Saline Enema Administration in Meconium Obstruction of Prematurity and Impact on the Resolution, Feeds, Microbiome, and Gut-brain Axis.

Very low birth weight infants (VLBW ≤ 1.5 kg) constitute more than 60% of bed occupancy in level III neonatal units. They face the risk of 10-50% long-term disability, and their initial healthcare cost ranges from S$50,000 to 1 million, an important healthcare issue.

The incidence of meconium obstruction of prematurity (MOP) is 20-30% in extremely low birth weight (ELBW ≤ 1 kg) infants. The intervention based on the current standard of care increase the risk of laparotomy necrotizing enterocolitis, intestinal perforation, and neurodevelopmental risks posed by general anaesthesia. Our published pilot RCT demonstrated that saline enema (SE) is an effective, feasible, and safe intervention to reduce the time to reach full enteral feeds and is a potentially effective treatment for MOP in ELBW (< 1 kg) infants.

Our primary hypothesis is that Infants with Twice-daily high-volume SE (20-40 ml/kg/day) intervention will result in reduced time to reach full enteral feeds compared to infants treated with conventional management with Glycerin suppository (GS) in (≤1.25kg) infants with MOP. Our exploratory hypothesis is that SE will have a protective effect on the gut microbiome, inflammatory and immune response in preterm infants.

Ninety-five infants born over three years in KK Hospital (KKH) and Singapore General Hospital (SGH) will be enrolled and randomized at 48 hours or later to receive SE or GS. The standardized protocol will be used for the accreditation and administration of SE. Primary, secondary, and exploratory outcomes data, including treatment failure data, will be recorded. Infants will be followed up to 36 weeks of gestation or discharge, whichever is earlier. Maternal and infant characteristics, inflammatory and immune response, and safety outcome data will be collected.

If the findings of our pilot trial are confirmed, the protocol can become the standard of care in preterm infants with MOP. Additionally, significant healthcare cost savings will be realized alongside an improved understanding of the Microbiome, immune and inflammatory response pertaining to the gut.

Inclusion criteria

• Criteria A: For infant presenting with early onset of MOP

• Birth weight 500 - 1250 gram
• ≥ 23 weeks gestation
• No BO for 48 hours
• BO present but with a small amount or stain of meconium
• Feeds intolerance or abdominal X-ray showing dilated loops of bowel
• Criteria B: For infant presenting with Late onset of MOP

• Birth weight 500 - 1250 gram
• ≥ 23 weeks gestation
• Infants who passed meconium initially and develop evidence of meconium obstruction at a later age (feed intolerance or vomiting and abnormal abdominal X-ray with or without abdominal distension)

Exclusion criteria

Infants that:

• Neuromuscular disorder
• Moderate or severe asphyxia
• Inability to start enteral feeding, which continued for 3 consecutive days before 2 weeks of post-natal age for reasons unrelated to meconium inspissation or its complication
• Without parental consent
• Aggravated medical instability
• Single mothers < 21 years