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Güngör D, Nadaud P, Dreibelbis C, et al. Shorter Versus Longer Durations of Any Human Milk Feeding and Food Allergies, Allergic Rhinitis, Atopic Dermatitis, and Asthma: A Systematic Review [Internet]. Alexandria (VA): USDA Nutrition Evidence Systematic Review; 2019 Apr.
Shorter Versus Longer Durations of Any Human Milk Feeding and Food Allergies, Allergic Rhinitis, Atopic Dermatitis, and Asthma: A Systematic Review [Internet].
Show detailsPLAIN LANGUAGE SUMMARY
What is the question?
- The question is: What is the relationship between shorter versus longer durations of any human milk feeding and food allergies, allergic rhinitis, atopic dermatitis, and asthma?
What is the answer to the question?
- Moderate evidence mostly from observational studies suggests that, among infants fed human milk, shorter versus longer durations of any human milk feeding are associated with higher risk of asthma in childhood and adolescence.Limited evidence does not suggest a relationship between the duration of any human milk feeding and allergic rhinitis or atopic dermatitis in childhood.Evidence about the relationship between shorter versus longer durations of any human milk feeding and atopic dermatitis from birth to 24 months is inconclusive, and there is insufficient evidence to determine the relationship of shorter versus longer durations of any human milk feeding with food allergies throughout the lifespan; allergic rhinitis from birth to 24 months, in adolescence, or in adulthood; asthma in adulthood; and atopic dermatitis in adolescence or in adulthood.
Why was this question asked?
- This important public health question was identified and prioritized as part of the U.S. Department of Agriculture and Department of Health and Human Services Pregnancy and Birth to 24 Months Project.
How was this question answered?
- A team of Nutrition Evidence Systematic Review staff conducted a systematic review in collaboration with a group of experts called a Technical Expert Collaborative.
What is the population of interest?
- The population of interest was generally healthy infants and toddlers (ages 0-24 months) who were in studies examining food allergies, allergic rhinitis, and atopic dermatitis throughout the lifespan and asthma from childhood through adulthood (ages 2 years and up).
What evidence was found?
- This review includes 35 articles.
- These articles compared infants fed human milk for shorter durations with infants fed human milk for longer durations. The infants could be fed any amount of human milk.
- These articles examined available evidence related to food allergies, allergic rhinitis, atopic dermatitis, and asthma.
- Most of the evidence examined allergic rhinitis, atopic dermatitis, and asthma through childhood.
- Children and adolescents who were fed human milk for shorter durations may have higher risk of asthma than children and adolescents who were fed human milk for longer durations.
- Children who were fed human milk for shorter durations and children who were fed human milk for longer durations do not seem to have different risk of allergic rhinitis or atopic dermatitis.
- There are limitations in the evidence as follows:
- There was not a lot of evidence about food allergies.
- There was not a lot of evidence in adolescents or adults.
- Some studies did not use strong methods to collect infant feeding data or measure outcomes.
- It is possible for factors other than infant feeding to impact the observed outcomes, and these factors were addressed differently by different studies.
- Some of the articles studied groups of children that may have been too small to detect whether there is a relationship between shorter versus longer durations of any human milk feeding and the outcomes.
- Atopic disease may impact the duration of any human milk feeding, because parents may decide, or receive medical advice, to continue or discontinue feeding human milk based on infants’ symptoms or because of a history of atopic disease in parents or older siblings.
How up-to-date is this review?
- This review includes literature from 01/1980 to 03/2016.
FULL REVIEW
Systematic review question
What is the relationship between shorter versus longer durations of any human milk feeding and food allergies, allergic rhinitis, atopic dermatitis, and asthma?
Conclusion statement
Moderate evidence mostly from observational studies suggests that, among infants fed human milk, shorter versus longer durations of any human milk feeding are associated with higher risk of asthma in childhood and adolescence.
Limited evidence does not suggest a relationship between the duration of any human milk feeding and allergic rhinitis or atopic dermatitis in childhood.
Evidence about the relationship between shorter versus longer durations of any human milk feeding and atopic dermatitis from birth to 24 months is inconclusive, and there is insufficient evidence to determine the relationship of shorter versus longer durations of any human milk feeding with food allergies throughout the lifespan; allergic rhinitis from birth to 24 months, in adolescence, or in adulthood; asthma in adulthood; and atopic dermatitis in adolescence or in adulthood.
Grade
Moderate: asthma in childhood and adolescence
Limited: allergic rhinitis and atopic dermatitis in childhood
Grade not assignable: food allergies throughout the lifespan, allergic rhinitis and atopic dermatitis outside of childhood, asthma in adulthood
Summary
- This systematic review examines comparisons of infants who were fed human milk for shorter durations with infants who were fed human milk for longer durations. Human milk feeding was defined as feeding human milk alone or in combination with infant formula and/or complementary foods or beverages such as cow’s milk. Human milk was defined as mother’s own milk provided at the breast (i.e., nursing) or expressed and fed fresh or after refrigeration or freezing. Donor milk (e.g., banked milk) was not examined in this review.
- This systematic review examines available evidence related to food allergies, allergic rhinitis, and atopic dermatitis from birth through adulthood and asthma from childhood through adulthood (outcomes prior to childhood may represent transient recurrent wheeze5).
- Thirty-five articles met the inclusion criteria for this systematic review, including 3 with evidence about food allergies, 7 with evidence about allergic rhinitis, 15 with evidence about atopic dermatitis, and 23 with evidence about asthma. Almost all of the evidence was from observational studies.
- Evidence about the association between shorter versus longer durations of any human milk feeding and higher risk of asthma in childhood and adolescence was moderate. Across the 20 independent studies (21 articles), 8 found statistically significant associations and, with 1 exception, they showed that shorter durations of any human milk feeding was associated with higher risk. The majority of nonsignificant associations were also consistent in suggesting higher risk of asthma in childhood and adolescence with shorter durations of any human milk feeding, and some of the inconsistency in statistical significance may be explained by insufficient statistical power. The ability to draw stronger conclusions was primarily limited by the limited statistical power in some studies and concerns about reverse causality and internal validity, such as the potential for confounding in a body of evidence primarily made up of observational studies.
- Evidence about the lack of an association between shorter versus longer durations of any human milk feeding and allergic rhinitis and atopic dermatitis in childhood was limited. Across the 5 independent studies (6 articles) that examined allergic rhinitis in children, the only significant association was from a subsample analysis of African-American children, and there were no comparable analyses with which to compare the result. Likewise, across the 8 independent studies (9 articles) that examined atopic dermatitis in children, the only significant associations were reported by a study with risk of multiple comparison bias. The ability to draw stronger conclusions was primarily limited by the small number of studies, limited statistical power in some studies, concerns with generalizability of the samples to diverse U.S. populations, and concern about the potential for confounding.
