The prenatal origins of lung cancer. II. The placenta

We have shown that people who were short at birth in relation to their weight are at increased risk of lung cancer. We suggested that this reflected low amino acid-high glucose delivery to the fetus and that this impaired the development of its antioxidant systems and made it vulnerable to tobacco smoke and other carcinogens in later life. Transfer of amino acids and glucose from mother to fetus depends on the placenta. We here examine how maternal and placental size are related to lung cancer. We studied two cohorts, totaling 20,431 people, born in Helsinki during 1924-1944. Their body size at birth and maternal body size had been recorded together with the weight of the placenta and two diameters of its surface. Of them, 385 had developed lung cancer. Three different maternal-placental-fetal phenotypes were associated with lung cancer. Common to each was a short mother and a newborn baby that was short in relation to its weight. Lung cancer was associated with either a small or a large placental surface area. In the three phenotypes, the hazard ratios associated with a 100 cm2 increase in placental surface were 0.36 (95% CI 0.14 to 0.87, P = 0.02), 2.31 (1.45 to 3.69, P < 0.001) and 2.04 (1.08 to 3.86, P = 0.03). We conclude that three different maternal-placental phenotypes were associated with later lung cancer. We suggest that each led to low amino acid-normal glucose transfer to the fetus, reflected in a newborn baby that was short in relation to its weight

Maternal cotyledons at birth predict blood pressure in childhood

INTRODUCTION: A small placental surface at birth has been shown to be associated with the development of hypertension in later life. In this study we extend this observation by looking at the relationship between the number of placental cotyledons and blood pressure in childhood. Because the number of cotyledons is correlated with the surface area, we hypothesized that fewer cotyledons would be associated with higher blood pressure.METHODS: The Alspac study is a longitudinal study of 13,971 children born in Bristol. Their placentas were stored in formalin. We photographed the placentas of a sample of the children and related the number of maternal cotyledons to their blood pressure levels at age 9 years.RESULTS: Contrary to our hypothesis, a greater number of maternal cotyledons was associated with higher blood pressure. Among boys, a greater number of cotyledons was associated with higher systolic and diastolic pressure but not with higher pulse pressure. Diastolic pressure rose by 2.2 mmHg (95% CI 0.6 to 3.7, p = 0.007) for every 10 additional cotyledons. Among girls, a greater number of cotyledons was associated with higher systolic pressure and pulse pressure but not with higher diastolic pressure. Pulse pressure rose by 2.7 mmHg (1.1-4.3, p < 0.001) for every 10 additional cotyledons. These associations were little changed by adjustment for placental surface area.CONCLUSION: Our study has shown that a large number of maternal cotyledons is associated with raised blood pressure in childhood. The associations differ in the two sexes

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

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 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.ConclusionsHigher 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

BackgroundTall 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/height2) 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.MethodsWe 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.ResultsShorter 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.ConclusionReduced 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