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OBJECTIVE: Although it is well documented that breastfeeding promotes health and development of very low birth weight (VLBW) infants, lactation initiation among mothers of VLBW infants is low. Mothers are anxious about the health of their children, and medical staff may be reluctant to promote breastfeeding out of concern for increasing that anxiety. Therefore, the purpose of this study was to examine whether mothers of VLBW infants who initially planned to formula feed were different in terms of their level of anxiety and maternal stress compared with mothers who had planned to breastfeed their infants. The aims of this study were to (1) determine whether counseling mothers of VLBW infants who had initially planned to formula feed on the benefits of breast milk would increase their stress and anxiety levels, (2) assess whether mothers who initially had not planned to breastfeed changed their plans after counseling to provide breast milk, and (3) measure the amount of breast milk expressed by mothers who initially planned to formula feed. Their results were compared with those of mothers of VLBW infants who initially planned to breastfeed. METHODS: Initial plan to breastfeed (initial breastfeed group [IBG]; n = 115) or formula feed (initial formula feed group [IFG]; n = 81) was determined before counseling. All participants received counseling on infant health benefits, collection and storage of breast milk, and breast pump procurement. Maternal anxiety was measured using the State-Trait Anxiety Inventory (STAI), which was administered to mothers before and after counseling and every 2 weeks until infant discharge. Maternal stress was measured after counseling with the Parental Stressor Scale: NICU. Infant breast milk intake was measured throughout hospitalization. An exit questionnaire that pertained to the perceived benefits and efforts of expressing milk was administered close to the time of infant discharge. RESULTS: After lactation counseling, 100% of the IBG and 85% of the IFG initiated breast milk expression (used the electric breast pump in the hospital) for a total lactation initiation rate of 94%. After adjustment for the mothers who initiated milk expression but did not provide any breast milk, the lactation initiation rate for the entire group was 84%. Non-Hispanic black mothers and Non-Hispanic white mothers initiated milk expression at similarly high rates (95% vs 93%). Also, milk expression initiation was similar for low-income and non-low-income mothers (95% vs 92%). IFG and IBG STAI and Parental Stressor Scale: NICU scores were not significantly different, and there were no significant differences between groups in the change in anxiety after counseling. In addition, the mean difference scores (after counseling - before counseling) for STAI anxiety "state" were not significantly different between groups, even when controlling for "trait" anxiety. State anxiety declined during the first 6 weeks of infant hospitalization in a similar manner for both groups. Maternal trait but not state anxiety scores were inversely correlated with total infant breast milk intake. Breast milk intake (mL/kg per day) was greater in the infants of mothers in the IBG compared with the IFG at each week during the first month and for their entire hospital stay. Infant breast milk intake increased from weeks 1 to 3 in both groups and continued to rise in the fourth week for the IBG. However, breast milk intake declined at week 4 for the IFG. IBG infants received breast milk for 83% of the total fed hospital days (days that feedings were given) compared with 44% of total fed days for the IFG. The proportion of enteral intake that was breast milk was also greater for the IBG compared with IFG during the first 4 weeks and for the total hospitalization. However, the mothers in IFG were able to provide at least 50% of their infants' enteral intake for the first 3 weeks, 48.8% for the fourth week, and 32.8% of the enteral intake for the entire hospitalization. Infants of low-income women received significantly lower amounts of breast milk than did infants of non-low-income mothers. Race and income accounted for 36% of the variance in breast milk intake. Of the 184 mothers who initiated breast milk expression, 72 (39%) completed the exit questionnaire. Infant health benefits were the most common reasons cited by both groups for expressing milk. The most common reasons that both groups reported for ceasing milk expression were (1) low milk supply, (2) returning to work or school, and (3) inability to pump as often as needed. Almost all of the mothers reported that pumping was worth the effort (IBG 100%, IFG 87%), and 100% said that they were glad that the staff helped them with milk expression. CONCLUSION: Counseling mothers of VLBW infants increases the incidence of lactation initiation and breast milk feeding without increasing maternal stress and anxiety.
