| Methods |
Three‐centre randomised controlled trial in Italy. |
| Participants |
Inclusion criteria: maternal questionnaire used to identify infants with well‐defined family history of allergic disease in either parent. |
| Interventions |
Infants randomised were those whose mothers did not wish to breast feed or had insufficient milk.
Treatment (n = 48): 'moderately' HF (Nidina HA, Nestle).
Control (n = 47): CMF (Nan, Nestle).
Formula feeding advised to 5 months.
Co‐interventions (both groups): maternal cow's milk and food avoidance measures for breast feeding mothers. For infants, cow's milk and allergenic foods avoided to 1 year. Advice given to modify environmental exposure (smoking, pets, carpets, avoiding infant community care to 2 years). |
| Outcomes |
Primary outcome(s): allergic manifestations and nutritional adequacy of formula.
Other outcomes: weight, length and head circumference at 6 months, 1 and 3 years. Physician‐diagnosed allergic disease.
Definitions
Atopic dermatitis: typical rash in at least 2 areas.
Recurrent wheezing: ≥ 3 episodes and physician diagnosed.
Recurrent urticaria: ≥ 2 episodes after exposure to particular antigen.
GI symptoms: vomiting and/or diarrhoea after exclusion of infection and lactose intolerance, not confirmed by blinded elimination/challenge.
Allergic rhinitis: ≥ 3 weeks rhinorrhoea.
RAST and SPTs also performed in affected individuals.
Follow‐up performed at 1, 2 (infant allergic disease) and 3 years (child allergic disease). |
| Notes |
Trial of prolonged supplemental or sole 'moderately' hydrolysed whey formula vs CMF feeding in high‐risk infants.
Co‐interventions in both groups.
Conflict of interest: none reported. |
| Risk of bias |
| Bias |
Authors' judgement |
Support for judgement |
| Random sequence generation (selection bias) |
Unclear risk |
Postnatal 'random' allocation of infants; method not reported. |
| Allocation concealment (selection bias) |
Unclear risk |
Method not reported. |
| Blinding of participants and personnel (performance bias)
All outcomes |
High risk |
quote: "Where artificial feeding was required... babies... randomly allocated to formula (a) or formula (b) ... (but the mothers were not blinded to the allocation)". |
| Blinding of outcome assessment (detection bias)
All outcomes |
Unclear risk |
Physicians "unaware of the dietary regimen", but insufficient information reported on blinding of personnel to allocation. |
| Incomplete outcome data (attrition bias)
All outcomes |
High risk |
Hydrolysed group losses 5 (10%) at 1 year, 6 (13%) at 2 years, 8 (17%) at 3 years.
Cow's milk group losses 6 (13%) at 1 year, 7 (15%) at 2 years, 9 (19%) at 3 years. |
| Selective reporting (reporting bias) |
Low risk |
Prespecified allergic disease outcomes. Standardised definitions. |
| Other bias |
Unclear risk |
Insufficient data reported at baseline for allergic disease risk factors between study groups. |