- Evidence about atopic dermatitis from birth to 24 months was inconclusive. Across 8 studies, the associations were inconsistent in direction. There was also concern about the specificity of diagnosing atopic dermatitis in this age group.
- Evidence related to food allergies throughout the lifespan, and outcomes beyond childhood, in general, was scant.
Description of the evidence
Thirty-five articles met the inclusion criteria for this systematic review question (1–35). Of these, 3 presented evidence related to food allergies (1–3), 7 presented evidence related to allergic rhinitis (4–10), 15 presented evidence related to atopic dermatitis (2, 4, 5, 7, 10–12, 18, 29–35), and 23 presented evidence related to asthma (5, 7–28) (some articles presented evidence for more than 1 outcome).
Food allergies
Three articles presented evidence about the relationship between shorter versus longer durations of any human milk feeding and food allergies (Table 1). One nested case-control study (1) and 1 prospective cohort study (2) presented outcomes from birth to 24 months, 1 prospective cohort study presented outcomes in childhood (3), and no studies examined outcomes in adolescence or adulthood.
The studies were from the US (3), UK (1), and Sweden (2). Participants were newborn at baseline. The US study included some ethnic diversity but the other studies did not report race/ethnicity. Participants in two of the studies were at risk for allergic disease (based on parent history of allergy) (2) or type 1 diabetes (based on genotype or family history) (3). The duration of any human milk feeding was collected prospectively by parent report and assessed as a continuous variable. The outcomes were food allergy by 18 months (2) and 2 years (1) of age and wheat allergy by 4 years of age (3). Only 1 of the studies controlled for confounding variables (3).
Allergic rhinitis
Seven articles presented evidence about the relationship between shorter versus longer durations of any human milk feeding and allergic rhinitis (Table 2). No studies examined outcomes in adolescence or adulthood.
One article (4) examined outcomes from birth to 24 months. It presented evidence from a Swedish birth cohort. Data about the duration of any human milk feeding were collected prospectively by parent report and assessed as a categorical variable (≥ 6 months vs < 6 months). The outcome was incidence of suspected allergic rhinitis by age 2 years, based on parent report of either symptoms or a doctor’s diagnosis of allergic rhinitis. The analysis included important adjustment variables.
Six articles presented outcomes in childhood (5–10). Kramer et al. (5) presented evidence from the Promotion of Breastfeeding Intervention Trial (PROBIT), a cluster randomized controlled trial of an intervention to promote prolonged duration and exclusivity of human milk feeding among mothers who chose to feed human milk. Study pediatricians collected human milk-feeding data at well-baby medical appointments, and the intervention group had higher rates of human milk feeding than the control group measured at 3, 6, 9, and 12 months. The outcomes, ever having hay fever symptoms or having hay fever symptoms in the previous 12 months, were assessed by study pediatricians using the validated instrument from the International Study of Asthma and Allergy in Childhood (ISAAC)6.
There were also 4 prospective cohort studies that presented evidence across 5 articles (6–10) (unique evidence from the Dampness in Buildings and Health (DBH) study was presented by Larsson et al. (7) and von Kobyletzki et al. (8)). Two of the studies examined high-risk cohorts (based on family history of allergic disease) (6, 10), and a third study examined children who were at risk for type 1 diabetes (9). Data about the duration of human milk feeding were collected by parent questionnaire and assessed as a continuous variable by Codispoti et al. (6) and as heterogeneous categorical variables by the other studies (7–10). Allergic rhinitis was defined based on parent responses to items from the ISAAC questionnaire (6–9), parent report of physician diagnosis (7), or positive skin prick test or allergen-specific IgE level ≥0.7 kU/l plus a history of symptoms (10). The comparisons of interest in 2 studies were unadjusted (7–9), and the remaining studies considered a range of confounders (6, 10).
Atopic dermatitis
Fifteen articles (2, 4, 5, 7, 10–12, 18, 29–35) presented evidence about the relationship between shorter versus longer durations of any human milk feeding and atopic dermatitis. Eight articles presented evidence from birth to 24 months (2, 4, 10, 18, 29–32) (Table 3), 9 articles presented evidence in childhood (5, 7, 10–12, 18, 33–35), and no articles presented outcomes in adolescence or adulthood (some articles presented evidence in more than one age group).
Birth to 24 months
The 8 articles that examined shorter versus longer durations of any human milk feeding and atopic dermatitis from birth to 24 months presented evidence from 1 cluster randomized controlled trial (32), 1 nested case-control study (29), and 6 prospective cohort studies (2, 4, 10, 18, 30, 31) (Table 3).
The cluster randomized controlled trial, PROBIT, was described previously in the section about allergic rhinitis. The outcome relevant to atopic dermatitis during the birth to 24 month period, atopic eczema by 12 months, was listed as a secondary outcome of the study7 and was diagnosed by study physicians.
The nested case-control study was from the Netherlands (29) and the prospective cohort studies were from Sweden (2, 4), Finland (10), Japan (30), New Zealand (31), and there was a multinational study from Finland, France, Germany, and Switzerland (18). All of these studies enrolled participants as newborns. Three studies specifically recruited individuals with family history of allergic disease (2, 10, 29). Data about human milk feeding duration were collected by parent report. The duration of any human milk feeding was assessed as a categorical variable by comparing specific ranges of duration (4, 10, 18, 30), and as a continuous variable (29, 31), including comparing the median duration of any human milk feeding between participants with and without atopic dermatitis (2). Atopic dermatitis was based on clinical examination (2, 10, 18, 29) or parent report of morbidity data and/or physician diagnosis (4, 18, 30, 31), and was measured from birth to 6 months (2), 15 months (31), 18 months (2), and 2 years of age (4, 18), and at 16 to 24 months (30), and 2 years of age (10). Kerkhof et al. (29) reported the expected probability of atopic dermatitis at 12 months. The studies varied in their selection and treatment of confounding variables. The comparisons of interest in 2 studies (2, 29) were unadjusted; however, the remaining studies considered a range of confounders.
Childhood
The 9 articles that examined shorter versus longer durations of any human milk feeding and atopic dermatitis in childhood presented evidence from 1 cluster randomized controlled trial (5), 6 prospective cohort studies that presented evidence across 7 articles (7, 10–12, 18, 33, 34) [Bergmann et al. (11, 33) presented evidence from the Multicentre Allergy Study across 2 articles] and 1 nested case-control study (35) (Table 4).
