NeoLifeS is a cohort follow up study that prospectively collects data of regular care of children born preterm in the University Medical Center Groningen (UMCG) and aims to improve the quality of care for these children.

NeoLifeS-Heart is a sub-study that focuses on the problem that a high proportion of preterm infants develop cardiovascular disorders. Related to the immaturity of their lungs, preterm infants are at risk to develop the condition Bronchopulmonary dysplasia (BPD). Also, the vasculature of the lungs is often not fully developed, making them more vulnerable for the development of Pulmonary Hypertension (PH), a high blood pressure in the lungs. 15-20% of the infants with extremely low birth weight are believed to develop PH, this proportion has been suggested to raise to 50% in infants with severe BPD. The presence of PH significantly worsens the prognosis and survival of these children.

The condition PH is insufficiently characterized. Knowledge of incidence, prevalence, risk factors for the development of PH and survival, will be the first step in improving detection strategies, possible treatment options and thereby prognosis and survival of these children.

Objective: To determine the incidence and prevalence of PH in preterm infants. In addition we aim to identify risk factors for the development of PH and determine the survival and prognosis of these preterm infants.

Study design: A prospective cohort study. Study population: All preterm infants, admitted at the neonatology UMCG, born <30 weeks and/or birth weight < 1000 gram, who participate in NeoLifeS Primary parameters: The occurrence of PH (Incidence and Prevalence).

Secondary parameters:

• Maternal and neonatal patient characteristics that are potential risk factors for the development of PH,
• Morbidity-score (quality of life and hospital admissions) and mortality.

Background:

The development is not complete in premature born children. For example, the lungs are not fully developed. This is associated with shortness of breath and an increased oxygen need. Some of these children will need ventilation support and develop the condition Bronchopulmonary dysplasia (BPD). BPD is considered with lung injury and more than 28 days of ventilation support. These children have more need for oxygen and are extra sensitive for infections. In the present era, BPD most often occurs in extremely premature infants born at 24-28 weeks' post menstrual age, who have showed less severe acute respiratory symptoms and require less respiratory support than BPD patients have traditionally had in the past. Histological examination of these 'new BPD' patients suggests that the extreme preterm birth in combination with perinatal lung injury affects the normal growth of the lung development, resulting in disrupted vascular growth and impaired alveolarization, which could result in PH, a high blood pressure in the lungs. The causal relation among prenatal factors, prematurity, BPD and PH are not fully known yet. In premature newborns, < 30 weeks, the prevalence of BPD has been estimated to be 30-60% , while the prevalence of occurrence of PH received significantly less attention and estimates vary from 18% in the total group and up to 30% in the BPD-group and 50% in the severe BPD-group. The development of PH complicates the postnatal course of extreme premature infants. Both early and late PH are associated with poor outcomes among preterm infants, with and without BPD. Recent reports suggests that morbidity and late mortality of PH in the 'new BPD' is high, with up to 48% mortality 2 years after diagnosis of PH. The pathogenesis of BPD is complex and known risk factors for the development of severe BPD includes maternal and neonatal factors, such as childbearing history, male gender, smoking mother during pregnancy, chorioamnionitis, low-birth-weight, gestational age, cholestasis and acute lung injury by high ventilator settings. Risk factors for the development of PH in extreme preterm infants are not well defined. Knowledge of prevalence and risk factors of PH in extreme premature infants will allow evidence-based screening guidelines for the infants. Also potentially leading to prevention of this complicating condition in the future, since an earlier intervention will be possible under guidance of known risk factors. Early detection will lead to early and thus potentially better treatment of PH in preterm born infants.

Objective of the study:

Primary:

To identify the incidence and prevalence of PH in premature born infants with and without BPD in the first year of life.

Secondary:

To identify risk factors for the development of PH in these patients To characterize morbidity and survival of these patients during the first 2 yrs of life.

Study design:

Prospective Observational Cohort study. Inclusion 2016-2018, Follow up for standardized care (including QoL) at: 6, 12 and 24 months corrected age.

For Neolifes-Heart: echocardiography and transcutaneous oxygen measurement will be performed at: 1) first week after birth, 2) 3 months corrected age, 3) 12 months corrected age.

Study population:

All premature infants, admitted at the neonatology UMCG, born <30 weeks or birth weight < 1000 gram, who participate in NeolifeS. Only children whom parents have given written informed consent are included in this study.

Primary study parameter:

The echocardiographic presence of PH (incidence and point-prevalence).

Secondary study parameters:

Morbidity, Mortality: Quality of life questionnaire and survival. Maternal factors: mode of conception, delivery, preterm premature rupture of membranes (PROM), maternal disease history, illnesses during gestation, tabacco and medication use. Perinatal variables: slow growth patterns in utero, prenatal echo findings, PROM, chorioamnionitis, oligohydramnios, birth events, placental histology. Neonatal variables: development of BPD, low birth weight, gestational age, skull circumference, pulmonary and artificial ventilation variables, oxygen need, presence of persistent arterial duct (PDA), medication, infections, renal function, complications (NEC), slow growth at gestational age (GA) 36wks and at discharge. other: demographics, slow growth, admissions, medication, feeding, neurological development, respiratory symptoms, lung clearing index.

Inclusion Criteria:

• All premature infants born <30 weeks or <100 gram
• admitted at the neonatology UMCG,
• participation in the study Neolifes

Exclusion Criteria:

• no informed consent

All premature infants, admitted at the neonatology UMCG, born <30 weeks or birth weight < 1000 gram, who participate in NeolifeS

Only in case of clinical need, the data of the echocardiograph will be available.