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 Table of Contents  
ORIGINAL ARTICLE
Year : 2021  |  Volume : 11  |  Issue : 4  |  Page : 167-171

Risk factors for feed intolerance in very low birth weight infants


Department of Neonatology, Sir Ganga Ram Hospital, New Delhi, India

Date of Submission02-Jul-2021
Date of Decision18-Jul-2021
Date of Acceptance28-Jul-2021
Date of Web Publication21-Aug-2021

Correspondence Address:
Prof. Satish Saluja
Department of Neonatology, Sir Ganga Ram Hospital, New Delhi
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/cmrp.cmrp_65_21

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  Abstract 


Background and Objectives: Very low birth weight (VLBW) neonates are at risk of feed intolerance (FI) and necrotising enterocolitis. We planned this study to evaluate the risk factors for FI in VLBW neonates.
Methods: Medical records of VLBW neonates admitted to the neonatal intensive care unit (NICU) during the study period were retrieved. Demographic and clinical characteristics of neonates with and without FI were studied. FI was defined as the presence of one or more of the following: Vomiting more than three times during the previous 24-h period, any episode of bile or blood-stained vomitus, an increase in abdominal girth of more 2 cm from baseline, abdominal wall erythema or tenderness, blood in stools. Factors associated with FI were identified by univariate analysis and those found significantly associated with FI were investigated using logistic regression analysis. Characteristics of neonates with Absent or reversed end diastolic doppler flow (AREDF), started on feeds within 24 h and after 24 h were also investigated.
Results: Of 129 VLBW neonates enrolled in the study, 72 (55.8%) neonates experienced FI during NICU stay. The mean (standard deviation) birth weights and gestation of neonates in FI and No-FI groups were 1075 (231) and 1265 (201) grams (P < 0.01) and 29.5 (2.1) and 31.2 (2.5) weeks (P < 0.01), respectively. On univariate analysis, birth weight, gestational age and male gender were significant risk factors associated with FI. On multivariate analysis, gestational age and male gender were independent risk factors for FI in VLBW neonates. Among neonates with AREDF, there was no difference in the incidence of FI in those initiated on feeds within 24 h, versus those initiated after 24 h; 47.4%, 69.2%, respectively (P = 0.14).
Conclusions: Lower gestation and male gender are significant risk factors for FI in VLBW infants. Early feeding <24 h in infants with abnormal Doppler flows is not associated with an increased risk of FI.

Keywords: Abnormal fetal Doppler flows, feed intolerance, very low birth weight infants


How to cite this article:
Fursule A, Modi M, Saluja S, Soni A. Risk factors for feed intolerance in very low birth weight infants. Curr Med Res Pract 2021;11:167-71

How to cite this URL:
Fursule A, Modi M, Saluja S, Soni A. Risk factors for feed intolerance in very low birth weight infants. Curr Med Res Pract [serial online] 2021 [cited 2021 Sep 25];11:167-71. Available from: http://www.cmrpjournal.org/text.asp?2021/11/4/167/324254




  Introduction Top


Nutrition plays an important role in the growth, development and survival of newborn infants. Early enteral feeding in neonates is associated with improved gut maturation, feed tolerance, fewer complications and better outcomes.[1],[2],[3],[4],[5],[6],[7],[8] Enteral feeds are often delayed in very low birth weight (VLBW) infants for the scare of feed intolerance (FI) and necrotising enterocolitis (NEC).[9] The reported incidence of FI in VLBW infants varies from 22% to 40%.[10],[11],[12],[13] The factors that contribute to FI include incompetent lower oesophageal sphincter, small gastric capacity, delayed gastric emptying time, intestinal hypomotility, theophylline therapy, sepsis, abnormal Doppler flow velocities in the foetal umbilical artery and suboptimal intestinal perfusion.[14],[15],[16],[17] FI is one of the predominant factors affecting the duration of hospitalisation in these infants.[18] We performed this study with the objective to identify the risk factors of FI in VLBW infants.


  Methods Top


This retrospective observational study was carried out in the neonatal intensive care unit (NICU), Sir Ganga Ram Hospital, New Delhi. Data of VLBW neonates admitted between January 2017 and October 2018 were retrieved from medical records. Neonates with a major congenital anomaly and those who expired or were taken to another health facility before they could reach full feed were excluded. Gestation was assessed based on first-trimester ultrasound, if not available based on last menstrual period or else by Ballard score.[19] Small for gestational age (SGA) was assigned as per Fenton's chart.[20] Abnormal Doppler flows were designated as per standard criteria.[21] Risk factors for FI, time of introduction of first enteral feed, time of first passage of stool, proportion of human milk, haemodynamically significant patent ductus arteriosus,[22] sepsis and need for inotropes were recorded.

