Infant benefits of breastfeeding

INTRODUCTION — Human milk is the optimal source of nutrition for virtually all infants. Exclusive breastfeeding is recommended for approximately the first six months of life, followed by continued breastfeeding, with the introduction of appropriate complementary solids for at least the first year of life and beyond. These recommendations are supported strongly by multiple medical and professional organizations, such as the American Academy of Pediatrics [1], American Academy of Family Physicians [2], American College of Obstetricians and Gynecologists [3], World Health Organization (WHO) [4], and Canadian Pediatric Society [5], based on both short- and long-term benefits for the mother and child. The WHO recommends continued breastfeeding at least through the child's second birthday. Suboptimal breastfeeding is associated with increased risk of infant and childhood morbidity and mortality, and increased risk of certain chronic conditions.

Benefits of breastfeeding that are specific to the infant and child will be reviewed here. Maternal, societal, and economic benefits are discussed separately. (See "Maternal and economic benefits of breastfeeding".)

Decisions about initiating and maintaining breastfeeding are influenced by the unique challenges and supports of the mother, infant, and family. These considerations and strategies for shared decision-making, addressing obstacles, and providing support are discussed in separate topic reviews. (See "Breastfeeding: Parental education and support" and "Common problems of breastfeeding and weaning".)

In analyzing the data, it is important to recognize that not all studies differentiate between exclusive breastfeeding and any breastfeeding, or quantify the differences between predominantly breastfed infants and partially breastfed. Dose dependency, in terms of duration, intensity, and quantity, in addition to exclusivity, has been shown to be important in quantifying the benefits of breastfeeding for both children and mothers.

BIOLOGICALLY ACTIVE COMPONENTS OF HUMAN MILK — Human milk is a living biologic substance that is much more complex than the sum of its nutritional components. Human milk contains not just macro- and micronutrients but also living cells, growth factors, and immunoprotective substances [6,7]. Many of these factors are resistant to digestive enzymes in the infant's gastrointestinal tract and are biologically active at mucosal surfaces.

Biologically active components include:

●Antimicrobial activity – Immunoglobulins (especially secretory immunoglobulin A [IgA]), lysozyme, lactoferrin, free fatty acids and monoglycerides, human milk bile salt-stimulated lipase, mucins, white blood cells, stem cells, human milk oligosaccharides (prebiotic and antimicrobial activities). These antimicrobial actions help to protect against gastrointestinal and other infections, as well as against developing necrotizing enterocolitis (NEC).

●Immunomodulatory activity – Platelet-activating factor acetylhydrolase, interleukin 10, polyunsaturated fatty acids, glycoconjugates. These factors help to protect against NEC [8-11].

●Factors that promote gastrointestinal development and function – Proteases (enzymes that help digest proteins), hormones (eg, cortisol, somatomedin C, insulin-like growth factors, insulin, and thyroid hormone), growth factors (eg, epidermal growth factor and nerve growth factor), gastrointestinal mediators (neurotensin, motilin), and amino acids that stimulate enterocyte growth (eg, taurine and glutamine) [12-17]. Human milk also influences optimal development of the gut microbiome and virome [18,19].

These biologically active components of human milk, as well as its nutritional characteristics (macronutrient and micronutrient content), are discussed in more detail separately. (See "Nutritional composition of human milk and preterm formula for the premature infant".)

SHORT-TERM BENEFITS WHILE BREASTFEEDING

Breastfeeding confers direct health benefits to the infant during the time of breastfeeding, some of which persist after weaning. The best studied benefits are the impacts on the development of the gastrointestinal and immunologic systems, as well as prevention of infection.

Neurobehavioral benefits — Breastfeeding appears to have some direct neurobehavioral benefits. The precise mechanisms have not been established, but some may be related more to skin-to-skin contact than the human milk feeding itself [20].

Early skin-to-skin contact between mothers and newborns has some short-term neurobehavioral benefits and may program other benefits during this sensitive period of adaptation to extrauterine life. In the short term, early skin-to-skin contact appears to reduce infant crying, increase blood glucose levels, and promote greater cardiorespiratory stability in late preterm infants [21]. Early skin-to-skin contact also helps to establish lactation and promote ongoing breastfeeding, which enhances the other benefits of breastfeeding outlined below.

