Neurodevelopmental origins of lifespan changes in brain and cognition

Neurodevelopmental origins of functional variation in older age are increasingly being acknowledged, but identification of how early factors impact human brain and cognition throughout life has remained challenging. Much focus has been on age-specific mechanisms affecting neural foundations of cognition and their change. In contrast to this approach, we tested whether cerebral correlates of general cognitive ability (GCA) in development could be extended to the rest of the lifespan, and whether early factors traceable to prenatal stages, such as birth weight and parental education, may exert continuous influences. We measured the area of the cerebral cortex in a longitudinal sample of 974 individuals aged 4–88 y (1,633 observations). An extensive cortical region was identified wherein area related positively to GCA in development. By tracking area of the cortical region identified in the child sample throughout the lifespan, we showed that the cortical change trajectories of higher and lower GCA groups were parallel through life, suggesting continued influences of early life factors. Birth weight and parental education obtained from the Norwegian Mother–Child Cohort study were identified as such early factors of possible life-long influence. Support for a genetic component was obtained in a separate twin sample (Vietnam Era Twin Study of Aging), but birth weight in the child sample had an effect on cortical area also when controlling for possible genetic differences in terms of parental height. Our results provide novel evidence for stability in brain–cognition relationships throughout life, and indicate that early life factors impact brain and cognition for the entire life course.

Download Full-text

FC 059EARLY LIFE FACTORS AND ADULT KIDNEY FUNCTION ESTIMATED BY CYSTATIN C AND CREATININE GLOMERULAR FILTRATION RATE EQUATIONS AND ALBUMINURIA: A SWEDISH COHORT STUDY

Nephrology Dialysis Transplantation ◽

10.1093/ndt/gfab144.002 ◽

2021 ◽

Vol 36 (Supplement_1) ◽

Author(s):

Agne Laucyte-Cibulskiene ◽

Shantanu Sharma ◽

Peter M Nilsson ◽

Anders Christensson

Keyword(s):

Regression Analysis ◽

Birth Weight ◽

Kidney Function ◽

Cystatin C ◽

Early Life ◽

Postnatal Growth ◽

Lower Birth Weight ◽

Adult Kidney ◽

Early Life Factors

Abstract Background and Aims Renal functional capacity is influenced by factors acting early in life, such as intrauterine environment, maturity, birth weight, length at birth, placental weight etc. Early life factors are responsible for the number of nephrons a person starts life with, and the consequence of a low nephron number is earlier kidney ageing and chronic kidney disease (CKD). Notably, most reports addressing early life factors in the context of adult kidney function use creatinine-based eGFR equations and/or albuminuria and lack longer follow-up (<30 years). Therefore, we aimed to identify early life factors associated with kidney function, determined by different creatinine and cystatin C equations and urinary albumin-to-creatinine ratio (UACR), more than 40 years later. Method 94 women and 494 men, born 1923-50, who participated in The Malmo Diet and Cancer (MDC) study were analyzed. Perinatal data records including birth weight (BW), birth length, head circumference, gestational age, placenta weight (PW) and mother related risk factors were collected from hospital and regional state archives. After a follow-up of 46 to 67 years study subjects underwent physical examination, blood pressure measurements and estimation of glomerular filtration rate (eGFR) using 4 different equations: Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) 2012 creatinine and cystatin C formula (CKD-EPI_creatinine, CKD-EPI_cystatin C), cystatin C eGFR equation based on Caucasian, Asian, pediatric, and adult cohorts (CAPA), the Lund-Malmö revised creatinine based eGFR equation (LM_rev). Urinary albumin-to-creatinine ratio (UACR) was measured in morning urine samples, albuminuria was defined as UACR ⩾3 mg/mmol. Birth weight z-scores (gender specific BWz and combined BWz) acquired by using the equation as reported by Marsal et al.(1996). Four growth mismatch phenotypes defined by combining low or high BW z-score (lowBWz or hiBWz respectively) with lower or higher body mass index at 20 years of age (lowBMI20 ir hiBMI20 respectively). Results Linear regression analysis of early life factors indicated that in females birth weight was positively associated with kidney function measured by both CAPA and CKD-EPI_cystatin C. In the whole population, birth weight adjusted for gestational age and sex, together with prematurity were independently associated to CKD-EPI_cystatin C, while BW/PW ratio was related to LM_rev. Logistic regression analysis showed that only gender specific BWz and combined BWz shared the same odds ratios for age and pulse pressure adjusted albuminuria in males (OR 0,75 (95%CI [0,58; 0,96]). While analyzing postnatal growth mismatch we found that females with hiBWz/lowBMI20 phenotype had significantly worse kidney function acquired by both cystatin C equations compared to those with lowBWz/lowBMI20 phenotype (p=0.044 for CAPA, p=0.040 for CKD-EPI_cystatin C). The logistic regression analysis revealed that hiBWz/hiBMI20 phenotype was related to lower risk of age and pulse pressure adjusted albuminuria (OR 0,35 (95%CI[0,12;0,93]) Conclusion Here we report that lower birth weight in females is associated with worse kidney function determined by cystatin C eGFR equations, while in males lower birth weight z-score is a risk factor for albuminuria in adulthood. Postnatal growth catch-up is not related to worse kidney function. We identified the protective phenotype (hiBWz/hiBMI20) for albuminuria in males and the unfavorable phenotype (hiBWz/lowBMI20) for kidney function in females. This suggests that lower birth weight and postnatal growth curve have a potential sex specific effect to kidney function and development of CKD in middle-aged Swedish subjects. Further studies are warranted to address early life factor prognostic accuracy in kidney function and outcomes prediction later in the lifetime.

