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Low birthweight, thinness and short body length at birth are now known to be associated with increased rates of cardiovascular disease and non-insulin dependent diabetes in adult life. The fetal origins hypothesis proposes that these diseases originate through adaptations which the fetus makes when it is undernourished. These adaptations may be cardiovascular, metabolic or endocrine. They permanently change the structure and function of the body. Prevention of the diseases may depend on prevention of imbalances in fetal growth or imbalances between prenatal and postnatal growth, or imbalances in nutrient supply to the fetus.

Background.Late preterm births constitute the majority of preterm births. However, most evidence suggesting that preterm birth predicts the risk of mental disorders comes from studies on earlier preterm births. We examined if late preterm birth predicts the risks of severe mental disorders from early to late adulthood. We also studied whether adulthood mental disorders are associated with post-term birth or with being born small (SGA) or large (LGA) for gestational age, which have been previously associated with psychopathology risk in younger ages.Method.Of 12 597 Helsinki Birth Cohort Study participants, born 1934–1944, 664 were born late preterm, 1221 post-term, 287 SGA, and 301 LGA. The diagnoses of mental disorders were identified from national hospital discharge and cause of death registers from 1969 to 2010. In total, 1660 (13.2%) participants had severe mental disorders.Results.Individuals born late preterm did not differ from term-born individuals in their risk of any severe mental disorder. However, men born late preterm had a significantly increased risk of suicide. Post-term birth predicted significantly increased risks of any mental disorder in general and particularly of substance use and anxiety disorders. Individuals born SGA had significantly increased risks of any mental and substance use disorders. Women born LGA had an increased risk of psychotic disorders.Conclusions.Although men born late preterm had an increased suicide risk, late preterm birth did not exert widespread effects on adult psychopathology. In contrast, the risks of severe mental disorders across adulthood were increased among individuals born SGA and individuals born post-term.

There may be regional specialisation in structure and function across the placental surface. In Riyadh, Saudi Arabia, the length and the breadth of the placental surface at birth were highly correlated, but the breadth was more closely associated with the size of the baby. To replicate this we studied 321 pregnant Saudi women in the town of Baish. We measured the size of the newborn babies and their placentas. The association of the length and breadth of the placental surface on the baby's body size differed in boys and girls. Among boys the breadth had a stronger association with all birth measurements except crown-heel length. This was similar to the findings in Riyadh. Placental surface length was related to crown-heel length. For each centimetre in surface length, crown-heel length increased by 0.27 cm (95% CI 0.09-0.44, p = 0.004). Among girls placental surface breadth was related to crown-heel length, whereas surface length was related to birth weight, head and thigh circumferences. For each centimetre in surface breadth, crown-heel length increased by 0.33 cm (0.13-0.53, p = 0.001). We conclude that, within Saudi Arabia, there are both geographical and sex differences in regional specialisation across the placental surface. In the adverse circumstances of Baish, linked to the mothers' short stature, boys were smaller at birth than girls. Boys may have compensated for under-nutrition by increasing the depth of spiral artery invasion rather than by recruiting additional spiral arteries. Girls may have had more effective regional specialisation across the placental surface.

Objectives Programming is the phenomenon whereby the body's structures and functions are permanently set by nutrition and other influences during early development. There is increasing evidence that programming in utero initiates cardiovascular disease. We hypothesized that susceptibility to developing chronic rheumatic heart disease on exposure to Streptococcus pyogenes is programmed. Methods We studied hospital admissions and deaths from chronic rheumatic heart disease in 20,431 people born in Helsinki, Finland, during 1924–1944. One hundred and one people, 56 men, and 45 women, had chronic rheumatic heart disease. Results The disease was not associated with body or placental size at birth. It was, however, associated with a long umbilical cord so that the hazard ratio for the disease was 1.23 (95% CI 1.04–1.45, P?=?0.02) for every 10 cm increase in cord length. This association was present in people with mitral valve disease, hazard ratio 1.5 (1.20–1.89, P? Conclusion Longer umbilical cords have more spirals and a greater density of spirals per unit of length. Increased spiraling will increase the resistance to flow and the pressure load on the fetal heart. This could affect the development of the heart's valves and make them more vulnerable to the autoimmune process initiated by Streptococcus pyogenes. The mitral valve may be more vulnerable than the aortic valve because the valve leaflets are larger and therefore have greater wall stress.

Prenatal and childhood growth influence the risk of developing the metabolic syndrome and type 2 diabetes. Both conditions are associated with non-alcoholic fatty liver disease (NAFLD). Our aim was to explore the associations between early growth and adult NAFLD.We studied 1587 individuals from the Helsinki Birth Cohort Study (HBCS) born 1934-44 for whom birth, childhood, and adult clinical data were available. NAFLD was defined using the NAFLD liver fat score and equation. The score was converted into a dichotomous variable, with outcomes defined as either a positive or negative score. The equation predicts liver fat percentage.A positive score was found in 43% of men and 22.5% of women. Several measurements of birth and childhood body size were negatively associated with both NAFLD outcomes after adjustment for adult BMI. Those from the smallest BMI tertile at age 2 who were obese in adulthood had an OR of 18.5 for a positive score compared to those from the same group who were normal weight in adulthood.A larger childhood body size was negatively associated with NAFLD outcomes. Individuals who are small during early childhood and obese as adults seem to be at the highest risk of developing NAFLD.

OBJECTIVES: Studies of the placenta in pregnancies complicated by pre-eclampsia have led to the suggestion that tissue along the length and breadth of its surface has different functions. A recent study in Saudi Arabia showed that the body size of newborn babies was related to the breadth of the surface at birth but not to its length. We have now examined whether the association between placental breadth and body size reflects large size of the baby from an early stage of gestation or rapid growth between early and late gestation. METHODS: We studied 230 women who gave birth to singleton babies in King Khalid Hospital, Riyadh, Saudi Arabia. In total, 176 had ultrasound measurements both before 28 weeks and at 28 weeks or later, which we define as early and late gestation. We used these to calculate growth velocities between early and late gestation, which we expressed as the change in standard deviation scores over a 10-week period. RESULTS: The breadth of the placental surface was correlated with fetal growth velocity. The correlation coefficients were 0.24 (P?=?0.002) for the head circumference, 0.24 (P?=?0.001) for the biparietal diameter and 0.34 (P? CONCLUSIONS: Tissue along the breadth of the placental surface may be more important than tissue along the length in the transfer of nutrients from mother to baby. This may be part of a wider phenomenon of regional differences in function across the placental surface.

