Maternal Azithromycin Does Not Impact Child Development

Study Methodology and Parameters

Clinical research regarding intrapartum azithromycin neurodevelopmental outcomes provides essential safety data for obstetricians in low-resource settings. A recent follow-up to the A-PLUS trial evaluated whether a single dose of maternal azithromycin influences the long-term cognitive health of children born with birth asphyxia. While the original study confirmed that azithromycin reduces maternal sepsis, this secondary analysis focused on children who faced respiratory challenges at birth. Consequently, these findings offer clarity on the pediatric safety profile of common intrapartum antibiotic interventions.

The study specifically targeted children born at or after 34 weeks of gestation who experienced birth asphyxia. Researchers defined asphyxia as a 5-minute Apgar score below seven or a requirement for bag-and-mask ventilation. Mothers originally participated in the A-PLUS trial, where they received either 2 grams of oral azithromycin or a placebo during labor. The follow-up occurred across six international sites, including two locations in India. Examiners utilized the Bayley Scales of Infant and Toddler Development (BSID-III) to assess cognitive, language, and motor skills. This assessment took place when the children reached a corrected age of approximately 24 months.

Findings on intrapartum azithromycin neurodevelopmental outcomes

The results showed no significant difference between the azithromycin and placebo groups regarding cognitive composite scores. Specifically, the azithromycin group averaged 90.9, while the placebo group also averaged 90.9. Furthermore, the researchers observed no variations in language or motor scores between the two cohorts. Subgroup analyses comparing regions like South Asia and sub-Saharan Africa yielded similar neutral results. Additionally, the Ages & Stages Questionnaires (ASQ-3) scores did not differ across any of the five evaluated domains. These findings suggest that maternal antibiotic prophylaxis does not adversely affect or improve neurodevelopment in this high-risk pediatric population.

Implications for Clinical Practice in India

For Indian clinicians, these results provide reassurance regarding the safety of prophylactic azithromycin in labor. Since the A-PLUS trial reduces maternal sepsis, doctors can implement this protocol without fearing long-term neurodevelopmental harm to the neonate. However, the study confirms that the antibiotic does not offer neuroprotective benefits for infants suffering from birth asphyxia. Physicians should continue to prioritize standard neonatal resuscitation protocols and postnatal care. Ultimately, this evidence supports using azithromycin for maternal health while maintaining a neutral stance on its pediatric developmental impact.

Frequently Asked Questions

Q1: Did intrapartum azithromycin improve cognitive scores in infants with birth asphyxia?

No, the study found no significant difference in cognitive composite scores between children whose mothers received azithromycin and those who received a placebo.

Q2: Is the single 2-gram dose of azithromycin safe for use in Indian settings?

Yes, the inclusion of Indian sites in the A-PLUS trial confirms the safety and lack of long-term neurodevelopmental harm associated with this maternal intervention.

References

1. Ramani M et al. Neurodevelopmental Pediatric Follow-Up After the Azithromycin Prevention in Labor Use Study. Obstet Gynecol. 2026 May 14. doi: 10.1097/AOG.0000000000006301. PMID: 42133947.
2. Tita AT et al. Azithromycin to Prevent Sepsis or Death in Women Planning a Vaginal Delivery. N Engl J Med. 2023 Mar 30;388(13):1161-1171.
3. ClinicalTrials.gov. Azithromycin-Prevention in Labor Use Study (A-PLUS). Identifier: NCT03871491.