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:

1. Baby born between 30 to 34 6/7 weeks gestational age (GA) at birth and admitted to
NICU

2. Baby with physiologic hyperbilirubinemia requiring phototherapy by current NICU
criteria.

3. Parental permission.

Exclusion Criteria:

1. Babies less than 30 weeks GA or greater than 34 6/7 weeks GA

2. 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.

3. Any infant with bilirubin level within 2 mg/dL of exchange transfusion.

4. Any infant who has phototherapy started prior to reaching light level (prophylactic)

5. Baby with any GI abnormalities such as NEC, intestinal perforation, gastroschisis,
omphalocele, malrotation and or volvulus, duodenal atresia, intestinal
strictures/adhesions, imperforate anus.

6. Any infant begun on triple or greater phototherapy at time of initiation of
treatment.

7. Any infant judged by the attending physician to be placed at increased risk by study
participation.