Assessing Omega-3 Fatty Acid Supplementation During Pregnancy and Lactation to Optimize Maternal Mental Health and Childhood Cognitive Development

Chelsea M Klemens; Kataneh Salari; Ellen L Mozurkewich

Clin Lipidology. 2012;7(1):93-109.

Mode of Placental Transport of Fatty Acids

The fetus is able to convert ALA to DHA, but this ability decreases with advancing gestational age.^[68] Therefore the fetus is largely dependent on the mother to transfer preformed DHA across the placenta.^[68] There are several factors influencing fatty acid transport across the placenta; these include maternal fatty acid status, placental function, as well as fatty acid transport proteins (FATP) and fatty acid binding proteins (FABP).^[68] Fatty acids from the maternal circulation pass across placenta cell membranes via passive diffusion as well as by active transport through a combination of binding proteins. These are termed plasma membrane fatty acid binding protein (FABPpm/GOT2), FABPs and FATPs, and fatty acid translocase (FAT/CD36).^[69] In a secondary analysis of data from a double-blind randomized DHA supplementation trial, Larque et al. demonstrated that FATP-1 and FATP-4 are most important for the transplacental transport of DHA to the fetal compartment.^[70]

Long-chain PUFA transport across the placenta is important because the fetus is able to elongate and desaturate the essential fatty acids ALA and LA to DHA and ARA, respectively, only to a limited degree.^[69] Interestingly, infants born preterm are able to convert EFA to long-chain PUFAs to a greater degree than infants born at term, although fetal capacity to synthesize ARA exceeds fetal ability to synthesize DHA.^[2] Thus, transport of the long-chain PUFAs is necessary to meet the needs of the developing brain and CNS.^[69]

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Table 1. Summary of randomized controlled trials of omega-3 fatty acids for the prevention or treatment of perinatal depression.
Study	Year	Inclusion criteria	Participants	Duration of supplementation	Composition and dose	Outcome measures	Results (significance)	Ref.
Llorente et al.	2003	Healthy lactating women	138 (37 drop-outs)	4 months during the postpartum period	200 mg DHA; placebo not described	BDI, EPDS and SCID	No significant differences	[45]
Krauss-Etschmann et al.	2007	Healthy pregnant women	311	From week 22 until delivery	500 mg DHA and 150 mg EPA/400 µg 5-MTHF/both/placebo; placebo not described	EPDS	No significant differences among the groups	[46]
Rees et al.	2008	Major depressive disorder diagnosed at baseline	26	Pregnancy and/or postpartum	6 g fish oil (27.3% DHA, 6.8% EPA), 80 mg vitamin E or placebo (sunola oil)	EPDS, HAM-D and MADRS	No difference between groups	[47]
Freeman et al.	2008	Major depressive disorder diagnosed at baseline	59	Pregnancy or postpartum	Supportive psychotherapy ± 1.1 g EPA plus 0.8 g DHA or placebo; maize oil with 1% fish oil placebo	EPDS and HAM-D	No difference between groups	[48]
Su et al.	2008	Major depressive disorder diagnosed at baseline	36	Pregnancy	2.2 g EPA plus 1.2 g DHA or placebo (olive oil ethyl esters)	HAM-D, EPDS and BDI	Significantly higher response rate and lower HAM-D, EPDS and BDI scores with intervention	[49]
Mattes et al.	2009	Healthy	98	Pregnancy (from 20 weeks' gestation until delivery)	4 g fish oil (56% DHA and 27.7% EPA) vs placebo (olive oil)	BDI	No difference between groups	[50]
Doornbos et al.	2009	Healthy	182	Pregnancy and postpartum	220 mg DHA vs 220 mg DHA + 220 mg ARA vs placebo (soy oil)	EPDS	No difference in outcomes	[51]
Makrides et al.	2010	Healthy	2399	From <21 weeks until delivery	800 mg DHA plus 100 mg EPA or vegetable oil	EPDS >12	No difference in outcomes	[44]

