SIP Cohort

Background: Infants born preterm may develop conditions that place them at higher risk for short-term health problems, long-term neurological complications, and even death. In high-income countries, most infants born preterm survive, but in the poorest regions of the world, babies born preterm are at very high risk of death; in the first month of life up to half may die. Few studies to date have examined the specific conditions that lead to death among preterm babies in low-income countries. Data collected in this study can be used to help plan interventions to reduce deaths among preterm infants.

Objectives: The primary objective of the study was to determine the most common causes of illness and mortality in preterm infants admitted to hospitals in Ethiopia. Secondary objectives included:

To determine the proportion of positive blood and cerebral spinal fluid cultures among preterm infants with a final diagnosis of sepsis
To determine the proportion of radiological findings consistent with RDS
To determine the proportion of head ultrasound findings consistent with intraventricular haemorrhage
To determine maternal/obstetric risk factors that are associated with preterm birth and mortality in preterm infants
To classify preterm infants based on gestational age (GA) and birth weight (if known) as extremely preterm (< 28 weeks) very preterm (28-32 weeks) preterm (32-37 weeks) in relation to the cause of death, to understand the GA where most of the deaths are concentrated and the corresponding birth weight if known
To compare the clinical final diagnosis of preterm infants that die with the results from the diagnosis obtained by standard autopsy and Minimally Invasive Tissue Sampling (MITS)

Methodology:

Geographic Location/Study Sites: 5 hospitals in 3 different regions of Ethiopia - Tikur Anbessa Hospital, Ghandi Memorial Hospital, and St Paul Hospital in Addis Ababa; Gondar University Hospital in northern Ethiopia; and Jimma University Hospital in southwest Ethiopia

Dates of Data Collection: July 2016 to June 2018

Study Design: Longitudinal cohort of preterm infants

Eligibility Criteria: The participants must have met the following

Inclusion criteria:

Mother delivered at or baby transferred to one of the participating study hospitals
Gestational age is <37 weeks as estimated with an algorithm using ultrasound, last menstrual period, or new Ballard Score
Live born defined as cry, breathing or movement after delivery or Apgar ≥ 1
Infant age is < 7 days when screened
Consent given for study participation

Exclusion criteria

Delivery is a result of an induced abortion
Gestational age cannot be reliably determined using study criteria

Data Collection: Participants were enrolled either when 1) a woman who had been seen for antenatal care in the study hospital went into preterm labor, and the infant was born alive at the study hospital or home, 2) a woman who came in preterm labor to the study hospital (either from home or referred from another health facility) delivered a live infant, or 3) a woman who delivered a preterm infant at home or in another hospital brought her infant to the NICU at < 7 days of life. Socio-demographic, obstetric, and maternal factors were collected at enrollment. Healthy infants underwent a physical examination and were discharged home. Infants admitted to the NICU were evaluated at least twice daily by a nurse while in the NICU, and clinical information and laboratory test results were documented. Upon discharge from the NICU, final diagnoses were recorded. Infants discharged alive were followed weekly by phone and face to face meetings (at least once) until the age of 28 days. Vital status was collected at each observation, and anthropometric measurements were collected at face to face visits. For infants who died, parents were asked whether they would consent to a post-mortem examination, either a whole body diagnostic autopsy or minimally invasive tissue sampling (MITS). The relevant clinical, laboratory, and autopsy data was made available for a panel of experts to evaluate cause of death.

Study Documentation:

Study protocol

Manual of Operations and Procedures
Pathology checklist

Data collection forms

Form 01: Eligibility
Form 02: Obsetetrics
Form 03A: Healthy newborn
Form 03B: NICU admission
Form 04: NICU monitoring
Form 05: Follow-up
Form 06: NICU discharge and final diagnosis
Form 08: Autopsy
Form 09: Microbiology results
Form 12A: Certification of cause of death by senior doctor
Form 12B: Certification of cause of death by panel

Consent forms

General consent form (in Amharic)
Autopsy consent (in Amharic)

ClinEpiDB Data Integration: Data files were provided to ClinEpiDB as flat csv files. Redundant or administrative columns were dropped from presentation on ClinEpiDB.org. All dates were obfuscated per participant through the application of a random number algorithm that shifted dates no more than seven days to comply with the ethical conduct of human subjects research.

Acknowledgements: We thank the administrative, clinical, nursing, microbiology, and pathology staff of all study hospitals. The following individuals worked as panel of experts and we would like to acknowledge their contributions: Riccardo Pfister (neonatologist) from University of Geneva, Switzerland, Robert Goldenberg (obstetrician) from Columbia University, USA, Sangappa M Dhaded (neonatologist) from KLE University's J N Medical College, India, Damte Shimelis and Ayalew Moges (pediatricians) from Addis Ababa University, Ethiopia, Hailu Berta (neonatologist) from Zewditu Hospital, Ethiopia, and Melisachew Mulatu Yeshi (pathologist) from Makelle Hospital, Ethiopia.

Financial Support: This study was funded by grants from the Bill & Melinda Gates Foundation (OPP1136965).

Ethics Statement: This study protocol was approved by the ethical review committees of participating institutions (Addis Ababa University, Jimma University and the University of Gondar, Ethiopia). Informed consent was obtained from all participants.

Last updated: March 2, 2021A longitudinal cohort study of preterm birth was conducted in 3 different regions of Ethiopia. Preterm infants <7 days old were enrolled and followed over the first 28 days of life or until death. Infants in the NICU were followed twice daily while infants discharged home were followed weekly. Autopsy or MITS was performed for infants who died with parental consent.