[Show abstract][Hide abstract] ABSTRACT: Background: Disturbed one-carbon (1-C) metabolism in the mother is associated with poor fetal growth but causality of this relationship has not been established. Methods: We studied the association between maternal total homocysteine and offspring birthweight in the Pune Maternal Nutrition Study (PMNS, Pune, India) and Parthenon Cohort Study (Mysore, India). We tested for evidence of causality within a Mendelian randomization framework, using a methylenetetrahydrofolatereductase (MTHFR) gene variant rs1801133 (earlier known as 677C -> T) by instrumental variable and triangulation analysis, separately and using meta-analysis. Results: Median (IQR) homocysteine concentration and mean (SD) birthweight were 8.6 mu mol/l (6.7,10.8) and 2642 g (379) in the PMNS and 6.0 mu mol/l (5.1,7.1) and 2871 g (443) in the Parthenon study. Offspring birthweight was inversely related to maternal homocysteine concentration-PMNS: -22 g/SD [95% confidence interval (CI): (-50, 5), adjusted for gestational age and offspring gender]; Parthenon: -57 g (-92, -21); meta-analysis: -40 g (-62, -17)]. Maternal risk genotype at rs1801133 predicted higher homocysteine concentration [PMNS: 0.30 SD/allele (0.14, 0.46); Parthenon: 0.21 SD (0.02, 0.40); meta-analysis: 0.26 SD (0.14, 0.39)]; and lower birthweight [PMNS: -46 g (-102, 11, adjusted for gestational age, offspring gender and rs1801133 genotype); Parthenon: -78 g (-170, 15); meta-analysis: -61 g (-111, -10)]. Instrumental variable and triangulation analysis supported a causal association between maternal homocysteine concentration and offspring birthweight. Conclusions: Our findings suggest a causal role for maternal homocysteine (1-C metabolism) in fetal growth. Reducing maternal homocysteine concentrations may improve fetal growth.
[Show abstract][Hide abstract] ABSTRACT: Background
Diabetes has been defined on the basis of different bio-markers, including fasting plasma glucose (FPG), 2-h plasma glucose in an oral glucose tolerance test (2hOGTT), and HbA1c. We assessed the effect of different diagnostic definitions on both the population prevalence of diabetes and the classification of previously undiagnosed individuals as having diabetes versus not having diabetes in a pooled analysis of data from population-based health examination surveys in different regions.
We used data from 96 population-based health examination surveys that had measured at least two of the bio-markers used for defining diabetes. Diabetes was defined using HbA1c (HbA1c ≥6·5% or history of diabetes diagnosis or using insulin or oral hypoglycemic drugs) compared with either FPG only or FPG-or-2hOGTT definitions (FPG ≥7·0 mmol/L or 2hOGTT ≥11·1 mmol/L or history of diabetes or using insulin or oral hypoglycemic drugs). We calculated diabetes prevalence, taking into account complex survey design and survey sample weights. We compared the prevalences of diabetes using different definitions graphically and by regression analyses. We calculated sensitivity and specificity of diabetes diagnosis based on HbA1c compared with diagnosis based on glucose among previously undiagnosed individuals (i.e., excluding those with history of diabetes or using insulin or oral hypoglycemic drugs). We calculated sensitivity and specificity in each survey, and then pooled results using a random-effects model. We assessed the sources of heterogeneity of sensitivity by meta-regressions for study characteristics selected a priori.
Population prevalence of diabetes based on FPG-or-2hOGTT was correlated with prevalence based on FPG alone (r=0·98), but was higher by 2–6 percentage points at different prevalence levels. Prevalence based on HbA1c was lower than prevalence based on FPG in 42·8% of age–sex–survey groups and higher in another 41·6%; in the other 15·6%, the two definitions provided similar prevalence estimates. The variation across studies in the relation between glucose-based and HbA1c-based prevalences was partly related to participants' age, followed by natural logarithm of per person gross domestic product, the year of survey, mean BMI, and whether the survey population was national, sub-national, or from specific communities. Diabetes defined as HbA1c 6·5% or more had a pooled sensitivity of 52·8% (95% CI 51·3–54·3%) and a pooled specificity of 99·74% (99·71–99·78%) compared with FPG 7·0 mmol/L or more for diagnosing previously undiagnosed participants; sensitivity compared with diabetes defined based on FPG-or-2hOGTT was 30·5% (28·7–32·3%). None of the preselected study-level characteristics explained the heterogeneity in the sensitivity of HbA1c versus FPG.
