Offspring Cardiometabolic Risk Research Articles

The association of maternal gestational weight gain with cardiometabolic risk factors in offspring: a systematic review and meta-analysis.

Gestational weight gain (GWG) is known to be a risk factor for offspring obesity, a precursor of cardiometabolic diseases. Accumulating studies have investigated the association of GWG with offspring cardiometabolic risk factors (CRFs), leading to inconsistent results. This study synthesized available data from cohort studies to examine the effects of GWG on offspring CRFs. Four electronic databases, including PubMed, Web of Science, Scopus, and Embase, were searched through May 2023. Cohort studies evaluating the association between GWG and CRFs (fat mass [FM], body fat percentage [BF%], waist circumference [WC], systolic blood pressure [SBP] and diastolic blood pressure, high-density-lipoprotein cholesterol [HDL-C] and low-density-lipoprotein cholesterol, triglyceride [TG], total cholesterol, fasting blood glucose, and fasting insulin levels) were included. Regression coefficients, means or mean differences with 95% confidence intervals [CIs], or standard deviations were extracted. Thirty-three cohort studies were included in the meta-analysis. Higher GWG (per increase of 1 kg) was associated with greater offspring FM (0.041 kg; 95% CI, 0.016 to 0.067), BF% (0.145%; 95% CI, 0.116 to 0.174), WC (0.154 cm; 95% CI, 0.036 to 0.272), SBP (0.040 mmHg; 95% CI, 0.010 to 0.070), and TG (0.004 mmol/L; 95% CI, 0.001 to 0.007), and with lower HDL-C (-0.002 mmol/L; 95% CI, -0.004 to 0.000). Consistently, excessive GWG was associated with higher offspring FM, BF%, WC, and insulin, and inadequate GWG was associated with lower BF%, low-density lipoprotein cholesterol, total cholesterol, and TG, compared with adequate GWG. Most associations went non-significant or attenuated with adjustment for offspring body mass index or FM. Higher maternal GWG is associated with increased offspring adiposity, SBP, TG, and insulin and decreased HDL-C in offspring, warranting a need to control GWG and to screen for cardiometabolic abnormalities of offspring born to mothers with excessive GWG. PROSPERO registration no. CRD42023412098.

Biological and behavioral pathways from prenatal depression to offspring cardiometabolic risk: Testing the developmental origins of health and disease hypothesis.

Given prior literature focused on the Developmental Origins of Health and Disease framework, there is strong rationale to hypothesize that reducing depression in the prenatal period will cause improvements in offspring cardiometabolic health. The current review outlines evidence that prenatal depression is associated with offspring cardiometabolic risk and health behaviors. We review evidence of these associations in humans and in nonhuman animals at multiple developmental periods, from the prenatal period (maternal preeclampsia, gestational diabetes), neonatal period (preterm birth, small size at birth), infancy (rapid weight gain), childhood and adolescence (high blood pressure, impaired glucose-insulin homeostasis, unfavorable lipid profiles, abdominal obesity), and into adulthood (diabetes, cardiovascular disease). In addition to these cardiometabolic outcomes, we focus on health behaviors associated with cardiometabolic risk, such as child eating behaviors, diet, physical activity, and sleep health. Our review focuses on child behaviors (e.g., emotional eating, preference for highly palatable foods, short sleep duration) and parenting behaviors (e.g., pressuring child to eat, modeling of health behaviors). These changes in health behaviors may be detected before changes to cardiometabolic outcomes, which may allow for early identification of and prevention for children at risk for poor adult cardiometabolic outcomes. We also discuss the methods of the ongoing Care Project, which is a randomized clinical trial to test whether reducing prenatal maternal depression improves offspring's cardiometabolic health and health behaviors in preschool. The goal of this review and the Care Project are to inform future research, interventions, and policies that support prenatal mental health and offspring cardiometabolic health. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Supplemental Material for Biological and Behavioral Pathways From Prenatal Depression to Offspring Cardiometabolic Risk: Testing the Developmental Origins of Health and Disease Hypothesis

