Neonatal morbidity and treatments and subsequent risk of developing cardiovascular diseases in childhood and early adulthood - an international population-based study.

Around 10% of all newborn infants receive treatments at neonatal intensive care units (NICUs), of which half are born preterm (=36 weeks) and half at term (=37 weeks). Due to highly specialized care at NICUs, neonatal mortality rates have substantially declined. This is especially true for preterm infants with high neonatal morbidity risks and also increased risks of cardiovascular morbidity later in life.

Little is known about long-term health consequences of neonatal morbidity and treatments, overall and in preterm infants. Currently, there is a paucity of high-quality research to guide much neonatal practice, leading to variation in both clinical care and neonatal outcomes. Objectives:

To fill the knowledge gap regarding neonatal morbidity and treatments and risks of cardiovascular diseases in childhood and early adulthood. We will use cutting edge epidemiological approaches in the analyses of uniquely rich population data sources available in Sweden and in British Columbia (BC), Canada. We propose to investigate:

1. The role of prenatal and neonatal complications (i.e. fetal growth restriction, neonatal morbidity, including asphyxia-related morbidity, and infections) on the development of cardiovascular diseases in children born preterm or term;

2. The role of neonatal treatments (i.e. antibiotic and respiratory treatments) on the development of cardiovascular diseases;

3. Whether associations between preterm birth and risks of cardiovascular diseases in childhood and early adulthood in children born preterm are mediated by neonatal morbidity or treatments;

4. Similar studies within full siblings, which by design controls for environmental and genetic factors shared by siblings. Work plan

Using registry information, we will include ˜3.1 million births from 1998-2020 in Sweden and BC, with information on birth characteristics, neonatal complications and treatments, and long-term cardiovascular outcomes. In BC we will have access to primary care data, not available in Sweden. This study will be the largest study ever conducted to examine such associations.

Significance:

As of all infants stay at NICUs and 5-12% of all infants are born preterm, addressing the evidence gap on neonatal interventions is likely to have broad application nationally and world-wide. Long-term outcome studies are imperative for subsequent NICU decision-making, intervention strategies and to enhance early identification of infants at at risk of cardiovascular diseases.