Different biomarkers and definitions for diabetes can provide different estimates of population prevalence of diabetes, and differentially identify people without previous diagnosis as having diabetes. Using an HbA1c-based definition alone in health surveys will not identify a substantial proportion of previously undiagnosed people who would be considered as having diabetes using a glucose-based test.
[Show abstract][Hide abstract] ABSTRACT: Motor development and cognitive development in childhood have been found to be fundamentally interrelated, but less is known about the association extending over the life course. The aim of this study was to examine the association between early motor development and cognitive performance in early old age. From men and women belonging to the Helsinki Birth Cohort Study, who were born between 1934 and 1944 and resided in Finland in 1971, 1279 participated in cognitive performance tests (CogState®, version 3.0.5) between 2001 and 2006 at an average age of 64.2 years (SD 3.0). Of these, age at first walking extracted from child welfare clinic records was available for 398 participants. Longer reaction times in cognitive tasks measuring simple reaction time (SRT), choice reaction time (CRT), working memory (WM), divided attention (DA), and associated learning (AL) indicated poorer cognitive performance. Adjustment was made for sex, age at testing, father's occupational status and own highest attained education, and occupation in adulthood. Average age of learning to walk was 12.2 months (SD 2.1). After adjusting for covariates, earlier attainment of learning to walk was associated with shorter reaction times in cognitive performance tasks (SRT 10.32 % per month, 95 % CI 0.48-21.12, p = 0.039; CRT 14.17 % per month, 95 % CI 3.75-25.63, p = 0.007; WM 15.14 % per month, 95 % CI 4.95-26.32, p = 0.003). People who learned to walk earlier had better cognitive performance in early old age. The earlier attainment of motor skills may track over to early old age and possibly reflect greater cognitive reserve in older age.
Age 06/2015; 37(3):9785. DOI:10.1007/s11357-015-9785-x · 3.45 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background:
There is some evidence linking sub-optimal prenatal development to an increased risk of disability pension (DP). Our aim was to investigate whether body size at birth was associated with transitioning into all-cause and cause-specific DP during the adult work career.
10 682 people born in 1934-44 belonging to the Helsinki Birth Cohort Study had data on birth weight extracted from birth records, and on time, type and reason of retirement between 1971 and 2011 extracted from the Finnish Centre for Pensions.
Altogether 21.3% transitioned into DP during the 40-year follow-up, mainly due to mental disorders, musculoskeletal disorders and cardiovascular disease. Average age of transitioning into DP was 51.3 (SD 8.4) for men and 52.2 (SD 7.6) for women. Cohort members who did not transition into DP retired 10 years later on average. Among men, higher birth weight was associated with a lower hazard of transitioning into DP, adjusted hazard ratio (HR) being 0.94 (95% confidence interval [CI] 0.88-0.99 for 1 SD increase in birth weight). For DP due to mental disorders the adjusted HR was 0.90, 95% CI 0.81, 0.99. A similar but non-significant trend was found for DP due to cardiovascular disease. Among women there were no associations between body size at birth and all-cause DP (p for interaction gender*birth weight on DP p = 0.007).
Among men disability pension, particularly due to mental disorders, may have its origins in prenatal development. Given that those who retire due to mental health problems are relatively young, the loss to the workforce is substantial.
PLoS ONE 04/2015; 10(4):e0122134. DOI:10.1371/journal.pone.0122134 · 3.23 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Maternal obesity has long-term consequences for the offspring's later health, including an increased risk of type 2 diabetes and cardiovascular disease. The underlying mechanisms explaining these associations are, however, not fully understood.