In addition, there appears to be an analgesic effect of breastfeeding, which may be due to the enhanced maternal-infant bonding. Breastfed infants experience less stress during painful procedures than formula-fed infants [22-24]. Skin-to-skin care during a single painful procedure appears to be both safe and effective as analgesia, as measured by composite pain indicators with both physiologic and behavioral indicators and, independently, using heart rate and crying time [25]. A possible mechanism is radiant warmth from the skin-to-skin contact [26,27]. Higher salivary cortisol levels found in breastfed infants, compared with formula-fed infants, also are postulated to mediate the analgesic effect of breastfeeding [28].

Gastrointestinal function — Human milk stimulates optimal growth, development, and function of the gastrointestinal system and influences optimal development of the microbiota [18]. Exclusive, early breastfeeding protects the infant's gastrointestinal system from exposure to highly antigenic substances.

When compared with formula, human milk has been shown to:

●Reduce the risk of gastroenteritis and diarrheal disease (see 'Prevention of illnesses while breastfeeding' below)

●Increase the rate of gastric emptying [29,30]

●Increase intestinal lactase activity in premature infants [31]

●Decrease the intestinal permeability early in life in premature infants [32,33]

●Reduce the risk of developing necrotizing enterocolitis (NEC) in preterm infants [34,35]

Several components of human milk stimulate gastrointestinal growth and motility, including growth factors and gastrointestinal mediators. Other factors are protective and decrease the risk of NEC and other infections, including immunoglobulins, platelet-activating factor acetylhydrolase, polyunsaturated fatty acids, epidermal growth factor, and interleukin 10. In addition, human milk influences optimal development of the microbiota, including neonatal intestinal colonization by the beneficial microbes of the Bifidobacteria and Lactobacillus species rather than potential enteropathogenic bacteria, such as streptococci and Escherichia coli [18,36,37] (see 'Biologically active components of human milk' above). The benefit of human milk in prevention of NEC is discussed in greater detail separately. (See "Neonatal necrotizing enterocolitis: Prevention", section on 'Human milk feeding' and "Human milk feeding and fortification of human milk for premature infants", section on 'Benefits of mother's milk'.)

For these reasons, the American Academy of Pediatrics recommends human milk, either mother's own or pasteurized donor milk, for all premature infants born weighing less than 1500 grams [38]. (See "Approach to enteral nutrition in the premature infant", section on 'Milk strength and content'.)

Prevention of illnesses while breastfeeding

In both resource-abundant and resource-limited settings, human milk, compared with infant formula, decreases the risk of acute illnesses during the time period in which the infant is fed human milk. Most of these benefits are related to protection from infectious diseases [1,39]. In one study, breastfeeding was associated with fewer serious infections requiring hospitalization during the first year of life, with a 4 percent reduction in hospitalization for every extra month of any breastfeeding [39].

The protective effect includes:

●Gastroenteritis and diarrhea – Breastfeeding lowers the risk of gastrointestinal infections and diarrhea in many populations, but this is particularly important in resource-limited settings [40-42]. In a meta-analysis that included studies from both resource-limited and resource-abundant settings, the risk of diarrhea in infants <6 months was lower in those who were breastfed (pooled relative risk 0.37, 95% CI 0.27-0.50) [40]. In a study in the United Kingdom, infants who were breastfed exclusively for six months had a decreased risk of severe or persistent diarrhea compared with infants who breastfed exclusively for less than four months [41]. The protective effects are greater for infants living in resource-limited settings, likely because formula-fed infants are more likely to be exposed to pathogens through improperly prepared formula and also because they tend to have worse nutritional status than breastfed infants.

●Respiratory disease – Breastfeeding lowers the risk of respiratory disease in the infant, based on results of studies from several different types of populations. As examples, in an study from the United Kingdom, infants who were exclusively breastfed for six months had a decreased risk of lower respiratory tract infections than infants who exclusively breastfed for less than four months [41]. In another study conducted in the United States and Europe, breastfeeding reduced the risk of respiratory infections in three- to six-month-old infants by approximately 20 percent [42]. Optimizing breastfeeding in the United States to current recommendations has been estimated to prevent almost 21,000 hospitalizations and 40 deaths for lower respiratory tract infections in the first year of life [43].

