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I. Effects on the Infant

An episode of diarrhea was significantly less likely to last for six or more days if an infant was breastfed for three or more months. Baker D et al. "Inequality in infant morbidity: causes and consequences in England in the 1990s." J Epidemiol Community Health 1998 Jul;52(7):451-8

The risk of developing diarrhea increases as the amount of breast milk an infant receives decreases. When compared with exclusively breastfed infants, infants who were exclusively formula-fed had an 80% increase in their risk of developing diarrhea. Scariati PD et al. "A longitudinal analysis of infant morbidity and the extent of breastfeeding in the United States." Pediatrics 1997 Jun;99(6):E5

The type of milk consumed before start of diarrhea episode was strongly associated with dehydration. Compared with infants exclusively breastfed, bottle-fed infants were at higher risk (odds ratio for cow's milk = 6.0, for formula milk = 6.9). Compared with those still breastfeeding, children who stopped in the previous two months were more likely to develop dehydrating diarrhea. Fuchs SC et al. "Case-control study of risk of dehydrating diarrhoea in infants in vulnerable period after full weaning. BMJ 1996 Aug 17;313(7054):391-4

In the first year of life the incidence of diarrheal illness among breastfed infants was half that of formula-fed infants. Dewey KG et al. "Differences in morbidity between breast-fed and formula-fed infants." J Pediatr 1995 May;126(5 Pt 1):696-702

Children less than 12 months of age had a lower incidence of acute diarrheal disease during the months they were being breastfed than children that were fed with formula during the same period. Lerman,Y. et al. "Epidemiology of acute diarrheal diseases in children in a high standard of living settlement in Israel". Pediatr Infect Dis J 1994; 13(2);116-22.

Strictly formula-fed children had an incidence of diarrhea over three times that of strictly breast-fed infants and twice that of breast-fed and supplementally fed children. Long KZ et al. Proportional hazards analysis of diarrhea due to enterotoxigenic Escherichia coli and breastfeeding in a cohort of urban Mexican children. Am J Epidemiol. 1994 Jan 15;139(2):193-205.

In this study of 500 Brazilian infants < or = 12 months old with diarrhea and 500 age-matched controls, breast-feeding infants < 6 months old (OR, 0.3) and boiling household drinking water (OR, 0.4) were protective. Breast-feeding was protective against enteropathogenic Escherichia coli infections (OR, 0.1). Blake PA, et al. "Pathogen-specific risk factors and protective factors for acute diarrheal disease in urban Brazilian infants." J Infect Dis 1993 Mar;167(3):627-32

The addition to the breast-milk diet of even water, teas, and other nonnutritive liquids doubled or tripled the likelihood of diarrhea. Supplementation of breast-feeding with additional nutritive foods or liquids further increased significantly the risk of diarrhea. Popkin BM et al. "Breast-feeding and diarrheal morbidity." Pediatrics 1990 Dec;86(6):874-82

2. Haemophilus Influenza

The protective effects of human milk against otitis media may be due in part to inhibition of nasopharyngeal colonization with H. influenzae by specific secretory IgA antibody. Harabuchi Y et al. "Human milk secretory IgA antibody to nontypeable Haemophilus influenzae: possible protective effects against nasopharyngeal colonization. J Pediatr 1994 Feb;124(2):193-8

The adjusted odds ratio for exposure to breastfeeding was 0.5. Arnold C, et al. "Day care attendance and other risk factors for invasive Haemophilus influenzae type b disease." Am J Epidemiol 1993 Sep 1;138(5):333-40

Invasive Haemophilus influenzae type b (Hib) disease occurred at a mean age of 8.7 months. Breastfeeding was significantly less common among cases than controls (odds ratio = 0.53). Petersen GM. "Effects of age, breast feeding, and household structure on Haemophilus influenzae type b disease risk and antibody acquisition in Alaskan Eskimos. Am J Epidemiol 1991 Nov 15;134(10):1212-21

In a population-based case-control study of risk factors for primary invasion of haemophilus influenza, type B disease, breastfeeding was protective of infants less than 6 months of age. Cochi, S.L. "Primary Invasive Haemophilus Influenza Type B Disease, A Population Based Assessment of Risk Factors". Journal of Pediatrics 1986 Jun;108(6):887-96.

3. Meningitis in Preterm Infants

The incidence of any infection and sepsis/meningitis are significantly reduced in human milk-fed VLBW infants compared with exclusively formula-fed VLBW infants. Hylander MA et al. "Human milk feedings and infection among very low birth weight infants." Pediatrics 1998 Sep;102(3):E38

4. Necrotizing Enterocolitis

The benefits of improved health (less sepsis and necrotizing enterocolitis) associated with the feeding of fortified human milk outweighed the slower rate of growth observed in this study of 108 preterm infants. Infants fed human milk were discharged an average of 15 days earlier than infants preterm formula. Schanler RJ, et al. "Feeding strategies for premature infants: beneficial outcomes of feeding fortified human milk versus preterm formula." Pediatrics 1999 Jun;103(6 Pt 1):1150-7

Although no specific intervention for NEC treatment exists, preventive therapy using either enteral IgA supplementation, breast milk feeding, antibiotic prophylaxis, or exogenous steroid administration have reduced the incidence of this overwhelming disease in small randomized trials. Caplan MS, et al. "Necrotizing enterocolitis: a review of pathogenetic mechanisms and implications for prevention."(review) Pediatr Pathol 1993 May-Jun;13(3):357-69

