Late preterm birth, post-term birth, and abnormal fetal growth as risk factors for severe mental disorders from early to late adulthood.

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.

Maternal hypertensive disorders during pregnancy: adaptive functioning and psychiatric and psychological problems of the older offspring.

OBJECTIVE: To study whether pre-eclampsia and hypertension without proteinuria during pregnancy are associated with adaptive functioning, and psychiatric and psychological problems, of older offspring. DESIGN: Retrospective longitudinal cohort study. SETTING: Participants in the Helsinki Birth Cohort 1934-44 Study. POPULATION: A cohort of 778 participants born after normotensive, pre-eclamptic, or hypertensive pregnancies, defined based on the mother's blood pressure and urinary protein measurements at maternity clinics and birth hospitals. METHODS: Pearson's chi-squared tests and multivariable logistic regression. MAIN OUTCOME MEASURES: Achenbach System of Empirically Based Assessment Older Adult Self-Report scores, completed at age 69.3 years (SD 3.1 years). RESULTS: Compared with offspring born after normotensive pregnancies, offspring born after pre-eclamptic pregnancies had increased odds of reporting total problems (aOR 4.00, 95%CI 1.64-9.77) and problems of particular concern to clinicians (critical items; aOR 5.28, 95%CI 1.87-14.96), as well as: anxious/depressed, functional impairment, memory, thought, and irritable/disinhibited problems on syndrome scales; depressive, somatic, and psychotic problems on Diagnostic and Statistical Manual of Mental Disorders scales; and adjustment problems in relationship satisfaction with spouse/partner. Maternal hypertension without proteinuria was not consistently associated with adjustment and problems (total problems, aOR 1.08, 95%CI 0.75-1.57; critical items, aOR 1.58, 95%CI 0.91-2.72). CONCLUSIONS: Maternal hypertensive disorders in pregnancy, during a period of expectant treatment, carry an increased risk of problems in adaptive functioning and mental wellbeing in the offspring seven decades later. Being the longest follow-up on transgenerational consequences of maternal hypertensive disorders reported thus far, our study points to the life-time increased risk of an adverse intrauterine environment.

Intergenerational effects of in utero exposure to Ramadan in Tunisia.

UNLABELLED: We have reported that changes in the lifestyle of pregnant women during Ramadan affect more than one generation. In a series of newborn babies in Saudi Arabia, those whose mothers had been in utero during Ramadan differed from those whose mothers had not been in utero during Ramadan. These were unexpected findings and require replication. METHODS: We examined body size at birth in 1,321 babies (682 boys and 639 girls) born in Gafsa, a small city in Tunisia. RESULTS: Babies whose mothers had been in utero during Ramadan were smaller and thinner, and had smaller placentas, than those whose mothers had not been in utero during Ramadan. After adjustment for sex, the babies were 93 g lighter (95% confidence interval, 32-153, P=0.003) than those whose mother had not been in utero during Ramadan, their mean ponderal index was 0.52 kg/m(3) lower (0.24-0.79, P<0.001) and their placental weight was 21 g lower (5-37, P=0.01). The findings did not differ by trimester of maternal exposure to Ramadan. They were similar in boys and girls and in primiparous and multiparous mothers CONCLUSION: This study provides further evidence that changes in lifestyle during Ramadan have intergenerational effects.

Growth from birth to adulthood and peak bone mass and density data from the New Delhi Birth Cohort.

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 < 0.01 all sites). BMI at 11 years, and BMI gain in childhood and adolescence, were correlated with aBMD and BMAD (p < 0.001 for all); these correlations strengthened with increasing age of BMI measurement. The associations with height and BMI in early life became non-significant after adjustment for adult height and BMI. CONCLUSIONS: Greater skeletal growth and BMI gain in utero and during infancy are associated with higher peak BMC, and greater BMI gain in childhood and adolescence is associated with higher peak aBMD and BMAD. These associations are mediated by the attainment of adult height and BMI, respectively.

Sir Richard Doll Lecture. Developmental origins of chronic disease.

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.