●Coronavirus disease 2019 (COVID-19) – Vaccination of pregnant people against COVID-19 is recommended, and vaccine-generated antibodies to the causative virus cross the placenta and into breast milk to confer passive immunity to newborn infants. Although antibodies persist in breast milk for at least several months, there is no definitive evidence regarding how much protection this confers on the infant or how long it might last [44,45]. (See "COVID-19: Overview of pregnancy issues", section on 'Vaccination in people planning pregnancy and pregnant or recently pregnant people'.)

●Otitis media – The incidence of otitis media and recurrent otitis media are reduced in breastfed compared with formula-fed infants, primarily for those younger than two years [42,46,47]. The incidence of two or more episodes of otitis media was reduced in infants breastfed for one year compared with infants fed formula (34 versus 54 percent) [48]. Feeding directly at the breast appears to be more beneficial than feeding expressed human milk [49].

●Urinary tract infection – In a case-control study conducted in Sweden, there was a significantly higher risk of urinary tract infection for infants who were not breastfed compared with those who were. Longer duration of exclusive breastfeeding reduced the probability of urinary tract infection, especially in females up to seven months of age [50]. A separate case-control study found that human milk feeding was associated with a lower risk of urinary tract infection in premature infants in the neonatal intensive care unit [51]. A mechanism for this protection has been suggested, based on observations that breastfed infants have greater contents of oligosaccharides, lactoferrin, and secretory IgA in their urine compared with formula-fed infants [52]. (See 'Biologically active components of human milk' above.)

●Sepsis – Early institution of exclusive breastfeeding decreases the risk of developing neonatal sepsis [53-56]. (See "Clinical features, evaluation, and diagnosis of sepsis in term and late preterm neonates".)

●Sudden infant death syndrome (SIDS) – Any breastfeeding is associated with a decreased risk of SIDS [57-59]. Exclusive breastfeeding and longer duration of breastfeeding confers the greatest protection [60,61]. (See "Sudden infant death syndrome: Risk factors and risk reduction strategies", section on 'Protective factors'.)

Mortality and hospitalization — In low- and middle-income countries, breastfeeding substantially decreases the risk of childhood mortality [62-64]. In a meta-analysis of 13 studies conducted in these populations, children exclusively breastfed through five months had lower risk of all-cause and infection-related mortality compared with those only partially or not breastfed [62]. Children aged 6 to 23 months who were not breastfed had higher risk of all-cause and infection-related mortality than children who continued breastfeeding. A separate systematic review showed that initiation of breastfeeding within one hour of birth decreased neonatal mortality compared with later initiation [63]. It has been estimated that improving global breastfeeding could prevent 823,000 annual deaths in children younger than five years [46].

Breastfeeding also reduces the risk of infant mortality in high-income countries. In a study of more than 3 million births in the United States, breastfeeding initiation was associated with reduced risk of mortality during the late perinatal period (7 to 28 days; adjusted odds ratio [AOR] 0.6, 95% CI 0.54-0.67) and the post-perinatal period (28 to 364 days; AOR 0.81, 95% CI 0.76-0.87) [59]. Significant effects were seen across different racial/ethnic groups and across all gestational age and birth weight groups, as well as for deaths due to infection, SIDS, and NEC. (See "Sudden infant death syndrome: Risk factors and risk reduction strategies", section on 'Protective factors' and "Neonatal necrotizing enterocolitis: Prevention".)

These data confirm and extend the findings from earlier smaller studies that also found a beneficial effect of breastfeeding on mortality [46,65,66], as well as associations between breastfeeding and lower rates of hospitalization and outpatient visits during the first year of life [46,67-70]. These findings suggest that severity of illness is reduced in the breastfed infant [48].

