Table 1.
In-Utero Supplementation Studies: Study Types and Participant Characteristics.
| Study type | Type/dosage of PUFAs | N | Length of intervention | Participant age range | Population characteristics | |
|---|---|---|---|---|---|---|
| Boucher et al. (2011) | Prospective, longitudinal | Fish eating community as setting; diet questionnaire | 153 | Non-intervention; 11-year follow-up | Mean = 11.3 | School-age Inuit children from Nunavik |
| Brei et al. (2017) | Follow-up of RCT | 1020 mg DHA+180 mg EPA+9 mg vitamin E | 130 | 15 weeks’ gestation through 4 months postpartum | In-utero/infancy at time of intervention; follow-up at 4-5 years | Healthy pregnant women |
| Campoy et al. (2011) | Follow-up study of the NUHEAL (Nutraceuticals for a Healthier Life) cohort | 500 mg DHA and 150 mg of EPA per day; 5-methyltetrahydro-folate (5-MTHF); both; or a placebo during pregnancy; infants in the intervention group received formula with .5% DHA and .4% AA | 270 in original study; 154 analyzed in follow-up | 20 weeks’ gestation through delivery; formula supplementation through 6 months | In-utero/infancy at time of intervention; follow-up at 6.5 years | Healthy pregnant women |
| Colombo et al. (2016) | RCT | 600 mg DHA per day | 350 randomized | Last two trimesters (14.5 weeks to delivery) | In-utero (follow-up at 4, 6, and 9 months) | n/s |
| Colombo et al. (2019) | RCT (follow-up) | 600 mg DHA per day | 78 in placebo and 83 in intervention completed 72-month follow-up | Last two trimesters (14.5 weeks to delivery) | 10 month-72-month follow-up | n/s |
| Daniels et al. (2004) | Observational | Fish intake measured by questionnaire | 7421 | Prenatal; non-intervention | Cognitive testing at 15 and 18 months | n/s |
| Dijck-Brouwer et al. (2005) | Observational | Umbilical artery and vein FA concentrations | 317 | Prenatal; non-intervention | Testing day 10-14 after birth | Born at 37-42 weeks’ gestation |
| Dunstan et al. (2008) | RCT | 1.1 g EPA and 2.2 g DHA per day | 98 | 20 weeks’ gestation through delivery | In-utero (follow-up at 2.5 years) | n/s |
| Escolano-Margarit et al. (2011) | RCT | 500 mg/d DHA +150 mg/d EPA), 400 mg/d 5-methyltetrahydrofolate, both, or placebo | 157 | 20 weeks’ gestation through delivery | In-utero (follow-up at 5.5 years) | Healthy pregnant women |
| Gould et al. (2014) | Secondary analysis of the DOMInO trial | 800 mg DHA/day | 185 | 20 weeks’ gestation through delivery | In-utero (follow-up at 27 ± 2 months) | 18-21 week-gestation singleton pregnancies; no fetal abnormalities |
| Gould et al. (2016) | Secondary analysis of the DOMInO trial | 800 mg DHA/day | 2399 randomized in original study; 646 in 4-year follow-up | 20 weeks’ gestation through delivery | In-utero (follow-ups at 18 months and 4 years) | 18-21 week-gestation singleton pregnancies; no fetal abnormalities |
| Helland et al. (2001) | RCT | 10 mL of cod liver oil (1183 mg of DHA, and 803 mg of EPA) per day | 590 recruited; 341 mothers completed intervention; 245 infants complied with follow-up request | 17-19 weeks’ gestation to 3 months after delivery | In-utero (follow-up at 6 and 9 months) | Healthy pregnant women |
| Helland et al. (2003) | RCT (follow-up—subgroup analysis) | Human milk containing 270% more DHA and 88% less AA than that of control group mothers | 76 | 18 weeks’ gestation to 3 months after delivery | In-utero and during lactation (follow-up at 4 years) | Healthy pregnant women; infants who were breastfed at 3 months of age |
| Helland et al. (2008) | RCT (follow-up) | 10 mL of cod liver oil (1183 mg of DHA, and 803 mg of EPA) per day | 590 recruited [. . . ] 84 tested for K-ABC at 4 years; 143 tested for K-ABV at 7 years | 17-19 weeks’ gestation to 3 months after delivery | In-utero (follow-up at 4 and 7 years) | Healthy pregnant women |
| Hibbeln et al. (2007) | Secondary analysis of Avon Longitudinal Study of Parents and Children | Food-frequency questionnaire | 11 875 | Non-intervention; seafood consumption at 32 weeks’ gestation assessed | In-utero; children assessed at 6, 18, 30, 42, and 81 months | n/s |
| Hurtado et al. (2015) | RCT | 400 mg DHA/day | 110 | 28th week of gestation and lactation period | In-utero and during lactation | Healthy; appropriate weight gain; no DHA supplementation during pregnancy |
| Makrides et al. (2010) | RCT (DOMInO trial) | 800 mg DHA/day | 2320 women evaluated for depressive symptoms; 694 children completed follow-up | 20 weeks’ gestation through delivery | In-utero; follow-up at 18 months | Singleton pregnancies; approached at > 21 weeks ‘gestation |
| Mendez et al. (2009) | Prospective cohort | Seafood consumption during pregnancy assessed | 392 | Non-intervention; results stratified by breastfeeding duration | Neurodevelopment assessed at age 4 | Full-term children; data on maternal diet during pregnancy |
| Mulder et al. (2018) | RCT (follow-up study) | 800 mg DHA/day | 98 in follow-up | 16 weeks’ gestation to delivery | In-utero; follow-up at 5-6 years | Follow-up only of singleton, term infants without neurological development affecting diseases |
| Oken et al. (2005) | Prospective cohort | Non-interventional; fish servings per week and hair mercury assessed | 135 | Non-intervention | In-utero; infants assessed at 6 months of age | Singleton pregnancy |
| Ostadrahimi et al. (2018) | RCT | 120 mg DHA and 180 mg EPA per day | 150 | 20 weeks’ gestation to 30 days postpartum | In-utero; follow-up at 4 and 6 months of age | Low-risk singleton pregnancy; follow-up of infants without major congenital deformities or metabolic disorders |
| Ramakrishnan et al. (2016) | RCT (follow-up of findings from the POSTGRAD study) | 400 mg DHA/day | 10 494 pregnant women randomized; 797 children included in follow-up | 18-22 weeks’ gestation through delivery | In-utero; follow-up at 5 years | n/s |
| Rees et al. (2019) | Observational | Non-intervention (food frequency questionnaire to estimate DHA levels) | 125 | Second and third trimester DHA levels assessed | In-utero; follow-up at 4.5 and 9 months | Single, healthy pregnancy; no significant health problems |
| Steer et al. (2013) | Secondary analysis of Avon Longitudinal Study of Parents and Children cohort | Maternal FAs in erythrocytes | 2839 | Non-intervention | In-utero; follow-up at 8 years | Pregnant women in Bristol; per original study |
| van Goor et al. (2010) | RCT | 220 mg per day of DHA, 220 mg of DHA and 220 mg AA per day, or a placebo | 119 | 17 weeks’ gestation through 20 weeks postpartum | In-utero; follow-up at 2 and 12 weeks postpartum | Healthy pregnant women |
| Vollet et al. (2007) | Secondary analysis of Upstate KIDS Study (birth cohort) | Non-intervention; self-reported consumption of fish oil before and during pregnancy | 5845 | Non-intervention | In-utero; children assessed from 4 months to 3 years of age | Mothers from the original study who had self-reported fish oil supplementation |