Introduction
Pregnancy is a critical life stage whereby maternal nutrition significantly impacts the immediate and long-term health of the mother and offspring [
1]. Globally, unhealthy diets, which are energy dense but lack nutritional quality, comprise a significant behavioural risk factor for the development of chronic disease [
2]. Sub-optimal pregnancy nutrition has been linked with increased inter-generational risk factors for cardiometabolic disease, including elevated blood lipids, hypertension, impaired glucose tolerance, and long-term obesity [
2‐
4].
Pregnancy has been regarded as a ‘stress test’ for development of cardiometabolic conditions including cardiovascular disease (CVD) [
5], a major cause of morbidity and mortality globally [
6]. Physiological adaptations that occur with pregnancy progression, including metabolic and haemodynamic changes, increase stress on the maternal cardiovascular system [
7]. In addition, common pregnancy complications including preeclampsia and gestational diabetes mellitus (GDM) often driven by obesity and excess gestational weight gain (GWG), determined by pre-pregnancy BMI [
7,
8], significantly increase the risk of postpartum maternal CVD and cardiometabolic disease [
8,
9]. Roughly two-thirds of all women gain more weight than recommended during pregnancy [
10]. Hypertensive disorders of pregnancy affect 10% of pregnancies globally [
9], and GDM prevalence is 14% [
11], with up to 28% in some pregnant populations [
11]. Pregnancy is therefore a unique opportunity to detect and manage risk factors for the development of future maternal CVD [
12].
Altered lipid physiology and lipid accumulation will naturally occur with pregnancy progression, in response to physiological adaptations to foetal demands. However, evidence has shown that dyslipidaemia can predict pregnancy complications and adverse health outcomes [
13,
14]. Specifically, dyslipidaemia has been linked extensively to the development of CVD [
6,
15]. However, assessment of traditional lipid biomarkers including total triglycerides (TGs) and cholesterol does not reflect the complex lipid metabolism which occurs during pregnancy and in response to pregnancy-specific complications such as GDM [
16]. Conversely, human lipidomic analysis has emerged as an in-depth and specialised approach to measuring a wide spectrum of lipid species [
17]. Since its inception, lipidomic techniques have vastly expanded our understanding of the complexity of lipid dysregulation in cardiometabolic disease [
17]. Lipidomic profiling during pregnancy may offer a novel tool for enhancing our understanding of altered lipid metabolism and identification of women who may require early pregnancy lifestyle intervention, such as healthy dietary modification, known to be associated with favourable lipid profiles [
18] and lower risk of cardiometabolic disease [
19‐
21].
Emerging research has shown that adherence to healthy dietary patterns including the Healthy Eating Index, Mediterranean Diet and the Dietary Approaches to Stop Hypertension (DASH) diet is associated with improved maternal health and reduced risk of pregnancy complications including GDM and gestational hypertension [
19,
22]. However, data from mostly prospective cohort studies have shown that adherence to a single, preferred dietary pattern for decreasing risk of adverse pregnancy outcomes is yet to be determined. Further, assessment of diet quality (DQ) defined by adherence to national dietary guidelines and the impact on maternal lipidomic profiling has seldom been explored. The purpose of this study was to assess the association of early pregnancy DQ with maternal plasma lipidomic profiles at early and mid-pregnancy, blood pressure (BP) throughout pregnancy, diagnosis of GDM and total GWG.
Discussion
To our knowledge, this study was the first to explore the relationship between the DGI and maternal lipids, utilising lipidomics. Our findings provide novel insights into the potential impact of early pregnancy diet on important lipid biomarkers. We also provide a unique assessment of DQ across pregnancy, and its association with important pregnancy outcomes as markers of maternal cardiometabolic health. Pregnancy has been regarded a ‘missed opportunity’ for CVD prevention [
53]. The novel and comprehensive application of lipidomic analysis in our study has shown it is possible to identify abnormalities across an extensive range of plasma lipids in pregnancy, which would otherwise go undetected.
The relationship between dietary guideline adherence and maternal lipid profile was strongest for the TG lipid species when the model was adjusted for a FDR of 0.2. A higher total DGI score at early pregnancy was associated with lower levels of six TGs at mid-pregnancy (27 ± 3 weeks gestation), all containing saturated and monounsaturated long-chain fatty acid tails. Specific NL observations with these lipids highlighted observing fatty acid 14:0, 18:0 and 18:1 within these TG headgroups. Whilst past research has shown that saturated fatty acids containing 12–16 carbon atoms have the greatest effect on LDL cholesterol concentration and subsequent CVD risk [
54], stearic acid has been shown to be a major contributor to development of ischemic heart disease [
54,
55], inflammation and lipotoxicity [
54]. Further, a significant, positive association was found between total DGI score and one monounsaturated TG, palmitoleic acid (16:1). The link between palmitoleic acid and cardiometabolic health is less clear. However, epidemiological studies have linked palmitoleic acid to cholesterol metabolism, increased insulin sensitivity and glucose tolerance [
56]. High dietary intakes of palmitoleic acid have also been shown to be associated with lower blood LDL cholesterol concentrations [
54,
57]. Our findings therefore suggest that healthier dietary intakes during pregnancy may have a potential role in modifying TG levels during a critical period when women are vulnerable to dyslipidaemia. Whilst further work is needed to understand the complex relationships between early pregnancy diet and TG levels, in the context of pregnancy-related cardiometabolic health, our findings have revealed the usefulness of utilising lipidomic assessment in examining this relationship.