LONG-TERM BENEFITS

Limitations of this evidence — Evidence supporting associations between breastfeeding and beneficial long-term outcomes is inherently limited because it is based primarily on longitudinal cohort studies, raising the concern of unmeasured or residual confounding from inadequately controlled factors associated with both breastfeeding and health outcomes [71]. In particular, breastfeeding in high-resource countries is associated with higher socioeconomic and educational status and lower rates of maternal obesity and smoking, and these variables may not be fully captured by available markers. Moreover, these long-term studies are limited by recall bias, especially for breastfeeding duration. Evidence from studies designed to better control for confounding (sibling-pair and cross-population studies and one randomized trial [72-74]) tends to show little or no effect on obesity or cognitive outcomes.

Nonetheless, certain long-term benefits have been reported in large studies and in a variety of populations, suggesting the possibility of a true causal effect. The mechanism for such associations is unclear and may vary among the health outcomes. Possible mediators include development of the microbiota in this early period [18]; modulation of the immune system development; and the beneficial impact of skin-to-skin contact on maternal-child bonding and interactions, with potential decrease in toxic stress [20].

Acute illnesses — Exclusive breastfeeding, compared with formula feeding, has a protective effect in reducing acute illnesses, even after breastfeeding is discontinued. As an example, infants in the first 12 months of life who were breastfed for more than six months had a lower incidence of recurrent otitis media (defined by ≥3 episodes within six months or ≥4 episodes within 12 months) compared with those who were breastfed for less than four months (10 versus 20.5 percent) [75]. This protective effect is observed after adjustment for confounding variables, such as socioeconomic status, family history of allergy, family size, use of daycare, and smoking. A systematic review and meta-analysis provides evidence that breastfeeding protects against acute otitis media until two years of age, but protection is greater for exclusive breastfeeding and breastfeeding of longer duration [47].

Post-breastfeeding protection against infectious illnesses appears to increase with the duration of breastfeeding [76,77]. This was illustrated in a secondary analysis of the National Health and Nutrition Examination Survey III (NHANES III) of 2277 children between 6 and 24 months of age [77]. After adjusting for demographic variables (including ethnicity and socioeconomic status), childcare, and smoking exposure, infants who were fully breastfed for 4 to <6 months compared with those fully breastfed 6 months or longer were more likely to develop pneumonia (odds ratio [OR] 4.3, 95% CI 1.3-14.4) or to have ≥3 episodes of otitis media (OR 1.95, 95% CI 1.1-3.6) during the 12-month period immediately preceding the survey. There were no differences between the groups in the likelihood of having ≥3 episodes of cold/influenza, developing wheezing, or having a first episode of otitis media before one year of age. In another survey, breastfeeding for ≥9 months was associated with continued protection against ear, throat, and sinus infections through six years of age but not upper or lower respiratory tract infections [78].

Chronic disease — There are reported associations between the duration of breastfeeding and a reduction in incidence of certain chronic conditions [1,46,79], such as obesity, type 1 and type 2 diabetes mellitus, adult cardiovascular disease, certain allergic conditions, celiac disease, and inflammatory bowel disease (IBD). Studies demonstrate the importance of a critical period in the first year of life, during which breastfeeding can promote long-term effects.

Moderate evidence of benefit

●Type 1 diabetes – Breastfeeding appears to substantially reduce the risk for developing type 1 diabetes. This was shown in an analysis of two large birth cohorts from Denmark and Norway. Children who were never breastfed had a twofold increased risk of type 1 diabetes compared with those who were breastfed for ≥12 months (hazard ratio [HR] 2.29, 95% CI 1.14-4.61) or those who were exclusively breastfed for ≥6 months (HR 2.31, 95% CI 1.11-4.80) [80]. Among the breastfed cohort studied, there was no evidence that greater duration or intensity of breastfeeding had additional protective effect. Systematic reviews (which did not include the above study), however, supported the protective effect of breastfeeding but concluded that longer breastfeeding duration was more protective than shorter durations [81,82].

Effects of breastfeeding on type 2 diabetes are discussed below. (See 'Limited evidence for benefit' below.)

●IBD – Breastfeeding probably reduces the risk of developing IBD. In a meta-analysis of 35 studies, any breastfeeding compared with no breastfeeding reduced the risk of Crohn disease (OR 0.71, 95% CI 0.59-0.85) and ulcerative colitis (OR 0.78, 95% CI 0.67-0.91) [83]. Moreover, longer durations of breastfeeding were associated with lower rates of IBD. Systematic reviews that included a subset of these studies also concluded that breastfeeding duration is associated with reduced risk of IBD, based on limited but consistent evidence [81,84].

