Video Abstract

Video Abstract

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BACKGROUND:

Studies on the association between breastfeeding and infections in children beyond the first year of life reveal conflicting results. In a population-based birth cohort, we investigated whether the duration of breastfeeding was associated with the number of hospitalizations due to infection and symptoms of infection at home.

METHODS:

In the Odense Child Cohort, text message questionnaires were used to register information on breastfeeding (weekly until end of weaning) and symptoms of infection (biweekly; 12–36 months of age). Hospitalization data were obtained from the Danish National Patient Registry.

RESULTS:

Of the 1087 invited, 815 mother-infant pairs were included. The median duration of any breastfeeding was 7.6 (interquartile range: 3.5–10.4) months and of exclusive breastfeeding was 2.1 (interquartile range: 0.7–4.4) months. Hospitalization due to infection was seen in 207 (25.4%) infants during the first 3 years of life. The adjusted incidence rate ratio (IRR) for hospitalization due to any infection decreased with a longer duration of any breastfeeding (adjusted IRR: 0.96; 95% confidence interval 0.93–0.99; P < .001). The strongest associations between the duration of any breastfeeding and hospitalizations due to infection were found within the first year of life, for lower respiratory tract infections, and other infections (P ≤ .05). For infants exclusively breastfed, the adjusted IRR for hospitalization was 0.88 (95% confidence interval: 0.80–0.96; P = .006). No protective associations were present between breastfeeding and infection symptoms registered at home from ages 12 to 36 months.

CONCLUSIONS:

The results suggest that increased duration of breastfeeding, especially exclusive breastfeeding, protects against infections requiring hospitalization in the first year of life but not hospitalizations or symptoms of infection at home beyond the first year.

What’s Known on This Subject:

Previous studies on breastfeeding and infections have revealed a protective effect of breastfeeding, although the duration and type of infection that benefitted differed. In most studies, researchers investigated this association only in the first year of life.

What This Study Adds:

We show that the duration of breastfeeding was associated with a decreased risk of hospitalization due to any infection in the first year of life, primarily due to exclusive breastfeeding. We show no association between breastfeeding and home-recorded symptoms of infection.

The benefits of breastfeeding on childhood health include a reduced risk of wheezing, atopic eczema, and infections.14  Some associations seem to depend on breastfeeding duration, with increased benefits seen with longer breastfeeding. However, the proportion of children being exclusively breastfed for ≥6 months, as recommended by the World Health Organization (WHO), is consistently low.5,6 

Longer duration of breastfeeding has been associated with a reduced risk of respiratory tract and gastrointestinal infections (GIs), which are both common causes of childhood illness.7,8  The suggested effect on infectious diseases is most pronounced in early childhood, whereas a potential effect in later life is more controversial with uncertain conclusions because most previous studies are based on questionnaire data collected at infrequent time points or weeks, months, or, even, years after breastfeeding has stopped.25,915 

In the current study, we aimed, in a population-based birth cohort, to investigate whether duration of breastfeeding was associated with the number of hospitalizations due to any infection and symptoms of infection recorded prospectively and frequently at home. We hypothesized that increased duration of breastfeeding would be associated with reduced morbidity from infections in early childhood, reaching beyond the cessation of breastfeeding.

This study was based on the prospective birth cohort, the Odense Child Cohort (OCC).16  Mothers giving birth between June 2010 and October 2013 were invited to participate in the OCC, and mothers giving birth from April 2012 to October 2013 were invited to participate in a short text message service (SMS)–based breastfeeding survey as a subproject.17  Thus, the project had a limited time frame, and inclusion of the entire birth cohort was not possible. For the current study, twins and children born before 32 weeks' gestation were excluded. For the study on symptoms of infection, the study population was composed of mother-child pairs participating in both the breastfeeding survey and a SMS-based survey of symptoms of infection conducted as described in the next section.

Participant Characteristics

Background information was collected from the Funen Patient Administrative System and questionnaires.16  Medical records were consulted if data were missing.

Breastfeeding Data

Data on breastfeeding were collected by using SMS questionnaires once every week.

