Dataset Information

Life Course Trajectories of Maternal Cardiovascular Risk Factors according to Offspring Birthweight: The HUNT Study.

ABSTRACT: Women with small or large for gestational age offspring are at increased risk of cardiovascular disease later in life. How their cardiovascular risk factors develop across the life course is incompletely known. We linked data from the population-based HUNT Study (1984-2008) and the Medical Birth Registry of Norway (1967-2012) for 22,487 women. Mixed effect models were used to compare cardiovascular risk factor trajectories for women according to first offspring birthweight for gestational age. Women with small for gestational age (SGA) offspring had 1-2 mmHg higher systolic and diastolic blood pressure across the life course, but lower measures of adiposity, compared to women with offspring who were appropriate for gestational age (AGA). In contrast, women with large for gestational age (LGA) offspring had higher measures of adiposity, ~0.1 mmol/l higher non-HDL cholesterol and triglycerides and 0.2 mmol/l higher non-fasting glucose, compared with mothers of AGA offspring. These differences were broadly stable from prior to first pregnancy until 60 years of age. Our findings point to different cardiovascular risk profiles in mothers of SGA versus LGA offspring, where giving birth to SGA offspring might primarily reflect adverse maternal vascular health whereas LGA offspring might reflect the mother's metabolic health.

SUBMITTER: Horn J

PROVIDER: S-EPMC7319986 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature

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Life Course Trajectories of Maternal Cardiovascular Risk Factors according to Offspring Birthweight: The HUNT Study.

Horn Julie J Haug Eirin B EB Markovitz Amanda R AR Fraser Abigail A Vatten Lars J LJ Romundstad Pål R PR Rich-Edwards Janet W JW Åsvold Bjørn O BO

Scientific reports 20200626 1

Women with small or large for gestational age offspring are at increased risk of cardiovascular disease later in life. How their cardiovascular risk factors develop across the life course is incompletely known. We linked data from the population-based HUNT Study (1984-2008) and the Medical Birth Registry of Norway (1967-2012) for 22,487 women. Mixed effect models were used to compare cardiovascular risk factor trajectories for women according to first offspring birthweight for gestational age. W ...[more]

PMID: 32591565

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Project description:BackgroundWomen who experience adverse pregnancy outcomes (APOs; gestational hypertension, preeclampsia (PE), gestational diabetes (GD), preterm birth (PTB), small or large for gestational age, miscarriage, multiple miscarriages, stillbirth, and offspring with major congenital anomalies) have increased risk of developing cardiovascular disease (CVD). We aimed to compare cardiometabolic health trajectories across the life course between women with and without APOs.MethodsWe studied 187,186 women with a registered pregnancy in the UK Clinical Practice Research Datalink (CPRD) GOLD linked to Hospital Episode Statistics. Fractional polynomial multilevel models were used to compare trajectories of cardiometabolic risk factors (body mass index [BMI], blood pressure [BP], cholesterol, and glucose) between women with and without a history of APOs (individual APOs in any pregnancy and number of APOs). We explored two underlying time axes: (1) time relative to first pregnancy (from 10 years before first pregnancy to 15 years after) and (2) age. Models controlled for age at first pregnancy, residential area deprivation, non-singleton pregnancy, parity, smoking status, ethnicity, and medications use.ResultsWomen with a history of PE, gestational hypertension, or GD had higher BMI, BP, and glucose 10 years before first pregnancy compared to women without these APOs. These differences persisted 15 years post-first pregnancy. Women with a history of GD had a steeper post-partum rise in glucose. Women who experienced multiple (3 +) miscarriage, stillbirth, and/or medically indicated PTB had higher BP and BMI before and after pregnancy, with BP trajectories converging 15 years after first pregnancy. Women who experienced multiple APOs had the most adverse measurements across all cardiometabolic risk factors, with more unfavourable mean levels with each additional APO. There was little difference in cardiometabolic trajectories between women with and without a history of 1 or 2 miscarriages or congenital anomalies.ConclusionsWomen with APOs had adverse cardiometabolic profiles before first pregnancy, persisting up to 15 years post-pregnancy. Findings highlight the potential for targeted public health interventions to promote good cardiometabolic health in young adults transitioning from contraceptive use to planning pregnancies. APOs may identify young women who could benefit from monitoring CVD risk factors and interventions to improve cardiometabolic health.

Project description:This study aims to evaluate the association of maternal DNA methylation (DNAm) during pregnancy and offspring birthweight. One hundred twenty-two newborn-mother dyads from the Isle of Wight (IOW) cohort were studied to identify differentially methylated cytosine-phosphate-guanine sites (CpGs) in maternal blood associated with offspring birthweight. Peripheral blood samples were drawn from mothers at 22-38 weeks of pregnancy for epigenome-wide DNAm assessment using the Illumina Infinium HumanMethylation450K array. Candidate CpGs were identified using a course of 100 repetitions of a training and testing process with robust regressions. CpGs were considered informative if they showed statistical significance in at least 80% of training and testing samples. Linear mixed models adjusting for covariates were applied to further assess the selected CpGs. The Swedish Born Into Life cohort was used to replicate our findings (n = 33). Eight candidate CpGs corresponding to the genes LMF1, KIF9, KLHL18, DAB1, VAX2, CD207, SCT, SCYL2, DEPDC4, NECAP1, and SFRS3 in mothers were identified as statistically significantly associated with their children's birthweight in the IOW cohort and confirmed by linear mixed models after adjusting for covariates. Of these, in the replication cohort, three CpGs (cg01816814, cg23153661, and cg17722033 with p values = 0.06, 0.175, and 0.166, respectively) associated with four genes (LMF1, VAX2, CD207, and NECAP1) were marginally significant. Biological pathway analyses of three of the genes revealed cellular processes such as endocytosis (possibly sustaining an adequate maternal-fetal interface) and metabolic processes such as regulation of lipoprotein lipase activity (involved in providing substrates for the developing fetus). Our results contribute to an epigenetic understanding of maternal involvement in offspring birthweight. Measuring DNAm levels of maternal CpGs may in the future serve as a diagnostic tool recognizing mothers at risk for pregnancies ending with altered birthweights.

Dataset Information

Life Course Trajectories of Maternal Cardiovascular Risk Factors according to Offspring Birthweight: The HUNT Study.

Publications

Life Course Trajectories of Maternal Cardiovascular Risk Factors according to Offspring Birthweight: The HUNT Study.

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