●Wheezing – Breastfeeding appears to be associated with a lower incidence of wheezing in early childhood [85]. This association may reflect a reduction in the number of upper respiratory infections because infections are a prominent cause of wheezing in infants and young children, which is not necessarily associated with later development of asthma. Associations between breastfeeding and wheezing later in childhood (eg, after six years, which is more likely to represent atopic asthma) and other atopic conditions have not been established. These issues are discussed in more detail separately. (See "The impact of breastfeeding on the development of allergic disease".)

●Dental health

•Malocclusion – Several systematic reviews and meta-analyses suggest that malocclusion is more prevalent among children who are not breastfed [86-88]. Exclusive breastfeeding and longer duration of breastfeeding (>12 months) has additional benefits, regardless of the type of occlusion disorder. (See "Preventive dental care and counseling for infants and young children", section on 'Dietary habits'.)

•Dental caries – Breastfeeding lowers the risk for developing dental caries compared with formula feeding from a bottle [89]. A systematic review showed that children with more breastfeeding exposure up to 12 months had reduced risk of dental caries [90]. There was an increase in dental caries after 12 months, which may be associated with night feedings and poor oral hygiene practices. (See "Preventive dental care and counseling for infants and young children", section on 'Dietary habits'.)

Limited evidence for benefit

●Leukemia – Breastfeeding has been associated with a modest reduction in the risk of developing childhood lymphoma and leukemia. In a population-based cohort study of more than 300,000 children from Denmark, exclusive breastfeeding for at least three months was associated with a decreased risk of hematologic cancers (adjusted HR 0.66, 95% CI 0.46-0.95), primarily B-cell precursor acute lymphoblastic leukemia [91]. A case-control study reported that ever breastfeeding was associated with decreased risk for childhood leukemia and lymphoma (OR 0.36, 95% CI 0.22-0.60), with a dose-response effect [92]. Similarly, a meta-analysis of 18 studies reported that breastfeeding for six or more months reduced the risk of childhood leukemia (OR 0.81, 95% CI 0.73-0.89) [93]. Although the relative risk reduction is significant in each of these studies, this translates to a very small change in the level of absolute risk. For other less common childhood cancers, there is insufficient evidence to determine an effect of breastfeeding.

●Allergic conditions – There is limited evidence for benefit of breastfeeding on atopic asthma in older children (after six years of age) or on eczema or allergic rhinitis (in all age groups). As noted above, breastfeeding appears to be associated with a lower incidence of wheezing in younger children, which may reflect reductions in upper respiratory infections rather than atopic wheezing (see 'Moderate evidence of benefit' above). These issues are discussed in more detail separately. (See "The impact of breastfeeding on the development of allergic disease".)

Limited evidence suggests that breastfeeding in the first four months of life may decrease the risk of cow's milk allergy in early childhood [94]. A more general or long-term impact of breastfeeding on food allergies has not been established. (See "The impact of breastfeeding on the development of allergic disease", section on 'Breastfeeding and food allergy'.)

●Obesity – Several large prospective cohort studies and meta-analyses report that breastfeeding or breastfeeding duration is associated with a modestly reduced risk for overweight or obesity during childhood [95-99]. As an example, a study of almost 200,000 children from low-income families in the United States reported that breastfeeding for 6 to 12 months was associated with a reduced risk of overweight among non-Hispanic White children compared with no breastfeeding (adjusted OR 0.70, 95% CI 0.50-0.99) [95]. No such effect was noted for Hispanic or Black children. In another study that included 8134 mother-infant dyads in the United States, exclusive breastfeeding for three months (versus not) was associated with lower child body mass index Z-score (BMIz) during early childhood regardless of maternal BMI category, although the differences were modest and of marginal statistical significance [100]. For mothers whose prepregnancy weight was healthy, the difference in child BMIz was -0.06 (95% CI -0.10 to -0.02), and, for mothers with obesity, the difference in child BMIz was -0.08 (95% CI -0.12 to -0.03). For mothers who were overweight, the difference in child BMIz was not significant (-0.05, 95% CI -0.10 to 0.005). A Canadian study found a dose-dependent protective effect of breastfeeding that was diminished, but not eliminated, if the breast milk was given by bottle rather than directly from the breast, suggesting that the effect might be related to the feeding method rather than the human milk itself [101]. A large randomized trial in Belarus, however, did not detect an effect of breastfeeding promotion on childhood obesity (OR 1.17, 95% CI 0.97-1.41) [72].