How did the study come about? Ecological studies conducted in the 1980s demonstrated a close geographic correlation between death rates from coronary heart disease during the years 1968–78 in different parts of England and Wales and the infant mortality rate in these areas 60 years earlier.1 These studies suggested that adverse environmental influences acting in utero and during infancy might increase the risk of cardiovascular disease in later life. However, this hypothesis required investigation using more robust epidemiological techniques. To yield results within a relatively short space of time, a cohort study was needed which linked information about the early environment of individuals born at least 60 years earlier to their health outcomes in later life. As part of a nationwide search of archives, staff working at the MRC Environmental Epidemiology Unit (MRC EEU), University of Southampton, discovered a large set of records maintained in Hertfordshire during the early 20th century.

Maternal thinness leads to metabolic challenges in the offspring, but it is unclear whether reduced maternal fat mass or muscle mass drives these metabolic changes. Recently, it has been shown that low maternal muscle mass--as measured by arm muscle area (AMA)--is associated with depressed nutrient transport to the fetus. To determine the role of maternal muscle mass on placental function, we analyzed the gene expression profiles of 30 human placentas over the range of AMA (25.2-90.8 cm(2)) from uncomplicated term pregnancies from the Southampton Women's Survey cohort. Eighteen percent of the ∼60 genes that were highly expressed in less muscular women were related to immune system processes and the interferon-γ (IFNG) signaling pathway in particular. Those transcripts related to the IFNG pathway included IRF1, IFI27, IFI30, and GBP6. Placentas from women with low muscularity are, perhaps, more sensitive to the effects of inflammatory cytokines than those from more muscular women.

Within the Helsinki Birth Cohort, men who were tall when they were 7 years old lived for 5 years longer than men who were short. In the present analyses we examined two other influences known to be associated with lifespan: having children and educational attainment. We hypothesized that tall stature, the ability to have children, and high educational attainment reflect three aspects of biological fitness that are acquired during development.We examined all-cause mortality in 6975 men and 6370 women born in Helsinki during 1934-1944, whose childhood growth, number of children, and educational attainment were recorded.In contrast to men, tall stature in childhood was not associated with longer lifespan among women. Men and women who had children lived for longer than those who had no children. Among women, having children was only associated with increased lifespan among those whose body mass index increased between 2 and 11 years. High educational attainment was associated with longer lifespan in both sexes. The trends of lower all-cause mortality with higher educational attainment were present in each socio-economic group. The men and women who had children, and attained upper tertiary education, lived for 16 years longer than those who had no children and only basic education.We suggest that the associations between having children, educational attainment, and lifespan reflect two different aspects of biological fitness that are acquired during early development.

Context: Memorial to Jim Tanner. Objective: To examine the links between early growth and chronic disease in later life. Methods: Literature review. Results: There is now a developmental model for the origins of chronic disease in which the causes to be identified are linked to normal variations in feto-placental, infant and childhood growth and development. These variations lead to variations in the supply of nutrients to the baby that permanently alters gene expression, a process known as ‘programming’. Conclusions: Variations in the processes of development programme the function of a few key systems that are linked to chronic disease—the immune system, anti-oxidant defences, inflammatory responses, the number and quality of stem cells, neuro-endocrine settings and the balance of the autonomic nervous system. There is not a separate cause for each different disease. Which chronic disease originates during development may depend more on timing than on qualitative differences in exposures to external inf...

Studies of pregnancies complicated by preeclampsia led to the suggestion that the surface of the placenta is aligned along two axes, measured by its breadth and length. It was hypothesised that tissue along the breadth serves as a nutrient sensor, responding to the mother's nutritional state and fetal nutritional demands, while tissue along the length has different functions. To develop this hypothesis we measured the breadth and length of the placental surface in 401 neonates born in the King Khalid Hospital, Riyadh, Saudi Arabia, and related these measurements to the baby's body size. The breadth and length of the placental surface were highly correlated (coefficient = 0.7). Nevertheless, in a simultaneous regression with both measurements, only the breadth was associated with neonatal body size. There were strong trends of increasing birth weight, ponderal index, and the circumferences of the head, chest, abdomen and thigh with increasing placental breadth. In contrast no measurement of baby's body size was related to placental length. Birth weight increased by 125 g per cm increase in placental breadth (95% confidence interval 88 to 162, p0.001) but only by 20 g per cm increase in placental length (-13 to 53, p = 0.2). The corresponding figures for head circumference were 0.28 cm (0.17-0.39, p0.001) and 0.03 (-0.07 to 0.14, p = 0.5). The associations between placental breadth and neonatal body size were strongest if the mother's height was below the median (157 cm). The associations between a larger breadth of the placental surface and a larger baby are consistent with the hypothesis that tissue along the breadth plays a key role in nutrient transfer from mother to baby. Mothers who are short in stature are known to have lower rates of protein turnover in pregnancy. In these circumstances the ability of the placenta to transfer amino acids to the fetus may be critical.

A number of studies suggest that breast-feeding has beneficial effects on an individual's cardiovascular risk factors in adulthood, although the mechanisms involved are unknown. One possible explanation is that adults who were breastfed differ in their health behaviours. In a historical cohort, adult health behaviours were examined in relation to type of milk feeding in infancy. From 1931 to 1939, records were kept on all infants born in Hertfordshire, UK. Their type of milk feeding was summarised as breastfed only, breast and bottle-fed, or bottle-fed only. Information about adult health behaviours was collected from 3217 of these men and women when they were aged 59–73 years. Diet was assessed using an administered FFQ; the key dietary pattern was a ‘prudent’ pattern that described compliance with ‘healthy’ eating recommendations. Of the study population, 60 % of the men and women were breastfed, 31 % were breast and bottle-fed, and 9 % were bottle-fed. Type of milk feeding did not differ according to social class at birth, and was not related to social class attained in adult life. There were no differences in smoking status, alcohol intake or reported physical activity according to type of milk feeding, but there were differences in the participants' dietary patterns. In a multivariate model that included sex and infant weight gain, there were independent associations between type of feeding and prudent diet scores in adult life (P= 0·009), such that higher scores were associated with having been breastfed. These data support experimental findings which suggest that early dietary exposures can have lifelong influences on food choice.

