Over Half of Asphyxiated Newborns in Uganda Show Liver Injury, Study Finds

When a newborn is deprived of oxygen around the time of birth, the consequences ripple far beyond the brain. Birth asphyxia, one of the leading causes of neonatal death and disability worldwide, has long been recognized for its devastating neurological effects, but its quieter toll on other organs has received far less attention, particularly in resource-limited settings. A new prospective study conducted at three tertiary hospitals in Uganda now provides some of the clearest evidence yet that the liver is a frequent and early casualty of perinatal oxygen deprivation, with more than half of affected newborns showing biochemical signs of hepatic injury within their first week of life.

The research, published in BMC Pediatrics by a team led by Oswald Kakule Maghuli of Kampala International University’s Western Campus, followed 421 term neonates who were born with perinatal asphyxia, defined in the study by an Apgar score of less than 7 at five minutes of age. The Apgar score is a rapid bedside assessment of a newborn’s condition, evaluating heart rate, breathing, muscle tone, reflexes, and color, and a low score at five minutes signals that the infant has not transitioned well to life outside the womb. These infants were enrolled across three tertiary referral hospitals in Uganda, institutions that handle the sickest newborns in their regions and where birth asphyxia remains a daily reality on pediatric wards.

The study’s design was deliberately rigorous. It was a hospital-based prospective cohort study, meaning that infants were enrolled at admission and followed forward in time rather than looking backward at existing records. Each participant provided two milliliters of venous blood at three fixed time points: within the first day of life, on the third day, and on the seventh day. The samples were analyzed for four liver-related enzymes: aspartate transaminase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP), and lactate dehydrogenase (LDH). These enzymes normally reside inside liver cells, and when hepatocytes are damaged, they leak into the bloodstream, making elevated levels a sensitive biochemical fingerprint of liver injury. The researchers set a conservative diagnostic threshold: a newborn was classified as having hypoxic hepatitis only if at least three of the four enzymes were deranged, reducing the chance that isolated, clinically insignificant fluctuations would inflate the results.

The findings were striking. Hepatic injury was detected in 214 of the 421 participants, or 50.8 percent, on the first day of life. By day three, the number had fallen to 137 infants, or 32.5 percent, and by day seven it had dropped further to 69 infants, or 16.4 percent. Overall, 222 newborns, slightly more than half of the cohort, showed hepatic injury at at least one point during the seven-day observation window, yielding an incidence of hypoxic hepatitis of 52.7 percent, with a 95 percent confidence interval of 48.2 to 57.5 percent. That confidence interval, which does not fall below 48 percent, indicates that even at the most conservative estimate, nearly one in two asphyxiated newborns in these hospitals experienced measurable liver injury.

Perhaps the most clinically consequential finding was the timing of the injury. Of the newborns who developed hypoxic hepatitis, 96.4 percent were first diagnosed on the first day of life. Only eight infants, or 3.6 percent, had the diagnosis first made on the third day, and not a single participant had hypoxic hepatitis first detected on the seventh day. In other words, the liver damage inflicted by oxygen deprivation is essentially an immediate event, unfolding in the hours immediately surrounding birth rather than emerging gradually over the first week. This temporal pattern mirrors the underlying biology: the liver is one of the most metabolically active organs in the newborn body, with high energy demands to support glucose production, protein synthesis, bilirubin processing, and the detoxification functions that a newborn suddenly must perform independently after the placenta is severed.

When oxygen delivery falters, the body responds by redistributing blood flow away from less critical organs toward the brain and heart, a survival mechanism known as the dive reflex. The liver, along with the kidneys and gastrointestinal tract, is among the first organs to be sacrificed in this redistribution. The resulting ischemia, combined with the reperfusion injury that occurs when oxygenated blood returns to the deprived tissue, generates a cascade of reactive oxygen species and inflammatory mediators that damage hepatocyte membranes. Because the neonatal liver is already operating near its metabolic capacity, this insult can quickly translate into measurable enzyme leakage, and in severe cases into coagulopathy, hypoglycemia, and impaired drug metabolism, all of which complicate the care of an already fragile infant.