A meta-analysis of 159 studies reported a 27 percent reduction in risk of overweight or obesity for children who were ever breastfed compared with those who were never breastfed (OR 0.73, 95% CI 0.71-0.76), but the effect for the 19 high-quality studies was marginal (OR 0.85, 95% CI 0.77-0.93) [99]. In general, the reported effect size is greater in studies that adjust for socioeconomic status and also greater in high-resource countries (where breastfeeding is more common among mothers with higher socioeconomic status) versus low- and middle-resource countries (where the opposite is true) [99,102,103]. Together, these observations suggest the possibility of residual confounding from socioeconomic status [71]. (See 'Limitations of this evidence' above.)

●Type 2 diabetes – A meta-analysis of 14 studies suggested that breastfeeding decreases the risk of developing type 2 diabetes (pooled OR 0.67, 95% CI 0.56-0.80) [104]. The protective effect of breastfeeding was higher for adolescents but also protective in adults [104]. Of note, this analysis did not adjust for BMI, so it is possible that the association is mediated by the effects of breastfeeding on obesity. A systematic review (which did not include the above study) found insufficient evidence to determine the association between breastfeeding and the risk of type 2 diabetes, prediabetes, or related biomarkers including hemoglobin A1c [81].

●Cardiovascular risk factors – Very limited evidence suggests an association between breastfeeding and cardiovascular risk factors. The best evidence is for effects on blood pressure. In a study of more than 1500 healthy children, breastfeeding for ≥12 months was associated with slightly lower blood pressure (reduction of approximately 1 mmHg), which may not be clinically significant [105]. A systematic review also concluded that breastfeeding is associated with lower blood pressure during childhood but found insufficient evidence to determine an effect on blood lipids or other cardiovascular disease risk factors [81,105,106]. Similarly, a protective effect of breastfeeding on metabolic syndrome or metabolic dysfunction-associated steatotic liver disease in the offspring is uncertain [106,107].

●Celiac disease – A few small case-control studies have reached conflicting conclusions regarding whether breastfeeding is associated with a lower risk for developing celiac disease, as summarized in systematic reviews [81,84]. However, the reviews concluded that there may be a protective effect because the two studies that controlled for confounding supported this conclusion [81]. An earlier meta-analysis reached a similar conclusion [108]. Interpretation of these and other studies is complicated by the potential relationship of breastfeeding to the timing and quantity of gluten introduction, which may affect the expression of celiac disease. (See "Epidemiology, pathogenesis, and clinical manifestations of celiac disease in children", section on 'Feeding practices in infancy and early childhood'.)

Contradictory evidence

●Colorectal cancer (CRC) risk – Analysis from two longitudinal prospective datasets in the United States have shown an association between having been breastfed and increased risk of CRC. In the Nurses' Health Study, having been breastfed was associated with a 23 percent increased risk of CRC (95% CI 10-38 percent) [109]. In a younger cohort (Nurses' Health Study II), there was an association between having been breastfed and increased risk of high-risk adenomas in those <50 years of age (OR 1.46, 95% CI 1.16-1.83) and increased risk of CRC among those <55 years of age (HR 1.38, 95% CI 1.06-1.80). This study adjusted for many known CRC risk factors and potential confounding factors, but the authors acknowledged the possibility of residual confounding. Similar findings were reported in a prospective study in the United Kingdom (the Million Women Study), which showed an increased incidence of CRC among women who had been breastfed versus not (risk ratio 1.18, 95% CI 1.12-1.24) [110]. By contrast, a large case-control study that included both males and females in the United Kingdom did not show a statistically significant correlation between early-onset CRC and having been breastfed as an infant (OR 1.04, 95% CI 0.84-1.29) [111].