Supplemental Material for Biological and Behavioral Pathways From Prenatal Depression to Offspring Cardiometabolic Risk: Testing the Developmental Origins of Health and Disease Hypothesis

Effect of common pregnancy and perinatal complications on offspring metabolic traits across the life course: a multi-cohort study

BackgroundCommon pregnancy and perinatal complications are associated with offspring cardiometabolic risk factors. These complications may influence multiple metabolic traits in the offspring and these associations might differ with offspring age.MethodsWe used data from eight population-based cohort studies to examine and compare associations of pre-eclampsia (PE), gestational hypertension (GH), gestational diabetes (GD), preterm birth (PTB), small (SGA) and large (LGA) for gestational age (vs. appropriate size for gestational age (AGA)) with up to 167 plasma/serum-based nuclear magnetic resonance-derived metabolic traits encompassing lipids, lipoproteins, fatty acids, amino acids, ketones, glycerides/phospholipids, glycolysis, fluid balance, and inflammation. Confounder-adjusted regression models were used to examine associations (adjusted for maternal education, parity age at pregnancy, ethnicity, pre/early pregnancy body mass index and smoking, and offspring sex and age at metabolic trait assessment), and results were combined using meta-analysis by five age categories representing different periods of the offspring life course: neonates (cord blood), infancy (mean ages: 1.1–1.6 years), childhood (4.2–7.5 years); adolescence (12.0–16.0 years), and adulthood (22.0–67.8 years).ResultsOffspring numbers for each age category/analysis varied from 8925 adults (441 PTB) to 1181 infants (135 GD); 48.4% to 60.0% were females. Pregnancy complications (PE, GH, GD) were each associated with up to three metabolic traits in neonates (P≤0.001) with some evidence of persistence to older ages. PTB and SGA were associated with 32 and 12 metabolic traits in neonates respectively, which included an adjusted standardised mean difference of −0.89 standard deviation (SD) units for albumin with PTB (95% CI: −1.10 to −0.69, P=1.3×10−17) and −0.41 SD for total lipids in medium HDL with SGA (95% CI: −0.56 to −0.25, P=2.6×10−7), with some evidence of persistence to older ages. LGA was inversely associated with 19 metabolic traits including lower levels of cholesterol, lipoproteins, fatty acids, and amino acids, with associations emerging in adolescence, (e.g. −0.11 SD total fatty acids, 95% CI: −0.18 to −0.05, P=0.0009), and attenuating with older age across adulthood.ConclusionsThese reassuring findings suggest little evidence of wide-spread and long-term impact of common pregnancy and perinatal complications on offspring metabolic traits, with most associations only observed for newborns rather than older ages, and for perinatal rather than pregnancy complications.

Parental Metabolic Syndrome and Offspring Cardiometabolic Risk From Prepuberty to Late Adolescence: Differences Between Boys and Girls in the QUALITY Cohort

Parental Metabolic Syndrome and Offspring Cardiometabolic Risk From Prepuberty to Late Adolescence: Differences Between Boys and Girls in the QUALITY Cohort

Associations between maternal iron supplementation in pregnancy and offspring growth and cardiometabolic risk outcomes in infancy and childhood.

