WHY IS NUTRITION IN THE WOMB IMPORTANT?

Coronary heart disease was rare one hundred years ago. Now it is the most common cause of death in the world. Diet, smoking, and lifestyles are blamed; but still we do not know why one person gets heart disease while another does not.

Young women who eat unvaried and monotonous diets are putting the future health of their children and grandchildren at risk.

New research has shown that poor nutrition in the womb changes the structure and function of the body for life, and makes people vulnerable to heart disease, diabetes, stroke, osteoporosis and cancer. People who were born at term but had low birth weight as full term babies have less healthy lives.

We are all aware that poor diets are bad for us. What is now known is that the diets of girls and young women determine the health of the next generation.

WHAT IS NUTRITION IN THE WOMB?

Nutrition in the womb is the process that delivers to the fetus what it needs to grow and develop into a healthy baby. A fetus receives its nutrition from two sources. The first source of nutrients is from the mother’s diet before and during pregnancy. Most people understand this.

The fetus receives the nutrition it needs to grow not only from what the mother eats during pregnancy but from the mothers own body.

The least known and probably more important source of nutrients is the mother’s body. All bodies undergo a turnover process. Turnover is the ever-changing state of breakdown and renewal of muscle, fat and bone which releases protein, fat and calcium into the bloodstream. In a pregnant woman these nutrients are important sources of food for a growing baby. Mothers who have good turnover rates for themselves are able to provide well for their babies. A mother acquires her body composition and turnover throughout her whole lifetime as a fetus, child, girl, adolescent and adult. The mother’s turnover and her diet work in harmony to provide nutrition in the womb through the placenta.

The placenta, which is part of the baby that attaches it to the womb, captures nutrients from the mother’s blood and transports them to the baby. The growth of the placenta and the food it supplies are the key to health for a lifetime. The placenta has three functions. It is the gate between mother and baby, transferring food from the mother and waste from the baby; it makes hormones that signal to the mother what the baby needs; and it protects the baby from the mother’s immune system, which could attack the baby because it is "foreign" to the mother’s body because half of its genes come from the father. The development of the placenta begins when the embryo implants into the lining of the mother’s womb, on the eighth day after conception. The organ becomes fully functional in the tenth week of pregnancy. At birth its surface is oval in shape. It seems that the tissue along the length of the surface has different functions to tissue along the breadth.

A baby that is undernourished may try to compensate by expanding the surface of its placenta to extract more nutrients from the mother. This is dangerous because the baby and the placenta have to share the available food between them. A larger placenta will require a larger share. The shape and size of the placental surface predict heart disease, high blood pressure and certain cancers in later life. The predictions vary with the mother’s nutritional state, as she is the ultimate source of food. The predictions also differ in boys and girls. Boys invest less than girls in placental growth but more readily expand the placental surface if they become undernourished.

WHY IS NUTRITION IN THE WOMB IMPORTANT?

Coronary heart disease was rare one hundred years ago. Now it is the most common cause of death in the world. Diet, smoking, and lifestyles are blamed; but still we do not know why one person gets heart disease while another does not.

Young women who eat unvaried and monotonous diets are putting the future health of their children and grandchildren at risk.

New research has shown that poor nutrition in the womb changes the structure and function of the body for life, and makes people vulnerable to heart disease, diabetes, stroke, osteoporosis and cancer. People who were born at term but had low birth weight as full term babies have less healthy lives.

We are all aware that poor diets are bad for us. What is now known is that the diets of girls and young women determine the health of the next generation.

BRAIN DEVELOPMENT

Intelligence, the ability to benefit from education, are largely determined before the age of three years. The Barker Foundation supports the Thailand longitudinal study of how growth in the womb, and growth, nutrition and health between birth and three years of age, influence the development of intelligence.