The cluster randomized controlled trial, PROBIT, was described previously in the section about allergic rhinitis. The outcome relevant to atopic dermatitis during childhood, eczema by 6.5 years, was listed as a secondary outcome of the study8 and was diagnosed by study physicians using the ISAAC instrument.
Across the prospective cohort and nested case-control studies, data about human milk feeding were collected by parent report. The duration of human milk feeding was assessed as a continuous variable (12, 33–35) and heterogeneous categorical variables (7, 10, 11, 18, 33, 35). Atopic dermatitis was defined based on parent responses to items from the ISAAC questionnaire (7, 35); by parent report of a physician’s diagnosis or a positive SCORring Atopic Dermatitis (SCORAD) score (18); and by physical examination plus parent-reported case history (11, 12, 33), a positive skin prick test on at least 1 occasion (10, 34) or an allergen-specific IgE level ≥0.7kU/l (10). Bergmann et al. (11, 33), Sandini et al. (10), and Kusel et al. (34) specifically recruited high-risk or “risk-enriched” samples based on family history of allergic disease and/or IgE levels. The comparisons of interest by Sariachvili et al. (35), Larsson et al. (7) and Kusel et al. (34) were unadjusted, whereas the remaining studies considered a range of confounders.
Asthma
Twenty-three articles (5, 7–28) presented evidence about the relationship between shorter versus longer durations of any human milk feeding and asthma. Two prospective cohort studies presented evidence in adults from Brazil (27) and Germany (28) (Table 6). Participants were newborn at baseline. Data about the duration of any human milk feeding duration was collected prospectively by parent report, and the studies compared categorical ranges of duration. The Brazilian study examined asthma at 18 years of age in a male-only subsample of the Pelotas Birth Cohort (27). The German study examined a “risk-enriched” sample based on family history of allergic disease or IgE levels and assessed asthma by 20 years of age (28). Outcomes were based on responses to validated ISAAC questionnaire items about symptoms, medication use, and physician diagnosis. Both studies included important adjustment variables.
Childhood and adolescence
Almost all of the articles examined asthma in children and adolescents (5, 7–26) (Table 5). These articles presented evidence from 1 experimental study and 19 independent observational studies (Larsson et al. (7) and von Kobyletzki et al. (8) presented unique evidence from the same study).
The experimental study, PROBIT (5), was described previously in the section about allergic rhinitis. The outcome relevant to childhood asthma, ever having asthma by 6.5 years, was a secondary outcome of the study9 assessed by study pediatricians using the ISAAC instrument.
The observational studies included 2 case-control studies from Kuwait (23) and Sri Lanka (14) and 17 independent prospective cohort studies from the US (15, 24), Sweden (7, 8, 16, 19, 20), Finland (9, 10, 25), Norway (26), Denmark (12), Germany (11), the UK (13), Brazil (22), Australia (17), New Zealand (21), and a multinational study from Finland, France, Germany, and Switzerland (18). The case-control studies sampled participants who were 1 to 10 (14) and 8 to 15 (23) years of age at the time of the study. With a few exceptions (7, 8, 19, 20, 25), the prospective cohorts followed participants from birth. A minority of articles reported race or ethnicity; the U.S. samples were mostly Non-Hispanic white (24) and “primarily Caucasian” (15), and the studies in Australia and New Zealand reported that the samples were 2.5% Aboriginal descent (17) and 14.6% Maori (21), respectively. A few studies recruited high-risk or “risk-enriched” samples based on IgE levels (11), a family history of allergic disease (10, 11, 15), or having had respiratory syncytial virus bronchiolitis in infancy (20). One study (9) recruited a sample with high risk for type 1 diabetes. Data about human milk feeding were collected by parent report. Asthma outcomes were based on physician diagnosis (7, 12–14, 20, 23), medical record (10, 15) or parent report of morbidity data and/or physician diagnosis (7–9, 15, 18, 19, 21, 22, 24–26). The studies varied in their selection and treatment of confounding variables; with the exception of 1 study (15), the studies considered a range of confounders.
Evidence synthesis
Food allergies
The available evidence was insufficient to determine the relationship between shorter versus longer durations of any human milk feeding and food allergies throughout the lifespan (Table 1). There were only 2 studies of outcomes from birth to 24 months (1, 2), 1 study of outcomes in childhood (3), and no studies of outcomes in adolescence or adulthood. This small number of studies examined both food allergy (1, 2) and wheat allergy (3), and included heterogeneous samples with regard to their risk for both allergic disease and type 1 diabetes. The studies also had limited methodological rigor; for example, only one study controlled for confounding variables (3).
Allergic rhinitis
The available evidence was insufficient to determine the relationship between shorter versus longer durations of any human milk feeding and allergic rhinitis in age groups other than childhood (Table 2). There was only 1 study of outcomes from birth to 24 months (4) and no studies of outcomes in adolescence or adulthood.
Limited evidence did not suggest a relationship between the duration of any human milk feeding and allergic rhinitis in childhood. The only experimental study, the PROBIT study, found no association between group status (the intervention group had higher rates of human milk feeding than the control group measured at 3, 6, 9, and 12 months) and ever having hay fever symptoms or having hay fever symptoms in the previous 12 months, both measured at age 6.5 years (5). Nearly all of the associations across the 4 prospective cohort studies were also nonsignificant, with no discernable trend in the direction of the point estimates. The only statistically significant association was by Codispoti et al. (6), which found that a longer duration of human milk feeding was associated with lower risk of allergic rhinitis in African American 3-year-olds (OR: 0.8; 95% CI: 0.6, 0.9). There were no comparable analyses in other studies in this body of evidence that would allow TEC members to examine whether this association is typical among African American children.
There are limitations to the adequacy, generalizability, and internal validity of the evidence in childhood. With regard to adequacy, there were only 5 independent studies and 1 sample may have been too small to have sufficient statistical power for the comparison of interest because the nonsignificant association had a wide confidence interval (10). Regarding generalizability, although all of the studies were conducted in countries listed as high or very high on the 2014 Human Development Index10, there was only 1 study from the US (6) and its sample was mostly white. The non-US samples did not report race/ethnicity. In addition, 1 study had participants with high risk for type 1 diabetes (9) and the comparison of interest for this systematic review was not adjusted for any type 1 diabetes risk-related variables. Confounding is possible because infant-feeding decisions can be strongly socially patterned; differences between feeding groups were only mitigated by randomization in the PROBIT study (5) and 2 of the observational studies did not address confounding variables in the analyses of interest (7–9). In addition, the DBH study may have been prone to attrition bias because there was high attrition (7, 8) that was differential with regard to 3 critical confounders: socioeconomic status, smoking, and family design.
