Glycerin Suppositories to Reduce Jaundice in Premature Infants

Neonatal jaundice is one of the most common clinical problems in the neonatal period (Maisels). Physiologic hyperbilirubinemia is usually benign and transient in nature. Bilirubin overproduction, delayed hepatic clearance, and increased enterohepatic circulation of bilirubin all contribute to neonatal jaundice (Bader). Previous studies have shown that delayed meconium evacuation might be an important contributing factor in the development and persistence of neonatal jaundice (Rosta and Porto). Once conjugated bilirubin is excreted from the liver to the small intestine, it is often deconjugated in the presence of alkaline media and beta-glucorinase enzymes which are present in abundance in premature infants. Once deconjugated, unconjugated bilirubin is reabsorbed leading to entero-hepatic circulation, which plays a significant role in the development on neonatal jaundice.

Previous studies have shown that early meconium evacuation was associated with lower total serum bilirubin levels and decreased risk for clinically significant neonatal jaundice (Jirsova, DeCarvalho, Boyer, Gourley, Salariya and Gourley). Other studies in healthy term neonates have shown no benefit from rectal glycerin in reducing peak serum bilirubin levels. Bader et al performed a prospective study to evaluate the general effect of glycerin suppository administration in reducing total serum bilirubin levels in healthy term neonates. Glycerin suppositories were given immediately after birth and every 4 hours thereafter, until evacuation of first stool. The suppositories had no effect on mean total serum bilirubin levels at 48 hours of age. It was concluded that glycerin suppositories should not be routinely recommended as a means for reducing the severity of neonatal jaundice. However, it was found that in a subgroup of male infants with blood group type A there were significantly lower mean total serum bilirubin levels after induction of earlier meconium evacuation with glycerin suppositories. Weisman et al performed a similar prospective study in healthy term neonates and found that giving glycerin suppositories does hasten the passage of meconium and transitional stool; however, there was no effect on peak serum bilirubin levels during the first 3 days of life and no effect on need for phototherapy. Chen et al described a prospective, randomized controlled trial with two groups of healthy term neonates. The experimental group received glycerin enemas at 30 minutes and 12 hours of life. Bilirubin levels were followed for the first 7 days of life. The intervention had no effect on peak serum bilirubin levels or serum bilirubin levels in the first 7 days of life.

No data exist on the use of glycerin suppositories in premature neonates, although its use is a common practice to increase meconium clearance and stooling in the case of hyperbilirubinemia. However, it may not be a justified practice, based on data for full-term infants. Experts argue that premature neonates may have upward of 25% more enterohepatic circulation than full-term neonates (S. Amin, personal communication). Therefore, because premature neonates have the potential to recirculate bilirubin, increasing stool frequency through schedule glycerin suppositories might play a therapeutic role in the management of hyperbilirubinemia in this population.

It is a common practice in our unit to provide glycerin suppositories every 8 hours to infants under phototherapy in an attempt to more rapidly reduce bilirubin levels by decreasing enterohepatic circulation of unconjugated bilirubin. This practice is not evidence-based, nor is it standard practice in many NICUs throughout the country. Glycerin suppositories are not without risk. They can lead to rectal fissures and tears, bloody stools and unnecessary vagal stimulation.

If administration of glycerin shaves decreases length of phototherapy to a clinically significant extent, there may be improved success with feedings including breastfeeding, improved infant-parent bonding, shortened length of stay and overall increased family satisfaction. However, if glycerin suppositories are not shown to reduce duration of phototherapy, reduce peak total serum bilirubin (TSB) levels, reduce the number of TSB levels drawn and increase the rate of decline of hyperbilirubinemia, then a potentially useless therapy with potential for untoward side effects may be avoided.

Inclusion criteria

• Baby born between 30 to 34 6/7 weeks gestational age (GA) at birth and admitted to NICU
• Baby with physiologic hyperbilirubinemia requiring phototherapy by current NICU criteria.
• Parental permission.

Exclusion criteria

• Babies less than 30 weeks GA or greater than 34 6/7 weeks GA
• Non-physiologic hyperbilirubinemia: (1) positive Coombs test and (2) hematocrit < 5th percentile for GA (see Jopling J, Henry E, Wiedmeier SE, Christensen RD, Reference. Ranges for Hematocrit and Blood Hemoglobin Concentration During the Neonatal Period: Data From a Multihospital Health Care System. Pediatrics 2009; 123(2):e333 -e337.) and (3) ABO or Rh incompatibility.
• Any infant with bilirubin level within 2 mg/dL of exchange transfusion.
• Any infant who has phototherapy started prior to reaching light level (prophylactic)
• Baby with any GI abnormalities such as NEC, intestinal perforation, gastroschisis, omphalocele, malrotation and or volvulus, duodenal atresia, intestinal strictures/adhesions, imperforate anus.
• Any infant begun on triple or greater phototherapy at time of initiation of treatment.
• Any infant judged by the attending physician to be placed at increased risk by study participation.