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.

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.

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.

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.

Placental programming of chronic diseases, cancer and lifespan: a review.

Particular paths of fetal growth are now known to predict a range of disorders in adult life. This is thought to reflect fetal programming, the phenomenon whereby nutrition and other influences during development set the body's organs and systems for life. The thesis of this review is that normal variations in the processes of placental development lead to variations in the supply of nutrients to the fetus and programme a small number of key systems that are linked to later disease. A baby's growth and nutrition depend both on the function of the placenta, reflected in its gross morphology at birth, and on the mother's lifetime nutrition, reflected in her height and weight. In many studies, the effects of placental size and shape on later disease have been examined within different categories of mother's body size. The review shows that variations in gross placental morphology at birth predict a wide range of disorders in later life. Any particular placental phenotype seems to predict a limited number of diseases. Further research into the links between the processes of placentation and the morphology of the placenta at birth is now required. We need to know more about the relative importance of nutrient flow, nutrient balance and the timing of nutritional events in determining disorders in later life. We also need to understand why, compared to other placental mammals, the human placenta is so variable in its morphology and functional capacity.

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.

Early life stress and blood pressure levels in late adulthood.

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 <30 kg m(-2)). Of these, 192 (14.1%) had been evacuated abroad during WWII. The remaining subjects served as controls. Blood pressure levels and use of blood pressure medication were studied. The separated subjects had significantly higher systolic blood pressure values than the non-separated (148.6+21.5 vs 142.2+19.6 mm Hg, P<0.0001) in adult life. Those subjects separated in early childhood had markedly higher systolic and diastolic blood pressure values in adult life compared with the non-separated (154.6 vs 142.5 mm Hg; 95% confidence interval (CI) 2.6-14.7; P<0.005 and 90.8 vs 87.7 mm Hg; 95% CI 1.0-7.3; P<0.02, respectively). Systolic blood pressure was also higher in the group separated for a duration of <1 year (151.7 vs 142.2 mm Hg; 95% CI 0.0-12.4; P<0.05) compared with the non-separated. Besides being separated, age at separation and duration of separation also influenced blood pressure levels in adult life. This could be due to early hormonal and metabolic programming, during plastic periods in early life, influencing blood pressure levels in adult life.

Resource allocation in utero and health in later life.

The way that a fetus obtains and allocates nutritional resources has profound consequences for its life-long health. Under the new developmental model for the origins of chronic disease, the causes to be identified are linked to normal variations in the processes of feto-placental development, that are associated with differences in the supply of nutrients to the baby. These differences programme the function of a few key systems that are linked to chronic disease, including the immune system, anti-oxidant defences, inflammation, and the number and quality of stem cells. 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 experience.

The breadth of the placental surface but not the length is associated with body size at birth.

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, p < 0.001) 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, p < 0.001) 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.

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 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.

Mother's lifetime nutrition and the size, shape and efficiency of the placenta.

BACKGROUND: Studies 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. METHODS: We 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. RESULTS: Higher 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 p < 0.0001) of the surface to birthweight. In a sub-sample of 51 mothers whose own birthweight was available, higher maternal birthweight was related to lower ratios of the length and breadth of the surface to birthweight (p = 0.01 and 0.002). Maternal height was unrelated to placental size or shape. CONCLUSIONS: Higher 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.

The lifespan of men and the shape of their placental surface at birth.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

The sex-specific effects of famine on the association between placental size and later hypertension.

BACKGROUND: People who had low birth weight are at increased risk of hypertension. This may reflect fetal programming by undernutrition. Placental size is also associated with hypertension. Maternal undernutrition during the Dutch famine reduced placental surface area. We examined whether maternal undernutrition altered the relationship between placental size and later hypertension. METHODS: Retrospective cohort study among 860 subjects born in Amsterdam during 1943-47. 216 subjects were taking anti-hypertensive medication. Birth records included placental length and breadth from which we calculated its area. RESULTS: Among men who were not in utero during the famine hypertension was associated with a small placental surface area due to a small placental breadth, and with an oval-shaped surface. The OR for hypertension was 0.83 (95% CI 0.70 to 1.00) for a 40 cm(2) increase in surface area. Among men who were in utero during the famine hypertension was associated with a large placental surface area due to a large placental breadth, and with a round-shaped surface. The OR for hypertension was 1.34 (95% CI 0.99 to 1.80) for a 40 cm(2) increase in surface area. The associations between placental size and hypertension in men who were and were not in utero during the famine were significantly different (p values for interaction = 0.008 for placental surface area, 0.001 for the breadth and 0.01 for the difference in the two diameters). Among women hypertension was not associated with placental size. CONCLUSIONS: Our study provides the first direct evidence that changes in maternal diet during pregnancy alter the relationship between placental size and later hypertension among men but not women. We suggest that among men who were not in utero during the famine, hypertension was related to impaired implantation, whereas among men who were in utero during the famine it was related to compensatory expansion of the placental surface.

Developmental origins of physical fitness: the Helsinki Birth Cohort Study.

BACKGROUND: Cardiorespiratory fitness (CRF) is a major factor influencing health and disease outcomes including all-cause mortality and cardiovascular disease. Importantly CRF is also modifiable and could therefore have a major public health impact. Early life exposures play a major role in chronic disease development. Our aim was to explore the potential prenatal and childhood origins of CRF in later life. METHODS/PRINCIPAL FINDINGS: This sub-study of the HBCS (Helsinki Birth Cohort Study) includes 606 men and women who underwent a thorough clinical examination and participated in the UKK 2-km walk test, which has been validated against a maximal exercise stress test as a measure of CRF in population studies. Data on body size at birth and growth during infancy and childhood were obtained from hospital, child welfare and school health records. Body size at birth was not associated with adult CRF. A 1 cm increase in height at 2 and 7 years was associated with 0.21 ml/kg/min (95% CI 0.02 to 0.40) and 0.16 ml/kg/min (95% CI 0.03 to 0.28) higher VO2max, respectively. Adjustment for adult lean body mass strengthened these findings. Weight at 2 and 7 years and height at 11 years became positively associated with CRF after adult lean body mass adjustment. However, a 1 kg/m(2) higher BMI at 11 years was associated with -0.57 ml/kg/min (95% CI -0.91 to -0.24) lower adult VO2max, and remained so after adjustment for adult lean body mass. CONCLUSION/SIGNIFICANCE: We did not observe any significant associations between body size at birth and CRF in later life. However, childhood growth was associated with CRF in adulthood. These findings suggest, importantly from a public point of view, that early growth may play a role in predicting adult CRF.

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.

Secular increase in placental weight in Saudi Arabia.

BACKGROUND: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.

Effects of famine on placental size and efficiency.

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 < 0.001). Babies who were in early gestation during the famine, or who were conceived after it had ended were 102 g heavier than would have been predicted from their placental area (p < 0.001). These latter babies were either longer or had larger head circumferences depending on when the mother experienced the famine. Among babies who were in early gestation during the famine the reduction in placental area was greater in boys than girls (p for interaction 0.03). CONCLUSION: Famine impaired the normal processes of placentation, even among babies who were conceived after it had ended. In babies who were in mid-late gestation during the famine, the placenta was less efficient. In babies who were in early gestation during the famine, or who were conceived after it had ended, the placenta was more efficient. The placentas of boys and girls responded differently to famine.