Legal, Clinical, and Scientific Perspectives on Formula Use and NEC Risk in Preterm Infants

Abstract

Recent legal verdicts implicate cow’s milk-based infant formulas, notably Similac and Enfamil, as contributing to the causation of select cases of necrotizing enterocolitis (NEC) in preterm infants. These rulings have intensified debate regarding the safety of formula use in neonatal care, leading to increased scrutiny of clinical practices and calls for clearer scientific evidence. This brief commentary reviews the current legal landscape, examines available research on NEC risk factors, and highlights the clinical implications of ongoing litigation. The report also argues for the importance of evidence-based standards for both legal and medical decision-making.

Introduction

Necrotizing enterocolitis (NEC), a multifactorial pathophysiologic process of the gastrointestinal tract, affects 5-10% of preterm infants with a birth weight ≤ 1500 grams ^1,2 and stands as a leading cause of surgical intervention ³, long-term complications ^4-7, mortality, and increased health care costs ^8,9. While human milk is recognized as protective ¹⁰, the role of cow's milk-based formula in NEC pathogenesis has been hypothesized for decades and remains without conclusive evidence to support causation ¹¹. Recently, lawsuits against Abbott Laboratories (Similac) and Mead Johnson Nutrition (Enfamil) have resulted in substantial damages awarded to plaintiffs, fueling concerns among clinicians and hospital systems regarding safety, efficacy, and evidence-based feeding practices ¹². In a recent Reuters report, the companies have denied the claims, saying that while breast milk protects against NEC, formula does not cause it, and that the benefits of breast milk have long been known to clinicians ¹². In addition to the federal cases, both companies face hundreds of state court cases across the country, which have already resulted in verdicts of $60 million against Mead Johnson and $495 million against Abbott ¹².

Legal Claims and Court Decisions

Plaintiffs argue that Similac and Enfamil carry a higher propensity to cause NEC in preterm infants than human-derived nutritional options. The core allegations include failure to warn ¹³ and misleading marketing practices ¹⁴. Several jury verdicts have held manufacturers liable, awarding millions in damages and potentially impacting the availability and perception of specialty formulas.

Clinical Implications

The current legal climate is contributing to a rise in defensive medicine. Neonatologists report increased use of diagnostic imaging, prolonged parenteral nutrition, extended antibiotic courses, and hesitation to use standard formulas which may inadvertently affect the developing gut microbiome, growth, and infant outcomes ¹⁵. This shift toward legally influenced decision-making risks undermining patient care and clinical judgment.

Scientific Evidence and Limitations

A population-based study in England found that 50% of NEC cases requiring surgery or resulting in death occurred in infants exclusively fed human milk ¹⁶, which does not link formula feeding to NEC. Neu et al. emphasized the lack of a universally accepted definition or mechanistic understanding of NEC, characterizing it as a heterogeneous syndrome with multifactorial causes ¹⁵. The authors caution that verdicts driven by public sentiment, rather than rigorous scientific, evidence, may harm patient care and erode trust between families and providers ¹⁵. Additional studies have reported that fortification of human milk with bovine-based fortifiers increases osmolality, but evidence that higher osmolality increases NEC risk is lacking and requires more research to reassess the safe upper threshold for osmolality in preterm infants ¹⁷. A meta-analysis ¹⁸ reported a higher NEC risk with formula compared to donor milk (RR 1.87; 95% CI, 1.23–2.85), though the findings were limited by the age and quality of the included studies. Most randomized controlled trials (RCTs) of formula and human milk were conducted in the 1970s and 1980s, with small sample sizes and inconsistent outcomes for key metrics such as mortality and sepsis. A recent RCT in extremely preterm infants fed minimal maternal milk, reported that neurodevelopmental outcomes at 22 to 26 months’ corrected age did not differ between infants receiving donor milk or preterm formula ¹⁹.

Milk Fortifiers and NEC:

A study comparing cow's milk-derived fortifier (CMDF) and human milk-derived fortifier (HMDF) in preterm infants fed only their mother's milk found that CMDF was linked to a higher risk of NEC, NEC surgery or death, and reduced head growth ²⁰. The findings should be interpreted with caution however, as the study represents a sub-analysis of randomized trials and is industry-sponsored. In contrast, a recent prospective randomized control trial evaluating supplementation with human milk based fortifier compared with cow’s milk based fortifier, did not demonstrate a reduction in the incidence of the composite outcome of NEC, sepsis, or death ²¹. As such, the results do not the support routine supplementation with human milk-based fortifier as a nutritional strategy to prevent NEC, sepsis, or death in extremely preterm infants exclusively fed human milk.

