Duration of Breastfeeding and Early Growth: A Systematic Review of Current Evidence

Abstract

Introduction:

Growth patterns of breastfed and formula-fed infants differ, but the influence of breastfeeding duration on early growth remains unclear. The objective of this study is to evaluate current evidence on the association of exclusive and partial breastfeeding duration with different growth parameters during infancy.

Materials and Methods:

In this systematic review, we searched MEDLINE, EMBASE, and additional sources from January 2011 until March 2018 to identify relevant cohort studies and randomized controlled trials (RCTs).

Results:

Twenty studies that recruited infants from the general population were included. In the developed setting, exclusive breastfeeding duration was inversely associated with weight and length gain during infancy in observational studies. Longer duration of exclusive breastfeeding was also associated with an earlier peak in infant body mass index (BMI). Inconsistent results were observed for the associations of exclusive breastfeeding duration with other infant BMI characteristics. In an RCT conducted in Iceland, exclusive breastfeeding for 4 versus 6 months did not affect infant growth patterns. In the developing setting, conflicting findings on the associations of exclusive breastfeeding duration with infant weight and length parameters were shown in observational studies. Shorter partial breastfeeding duration was associated with higher weight gain during infancy, with limited or inconclusive data regarding other growth parameters.

Conclusions:

Longer duration of exclusive and partial breastfeeding tended to be associated with slower growth rates during infancy in the developed setting only. These associations seem to be dose dependent and more pronounced in exclusively versus partially breastfed infants.

Introduction

Early postnatal nutrition is one of the major determinants of growth during infancy. Growth patterns of breastfed infants are known to differ from those of formula-fed infants and are considered as the normative model of optimal growth in terms of various health outcomes.¹ Breastfeeding is associated with lower weight gain after the first 3–4 months of life compared with formula feeding, which has been considered as one of the plausible mechanisms for its protective effect against later obesity.² The unique composition of human milk in terms of nutrient contents, such as protein concentration and its qualitative features, or hormone contents, provides potential explanation for this effect of breastfeeding on growth.^2,3

Another mechanism that has been suggested, focuses on the behavioral influence of breastfeeding and better self-regulation of energy intake as compared with formula feeding.^2,3 In turn, it has been suggested that rapid weight gain during infancy, as a consequence of high nutrient intake, might result in adverse long-term health outcomes, including increased risk of childhood obesity.^4–7 This can be explained by the hypothesis that assumes that metabolic alterations related to postnatal accelerated growth lead to permanent structural and physiological changes, which further affect the risk of childhood and adulthood adiposity.⁸ Although breastfeeding has been shown to be associated with a moderately lower risk of overweight and obesity in childhood and adulthood, the effects of duration of breastfeeding on both early growth and later adiposity remain unclear.^9,10

One of the most up-to-date systematic reviews found the existing evidence as “probable that exclusive breastfeeding for longer than 4 months is associated with slower weight gain during the second half of the first year”.⁹ However, the results of the identified observational studies were not consistent, and no experimental studies with an adequate follow-up period, which specifically focused on the duration of breastfeeding in the developed setting, were included. In another review, performed within the Cochrane Collaboration, no growth deficit was observed in infants exclusively breastfed for 6 months or longer versus 3–4 months from both developed and developing countries.¹¹

However, little is known as to whether a longer duration of breastfeeding is protective against rapid weight gain. Recently, a number of observational studies, as well as single experimental reports, in this field have been published. Methodological differences between these studies are one of the factors that might have led to the inconsistencies in the obtained results. This current evidence on breastfeeding duration and early growth, critical for determining long-term outcomes, may provide more insight into our understanding as to what constitutes the optimal duration of breastfeeding.

In the present review, we aimed to systematically assess current evidence on the association of the duration of exclusive breastfeeding and partial breastfeeding with growth during infancy.

Materials and Methods

This systematic review was performed as part of project EarlyNutrition based on a previously prepared and discussed written protocol.

Inclusion and exclusion criteria

We defined our population of interest as infants representing the general population in terms of health and disease. We did not include studies that focused exclusively on special populations (e.g., preterm infants, twins, or small-for-gestational-age infants) or studies involving children with chronic disorders. Studies conducted in different settings, both developed and developing (based on Human Development Index) countries, were eligible for inclusion. Breastfeeding, either exclusive or partial, of any pattern and any duration, was the exposure or intervention of our interest. Studies that enrolled infants who were breastfed exclusively or partially for a different time period as a control group were included.

Only prospective observational studies and randomized control trials (RCTs) were eligible for inclusion. Cohort studies in which early growth was not analyzed as an outcome, but rather considered as a mediator were excluded from our review. This was because we considered it not informative enough to make conclusions on the effect size of the association between breastfeeding duration and growth based solely on data from mediation analysis with growth as a mediator variable.

We assessed different growth parameters, such as body mass index (BMI); weight, length, and head circumference (as reported by the authors); gains in any of these parameters; as well as growth curves/trajectories, if available. We focused on growth within the first year of life. However, when data extraction solely for the first year of life was not feasible (i.e., studies assessing growth patterns including and beyond the first year of life), this age period was extended until the first 24 months of life.

Search strategy

To identify eligible studies, two of three reviewers (A.P., B.M.Z., or B.P.-G.) independently searched the following electronic databases: Medline (through PubMed) and Embase. Additionally, we performed a hand search of the reference list of each included article. The timeframe for our search was from January 2011 to March 2018. This was determined by the times of the searches for previously published systematic reviews in this field.

