Yajun Liang

Background: Obesity is increasingly common among women of childbearing age worldwide. Maternal obesity during pregnancy may have long-term implications for offspring health, but its association with offspring mortality remains not well understood. In this nationwide cohort study, we examined the associations of maternal body mass index (BMI) in early pregnancy with all-cause and cause-specific mortality in offspring. Methods and findings: We included 2,606,684 live births in Sweden during 1982–2014 (except for 1990 and 1991) and followed them from birth until death, emigration from Sweden, or December 31, 2023, whichever came first. Information on maternal BMI during early pregnancy was obtained from the Medical Birth Register and was categorized as: underweight (BMI 2 ), normal weight (18.5–24.9 kg/m ² ), overweight (25.0–29.9 kg/m ² ), obesity grade I (30.0–34.9 kg/m ² ), obesity grade II (35.0–39.9 kg/m ² ), and obesity grade III (≥40.0 kg/m ² ). Data on all-cause and cause-specific mortality in offsprings were obtained from the Cause of Death Register. Cox proportional hazard models were performed to estimate hazard ratios (HRs) and 95% confidence intervals (95% CI) for offspring mortality according to maternal BMI (both as a continuous and as a categorical variable), adjusting for maternal characteristics (age, education, and income at the childbirth, marital status, country of birth, smoking status in early pregnancy, psychiatric disorders and cardiovascular diseases before the childbirth). We used cousin comparison analysis to explore the potential influence of familial confounding factors. During a median follow-up of 22.4 years (interquartile range 14.9–30.7 years), 21,981 (0.8%) offspring died. Maternal BMI was positively associated with all-cause mortality in offspring: HR 1.03 (95% CI [1.02, 1.03]; p < 0.001) per 1 unit increase in BMI. Offspring of mothers with overweight or obesity (regardless of grade) during early pregnancy had higher risks of all-cause mortality than their counterparts with normal maternal BMI at the reference category; the corresponding HRs were HR 1.11 (95% CI [1.07, 1.15]; p < 0.001) for overweight, HR 1.27 (95% CI [1.20, 1.35]; p < 0.001) for obesity grade I, HR 1.68 (95% CI [1.52, 1.86]; p < 0.001) for obesity grade II, and HR 1.92 (95% CI [1.59, 2.33]; p < 0.001) for obesity grade III, respectively. The associations were similar for several of the most common underlying causes of death in young age, i.e., respiratory diseases, cardiovascular diseases, and congenital anomalies. The associations were attenuated but remained in the cousin comparison analysis. The main limitation was the potential for residual confounding; the observed associations should not be interpreted as evidence of a causal effect of maternal BMI in early pregnancy on offspring mortality. Conclusions: Offspring born to mothers with overweight or obesity during early pregnancy had an increased risk of premature mortality up to early adulthood. Given the rising obesity rate in women of childbearing age, our findings underscore the need to better understand the underlying mechanisms for this association. If confirmed by further studies, these results highlight the importance of achieving a healthy maternal BMI prior to conception as a potential strategy to improve child health.

Compelling evidence suggests that a healthy lifestyle may reduce the risk of cardiovascular diseases (CVDs). Knowledge regarding the role of early-life factors in the association between dynamic patterns of lifestyle and CVDs is limited. This study aims to investigate whether fetal growth modifies the association between dynamic lifestyle patterns and the risk of CVDs in adulthood. Data were from the Stockholm Public Health Cohort. A total of 11,218 participants who completed at least two surveys during 2002–2021 and had birth information from the Medical Birth Register were included in this study. Information on lifestyle factors was collected using questionnaires. We defined a composite score of behavioral health metrics including four lifestyle factors, i.e., smoking, physical activity, fruits intake, and body mass index. Data on birth weight for gestational age and CVDs were obtained from nationwide population-based registers. Cox regression was performed to estimate hazard ratios (HR) and 95% confidence intervals (CI). Compared with the consistently poor level of lifestyle, the persistently good level of lifestyle was associated with a lower risk of CVDs; the fully adjusted HR (95% CI) was 0.74 (0.56–0.98). The associations between composite lifestyles and CVDs were mainly driven by body mass index (HR = 0.47, 95% CI = 0.34–0.65) and smoking (HR = 0.68, 95% CI = 0.49–0.97). Although the CVD risk reduction associated with lifestyle improvements appeared to vary by birth weight for gestational age, this modifying effect did not reach statistical significance. The findings imply that improvement of lifestyle is crucial for the prevention of CVDs, and restricted fetal growth does not modify this association.