Growth in childhood predicts hip fracture risk in later life.

UNLABELLED: The incidence of hip fracture was estimated in 6,370 women born in Helsinki between 1934 and 1944. Women in the lowest quarter of adiposity gain had an 8.2-fold increase in hip fracture risk compared with those in the highest quarter (p < 0.001). These data point to a relationship between childhood growth and fracture risk during later life. INTRODUCTION: Previous findings show that discordance between childhood increase in height and weight is associated with an increased risk of osteoporotic fractures during later life. METHODS: We studied 6,370 women born in Helsinki between 1934 and 1944. Each woman's birth weight and length at birth was recorded, as well as her height and weight through childhood. We identified the occurrence of hip fracture through the National Finnish Hospital discharge register. RESULTS: There were 49 hip fractures in the 6,370 women over 187,238 person-years of follow-up. Hip fracture was associated with increasing Z-scores for height between 1 and 12 years, not matched by a corresponding increase in weight. Therefore, reduction in the Z-score for body mass index was associated with increased risk of hip fracture. Women in the lowest quarter of change in Z-scores for body mass index had an 8.2-fold increase in hip fracture risk (95% CI 1.9 to 35), compared with those in the highest quarter (p < 0.001). CONCLUSION: Thinness in childhood is a risk factor for hip fracture in later life. This could be a direct effect of low fat mass on bone mineralization, or represent the influence of altered timing of pubertal maturation.

Sex differences in birth size and intergenerational effects of intrauterine exposure to Ramadan in Saudi Arabia.

OBJECTIVES: 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. METHODS: We examined body size at birth among 967 babies (479 boys and 488 girls) born in Unizah, a small city in Saudi Arabia. RESULTS: Large head circumference was the strongest single predictor of male sex. In a simultaneous regression, female sex was predicted by small head circumference (P < 0.001), 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 (P < 0.001). 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). CONCLUSION: 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.

Prenatal growth, postnatal growth and trait anxiety in late adulthood - the Helsinki Birth Cohort Study.

OBJECTIVE: Trait anxiety may predispose to anxiety disorders and cardiovascular events. We tested whether prenatal growth or postnatal growth from birth to 11 years of age and in adulthood predict trait anxiety in late adulthood. METHOD: Women (n = 951) and men (n = 753) reported trait anxiety using the Spielberger Trait Anxiety Scale at an average age of 63.4 years and growth was estimated from records. RESULTS: Higher trait anxiety was predicted by smaller body size at birth, in infancy and in adulthood. Moreover, faster growth particularly from seven to 11 years of age and slower growth between 11 and 63 years predicted higher trait anxiety. CONCLUSION: We found a pattern of pre- and postnatal growth that predisposed to higher trait anxiety in late adulthood. This pattern resembles that found to increase the risk of cardiovascular events and, thus, points to a shared common origin in a suboptimal prenatal and childhood developmental milieu.

Depressive symptoms in adulthood and intrauterine exposure to pre-eclampsia: the Helsinki Birth Cohort Study.

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 < 0.04) higher depressive symptom scores in adulthood compared with those born after a primiparous normotensive pregnancy. We found no evidence of the association between pre-eclampsia and depression among participants born after multiparous pregnancies. Gestational hypertension and depressive symptoms were not significantly associated. The models adjusting for mother's age and BMI at delivery, the participant's body size at birth/length of gestation, sex, childhood socio-economic status, age and educational attainment at testing did not change the results. CONCLUSION: Pre-eclampsia is associated with later depressive symptoms in individuals born at term and after a primiparous pregnancy. These findings are compatible with the adverse fetal 'programming' by a suboptimal prenatal environment.

Childhood growth and future risk of the metabolic syndrome in normal-weight men and women.

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 to 25 kg/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.

Role of childhood growth on the risk of metabolic syndrome in obese men and women.