Our search strategy for electronic databases involved use of a combination of different groups of keywords [free text and MeSH (Medical Subject Headings) terms] that described the populations, exposures, and outcomes of interest (Supplementary Table S1). We limited our search to studies indexed as “Humans”. Furthermore, only articles published in English were included. The first stage of the study selection process was based on titles and abstract screening for all identified records. If, however, uncertainty regarding the appropriateness of inclusion of a study remained after this initial screening, full text articles were obtained and screened.

Data collection

Three reviewers (A.P., B.M.Z., or B.P.-G.) were involved in data extraction that was performed independently. We collected the following information: first author's name; year of publication; study design, setting, and population; information on the exposure and the comparison; and results. Furthermore, we extracted data necessary for the assessment of the risk of bias for each individual study.

We adapted the Newcastle–Ottawa scale for the purpose of assessment of the risk of bias within cohort studies.¹² The original (unadapted) scale requires one to choose the most relevant confounding factor for further assessment in the comparability domain. However, based on the existing literature, we considered maternal education, socioeconomic status, birth weight, and gestational age at birth, all to be the most important confounding factors, so we awarded stars based on the number of confounding factors for which a study controlled. This approach based on arbitrarily chosen confounders is a limitation of our assessment.

Following the Center for Evidence-Based Medicine, “a rule of thumb states that <5% attrition leads to little bias, while >20% poses serious threats to validity.” Therefore, for adequacy of follow-up in the outcome domain, we considered a rate of loss to follow-up exceeding 20% as likely to introduce bias. For assessment of the risk of bias within RCTs, we used The Cochrane Collaboration's tool that takes into account methods of sequence generation, allocation concealment, blinding, completeness of outcome data, and selective reporting.¹³

Data analysis

We synthesized data obtained from the included studies in a narrative way. Due to substantial methodological and clinical differences between the studies, we did not consider undertaking a meta-analysis. A priori we planned to analyze our data in subgroups based on the types of exposure (exclusive versus any breastfeeding) and study setting (developed versus developing countries). All discrepancies between the reviewers regarding the study selection process, data extraction, synthesis, and interpretation were discussed to reach a final agreement.

Results

Study characteristics

Out of 5,064 records retrieved after applying our search strategy, 20 studies met our inclusion criteria (Supplementary Fig. S1). The characteristics of the included studies are summarized in Table 1. The majority of the studies was birth cohort studies; only one RCT,¹⁴ in which random assignment based on the breastfeeding duration, was included. Study participants were infants from the general population. For one study, only offspring of obese mothers were enrolled.¹⁵ The ages of the children at outcome assessment varied greatly between the studies, ranging from 1 week to 24 months of age.

Table 1.

