Glycerin Suppositories to Reduce Jaundice in Premature Infants

NCT ID: NCT01746511

Last Updated: 2015-12-09

Study Results

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

NA

Total Enrollment

79 participants

Study Classification

INTERVENTIONAL

Study Start Date

2012-07-31

Study Completion Date

2013-09-30

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Idiopathic Hyperbilirubinemia Neonatal Hyperbilirubinemia Prematurity

Keywords

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glycerin suppositories glycerin shaves neonatal hyperbilirubinemia idiopathic hyperbilirubinemia jaundice neonatal jaundice prematurity

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

TRIPLE

Participants Investigators Outcome Assessors

Study Groups

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Glycerin Suppository

Based on our institution's protocol, infant will receive a glycerin shave within one hour of initiation of phototherapy and then every eight hours while under phototherapy.

Subjects will be block randomized (varying block sizes of 2 to 8). Babies in both groups will be fed according to NICU standard birth weight protocols. Stratified enrollment will occur with 2 separate groups:

1. Infants who are NPO (\< 20 mL/kg/day of fluids enterally at the time of therapy) vs.
2. Those being enterally fed at least 20 mL/kg/day of total fluids at the time of therapy.

Group Type ACTIVE_COMPARATOR

Phototherapy

Intervention Type PROCEDURE

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.

glycerin suppository

Intervention Type DRUG

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.

No Glycerin Suppository

Infants will receive no scheduled glycerin suppositories, while under phototherapy (unless otherwise directed by attending physician).

Subjects will be block randomized (varying block sizes of 2 to 8). Babies in both groups will be fed according to NICU standard birth weight protocols. Stratified enrollment will occur with 2 separate groups:

1. Infants who are NPO (\< 20 mL/kg/day of fluids enterally at the time of therapy) vs.
2. Those being enterally fed at least 20 mL/kg/day of total fluids at the time of therapy.

Group Type EXPERIMENTAL

Phototherapy

Intervention Type PROCEDURE

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.

Interventions

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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.

Intervention Type PROCEDURE

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.

Intervention Type DRUG

Other Intervention Names

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Bili light glycerin shave

Eligibility Criteria

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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.
Minimum Eligible Age

30 Weeks

Maximum Eligible Age

35 Weeks

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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University of Rochester

OTHER

Sponsor Role lead

Responsible Party

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Carl D'Angio

Associate Professor of Pediatrics, Neonatology and Medical Humanities; Director, Neonatal Clinical Research; Director, Pediatric Clinical Research Office

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Meggan Butler-O'Hara, RN, MSN, PNP

Role: PRINCIPAL_INVESTIGATOR

University of Rochester

Locations

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University of Rochester Medical Center NICU

Rochester, New York, United States

Site Status

Countries

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United States

References

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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.

Reference Type BACKGROUND

Rosta J, Makoi Z, Kertesz A. Delayed meconium passage and hyperbilirubinaemia. Lancet. 1968 Nov 23;2(7578):1138. doi: 10.1016/s0140-6736(68)91603-6. No abstract available.

Reference Type BACKGROUND
PMID: 4177180 (View on PubMed)

Porto SO. Jaundice in congenital malrotation of the intestine. Am J Dis Child. 1969 Jun;117(6):684-8. doi: 10.1001/archpedi.1969.02100030686011. No abstract available.

Reference Type BACKGROUND
PMID: 5771508 (View on PubMed)

Jirsova V, Janovsky M. Hyperbilirubinemia connected with parenteral administration of higher amounts of fluids in premature infants. Biol Neonate. 1978;33(3-4):132-4. doi: 10.1159/000241062.

Reference Type BACKGROUND
PMID: 98182 (View on PubMed)

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. doi: 10.1016/s0022-3476(85)80418-2.

Reference Type BACKGROUND
PMID: 4056981 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 3646618 (View on PubMed)

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. doi: 10.1055/s-2005-871529.

Reference Type BACKGROUND
PMID: 16118723 (View on PubMed)

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. doi: 10.1001/archpedi.1983.02140330050013.

Reference Type BACKGROUND
PMID: 6858980 (View on PubMed)

Chen JY, Ling UP, Chen JH. Early meconium evacuation: effect on neonatal hyperbilirubinemia. Am J Perinatol. 1995 Jul;12(4):232-4. doi: 10.1055/s-2007-994460.

Reference Type BACKGROUND
PMID: 7575822 (View on PubMed)

Amin, S. (2011). Personal communication.

Reference Type BACKGROUND

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.

Reference Type BACKGROUND
PMID: 19171584 (View on PubMed)

Other Identifiers

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RSRB00040723

Identifier Type: -

Identifier Source: org_study_id