Biomedical subjects

Clive Osmond

Publications and source records attributed to Clive Osmond.

At least 19 recordsLinked to original sources

PubMed2007

Infant growth and stroke in adult life: the Helsinki birth cohort study.

BACKGROUND AND PURPOSE: People who had low birth weight are at increased risk of stroke. Little is known about the effects of early postnatal growth on stroke risk. METHODS: We followed-up 12 439 people born in Helsinki during 1934 to 1944. Their body size was measured at birth and, on average, 9 times between birth and age 2 years; 507 of them were hospitalized with stroke or died from the disease. RESULTS: Hazard ratios for stroke declined progressively with increasing gain in weight between birth and age 2 years. The hazard ratio was 0.85 (95% CI, 0.78 to 0.93; P=0.0004) per standard deviation increase in the difference between the weight attained at age 2 years and that predicted from birth weight. A 1-standard deviation increase in body mass index at 2 years of age was associated with a hazard ratio for stroke of 0.84 (95% CI, 0.77 to 0.92; P=0.0002). This association was little changed by adjustment for measures of socio-economic status. Change in body size after the age of 2 years had little effect on the risk of later stroke. People whose mothers had a small external conjugate diameter of the pelvis had an increased risk of stroke. The hazard ratio associated with a diameter of < or =18 cm was 1.62 (95% CI, 1.30 to 2.02; P<0.0001). CONCLUSIONS: Thinness during infancy is associated with an increased risk of stroke in later life. This association may be the result of maternal influences which originated in the mother's infancy when her pelvic shape was established.

Aged↗

PubMed2007

Maternal low protein diet restricted to the preimplantation period induces a gender-specific change on hepatic gene expression in rat fetuses.

It has been shown previously that maternal low protein diet (LPD) throughout rat gestation altered hepatic gene expression and enzyme activities in offspring. Here, we investigate the effect of maternal LPD (9% casein vs. 18% control) exclusively during the preimplantation period (switched diet group) or provided throughout gestation on hepatic gene expression in day 20 fetuses. Using quantitative competitive PCR, we found that switched diet induced a two-fold increase (P = 0.008) in hepatic gene expression of phosphoenolpyruvate carboxykinase (PEPCK, a rate limiting enzyme for gluconeogenesis) in male fetuses and a 17% increase (P = 0.005) in 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1, acts primarily as a reductase to produce active glucocorticoid) in female liver compared with control fetuses. Maternal LPD administered throughout gestation increased 11beta-HSD1 expression in male fetal liver by 27% (P = 0.042) compared with controls. However, maternal LPD fed for either period did not affect fetal hepatic insulin receptor (IR), glucocorticoid receptor (GR), glycogen synthase (GS) nor placental glucose transporter 1 (Glut1) and 3 (Glut3) transcript levels. The alteration in fetal hepatic gene expression could not be attributed specifically to known regulators including insulin or glucose concentrations in fetal blood nor alteration in cAMP in fetal liver, although a combination of these regulatory factors may be responsible. Fetal hepatic glycogen level was unaffected by maternal diet. The present findings show that the long term potential of the preimplantation embryo is sensitive to maternal LPD such that basal levels of hepatic gene expression in day 20 fetuses are altered in a gender-specific manner.

11-beta-Hydroxysteroid Dehydrogenase Type 1↗

PubMed2006

Cortisol responses to psychological stress in adults after prenatal exposure to the Dutch famine.