PUBLIC HEALTH

Coronary heart disease was almost unknown a hundred years ago. Now it is the commonest cause of death in the world. There is a rising epidemic of diabetes, which causes heart disease, and soon 350 million people will have the disease. Patients are told that they are sick because of the way they live. When they reply that they live like others, who are healthy, they are told their genes are at fault. When they ask which genes, no one knows. When they ask how genes could cause an epidemic, there is no reply. The long and largely fruitless search for the causes of coronary heart disease contrasts sharply with the progress made with its treatment. There is constant pressure on doctors to improve treatment, but little pressure to prevent disease. This is surprising since, while patients are grateful for better treatments, they would prefer not to be ill in the first place. A Chinese physician wrote that inferior doctors treat the sick while mediocre doctors diagnose illness before it becomes apparent; but superior doctors prevent illness!

Across western countries poorer people have the highest rates of heart disease. In the US the disease is most common in historically poorer states such as West Virginia and Kentucky. In the UK it is most common in the industrial towns that grew up during the industrial revolution and in poor rural areas. The maps show that the distribution of deaths from coronary heart disease across England and Wales is remarkably similar to the distribution of infant mortality during the early years of the last century. High infant mortality indicates that babies have a poor environment in the womb and after birth. This link between coronary heart disease and poverty is a paradox. The disease increases rapidly as countries become more affluent so why does it settle among the poor? No aspect of the lifestyles of the poor can explain this. An alternative explanation is that poorer people are more vulnerable to damaging components of a western lifestyle shared by rich and poor alike. New research now suggests that poor people are made vulnerable to heart disease through the adverse conditions they experience in the womb.

In adverse conditions, due to lack of food, stress or other hardships, living things grow more slowly. Babies are no exception. Studies around the world have now shown that people who had low birthweight are at higher risk of heart disease. This is a graded relation. People who weighed 8 pounds are at higher risk than those who weighed 9 pounds: 6-pound babies are at higher risk than 7 pound ones. The people at risk are those who were small at birth because they grew slowly, rather than because they were born prematurely. Low weight gain in the first two years after birth also increases the risk of later heart disease.

Like all living things as they develop babies are plastic and are moulded by the food they receive. This determines how fast they grow and the quality of the systems and structures they develop. During what are called “critical periods” of development undernutrition changes a tissue or system permanently. When the sensitive period is over the effects of undernutrition will have become “hard-wired” in the body, preserved for a lifetime. For most organs and tissues the critical period occurs before birth.

Research is showing why people who had low birthweight are more vulnerable to heart disease, stroke, hypertension, diabetes, osteoporosis and certain cancers. In the womb the heart has to pump blood through the placenta, and in small babies the high pressures in the placenta circulation weaken the heart for life. A baby protects the growth of its brain at the expense of other parts of the body, such as the lung and kidney. Protecting these is not an immediate priority as, until birth, the mother performs many of their functions on the baby’s behalf. These organs are ‘traded off’. We are beginning to understand how ‘trading-off’ can permanently change an organ’s function and lead to disease in later life. The organs of people who had low birthweight have reduced functional capacity. These people also have different hormonal profiles and different metabolism when compared with people who were heavier at birth.

A baby’s growth does not depend only on what its mother eats each day. That would make it too vulnerable to the mother becoming temporarily short of food or ill. It is nourished by its mother’s muscles, fat and bones. Protein, fat and calcium are released from them each day and then re-incorporated back into the tissues. This process, ‘turnover’, constantly enriches the mother’s blood. A woman’s turnover, and her ability to re-fashion food, are built up in response to her dietary experiences through her life. Experience in early life seems to have the greatest impact. Chronic disease is a legacy from malnutrition and poor living conditions among previous generations of girls and young women. The geography of diabetes, heart disease and stroke within any country was laid down by the malnourished mothers of the past. The composition of a good diet was widely agreed many years ago but today the diets of many girls and young women remain unbalanced and monotonous.

Infancy lasts from birth to two years of age. People grow more rapidly during this time than they do at any later age. Almost one quarter of the energy available to an infant is used for growth. The brain remains plastic for some years after birth. Infants who grow slowly tend to achieve less at school and during their working lives and are at increased risk of high blood pressure, heart disease, stroke and diabetes in later life.

The growth of living things does not proceed with all possible speed until some mechanical constraint is reached and they can grow no faster. Rather growth is optimized, limited so that the benefits of larger body size are not outweighed by the nutritional costs of growth. At some age around two years a child’s rate of growth becomes ‘set’ by the internal environment and is less sensitive to the day-to-day supply of food. Until then food has commanded the rate of growth. Now the rate of growth commands the need for food. Excess food will not lead to more growth, but to fatness.