Objectives: Lower birth weight within the normal range predicts adult chronic diseases, but the same birth weight in different ethnic groups may reflect different patterns of tissue development. Neonatal body composition was investigated among non-Hispanic Caucasians and African Americans, taking advantage of variability in gestational duration to understand growth during late gestation. Methods: Air displacement plethysmography assessed fat and lean body mass among 220 non-Hispanic Caucasian and 93 non-Hispanic African American neonates. The two ethnic groups were compared using linear regression. Results: At 36 weeks of gestation, the average lean mass of Caucasian neonates was 2,515 g vs. that of 2,319 g of African American neonates (difference, P = 0.02). The corresponding figures for fat mass were 231 and 278 g, respectively (difference, P = 0.24). At 41 weeks, the Caucasians were 319 g heavier in lean body mass (P < 0.001) but were also 123 g heavier in fat mass (P = 0.001). The slopes for lean mass vs. gestational week were similar, but the slope of fat mass was 5.8 times greater (P = 0.009) for Caucasian (41.0 g/week) than for African American neonates (7.0 g/week). Conclusions: By 36 weeks of gestation, the African American fetus developed similar fat mass and less lean mass compared with the Caucasian fetus. Thereafter, changes in lean mass among the African American fetus with increasing gestational age at birth were similar to the Caucasian fetus, but fat accumulated more slowly. We hypothesize that different ethnic fetal growth strategies involving body composition may contribute to ethnic health disparities in later life. Am. J. Hum. Biol. 2012. © 2012 Wiley Periodicals, Inc.

Hypertensive disorders may affect the fetal developmental milieu and thus hint at mechanisms by which prenatal adversity associates with mental disorders in later life. We examined if hypertension without proteinuria and preeclampsia in pregnancy predict serious mental disorders in the offspring, and if sex, childhood socioeconomic status, length of gestation and parity modify these associations.We included 5970 women and men born after a normotensive, hypertensive or preeclamptic pregnancy defined by using mother's blood pressure and urinary protein measurements at maternity clinics and birth hospitals. Mental disorders requiring hospitalization or contributing to death were identified from the Finnish Hospital Discharge and Causes of Death Registers between years 1969 and 2004.In comparison to the offspring born after normotensive pregnancies, offspring born after pregnancies complicated by hypertension without proteinuria were at 1.19-fold (CI: 1.01-1.41, P-value = 0.04) higher risk of any mental disorder and 1.44- (CI: 1.11-1.88, P-value0.01) and 1.39-fold (CI: 0.99-1.93, P-value = 0.05) higher risk of mood and anxiety disorder, respectively. In contrast, preeclampsia was associated, with a lower risk of any mental disorder in the male offspring (P-value = 0.02; P-value = 0.04 for interaction 'sex × normotension/preeclampsia').Hypertension without proteinuria in pregnancy was associated with a higher risk of serious mental disorders in the offspring in adulthood. Preeclampsia seems to, in turn, associate with lower risk of severe mental disorders in male offspring.

Coronary heart disease, type 2 diabetes, breast cancer and many other chronic diseases are unnecessary. Their occurrence is not mandated by genes passed down to us through thousands of years of evolution. Chronic diseases are not the inevitable lot of humankind. They are the result of the changing pattern of human development. We could readily prevent them, had we the will to do so. Prevention of chronic disease, and an increase in healthy ageing require improvement in the nutrition of girls and young women. Many babies in the womb in the Western world today are receiving unbalanced and inadequate diets. Many babies in the developing world are malnourished because their mothers are chronically malnourished. Protecting the nutrition and health of girls and young women should be the cornerstone of public health. Not only will this prevent chronic disease, but it will produce new generations who have better health and well-being through their lives.

Severe stress experienced in early life may have long-term consequences on adult physiological functions. We studied the long-term effects of separation on blood pressure levels in non-obese subjects who were separated temporarily in childhood from their parents during World War II (WWII). The original clinical study cohort consists of people born during 1934-1944 in Helsinki, Finland. This substudy includes 1361 non-obese subjects (body mass index

Objectives: Among women attending antenatal clinics during 1934–1944 a large intercristal diameter, the maximum distance between the pelvic iliac crests, was associated with a raised incidence of breast and ovarian cancer in the daughters in later life. At puberty, the intercristal diameter of girls enlarges rapidly under the influence of estrogen. We speculated that high maternal estrogen concentrations during pregnancy initiate hormonal cancers in their daughters. Here, we examine the association between the mothers' intercristal diameters and prostate cancer in their sons. Methods: Using the national cancer registry we identified 221 cases of prostate cancer among 6,975 men born during 1934–1944 in Helsinki, Finland. Four thousand four hundred and one of these men had their mother's bony pelvic measurements recorded: there were 149 cases among them. Results: Hazard ratios for prostate cancer rose as the mother's intercristal diameter increased; but this association was restricted to men who were born before 40 weeks of gestation. Among these men the hazard ratio was 1.27 (95% CI 1.09–1.48; P = 0.002). The hazard ratio was 2.2 (1.3–3.7; P < 0.001) in men whose mothers weighed more than 80 kg in late pregnancy compared with those whose mothers weighed 60 kg or less. Conclusions: These findings are consistent with a conceptual framework for the origins of hormonally dependent cancers that invokes exposure of embryonic tissue to maternal sex hormones followed by resetting of the fetal hypothalamic-gonadotropin axis in late gestation. We hypothesize that compensatory prepubertal growth among girls is associated with hormonal cancers in the next generation. Am. J. Hum. Biol. © 2012Wiley Periodicals, Inc.

