Evaluating the Health-Economic Benefit of Usage of Human Milk Fortifier – A Physician Reported Survey Outcome: HERO Study

Introduction

World Health Organization (WHO) defines preterm birth as the birth before 37 weeks of gestation.¹ Worldwide, approximately 13.4 million preterm newborns (1 in every 10 newborns) were delivered in the year 2020 with India accounting for the highest global incidence of 3 million preterm births.^2,3 As per 2019–21, Indian demographic health survey data, published in 2025, India has a preterm birth rate of 13%.⁴

Preterm birth is one of the leading causes of under-5 mortality and in 2022, the annual mortality rate in neonates was 1 million due to preterm birth complications worldwide.³ Although survival rates have improved over the years^5,6 increased survival has been associated with risk of significant health complications and lifetime disabilities.^7,8

Preterm babies are at high risks of extrauterine growth restriction (EUGR),⁹ necrotizing enterocolitis (NEC),⁶ bronchopulmonary dysplasia,⁹ retinopathy of prematurity,¹⁰ and sepsis¹¹ including late onset sepsis¹² which is associated with higher in-hospital morbidities and mortalities among survivors and a higher risk for delay in neurodevelopment growth later years.¹³ These adverse sequelae impose a considerable burden on limited healthcare resources, and the treatment of very low birth weight (VLBW) infants is costly.¹⁴

The World Health Organization and United Nations Children’s Fund recommend to initiate breastfeeding the newborn within one hour of birth and to exclusively breastfeed for at least six months.¹⁵ Breast milk is universally considered as the most complete food for infants¹⁶ as it contains carbohydrates, proteins, fats, and innumerable bioactive components including vitamins, minerals, polyunsaturated fatty acids, oligosaccharides, growth factors, immune-components such as cytokines, leukocytes, lactoferrin, interferon-γ, and others.^17,18 However, evidence suggests that mother’s milk or donor milk may not be sufficient to provide adequate nutrition to high-risk, vulnerable infants, as the nutritional demands are high for achieving optimal growth during hospitalization.^19–21

European Milk Bank Association (EMBA) Working Group recommends fortifying human milk with nutrients such as protein, calcium, and phosphate to meet the high requirements of VLBW babies (<1800 g), as human milk alone may not provide adequate amounts.²¹ The American Academy of Pediatrics recommends fortification of human milk for all VLBW infants.¹⁹ Studies have shown a significant beneficial impact of human milk fortifiers (HMF) on weight gain in VLBW neonates and considered it safe to use.²² Significant improvement in growth and neurodevelopmental outcomes has been observed with fortification of human milk with HMF in VLBW infants without an increased risk of NEC or feeding intolerance.^23–25 Use of HMF and human milk diet has been associated with lower incidence of feed intolerance, NEC, sepsis, and duration of hospital stay.^17,24–26

Preterm neonates and VLBW need specialized care in the neonatal intensive care unit (NICU). As per the 2007 report by the Institute of Medicine, the average length of stay (LOS) for preterm babies was 13 days, 9 times more as compared to babies born at term (1.5 days)²⁶ suggesting the need for more infrastructure and economic burden on the NICU due to prolonged occupancy of the NICU beds by the same patient.

India already struggles with NICU infrastructure as experts suggest a need for extra 20,000–30,000 level 3 NICU beds and 75,000–1,00,000 level 2 special newborn care beds for India.²⁷ Hospitals in India may need to treat more than one sick neonate on a single bed.²⁸