Taken together, these large observational studies in several different cohorts suggest an association between having been breastfed and increased risk of CRC but do not demonstrate causation. Further research is needed to identify biologic plausibility and the impact of human milk feeding on the microbiome and the developing gastrointestinal tract, especially because having been breastfed is associated with many positive benefits, including the decreased risk of IBD [83].

Neurodevelopmental outcomes — Moderate-quality evidence from a variety of populations suggests that human milk feeding may be associated with slightly improved neurodevelopmental outcomes compared with formula feeding. However, as for the chronic disease outcomes discussed above, the evidence is limited by lack of randomized trials, and the findings may be affected by residual confounding or reverse causation. (See 'Limitations of this evidence' above.)

Although a mechanism has not been established, proposed mediators are the long-chain polyunsaturated fatty acids and, particularly, docosahexaenoic acid (DHA) and arachidonic acid in human milk, which may promote myelinization of and development of the nervous system. However, trials of DHA supplementation for preterm infants or formula-fed infants are inconsistent for cognitive or visual outcomes, as outlined in a separate topic review. (See "Long-chain polyunsaturated fatty acids (LCPUFA) for preterm and term infants".)

●Cognitive development – A meta-analysis shows that breastfeeding may be associated with slightly improved performance in intelligence tests, and this association persists after adjustment for maternal intelligence quotient (IQ) [112]. Children who were ever breastfed scored an average of 3.4 points higher on intelligence tests than those who were never breastfed. Among the studies that adjusted for maternal intelligence, a breastfeeding benefit of 2.6 points was revealed (95% CI 1.25-3.98). As with many other studies of long-term breastfeeding outcomes [113], these conclusions are limited by the possibility of residual confounding and thus do not establish a causal relationship between breastfeeding and cognitive development. Indeed, sibling-pair studies (which tend to have less residual confounding) show a smaller effect of breastfeeding (<1 point) [74]. Similarly, a Cochrane meta-analysis found no significant effect of donor breast milk versus formula feeding on neurodevelopmental outcomes in preterm infants [35]. (See 'Limitations of this evidence' above.)

Other studies suggest that these effects are also seen in adulthood. A prospective, population-based birth cohort study from Brazil reported that by age 30 years, participants who were breastfed for 12 months or more had higher IQ scores of 3.8 points, more years of education, and higher monthly incomes compared with those who were breastfed for less than one month in the adjusted analysis [114]. The analysis suggested that IQ was responsible for 72 percent of the effect on income. This long-term cohort study is also limited by potential residual confounding, similar to the shorter-term studies described above.

●Visual function – Several studies have indicated that human milk-fed term and premature infants have improved visual function compared with formula-fed infants [115]. The severity and incidence of retinopathy of prematurity is lower among breastfed compared with formula-fed infants [116-119]. In a randomized trial, severe retinopathy of prematurity was less common in infants fed mother's milk (5 percent) compared with donor human milk (19 percent) or preterm formula (14 percent), suggesting that the effect may not be related to human milk per se [118].

These benefits have been attributed to DHA, a component of phospholipids found in brain, retina, and red cell membranes and found in human milk but not in bovine milk [120,121]. These associations also may relate to the substantial antioxidant capacity of human milk compared with infant formula [122]. However, trials of DHA supplementation for preterm infants or formula-fed infants are inconsistent for visual or cognitive outcomes, as outlined in separate topic reviews. (See "Long-chain polyunsaturated fatty acids (LCPUFA) for preterm and term infants".)

●Auditory function – Auditory-evoked responses mature faster in breastfed premature infants [123].

●Attention deficit hyperactivity disorder (ADHD) – A meta-analysis revealed that children with ADHD had significantly less breastfeeding duration than controls and were less likely to have been breastfed for 6 to 12 months (OR 0.69, 95% CI 0.49-0.98) or >12 months (OR 0.58, 95% CI 0.35-0.97) [124]. Affected children were more likely to not have been breastfed (OR 3.71, 95% CI 1.94-7.11). Similar findings were reported from a large dataset from the 2011-2012 National Survey of Children's Health in the United States, in which exclusive breastfeeding for at least six months was associated with a 60 percent reduction (95% CI 0.15-0.99) in risk of ADHD in preschool-aged children [125].

