A nested case–control study on mortality and outcome of neonates admitted to a tertiary neonatal intensive care unit

INTRODUCTION

Health in the early years – from preconception through pregnancy to the first 5 years of life – forms the foundation for lifelong health, productivity and national prosperity. The Developmental Origins of Health and Disease framework demonstrates that early-life exposures profoundly shape health trajectories, as this is a critical period for organogenesis and long-term biological programming. Early interventions can, therefore, yield cumulative long-term benefits and substantially reduce future healthcare burdens.

Evidence from the United States suggests that high-quality early childhood programs yield approximately 13% annual returns on investment throughout life.^[1] Therefore, prevention of preterm birth and minimising the risk if preterm birth happens is essential. Midwife-led community antenatal care by bridging the gap between mother and obstetrician, continuous monitoring and implementation of early childhood health policies are vital to achieve this goal.

Preterm birth is defined as birth before 37 completed weeks of gestation and is subcategorised into extremely preterm (<28 weeks), very preterm (28–32 weeks) and moderate-to-late preterm (32–37 weeks). Globally, about 15 million infants are born preterm annually, and nearly one million die from complications of prematurity.^[2] The World Health Organisation recommends implementing measures and providing high-quality care to prevent preterm birth and associated complications.^[3]

In low-resource settings, nearly up to 50% of infants born before 32 weeks die due to lack of basic neonatal interventions (e.g. thermal care, infection control and respiratory support). In contrast, in high-income settings, survival is high but often accompanied by significant long-term disabilities.^[3] Very low birth weight preterm babies are vulnerable to respiratory distress syndrome, necrotising enterocolitis (NEC), intraventricular haemorrhage (IVH), chronic lung disease, sepsis and long-term neurological and visual impairment. Even among those who survive, risks of short bowel syndrome, malnutrition, learning difficulties and reduced pulmonary function are increased.^[4-7]

In this study, we compare profiles of preterm infants who died in the 1^st year with those who survived with preterm-related morbidities in a tertiary NICU in Saudi Arabia, to identify key predictors of mortality and morbidity in preterm infants.

MATERIAL AND METHODS

RESULTS

A total of 49 preterm infants were analysed, 15 preterm babies that died (cases) and 34 survived with morbidities (controls). Comparison of demographic and birth details of preterm babies of the two groups is given in Table 1.

DISCUSSION

Optimising neonatal and early childhood care is vital for improving survival, long-term health and national productivity. The Royal Foundation and the London School of Economics estimated that preventable early childhood adversities cost the UK £16.13 billion annually, excluding lifetime productivity losses.^[11,12]

Well-known Epicure cohort studies also suggest that extreme preterm babies are surviving but with long-term health problems, putting greater demands on health, education and social services.^[13]

Our findings confirm that lower gestational age (24–26 weeks), very low birth weight, absence of antenatal steroid exposure, seizures, severe NEC, grade 4 IVH and large PDA are major predictors of adverse outcome among preterm infants.

Antenatal steroid and magnesium sulphate administration to expectant mother of preterm baby has shown remarkable improvement in outcome. Primarily antenatal steroid, which not only helps in lung maturity but also prevent IVH and NEC.^[14] Magnesium sulphate has a role in the neuroprotective effect if given before preterm delivery or caesarean section.

The study design of nested case–control enabled us to generate a higher level of evidence.

Although PDA, NEC, ROP and IVH were nearly common in both groups, the severity of these complications were more in the case group, compared to the control group. Such as severe NEC which required surgical repair, were predominant in the case group in three cases.^[15,16] Similarly, moderate-to-large PDA were noted significantly in case group in comparison to the control group in which most of them had small PDA.

Extreme preterm babies are very fragile nutrition and growth are very challenging to achieve, careful use of parenteral nutrition, maximising gradual and early introduction of expressed breast milk to colonise the gut with vigilant monitoring, keeping close observation of feeding tolerance, and optimised use of probiotics could be helpful in the prevention of severe NEC. In our study, three cases had severe NEC, who did not reach full feeds, they just reached nearer to 50% of full feeds.They did not responded to conservative management and needed surgery.^[17,18]

The ROP prevalence (16%) aligns with global surveys (18.8%).^[19] Seizures and grade 4 IVH were more noted in the case group, which warns that the fragile preterm neonates’ brains need meticulous care, optimised fluid, inotropes and vigilant monitoring to detect it early. Neurological injury can cause significant compromise in further neurodevelopment milestones and sensory motor functions. We did not have sufficient data about their long-term development. Study with a track record of developmental assessment, as per the Bayley scales of infant and toddler, may help to assess the long-term impact on development.^[20,21]

Seizure incidence may also reflect electrolyte disturbances or hypoxic injury, warranting vigilant monitoring in preterm care such as early cranial ultrasound of head at bed side in NICU on (Day 0, 3 and 7) by in house trained doctor to prevent delay due to input from radiologist which may take time, strict fluid policy, optimised use of saline bolus only if required could be very helpful in prevention of severe IVH.^[22]

Sepsis was similarly frequent in both groups; the causative group of pathogens observed was Gram-positive cocci and Gram-negative bacteria among both groups. However, Gram-positive cocci infection (coagulase-negative staph aureus) was predominant in the case group, in which three babies had severe NEC requiring surgical repairs. The majority of preterm babies require umbilical lines and long lines for parenteral nutrition, inotropic infusion and for frequent blood sampling for blood investigations. They are at risk of line sepsis; coagulase-negative staphylococci are very commonly observed organisms in line sepsis. Diagnosis of neonatal sepsis remains challenging; risk calculators, strict line sepsis prevention practice, effective hand hygiene while handling umbilical and long lines and closed circuit arterial line for blood collection from artery may be very useful to curtail line sepsis.

BPD and air leak were relatively uncommon and did not differ significantly, perhaps reflecting advances in respiratory management and good ventilation strategies.^[23]

Although advances in NICU care have improved survival, still persistent morbidities highlight the need for improved multidisciplinary management and robust risk prevention strategies, effective parental counselling and long-term follow-up planning. Neonatal sepsis remains a challenge, requiring careful diagnosis and rational antibiotic use. Improved ventilation strategies and pharmacotherapy continue to reduce mortality from BPD.^[23]

Midwife-led continuity care models have been shown to reduce preterm births by 24%.^[24] In the United Kingdom, the midwife-led community model of antenatal care has been in practice for many years and has shown very potential beneficial results. Expanding such a care model and program could be helpful in optimising antenatal care by bridging the gap between obstetrician and families, which may help in reducing preterm birth and subsequently preterm birth-related complications and could significantly reduce health and economic burden to families and health care providers.

CONCLUSION

Providing care for preterm babies in the NICU remains a high-stakes balance between survival and minimising lifelong morbidity. Despite improvements in neonatal care, many survivors face significant comorbidities that challenge health care systems, education, social services and families.^[25] Integrated approach – encompassing improvement and strengthening antenatal care, staff training, parental support and long-term follow-up – is essential. Midwife-led antenatal care module, innovative interventions and policy support could be helpful to reduce preterm birth and preterm birth-related morbidities which could optimise long-term health outcomes and minimise burden on health care and social services.