Atopic dermatitis
The available evidence was insufficient to draw conclusions about the relationship between shorter versus longer durations of any human milk feeding and atopic dermatitis in age groups other than childhood. The evidence from birth to 24 months was inconclusive, as described below, and no articles presented outcomes in adolescence or adulthood.
Birth to 24 months
Eight articles presented inconclusive evidence on shorter versus longer durations of any human milk feeding and atopic dermatitis from birth to 24 months (2, 4, 10, 18, 29–32) (Table 3). Kramer et al. (32) provided compelling evidence from the PROBIT study (a cluster randomized controlled trial) that the experimental group had lower risk of atopic dermatitis at 12 months of age than the control group (OR: 0.54; 95% CI: 0.31, 0.95). Yet, evidence from 7 observational studies (2, 4, 10, 18, 29–31) was inconsistent with evidence from the PROBIT study. Miyake et al. (30) found that feeding human milk ≥6 months, in comparison to <6 months, was associated with significantly higher odds of atopic dermatitis in the absence of parental atopic history (OR: 3.39; 95% CI: 1.20, 12.36), and evidence from the remaining studies lacked statistical significance and had point estimates that were inconsistent in direction. Furthermore, TEC members had concerns about reverse causality and the specificity of detecting atopic dermatitis during the birth to 24 month period.
Childhood
The available evidence does not suggest a relationship between shorter versus longer durations of any human milk feeding and atopic dermatitis in childhood (Table 4).
The PROBIT study (a cluster randomized controlled trial) (5) found no association between group status and ever having eczema by 6.5 years. Likewise, most of the associations between the duration of any human milk feeding and atopic dermatitis in childhood across the observational studies were nonsignificant. Only Bergmann et al. (33) found a positive association between the duration of any human milk feeding (assessed as a continuous variable) and atopic eczema through 7 years of age (OR: 1.029; 95% CI: 1.002, 1.057) and between being fed human milk ≥2 months, in comparison to <2 months, and higher odds of atopic eczema through 7 years of age (OR: 1.384; 95% CI: 1.025, 1.869). However, the significant associations were limited to 1 (33) of 2 articles (11, 33) with data from the Multicentre Allergy Study, and to 2 of the 10 relevant analyses in the article.
There are limitations to the adequacy, generalizability, and internal validity of the evidence. With regard to adequacy, there were only 8 independent studies (with evidence across 9 articles) and the samples in 4 of the studies (5, 10, 11, 18) may have been too small to have sufficient statistical power to examine the comparisons of interest for this systematic review, as they had wide confidence intervals around their nonsignificant associations. Regarding generalizability, although all of the studies were conducted in countries listed as high or very high on the 2014 Human Development Index11, no studies were conducted in the US or reported race/ethnicity. Confounding is possible because infant-feeding decisions can be strongly socially patterned; differences between feeding groups were only mitigated by randomization in the PROBIT study (5) and 3 of the observational studies did not address confounding variables in the analyses of interest (7, 34, 35). In addition, some studies may have prone to attrition bias due to high and/or differential attrition (7, 11, 12, 33, 34).
Asthma
The available evidence was insufficient to determine the relationship between shorter versus longer durations of any human milk feeding and asthma in adulthood (Table 6). There were only 2 studies (27, 28), generalizability was limited because one study examined asthma in male participants, only (27), and there was high attrition.
Childhood and adolescence
Across the studies that examined asthma in childhood and adolescence (5, 7–26) (Table 5), statistically significant associations were reported by 6 prospective cohort studies (7, 9, 16, 21, 24, 26) and both case-control studies (14, 23). With 1 exception (24), these studies found inverse associations between the duration of any human milk feeding and asthma risk in children and adolescents, and suggested that the predominant difference between the statistically significant and nonsignificant associations was statistical power.
Specifically, in the study by Hovland et al. (26) a larger proportion of the participants who never had asthma (N=322) were fed human milk >4 months than participants who had asthma. However, the difference was only significant with the subsample of participants with asthma in remission during puberty [10 to 16 years of age (OR: 0.22; 95% CI: 0.08, 0.65)], and not in the subsamples with asthma during puberty.
Kull et al. (16) examined shorter versus longer durations of exclusive plus additional partial human milk feeding. Being fed human milk ≥3 months after 3 to 4 months of exclusive human milk feeding, and being fed human milk ≥5 months after ≥3 months of exclusive human milk feeding (i.e., longer durations), in comparison to being fed human milk 0 to 2 months after to 0 to 2 months of exclusive human milk feeding (i.e., a shorter duration) were associated with lower odds of asthma at 4 years of age (OR: 0.44; 95% CI: 0.21, 0.87 and OR: 0.43; 95% CI: 0.25, 0.74, respectively). The nonsignificant associations were in the same direction but had wider confidence intervals indicative of suboptimal statistical power.
In the DBH study, Larsson et al. (7) and von Kobyletzki et al. (8) examined the 5-year cumulative incidence of asthma by 6 to 7 (8) and 6 to 9 (7) years of age in a sample of children who did not have asthma at baseline, and in subsamples of children who did (7) and did not (7, 8) have wheezing at baseline. In the subsample of children with wheezing at baseline, Larsson et al. (7) found higher odds of asthma in children fed human milk <3 months and 3 to 6 months in comparison to >6 months (OR: 2.11; 95% CI: 1.12, 3.00 and OR: 1.84; 95% CI: 1.09, 3.11, respectively). In analyses of the full sample and the subsample with no wheezing at baseline, the nonsignificant associations were in the same direction and had wide confidence intervals indicative a lack of statistical power (7, 8).
In a sample with high risk for type 1 diabetes, Nwaru et al. (9) found higher hazard ratios among children fed human milk <5 months and 5 to 9.5 months in comparison to >9.5 months (HR: 1.91; 95% CI: 1.21, 3.02 and HR: 1.97; 95% CI: 1.28, 3.02, respectively).
Silvers et al. (21) examined the duration of any human milk feeding as a continuous variable and found lower odds of asthma at 3 and 4 years of age as the number of months of human milk feeding increased (OR: 0.94; 95% CI: 0.91, 0.97 and OR: 0.96; 95% CI: 0.92, 0.99, respectively). At 5 years of age the upper limit of the confidence interval was 1.00, and at 6 years of age the confidence interval included the null.