Characteristics of Included Studies

Study ID	Study design	Study setting and population	Exposure and comparison	Definition of exclusive breastfeeding (if analyzed)	Growth outcomes and age at assessment	Growth reference	Results	Comments
Aris et al. (2017)¹⁷	Prospective cohort study	N = 1,020 (GUSTO cohort) Age: 0–18 months Country: Singapore HDI: very high Years recruited: 2009–2010	Duration of any breastfeeding and EBF; <4 versus ≥4 (months)	Breast milk (including milk expressed or from a wet nurse), allowed: ORS, drops, and syrups (vitamins, minerals, medicines) only	BMI peak characteristics: age (months), magnitude (kg/m²), prepeak velocity (kg/m²/month)	Local, Singapore reference	Longer duration of any breastfeeding and EBF associated with an earlier age of BMI peak and higher average prepeak velocity (β coefficients (95% CI) from multiple weighted linear regression): Any breastfeeding: Age of peak <4 months: −0.29 (−0.84 to 0.27) ≥4 months: −0.57 (−1.13 to 0.01 Magnitude: <4 months 0.22 (−0.21 to 0.65) ≥4 months 0.29 (−0.15 to 0.72) Prepeak velocity: <4 months: 0.12 (0.01–0.22) ≥4 months: 0.15 (0.04–0.25) EBF: Age of peak <4 months: −0.62 (−1.01 to 0.23) ≥4 months: −0.30 (−0.60 to −0.01) Magnitude: <4 months: −0.25 (−0.56 to 0.06) ≥4 months: 0.17 (−0.07 to 0.42) Prepeak velocity <4 months: 0.04 (−0.04 to 0.11) ≥4 months: 0.11 (0.05–0.17)	Both direct breastfeeding and expressed breast milk intakes were classified as breastfeeding. “No breastfeeding” as reference in analyses for <4 months versus ≥4 months
Agarwal et al. (2013)²⁵	Prospective follow up-pilot study	N = 71 (subgroup of 56 infants with ≥2.5 kg birth weight) Age: 0–18 months Country: India HDI: medium Years recruited: 2006–2007	Duration of EBF; <6 versus ≥6 (months)	Only breast milk, no other milk, food, drink, or water	Length (cm) and weight (kg) gains from birth to 18 months of age	WHO growth reference	Higher length and weight gain in infants EBF <6 versus ≥6 months (mean, SD) • Length gain 0–18 months: 35.7, SD 9.9 versus 30.2, SD 6.7 (p < 0.018) • Length at 5–7 months: “similar in both groups” • Length gain from 8 month onward: higher in EBF <6 months with a 3.4 cm difference at 18 months (p < 0.073) • Weight gain 0–18 months: 8.8, SD 2.6 versus 8.2, SD 1.7 (p < 0.263) • Weight gain from 8 month onward: 0.8 kg higher in <6 months EBF at 18 months • Growth curves for infants EBF ≥6 months (with birth weight ≥2.5kg) similar (p > 0.05) to the WHO growth curves	Pilot study with a very small sample size
Betoko et al. (2014, 2017)^21,22	Prospective cohort	N = 1239 (EDEN cohort) Age: 0–4 months Country: France HDI: very high Years recruited: 2003–2006 N = 1022	Duration of EBF (months)	Only breast milk as milk feeds	ΔWAZ, WLZ, LAZ between birth and 4 months; BMI, weight, height at 12 months and change in these parameters from 0 to 1 year	WHO growth reference	Infants breastfed longer had lower WAZ and LAZ change (β coefficient, 95% CI from adjusted analyses): • ΔWAZ −0.08 (−0.12 to 0.04) • ΔWLZ −0.04 (−0.11 to 0.03) • ΔLAZ −0.08 (−0.12 to −0.03) Breastfeeding duration (when adjusted for the residuals of other feeding practices) was negatively related to weight, height, and BMI at 1 year and changes in these parameters from birth to 1 year (results reported on a figure only)	The mean EBF duration was very short (0.9 month)
Budree et al. (2017)²⁷	Prospective cohort	N = 386/1076 Age: 0–12 months Country: South Africa HDI: Medium Years recruited: 2012–2015	Duration of EBF (months)	Definition of EBF as specified by WHO	BMIZ, HAZ, WAZ at 12 months	WHO	Longer duration of EBF associated with a lower HAZ at 1 year, and tended to be also associated with lower WAZ, but not BMIZ (regression coefficients, [95% CI]) • BMIZ unadjusted −0.001 (−0.1 to 0.1) • HAZ Unadjusted: −0.1 (−0.2 to −0.1) Adjusted: −0.1 (−0.2 to −0.03) • WAZ Unadjusted: −0.1 (−0.1 to −0.01) Adjusted: −0.1 (−0.1 to 0.01)	High proportion of preterm (17%), low birth weight (16%), or small for gestational age (25%) infants in the study sample
Carling et al., (2015)³²	Prospective cohort	N = 438 (The Bassett Mothers Health Project) Age: 0–24 months Country: United States of America HDI: very high Years recruited: 1994–1996	Duration of any breastfeeding; <2 versus 2–4 versus >4 months	—	Weight gain trajectories for infants' WLZ from 0 to 24 months across different obesity risk groups	WHO growth reference	High-risk infants breastfeeding for <2 versus >4 months only were more likely to belong to a rising rather than stable weight gain trajectory; OR (95% CI) for different risk groups: • High risk: 2.55 (1.14–5.72) • Medium risk: 1.64 (0.82–3.26) • Low risk: 0.42 (0.16–1.11)	The obesity risk index included maternal BMI, education, and smoking during pregnancy
Carlsen et al. (2013)¹⁵	Prospective cohort within an RCT	N = 226 (children of obese mothers from Treatment of Obese Pregnant women study) Age: 0–6 months Country: Denmark HDI: very high Years recruited: 2010–2012	Duration of EBF (days) and partial breastfeeding (days)	Breastfeeding only supplemented with vitamins, mineral supplements, and water (WHO definition)	Weight (g/day) and length (cm/day) gain at 6 months	WHO growth reference	Days of EBF inversely associated with weight (β coefficient [95% CI]): (β = −4.39 [−0.66 to −8.11]) and length (β = −0.012 [−0.004 to −0.02]) in covariate adjusted analyses. No association between days of partial breastfeeding and weight (p = 0.23) or length (p = 0.09) gain at 6 months (effect estimates not reported)	Analyses within RCT
