Of all the complications of prematurity, necrotizing enterocolitis (NEC) is among the most catastrophic, causing significant mortality and short- and long-term morbidity. NEC affects ~5–10% of very low birthweight (VLBW) infants ≤1500 g and the incidence is inversely proportional to gestational age.1 Overall mortality is ~24%, and NEC accounts for one in ten neonatal deaths. Mortality more than doubles to 51% in infants with birthweights ≤1000 g who require surgical intervention.1,2,3,4,5 Survivors are at risk for intestinal failure, short gut syndrome, liver disease, and neurodevelopmental disability.1,6,7 Taking into account the increased need for medical and surgical intervention in the neonatal period and continued healthcare utilization beyond the neonatal intensive care unit (NICU), NEC is associated with a significant increase in direct healthcare costs.8,9 Care for an infant with surgical NEC may cost >$300,000.10 Given the clinical burden, patient impact, and strain on healthcare resources, NEC has long been a focus of pediatric research. Leveraging the primary role of inflammation in NEC, two articles in this issue explore novel strategies to reduce the impact of the disease. In an experimental mouse model of NEC, Li et al. demonstrate that pretreatment with an intraperitoneal amniotic fluid stem cell preparation attenuates interleukin-6 messenger RNA expression in the distal ileum and reduces the severity of histopathological injury, potentially by promoting cell proliferation of the epithelium.11 Within a larger prospective study of VLBW infants across two centers, Tetreault et al. analyzed eight cases of stage 3 NEC compared to 14 matched, non-NEC controls, identifying a combination of potential stool biomarkers with 80% sensitivity and 70% specificity in predicting the development of NEC within 10 days.12

Although the pathogenesis of NEC is not fully understood, many strategies and therapies for the prevention of NEC have been explored. A human milk-based diet, in the form of mother’s own milk, donor human milk and/or human milk-based fortification shows the largest potential for clinical impact and cost savings. Pasteurized donor human milk’s (DBM) protective effect against NEC may also be dose-dependent.13,14 Reducing exposure to artificial formula reduces the risk of NEC by almost 50%.13,14 Multiple studies have demonstrated the benefits of DBM in reducing NEC in VLBW infants and increasing the eventual use of maternal breast milk.14,15,16,17,18 Even in settings where the mother’s own milk use is high, DBM does not incur extra overall costs, although savings may take up to 18 months to be realized.3 Within one state collaborative, greater availability of DBM resulted in a 10% increase in maternal breast milk feeding.19 Use of DBM may also decrease feeding intolerance and thus the length of stay and need for total parenteral nutrition, but may result in the risk of decreased short-term in-hospital weight gain and potentially reduced cognitive performance compared to maternal breastmilk-fed infants or those who also receive preterm formula.20,21

Given these overall benefits, the American Academy of Pediatrics has recommended DBM as the preferred nutrition for preterm infants (if maternal breast milk is unavailable) since 2012.22 As neonatal care improves and survival of preterm infants increases, so does the number of babies at risk for NEC, making DBM use a sound public health strategy for morbidity and mortality reduction and cost savings.

Despite these benefits, DBM is not universally available in the United States and its use varies widely in NICUs nationwide.19,23 Infants of color and those cared for in low-resource hospitals receive less human milk feedings, both mother’s own milk and DBM, and their mothers receive less breastfeeding support.24,25,26,27 Black and Hispanic infants are more likely to receive care in safety-net hospitals that serve a large proportion of Medicaid patients and thus disproportionally bear the burden of heightened vulnerability to NEC that results from decreased access to DBM. This places NEC within the greater context of neonatal health disparities, which have been well-described and include higher rates of intraventricular hemorrhage, infection, retinopathy of prematurity, and chronic lung disease in infants of color.24,28,29 Black infants are also less likely to receive high-risk or early intervention follow-up referrals and have decreased opportunities for kangaroo care.26,28,30,31 Other studies demonstrate racial/ethnic differences in NICU care based on process and outcomes measures of NICU quality.31

Medicaid insures roughly 1/2 of all preterm births and 2/3 of all Black and Hispanic births. By providing health insurance coverage for DBM, Medicaid is an ideal tool for reducing the disparity in DBM access.32,33,34 The first major Medicaid coverage provision for DBM occurred in 1998 in California, but there has been a recent acceleration of state-based regulations, with ten states (including the District of Columbia) passing coverage rules in the past 4 years.35 However, only 15 states have any type of coverage for the use of DBM and there is significant variation in the indications for, and duration of, coverage across states, as well as payment levels. For example, New York provides in-hospital coverage for DBM for infants born ≤1500 g who have either Medicaid or commercial insurance. Payment levels are tied to the per-ounce purchase price of DBM from non-profit human milk banks and do not include outpatient coverage.36 Meanwhile, Kansas provides DBM coverage for Medicaid-insured infants in the NICU and only upon receipt of a prescription and a state determination of medical necessity, with no outpatient coverage and a maximum duration of 3 months.37 Currently, seven additional states (MA, SC, GA, ME, NV, VA, and OK) have actively proposed DBM coverage plans that are awaiting legislative review (Fig. 1).

Fig. 1: State-based overview of legislative activity related to Medicaid payment for pasteurized human donor milk.
figure 1

Preliminary information first presented from ref. 34 Adapted from Denise O’Connor, personal communication.

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Within Medicaid, states provide input and make decisions regarding which benefits may be covered above federal requirements, leading to inconsistent access to a variety of therapies. Standardizing DBM coverage can ensure all high-risk infants have access to this therapy, irrespective of what state they are born in. This is a key aspect of neonatal health equity for these infants, which should be a goal for all states. While the novel diagnostic biomarkers and future treatments outlined in the articles by Li et al. and Tetreault et al. show promise, prevention of NEC using cost-effective prophylactic therapies such as DBM should be an advocacy goal for all those who care for preterm infants and their mothers.

However, barriers exist for those promoting greater DBM coverage. Across states, the classification of DBM varies, with some states considering it a nutritional product and others a tissue or blood product—each with a unique set of governing regulations. Further, given the lack of awareness or knowledge of the benefits of DBM among policymakers, advocates must overcome a significant educational burden in counseling legislators to champion this issue. Another complication is that the cost-effectiveness of DBM may differ based on not only the cost of the DBM product but also on the structure of the Medicaid contract with a providing hospital. For example, a state paying a flat per diem charge based on NICU acuity may only realize cost savings based solely on a reduced length of stay. Conversely, a state Medicaid program which pays for specific aspects of care may see additional cost benefit from reduced need for total parenteral nutrition and indwelling central catheters related to improved feeding tolerance, fewer antibiotic days, or decreased operating room time for surgical NEC.

Yet, as states that have enacted provisions aimed at improving DBM access have demonstrated, it is possible to overcome these obstacles. Templates and resources exist for those willing to engage policymakers on behalf of high-risk infants.35,36 In addition, improving care for preterm infants and assisting with breast milk availability galvanizes a natural coalition of pediatricians, neonatologists, obstetricians, midwives, lactation consultants, parents, NEC survivors, and hospital administrators to articulate the need for DBM and amplify pertinent messaging. At a time when there is heightened focus on public health and increased universal understanding of the impact of disparities on adult and child healthcare outcomes, as well as renewed efforts on mitigating them by policymakers—improving access to DBM is one way to ensure newborns are not left out of this national focus.