Intended for healthcare professionals

Letters

Adult obesity and growth in childhood

BMJ 2002; 324 doi: https://doi.org/10.1136/bmj.324.7338.674/a (Published 16 March 2002) Cite this as: BMJ 2002;324:674

Fuel mediated teratogenesis driven by maternal obesity may be responsible for pandemic of obesity

  1. David Simmons (dsimmons{at}unimelb.edu.au), foundation chair in rural health,
  2. Bernhard H Breier, associate professor
  1. Department of Rural Health, University of Melbourne, PO Box 6500, Shepparton, Victoria 3630, Australia
  2. Faculty of Medical and Health Sciences, University of Auckland, Private Bag 92019, Grafton, Auckland, New Zealand
  3. Section of Reproductive and Developmental Medicine, University of Sheffield, Sheffield S10 2SF
  4. Derby City Hospital, Derby DE22 3NE
  5. Division of Gastroenterology and Nutrition, Children's Hospital of Philadelphia, Philadelphia, PA 19104-4399, USA
  6. Department of Medicine, University of Auckland, Auckland 1001, New Zealand
  7. Division of Nutritional Biochemistry, University of Nottingham, School of Biosciences, Loughborough LE12 5RD

    EDITOR—Parsons et al highlight the importance of maternal weight on birth weight and future obesity in the offspring.1 They emphasise the importance of genetics and debate the relation between reduced intrauterine growth on future obesity but do not discuss the role of fuel mediated teratogenesis during fetal development.2

    Fuel mediated teratogenesis proposes that intrauterine exposure of the fetus of women with diabetes in pregnancy to an excess of fuel (for example, glucose) causes permanent fetal change, leading to malformations, greater birth weight, and an increased risk of developing type 2 diabetes in later life.2 More recently, obesity in the offspring has been included as an outcome of fuel mediated teratogenesis in pregnancies complicated by diabetes. 3 4 However, maternal fuel supply across a population is a continuum, and the criteria for gestational diabetes may not be sufficient to differentiate between a diabetogenic and a non-diabetogenic intrauterine milieu.

    We investigated the relation between first trimester body mass index and glycaemia at 36 weeks' gestation and birth weight and umbilical cord insulin concentrations in the pregnancies of 63 Polynesian women without gestational diabetes.5 We found that the greater the maternal body mass index (divided into thirds (<25.0, 25.0-31.7, ≥31.8 kg/m2)) the bigger the baby, the higher the maternal fasting glucose concentration (5.1 (SD 0.6), 5.0 (0.5), 5.3 (0.5) mmol/l; P=0.097), and the higher the geometric mean of the umbilical cord insulin concentration (10.0, 14.0, 14.9 μmol/l; P=0.015). There were no differences across the thirds of body mass index in concentrations of cord leptin or insulin-like growth factor-I.

    We hypothesised that increasing maternal obesity is associated with increasing maternal glycaemia, thereby stimulating fetal insulin secretion and raising the potential for obesity in the offspring. As plasma glucose is a continuous variable the relation between glycaemia and the future development of diabetes and obesity in the offspring that is found in diabetes in pregnancy 3 4 is also likely to be present in those offspring at the upper end of the normal range. This is relevant for the debate over diagnostic criteria and management of gestational diabetes.

    The public health implications of the hypothesis that fuel mediated teratogenesis may be driven by maternal obesity are enormous. If the hypothesis is confirmed attention should be directed towards controlling obesity and maximising fitness among women before pregnancy. More aggressive approaches to hyperglycaemia during pregnancy through a lowering of the criteria for gestational diabetes and more widespread use of insulin treatment in gestational diabetes may also need to be considered.

    References

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    5. 5.

