Influence of environmental factors in early ontogenesis on aging and life span

A possible dependence of aging and life span in man on specific features of early ontogenesis has been analyzed on the basis of published and author's data. It was shown that the life span depended on climatic factors acting during prenatal and/or early postnatal period. When analyzing a sample of 101,634 humans died in Kiev in 1990-2000, a reliable relationship was established between the age of death and month of birth. The lowest and highest death ages were observed in persons born in April-June and in the end of the year, respectively. The lowest and highest average monthly values of death age differed in men and women by 2.6 and 2.3 years, respectively. In persons survived for more than 60 years, a "birthday" effect was demonstrated: dependence of the mortality level on the month of individual annual cycle was the highest in its first and last month. It has been proposed that this effect is related imprinting of the "birth stress" in the structure of biological rhythms, which may lead to periodic changes in viability during the individual annual cycle. The mechanisms underlying long-term effects of stresses in early ontogenesis have been studied on Drosophila melanogaster. X-irradiation of eggs at 0.50 and 0.75 Gy led to an increased level of survival of imago. The described radiation hormesis was accompanied by an increased resistance of DNA to S1-nuclease, which could be due to a long-term activation of the repair system in irradiated insects. The results obtained suggest that long-term changes in the range of gene expression induced by mild stresses in early ontogenesis can be a key mechanism of early "programming" of the potential of longevity and hormesis for life span.     

Premature Adult Death in Individuals Born Preterm: A Sibling Comparison in a Prospective Nationwide Follow-Up Study

BackgroundClose to one in ten individuals worldwide is born preterm, and it is important to understand patterns of long-term health and mortality in this group. This study assesses the relationship between gestational age at birth and early adult mortality both in a nationwide population and within sibships. The study adds to existing knowledge by addressing selected causes of death and by assessing the role of genetic and environmental factors shared by siblings.MethodsStudy population was all Norwegian men and women born from 1967 to 1997 followed using nation-wide registry linkage for mortality through 2011 when they were between 15 and 45 years of age. Analyses were performed within maternal sibships to reduce variation in unobserved genetic and environmental factors shared by siblings. Specific outcomes were all-cause mortality and mortality from cardiovascular diseases, cancer and external causes including accidents, suicides and drug abuse/overdoses.ResultsCompared with a sibling born in week 37–41, preterm siblings born before 34 weeks gestation had 50% increased mortality from all causes (adjusted Hazard Ratio (aHR) 1.54, 95% confidence interval (CI) 1.17, 2.03). The corresponding estimate for the entire population was 1.27 (95% CI 1.09, 1.47). The majority of deaths (65%) were from external causes and the corresponding risk estimates for these deaths were 1.52 (95% CI 1.08, 2.14) in the sibships and 1.20 (95% CI 1.01, 1.43) in the population.ConclusionPreterm birth before week 34 was associated with increased mortality between 15 and 45 years of age. The results suggest that increased premature adult mortality in this group is related to external causes of death and that the increased risks are unlikely to be explained by factors shared by siblings.     

Role of seasonal factors in pre-and postnatal ontogenesis in etiology of type 1 diabetes mellitus

Type 1 diabetes mellitus is a chronic disease characterized by autoimmune degradation of insulinproducing β-cells. Seasonality of birth of children with type 1 diabetes has been shown in a number of epidemiological studies. It could testify that autoimmune process began during fetal and postnatal development. No such studies were carried out in the former Soviet Union countries. The aim of the present study is to compare the seasonal birth month pattern in patients with type 1 diabetes (10780 men and 9337 women) born in 1960–2003 to that in the total population of Ukraine (14 995768 men and 14 109792 women) born during the same period. Significant differences were found between these two populations: χ ² = 103.97, p < 0.0001 and 135.17, p < 0.0001 in men and women, respectively. The results of cosinor analysis showed similar sinusoidal birth patterns of patients with type 1 diabetes in all subgroups, irrespective of the age of clinical disease manifestation: 0–9, 10–19, or 20–29 years. In all cases, the highest and lowest predispositions to type 1 diabetes were inherent in the people born in spring and autumn, respectively. In all groups, the highest incidence rate was in persons born in spring and early summer and the lowest ones, in those born in autumn and early winter. We propose that seasonality of birth of patients with type 1 diabetes in the two above populations could be due to long-term programming of glucose-insulin metabolism caused by the effect of certain seasonal factors during early ontogenesis.     