The women were asked if they were breastfeeding, if they were using infant formula, and if they had introduced complementary foods.17  For the current study, participants with any missing answers were omitted in the main analyses. Breastfeeding status was classified as never breastfed, any breastfeeding, or exclusive breastfeeding, according to WHO definitions.1  If an infant was given infant formula within the first few days after birth and, thereafter, exclusively breastfed, the first week was counted as exclusive breastfeeding. The duration of exclusive breastfeeding was defined as the time to the first introduction to infant formula or complementary foods. The duration of any breastfeeding was categorized into 5 groups: breastfed for 0 to 3 months (including mothers who did not breastfeed), breastfed for 4 to 6 months, breastfed for 7 to 9 months, breastfed for 10 to 12 months, and breastfed for ≥13 months. Exclusive breastfeeding was grouped into 3 categories: never or partially breastfed, exclusive breastfeeding for 0.1 to 3 months, and exclusive breastfeeding for ≥4 months.

Data on Hospitalization

Information on hospitalization was retrieved from the Danish National Patient Registry, a national database of hospital activity that includes discharge diagnoses, validated for several disease entities.18  Data were collected from April 1, 2012, to August 31, 2015, ie, from the start of inclusion in the breastfeeding survey and ∼3 years of follow-up. Hospitalizations with an infection as the primary or underlying International Classification of Diseases, 10th Revision (ICD-10) diagnosis were included. Infections were grouped as any infection and in organ-specific groups, for example, upper respiratory tract infections (URTIs), lower respiratory tract infections (LRTIs), GIs, or other infections. Other infections were mainly unspecified viral infections, urinary tract infections, and unspecified fever. For a full list of the types of infections in each group, see Supplemental Table 5.

Data on Symptoms of Infection at Home

A text message survey was conducted between August 17, 2014, and August 15, 2015. Parents received a text message every 2 weeks asking whether their child had experienced any symptoms of infection at home during the past 14 days. Fever was only recorded if a temperature >38.5°C was measured by using a rectal thermometer. A pilot study (n = 10) was conducted before the onset of the survey.19  The child’s age and the season of year were registered at each SMS response.

Descriptive statistics were used for population characteristics. Drop-out analyses were performed to investigate differences in baseline characteristics between the participants and nonparticipants in the breastfeeding survey. Independent 2-sample t tests, Mann–Whitney U tests, and χ2 analyses were used as applicable.

Breastfeeding

Breastfeeding was the independent variable in all analyses. The variable was included in regression models as a dichotomous variable (breastfed [any duration, partial, or exclusive] or never breastfed), as a continuous variable (duration of breastfeeding depicted in months), and as a categorical variable. For the main outcomes (hospitalization due to any infection and any symptom of infection), associations to breastfeeding were analyzed with breastfeeding as a dichotomous variable (any versus never breastfed), as a continuous variable (the duration of any breastfeeding and duration of exclusive breastfeeding), and as a group variable (both any and exclusive breastfeeding). For subanalyses and sensitivity analyses, the breastfeeding variable was depicted as the duration of any breastfeeding.

Hospitalizations Due to Infections

Hospitalizations were treated as a count variable in which each admission counted as one event. Readmissions within 7 days after discharge were treated as the same event. Hospitalizations within the first 7 days of life were censored to avoid prenatally acquired infections. Admissions were depicted as rates of hospitalization per 100 person-years at risk. Time at risk was defined as the time at risk for being admitted, and, thus, we subtracted the first 7 days of life, the days of admission, and the 7 days after discharge from the observation time.

Because of overdispersion, a negative binomial regression model was fitted by using generalized linear models. Potential confounders were chosen a priori. Models were adjusted for maternal educational level, maternal smoking during pregnancy, mode of delivery, and the child’s sex, gestational age, and number of siblings at birth. Interaction between breastfeeding and sex was tested, and sex-stratified analyses were performed for P values <.1.

The main outcome was the number of hospitalizations due to any infection and associations were depicted as incidence rate ratios (IRRs). Subanalyses were done on hospitalization for organ-specific infections and for the age groups of 0 to 11, 12 to 23, and ≥24 months.

