Gestational dyslipidaemia and adverse birthweight outcomes: a systematic review and meta‐analysis

Wang, Jingya; Moore, David; Subramanian, Anuradhaa; Cheng, Kar Keung; Toulis, Konstantinos; Qiu, Xiu; Saravanan, Ponnusamy; Price, Malcolm J; Nirantharakumar, Krishnarajah

doi:10.1111/obr.12693

Cited by 67 publications

(59 citation statements)

References 76 publications

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“…However, we assume that the contribution of the foetal metabolism will be ignorable or very little in early pregnancy, and therefore, we expect that this will have a limited effect on our results. Our results are in line with a meta-analysis of Wang et al describing a positive association of triglycerides with LGA and birth weight and a negative association of HDL-c with birth weight [53]. The associations were even stronger in overweight or obese women prior to pregnancy.…”

Section: Discussionsupporting

confidence: 93%

Maternal lipid profile in early pregnancy is associated with foetal growth and the risk of a child born large-for-gestational age: a population-based prospective cohort study

Adank

Benschop

Kors

et al. 2020

BMC Med

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Background Lipids such as cholesterol and triglycerides play an important role in both maternal and foetal energy metabolism. Little is known about maternal lipid levels in pregnancy and their effect on foetal growth. The aim of this study was to assess maternal lipid levels, foetal growth and the risk of small-for-gestational age (SGA) and large-for-gestational age (LGA). Methods We included 5702 women from the Generation R Study, a prospective population-based cohort. Maternal lipid levels (total cholesterol, triglycerides and high-density lipoprotein cholesterol [HDL-c]) were measured in early pregnancy (median 13.4 weeks, 90% range [10.5 to 17.2]). Low-density lipoprotein cholesterol (LDL-c), remnant cholesterol and non-HDL-c were calculated. Foetal growth was measured repeatedly by ultrasound. Information on birth anthropometrics was retrieved from medical records. A birth weight below the 10th percentile was defined as SGA and above the 90th percentile as LGA. Results Maternal triglyceride and remnant cholesterol levels were associated with increased foetal head circumference and abdominal circumference growth rates. Triglycerides and remnant cholesterol were positively associated with the risk of LGA (odds ratio [OR] 1.11, 95% confidence interval [CI] [1.01 to 1.22] and OR 1.11, 95% CI [1.01 to 1.23], respectively). These associations were independent of maternal pre-pregnancy body mass index, but not maternal glucose levels. We observed no association between maternal lipids in early pregnancy and SGA. Conclusions Our study suggests a novel association of early pregnancy triglyceride and remnant cholesterol levels with foetal growth, patterns of foetal growth and the risk of LGA. Future studies are warranted to explore clinical implication possibilities.

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Section: Discussionsupporting

confidence: 93%

Maternal lipid profile in early pregnancy is associated with foetal growth and the risk of a child born large-for-gestational age: a population-based prospective cohort study

Adank

Benschop

Kors

et al. 2020

BMC Med

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“…In a recent meta-analysis, we reported that maternal low HDL-C and high triglycerides at different trimesters of pregnancy are associated with higher birthweight, higher risk of large for gestational age and macrosomia 29 . The present study showed that lower B12 was associated with lower HDL-C levels in early pregnancy.…”

Section: Discussionmentioning

confidence: 98%

Vitamin B12 deficiency and altered one-carbon metabolites in early pregnancy is associated with maternal obesity and dyslipidaemia

Adaikalakoteswari

Wood

Mina

et al. 2020

Sci Rep

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Vitamin B12 (B12) is a micronutrient essential for one-carbon (1C) metabolism. B12 deficiency disturbs the 1C cycle and alters DNA methylation which is vital for most metabolic processes. Studies show that B12 deficiency may be associated with obesity, insulin resistance and gestational diabetes; and with obesity in child-bearing women. We therefore hypothesised that the associations between B12 deficiency, BMI and the metabolic risk could be mediated through altered 1C metabolites in early pregnancy. We explored these associations in two different early pregnancy cohorts in the UK (cohort 1; n = 244 and cohort 2; n = 60) with anthropometric data at 10-12 weeks and plasma/serum sampling at 16-18 weeks. B12, folate, total homocysteine (tHcy), methionine, MMA, metabolites of 1C metabolism (SAM, SAH) and anthropometry were measured. B12 deficiency (< 150 pmol/l) in early pregnancy was 23% in cohort 1 and 18% in cohort 2. Regression analysis after adjusting for likely confounders showed that B12 was independently and negatively associated with BMI (Cohort 1: β = − 0.260, 95% CI (− 0.440, − 0.079), p = 0.005, Cohort 2: (β = − 0.220, 95% CI (− 0.424, − 0.016), p = 0.036) and positively with HDL cholesterol (HDL-C) (β = 0.442, 95% CI (0.011,0.873), p = 0.045). We found that methionine (β = − 0.656, 95% CI (− 0.900, − 0.412), p < 0.0001) and SAH (β = 0.371, 95% CI (0.071, 0.672), p = 0.017) were independently associated with triglycerides. Low B12 status and alteration in metabolites in 1C metabolism are common in UK women in early pregnancy and are independently associated with maternal obesity and dyslipidaemia. Therefore, we suggest B12 monitoring in women during peri-conceptional period and future studies on the pathophysiological relationship between changes in 1C metabolites and its association with maternal and fetal outcomes on larger cohorts. This in turn may offer potential to reduce the metabolic risk in pregnant women and their offspring. Abbreviations 1CM One-carbon metabolism B12 Vitamin B12 GDM Gestational diabetes tHcy Total homocysteine IR Insulin resistance MMA Methylmalonic acid

