Early life factors as predictors of age-associated deficit accumulation across 17 years from midlife into old age

Background Early life exposures have been associated with the risk of frailty in old age. We investigated whether early life exposures predict the level and rate of change in a frailty index (FI) from midlife into old age. Methods A linear mixed model analysis was performed using data from three measurement occasions over 17 years in participants from the Helsinki Birth Cohort Study (n=2000) aged 57-84 years. A 41-item FI was calculated on each occasion. Information on birth size, maternal body mass index (BMI), growth in infancy and childhood, childhood socioeconomic status (SES), and early life stress (wartime separation from both parents), was obtained from registers and healthcare records. Results At age 57 years the mean FI level was 0.186 and the FI levels increased by 0.34 percent/year from midlife into old age. Larger body size at birth associated with a slower increase in FI levels from midlife into old age. Per 1kg greater birth weight the increase in FI levels per year was -0.087 percentage points slower (95% CI=-0.163, -0.011; p=0.026). Higher maternal BMI was associated with a higher offspring FI level in midlife and a slower increase in FI levels into old age. Larger size, faster growth from infancy to childhood, and low SES in childhood were all associated with a lower FI level in midlife but not with its rate of change. Conclusions Early life factors seem to contribute to disparities in frailty from midlife into old age. Early life factors may identify groups that could benefit from frailty prevention, optimally initiated early in life.

Is increased size at birth associated with longevity on the population level? – A historical and comparative analysis of regions in Sweden

Increased population longevity could be influenced by early life factors. Some areas have long-lived populations, also in a historical perspective. We aimed to study these factors in Halland, an area with the highest life expectancy in Sweden. We collected archival data on gestational age and birth characteristics from 995 live singleton full-term births at the Halmstad Hospital, Halland, from the period 1936 to 1938 and compared these to 3364 births from three hospitals in nearby Scania for the period 1935–1945. In addition, data were obtained on maternal and offspring characteristics from the national Swedish Medical Birth Register during 1973–2013. The results show that when controlling for background maternal and offspring characteristics, mean birth weight (BW) and mean birth length were higher in Halland than in Scania, but the proportion of low birth weight (LBW) and small for gestational age (SGA) was lower. However, mean BW for Halland did not differ from the rest of Sweden in recent years 2004–2013. We also conducted a mortality follow-up for children born in Scania, which showed that LBW, being born SGA, or short birth length reduced survival. In conclusion, the high mean life expectancy in Halland compared to the rest of Sweden could have been associated with beneficial early life factors influencing birth size in the past. In more recent decades the mean BW of Halland is not different from the national mean. Thus, longevity could be expected to become more equal to the national mean in the future.

Pre-Birth and Early-Life Factors Associated With the Timing of Adiposity Peak and Rebound: A Large Population-Based Longitudinal Study

Background: The late occurrence of adiposity peak (AP) and the early occurrence of adiposity rebound (AR) are considered the earliest indicators for obesity and its related health conditions later in life. However, there is still limited information for their upstream factors. Therefore, in this study, we aimed to identify the parental and child factors associated with the timing of AP and AR in the early stage of life.Methods: This is a population-based longitudinal study conducted in Shanghai, China. The BMI data of children born between September 2010 and October 2013 were followed from birth to 80 months. Subject-specific body mass index trajectories were fitted by non-linear mixed-effect models with natural cubic spline functions, and the individual's age at AP and AR was estimated. The generalized linear regression models were applied to identify the upstream factors of late occurrence of AP and early occurrence AR.Results: For 7,292 children with estimated AP, boys were less likely to have a late AP [adjusted risk ratio (RR) = 0.83, 95% confidence interval (CI): 0.77–0.90, p < 0.001], but preterm born children had a higher risk of a late AP (adjusted RR = 1.25, 95% CI: 1.07–1.47, p < 0.01). For 10,985 children with estimated AR, children with breastfeeding longer than 4 months were less likely to have an early AR (adjusted RR = 0.80, 95% CI: 0.73–0.87, p < 0.001), but children who were born to advanced-age mothers and who were born small for gestational age had a higher risk of having an early AR (adjusted RR = 1.21, 95% CI: 1.07–1.36, p < 0.01; adjusted RR = 1.20, 95% CI: 1.04–1.39, p = 0.01).Conclusions: Modifiable pre-birth or early-life factors associated with the timing of AP or AR were found. Our findings may help develop prevention and intervention strategies at the earliest stage of life to control later obesity and the health conditions and diseases linked to it.

