Briefly Noted: Breastfeeding and Microbiome Diversity

A recent study (JH Savage et al J Pediatr 2018; 203: 47-54) examined the impact of breastfeeding compared with formula on microbiome diversity in 323 infants; this included 95 exclusively breastfed, 169 exclusively formula fed at time of stool collection.

Breastfed infants were more likely to have been born vaginally (74% vs 62%) and less likely to be African-American (11% vs. 36% for hispanic infants, and 52% for caucasian).

Key finding:

  • Breastfeeding was independently associated with infant intestinal microbiome diversity at age 3-6 months
  • Maternal diet during pregnancy and solid food introduction were less associated with infant gut microbiome changes than breastfeeding status

My take: We still don’t understand the long-term implications of these differences in microbiome alterations between breastfeeding and formula.  That being said, the development/evolution of breastmilk has taken place over thousands of years and it is likely that formula, while an important substitute, will never replicate all of the useful components.

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IBD Shorts -November 2018

G Horneff et al. J Pediatr 2018; 201: 166-75.  This industry-funded analysis of 577 pediatric patients who received adalimumab (1440 patient-years) identified no new safety signals.  The most common serious infection was pneumonia (0.6 events per 100 patient-years).  The most common adverse events were respiratory tract infections/nasopharyngitis. Serious infections were more common in the subset of patients with Crohn’s disease (CD), (n=189), occurring in 13%.

PS Dulai et al. Gastroenterol 2018; 155: 687-95.  This study, using data from GEMINI 2 phase 3 trial with 814 patients, developed a clinical prediction tool for determining the likelihood of a clinical response to vedolizumab.  Common predictors for response:

  • No prior bowel surgery
  • No prior anti-TNF exposure
  • No prior fistulizing disease
  • Higher baseline albumin
  • Lower baseline CRP

R Matro et al. Gastroenterol 2018; 155: 696-704.  The authors performed a prospective study of women with IBD and their infants (n=72).  They “detected low concentrations of infliximab, adalimumab, certolizumab, natalizumab, and ustekinumab in breast milk samples.  We found breastfed intants of mothers on biologics, immunomodulators, or combination therapies to have similar risks of infection …compared to non-breastfed infants or infants unexposed to these drugs.”

 

With Regard to Avoiding Excessive Weight Gain, Breastfeeding is Best

A recent study (AR Goetz et al J Pediatr 2018; 201: 27-33) examines the impact of breastfeeding on the growth of infants with high birth weight (HBW).

Background: “Exclusive breastfeeding is protective against high weight and is recommended by” the AAP for the first 6 months.  In this study, the authors hypothesized that “HBW infants would receive a lower percentage of breast milk and consume more formula than NBW infants.”

Key findings:

  • HBW infants with high weights at 7-12 months of age demonstrated a rapid decline in the percentage of breast milk feedings compared with HBW infants with normal weights at 7-12 months of age.
  • Normal birth weight infants with high weights at 7-12 months of age received a lower percentage of breast milk and more formula intake that those with normal weights at 7-12 months of age.

Because HBW is associated with later risk of obesity/overweight, identifying strategies early in life is important.  Furthermore, as a recent study in NEJM has shown (M Geserick et al. NEJM 2018; 379: 1303-12), a lot of weight gain issues happen in the first years of life:

  • Almost 90% of children who were obese at 3 years of age were overweight or obese in adolescence
  • Among obese adolescents, the most rapid weight gain had occurred between 2 and 6 years of age

My take: This study further shows a strong association between consumption of breast milk and normal weights at 7-12 months of age, both in HBW and NBW.

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Laying to Rest a Breast-Feeding Myth

A recent study (VJ Flaherman et al. J Pediatr 2018; 196: 84-90) examines whether early limited formula feeding undermines breastfeeding.

Background: The authors note that women have been discouraged from using formulas for newborns during the birth hospitalization due to concerns that this will diminish the frequency/success of breastfeeding.

Besides the concern that supplemental formula could increase the risk of breastfeeding cessation, some have expressed concern that supplemental formula could undermine benefits of breastmilk on the intestinal microbiome.  In addition, some have worried that if mothers perceived formula-feeding to be easier, that this could lower satisfaction with breastfeeding.

Yet, on the other side of the ledger, there are “about 80,000 newborns who require readmission after discharge” with the majority related to dehydration and hyperbilirubinemia.  Both of these conditions could be ameliorated by formula supplementation.  Thus, to address whether supplemental formula may be of benefit, the authors devised an “early limited formula” (ELF) trial.  The authors only enrolled infants >2500 gm and who had a weight loss >75th percentile on The Newborn Weight Tool (www.newbornweight.org). The authors excluded those with >10% of their birth weight due to routine practice of supplementation.