de Hoog et al. (2011)¹⁹	Prospective cohort	N = 2998 (ABCD multiethnic cohort) Age: 0–6 months Country: The Netherlands HDI: very high Years recruited: 2003–2004	Duration of any breastfeeding; <1; 1–3; 4–6; versus ≥6 months	—	ΔWAZ, LAZ, WLZ from 4 weeks to 6 months	Internal growth reference	Shorter duration of any breastfeeding associated with higher gain in WAZ, LAZ, and WLZ (β coefficients [95% CI]) for the association of breastfeeding duration categories and growth rates): • ΔWAZ (unadjusted analyses): <1 month: 0.67 (0.51–0.83) 1–3 months: 0.48 (0.39–0.57) 4–6 months: 0.11 (0.04–0.19) • ΔWAZ (adjusted analyses): <1 month: 0.50 (0.35–0.65) 1–3 months: 0.37 (0.29–0.45) 4–6 months: 0.11 (0.04–0.18) • ΔLAZ (unadjusted analyses): <1 month: 0.45 (0.29–0.62) 1–3 months: 0.43 (0.34–0.52) 4–6 months: 0.16 (0.08–0.24) • ΔLAZ (adjusted analyses): <1 month: 0.37 (0.21–0.52) 1–3 months: 0.35 (0.26–0.43) 4–6 months: 0.16 (0.09–0.24) • ΔWLZ (unadjusted analyses): <1 month: 0.48 (0.27–0.68) 1–3 months: 0.21 (0.10–0.32) 4–6 months: −0.01 (−0.11 to 0.09) • ΔWLZ (adjusted analyses): <1 month: 0.37 (0.17–0.58) 1–3 months: 0.17 (0.06–0.29) 4–6 months: −0.02 (−0.12 to 0.08)
Durmus et al. (2011)¹⁸	Prospective cohort	N = 5074 (the Generation R study)Age: 0–3 yearsCountry: The NetherlandsHDI: very highYears recruited: 2002–2006	Duration of any breastfeeding; <3 versus 3–6 versus ≥6 (months)	—	ΔWAZ, LAZ, BMIZ (0–3 months; 3–6 months; 6–12 months); BMI, overweight, obesity at 1 year	National (Dutch) growth reference	Shorter breastfeeding duration associated with an increased gain for length, weight and BMI SDS (p for trend 0.05) between 3 and 6 months of age only.No associations between breastfeeding duration and growth rates <3 and 6–12 months of age observedRegression coefficient (95% CI) from covariate adjusted models for breastfeeding duration and growth rates between 3 and 6 months: • Length SDS: 0.19 (0.15–0.24) • Weight SDS: 0.14 (0.10–0.18) • BMI SDS: 0.02 (−0.03 to 0.08)No consistent association of breastfeeding duration with the risks of overweight and obesity at 1, 2, and 3 years	In total, 65.7% of all children were partially breastfeeding until the age of 4 months, and 24.1% of all children were EBF until the age of 4 months
Eriksen et al. (2017)²⁸	Prospective cohort within an RCT	N = 502 (subgroup)(ENID trial + ENID growth study)Age: 0–2 yearsCountry: The GambiaHDI: LowYears recruited: 2010–2015	Duration of EBF;3–4 versus 6 (months)	Breast milk only	LAZ, WAZ, WLZ at 6, 12 months	WHO growth standards	No difference in LAZ between groups at any time point (β coefficient [95% CI]) and p values from adjusted models): • 6 months: 0.005 (−0.163 to 0.173, p = 0.9) • 12 months: 0.101 (−0.083 to 0.286, p = 0.3)Higher WAZ and WLZ at 6 months: • Higher WAZ in EBF to 6 months: 0.216 (0.027–0.404, p = 0.03) • Higher WLZ in EBF to 6 months: 0.289 (0.093–0.485, p = 0.004)but not at 12: • WAZ in EBF to 6 months: 0.120 (−0.100 to 0.339, p = 0.3) • WLZ in EBF to 6 months: 0.099 (−0.118 to 0.317, p = 0.4)and 24 months: • WAZ in EBF to 6 months: 0.048 (−0.139 to 0.236, p = 0.6) • WLZ in EBF to 6 months: 0.034 (−0.158 to 0.227, p = 0.7)	Post hoc analysis not planned originally.Female and EBF to 3–4 months (±0.5 months) as reference for analysesOnly 502 infants were included in this analysis, with 130 (26%) being exclusively breastfed to age 3–4 months.
Gubbels et al. (2011)³³	Prospective cohort	N = 2111 (KOALA cohort)Age: 0–4 yearsCountry: the NetherlandsHDI: very highYear recruited: 2000	Duration of any breastfeeding (months)	—	Weight gain (g) at 12 months;BMIZ at 1 year;overweight at 1 year	National growth reference	Each additional month of breastfeeding associated (regression coefficient β [95% CI] from adjusted analyses) with: • Less weight gain in the first year: −37.6 g (−48.2 to −27.1) • Lower BMIZ at age 1 year: β = −0.02 (−0.03 to −0.01) • Lower odds of being overweight at age 1 year: OR = 0.96 (0.93–1.00)
Jensen et al. (2015)²³	Prospective cohort	N = 311 (SKOT cohort)Age: 0–3 yearsCountry: DenmarkHDI: very highYear recruited: 2007	Duration of: EBF and any (months)	No other oral intake, but breast milk, water, or vitamins	Prepeak BMI growth velocity (kg/m² per month);age (months) and BMI at peak based on BMI growth curves for the age span from 14 days to 19 months	WHO growth reference	In multivariate models, children EBF for a longer period had a lower prepeak velocity and an earlier peak.Regression coefficient β (95% CI): • BMI value at peak: not significant • Age at peak: −0.05 (−0.07 to −0.03) • Prepeak velocity: −0.02 (−0.02 to −0.01)Duration of any breastfeeding was not associated with any of the BMI growth characteristics	Duration of any breastfeeding studied in a subanalysis(only including 138 children with a BMI peak after end of all breastfeeding)
Jonsdottir et al. (2014)¹⁴	RCT	N = 100Age: 0–38 monthsCountry: IcelandHDI: very highYears recruited: 2007–2009	Duration of EBF;4 versus 6 (months)	Breastfeeding with no additional liquid or solid foods other than vitamins and medications	Change in WAZ, LAZ, HCZ, BMIZ (at birth, 6 weeks, 3–6 months, and at 8, 10, 12, and 18 months)	WHO growth reference	No differences among groups in WAZ (p = 0.78), LAZ (p = 0.59), HCZ (p = 0.82), and BMIZ (p = 0.61) changes, using repeated measurements ANOVA	The use of up to 10 feedings of formula or water during the first 6 months was allowed.