Download Full-text

Early life factors and their relevance to intima-media thickness of the common carotid artery in early adulthood

Proceedings of The Nutrition Society ◽

10.1017/s002966512000169x ◽

2020 ◽

Vol 79 (OCE2) ◽

Author(s):

Juliana Nyasordzi ◽

Katharina Penczynski ◽

Thomas Remer ◽

Anette Buyken

Keyword(s):

Birth Weight ◽

Carotid Artery ◽

Young Adulthood ◽

Early Life ◽

Maternal Age ◽

Early Adulthood ◽

Intima Media Thickness ◽

Paternal Age ◽

Child Birth ◽

Early Life Factors

AbstractIntroductionEarly life factors may predispose an offspring to cardiovascular risk factors in later life. It is plausible a range of exposures in early life may be involved in this predisposition, which may extend to “healthy” populations in Western populations.We examined the association between a number of early life factors with the carotid intima-media thickness (IMT), a surrogate marker of atherosclerosis, in early adulthood of a healthy German population.MethodsWe studied term participants (n = 265) of the DONALD Study, with a bilateral sonographic measurement of the IMT in young adulthood (18–40 years) and data on early life factors (maternal and paternal age at child birth, birth weight (including appropriateness of birth weight- for gestational age), gestational weight gain and full breastfeeding (breastfeeding > 17weeks). Sonographic IMT measurements were performed on the left and right common carotid artery using a minimum of 4 measurements. Mean IMT values were obtained averaging the measurements from both sides, an overall average obtained from 8 and 16 measurement of both sides was used for this analysis. Information on gestation and birth were abstracted from the “Mutterpass”, maternal and paternal age at birth were inquired at study entry and breastfeeding information was assessed prospectively. Prospective association between early life factors and IMT were analyzed using multivariable linear regression models, considering age at IMT measurement, physician taking the measurement, in addition: birth year, first born status, maternal and paternal educational status, maternal overweight, presence of smokers in the household tested for potential confounding.ResultsMean adult IMT was 0.56mm ± 0.03, range: 0.41mm-0.78 mm. Maternal age at child birth was of prospective relevance for IMT in young adulthood, however, this association was sex specific: Increased maternal age at child birth was independently associated with an increased IMT among female offspring during young adulthood (β 0.029, SE 0.009) mm/decade, P = 0.003) only, this was not mediated by adult waist circumference. None of the remaining early life factors showed relevance for adult IMT levels among males and females in early adulthood.ConclusionThis study suggests that advanced maternal age at child birth is of prospective relevance for IMT levels in younger adulthood in a healthy Western population. This association appears to be sex specific, with maternal age at child birth positively associated with IMT in females in early adulthood only.