UNLABELLED: Growth in early life may predict adult bone health. Our data showed that greater height and body mass index (BMI) gain in utero and infancy are associated with higher peak bone mass, and greater BMI gain in childhood/adolescence with higher peak bone density. These associations are mediated by attained adult height and BMI. INTRODUCTION: To study the relationship of height and BMI during childhood with adult bone mineral content (BMC), areal density (aBMD) and apparent density (BMAD, estimated volumetric density). METHODS: Participants comprised 565 men and women aged 33-39 years from the New Delhi Birth Cohort, India, whose weight and height were recorded at birth and annually during infancy (0-2 years), childhood (2-11 years) and adolescence (11 years-adult). Lumbar spine, femoral neck and forearm BMC and aBMD were measured using dual X-ray absorptiometry; lumbar spine and femoral neck BMAD were calculated. RESULTS: Birth length, and height and height gain during infancy, childhood and adolescence were positively correlated with adult BMC (p≤0.01 all sites except birth length with femoral neck). Correlations increased with height from birth to 6 years, then remained constant for later height measurements. There were no associations with BMAD. BMI at birth, and during childhood and adolescence was also positively correlated with BMC (p

BackgroundStudies have shown that the shape and size of the placenta at birth predict blood pressure in later life. The influences that determine placental morphology are largely unknown. We have examined the role of mother’s body size. MethodsWe studied 522 neonates who were born in a maternity hospital in Mysore, South India. The weight of the placenta and the length and breadth of its surface, were measured after delivery.ResultsHigher maternal fat mass predicted a larger placental surface (p=0.02), while larger maternal head circumference predicted a more oval placental surface (p=0.03). Higher maternal fat mass and larger maternal head circumference were associated with greater placental efficiency, indicated by lower ratios of the length (p=0.0003 and p=0.0001 respectively) and breadth (p=0.0002 and pConclusionsHigher maternal fat mass, reflecting the mother’s current nutritional state, and larger maternal head circumference, reflecting the mother’s fetal/infant growth, are associated with changes in the shape and size of the placental surface and greater placental efficiency. We suggest that these associations reflect effects of the mother’s nutrition at different stages of her lifecourse on the development of the placenta and on materno-placento-fetal transfer of nutrients.

Tall men generally lead longer lives than short men. Within the Helsinki Birth Cohort, however, there is a group of boys among whom being tall when they entered school was associated with reduced lifespan. These boys had birthweights and maternal heights above the median for the cohort; but they tended to be lighter at birth than their mother's body mass index (weight/height(2)) in pregnancy predicted. We suggested that, while they had grown rapidly in utero, their growth had faltered at some point; and their tallness at age seven was the result of a resumption during infancy of their rapid growth trajectory. We here examine the size and shape of their placentas at birth to gain further insight into their path of fetal growth.We examined all cause mortality in the 1217 men who had birthweights and maternal heights above the median for the cohort. Their birth measurements included placental weight and the length and breadth of the placental surface.Shorter length of the placental surface was associated with increased mortality (p = 0.002). There was no similar trend with the breadth. Mortality rose as the difference between the length and breadth decreased, that is as the surface became rounder. The hazard ratio was 1.10 (1.03-1.18, p = 0.007) for every cm decrease in the difference. Among men with a round placental surface (length-breadth difference 2 cm or less) increased mortality was associated with lower birthweight (p = 0.03 or 0.005 allowing for mother's body mass index) and shorter gestation, but not with lower head circumference or length.Reduced lifespan among men is associated with a particular path of early growth. After rapid growth in early gestation, associated with tall maternal stature, soft tissue growth falters in mid-gestation. Rapid growth resumes in late gestation and continues through infancy.

We examined the effects of early life stress (ELS) on intellectual ability in 2,725 20-year-old male participants, of whom 321 were separated temporarily (mean 1.7 years) from both their parents during World War II, at an average age of 4.3 years. Intellectual ability was tested when entering compulsory military service. The separated men had − 0.28 (95% CI − 0.39, − 0.16), − 0.13 (95% CI − 0.25, − 0.01), − 0.18 (95% CI − 0.29, − 0.06), and − 0.19 (95% CI − 0.30, − 0.07) SD units lower verbal, visuospatial, arithmetic, and composite score of intellectual ability, respectively, compared to non-separated. Participants who were separated for more than a year and between two and four years had the lowest ability scores. ELS showed most consistent associations with verbal ability, but were not limited to it. Children beyond infancy and before their school-age may be the most vulnerable to the adverse effects of the ELS.

Aims People whose birthweights were towards the lower end of the normal range are at increased risk of coronary heart disease. This is attributed to foetal programming through malnutrition, but the cause of the malnutrition is unknown. Methods and results We studied 6975 men born in Helsinki during 1934–44. Their size at birth was recorded. Babies who later developed coronary heart disease tended to have a low ponderal index (birthweight/length3). Three different placental phenotypes predicted the disease. In primiparous mothers who were short, having below median height, the hazard ratio for the disease was 1.14 (95% confidence interval 1.08–1.21, P < 0.0001) for each centimetre increase in the difference between the length and breadth of the placental surface. In tall mothers whose body mass index was above the median, the hazard ratio was 1.25 (1.10–1.42, P = 0.0007) per 40 cm2 decrease in the surface area. In tall mothers whose body mass index was below the median, the hazard ratio was 1.07 (1.02–1.13, P = 0.01) per 1% increase in the placental weight/birthweight ratio. Conclusions Three different combinations of maternal and placental size predicted coronary heart disease. The mother's body size determines the availability of nutrients and is linked to the development and function of the placenta, reflected in its shape and size. We speculate that variations in three processes of normal placental development lead to foetal malnutrition. The processes are (i) implantation and spiral artery invasion, (ii) growth of the chorionic surface, and (iii) compensatory expansion of the chorionic surface.