People who develop chronic diseases grow differently as children. A large group of children born in Helsinki, Finland, has been followed up for 65 years. At eleven years of age those who suffered strokes in later life were short and thin; those who developed heart disease were short and of average fatness; while those who developed diabetes were overweight. These children would not have stood out from other children in the class. What distinguished them was the path of growth by which they had attained their body size. This path was characterised by slow growth in the womb and during the first two years after birth followed, in some children, by rapid ‘compensatory’ weight gain. This path of growth leads to a high proportion of fat to muscle in the body, which is known to predispose to heart disease and diabetes. All children should have their growth charted. This is done routinely in some European countries.

The places where life expectancy is longest are those where people are not only healthier but biologically younger. In healthy places seventy-five year old people may be biologically similar to 65 year old people in less healthy places. There are two challenges in later life. One is to avoid age-related diseases, which include heart disease and diabetes: the other is to slow the rate of biological aging. The two challenges are linked but disease is not an inevitable consequence of aging. In later life people who had low birthweight are both at increased risk of disease and are more frail.

Today in the western world mothers should trust nature and enter pregnancy with confidence. They are the custodians of a marvellous system handed down to them through millions of years of evolution. Natural selection has honed the system for success. Growth and survival of the baby is a centrepiece of evolutionary strategy. Most of the process is controlled by nature: the egg’s journey to the womb, the embryo’s implantation, the growth of the placenta, all occur without a mother’s knowledge. The long and complex supply line which brings food from the mother to the baby develops without her consent. She is the arena for nature’s performance but she is the source of food that fuels it. If we protect the health and nutrition of girls and young women we can prevent chronic disease in the next generation. Each year the lives of millions of people will be spared. Many more will be saved from chronic ill health.

Boys Live Dangerously In The Womb

The growth of every human fetus is constrained by the limited capacity of the mother and placenta to deliver nutrients to it. At birth boys tend to be longer than girls at any placental weight. Boy’s placentas may therefore be more efficient than girls, but may have less reserve capacity. In the womb boys grow faster than girls and are therefore at greater risk of becoming undernourished. Fetal undernutrition leads to small size at birth and cardiovascular disorders, including hypertension, in later life. We studied 2003 men and women aged around 62 years who were born in Helsinki, Finland. 644 had hypertension: we examined their body and placental size at birth. In both sexes, hypertension was associated with low birth weight. In men, hypertension was also associated with a long minor diameter of the placental surface. The dangerous growth strategy of boys may be compounded by the costs of compensatory placental enlargement in late gestation. In women, hypertension was associated with a small placental area, which may reduce nutrient delivery to the fetus. In men hypertension was linked to the mothers’ socioeconomic status, an indicator of their diets: in women it was linked to the mothers’ heights, an indicator of their protein metabolism. Boys’ greater dependence on their mothers’ diets may enable them to capitalize on an improving food supply, but it makes them vulnerable to food shortages. The ultimate manifestation of their dangerous strategies may be that men have higher blood pressures and shorter lives than women.

INTRODUCTION

Pregnancies are more likely to have bad outcomes if the baby is a boy (Boklage 2005; Ingemarsson 2003; Di Renzo 2007). Boys grow faster than girls from an early stage of gestation, even from before implantation, and this makes them more vulnerable if their nutrition is compromised (Pedersen, 1980; Tanner, 1989). More newborn boys than girls have retarded growth and placental abnormalities and more of them die during the perinatal period (Ingemarsson, 2003; Di Renzo et al, 2007). In the famine in Holland during the Second World War the number of boys born fell in relation to the number of girls (Ravelli et al, 1999).