Download Full-text

Birth Weight, Breastfeeding, Maternal Smoking and Caries Trajectories

Journal of Dental Research ◽

10.1177/0022034516678181 ◽

2016 ◽

Vol 96 (2) ◽

pp. 171-178 ◽

Cited By ~ 25

Author(s):

E. Bernabé ◽

H. MacRitchie ◽

C. Longbottom ◽

N.B. Pitts ◽

W. Sabbah

Keyword(s):

Birth Weight ◽

Low Birth Weight ◽

Early Life ◽

Maternal Smoking ◽

Rate Of Change ◽

Primary Tooth ◽

Caries Increment ◽

Early Life Factors ◽

Over Time ◽

Childhood Caries

Evidence for the effects of low birth weight, breastfeeding and maternal smoking on childhood caries is mainly cross-sectional. We examined the association of these 3 putative early life factors with caries increment over a 4-y period among young children. We used data from a 4-y longitudinal caries-risk assessment study carried out among Scottish children. Early life factors were measured when children were aged 1 y (baseline). Caries assessment was repeated annually from ages 1 to 4, and the number of decayed, missing and filled primary tooth surfaces (dmfs) were used as a repeated outcome measure. The associations of low birth weight, breastfeeding and maternal smoking with dmfs at baseline and over time (trajectories) were assessed in linear mixed models. A total of 1,102 children were included in this analysis. Birth weight, breastfeeding and maternal smoking were not associated with dmfs at baseline. However, low birth weight and maternal smoking were associated with the rate of change in dmfs. By wave 4, the predicted mean difference in dmfs was 1.86 between children with low and normal birth weight, and 1.66 between children of smoking and non-smoking mothers. Children with low birth weight and smoking mothers had greater caries increments than those with normal weight and non-smoking mothers, respectively. There was no association between breastfeeding duration and childhood caries, either at baseline or over time.

Download Full-text

Metabolic syndrome and its associated early-life factors in children and adolescents: a cross-sectional study in Guangzhou, China

Public Health Nutrition ◽

10.1017/s1368980015002542 ◽

2015 ◽

Vol 19 (7) ◽

pp. 1147-1154 ◽

Cited By ~ 14

Author(s):

Jiao Wang ◽

Yanna Zhu ◽

Li Cai ◽

Jin Jing ◽

Yajun Chen ◽

...

Keyword(s):

Metabolic Syndrome ◽

Birth Weight ◽

Children And Adolescents ◽

Breast Feeding ◽

Abdominal Obesity ◽

South China ◽

Early Life ◽

Large City ◽

High Birth Weight ◽

Early Life Factors

AbstractObjectiveThe present study aimed to investigate the prevalence of metabolic syndrome (MetS) in 7- to 17-year-old children and adolescents in China and to examine the relationship between MetS and its associated early-life factors.DesignData were collected using a standard parent/guardian questionnaire in a face-to-face interview. Each participant underwent a complete anthropometric evaluation. MetS was defined according to the criteria of the International Diabetes Federation (IDF; 2007) for children and adolescents.SettingGuangzhou, a large city in South China, September 2013.SubjectsA total of 1770 children and adolescents were enrolled in the study, including 913 girls (51·6 %) and 857 boys (48·4 %).ResultsThe overall prevalence of MetS in children and adolescents was 1·1 % (n 19), which was higher in boys (1·4 %) than in girls (0·8 %). Multivariate analysis indicated that high birth weight was significantly associated with abdominal obesity (OR=2·86; 95 % CI 1·62, 5·06) and MetS (OR=3·61; 95 % CI 1·33, 9·82). Furthermore, >6 months of maternal breast-feeding was inversely associated with MetS (OR=0·39; 95 % CI 0·16, 0·98).ConclusionBased on IDF criteria, the prevalence of MetS among southern Chinese children was significantly lower than that in other populations. High birth weight was significantly associated with abdominal obesity and MetS, and breast-feeding for longer than 6 months was inversely associated with MetS in South China.