It was previously observed that maternal iron supplementation in pregnancy was associated with increased offspring size and adiposity at birth, possibly mediated through increased risk of gestational diabetes. In this study we investigated potential long-term associations of maternal iron supplementation in pregnancy with offspring growth in infancy, and growth and cardiometabolic risk factors in mid-childhood to seek evidence of nutritional programming. Using a nested case-control format, markers of growth and adiposity were measured at 3, 12 and 24 months of age in 341 infants from the Cambridge Baby Growth Study whose mothers supplemented with iron in pregnancy and 222 infants whose mothers did not. Measures of growth, glucose tolerance (using a 30 minute 1.75 g glucose/kg body weight oral glucose tolerance test), insulin sensitivity (HOMA IR) and blood pressure were collected in 122 and 79 of these children, respectively, at around 9.5 years of age. In infancy adiposity-promoting associations with maternal iron supplementation in pregnancy were evident at 3 months of age (e.g. mean difference in skinfold thickness: β = +0.15 mm, p = 0.02, in n = 341 whose mothers supplemented versus 222 that did not; waist circumference: β = +0.7 cm, p = 0.04, in n = 159 and 78, respectively) but differences lessened after this time (e.g. 3–12 month change in mean difference in skinfold thickness: β = -0.2 mm, p = 0.03, in n = 272 and 178, respectively). At ~9.5 years of age children whose mothers supplemented with iron in pregnancy had lower mean arterial blood pressures (β = -1.0 mmHg, p = 0.03, in n = 119 and 78, respectively). There were no apparent differences in markers of growth or other cardiometabolic factors. These results suggest that most of the associations of maternal iron supplementation in pregnancy on growth and adiposity evident at birth disappear during infancy, but there may be some evidence of long-term nutritional programming of blood pressure in mid-childhood.

Maternal prenatal anxiety and depression and trajectories of cardiometabolic risk factors across childhood and adolescence: a prospective cohort study

ObjectivesQuantifying long-term offspring cardiometabolic health risks associated with maternal prenatal anxiety and depression can guide cardiometabolic risk prevention. This study examines associations between maternal prenatal anxiety and depression, and offspring...

Abstract P230: Prevention Of Maternal Obesity Attenuates Adverse Offspring Cardiometabolic Outcomes In Preeclamptic-like Mouse Model

Preeclampsia (PE) is a hypertensive disorder of pregnancy and a leading cause of maternal and fetal mortality with maternal obesity as a risk factor. Decreasing white adipose tissue (WAT) via calorie restriction during the first half of pregnancy may alter the maternal-fetal environment to improve offspring outcomes. We hypothesized that pair-feeding BPH/5 dams during pregnancy will improve cardiometabolic risk and WAT pro-inflammatory cytokine expression in BPH/5 offspring in a sex-dependent manner. Previously, we showed that BPH/5 males, unlike females, have similar body weights, daily food intake, and circulating leptin levels as compared to age-matched control mice. Although, adult BPH/5 females and males have cardiomegaly and increased subcutaneous and peri-renal WAT mass compared to lean control mice. To investigate the prevention of maternal obesity on offspring outcomes, BPH/5 dams were pair-fed (PF) beginning at embryonic day (e)0.5 to C57 pregnant mice. Offspring cardiometabolic risk and WAT pro-inflammatory cytokine mRNA were measured using real time PCR in adult ad libitum fed offspring. Compared to controls, peri-renal WAT from BPH/5 males showed a 5-fold increase while females had a 15-fold increase in TNFa (n=3-6; p<0.05), 6-fold increase in PTGS-2 for males and 5-fold increase for females (n=3-6; p<0.05), and 3-fold increase in IL-6 for males and 1.25-fold increase for females (n=3-6; p<0.05) in subcutaneous WAT. Adult offspring born to PF BPH/5 dams had decreased expression in TNFa (male: 4-fold and female: 7-fold), PTGS-2 (male: 5-fold and female: 4-fold), and IL-6 (male: 10-fold; n=3-6; p<0.05). In conclusion, prevention of maternal obesity in BPH/5 dams attenuates cardiometabolic risks and reduces the pro-inflammatory WAT milieu in male and female offspring. The transgenerational effects during pregnancy is believed to be caused by an alteration in the maternal-fetal environment due to WAT pro-inflammatory adipokines. Future investigations are necessary to understand the differences observed in BPH/5 male versus female mice into adulthood as well as the transgenerational impact of attenuated maternal obesity in pregnancy.

Association between maternal prepregnancy body mass index with offspring cardiometabolic risk factors: analysis of three Brazilian birth cohorts.