BACKGROUND: Adverse pregnancy outcomes (APOs) are increasingly recognized as early indicators of maternal cardiovascular risk. However, their associations with nontraumatic subarachnoid hemorrhage (SAH) remain poorly understood. METHODS: We conducted a nationwide cohort study of 1 785 088 primiparous women in the Swedish Medical Birth Register between 1973 and 2014, followed from first birth through December 31, 2023. APOs included hypertensive disorders of pregnancy, gestational diabetes, placental abruption, preterm birth, abnormal fetal growth, and stillbirth. SAH was the primary outcome, with aortic aneurysm rupture or dissection and spontaneous coronary artery dissection as secondary outcomes. Hazard ratios (HRs) and 95% CIs were estimated using Cox regression, adjusting for calendar year, parity, maternal sociodemographic characteristics, and psychiatric disorders, with sibling analyses to account for shared familial and genetic factors. RESULTS: Mean maternal age was 28.2 years, and abnormal fetal growth was the most common APO category. Over up to 50 years, 759 722 (42.6%) women experienced at least 1 APO; there were 5751 (0.32%) events of SAH. Women with APOs had increased risks of SAH compared with those without, particularly after placental abruption (HR, 1.62 [95% CI, 1.29–2.04]), hypertensive disorders of pregnancy (HR, 1.58 [95% CI, 1.41–1.77]), gestational diabetes (HR, 1.40 [95% CI, 1.04–1.90]), preterm birth (HR, 1.35 [95% CI, 1.24–1.47]), and small for gestational age (HR, 1.34 [95% CI, 1.26–1.43]). The associations were consistent in sibship analyses. The excess SAH risk was greatest in the first years after delivery and attenuated over time. Increased risks of aortic aneurysm rupture or dissection were observed after hypertensive disorders of pregnancy, preterm birth, and severely large for gestational age (HRs ranged from 1.43 to 1.66), whereas associations with spontaneous coronary artery dissection differed in direction. CONCLUSIONS: APOs were associated with increased maternal risk of SAH, with variation by the timing, severity, and accumulation of pregnancy complications, suggesting underlying vascular vulnerability.

Background: Inappropriate gestational weight gain (GWG) is associated with adverse pregnancy and perinatal outcomes, and emerging evidence suggests that its implications for women’s health may extend well beyond pregnancy. We investigated the association between GWG and subsequent cardiovascular disease (CVD) risk and assessed the extent to which shared familial factors may account for this association.Methods: We conducted a nationwide register-based cohort study in Sweden, including 540 498 nulliparous women with a live singleton birth during 1982-2014. Women were followed from the birth of the first child until the first diagnosis of CVD, death, emigration from Sweden, or December 31, 2023, whichever came first. GWG was calculated as the difference between the weight measured at delivery and the weight in early pregnancy, standardized for gestational age into z-scores using the Swedish chart. We estimated hazard ratios (HRs) and 95% confidence intervals (95% CI) for overall and specific types of CVD by GWG category using Cox proportional hazard models. We conducted full sibling comparison analyses to adjust for shared familial (genetic and environmental) factors.Findings: A total of 129 607 women (24.0%) were diagnosed with CVD during a median follow-up of 24.7 years (interquartile range, 15.2 to 34.7 years). Compared with women whose GWG z-scores were in the reference group (-1 to 1), women with high GWG had increased risks of CVD; the HRs (95% CI) for any CVD were 1.17 (1.15 to 1.19) in case of z-scores >1 to 1 to <2 and 2.18 (1.83 to 2.60) in case of pre-pregnancy obesity and GWG z-scores ≥2. Higher GWG in the first pregnancy was a more important determinant of CVD risk than high GWG in the second pregnancy. Lower GWG was also associated with an increased risk of several types of CVD.Interpretation: Sub-optimal GWG is associated with an increased risk of subsequent CVD. These findings highlight the potential importance of GWG for identifying women at elevated risk of long-term CVD.

