Dataset Information

Race-ethnic differences in the associations of maternal lipid trait genetic risk scores with longitudinal fetal growth.

ABSTRACT:

Background

Fetal growth, an important predictor of cardiometabolic diseases in adults, is influenced by maternal and fetal genetic and environmental factors.

Objective

We investigated the association between maternal lipid genetic risk score (GRS) and fetal growth among 4 US racial-ethnic populations (Whites, Blacks, Hispanics, and Asians).

Methods

We extracted genotype data for 2008 pregnant women recruited in the National Institute of Child Health and Human Development Fetal Growth Studies-Singleton cohort with up to 6 standardized ultrasound examinations. GRS was calculated using 240 single-nucleotide polymorphisms previously associated with higher total cholesterol (GRS_TChol), low-density lipoprotein cholesterol (GRS_LDLc), and triglycerides (GRS_TG) and lower high-density lipoprotein cholesterol (GRS_HDLc).

Results

At 40 weeks' gestation, a unit increase in GRS_TG was associated with 11.4 g higher fetal weight (95% confidence interval [CI] 2.8-20.0 g) among normal-weight Whites, 26.3 g (95% CI 6.0-46.6 g) among obese Blacks, and 30.8 g (95% CI 6.3-55.3 g) among obese Hispanics. Higher GRS_HDLc was associated with increased fetal weight across 36 to 40 weeks among normal-weight Whites and across 13 to 20 weeks among normal-weight Asians, but with decreased fetal weight across 26 to 40 weeks among normal-weight Hispanics. Higher GRS_TChol was suggestively associated with increased fetal weight in males and decreased in females. Associations remained consistent after adjustment for serum lipids.

Conclusion

Associations between fetal weight and maternal lipid GRS appear to vary by maternal race-ethnic group, obesity status, and offspring sex. Genetic susceptibility to unfavorable lipid profiles contributes to fetal growth differences even among normal-weight women suggesting a potential future application in predicting aberrant fetal growth.

SUBMITTER: Ouidir M

PROVIDER: S-EPMC6885118 | biostudies-literature | 2019 Sep - Oct

REPOSITORIES: biostudies-literature

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Publications

Race-ethnic differences in the associations of maternal lipid trait genetic risk scores with longitudinal fetal growth.

Ouidir Marion M Mendola Pauline P Workalemahu Tsegaselassie T Grewal Jagteshwar J Grantz Katherine L KL Zhang Cuilin C Wu Jing J Tekola-Ayele Fasil F

Journal of clinical lipidology 20190629 5

<h4>Background</h4>Fetal growth, an important predictor of cardiometabolic diseases in adults, is influenced by maternal and fetal genetic and environmental factors.<h4>Objective</h4>We investigated the association between maternal lipid genetic risk score (GRS) and fetal growth among 4 US racial-ethnic populations (Whites, Blacks, Hispanics, and Asians).<h4>Methods</h4>We extracted genotype data for 2008 pregnant women recruited in the National Institute of Child Health and Human Development Fe ...[more]