Evidence suggests that maternal prepregnancy body mass index (BMI) is associated with offspring cardiometabolic risk factors. This study was aimed at assessing the association of maternal prepregnancy BMI with offspring cardiometabolic risk factors in adolescence and adulthood. We also evaluated whether offspring BMI was a mediator in this association. The study included mother-offspring pairs from three Pelotas birth cohorts. Offspring cardiometabolic risk factors were collected in the last follow-up of each cohort [mean age (in years) 30.2, 22.6, 10.9]. Blood pressure was measured using an automatic device, cholesterol by using an enzymatic colorimetric method, and glucose from fingertip blood, using a portable glucose meter. In a pooled analysis of the cohorts, multiple linear regression was used to control for confounding. Mediation analysis was conducted using G-computation formula. In the adjusted model, mean systolic blood pressure of offspring from overweight and obese mothers was on average 1.25 (95% CI: 0.45; 2.05) and 2.13 (95% CI: 0.66; 3.59) mmHg higher than that of offspring from normal-weight mothers; for diastolic blood pressure, the means were 0.80 (95% CI: 0.26; 1.34) and 2.60 (95% CI: 1.62; 3.59) mmHg higher, respectively. Non-HDL cholesterol was positively associated with maternal BMI, whereas blood glucose was not associated. Mediation analyses showed that offspring BMI explained completely the association of maternal prepregnancy BMI with offspring systolic and diastolic blood pressure, and non-HDL cholesterol. Our findings suggest that maternal prepregnancy BMI is positively associated with offspring blood pressure, and blood lipids, and this association is explained by offspring BMI.

A cautionary note on using Mendelian randomization to examine the Barker hypothesis and Developmental Origins of Health and Disease (DOHaD).

Recent studies have used Mendelian randomization (MR) to investigate the observational association between low birth weight (BW) and increased risk of cardiometabolic outcomes, specifically cardiovascular disease, glycemic traits, and type 2 diabetes (T2D), and inform on the validity of the Barker hypothesis. We used simulations to assess the validity of these previous MR studies, and to determine whether a better formulated model can be used in this context. Genetic and phenotypic data were simulated under a model of no direct causal effect of offspring BW on cardiometabolic outcomes and no effect of maternal genotype on offspring cardiometabolic risk through intrauterine mechanisms; where the observational relationship between BW and cardiometabolic risk was driven entirely by horizontal genetic pleiotropy in the offspring (i.e. offspring genetic variants affecting both BW and cardiometabolic disease simultaneously rather than a mechanism consistent with the Barker hypothesis). We investigated the performance of four commonly used MR analysis methods (weighted allele score MR (WAS-MR), inverse variance weighted MR (IVW-MR), weighted median MR (WM-MR), and MR-Egger) and a new approach, which tests the association between maternal genotypes related to offspring BW and offspring cardiometabolic risk after conditioning on offspring genotype at the same loci. We caution against using traditional MR analyses, which do not take into account the relationship between maternal and offspring genotypes, to assess the validity of the Barker hypothesis, as results are biased in favor of a causal relationship. In contrast, we recommend the aforementioned conditional analysis framework utilizing maternal and offspring genotypes as a valid test of not only the Barker hypothesis, but also to investigate hypotheses relating to the Developmental Origins of Health and Disease more broadly.

Mendelian randomization study of maternal influences on birthweight and future cardiometabolic risk in the HUNT cohort

There is a robust observational relationship between lower birthweight and higher risk of cardiometabolic disease in later life. The Developmental Origins of Health and Disease (DOHaD) hypothesis posits that adverse environmental factors in utero increase future risk of cardiometabolic disease. Here, we explore if a genetic risk score (GRS) of maternal SNPs associated with offspring birthweight is also associated with offspring cardiometabolic risk factors, after controlling for offspring GRS, in up to 26,057 mother–offspring pairs (and 19,792 father–offspring pairs) from the Nord-Trøndelag Health (HUNT) Study. We find little evidence for a maternal (or paternal) genetic effect of birthweight associated variants on offspring cardiometabolic risk factors after adjusting for offspring GRS. In contrast, offspring GRS is strongly related to many cardiometabolic risk factors, even after conditioning on maternal GRS. Our results suggest that the maternal intrauterine environment, as proxied by maternal SNPs that influence offspring birthweight, is unlikely to be a major determinant of adverse cardiometabolic outcomes in population based samples of individuals.