Colen et al. (24) conducted the only prospective cohort study with a statistically significant association that showed that a longer versus shorter duration of any human milk feeding was associated with a higher risk of asthma. It examined asthma from 4 to 14 years using a between-family estimate from the full sample as well as a within-family estimate from a subsample of sibling participants. In the full sample, each additional week of feeding human milk tended to increase asthma; however, the effect size was small (β: 0.004; SE: 0.002; p<0.05) and a nonsignificant and similarly small effect size was found in the sibling subsample analysis.
Statistically significant associations were also reported by both case-control studies (14, 23), which provided additional evidence of an inverse association between the duration of any human milk feeding and asthma risk in children and adolescents. Karunasekera et al. (14) reported that being fed human milk ≤6 months versus >6 months was associated with higher odds of asthma at 1 to 10 years of age (OR: 2.0; 95% CI: 1.2, 3.2), and Al-Mousawi et al. (23) reported that being fed human milk >2 months versus <2 months was associated with lower odds of asthma at 8 to 15 years of age (OR: 0.54; 95% CI: 0.30, 0.96).
The nonsignificant associations provided further evidence of an inverse relationship between the duration of any human milk feeding and asthma because they were consistent in direction with the significant associations (7, 8, 10–13, 16, 17, 20–22, 26) and some of the non-significance was explainable due to inadequate power. The minority of studies had nonsignificant associations that were discrepant (5, 18, 19, 25) or did not report point estimates so direction could not be assessed (15).
The evidence related to shorter versus longer durations of any human milk feeding and asthma in childhood and adolescence was graded moderate after considering the adequacy, consistency, impact, generalizability, and internal validity of the evidence. Twenty independent studies examined the duration of any human milk feeding and asthma in children and adolescents and, with 1 exception (24), the statistically significant associations showed that shorter versus longer durations associate with higher risk of asthma (7, 9, 14, 16, 21, 23, 26). The majority of nonsignificant associations were also consistent in suggesting higher risk with shorter versus longer durations of any human milk feeding, and some of the inconsistency in statistical significance may be explained by insufficient statistical power resulting in wide confidence intervals. Evidence was consistent despite heterogeneous independent variables resulting from not defining shorter or longer for the systematic review, and instead including all relevant comparisons. However, the consistency was limited to observational studies because the single experimental study had a nonsignificant association (5).
In the NESR grading rubric, the impact of the evidence takes into consideration the directness with which the study designs examined the link between the exposure and outcome of interest in the systematic review question, and the clinical significance of the evidence. Although some studies’ original objectives were not explicitly stated, most studies described objectives related to examining the link between feeding human milk and asthma; 6 studies were indirect (7–10, 17, 20, 22). Regarding clinical significance, asthma affects the quality of life for millions of children in the U.S. and can be life-threatening; therefore, even small decreases in the risk for asthma have the potential to be of public health importance.
The generalizability of the evidence to U.S. populations had a few limitations, but was sound overall. There were 2 U.S. studies of shorter versus longer durations of any human milk feeding and asthma in childhood and adolescence; however, they lacked racial and ethnic diversity. In addition, 1 sample was high-risk for type 1 diabetes and the evidence of interest for this systematic review did not include any corresponding model adjustments (9). The samples were from countries that were high or very high on the 2014 Human Development Index12 and therefore had a level of human development likely generalizable to the U.S.
There were some concerns about internal validity. Infant milk-feeding research can be prone to detection bias because infant milk-feeding data are often collected using parent reporting methods that may not be valid and reliable; however, most studies collected these data prospectively, which reduces recall bias. Confounding can arise because differences between feeding groups are rarely mitigated by randomization (due to ethical issues around allocating infants to be fed no human milk) and infant-feeding decisions can be strongly socially patterned. However, most studies adjusted for confounding variables deemed important and feasible to control, although the specific adjustment variables varied between studies. Reverse causation can be a major concern because parents may decide, or receive medical advice, to continue or discontinue feeding human milk based on infants’ symptoms and because atopic disease in parents or older siblings may influence parents’ feeding decisions as they try to prevent asthma. However, the majority of studies found no baseline differences in family history of atopic disease between groups or included family history of atopic disease as an adjustment variable (5, 7–11, 13, 14, 16, 18, 20–23, 25, 26). Attrition bias, due to high attrition, differential attrition, or both, may have existed among some of the studies in the body of evidence (7, 8, 11, 12, 17, 24–26); however, these studies were not more concentrated among the studies with significant versus nonsignificant associations.
Research recommendations
Studies need to be designed and conducted to examine topics where there are gaps in evidence or limited evidence; this includes the relationships between shorter versus longer durations of any human milk feeding and food allergies, allergic rhinitis, and atopic dermatitis throughout the lifespan, and asthma in adulthood. In addition, it would be beneficial to have more research with representative U.S. samples to confirm current evidence. We propose that researchers study the duration of human milk feeding among infants fed human milk (i.e., assess infants who were never fed human milk separately from humans who were fed human milk).
Infant-feeding research will continue to rely on observational designs, because of ethical issues related to randomizing infant to be fed less or no human milk; however, researchers should endeavor to minimize bias through sound research design and conduct. In general, infant-feeding researchers should:
- Move toward collecting data consistently using valid and reliable methods
- Increase the precision with which they define infant-feeding variables
- Incorporate effect modification into their study design whenever possible in case different biological or environmental characteristics modify the impact of infant feeding on the outcomes
- Assess baseline differences in critical confounding variables between comparison groups, and make statistical adjustments as necessary
- Address temporality and reverse causality when outcomes are measured from birth to 24 months
Included articles
- 1.
- Grimshaw KE, Maskell J, Oliver EM, Morris RC, Foote KD, Mills EN, Roberts G, Margetts BM. Introduction of complementary foods and the relationship to food allergy. Pediatrics 2013;132(6):e1529–38. [PubMed: 24249826]
- 2.
- Hesselmar B, Saalman R, Rudin A, Adlerberth I, Wold A. Early fish introduction is associated with less eczema, but not sensitization, in infants. Acta Paediatr 2010;99(12):1861–7. [PubMed: 20670305]
- 3.
- Poole JA, Barriga K, Leung DY, Hoffman M, Eisenbarth GS, Rewers M, Norris JM. Timing of initial exposure to cereal grains and the risk of wheat allergy. Pediatrics 2006;117(6):2175–82. [PubMed: 16740862]
- 4.
- Kull, I, Wickman, M, Lilja, G, Nordvall, S L, Pershagen, G. Breast feeding and allergic diseases in infants-a prospective birth cohort study. Arch Dis Child 2002;87(6):478–81. [PMC free article: PMC1755833] [PubMed: 12456543]
- 5.