The nutrition of a fetus depends on various aspects of the mother’s nutrition, including her diet, her nutritional stores and her metabolism, which is the product of her lifetime’s nutrition (Jackson, 2000). Fetal nutrition also depends on the placenta’s ability to transport nutrients from mother to fetus (Harding, 2001). This ability is reflected in its size. Small babies generally have small placentas. We have previously examined the differences in fetal and placental size at birth among boys and girls born in Helsinki, Finland (Forsen et al, 1999). We found that the small differences in average body measurements concealed large differences in body proportions. Boys tended to be longer than girls at any placental weight. This suggests that boy’s placentas are more efficient but may have less reserve capacity, which increases their vulnerability to undernutrition. Boys tend to have larger head circumferences at birth but are thinner than girls. This suggests that they may trade off visceral development to protect brain growth. The growth of every human fetus is constrained by the limited capacity of the mother and placenta to deliver nutrients to it (Ounsted et al, 1986). The male fetus, by growing more rapidly and investing in brain growth rather than placental growth, is adopting a more dangerous strategy that puts it at greater risk of becoming undernourished.

An immediate consequence of fetal undernutrition is reduced growth and low birthweight (Harding, 2001) ; a long-term consequence is vulnerability to cardiovascular disorders, including hypertension, later in life (Barker, 1995). Men and women whose birth weights were towards the lower end of the normal range are at increased risk of cardiovascular disease (Barker et al. 1989; Frankel et al, 1996; Rich-Edwards et al, 1997; Leon et al, 1998; Barker et al, 2005). This is thought to reflect fetal programming, the process by which early malnutrition leads to lifelong changes in the body’s organs and systems and thereby initiates disease in later life (Barker, 1995; Bateson et al, 2004). Hypertension can be programmed experimentally by manipulating the diets of pregnant animals (Barker et al, 2006). One mechanism underlying the fetal origins of hypertension is a lifelong reduction in the number of nephrons. During development the kidney has low priority because the placenta performs most its functions, and renal development may be traded off to protect more important organs, including the brain. The higher blood pressure of men than women could indicate that boys more readily trade off their kidneys than girls do.

Not only are boys more vulnerable to undernutrition than girls, but their different path of intrauterine growth could make them respond to different aspects of maternal nutrition and have different placental growth. We here present findings showing that two markers of maternal nutrition, together with the size of the placenta, program hypertension differently in the two sexes.

METHODS

The study sample was selected from men and women who were born during 1934 to 1944 in the Helsinki University Central Hospital and who visited infant welfare clinics in the city. Details of the birth records, child welfare clinic records and school health records have been previously described (Barker et al, 2005). Their birth records included birthweight, the mother’s height and data on the father’s occupation, grouped into middle and lower class, on the basis of an original classification from Statistics Finland. The records also included the weight of the placenta, together with the maximal width of the surface and a lesser width bisecting it at right angles. The mean values of the maximal and lesser diameters were 19.4 (SD 2.2) and 16.9 cm (SD 2.2), respectively. Their lengths were highly correlated with each other (r=0.6) and with birthweight (r=0.5). We used these so-called diameters to estimate the surface area of the placenta. Assuming an elliptical surface, we estimated the area of the placenta as maximal x lesser diameter x π/4.

We identified 8760 men and women, born as singletons, who were living in Finland in 1971, when a unique identification number was allocated to each member of the Finnish population. We used random number tables to select a sample of people within the cohort who were still alive and living in Finland. In order to achieve a sample size in excess of 2000 people we selected 2902 subjects and invited them to a clinic. 928 men and 1075 women visited the clinic, which was held at the National Public Health Institute in Helsinki. Their average age was 62 years (range 57 to 70 yr). The procedures used at the clinic have been previously described (Barker et al, 2005). Written informed consent was obtained from each subject before any procedures were carried out. The Ethics Committee at the National Public Health Institute, Finland approved the study.

Six hundred forty-four of the subjects, 310 men and 334 women, had been diagnosed as having hypertension giving a prevalence of 32% (Eriksson et al, 2007). We calculated odds ratios for hypertension and assessed their associations with maternal and placental measurements using multiple logistic regressions. Odds ratios for hypertension increased with age and waist circumference and we adjusted for these as in our previous analyses (Eriksson et al, 2007). Measurements of birth, placental and maternal size were analysed as continuous variables although presented in Table 1 as groups. Tests for interaction used the product of the variables being studied.

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