Sensitivity analyses were performed, excluding those admitted for <24 hours, to avoid the inclusion of outpatients who were only seen in need of a second opinion. Additionally, we included participants with missing answers on breastfeeding duration. Analyses were run with missing answers counted, first as breastfeeding and then as not breastfeeding. Finally, a sensitivity analysis excluding all observations ≥24 months of age was performed because <10% of all hospitalizations occurred after the age of 24 months.

Symptoms of Infection at Home

Symptoms of infection at home were depicted as prevalence proportions. Each answer corresponded to a 14-day period. A total of 26 text messages were sent, giving a possible total observation of 364 days.

Regression analyses of the association between breastfeeding and symptoms of infection were modeled by a generalized estimating equation with a negative binomial family to incorporate two time-dependent covariates. An independent correlation matrix was chosen by using the quasi likelihood under the independence model criterion. Confounders were chosen a priori and included those in the model for hospitalizations. In addition, the child’s age and the season of year at each SMS were included as covariates with a time variance. Interaction between duration of breastfeeding and child sex was tested by using contrast. Sex-stratified analyses were performed for P values <.1.

The main outcome was the number of days with any symptom of infection, which was a group variable comprising all days with any symptom of infection at home. For subanalyses, a respiratory tract symptom (stuffed or runny nose), gastrointestinal symptom (diarrhea), and general symptom of infection (fever) were analyzed. Because of high correlation between symptoms, only these 3 were chosen. Sensitivity analyses were done excluding participants who reported a prevalence proportion of any symptom of infection of 0 or 1. As before, analyses were run with missing answers counted, first as breastfeeding and then as not breastfeeding.

The Helsinki Declaration II was followed. The study was approved by the Regional Committee on Health Research Ethics (project number S-20090130) and Danish Data Protection Agency (project number 2008-58-0035). The STROBE (Strengthening the Reporting of Observational studies in Epidemiology) guidelines for observational cohort studies were followed.

Out of 2500 mothers included in the OCC, 1087 singleton mothers and their infants were invited to participate in the breastfeeding survey (Fig 1). Of these, 24 never received their invitation, and 3 did not reply to any text messages. An additional 195 participants, who had incomplete text message answers on breastfeeding, were excluded from the main analyses. A total of 815 participants were finally included. For the additional study on symptoms of infection at home, 413 infants of the 815 had participated in both surveys.

FIGURE 1

Flow of participants.

FIGURE 1

Flow of participants.

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Demographic data are shown in Table 1. Of the 815 participants, 777 (95.3%) initiated breastfeeding. The median duration of any breastfeeding was 7.6 months (interquartile range [IQR]: 3.5–10.4). Only 15.6% (n = 127) received any breastfeeding for ≥12 months. Six hundred twenty-six (76.8%) were exclusively breastfed, with a median duration of 2.1 months (IQR: 0.7–4.4). Nine children (1%) were exclusively breastfed at 6 months of age. Drop-out analyses are shown in Supplemental Table 6.