Experimental studies in animals show that prenatal undernutrition leads to lifelong alterations in the activity of the hypothalamic-pituitary-adrenal (HPA) axis. Some studies have shown associations between low birth weight and an increased HPA response to psychological stress. We tested the hypothesis that prenatal exposure to the Dutch 1944-1945 famine leads to an elevated HPA response to psychological stress in adult life. We measured salivary cortisol responses to a psychological stress protocol among 694 adults who were born as term singletons in Amsterdam, the Netherlands, around the time of the 1944-1945 Dutch famine. We compared cortisol profiles of participants exposed to famine during late (n=120), mid (n=100), or early gestation (n=62) to profiles of participants unexposed to famine during gestation (n=412). The mean increase in cortisol concentrations from baseline was 30% (95% CI 23-37). There were no statistically significant differences in the mean profile of cortisol response to the psychological stress protocol between participants exposed and unexposed to famine in utero. The mean sex and BMI adjusted difference in cortisol response for those exposed compared to those unexposed was -6% (95% CI: -15 to 2). The cortisol profiles of those exposed in late (-4% [95% CI: -16 to 7]), mid (-9% [95% CI: -22 to 3]) or early gestation (-4% [95% CI: -20 to 10]) did not differ from the profile of those unexposed to famine. We conclude that prenatal exposure to famine does not seem to be associated with the response of the HPA axis to psychological stress. However, the stress protocol we have used may have been unsuccessful in inducing a strong enough HPA axis activation to be able to detect famine related differences.

Cohort Studies↗

PubMed2006

Spontaneous hypothyroidism in adult women is predicted by small body size at birth and during childhood.

BACKGROUND: The relationships of early growth with coronary heart disease and type 2 diabetes have received considerable attention. It is not known whether fetal or childhood growth is linked with autoimmune disorders. OBJECTIVE: Our objective was to assess whether the risk of adult-onset spontaneous hypothyroidism is predicted by body size at birth and during childhood. DESIGN AND SETTING: We conducted a birth cohort study in Helsinki, Finland. PARTICIPANTS: A total of 293 women who were born between 1934 and 1944 and had their heights and weights recorded at birth and during childhood participated in the study. MEASUREMENTS: We measured spontaneous hypothyroidism, defined as: 1) a disease history confirmed from medical records, or 2) previously undiagnosed hypothyroidism (TSH > 10 mU/liter). RESULTS: Twenty women (6.8%) had spontaneous hypothyroidism; 18 had been diagnosed previously, between 43 and 65 yr of age, and two had undiagnosed subclinical hypothyroidism. In addition, 59 women were thyroid peroxidase antibody positive. Compared with the 214 thyroid peroxidase antibody-negative women with no thyroid disorder, those with spontaneous hypothyroidism had on average 252 g [95% confidence interval (CI), 61 to 443 g; P = 0.01] lower birth weight and 1.2 cm (95% CI, 0.5 to 2.0 cm; P = 0.002) shorter length at birth. The odds of developing hypothyroidism increased 4.4-fold per kilogram decrease in birth weight (95% CI, 1.4 to 14.1). Hypothyroid subjects had been shorter in early childhood and had lower body mass index during later childhood. CONCLUSIONS: Small body size at birth and during childhood increases the risk of spontaneous hypothyroidism in adult women.

Adult↗

PubMed2006

Associations of body size at birth with late-life cortisol concentrations and glucose tolerance are modified by haplotypes of the glucocorticoid receptor gene.

CONTEXT: Small body size at birth is associated with cardiovascular disease and type 2 diabetes in adult life. This link may be in part mediated by early-life programming of the hypothalamic-pituitary-adrenal axis (HPAA) function. OBJECTIVE: Our objective was to assess whether haplotypes of the glucocorticoid receptor (GR) gene modify this link. DESIGN AND PARTICIPANTS: We conducted a birth cohort study that included 437 men and women born in Helsinki, Finland, during 1924-1933, whose birth measurements were recorded. MAIN OUTCOME MEASURES: We studied how the oral glucose tolerance test and fasting plasma total and free cortisol concentrations and, in a subset of 162 women, a more detailed HPAA evaluation, are predicted by body size at birth and haplotypes of the GR locus. We also measured the haplotype-specific relative mRNA expression level for the haplotype of interest. RESULTS: One of the haplotypes was associated with lower birth weight and length and higher fasting plasma and mean 24-h salivary cortisol. Moreover, this haplotype modified the association of length at birth with adult phenotypes; in carriers, short length at birth was associated with increased fasting plasma cortisol, cortisol/corticosteroid-binding globulin ratio, impaired glucose tolerance or diabetes [1 cm decrease corresponded to 1.36-fold odds ratio; 95% confidence interval (CI), 1.09-1.70; P = 0.007], and higher 120-min glucose (5.8%; 95% CI, 2.5-9.1%; P = 0.0007), but no association was seen in noncarriers (P for interaction was 0.06, 0.01, 0.02, and 0.01, respectively). The mRNA expression level of this haplotype was 93.7% (95% CI, 90.5-96.8%; P = 2.2 x 10(-4)) of the expression level of the other haplotypes. CONCLUSIONS: A common GR haplotype may contribute to and modify the association of short length at birth with adult glucose tolerance and HPAA function by a mechanism that affects regulation of GR expression.