Studies emphasise the potential to lower the cost associated with management of preterm baby if we can reduce the time spent in the NICU.¹⁴ Fortification of human milk has also shown to reduce healthcare costs due to early discharge.²⁹ Studies have demonstrated reduced length of stay and significantly lower physician and total hospitalization costs per infant, who received a fortified exclusive human milk diet when compared with the other diets.³⁰ With high preterm birth rate along with restrained NICU infrastructure and high economic burden associated with the management of neonates in NICU, it is important to understand the current clinical practices of the paediatricians and NICU specialists and economic consequences of preterm birth that can provide an invaluable resource for clinical decision-makers and hospital administration. There is a lack of literature from India that focuses on the economic impact of nutritional intervention on in-hospital management of preterm infants and for any potential economic benefits of providing HMF to the preterm infants. This survey is an attempt to gather insights into the NICU patient flow, nutritional interventions, duration of NICU stay and economic implications during management of neonates. Through this survey, we intend to assess the role of nutritional intervention during in-hospital management of neonates in regard to health benefit and economic implications for the caregivers and the hospital. We hypothesised that providing optimal nutrition with early fortification of human milk is associated with better growth outcomes and early discharge of the preterm infant from the hospital, thereby reducing the overall economic cost associated with the management of neonates in the NICU setting.

Materials and Methods

Survey Design

This quantitative survey-based study was conducted in 5 institutions, including government and private hospitals across Tier-1 cities of India: Ludhiana, Mumbai, Kolkata, Gurgaon, and Bangalore.

Hospitals were included on the basis of:

• Number of NICU beds
• Hospitals could be either government or private, with at least 30 NICU beds
• Hospitals have a usual practice of using human milk fortifier as part of nutritional intervention

The hospitals included had at least 30 NICU beds, excluding the NICU beds equipped with a ventilator. A structured questionnaire was developed specifically for this study to understand the hospital infrastructure, patient volume, feeding practices of preterm infants, economic burden, and clinical outcomes. The questionnaire was developed through a comprehensive review of current clinical guidelines and the available peer-reviewed literature regarding nutritional practices, growth parameters, and the expenditure involved in the management of neonates during their NICU stay.

Data was collected using a survey questionnaire (see Table 1) consisting of 22 questions. The survey was duly filled by the physicians and by voluntary participation through an interview or online forms once there was a complete understanding of the questionnaire. The questionnaire was designed with an aim to understand the average patient flow and admissions to the NICU, feeding practices being followed during the NICU stay, NICU costs from the physician, and hospital administration perspective, resource utilization including manpower and operational factors that can impact the work processes of NICU and other general recommendations and feedback. The physician’s opinions surveyed were based on their clinical practice pattern and hospital administration information The average response for each question was calculated and mentioned in numbers and percentages. The focus of this survey was to provide a physician’s view of the feeding interventions, growth outcomes, and the costs involved in the management of a neonate during the NICU stay.

Table 1 Survey Questionnaire on NICU Care Practices, Feeding, and Recovery Outcomes

Statistical Analysis

Survey data was analysed using MS Office 365 excel statistical tools. The data collected through the survey was collected, and the responses were summarized using descriptive statistical analysis. The results represent averages in the form of per day and per month analysis and are not analysed individually for each institution.

Ethical Compliance

Ethical approval for this study was not needed as it is a survey-based investigation with voluntary participation from physicians and does not involve patient participation.

Results

Feeding Practices in NICU

Physicians reported that of all the hospitalized neonates, 75% (7.5/10) neonates (~8 patients) are admitted to the NICU. The common feeding practices in the NICU include human milk fortification, unfortified feeding (without HMF), and mixed feeding (breast milk and formula).

60% (6/10) (6 patients) of the neonates admitted to NICU are introduced to human milk fortifier (HMF), while ~23% (2 patients) are given unfortified feeds and remaining 1 patient is given mixed feed. As per the physicians, HMF feeds are introduced when enteral feeds reach a volume of 100–150mL/kg/d as per the usual clinical practice.

Improved Growth Parameters

An estimated weight gain of ~10–20 g/kg/d has been reported by the physicians in neonates admitted to NICU and provided HMF as compared to unfortified human milk feeds. A 40–50% of delay in expected growth or recovery time is seen in babies given unfortified human milk feeds.

Decreased Length of Hospital Stay

The survey findings suggest that the average hospital stay of a neonate provided with unfortified feeds (without HMF) is around 15 days while it is approximately 9 days in neonates given fortified feeds (with HMF). An estimated 40% lesser days of hospitalization can be observed for infants provided with fortified (with HMF) feeds (Figure 1).