The relation of small head circumference and thinness at birth to death from cardiovascular disease in adult life.

OBJECTIVE--To determine how fetal growth is related to death from cardiovascular disease in adult life. DESIGN--A follow up study of men born during 1907-24 whose birth weights, head circumferences, and other body measurements were recorded at birth. SETTING--Sheffield, England. SUBJECTS--1586 Men born in the Jessop Hospital. MAIN OUTCOME MEASURE--Death from cardiovascular disease. RESULTS--Standardised mortality ratios for cardiovascular disease fell from 119 in men who weighed 5.5 pounds (2495 g) or less at birth to 74 in men who weighed more than 8.5 pounds (3856 g). The fall was significant for premature cardiovascular deaths up to 65 years of age (chi 2 = 5.0, p = 0.02). Standardised mortality ratios also fell with increasing head circumference (chi 2 = 4.6, p = 0.03) and increasing ponderal index (weight/length3) (chi 2 = 3.8, p = 0.05; for premature deaths chi 2 = 6.0, p = 0.01). They were not related to the duration of gestation. Among men for whom the ratio of placental weight to birth weight was in the highest fifths the standardised mortality ratio was 137. CONCLUSION--These findings show that reduced fetal growth is followed by increased mortality from cardiovascular disease. They suggest that reduction in growth begins early in gestation. They are further evidence that cardiovascular disease originates through programming of the body''s structure, physiology, and metabolism by the environment during fetal life. Maternal nutrition may have an important influence on programming.     

Causes of neonatal mortality in Spain (1975-98): influence of sex, rural-urban residence and age at death

Neonatal mortality during the first week of life, corresponding to the years 1975-1998, was studied in Spain. The first week of life is the time in which the highest number of deaths occur. The temporal decrease of the neonatal mortality rate (NMR) was modelled according to log10(NMR+1)= 2.784 - 0.023 per year. This decline cannot be explained by an increase in the mean birth weight (MBW=23440.835 - 10.107 g per year). From the most frequent of the causes of death to the least were: congenital anomalies, preterm born or low birth weight, respiratory problems, pregnancy difficulties, hypoxaemia/asphyxia, delivery difficulties and infectious diseases. This sequence changed when the specific age at death was considered. The NMR descended evenly for both sexes for the causes indicated above, except for preterm born or low birth weight, in which the male mortality decrease was greater since its rate was more elevated at the beginning of the period studied. For all the causes listed, NMR was more elevated both in urban areas and for males. Early neonatal mortality (first 24 hours) was higher for pregnancy difficulties, preterm born or low birth weight, congenital anomalies and hypoxaemia/asphyxia.     

Association of Gestational Age at Birth with Reasons for Subsequent Hospitalisation: 18 Years of Follow-Up in a Western Australian Population Study

Background

Preterm infants are at a higher risk of hospitalisation following discharge from the hospital after birth. The reasons for rehospitalisation and the association with gestational age are not well understood.

Methods

This was a retrospective birth cohort study of all live, singleton infants born in Western Australia between 1^st January 1980 and 31^st December 2010, followed to 18 years of age. Risks of rehospitalisation following birth discharge by principal diagnoses were compared for gestational age categories (<32, 32–33, 34–36, 37–38 weeks) and term births (39–41weeks). Causes of hospitalisations at various gestational age categories were identified using ICD-based discharge diagnostic codes.

Results

Risk of rehospitalisation was inversely correlated with gestational age. Growth-related concerns were the main causes for rehospitalisation in the neonatal period (<1 month of age) for all gestational ages. Infection was the most common reason for hospitalisation from 29 days to 1 year of age, and up to 5 years of age. Injury-related hospitalisations increased in prevalence from 5 years to 18 years of age. Risk of rehospitalisation was higher for all preterm infants for most causes.

Conclusions

The highest risks of rehospitalisation were for infection related causes for most GA categories. Compared with full term born infants, those born at shorter GA remain vulnerable to subsequent hospitalisation for a variety of causes up until 18 years of age.     

