Achieving optimal enteral feeding is crucial for the growth of the newborn, and delay in establishing full enteral feed is associated with adverse short term and long term outcomes [1]. Advancement of enteral nutrition in preterm neonates is hampered by gastric residuals and feeding intolerance. Gastrointestinal hypomotility and non-development of coordinated peristalsis are the postulated reasons for feeding intolerance [2-5].

Various feeding strategies (like trophic feeding and slow feeding advancement), medications (like antenatal steroids and prokinetics), and meconium evacuation are used to improve feeding intolerance [6-9]. Immature intestinal motor mechanism and neurotransmitter system is considered to be responsible for delay in passage of meconium in preterm infants. Retained thick tenacious meconium leads to functional obstruction, abdominal distension, gastric residuals and feeding intolerance [10-12]; and total meconium evacuation may improve feeding volume [11,13,14]. We hypothesized that glycerin suppository – by acting as osmotic laxative – will facilitate early meconium evacuation and accelerate feed tolerance and advancement in preterm very-low-birthweight (VLBW) neonates. Our specific objective was to compare the efficacy of glycerin suppository versus no glycerin suppository in preterm VLBW neonates on time required to achieve full enteral feeds.

This randomized controlled trial was conducted in a Level III neonatal unit in Mumbai, India from March 2010 to April 2011. The study was approved by the hospital’s Academic research ethics committee. Infants were enrolled after obtaining written informed consent from parents or legal guardians.

Infants admitted to neonatal intensive care unikt (NICU) on day-1 of life, with a birthweight between 1000 to 1500 grams, and gestational age between 28 to 32 weeks were eligible for inclusion in the study. Infants with gastrointestinal or other systemic malformations were excluded. Infant with hemodynamic instability and features of shock were also excluded.

Standards of care of infants in the NICU did not change throughout the study period. Grading up of intravenous fluids, parenteral nutrition and starting of trophic feeds was done as before as per the standard protocol of the unit. The regimen of parenteral nutrition used for both groups remained same and it consisted of solution of 10% dextrose, amino acids and electrolytes. Parenteral nutrition was started on day-2 of life in all infants and advanced daily to meet each infant’s total estimated fluid and nutritional requirements.

The primary outcome was time required by the infant to achieve full enteral feeds. (when the infant tolerated a volume of 180 mL/kg/day for at least 24 hours). Secondary outcomes were: time required to regain birth weight, age of achieving a weight of 1700 grams, necrotizing enterocolitis (Bell classification) [15], proportion of infants in whom feeds were withheld for any reasons, and age at the time of discharge from hospital. All infants were followed up till the time of discharge from the hospital or transfer to other hospital. All the data were recorded in predesigned study case record forms.

Sample size was calculated by using the formula for the hypothesis of 2-parallel sample means. In our unit, with the existing feeding practices, the average time taken by an infant with birth weight of 1000 to 1500 gram to reach full feeds was 15 days (SD 3 days). We hypothesized that the glycerin suppository group will reach full feeds by day 12 of life. For a difference of 3 days, with an error of 0.05 and power 90%, the estimated sample size was 22 in each group. To account for loss to follow up, 25 infants were to be enrolled in each group.

Data were analyzed by using IBM SPSS version 18 software. Categorical variables were compared using the Fisher’s exact test. Continuous measures between groups were compared using two sample t test or Mann-Whitney U test as appropriate. P value <0.05 was considered significant.

The flow chart of participants in the study is presented in Fig. 1. A total of 50 infants were randomized; 25 to glycerin suppository group and 25 to control group.

Fig.1 Flow of participants in the study.

The baseline clinical and demographic characteristics of the two study groups were similar (Table I). Table II depicts the outcomes in the two study groups. The time required to reach full enteral feeds was similar in both groups. Glycerin suppository group regained birth weight 2 days earlier than control group but this difference was not statistically significant. The age of achieving a weight of 1700 grams, proportion of infants with NEC, proportion of infants in whom feeds were withheld, and age at discharge from hospital were similar in both study groups.

TABLE I	Baseline Demographic and Clinical Characteristics of The Study Participants

TABLE II  Comparison of Outcomes in Glycerine Suppository vs. Control Groups

In this randomized controlled trial on 50 VLBW neonates, we could not detect any difference in time required by the infant to achieve full enteral feeds in children receiving glycerin suppository and those not receiving it.

We did not enroll infants <1000 grams in our study because of perceived risk and difficulty in administering 1g infant glycerin suppository in this population. The main limitations of our study was the assessment of only short term outcomes. Moreover, our study was not powered for outcomes like NEC. We calculated sample size for 3 days reduction in time required to reach full enteral feeds. A smaller reduction that may still be clinically meaningful may have been missed as it requires a large sample size.

Shim, et al. [4], in an observational study, reported a significant reduction in time to achieve full enteral feeds. A recent randomized controlled trial by Khadr, et al. [1] showed that the median time to full feeds was 1.6 days shorter in glycerin suppository group; however, it was not statistically significant. Haiden, et al. [6] used gastrografin osmotic contrast for evacuation of meconium in preterm infants, and observed that the median time to reach full enteral feedings was shorter in intervention group as compared to control group. Two systematic reviews evaluating glycerin suppository for meconium evacuation did not report any benefit on feeding intolerance or hyperbilirubinemia [16,17]. It may be possible that glycerin application every 24 hour until complete achievement of full feeds may be too low to be efficient. A more frequent application (e.g.12 hourly) or higher dose may be more effective in accelerating meconium evacuation [18]. It is also possible that meconium evacuation cannot be accelerated by suppositories because rapid and sufficient meconium passage indicates a correct functionality of the digestive tract.

IIn conclusion, once daily application of glycerin suppository does not seem to offer any advantage in premature infants in terms of accelerating achievement of full enteral feeding.