A total of 2003 individuals from the Helsinki Birth Cohort Study born 1934-44, underwent measurements of body size, body composition, and clinical characteristics at a mean age of 62 years. Data on maternal anthropometry were available from hospital records.
Maternal BMI was positively associated with BMI in the offspring. Higher maternal BMI was associated with less favorable body composition in the offspring. There was a significant interaction between birth weight and maternal BMI on offspring body fat percentage (P for interaction 0.003). In mothers with low BMI, a higher offspring birth weight was associated with lower fat percentage, while among those with maternal BMI in the highest fourth, higher offspring birth weight predicted higher body fat percentage.
Our findings suggest that a disadvantageous body composition is programmed in early life. This may in part underlie the association between maternal obesity and later cardio-metabolic health of the offspring. These findings support the importance of prevention of overweight in women of child-bearing age.
Annals of Medicine 03/2015; 47(2):1-6. DOI:10.3109/07853890.2015.1004360 · 3.89 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The Åland Islands were recently ranked as Finland’s healthiest region with lower prevalence of several non-communicable diseases compared with the national mean. We have compared birth characteristics of 1697 individuals born on the Åland Islands between 1937 and 1944 with contemporaneous data from the Helsinki Birth Cohort Study (HBCS;
=11,808). This is a first step towards a potential future analysis of Ålandic health from a life-course perspective. Mean birth weight and length were calculated for both cohorts. Birth weight was entered into a multiple linear regression model with sex, maternal age, marital status and birth year as predictors. Mean birth weight in the Åland cohort was 3499 g, 87 g (95% CI 62; 111) higher compared with the HBCS. Sex and maternal marital status were the strongest predictors of birth weight. More detailed studies are needed to explore the potential effects of this difference in average birth weight between cohorts.
Journal of Developmental Origins of Health and Disease 02/2015; 6(04):1-5. DOI:10.1017/S2040174415000136 · 0.75 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Osteoporosis is a chronic disease, carrying an elevated risk of fractures, morbidity and death. Long term treatment may be required but the long term risks with osteoporosis drugs remain incompletely understood. The competing risk of death may be a barrier to treating the oldest, yet this may not be rational if the risk of death is reduced by treatment. It is difficult to devise goal directed long term strategies for managing osteoporosis without firm information about residual lifetime expectancy in treated patients. We conducted an observational study in Danish national registries tracking prescriptions for osteoporosis drugs, comorbid conditions and deaths. We included 58,637 patients and 225,084 age- and gender matched control subjects. Information on deaths until the end of 2013 was retrieved, providing a follow-up period of 10-17 years. In men below age 80 and women below age 60, the relative risk of dying declined from being strongly increased in the first year to a stable but elevated level in subsequent years. In women older than 65-70 years of age there was only a small elevation in risk in the first year of treatment followed by lower than background mortality. The residual life expectancy of a 50-year old man beginning osteoporosis treatment was estimated to be 18.2 years and 7.5 years in a 75-year old man. Estimates in women were 26.4 years and 13.5 years. This study shows an excess mortality in men and in women below age 70 who are treated for osteoporosis, compared with the background population. This excess risk is more pronounced in the first few years on treatment. The average life expectancy of osteoporosis patients is in excess of fifteen years in women below the age of 75 and in men below the age of 60, highlighting the importance of developing tools for long term management. This article is protected by copyright. All rights reserved.
This article is protected by copyright. All rights reserved.