The importance of dietary intakes which adhere to dietary guidelines during pregnancy extends beyond the need to support optimal growth and development of the foetus, but importantly, to positively impact maternal health. Recent evidence has shown that maternal dyslipidaemia is linked with multiple, adverse maternal and foetal outcomes [
53,
58,
59]. Specifically in relation to TGs, elevated saturated/low unsaturated levels have been shown to predict GDM in the few studies that have used lipidomics to quantify lipid profiles in pregnancy [
16,
60]. The impact of dyslipidaemia on maternal health can also persist far beyond pregnancy. For example, data from the Generation R study, (
n = 5690) assessed early pregnancy maternal lipid profiles at 13 weeks gestation and found that TG and remnant cholesterol levels in early pregnancy were associated with long-term postpartum hypertension at 6 and 9 years [
13]. Therefore, pregnancy is a unique life-stage which offers an opportunity to identify and appropriately manage, risk factors for current and future cardiometabolic disease in the clinical setting.
We found that DQ scores reflected low adherence to the Australian Dietary Guidelines, findings similar to other studies which have assessed dietary intake during pregnancy [
61‐
63] and across non-pregnant populations [
64]. In our study, intake of fruit and vegetables and discretionary food items did not adhere to guidelines. Whilst many barriers to implementation of dietary guidelines during pregnancy have been identified, including pregnancy symptoms such as fatigue and nausea [
63,
65] inadequate provision of nutrition counselling from antenatal healthcare providers [
65,
66] and a lack of knowledge regarding healthy eating during pregnancy [
61,
67], adherence to dietary guidelines assessed via DQ indices has been consistently shown to reduce the risk of cardiometabolic disease [
32,
68]. This indicates the overall potential long-term benefit of achieving dietary intakes which adhere to dietary guidelines and underpins pregnancy a critical period. Pregnancy care practices should ensure women are adequately supported to achieve optimal dietary intakes for both short- and long-term health benefit.
Aside from an association between DQ and diastolic BP at late pregnancy, we found no other significant associations between DQ and BP or GDM. Previous studies have shown a reduced risk of GDM with dietary intakes high in fruit and vegetables, whole grains and legumes, yet overall, findings have been mixed [
69]. In the only systematic review and meta-analysis to date to have evaluated the impact of DQ using defined adherence to dietary guidelines during preconception and pregnancy on adverse perinatal outcomes [
22], pooled data from 33 prospective cohort studies showed that higher DQ was associated with lower risk for GDM and preeclampsia [
22]. Specifically, the Mediterranean Diet and the Dietary Approaches to Stop Hypertension (DASH) diets have shown promising results in reducing risk for pregnancy complications, including gestational hypertension. They have previously been associated with improved glucose and lipid metabolism and with lower systolic and diastolic BP [
19,
70]. Variation in dietary approaches across DQ assessment (e.g. Mediterranean diet, Prime Diet Quality Score, the Alternative Healthy Eating Index and the Nordic Diet) points to the need for further large prospective cohort and population studies which assess DQ with pregnancy outcomes, to determine a preferred dietary pattern for use in early pregnancy interventions.
We found no association between DQ at early pregnancy and total GWG, a finding consistent with the literature to date reporting this relationship [
22]. Perhaps not surprisingly, overall energy intake rather than DQ has been suggested to be the main driver of GWG during pregnancy [
22,
71]. Excess GWG is a significant contributing factor to postpartum weight retention [
72] and should be routinely monitored as part of screening for risk factors which impact women’s cardiometabolic health during pregnancy.
Strengths and limitations
A major strength of our study was the utilisation of comprehensive human lipidomic analysis. This robust method has enabled insights into the potential impact of diet on lipid metabolism at the molecular level in pregnant women. This was also the first study to our knowledge, to have assessed the relationship between DQ and maternal plasma lipidomics during pregnancy, including measures across two trimesters. An additional strength of this study was using the Australian DGI to calculate DQ at both early and late pregnancy. Dietary intake assessment has shifted from evaluating individual nutrient intake to whole foods and food patterns [
73] to account for important interactions of nutrients and non-nutrient components [
73]. Therefore, a major strength of the DGI is that it is a validated, food-based index and is translatable to public health messages related to the whole diet [
74]. Our study also has some limitations. Recruitment of a high proportion (64%) of tertiary educated women with low-risk pregnancies means that findings are not generalizable to all pregnant women, especially those at ‘high risk’ of maternal complications. Assessment of DQ in less educated populations would enable important identification of vulnerable pregnant women, as poorer DQ may be expected in women of lower socioeconomic status and lower education level. Future research might also recruit women with more complicated pregnancies or women who are at high risk for adverse pregnancy outcomes, specifically women with a pre-pregnancy BMI > 30 kg/m
2. A further limitation was the use of self-reported dietary data which may be prone to recall bias or social desirability (e.g. overreported fruit and vegetable intake). However, as mean DGI scores of healthy foods including fruit and vegetables fell short of meeting dietary guidelines, this would suggest that women did not overreport intake of healthy foods. The DQES is commonly used to assess usual intake over the past 12 months and despite having been previously validated against weighed food records, it may not entirely reflect usual dietary intake due to recall of intake over a relatively long timeframe. Further, we did not account for women’s physical activity levels in our study, which is important when considering the effect on plasma TGs. We recognise that there is a need to consider the effect of lifestyle factors including physical activity in interpreting lipidomic profiles in pregnancy, as physical activity has shown positive effects on lowering fasting and postprandial blood glucose levels and blood triglyceride concentrations [
75]. Finally, as this was a low-risk sample of pregnant women without serious complications, we could not assess associations of DQ with preeclampsia. However, including BP outcomes across pregnancy was an important aspect of our study as BP monitoring of levels below clinical thresholds of gestational hypertension or preeclampsia is still important in the assessment of overall CVD-related health.