Month-of-birth effect on further body size in a pig model

Previous studies unanimously confirmed the existence of a dependence of human body size on the month of birth. The cause of the phenomenon has not been identified yet, although some possible causes were proposed e.g. seasonal changes of climatic and nutritional conditions. This study explored the issue in an animal model of 20,513 pigs. We found that body weights of 6-month-old pigs were the highest for subjects born in February, but for 2-month-old pigs the peak fell in May. Any statistical correlation between the month of birth and later body weight may be induced by (1) a long-term effect of the month of birth on further growth potential (LTE), or by (2) a short-term effect of seasonal factors differentiating the growth rate (STE), so we developed a mathematical method to separate the effects. The analysis proved that (1) the observed correlations resulted only from the STE, with May-June being the months of the highest growth tempo, and that (2) there was no significant LTE. The short-term effect was responsible for differences between patterns of weight for 2- and 6-month-old animals by the month of birth: since a pig monthly gain of weight increases with age, it is favorable for it to be born in February to attain the greatest weight at the age of 6 months, whereas 2-month-old piglets are heaviest when born a month or two before the May/June optimum for growth. The lack of a long-term effect of the month of birth on pigs’ weight supports the hypothesis of the cultural character of factor(s) responsible for the relationship between the month of birth and later body size in humans.     

Role of seasonal factors in pre- and postnatal ontogenesis for etiology of type 1 diabetes mellitus

Type 1 diabetes mellitus is a chronic disease characterized by autoimmune degradation of insulin-producing beta-cells. It was shown in a number of epidemiological studies of seasonality of birth in children with type 1 diabetes that the autoimmune process began during fetal and postnatal development. No such studies were carried out in the former Soviet Union countries. The aim of the present study is to compare the seasonal birth month pattern in patients with type 1 diabetes (10780 men and 9337 women) born in 1960-2002 to that in the total population of Ukraine (14 785601 men and 13 911370 women) born during the same period. Significant differences were found between these two populations: chi-squared = 103.97, p < 0.0001 and 135.17, p < 0.0001 in men and women, respectively. The results of cosinor analysis showed similar sinusoidal birth patterns of patients with type 1 diabetes in all sub-groups, irrespective of the age of clinical disease expression: 0-9, 10-19, or 20-29 years. In all cases, the highest and lowest predispositions to type 1 diabetes were inherent in the people born in spring and autumn, respectively. We propose that seasonal differences in the birth pattern in the two above populations could be due to long-term programming of glucose-insulin metabolism determined by the effect of certain seasonal factors during early ontogenesis.     

Early growth and death from cardiovascular disease in women.

OBJECTIVE--To determine whether the link suggested between growth in utero and during infancy and death from cardiovascular disease in men is also present in women. DESIGN--Follow up study of women and men whose birth weight and weight at 1 year of age had been recorded. SETTING--Hertfordshire, England. SUBJECTS--5585 women and 10,141 men born during 1911-30. MAIN OUTCOME MEASURES--Standardised mortality ratios for cardiovascular disease. RESULTS--Among women and men death rates from cardiovascular disease fell progressively between the low and high birth weights groups (chi 2 = 4.3, p = 0.04 for women, chi 2 = 8.5, p < 0.005 for men). Cardiovascular deaths in men but not women were also strongly related to weight at 1 year, falling progressively between the low and high weight groups (chi 2 = 27.5, p < 0.0001). The highest cardiovascular death rates in women were among those with below average birth weight but above average weight at 1 year. In men the highest rates were among those with below average birth weight and below average weight at 1 year. CONCLUSION--Relations between cardiovascular disease and birth weight are similar in men and women. In men cardiovascular disease is also related to weight gain in infancy.     