AIM: Although obesity is the key characteristic of the metabolic syndrome, not all obese individuals develop the syndrome. Our aim was to identify characteristics of early growth that protect these individuals from the metabolic syndrome. METHODS: We examined 2003 subjects born in Helsinki, Finland, between 1934 and 1944. We focused on the 499 who were obese (BMI> or =30 kg/m(2)), 400 of whom had the metabolic syndrome according to IDF 2005 criteria. The subjects had a median of seven measurements of height and weight from birth to two years of age, and eight measurements from two to 11 years of age. RESULTS: Among obese individuals, those with the metabolic syndrome had a higher mean body mass index (BMI) and larger waist circumference than those who did not. The two groups were similar in body size at birth but, by two years of age, those who later developed the metabolic syndrome were lighter and thinner, and remained so up to age 11 years. The period when BMI changes were predictive of the syndrome was from birth to seven years. OR was 0.72 (95% CI: 0.57-0.92) per 1 S.D. increase in BMI from birth to two years and 0.63 (95% CI: 0.49-0.81) per 1 S.D. increase in BMI from two to seven years. CONCLUSION: Among obese individuals, those who develop the metabolic syndrome were lighter and thinner from the age of two to 11 years compared with those who did not. These findings support the importance of early childhood growth in determining the metabolic consequences of obesity.

Childhood growth and cardiovascular reactivity to psychological stressors in late adulthood.

OBJECTIVE: Specific childhood growth patterns relate to risk of cardiovascular (CV) disease later in life, but the underlying mechanisms are unclear. We studied whether CV reactivity, a predictor of CV disease risk, is associated with childhood growth trajectories. METHODS: A total of 144 (77 women and 67 men) participants of the Helsinki Birth Cohort Study born 1934-1944, whose height and weight were recorded repeatedly during the first 11 years, underwent the Trier Social Stress Test at the average age of 63 years. Beat-to-beat blood pressure was monitored via noninvasive finger photoplethysmograph (Finometer), and CV reactivity scores were determined as the mean increment from baseline. RESULTS: In both women and men, systolic blood pressure (SBP) reactivity increased by 3.8 mmHg (95% CI 0.8-6.9) and diastolic BP (DBP) reactivity by 1.4 mmHg (95% CI 0.0-2.8) for every standard deviation increase in gain in body mass index (kg m(-2)) between 7 and 11 years. By contrast, effects of height gain were dissimilar between sexes. In women, higher DBP reactivity was associated with a slow gain in height between 0 and 2 years, whilst in men higher SBP reactivity was associated with a slow gain in height between 2 and 7 years, which was preceded by a more rapid gain in height between 0 and 2 years. Adjusting for adult body size, body size at birth or childhood socio-economic status did not change the results. CONCLUSIONS: We found that growth during childhood is associated with CV reactivity to stress later in adulthood. Early life programming of CV reactivity may partly underlie the link between early growth and CV disease.

Reduced intima media thickness in adults after prenatal exposure to the Dutch famine.

BACKGROUND: Restricted prenatal growth is associated with an increased risk of coronary heart disease morbidity and mortality. We studied the effects of exposure to famine during gestation on intima media thickness (IMT) in later life. METHODS AND RESULTS: We studied 730 people aged 58 years who were born as term singletons around the time of the 1944-45 Dutch famine. Persons exposed to famine during gestation (n=293) had reduced carotid artery IMT compared to people who had not been exposed to famine in utero (n=437) (mean 0.71 mm, S.D. 0.16 mm compared to 0.75 mm, S.D. 0.15 mm, sex adjusted p=0.001). Femoral artery IMT was also thinner among people exposed to famine during gestation compared to people unexposed in utero (mean 0.64 mm, S.D. 0.20mm, compared to 0.68 mm, S.D. 0.24), although the difference did not achieve statistical significance. CONCLUSION: Exposure to famine in utero may reduce IMT. However, it does not reduce the risk of coronary heart disease among famine exposed people.

Cardiovascular reactivity to psychological stressors in late adulthood is predicted by gestational age at birth.