OBJECTIVES: To ascertain whether the number of sudden infant deaths as a result of suffocation in cribs, in adult beds, on sofas or chairs, and on other sleep surfaces was increasing whether attributable to increased reporting, diagnostic shift, or an actual increase in suffocation deaths and to compare the risk of reported accidental suffocation for infants on sleep surfaces designed for infants with the risk on adult beds. METHODS: We reviewed all accidental suffocation deaths among infants < or =11 months of age reported to the United States Consumer Product Safety Commission from 1980 through 1983 and 1995 through 1998. We compared infants' ages and other demographic data, the sleep location and surface used, and the reported mechanism or pattern of death. For 1995-1998, we used data on sleep location from an annual survey of randomly selected households of living infants younger than 8 months, collected as part of the National Infant Sleep Position Study at the National Institute of Child Health and Human Development, to calculate risk for death as a result of suffocation in cribs, in adult beds, and on sofas or chairs. METHODS: The number of reported suffocation deaths by location were compared between the 1980s and 1990s using logistic regression modeling to calculate odds ratios (OR), 95% confidence intervals (CI), and P values. Comparative risks for suffocation deaths on a given sleep surface for infants in the 1990s were examined by calculating rates of death per 100 000 exposed infants and comparing the 95% CI for overlap. RESULTS: From the 1980s, 513 cases of infant suffocation were considered; from the 1990s, 883 cases. The number of reported suffocation deaths in cribs fell from 192 to 107, the number of reported deaths in adult beds increased from 152 to 391, and the number of reported deaths on sofas or chairs increased from 33 to 110. Using cribs as the reference group and adjusting for potential confounders, the multivariate ORs showed that infant deaths in adult beds were 8.1 times more likely to be reported in the 1990s than in the 1980s (95% CI: 3.2-20.3), and infant deaths on sofas and chairs were 17.2 times more likely to be reported in the 1990s than in the 1980s (95% CI: 5.0-59.3). The sleep location of a subset of cases from the 1990s, 348 infants younger than 8 months at death, was compared with the sleep location of 4220 living infants younger than 8 months. The risk of suffocation was approximately 40 times higher for infants in adult beds compared with those in cribs. The increase in risk remained high even when overlying deaths were discounted (32 times higher) or the estimate of rates of bedsharing among living infants doubled (20 times higher). CONCLUSIONS: Reported deaths of infants who suffocated on sleep surfaces other than those designed for infants are increasing. The most conservative estimate showed that the risk of suffocation increased by 20-fold when infants were placed to sleep in adult beds rather than in cribs. The public should be clearly informed of the attendant risks.
BACKGROUND: Growing ex-preterm infants who undergo general anesthesia for surgery at about term-equivalent age may have episodes of apnea, cyanosis and bradycardia during the early postoperative period. Caffeine treatment given at the time of operation might prevent these episodes. OBJECTIVES: In ex-preterm infants who undergo general anesthesia for surgery, does the prophylactic use of caffeine prevent episodes of apnea, cyanosis and bradycardia during the postoperative period without clinically important side effects? SEARCH STRATEGY: The standard strategy of the Neonatal Review Group was used. This included searches of the Oxford Database of Perinatal trials, Medline, previous reviews including cross references, abstracts, conferences and symposia proceedings, expert informants and journal handsearching mainly in the English language. SELECTION CRITERIA: All trials utilising random or quasi-random patient allocation, in which treatment was compared with placebo or no treatment, were included. DATA COLLECTION AND ANALYSIS: The standard methods of the Cochrane Collaboration and its Neonatal Review Group were used to select trials, evaluate quality and to extract data. The methodological quality of each trial was reviewed by the second author blinded to trial authors and institution(s). Each author extracted data separately, compared and resolved differences. Meta-analysis used relative risk and risk difference. MAIN RESULTS: In each trial apnea/bradycardia occurred in fewer treated than control infants. In two trials (Welborn 1989, LeBard 1989) continuous recordings of oxygen saturation detected hypoxaemic episodes (<90 %) in fewer treatment than control infants. No infant in any trial required intubation and mechanical ventilation. No adverse effects were reported. REVIEWER'S CONCLUSIONS: Implications for practice. Caffeine can be used to prevent postoperative apnea/bradycardia and episodes of oxygen desaturation in growing preterm infants if this is deemed clinically necessary. In view of the small numbers of infants studied in these trials and uncertainty concerning the clinical significance of the episodes, caution is warranted in applying these results to routine clinical practice. Implications for research. There is a need to determine which infants might benefit most by this treatment. Studies confined to those most at risk of apnea (prior history, younger postmenstrual age) and those that might require mechanical ventilation (chronic lung disease) would be of value.