Based on both laboratory and clinical studies, human milk feeding appears to have protective effects against development of necrotizing enterocolitis. Buescher ES. "Host defense mechanisms of human milk and their relations to enteric infections and necrotizing enterocolitis."(review) Clin Perinatol 1994 Jun;21(2):247-62

Among babies born at more than 30 weeks gestation, confirmed necrotizing enterocolitis was rare in those whose diet included breast milk; it was 20 times more common in those fed formula only. Lucas, A., Cole, T.J., "Breast Milk and Neonatal Necrotizing Enteral Colitis". Lancet 1990; 336:1519-23

5. Otitis Media (Middle Ear Infection)

The risk of developing an ear infection increases as the amount of breast milk an infant receives decreases. When compared with exclusively breastfed infants, infants who were exclusively formula-fed had a 70% increase in their risk of developing an ear infection. Scariati PD et al. "A longitudinal analysis of infant morbidity and the extent of breastfeeding in the United States." Pediatrics 1997 Jun;99(6):E5

In infants who were breast fed until at least 12 months of age, the percentage of any otitis media was 19% lower, and of prolonged episodes (> 10 days) was 80% lower than formula-fed infants. The mean duration of episodes of otitis media was longer in formula-fed than breastfed infants (8.8 vs 5.9 days, respectively). Dewey KG et al. "Differences in morbidity between breast-fed and formula-fed infants." J Pediatr 1995 May;126(5 Pt 1):696-702

Infants exclusively breast-fed for 4 or more months had half the number of acute otitis media episodes as did those not breastfed at all, and 40% less than those infants whose diets were supplemented with other foods prior to 4 months. The recurrent otitis media rate in infants exclusively breast-fed for 6 months or more was 10% and was 20.5% in those infants who breast-fed for less than 4 months. Duncan B et al. "Exclusive breast-feeding for at least 4 months protects against otitis media." Pediatrics 1993 May;91(5):867-72

Short duration of breastfeeding involved another significant risk of recurrent respiratory infections and otitis media. Alho, O., "Risk Factors for Recurrent Acute Otitis Media and Respiratory Infection in Infancy". INT J PED OTORHINOLARYNGOLOGY 1990; 19:151-61

Significantly increased risk for acute otitis media as well as prolonged duration of middle ear effusion were associated with male gender, sibling history of ear infection and not being breast fed. Teele, D.W., Epidemiology of Otitis Media During the First Seven Years of Life in Greater Boston: A prospective, Cohort Study". J of INFEC DIS.1989.

(See also: Duffy 1997, Aniansson 1994, Harabushi 1994, Paradise 1994, Sassen 1994, Owen 1993, Gulick 1986, Saarinen 1982)

6. Pneumococcal Disease

Among children 2 to 59 months, invasive pneumococcal disease was strongly associated with underlying disease and with day care attendance in the previous 3 months. Among 2- to 11-month-olds, current breastfeeding was associated with a decreased likelihood of invasive pneumococcal disease. Levine OS et al. "Risk factors for invasive pneumococcal disease in children: a population-based case-control study in North America." Pediatrics 1999 Mar;103(3):E28

7. Respiratory Infections (general)

Infants who were not being breast fed were 17 times more likely than those being breast fed exclusively to be admitted to hospital for pneumonia. Cesar JA et al. "Impact of breast feeding on admission for pneumonia during postneonatal period in Brazil: nested case-control study. BMJ 1999 May 15;318(7194):1316-1320

In a cohort of 1,202 healthy infants, born in Albuquerque, New Mexico, the daily occurrences of respiratory symptoms and breastfeeding status were reported by the mothers every 2 weeks during the first 6 months of life. After adjustment for potential confounding factors, full breastfeeding was associated with a reduction in lower respiratory illness risk (odds ratio=0.81) and significantly reduced the duration of respiratory illness. Cushing AH, et al. "Breastfeeding reduces risk of respiratory illness in infants." Am J Epidemiol 1998 May 1;147(9):863-70

Children who were not fed human milk had a 1.8-fold increased risk of respiratory disease at each level of exposure to passive cigarette smoke, in comparison with children who were fed human milk for at least 1 month. Jin C, Rossignol AM. "Effects of passive smoking on respiratory illness from birth to age eighteen months, in Shanghai, People's Republic of China. J Pediatr 1993 Oct;123(4):553-8

The authors presented results found in infants with two or more episodes of acute chronic bronchitis. They found that approximately twice as many bottle-fed infants presented with the problem as those who were breastfed. deDuran, C.M. "Cytologic Diagnosis of Milk Micro Aspiration". IMM ALLERGY PRACTICE 1991; xiii (10);402-5

Odds of respiratory illness with maternal smoking were 7 times higher among children who were never breastfed then among those who were breastfed. Woodward A et al. "Acute Respiratory Illness in Adelaide Children: BreastFeeding Modifies the Effect of Passive Smoking". J Epidemiol Community Health 1990 Sep;44(3):224-30

8. Respiratory Syncytical Virus (RSV)

Breastfeeding was associated with a lower incidence of RSV infection during the first year of life. Holberg,C.J., "Risk Factors for RSV Associated Lower Respiratory Illnesses in the First Year of Life". AM J Epidemiol 1991; 133 (135-51)

9. Sepsis in Preterm Infants

10. Urinary Tract Infections (UTI)

Breastfed infants have a relative risk of developing a UTI of 0.38 compared to formula-fed infants. Pisacane A et al. "Breast-feeding and urinary tract infection." J Pediatr 1992 Jan;120(1):87-9