The Magnitude and Directions of the Associations between Early Life Factors and Metabolic Syndrome Differ across Geographical Locations among Migrant and Non-Migrant Ghanaians—The RODAM Study

Background: Early-life factors (ELFs) such as childhood nutrition and childhood socio-economic status could be the drivers of the increase in metabolic syndrome (MetSyn) among African populations, but data are lacking. This study evaluated whether markers of childhood nutritional status and childhood socio-economic status were associated with MetSyn in adulthood among migrant Ghanaians living in Europe and non-migrant Ghanaians living in Ghana. Methods: Data from the Research on Obesity and Diabetes among African Migrants (RODAM) study, involving 2008 migrants and 2320 non-migrants aged ≥25 years, were analysed for this study. We used leg-length to height ratio (LHR), which is an anthropometric marker of childhood nutritional status, and parental education, which is a marker of childhood socio-economic status, as proxies. Adjusted odds ratios (AOR) and 95% confidence intervals (95% CI) were calculated by logistic regression with adjustments for demographic and lifestyle factors. Results: Parental education was higher among Ghanaians in Europe than among residents in rural and urban Ghana. The prevalence of MetSyn was 18.5%, 27.7% and 33.5% for rural, urban, and migrant residents, respectively. LHR was inversely associated with MetSyn among migrants. Compared with high paternal education, individuals with low paternal education had lower odds of MetSyn in migrants (AOR 0.71 95% CI 0.54–0.94). In contrast, compared with high maternal education, individuals with intermediate maternal education had higher odds of MetSyn in urban Ghanaians (AOR 4.53 95% CI 1.50–3.74). No associations were found among rural Ghanaians. Conclusion: The magnitude and direction of the associations between ELFs and MetSyn differ across geographical locations. Intermediate maternal education was positively associated with MetSyn among urban Ghanaians, while LHR and low paternal education were inversely associated with MetSyn among migrant Ghanaians. Further research into the interplay of genetics, environment and behaviour is needed to elucidate the underlying pathological mechanisms of MetSyn amongst migrants.

Natural history and associated early life factors of childhood asthma: a population registry-based cohort study in Denmark

ObjectiveAsthma is a common chronic disease that imposes a substantial burden on individuals and society. However, the natural history of childhood asthma in a large population remained to be studied. This study aimed to describe the natural course of childhood asthma and examine the association between early life factors and childhood asthma.DesignA population-based cohort study.SettingThis study was based on the national registry data in Denmark.ParticipantsAll liveborn singletons in Denmark during 1995–1997 were identified and followed them till the end of 2009. Finally, 193 673 children were eligible for our study.ExposuresThe following characteristics were examined as potential early life factors associated with childhood asthma, including parity, maternal asthma history, maternal smoking during pregnancy, maternal social status, delivery method and gender.Main outcomes and measuresAsthma cases were identified on the basis of hospitalisation for asthma and prescriptions for antiasthmatic medications. Asthma remission was defined as no hospitalisation or prescription recorded for 2 years. Cox proportional hazards’ regression and logistic regression were used to evaluate the association between early life factors and the occurrence and remission of childhood asthma.ResultsThe cumulative occurrence rate of asthma in children aged 3–14 years was 13.3% and the remission rate was 44.1%. The occurrence rate decreased with age. Being female had a lower risk of asthma (HR: 0.72, 95% CI 0.70 to 0.74) and higher remission rate of asthma (HR: 1.18, 1.13 to 1.22), while maternal asthma was associated with a higher risk of asthma (HR: 2.15, 2.04 to 2.26) and decreased remission rate of asthma (HR: 0.79, 0.73 to 0.85). These patterns remained the same for early onset asthma.ConclusionsFemale gender had a lower risk of asthma and a better chance of remission, while maternal asthma history had an opposite effect. The early life factors may influence the natural course of childhood asthma.

Early life factors in relation to albuminuria and estimated glomerular filtration rate based on cystatin C and creatinine in adults from a Swedish population-based cohort study

Background Early life factors influence the number of nephrons a person starts life with and a consequence of that is believed to be premature kidney ageing. Thus, we aimed to identify early life factors associated with cystatin C and creatinine-based estimated glomerular filtration (eGFR) rate equations and urine -albumin-to-creatinine ratio after a follow-up of 46–67 years. Methods The study included 593 Swedish subjects without diabetes mellitus from the Malmo Diet Cancer Cohort. Perinatal data records including birth weight, gestational age, placenta weight and maternal related risk factors were analysed. eGFR was determined by Chronic Kidney Disease Epidemiology (CKD-EPI), the Lund-Malmö revised and Caucasian, Asian, Paediatric, and Adult (CAPA) equations. Postnatal growth phenotypes were defined as low (≤ 0) or high (> 0) birth weight z-score, or low (≤ median) or high (> median) body mass index at 20 years of age. Results In women, lower birth weight was associated with lower eGFR (CAPA; CKD-EPI cystatin C). Birth weight z-score predicted adult albuminuria specifically in men (OR 0.75, 95% CI [0.58; 0.96]). Women with high birth weight z-score and low BMI at 20 years had lower eGFR (CAPA; CKD-EPI cystatin C; p = 0.04). Men with high birth weight z-score and high BMI at 20 years had lower risk for albuminuria (OR 0.35, 95% CI [0.12; 0.93]). Conclusions Lower birth weight, prematurity and postnatal growth curve have a potential sex- specific effect of early exposure to an adverse environment on lower cystatin C-based eGFR and albuminuria later in life. Cystatin C compared to creatinine -eGFR equations shows a higher ability to detect these findings. Graphic abstract