BACKGROUND: This section is under preparation and will be included in the next issue. OBJECTIVES: To compare the effect of prophylactic surfactant administration to surfactant treatment of established respiratory distress syndrome in premature infants. SEARCH STRATEGY: Searches were made of the Oxford Database of Perinatal Trials, Medline (MeSH terms: pulmonary surfactant; limits: age groups, newborn infants), previous reviews including cross-references, abstracts, conference and symposia proceedings, expert informants, and journal handsearching in the English language. SELECTION CRITERIA: Randomized controlled trials which compared the effects of prophylactic surfactant administration to surfactant treatment of established respiratory distress syndrome in premature infants were included in the analysis. DATA COLLECTION AND ANALYSIS: Data regarding clinical outcomes including the incidence of pneumothorax, pulmonary interstitial emphysema, patent ductus arteriosus, necrotizing enterocolitis, intraventricular hemorrhage (any grade and severe intraventricular hemorrhage), bronchopulmonary dysplasia, mortality, bronchopulmonary dysplasia or death, and retinopathy of prematurity were excerpted from the reports of the clinical trials by the reviewers. Data analysis was done in accordance with the standards of the Cochrane Neonatal Review Group. MAIN RESULTS: The majority of included studies noted an initial improvement in the respiratory status and a decrease in the incidence of respiratory distress syndrome in infants who received prophylactic surfactant. The meta-analysis supports a decrease in the incidence of pneumothorax, a decrease in the incidence of pulmonary interstitial emphysema, a decrease in the incidence of mortality and a decrease in the incidence of bronchopulmonary dysplasia or death associated with prophylactic administration of surfactant. No significant untoward effects of prophylactic surfactant administration are noted. REVIEWER'S CONCLUSIONS: Prophylactic surfactant administration to infants judged to be at risk of developing respiratory distress syndrome (intubated infants less than 30-32 weeks gestation) has been demonstrated to improve clinical outcome. Infants who receive prophylactic surfactant have a decreased incidence of pneumothorax, a decreased incidence of pulmonary interstitial emphysema and a decreased incidence of mortality. However, it remains unclear exactly which criteria should be used to judge "at risk" infants who would require prophylactic surfactant administration.