Background: The lipid accumulation product (LAP) index, a sex-specific indicator of abdominal lipid accumulation, has emerged as a predictor for cardiometabolic disease. However, its association with dementia has been rarely explored in population-based studies. Objective: We sought to investigate the associations of LAP index with all-cause dementia, Alzheimer's disease (AD), and vascular dementia (VaD) as well as with serum inflammatory cytokines among rural-dwelling older adults in China. Methods: This cross-sectional study included 5670 participants (age ≥ 60 years), with data available in 1851 individuals on serum inflammatory cytokines (interleukin-6, tumor necrosis factor-α, and monocyte chemoattractant protein-1). Dementia and subtypes were diagnosed following the international criteria. The LAP index was calculated as [waist circumference (cm)-65] × triglycerides (mmol/L) for men and [waist circumference (cm)-58] × triglycerides (mmol/L) for women. Data were analyzed using multiple logistic and linear regression models. Results: Of the 5670 participants, dementia was diagnosed in 305 persons (194 with AD and 100 with VaD). As a continuous variable, the LAP index was associated with multivariable-adjusted odds ratios of 1.28 (95% confidence interval: 1.01–1.61) for all-cause dementia, 1.40 (1.05–1.86) for AD, and 1.12 (0.75–1.66) for VaD. As a categorical variable, the highest (versus lowest) quintile of LAP index was associated with multivariable-adjusted odds ratios of 1.91 (1.17–3.12) for dementia, 2.18 (1.19–3.99) for AD, and 1.88 (0.78–4.53) for VaD. A higher LAP index was significantly correlated with serum inflammatory cytokines ( p < 0.05). Conclusions: High LAP index is linked with dementia and AD in older adults and chronic systemic inflammation might represent a plausible biological pathway.

Background: Appropriate sleep duration is essential for maintaining normal cognitive function, but evidence is scarce in rural elderly population. This study aims to determine the associations between sleep duration and cognitive function among older adults in rural China. Methods: This population-based cross-sectional study used data from the Confucius Hometown Aging Project in Shandong, China. Data on demographics, lifestyles, and chronic health conditions were collected through questionnaire surveys, clinical examinations, and laboratory tests. Sleep duration per day was classified into four groups (≤5 h, 6 h, 7 h, and ≥8 h). The Mini-Mental State Examination (MMSE) was used to assess the global and domain-specific cognitive function. Linear and logistic regressions were performed to determine the associations between sleep duration and cognitive function. Results: Compared with 6 h sleep per day, sleep ≤5 h per day was associated with a higher odd of cognitive impairment with odds ratio (95% confident interval) being 1.70 (1.05, 2.74), but the association was attenuated and insignificant after the adjustment of covariates. Compared to those with 6 h sleep, individuals reporting short (≤5 h) or long (≥ 8 h) sleep duration per day had a lower MMSE score, and the adjusted β coefficient (95% confidence interval) was −0.36 (−0.71, −0.02) for sleep ≤5 h and −0.68 (−1.06, −0.30) for sleep ≥8 h. The patterns were similar for cognitive subdomains in orientation, attention and calculation. Conclusions: Our study showed that abnormal sleep duration was associated with poor cognitive function in older adults in China. Specifically, longer or shorter sleep duration was associated with lower cognitive function.

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Background: There is limited research providing an overall understanding of bone mineral density (BMD) changes throughout different stages of life. This study aimed to investigate the pattern of BMD changes across childhood, adolescence, adulthood, and old age, as well as exploring the critical time of peak BMD (PBMD). Methods: Participants of three major ethnicities from National Health and Nutrition Examination Survey 1999 to 2018 were involved: 46,381 and 20,944 participants aged 8–85 years old were included in the Lumbar spine BMD (LSBMD) and femoral neck BMD (FNBMD) studies, respectively. BMD was measured using dual-energy X-ray absorptiometry. The generalized additive model was used to construct smoothed percentile curves. Results: Both males and females experienced a sharp increase in LSBMD during puberty, with females reaching their PBMD earlier than males. Females’ LSBMD remained higher than males’ before the age of approximately 50, except for Non-Hispanic Blacks. For males, LSBMD reached a plateau at around 30 years old after reaching the peak value. Females exhibited two peak points on the fitted curves, with the second PBMD occurring around 36–37 years old. Ethnic variations were observed, with Non-Hispanic Blacks displaying the highest BMD levels at all ages. Non-Hispanic Whites and Mexican Americans had lower BMD levels, with Mexican Americans generally exhibiting the lowest BMD. FNBMD reached its peak earlier than LSBMD, and males consistently had higher FNBMD than females. Conclusions: This nationally representative study contributes to the understanding of BMD changes across the lifespan, and might provide guidance for bone health interventions in different population groups.