What is the problem?

Babies born before their due date for delivery(preterm) and babies born small for gestational age (SGA) infants have 2-10 times higher risk of death than infants born at term and with normal birth weight, and are particularly vulnerable to infection, malabsorption, severe bowel infection, difficulty feeding, and growth failure. Improvements in outcomes in preterm and SGA infants have been slow in all countries, especially low- and middle- income countries (LMICs), due to the complexities of preventing complications and providing medical care for small and vulnerable infants.

What question are we trying to answer?

We aim to test the effect of probiotic supplementation on death, diseases, and growth in preterm or term SGA infants in the first 6 months of life in South Asia and Sub-Saharan Africa.

Where is the study taking place? 

The study will be conducted in five hospitals in Kenya namely; Migori County Referral Hospital, Homabay County Referral Hospital, Kisii Teaching and Referral Hospital and Jaramogi Oginga Odinga Teaching and Referral Hospital. Recruitment may also take place at St. Joseph’s Mission Hospital and Kendu Bay Mission Hospital. Other participating countries include Bangladesh, Pakistan, Ethiopia and Nigeria.

How many people does it involve and how are they selected?

The study will enroll 2,900 eligible infants in Kenya (14,000 across the 5 participating countries). Eligible infants include preterm (AGA or SGA) or term SGA infants, aged less than 48 hours at the time of enrollment and likely to be in the study area for the next 6 months. Infants who are less than 28 weeks gestation, not able to take orall feeds, confirmed blood stream infection at the time of enrolment, indwelling umbilical catheter/central venous line and multiple births (e.g., twins, triplets) will be excluded.

What does the study involve for those who are in it?

Study staff will ask the infant caregivers for their informed written consent to conduct the screening procedures (i.e., measure the infant’s weight, review the mother’s and infant’s hospital records and determine inclusion and exclusion criteria). Some infants (30%) will be randomly selected to provide stool sample at enrollment, day 7, week 4 and month 6 of age. Mothers of these babies will also be asked for a stool sample collected within 48 hours of giving birth. Randomized infants will receive the study supplements daily for 28 days and followed up monthly until month 6.

What are the benefits and risks of the study for those involved?

There is no direct benefit for taking part in the study, however, participants will receive examination and advice for treatment of illnesses. There is a small risk that the organisms in the probiotic could enter the blood stream and cause infection.

How will the study benefit society?

The study results will help answer important research questions about probiotics in preterm and SGA babies under six months.

When does the study start and finish?

Participant recruitment will begin after receipt of ethical and regulatory approvals and be completed within 28 months.

Preterm and small for gestational age (SGA) infants have a 2- to 10-fold higher risk of mortality than infants born at term and with normal birth weight, and are particularly vulnerable to infection, malabsorption, necrotizing enterocolitis, difficulty feeding, and growth failure. Numerous trials conducted in the last ten years have reported that probiotics can improve short- and long-term mortality, necrotizing enterocolitis and sepsis rates, and growth and neurodevelopment in preterm and low birth weight infants. However, most trials have been small and with high to moderate risk of bias. There have been no trials in SGA infants. The World Health Organization (WHO) guideline development group (GDG) and other organizations have recommended that further large high-quality trials are implemented to provide evidence of sufficient quality and applicability to inform policy and practice. The overall aim of this trial is to assess the effect of probiotic supplementation on mortality, morbidity, and growth in preterm or term SGA infants in the first 6 months of life in South Asia and Sub-Saharan Africa. The trial is a multi-country multi-centre individually-randomised double-blind parallel-group placebo-controlled superiority trial implemented in five countries: two in Asia (Bangladesh, Pakistan) and three in Africa (Ethiopia, Nigeria, Kenya). A total of 14,000 (2900 in Kenya) eligible infants will be enrolled across the 5 participating countries and randomly assigned to either the intervention or control group separately for the preterm and term SGA infants. Each randomized infant will receive the study supplements (probiotics or placebo) daily for 28 days and followed up monthly for primary and secondary outcome endpoint assessment by an independent outcome assessment team until the infant reaches 6 months of age. Endpoint data will also be collected on all infants admitted to study hospitals. Results from this trial will help inform policy and practice for probiotic supplementation in preterm and SGA infants, improve the certainty of evidence on critical outcomes and strengthen the understanding of optimal strains, dosing and duration of probiotic supplementation and related impact in high burden LMICs.