The oligosaccharide content of breast-milk and urine from nursing mothers is very similar, and the pattern of oligosaccharides excreted by infants is also strongly correlated with that of breastmilk. The oligosaccharides cause inhibition of bacterial adhesion, suggesting that breastfeeding may have a preventive effect on urinary tract infection in both mother and infant. Coppa GV et al. "Preliminary study of breastfeeding and bacterial adhesion to uroepithelial cells." Lancet 1990 Mar 10;335(8689):569-71

B. Childhood Illnesses

1. Autoimmune Thyroid Disease

Feeding practices in infancy may affect the development of various autoimmune diseases later in life. Thyroid alterations are among the most frequently encountered autoimmune conditions in children. A detailed history of feeding practices was obtained in 59 children with autoimmune thyroid disease, their 76 healthy siblings, and 54 healthy nonrelated control children. The frequency of feedings with soy-based milk formulas in early life was significantly higher in children with autoimmune thyroid disease (prevalence 31%) as compared with their siblings (prevalence 12%), and healthy nonrelated control children (prevalence 13%). Fort P, et al. Breast and soy-formula feedings in early infancy and the prevalence of autoimmune thyroid disease in children. J Am Coll Nutr. 1990 Apr;9(2):164-7.

2. Cryptorchidism (Undescended Testicle)

This case-controlled study showed a significant association of cryptorchidism and lack of breastfeeding. Mori, M. "Maternal and other factors of cryptorchidism: a case-control study in Japan" Kurume Med J, 1992:39:53-60

3. Gastroesophageal Reflex

Breastfed neonates demonstrate gastroesophageal reflux episodes of significantly shorter duration than formula fed neonates. Heacock, H.J., "Influence of Breast vs. Formula Milk in Physiologic Gastroesophageal Reflux in Health Newborn Infants". J. Pediatr Gastroenterol Nutr, 1992 January; 14(1): 41-6

4. General Morbidity

The association between breastfeeding dose and illnesses in the first 6 months of life was analyzed for 7092 infants. Breastfeeding dose (ratio of breast-feedings to other feedings) was categorized as "full," "most," "equal," "less," or "no" breastfeeding. Compared with no breastfeeding, full breast-feeding infants had lower odds ratios of diarrhea, cough or wheeze, and vomiting and lower mean ratios of illness months and sick baby medical visits. "Most" breastfeeding infants had lower odds ratios of diarrhea and cough or wheeze, and "equal" breast-feeding infants had lower odds ratios of cough or wheeze. "Full," "most," and "equal" breastfeeding infants without siblings had lower odds ratios of ear infections and certain other illnesses, but those with siblings did not. "Less" breastfeeding infants had no reduced odds ratios of illness. Findings did not vary by income. Raisler J et al. "Breast-feeding and infant illness: a dose-response relationship? J Public Health 1999 Jan;89(1):25-30

During the first 6 months of life, breastfeeding has a protective effect of against respiratory illnesses, gastrointestinal illnesses, and on all illnesses. Beaudry M et al. "Relation between infant feeding and infections during the first six months of life." J Pediatr 1995 Feb;126(2):191-7

Jones EG et al. "Relationship between infant feeding and exclusion rate from child care because of illness." J Am Diet Assoc 1993 Jul;93(7):809-11

There is an inverse relationship to breastfeeding and morbidity. This was most prominent in the first year of life, but it was also present in the first three years. Van Den Bogaard, C. "Relationship Between Breast Feeding in Early Childhood and Morbidity in a General Population". Fan Med, 1991; 23:510-515

5. Immunologic Development

Review article: Protection against infections has been well evidenced during lactation against, e.g., acute and prolonged diarrhea, respiratory tract infections, otitis media, urinary tract infection, neonatal septicemia, and necrotizing enterocolitis. There is also interesting evidence for an enhanced protection remaining for years after lactation against diarrhea, respiratory tract infections, otitis media, Haemophilus influenzae type b infections, and wheezing illness. In several instances the protection seems to improve with the duration of breastfeeding. A few factors in milk like anti-antibodies (anti-idiotypic antibodies) and T and B lymphocytes have in some experimental models been able to transfer priming of the breastfed offspring. This together with transfer of numerous cytokines and growth factors via milk may add to an active stimulation of the infant's immune system. Such an enhanced function could also explain why breastfeeding may protect against immunologic diseases like celiac disease and possibly allergy. Suggestions of protection against autoimmune diseases and tumors have also been published. Hanson LA. "Breastfeeding provides passive and likely long-lasting active immunity. Ann Allergy Asthma Immunol 1998 Dec;81(6):523-33; quiz 533-4, 537

Secretory IgA concentration increased more rapidly during the first 6 months after birth in infants exclusively breastfed than in those exclusively bottle fed. Fitzsimmons SP, et al. "Immunoglobulin A subclasses in infants' saliva and in saliva and milk from their mothers." J Pediatr 1994 Apr;124(4):566-73

Enhanced fecal SIgA in breastfed infants is not caused solely by the presence of IgA in breast milk; it represents a stimulatory effect of breast milk on the gastrointestinal humoral immunologic development. Koutras, A.K., "Fecal Secretory Immunoglobulin A in Breast Milk vs. Formula Feeding in Early Infancy". J Ped Gastro Nutr, 1989.

