Mother’s Milk May Shape the Developing Heart in Critically Ill Newborns

A brief letter published in Pediatric Research has ignited a conversation that reaches far beyond its modest length. Written by Sergio Verd of the Balearic Islands Health Research Institute, pediatric cardiologist Alcia Serra of 12 Octubre University Hospital in Madrid, and Juan Antonio Costa-Orvay of Can Misses Hospital in Ibiza, the correspondence responds to a randomized trial by Blanco and colleagues that followed infants with single-ventricle physiology through their first six months of life. The trial, published in the same journal, reported that babies with this severe congenital heart defect grew at similar velocities whether or not they received an exclusive mother’s milk diet. Verd and his co-authors argue that this finding, while reassuring on growth, should not distract from a far more compelling question: what does human milk do to the developing cardiovascular system of the sickest newborns?

Single-ventricle physiology represents one of the most daunting challenges in pediatric cardiology. In these infants, effectively only one of the heart’s two pumping chambers functions properly, meaning a single ventricle must shoulder the work of supplying both the lungs and the rest of the body. These babies traditionally face growth failure, repeated hospitalizations, and substantial morbidity across the staged surgical palliation that keeps them alive. Against that backdrop, the demonstration by Blanco’s team that exclusive human milk feeding did not compromise growth velocity at three and six months is genuinely significant. Growth failure has long been considered almost inevitable in this population, and nutritional strategies are fiercely debated. The letter’s authors open by commending the trialists precisely because showing comparable growth with or without exclusive mother’s milk feeding challenges the assumption that human milk diets, which are calorically and compositionally different from formula, inevitably slow weight gain in cardiac infants.

Yet the correspondents push the interpretation further. They contend that judging human milk solely by anthropometric outcomes—weight, length, and head circumference—misses the deeper biological story. Human milk is not merely a delivery vehicle for calories and protein; it is a bioactive fluid containing hormones, growth factors, stem cells, oligosaccharides, and long-chain polyunsaturated fatty acids that participate directly in organ programming. The cardiovascular system, they argue, is among the organs most plausibly influenced by early nutrition, and the evidence for this influence now spans from the cellular level to decades of human life. Their letter assembles that evidence into a narrative they believe the field has underweighted when designing and interpreting feeding trials in critically ill neonates.

The conceptual backbone of their argument draws on the developmental origins of health and disease framework, crystallized in the influential hypothesis articulated by Atul Singhal and Alan Lucas in The Lancet more than two decades ago. That hypothesis proposed that early nutritional exposures leave lasting imprints on cardiovascular risk, with faster early growth in infancy paradoxically associated with later adverse cardiovascular profiles. In this view, the slower, more regulated growth supported by human milk is not a deficiency to be corrected but a programmed trajectory that favors long-term vascular and metabolic health. Applied to infants with congenital heart disease, the implication is striking: the population most vulnerable to cardiovascular complications across life may be precisely the population in which early milk feeding could exert its most meaningful protective programming.

Empirical support for that idea comes from several longitudinal studies the letter cites. Andrew Lewandowski and colleagues at the University of Oxford reported in Pediatrics that preterm infants who consumed more breast milk showed measurable differences in cardiac shape and function in young adulthood, with hearts that more closely resembled those of healthy term-born controls. In a remarkable piece of long-term epidemiology, Richard Martin and colleagues traced members of the Boyd Orr cohort to age sixty-five and found that individuals who had been breastfed as infants showed differences in carotid intima-media thickness and atherosclerotic plaque, structural markers of cardiovascular aging. More recently, Afif El-Khuffash and colleagues demonstrated in JAMA Network Open that among preterm infants, greater maternal breast milk intake in the first weeks of life was associated with better cardiac performance measures throughout the first year. And a 2025 study by Zhenjian Wang and colleagues in the European Journal of Clinical Nutrition extended the timeline again, associating breastfeeding duration with cardiac structure and function measured at four years of age.

