Prematurity and respiratory outcomes program (PROP): study protocol of a prospective multicenter study of respiratory outcomes of preterm infants in the United States

Abstract

Background: With improved survival rates, short- and long-term respiratory complications of premature birth are increasing, adding significantly to financial and health burdens in the United States. In response, in May 2010, the National Institutes of Health (NIH) and the National Heart, Lung, and Blood Institute (NHLBI) funded a 5-year $18.5 million research initiative to ultimately improve strategies for managing the respiratory complications of preterm and low birth weight infants. Using a collaborative, multi-disciplinary structure, the resulting Prematurity and Respiratory Outcomes Program (PROP) seeks to understand factors that correlate with future risk for respiratory morbidity.

Methods/design: The PROP is an observational prospective cohort study performed by a consortium of six clinical centers (incorporating tertiary neonatal intensive care units [NICU] at 13 sites) and a data-coordinating center working in collaboration with the NHLBI. Each clinical center contributes subjects to the study, enrolling infants with gestational ages 23 0/7 to 28 6/7 weeks with an anticipated target of 750 survivors at 36 weeks post-menstrual age. In addition, each center brings specific areas of scientific focus to the Program. The primary study hypothesis is that in survivors of extreme prematurity specific biologic, physiologic and clinical data predicts respiratory morbidity between discharge and 1 year corrected age. Analytic statistical methodology includes model-based and non-model-based analyses, descriptive analyses and generalized linear mixed models.

Discussion: PROP incorporates aspects of NICU care to develop objective biomarkers and outcome measures of respiratory morbidity in the <29 week gestation population beyond just the NICU hospitalization, thereby leading to novel understanding of the nature and natural history of neonatal lung disease and of potential mechanistic and therapeutic targets in at-risk subjects.

Trial registration: Clinical Trials.gov NCT01435187.

Figures

Figure 1

Prematurity and Respiratory Outcomes Program (PROP) Structure and Logo.

Figure 2

PROP Study Protocol Time Line spans from birth to one year of corrected age collecting health data and biospecimens. *Tracheal aspirate samples were collected if the infant was intubated and clinically required suctioning. #Physiologic challenge testing was either from oxygen to room air (21% oxygen, the “Room Air Challenge”) or from room air to 15% oxygen (“hypoxia challenge”) depending on status. NIRA: Non-invasive respiratory assessment; GERD: gastroesophageal reflux disease; iPFT: infant pulmonary function testing.

Figure 3

Non-Invasive Respiratory Assessment (NIRAs) Decision Diagram. The indicated oxygen reduction tests and respiratory inductive plethysmography (RIP) (with associated tests of oxygen saturations during sleep and oral feeding) were preformed on individual days determined by corrected age, degree of respiratory support required and anticipation of hospital discharge.

Figure 4

PROP Consort Diagram. * ‘Other’ reasons for not approaching parents for consent included maternal age and comprehension (9), parents objected to being approached for research (8), baby transferred less than 7 days (3), and screening oversight (3). ** ‘Other’ reasons for failure to consent included: language barrier (9), parent(s) overwhelmed (8), maternal illness (5), aged out prior to consent (4), baby died between consent discussion and decision (2), maternal comprehension (2), baby Illness (1).