Journal of bone and mineral research: the official journal of the American Society for Bone and Mineral Research 02/2015; 30(9). DOI:10.1002/jbmr.2478 · 6.83 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Objective
Type 2 diabetes (T2D) is a heterogeneous disorder. The aim of this study was to examine the trajectories of childhood growth associated with T2D.Design and subjectsA total of 13,345 individuals born in Helsinki, Finland between 1934 and 1944 were included in the study. The participants’ growth had been recorded in detail during childhood, and 11.7% (n = 1558) had been diagnosed with T2D. We divided the cohort around the median body mass index (BMI) at 11 years. Body composition and glucose tolerance were assessed in a clinical subsample (n = 2003) in adulthood.ResultsTwo pathways of growth were associated with T2D. Both began with low weight and BMI at birth. In one, persistent low BMI through infancy was followed by a rapid increase in BMI in childhood. Among individuals with a BMI at 11 years above the median value, the odds ratio for T2D associated with a one z-score increase in BMI between 2 and 11 years was 1.31 (95% confidence interval 1.21 to 1.42, P < 0.001). In the other pathway, low BMI at birth, accompanied by short length at birth, was followed by low BMI in childhood. Most women who developed diabetes followed this trajectory; they developed T2D at a lower BMI and lower fat percentage than women with a BMI above the median at 11 years of age.Conclusions
Two pathways of early growth trigger T2D. Low fat deposition leading to thinness at birth and during infancy results in fat acquisition during childhood. Reduced linear growth leading to short length at birth is associated with lower body fat percentage in adulthood but increased risk of developing diabetes.This article is protected by copyright. All rights reserved.
Journal of Internal Medicine 02/2015; 278(2). DOI:10.1111/joim.12354 · 6.06 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Previous studies have shown that maternal grand multiparity may predict an increased risk of mental disorders in young adult offspring, but whether such effects persist throughout adulthood remains unknown. The current study examined if maternal grand multiparity predicts the risks of severe mental disorders, suicides, suicide attempts and dementias throughout adult life.
Our study sample comprised 13243 Helsinki Birth Cohort Study 1934-1944 participants (6905 men and 6338 women). According to hospital birth records, 341 offspring were born to grand multiparous mothers. From Finnish national hospital discharge and causes of death registers, we identified 1682 participants diagnosed with mental disorders during 1969-2010.
Maternal grand multiparity predicted significantly increased risks of mood disorders (Hazard Ratio = 1.64, p = 0.03), non-psychotic mood disorders (Hazard Ratio = 2.02, p = 0.002), and suicide attempts (Hazard Ratio = 3.94, p = 0.01) in adult offspring. Furthermore, women born to grand multiparous mothers had significantly increased risks of any severe mental disorder (Hazard Ratio = 1.79, p = 0.01), non-psychotic substance use disorders (Hazard Ratio = 2.77, p = 0.02) schizophrenia, schizotypal and delusional disorders (Hazard Ratio = 2.40, p = 0.02), mood disorders (Hazard Ratio = 2.40, p = 0.002), non-psychotic mood disorders (Hazard Ratio = 2.91, p<0.001), and suicide attempts (Hazard Ratio = 5.05, p = 0.01) in adulthood. The effects of maternal grand multiparity on offspring psychopathology risk were independent of maternal age and body mass index at childbirth, and of year of birth, sex, childhood socioeconomic position, and birth weight of the offspring. In contrast, no significant effects were found among men.
Women born to grand multiparous mothers are at an increased risk of severe mental disorders and suicide attempts across adulthood. Our findings may inform the development of preventive interventions for mental disorders.
