The goal of this clinical trial is to study the effect of twice-daily saline enema (SE) in the treatment obstruction of prematurity (MOP) in infants with the birth weight ≤1.25kg. The main questions, the trial aims to answer are
1. To validate the finding of our pilot study which had shown that twice-daily SE reduces the time to reach full enteral feeds in premature infant as compared to premature infant treated with Glycerine Suppository (GS), in a larger cohort. Infant with MOP fails to pass meconium in the first 48 hours of life and develop symptoms and signs like abdominal distension and feed intolerance. 2. The other aims of this study are to test whether the intervention is
1. Effective treatment for MOP 2. Reduce the duration of ICU stay 3. Reduce the rate of necrotizing enterocolitis, sepsis, Total Parenteral Nutrition (TPN) days and number of intravenous catheter days 3. The study also wants to explore the impact of this intervention on the gut microbiome, gut-brain interaction and immune response of the new-born.
Criteria A: For infant presenting with early onset of MOP
Birth weight 500 - 1250 gram
≥ 23 weeks gestation
No BO for 48 hours
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
Parallel
Saline Enema (SE)
Procedure/Surgeryinfant who allocated with intervention group will proceed with SE with normal saline (20-40ml/kg twice daily) at 48 hours of age. Then continue until 2 days of yellow stools/ 110ml/kg/day of oral feeds; whichever is earlier. SE are recommended if baby do not do bowel opening (BO) for 2 days before reaching full feeds Failure to resolve the MOP with SE will be designated as treatment failure and managed with contrast enema or Laparotomy by paediatric surgeons, following a formal referral.GS is not allowed in intervention arm
Glycerin Suppository
DrugInfants randomized to GS received the standard management protocol for meconium retention in the unit. GS (2,000 mg, a quarter unit, four doses 12 h apart) were administered to infants earliest at 48 hour to 72 hours of birth, with subsequent once-daily GS being administered at the discretion of the managing team. Infants who were diagnosed with meconium obstruction later in the first 2 weeks of life were also treated with glycerin suppositories for 48 hrs, with subsequent once-daily GS being administered at the discretion of the managing team. Infants who failed to respond to glycerin suppositories were referred to the surgical team by the managing team The subsequent management of meconium retention was at the surgeon's discretion and included continued GS by the surgical team, contrast enema or surgical interventions performed in escalating order as mentioned.
Time to reach full enteral feeds in days
Time to reach full enteral feeds is measured from birth to the time infant reaches full oral milk feeds. Full oral milk feed is defined as milk volume of 110ml/kg/day. The total parenteral nutrition is discontinued when infant reaches milk feed volume of 110ml/kg/day. Rationale: SE loosens the thick and sticky meconium by saline absorption and triggers effective and strong peristaltic contractions, thereby leading to the evacuation of meconium from the gut. The evacuation of meconium leads to the resolution of the gut obstruction, thereby enhancing feed tolerance in premature infants with meconium obstruction of prematurity.
Rate of treatment failure
Treatment failure is defined as the need to use additional treatment measures, apart from the study intervention to resolve MOP in the study cohort.
Rate of (a) Culture positive sepsis (b) Necrotising enterocolitis.
Rationale: If twice daily SE leads to the shortening of time to reach full enteral feeds, resolution of MOP, and promote friendly bacteria microbiome, then it has the potential to reduce NICU stay, risk of necrotising enterocolitis, risk of sepsis, duration of total parenteral nutrition, duration of PICC and overall cost of care.
Duration in days of (a) ICU stay (b) Total parenteral nutrition (c) PICC days.
Rationale: If twice daily SE leads to the shortening of time to reach full enteral feeds, resolution of MOP, and promote friendly bacteria microbiome, then it has the potential to reduce NICU stay, risk of necrotising enterocolitis, risk of sepsis, duration of total parenteral nutrition, duration of PICC and overall cost of care.
Overall cost of care calculated in SGD at the time of discharge
Rationale: If twice daily SE leads to the shortening of time to reach full enteral feeds, resolution of MOP, and promote friendly bacteria microbiome, then it has the potential to reduce NICU stay, risk of necrotising enterocolitis, risk of sepsis, duration of total parenteral nutrition, duration of PICC and overall cost of care.
Identification and quantification of bacteria from meconium/stool samples by DNA sequencing and analysis of top 50 bacteria Genus
Bacteria are identified from meconium/stools samples, collected at birth and weekly interval till discharge or 36 weeks of gestation
To measure the serum level of IL 6 in pg/ml
Use Olink Target 48 platform to measure Rationale: To explore the relationship between gut microbiome and gut-brain axis
To measure the serum level of neurotransmitters noradrenaline in pg/L
Use Norepinephrine ELISA Kit from abcam to measure
Measure serum levels of dopamine in arbitrary units (peak area of analyte divided by peak area of an internal standard)
Use Norepinephrine ELISA Kit from abcam to measure
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KK Women's and Children's Hospital
Lead sponsor
Singapore General Hospital
Collaborator
Genome Institute of Singapore
Collaborator
Translational Immunology Institute
Collaborator
Duke-NUS Graduate Medical School
Collaborator
