Effect of Prenatal Docosahexaenoic Acid Supplementation on Blood Pressure in Children With Overweight Condition or Obesity: A Secondary Analysis of a Randomized Clinical Trial

Abstract

Importance: The blood pressure-lowering property of docosahexaenoic acid (DHA) in children and adults is known, and an observational study from the Netherlands has linked higher intrauterine DHA exposure to lower childhood blood pressure. However, the association of prenatal intake of DHA supplement with childhood blood pressure has not been evaluated in randomized clinical trials.

Objective: To determine the effect of DHA supplementation during pregnancy on childhood blood pressure.

Design, setting, and participants: This prespecified secondary analysis of the Kansas University DHA Outcome Study (KUDOS), a phase 3, double-blind, randomized, placebo-controlled clinical trial was conducted at several local hospitals in the Kansas City, Kansas, metropolitan area. Pregnant women (n = 350) were enrolled in the KUDOS trial between January 10, 2006, and November 17, 2009, and were followed up until their children were 18 months of age. During pregnancy, the women received either 3 capsules per day of placebo or 600 mg per day of DHA from a mean (SD) of 14.5 (3.7) weeks' (all before 20 weeks) gestation until birth. The parents of 190 children consented to additional follow-up of their children until 6 years, which ended April 29, 2016. Study personnel involved in testing were blind to the randomization until all children had completed the trial. Data analysis was performed from May 23, 2017, to July 10, 2018.

Interventions: Pregnant women were assigned to either 600 mg per day of DHA or a placebo that was half soy and half corn oil. Both placebo and DHA were provided in 3 capsules per day.

Main outcomes and measures: Childhood blood pressure was a planned secondary outcome of a study powered to measure cognitive development. The hypothesis was that DHA would lower blood pressure prior to data analysis. Systolic blood pressure (SBP) and diastolic blood pressure (DBP) were measured at 4, 4.5, 5, 5.5, and 6 years and were analyzed for possible covariates using mixed models to generate a final model.

Results: In total, 171 children (88 [51.5%] female) were included in this analysis. Of these children, 89 (52.0%) were randomized to the DHA group and 82 (47.9%) to the placebo group. A statistically significant interaction was found between treatment (placebo or DHA) and child weight status (5-year body mass index ≤85th or >85th percentile) for both SBP and DBP. Children who were overweight or obese whose mothers received placebo during pregnancy had higher SBP and DBP compared with children who were overweight or obese whose mothers received DHA (mean [SE] SBP, 104.28 [1.37] mm Hg vs 100.34 [1.02] mm Hg; DBP, 64.7 [1.23] mm Hg vs 59.76 [0.91] mm Hg). No differences in the SBP and DBP were found between children who were overweight or obese whose mothers received DHA and children who were not overweight or obese. In the mixed model analysis, the child's age at blood pressure measurement and the maternal prepregnancy body mass index were the only other statistically significant variables (child age, SBP: F = 7.385; P = .001; DBP: F = 7.39; P = .001; prepregnancy BMI, SBP: r = 0.284; P = .001; DBP: r = 0.216; P = .01).

Conclusions and relevance: Maternal docosahexaenoic acid intake during pregnancy appeared to mitigate the association between childhood overweight condition or obesity and blood pressure.

Trial registration: ClinicalTrials.gov Identifier: NCT02487771.

Conflict of interest statement

Conflict of Interest Disclosures: Mss Kerling, Hilton, and Thodosoff reported receiving grants from Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) during the conduct of the study as well as nonfinancial support from DSM Nutritional Products outside of the submitted work. Dr Colombo reported receiving honoraria from Mead Johnson Nutrition (now RB) and Fonterra as well as being an occasional consultant for several companies that make maternal or infant nutritional products. Dr Carlson reported receiving nonfinancial support from DSM, grants from NICHD during the conduct of the study, grants and other research support from DSM, and personal fees from Mead Johnson Nutrition (now RB) outside the submitted work; she also reported consulting for and receiving honoraria from Mead Johnson Nutrition (now RB), Baxter, and DSM. No other disclosures were reported.

Figures

Figure 1.. CONSORT Flow Diagram

BMI indicates body mass index; DHA, docosahexaenoic acid.

Figure 2.. Systolic and Diastolic Blood Pressure at Each Age by Maternal Docosahexaenoic Acid (DHA) Randomization

BMI indicates body mass index. Error bars indicate SE