Methods: 163 mother-infant pairs were randomly assigned to either ELF along with breastfeeding or breastfeeding exclusively.  ELF involved giving infants 10 mL of a hydrolysate formula with a feeding syringe after each breastfeeding until the onset of copious breast milk

Key findings:

  • Mothers using ELF averaged 5.4 times/day for a median of 2 days.
  • Breastfeeding rates at one month of age: 86.5% of ELF group and 89.7% of controls; 54.6% of ELF and 65.8% of controls were breastfeeding exclusively at 1 month of age.
  • Readmission occurred in 4 (4.8%) of control infants and none of the infants in the ELF cohort (P=.06)
  • Using a subset of 15 (8 with ELF), the authors did not identify significant changes in microbiome of ELF group compared with the exclusively fed group when examined at 1 week and 1 month (as well as baseline)

Limitations of this study include the relatively small number of participants.  Furthermore, some populations that are at increased risk for breastfeeding cessation, namely mothers <25 years and African-American mothers were underrepresented.

My take: This study indicates that ELF is safe and does not appear to significantly increase breastfeeding cessation.

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Infant Feeding, Opportunity, and Asthma

A recent study (A Kloop et al. J Pediatr 2017; 190: 192-9) examined the relationship between mode of infant feeding and the development of asthma.  The authors used prospective data from 3296 Canadian children in the Canadian Healthy Infant Longitudinal Development (“CHILD” study) cohort.

Key finding:

  • “Compared with infants who received direct breast milk only [at 3 months of age], those who received some expressed milk had a 43% increased odds [of asthma at 3 years of life] …and those who received only formula had a 79% increased odds.”

The authors speculate that the direct breastfeeding may offer some advantages over expressed breast milk:

  • There may be alteration in breast milk components with storage
  • A nursing infant may trigger an increased immune response and be directly exposed to some beneficial commensal bacteria

Since this is an observational study and patients were not randomized there may be other unrecognized confounding variables.

Another study in the same issue (AF Beck et al. J Pediatr 2017; 190: 200-6) assessed whether the Child Opportunity Index (COI) was associated with asthma outcomes in a retrospective cohort of 5462 children in Hamilton County, Ohio.  The COI (see below for the measures in this index) has previously been linked to life expectancy, low birth weight, and prematurity.  Interestingly, one can go to diversitydatakids.org to see how this affects your location (here is the link for a heat map of this index in the Atlanta area: Atlanta COI)

Key finding:

  • Median hospitalization rates varied based on COI –those with very high opportunity had a rate of 1.8 per 1000.  The other quintiles of COI were the following: high opportunity 2.1, moderate opportunity 4.6, low opportunity 7.6, and very low 9.1

My take: The first study indicates that direct breastfeeding is associated with lower rates of asthma.  The second study shows that issues related to education, environment, and social/poverty have an enormous impact on need for asthma-related hospitalization.

 

 

Breastfeeding: Protection from Inflammatory Bowel Disease

Xu L, et al. Systematic review with meta-analysis: breastfeeding and the risk of Crohn’s disease and ulcerative colitisAliment Pharmacol Ther2017;46:780-789.

https://doi.org/10.1111/apt.14291Thanks to Mike Hart for this reference.

From abstract:

Results

A total of 35 studies were included in the final analysis, comprising 7536 individuals with CD, 7353 with UC and 330 222 controls. Ever being breastfed was associated with a lower risk of CD (OR 0.71, 95% CI 0.59-0.85) and UC (OR 0.78, 95% CI 0.67-0.91). While this inverse association was observed in all ethnicity groups, the magnitude of protection was significantly greater among Asians (OR 0.31, 95% CI 0.20-0.48) compared to Caucasians (OR 0.78, 95% CI 0.66-0.93; P = .0001) in CD. Breastfeeding duration showed a dose-dependent association, with strongest decrease in risk when breastfed for at least 12 months for CD (OR 0.20, 95% CI 0.08-0.50) and UC (OR 0.21, 95% CI 0.10-0.43) as compared to 3 or 6 months.

From associated editorial by David Rakel:

This meta-analysis of 35 studies shows that there is a dose–response protective effect of the duration of breastfeeding on inflammatory bowel disease. The association shows as much as an 80% reduction in risk for both Crohn’s disease and ulcerative colitis for breastfeeding more than 12 months.

Breast Feeding Graph

Inflammatory bowel disease arises from a complex set of interactions related to genetic susceptibility, environmental exposures, and a dysregulated immune response to dysbiotic intestinal microbiota, according to the study authors. These data will give us one more reason to encourage breastfeeding, ideally for a year or more.

Related blog post: Nutrition Week (Day 7) Connecting Diet and Epidemiology in IBD