    Obstetricians seem reluctant to consider interventions to reduce mean birth weight

    1. Robert Fraser (g.m.burkinshaw{at}sheffield.ac.uk), reader in obstetrics and gynaecology.,
    2. Hora Soltani, research midwife
    1. Department of Rural Health, University of Melbourne, PO Box 6500, Shepparton, Victoria 3630, Australia
    2. Faculty of Medical and Health Sciences, University of Auckland, Private Bag 92019, Grafton, Auckland, New Zealand
    3. Section of Reproductive and Developmental Medicine, University of Sheffield, Sheffield S10 2SF
    4. Derby City Hospital, Derby DE22 3NE
    5. Division of Gastroenterology and Nutrition, Children's Hospital of Philadelphia, Philadelphia, PA 19104-4399, USA
    6. Department of Medicine, University of Auckland, Auckland 1001, New Zealand
    7. Division of Nutritional Biochemistry, University of Nottingham, School of Biosciences, Loughborough LE12 5RD

      EDITOR—Law's editorial contains the suggestion that “interventions to prevent obesity in women of childbearing age give long term benefit to their children and to the women themselves.” 1 We have found that birth weight is positively correlated with maternal body mass index in early pregnancy and maternal fasting plasma glucose concentrations in the third trimester. 2 3

      We have shown a positive relation between maternal body mass index in early pregnancy and cord plasma insulin concentrations, which has since been confirmed by others.4 Fetal insulinisation is a marker of variation in birth weight, particularly in respect of the size of the newborn fat organ, as is well known from the example of maternal diabetes complicating pregnancy. The mechanism for this is that maternal fat mass is related to maternal insulin resistance, which determines the fasting and postabsorptive plasma glucose concentration.

      Healthy non-diabetic pregnant women spend about 16 hours a day in the fasting or postabsorptive state, and glucose crosses the placenta by facilitated diffusion. Thus even the relatively modest graded changes in fasting and postabsorptive plasma glucose concentration that we observed (body mass index <26, 4.13 mmol/l; 26-30, 4.63 mmol/l; and >30, 4.96 mmol/l), in persisting for the whole of the second half of pregnancy, are responsible for a considerable excess provision of substrate to the fetuses of obese gravida. This increased transfer of glucose stimulates fetal insulin production.

      We also studied postpartum body composition in relation to maternal body mass index in early pregnancy. We noted that the obese women, but not the normal weight or overweight women, failed to lose fat gained in pregnancy at the suprailiac skinfold six months after delivery. This was reflected in an increase in the waist:hip ratio, a marker for the risk of subsequent diabetes.5

      We have suggested that randomised controlled trials of diet and supervised exercise targeted at obese women in the year after childbirth might result in longterm health benefits for the women and lower birth weights of any future children they might have. These suggestions have failed to interest any bodies that give research grants. This may be because obstetricians' obsession with avoiding low birth weight means that they are reluctant to consider any intervention that might reduce mean birth weight, however beneficial that might be.

      References

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      Association of birth weight with adult weight is confounded by maternal body mass index

      1. Nicolas Stettler (nstettle{at}cceb.med.upenn.edu), assistant professor of paediatrics and epidemiology,
      2. Virginia A Stallings, professor of paediatrics
      1. Department of Rural Health, University of Melbourne, PO Box 6500, Shepparton, Victoria 3630, Australia
      2. Faculty of Medical and Health Sciences, University of Auckland, Private Bag 92019, Grafton, Auckland, New Zealand
      3. Section of Reproductive and Developmental Medicine, University of Sheffield, Sheffield S10 2SF
      4. Derby City Hospital, Derby DE22 3NE
      5. Division of Gastroenterology and Nutrition, Children's Hospital of Philadelphia, Philadelphia, PA 19104-4399, USA
      6. Department of Medicine, University of Auckland, Auckland 1001, New Zealand
      7. Division of Nutritional Biochemistry, University of Nottingham, School of Biosciences, Loughborough LE12 5RD

        EDITOR—Parsons et al showed that the association between birth weight and adult body mass index is largely explained by self reported maternal body weight.1 Although the authors said that this was the first report that maternal weight and other confounding variables may explain the association between birth weight and adult weight, we published similar conclusions after studying a North American cohort of African descent.2

        In the 354 subjects in our study we also investigated the influence of birth weight on adiposity in young adulthood and the impact of potential confounding factors on this association. The adulthood adiposity (expressed in standard deviations of triceps and subscapular skinfold thickness measured at age 20) increased with increasing fifths of birth weight, adjusted for gestational age, in the univariate analysis (test for trend: z=2.84, P=0.004). After adjustment, with multiple regression, for pre-pregnancy maternal body mass index, birth order, and sex, however, this association disappeared (P=0.39).

        We therefore concluded, as Parsons et al did, that in this North American cohort “an observed association of birth weight and adult weight might be confounded by other important factors in the absence of adjustment for these factors,”2 in particular by maternal body mass index.