PLoS ONE 12/2014; 9(12):e114679. DOI:10.1371/journal.pone.0114679 · 3.23 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Context: Altered endocrinal and autonomic nervous system responses to stress may link impaired intra-uterine growth with later cardiovascular disease. Objective: To test the hypothesis that offspring of gestational diabetic mothers (OGDM) have high cortisol and cardio-sympathetic responses during the Trier Social Stress Test for Children (TSST-C). Design: Adolescents from a birth cohort in India (N=213, mean age:13.5 years) including 26 OGDM, 22 offspring of diabetic fathers (ODF) and 165 offspring of non-diabetic parents (controls) completed five minutes each of public speaking and mental arithmetic tasks in front of two unfamiliar 'evaluators' (TSST-C). Salivary cortisol concentrations were measured at baseline and at regular intervals after the TSST-C. Heart rate, blood pressure (BP), stroke volume, cardiac output and total peripheral resistance (TPR) were measured continuously at baseline, during and for 10 minutes after the TSST-C using a finger cuff; the beat-to-beat values were averaged for these periods. Results: Cortisol and cardio-sympathetic parameters increased from baseline during stress (P<0.001). OGDM had greater systolic BP (mean difference: 5.6 mmHg), cardiac output (0.5 L/min), and stroke volume (4.0 mL) rises and a lower TPR rise (125 dyn.s/cm(5)) than controls during stress. ODF had greater systolic BP responses than controls (difference: 4.1 mmHg); there was no difference in other cardio-sympathetic parameters. Cortisol responses were similar in all three groups. Conclusions: Maternal diabetes during pregnancy is associated with higher cardio-sympathetic stress-responses in the offspring, which may contribute to their higher cardiovascular disease risk. Further research may confirm stress-response programming as a predictor of cardiovascular risk in OGDM.
[Show abstract][Hide abstract] ABSTRACT: Background:
Growth and feeding during infancy have been associated with later life body mass index. However, the associations of infant feeding, linear growth and weight gain relative to linear growth with separate components of body composition remain unclear.
Of 5551 children with collected growth and infant-feeding data in a prospective cohort study (Amsterdam Born Children and their Development), body composition measured using bioelectrical impedance analysis at the age of 5-6 years was available for 2227 children. We assessed how feeding (duration of full breastfeeding and timing of introduction of complementary feeding) and conditional variables representing linear growth and relative weight gain were associated with childhood fat-free mass (FFM) and fat mass (FM).
Birth weight was positively associated with both FFM and FM in childhood, and more strongly with FFM than FM. Faster linear growth and faster relative weight gain at all ages in infancy were positively associated with childhood FFM and FM. The associations with FM were stronger for relative weight gain than for linear growth (FM z score: β coefficient 0.23 (95% con 0.19 to 0.26), P<0.001 and 0.14 (0.11 to 0.17), P<0.001 per s.d. change in relative weight gain and linear growth between 1 and 3 months, respectively). Compared with full breastfeeding <1 month, full breastfeeding >6 months was associated with lower FM (FM z score: -0.17 (-0.28 to -0.05), P=0.005) and lower FFM (FFM z score: -0.13 (-0.23 to -0.03), P=0.015), as was the introduction of complementary feeding >6 months (FM z score: -0.22 (-0.38 to -0.07), P=0.004), compared with <4 months.
Faster infant weight gain is associated with a healthier childhood body composition when it is caused by faster linear growth. Full breastfeeding >6 months and introduction of complementary feeding >6 months are associated with lower childhood FM.
International journal of obesity (2005) 12/2014; 39(4). DOI:10.1038/ijo.2014.200 · 5.00 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background:
Overweight and obesity in childhood have been linked to an increased risk of adult mortality, but evidence is still scarce.
We identified trajectories of body mass index (BMI) development in early life and investigated their mortality risk. Data come from the Helsinki Birth Cohort Study, in which 4943 individuals, born 1934-1944, had serial measures of weight and height from birth to 11 years extracted from health care records, weight and height data in adulthood, and register-based mortality data for 2000-2010.
Three early BMI trajectories (increasing, average, and average-to-low for men and increasing, average, and low-to-high BMI for women) were identified. Women with an increasing or low-to-high BMI (BMI lower in early childhood, later exceeded average) trajectory had an increased risk of all-cause mortality compared to those with an average BMI trajectory (HR 1.55, 95% CI 1.07-2.23; and HR 1.57, 95% CI 1.04-2.37, respectively). Similar associations were observed for cancer mortality. Among men, BMI trajectories were not associated with all-cause mortality, but those with average-to-low BMI (BMI first similar then dropped below average) had an increased risk of cancer mortality.
An increasing BMI in early life may shorten the lifespan of maturing cohorts as they age, particularly among women.
Annals of Medicine 10/2014; 47(1):1-6. DOI:10.3109/07853890.2014.963664 · 3.89 Impact Factor