Higher Oily Fish Consumption in Late Pregnancy Is Associated With Reduced Aortic Stiffness in the Child at Age 9 YearsNovelty and Significance
Rationale: Higher pulse wave velocity (PWV) reflects increased arterial stiffness and is an established cardiovascular risk marker associated with lower long-chain n-3 polyunsaturated fatty acid intake in adults. Experimentally, maternal fatty acid intake in pregnancy has lasting effects on offspring arterial stiffness.
Objective: To examine the association between maternal consumption of oily fish, a source of long-chain n-3 polyunsaturated fatty acids, in pregnancy and child’s aortic stiffness age 9 years.
Methods and Results: In a mother–offspring study (Southampton Women’s Survey), the child’s descending aorta PWV was measured at the age of 9 years using velocity-encoded phase-contrast MRI and related to maternal oily fish consumption assessed prospectively during pregnancy. Higher oily fish consumption in late pregnancy was associated with lower childhood aortic PWV (sex-adjusted β=−0.084 m/s per portion per week; 95% confidence interval, −0.137 to −0.031; P=0.002; n=226). Mother’s educational attainment was independently associated with child’s PWV. PWV was not associated with the child’s current oily fish consumption.
Conclusions: Level of maternal oily fish consumption in pregnancy may influence child’s large artery development, with potential long-term consequences for later cardiovascular risk.
Greater aortic stiffness increases systolic blood pressure (BP) with age1 and predicts future cardiovascular risk and all-cause mortality.2 Higher pulse wave velocity (PWV) reflects increased arterial stiffness and is an established cardiovascular risk marker.3,4 There is now evidence that early developmental factors may partly set such risk.5
Long-chain n-3 polyunsaturated fatty acids (LC-PUFAs) are associated with reduced cardiovascular risk; consumption in adulthood reduces arterial stiffness.6 Conversely, in rats, increased saturated fatty acid intake in pregnancy increases offspring arterial stiffness,7 suggesting that variations in maternal diet have long-term consequences for later arterial stiffness and cardiovascular risk. We examined maternal consumption of oily fish, a source of LC-PUFAs, in pregnancy in relation to the child’s arterial stiffness age 9 years.
In a UK mother–offspring study (Southampton Women’s Survey8), maternal early and late pregnancy diet and child’s diet age 9 years were assessed using administered questionnaires.9 Aortic PWV was measured in 234 children aged 9 years, with approval from the local ethics committee and informed written assent/consent.
MRI phase-contrast velocity encoding sequences were acquired in the plane perpendicular to the aortic long axis, in the proximal descending aorta (level of the pulmonary trunk) and the distal descending aorta (above the aortic bifurcation; Figure 1). A phase-contrast flow mapping sequence was used with free breathing and retrospective ECG gating. A velocity encoding gradient of 150 to 200 cm/s was applied in the through plane direction. Right brachial BP was recorded using a pediatric cuff immediately after the flow sequence acquisitions (Invivo MRI compatible patient monitor). Velocity flow curves were generated using open source software (Osirix). PWV (m/s) was calculated using Matlab (MathWorks, Natick, MA) and the transit time method10 from Δd/Δt (Δd=distance, Δt=transit time of the systolic wavefront between the 2 flow acquisition sites; Figure 1).
Univariate linear regression analyses were performed (Stata version 13.0; Statacorp LP, College Station, TX) to relate child’s PWV with maternal oily fish consumption and other maternal, infant, and childhood factors shown in Table 1; multivariate analysis included variables with significant associations. β-coefficients reflect the change in outcome when compared with the reference category.
A total of 256 participants attended for MRI; 4 declined, 7 proved claustrophobic, 10 did not complete the protocol/had substandard images from motion artifacts. One extreme outlier, attributed to measurement error, was excluded. Table 1 shows characteristics of the remaining 234 children (116 boys); mean PWV was 3.5 m/s (within previously reported childhood ranges11) and body mass index was 17.3 kg/m2. 26.9% of mothers smoked prepregnancy.
Analyzed as a continuous variable, higher late pregnancy maternal oily fish consumption was associated with lower childhood aortic PWV (sex-adjusted β=−0.084 m/s per portion per week [95% confidence interval, −0.137 to −0.031]; P=0.002; Figure 2), with a similar association for early pregnancy oily fish consumption (β=−0.062 [−0.124 to −0.001]; P=0.046). Higher mother’s educational attainment (3 levels; Table 1) was associated with lower childhood PWV (β=−0.175 m/s per level [−0.278 to −0.072]; P=0.002), as was higher social class (Table 2). The coefficients above hardly changed in multivariate analysis simultaneously including both mother’s educational attainment and late pregnancy oily fish consumption; both P values remained 0.002. Additional inclusion of maternal, neonatal, and childhood characteristics significant at P<0.1 (Table 2) had little influence on these associations (Table 3).
PWV showed the expected associations with childhood systolic and diastolic BP, mean arterial pressure, and heart rate (Table 2). After adjusting for mother’s qualification level and child’s sex, maternal oily fish consumption was not associated with childhood heart rate or BP (Online Table I). Childhood PWV showed no associations with birthweight, or child’s height, body mass index, and oily fish consumption at 9 years.
Greater maternal oily fish consumption in early or late pregnancy was associated with lower child’s aortic PWV and aortic stiffness at the age of 9 years. LC-PUFAs in oily fish and fish oils have anti-inflammatory properties, reduce BP, and increase endothelial relaxation, vascular compliance, and heart rate variability12; supplementation in adults reduces arterial stiffness.6 LC-PUFA levels in the fetal circulation increase in late pregnancy, when fetal docosahexaenoic acid correlates with maternal levels.13 This may explain the stronger association between child’s PWV and late versus early pregnancy maternal oily fish consumption.