●Autism spectrum disorder (ASD) – The association between breastfeeding and ASD is unclear, and analyses are limited by the possibility of reverse causation. In a sibling case-control study, exclusive breastfeeding was associated with lower odds for ASD, while early introduction of supplemental formula was associated with higher odds of ASD [126]. Similarly, a meta-analysis showed that children with ASD were less likely to have been breastfed (OR 0.61, 95% CI 0.45-0.83) [127]. In a multisite, case-control study, breastfeeding initiation rates were no different comparing children diagnosed with ASD versus not, after adjusting for sociodemographic and pregnancy characteristics [128]. Among those who were breastfed, children with ASD had a shorter duration of breastfeeding, which remained significant after adjusting for confounding variables. While this could result in fewer nutrients available to support neurodevelopment, the authors postulated that children who later developed ASD may be more difficult to breastfeed or may have early disturbances in emotion, motor development, or sucking activity, leading to shorter breastfeeding duration, reflecting reverse causation. Analysis of data from the National Survey of Children's Health in 2007 and 2011 showed no association between ASD and breastfeeding (adjusted OR 0.97, 95% CI 0.97-1.10) for each additional month of breastfeeding and for each additional month of exclusive breastfeeding (adjusted OR 1.04, 95% CI 0.96-1.13) [129]. These data, collected by phone survey, may be impacted by low response rates and recall bias.

●Child behavior – Data from the English Millennium Cohort study suggests that breastfeeding for four months or longer was associated with a lower risk of behavior problems in children at five years of age compared with a shorter duration of breastfeeding [130].

Abuse and neglect — Data from the National Longitudinal Study of Adolescent to Adult Health found adolescents breastfed for nine months or longer had a reduced odds of having experienced neglect (OR 0.54 [0.35-0.83]) and sexual abuse (OR 0.47 [0.24-0.93]) compared with adolescents never breastfed, after controlling for covariates [131].

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Breastfeeding and infant nutrition".)

SUMMARY

●Overview of benefits – Breastfeeding for virtually all infants is strongly supported by both governmental and medical professional organizations because of its acknowledged direct benefits to the infant's nutrition, gastrointestinal function, host defense, and psychological well-being. The unique composition of human milk, which contains antiinfective and antiinflammatory factors, along with the skin-to-skin contact from direct breastfeeding, promotes optimal health, protects from environmental exposures, and promotes development of the child's innate immune system. (See 'Biologically active components of human milk' above.)

In addition to its health benefits for the infant, breastfeeding has some health benefits for the mother and economic benefits for the family. (See "Maternal and economic benefits of breastfeeding".)

●Short-term health benefits to the infant

•The best-established health benefits of human milk feeding are prevention of illnesses during the period that the infant is breastfed. These benefits are most impactful in low- and middle-resource countries, in which lack of breastfeeding is associated with higher mortality. (See 'Prevention of illnesses while breastfeeding' above and 'Mortality and hospitalization' above.)

•Human milk, compared with infant formula, also appears to provide continued protection against acute illnesses, such as otitis media and pneumonia, even after discontinuation of breastfeeding, during the first few years of life. (See 'Acute illnesses' above.)

●Long-term health benefits to the infant – Breastfeeding has been associated with long-term benefits by reducing risk for several chronic diseases. The evidence for these long-term effects is based primarily on observational cohort studies, which are necessarily limited by the possibility of residual confounding. (See 'Limitations of this evidence' above.)

•Moderate-quality evidence exists for prevention of type 1 diabetes mellitus, inflammatory bowel disease (IBD), and wheezing in young children. (See 'Moderate evidence of benefit' above.)

•Effects of breastfeeding may exist but are not as well established for leukemia, atopic asthma, eczema, food allergies, obesity, and neurodevelopmental outcomes. (See 'Limited evidence for benefit' above and 'Neurodevelopmental outcomes' above.)

ACKNOWLEDGMENT — The UpToDate editorial staff acknowledges Richard J Schanler, MD, who contributed to earlier versions of this topic review.