Adiposity and cardiovascular outcomes in three-year-old children of participants in UPBEAT, an RCT of a complex intervention in pregnant women with obesity.

Maternal obesity is associated with offspring cardiometabolic risk. UPBEAT was a randomised controlled trial of an antenatal diet and physical activity intervention in 1555 women with obesity. The intervention was associated with lower gestational weight gain, healthier diet and metabolic profile in pregnancy, and reduced infant adiposity at six months. We have investigated whether the UPBEAT intervention influenced childhood cardiometabolic outcomes or was associated with sustained improvements in maternal lifestyle 3-years after delivery. In UPBEAT mother-child dyads at the 3-year follow-up, we assessed childhood blood pressure, resting pulse rate, and adiposity (body mass index, skinfold thicknesses, body fat, waist and arm circumferences) and maternal diet, physical activity, and anthropometry. 514 three-year-old children attended the appointment (49% intervention, 51% standard care). There was no difference in the main outcome of interest, subscapular skinfold thickness, between the trial arms (-0.30 mm, 95% confidence interval: -0.92, 0.31). However, the intervention was associated with a lower resting pulse rate (-5 bpm [-8.41, -1.07]). There was also a non-significant lower odds of overweight/obesity (OR 0.73; 0.50, 1.08). Maternal dietary improvements observed in the UPBEAT trial, including glycaemic load and saturated fat were maintained 3-years postpartum. This study has demonstrated that an antenatal dietary and physical activity intervention in women with obesity is associated with lower offspring pulse rate and sustained improvement in maternal diet. Whilst larger than previous cohorts, there remains potential for bias from attrition and these findings require validation in future cohorts.

Association Between Maternal Prepregnancy Body Mass Index and Anthropometric Parameters, Blood Pressure, and Retinal Microvasculature in Children Age 4 to 6 Years

Maternal prepregnancy body mass index (BMI; calculated as weight in kilograms divided by height in meters squared) has previously been associated with offspring cardiometabolic risk factors, such as fat mass, glucose and insulin levels, and blood pressure, but these associations appear to be largely mediated by offspring BMI. To our knowledge, no studies have assessed alterations in the retinal microvasculature in association with maternal prepregnancy BMI. To investigate the association between maternal prepregnancy BMI and anthropometric parameters, blood pressure, and retinal vessel parameters in children age 4 to 6 years. Participants included mother-child pairs of the population-based Environmental Influence on Early Aging (ENVIRONAGE) birth cohort study (Flanders, Belgium) who were recruited at birth from February 2010 to June 2014 and followed-up at age 4 to 6 years between October 2014 and July 2018. Data were analyzed from February 2019 to April 2019. Maternal prepregnancy BMI based on height and weight measurements at the first antenatal visit (weeks 7-9 of gestation). Children's anthropometric, blood pressure, and retinal microcirculation measurements at age 4 to 6 years. Retinal vessel diameters and the tortuosity index, a measure for the curvature of the retinal vasculature, were obtained by fundus image analysis. This study included 240 mothers and children with a mean (SD) age of 29. 9 (4.2) years and 54.8 (4.7) months, respectively. Of these, 114 children (47.5%) were boys. Maternal prepregnancy BMI was positively associated with the child's birth weight, BMI, waist circumference, blood pressure, and retinal vessel tortuosity. A 1-point increase in maternal prepregnancy BMI was associated with a 0.26-mm Hg (95% CI, 0.08-0.44) higher mean arterial pressure for their children, with similar estimates for systolic and diastolic blood pressure. Independent from the association with blood pressure, a 1-point increase in maternal prepregnancy BMI was associated with a 0.40 (95% CI, 0.01-0.80) higher retinal tortuosity index (× 103). The hypothesis that these associations reflect direct intrauterine mechanisms is supported by the following observations: associations were independent of the current child's BMI and the estimates for paternal BMI at the follow-up visit did not reach significance. Considering that blood pressure tracks from childhood into adulthood and microvascular changes may be early markers of cardiometabolic disease development, our results suggest that maternal prepregnancy BMI is an important modifiable risk factor for later-life cardiovascular health of the offspring.