In Europe, boys and girls have different body proportions at birth. We examined newborn babies in Saudi Arabia to determine the sex differences and whether fetal growth differed if the mother was in utero during Ramadan.We examined body size at birth among 967 babies (479 boys and 488 girls) born in Unizah, a small city in Saudi Arabia.Large head circumference was the strongest single predictor of male sex. In a simultaneous regression, female sex was predicted by small head circumference (P0.001), low birth weight (P = 0.002), and large chest circumference (P = 0.008). The mothers of boys were heavier in pregnancy than the mothers of girls and had a higher body mass index, 31.7 kg/m(2) compared to 30.2 (P0.001). The mothers of girls, however, were taller than the mothers of boys, 158.6 cm compared to 157.4 (P = 0.001). Compared to babies whose mothers were not in utero during Ramadan boys whose mothers were in mid gestation during Ramadan were 1.2 cm longer (P = 0.005) while girls had a 0.4 week shorter gestation period (P = 0.04).Our findings are consistent with other evidence that boys are more ready than girls to trade off visceral development in utero to protect somatic and brain growth. They also support the hypothesis that boys are more responsive to their mother's current diet than girls, who respond more to their mother's life time nutrition and metabolism. They provide the first evidence that changes in the life style of pregnant women during Ramadan affect more than one generation.

Ramadan is an annual period of day-time fasting during which people in Saudi Arabia, including pregnant women, change their diets and physical activity. We recently reported that among babies who were in the second or third trimester of gestation during Ramadan placental growth slowed. We also found that, over the four years of the study, placental weight increased by 29 g per year. We have now extended our data collection in order to examine this trend in more detail.We studied the birth records of 17 660 singletons born in King Saud Hospital, Unizah, Saudi Arabia, over a ten year period. The records included birth weight, placental weight and gestational age.During the first six years of the study period mean placental weight rose by more than 100 g while mean birth weight was unchanged. This secular increase in placental weight was accompanied by a change in the placenta's response to Ramadan. During the first half of the study period babies who were in their second or third trimester of gestation during Ramadan had reduced placental weight (475 g and 476 g compared with 484 g, p 0.001 for both). During the second half of the study period babies who were in their first trimester of gestation during Ramadan had reduced placental weight (533 g compared with 539 g, p = 0.03).We suggest that the secular increase in placental weight reflects changes in maternal body composition. These have altered placental responses to the dietary changes during Ramadan. The biological processes underlying these responses are not known.

Background: Epidemiologic evidence suggests that prenatal growth influences adult blood pressure. Nutritional factors also influence blood pressure, among them salt intake. However, it is unknown whether prenatal growth modifies the association between salt intake and blood pressure in later life. Objective: Our aim was to examine whether the relation between salt intake and adult blood pressure is modified by birth weight. Design: We studied 1512 participants of the Helsinki Birth Cohort Study who were born between 1934 and 1944. Information on birth weight was abstracted from birth records, and preterm births were excluded. During a clinical study, at the mean age of 62 y, blood pressure, weight, and height were measured. Diet was assessed with a validated food-frequency questionnaire. The relation between salt intake and blood pressure was tested by a piecewise multivariate regression analysis with the best fitting breakpoints to birth weight and salt intake. Results: An inverse association was observed between birth weight and systolic blood pressure (SBP) (P = 0.02). No significant association between salt intake and SBP was observed in the whole study population. Of those whose birth weight was ?3050 g, a 1-g higher daily salt intake was associated with a 2.48-mm Hg (95% CI: 0.40, 4.52 mm Hg) higher SBP (P = 0.017) until the saturation point of 10 g. Of those whose birth weight exceeded 3050 g, SBP was not significantly associated with salt intake. For diastolic blood pressure, no significant relations were observed. Conclusion: Adult individuals with low birth weight may be particularly sensitive to the blood pressure–raising effect of salt.

Aim: To determine whether the size and shape of the placental surface predict blood pressure in childhood. Methods: We studied blood pressure in 471 nine-year-old Indian children whose placental length, breadth and weight were measured in a prospective birth cohort study. Results: In the daughters of short mothers (

Background: Placental growth responds to maternal influences including diet. We have examined placental size, shape and efficiency among babies born around the time of the 5-month wartime famine in Holland 1944-1945. Methods: We examined the birth records of 2414 term singleton babies born in Amsterdam during 1943 -1947. The records included the size of the baby and the thickness of the placental surface, together with its length and breadth which we used to calculate its area and volume. Results: Compared to babies born before the famine babies who were in utero during the famine had smaller placental areas. Babies whose mothers conceived after the famine ended also had smaller placental areas. Famine was associated with a 19 cm(2) decrease in area. Babies who were in mid-late gestation during the famine were 160 g lighter than would have been predicted from their placental area (p

Background: Physical activity plays an important role in prevention of chronic diseases. Animal studies have suggested that lifestyle and exercise habits may have a prenatal origin. Our aim was to assess the role of early growth on leisure time physical activity (LTPA) in later life among 57–70-years-old men and women. Methods: We examined 2003 individuals born in Helsinki, Finland between 1934 and 1944. Of them, 1967 individuals with adequate information on their LTPA in adult life were included in this study. LTPA was assessed by a validated exercise questionnaire (KIHD Study 12 month physical activity history). Subjects’ birth and serial growth measurements were obtained from birth, child welfare and school health records. Results: Participants with higher engagement in LTPA showed a more favourable adult anthropometric and body composition profile than those who were less active. LTPA was positively associated with adult social class. Higher weight and length at birth, and weight at 2 years after adult BMI adjustment, predicted higher intensity of total LTPA (P?=?0.04, P?=?0.01 and P?=?0.03), respectively. Higher height at 2, 7 and 11 years predicted higher intensity of conditioning LTPA (P?=?0.01, P?=?0.04 and P?=?0.004). Higher weight and height at 2, 7 and 11 years predicted higher energy expenditure (EE) of total LTPA (P-values being from 0.01 to 0.03). Furthermore, higher height at 2 and 11 years predicted higher EE of conditioning LTPA (P?=?0.02 and P?=?0.03). Conclusion: People who as children were taller and weighed more engage more in leisure time physical activity in late adulthood.