Kattula et al. (2014)²⁶	Prospective cohort	N = 414Age: 0–38 monthsCountry: IndiaHDI: mediumYears recruited: 2009–2010	Duration of EBF;6 versus <6 months	Definition of EBF for less than 6 months were as specified by WHO	Monthly gain in weight (kg) and length (cm) calculated based on length and weight at birth and 2 years	WHO growth reference	EBF children until 6 months had lower monthly gain of height and weight β coefficient (95% CI) for height: • Univariate: −0.05 (−0.11 to 0.003); p = 0.06 • Multivariate: −0.06 (−0.10 to −0.01); p = 0.006 β coefficient (95% CI) for weight: • Univariate: −0.014 (−0.03 to 0.0003); p = 0.05 • Multivariate: −0.013 (−0.02 to 0.0004); p = 0.06	17% of children classified as low birth weight; high rates of stunting, wasting, and underweight at 24 months
Nguyen et al. (2013)²⁴	Prospective cohort	N = 964 (from rural and urban setting)Age: 0–2 yearsCountry: VietnamHDI: mediumYears recruited: 2009–2010	Duration of EBF (unit of measurement not reported)	Breast milk from mothers/wet nurse breast or expressed, oral intake of rehydration solutions or medication, including vitamins or minerals only	Attained weight and length at 2 years	WHO growth reference	Correlation coefficients between weight and length residuals and duration of EBF: Attained weight: • Unadjusted: 0.1211 • Adjusted: 0.0404 Attained length: • Unadjusted: −0.0051 • Adjusted: −0.0200
Oddy et al. (2014)³⁴	Prospective cohort	N = 2868 (RAINE study);Age: 0–20 yearsCountry: AustraliaHDI: very highYear recruited: 1989	Duration of any breastfeeding (months)	—	ΔWAZ between birth and 1 year of age	WHO growth reference	Longer breastfeeding associated with reductions in WAZ: adjusted β coefficient = −0.027; SE 0.004; p < 0.001 Mean WAZ at 1 year: Breastfeeding ≤4 months: 0.31 (0.22–0.40) Breastfeeding 5–8 months: 0.17 (0.06–0.27) Breastfeeding 9–12 months: 0.11 (0.01–0.22) Breastfeeding >12 months: −0.16 (−0.28 to −0.04)
Olaya et al. (2017)²⁹	Prospective cohort within an RCT	N = 108Age: 0–6 monthsCountry: ColombiaHDI: highYears recruited: not stated	Duration of EBF; 4–5 versus ≥6 (months)	Only breast milk without any other food, liquids, or supplements and complementary feeding	WLZ, LAZ, WAZ at 6 months; change from 0–6 months; proportion of children with LAZ <2SD, WAZ <2SD at 6 months	WHO growth reference	No difference among groups in LAZ,WLZ, WAZ at 6 months and changes in these parameters (unadjusted analyses): Mean difference (95% CI) • LAZ: −0.08 (−0.72 to 0.3) • WLZ: −0.18 (−0.55 to 0.19) • WAZ: −0.21 (−0.57 to 0.15) Change from 0 to 6 months: • LAZ: −0.09 (−0.56 to 0.39) • WLZ: −0.30 (−1.03 to 0.44) • WAZ: −0.26 (−0.65 to 0.14) No significant difference between groups in the proportion of children with LAZ <2SD and WAZ <2SD (2 [3.8%] versus 2 [3.6%], p = 0.9) at 6 months	Greater proportion of boys had LAZ <2SD (12 [21.4%] versus 1 [2.0%] girl, p = 0.002)
Queiroz et al. (2012)³⁰	Prospective cohort	N = 373Age: 0–2 yearsCountry: BrazilHDI: medium (as of 2006)Years recruited: 2005–2006	Duration of EBF (days)	Breast milk, including expressed breast milk, with only medications and vitamins oral intake	LAZ at12 months	WHO growth reference	Increased duration of EBF had a positive impact on the variation in LAZ based on the multivariate mixed effects analysis (β = 0.0031, SE 0.0008, p < 0.001)	A total of 23.7% of the pairs potentially eligible for the sample did not complete follow-up
Rogers and Blissett (2017)³⁵	Prospective cohort	N = 81Age: 0–12 monthsCountry: United KingdomHDI: very highYears recruited: not stated	Any breastfeeding		1-Week; 1, 6, 12-month weight SDS; SDS weight gain 1–6 and 1–12 months	UK-WHO growth reference	Any breastfeeding negatively associated with infant weight SDS at 6- and 12-months and weight gain SDS from 1- to 6- and 1- to 12-months, but not with infant weight SDS at 1-week or 1-month (partial correlation coefficients between breastfeeding duration and weight SDS): 1-week: −0.001, p = 0.50 1-month: −0.15, p = 0.12 6 months: −0.33, p = 0.004 12 months: −0.39, p = 0.001 1–6 months: −0.30, p = 0.01 1–12 months: −0.38, p = 0.001
Woo et al. (2013)²⁰	Multi-country prospective cohort	N = 285Age: 0–1 yearCountries: United States, China, MexicoHDI: very high/medium/high (as of 2008)Years recruited: 2007–2008	Duration of EBF (months)	Not reported	WAZ, LAZ, BMIZ at 1 year	WHO growth reference	EBF duration inversely associated with WAZ, but not LAZ or BMIZ WAZ • Unadjusted: β = −0.08, SE 0.03, p ≤ 0.01 • Adjusted: β = −0.07, SE 0.03, p ≤ 0.05 LAZ • Unadjusted: β−0.05, SE 0.03, p > 0.05 and <0.2 • Adjusted: β = −0.05, SE 0.03, BMIZ • Unadjusted: β = −0.07, SE 0.03, p ≤ 0.05 • Adjusted: β = −0.04, SE 0.03	The median EBF duration was 4.9, 13.7 and 7.1 weeks in China, United States of America, and Mexico, respectively
Zhang et al. (2017)³¹	Prospective cohort	N = 495/626Age: 0–2 yearsCountry: BangladeshHDI: mediumYears recruited:2008–2012	Duration of EBF; ≤6 versus >6 (months)	Human milk without supplementation (including water but excluding medications)	Downward change in HAZ (functional principal component analysis) from birth to 2 years	WHO growth reference	Longer EBF duration associated with growth faltering in boys, but not girlsGrowth faltering measure (adjusted-FPCC2 score), β coefficients: • Boys: ≤6 months EBF = 0.013, p = 0.6680; adjusted p = 0.7515 >6 months EBF = 0.056, p = 0.0071; adjusted p = 0.0213 • Girls: ≤6 months EBF = −0.014, p = 0.4498; adjusted = 0.5784 >6 months EBF = −0.015, p = 0.2602; adjusted p = 0.3603