None of these studies focused specifically on infants with single-ventricle physiology, and the letter’s authors are careful to frame them as convergent rather than conclusive. But the cardiac population is not without its own human-milk evidence. A 2022 systematic review by Kayla Elgersma and colleagues in Breastfeeding Medicine examined outcomes for infants with congenital heart disease and found associations between human milk feeding and improved clinical outcomes. A follow-up analysis published in 2023 in the Journal of the American Heart Association used propensity score matching within the National Pediatric Cardiology Quality Improvement Collaborative registry to show that human milk feeding and direct breastfeeding were linked to better outcomes for infants with single-ventricle congenital heart disease specifically. Propensity matching matters here, because it attempts to separate the effect of milk itself from the confounding influence of families who are, on average, more resourced and more engaged with care.

The letter also widens the lens beyond the heart to the lungs, an organ system inseparable from cardiovascular performance in neonates with compromised circulation. Verd and colleagues reference their own prior work arguing that human milk feeding deserves greater emphasis in preventing neonatal respiratory morbidity, alongside a systematic review and meta-analysis by Enrique Villamor-Martínez and colleagues showing that donor human milk protects against bronchopulmonary dysplasia, the chronic lung disease of prematurity. A 2022 study by Elena Moliner-Calderón and colleagues suggested that human milk feeding in septic newborns might reduce their exposure to ventilation therapy. For a baby with a single functioning ventricle, pulmonary vascular health is not a side issue; the entire palliation strategy depends on balanced pulmonary blood flow, and any intervention that reduces ventilator days or lung injury carries direct hemodynamic consequences.

What emerges from the correspondence is a methodological critique as much as a scientific one. The letter implicitly asks whether trials of exclusive human milk diets in cardiac neonates are being powered and designed around the wrong endpoints. Growth velocity is easy to measure and clinically important, but if the true benefits of human milk operate through cardiovascular programming, immune modulation, and pulmonary protection, then six-month growth curves may systematically underestimate the intervention’s value. The correspondents point to the Cochrane review by Fabrizio and colleagues on individualized versus standard fortification of human milk for preterm infants as evidence of how much methodological uncertainty still surrounds even basic questions of how to optimize milk-based feeding, let alone how to capture its long-term effects. Fortification itself—adding human milk-derived or bovine-based supplements to meet the elevated protein and mineral demands of fragile infants—remains an area where individualized approaches have not clearly outperformed standard protocols.

The clinical stakes are considerable. Infants with single-ventricle physiology undergo staged palliation beginning in the first days of life, and their nutritional status at each surgical stage influences operative risk, neurodevelopment, and survival. If human milk confers even modest cardiovascular and pulmonary advantages in this group, feeding protocols in cardiac intensive care units would need to change, and lactation support for mothers of critically ill newborns would become a therapeutic intervention rather than a wellness amenity. The letter’s authors, who span primary care pediatrics, research, and children’s heart units, are positioned to see both the bedside reality and the population-level evidence, and their argument is that the two have drifted apart: bedside practice often treats milk feeding as optional in cardiac infants, while the accumulating literature suggests it may be among the few modifiable factors with plausible lifelong impact.

Verd, Serra, and Costa-Orvay close their correspondence having made a focused case rather than a sweeping claim. They do not assert that mother’s milk reshapes the single ventricle, nor do they dispute the growth findings of the trial they address. What they do is redirect attention: growth equivalence is a floor, not a ceiling, for what human milk may achieve in critically ill neonates. The evidence they marshal—from sixty-five-year cohort follow-ups to propensity-matched cardiac registries—points toward early nutrition as a formative influence on the cardiovascular system, with the sickest newborns standing to gain the most. As randomized evidence in this population accumulates, the letter argues, trial designers should look beyond the growth chart and toward the heart itself, because that is where the milk may be doing its most important work.

Subject of Research: Effects of human milk feeding on cardiovascular development in critically ill neonates with congenital heart disease

Article Title: Cardiovascular development of critically ill neonates on mother’s milk

Article References: Verd, S., Serra, A., & Costa-Orvay, J. A. (2026). Cardiovascular development of critically ill neonates on mother’s milk. Pediatric Research. https://doi.org/10.1038/s41390-026-05510-6

Image Credits: AI Generated

DOI: 10.1038/s41390-026-05510-6

Keywords: human milk, single-ventricle physiology, congenital heart disease, neonatal nutrition, cardiovascular development, breastfeeding, pediatric cardiology, growth outcomes, bronchopulmonary dysplasia, developmental origins, preterm infants, Pediatric Research