Risk factors for impaired motor development in late preterm infants: A prospective cohort study

Background. Approximately 11.1% of children are born prematurely each year. Advances in modern neonatal care technologies have significantly improved the survival rates of newborns, including preterm infants, over the past few decades. However, despite the annual decrease in infant mortality, high risks of developing central nervous system pathologies among preterm infants still exist, including motor impairments, with cerebral palsy among them. Currently, the options for specific treatment of hypoxic perinatal lesions of the central nervous system in preterm infants are limited. Consequently, drawing up rehabilitation programs for preterm infants who have undergone neonatal resuscitation, taking into account diagnostic criteria, remains a pressing issue. 

Objectives. To determine the incidence of motor impairments in late preterm infants requiring neonatal intensive care by 18 months of corrected age, considering the levels of matrix metalloproteinase-2 (MMP-2) in serum at 40 weeks postmenstrual age.

Methods. A prospective cohort study was conducted on the basis of Children’s Regional Clinical Hospital, Krasonodar, Russia. Out of 215 preterm neonates born at 34–36 weeks of gestation who required intensive care after birth, 136 children with either high or low levels of matrix metalloproteinases-2  at 40 weeks postmenstrual age were included in the study. Group 1 consisted of 44 children with a matrix metalloproteinase-2 level greater than 350 ng/mL, while Group 2 comprised 92 children with a matrix metalloproteinase-2 level less than 160 ng/mL. The study assessed pregnancy history, delivery, neonatal period, neurological status, and neuroimaging data (neurosonography). At 18 months of corrected age, motor development was evaluated based on the Infant Neurological International Battery (INFANIB) score.

Results. No significant differences were observed in the course of pregnancy, delivery, neonatal period, or symptoms of perinatal lesions of the nervous system between the study groups, except for the incidence of chronic fetoplacental insufficiency (Group 1 — 81.8%, Group 2 — 42.4%, p < 0.05). No significant differences in neurological status at 40 weeks postmenstrual age were noted between the groups. Neurosonography revealed periventricular ischemia in all cases, while intraventricular hemorrhages and periventricular leukomalacia were more frequently recorded in Group 1 (intraventricular hemorrhages: Group 1 — 63.6%, Group 2 — 32.6%, p < 0.05; p < 0.05; periventricular leukomalacia: Group 1 — 40.9%, Group 2 — 15.2%, p < 0.05). Significant differences in motor development levels were identified by 18 months of corrected age. Cerebral palsy (68 points or fewer on the INFANIB scale) developed in 25% of Group 1 and in 3.3% of Group 2 (p < 0.05). Delayed motor development (69–81 points) was observed in 54.6% of Group 1 and in 27.2% of Group 2 (p < 0.05), while normal motor development (82 points or more) was recorded in 20.4% of Group 1 and in 69.5% of Group 2 (p < 0.05). Additionally, a statistically significant inverse correlation was of moderate strength according to Cheddok (ρ = –0.366; p < 0.001). In late preterm infants requiring intensive care after birth, those with high levels of MMP-2 at 40 weeks postmenstrual age were seven times more likely to develop cerebral palsy by 18 months of corrected age compared to those with low levels of MMP-2; they also experienced twice the incidence of delayed motor development and three times less frequent normal motor development.

Conclusion. The determination of matrix metalloproteinase-2 levels in serum at 40 weeks postmenstrual age will support the strategy for early intervention in cases of elevated matrix metalloproteinase-2 levels. This strategy will include dynamic monitoring by a neurologist and a comprehensive set of intensive rehabilitation measures (early initiation of active and passive kinesiotherapy, physiotherapy interventions, and, if necessary, pharmacological correction).

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