TABLE 1

Characteristics of the Study Population

AllDuration of Any Breastfeeding
0–3 mo4–6 mo7–9 mo10–12 mo≥13 mo
No. of participants (%) 815 (100) 227 (27.9) 140 (17.2) 219 (26.9) 141 (17.3) 88 (10.8) 
Age at follow-up, y, mean (SD) 2.8 (0.4) 2.8 (0.4) 2.8 (0.4) 2.8 (0.4) 2.7 (0.4) 2.8 (0.4) 
Sex, male, No. (%) 432 (53.0) 118 (52.0) 74 (52.9) 110 (50.2) 85 (60.3) 45 (51.1) 
Gestational age, wk, median (IQR) 40.1 (39.1–41.0) 40.0 (39.0–40.9) 40.3 (39.0–41.1) 40.0 (39.1–41.0) 40.1 (39.3–41.1) 40.4 (39.5–41.1) 
Premature, <37 wk, No. (%) 31 (3.8) 11 (4.9) 10 (7.1) 6 (2.7) 3 (2.1) 1 (1.1) 
Siblings, ≥1 sibling at birth, No. (%) 348 (42.7) 94 (41.4) 65 (46.4) 90 (41.1) 63 (44.7) 36 (40.9) 
Maternal age at birth, y, mean (SD) 30.7 (4.5) 30.3 (5.2) 30.6 (4.3) 30.7 (4.0) 30.9 (4.1) 31.8 (4.2)* 
Maternal educational level,a No. (%)       
 High school or less 222 (27.9) 91 (41.9) 44 (32.1) 39 (17.8)* 28 (20.4)* 20 (23.5)* 
 High school + 1–3 y 418 (52.6) 103 (47.5) 68 (49.6) 128 (58.5)* 81 (59.1)* 38 (44.7)* 
 High school + ≥4 y 155 (19.5) 23 (10.6) 25 (18.3) 52 (23.7)* 28 (20.4)* 27 (31.8)* 
Maternal pregestational BMI, median (IQR) 23.4 (21.3–26.4) 24.7 (21.9–28.5) 23.4 (21.6–25.7)* 22.8 (20.9–25.8)* 22.5 (20.7–24.7)* 23.0 (21.2–26.2)* 
Smoking during pregnancy, No. (%) 31 (3.8) 19 (8.4) 3 (2.1)* 4 (1.8)* 1 (0.7)* 4 (4.6) 
Type of birth, No. (%)       
 Vaginal 640 (78.5) 168 (74.0) 105 (75.0) 173 (79.0) 116 (82.3) 78 (88.6)* 
 Elective cesarean delivery 92 (11.3) 32 (14.1) 22 (15.7) 24 (11.0) 10 (7.1) 4 (4.6)* 
 Acute cesarean delivery 83 (10.2) 27 (11.9) 13 (9.3) 22 (10.0) 15 (10.6) 6 (6.8)* 
AllDuration of Any Breastfeeding
0–3 mo4–6 mo7–9 mo10–12 mo≥13 mo
No. of participants (%) 815 (100) 227 (27.9) 140 (17.2) 219 (26.9) 141 (17.3) 88 (10.8) 
Age at follow-up, y, mean (SD) 2.8 (0.4) 2.8 (0.4) 2.8 (0.4) 2.8 (0.4) 2.7 (0.4) 2.8 (0.4) 
Sex, male, No. (%) 432 (53.0) 118 (52.0) 74 (52.9) 110 (50.2) 85 (60.3) 45 (51.1) 
Gestational age, wk, median (IQR) 40.1 (39.1–41.0) 40.0 (39.0–40.9) 40.3 (39.0–41.1) 40.0 (39.1–41.0) 40.1 (39.3–41.1) 40.4 (39.5–41.1) 
Premature, <37 wk, No. (%) 31 (3.8) 11 (4.9) 10 (7.1) 6 (2.7) 3 (2.1) 1 (1.1) 
Siblings, ≥1 sibling at birth, No. (%) 348 (42.7) 94 (41.4) 65 (46.4) 90 (41.1) 63 (44.7) 36 (40.9) 
Maternal age at birth, y, mean (SD) 30.7 (4.5) 30.3 (5.2) 30.6 (4.3) 30.7 (4.0) 30.9 (4.1) 31.8 (4.2)* 
Maternal educational level,a No. (%)       
 High school or less 222 (27.9) 91 (41.9) 44 (32.1) 39 (17.8)* 28 (20.4)* 20 (23.5)* 
 High school + 1–3 y 418 (52.6) 103 (47.5) 68 (49.6) 128 (58.5)* 81 (59.1)* 38 (44.7)* 
 High school + ≥4 y 155 (19.5) 23 (10.6) 25 (18.3) 52 (23.7)* 28 (20.4)* 27 (31.8)* 
Maternal pregestational BMI, median (IQR) 23.4 (21.3–26.4) 24.7 (21.9–28.5) 23.4 (21.6–25.7)* 22.8 (20.9–25.8)* 22.5 (20.7–24.7)* 23.0 (21.2–26.2)* 
Smoking during pregnancy, No. (%) 31 (3.8) 19 (8.4) 3 (2.1)* 4 (1.8)* 1 (0.7)* 4 (4.6) 
Type of birth, No. (%)       
 Vaginal 640 (78.5) 168 (74.0) 105 (75.0) 173 (79.0) 116 (82.3) 78 (88.6)* 
 Elective cesarean delivery 92 (11.3) 32 (14.1) 22 (15.7) 24 (11.0) 10 (7.1) 4 (4.6)* 
 Acute cesarean delivery 83 (10.2) 27 (11.9) 13 (9.3) 22 (10.0) 15 (10.6) 6 (6.8)* 
*

P value <.05, compared with 0 to 3 months of any breastfeeding.

a

Missing, n = 20.