Maternal Glucose Concentrations in Early Pregnancy and Cardiometabolic Risk Factors in Childhood.

ObjectiveThis study aimed to examine the associations of maternal early‐pregnancy glucose and insulin concentrations with offspring cardiometabolic risk factors and fat distribution.MethodsIn a population‐based prospective cohort study among 3,737 mothers and their children, random maternal glucose and insulin concentrations were measured at a median gestational age of 13.2 (95% range 10.5‐17.1) weeks. Childhood fat, blood pressure, and blood concentrations of lipids, glucose, and insulin at the age of 10 years were measured.ResultsHigher maternal early‐pregnancy glucose and insulin concentrations were associated with a higher risk of childhood overweight, and higher maternal early‐pregnancy insulin concentrations were associated with an increased childhood risk of clustering of cardiometabolic risk factors (all P < 0.05). These associations were explained by maternal prepregnancy BMI. Independent of maternal prepregnancy BMI, one SD score (SDS) higher maternal early‐pregnancy glucose and insulin concentrations were associated with higher childhood glucose (0.08 SDS, 95% CI: 0.04‐0.11) and insulin concentrations (0.07 SDS, 95% CI: 0.03‐0.10), but not with childhood blood pressure, lipids, and fat measures.ConclusionsThese results suggest that maternal early‐pregnancy random glucose and insulin concentrations are associated with childhood glucose and insulin concentrations but not with other childhood cardiometabolic risk factors.

Maternal B12, Folate and Homocysteine Concentrations and Offspring Cortisol and Cardiovascular Responses to Stress.

ContextImbalances in maternal 1-carbon nutrients (vitamin B12, folate) have been shown to be associated with higher offspring cardiometabolic risk markers in India.ObjectiveWe examined the hypothesis that low plasma vitamin B12 (B12) and high folate and homocysteine concentrations in the mother are associated with higher hypothalamic–pituitary–adrenal axis (cortisol) and cardiovascular responses during the Trier Social Stress Test for Children (TSST-C) in an Indian birth cohort.MethodsAdolescents (n = 264; mean age: 13.6 years), whose mothers’ plasma B12, folate and total homocysteine concentrations had been measured during pregnancy, completed 5-minutes each of public speaking and mental arithmetic tasks in front of 2 unfamiliar “judges” (TSST-C). Baseline and poststress salivary cortisol concentrations were measured. Heart rate, blood pressure, stroke volume, cardiac output, and total peripheral resistance were measured continuously at baseline, during the TSST-C, and for 10 minutes after the TSST-C using a finger cuff; beat-to-beat values were averaged for these periods, respectively. ResultsMaternal low B12 status (plasma B12 < 150 pmol/L) was associated with greater cortisol responses to stress in the offspring (P < .001). Higher homocysteine concentrations were associated with greater offspring heart rate response (P < .001). After adjustment for multiple comparisons, there were nonsignificant associations between higher maternal folate concentrations and offspring total peripheral resistance response (P = .01).ConclusionOur findings suggest that maternal 1-carbon nutritional status may have long-term programming implications for offspring neuroendocrine stress responses.

Gestational Diabetes But Not Prepregnancy Overweight Predicts for Cardiometabolic Markers in Offspring Twenty Years Later.