Starvation as cause of death in the Croatian Quarnero and hinterland between 1816 and 1825

Our aim is to investigate starvation as cause of death and social and demographic consequences in the Croatian Quarnero and its hinterland between 1816 and 1825, paying particular attention to the infamous "year of famine" 1817. Our sources were: registers of births, marriages, and deaths from 21 parishes kept at the Croatian State Archives in Rijeka and Zagreb. We collected and processed data for statistical analysis according to the date of baptism (birth), marriage, and death, and according to sex and age. Our focus was on recorded causes of death. Between 1816 and 1825, 15,701 children were baptised (born), and 11,021 people died. Starvation was recorded as cause of death in 255 cases, of which 198 were recorded in the infamous 1817. It was the only year with negative growth in virtually all parishes, with the birth-to-death ratio of 1147:1545. In 1817, the proportion of death by starvation to the total death rate was 12.8% for the entire area, with the highest share recorded in Veprinac (33.3%), Crikvenica (23.3%), and Kastav (15.8%). Death by starvation was more common in men than in women (56.7% vs. 43.3%, respectively). Age distribution was as follows; in the population below 20 years of age the death rate was 42 (16.5% of total deaths), but the most affected age group were infants and children aged 1-4 years (69.0%) whereas in adult population the death rate was 213 (83.5% of total deaths) and the most affected group were the elderly between 60 and 69 years (26.3%). Analysis shows lower birth and marriage rates between 1816 and 1818, followed by a steep rise and a plateau with minimal variation. This study shows that the Croatian Quarnero and its hinterland suffered a great famine in the early 19th century and 1817 in particular, which had left a deep mark on local demography, just like in the neighbouring parts of Croatia and Europe.     

Reproductive efficiency of captive Chinese- and Indian-origin rhesus macaque (Macaca mulatta) females

Reproductive and survival records (n=2,913) from 313 Chinese-origin and 365 Indian-derived rhesus macaques at the Tulane National Primate Research Center (TNPRC) spanning three generations were studied. Least-squares analysis of variance procedures were used to compare reproductive and infant survival traits while proportional hazards regression procedures were used to study female age at death, number of infants born per female, and time from last birth to death. Chinese females were older at first parturition than Indian females because they were older when placed with males, but the two subspecies had similar first postpartum birth interval (1st PPBI) and lifetime postpartum birth interval (LPPBI). Females that gave birth to stillborn infants had shorter first postpartum birth intervals (1st PPBI) than females giving birth to live infants. Postpartum birth intervals decreased in females from age 3 to 12 but then increased again with advancing age. Chinese infants had a greater survival rate than Indian infants at 30 days, 6 months, and 1 year of age. Five hundred and forty-three females (80.01%) had uncensored, or true records for age at death, number of infants born per female, and time from the birth until death whereas 135 females (19.91%) had censored records for these traits. Low- and high-uncensored observations for age at death were 3 and 26 years for Chinese, and 3 and 23 years for Indian females. Uncensored number of infants born per female ranged from 1 to 15 for Chinese females and 1 to 18 for Indian females. Each of these traits was significantly influenced by the origin×generation interaction in the proportional hazards regression analyses, indicating that probabilities associated with age at death, number of infants born per female, and time from last birth to death for Chinese and Indian females did not rank the same across generations.     

Gestational and Early Infancy Exposure to Margarine Fortified with Vitamin D through a National Danish Programme and the Risk of Type 1 Diabetes: The D-Tect Study

The objective of the study was to assess whether gestational and early infancy exposure to low dose vitamin D from a mandatory margarine fortification programme in Denmark influenced the risk of developing type 1 diabetes (T1D) before age of 15 years. The study population included all individuals born in Denmark from 1983 to 1988 and consisted of 331,623 individuals. The 1^st of June 1985, which was the date of issue of the new ministerial order cancelling mandatory fortification of margarine with vitamin D in Denmark, served as a reference point separating the studied population into various exposure groups. We further modelled birth cohort effects in children developing T1D as a linear spline, and compared the slopes between the birth cohorts with various prenatal and infancy exposures to vitamin D fortification. In total, 886 (0.26%) individuals developed T1D before the age of 15 years. The beta coefficients (95% CI), or slopes, for linear birth cohort effect in log Hazard Ratio (HR) per one month of birth in individuals born during the periods of gestational exposure, wash-out, and non-exposure were: 0.010 (-0.002/0.021), -0.010 (-0.035/0.018), and 0.008 (- 0.017/0.032), respectively. The beta coefficients (95% CI) for individuals born during the periods of first postnatal year exposure, wash-out, and non-exposure were: 0.007 (-0.016/0.030), 0.006 (-0.004/0.016), and 0.007 (-0.002/0.016), respectively. In conclusion, we found no evidence to support that exposure to low dose vitamin D from the Danish mandatory margarine fortification regimen during gestational and first postnatal year of life changed the risk of developing T1D before the age of 15 years.     