A total of 207 infants (25.4%) experienced ≥1 hospitalizations due to an infection. The mean incidence rate of hospitalization for any infection was 14.63 (95% confidence interval [CI]: 12.34–16.92) per 100 person-years at risk (Supplemental Table 7). For organ-specific subgroups, the incidence rates of hospitalization for URTIs, LRTIs, and other infections were almost equal, whereas rates for GIs were lower.

Breastfed infants (any duration, partial or exclusive) had the same hospitalization rate for any infection as infants who were never breastfed (adjusted IRR: 0.90; 95% CI: 0.49–1.65; P = .74).

An inverse relationship was present between the duration of any breastfeeding and the rate of hospitalization due to any infection (Fig 2). For every extra month of any breastfeeding, univariate analysis revealed a 5% reduced rate of hospitalization due to any infection (crude IRR: 0.95; 95% CI: 0.93–0.98; P < .001). Adjusted analysis revealed a similar reduction of 4% (adjusted IRR: 0.96; 95% CI: 0.93–0.99; P < .001). When analyzed as a categorical variable with breastfed for 0 to 3 months as a reference, the IRR for hospitalization due to any infection decreased for any breastfeeding >6 months (P < .05; Table 2). After adjusting for potential confounders, any breastfeeding for 10 to 12 and ≥13 months reduced the IRR of hospitalization for the first 24 to 36 months of life, but any breastfeeding for <10 months did not.

FIGURE 2

Incidence rate of hospitalization due to any infection by the duration of any breastfeeding.

FIGURE 2

Incidence rate of hospitalization due to any infection by the duration of any breastfeeding.

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TABLE 2

Association Between the Duration of Any Breastfeeding and Hospitalization Due to Any Infection

Any Breastfeeding GroupIRR (95% CI)P
Crude analyses   
 0–3 mo Reference — 
 4–6 mo 0.76 (0.52–1.1) .15 
 7–9 mo 0.67 (0.48–0.93) .02 
 10–12 mo 0.49 (0.32–0.75) .001 
 ≥13 mo 0.48 (0.29–0.80) .005 
Adjusted analysesa   
 0–3 mo Reference — 
 4–6 mo 0.76 (0.51–1.12) .16 
 7–9 mo 0.72 (0.51–1.03) .07 
 10–12 mo 0.52 (0.33–0.82) .004 
 ≥13 mo 0.58 (0.34–0.98) .04 
Any Breastfeeding GroupIRR (95% CI)P
Crude analyses   
 0–3 mo Reference — 
 4–6 mo 0.76 (0.52–1.1) .15 
 7–9 mo 0.67 (0.48–0.93) .02 
 10–12 mo 0.49 (0.32–0.75) .001 
 ≥13 mo 0.48 (0.29–0.80) .005 
Adjusted analysesa   
 0–3 mo Reference — 
 4–6 mo 0.76 (0.51–1.12) .16 
 7–9 mo 0.72 (0.51–1.03) .07 
 10–12 mo 0.52 (0.33–0.82) .004 
 ≥13 mo 0.58 (0.34–0.98) .04 

—, not applicable.

a

Adjusted for maternal educational level, maternal smoking during pregnancy, mode of delivery, child’s sex and gestational age, and number of siblings at birth.

Stratified by infant age groups, the association between the duration of any breastfeeding and hospitalizations for any infection revealed an IRR of 0.96 (95% CI: 0.92–1.00; P = .05) for ages 0 to 11 months, whereas no association was present for the age groups 12 to 23 and ≥24 months (Supplemental Table 8). Omitting hospitalizations with a duration of <24 hours in a sensitivity analysis altered the association between any breastfeeding and hospitalization due to any infection (adjusted IRR: 0.98; 95% CI: 0.94–1.02; P = .36). Including participants with unknown breastfeeding status did not alter the association. Excluding observations ≥24 months of age did not change our estimate (Table 3).