Please cite this paper as: Tuovinen S, Raikkonen K, Kajantie E, Pesonen A, Heinonen K, Osmond C, Barker D, Eriksson J. Depressive symptoms in adulthood and intrauterine exposure to pre-eclampsia: the Helsinki Birth Cohort Study. BJOG 2010;117:1236–1242. Objective We studied whether pre-eclampsia predicts depressive symptoms in offspring. Design Retrospective longitudinal cohort study. Setting Participants in the Helsinki Birth Cohort 1934–44 Study. Population We classed 788 women and men born at term after a normotensive, hypertensive or pre-eclamptic pregnancy, by using the mother’s blood pressure and urinary protein measurements, at maternity clinics and birth hospitals. Methods Linear and logistic regression analyses. We made adjustments for the mother’s age and body mass index (BMI) at delivery, the participant’s body size at birth/length of gestation, sex and childhood socio-economic status, age and educational attainment at testing. Main outcome measures Beck depression inventory (BDI) scores completed twice, at the ages of 60 and 63 years. Result Participants born after a primiparous pregnancy complicated by pre-eclampsia had over 30% (P

People differ in their susceptibility to developing cancer on exposure to carcinogens such as tobacco. What causes this is largely unknown. One possibility is that it is determined by nutritional influences during development that permanently change the structure and function of the baby's body. We studied an older and a younger cohort, totaling 20,431 men and women, born in Helsinki during 1924-1933 and 1934-1944. Their body size at birth had been recorded. Of them, 385 had developed lung cancer. Smoking history was known for 6,822 people. At birth, babies who later developed lung cancer had a high ponderal index (birthweight/length(3)). This association was confined to people whose mother's height was below the median. Among these people in the older cohort, the hazard ratio associated with a ponderal index >30 kg/m(3) was 3.1 (95% CI 1.6-5.9), in comparison to those with a ponderal index of 26 kg/m(3) or less (P for trend < 0.001). The equivalent figures for the younger cohort were 2.9 (1.2-7.0, P for trend = 0.001) and this association was independent of smoking. We suggest that a high ponderal index in babies born to short mothers is the result of low amino acid delivery to the fetus in relation to glucose delivery. We hypothesize that this impairs the development of the babies' antioxidant systems and makes them vulnerable to oxidative stress in later life. This is the first evidence that fetal programming may determine vulnerability to carcinogens in humans.

To study the relationship of newborn size and post-natal growth to glucose intolerance in south Indian adults.2218 men and women (mean age 28 years) were studied from a population-based birth cohort born in a large town and adjacent rural villages. The prevalence of adult diabetes mellitus [DM] and impaired glucose tolerance [IGT], and insulin resistance and insulin secretion (calculated) were examined in relation to BMI and height at birth, and in infancy, childhood and adolescence and changes in BMI and height between these stages.Sixty-two (2.8%) subjects had Type 2 diabetes (DM) and 362 (16.3%) had impaired glucose tolerance (IGT). IGT and DM combined (IGT/DM) and insulin resistance were associated with low childhood body mass index (BMI) (p0.001 for both) and above-average BMI gain between childhood or adolescence and adult life (p0.001 for both). There were no direct associations between birthweight or infant size and IGT/DM; however, after adjusting for adult BMI, lower birthweight was associated with an increased risk.The occurrence of IGT and Type 2 DM is associated with thinness at birth and in childhood followed by accelerated BMI gain through adolescence.

Evidence that long-term health is shaped by the environment in early life calls for prenatal interventions to tackle chronic disease, argue David Barker and colleagues.

Background People who score poorly in intellectual ability tests have shorter life expectancy. A study was undertaken to determine whether this association is different in people from different socioeconomic backgrounds. Methods The mortality of 2786 men born in Helsinki, Finland during 1934–1944 who, as military conscripts, underwent a standardised intellectual ability test comprising verbal, visuospatial and arithmetic reasoning subtests was studied. Mortality data came from the Finnish Death Register. Results Comparing men in the lowest and highest test score quartiles, HRs for all-cause mortality were 1.9 (95% CI 1.4 to 2.5) for verbal reasoning, 2.2 (95% CI 1.6 to 3.0) for visuospatial reasoning and 1.9 (95% CI 1.4 to 2.5) for arithmetic reasoning, corresponding to 2.6, 3.4 and 2.6 excess years of life lost, respectively. Associations were similar for cardiovascular and non-cardiovascular mortality. Intellectual ability scores were stronger predictors in men who grew up in middle-class families. Compared with middle-class men in the highest quartile of the visuospatial reasoning score, middle-class men in the lowest quartile lost 6.5 years of life while men from families of manual workers in the highest quartile lost 2.8 years and men in the lowest quartile lost 5.6 years. Conclusions High intellectual ability in men aged 20 protects them from mortality in later life. This effect is stronger in men who grew up in middle-class families than in those who grew up in manual worker families. This finding suggests that early life conditions that are unfavourable to the development of cognitive abilities negate the life expectancy benefits of being born into a more affluent family.

Aim The aim of this study was to examine the effects of early growth on the risk of developing the metabolic syndrome in normal-weight individuals. Methods We examined 2003 subjects born in Helsinki, Finland, between 1934 and 1944, focusing on 588 individuals who were normal weight (body mass index [BMI] less than or equal to25kg/m 2 ). These subjects had a median of seven measurements of height and weight from birth to 2 years, and eight measurements from 2 to 11 years of age. The metabolic syndrome was defined according to the 2005 criteria of the International Diabetes Federation. Results Individuals with the metabolic syndrome were heavier, had higher mean BMI and higher body fat percentages than those without the syndrome. No differences were seen in body size at birth and at 2 years but, by the age of 7 years, those men who later developed the metabolic syndrome were thinner ( P =0.01). Changes in BMI during infancy were predictive of the syndrome, with an OR of 0.57 (95% CI: 0.36–0.90) per one S.D. increase in BMI from birth to 2 years. In women, these associations paralleled those in men, but did not reach statistical significance. Conclusion Among normal-weight men, those who developed the metabolic syndrome in adulthood had smaller gains in BMI during infancy and were thinner at age 7 years. These results support findings that early growth may play an important role in the development of the metabolic syndrome.

Diabetes in pregnancy has been shown to induce long-term effects in offspring. While considerable attention is focused on the increased incidence of type 2 diabetes mellitus (T2DM) in adult offspring from diabetic mothers, cardiovascular alterations, including hypertension, are also part of lifelong consequences of in-utero exposure to increased glucose concentrations. This review examines the epidemiologic and mechanistic issues involved in the developmental programming of long-term consequences in offspring of diabetic mothers, with a particular emphasis on the renal and vascular mechanisms of hypertension. The factors of increased incidence of T2DM and of obesity in adults born after exposure to diabetes during pregnancy are also discussed, as evidence is accumulating that a vicious circle involving lifelong consequences of diabetes in pregnancy in offspring contributes to the current worldwide epidemic of T2DM.

