and development of the hypothalamic kisspeptin system. Endocrinology, 2011; 152:3396–3408.

Caron

, Ciofi

, Prevot

, et al. Alteration in neonatal nutrition causes perturbations in hypothalamic neural circuits controlling reproductive function. J Neurosci, 2012; 32:11486–11494.

Foucaut

A-M

, Faure

, Julia

, et al. Sedentary behavior, physical inactivity and body composition in relation to idiopathic infertility among men and women. PLoS One, 2019; 14:e0210770.

10.

Binns

, Lee

, Low

. The long-term public health benefits of breastfeeding. Asia Pac J Public Health, 2016; 28:7–14.

11.

Barker

DJP

, Eriksson

, Forsén

, et al. Fetal origins of adult disease: Strength of effects and biological basis. Int J Epidemiol, 2002; 31:1235–1239.

12.

Why 1,000 Days. 1,000 Days. https://thousanddays.org/why-1000-days/ (accessed December 9, 2019).

13.

Victora

, Adair

, Fall

, et al. Maternal and child undernutrition: Consequences for adult health and human capital. Lancet, 2008; 371:340–357.

14.

Faure

, Dupont

, Chavatte-Palmer

, et al. Are semen parameters related to birth weight?. Fertil Steril, 2015; 103:6–10.

15.

Dupont

, Hulot

, Jaffrezic

, et al. Female ponderal index at birth and idiopathic infertility. J Dev Orig Health Dis, 2019; 11:154–158.

16.

Bouret

, Levin

, Ozanne

. Gene-environment interactions controlling energy and glucose homeostasis and the developmental origins of obesity. Physiol Rev, 2015; 95:47–82.

17.

Lukaszewski

M-A

, Eberlé

, Vieau

, et al. Nutritional manipulations in the perinatal period program adipose tissue in offspring. Am J Physiol Endocrinol Metab, 2013; 305:E1195–E1207.

18.

Heinig

, Nommsen

, Peerson

, et al. Intake and growth of breast-fed and formula-fed infants in relation to the timing of introduction of complementary foods: The DARLING study. Davis Area Research on Lactation, Infant Nutrition and Growth. Acta Paediatr, 1993; 82:999–1006.

19.

Michaelsen

, Petersen

, Greisen

, et al. Weight, length, head circumference, and growth velocity in a longitudinal study of Danish infants. Dan Med Bull, 1994; 41:577–585.

20.

Lucas

, Blackburn

, Aynsley-Green

, et al. Breast vs bottle: Endocrine responses are different with formula feeding. Lancet, 1980; 315:1267–1269.

21.

Sacco

, de Castro

, Euclydes

VLV

, et al. Birth weight, rapid weight gain in infancy and markers of overweight and obesity in childhood. Eur J Clin Nutr, 2013; 67:1147–1153.

22.

Pietrobelli

, Agosti

, MeNu

Group

. Nutrition in the first 1000 days: Ten practices to minimize obesity emerging from published science. Int J Environ Res Public Health, 2017; 14:1491.

23.

Kang

. The adiposity rebound in the 21st century children: Meaning for what?. Korean J Pediatr, 2018; 61:375–380.

24.

Wang

, Zou

, Mo

, et al. Early pubertal timing is associated with lower sperm concentration in college students. Oncotarget, 2018; 9:24178–24186.

25.

Handelsman

. Estrogens and falling sperm counts. Reprod Fertil Dev, 2001; 13:317–324.

26.

Bellastella

, Menafra

, Puliani

, et al. How much does obesity affect the male reproductive function?. Int J Obes Suppl, 2019; 9:50–64.

27.

Talmor

, Dunphy

. Female obesity and infertility. Best Pract Res Clin Obstet Gynaecol, 2015; 29:498–506.

28.

Dupont

, Faure

, Daoud

, et al. Metabolic syndrome and smoking are independent risk factors of male idiopathic infertility. Basic Clin Androl, 2019; 29:9.

29.

Broughton

, Moley

. Obesity and female infertility: Potential mediators of obesity's impact. Fertil Steril, 2017; 107:840–847.

30.

Miralles

, Sánchez

, Palou

, et al. A physiological role of breast milk leptin in body weight control in developing infants*. Obesity (Silver Spring, Md), 2006; 14:1371–1377.

31.

Palou

, Picó

, Palou

. Leptin as a breast milk component for the prevention of obesity. Nutr Rev, 2018; 76:875–892.

32.

Steppan

, Swick

. A role for leptin in brain development. Biochem Biophys Res Commun, 1999; 256:600–602.

33.

Bouret

, Simerly

. Developmental programming of hypothalamic feeding circuits. Clin Genet, 2006; 70:295–301.

34.

Palou

, Picó

, McKay

, et al. Protective effects of leptin during the suckling period against later obesity may be associated with changes in promoter methylation of the hypothalamic pro-opiomelanocortin gene. Br J Nutr, 2011; 106:769–778.

35.

Munch

, Harris

, Mohammad

, et al. Transcriptome profiling of microRNA by next-gen deep sequencing reveals known and novel miRNA species in the lipid fraction of human breast milk. PLoS One, 2013; 8:e50564.

36.

Horta

, Bahl

, Martinés

, et al.

Evidence on the Long-Term Effects of Breastfeeding: Systematic Review and Meta-Analyses. World Health Organization; 2007.

https://apps.who.int/iris/handle/10665/43623 (accessed February 27, 2020).

37.

Arenz

, Rückerl

, Koletzko

, et al. Breast-feeding and childhood obesity—A systematic review. Int J Obes, 2004; 28:1247–1256.

38.

Chivers

, Hands

, Parker

, et al. Body mass index, adiposity rebound and early feeding in a longitudinal cohort (Raine Study). Int J Obes (Lond), 2010; 34:1169–1176.

39.

, Lye

, Briollais

. The role of early life growth development, the FTO gene and exclusive breastfeeding on child BMI trajectories. Int J Epidemiol, 2017; 46:1512–1522.