Download Full-text

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

Journal of Nephrology ◽

10.1007/s40620-021-01159-y ◽

2021 ◽

Author(s):

Agne Laucyte-Cibulskiene ◽

Shantanu Sharma ◽

Anders Christensson ◽

Peter M. Nilsson

Keyword(s):

Birth Weight ◽

Glomerular Filtration ◽

Cystatin C ◽

Early Life ◽

Postnatal Growth ◽

High Birth Weight ◽

Z Score ◽

Lower Birth Weight ◽

Lower Egfr ◽

Early Life Factors

Abstract 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

Download Full-text

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

Journal of Developmental Origins of Health and Disease ◽

10.1017/s2040174421000684 ◽

2021 ◽

pp. 1-11

Author(s):

Luciana Quaranta ◽

Ankita Sharma ◽

Åsa Pontén ◽

Karin Källén ◽

Peter M. Nilsson

Keyword(s):

Birth Weight ◽

Life Expectancy ◽

Gestational Age ◽

Early Life ◽

Population Level ◽

Birth Length ◽

Medical Birth Register ◽

Swedish Medical ◽

Birth Characteristics ◽

Early Life Factors

Abstract 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.

Download Full-text

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

International Journal of Environmental Research and Public Health ◽

10.3390/ijerph182211996 ◽

2021 ◽

Vol 18 (22) ◽

pp. 11996

Author(s):

Thijs G. W. van der Heijden ◽

Felix P. Chilunga ◽

Karlijn A. C. Meeks ◽

Juliet Addo ◽

Ina Danquah ◽

...

Keyword(s):

Metabolic Syndrome ◽

Early Life ◽

Parental Education ◽

Maternal Education ◽

Economic Status ◽

Paternal Education ◽

Socio Economic Status ◽

Early Life Factors ◽

Rodam Study ◽

Geographical Locations

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.

Download Full-text

Early life predictors of cerebral small vessel disease in four prospective cohort studies.

10.1101/2021.09.13.21252900 ◽

2021 ◽

Author(s):

Ellen V Backhouse ◽

Joanna M Wardlaw ◽

Susan D Shenkin ◽

Andrew M McIntosh ◽

Mark Bastin ◽

...

Keyword(s):

Risk Factors ◽

Birth Weight ◽

Cohort Studies ◽

Early Life ◽

Small Vessel Disease ◽

Cerebral Small Vessel Disease ◽

Vascular Risk ◽

Vessel Disease ◽

Prospective Cohort Studies ◽

Early Life Factors

Development of cerebral small vessel disease (SVD), a major cause of stroke and dementia, may be influenced by early life factors. It is unclear whether these relationships are independent of each other, of adult socioeconomic status (SES) or of vascular risk factor exposures. We examined associations between factors from birth (ponderal index, birth weight), childhood (IQ, education, SES), adult SVD, and brain volumes, using data from four prospective cohort studies: STratifying Resilience And Depression Longitudinally (STRADL) (n=1080; mean age=59 years); The Dutch Famine Birth cohort (n=118; mean age=68 years); the Lothian Birth Cohort 1936 (LBC1936; n=617; mean age=73 years), and the Simpsons cohort (n=110; mean age=78 years). We analysed each SVD feature individually and summed to give a total SVD score (range 1-4) in each cohort separately, then in meta-analysis, adjusted for vascular risk factors and adult SES. Higher birth weight was associated with fewer lacunes (OR per 100g, 0.93 95%CI=0.88-0.99, p=0.01), fewer infarcts (OR=0.94 95%CI=0.89-0.99, p=0.01), and fewer perivascular spaces (OR=0.95 95%CI=0.91-0.99, p=0.02). Ponderal index was not associated with SVD. Higher childhood IQ was associated with lower white matter hyperintensity burden (OR per IQ point=0.99 95%CI 0.98-0.998, p=0.03), fewer infarcts (OR=0.98, 95%CI=0.97-0.998, p=0.03), fewer lacunes (OR=0.98, 95%CI=0.97-0.999, p=0.04), and lower total SVD burden (OR=0.98, 95%CI=0.96-0.999, p=0.04). Low education was associated with more micro-bleeds (OR=1.90 95%CI=1.33-2.72, p<0.001) and lower total brain volume (MD=-178.86cm3, 95%CI=-325.07- -32.66, p=0.02). Low childhood SES was associated with with fewer lacunes (OR=0.62, 95%CI=0.40-0.95, p=0.03). Early life factors are associated with worse SVD in later life, independent of each other, vascular risk factors and adult SES. Risk for SVD may originate in early life and provide a mechanistic link between early life factors and risk of stroke and dementia. Policies investing in early child development may contribute to improve lifelong brain health to prevent dementia and stroke in older age.

Download Full-text