TABLE 3

Association Between the Duration of Any Breastfeeding and Hospitalization Due to Any Infection Stratified by Age

Age Group, moIRR (95%CI)aP
0–11 0.96 (0.92–1.00) .05 
12–23 0.97 (0.93–1.01) .12 
>23 0.92 (0.85–1.01) .07 
Age Group, moIRR (95%CI)aP
0–11 0.96 (0.92–1.00) .05 
12–23 0.97 (0.93–1.01) .12 
>23 0.92 (0.85–1.01) .07 

Duration of any breastfeeding is analyzed in months.

a

Adjusted for maternal educational level, maternal smoking during pregnancy, mode of delivery, child’s sex and gestational age, and number of siblings at birth.

Increased duration of exclusive breastfeeding was also associated with a lower rate of hospitalization of any infection for the first 24 to 36 months of life (crude IRR: 0.88; 95% CI: 0.81–0.96; P = .003; adjusted IRR: 0.88; 95% CI: 0.80–0.96; P = .006). Compared with the never or partially breastfed group, the exclusive breastfeeding group for ≥4 months lowered the IRR for hospital admissions for any infection for the first 24 to 36 months of life (adjusted IRR: 0.45; 95% CI: 0.27–0.75; P = .002; Table 4).

TABLE 4

Association Between Exclusive Breastfeeding and Hospitalization Due to Any Infection

IRR (95% CI)P
Crude analyses, never or partially breastfed Reference — 
 0.1–3 mo 0.82 (0.57–1.17) .27 
 >4 mo 0.45 (0.28–0.73) .001 
Adjusted analyses,a never or partially breastfed Reference — 
  0.1–3 mo 0.76 (0.52–1.12) .16 
  ≥4 mo 0.45 (0.27–0.75) .002 
IRR (95% CI)P
Crude analyses, never or partially breastfed Reference — 
 0.1–3 mo 0.82 (0.57–1.17) .27 
 >4 mo 0.45 (0.28–0.73) .001 
Adjusted analyses,a never or partially breastfed Reference — 
  0.1–3 mo 0.76 (0.52–1.12) .16 
  ≥4 mo 0.45 (0.27–0.75) .002 

—, not applicable.

a

Adjusted for maternal educational level, maternal smoking during pregnancy, mode of delivery, child’s sex and gestational age, and number of siblings at birth.

When stratified by infection type, every extra month of any breastfeeding lowered the risk of LRTI (adjusted IRR: 0.95; 95% CI: 0.90–1.00; P = .03) and of other infections (adjusted IRR: 0.95; 95% CI: 0.90–1.00; P = .04).

In the subgroup of 413 children home-monitored from a mean age of 1.74 years, the mean prevalence proportion of any symptom of infection was 0.27 (95% CI: 0.25–0.29; Supplemental Table 8). Respiratory tract symptoms were the most prevalent.

Children who were previously breastfed had an increased prevalence of any symptom of infection compared with those who were never breastfed (adjusted IRR: 1.36; 95% CI: 1.02–1.82; P = .035).

A nonuniform relationship was present between the duration of any breastfeeding and prevalence proportion of any symptom of infection at 12 to 36 months of age (Fig 3). Crude analysis revealed no association between the duration of any breastfeeding and prevalence of any symptom of infection (IRR: 1.01; 95% CI: 1.00–1.02; P = .12). Adjusting for potential confounders did not alter the lack of association (Supplemental Table 9). Likewise, no association was present between the duration of exclusive breastfeeding and any symptom of infection at 12 to 36 months of age. Sensitivity analyses did not alter the results.

FIGURE 3

Prevalence proportion of any symptom of infection at home by the duration of any breastfeeding.

FIGURE 3

Prevalence proportion of any symptom of infection at home by the duration of any breastfeeding.

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Subanalyses revealed no association between the duration of any breastfeeding and a stuffed or runny nose (adjusted IRR: 1.02; 95% CI: 1.00–1.03; P = .09) or diarrhea (adjusted IRR: 1.00; 95% CI: 0.97–10.2; P = .72) at 12 to 36 months of age. Univariate and adjusted analyses revealed a 3% increase in the prevalence of fever with an increasing duration of any breastfeeding (IRR: 1.03; 95% CI: 1.00–1.06; P = .03 and adjusted IRR: 1.03; 95% CI: 1.00–1.06; P = .03).