BACKGROUND: Recurrent apnea is common in preterm infants, particularly at very early gestational ages. These episodes of loss of effective breathing can lead to hypoxemia and bradycardia which may be severe enough to require resuscitation including use of positive pressure ventilation. Theophylline stimulation of breathing and continuous positive airways pressure have been used to prevent apnea and its consequences. OBJECTIVES: The main objective was to determine in preterm infants with recurrent apnea, if treatment with CPAP compared with treatment with theophylline leads to a clinically important reduction in apnea or use of mechanical ventilation, without clinically important side effects. SEARCH STRATEGY: The standard search strategy of the Neonatal Review Group was used. This includes searches of the Oxford Database of Perinatal Trials, Cochrane Controlled Trials Register, MEDLINE, previous reviews including cross references, abstracts, conferences, symposia proceedings, expert informants and journal hand searching mainly in the English language. SELECTION CRITERIA: All trials using random or quasi-random allocation to CPAP or theophylline in preterm infants with clinical recurrent apnea/bradycardia were eligible. DATA COLLECTION AND ANALYSIS: Data were extracted using standard methods of the Cochrane Collaboration and its Neonatal Review Group, with separate evaluation of trial quality and data extraction by each author and synthesis of data using relative risk. MAIN RESULTS: The use of mask CPAP is associated with a higher treatment failure rate as measured by less than a 50% reduction in apnea or use of the alternative treatment [RR 2.89 (95% CI 1.12,7.47); RD 0.42 (95% CI 0. 11, 0.74)]. For every 2.4 infants (95% CI 1.4, 9.5) treated with mask CPAP rather than theophylline, there results one treatment failure. In the mask CPAP group there is more use of IPPV [RR 3.09 (1.42,6.70; RD 0.58 (95% CI 0.30, 0.86). For every 1.7 infants (95% CI 1.2, 3.3) treated with mask CPAP rather than theophylline, one infant is intubated for IPPV. In the mask CPAP group, there are trends towards more deaths in the first year, and in death or major disability in survivors at follow up, which do not reach significance. There are no differences in rates of necrotizing enterocolitis or major disability in survivors at follow up. REVIEWER'S CONCLUSIONS: Theophylline is more effective than mask CPAP for preterm infants with apnea. Since CPAP is no longer administered by mask, the results of this review have limited importance for current clinical practice. Further evaluation of the benefits and harms of CPAP vs theophylline for preterm infants with apnea requires further trials in which CPAP is administered by current methods.
My colleagues and I compared the biochemical status and rates of growth of three groups of preterm infants: one group was fed milk obtained early from mothers of preterm infants; one group received milk produced during the mature stage of lactation by mothers of term infants; and one group received a whey-based infant formula. Sixty healthy preterm infants with birth weights of 1600 g or less were randomly assigned to one of the three feedings groups. The 20 infants in each group were followed until they reached a weight of 1800 g. The mean (+/- S.E.M.) number of days required to regain birth weight was similar for infants receiving the formula (10.3 +/- 0.8) and those receiving milk from mothers of preterm infants (11.4 +/- 0.8); both were significantly less than the number (18.8 +/- 1.7) for infants receiving milk from mothers of term infants (P less than 0.001). Subsequent rates of weight gain were greater for the groups receiving formula (27.0 +/- 0.8 g per day) and milk from mothers of preterm infants (23.7 +/- 1.1) than for the group receiving milk from mothers of term infants (15.8 +/- 0.8) (P less than 0.001). Similarly, the average increments in crown-to-heel length and in the head circumference were significantly greater for the groups given formula and milk from mothers of preterm infants (P less than 0.005 and P less than 0.001, respectively). These data indicate that feeding with either milk from mothers of preterm infants or a whey-based infant formula results in more appropriate growth in preterm infants than feeding with milk from mothers of term infants.
Female macaques and baboons are intensely interested in other females' infants, but provide little direct care for them. The selective factors that shape this strong attraction to neonates may differ from those that shape alloparental care in other taxa. The attraction to neonates may have evolved because (1) it enhances young females' acquisition of maternal skills, (2) it is a form of reproductive competition among females, or (3) it is a by-product of selection for appropriate maternal care. I studied patterns of infant handling in a large group of bonnet macaques, Macaca radiata, at the California Primate Research Center at the University of California, Davis. Infant handling was generally gentle and nonintrusive, although females sometimes tugged on infants. Females were more strongly attracted to infants than were males, regardless of their age. Adult females handled infants as often as subadult females did. Male and female infants were handled at equal rates, and rates of handling towards all infants declined sharply as infants matured. Infants were handled by related females at higher rates than by unrelated females, and at higher rates by higher-ranking females than by lower-ranking females. The data provide little support for the 'learning to mother' hypothesis, because older females were as interested in infants as were subadult females. Although mothers were reluctant to allow their infants to be handled, the data do not support the reproductive competition hypothesis because patterns of infant handling did not match patterns of harassment of infants. The data provide a better fit to the by-product hypothesis. Females were most strongly attracted to infants when maternal care was most critical for infant survival and females of all ages were strongly attracted to infants. Taken together, these data suggest that a strong attraction to infants is favoured by selection because females that are highly responsive to infants make good mothers. Copyright 1999 The Association for the Study of Animal Behaviour.