Table 2. Summary of randomized controlled trials of maternal omega-3 fatty acid supplementation during pregnancy and/or lactation for optimization of infant cognitive development.
Author	Year	Participants	Duration of supplementation	Intervention	Control	Outcome	Length of follow-up	Results (significance)	Ref.
Dunstan et al.	2008	98	From 20 weeks' gestation until delivery	Fish oil (DHA 2.2 g/day plus EPA 1.1 g/day)	Olive oil 2.7 g/day	GMDS; PPVT; CBC (age 2.5 years)	2.5 years	Children in supplemented group had improved hand–eye coordination	[74]
Judge et al.	2007	29	From 24 weeks' gestation until delivery	DHA-containing cereal bars (˜214 mg/day DHA)	Corn oil-containing cereal bars	Two-step problem-solving test from Willatts; FTII (9 months)	9 months	Significant improvement in problem-solving tasks; no difference in FTII	[78]
Tofail et al.	2006	400 (249 assessed)	From 25 weeks' gestation until delivery	Fish oil containing 1.2 g DHA and 1.8 g EPA daily	Soy oil placebo; LA 2.25 g/day plus ALA 0.27 g/day	BSID, WMBA (10 months)	10 months	No significant differences	[79]
Jensen et al.	2005	227	For 4 months after delivery in breastfeeding mothers	Algal oil capsules ˜200 mg DHA/day	Vegetable oil capsules: LA 56.3%; ALA 3.9%	PSI and MDI (30 months); GDI (12 and 30 months); CLAMS, visual–motor problem-solving (12 and 30 months); CAT (12 and 30 months)	30 months	PSI at 30 months of age significantly increased compared with controls	[80]
Lauritzen et al. and Cheatham et al.	2005, 2011	122	For 4 months after delivery in breastfeeding mothers	Microencapsulated fish oil added to muesli bars or to cookies or as capsules containing 900 mg/day of DHA, low content of EPA	Microencapsulated olive oil added to muesli bars or cookie or as capsules	IPT at 9 months; CDI at 1 and 2 years; ST and SDQ at 7 years	7 years	Passive vocabulary reduced in fish oil group compared with controls at 1 year of age; no difference at 2 years of age; no difference at 7 years of age	^[81,82]
Helland et al.	2001, 2003, 2008	341	From 18 weeks until 3 months after delivery	Cod liver oil containing DHA 1.183 g/day plus EPA 0.803 g/day, vitamins A, D and E	Corn oil containing LA 4.747 g/day, ALA 0.092 g/day, vitamins A, D and E	FTII at 6 and 9 months, K-ABC at 4 years; K-ABC at 7 years	7 years	No difference in outcomes at 6 and 9 months; improvements in verbal IQ scores of children whose mothers received DHA; no difference in outcomes at 7 years of age	^[75,76,83]
Makrides et al.	2010	726	From <21 weeks until delivery	800 mg DHA plus 100 mg EPA	Vegetable oil	Bayley III (18 months)	18 months	No difference in outcomes at 18 months	[44]
Escolano-Margarit et al. and Campoy et al.	2011	161	From 20th week of pregnancy until delivery	500 mg DHA and 150 mg EPA/400 µg 5-MTHF/both	Placebo not described	HE (4 years); TE (5.5 years); K-ABC (5.5 and 6.5 years)	6.5 years	No significant differences	[84,85]
van Goor et al.	2011	114	From 15.6–17.4 weeks' gestation through pregnancy and the first 3 months of lactation	DHA (220 mg), DHA plus ARA (220 mg DHA plus 220 mg ARA)	Soy oil placebo	HE, BSID (both at 18 months)	18 months	No difference in outcomes	[86]

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Assessing Omega-3 Fatty Acid Supplementation During Pregnancy and Lactation to Optimize Maternal Mental Health and Childhood Cognitive Development

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