        References

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        Mothers tend to pass their dietary habits on to their children

        1. Tim Cundy (t.cundy{at}auckland.ac.nz), associate professor
        1. Department of Rural Health, University of Melbourne, PO Box 6500, Shepparton, Victoria 3630, Australia
        2. Faculty of Medical and Health Sciences, University of Auckland, Private Bag 92019, Grafton, Auckland, New Zealand
        3. Section of Reproductive and Developmental Medicine, University of Sheffield, Sheffield S10 2SF
        4. Derby City Hospital, Derby DE22 3NE
        5. Division of Gastroenterology and Nutrition, Children's Hospital of Philadelphia, Philadelphia, PA 19104-4399, USA
        6. Department of Medicine, University of Auckland, Auckland 1001, New Zealand
        7. Division of Nutritional Biochemistry, University of Nottingham, School of Biosciences, Loughborough LE12 5RD

          EDITOR—Parsons et al examined the relation between birth weight and body mass index at age 33 in a large, prospectively studied British cohort.1 Numerous potential confounders were examined, but the most important seemed to be that the pre-pregnancy body mass index of these children's mothers (but not their fathers) was the main determinant of adult obesity.

          The authors conclude that their results do not support the theory that fetal growth has an effect on adult obesity. They describe their main finding as unsurprising but do not say why. The explanation is presumably a prosaic one: mothers (rather than fathers) are the parents who usually buy and prepare food and feed small children. Eating patterns and food preferences are established in early life and are difficult to change. Overweight mothers are likely to pass on to their children dietary habits that will predispose to adult obesity—a reminder, in this era of genetics, that there is more than one mode of inheritance.

          References

          1. 1.

          Factors that programme resistance to obesity must be identified

          1. Simon Langley-Evans (simon.langley-evans{at}nottingham.ac.uk), lecturer in human nutrition
          1. Department of Rural Health, University of Melbourne, PO Box 6500, Shepparton, Victoria 3630, Australia
          2. Faculty of Medical and Health Sciences, University of Auckland, Private Bag 92019, Grafton, Auckland, New Zealand
          3. Section of Reproductive and Developmental Medicine, University of Sheffield, Sheffield S10 2SF
          4. Derby City Hospital, Derby DE22 3NE
          5. Division of Gastroenterology and Nutrition, Children's Hospital of Philadelphia, Philadelphia, PA 19104-4399, USA
          6. Department of Medicine, University of Auckland, Auckland 1001, New Zealand
          7. Division of Nutritional Biochemistry, University of Nottingham, School of Biosciences, Loughborough LE12 5RD

            EDITOR—In her rapid response to Law's editorial Miller states that modern trends in food production and marketing and the exceptionally effective marketing of unhealthy food are strong contributors to obesity. 1 2 Unfortunately, her argument misses another side of the story, also totally ignored by Law—namely, the plunging levels of physical activity among children and adults alike.

            Clearly, diet alone does not explain the fact that more than half of British adults are overweight or obese. The public health message promoting low fat diets has been widely accepted since the early 1980s and is now almost universally known, and yet over the same time rates of obesity have more than doubled.

            Children in the United Kingdom today are destined to become the fattest generation of adults yet seen. Fewer than 1 in 10 now walk to school, with most parents opting to use their car for the school run. In the school curriculum physical activity is less important than literacy and numeracy, as the government insists on high standards. In many primary schools children may take part in less than half an hour of organised exercise after time for changing is allowed. In leisure time children are predominantly sedentary, using computers and television for an average of five hours a day.3

            There is no strong evidence that obese children go on to become obese adults or to have an increased risk of later disease related to obesity.4 Clearly, though, establishing a sedentary habit in the developing years will increase the chances that the same patterns of behaviour will persist into adulthood. Given that most adults are now in non-manual, sedentary occupations, the low levels of energy expenditure associated with preferred leisure activities will surely lead to a further progression of the current epidemic of obesity.

            Interest in the relation between early life events and later health is clearly important to public health. With regard to obesity, however, it is more imperative to study the lifestyle behaviours of families prone to obesity than to look for possible biological explanations. Attempts to establish associations between fetal life and long term body composition would be better directed at identifying factors that programme resistance to obesity and offer some hope for reversing current trends.

            References

            1. 1.
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