6. Infant Survival

There is association between breastfeeding up to 6 months of age and survival of infants throughout the first year of life. The younger the infant and the longer the breastfeeding, the greater the estimated benefits in terms of death averted. Habicht, J.P., "Does Breast Feeding Really Save Lives, or Are Apparent Benefits due to Biases?" Am J Epidemiology, 1986

7. Inguinal Hernia

Human milk contains gonadotropin releasing hormone, which may affect the maturation of neonatal testicular function. This case-control study showed breastfed infants had a significant dose response reduction in inguinal hernia. Pisacane, A. "Breast-feeding and inguinal hernia" Journal of Pediatrics 1995:Vol 127, No. 1, pp 109-111

8. Pyloric Stenosis

Infants with pyloric stenosis were less likely to have been breastfed during the first week of life. Pisacane A, et al. Breast feeding and hypertrophic pyloric stenosis: population based case-control study. BMJ. 1996 Mar 23;312(7033):745-6.

9. SIDS

Sixty-three infants who died suddenly and unexpectedly were classified into 3 groups: SIDS (19 cases), borderline SIDS (30 cases) and non-SIDS (14 cases). Non-SIDS cases received more breastfeeding, the parents hardly smoked during pregnancy and after birth, a firm mattress had been used, and more often signs of illness had been reported by the parents, compared with the SIDS and borderline SIDS cases. L'Hoir MP et al. "Sudden unexpected death in infancy: epidemiologically determined risk factors related to pathological classification." Acta Paediatr 1998 Dec;87(12):1279-87

Not breastfeeding at discharge from an obstetric hospital at any stage of the infant's life was associated with an increased risk of SIDS. Mitchell, A. "Results from the First Year of The New Zealand Count Death Study". N.Z. Med A, 1991; 104:71-76

A study indicated that breastfeeding was protective against SIDS, consistent with an effect mediated through the prevention of gastrointestinal and/or respiratory disease. Hoffman, H.J., "Risk Factors for SIDS: Results of the National Institute of Child Health and Human Development SIDS Cooperative Epidemiologic Study". Ann NY ACAD Sci, 1988.

10. Toddler Health

Mothers of 67 infants were questioned about the types and duration of illness episodes requiring medical care between 16 and 30 months of age. Breastfeeding was noted to decrease the number of infant illnesses and indirectly improve toddler health. Gulick, E.E. "The Effects of Breastfeeding on the Toddler Health." Pediatric Nursing, 1986 Jan-Feb;12(1):51-4.

11. Wheezing

Infants who were breastfed for three or more months were significantly less likely to have three or more episodes of wheezing in the first six months after birth. Baker D et al. "Inequality in infant morbidity: causes and consequences in England in the 1990s." J Epidemiol Community Health 1998 Jul;52(7):451-8

Children who had ever been breast fed had a lower incidence of wheeze than those who had not (59% and 74% respectively). The effect persisted to age 7 years in the non-atopics only, the risk of wheeze being halved in the breast fed children. Burr ML, et al. "Infant feeding, wheezing, and allergy: a prospective study." Arch Dis Child 1993 Jun;68(6):724-8

Within the group who had had early wheezing, infants who had been breastfed for at least one month subsequently had less severe wheezing. Porro E, et al. "Early wheezing and breast feeding." J Asthma 1993;30(1):23-8

Breastfeeding seems to protect against wheezing respiratory tract illnesses in the first 4 months of life, particularly when other risk factors are present. Wright, A.L., "Breastfeeding and lower respiratory Tract Illnesses in the First Year of Life". British Medical Journal, 1989.

C. Allergies

1. Allergies in general

2187 children were followed to age 6 years to study the association between duration of exclusive breast feeding and asthma or atopy. After adjustment for confounders, the introduction of milk other than breastmilk before 4 months of age was a significant risk factor for all asthma and atopy related outcomes in children aged 6 years. A significant reduction in the risk of childhood asthma at age 6 years occurs if exclusive breast feeding is continued for at least the 4 months after birth.

Oddy WH et al. "Association between breast feeding and asthma in 6 year old children: findings of a prospective birth cohort study." BMJ 1999 Sep 25;319(7213):815-9

A birth cohort was followed-up to age 4 years. By age 4 years, 27% of the children had symptoms of allergic disease. Family history of atopy was the single most important risk factor for atopy in children. Sibling atopy was a stronger predictor of clinical disease than maternal or paternal atopy. Formula-feeding before 3 months of age predisposed to asthma at age 4 years (OR: 1.8). Tariq SM, et al. The prevalence of and risk factors for atopy in early childhood: a whole population birth cohort study. J Allergy Clin Immunol. 1998 May;101(5):587-93.

The factors most important in the pathogenesis of allergic symptoms were: (i) formula implementation begun in the first week of life; (ii) early weaning (< 4 months); (iii) feeding beef (< 6 months); (iv) early introduction of cow's milk (< 6 months); and (v) parental smoking in the presence of the babies and early day care admission (< 2 years of life). All the preventive measures used in this study (exclusive breastfeeding and/or hydrolyzed milk feeding, delayed and selective introduction of solid foods, and environmental advice) were effective at the third year of follow-up, greatly reducing allergic manifestations in high atopic risk babies in comparison with those not receiving these interventions Marini A et al. "Effects of a dietary and environmental prevention programme on the incidence of allergic symptoms in high atopic risk infants: three years' follow-up. Acta Paediatr Suppl 1996 May;414:1-21

Breastfeeding, even for short periods was clearly associated with lower incidence of wheezing, prolonged colds, diarrhea, and vomiting. Merrett, T.G., "Infant Feeding & Allergy: 12 Month Prospective Study of 500 Babies Born into Allergic Families". American Allergies, 1988.