- Kramer, M S, Matush, L, Vanilovich, I, Platt, R, Bogdanovich, N, et al. Effect of prolonged and exclusive breast feeding on risk of allergy and asthma: cluster randomised trial. BMJ 2007;335(7624):815. [PMC free article: PMC2034727] [PubMed: 17855282]
- 6.
- Codispoti, C D, Levin, L, LeMasters, G K, Ryan, P, Reponen, T, et al. Breast-feeding, aeroallergen sensitization, and environmental exposures during infancy are determinants of childhood allergic rhinitis. J Allergy Clin Immunol 2010;125(5):1054–60 e1. [PMC free article: PMC4910509] [PubMed: 20392478]
- 7.
- Larsson, M, Hagerhed E, L, Sigsgaard, T, Janson, S, Sundell, J, et al. Incidence rates of asthma, rhinitis and eczema symptoms and influential factors in young children in Sweden. Acta Paediatr 2008;97(9):1210–5. [PubMed: 18624993]
- 8.
- von Kobyletzki LB, Bornehag CG, Hasselgren M, Larsson M, Lindstrom CB, Svensson A. Eczema in early childhood is strongly associated with the development of asthma and rhinitis in a prospective cohort. BMC Dermatol 2012;12:11. [PMC free article: PMC3469362] [PubMed: 22839963]
- 9.
- Nwaru BI, Takkinen HM, Niemela O, Kaila M, Erkkola M, Ahonen S, Haapala AM, Kenward MG, Pekkanen J, Lahesmaa R, et al. Timing of infant feeding in relation to childhood asthma and allergic diseases. J Allergy Clin Immunol 2013;131(1):78–86. [PubMed: 23182171]
- 10.
- Sandini, U, Kukkonen, A K, Poussa, T, Sandini, L, Savilahti, E, et al. Protective and risk factors for allergic diseases in high-risk children at the ages of two and five years. Int Arch Allergy Immunol 2011;156(3):339–48. [PubMed: 21720181]
- 11.
- Bergmann, R L, Edenharter, G, Bergmann, K E, Lau, S, Wahn, U. Socioeconomic status is a risk factor for allergy in parents but not in their children. Clin Exp Allergy 2000;30(12):1740–5. [PubMed: 11122212]
- 12.
- Grandjean, P, Poulsen, L K, Heilmann, C, Steuerwald, U, Weihe, P. Allergy and sensitization during childhood associated with prenatal and lactational exposure to marine pollutants. Environ Health Perspect 2010;118(10):1429–33. [PMC free article: PMC2957924] [PubMed: 20562055]
- 13.
- Karmaus, W, Dobai, A L, Ogbuanu, I, Arshard, S H, Matthews, S, et al. Long-term effects of breastfeeding, maternal smoking during pregnancy, and recurrent lower respiratory tract infections on asthma in children. J Asthma 2008;45(8):688–95. [PMC free article: PMC2700345] [PubMed: 18951262]
- 14.
- Karunasekera, K A, Jayasinghe, J A, Alwis, L W. Risk factors of childhood asthma: a Sri Lankan study. J Trop Pediatr 2001;47(3):142–5. [PubMed: 11419676]
- 15.
- Klinnert, M D, Nelson, H S, Price, M R, Adinoff, A D, Leung, D Y, et al. Onset and persistence of childhood asthma: predictors from infancy. Pediatrics 2001;108(4):E69. [PubMed: 11581477]
- 16.
- Kull, I, Almqvist, C, Lilja, G, Pershagen, G, Wickman, M. Breast-feeding reduces the risk of asthma during the first 4 years of life. J Allergy Clin Immunol 2004;114(4):755–60. [PubMed: 15480312]
- 17.
- Oddy, W H, Holt, P G, Sly, P D, Read, A W, Landau, L I, et al. Association between breast feeding and asthma in 6 year old children: findings of a prospective birth cohort study. BMJ 1999;319(7213):815–9. [PMC free article: PMC314207] [PubMed: 10496824]
- 18.
- Orivuori, L, Loss, G, Roduit, C, Dalphin, J C, Depner, M, et al. Soluble immunoglobulin A in breast milk is inversely associated with atopic dermatitis at early age: the PASTURE cohort study. Clin Exp Allergy 2014;44(1):102–12. [PubMed: 24102779]
- 19.
- Ronmark E, Perzanowski M, Platts-Mills T, Lundback B. Incidence rates and risk factors for asthma among school children: a 2-year follow-up report from the obstructive lung disease in Northern Sweden (OLIN) studies. Respir Med 2002;96(12):1006–13. [PubMed: 12477216]
- 20.
- Sigurs, N, Bjarnason, R, Sigurbergsson, F, Kjellman, B, Bjorksten, B. Asthma and immunoglobulin E antibodies after respiratory syncytial virus bronchiolitis: a prospective cohort study with matched controls. Pediatrics 1995;95(4):500–5. [PubMed: 7700748]
- 21.
- Silvers KM, Frampton CM, Wickens K, Pattemore PK, Ingham T, Fishwick D, Crane J, Town GI, Epton MJ, New Zealand A, et al. Breastfeeding protects against current asthma up to 6 years of age. J Pediatr 2012;160(6):991–6 e1. [PubMed: 22289356]
- 22.
- Strassburger, S Z, Vitolo, M R, Bortolini, G A, Pitrez, P M, Jones, M H, et al. Nutritional errors in the first months of life and their association with asthma and atopy in preschool children. J Pediatr (Rio J) 2010;86(5):391–9. [PubMed: 20938590]
- 23.
- Al-Mousawi MS, Lovel H, Behbehani N, Arifhodzic N, Woodcock A, Custovic A. Asthma and sensitization in a community with low indoor allergen levels and low pet-keeping frequency. J Allergy Clin Immunol 2004;114(6):1389–94. [PubMed: 15577842]
- 24.
- Colen CG, Ramey DM. Is breast truly best? Estimating the effects of breastfeeding on long-term child health and wellbeing in the United States using sibling comparisons. Social Science & Medicine 2014;109:55–65. [PMC free article: PMC4077166] [PubMed: 24698713]
- 25.
- Fredriksson, P, Jaakkola, N, Jaakkola, J J. Breastfeeding and childhood asthma: a six-year population-based cohort study. BMC Pediatr 2007;7:39. [PMC free article: PMC2228279] [PubMed: 18045471]
- 26.