Aged↗

PubMed2006

Fetal growth and the adrenocortical response to psychological stress.

CONTEXT: Experimental studies in animals show that adverse prenatal environments lead to lifelong alterations in the activity of the hypothalamic-pituitary-adrenal axis, which mediates the stress response through secretion of glucocorticoid hormones. The extent to which such prenatal hypothalamic-pituitary-adrenal axis adaptations occur in humans is unknown. OBJECTIVE: The objective of the study was to determine whether smaller but otherwise healthy term babies are more likely to demonstrate increased glucocorticoid responses to psychological stress in childhood. DESIGN AND PARTICIPANTS: This was a cross-sectional study of 68 boys and 72 girls (aged 7-9 yr) who have been followed up since 12 wk gestation when their mothers took part in a study of healthy children born in Southampton, United Kingdom. MAIN OUTCOME MEASURE: Salivary cortisol responses to psychological stress were measured. RESULTS: In boys, birth weight was inversely related to salivary cortisol responses to stress (r = -0.56, P < 0.001) but not morning cortisol levels, whereas in girls, morning peak cortisol was inversely related to birth weight (r = -0.36, P < 0.05). These associations were independent of gestational age and potential confounding factors including obesity, social class, and educational achievement. CONCLUSIONS: This study suggests that processes occurring during fetal life, resulting in smaller newborns, have a lasting effect on adrenocortical responses to stress in boys and on basal adrenocortical activity in girls. Given the known associations between small alterations in adrenocortical activity and features of the metabolic syndrome such as raised blood pressure and glucose intolerance, these effects warrant further investigation of their potential impact on the future health of prepubertal children.

Adrenal Cortex↗

PubMed2006

Geographical variation in relationships between parental body size and offspring phenotype at birth.

BACKGROUND: Size and body proportions at birth are partly determined by maternal body composition, but most studies of mother-baby relationships have only considered the effects of maternal height and weight on offspring birth weight, and few have examined the size of effects. Paternal size and body composition also play a role, primarily through the fetal genome, although few studies have investigated relationships with neonatal phenotype. METHODS: Data from the UK, Finland, India, Sri Lanka, China, DR Congo, Nigeria and Jamaica were used to investigate the effects of maternal measures (derived at 30 weeks' gestation, n=16,418), and also paternal size (n=3,733) on neonatal phenotype, for singleton, live-born, term births. RESULTS: After accounting for variation in maternal size and shape across populations, differences in neonatal phenotype were markedly reduced. Mother-baby relationships were similar across populations, although some were stronger in developing countries. Maternal height was generally the strongest predictor of neonatal length, maternal head circumference of neonatal head and maternal skinfold thickness of neonatal skinfolds. Relationships with maternal arm muscle area were generally weak. Effects of paternal height and body mass index were weaker than the equivalent maternal measurements in most studies. CONCLUSIONS: Differences in maternal body composition account for a large part of the geographical variation in neonatal phenotype. The size of the effects of all maternal measures on neonatal phenotype suggests that nutrition at every stage of the mother's life cycle may influence fetal growth. Further research is needed into father-baby relationships and the genetic mechanisms that influence fetal growth.

Adult↗

PubMed2006

Geographical variation in neonatal phenotype.