HDI, Human Development Index; EBF, exclusive breastfeeding/exclusively breastfed; WHO, World Health Organization; SD, standard deviation; WAZ, weight-for-age z-score; WLZ, weight-for-length z-score; LAZ, length-for-age z-score; CI, confidence interval; BMI, body mass index; RCT, randomized controlled trial; BMIZ, body mass index z-score; SDS, Standard deviation score; OR, odds ratio; HCZ, head circumference for age z-score; SE, standard error; ANOVA, analysis of variance; ORS, oral rehydration solution; ENID, Early Nutrition and Immune Development; GUSTO, Growing Up in Singapore Towards healthy Outcomes; ABCD, Amsterdam Born Children and their Development; RAINE, Raine Medical Research Foundation.

Among studies that focused on exclusive breastfeeding, five were conducted in developed countries and eight were conducted in developing countries; one study included populations from different settings (both developed and developing countries). With respect to any breastfeeding, all of the included studies were performed in developed countries. Duration of breastfeeding was measured by the authors, either continuously or as categorical variable defined in various ways (e.g., <6 versus ≥6 months; <1 versus 1–3 versus 4–6 versus ≥6 months). The definition of exclusive breastfeeding used was mainly in accordance with the World Health Organization¹⁶ criteria and is provided for each study in Table 1.

The included studies differed in terms of growth parameters assessed and the timing of their assessment. The authors attempted to either report the pattern of growth, expressed as gains in growth parameters and growth trajectories, or report growth measures at a single time point only. WHO growth standards were used most often as the growth reference. However, in some studies, national^17,18 or internal¹⁹ growth references were applied, as shown in Table 1.

Risk of bias

The risk of bias differed between observational studies, particularly with regard to controlling for confounding factors. Seven studies awarded with two stars (controlling for child's age, sex, and three of four of the following factors: maternal education, socioeconomic status, birth weight, and gestational age at birth) also adjusted for a number of other confounding factors; all of them additionally took into account the role of maternal BMI, and six of seven controlled for maternal smoking. For other studies awarded fewer stars, controlling for maternal smoking and parental weight or height was the most common adjustment. Ascertainment of exposure (a method of obtaining data on breastfeeding duration, e.g., questionnaire filled by a mother or a structured interview) was of high risk of bias in many studies.

In the single RCT,¹⁴ high risk of bias was mainly due to the lack of blinding. A detailed assessment of the risk of bias in the RCTs and in cohort studies, as well as an information on confounding factors for which studies controlled, is provided in Supplementary Tables S2, S3 and S4.

Exclusive breastfeeding—studies from developed and mixed settings

Weight and length parameters

Longer duration of exclusive breastfeeding was found to be associated with a lower weight-for-age z-score at 1 year of age, also after adjustment for maternal and child's birth characteristics, in children from a multicenter cohort study conducted in the United States of America, Mexico, and China.²⁰ However, no apparent association of exclusive breastfeeding duration with the length-for-age z-score at 1 year of age was observed in this study.

In Danish infants born to obese mothers, exclusive breastfeeding was inversely associated with infant weight (g/day) and length (cm/day) at the age of 6 months after adjustment for maternal and child's birth and feeding characteristics.¹⁵ In line with these findings, infants in a French cohort study who were exclusively breastfed longer gained less weight- and length-for-age z-scores between 0 and 4 months of age, as well as between 0 and 1 year, than those breastfed for a shorter period.^21,22 No significant association of duration of exclusive breastfeeding with change in infant's weight-for-length z-score was found from birth to 4 months of age in this study.

Similar growth during infancy was reported in children breastfed for four compared with 6 months in an RCT conducted in Iceland.¹⁴ The authors of this study reported no significant difference in change in weight- and length-for-age z-scores between study groups for all time points, from birth to 29–38 months of age. The authors concluded that as all observed changes were within 1 z-score (sex and age adjusted) of the standard WHO reference values, they were not considered to be of clinical importance. However, the effect estimates for observed differences between the groups were not reported in this study; this substantially limits the interpretation of the results, especially when the small sample size is one of the most important methodological limitations of this study.