The relationships of body size and gestational age at birth with adult blood pressure (BP) are relatively modest compared to their stronger associations with cardiovascular disease. BP reactivity is a strong predictor of cardiovascular morbidity, and it is possible that reactivity, rather than resting level, is determined in utero. We investigated whether body size and gestational age at birth predict BP reactivity during experimentally induced psychosocial stress in late adulthood. A total of 73 men and 80 women born after 36 weeks' gestation in Helsinki, Finland, during 1934-1944 underwent the Trier Social Stress Test (TSST); a standardized psychosocial stress test consisting of a public speech and an arithmetic task. Changes in BP were monitored continuously by a non-invasive finger photoplethysmography (Finometer, FMS, Amsterdam, The Netherlands). The results showed that the most robust early determinant of BP reactivity was gestational age; however, with opposite relationships between the sexes (P for interaction <0.001). A 1-week increase in gestational age was associated with a 3.1 mm Hg (95% confidence interval (CI), 0.2 to 6.0) and 1.2 mm Hg (95% CI, -0.1 to 2.6) decreases in systolic and diastolic BP reactivity in women, but with 5.2 mm Hg (95% CI, 1.9 to 8.4) and 2.3 mm Hg (95% CI, 0.9 to 3.8) increases in men. In conclusion, normal variation in gestational age at birth predicts cardiovascular stress reactivity in later adulthood. Given that hypothalamic-pituitary-adrenal axis contributes to the regulation of autonomic nervous system function and the timing of parturition, and shows well-established sex differences, we speculate a role for early programming of this axis in explaining the findings.

Neonatal fatty acid profiles are correlated with infant growth measures at 6 months.

Rapid weight gain in infancy and low levels of n-3 long chain polyunsaturated fatty acids (LCPUFA) at birth are associated with increased adiposity later in life. The association between placental LCPUFA delivery and weight gain in infancy is poorly understood. We sought to determine the relationships between maternal phenotype, placental fatty acid transporter expression and offspring growth patterns over the first 6 months. Placental tissue and cord blood were collected at term delivery from women with uncomplicated pregnancies. Offspring body composition measurements were recorded 1 day and 6 months after birth. Body mass index (BMI) z-scores were determined using World Health Organization 2006 reference data. Body phenotype patterns were compared among offspring who had an increase in BMI z-score and those who had a decrease. High skinfold thickness at birth and positive change in BMI z-scores during infancy were associated with low neonatal n-3 LCPUFA plasma levels (r=-0.46, P=0.046) and high saturated fatty acids levels (r=0.49, P=0.034). Growth of skinfolds over 6 months of age was associated with placental fatty acid transporter gene expression. Change in BMI z-score in the first 6 months of life correlated with arm muscle area growth, a measure of lean mass (r=0.62, P=0.003), but not with growth in skinfold thickness. Early infancy weight gain was associated with poor plasma LCPUFA status at birth, and fat deposition in infancy was related to changes in placental lipid handling. Thus, neonatal fatty acid profiles may influence the trajectory of infant growth and fat and lean mass deposition.

Fetal origins of adult disease: strength of effects and biological basis.

BACKGROUND: Low birthweight has been consistently shown to be associated with coronary heart disease (CHD) and its biological risk factors. The effects of low birthweight are increased by slow infant growth and rapid weight gain in childhood. To quantify the importance of developmental processes in the genesis of CHD it is necessary to establish the impact of fetal, infant and childhood growth on major pathological events in later life-death, hospital treatment and the need for medication. METHODS: Longitudinal study of 13 517 men and women who were born in Helsinki University Hospital during 1924-1944, whose body sizes at birth and during childhood were recorded, and in whom deaths, hospital admissions, and prescription of medication for chronic disease are documented. RESULTS: The combination of small size at birth and during infancy, followed by accelerated weight gain from age 3 to 11 years, predicts large differences in the cumulative incidence of CHD, type 2 diabetes and hypertension. CONCLUSIONS: Coronary heart disease and type 2 diabetes may originate through two widespread biological phenomena-developmental plasticity and compensatory growth.

Impact of educational attainment on the quality of young women's diets.