2. Asthma

Introducing milk other than breast milk to infants younger than 4 months old increases the risk of asthma and atopy (a predisposition to certain allergies). The investigators followed 2,187 children from before birth through their 6th birthday. Children who were fed milk other than breast milk before 4 months of age experienced higher rates of all indicators of asthma and allergy. Such children were 25% more likely to be diagnosed with allergy and 30% more likely to have a positive skin test for allergies than were children who received only breast milk during their early months. The total duration of exclusive breastfeeding was less important, though longer breastfeeding was associated with less asthma and allergy. The researchers also found increased risks of asthma and atopy among boys, infants born prematurely, and children living in households where smoking took place. Oddy W et al. British Medical Journal Sep 1999;319:815-819.

3. Eczema

Prospective randomized double-blind study of high-risk infants with a family history of atopy followed until 5 years of age showed a significant lowering in the incidence of atopic disease in the breast-fed and the whey hydrolysate groups, compared with the conventional cow's milk group. Soy formula was not effective. The occurrence of both eczema and asthma was lowest in the breast-fed and whey hydrolysate groups and was comparable in the cow's milk and soy groups. Chandra RK. "Five-year follow-up of high-risk infants with family history of allergy who were exclusively breast-fed or fed partial whey hydrolysate, soy, and conventional cow's milk formulas." J Pediatr Gastroenterol Nutr 1997 Apr; 24(4):380-8

Eczema was less common and milder in babies who were breast fed (22%) and whose mothers were on a restricted diet (48%). In infants fed casein hydrolysate, soymilk or cows milk, 21%, 63%, and 70% respectively, developed atopic eczema. Chandra R.K., "Influence of Maternal Diet During Lactation and the Use of Formula Feed and Development of Atopic Eczema in the High Risk Infants". Br Med J. 1989

D. Development and Intelligence

1. Cognitive Development

96 healthy term infants, aged between 10 and 14 months were assessed using the Bayley Scales of Infant Development. Duration of breast-feeding significantly predicted mental development scores for boys, but not for girls. Duration of breast-feeding did not predict psychomotor development scores. Paine BJ, Makrides M, Gibson RA. “Duration of breast-feeding and Bayley's Mental Developmental Index at 1 year of age.” J Paediatr Child Health 1999 Feb;35(1):82-5.

Increasing duration of breastfeeding was associated with consistent and statistically significant increases in 1) intelligence quotient assessed at ages 8 and 9 years; 2) reading comprehension, mathematical ability, and scholastic ability assessed during the period from 10 to 13 years; 3) teacher ratings of reading and mathematics assessed at 8 and 12 years; and 4) higher levels of attainment in school leaving examinations. Breastfeeding is associated with small but detectable increases in child cognitive ability and educational achievement. These effects are 1) pervasive, being reflected in a range of measures including standardized tests, teacher ratings, and academic outcomes in high school; and 2) relatively long-lived, extending throughout childhood into young adulthood. . Horwood LJ, Fergusson DM. "Breastfeeding and later cognitive and academic outcomes." Pediatrics 1998 Jan;101(1):E9

Supplementary regression analysis examining the strength of relationship between duration of breastfeeding and cognitive development show small but significant relationship between duration of breastfeeding and scores on the mental development index of the Bayley Scales at 1 and 2 years. Morrow-Tlucak, M. "Breast Feeding and Cognitive Development During the First 2 years of Life. "Soc Sci Med, 1988, 26(6):635-9.

In 771 low birth weight infants, babies whose mothers chose to provide breast milk had an 8 point advantage in mean Bayley's mental developmental index over infants of mother choosing not to do so. Morley, R., "Mothers Choice to provide Breast Milk and Developmental Outcome". Arch Dis Child, 1988

2. Gastrointestinal and Immune Development

This article summarizes the published data on the intestinal microflora in breastfed infants published during the last 15 y. Acetic acid is found in higher concentrations in breastfed than in formula-fed infants. Degradation of mucin starts later in breastfed than in formula-fed infants. The conversion of cholesterol to coprostanol is also delayed by breastfeeding. Orrhage K and Nord CE. "Factors controlling the bacterial colonization of the intestine in breastfed infants." Acta Paediatr Suppl 1999 Aug;88(430):47-57

Nucleotides (NT) and their related metabolic products play key roles in many biological processes. Most dietary NT are rapidly metabolized and excreted. However, some are incorporated into tissues, particularly at younger ages. Under conditions of limited NT intake, rapid growth or certain disease states, dietary NT may spare the cost of de novo NT synthesis and optimize the function of rapidly dividing tissues such as those of the gastrointestinal and immune systems. Animals fed NT-supplemented versus non-NT supplemented diets have enhanced gastrointestinal growth and maturation, and improved recovery following small and large bowel injury. Indices of humoral and cellular immunity are enhanced, and survival rates are higher following infection with pathogens. Infants receive NT in human milk, where they are present as nucleic acids, nucleosides, nucleotides and related metabolic products. The NT content of human milk is significantly higher than most cow's milk-based infant formulae. Dietary NT are reported to enhance the gastrointestinal and immune systems of formula-fed infants. Infants fed NT-supplemented versus non-supplemented formula have a lower incidence of diarrhea, higher antibody titers following Haemophilus influenzae type b vaccination and higher natural killer cell activity. These data suggest that human milk NT may contribute to the superior clinical performance of the breastfed infant. Carver JD. "Dietary nucleotides: effects on the immune and gastrointestinal systems." Acta Paediatr Suppl 1999 Aug;88(430):83-8

3. Hormones

Hormones, growth factors, cytokines and even whole cells are present in breast milk and act to establish biochemical and immunological communication between mother and child. In addition, milk nutrients such as nucleotides, glutamine and lactoferrin have been shown to influence gastrointestinal development and host defense. Bernt KM and Walker WA. "Human milk as a carrier of biochemical messages." Acta Paediatr Suppl 1999 Aug;88(430):27-41.