BACKGROUND: Recent studies have shown associations between size and body proportions at birth and health outcomes throughout the life cycle, but there are few data on how neonatal phenotype varies in different populations around the world. METHODS: Data from the UK, Finland, India, Sri Lanka, China, DR Congo, Nigeria, and Jamaica (n=22,067) were used to characterize geographical differences in phenotype in singleton, live-born newborns. Measurements included birth weight, placental weight, length, head, chest, abdominal and arm circumferences, and skinfolds. RESULTS: Neonates in Europe were the largest, followed by Jamaica, East Asia (China), then Africa and South Asia. Birth weight varied widely (mean values 2,730-3,570 g), but in contrast, head circumference was similar in all except China (markedly smaller). The main difference in body proportions between populations was the head to length ratio, with small heads relative to length in China and large heads relative to length in South Asia and Africa. CONCLUSIONS: These marked geographical differences in neonatal phenotype need to be considered when investigating determinants of fetal growth, and optimal phenotype for short-term and long-term outcomes.

Anthropometry↗

PubMed2006

Early onset of coronary artery disease after prenatal exposure to the Dutch famine.

BACKGROUND: Limited evidence suggests that maternal undernutrition at the time of conception is associated with increased cardiovascular disease risk in adult offspring. OBJECTIVE: We investigated whether persons conceived during the Dutch famine of World War II had an early onset of coronary artery disease (CAD). DESIGN: We compared the age at onset and cumulative incidence of CAD between persons born as term singletons who were exposed to the 1944-1945 Dutch famine during late (n = 160), mid- (n = 138), or early (n = 87) gestation and 590 unexposed subjects at age 50 or 58 y. Age at CAD onset was defined as the age at which angina pectoris was identified (according to the Rose questionnaire), Q waves were observed on an electrocardiogram (Minnesota codes 1-1 or 1-2), or coronary revascularization was performed (by angioplasty or bypass surgery). RESULTS: Of the 83 CAD cases identified, persons conceived during the famine were 3 y younger than the unexposed persons at the time of CAD diagnosis (47 y compared with 50 y) and had a higher cumulative incidence of CAD [13%; hazard ratio (HR) adjusted for sex: 1.9; 95% CI: 1.0, 3.8] than did the unexposed persons. The HR changed little after adjustment for smoking (HR: 1.8), social class (HR: 2.0), or size at birth (HR: 2.0). CONCLUSIONS: We found an earlier onset of CAD among persons conceived during the famine, which suggests that maternal nutrition in early gestation may play a role in the onset of CAD. This finding agrees with evidence from animal experiments that identify periconceptional maternal diet as important in the offspring's adult health.

Age of Onset↗

PubMed2006

Blood pressure response to psychological stressors in adults after prenatal exposure to the Dutch famine.

OBJECTIVE: There is increasing evidence that restricted prenatal growth is associated with exaggerated blood pressure responses to stress. We investigated the effect of maternal undernutrition on the adult offspring's stress response. DESIGN: A historical cohort study. METHODS: We performed continuous blood pressure and heart rate measurements during a battery of three 5-min physiological stress tests (Stroop test, mirror-drawing test and a public speech task) in 721 men and women, aged 58 years, born as term singletons in Amsterdam at about the time of the Dutch 1944-1945 famine. RESULTS: During the stress tests, the systolic blood pressure (SBP) rose from baseline by 20 mmHg during the Stroop test, by 30 mmHg during the mirror-drawing test and by 47 mmHg during the public speech task. The SBP and diastolic blood pressure increase during stress was highest among individuals exposed to famine in early gestation compared with unexposed subjects (4 mmHg extra systolic increase, P = 0.04; 1 mmHg diastolic increase, P = 0.1, both adjusted for sex). Exposure during mid and late gestation was not associated with a stress-related increment of blood pressure (P adjusted for sex > 0.6). Correcting for confounders in a multivariable model did not attenuate the association between famine exposure in early gestation and the SBP increment. The heart rate increment was not related to famine exposure during any part of gestation. CONCLUSION: We found a greater blood pressure increase during stress among individuals exposed to famine in early gestation. Increased stress responsiveness may underlie the known association between coronary heart disease and exposure to famine in early gestation.

Birth Weight↗

PubMed2006

Hypothalamic-pituitary-adrenal axis activity in adults who were prenatally exposed to the Dutch famine.

