C H APTER 4
Fetal and Infant Origins
of Obesity
Key points
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CASE STUDIES
Case study 1
SB, a 29-year-old woman with a BMI of 31 kg/m2, consults you after being recently
diagnosed with GDM. She asks whether this could have an effect on her baby’s risk of
obesity or diabetes.
Practical Manual of Clinical Obesity, First Edition. Robert Kushner, Victor Lawrence
and Sudhesh Kumar.
© 2013 John Wiley & Sons, Ltd. Published 2013 by John Wiley & Sons, Ltd.
33
34 Part 1: The Biology of Obesity—Why It Occurs
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Case study 2
CM, a 24-year-old woman with a strong family history of obesity and diabetes, has
recently had her first pregnancy confirmed with an estimated gestation of 7 weeks.
Her BMI is 27.3 kg/m. She asks if there is anything she can do during pregnancy and
early infancy to reduce her child’s risk of becoming obese and/or developing diabetes
later in life
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Introduction
Although the diagnosis and management of obesity in childhood is outside
the remit of this discussion, it is increasingly clear that events before con-
ception, during pregnancy, and in very early infant life have lasting effects
on body composition. It is therefore important to have some understanding
of the practical and methodological issues inherent in assessing and
defining obesity in early childhood and in linking such anthropomorphic
data to events later on in life. Genetic factors are discussed elsewhere; the
focus of the present chapter is on the pre-natal, intra-uterine, infant, and
childhood environmental determinants of obesity. The major current
conceptual frameworks of “life course” and “developmental origins” are
discussed.
Chapter 4: Fetal and Infant Origins of Obesity 35
Measurement
As with adults, BMI is a convenient measure of obesity in children but has
drawbacks of being poorly applicable to children under the age of 2, largely
due to difficulties inherent in accurate length/height measurement in
young children (with a tendency to over-estimate) and in poor correla-
tions with adiposity particularly at the lower percentiles of BMI. Under the
age of 2 years, Centre for Disease Control (CDC) or World Health
Organization (WHO) weight-for-length charts are commonly used, with
overweight and obesity being defined in those exceeding the 85th and
95th percentiles, respectively.
In research practice, measures of body composition may be preferable.
Dual-energy X-ray absorptiometry (DEXA) and PEA POD (infant-sized air-
displacement plethysmograph) techniques may be used, although DEXA is
constrained by the need to administer a small dose of radiation. Skinfold
thickness measurement is safe and convenient and, in well-trained hands,
gives a reasonable estimate of body fat content. Bioimpedance measure-
ments are not accurate in very young children.
Conceptual framework of early origins of obesity
The two most prevalent conceptual frameworks linking environmental
events early in life to later obesity and its complications are the so-called “Life
Course” and developmental origins theories, which are introduced as follows.
Life course approach to chronic diseases
This theory holds that external (environmental) factors act in the pre-
conceptual, pre-natal, infant, and childhood phases of development. These
factors interact and have different importance at different stages of
development. “Programming” is said to exist when a particular factor
exerts its influence at a critical or sensitive developmental stage and leads
to lasting or permanent consequences, for example, maternal GDM. “Risk”
accrues when a particular factor is present over a longer time frame, for
example, chronic exposure to elevated serum lipid concentrations risks
later predisposition to atherosclerosis.
Developmental origins of health and disease (DOHaD)
The DOHaD theory focuses on the pre-natal period and early infancy and is
concerned with exposures that are complete by the first years of life. Later
factors only modify the trajectories set by the earlier events. An example of
this conceptualization is the increased cardiovascular risk of low-birth-
weight infants, often referred to as the “thrifty phenotype hypothesis.”
36 Part 1: The Biology of Obesity—Why It Occurs
Modifiable developmental disease determinants
Experimental data relating early events to the later development of disease
(e.g., by uterine artery ligation to cause fetal malnutrition) are difficult to
obtain in humans for obvious reasons, and prospective cohort data may
take many years to obtain even if the right questions were asked and the
correct data stored. Observational data suffer from confoundment and
may be difficult to interpret. Nevertheless, despite all these limitations, it is
becoming increasingly possible to identify a number of modifiable devel-
opmental disease determinants and advise patients and populations
accordingly. These have been summarized in a recent workshop report—
“Influence of Pregnancy Weight on Maternal and Child Health: Workshop
Report”—from the Institute of Medicine (IOM) and National Research
Council (see Key web links), and some of these are now discussed.
Pre-natal modifiable determinants
Modifiable factors acting in utero include the following:
1 High maternal pre-pregnancy BMI and gestational weight gain are both
associated with childhood overweight. Recommendations for maternal
gestational weight gain dependent on pre-pregnancy BMI have recently
been produced by the IOM (see Table 4.1 and Key web links).
2 Fetal nutrition (dependent on maternal nutrition, uterine blood flow,
and other factors).
3 Maternal smoking (50% increased adjusted odds ratio for obesity in
affected offspring).
4 GDM (a possible factor in the amplification of the obesity epidemic: maternal
obesity leading to fetal macrosomia and late effects including increased fetal
risk of obesity and diabetes mellitus). Gestational diabetes risk is known to
be reduced with appropriate exercise before and during early pregnancy
and with limitation of pregnancy-associated weight gain. The adverse fetal
effects of maternal GDM are known to be reduced by diagnosis and appro-
priate management of the condition. The risk of the mother going on to
develop T2DM may be reduced by appropriate dietary counseling and
Table 4.1 Recommendations for maternal gestational weight gain dependent on
pre-pregnancy BMI as recommended by the IOM
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Chapter 4: Fetal and Infant Origins of Obesity 37
exercise programs, and pharmacotherapy, for example, with metformin,
may be considered alongside these interventions. Testing for the condition
6 weeks after delivery and annually thereafter for life is generally advised.
