Born just a few weeks early… is this relevant? : Insights into brain lesions, brain growth, and outcome in moderate-late preterm infants

Abstract

This thesis gives insights into neonatal brain injury, brain growth and neurodevelopmental outcome in moderate-late preterm (MLPT) infants, born at 32–36 weeks’ gestation. Additionally, we describe the neurodevelopmental outcome of preterm infants with cerebellar hemorrhage (CBH). In Chapter 2 we give an overview of the literature regarding brain injury and development in MLPT infants. Most frequently studied types of brain injury were intraventricular hemorrhage (IVH) and periventricular leukomalacia (PVL). Incidences of other forms of brain injury were sparsely reported. In addition, there is a lack of knowledge regarding the effect of brain injury on neurodevelopmental outcome in MLPT infants. In Chapter 3, we investigate current practice regarding neurological surveillance in MLPT infants in the Netherlands and Canada. We found variations in local practices regarding e.g. admission criteria, neuroimaging and follow-up. This may partially be explained by the lack of guidelines regarding care of MLPT infants. The above indicates that considerable knowledge about MLPT infants is still lacking. By conducting a prospective cohort study, we sought to fill some of the gaps in knowledge. The BIMP-study (Brain Imaging in Moderate-late Preterm infants) was performed between 2017-2019 at the Isala Women and children’s Center in Zwolle, the Netherlands. MLPT infants underwent cranial ultrasound and MRI. In the BIMP-cohort (n= 166), a high incidence of mild brain lesions (71.7%) was found. Frequent findings were signs suggestive of white matter injury, and small hemorrhages, including CBH. Moderate-severe brain lesions were seen in 3.6% of infants. We compared linear measurements of brain structures between MLPT and full-term infants. Biparietal diameter and basal ganglia width were smaller in MLPT infants. We found no differences in linear measurements or in brain volumes between moderate preterm (MP, 32+0–33+6 weeks) and late preterm infants (LP, 34+0–35+6 weeks). Mild brain lesions had no effect on brain volumes (Chapters 4, 5 and 6). In Chapter 7, we present a preliminary overview of the follow-up of 85 MLPT infants who have now reached 24 months of age. Almost one in three (30.6%) had an suboptimal outcome score. Given the descriptive nature of this overview and the fact that follow-up is still ongoing, we could not yet draw any further conclusions. In Chapter 8, we explore the association between the size and location of CBH in preterm infants ≤34 weeks (n = 218) and neurological outcome around two years of age. All infants with massive CBH and involvement of the vermis on neonatal MRI had a less favorable outcome. Infants with limited CBH had a more favorable outcome than infants with massive CBH. Although much research is still needed to provide strict recommendations, we advise the following based on our findings and the current literature: - Standard neuroimaging in MLPT infants does not seem warranted at present. - Use a low threshold for accepting MLPT infants in neurodevelopmental follow-up programs and interventions as they are at risk of neurodevelopmental and behavioral problems. - Assess CBH based on size and location. With a special note on vermian involvement.