Effects of maternal birth season on birth seasonality in the Canadian population during the seventeenth and eighteenth centuries

Birth records of the French-Canadian population for the period 1621-1765 were analyzed retrospectively to examine the effect of maternal birth season on the seasonal distribution of births. Preliminary examination indicated that there was a bimodal pattern in birth seasonality: a major peak in early spring, a trough in early summer, a minor peak in autumn, and a trough around December. Because this seasonality was strongly biased at the level of the first birth by the month of marriage, which was concentrated in November, the seasonality of nonfirst births (n = 32,926) was examined in relation to the four seasons of maternal birth. Mothers born in May-July showed a flatter monthly distribution of nonfirst births at a maternal age of 28 years or more. Analysis of marriage-first birth intervals indicated that mothers who married in August-October showed a lower percentage of immediate conception (intervals of 8-10 months), whereas those mothers born in May-July had a higher percentage of immediate conception. This difference in birth seasonality shown by mothers born in May-July is similar to results from early twentieth-century Japan. Some seasonal infertility factors could have affected the embryos at the earliest stage of pregnancy, modifying a part of the seasonal variation in birth rate.     

Using birth defects registry data to evaluate infant and childhood mortality associated with birth defects: an alternative to traditional mortality assessment using underlying cause of death statistics

BACKGROUND: Although birth defects are a leading cause of death in infancy and early childhood, the proportion of all deaths to children with clinically diagnosed birth defects is not well documented. The study is intended to measure the proportion of all deaths to infants and children under age 10 occurring to children with birth defects and how and why this proportion differs from the proportion of deaths due to an underlying cause of congenital anomalies using standard mortality statistics. METHODS: A linked file of Michigan livebirths and deaths was combined with data from a comprehensive multisource birth defects registry of Michigan livebirths born during the years 1992 through 2000. The data were analyzed to determine the mortality rate for infants and children with birth defects and for children with no reported birth defect. Mortality risk ratios were calculated. The underlying causes of death for children with birth defects were also categorized and compared to cause- specific mortality rates for the general population. RESULTS: Congenital anomalies were the underlying cause of death for 17.8% of all infant deaths while infants with birth defects were 33.7% of all infant deaths in the study. Almost half of all Michigan deaths to children aged 1 to 2 were within the birth defects registry, though only 15.0% had an underlying cause of death of a congenital anomaly based upon standard mortality statistics. The mortality experience among children with birth defects was significantly higher than other children throughout the first 9 years of life, ranging from 4.6 for 5 year olds to 12.8 for children 1 to 2. Mortality risk ratios examined by cause of death for infants with birth defects were highest for other endocrine (28.1), other CNS (28.1), and heart (21.9) conditions. For children 1 through 9, the highest differential risk was seen for other perinatal conditions (39.0), other endocrine (29.7), other CNS (24.5), and heart (21.4). CONCLUSIONS: Childhood mortality analyses that incorporate birth defects registry data provide a more comprehensive picture of the full burden of birth defects on mortality in infant and children and can provide an effective mechanism for monitoring the survival and mortality risks of children with selected birth defects on a population basis.     

Season of birth affects short- and long-term survival

Recent research findings have highlighted the importance of early life conditions as risk factors for adult diseases and therefore determinants of subsequent survival. Given that individuals born during different seasons in seasonal environments experience different early-developmental conditions, an analysis of the effects of the season of birth on survival is considered an effective approach in clarifying the influence of early life conditions on survival in later life. In the present study, we analyzed the long-term effects of early developmental conditions in a historical population in which both nutritional levels and the burden of infectious diseases showed a seasonal variation. Using a semi-computerized linkage process, we were able to match birth and death data for 4,646 individuals born between 1634 and 1870 in the village of Es Mercadal (Minorca Island, Spain). To determine ecological differences associated with the season of birth, we first evaluated the association between season of birth and early life survival. This analysis helped us to determine seasonal variations in early life conditions such as infectious burden and nutritional levels. The season of birth had a significant effect on long-term survival in the birth cohort 1800-1870: summer births had a lower risk of death after age 15. We explain these results in terms of lower susceptibility to degenerative diseases in adult years due to superior in utero nutrition for summer births. These findings support the fetal origin hypothesis which states that the early life environment plays a key role in shaping the subsequent phenotype and risk of adult disease.     

