Early Formula Introduction and Risk of Cow’s Milk Allergy
by Anne Eglash MD, IBCLC, FABM
In 1935, Bret Ratner MD published an article on the treatment of milk allergy in the Journal of the American Medical Association. One of a few recommendations to prevent milk allergy was to avoid isolated feedings of raw cow’s milk to the breastfed infant during the newborn period. His reasoning was that during the newborn period, there is increased gut wall permeability, allowing increased passage of proteins into the newborn’s blood stream. This allows for early sensitization to the cow’s milk protein, such that when infants are introduced to cow’s milk protein later during infancy, they have a higher risk of cow’s milk allergy. A meta-analysis published in 2012 found that breastfed infants given cow’s milk formula supplementation in the first few weeks of life had a 1.75 times risk of cow’s milk allergy as compared to breastfed infants who were not supplemented.
The authors of this week’s CQW performed a retrospective study in Ireland among 55 children diagnosed with cow’s milk allergy by an allergist. They compared their likelihood of formula supplementation in the first 24 hours of life to a control group of 55 children, age and sex matched, who did not have a diagnosis of cow’s milk allergy. They used hospital records to determine the incidence of formula supplementation. All formula used for supplementation was known to be cow’s milk based.
Although I don’t typically rely on small studies for a LactFact, this effect has been observed in the medical profession since at least 1935, and a 2012 meta-analysis also supports this association. This study provides more data on the topic.
- The exclusively formula fed infants had a lower risk of cow’s milk allergy as compared to the exclusively (unsupplemented) breastfed infants.
- Among the breastfed infants supplemented with formula in the first 24 hours of life, only those with a family history of allergies developed cow’s milk allergy.
- For breastfed infants, having a parent with allergies was a greater risk of future cow’s milk allergy than receiving cow’s milk formula in the first 24 hours of life.
- Exclusively formula fed infants had a 16 times higher rate of cow’s milk allergy than breastfed infants who were supplemented with cow’s milk formula in the first 24 hours of life.
- Breastfed infants who were given formula in the first 24 hours were 7 times more likely to have cow’s milk allergy than those who were exclusively breastfed in the first 24 hours.
See the Answer
Many breast fed babies in Ireland receive formula supplementation within 24 hours of birth. We explored (i) impact of formula supplementation on the likelihood of developing Cow's Milk Protein Allergy (CMPA), and (ii) current practice of formula supplementation (<24h) among mothers intending to breast feed.
55 CMPA-diagnosed children, fed at <24h of age (breast only, formula only or breast with formula supplementation) were recruited and 55 milk-tolerant age- and sex-matched controls were identified retrospectively in Cork University Maternity Hospital. Two Logistic regressions (LoR) examined neonatal feed types on likelihood of developing CMPA while controlling for parental atopy and infant sex. Formula supplementation was then prospectively measured among a separate group of 179 breast-feeding mothers. Linear regression (LiR) analysis was used to examine; the subjective and objective reasons for formula supplementation, in addition to examining pre-existing factors.
Two LoR examined the infant groups: exclusively breast fed, exclusively formula fed or breast fed with formula supplementation. The first LoR model, showed only formula supplementation was significant in prediction of development of CMPA, (χ² (3) = 25.74, p < 0.05) with 74% diagnostic accuracy when parental atopy and infant sex were controlled for. Breast-fed infants given formula supplements were 7.03 (95% CI, 1.82 - 27.25) times more likely to exhibit CMPA than those who were exclusively breast-fed. Formula supplementation was significant (OR 16.62, 95%C.I. 3.89 –71.11), indicating that breast-fed infants who were given formula supplements were 16 times more likely to exhibit CMPA than those who were exclusively bottle-fed. Exclusively formula-fed infants (Odds Ratio 0.42, 95%C.I., 0.16 – 1.07) were not significantly more likely to exhibit CMPA than those who were exclusively breast-fed in either model (p>0.05). 45.8% breast-fed infants (<24h) received supplemental formula. LiR investigated importance of the subjective and objective reasons, in predicting formula supplementation. This model was significant F(8,170)=66.95, p<0.05) explaining 75% total variance. The subjective factors ‘no latch’ and ‘Mum unwell’ were the strongest predictors (β>0.45). Objective factors and pre-existing factors had lower ß values with only mode of delivery and infant hypoglycaemia being significant.
Breast fed babies are still being put at significantly increased risk of CMPA by receiving supplemental formula in the 1st 24 hours of life, despite the major predictors of supplementation being subjective and remediable in other ways. Mothers and health care providers should be better educated on the benefits of exclusive breast feeding and resourced adequately to avoid unnecessary formula supplementation to reduce risk of development of CMPA.
The results of this study were consistent with previous research showing that breastfed infants receiving small amounts of formula within 24 hours of life are much more likely to develop cow’s milk allergy later in life as compared to infants who have a much greater exposure to formula early in life, such as infants who are exclusively formula fed. In this study, the breastfed infants exposed to a small amount of formula in the first 24 hours were 16 times more likely to develop cow’s milk allergy as compared to exclusively formula fed infants. Formula fed infants had the same rate of cow’s milk allergy as exclusively (unsupplemented) breastfed infants. Authors have hypothesized that exclusively formula fed infants develop a tolerance to formula over time because of repeated exposure.
The researchers in this study controlled for parental allergies, and found that a history of parental allergies was not as strongly associated with childhood cow’s milk allergy as compared to formula supplementation in the first 24 hours.
This research has been flying under the radar, and we need to bring it into focus. The take home message for clinical practice is that there seems to be enough evidence to recommend that infants needing supplementation in the first 24 hours receive either donor human milk or a hydrolyzed or elemental formula in order to avoid the risk of cow’s milk allergy.