Human milk as well as the milk of several mammalian species contains a group of biologically active substances that directly influence the newborn's metabolism and promote growth and differentiation of organs and target tissues. The biological significance of hormones and growth factors in milk is an area of active research. Murphy MS. "Growth factors and the gastrointestinal tract." Nutrition 1998 Oct;14(10):771-4

Erythropoietin stimulates production of red blood cells and is used in the treatment of anemia of prematurity. Human milk contains considerable amounts of erythropoietin which resist degradation after exposure to gastric juices at physiologic pH levels. Kling PJ et al. "Human milk as a potential enteral source of erythropoietin." Pediatr Res 1998 Feb;43(2):216-21

Prolactin may be important for lung maturation and surfactant synthesis, and may play a role in the growth of the gut and intestinal absorption of fluid and ions. In a study of 280 infants weighing less that 1850 grams at birth, higher plasma prolactin levels were associated with fewer days on ventilator, faster transition to full enteral feedings, and greater gain in length. Lucas A et al. "Plasma prolactin and clinical outcome in preterm infants." Archives of Disease in Childhood, 1990, 65:977-983.

4. IQ

A review of 20 published studies on the effects of breastfeeding on infant IQ found that breastfed babies' IQs may be 3 to 5 points higher than those of formula-fed babies. The longer a baby is breast-fed, the greater the benefits to his or her IQ. These benefits were seen from age 6 months through 15 years. Anderson JW et al. American Journal of Clinical Nutrition, Oct 1999, 70.

School-age phenylketonuric children who had, as infants, been breastfed 20-40 days prior to dietary intervention scored significantly better (IQ advantage of 14.0 points, p = 0.01) than children who had been formula fed. A 12.9 point advantage persisted also after adjusting for social and maternal education status. Riva E et al. "Early breastfeeding is linked to higher intelligence quotient scores in dietary treated phenylketonuric children. Acta Paediatr 1996 Jan;85(1):56-8

Children who had consumed mother's milk by tube in early weeks of life had a significantly higher IQ at 7.5 to 8 years, than those who received no maternal milk, even after adjustment for differences between groups and mothers' educational and social class. Lucas, A., "Breast Milk and Subsequent Intelligence Quotient in Children Born Preterm". Lancet 1992;339:261-62

5. Psychomotor and Social Development

Infants (4 to 6 months old) looked at a mobile significantly longer when tested after breastfeeding. This finding suggests that breastfeeding has a substantial effect on infants' attentiveness to and interaction with their environment. Gerrish CJ and Mennella JA. "Short-term influence of breastfeeding on the infants' interaction with the environment. Dev Psychobiol 2000 Jan;36(1):40-48.

Motor skills and early language development were evaluated in 1656 8-month-olds. The proportion of infants who mastered the specific milestones increased consistently with increasing duration of breastfeeding. The relative risk for the highest versus the lowest breastfeeding category was 1.3 for crawling, 1.2 for pincer grip and 1.5 for polysyllable babbling. Little change was found after adjustment for confounding factors. In conclusion, data support the hypothesis that breastfeeding benefits neurodevelopment. Vestergaard M et al. Duration of breastfeeding and developmental milestones during the latter half of infancy. Acta Paediatr 1999 Dec;88(12):1327-32

Children breastfed for 9 months or more present significantly less suspected developmental delay (25.5%, measured by the Denver II test) than those breast fed for less than 1 month (42.4%). Barros FC. "Breast feeding, pacifier use and infant development at 12 months of age: a birth cohort study in Brazil." Paediatr Perinat Epidemiol 1997 Oct;11(4):441-50

A prospective study of measured psychomotor development between 18 and 29 months using the Bayley scales. Lower results on the Index of Mental Development were associated with bottle-fed infants. Temboury MC et al. "Influence of breast-feeding on the infant's intellectual development." J Pediatr Gastroenterol Nutr 1994 Jan;18(1):32-6

The psychomotor and social development of breastfed babies clearly differs from that of bottle-fed ones and leads at the age of 12 months to significant advantages of the psychomotor and social capabilities. Baumgartner, C., "Psychomotor and Social Development of Breast Fed and Bottle Fed babies During their First year of Life". Acta Paediatrica Hungarica, 1984 25(4):409-17.

6. Thymus development

At 10 months the thymic index was significantly higher in those still being breast-fed compared to infants who had stopped breast-feeding between 8 and 10 months of age. In infants still breast-fed at 10 months there was a significant correlation between the number of breast-feeds per day and their thymic index. Hasselbalch H et al, "Breast-feeding influences thymic size in late infancy." Eur J Pediatr 1999 Dec;158(12):964-7

Forty-seven healthy infants were examined as neonates and re-examined at 4 months of age. Thirty-seven of the infants were also re-examined at 8, 10, and 12 months of age. The thymus size was measured. Infants exclusively breast-fed during the first 4 months of their lives had a larger thymic index at 10 months than formula-fed infants. Infants with fever episodes from 10 to 12 months had a smaller thymic index at 12 months. The thymus size in healthy infants increases from birth to 4 and 8 months of age and then decreases. Hasselbalch H et al. Thymus size evaluated by sonography. A longitudinal study on infants during the first year of life. Acta Radiol 1997 Mar;38(2):222-7