Background and Purpose— Women who develop pre-eclampsia in pregnancy are at increased risk of cardiovascular disease. The offspring from pregnancies complicated by pre-eclampsia have higher blood pressures during childhood, but little is known about their long-term health. We hypothesized that pre-eclampsia would lead to an increased risk of cardiovascular disease in the offspring. Methods— We traced 6410 babies born in Helsinki, Finland, from 1934 to 1944. We used the mothers’ blood pressure levels and the presence of proteinuria during pregnancy to define pre-eclampsia and gestational hypertension without proteinuria according to modern criteria. Results— Two hundred eighty-four of the pregnancies were complicated by pre-eclampsia (120 with nonsevere and 164 with severe disease) and 1592 by gestational hypertension. The crude hazard ratio for all forms of stroke among people whose mothers had pre-eclampsia was 1.9 (1.2 to 3.0; P =0.01); among people whose mothers had gestational hypertension, it was 1.4 (1.0 to 1.8; P =0.03). There was no evidence that these pregnancy disorders were associated with coronary heart disease in the offspring. Pre-eclampsia, in particular severe disease, was associated with a reduced mean head circumference at birth, whereas gestational hypertension was associated with an increased head circumference in relation to body length. Conclusions— People born after pregnancies complicated by pre-eclampsia or gestational hypertension are at increased risk of stroke. The underlying processes may include a local disorder of the blood vessels of the brain as a consequence of either reduced brain growth or impaired brain growth leading to “brain-sparing” responses in utero.

There is now clear evidence that the pace and pathway of early growth is a major risk factor for the development of a group of chronic diseases that include coronary heart disease, stroke, type 2 d...

OBJECTIVE—The purpose of this study was to describe patterns of infant, childhood, and adolescent BMI and weight associated with adult metabolic risk factors for cardiovascular disease. RESEARCH DESIGN AND METHODS—We measured waist circumference, blood pressure, glucose, insulin and lipid concentrations, and the prevalence of metabolic syndrome (National Cholesterol Education Program Adult Treatment Panel III definition) in 1,492 men and women aged 26–32 years in Delhi, India, whose weight and height were recorded every 6 months throughout infancy (0–2 years), childhood (2–11 years), and adolescence (11 years–adult). RESULTS—Men and women with metabolic syndrome (29% overall), any of its component features, or higher (greater than upper quartile) insulin resistance (homeostasis model assessment) had more rapid BMI or weight gain than the rest of the cohort throughout infancy, childhood, and adolescence. Glucose intolerance (impaired glucose tolerance or diabetes) was, like metabolic syndrome, associated with rapid BMI gain in childhood and adolescence but with lower BMI in infancy. CONCLUSIONS—In this Indian population, patterns of infant BMI and weight gain differed for individuals who developed metabolic syndrome (rapid gain) compared with those who developed glucose intolerance (low infant BMI). Rapid BMI gain during childhood and adolescence was a risk factor for both disorders.

Objectives: To assess whether serial measurements of childhood body mass index (BMI) give clinically useful predictions of the risk of developing adult metabolic syndrome and impaired glucose tolerance or type 2 diabetes. Design/setting: Follow-up of a community-based birth cohort in Delhi, India. Participants: 1,492 men and women aged 26-32 years whose BMI was recorded 6-monthly throughout childhood. Main outcome measures: The predictive value of childhood BMI for adult metabolic syndrome (MS) defined using waist circumference, blood pressure and fasting glucose, triglyceride and HDL-cholesterol concentrations, and impaired glucose tolerance (IGT) and diabetes (DM) diagnosed by oral glucose tolerance tests. Results: Twenty-five percent of subjects had MS and 15% had IGT/DM. Both outcomes were associated with greater childhood BMI gain (MS: OR 1.63 [95% CI 1.44 to 1.85]; IGT/DM: 1.39 [1.20 to 1.60] per unit increase in within-cohort BMI SD-score between 5-14 years). Best predictions of adult disease were obtained using a combined test comprising i) any increase in BMI SD-score between 5-14 years and ii) a BMI SD-score >0 at 14 years (MS: sensitivity 45%, specificity 78%; IGT/DM: 37%, 73%). Likelihood ratios were low (MS: 1.4-2.0; IGT/DM: 1.2-1.4). A single high BMI measurement at 14 years (overweight or obese, International Obesity Task Force criteria) was highly specific but insensitive (MS: sensitivity 7%, specificity 97%; IGT/DM: 8%, 97%). Charts for plotting BMI SD-scores through childhood were produced. Conclusions: Serial measurements of childhood BMI give useful predictions of adult risk and could guide advice to children and parents on preventing later disease.

This report summarizes a longitudinal study of maternal health and pregnancy outcomes including mothers from urban and rural areas of the North Arcot district in India. It describes the study sample the follow up attrition measurements the findings and the strengths and weaknesses of the study.

Small birth size predicts various psychiatric outcomes, including depression. While biologically based temperamental traits may constitute a vulnerability factor for depression, the extent to which birth size predicts these traits in adulthood is not known. We studied, in 1369 women and men identified from a cohort born in 1934-44 in Helsinki, Finland, whether birth size predicts the temperamental traits measured with Cloninger's Tridimensional Personality Questionnaire at an average age of 63 years. Moreover, we examined whether socio-economic status (SES) in childhood modified the associations. Data on birth size were obtained from birth records, and SES in childhood was obtained from school records. Weight and length at birth showed curvilinear, reverse J-shaped effects on harm avoidance (HA), such that the highest HA scores were most characteristic of those born small. Furthermore, high HA was confined to those belonging to a low SES group in childhood regardless of birth size, and to those belonging to the high SES group in childhood if their birth size was small. The associations were independent of several confounders. Since small birth size as well as high HA in adulthood may associate with subsequent depression, our findings might shed light on understanding the early neurodevelopmental processes that predispose to depression through vulnerability characteristics.