Post-natal modifiable determinants
1 Infant growth (specifically weight gain in excess of linear growth). Increased
obesity risk has been shown in one study even when excessive growth
occurred in just the first week of life in formula-fed infants, including
those showing “catch-up growth.” However, it is important to add that
other studies have been conflicting in this regard and on present evi-
dence, the well-established benefits, for example, in neuro-cognitive
outcomes of pre-term infants who achieve rapid catch-up growth should
not be denied them on the basis of a putative risk of later obesity.
2 Infant nutrition. Breastfeeding has been shown in one study to reduce
obesity by 4% for each month of breastfeeding with a total possible risk
reduction of 13–22%. However, this finding appears limited to a White
US population, and other studies have shown conflicting results.
Nevertheless, it appears reasonable on the basis of current data to con-
clude that breastfeeding does not increase the risk of later developing
obesity and may perhaps reduce it. There is some evidence that failure
to initiate or to sustain breastfeeding may be associated with raised pre-
pregnancy BMI and excessive gestational weight gain, although whether
this association is causal is unclear.
3 Sleep duration. In adults, reduced sleep correlates with increased obesity
risk. In infants, sleeping for less than 12 h a day doubles the obesity risk
of the child at 3 years.
Combination of pre- and post-natal factors
Combinations of
1 smoking
2 greater maternal weight increase during pregnancy
3 breastfeeding duration, and
4 infant sleep
have been proven in one study to be a powerful predictor of later obesity,
conferring an absolute risk of 6% with optimal levels of all factors and
29% with adverse levels of all risks, with a continuum of risk in between
these two extremes, as depicted in Figure 4.1.
Summary
Events taking place during pregnancy and in early childhood may act
either at a critical point in development or over a period of time to change
38 Part 1: The Biology of Obesity—Why It Occurs
0.50
Probability of obesity
0.40
0.30
0.20
0.10
0.00
Combinations of four risk factors
Smoking – – – + – – + – + – + + – + + +
Gest. weight gain – + – – – + + + – – – + + + – +
Breastfeeding – – + – – + – – + + – + + – + +
Sleep – – – – + – – + – + + – + + + +
Probability 0.06 0.08 0.09 0.10 0.11 0.12 0.13 0.14 0.15 0.16 0.17 0.19 0.20 0.22 0.24 0.29
Prevalence in Project Viva
8.7% 7.9% 23.5% 0.2% 5.0% 22.8% 0.2% 4.7% 1.7% 8.7% 0.3% 4.2% 8.8% 0.3% 1.5% 1.4%
Figure 4.1 Predicted probability of obesity (BMI greater than 95th percentile) at
3 years of age for 16 combinations of 4 modifiable risk factors during pregnancy
and infancy. Bars show 95% confidence limits. Also shown is prevalence for each
depicted combination of factors among 1110 mother–child pairs participating in
Project Viva. Probabilities are adjusted for maternal education and BMI, household
income, and child race/ethnicity. Reproduced from Kopelman et al. (eds) (2010)
Clinical Obesity in Adults and Children, 3rd edn, Blackwell Publishing, Oxford, with
permission from Blackwell Publishing.
susceptibility to later obesity and its associated metabolic disorders. Some
of these influences (e.g., maternal body weight, smoking, infant feeding,
diagnosis and management of GDM) are modifiable and some (e.g., some
gene–environment interactions) may not be. Increased understanding of
the developmental origins of disease will pave the way for better individual-
and population-based strategies for harm reduction and has the potential
to break the cycle through which the consequences of obesity may be
passed on to future generations.
Pitfalls
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Chapter 4: Fetal and Infant Origins of Obesity 39
Key web links
Institute of Medicine Report. [Link]
[Link]
[accessed on December 29, 2012].
Institute of Medicine Report. [Link]
[Link] [accessed on December 29, 2012].
National Institute for Health and Clinical Excellence. Guideline for the management of
diabetes in pregnancy from preconception to the postnatal period. [Link]
[Link]/CG063fullguideline [accessed on December 29, 2012].
Centre for Maternal and Child Enquiries and the Royal College of Obstetricians and
Gynaecologists Guideline ‘Management of Women with Obesity in Pregnancy’. http://
[Link]/files/rcog-corp/CMACERCOGJointGuidelineManagementWomen
[Link] [accessed on December 29, 2012].
Further reading
Calkins, K. & Devaskar, S.U. (2011) Fetal origins of adult disease. Current Problems in
Pediatric and Adolescent Health Care, 41, 158–176.
McMillen, I.C., Rattanatray, L., Duffield, J.A. et al. (2009) The early origins of later obe-
sity: Pathways and mechanisms. Advances in Experimental Medicine and Biology, 646,
71–81.
Muhlhausler, B.S. & Ong, Z.Y. (2011) The fetal origins of obesity: Early origins of altered
food intake. Endocrine, Metabolic & Immune Disorders Drug Targets, 11, 189–197.
Ong, K.K. (2010) Early determinants of obesity. Endocrine Development, 19, 53–61.
Stocker, C.J., Arch, J.R. & Cawthorne, M.A. (2005) Fetal origins of insulin resistance and
obesity. Proceedings of the Nutrition Society, 64, 143–151.
Wax, J.R. (2009) Risks and management of obesity in pregnancy: Current controversies.
Current Opinion in Obstetrics & Gynecology, 21, 117–123.