OBJECTIVE: The hypothalamic-pituitary-adrenal (HPA) axis has been proposed to be susceptible to fetal programming, the process by which an adverse fetal environment elicits permanent physiological and metabolic alterations predisposing to disease in later life. It is hypothesized that fetal exposure to poor circumstances alters the set point of the HPA axis, leading to increased HPA axis activity and subsequent increased cortisol concentrations. In this study, we tested the hypothesis that prenatal exposure to famine during different periods of gestation is associated with increased activity of the HPA axis. DESIGN AND METHODS: We assessed plasma cortisol concentrations after a dexamethasone suppression and an ACTH1-24 -stimulation test in a group of 98 men and women randomly sampled from the Dutch famine birth cohort. Cohort members were born as term singletons around the 1944-1945 Dutch famine. RESULTS: Cortisol profiles after dexamethasone suppression and ACTH1-24 stimulation were similar for participants exposed to famine during late, mid- or early gestation (P = 0.78). Cortisol concentrations after dexamethasone suppression test did not differ between those exposed and those unexposed to famine in utero (mean difference -2% (95% confidence interval (CI) -27 to 23)). Neither peak cortisol concentration (20 nmol/l (95% CI -27 to 66)), cortisol increment (-5 nmol/l (95% CI -56 to 47)) or cortisol area under the curve post-ACTH1-24 injection (4% (95% CI -4 to 12)) differed between exposed and unexposed participants. CONCLUSIONS: Prenatal famine exposure does not seem to affect HPA axis activity at adult age, at least not at the adrenal level. This does not exclude altered HPA axis activity at the levels of the hippocampus and hypothalamus.

Adult↗

PubMed2006

Imprinted gene expression in the rat embryo-fetal axis is altered in response to periconceptional maternal low protein diet.

In our previous study, we have shown that maternal low protein diet (LPD, 9% casein vs 18% casein control) fed exclusively during the rat preimplantation period (0-4.25 day postcoitum) induced low birth weight, altered postnatal growth and hypertension in a gender-specific manner. In this study, we investigated the effect of maternal LPD restricted only to the preimplantation period (switched diet) or provided throughout gestation on fetal growth and imprinted gene expression in blastocyst and fetal stages of development. Male, but not female, blastocysts collected from LPD dams displayed a significant reduction (30%) in H19 mRNA level. A significant reduction in H19 (9.4%) and Igf2 (10.9%) mRNA was also observed in male, but not in female, fetal liver at day 20 postcoitum in response to maternal LPD restricted to the preimplantation period. No effect on the blastocyst expression of Igf2R was observed in relation to maternal diet. The reduction in H19 mRNA expression did not correlate with an observed alteration in DNA methylation at the H19 differentially methylated region in fetal liver. In contrast, maternal LPD throughout 20 days of gestation did not affect male or female H19 and Igf2 imprinted gene expression in fetal liver. Neither LPD nor switched diet treatments affected H19 and Igf2 imprinted gene expression in day 20 placenta. Our findings demonstrate that one contributor to the alteration in postnatal growth induced by periconceptional maternal LPD may derive from a gender-specific programming of imprinted gene expression originating within the preimplantation embryo itself.

Animals↗

PubMed2006

Impaired insulin secretion after prenatal exposure to the Dutch famine.

OBJECTIVE: We previously reported that people prenatally exposed to famine during the Dutch Hunger Winter of 1944-1945 have higher 2-h glucose concentrations after an oral glucose tolerance test in later life. We aimed to determine whether this association is mediated through alterations in insulin secretion, insulin sensitivity, or a combination of both. RESEARCH DESIGN AND METHODS: We performed a 15-sample intravenous glucose tolerance test in a subsample of 94 normoglycemic men and women from the Dutch Famine Birth Cohort. We used the disposition index, derived as the product of insulin sensitivity and the first-phase insulin response to glucose as a measure of the activity of the beta-cells adjusted for insulin resistance. In all analyses, we adjusted for sex and BMI. RESULTS: Glucose tolerance was impaired in people who had been prenatally exposed to famine compared with people unexposed to famine (difference in intravenous glucose tolerance test K(g) value -21% [95% CI -41 to -4]). People exposed to famine during midgestation had a significantly lower disposition index (-53% [-126 to -3]) compared with people unexposed to famine. Prenatal exposure to famine during early gestation was also associated with a lower disposition index, but this difference did not reach statistical significance. CONCLUSIONS: Impaired glucose tolerance after exposure to famine during mid-gestation and early gestation seems to be mediated through an insulin secretion defect.