Maternal gestational diabetes mellitus (GDM) and prepregnancy overweight/obesity [body mass index (BMI) ≥25 kg/m2] might adversely affect offspring cardiometabolic health. To assess the associations between maternal GDM and prepregnancy overweight/obesity with adult offspring cardiometabolic risk factors. Longitudinal cohort study (ESTER Maternal Pregnancy Disorders Study and the Arvo Ylppö Longitudinal Study). Province of Uusimaa and Northern Finland. At a mean age of 24.1 ± 1.3 years, we classified offspring as offspring of mothers with GDM regardless of the prepregnancy BMI (OGDM; n = 193); normoglycemic mothers with prepregnancy overweight/obesity (ONO; n = 157); and normoglycemic mothers with prepregnancy BMI <25 kg/m2 (controls; n = 556). We assessed the cardiometabolic biomarkers from blood and measured the blood pressure at rest and heart rate. Compared with the controls, the OGDM and ONO groups had greater fasting glucose (1.6%; 95% CI, 0.1% to 3.1%; and 2.3%; 95% CI, 0.5% to 4.3%, respectively) and insulin (12.7%; 95% CI, 4.4% to 21.9%; and 8.7%; 95% CI, 0.2% to 17.8%). These differences attenuated to nonsignificance when adjusted for confounders and/or current offspring characteristics, including BMI or body fat percentage. The OGDM group had lower SHBG (men, -12.4%; 95% CI, -20.2% to -3.9%; women, -33.2%; 95% CI, -46.3% to -16.8%), high-density lipoprotein (-6.6%; 95% CI, -10.9% to -2.2%), and apolipoprotein A1 (-4.5%; 95% CI, -7.5% to -1.4%). These differences survived the adjustments. The heart rate and other biomarkers were similar among the groups. Adult offspring of mothers with GDM have increased markers of insulin resistance and a more atherogenic lipid profile. These were only partly explained by confounders or current offspring adiposity. Maternal prepregnancy overweight/obesity was associated with impaired offspring glucose regulation, which was explained by confounders and/or current adiposity.

Intrauterine metformin exposure and offspring cardiometabolic risk factors (PedMet study): a 5–10 year follow-up of the PregMet randomised controlled trial

Metformin is increasingly used to treat gestational diabetes and type 2 diabetes in pregnancy, and in attempts to improve pregnancy outcomes in polycystic ovary syndrome and obesity. It passes across the placenta with possible long-term consequences for the offspring. We previously explored the effect of metformin, given to women with polycystic ovary syndrome during pregnancy, on children's growth up to 4 years of age. In this 5-10 year follow-up, we examined the cardiometabolic risk factors in these children. This is a follow-up of children from the PregMet study, a double-blind, randomised controlled trial comparing metformin with placebo in polycystic ovary syndrome pregnancies. In the PregMet study, between Feb 4, 2005, and Jan 27, 2009, 257 pregnant women aged 18-45 years with polycystic ovary syndrome according to the Rotterdam criteria were included with 274 singleton pregnancies at 5-12 weeks of gestation at 11 study centres in Norway. 17 women participated twice. Pregnant women were randomised to metformin (2000 mg/day) or placebo from inclusion in the first trimester to birth. Randomisation was stratified according to metformin use at conception. In this follow-up, the primary endpoint was body-mass index (BMI) in the offspring at 5-10 years of age assessed by the standard deviation score (Z score). The primary endpoint was analysed with independent sample t tests. ClinicalTrials.gov number NCT00159536. Of the 255 invited children from the PregMet study, 141 (55%) consented to participate and were included between April 29, 2014, and July 12, 2016. Maternal baseline characteristics in the first trimester were similar between groups. Children in the metformin group had a higher BMI Z score than those in the placebo group (difference in means=0·41, 95% CI 0·03-0·78, p=0·03). The increased BMI in metformin-exposed children might indicate a potential risk of inferior cardiometabolic health. Implications for adult health cannot be excluded. The Research Council of Norway, Novo Nordisk Foundation, St Olavs University Hospital, and the Norwegian University of Science and Technology.