Influence of Environmental Factors in Early Ontogenesis on Aging and Life Span

A possible dependence of aging and life span in humans on specific features of early ontogenesis has been analyzed on the basis of published data and results of the author. It was shown that the life span depended on climatic factors that acted during the prenatal and/or early postnatal period. Analysis of a sample of 101634 persons who died in Kiev between 1990 and 2000 showed a reliable relationship between the age of death and the month of birth. The lowest and highest death ages were observed for persons born from April to June and at the end of the year, respectively. The lowest and highest average monthly values of death age differed in men and in women by 2.6 and 2.3 years, respectively. In persons surviving for more than 60 years, a birthday effect was demonstrated: dependence of the mortality level on the month of the individual annual cycle was the highest in its first and last months. It has been proposed that this effect is related to imprinting of the birth stress in the structure of biological rhythms, which may lead to periodic changes in viability during the individual annual cycle. The mechanisms underlying long-term effects of stresses in early ontogenesis have been studied in Drosophila melanogaster. X-irradiation of eggs at 0.50 and 0.75 Gy led to an increased level of survival of the imago. The described radiation hormesis was accompanied by an increased resistance of DNA to S1-nuclease, which could be due to a long-term activation of the repair system in irradiated insects. The results obtained suggest that long-term changes in the pattern of gene expression induced by mild stresses in early ontogenesis can be a key mechanism of early programming of the potential for longevity and hormesis for the life span.     

Biodemography of exceptional longevity: early-life and mid-life predictors of human longevity

This study explores the effects of early-life and middle-life conditions on exceptional longevity using two matched case-control studies. The first study compares 198 validated centenarians born in the United States between 1890 and 1893 to their shorter-lived siblings. Family histories of centenarians were reconstructed and exceptional longevity validated using early U.S. censuses, the Social Security Administration Death Master File, state death indexes, online genealogies, and other supplementary data resources. Siblings born to young mothers (aged less than 25 years) had significantly higher chances of living to 100 compared to siblings born to older mothers (odds ratio = 2.03, 95% CI = 1.33-3.11, p = .001). Paternal age and birth order were not associated with exceptional longevity. The second study explores whether people living to 100 years and beyond differ in physical characteristics at a young age from their shorter-lived peers. A random representative sample of 240 men who were born in 1887 and survived to age 100 was selected from the U.S. Social Security Administration database and linked to U.S. World War I civil draft registration cards collected in 1917 when these men were 30 years old. These validated centenarians were then compared to randomly selected controls who were matched by calendar year of birth, race, and place of draft registration in 1917. Results showed a negative association between "stout" body build (being in the heaviest 15 percent of the population) and survival to age 100. Having the occupation of "farmer" and a large number of children (4 or more) at age 30 increased the chances of exceptional longevity. The results of both studies demonstrate that matched case-control design is a useful approach in exploring effects of early-life conditions and middle-life characteristics on exceptional longevity.     

Research on alpine isolates in Switzerland

This study explores the effects of early-life and middle-life conditions on exceptional longevity using two matched case-control studies. The first study compares 198 validated centenarians born in the United States between 1890 and 1893 to their shorter-lived siblings. Family histories of centenarians were reconstructed and exceptional longevity validated using early U.S. censuses, the Social Security Administration Death Master File, state death indexes, online genealogies, and other supplementary data resources. Siblings born to young mothers (aged less than 25 years) had significantly higher chances of living to 100 compared to siblings born to older mothers (odds ratio = 2.03, 95% CI = 1.33–3.11, p = .001). Paternal age and birth order were not associated with exceptional longevity. The second study explores whether people living to 100 years and beyond differ in physical characteristics at a young age from their shorter-lived peers. A random representative sample of 240 men who were born in 1887 and survived to age 100 was selected from the U.S. Social Security Administration database and linked to U.S. World War I civil draft registration cards collected in 1917 when these men were 30 years old. These validated centenarians were then compared to randomly selected controls who were matched by calendar year of birth, race, and place of draft registration in 1917. Results showed a negative association between “stout” body build (being in the heaviest 15 percent of the population) and survival to age 100. Having the occupation of “farmer” and a large number of children (4 or more) at age 30 increased the chances of exceptional longevity. The results of both studies demonstrate that matched case-control design is a useful approach in exploring effects of early-life conditions and middle-life characteristics on exceptional longevity.     

