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. 2015 Jul 22;2015(7):CD010085. doi: 10.1002/14651858.CD010085.pub2

Makrides 2010.

Methods Randomised controlled trial.
Makrides 2010 was the main trial with 10 publications. All 10 publications and 1 thesis are included in the references to included studies.
Participants Setting: Australian maternity hospitals.
Recruitment to primary 'DOMInO' trial (Makrides 2010): women with singleton pregnancies at less than 21 weeks’ gestation.
Excluded were women already taking a prenatal supplement with DHA, with a bleeding disorder in which tuna oil was contraindicated, were taking anticoagulant therapy, had a documented history of drug or alcohol abuse, were participating in another fatty acid trial, fetus had a known major abnormality, or were unable to give written informed consent or if English was not the main language spoken at home (n = 2399).
Pregnant women were approached to enter the allergy follow‐up (Palmer 2012) after randomisation into the DOMInO trial. Only Adelaide‐based women were eligible for the allergy follow‐up. Women were eligible if the unborn baby had a mother, father, or sibling with a history of any medically diagnosed allergic disease (asthma, allergic rhinitis, eczema) (n = 706).
Interventions Intervention: 3 x 500 mg capsules daily of DHA rich fish oil concentrate, providing 800 mg of DHA and 100 mg of EPA per day.
Control: 3 500 mg vegetable oil capsules daily without DHA.
Outcomes 1. Makrides 2010 reported
Primary outcome ‐ maternal postnatal depression at 6 weeks and 6 months; child neurodevelopment at 18 months of age.
Secondary outcomes included a range of clinical outcomes including postpartum haemorrhage.
2. Palmer 2012 reported
Primary outcome: At 1 year of age
1) IgE‐associated allergic diseases including:
food allergy, eczema, asthma, allergic rhinitis and any allergy with sensitisation .
2) Medically diagnosed allergic diseases with or without IgE‐mediated allergic diseases including:
food allergy, eczema, asthma/wheeze, allergic rhinitis and any allergy with or without sensitisation based on medically diagnosed allergy at the age of 1 year.
Secondary outcomes included IgE sensitisation ‐ SPT at 1 year of age. Infants with respiratory tract infections between birth and 1 year.
3. Palmer 2013 reported
the 3‐year follow‐up of the same children in Palmer 2012 to evaluate medically diagnosed allergy.
Reported IgE‐associated allergic diseases including food allergy, eczema, asthma, allergic rhinitis and any allergy with sensitisation at 3 years of age.
Obtained medically diagnosed allergic diseases with or without IgE‐mediated allergic diseases including: food allergy, eczema, asthma/wheeze, allergic rhinitis and any allergies with or without sensitisation at the age of 3 years.
4. Gunaratne 2014 reported
parental reports of doctor diagnosed allergy outcomes including food allergy, eczema, asthma, allergic rhinitis and any allergy below 36 months of age.
 Modified ISAAC questions were used to collect parent report of doctor diagnosed eczema, allergic rhinitis and asthma from birth to 3 years of age. (The ISAAC questions are not validated for this age group.)
Notes Supported by grants from the Australian National Health and Medical Research council and Australian Egg Corporation Limited. Treatment and placebo capsules were donated by Efamol, UK.
Risk of bias
Bias Authors' judgement Support for judgement
Random sequence generation (selection bias) Low risk Quote " Women were randomly allocated to a unique number that corresponded to treatment or control through a computer driven telephone randomisation service according to an independently generated randomisation schedule, with balanced variable sized blocks. Stratification was by centre and parity".
Allocation concealment (selection bias) Low risk Computer‐driven telephone randomisation service.
Blinding of participants and personnel (performance bias) 
 All outcomes Low risk To maintain the blind, both active and placebo capsules were identical in appearance.
Blinding of outcome assessment (detection bias) 
 All outcomes Low risk Neither the parents nor the research staff were aware of the treatment allocated. Described as "double‐blind".
Incomplete outcome data (attrition bias) 
 All outcomes Low risk 681/706 (96.5%) infants (intervention: 357/368, 97%,placebo: 324/338, 96%) attended their 1‐year medical review and 666/706 (94.3%) infants had SPT results. Missing data were imputed for all IgE‐mediated allergy outcomes and medially diagnosed food allergy, eczema and any allergy but not imputed for medically diagnosed asthma (wheeze) and allergic rhinitis. In secondary outcomes missing data were imputed for egg, cow's milk. peanut and any SPT sensitisation but not for wheat, fish, pollen, house dust mite and cat allergens.
638/706 (90.4%) infants (intervention: 333/368, 90.5%placebo: 305/338, 90.2%) attended their 3‐year medical review and 587/706 (83.1%) infants had SPT results; missing data were imputed for all IgE‐mediated allergy outcomes and medically diagnosed food allergy, eczema and any allergy but not imputed for medically diagnosed asthma (wheeze) and allergic rhinitis. In secondary outcomes missing data were imputed for egg, wheat, peanut, fish, cat and any allergens but not for pollens and house dust mite allergens. Parent reported allergy: below 12 months of age ‐ 695/706 (98.4%) (intervention: 362/368, 98.4%, placebo: 335/338, 99%), between 12‐ 36 months of age ‐ 698/706 (99%), (intervention: 365/368, 99%, placebo: 333/338, 98.5%) and at 36 months of age ‐ 638/706 (90%) (intervention: 333/368, 90.5%, placebo: 305/338, 90%) were available. Missing data were not imputed for any parent reported allergy outcomes.
Results using imputed data were reported to differ little from raw data (Palmer 2012; Palmer 2013).
Selective reporting (reporting bias) Low risk Trial registered at anzctr.org.au Identifier: ACTRN12605000569606
Prespecified outcomes were reported in this trial according to their protocol. Most of the outcomes of interest to the review are reported.
Other bias Unclear risk Of the original DOMInO trial (n = 2399), a subgroup of mothers whose unborn child had a family history of allergies were included.