At 4 months the geometric mean thymic index was 38.3 in exclusively breastfed infants (n = 21), 27.3 in partially breastfed infants (n = 13) and 18.3 in formula fed infants (n = 13). This finding was independent of weight, length, sex and previous or current illness. There was no significant difference in mean thymic index at birth between the three feeding groups and mean thymic index had increased in all three groups from birth to 4 months. Conclusion: the thymus is considerably larger in breastfed than in formula-fed infants at the age of 4 months. The cause of this difference is unknown but human milk contains many immune modulating factors that might cause this effect. Hasselbalch H et al. Decreased thymus size in formula-fed infants compared with breastfed infants. Acta Paediatr 1996 Sep;85(9):1029-32

E. Physiologic Response During Feedings

Preterm infants demonstrated a higher oxygen saturation and a higher temperature during breastfeeding than during bottle feeding, and were less likely to desaturate to <90% oxygen during breastfeeding. Blaymore Bier JA et al. "Breastfeeding infants who were extremely low birth weight. Pediatrics 1997 Dec;100(6):E3

In infants with congenital heart disease, oxygen saturations during breastfeeding were higher on average and less variable than during bottle feedings, indicating that there is less cardiorespiratory stress with breastfeeding. Marino BL et al. "Oxygen saturations during breast and bottle feedings in infants with congenital heart disease." J Pediatr Nurs 1995 Dec;10(6):360-4

Supine bottle feeding has a significant effect on middle-ear pressure dynamics, probably caused by the aspiration of milk into the ear. Tully SB et al. "Abnormal tympanography after supine bottle feeding." J Pediatr 1995 Jun;126(6):S105-11

F. Long Term Effects

1. Appendicitis

Pisacane A, et al. Breast feeding and acute appendicitis. BMJ. 1995 Apr 1;310(6983):836-7.

2. Bone mass

In this study of 330 8-year-old children from Southern Tasmania, those who were breastfed had higher bone mineral density at the femoral neck, lumbar spine and total body compared with those who were bottle-fed. This association remained significant after adjustment for size, lifestyle factors and socioeconomic factors. Breastfeeding for less than 3 months was not associated with increased bone mass at any site. Jones G, Riley M, Dwyer T. Breastfeeding in early life and bone mass in prepubertal children: a longitudinal study. Osteoporos Int 2000;11(2):146-52

3. Cancer

a) Breast Cancer in Adulthood

Having been breastfed as an infant has been associated with a 20-35% reduction in risk of premenopausal breast cancer in four of six studies evaluating this factor. Potischman-N; Troisi-R. "In-utero and early life exposures in relation to risk of breast cancer." Cancer-Causes-And-Control. 1999; 10 (6): 561-573

Women who were breastfed as infants, even if only for a short time, showed an approximate 25% lower risk of developing premenopausal or postmenopausal breast cancer, compared to women who were bottle-fed as an infant. Freudenheim, J. "Exposure to breast milk in infancy and the risk of breast cancer." Epidemiology 1994 5:324-331

b) Childhood Cancer

In a case-controlled study of 593 cases of cancer in Moscow children 0 to 14 years of age, the positive trend of increased risk of cancer with decreasing duration of breastfeeding was significant for all cancer combined. Smulevich VB, Solionova LG, Belyakova SV. “Parental occupation and other factors and cancer risk in children: I. Study methodology and non-occupational factors.” Int J Cancer 1999 Dec 10;83(6):712-7.

Children who are artificially fed or breastfed for only 6 months or less, are at an increased risk of developing cancer before age 15. The risk of artificially-fed children was 1-8 times that of long-term breastfed children, and the risk for short term feeders was 1-9 times that of long term breast feeders. Davis, M.K. "Infant Feeding and Childhood Cancer." Lancet 1988 13;2(8607):365-8.

c) Hodgkin's Disease

This review of 9 published case-control studies suggests that children who are never breast-fed or are breast-fed short-term have a higher risk than those breast-fed for > 6 months of developing Hodgkin's disease, but not non-Hodgkin's lymphoma or acute lymphoblastic leukemia. Davis MK. "Review of the evidence for an association between infant feeding and childhood cancer." Int J Cancer Suppl 1998;11:29-33

A statistically significant protective effect against Hodgkin's disease among children who are breastfed at least 8 months compared with children who were breastfed no more than 2 months. Schwartzbaum, J. "An Exploratory Study of Environmental and Medical Factors Potentially Related to Childhood Cancer." Medical & Pediatric Oncology, 1991; 19 (2):115-21.

d) Leukemia and Lymphoma

This case-controlled study of 117 Bedouin Arab children showed that breastfeeding for less than six months was associated with an odds ratio of 2.79 for contracting a lymphoid malignancy compared with children breastfed longer than six months. European Journal of Cancer2001 January;37:234-238.

A total of 1744 children with acute lymphoblastic leukemia (ALL) and 1879 matched control subjects, aged 1-14 years, and 456 children with acute myeloid leukemia (AML) and 539 matched control subjects, aged 1-17 years, were studied. Ever having breast-fed was found to be associated with a 21% reduction in risk of childhood acute leukemias. The inverse associations were stronger with longer duration of breast-feeding. Shu XO etal, "Breast-feeding and risk of childhood acute leukemia. J Natl Cancer Inst 1999 Oct 20;91(20):1765-72

In interviews with the mothers of 2,200 children affected by either acute lymphoblastic leukemia (ALL) or acute myeloid leukemia (AML), the infant-feeding history of each of these children was compared with that of over 2,400 healthy controls. The investigators found that a history of breastfeeding was associated with a reduction in risk of childhood acute leukemias. Babies who are breast-fed for as little as one month have a 20% lower risk of childhood leukemia than bottle-fed babies, and babies breast-fed for more than 6 months have an even lower risk -- 30% less. Robison L et al. Journal of the National Cancer Institute 1999;91:1765-1772.