Relation of birth weight and childhood respiratory infection to adult lung function and death from chronic obstructive airways disease.

OBJECTIVE--To examine whether birth weight, infant weight, and childhood respiratory infection are associated with adult lung function and death from chronic obstructive airways disease. DESIGN--Follow up study of men born during 1911-30 whose birth weights, weights at 1 year, and childhood illnesses were recorded at the time by health visitors. SETTING--Hertfordshire, England. SUBJECTS--5718 men born in the county during 1911-30 and a subgroup of 825 men born in the county during 1920-30 and still living there. MAIN OUTCOME MEASURES--Death from chronic obstructive airways disease, mean forced expiratory volume in one second (FEV1) and forced vital capacity (FVC), and respiratory symptoms. RESULTS--55 men died of chronic obstructive airways disease. Death rates fell with increasing birth weight and weight at 1 year. Mean FEV1 at age 59 to 70 years, adjusted for height and age, rose by 0.06 litre (95% confidence interval 0.02 to 0.09) with each pound (450 g) increase in birth weight, independently of smoking habit and social class. Bronchitis or pneumonia in infancy was associated with a 0.17 litre (0.02 to 0.32) reduction in adult FEV1 and with an increased odds ratio of wheezing and persistent sputum production in adult life independently of birth weight, smoking habit, and social class. Whooping cough in infancy was associated with a 0.22 litre (0.02 to 0.42) reduction in adult FEV1. CONCLUSIONS--Lower birth weight was associated with worse adult lung function. Intrauterine influences which retard fetal weight gain may irrecoverably constrain the growth of the airways. Bronchitis, pneumonia, or whooping cough in infancy further reduced adult lung function. They also retarded infant weight gain. Consistent with this, death from chronic obstructive airways disease in adult life was associated with lower birth weight and weight at 1 year. Promoting lung growth in fetuses and infants and reducing the incidence of lower respiratory tract infection in infancy may reduce the incidence of chronic obstructive airways disease in the next generation.     

Long-Term Survival of Individuals Born Small and Large for Gestational Age

Background

Little is known on long-term survival and causes of death among individuals born small or large for gestational age. This study investigates birth weight in relation to survival and causes of death over time.

Methods

A national cohort of 1.7 million live-born singletons in Denmark was followed during 1979–2011, using the Danish Civil Registration System, the Medical Birth Registry and the Cause of Death Registry. Cox proportional hazards were estimated for the impact of small (SGA) and large (LGA) gestation weight and mortality overall, by age group and birth cohort.

Results

Compared to normal weight children, SGA children were associated with increased risk of dying over time. Though most of the deaths occurred during the first year of life, the cumulative mortality risk was increased until 30 years of age. The hazard ratios [HR] for dying among SGA children ages <2 years were: 3.47 (95% CI, 3.30–3.64) and 1.06 (95% CI, 0.60–1.87) in 30 years and older. HR for dying among SGA adults (20–29 years) were: 1.20 (95% CI, 0.99–1.46) in years 1979–1982 and 1.61 (95% CI, 1.04–2.51) in years 1989–1994. The SGA born had increased risk of dying from infection, heart disease, respiratory disease, digestive disease, congenital malformation, perinatal conditions, and accidents, suicide, and homicide. Individuals born LGA were associated with decreased mortality risk, but with increased risk of dying from malignant neoplasm.

Conclusions

Survival has improved independently of birth weight the past 30 years. However, children born SGA remain at significantly increased risk of dying up till they turn 30 years of age. Individuals born LGA have lower mortality risk but only in the first two years of life.