Figure 1 Length of NICU stay (in days) with or without use of HMF.

Cost Saving per Patient

Physicians reported an average NICU cost for management of a neonate equals to INR 30,000 per day. This amounts to an expense of 4.5 L for 15 days and 2.7 L for 9 days of NICU stay for neonate provided with unfortified feeds (without HMF) and fortified feeds (with HMF), respectively, while keeping the costs consistent till discharge, hence, a cost saving of 1.8 L per neonate when provided with fortified feeds (Figure 2).

Figure 2 NICU expense for management of neonates with or without use of HMF.

Economic Outcomes: Hospital Perspective

The average per-day NICU cost is 30,000 INR for managing a neonate. Considering 60 neonates being admitted to NICU in a month and given unfortified feeds and the duration of stay is 15 days, then an estimated per month NICU cost for the management of these infants would be 2.7 Cr. For neonates provided with fortified feeds, the estimated monthly NICU cost for the management of these infants would be 1.62 Cr considering each neonate stays in the NICU for 9 days. So, considering a 40% reduction in length of NICU stay with the use of HMF, use of unfortified feeds in neonates can amount to 40% missed saving of 1.08 Cr per month.

However, the cost of NICU care generally decreases over LOS, with the initial days typically being most expensive (~25–30% higher) due to intensive interventions, continuous monitoring, and higher resource utilization required for stabilization (Figure 3).

Figure 3 Variation in expense in management of neonates during NICU stay.

Cost Saving in Manpower and Non-Consumables

As per the survey findings, on average, 5 nurses and 3 admin staff are required in the NICU.

With the actual cost of infrastructure, non-consumables and salaries of manpower remaining constant, along with early availability of beds by the introduction of HMF, this may eventually turn into 30–40% per month savings for the hospital and an increase in hospital revenue.

Discussion

Preterm neonatal care imposes a burden on the healthcare infrastructure and also societal outcomes as a bigger picture. Major cost contributors include hospitalization, indirect costs (eg, transport, food, loss of productivity, etc.) along with the intangible cost of anxiety and stress that the family is going through during this period.

This survey, as per our knowledge, provides the first of its kind insights into the nutritional interventions including fortified and unfortified feeds being used for neonates, their growth trends, and economic burden of the management of neonates during their NICU stay as shared by the neonatologists from five tertiary care hospitals in India.

The survey findings suggested that neonates who receive HMF during their hospital stay have improved growth parameters in terms of weight gain while preterm infants who receive unfortified feeds may experience a relative delay in expected growth or recovery time.

Findings of a randomized controlled trial including 166 preterm infants weighing <1500 grams and <34 weeks of gestation supports the survey findings, where the use of HMF during the NICU stay was associated with weight gain of 15.1 vs 12.9 g/kg/day (P < 0.001) as compared to infants receiving unfortified feeds. Significant improvement in the length (1.04 and 0.86 cm/week, P = 0.017) and head circumference (0.83 and 0.75cm/week, P < 0.001) have also been observed in the fortified group.³¹

Studies suggest improved energy, protein, and mineral intake with early fortification of human milk in preterm infants that may lower the risk of undernutrition, help in faster regain of birth weight,^32,33 enhance postnatal growth, and lower the risk of EUGR.³² Along with its impact on the growth and long-term health of babies, management of preterm births is also associated with substantial economic impact on the caregiver and the hospitals. Gilbert et al 2003 estimated total per-patient neonatal hospital costs of 202,700 USD for a surviving baby born during the 25^th week and 2600 USD for babies born during the 36^th week, decreasing to only 1100 USD for a 38-week newborn.³⁴

Our survey findings suggest a trend towards reduced LOS in the NICU for preterm infants who are given HMF which may be attributed to the crucial role of adequate nutrition in improving weight gain and other growth parameters in preterm infants. Our survey findings share a trend towards a shorter duration of NICU stay by almost 40% which can be further translated into reduced economic burden and can be perceived as the opportunity cost in pharmacoeconomic terms with implications for the caregivers, health care providers and payers (eg insurance providers). Literature supports that adequate nutrition and growth of the newborns promotes improved long-term neurodevelopment, reduced hospital LOS, and other socioeconomic benefits.³⁵ An average preterm infant hospital stay costs 15,100 USD with a mean LOS of 12.9 days while for other newborns, an average cost for stay is 600 USD and the mean LOS is 1.9 days.³⁶