Blood Glucose↗

PubMed2006

The effects of the Pro12Ala polymorphism of the peroxisome proliferator-activated receptor-gamma2 gene on glucose/insulin metabolism interact with prenatal exposure to famine.

OBJECTIVE: An adverse fetal environment may permanently modify the effects of specific genes on glucose tolerance, insulin secretion, and insulin sensitivity. In the present study, we assessed a possible interaction of the peroxisome proliferator-activated receptor (PPAR)-gamma2 Pro12Ala polymorphism with prenatal exposure to famine on glucose and insulin metabolism. RESEARCH DESIGN AND METHODS: We measured plasma glucose and insulin concentrations after an oral glucose tolerance test and determined the PPAR-gamma2 genotype among 675 term singletons born around the time of the 1944-1945 Dutch famine. RESULTS: A significant interaction effect between exposure to famine during midgestation and the PPAR-gamma2 Pro12Ala polymorphism was found on the prevalence of impaired glucose tolerance and type 2 diabetes. The Ala allele of the PPAR-gamma2 gene was associated with a higher prevalence of impaired glucose tolerance and type 2 diabetes but only in participants who had been prenatally exposed to famine during midgestation. Similar interactions were found for area under the curve for insulin and insulin increment ratio, which were lower for Ala carriers exposed to famine during midgestation. CONCLUSIONS: The effects of the PPAR-gamma2 Pro12Ala polymorphism on glucose and insulin metabolism may be modified by prenatal exposure to famine during midgestation. This is possibly due to a combined deficit in insulin secretion, as conferred by pancreatic beta-cell maldevelopment and carrier type of the Ala allele in the PPAR-gamma2 gene.

Aged↗

PubMed2005

The influence of mouse Ped gene expression on postnatal development.

The Ped (preimplantation embryo development) gene, whose product is Qa-2 protein, is correlated with a faster rate of preimplantation development (Ped fast phenotype) in mice that express Qa-2 protein compared with mice with an absence of Qa-2 protein (Ped slow phenotype). In the current study, we have used two congenic mouse strains differentially expressing the Ped gene, strain B6.K1 (Ped slow; Qa-2 negative) and strain B6.K2 (Ped fast; Qa-2 positive), to investigate the effects of Ped gene expression on postnatal growth profiles, systolic blood pressure and adult organ allometry. At birth, B6.K1 mice were moderately lighter than B6.K2 mice. B6.K1 mice became heavier during postnatal life (P < 0.05) and had elevated systolic blood pressure at 21 weeks of age when compared with B6.K2 mice (P = 0.006). B6.K1 mice also demonstrated elevated serum angiotensin-converting enzyme (ACE) activity, a known regulator of blood pressure (P = 0.037). Altered organ:body weight ratios were also observed, with the B6.K1 females having a higher ratio for lungs than B6. K2 females (P = 0.014). These data provide evidence of an association between the rate of preimplantation embryo development, postnatal growth and later cardiovascular function.

Animals↗

PubMed2005

Trajectories of growth among children who have coronary events as adults.

