Using longitudinal ultrasounds as an improved fetal growth marker, we aimed to investigate if fetal growth deceleration followed by rapid postnatal weight gain is associated with childhood cardiometabolic risk biomarkers in a contemporary well-nourished population. We defined fetal growth deceleration (FGD) as ultrasound-measured 2^nd-3rd-trimester abdominal circumference decrease by ≥0.67 standard deviation score (SDS) and rapid postnatal weight gain (RPWG) as 0–2-year-old weight increase by ≥0.67 SDS. In the GUSTO mother-offspring cohort, we grouped 797 children into four groups of FGD-only (14.2%), RPWG-only (23.3%), both (mismatch, 10.7%) or neither (reference, 51.8%). Adjusting for confounders and comparing with the reference group, we tested associations of these growth groups with childhood cardiometabolic biomarkers: magnetic resonance imaging (MRI)-measured abdominal fat (n = 262), liver fat (n = 216), intramyocellular lipids (n = 227), quantitative magnetic resonance-measured overall body fat % (BF%) (n = 310), homeostasis model assessment of insulin resistance (HOMA-IR) (n = 323), arterial wall thickness (n = 422) and stiffness (n = 443), and blood pressure trajectories (ages 3–6 years). Mean±SD birthweights were: FGD-only (3.11 ± 0.38 kg), RPWG-only (3.03 ± 0.37 kg), mismatch (2.87 ± 0.31 kg), reference (3.30 ± 0.36 kg). FGD-only children had elevated blood pressure trajectories without correspondingly increased BF%. RPWG-only children had altered body fat partitioning, higher BF% [BF = 4.26%, 95% confidence interval (CI) (2.34, 6.19)], HOMA-IR 0.28 units (0.11, 0.45)] and elevated blood pressure trajectories. Mismatch children did not have increased adiposity, but had elevated ectopic fat, elevated HOMA-IR [0.29 units (0.04,0.55)] and the highest blood pressure trajectories. Associations remained even after excluding small-for-gestational-age infants from analyses. Fetal growth deceleration coupled with rapid postnatal weight gain was associated with elevated childhood cardiometabolic risk biomarkers without correspondingly increased BF%.

The COVID-19 pandemic has led to concern about the potential outcomes of school closures and movement restrictions on the health and well-being of children.^1-6 Although there is growing evidence of changes in child behaviors, such as sedentary behavior or screen time, physical activity, diet, and sleeping duration, during lockdown in several countries,^4-16 given the adoption of a diverse spectrum of policies across the globe, there has been little systematic evidence on the persistence of effects (or the spectrum of COVID-19–related life events that may cause them) after strict COVID-19–related control measures have ended. This is particularly true for regions where lockdown measures were stringent and effective and where daily activities, such as schooling and extracurricular activities, have largely resumed. It is unclear whether postulated harms, such as deteriorating familial relationships or acquisition of maladaptive behaviors (eg, inactivity,^4-16 increased leisure screen time,^7-12,14-16 or change in sleep patterns^7,8,14), continue to persist after lockdown. Early studies have shown that these behavior changes during lockdown may continue after lockdown among youths in China¹⁷ and primary school children in Cyprus.¹⁸ Although it has been speculated that such changes may exacerbate trends in childhood obesity,^19,20 studies thus far have only shown changes in child adiposity immediately after lockdown.^17,21,22 There are no studies, to our knowledge, of longer-term consequences and whether child outcomes may differ by developmental stage or family sociodemographic characteristics.

Aims: To examine associations of assisted reproductive technology (ART) conception (vs. natural conception: NC) with offspring cardiometabolic health outcomes and whether these differ with age. Methods and results: Differences in systolic (SBP) and diastolic blood pressure (DBP), heart rate (HR), lipids, and hyperglycaemic/insulin resistance markers were examined using multiple linear regression models in 14 population-based birth cohorts in Europe, Australia, and Singapore, and results were combined using meta-analysis. Change in cardiometabolic outcomes from 2 to 26 years was examined using trajectory modelling of four cohorts with repeated measures. 35 938 (654 ART) offspring were included in the meta-analysis. Mean age ranged from 13 months to 27.4 years but was <10 years in 11/14 cohorts. Meta-analysis found no statistical difference (ART minus NC) in SBP (−0.53 mmHg; 95% CI:−1.59 to 0.53), DBP (−0.24 mmHg; −0.83 to 0.35), or HR (0.02 beat/min; −0.91 to 0.94). Total cholesterol (2.59%; 0.10–5.07), HDL cholesterol (4.16%; 2.52–5.81), LDL cholesterol (4.95%; 0.47–9.43) were statistically significantly higher in ART-conceived vs. NC offspring. No statistical difference was seen for triglycerides (TG), glucose, insulin, and glycated haemoglobin. Long-term follow-up of 17 244 (244 ART) births identified statistically significant associations between ART and lower predicted SBP/DBP in childhood, and subtle trajectories to higher SBP and TG in young adulthood; however, most differences were not statistically significant. Conclusion: These findings of small and statistically non-significant differences in offspring cardiometabolic outcomes should reassure people receiving ART. Longer-term follow-up is warranted to investigate changes over adulthood in the risks of hypertension, dyslipidaemia, and preclinical and clinical cardiovascular disease.

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Assisted reproductive technologies (ART) are increasingly used, however little is known about the long-term health of ART-conceived offspring. Weak selection of comparison groups and poorly characterized mechanisms impede current understanding. In a prospective cohort (Growing Up in Singapore Towards healthy Outcomes; GUSTO; Clinical Trials ID: NCT01174875) including 83 ART-conceived and 1095 spontaneously-conceived singletons, we estimate effects of ART on anthropometry, blood pressure, serum metabolic biomarkers, and cord tissue DNA methylation by emulating a pragmatic trial supported by machine learning-based estimators. We find ART-conceived children to be shorter (−0.5 SD [95% CI: −0.7, −0.2]), lighter (−0.6 SD [−0.9, −0.3]) and have lower skinfold thicknesses (e.g. −14% [−24%, −3%] suprailiac), and blood pressure (−3 mmHg [−6, −0.5] systolic) at 6-6.5 years, with no strong differences in metabolic biomarkers. Differences are not explained by parental anthropometry or comorbidities, polygenic risk score, breastfeeding, or illnesses. Our simulations demonstrate ART is strongly associated with lower NECAB3 DNA methylation, with negative control analyses suggesting these estimates are unbiased. However, methylation changes do not appear to mediate observed differences in child phenotype.