Feeding protocol

During the study period, in haemodynamically stable neonates with birth weight <1000 gm, enteral feeds were initiated at 10–20 ml/kg/day on the 1st day of life. Subsequently, increments of 20–30 ml/kg/day were made till 180 ml/kg/day of feeds were achieved. In neonates with birth weight 1000–1499 gm, 80 ml/kg/day feeds were initiated on 1st day of life with subsequent increments of 20–30 ml/kg/day to achieve 180 ml/kg/day. In neonates with absent or reversed end-diastolic Doppler flows (AREDFs), enteral feeds were preferably started after 24 h of birth at 10–20 ml/kg/day, followed by daily increments of 20–30 ml/kg, as tolerated. Mother's own milk was preferred, if not available low birth weight formula with a calorie content of 80 kcal/100 ml was used. Orogastric feeds were given, as a bolus over 10–20 min at 2–3 h intervals. Neonates not on significant enteral feeds, received parenteral nutrition to meet the daily fluid and nutritional requirements. Parenteral nutrition was discontinued once the neonates tolerated 100 ml/kg/day of enteral feeds for 24 h.

Feed intolerance was defined as the presence of one or more of the following

Vomiting more than three times during the previous 24 h period, any episode of bile or blood-stained vomitus, an increase in abdominal girth of more 2 cm from baseline, abdominal wall erythema or tenderness, blood in stools.[12] Prefeed aspirates were performed, if the Abdominal Girth (AG) increased by >2 cm; if the aspirate was milky and <50% of the previous feed volume, one feed was omitted, if >50% or abnormal coloured aspirate, the feeds were discontinued for 24 h. Total parenteral nutrition was given during periods of FI. Subsequent feeding decisions were based on abdominal assessment and girth measurement. Enteral feeds were also discontinued if the neonate became haemodynamically unstable and needed inotropic support. We also assessed the characteristics of VLBW neonates with absent or reversed end-diastolic flows (AREDF), who were started on feeds early (<24 h) or late (>24 h) after birth.

Data collection and statistical analysis

Data were collected in a pre-designed pro forma in Microsoft Excel software (Microsoft Excel, 2007, US). Enrolled neonates were divided into the FI group and No FI group. Continuous variables are presented as mean (standard deviation [SD]) or median (interquartile range). Categorical variables are presented as proportions. Quantitative data with normal distribution were compared using Student's t-test or Mann–Whitney U test as applicable. Proportions were compared using the Chi-square test or Fisher's exact test as applicable. A two-sided P < 0.05 was considered significant. SPSS software version 17.0 (IBM SPSS statistics for windows, version 17.0, Chicago, US) was used for the analysis.


  Results Top


During the study period, of 2071 admissions to NICU, 186 (89.8%) were VLBW infants. Fifty-seven were excluded due to various reasons [Figure 1]. The characteristics and risk factors of enrolled subjects are displayed in [Table 1]. Seventy-two (55.8%) neonates developed at least one episode of FI. The mean (SD) birth weights and gestation of neonates in FI and No-FI groups were 1075 (231) and 1265 (201) grams (P < 0.01) and 29.5 (2.1) and 31.2 (2.5) weeks (P < 0.01), respectively.
Figure 1: Study flow chart

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Table 1: Characteristics, risk factors and outcomes of enrolled subjects

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On univariate analysis, birth weight, gestational age and male gender were significant risk factors associated with FI. On multivariate analysis, gestational age and male gender were independent risk factors for FI in VLBW neonates [Table 2].
Table 2: Independent risk factors for feed intolerance in enrolled very low birth weight neonates

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Clinical characteristics of VLBW neonates with absent or reversed end-diastolic flows, who were started on feeds early (<24 h) or late (>24 h) are displayed in [Table 3]. Mean birth weight and gestational age were significantly higher in neonates who were started feeds within 24 h of birth. The incidence of FI and NEC was 47.4% and 5.2% in neonates initiated early (<24 h) and 69.2% and 0%, respectively, in those initiated after 24 h. Lower gestation was the only significant risk factor for initiation of feeds after 24 h with an adjusted odds ratio (95% confidence interval) of 2.26 (1, 4.78) on multivariate analysis.
Table 3: Characteristics, risk factors and outcomes of infants with absent reverse end diastolic velocity started on enteral feeds within or after 24 h of birth