As per an Indian study, even when the government offered to cover all the direct medical costs through its initiatives such as Janani Shishu Suraksha Karyakrama, there were other expenses involved and higher out of pocket expenses were borne by the caregiver during the management of preterm and low birth weight babies and when LOS was beyond 11 days.³⁷ Early discharge is also associated with better emotional well-being of the family, less out of work days for the caregivers,³⁸ and better neurodevelopment at two years with hospital assisted home care.³⁹

Higher LOS for preterm infants increases the risk of hospital-based complications, cost of hospitalization, and the financial burden on the caregiver.⁴⁰ Higher LOS also decreases the bed availability in the hospitals and causes inefficient resource utilization.⁴⁰

Russell RB et al, studied the cost of hospitalization for preterm and low birth weight infants in the United States and determined that preterm/low birth weight admissions amount to USD 5.8 billion (47% of all infant hospitalization cost).³⁶ A retrospective analysis by Assad et al, including preterm and VLBW observed that infants fed with exclusive human milk-based diet had significantly lower feeding intolerance, incidence of NEC, and total hospitalization costs per infant as compared to other diets and the LOS was shorter by 4.5 to 22 days.³⁰

High prevalence of preterm births can reduce the hospital bed availability, which could be a concern for hospital administration. Early patient discharge reduces LOS in the hospitals and improves bed turnover and faster availability of the beds for other patients which is a critical aspect for saving lives in NICU. Delayed discharge increases bed occupancy and hence the cost; studies recommend to take initiatives to reduce the LOS for better clinical and economical outcomes and to improve operational efficiency of the hospitals.⁴¹ The initial days of NICU stay are more expensive due to intensive interventions, continuous monitoring, and higher resource utilization required for stabilization. As a baby’s condition improves and the intensity of care and expenditure involved decrease over time, the fixed costs (including infrastructure and manpower) remain the same for the hospital. This also translates into improved manpower and non-consumable utilization and hence improved economic benefits for the hospital.

Use of fortified feeds may help in early discharge and early bed availability which in turn may improve patient turnout and revenue for the hospital. The survey findings suggest improved cost savings both from the caregiver and the hospital perspective with the introduction of HMF.

The strength of this survey lies in including healthcare professionals working with the paediatric or neonatology units of the hospitals and it comprised of both qualitative and quantitative questions related to the nutritional management of neonates during the NICU stay. However, survey-based research is generally limited by the generalized responses and potential recall and subjective bias of the participants inherent for survey-based self-reported studies. The survey being conducted with physicians from hospitals of Tier-1 cities limits its generalization across diverse healthcare systems due to inter-hospital variability. However, we are of the opinion that these considerations regarding HMF and impact on LOS would be even more important where infrastructure is limited. The cross-sectional nature limits its ability to establish causality and assess long-term implications. The results being descriptive in nature and lack of patient-level validations requires a cautious approach to interpret the findings. Small sample size of the survey participants is another limitation which we suggest should be further replicated with a larger sample size involving patient centric validations to strengthen these observations.

Future studies with robust methodologies, such as prospective, longitudinal, randomized controlled studies are suggested for better establishment of the impact of providing fortified human milk to preterm infants during their NICU stay on health and economic outcomes.

Conclusion

This survey study intended to explore the physician’s insights into the role of nutritional interventions in the management of neonates during their NICU stay. The survey findings hypothesise that introduction of human milk fortifiers can meet the higher nutritional demands of the neonates during their NICU stay and support better weight gain and early recovery. The survey findings suggest early hospital discharge in neonates fed with human milk fortifiers which may further translate into lesser economic burden for the caregiver as well for the hospital with early bed availability.