BACKGROUND: Young infants are at risk of vitamin A deficiency. Supplementation of breastfeeding mothers improves the vitamin A status of their infants, but there are no data regarding its effect on infant mortality, and data on the effect of directly supplementing infants during the first few weeks of life are conflicting. OBJECTIVE: The objective was to measure the effect on infant mortality of supplementing neonates and their HIV-negative mothers with single, large doses of vitamin A during the immediate postpartum period. DESIGN: A randomized, placebo-controlled, 2-by-2 factorial design trial was conducted in 14,110 mothers and their infants; 9208 of the mothers were HIV-negative at delivery, remained such during the postpartum year, and were retained in the current analysis. The infants were randomly assigned within 96 h of delivery to 1 of 4 treatment groups: mothers and infants received vitamin A (Aa), mothers received vitamin A and infants received placebo (Ap), mothers received placebo and infants received vitamin A (Pa), and both mothers and infants received placebo (Pp). The vitamin A dose in the mothers was 400,000 IU and in the infants was 50,000 IU. The mother-infant pairs were followed to 12 mo. RESULTS: Hazard ratios (95% CI) for 12 mo mortality among infants in the maternal-supplemented and infant-supplemented groups were 1.17 (0.87, 1.58) and 1.08 (0.80, 1.46), respectively. Hazard ratios (95% CI) for the Aa, Ap, and Pa groups compared with the Pp group were 1.28 (0.83, 1.98), 1.27 (0.82, 1.97), and 1.18 (0.76, 1.83), respectively. These data indicate no overall effect. Serum retinol concentrations among a subsample of women were similar to reference norms. CONCLUSION: Postpartum maternal or neonatal vitamin A supplementation may not reduce infant mortality in infants of HIV-negative women with an apparently adequate vitamin A status.
BACKGROUND: In a recent meta-analysis, human milk feeding of low birth-weight (LBW) infants was associated with a 5.2 point improvement in IQ tests. However, in the studies in this meta-analysis, feeding regimens were used (unfortified human milk, term formula) that no longer represent recommended practice. OBJECTIVE: To compare the growth, in-hospital feeding tolerance, morbidity, and development (cognitive, motor, visual, and language) of LBW infants fed different amounts of human milk until term chronologic age (CA) with those of LBW infants fed nutrient-enriched formulas from first enteral feeding. METHODS: The data in this study were collected in a previous randomized controlled trial assessing the benefit of supplementing nutrient-enriched formulas for LBW infants with arachidonic acid and docosahexaenoic acid. Infants (n = 463, birth weight, 750-1,800 g) were enrolled from nurseries located in Chile, the United Kingdom, and the United States. If human milk was fed before hospital discharge, it was fortified (3,050-3,300 kJ/L, 22-24 kcal/oz). As infants were weaned from human milk, they were fed nutrient-enriched formula with or without arachidonic and docosahexaenoic acids (3,300 kJ/L before term, 3,050 kJ/L thereafter) until 12 months CA. Formula fed infants were given nutrient-enriched formula with or without added arachidonic and docosahexaenoic acids (3,300 kJ/L to term, 3,050 kJ/L thereafter) until 12 months CA. For the purposes of this evaluation, infants were categorized into four mutually exclusive feeding groups: 1) predominantly human milk fed until term CA (PHM-T, n = 43); 2) >/= 50% energy from human milk before hospital discharge (>/= 50% HM, n = 98); 3) < 50% of energy from human milk before hospital discharge (< 50% HM, n = 203); or 4) predominantly formula fed until term CA (PFF-T, n = 119). RESULTS: PFF-T infants weighed approximately 500 g more at term CA than did PHM-T infants. This absolute difference persisted until 6 months CA. PFF-T infants were also longer (1.0-1.5 cm) and had larger head circumferences (0.3-1.1 cm) than both PHM-T and >/= 50% HM infants at term CA. There was a positive association between duration of human milk feeding and the Bayley Mental Index at 12 months CA (P = 0.032 full and P = 0.073 reduced, statistical models) after controlling for the confounding variables of home environment and maternal intelligence. Infants with chronic lung disease fed >/= 50% HM until term CA (n = 22) had a mean Bayley Motor Index about 11 points higher at 12 months CA compared with infants PFF-T (n = 24, P = 0.033 full model). CONCLUSION: Our data suggest that, despite a slower early growth rate, human milk fed LBW infants have development at least comparable to that of infants fed nutrient-enriched formula. Exploratory analysis suggests that some subgroups of human milk fed LBW infants may have enhanced development, although this needs to be confirmed in future studies.
