Makrides 2010.

Methods	RCT: ACTRN012605000569606 (DOMInO main trial); allergy follow‐up: ACTRN12610000735055; 3‐ and 5‐year follow‐ups: ACTRN12611001127998; 4‐year follow‐up: ACTRN12611001125910; 7‐year follow‐up: ACTRN12614000770662
Participants	2399 women randomised Inclusion criteria: singleton pregnancy < 21 weeks GA, no known fetal abnormality, and not taking medication where tuna oil was contraindicated Exclusion criteria: women already taking a DHA supplement, with a bleeding disorder in which tuna oil was contraindicated, 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 Setting: 5 Australian perinatal centres, recruiting from October 2005 to January 2008 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	SUPPLEMENTATION: DHA + EPA versus placebo Group 1: DHA‐rich fish oil capsules: 3 x 500 mg/day (providing 800 mg DHA + 100 mg EPA per day): n = 1197 Group 2: matching placebo vegetable oil blend of 3 non‐genetically modified oils (rapeseed, sunflower, palm) in equal proportions: n = 1202 Timing of supplementation: from trial entry (˜20 weeks) to birth DHA + EPA dose/day: mid: 800 mg DHA + 100 mg EPA
Outcomes	Women/birth: length of gestation; adherence (28 weeks); PPH; log blood loss at birth; preterm birth < 37 weeks; early preterm birth < 34 weeks; PIH; PE; PE (clinical diagnosis in medical records); caesarean section; post‐term induction or post‐term prelabour caesarean; post‐term induction; serious morbidity composite; renal failure; liver failure; death; eructations (28 and 36 weeks); diarrhoea; gestational diabetes (based on glucose tolerance test); gestational diabetes (based on clinical diagnosis in medical record); postnatal depression (all women: EPDS > 12 at 6 weeks, 6 months postpartum); postnatal depression (women with previous or current depression at trial entry: EPDS > 12 at 6 weeks, 6 months postpartum); new diagnosis of depression in study period; new or existing diagnosis of depression during study period; antenatal admission to hospital; maternal admission to intensive care unit (level III antenatal hospitalisation); vitamin D concentrations (cord blood) Babies/infants/children: perinatal death; birthweight; birth length; head circumference at birth; birthweight z score; birth length z score; head circumference at birth z score; low birthweight < 2.5 kg); SGA (weight < 10th percentile), length, head circumference); LGA (weight (> 90th percentile), length, head circumference); birthweight > 4 kg; any serious adverse event; IVH (and grade); NEC; sepsis; convulsion; BPD (oxygen required for treatment of chronic lung disease); neonatal hypoglycaemia; resuscitation at birth; bone fracture; NICU admission; breastfeeding; morbidities up to 5 years; BSID at 18 months in 600 randomly selected infants; visual development outcomes at 4 months; attention and working memory and inhibitory control at 27 months; general cognitive function (DAS II), executive function, language, behaviour at 4 years; BMI z‐scores; body fat; BP; and insulin sensitivity at 3 and 5 years (HOMA‐IR); BMI z‐score and percentage body fat at 3 and 5 years of age (Allergy outcomes are reported in another Cochrane review (Gunaratne 2015)).
Notes	Funding: 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 and Croda Chemicals. Declarations of interest: Professor Makrides reported serving on scientific advisory boards for Nestle, Fonterra, True Origins and Nutricia. Professor Gibson reported serving on scientific advisory boards for Nestle and Fonterra. Associated honoraria for Professors Makrides and Gibson were paid to their institutions to support conference travel and continuing education for postgraduate students and early career researchers. Dr Makrides reported receiving non financial support from Clover Corporation and Nestle Nutrition. Dr Makrides, through the Women's & Children's Health Research Institute, has a patent pending: "Methods and compositions for promoting the neurological development of an infant". Dr Gould reports honoraria paid to her institution from the Nestle Nutrition Institute. Dr John Colombo served on the advisory boards for Nestle, Fonterra and Nutricia. Dr Muhlhausler had given lectures on maternal nutrition for Aspen Nutrition and Danone Nutritia. Linda Tapsell served on the Science Advisory Committees of the California Walnut Commission and the McCormicks Science Institute. Dr Palmer had consulted for and received payment for lectures from Nestle Nutrition. Dr Prescott reported receiving honorariums from the Nestle Nutrition Institute and Fonterra and being paid for lectures by the World Allergy Association and the American Academy of Asthma, Allergy and Immunology. Dr Heddle reported being paid for expert testimony from Analysis Plus and Rodika Research Services, and receiving grants from Commonwealth Serum Laboratories, Vaxine, GLaxoSmithKline, and Healthed. Dr Beverley Muhlhausler had given lectures on maternal nutrition for Aspen Nutrition and Danone Nutricia. No other author declarations.
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Quote: "Women were randomly assigned a unique study number and treatment group allocation through a computer‐driven telephone randomization service according to an independently generated randomization schedule"
Allocation concealment (selection bias)	Low risk	As above
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Quote: "All capsules were similar in size, shape and color", and, "trial investigators, staff and participants were unaware of the treatment allocation"; however more women in the treatment group guessed that they were taking fish oil capsules (67% in the treatment group compared with 13% in the control group)
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Described as "double blind"; Zhou 2012* describes a "blinded audit of medical records"; Smithers 2011* describes "a blinded assessment of a subset of healthy full‐term infants; Makrides 2014* specifies "with a psychologist who was blinded to group allocation" *These references are listed under Makrides 2010.
Incomplete outcome data (attrition bias) All outcomes	Low risk	1179/1197 (98%) women in the omega‐3 group and 1166/1202 (97%) in the placebo group completed 6‐month postpartum follow‐up (though all women were included in the primary analyses): "adequate data for the analysis of the primary outcome were available for 2320 women (97.3% in the DHA group and 96.1% in the control group)". 18 month follow‐up: 726 infants; 333/351 (95%) of infants in the omega‐3 group and 361/375 (96%) in the placebo group completed the 18‐month BSID III (though all infants were included in analyses: "694 children (95.6% of those selected for follow‐up) were assessed at 18 months". 4‐month visual acuity tests: 185 children were enrolled (91 omega‐3 and 94 control); 89/91 (98%) and 93/94 (99%) were included in analyses. 27‐month follow‐up: 184 children were eligible (1 had died): rates of loss to follow‐up were 8.8% in the omega‐3 group and 18.1% in the placebo group: "The follow‐up sample was comparable to that in the overall DOMInO trial, with the exception of the proportion of mothers in the follow‐up group who had completed tertiary education ... and compliance was slightly higher in the follow‐up group". 3‐year follow‐up: of the 1531 children (95% of those eligible) participating, there were BMI z‐scores for 96% and body fat measurements for 83%. 4‐year follow‐up: of the 726 children selected for 18 month follow‐up, 703 were eligible for 4 year follow‐up and 646 (92%) were included in the analyses. 5‐year follow‐up: of the 1531 children (95% of those eligible) participating, there were BMI z‐scores for 88% and body fat measurements for 73%. 7‐year follow‐up: 232 children (113 omega‐3; 119 control completed 7‐year follow‐up for the outcomes of body fat (Wood 2017).
Selective reporting (reporting bias)	Low risk	No indication of selective reporting bias.
Other bias	Low risk	The demographic and clinical characteristics of the women at randomisation were comparable between the 2 groups, though some divergence was seen over time in the follow‐ups, particularly with regard to sociodemographic characteristics.