The Association of Mediterranean Diet during Pregnancy with Longitudinal Body Mass Index Trajectories and Cardiometabolic Risk in Early Childhood

To evaluate the associations between maternal adherence to the Mediterranean diet during pregnancy and their offspring's longitudinal body mass index (BMI) trajectories and cardiometabolic risk in early childhood. We included mother-child pairs from the Infancia y Medio Ambiente (INMA) longitudinal cohort study in Spain. We measured dietary intake during pregnancy using a validated food frequency questionnaire and calculated the relative Mediterranean diet score (rMED). We estimated offspring's BMI z score trajectories from birth to age 4 years using latent class growth analyses (n = 2195 mother-child pairs). We measured blood pressure, waist circumference, and cardiometabolic biomarkers to construct a cardiometabolic risk score at 4 years (n = 697 mother-child pairs). We used multivariable adjusted linear and multinomial regression models. A higher maternal rMED in pregnancy was associated with a lower risk in offspring of larger birth size, followed by accelerated BMI gain (reference trajectory group: children with average birth size and subsequent slower BMI gain) (relative risk of high vs low rMED score, 0.68; 95% CI, 0.47-0.99). rMED score during pregnancy was not associated with the cardiometabolic risk score, its components, or related biomarkers. Higher adherence to the Mediterranean diet in pregnancy was associated with lower risk of having offspring with an accelerated growth pattern. This dietary pattern was not associated with the offspring's cardiometabolic risk at 4 years.

Intergenerational effects of maternal early life adversity on infant DNA methylation of NR3C1

Maternal smoking during pregnancy increases risk of adverse pregnancy outcomes. However, little is known regarding in utero smoke exposure and offspring cardiometabolic risk. Thus, we examined the association between in utero smoke exposure and cardiometabolic risk factors and the metabolic syndrome (MetS) in adolescents.Participants included 7464 adolescents aged 12–15 years identified from the National Health and Nutrition Examination Survey (1999–2014). Multiple logistic and linear regression analyses estimated sex-specific means and odds ratios (ORs) for the association between in utero smoke exposure and MetS and cardiometabolic risk factors.MetS prevalence was 9.0% in exposed versus 5.9% in unexposed adolescents. In utero smoke exposure was significantly associated with increased odds of MetS among males in models controlling for adolescent age, maternal age, and race/ethnicity (OR: 2.48, 95% confidence interval: 1.19, 5.20), with attenuation of this effect in subsequent models. In utero smoke exposure was associated with significantly elevated mean body mass index and waist circumference percentiles among female adolescents across most models in regression analyses.In utero smoke exposure appears to be associated with an increased likelihood of high waist circumference and body mass index percentiles, especially among female adolescents. Our study demonstrates the long-term cardiometabolic impact in offspring, highlighting the importance of prepregnancy smoking cessation.

In utero exposure to tobacco smoke, subsequent cardiometabolic risks, and metabolic syndrome among U.S. adolescents

PurposeMaternal smoking during pregnancy increases risk of adverse pregnancy outcomes. However, little is known regarding in utero smoke exposure and offspring cardiometabolic risk. Thus, we examined the association between in utero smoke exposure and cardiometabolic risk factors and the metabolic syndrome (MetS) in adolescents. MethodsParticipants included 7464 adolescents aged 12–15 years identified from the National Health and Nutrition Examination Survey (1999–2014). Multiple logistic and linear regression analyses estimated sex-specific means and odds ratios (ORs) for the association between in utero smoke exposure and MetS and cardiometabolic risk factors. ResultsMetS prevalence was 9.0% in exposed versus 5.9% in unexposed adolescents. In utero smoke exposure was significantly associated with increased odds of MetS among males in models controlling for adolescent age, maternal age, and race/ethnicity (OR: 2.48, 95% confidence interval: 1.19, 5.20), with attenuation of this effect in subsequent models. In utero smoke exposure was associated with significantly elevated mean body mass index and waist circumference percentiles among female adolescents across most models in regression analyses. ConclusionsIn utero smoke exposure appears to be associated with an increased likelihood of high waist circumference and body mass index percentiles, especially among female adolescents. Our study demonstrates the long-term cardiometabolic impact in offspring, highlighting the importance of prepregnancy smoking cessation.