OBJECTIVE: New findings, that relate poor foetal growth to long-term outcomes, highlight the need to understand more about the nature of women's diets before and during pregnancy. This study examines the influence of sociodemographic and anthropometric factors on the quality of the diets of young women in the UK. DESIGN: Diet was assessed by an interviewer-administered food frequency questionnaire. A single diet score was calculated for each woman using the first component defined by principal components analysis. SETTING: Southampton, UK. SUBJECTS: A total of 6125 non pregnant women aged 20-34 y. RESULTS: The diets of women with low diet scores were characterised by low intakes of fruit and vegetables, wholemeal bread, rice and pasta, yogurt, and breakfast cereals, but high intakes of chips and roast potatoes, sugar, white bread, red, and processed meat and full-fat dairy products. Educational attainment was the most important factor related to the diet score. In all, 55% (95% CI 50-59%) of women with no educational qualifications had scores in the lowest quarter of the distribution, compared with only 3% (95% CI 2-4%) of those who had a degree. Smoking, watching television, lack of strenuous exercise, and living with children were also associated with lower diet scores. After taking these factors into account, no other factor including social class, the deprivation score of the neighbourhood, or receipt of benefits added more than 1% to the variance in the diet score. CONCLUSIONS: Poor achievement at school defines a substantial group of women in the UK who may be vulnerable. Many of these women have poor diets that are not simply a result of the level of deprivation in their neighbourhood, or of living at a level of poverty that entitles them to benefits. We suggest that it is a priority to identify and to address the barriers that prevent these women from improving the quality of their diets. SPONSORSHIP: The study was funded by the Dunhill Medical Trust, the University of Southampton and the Medical Research Council.

The developmental origins of chronic adult disease.

Low birthweight is now known to be associated with increased rates of coronary heart disease and the related disorders stroke, hypertension and non-insulin-dependent diabetes. These associations have been extensively replicated in studies in different countries and are not the result of confounding variables. They extend across the normal range of birthweight and depend on lower birthweights in relation to the duration of gestation rather than the effects of premature birth. The associations are thought to be consequences of developmental plasticity, the phenomenon by which one genotype can give rise to a range of different physiological or morphological states in response to different environmental conditions during development. Recent observations have shown that impaired growth in infancy and rapid childhood weight gain exacerbate the effects of impaired prenatal growth. Coronary heart disease and the disorders related to it arise through a series of interactions between environmental influences and the pathways of development that preceded them. These diseases are the product of branching pathways of development in which the branchings are triggered by the environment before and after birth.

Small head circumference at birth and early age at adiposity rebound.

AIMS: The adiposity rebound is the age in childhood when body mass index is at a minimum before increasing again. The age at rebound is highly variable. An early age is associated with increased obesity in later childhood and adult life. We have reported that an early rebound is predicted by low weight gain between birth and 1 year of age and resulting low body mass index at 1 year. Here, we examine whether age at adiposity rebound is determined by influences during infancy or is a consequence of foetal growth. Our hypothesis was that measurements of body size at birth are related to age at adiposity rebound. METHODS: Longitudinal study of 2877 children born in Helsinki, Finland, during 1934-1944. RESULTS: Early age at adiposity rebound was associated with small head circumference and biparietal diameter at birth, but not with other measurements of body size at birth. The mean age at adiposity rebound rose from 5.8 years in babies with a head circumference of ≤33 cm to 6.2 in babies with a head circumference of >36 cm (P for trend = 0.007). The association between thinness in infancy and early rebound became apparent at 6 months of age. It was not associated with adverse living conditions. In a simultaneous regression, small head circumference at birth, high mother's body mass index and tall maternal stature each had statistically significant trends with early adiposity rebound (P = 0.002, <0.001, 0.004). CONCLUSION: We hypothesize that the small head size at birth that preceded an early adiposity rebound was the result of inability to sustain a rapid intra-uterine growth trajectory initiated in association with large maternal body size. This was followed by catch-up growth in infancy, and we hypothesize that this depleted the infant's fat stores.

Sex differences in regional specialisation across the placental surface.

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.