BACKGROUND: Recurrent apnea is common in preterm infants, particularly at very early gestational ages. These episodes of loss of effective breathing can lead to hypoxemia and bradycardia which may be severe enough to require resuscitation including use of positive pressure ventilation. Doxapram has been used to stimulate breathing and so prevent apnea and its consequences. OBJECTIVES: In preterm infants with recurrent apnea, does treatment with doxapram lead to a clinically important reduction in apnea and use of Intermittent positive airways pressure (IPPV), without clinically important side effects? SEARCH STRATEGY: Searches were made of the Oxford Database of Perinatal trials, the Cochrane Collaboration Clinical Trials Register, MEDLINE (using text words 'doxapram', 'apnea or apnoea' and Mesh term 'infant, premature') previous reviews including cross references, abstracts, conferences and symposia proceedings, expert informants, mainly in the English language. Also an expert informant's search in the Japanese language was made by Prof. Y. Ogawa in 1996. SELECTION CRITERIA: All trials utilising random or quasi-random patient allocation, in which doxapram was used for the treatment of apnea in preterm infants were included. DATA COLLECTION AND ANALYSIS: Each author evaluated the papers for quality and inclusion criteria. Independent data extraction was carried out. MAIN RESULTS: Only one trial, which randomized 11 infants to intravenous doxapram and 10 infants to placebo, was found. There were fewer treatment failures after 48 hours in the group of preterm infants treated with doxapram (4/11) compared with the group treated with placebo (8/10). The wide confidence intervals made this result non-significant [RR 0.45 (0.20, 1.05)]. Only one infant, who was from the placebo group, was given IPPV. Of the seven responders by 48 hours in the group of 11 who received doxapram, five failed to respond between 48 hours and seven days after commencement of therapy. This gives a late failure rate of 9/11, similar to the short term failure rate in the placebo group of 8/10. It is not possible to evaluate the late responses of all those in the placebo group since they crossed over to a treatment arm. REVIEWER'S CONCLUSIONS: Although intravenous doxapram might reduce apnea within the first 48 hours of treatment, there are insufficient data to evaluate the precision of this result or to assess potential adverse effects. No longterm outcomes have been measured. Further studies are needed to determine the role of this treatment in clinical practice.