- Hovland V, Riiser A, Mowinckel P, Carlsen KH, Lodrup Carlsen KC. Early risk factors for pubertal asthma. Clin Exp Allergy 2015;45(1):164–76. [PubMed: 25220447]
- 27.
- da Costa L, R, Victora, C G, Menezes, A M, Barros, F C. Do risk factors for childhood infections and malnutrition protect against asthma? A study of Brazilian male adolescents. Am J Public Health 2003;93(11):1858–64. [PMC free article: PMC1448063] [PubMed: 14600053]
- 28.
- Grabenhenrich LB, Gough H, Reich A, Eckers N, Zepp F, Nitsche O, Forster J, Schuster A, Schramm D, Bauer CP, et al. Early-life determinants of asthma from birth to age 20 years: a German birth cohort study. J Allergy Clin Immunol 2014;133(4):979–88. [PubMed: 24461583]
- 29.
- Kerkhof, M, Koopman, L P, van S, R T, Wijga, A, Smit, H A, et al. Risk factors for atopic dermatitis in infants at high risk of allergy: the PIAMA study. Clin Exp Allergy 2003;33(10):1336–41. [PubMed: 14519137]
- 30.
- Miyake, Y, Tanaka, K, Sasaki, S, Kiyohara, C, Ohya, Y, et al. Breastfeeding and atopic eczema in Japanese infants: The Osaka Maternal and Child Health Study. Pediatr Allergy Immunol 2009;20(3):234–41. [PubMed: 19438982]
- 31.
- Silvers, K M, Frampton, C M, Wickens, K, Epton, M J, Pattemore, P K, et al. Breastfeeding protects against adverse respiratory outcomes at 15 months of age. Matern Child Nutr 2009;5(3):243–50. [PMC free article: PMC6860616] [PubMed: 20572927]
- 32.
- Kramer MS, Chalmers B, Hodnett ED, Sevkovskaya Z, Dzikovich I, Shapiro S, Collet JP, Vanilovich I, Mezen I, Ducruet T, et al. Promotion of Breastfeeding Intervention Trial (PROBIT): a randomized trial in the Republic of Belarus. JAMA 2001;285(4):413–20. [PubMed: 11242425]
- 33.
- Bergmann, R L, Diepgen, T L, Kuss, O, Bergmann, K E, Kujat, J, et al. Breastfeeding duration is a risk factor for atopic eczema. Clin Exp Allergy 2002;32(2):205–9. [PubMed: 11929483]
- 34.
- Kusel, M M, Holt, P G, de K, N, Sly, P D. Support for 2 variants of eczema. J Allergy Clin Immunol 2005;116(5):1067–72. [PubMed: 16275378]
- 35.
- Sariachvili M, Droste J, Dom S, Wieringa M, Hagendorens M, Stevens W, van Sprundel M, Desager K, Weyler J. Early exposure to solid foods and the development of eczema in children up to 4 years of age. Pediatr Allergy Immunol 2010;21(1 Pt 1):74–81. [PubMed: 19573205]
ANALYTIC FRAMEWORK
The analytic framework (Figure 1) illustrates the overall scope of the systematic review, including the population, exposures, comparators, and outcomes of interest. It also includes definitions of key terms. This is the analytic framework for the systematic review conducted to examine the relationship between shorter versus longer durations of any human milk feeding and food allergies, allergic rhinitis, atopic dermatitis, and asthma.
SEARCH PLAN AND RESULTS
Inclusion and exclusion criteria
The inclusion and exclusion criteria (Table 7) are a set of characteristics to determine which studies will be included or excluded in the systematic review. This table provides the inclusion and exclusion criteria for the systematic review question: What is the relationship between shorter versus longer durations of any human milk feeding and food allergies, allergic rhinitis, atopic dermatitis, and asthma?
Search terms and electronic databases used
PubMed
- Dates searched: Dec 4, 2015 and March 28, 2016 to refine/limit search terms and remove pub type indexing
- Search Terms:(breast feeding[mh] OR breastfeeding[tiab] OR breast feeding*[tiab] OR breast-feeding*[tiab] OR breastfed[tiab] OR breast-fed[tiab] OR breastfeed*[tiab] OR “breast feed”[tiab]) OR (Milk, human[mh] OR “breast milk”[tiab] OR breast-milk[tiab] OR “human milk”[tiab] OR “mother’s milk”[tiab] OR breastmilk[tiab]) OR (Bottle feeding[mh] OR bottle feeding*[tiab] OR “bottle feeding”[tiab] OR bottle-feeding*[tiab] OR bottle-fed[tiab] OR “bottle fed”[tiab])NOT ((aids[ti] AND “Acquired Immunodeficiency Syndrome”[Mesh]) OR hiv[ti] OR HIV/AIDS[ti] OR human immunodefic*[ti] OR Acquired Immunodefic*[ti] OR “low birth weight”[ti] OR lbw[ti] OR vlbw[ti] OR elbw[ti] OR pcb[ti] OR pcbs[ti] OR Polychlorinated Biphenyl*[ti] OR Polychlorobiphenyl Compound*[ti] OR dioxin*[ti] OR (breast[ti] AND (tumor*[ti] OR tumour*[ti] OR cancer*[ti] OR carcinoma*[ti] OR disease*[ti]))) NOT (breastfeed*[ti] OR breastfed*[ti] OR feed*[ti] OR fed[ti] OR milk[ti])NOT (editorial[ptyp] OR comment[ptyp] OR news[ptyp] OR letter[ptyp] OR review[ptyp] OR systematic[sb])Limiters; Engl/humans; 1980-
Embase
- Date searched: Dec 5, 2015
- Search Terms:‘bottle feeding’/exp OR ‘bottle feeding’:ab,ti OR ‘bottle feedings’:ab,ti OR ‘bottle fed’:ab,ti OR bottle* NEAR/3 feed* AND [english]/lim AND [humans]/lim AND [1980-2015]/py OR ‘breast milk’/exp OR ‘human milk’:ab,ti OR ‘breast milk’:ab,ti OR breastmilk:ab,ti OR mother* NEAR/2 milk OR ‘maternal milk’:ab,ti AND [english]/lim AND [humans]/lim AND [1980-2015]/py OR ‘breast feeding’/exp OR breastfeed*:ab,ti OR ‘breast feed’:ab,ti OR ‘breast feeding’:ab,ti OR breastfed:ab,ti OR ‘breast fed’:ab,ti OR feeding NEAR/3 breast AND [english]/lim AND [humans]/lim AND [1980-2015]/pyUsing Citation manager to filter out title key words:NOT (aids AND “Acquired Immunodeficiency Syndrome”) OR hiv OR HIV/AIDS OR human immunodefic* OR Acquired Immunodefic* OR “low birth weight” OR lbw OR vlbw OR elbw OR pcb OR pcbs OR Polychlorinated Biphenyl* OR Polychlorobiphenyl Compound* OR dioxin* OR (breast AND (tumor* OR tumour* OR cancer* OR carcinoma* OR disease*)) OR preterm OR premature
CINAHL
- Date searched: Dec 8, 2015