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  Discussion Top


We performed this study to identify the risk factors for FI in VLBW infants. More than half of VLBW infants in our study experienced at least one episode of FI, that is similar to the incidence of 64.4%, reported by Boo et al.[14] Nangia et al. reported an incidence of FI 14% to 22% in neonates between 1000 and 1500 g on partial or exclusive enteral feeds.[12] They excluded neonates <28 weeks of gestation and <1000 g birth weight. Khashana et al. reported signs of FI in 2.6% of pre-term neonates between the gestation 28–37 weeks.[23] The incidence of FI in a study by Aradhya et al. that included infants with REDF was 45%.[24] The variations in the incidence of FI across these studies could be due to different population characteristics.

Various factors that have been suspected to be associated with FI include poor coordination of sucking and swallowing, incompetent lower oesophageal sphincter, small gastric capacity, delayed gastric emptying time, intestinal hypomotility, theophylline therapy, oxygen support, sepsis, abnormal Doppler flow velocities in the fetal umbilical artery and suboptimal intestinal perfusion.[14],[15],[16],[17] We observed that pre-maturity and male gender were independent risk factors for FI. Boo et al. in their study in VLBW infants, did not find birth weight and gestation to be a significant risk factor for FI, possibly due to higher gestation and birth weights of enrolled subjects.[14] Many other studies reported similar findings and had enrolled infants with higher birth weight and gestation.[23] Aradhya et al. reported birth weight to be independent risk factor for FI and SGA to be protective for FI. We did not find growth restriction to be a significant factor for FI. This could be due to differences in the severity of growth restriction.[24] In a recent study, birth weight <1000 g, the use of caffeine citrate and formula feeding were reported to be the risk factors for FI.[25] Extreme pre-maturity and lower birth weight appear to be significant risk factors for FI.[25] Our finding of male gender associated with a higher incidence of FI may be an incidental finding and needs to be confirmed in further studies.

Enteral feeds are often delayed in VLBW infants due to the possible risk of FI or NEC leading to a prolonged need for parenteral nutrition and associated risk for nosocomial sepsis. However, an association between FI and NEC is not clear. Early introduction of feeds has not been shown to be associated with NEC.[3],[5] Boo et al. observed a significantly higher incidence of FI associated with the delaying of initiation of feeds. For infants started first feed at 4, 24 and 48 h of age, the incidence of FI was 44.6%, 59.4% and 73.2%, respectively. Each hour delay in age at initiation of feeds was associated with a higher incidence of FI. The authors proposed that VLBW infants should be started on enteral feeds as soon as possible after birth, to improve feed tolerance.[14] We also found a significantly higher incidence of FI among neonates who were started on enteral feeds beyond 24 h of birth. In clinical settings, the time to initiate enteral feeds is often decided based on gestation, birth weight and haemodynamic stability. The average birth weight and gestation were significantly higher in neonates, who were started on enteral feeds earlier, the possible reason for better feed tolerance in this group.

In neonates born with absent or reversed end-diastolic umbilical flows, the enteral feeds often are delayed. The landmark ADEPT trial and a recent randomised controlled trial by Tiwari et al. did not find a significantly higher incidence of NEC or FI in SGA neonates born with abnormal umbilical blood flows.[26],[27] In our study, in infants with abnormal Doppler flows (ARED flow), early feeding (<24 h) did not result in statistically significant increased FI after adjustment for a period of gestation, birth weight, gender. There is a need to develop criteria to identify neonates with ARDEF who can be started on early enteral feeds without a higher risk of FI and NEC.

Delayed passage of stools has been suggested as a factor for the higher incidence of FI in pre-term neonates. Goyal et al. in a retrospective study reported that early passage of meconium within the first 48 h of age was associated with a lower incidence of FI.[28] We did not observe any association between the passage of first stool and the incidence of FI.

The strength of our study includes a larger sample size, smaller mean gestational age which could instill more confidence in future research. The retrospective design, small sample size and a smaller number of babies with AREDV are limitations of this study.


  Conclusions Top


Lower gestation and male gender are significant risk factors for FI in VLBW infants. Early feeding <24 h in infants with abnormal Doppler flows with higher gestational age did not result in statistically significant increased FI after adjustment for a period of gestation, birth weight, gender. This study provides an anecdotal evidence for early initiation of feed in babies with abnormal Doppler flows and hence should stimulate further research.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
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  [Full text]  
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