Infection and Formula Feeds:

Cronobacter sakazakii is known to cause acute meningitis and necrotizing enterocolitis in neonates and immunocompromised individuals. This human-pathogenic microorganism has been isolated from a variety of food and environmental samples and has also been linked to foodborne outbreaks associated with powdered infant formula ²² . From September 16, 2021, to January 5, 2022, Centers for Disease Control and Prevention (CDC) received reports of three Cronobacter cases in infants that were later included in Food and Drug Administration’s (FDA) ongoing investigation ²³. The infants who were reported to have consumed powdered infant formula products were from Abbott Nutrition’s Sturgis, Michigan, facility. The CDC performed whole genome sequencing (WGS) on the Cronobacter isolates from two available patient samples and compared them with environmental samples taken at the facility. WGS did not find the patient isolates to be closely genetically related to the multiple strains of Cronobacter found in the environmental samples obtained from Abbott Nutrition's Sturgis, MI facility. Furthermore, WGS showed that bacteria from available patient samples were not closely related to one another ²³, suggesting that a causal relationship was highly unlikely.

Regulatory and Institutional Positions

FDA, NIH, and CDC position:

In response to rising public concern, a joint statement from the FDA, National Institutes of Health (NIH), and CDC clarified that no conclusive evidence links preterm formula to NEC, though human milk shows a protective association ²⁴. The statement affirmed that while maternal milk is optimal and donor milk is a valuable alternative, preterm formulas remain a critical component of care when human milk is unavailable or insufficient.

This year, the Department of Health and Human Services revealed a new federal initiative, named “Operation Stork Speed”, with the intention of reviewing the nutritional adequacy of infant formulas and determining their safety, including an in-depth analysis of potential heavy metal contaminants ²⁵ . This multicomponent undertaking involves numerous federal and non-governmental agencies as well as the private sector ²⁵. It should be noted, that Operation Stork Speed does not appear to directly address premature infant formula’s role, if any, in the development of NEC, nor does it advocate for breastfeeding as the ideal nutrition for newborns. Presently, both the organizations involved and the processes for bias-free investigation remain to be defined²⁵.

American Academy of Pediatrics position:

The NEC working group of the of the National Advisory Council of Child Health and Human Development also called for more research to help parents and health care providers determine the best nutrition plan for premature infants ²⁶. The group advocated for all infants to be fed as soon as medically feasible, by whatever means possible ²⁶. In particular, the AAP appears concerned that lawsuits against specialty formula makers threaten the availability of formulas that provide important nutrition for a large number of preterm infants ²⁷. “Courtrooms are not the best place to determine clinical recommendations for the care of infants,” ²⁷ and “feeding decisions should be made by clinicians and families. These need to be individualized in the context of human milk availability, specific patient needs, and individual family preferences” ²⁷. Clearly there is a need for a nutritionally appropriate formula for this vulnerable population when mother’s own milk is not available ²⁸. In order to promote breast feeding, British Medical Journals stopped advertising the breastmilk substitutes ²⁹. Similarly, European pediatric societies have been urged to no longer interact with breast milk substitute companies based on the assumption that such interactions may lead to decreased advocation for breastfeeding ³⁰. Several experts and learned European Pediatric Societies have published letters/statements both commending such an approach but also noting that some products made by these companies are important for pediatric care and could be considered essential medicines, meaning that some academic pediatric engagement with these companies is necessary. ^29,31

Conclusion

The evidence to date supports the protective role of human milk against NEC and does not conclusively establish formula as a cause or contributor to NEC pathology ¹¹. As these lawsuits progress, both the medical and legal communities must rely on sound, verifiable, scientific methodology and a nuanced understanding of the evidence to guide decisions affecting vulnerable neonatal populations. To advance NEC research and foster collaboration across clinical, legal, corporate, and research communities, we need to develop a taxonomic definition for intestinal injuries which reflect specific pathophysiology. In the meantime, increasing resources for antenatal care and lactation support may improve breastfeeding outcomes and potentially reduce NEC risk. Establishing standardized parent and product disclosure guidelines will be important to build trust and to ensure transparency between providers and families.

Impact:

1. The increase in lawsuits against formula companies contributes to a rise in defensive medicine.

2. The evidence to date supports the protective role of human milk.

3. Developing standardized parent and product disclosure guidelines is important to build trust and ensure transparency between providers and families.