| Methods |
Multi‐centre quasi‐randomised (alternation) controlled trial in Denmark. |
| Participants |
Inclusion criteria: infants with bi‐parental atopy or uniparental atopy and cord IgE ≥ 0.3 kU/L. |
| Interventions |
Supplemental or sole formula feeding with:
Treatment 1 (n = 79): extensively hydrolysed casein formula (Nutramigen).
Treatment 2 (n = 82): extensively hydrolysed whey formula (Profylac).
Control (n = 85): pHWF (NAN‐HA).
Recommended duration of feeding: 4 months.
Co‐interventions (all infants): delay solids and cow's milk to 4 months; avoid smoke, pets, damp housing. |
| Outcomes |
Primary outcome(s): allergic disease.
Other outcomes: physician examination at 6, 12 and 18 months (infant allergic disease).
Definitions
Any atopy: symptoms of asthma, atopic dermatitis, allergic rhino conjunctivitis or at least 2 episodes of allergic urticaria.
Asthma: clinician diagnosed, ≥ 3 episodes of recurrent wheezing needing bronchodilators.
Atopic dermatitis: physical examination, ≥ 3 months' duration.
Allergic rhino conjunctivitis: ≥ 1 month or recurrent symptoms.
Food allergy: confirmed by unblinded elimination/challenge.
CMA/CMPI: confirmed by unblinded elimination/challenge and exclusion of lactose intolerance and infection. |
| Notes |
Trial of supplemental or sole pHWF vs extensively hydrolysed casein formula vs extensively hydrolysed whey formula in high‐risk infants.
Control group of non‐randomly allocated breast fed infants not included in analysis.
Conflict of interest: funded by the Danish Dairy Foundation. Companies provided formula and funding. |
| Risk of bias |
| Bias |
Authors' judgement |
Support for judgement |
| Random sequence generation (selection bias) |
High risk |
Quasi‐random. Postnatal allocation by date of birth. |
| Allocation concealment (selection bias) |
Unclear risk |
Allocation predictable but intervention blinded. |
| Blinding of participants and personnel (performance bias)
All outcomes |
Low risk |
Used formula tins labelled 'A, B or C'. |
| Blinding of outcome assessment (detection bias)
All outcomes |
Low risk |
‘The blinded coding of the products was not revealed until all the data registration was complete’. |
| Incomplete outcome data (attrition bias)
All outcomes |
High risk |
Unclear as to exact numbers in each group not completing the study. Of initial population of 595 infants, 92% were included in study and 80% completed follow‐up. Reasons for losses included parental refusal (19), received other formula in first days (23), 'dropped out' (36), not seen at 18 months, did not fulfil inclusion criteria (4) and non‐compliance (32). |
| Selective reporting (reporting bias) |
High risk |
Not intention‐to‐treat analysis. |
| Other bias |
High risk |
Some baseline differences between study groups (bi‐parental atopy: Nutramigen 38%, Profylac 22%, Nan HA 39%). |
