Newborn boys are significantly more likely to suffer from hypoxic-ischemic encephalopathy (HIE), resulting from a lack of oxygen to the brain before or shortly after birth, causing brain damage along with impacting the central nervous system, according to researchers from the University of Texas Southwestern Medical Centre (UTSW).

The findings, published in JAMA Network Open, could lead to more effective HIE interventions for both boys and girls.

Commenting on the findings, study leader Prof. Lina Chalak, Professor of Paediatrics and Psychiatry, Interim Chief of the Division of Neonatal-Perinatal Medicine, and founder and director of the Foetal Neonatal Neurology Programme at UT Southwestern, who co-led the study with Prof. Catherine Spong, Professor and Chair of Obstetrics and Gynaecology at UTSW, said, “The effect of sex needs to be considered in all future neuroprotective interventions for birth asphyxia.”

“Boys may have different molecular pathways than girls, so we might need to address this with different therapies,” she added.

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Hypoxic-ischemic encephalopathy is a common reason for seizures in newborns, both in full-term and premature babies, and makes up about half of the causes of seizures in them. In babies born full-term with this condition, the seizures can be quite frequent, and in 10% to 15% of cases, they might experience continuous seizures.

HIE affects millions of newborns worldwide, causing harm when oxygen or blood flow to the brain is decreased or halted before delivery. Male animals appear to be more vulnerable to birth asphyxia than females, owing to the protection provided by the female hormone oestrogen. Females have superior results across a wide range of neurological injuries, including strokes, traumatic brain injuries, and preterm. Previous clinical investigations, however, have not demonstrated an increased prevalence of HIE in male neonates because most research into this issue has included a limited number of newborns.

For this study, the researchers used data from one of the largest U.S. single-site clinical groups of babies through a unique collaboration between UTSW’s Department of Obstetrics and Gynaecology and the Department of Paediatrics’ Division of Neonatal-Perinatal Medicine, both of which have combined databases that track newborn statistics and outcomes at Parkland Memorial Hospital. Parkland, the primary teaching hospital for UT Southwestern, has one of the busiest maternity wards in the country, having delivered 12,179 babies in fiscal year 2022.

Among singleton births between Dec. 1, 2005, and Dec. 1, 2020, the researchers identified 157,538 newborns. For about 99%, lab results on the infants’ umbilical cord blood were available, revealing that 5,590 had significantly acidified blood, indicating a risk for HIE.

Although the sex of the newborns was nearly evenly divided, HIE diagnoses followed a different pattern: 54% were in males and 46% in females.

Dr Chalak, who is also a neonatologist at Children's Health, said these findings could affect the counselling of new parents whose babies have been diagnosed with HIE, as well as the development of new interventions.