BACKGROUND: Most premature infants are not sufficiently mature physiologically to take all of their required water and nutrients orally, and so they cannot regulate their own water intake. Thus, the caregiver must determine the amount of water to be given each day to such infants. OBJECTIVES: The objective of this review is to examine the effects of water intake on postnatal weight loss and on the risks of dehydration, patent ductus arteriosus, necrotizing enterocolitis, bronchopulmonary dysplasia, intracranial hemorrhage, and death in premature infants. SEARCH STRATEGY: Randomized clinical trials were sought that compared the outcomes of interest in groups of premature infants who were given different levels of water intake according to experimental protocol. Such trials were sought in a previous review by one of the authors (Bell EF. Fluid therapy. In: Effective Care of the Newborn Infant, eds JC Sinclair, MB Bracken. Oxford: Oxford University Press, 1992: 59-72, approximately approximately Bell 1992 approximately approximately ), in a list of trials provided by the Cochrane Neonatal Review Group, and in the authors' personal files. SELECTION CRITERIA: Only randomized clinical trials of varying water intake in premature infants are included. The review was limited to trials that included infants whose water intake was provided mainly or entirely by parenteral means. Studies were included regardless of outcomes examined. DATA COLLECTION AND ANALYSIS: Trials were selected by two reviewers, who also assessed the methodological quality of each trial. Data were independently extracted by the reviewers, and differences were reconciled. The data were then entered into tables using RevMan 3.1 for Windows. The adverse event rates were calculated for the restricted and liberal water intake groups for each dichotomous outcome, and the relative risk was computed. In addition, the maximal weight loss results were recorded, and the weighted mean difference was computed. The analyses (including calculation of relative risk, risk difference, and weighted mean difference) and tests of heterogeneity were accomplished with MetaView 3.1 software and a fixed effects model. No subgroup analyses were conducted. MAIN RESULTS: The analysis of the four studies taken together indicates that restricted water intake significantly increases postnatal weight loss and significantly reduces the risks of patent ductus arteriosus, necrotizing enterocolitis, and death. With restricted water intake, there are trends toward increased risk of dehydration and reduced risk of bronchopulmonary dysplasia, but these trends are not statistically significant. REVIEWER'S CONCLUSIONS: Based on this analysis, the most prudent prescription for water intake to premature infants would seem to be careful restriction of water intake so that physiological needs are met without allowing significant dehydration. This practice could be expected to decrease the risks of patent ductus arteriosus and necrotizing enterocolitis--and perhaps the overall risk of death--without significantly increased risk of adverse consequences.
BACKGROUND: Functional immaturity of gastointestinal motility predisposes preterm infants to feeding intolerance. Motilin, a gastrointestinal peptide, stimulates propagative contractile activity during phase III of the migratory motor complex in the interdigestive state. Erythromycin (EM) is a motilin agonist with prokinetic effect at low doses (1-3mg/kg). OBJECTIVES: To evaluate the effectiveness of EM in promoting gastrointestinal motility in preterm infants with feeding intolerance and assess clinically significant adverse effects associated with its use. SEARCH STRATEGY: Systematic literature search in accordance with the Cochrane Neonatal Collaborative Review Group search strategy. Randomized and quasi-randomized controlled trials of EM use, at any dose, in preterm infants to promote gastrointestinal motility were identified by searching MEDLINE, EMBASE, CINAHL, the Cochrane Library, reference lists of published studies, personal files, and abstracts published in Pediatric Research. SELECTION CRITERIA: Randomized controlled trials of oral or intravenous EM use at dose range of 3 to 12 mg/kg/day in preterm infants less than or equal to 36 weeks gestational age with feeding tolerance were included in this review. DATA COLLECTION AND ANALYSIS: Data regarding the primary clinical outcome of days to achieve full enteral feeding were compared among studies. Data on secondary outcomes including adverse effects associated with the use of EM (diarrhea, nosocomial infections, cardiac arrhythmias, or theophylline toxicity), duration of parenteral nutrition, weight gain, incidence of necrotizing enterocolitis (NEC), hypertrophic pyloric stenosis, and length of hospital stay were assessed. MAIN RESULTS: Two randomized controlled studies of EM use in preterm infants for improving gastrointestinal motility were identified. Since both studies involved preterm infants treated with EM at dose >12mg/kg/day at commencement of feeding, they did not meet inclusion criteria defined a priori for this review. There was no statistically significant difference in the incidence of NEC (RR 0.59, 95%CI 0.11, 3.01; RD -0.021, 95%CI -0. 087, 0.045). No statistically significant difference was noted in days to achieve full enteral feeds, length of hospital stay, and adverse events between groups. REVIEWER'S CONCLUSIONS: EM at antimicrobial doses may not be effective in preterm infants with feeding intolerance. Further studies are needed to determine whether EM in lower doses is effective as a prokinetic agent in such infants.