The study cohort was composed slightly more of males than females, with 53.4 percent boys and 46.6 percent girls, a distribution consistent with the well-documented male vulnerability to perinatal complications. The researchers note that the burden of birth asphyxia and its complications falls disproportionately on resource-limited settings such as Uganda, where access to advanced neonatal intensive care, therapeutic hypothermia, and sophisticated monitoring is limited. In such environments, a complication like hypoxic hepatic injury can be easily overlooked, because clinical attention is understandably dominated by the neurological manifestations of hypoxic-ischemic encephalopathy, including seizures, poor feeding, and altered consciousness. Yet unrecognized liver dysfunction can undermine the very treatments being delivered, altering the pharmacokinetics of anticonvulsant drugs and worsening bleeding risk during procedures.

Based on their findings, the authors recommend that all neonates with birth asphyxia be routinely screened for hepatic injury, and critically, that this screening be performed within the first 72 hours of life. The recommendation is grounded directly in the study’s temporal data: since virtually all cases were detectable by day one and none first appeared by day seven, a single early liver function test panel would capture the overwhelming majority of affected infants. In practical terms, this means that the same blood draw already being used for other neonatal assessments could be extended to include AST, ALT, ALP, and LDH, adding relatively little cost while potentially changing management for more than half of asphyxiated newborns in similar settings.

The implications extend beyond Uganda. Birth asphyxia accounts for a substantial share of the roughly 2.3 million neonatal deaths that occur globally each year, the majority concentrated in sub-Saharan Africa and South Asia. If the incidence observed in this Ugandan cohort is representative, hypoxic hepatic injury may be one of the most common, and most underdiagnosed, complications of perinatal oxygen deprivation worldwide. The study also highlights the value of prospective, multi-site designs in resource-limited settings, where much of the existing literature on neonatal organ injury derives from high-income countries with very different patient populations and care standards. By documenting the natural history of liver enzyme derangement across the first week of life, the researchers have created a baseline against which future interventions, whether hepatoprotective therapies, modified resuscitation protocols, or structured screening programs, can be evaluated.

For clinicians on the front lines, the message is direct: the liver is not a silent bystander in birth asphyxia. It is injured early, in most babies who are injured at all, and it can be detected with a simple, widely available panel of blood tests. For researchers, the study opens questions that the current data cannot answer, including how hepatic injury severity correlates with the degree of encephalopathy, whether early biochemical injury predicts longer-term outcomes such as growth and neurodevelopment, and whether targeted supportive care in the first days of life can attenuate the hepatic damage. What is already clear is that in the crowded pediatric wards of Uganda’s tertiary hospitals, and likely far beyond them, more than half of oxygen-deprived newborns carry a hidden hepatic burden that modern neonatal care can no longer afford to ignore.

Subject of Research: Hypoxic hepatic injury in term neonates with birth asphyxia in Uganda

Article Title: Incidence of hepatic injury in term asphyxiated neonates admitted in three tertiary hospitals in Uganda: a prospective study

Article References: Maghuli, O. K., Kitsamuli, J. N., Paluku Isombi, J., Shamavu, G. K., Mbekeeka, P., Nankunda, J., & Eldeen Mohamed, A. N. (2026). Incidence of hepatic injury in term asphyxiated neonates admitted in three tertiary hospitals in Uganda: a prospective study. BMC Pediatrics. https://doi.org/10.1186/s12887-026-06915-2

Image Credits: AI Generated

DOI: 10.1186/s12887-026-06915-2

Keywords: birth asphyxia, hypoxic hepatitis, hepatic injury, neonates, liver enzymes, Uganda, Apgar score, AST, ALT, neonatal care, resource-limited settings, prospective cohort study