In this population-based cohort, a longer duration of any breastfeeding was associated with a 4% lower rate of hospitalization due to any infection, and, specifically, LRTIs and other infections decreased by 5% for every extra month of any breastfeeding. This association with hospitalization for any type of infection was only present for infants aged 0 to 11 months and was primarily due to exclusive breastfeeding. Indeed, exclusive breastfeeding for ≥4 months more than halved the risk of hospitalization during the first 24 to 36 months of life due to any infection, compared with partial or no breastfeeding.

No such protective associations of any breastfeeding were found for any symptom of infection registered at home 0 to 30 months later. The subgroup of children monitored for symptoms at home revealed that children who had been previously breastfed had more frequent symptoms of infection than children not breastfed and that a longer duration of any breastfeeding was associated with a 3% increased prevalence of fever for every extra month of any breastfeeding.

Strengths of this study include the meticulous method of collecting data in the OCC. The available data covered relevant confounders, with only a few missing observations on key variables. Information on breastfeeding and symptoms at home was collected by using a SMS survey at short intervals, thus reducing the risk of recall bias and increasing the response rate. In addition, the Danish National Patient Registry covers all admissions for infections and has, generally, a high positive predictive value for correct diagnoses from pediatric departments.20  In the event of an uncertain primary diagnosis, the medical records were consulted, adding to the robustness of our data.

The study has some limitations. Mothers in the OCC were older, better educated, and had a higher proportion of ethnic Danes than the general population.16  In a sensitivity analysis of the association between the duration of any breastfeeding and hospitalization, with removal of those hospitalized for <24 hours, the estimate was slightly changed, with the CI reaching across 1. Short-term hospitalization may occur because of a number of reasons, including lower socioeconomic status, which is associated with a shorter duration of breastfeeding, so a social bias may confound the present findings.21,22 

In the analysis of symptoms of infection at home, adjustment for potential over- or under-reporting did not alter the association. Day care attendance was not included in the analyses of the current study because all but 2 children in the cohort attended day care. In addition, children in the municipality of Odense cannot attend public day care before 6 months of age, and, because only 9 infants were exclusively breastfed beyond this age, a potential bias seems unlikely. Lastly, hospitalization for infection occurred for 19 infants before the ending of exclusive breastfeeding and 69 infants before any breastfeeding ended. Therefore, a time overlap between exposure and outcome does not allow us to completely exclude reverse causation because infection in these cases may have led to the cessation of breastfeeding.

For the symptom analyses, some of the reported symptoms, for example, wheezing or whistling breathing, eye inflammation, and unwell feelings, may be due to noninfectious reasons. However, these symptoms only account for a small proportion of all symptoms of infection and are not likely to cause a systematic bias.

Despite the WHO recommendations, only 9 children (1%) were exclusively breastfed for 6 months, comparable to other European countries.6  The proportion of children hospitalized was similar to other reports.9 

In previous studies, researchers have indicated a reduced risk of infections in breastfed children in both developed and developing countries.8  Studies have primarily addressed children 0 to 12 months of age, and the effect of breastfeeding on infections after the first 12 months of life is less uniform.25,915,2326  The association between breastfeeding and hospitalization for any infection was investigated in 2 studies that primarily revealed an inverse association.12,14  For organ-specific infections, breastfeeding was inversely associated to hospitalization for URTI,9,1315,25  LRTI,5,9,1215,25  urinary tract infections,9  and fever.9,26  In some studies, the association differed, depending on age group or type of breastfeeding.9,1215 

Breastfeeding patterns and infections not requiring hospitalization have been studied, especially for respiratory tract infections and GIs.25,1013,2325,27  Only one previous study12  revealed an association between exclusive breastfeeding and a reduction in any infections. The evidence is inconsistent for URTIs, with only 23,25  of 5 studies3,4,24,25,27  suggesting a protective effect of breastfeeding. Although most studies on LRTIs25,13,24,25,27  reveal a decrease in illness if the duration of breastfeeding is increased, one-half of the studies have inconsistencies in their results.2,13,25,27  Breastfeeding has been shown to reduce the risk of diarrhea, but the association was mainly present in the first 6 months of life.2,3,5,12,13,23  In one study on unexplained fever, researchers observed no association with breastfeeding status.23  Most studies25,1113,23,25  have used questionnaires or interviews, with recall up to several years, and may have considerable bias in their exposure variable. In only 3 previous studies did researchers administer questionnaires or have interviews with less than monthly intervals.10,24,27  This may explain the inconsistencies in previous studies.