PMID: 31383602

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Project description:ImportanceEvidence on the timing of fetal growth alterations associated with gestational diabetes or on the association of the maternal glycemic trajectory with fetal growth during pregnancy remains lacking.ObjectiveTo examine the associations between maternal glucose levels and offspring intrauterine growth.Design, setting, and participantsThis cohort study used data from 4574 eligible pregnant women and their offspring in the Shanghai Maternal-Child Pairs Cohort collected from April 10, 2016, to April 30, 2018. Group-based trajectory modeling was used to classify fasting plasma glucose levels during pregnancy into 3 glycemic trajectories (trajectory 1, consistently normal glucose levels in all 3 trimesters; trajectory 2, hyperglycemia only in late pregnancy; and trajectory 3, hyperglycemia in all 3 trimesters [ie, consistently high glucose levels]). Statistical analysis was performed from April 25, 2020, to October 1, 2021.ExposuresGestational diabetes, which was defined using the results of an oral glucose tolerance test.Main outcomes and measuresLongitudinal fetal biometrics during gestational weeks 11 to 40 and birth outcomes were obtained from medical records. Pregnancy was partitioned into 3 periods (<24, 24-34, and >34 weeks' gestational age). The differences in offspring growth (log-transformed) and maternal glucose levels were compared using generalized linear mixed models.ResultsA total of 4121 pregnant women had oral glucose tolerance test results (mean [SD] age, 28.8 [4.1] years), 3746 of whom had glycemic trajectory data (mean [SD] age, 28.6 [4.1] years); 983 women (23.8%) had gestational diabetes. Throughout the pregnancy period and compared with the women without gestational diabetes or with women in the trajectory 1 group, the fetal biometrics for the women with gestational diabetes or for those in the trajectory 3 group were significantly higher (except for biparietal diameter), with an estimated increase in fetal weight in the group with gestational diabetes (β = 1.82; 95% CI, 1.03-2.61) and in the trajectory 3 group (β = 1.50; 95% CI, 0.54-2.47; P = .002). Fetal biometric alterations among women with gestational diabetes appeared before 24 weeks' gestational age, with neonatal birth weight significantly higher than in the group without gestational diabetes at 40.4 g (95% CI, 9.8-71.1 g) along with an increased risk of large size for gestational age (odds ratio, 1.36; 95% CI, 1.05-1.75) and macrosomia (odds ratio, 1.47; 95% CI, 1.12-1.94). However, pregnant women in the trajectory 2 group manifested significantly reduced fetal biometrics, and abdominal circumference was significantly augmented after 34 weeks' gestational age (increase, β = 1.92; 95% CI, 0.87-2.99).Conclusions and relevanceIn this cohort study, pregnant women who received a diagnosis of gestational diabetes in midpregnancy or had hyperglycemia during all 3 trimesters showed an association with altered fetal growth patterns, including increased estimated fetal weight that appeared before 24 weeks' gestational age, increased birth weight, and the risk for large size for gestational age and macrosomia.

Project description:BackgroundImprinted genes, which are expressed in a parent of origin-specific manner, are thought to mediate the genetic priorities of each parent in pregnancy. Recently we reported that some fetal imprinted gene variants are associated with maternal glucose concentrations and blood pressures in pregnancy. We suggest that the conflict between the effects of paternal and maternal transmitted genes starts at conception and may already be evident in measures of maternal metabolism in early pregnancy, before gestational diabetes is manifest.MethodsLipid fractions in maternal non-fasting serum collected around week 15 of pregnancy were profiled using direct infusion mass spectrometry in a subset Discovery Cohort (n = 200) of women from the Cambridge Baby Growth Study using direct infusion mass spectrometry. Associations between 151 haplotype-tag fetal polymorphisms in 16 imprinted genes and lipids were determined using partial least squares discriminant analysis. Variable importance in projection scores were used to identify those lipid species that contribute most to the underlying variation in the lipid profile and the concentrations of these species tested for associations with fetal imprinted gene alleles using linear regression. In an internal Validation Cohort (n = 567 women from the same cohort) the lipid fraction was profiled using liquid chromatography-mass spectrometry and tested for associations with the same fetal imprinted gene variants as above, followed by meta-analysis of associations from the Discovery and Validation Cohorts.ResultsThe most significant associations were between a monounsaturated triglyceride (44:1) and both paternally-transmitted fetal H19 rs7950932 (R = 0.14, p = 2.9 × 10- 3, n = 386) and maternally-transmitted fetal FAM99A rs7131362 (R = 0.18, p = 6.2 × 10- 3, n = 351; association with maternal-untransmitted allele R = 0.08, p = 0.07, n = 328). This same triglyceride isoform was also associated with subsequent week 28 fasting glucose concentrations (R = 0.09, p = 9.9 × 10- 3, n = 673) and homeostasis model assessment of insulin resistance (R = 0.09, p = 0.01, n = 664).ConclusionsFetal imprinted genes may influence maternal circulating clinically relevant triglyceride concentrations early in pregnancy.

Dataset Information

Race-ethnic differences in the associations of maternal lipid trait genetic risk scores with longitudinal fetal growth.

Background

Objective

Methods

Results

Conclusion

Publications

Race-ethnic differences in the associations of maternal lipid trait genetic risk scores with longitudinal fetal growth.

Similar Datasets

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