Effects of Anesthesia and Surgery on the Morphologic and Functional Development of the Premature Neonatal Brain: A Systematic Review and Meta-Analysis.

The percentage of preterm infants requiring surgery before 44 weeks of postmenstrual age (PMA) varies between 19% and 36%. The potential impact of general anesthesia on the vulnerable developing brain of preterm infants remains unknown. A systematic review and meta-analysis on the impact of general anesthesia on brain integrity and neurodevelopmental outcomes in preterm infants undergoing surgery before 44 weeks PMA was conducted. Studies were identified via a PubMed, EMBASE (Ovid), and Cochrane CENTRAL search conducted from inception until 8 March 2023, following PRISMA guidelines. Brain abnormality was assessed using MRI-based brain volume and abnormality scores. Neurodevelopment was evaluated through Bayley Infant and Toddler Development (BSID) or Wechsler Preschool and Primary Scale of Intelligence (WPPSI) tests. Quality was assessed via the Cochrane ROBINS-I tool and GRADE. Our systematic search identified 2883 records, leading to the inclusion of 12 observational studies. Very low-quality evidence suggests that preterm infants exposed to anesthesia were more likely to show postoperative brain abnormalities on MRI (OR 2.01, 95%CI 1.24-3.25, = 0.005). They had lower neurodevelopmental scores on the BSID II and III (psychomotor developmental index: mean difference (MD) -10.98; 95%CI -12.04 to -9.91; < 0.001 and cognitive composite score: (MD) -10.11; 95%CI -11.06 to -9.16; < 0.001 at two years of age compared to preterm infants not exposed to anesthesia. Exposure to surgery and anesthesia before term age is associated with brain abnormalities and neurodevelopmental delay at two years, but conclusions are limited by low evidence quality, uncontrolled confounders, and the methodological biases of the included studies; thus further robust studies are required (PROSPERO:CRD42021255907).