4. Cardiovascular Disease, Cholesterol Concentration

Exclusive breast feeding seems to have a protective effect against some risk factors for cardiovascular disease in later life. In this study of 625 adults aged 48-53 years, those who were bottle fed had a higher mean plasma glucose concentration after a standard oral glucose tolerance test than those who were exclusively breast fed. They also had a higher plasma low density lipoprotein (LDL) cholesterol concentration, a lower high density lipoprotein (HDL) cholesterol concentration, and a higher LDL/ HDL ratio. Systolic blood pressure and body mass index were not affected by the method of infant feeding. Ravelli-ACJ et al. "Infant feeding and adult glucose tolerance, lipid profile, blood pressure, and obesity." Archives-Of-Disease-In-Childhood. MAR 2000; 82 (3) : 248-252.

After adjustment for age, height, and sibship, and taking into account current diet and parental hypercholesterolemia, cholesterol concentration was lower in boys who had been breast fed This study provides evidence that diet in infancy may have longstanding effect on lipid metabolism. Plancoulaine-S et al. "Infant-feeding patterns are related to blood cholesterol concentration in prepubertal children aged 5-11y. European Journal of Clinical Nutrition. Feb 2000; 54 (2) : 114-119.

Age of weaning and method of infant feeding may influence adult serum low density lipoprotein cholesterol concentrations and mortality from ischemic heart disease. Fall CH et al. "Relation of infant feeding to adult serum cholesterol concentration and death from ischaemic heart disease." BMJ 1992 Mar 28;304(6830):801-5

5. Celiac Disease

Celiac disease is characterized by lethargy, megoblastic anemia, malabsorption, and GI symptoms caused by allergy to gluten. Prolonged breastfeeding, at least until the 6th month, and gluten introduction started at least at the 5th month of life, significantly delay the onset of the disease. Gluten introduction should be done progressively and under breast feeding protection. Introduction of gluten 2 months before weaning has a protective effect. Bouguerra F et al. [Breast feeding effect relative to age of onset of celiac disease]. Arch Pediatr 1998 Jun;5(6):621-6

Children formula-fed from birth, or breast-fed for less than 30 days, were found to have a relative risk of developing symptoms of celiac disease four times higher than children breast-fed for more than 30 days. Auricchio S et al. "Does breast feeding protect against the development of clinical symptoms of celiac disease in children?" J Pediatr Gastroenterol Nutr 1983;2(3):428-33

6. Dental Health

In this study of 260 children ages 3-5, the authors concluded that breastfeeding for more than 40 days may act preventively and inhibit the development of nursing caries in children. Oulis CJ et al. “Feeding practices of Greek children with and without nursing caries.” Pediatr Dent 1999 Nov-Dec;21(7):409-16

This study estimated the prevalence of early childhood caries and related behavioral risk factors in a population of low-income, Mexican-American children in Stockton, California. Data was collected on 220 children ages six years or less using a parent-completed questionnaire and clinical dental examinations. Mean age at weaning from breast-or bottle-feeding and patterns of bottle use during sleep did not differ significantly between children with caries and those without. Ramos-Gomez-FJ et al. "Assessment of early childhood caries and dietary habits in a population of migrant Hispanic children in Stockton, California." Journal-Of-Dentistry-For-Children 1999; 66 (6): 395-403, 366

This in-vivo and in-vitro study showed that human breast milk is not cariogenic. Erickson PR, Mazhari E. "Investigation of the role of human breast milk in caries development." Pediatr Dent 1999 Mar-Apr;21(2):86-90

Children who were either never breast-fed or only until 3 months exhibited a significantly higher caries prevalence than those breast-fed for a longer time. Mattos-Graner RO et al. "Association between caries prevalence and clinical, microbiological and dietary variables in 1.0 to 2.5-year-old Brazilian children. Caries Res 1998;32(5):319-23

A strong association was found between exclusive bottle-feeding and anteroposterior malocclusion. Davis DW, Bell PA. "Infant feeding practices and occlusal outcomes: a longitudinal study." J Can Dent Assoc 1991 Jul;57(7):593-4

Among breastfed infants, the longer the duration of nursing the lower the incidence of malocclusion. Labbok, M.H. "Does Breast Feeding Protect against Malocclusion? An Analysis of the 1981 Child Health Supplement to the National Health Interview Survey". American Journal of Preventive Medicine, 1987.

7. Diabetes Mellitus

A population-based case-control study of 196 children with type 1 diabetes and 325 age- and sex-matched control subjects found a significantly raised risk for illnesses in the neonatal period (OR 1.61), the majority of which were infections and respiratory difficulties. Exclusive breast feeding as the initial feeding method was significantly protective (OR 0.65). McKinney et al. “Perinatal and neonatal determinants of childhood type 1 diabetes. A case-control study in Yorkshire, U.K.” Diabetes Care 1999 Jun;22(6):928-32

Diabetes is less common among breast-fed children (6.9 and 30.1% among offspring of nondiabetic and diabetic women, respectively) than among bottle-fed children (11.9 and 43.6%, respectively). Pettitt DJ, Knowler WC. "Long-term effects of the intrauterine environment, birth weight, and breast-feeding in Pima Indians." Diabetes Care 1998 Aug;21 Suppl 2:B138-41

Children who developed IDDM in New South Wales, Australia, were compared to healthy children of the same sex and age. Those who were exclusively breastfed during their first three months of life had a 34% lower risk of developing diabetes than those who were not breastfed. Children given cow's-milk-based formula in their first three months were 52% more likely to develop I