Hauner 2012.

Methods	RCT: NCT00362089 (INFAT ‐ The Impact of Nutritional Fatty acids during pregnancy and lactation for early human Adipose Tissue development)
Participants	208 women randomised Inclusion criteria: healthy pregnant women < 15 weeks GA, aged 18‐43 years, BMI at conception between 18 and 30, sufficient German language; for infants at follow‐up, GA at birth between 37‐42 weeks, appropriate size for GA, and Apgar score > 7 at 5 minutes Exclusion criteria: high‐risk pregnancy (multiple pregnancy, hepatitis B or C infection, parity > 4), hypertension, chronic diseases such as diabetes or gastrointestinal disorders, psychiatric disorders, supplementation with omega‐3 fatty acids before randomisation, alcohol abuse, hyperemesis gravidarum, smoking; known metabolic defects Characteristics: mean baseline BMI of 22; women were relatively well educated Setting: University Hospital Klinikum rechts der Isar, Technische Universität München, Germany (women recruited between 2006 and 2009)
Interventions	SUPPLEMENTATION + DIET ADVICE: DHA + EPA + diet advice versus diet advice Group 1: omega‐3 LCPUFA (180 mg EPA and 1020 mg DHA (= 1200 mg omega‐3) and 9 mg vitamin E), taken as 3 capsules per day and requested to restrict consumption of AA‐rich foods (e.g. meat (500 g a week = 2‐3 portions), meat products and eggs); n = 104 Group 2: brief semi‐structured counselling on a healthy diet according to the guidelines of the German Nutrition Society for a healthy balanced diet; women in the control group were specifically asked to refrain from taking fish oil or DHA supplements: n = 104 All women: participants of both groups were also offered individual nutrition counselling based on the 7‐day dietary record. Timing of supplementation: women were randomised and began the study at 15 weeks GA and continued supplementation until 4 months lactating (or time when ceased breastfeeding if earlier) DHA + EPA dose/day: high: 1020 mg DHA + 180 mg EPA
Outcomes	Women: adherence; preterm birth; post‐term birth; induction (all at term); GWG; blood loss at birth; gestational diabetes; pathological cardiotocography; cessation of labour; retained placenta; mode of birth (spontaneous birth, caesarean section, vacuum extraction); breastfeeding; blood lipid concentrations (triglycerides, total cholesterol, high‐ and low‐density lipoproteins) at baseline, 32 weeks GA, birth, 6 weeks and 4 months postpartum in pregnant and lactating women; leptin; fatty acid pattern in erythrocytes and plasma in maternal blood as well as umbilical cord blood samples and adipokines in maternal plasma, as well as umbilical cord plasma samples and breastmilk samples at 6 weeks and 4 months; maternal 7‐day dietary questionnaire (energy, protein, carbohydrates, lipids, AA); maternal plasma levels of DHA, EPA and AA reported as per cent weight of total fatty acids; maternal RBC fatty acid baseline (16‐21 weeks GA) – before study drug was dispensed (reported in Hauner 2009 only by fish consumption), insulin resistance; maternal leptin; cord blood insulin concentrations Babies/infant/children: Apgar score; LGA > 90th percentile; adipose tissue mass (skinfold thickness) 3‐5 days after birth, 6 weeks, 4 and 12 months postpartum; subgroup: subcutaneous and visceral fat mass ultrasonography at 6 weeks, 4 and 12 months postpartum and MRI at 6 weeks and 4 months postpartum; birthweight; birth length; head circumference; upper arm circumference); body weight and length, head circumference and upper arm circumference, BMI (kg/m²) ‐ all at birth/3‐5 days after birth, 6 weeks, 4 and 12 months postpartum; weight/length (g/cm) at birth; ponderal index (kg/m³) at birth; fetal leptin; annual body‐composition measurements including skinfold thickness measurements (primary outcome) ‐ up to 5 years, a sonographic assessment of abdominal subcutaneous and preperitoneal fat, and child growth at 2, 3, 4 and 5 years (weight, height, head circumference, BMI percentile, waist circumference); abdominal MRI was performed in a subgroup of 5‐year‐old children; dietary intake at 3, 4 and 5 years; physical activity at 3, 4 and 5 years; Child Development Inventory at 4 and 5 years; hand movement test at 5 years (mirror movements reported as medians).
Notes	Funding: Else Krӧner‐Fresenius Foundation, Bad Hamburg, the International Unilever Fund, EU‐funded EARNEST Consortium (subcontractor Numico, Frankfurt), and the German Ministry of Education and Research via the Competence Network on Adiposity; Danone Research‐Centre for Specialised Nutrition, Friedrichsdorf, Germany. The analysis of fatty acids was performed by the laboratory of Lipid Research, Danone Research–Centre for Specialised Nutrition by using coded samples. "There was no intervention from any sponsor with any of the research aspects of the study including study design, intervention, data collection, data analysis and interpretation as well as writing of the manuscript." "Danone as a Funding source and cooperation partner in fatty acid analysis was recruited after the study design was fully established." Declarations of interest: "HH has received grants from Riemser and Weight Watchers for clinical trials and payment for lectures from Novartis, Roche Germany, and Sanofi‐Aventis". The other authors reported no conflicts of interest related to the study.
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Computerised randomisation
Allocation concealment (selection bias)	Unclear risk	Quote: “randomly assigned”
Blinding of participants and personnel (performance bias) All outcomes	High risk	Not blinded; “open label”
Blinding of outcome assessment (detection bias) All outcomes	High risk	No (except for US measurements, e.g. for fat mass measurements)
Incomplete outcome data (attrition bias) All outcomes	High risk	Omega 3: 17/104 (16%) lost at 12 months postpartum: 8 personal reasons 3 lost to follow‐up 1 with group allocation 2 intolerance to supplements 1 moved away 1 repeated non‐attendance 1 genetic disorder in child diagnosed Control: 21/104 (20%) lost at 12 months: 3 personal reasons 2 lost to follow‐up 6 unhappy with group allocation 4 moved away 3 repeated non‐attendance 3 preterm birth 2 years and longer: 118 children remained at 2 years of age (56.7%) 120 children at 3 years of age (57.7%) 107 children at 4 years of age (51.4%), and 114 children at 5 years of age (54.8%), with similar numbers between study groups (at 5 years: intervention group, n = 58; control group, n = 56). The most common reasons for dropout were a lack of time or relocation. Unclear why 3/4 preterm births in the control group were treated as exclusions, whereas none of the 3 preterm births in the omega‐3 group were.
Selective reporting (reporting bias)	Unclear risk	Focus on biochemical and skinfold measurements rather than clinical outcomes
Other bias	Unclear risk	Baseline demographics and characteristics were comparable, except for higher rates of smoking and alcohol use during pregnancy in the control group.