Background: The relation between the change in body mass index (BMI) through childhood and body composition in adult life is important because body composition is known to affect adult health. Objective: The objective was to examine how the change in BMI throughout childhood is related to adult lean and fat mass. Design: We examined how the change in BMI in childhood was related to adult body composition in 885 men and 1032 women born during 1934–1944, whose weights and heights during childhood were recorded serially. Adult lean and fat mass were measured by bioelectrical impedance with an 8-polar tactile electrode system. Results: In these 56–70-y-old men and women, adult lean body mass index (lean mass/height2; in kg/m2) was positively associated with BMI at birth (0.24 and 0.20 higher for each 1-SD increase in BMI at birth, respectively) and with more rapid gain in BMI from birth to 1 y (0.17 and 0.22), 1–2 y (0.21 and 0.20), 2–7 y (0.44 and 0.46), and 7–11 y (0.32 and 0.26) of age. Fat mass index (fat mass/height2) was positively associated with more rapid increases in BMI between 2 and 11 y of age. Conclusions: Rapid gain in BMI before the age of 2 y increased adult lean body mass without excess fat accumulation, whereas rapid gain in BMI in later childhood, despite the concurrent rise in lean mass, resulted in relatively larger increases in fat mass

One hypothesis for the origins of breast cancer is that it is initiated by exposure of developing breast tissue in utero to maternal sex hormones. The sex hormone profile is established at puberty, when it regulates growth of the pelvic bones. The pubertal growth of girls is characterized by broadening and rounding of the pelvis. The maximal width between their iliac crests, the intercristal width, increases more rapidly than in boys. We hypothesized that higher sex hormone concentrations at puberty produce larger intercristal widths, and these are markers of increased breast cancer risk in the next generation. We followed up 6,370 women who were born in Helsinki during 1934-1944, and whose mothers' pelvic bones were measured during routine antenatal care. Women whose mothers had large intercristal widths had higher rates of breast cancer. In those born at or after 40 weeks gestation, the hazard ratio for breast cancer was 3.7 (95% CI: 2.1-6.6) if their mother's intercristal width was greater than 30 cm. Among women born to multiparous mothers this hazard ratio rose to 7.2 (3.4-15.4). Hazard ratios for breast cancer were also higher in the daughters of mothers with round iliac crests. Pelvic bone measurements which increase similarly in girls and boys at puberty did not predict breast cancer. We conclude that the intercristal width, and the roundness of the iliac crests, are markers of mothers' sex hormones, and postulate that high concentrations cause genetic instability in differentiating breast cells in their daughters in utero.

We previously reported that in 2003 people from the Helsinki birth cohort whose blood pressures were measured, 2 different paths of growth preceded the development of hypertension. People already diagnosed with hypertension were small at birth but of average body size at age 11 years. People newly diagnosed with hypertension grew slowly in utero and through childhood. We have now examined how the mother’s body size, placental size, and living conditions after birth, 3 influences that affect growth, affect hypertension. Diagnosed hypertension was associated with low placental weight and poor living conditions after birth. The odds ratios were 1.6 (95% CI, 1.1 to 2.3) in people with placental weights 750 g, and 2.2 (95% CI, 1.5 to 3.3) in people whose fathers were laborers compared with those in upper middle-class families. Newly diagnosed hypertension was associated with a small anteroposterior diameter of the mother’s bony pelvis, a known consequence of rickets or lesser degrees of malnutrition in infancy. The odds ratio was 2.2 (95% CI, 1.4 to 3.5) in people whose mothers’ pelvic external conjugate diameters were

BackgroundA non-optimal foetal environment, reflected in smaller birth size and shorter duration of gestation, is a risk factor for compromised health later in life.AimsTo examine whether smaller birth size and shorter gestation predict depressive symptoms.MethodA total of 1371 members of a cohort born between 1934 and 1944 at term (259–294 days' gestation) in Helsinki, Finland, completed the Beck Depression Inventory (BDI) and the Center for Epidemiological Studies Depression scale (CES–D) at an average age of 61.5 years (BDI) and 63.4 years (BDI and CES–D).ResultsGestational length predicted depressive symptoms linearly and independently of gender and birth weight: per day decrease in gestational length, depressive symptoms scores increased by 0.8-0.9% (95% CI 0.2-1.4, PConclusionsSusceptibility to depressive symptoms may relate to shorter length of gestation.

Current orthodoxy states that coronary heart disease results from the unhealthy lifestyles of westernized adults together with a contribution from genetic inheritance. This does not provide a secure basis for prevention of the disease. Geographical studies gave the first clue that the disease originates during intra-uterine development. Variations in mortality from the disease across England and Wales were shown to correlate closely with past differences in death rates among newborn babies. In the past most deaths among newborns were attributed to low birthweight. This led to the hypothesis that undernutrition in utero permanently changes the body's structure, function and metabolism in ways that lead to coronary heart disease in later life. The association between low birthweight and coronary heart disease has been confirmed in longitudinal studies of men and women around the world. The developmental model of the origins of the disease offers a new way forward.

Low birth weight has been linked to lower lean body mass and abdominal obesity later in life, whereas high birth weight has been suggested to predict later obesity as indicated by high body mass index (BMI). We examined how birth weight was related to adult body size, body composition and grip strength. Cross-sectional study on 928 men and 1075 women born in 1934–1944, with measurements at birth recorded. Height, weight, waist and hip circumference and isometric grip strength were measured. Lean and fat body mass were estimated by bioelectrical impedance with an eight-polar tactile electrode system. A 1 kg increase in birth weight corresponded in men to a 4.1 kg (95% CI: 3.1, 5.1) and in women to a 2.9 kg (2.1, 3.6) increase in adult lean mass. This association remained significant after adjustment for age, adult body size, physical activity, smoking status, social class and maternal size. Grip strength was positively related to birth weight through its association with lean mass. The positive association of birth weight with adult BMI was explained by its association with lean mass. Low birth weight was related to higher body fat percentage only after adjustment for adult BMI. Abdominal obesity was not predicted by low birth weight. Low birth weight is associated with lower lean mass in adult life and thus contributes to the risk of relative sarcopenia and the related functional inability at the other end of the lifespan. At a given level of adult BMI, low birth weight predicts higher body fat percentage.