Purpose : Despite improvements in preterm neonatal care, the incidence of bronchopulmonary dysplasia (BPD) has not decreased. Systemic glucocorticoids minimize BPD, but they may interfere with brain development. The impact of intratracheal budesonide along with surfactant on the incidence of BPD in extremely preterm infants is unknown. Methods: This two arm parallel pilot trial over a period of 18 months recruited extreme preterm (<28 weeks) and extreme low birth weight (ELBW) neonates who were diagnosed with severe RDS (respiratory distress syndrome). Neonates were randomly allocated to one of two groups (54 intervention and 55 control). Intratracheal surfactant and budesonide were administered to the intervention group, while surfactant alone was administered to the control group. Results: The study population had a mean gestational age of 26.1 ± 0.2 weeks and birth weight of 770.5 ± 31.5 grams. Death ( RR 0.65 [0.30-1.38]; p = 0.267) and combined BPD or death (RR 0.88 [0.73-1.06]; p = 0.211) exhibited a non-significant decreasing trend; however, a significant reduction in the combined outcome of severe BPD or death (RR 0.57(0.33-0.97);p=0.040) was observed in the intervention group. Conclusion: Intratracheal budesonide with surfactant administration is feasible . This may minimize severe BPD or death in extremely preterm infants with severe RDS without any harm.

Methylenetetrahydrofolate reductase (MTHFR) deficiency is a rare autosomal recessive inherited inborn error of metabolism, which presents with various severity depending on the level of residual enzyme activity. In neonates, it can present with recurrent hypoventilation episodes, persistent encephalopathy with or without microcephaly. MTHFR deficiency also results in hyperhomocysteinemia, homocystinuria and hypomethionemia. We report a male neonate with severe MTHFR deficiency presenting to us on third week of life with progressive encephalopathy, microcephaly, seizures, central hypoventilation. There was similar history in the previous sibling. The patient’s blood lactate, ammonia, tandem mass spectrometry for amino acids and acyl carnitine were normal. He remained encephalopathic with progressive increase in need of respiratory support in spite of supportive treatment and metabolic cocktail consisting of riboflavin, pyridoxine, coenzyme Q and carnitine. This neonate had novel homozygous mutation, which results in MTHFR deficiency. In newborn with hypoventilation or recurrent apnoea with encephalopathy and microcephaly, MTHFR deficiency should be considered as a differential diagnosis. Mutation study helps in confirming diagnosis; however, extended newborn metabolic screening with homocysteine level could help in early diagnosis of these cases.