Body mass index

No association of duration of exclusive breastfeeding with the BMI-for-age z-score was observed in children at 1 year of age in the multicenter cohort study conducted in the United States of America, Mexico, and China after adjustments for maternal and child's birth characteristics.²⁰ Similarly, no significant differences were found between children exclusively breastfed for 4 versus 6 months in BMI-for-age z-score change for different time points from birth to 29–38 months of age in the RCT performed in Iceland.¹⁴ In the French cohort, BMI and BMI change from 0 to 1 year seemed to be only slightly lower in children who were breastfed longer.²²

Based on the estimated BMI growth curves for the ages of 14 days to 19 months, the BMI growth velocity before peak as well as age and the BMI at peak were assessed in relation to the duration of exclusive breastfeeding among 311 Danish children.²³ An earlier peak in infant BMI and a lower prepeak velocity were observed in those who were exclusively breastfed for a longer period. Although not a subject of this review, we considered it important to the interpretation of the above findings that BMI at both peak and prepeak velocity were significantly positively associated with fat and fat-free mass at the age of 3 years; a later age at peak was associated with a lower fat mass, fat mass index, and fat-free mass index in this study. Finally, longer duration of exclusive breastfeeding was associated with an earlier age at BMI peak and a higher BMI prepeak velocity in infants from a Singapore cohort study.¹⁷

Head circumference

In the Icelandic RCT described in more detail above, no significant differences were found between children exclusively breastfed for 4 versus 6 months in the head circumference-for-age z-score change for different time points ranging from birth to 29–38 months of age.¹⁴

Exclusive breastfeeding—studies from developing setting

Weight and length parameters

In a cohort study conducted in Vietnam, the duration of exclusive breastfeeding was not significantly correlated with attained weight and length at 2 years.²⁴ The duration of exclusive breastfeeding in this study was <2 months in the majority of cases, which might have affected the obtained results. In a pilot cohort study conducted in India, a subgroup of infants born with a birth weight ≥2.5 kg who were exclusively breastfed for <6 versus ≥6 months had a higher mean weight and length gain from birth to 18 months of age,²⁵ although these differences were not statistically significant. It needs to be emphasized, however, that the study sample consisted of 71 participants, which limits the reliability of the findings.

In another cohort study, exclusive breastfeeding until 6 months compared with <6 months was inversely associated with the average monthly weight and length gain in infants from India during the first 2 years of life.²⁶ Similarly, duration of exclusive breastfeeding was inversely associated with the length-for-age z-score at 12 months of age in an adjusted analysis, and also tended to be inversely associated with weight-for-age z-score, in a cohort of infants from South Africa.²⁷ No association of duration of exclusive breastfeeding with the weight- and length-for-age, as well as weight-for-length z-scores at 12 months was observed in Gambian infants, although children from this cohort seemed to have higher weight and weight-for-length at the age of 6 months when breastfed longer.²⁸

No differences in the weight- and length-for-age, as well as weight-for-length z-scores, at 6 months nor changes in these parameters from 0 to 6 months, were also found between infants exclusively breastfed 4–5 versus ≥6 months in an observational analysis conducted in Colombia.²⁹ In addition, no difference in the proportion of children with a weight-for-age z-score <2 standard deviation was found between these two groups of exclusively breastfed infants at 6 months.

Finally, two cohort studies that focused solely on linear growth revealed that a longer duration of exclusive breastfeeding had a positive impact on the mean length-for-age z-score at 12 months in Brazilian infants, while inconsistent sex-dependent associations in terms of growth faltering were observed in infants from Bangladesh.^30,31

Body mass index

Duration of exclusive breastfeeding was not associated with BMI-for-age z-score at 12 months of age in the cohort of infants from South Africa.²⁷

Any breastfeeding—studies from developed setting

Weight and length parameters

Weight gain trajectories were identified for weight-for-length z-scores in 438 infants ranging from 0 to 24 months of age in a United States prospective cohort study, with rising trajectories indicating accelerated growth.³² Infants were assigned to three different obesity risk groups: low, medium, and high risk—based on the number of significant risk factors to which they were exposed (such as maternal BMI, education, smoking during pregnancy). Additionally, the analyses were adjusted for maternal age and Ponderal index. The associations of breastfeeding duration with weight gain trajectories varied across the groups. An increased risk of being in a rising weight gain trajectory rather than in a stable trajectory was observed in infants breastfed for <2 compared with >4 months from the medium- and high-risk obesity groups.

In another cohort study, among 2,998 infants from a multiethnic Dutch population, shorter duration of any breastfeeding compared with any breastfeeding ≥6 months was associated with a higher weight- and length-for-age z-score as well as weight-for-length z-score gain from 4 weeks to 6 months of age.¹⁹ These associations only slightly attenuated after adjustment for important confounding factors, and were the strongest for <1 versus ≥6 months breastfeeding duration.

In another Dutch cohort study, shorter duration of any breastfeeding was also associated with a higher gain in weight and length z-scores between 3 and 6 months of age in models additionally adjusted for several important confounding factors.¹⁸ However, no association was observed for weight and length gain from 0 to 3 months and from 6 to 12 months in this study.

Furthermore, in another study conducted in the Netherlands, each additional month of breastfeeding was associated with an average 37.6 g less of weight gain during the first year of life in an analysis adjusted for several potential confounding factors.³³ In line with these findings, duration of any breastfeeding was positively and independently associated with reductions in weight-for-age z-scores between birth and 1 year in Australian infants after adjustment for several confounding factors.³⁴ Similar findings were observed in the most recent United Kingdom cohort study in the analysis adjusted for potential confounding factors.³⁵

In contrast, in Danish infants born to obese mothers, partial breastfeeding was not associated with a gain in weight and length at the age of 6 months.¹⁵

BMI, overweight, and obesity

Shorter duration of any breastfeeding was associated with a higher gain in BMI-for-age z-scores in infants between 3 and 6 months of age, but not in other age ranges during the first year of life, in models adjusted for important confounding factors.¹⁸ In this large cohort study performed in the Netherlands, no consistent associations of breastfeeding duration with the risks of overweight and obesity were observed at the ages of 1, 2, and 3 years. Based on models adjusted for confounding factors, any breastfeeding was associated with a lower BMI-for-age z-score and lower odds of being overweight at 1 year of age in another Dutch cohort study.³³