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“…Similarly, R-J Hou, et al [27]proposed that LDL-C concentrations of pregnancy women who gave birth to LGA newborns were lower than those who gave birth to appropriate-for-gestational age (AGA) newborns. However, meta-analysis [13] and other research [12,15,16]failed to observe the relationships. The differences in maternal LDL levels, maternal basic characteristics, and covariates may explain the inconsistency of the ndings.…”

Section: Discussionmentioning

confidence: 99%

Association between maternal serum lipids during late pregnancy and adverse birth outcomes

Dai

Wang

Wu³

et al. 2020

Preprint

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Background: Adverse birth outcomes have short- and long-term impacts on maternal and child health. Maternal dyslipidemia during late pregnancy has been found to be associated with increased risk of adverse birth outcomes. However, similar evidence on association between maternal blood lipid levels and adverse birth outcomes is limited in China.Methods: The data were extracted from Guangdong Women and Children Hospital Information System from September 2014 to March 2018. A total of 3951 mother-newborn pairs were included in our study. Logistic regression model and linear trend analysis were conducted to analyze the correlation between maternal blood lipid levels and adverse birth outcomes after controlling potential confounders including gestational age, pre-pregnancy body mass index, fetal sex, and parity. Results: Among the 3951 subjects, the rates of macrosomia, large-for-gestational age (LGA), low birth weight infants (LBW), and preterm birth were 3.9% (154/3951), 8.5% (334/3951), 9.5% (377/3951), and 9.8% (388/3951), respectively. LDL was a risk factor for preterm birth (OR: 1.20; 95% CI: 1.08-1.34) while HDL was a protective factor (OR: 0.73; 95% CI: 0.55-0.96) after adjusting for covariates. As every unit increase in TG, the risk of macrosomia and LGA increased by 25% (adjusted OR: 1.25; 95% CI: 1.12-1.38) and 16% (adjusted OR: 1.16; 95% CI: 1.07-1.26), respectively. However, every unit increase in HDL concentration was associated with decreased risk for LGA (adjusted OR: 0.60; 95% CI: 0.44-0.81) and macrosomia (adjusted OR: 0.64; 95% CI: 0.41-0.99). High LDL concentrations were associated with a decreased risk of macrosomia (adjusted OR: 0.82; 95% CI: 0.68-0.99) and LGA (adjusted OR: 0.86; 95% CI: 0.76-0.98) but an increased risk of LBW (adjusted OR: 1.16; 95% CI: 1.04-1.30). The results of linear trend analysis were similar to those of logistic regression model.Conclusions: Maternal dyslipidemia during the third trimester is closely related to adverse birth outcomes. Monitoring and managing maternal blood lipid levels in an appropriate range may help to reduce the burden of adverse birth outcomes.

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Gestational dyslipidaemia and adverse birthweight outcomes: a systematic review and meta‐analysis

Abstract: This meta-analysis suggested that the potential under-recognized adverse effects of intrauterine exposure to maternal dyslipidaemia may warrant further investigation into the relationship between maternal dyslipidaemia and birthweight in large prospective cohorts or in randomized trials.

Cited by 67 publications

References 76 publications

Maternal lipid profile in early pregnancy is associated with foetal growth and the risk of a child born large-for-gestational age: a population-based prospective cohort study

Maternal lipid profile in early pregnancy is associated with foetal growth and the risk of a child born large-for-gestational age: a population-based prospective cohort study

Vitamin B12 deficiency and altered one-carbon metabolites in early pregnancy is associated with maternal obesity and dyslipidaemia

Association between maternal serum lipids during late pregnancy and adverse birth outcomes

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