BACKGROUND: Low birth weight is a risk factor for coronary heart disease. It is uncertain how postnatal growth affects disease risk. METHODS: We studied 8760 people born in Helsinki from 1934 through 1944. Childhood growth had been recorded. A total of 357 men and 87 women had been admitted to the hospital with coronary heart disease or had died from the disease. Coronary risk factors were measured in a subset of 2003 people. RESULTS: The mean body size of children who had coronary events as adults was below average at birth. At two years of age the children were thin; subsequently, their body-mass index (BMI) increased relative to that of other children and had reached average values by 11 years of age. In simultaneous regressions, the hazard ratios associated with a 1 SD increase in BMI were 0.76 (95 percent confidence interval, 0.66 to 0.87; P<0.001) at 2 years and 1.14 (95 percent confidence interval, 1.00 to 1.31; P=0.05) at 11 years among the boys. The corresponding figures for the girls were 0.62 (95 percent confidence interval, 0.46 to 0.82; P=0.001) and 1.35 (95 percent confidence interval, 1.02 to 1.78; P=0.04). Low BMI at 2 years of age and increased BMI from 2 to 11 years of age were also associated with raised fasting insulin concentrations (P<0.001 for both). CONCLUSIONS: On average, adults who had a coronary event had been small at birth and thin at two years of age and thereafter put on weight rapidly. This pattern of growth during childhood was associated with insulin resistance in later life. The risk of coronary events was more strongly related to the tempo of childhood gain in BMI than to the BMI attained at any particular age.

Aged↗

PubMed2005

Size at birth as a predictor of mortality in adulthood: a follow-up of 350 000 person-years.

BACKGROUND: Small body size at birth, as a marker of an adverse intrauterine environment, has recently emerged as an important risk factor for death from cardiovascular disease. Our aim was to study the relationship between small size at birth and all-cause and non-cardiovascular mortality, which has been poorly documented. METHODS: We studied 13 830 individuals born between 1924 and 1944 in Helsinki, Finland, at term as singletons. Dates and primary causes of death between 1971 and 1998 were obtained from the Finnish National Death Register. RESULTS: 1668 men and 671 women died during the follow-up at the mean age of 56.0 (range 26.7-74.9) years. Lower birthweight was associated with increased all-cause mortality in females (Odds ratio (OR) for 1 kg decrease in birthweight 1.25, 95% CI 1.05-1.49; P = 0.01) but not in males (OR 1.08; 0.96-1.19; P = 0.2; P for sex-birthweight interaction = 0.09). Similarly, short length at birth was a predictor of all-cause mortality in females (OR for 1 cm decrease 1.10; 1.05-1.15; P < 0.0001) but not in males (OR 1.01; 0.98-1.02; P = 0.4; P for sex-length at birth interaction = 0.002). Low birthweight and short length at birth predicted premature death in adulthood (<55 years) in both sexes. In males, death from cardiovascular disease (n = 654) was associated with lower birthweight (OR for 1 kg decrease 1.33; 1.12-1.59; P = 0.001), and length (OR 1.05; 1.00-1.10; P = 0.03), and in females death from cardiovascular disease (n = 179) was associated with short length at birth (OR 1.11; 1.02-1.20; P = 0.02). In females death from non-cardiovascular diseases was predicted by low birthweight (OR 1.25; 1.01-1.54; P = 0.04) and short length at birth (OR 1.09; 1.03-1.15; P = 0.003) (n = 475), but not in males (n = 975; P for interaction = 0.02 and 0.004, respectively). Cancer-related death was associated with higher birthweight (OR for 1 kg decrease 0.76; 0.61-0.95; P = 0.02) and ponderal index (OR for 1 kg/m(3) increase 0.95; 0.91-0.99; P = 0.01) in males (n = 361) but not in females (n = 269). CONCLUSIONS: Small size at birth is associated with increased all-cause mortality at all ages among adult women but only with premature death in adult men. Among women death from both cardiovascular and non-cardiovascular causes is associated with small body size at birth. Among men an association between small birthsize and later cardiovascular disease is counterbalanced by an association between large body size at birth and later cancer.

Adult↗

PubMed2005

Adult mortality at age 57 after prenatal exposure to the Dutch famine.

Prenatal famine exposure has previously been shown to be associated with cardiovascular disease and type II diabetes in adulthood. In the current study, we could not demonstrate an effect of prenatal exposure to famine in 2254 term singletons born during the 1944-1945 Dutch famine on adult mortality up to the age of 57 years. Follow-up of this cohort will resolve whether famine exposure is linked to increased adult mortality.

Age Factors↗