A value below 7.05 is the threshold Sweden uses to define neonatal acidemia, a state of excess acidity in the blood that has been consistently linked to low Apgar scores, resuscitation requirements, and neonatal intensive care admission. Cord blood samples in the register were collected with pre-heparinized syringes and analyzed within ten to fifteen minutes on blood gas analyzers located in the maternity units themselves, and all pH values had been validated before the study began. Of the infants studied, 51.6 percent were male.

Acidemia, defined as UApH below 7.05, occurred in 2.1 percent of boys compared with 1.8 percent of girls. After statistical adjustment, male sex carried an 18 percent higher odds of acidemia, with an odds ratio of 1.18 and a 95 percent confidence interval of 1.07 to 1.30. The association with a five-minute Apgar score below 7, a clinical sign that a newborn is not transitioning well outside the womb, was stronger still: boys had 33 percent higher adjusted odds, at an odds ratio of 1.33.

The researchers also applied a Bonferroni-corrected significance threshold of 0.0071 to account for the seven outcomes tested simultaneously, and the associations with acidemia, Apgar score, breathing support, intensive care admission, hypoxic-ischemic encephalopathy, and central nervous system disease all survived that stricter test. The differences in respiratory and neurological outcomes were more pronounced in relative terms. Male neonates required continuous positive airway pressure, or CPAP, a non-invasive form of breathing support delivered through the nose, at 66 percent higher adjusted odds than females.

Admission to the neonatal intensive care unit was 51 percent more likely for boys. Hypoxic-ischemic encephalopathy, a serious condition in which the brain is deprived of oxygen and blood flow around the time of birth, showed the largest effect size of all, with boys facing more than double the adjusted odds at an odds ratio of 2.24. A broader registry variable capturing suspected or confirmed pathology of the brain or spinal cord during the first four weeks of life was also elevated in males, at an odds ratio of 1.52.

The raw numbers behind these odds ratios remain small in absolute terms, a point the authors themselves emphasize. Hypoxic-ischemic encephalopathy was diagnosed in 45 of 45,356 boys, or roughly one in a thousand, compared with 18 of 42,484 girls. Seizures occurred in 62 boys and 39 girls, an association that reached statistical significance in the primary analysis with an odds ratio of 1.55 but failed to hold up under the Bonferroni correction.

The acidemia gap amounts to roughly three additional cases per thousand male births. These modest absolute differences matter for interpretation: the study identifies a consistent pattern across a very large population rather than a dramatic shift in risk for any individual infant. Why boys might be more vulnerable in the hours and days surrounding birth remains an open question, but the study reviews several plausible biological mechanisms.

Research on placental histology has found significantly more chronic inflammatory lesions at the implantation site in placentas carrying male fetuses, particularly in very preterm births before 32 weeks of gestation. One proposed explanation is that these lesions represent a maternal immune response against the invading trophoblast cells of a male fetus, suggesting that the maternal-fetal interface itself behaves differently depending on the sex of the offspring. A second line of thinking concerns how male and female fetuses respond to a stressed intrauterine environment.

According to a review cited in the study, male fetuses tend to continue growing even under adverse conditions such as chronic maternal asthma, which leaves them larger and more exposed when an acute stressor such as an asthma exacerbation strikes, potentially culminating in preterm birth or stillbirth. Female fetuses, by contrast, appear to adapt by slowing their growth, conserving resources and tolerating lower oxygen availability. This growth-restraint strategy may render female neonates more resilient to perinatal stress, while the male strategy of persistent growth carries greater risk when the environment deteriorates.

Hormonal and maternal physiological differences have also been investigated. One study examined fetal sex steroid concentrations and their metabolites in cord blood as a possible origin of sex-based differences in fetal physiology, though it found no significant differences between the sexes. Separately, researchers have reported higher salivary cortisol concentrations in mothers carrying male fetuses during gestational weeks 24 to 30, raising the possibility that a male fetus may amplify maternal physiological stress, which could in turn influence postnatal outcomes.

None of these mechanisms has been definitively established, and the current study was not designed to test them directly. The study's strengths lie in its scale and its data quality. By drawing on the Perinatal Revision South Register, a regional clinical quality register covering most maternity units in southern Sweden over a 20-year span, the investigators captured enough births to represent even uncommon perinatal events, which strengthens the generalizability of the findings to comparable high-income settings.

The validation of cord blood samples was particularly rigorous: cases with a veno-arterial pH difference of 0.02 or less were excluded to ensure that paired samples truly came from different vessels, and extreme outliers were removed. This screening eliminated nearly a third of the original 104,072 births, a trade-off the authors acknowledge as a potential source of selection bias, but one they consider essential for data integrity. The limitations are equally important for readers to weigh.

The register contained no data on maternal comorbidities such as hypertensive disorders, so the adjusted models could not account for them, and residual confounding cannot be excluded. Variables such as labor induction and instrumental vaginal birth, both of which were more common among male infants in this cohort, were not included in the multivariable models. Body mass index and smoking status had substantial missing data and were likewise omitted.

NICU admission was based on clinical judgment and local hospital guidelines rather than uniform national criteria, mortality data were unavailable, and the registry's catch-all CNS disease variable did not distinguish between specific diagnoses. Follow-up was limited to the first 28 days of life, so neurological disorders diagnosed later in childhood were not captured. The authors stress that neonatal sex is not currently considered in clinical risk assessment during pregnancy, and that further prospective research is needed before these findings could inform risk stratification or management in maternity care.

Subject of Research: Sex differences in adverse neonatal outcomes and umbilical cord arterial pH at birth

Article Title: Sex-specific adverse neonatal outcomes and umbilical cord arterial ph at birth: a population-based cohort study

Article References: Akel, W. N., Abdulilah, S., & Zaigham, M. (2026). Sex-specific adverse neonatal outcomes and umbilical cord arterial ph at birth: a population-based cohort study. BMC Pediatrics, 26(1), Article 1071. https://doi.org/10.1186/s12887-026-07865-5

Image Credits: AI Generated

DOI: 10.1186/s12887-026-07865-5

Keywords: neonatology, umbilical artery pH, neonatal acidemia, Apgar score, hypoxic-ischemic encephalopathy, NICU admission, neonatal sex differences, placental inflammation, population-based cohort, perinatal outcomes, Sweden, CPAP