Glycerin Suppositories to Reduce Jaundice in Premature Infants

Prematurity Clinical Trial

Official title:

The Use of Glycerin Suppositories to Reduce Hyperbilirubinemia in Premature Infants Requiring Phototherapy

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01746511
• Other study ID #: RSRB00040723
• Status: Completed
• Phase: N/A
• First received: October 8, 2012
• Last updated: November 4, 2015
• Start date: July 2012
• Est. completion date: September 2013

Study information

• Verified date: November 2015
• Source: University of Rochester
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to find out if giving glycerin suppositories will help decrease the length of time premature infants need phototherapy.

The investigators hypothesize that glycerin suppositories (initiated along with phototherapy) will have no effect on reducing duration of phototherapy in premature infants with jaundice.

Description:

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 79
• Est. completion date: September 2013
• Est. primary completion date: September 2013
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 30 Weeks to 35 Weeks

Eligibility

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.

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Hyperbilirubinemia
• Hyperbilirubinemia, Neonatal
• Idiopathic Hyperbilirubinemia
• Neonatal Hyperbilirubinemia
• Premature Birth
• Prematurity

Intervention

Procedure:
• Phototherapy
Light therapy is used to treat cases of neonatal jaundice through the isomerization of the bilirubin and consequently transformation into compounds that the newborn can excrete via urine and stools.

Drug:
• glycerin suppository
Promotes stooling through rectal stimulation and softening of stool. Given every 8 hours rectally. A pediatric glycerin suppository is 1.2 grams. All infants in this study arm will receive our standard dose of glycerin suppository which is 0.25 of the pediatric suppository or 0.3 grams.

Locations

Country	Name	City	State
United States	University of Rochester Medical Center NICU	Rochester	New York

Sponsors (1)

Lead Sponsor	Collaborator
University of Rochester

Country where clinical trial is conducted

United States, 

References & Publications (11)

Amin, S. (2011). Personal communication.

Bader D, Yanir Y, Kugelman A, Wilhelm-Kafil M, Riskin A. Induction of early meconium evacuation: is it effective in reducing the level of neonatal hyperbilirubinemia? Am J Perinatol. 2005 Aug;22(6):329-33. — View Citation

Boyer DB, Vidyasagar D. Serum indirect bilirubin levels and meconium passage in early fed normal newborns. Nurs Res. 1987 May-Jun;36(3):174-8. — View Citation

Chen JY, Ling UP, Chen JH. Early meconium evacuation: effect on neonatal hyperbilirubinemia. Am J Perinatol. 1995 Jul;12(4):232-4. — View Citation

De Carvalho M, Robertson S, Klaus M. Fecal bilirubin excretion and serum bilirubin concentrations in breast-fed and bottle-fed infants. J Pediatr. 1985 Nov;107(5):786-90. — View Citation

Jirsová V, Janovský M. Hyperbilirubinemia connected with parenteral administration of higher amounts of fluids in premature infants. Biol Neonate. 1978;33(3-4):132-4. — View Citation

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 Feb;123(2):e333-7. doi: 10.1542/peds.2008-2654. — View Citation

Maisels MJ. Jaundice. In: Avery GB, Fletcher MA, MacDonald MG, eds. Neonatology: Pathophysiology and Management of the Newborn. Philadelphia: Lippincott Williams and Wilkins; 1999:765-819.

Porto SO. Jaundice in congenital malrotation of the intestine. Am J Dis Child. 1969 Jun;117(6):684-8. — View Citation

Rosta J, Makói Z, Kertész A. Delayed meconium passage and hyperbilirubinaemia. Lancet. 1968 Nov 23;2(7578):1138. — View Citation

Weisman LE, Merenstein GB, Digirol M, Collins J, Frank G, Hudgins C. The effect of early meconium evacuation on early-onset hyperbilirubinemia. Am J Dis Child. 1983 Jul;137(7):666-8. — View Citation

* Note: There are 11 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Total Number of Hours of Required Phototherapy		from time of enrollment to time of discharge, for a maximum of 10 weeks	No
Secondary	Number of Episodes of Repeat Phototherapy	Bilirubin levels are checked at regular intervals after phototherapy is discontinued to make sure levels are safe. Depending on rate of rise and predetermined "unsafe" bilirubin level, phototherapy may be restarted.	from time of enrollment to time of discharge, for a maximum of 10 weeks	No
Secondary	Peak Total Serum Bilirubin Level	Bilirubin levels were checked every 12 hours while the infant was under phototherapy. A bilirubin level was then to be checked at least twice, 8-12 hours or longer apart, following discontinuation of phototherapy.	from time of enrollment to time of discharge every 12 hours while under phototherapy, for a maximum of 10 weeks	No
Secondary	Rate of Decline in Bilirubin Levels (mg/dL/hr)	Absolute change over time from peak to first discontinuation of phototherapy lights	from time of enrollment to time of discharge, for a maximum of 10 weeks	No
Secondary	Length of Initial Round of Phototherapy	time start to time finally off phototherapy, including any breaks during which they were off	from time of enrollment to time of discharge, for a maximum of 10 weeks	No