Thursday, July 7, 2016

Breast Milk Consumption in Preterm Neonates and Cardiac Shape in Adulthood

Introduction
- Preterm birth relates to long-term alteration in cardiac morphology and function
- We hypothesized that fed human breast milk during early postnatal life is beneficial to long-term cardiac structure and function in preterm-born individuals compared with infant formulas.

Methods
-926 preterm-born infants originally took part in RCT of postnatal milk-feeding regimes between 1982 and 1985 across 5 different UK centres.
- These individuals had birth weight of <1850g and had no major congenital anomalies
- They were randomly assigned to either breast milk donated by unrelated lactating women or nutrient-enriched formulas.
- 102 individuals from this cohort were followed: 30 were fed exclusively human milk (EHM) and 16 were fed exclusively formula (EFF)
- Comparison group: 102 individual born term to uncomplicated pregnancies with age and sex distribution similar to those of the preterm-born young adults
- Cardiac morphology and function were assessed by MRI (1.5-T Siemens Sonata scanner)
- All data were coded with subject- and study-specific IDs to ensure anonymity and blinded analysis

Results
- No significant differences in both groups in perinatal characteristics or anthropometrics, demographics, blood biochemistry, or blood pressure in young adulthood (Table 1)
- However, both groups had altered blood biochemistry profiles and increased blood pressures compared with young adults born term
- There were no significant differences in number of smokers, personal and family medical history, or lifestyle factors, such as socioeconomic status, physical activity, or diet (P > .05) between the 2 milk-feeding preterm groups, nor with control group.



Left and Right Ventricular Size and Function
Compared with preterm-born individuals who were exclusively formula fed as infants, preterm-born individuals fed exclusively human milk as infants had:
- Increased left and right ventricular end-diastolic volume index (+9.73%, P = .04 and +18.2%, P < .001) and
- Increased left and right stroke volume index (+9.79%, P = .05 and +22.1%, P = .01)

- Although both feeding groups still had significantly smaller left ventricular end-diastolic volume index and stroke volume index than adults born term, the reduction in the group fed EHM was only 9% compared with 18% in the group fed EFF for both left ventricular end diastolic volume index and stroke volume index.

- Both preterm-born groups had similar left ventricular mass index and ejection fraction, although the preterm group fed EFF had significantly shorter left ventricles with reduced left ventricular luminal diameters.
- Right ventricular mass index and length were similar between preterm groups (Table 2). However, preterm-born young adults fed EHM had similar right ventricular ejection fractions as term-born young adults, whereas preterm-born young adults fed EFF showed reduced right ventricular ejection fractions compared with term-born controls.

Left Ventricular Shape and Native T1 Imaging
- Shape analysis confirmed the differences in size observed by using standard metrics (Fig 3), which particularly highlighted the significant increase in left ventricular length (P < .001) in the EHM group compared with the preterm individuals fed EFF
- Importantly, there were no other major geometric variations identified between preterm-born individuals fed EHM and those fed EFF (Fig 3) or term-born adults.
- We did not observe significant differences in myocardial tissue characterization by T1 mapping


Predictors of Cardiac Changes
- In multivariable models including gestational age, sex, postnatal milkfeeding group, and postnatal weight gain, gestational age remained an independent predictor for all 4 cardiac measures (P < .001); however, being fed EHM was also an independent predictor of left ventricular end-diastolic volume index (P = .007), left ventricular stroke volume index (P = .03), right ventricular end-diastolic volume index (P = .002), and right ventricular stroke volume index (P = .004).
- In line with the changes between preterm feeding groups being greater for the right ventricle, in a multivariable regression model across the entire preterm group (n = 102) with gestational age, sex, percentage of human milk in the diet, and postnatal weight gain as the predictors, the percentage of human milk was positively related to both right ventricular end-diastolic volume index (P = .009) and stroke volume index (P = .04), but not left ventricular parameters.
- There were no correlations between percentage of expressed milk and cardiac measures within the group fed EHM.

Thoracic Cavity Size and Pulmonary Artery Diameters
- Preterm-born young adults fed EFF had reduced thoracic cavity dimensions compared with those fed EHM
- No difference in aortic diameters
- EFF groups had increased main pulmonary artery diameters and pulmonary artery to aortic diameter ratios. Pulmonary artery to aortic diameter ratios were inversely related to right ventricular end-diastolic volume index and stroke volume index but not left ventricular parameters.

Discussion
- Breast milk contains a greater bioactivity and bioavailability of a number of growth factors, enzymes, and antibodies compared with even the best infant formulas. These factors are relevant to normal growth and development, as well as improving preterm infant health
- The data suggest that breast milk may reduce the risk of pulmonary arterial hypertension and future cardiopulmonary disease in preterm-born individuals
- These findings suggest the changes in cardiac morphology observed in preterm-born individuals relate primarily to size rather than geometric alterations, and that breast milk leads to proportional normalization of size.
- support the necessity of breast milk as part of early nutrition for individuals born to pregnancy complications as a protective mechanism to cardiovascular development
  
- Although our data suggest that it is not possible to reverse all cardiac changes related to the degree of prematurity through breast milk feeding, the magnitude of the differences between preterm-born adults fed EHM and those fed EFF is substantial and occurs independent of gestational age.
- Our finding that percentage of human milk consumed was positively associated with right ventricular morphology and function suggests that even small amounts of human milk in the preterm postnatal diet may be beneficial

Limitation
- This study does not prove causality
- Number of participants were relatively small compared with the size of the original cohort
- This study was not fully randomized, and as such, there is risk of ascertainment bias.

Strength
- Our preterm groups were similar in baseline demographics and demographic characteristics in young adulthood
- Unlike other studies that often rely on questionnaires and recall, we can be certain of the exact dietary intake of our preterm-born individuals during early postnatal life
  
Conclusion
- This is the first evidence of a beneficial association between breast milk and cardiac morphology and function in adult life for those born preterm
- Support promotion of human milk for the care of preterm infants to reduce long-term cardiovascular risk

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