We found no association between child’s current oily fish consumption and vascular stiffness. In keeping with this, LC-PUFA supplementation during childhood offers few long-term cardiovascular benefits in terms of BP, heart rate, or arterial distensibility assessed several years after the supplementation.14–16 Cardiovascular measures taken in infants during a period of supplementation with fish oil, and docosahexaenoic acid or LC-PUFA supplemented infant formulae, did however show favorable heart rate and BP changes.17–19 These studies, together with our data showing an effect of prenatal nutrition, suggest that nutritional interventions instituted early in the lifecourse may be most effective.
PWV was linked to the child’s BP, but there was no association between maternal oily fish consumption and BP. Arterial stiffening is the principal cause of increased cardiac afterload and increasing systolic BP with advancing years1; even without an independent effect on childhood BP, structural changes in the vascular wall induced by maternal diet during development may have implications for adult cardiac function and BP. Higher childhood PWV has uncertain predictive value and does not itself cause disease, but baseline PWV does predict later aortic dilatation in children with tetralogy of Fallot.20
Participants in this study are part of a prospective longitudinal cohort study covering a wide socioeconomic background. Vascular stiffness was assessed at the age of 9 years, before the acquisition of significant risk burden, ensuring minimal influence of other lifestyle risk factors such as smoking. Our results are thus unlikely to be confounded by the influence of other cardiovascular risk factors.
In summary, our findings suggest that normal variations in maternal oily fish consumption in pregnancy influence vascular development of the fetus, changing childhood aortic compliance, with implications for later cardiovascular disease. The findings raise the question of the major influences on maternal diet. The quality of women’s diets is strongly dependent on their nutrition literacy and level of educational attainment,21 and we found an independent and additive effect of maternal educational attainment on childhood vascular stiffness, perhaps reflecting other nutritional influences. The findings raise the possibility that interventions that improve educational attainment and nutrition literacy could reduce cardiovascular risk in the next generation.
We are grateful to the women of Southampton and their children who gave their time and to the staff who collected and processed the data.
Sources of Funding
The Medical Research Council, British Heart Foundation, NIHR (National Institute for Health Research) Southampton Biomedical Research Centre and the European Union’s Seventh Framework Programme project EarlyNutrition (FP7/2007–2013, no. 289346).
K.M. Godfrey has received reimbursement for speaking at conferences sponsored by companies selling nutritional products and is part of an academic consortium that has received research funding from Abbott Nutrition, Nestec and Danone. The other authors report no conflicts.
In January 2015, the average time from submission to first decision for all original research papers submitted to Circulation Research was 14.7 days.
The online-only Data Supplement is available with this article at http://circres.ahajournals.org/lookup/suppl/doi:10.1161/CIRCRESAHA.116.305158/-/DC1.
- Nonstandard Abbreviations and Acronyms:
- blood pressure
- long-chain n-3 polyunsaturated fatty acid
- pulse wave velocity
- Received August 29, 2014.
- Revision received February 16, 2015.
- Accepted February 19, 2015.
- © 2015 American Heart Association, Inc.
- Mitchell GF,
- Hwang SJ,
- Vasan RS,
- Larson MG,
- Pencina MJ,
- Hamburg NM,
- Vita JA,
- Levy D,
- Benjamin EJ
- Barker DJ
- Pase MP,
- Grima NA,
- Sarris J
- Armitage JA,
- Lakasing L,
- Taylor PD,
- Balachandran AA,
- Jensen RI,
- Dekou V,
- Ashton N,
- Nyengaard JR,
- Poston L
- Inskip HM,
- Godfrey KM,
- Robinson SM,
- Law CM,
- Barker DJ,
- Cooper C
- Ulbak J,
- Lauritzen L,
- Hansen HS,
- Michaelsen KF
- Ayer JG,
- Harmer JA,
- Xuan W,
- Toelle B,
- Webb K,
- Almqvist C,
- Marks GB,
- Celermajer DS
- de Jong C,
- Boehm G,
- Kikkert HK,
- Hadders-Algra M
- Damsgaard CT,
- Schack-Nielsen L,
- Michaelsen KF,
- Fruekilde MB,
- Hels O,
- Lauritzen L
Novelty and Significance
What Is Known?
Experimental studies have shown that a mother’s fatty acid intake in pregnancy has lasting effects on arterial stiffness in the offspring.
In human pregnancy, little is known about whether a mother’s diet influences arterial stiffness and cardiovascular risk in her children.
What New Information Does This Article Contribute?
Children whose mothers had higher oily fish consumption in pregnancy had lower aortic stiffness at the age of 9 years, measured by MRI.
The findings provide further evidence that nutritional interventions instituted early in the lifecourse could be effective in reducing cardiovascular risk in the offspring.
Prenatal influences contribute to the risk of cardiovascular disease in adulthood, but the developmental exposures and underlying mechanisms are poorly understood. One possible mechanism is large artery structure and stiffness; this is partly determined in utero and greater stiffness is the principal cause of increased cardiac afterload and increasing blood pressure with age. Here, we show that higher maternal oily fish intake in pregnancy is associated with lower aortic stiffness in children aged 9 years. The findings highlight the importance of prenatal vascular development and suggest that interventions that improve a mother’s nutrition could reduce cardiovascular risk in the next generation.