- Search Terms:(MH “Breast Feeding+” OR breast-fed OR “breast fed” OR breastfeeding OR breast feeding OR breast-fed) OR MH “Milk, Human” OR “Human Milk” OR “Breast Milk” OR Breastmilk OR breast-milk OR ((maternal OR mother*) n3 milk) OR (MH “Bottle Feeding”) OR “bottle feeding” OR (bottle n3 feed*) OR bottle-feeding OR bottle-feedings OR “bottle fed” OR “bottle-fed”)Using Citation manager to filter out title key words:NOT (aids AND “Acquired Immunodeficiency Syndrome”) OR hiv OR HIV/AIDS OR human immunodefic* OR Acquired Immunodefic* OR “low birth weight” OR lbw OR vlbw OR elbw OR pcb OR pcbs OR Polychlorinated Biphenyl* OR Polychlorobiphenyl Compound* OR dioxin* OR (breast AND (tumor* OR tumour* OR cancer* OR carcinoma* OR disease*)) OR preterm OR premature
Cochrane
- Date searched: Dec 8, 2015
- Search Terms:“Breast Feeding”OR breast-fed OR “breast fed” OR breastfeeding OR “breast feeding” OR “breast feed” OR “breast feeds” OR breast-feed OR breast-feeds OR (breast NEAR/3 feed*) OR “human milk” OR “breast milk” OR breastmilk OR “mother’s milk” OR “maternal milk” OR ((mother* OR maternal OR donor* OR donate*) NEAR/3 milk) OR “Bottle feeding” OR “bottle feedings” OR “bottle-feeding” OR “bottle-feedings” OR (bottle NEAR/3 feed*)Using Citation manager to filter out title key words:NOT (aids AND “Acquired Immunodeficiency Syndrome”) OR hiv OR HIV/AIDS OR human immunodefic* OR Acquired Immunodefic* OR “low birth weight” OR lbw OR vlbw OR elbw OR pcb OR pcbs OR Polychlorinated Biphenyl* OR Polychlorobiphenyl Compound* OR dioxin* OR (breast AND (tumor* OR tumour* OR cancer* OR carcinoma* OR disease*)) OR preterm OR premature
This flow chart illustrates the literature search and screening results for articles examining the relationship between infant milk-feeding practices, including shorter versus longer durations of any human milk feeding, and several outcomes, including food allergies, allergic rhinitis, atopic dermatitis, and asthma. The results of the electronic database searches were screened independently by two NESR analysts in a step-wise manner by reviewing titles and abstracts, and then full text articles to determine which articles met the criteria for inclusion. A manual search was done to ascertain articles not identified through the electronic database search. The systematic review on shorter versus longer durations of any human milk feeding and food allergies, allergic rhinitis, atopic dermatitis, and asthma included 35 articles.
Footnotes
- 5
Stein RT, Holberg CJ, Morgan WJ, Wright AL, Lombardi E, Taussig L, Martinez FD. Peak flow variability, methacholine responsiveness and atopy as markers for detecting different wheezing phenotypes in childhood. Thorax 1997;52(11):946–52. [PMC free article: PMC1758449] [PubMed: 9487341]
- 6
International Study of Asthma and Allergies in Childhood. Version 5 April 2017. Internet: https://www
.cancer.gov /types/leukemia/hp /child-all-treatment-pdq (accessed April 13 2018). - 7
U.S. National Library of Medicine. Clinicaltrials
.gov. Version 10 October 2013. Internet: https: //clinicaltrials .gov/ct2/show/NCT01561612#wrapper (accessed February 16, 2018). - 8
U.S. National Library of Medicine. Clinicaltrials
.gov. Version 10 October 2013. Internet: https: //clinicaltrials .gov/ct2/show/NCT01561612#wrapper (accessed February 16, 2018). - 9
U.S. National Library of Medicine. Clinicaltrials
.gov. Version 10 October 2013. Internet: https: //clinicaltrials .gov/ct2/show/NCT01561612#wrapper (accessed February 16, 2018). - 10
United Nations Development Programme. Human Development Report 2014. Sustaining Human Progress: Reducing Vulnerabilities and Building Resilience. New York, 2014
- 11
United Nations Development Programme. Human Development Report 2014. Sustaining Human Progress: Reducing Vulnerabilities and Building Resilience. New York, 2014
- 12
United Nations Development Programme. Human Development Report 2014. Sustaining Human Progress: Reducing Vulnerabilities and Building Resilience. New York, 2014
- 13
In 1980 the Infant Formula Act was passed (13), and December 2015 was when the literature search occurred
- 14
U.S. Food and Drug Administration. Version 19 December 2013. Internet: https://www
.fda.gov/Food /GuidanceRegulation /GuidanceDocumentsRegulatoryInformation /InfantFormula/ucm136118 .htm#manufacture (accessed March 23, 2018). - 15
Food and Agriculture Organization of the United Nations. World Health Organization. Codex Alimentarius. International Food Standards. Standard for infant formula and formulas for special medical purposes intended for infants. Codex Stan 72-1981. 2007.
- 16
United Nations Development Programme. Human Development Report 2014. Sustaining Human Progress: Reducing Vulnerabilities and Building Resilience. New York, 2014.
- 17
Stein RT, Holberg CJ, Morgan WJ, Wright AL, Lombardi E, Taussig L, Martinez FD. Peak flow variability, methacholine responsiveness and atopy as markers for detecting different wheezing phenotypes in childhood. Thorax 1997;52(11):946–52. [PMC free article: PMC1758449] [PubMed: 9487341]
- WHAT IS THE RELATIONSHIP BETWEEN SHORTER VERSUS LONGER DURATIONS OF ANY HUMAN MI...WHAT IS THE RELATIONSHIP BETWEEN SHORTER VERSUS LONGER DURATIONS OF ANY HUMAN MILK FEEDING AND FOOD ALLERGIES, ALLERGIC RHINITIS, ATOPIC DERMATITIS, AND ASTHMA? - Shorter Versus Longer Durations of Any Human Milk Feeding and Food Allergies, Allergic Rhinitis, Atopic Dermatitis, and Asthma: A Systematic Review
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