In contrast to exclusive breastfeeding, based on estimated BMI growth curves for the ages of 14 days to 19 months, the duration of any breastfeeding was not associated with BMI growth velocity before peak, as well as age and BMI at peak in a Danish cohort study.²³ However, an earlier age at BMI peak was observed in a Singapore cohort study in those infants that were breastfed for ≥4 compared with <4 months.¹⁷

Discussion

Summary of findings

In this systematic review of current evidence, longer duration of exclusive and partial breastfeeding tended to be associated with slower growth rates in infancy in the developed setting only. Overall, these inverse associations seem to be dose dependent (i.e., the longer the duration of breastfeeding, the more pronounced the effect on growth rate reduction).

A clear dose dependency with respect to breastfeeding duration has been previously shown also in association with other childhood outcomes such as the risk of overweight and obesity and intelligence (IQ points).³⁶ While the aim of our review was to assess the role of breastfeeding duration in infant growth, exclusive breastfeeding duration for 4 versus 6 months is of particular importance in the context of the timing of introduction of complementary feeding. Uncertainty regarding the accurate timing for the transition from exclusive breastfeeding to complementary feeding has been reflected in regional practice differences as well as in discrepancies across the existing nutritional recommendations.³⁷

Overall, our findings further support the results from a previous review in which differences in growth between normal-weight infants exclusively breastfed for 4 months or 6 months were described as being “little”.⁹ Based on the results from observational studies included in our review, we did observe slight differences in infant growth parameters in relation to exclusive breastfeeding duration (although mainly measured continuously). However, the small RCT performed in a developed setting (Iceland) identified in our review, which focused specifically on 4 versus 6 months of exclusive breastfeeding in relation to infant growth, does not support these findings. The need for high-quality, large RCTs in this field is further acknowledged by this review.

Our findings also suggest some areas that require additional investigation. Along with infant growth itself, its mediating effect in the associations between breastfeeding duration and later childhood obesity, requiring an adequately long follow-up period, should be further investigated. Similar to exclusive breastfeeding, we did observe that longer duration of any breastfeeding tended to be associated with slower growth rates in infancy. However, direct comparison of the associations observed for exclusive and partial breastfeeding was possible only in two studies.^23,32 These findings suggest stronger associations in exclusively rather than partially breastfed infants. Finally, our results are also consistent with those in a previous review, in which exclusive breastfeeding for 6 months was regarded as being safe in terms of not causing a growth deficit.¹¹

Study strengths and limitations

One of the strengths of our review is that we applied the methodology proposed by the Cochrane Collaboration. The initial protocol preparation, with prespecified criteria for study inclusion, methodological assessment, data synthesis methods, further comprehensive literature search, and duplicate data abstraction, are some of the elements applied to reduce potential bias in our review.

Given the risk of poor indexing and description of an outcome in the title or abstract of observational studies, we cannot exclude the omission of relevant studies; however, efforts were made to reduce this risk. Furthermore, our search was limited to studies published in the English language only. The aim of this review was to provide a systematic summary of current evidence only; thus, it does not provide the totality of evidence in terms of less recent publications, but rather complements previously published reviews. We focused mainly on breastfeeding duration in relation to growth in the first year of life; however, growth in subsequent years of early childhood is clearly of importance too.

Our analysis does not overcome the potential limitations of the identified studies, which include small sample sizes, the lack of adjustment for important confounding factors (such as maternal education, socioeconomic status, birth weight, and gestational age at birth), suboptimal ascertainment of exposure, and poor reporting in some studies. The controlling for confounding factors differed across the studies. Still, we did not observe any apparent pattern of the associations that would depend on the extent of controlling for confounding factors. Importantly, the results from the single RCT, which by its design minimized confounding, showed no apparent differences in growth patterns between the groups in relation to breastfeeding duration.

We need to emphasize that ascertainment of exposure was often a limitation of the included studies and is the source of potential risk of bias. Information on breastfeeding duration was obtained by questionnaires in the majority of the studies, often with no detailed reporting on the breastfeeding exclusiveness indicators used. Although the problem with accuracy in measuring the duration of exclusive breastfeeding is well known and complex (among others due to its definition), no consensus on the best approach has been established.³⁸ The measurements of infants' growth parameters across included studies were mainly obtained by trained medical staff, which minimized the risk of measurement error. However, not all of the included studies attempted to assess patterns of growth but often rather assessed growth parameters at single time points.

We consider existing heterogeneity among the included studies in terms of their design and conduct, and most importantly, measures of the exposures and outcomes, as a major challenge for data synthesis and interpretation.

Conclusions

Longer duration of exclusive and partial breastfeeding tends to be associated with slower growth rates in infancy in the developed setting. These associations seem to be dose dependent and more pronounced in exclusively rather than partially breastfed infants. The relevance of these early growth patterns associated with breastfeeding duration to important long-term outcomes, including later risk of overweight and obesity and body composition, needs further evaluation.

Footnotes

Acknowledgments

The research leading to these results has received funding from the European Union's Seventh Framework Program (FP7/2007-2013), project EarlyNutrition under grant agreement no (289346), and Polish Ministry of Science and Higher Education (MNiSW) grant agreement no (2464/7.PR/2012/2), related to (W48/7PRCOOPERATION/2012).

Disclosure Statement

No competing financial interests exist.

Supplementary Material

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Supplementary Material

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