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QUESTION: Is whey hydrolysate formula effective in the treatment of infantile colic in formula fed infants in a primary care setting?
Randomised (allocation concealed), blinded (research nurses and parents), placebo controlled trial with follow up immediately after 1 week of intervention.
Community based, well baby clinics in 6 regions of the Netherlands.
43 healthy, thriving, formula fed (≥1 formula feeding per d) infants <6 months old who cried for >3 hours/day on ≥3 days/week (average >4.5 h/d). Exclusion criteria included participation in a previous trial of hypoallergenic feeding, anaphylactic reactions to cows' milk, and non-Dutch speaking parents. 5 infants (12%) did not complete the trial but were included in the analysis. For the 38 who did complete the trial, 53% were boys and the mean weight was 4.7 kg.
After a 1 week qualification period, 23 infants were allocated to whey hydrolysate formula (Nutrilon Pepti) and 20 to standard cows' milk formula (Nutrilon Premium) for a 1 week intervention period. Every infant was provided with 2 cans of formula powder, each can con-taining 400 g. To make the taste, smell, and appearance of the 2 formulas similar, a quarter of the powder in each can of standard formula was substituted with hydrolysate powder.
Main outcome measures
The primary outcome was difference in duration of crying (min/d) between the qualification week and intervention week. The secondary outcome was proportion of infants no longer fulfilling the inclusion criteria (ie, having infantile colic).
Analysis was by intention to treat. The crying of infants allocated to whey hydrolysate formula decreased by 63 minutes/day (when adjusted for sex and amount of crying before intervention) more than the crying of infants allocated to standard formula (p=0.05). Of those completing the trial (38 infants, 88%), the proportion of infants no longer fulfilling the inclusion criteria did not differ between the 2 groups (whey hydrolysate 40% v standard formula 28%, p=0.65).
In formula fed infants with infantile colic, crying time was reduced with whey hydrolysate formula.
Infantile colic is common during the first months of life and, despite extensive study, its cause remains unclear. This is reflected in the numerous approaches to treatment that have been recommended and studied. Although its symptoms usually resolve by 4–5 months of age, colic causes appreciable distress to parents and creates needs for teaching and counselling by nurses. It is therefore an important issue for antepartum and postpartum nurses working in hospital and community settings.
The 2 studies presented here used the same diagnostic definition of infantile colic.1 The infants in both studies and in both groups, however, had very high levels of crying (>4.5 h/d compared with the diagnostic cut off of >3 h/d, for >3 d/wk). This initially high crying time made it more difficult to achieve large enough reductions to meet one of the outcome criteria: a reduced proportion of infants meeting the diagnostic definition of colic. The high crying time among study participants also may reflect the presence of other confounding factors.
In the study of chiropractic treatment by Olafsdottir et al, there was reduced infant crying and parents reported an improvement in both the intervention and placebo groups, with no statistically significant differences between them. The similar improvement may be the result of a placebo effect (ie, the counselling and support provided to parents in both groups) and/or the natural course of infantile colic. The lack of effect from spinal manipulation differs from other trial results, possibly because this study had the critical methodological strength of blinding the parents to the intervention, minimising the potential for bias arising from parental expectations. These findings are important in locales where chiropractic treatment is an accepted treatment for colic and nurses are asked for advice about this treatment.
The study of whey hydrolysate by Lucassen et al presents results that are consistent with findings from a systematic review of treatments for colic, which concluded that replacement of cows' milk protein with a hydrolysate is effective.2 It is not clear, however, how much formula the infants in this study consumed because the inclusion criterion was at least 1 formula feeding a day, and the amount of breast feeding in the sample group, before and during the study, was not reported. It is important to know the extent of breast feeding in the 2 groups as this may have affected the differences in outcomes. It is also not stated whether only formula feedings, or breast milk feedings as well, were replaced with whey hydrolysate. This limits the generalisability of results, and does not provide any evidence to support replacement of breast milk with whey hydrolysate formula.
The study sample size was much smaller than anticipated: over a 2 year period, 38 completed the trial although the anticipated sample size was 150. This speaks to the challenges of recruitment, particularly when there is a strict definition of colic and a measurement instrument to be completed by parents who are already overburdened with coping with a colicky infant. The high average crying time in recruited infants may be related to their parents' motivation to enter the study. With such a small number of infants in the trial, it is not surprising that the treatment and control groups differed in age, sex, crying and crying/fussing levels, and the presence of a food allergy at baseline. As a result, we must rely on the adjusted analysis which just achieves statistical significance with a p value of 0.05.
The findings from these 2 studies have important implications for nurses in clinical practice and research. When providing anticipatory guidance to prospective parents, and when counselling parents of newborns about infant crying, nurses need to present parents with realistic expectations, common causes, and practical relief measures. If crying is consistently in excess of 3 hours/day, then a detailed assessment is required. Other disorders need to be ruled out. Reassurance, teaching, counselling, and support always should be the first intervention measures. The evidence from these studies supports a switch from cows' milk formula to whey hydrolysate formula in formula fed infants with colic, but not the use of spinal manipulation. Nurses have an important part to play in educating new parents and other health professionals in this area.
This evidence highlights the continuing need for research on the causes of infantile colic and the effectiveness of dietary and alternative treatments, particularly with the increasing interest in complementary medicine. Attention must be paid to the role of breast feeding with any dietary interventions. Studies need to replicate the strong methodology here, with sufficient sample size, placebo control, and blinding. The influence of social factors on colic is another potential area of research. Nurses have a responsibility to advocate for, and participate in, rigorous studies on infantile colic, and to disseminate their findings.
Sources of funding: Praeventie Fonds; formulas provided by Nutricia.
For correspondence: Dr P L Lucassen, Akkerroosstraat 18, 5761 EX, Bakel, the Netherlands. Fax +31 492 343975.
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