Maternal plasma n-3 and n-6 polyunsaturated fatty acids during pregnancy and features of fetal health: Fetal growth velocity, birth weight and duration of pregnancy

Highlights

• The maternal n-3:n-6 PUFA ratio is positively associated with fetal growth velocity and duration of pregnancy.

• In particular a higher n-3 PUFA status is proposed for favourable pregnancy outcomes.

• An optimal balance between maternal n-3 and n-6 PUFA’s is important for fetal health.

Summary

Background & aims

Maternal fatty acids are essential for fetal growth and development. Here, we examine associations between maternal mid-pregnancy plasma n-3 and n-6 polyunsaturated fatty acids (PUFAs) and fetal health determined by fetal growth velocity, birth weight and duration of pregnancy.

Methods

Participants were 6974 pregnant women and their infants from a population-based birth cohort, the Generation R Study. Maternal plasma n-3:n-6 PUFA ratio and n-3 and n-6 PUFA percentage in glycerophospholipids in mid-pregnancy were related to fetal growth velocity calculated from repeatedly measured weight, length and head circumference, birth weight, and duration of pregnancy.

Results

A higher maternal mid-pregnancy n-3:n-6 PUFA ratio was associated with a higher growth velocity of the fetal weight (β = 0.082 SD-score/week, 95% CI 0.055; 0.108, P < 0.001), length (β = 0.085 SD-score/week, 95% CI 0.052; 0.119, P < 0.001); and head (β = 0.055 SD-score/week, 95% CI 0.019; 0.091, P = 0.003).

We also observed positive associations between n-3:n-6 PUFA ratio and birth weight (β = 0.76 SD-score, 95% CI 0.22; 1.29, P = 0.006), and duration of pregnancy (β = 1.32 weeks, 95% CI 0.24; 2.40, P = 0.02).

Conclusions

These results are consistent with the hypothesis that a higher n-3:n-6 PUFA ratio is important for fetal health.

Introduction

Derangements in fetal growth, low birth weight and preterm birth are features of fetal health and the leading causes of infant death and long-term metabolic and neurological disabilities [1]. Low birth weight can be the result of preterm birth or fetal growth restriction or both. A better understanding of the factors that underlie preterm or small-for gestational age (SGA) births can help to improve fetal health and reduce mortality, morbidity and associated health care costs.

Even in well-nourished populations, the quality of dietary patterns is associated with the course and outcome of pregnancy [2], [3]. As humans are incapable of synthesizing polyunsaturated fatty acids (PUFAs) they depend on dietary intake. As these PUFAs have implications for many different biological properties including energy storage, oxygen transport, conformation of cell membranes, and regulation of cell proliferation and inflammation, they are considered as potential biomarkers and determinants of preterm and SGA births [4], [5].

These studies, that mostly relied on estimated intake of fatty acids, suggest that in particular excessive intake of n-6 PUFAs relative to n-3 PUFAs may increase the probability of adverse pregnancy outcomes [6], although results are not consistent. Observational studies have associated higher intakes of n-3 PUFA during pregnancy with a longer duration of pregnancy [7]. Different meta-analyses confirmed the results on higher birth weight and length of gestation after n-3 PUFA supplementation during pregnancy [8], [9]. The use of n-3 PUFA supplements to reduce the risk of adverse birth outcomes, however, is not generally accepted [10]. In addition, no consensus about the type, dose, timing and duration of the used n-3 PUFA supplements have been reached.

Against this background, we aimed to explore the association between the percentage of maternal plasma n-3 and n-6 PUFAs in glycerophospholipids and features of fetal health. In a large population-based cohort study, percentage of n-3 and n-6 PUFAs in glycerophospholipids were measured in mid-pregnancy and related to duration of pregnancy, birth weight and parameters of fetal growth (weight, length and head circumference) based on three repeated ultrasounds in early, mid and late pregnancy. As a higher maternal n-3:n-6 PUFA ratio has been reported to predict the infant size at birth, we hypothesised that a higher maternal n-3:n-6 PUFA ratio is positively associated with the fetal growth velocity from mid-pregnancy onward.