We found no association between the duration of any breastfeeding and any symptom of infection, stuffed or runny nose, or diarrhea 0 to 30 months later. Previous studies on children >12 months of life reveal no association between breastfeeding and parent reported URTI and GI, supporting our findings.4,13,23  Studies mainly reveal an association in children aged <12 months.35,1013,2325,27  We were not able to test an association between any breastfeeding and symptoms at home in this early age group because symptoms were not assessed until the children were 12 to 36 months old.

Surprisingly, we observed an increased IRR for any symptom of infection for breastfed versus nonbreastfed infants and an increased IRR for reporting fever with increased duration of any breastfeeding for infants aged >12 months. These associations may be explained as chance findings or residual confounding because both lack a logical biological explanation.

The immunologic basis for a positive effect of breastfeeding on infections is well documented in several studies, and breast milk contains immune components, including secretory immunoglobulin A, lactoferrin, human milk oligosaccharides, and memory B cells and T cells, affecting both local and systemic immunity.2830  These immune components may also affect the neonatal microbiota.28  Experimental studies highlight the possibility of short- and long-term protection against infections both locally in the gut and in the systemic circulation.2830 

Our study strongly supports exclusive breastfeeding for ≥4 months to decrease the risk of infections in early childhood.

We thank the staff at the OCC for their meticulous work and Claire Gudex, medical writer at the University of Southern Denmark, for language correction.

Dr Christensen prepared the original protocol and overall design of the study, collected the data on infections, conducted data management and statistical analyses, and drafted and revised the manuscript; Drs Husby, Søndergaard, Christesen, and Fisker prepared the original protocol and overall design of the study, supervised data collection on infections and statistical analyses, and reviewed and revised the manuscript; Drs Bruun and Zachariassen prepared the original protocol and overall design of the study, collected data on breastfeeding, and reviewed and revised the manuscript; Dr Sangild prepared the original protocol and overall design of the study and reviewed and revised the manuscript; and all authors approved the final manuscript as submitted and agree to be accountable for all aspects of the work.

FUNDING: Supported by the Innovation Fund Denmark (NEOMUNE) and the University of Southern Denmark in Odense, Denmark. Dr Christensen received funding from the Region of Southern Denmark, University of Southern Denmark, Hans Christian Andersen Children’s Hospital, A.P. Møller Foundation, and Arla Foods Ingredients Group P/S.

     
  • CI

    confidence interval

  •  
  • GI

    gastrointestinal infection

  •  
  • ICD-10

    International Classification of Diseases, 10th Revision

  •  
  • IQR

    interquartile range

  •  
  • IRR

    incidence rate ratio

  •  
  • LRTI

    lower respiratory tract infection

  •  
  • OCC

    Odense Child Cohort

  •  
  • SMS

    short message service

  •  
  • URTI

    upper respiratory tract infection

  •  
  • WHO

    World Health Organization

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Competing Interests

POTENTIAL CONFLICT OF INTEREST: Dr Bruun is an employee at Arla Foods Ingredients Group P/S; Dr Sangild has received research grants from Arla Foods, Danone, and Biofiber-Damino A/S unrelated to the current study; the other authors have indicated they have no potential conflicts of interest to disclose.

FINANCIAL DISCLOSURE: Dr Christensen received funding from the Region of Southern Denmark, University of Southern Denmark, Hans Christian Andersen Children’s Hospital, A.P. Møller Foundation, and Arla Foods Ingredients Group P/S; Dr Bruun is an employee at Arla Foods Ingredients Group P/S; the other authors have indicated they have no financial relationships relevant to this article to disclose.

Supplementary data