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Anthropometric measures in middle age after exposure to famine during gestation: Evidence from the Dutch famine

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Few studies in humans have related maternal undernutrition to the size of the adult offspring. The objective was to assess whether reductions in food intake by pregnant women during the Dutch famine of 1944-1945 were related to offspring length, weight, and indexes of adiposity in middle age. We recruited 1) exposed persons born in western Netherlands between January 1945 and March 1946 whose mothers experienced famine during or immediately preceding pregnancy, 2) unexposed persons born in the same 3 institutions during 1943 or 1947 whose mothers did not experience famine during this pregnancy, and 3) unexposed same-sex siblings of persons in series 1 or 2. Anthropometric measurements (n = 427 males and 529 females) were obtained between 2003 and 2005. We defined 4 windows of gestational exposure (by ordinal weeks 1-10, 11-20, 21-30, and 31 through delivery) on the basis of exposure to a ration of <900 kcal/d during the whole 10-wk interval. Exposure to reduced rations was associated with increased weight and greater indexes of fat deposition at several tissue sites in women but not in men (P for interaction <0.01). Measures of length and linear proportion were not associated with exposure to famine. Reduced food availability may lead to increased adiposity later in life in female offspring.
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Anthropometric measures in middle age after exposure to famine
during gestation: evidence from the Dutch famine
14
Aryeh D Stein, Henry S Kahn, Andrew Rundle, Patricia A Zybert, Karin van der Pal– de Bruin, and LH Lumey
ABSTRACT
Background: Few studies in humans have related maternal under-
nutrition to the size of the adult offspring.
Objective: The objective was to assess whether reductions in food
intake by pregnant women during the Dutch famine of 1944 –1945
were related to offspring length, weight, and indexes of adiposity in
middle age.
Design: We recruited 1) exposed persons born in western Nether-
lands between January 1945 and March 1946 whose mothers expe-
rienced famine during or immediately preceding pregnancy, 2) un-
exposed persons born in the same 3 institutions during 1943 or 1947
whose mothers did not experience famine during this pregnancy, and
3) unexposed same-sex siblings of persons in series 1 or 2. Anthro-
pometric measurements (n ҃ 427 males and 529 females) were
obtained between 2003 and 2005. We defined 4 windows of gesta-
tional exposure (by ordinal weeks 1–10, 11–20, 21–30, and 31
through delivery) on the basis of exposure to a ration of 900 kcal/d
during the whole 10-wk interval.
Results: Exposure to reduced rations was associated with increased
weight and greater indexes of fat deposition at several tissue sites in
women but not in men (P for interaction 0.01). Measures of length
and linear proportion were not associated with exposure to famine.
Conclusion: Reduced food availability may lead to increased adi-
posity later in life in female offspring. Am J Clin Nutr 2007;85:
869 –76.
KEY WORDS Anthropometric measures, body composition,
body mass index, body size, famine, maternal and infant health,
Netherlands, nutrition, obesity
INTRODUCTION
Adult body mass is a function of height, girth, and tissue mass
and distribution. Each of these measures has independent asso-
ciations with risk of disease and may have specific associations
with early development. Attained height, which is inversely as-
sociated with risk of cardiovascular disease (1), is strongly as-
sociated with birth length (2). Variations in body proportions,
such as the ratio of the leg to trunk lengths, may have their origin
in childhood (3) and are independent predictors of the risk of later
morbidity and mortality (4). Little is known about the role, if any,
of prenatal nutrition in the ontogeny of body proportions.
Birth weight, especially when adjusted for birth length, is
positively associated with measures of body size in later life (2).
Even so, and despite the consistent association between adult
overweight and type 2 diabetes or cardiovascular disease (5), an
increased birth weight is also associated with a decreased risk of
major chronic diseases (6). An explanation for this apparent
paradox might come from information on the sources of variation
in size at birth (7), but few studies of humans can document the
complex relations extending from maternal nutrition through
fetal development and risk of adult disease.
The Dutch famine of 1944 –1945 provides a rare opportunity
to study the long-term consequences of maternal undernutrition
in defined stages of gestation (8, 9). The Dutch famine affected
the western Netherlands (10 –12). Official rations, which by the
end of the famine consisted almost exclusively of bread and
potatoes, fell below 900 kcal/d by 26 November 1944 and were
as low as 500 kcal/d by April 1945. The famine ceased immedi-
ately after liberation. This extraordinary period of deprivation
affected fertility, weight gain during pregnancy, maternal blood
pressure, and infant size at birth (13–15). The reduction in fer-
tility was greater among manual than among nonmanual occu-
pational classes (8). The decline in mean birth weight of 300 g
was restricted to exposure to maternal undernutrition during the
third trimester (16, 17).
An earlier investigation of Dutch men aged 19 y found a
doubling of the prevalence of overweight with maternal exposure
to famine in midgestation (18). A second study, with data col-
lected when the famine-exposed birth cohort was aged 50 y,
reported increased body mass index (BMI; in kg/m
2
) in women
(but not in men) who were exposed to famine in early gestation
(19). To date, no studies have reported on other anthropometric
indexes of adiposity after gestation during the Dutch famine. The
present study was conducted to replicate the earlier findings,
extend follow-up through age 59 y, and analyze a wider array of
measures of tissue distribution. We also accounted statistically
1
From the Rollins School of Public Health, Emory University, Atlanta,
GA (ADS); the Division of Diabetes Translation, Centers for Disease Control
and Prevention, Atlanta, GA (HSK); the Mailman School of Public Health,
Columbia University, New York, NY (AR, PAZ, and LHL); and TNO Qual-
ity of Life, Leiden, Netherlands (KvdP).
2
The findings and conclusions in this report are those of the authors and do
not necessarily represent the views of the Centers for Disease Control and
Prevention.
3
Supported by grant RO1 HL067914 (Principal Investigator: LHL), Na-
tional Institutes of Health, Bethesda, MD.
4
Address reprint requests to LH Lumey, Department of Epidemiology,
Mailman School of Public Health, 722 West 168th Street, New York, NY
10032. E-mail: lumey@columbia.edu.
Received July 6, 2006.
Accepted for publication October 12, 2006.
869Am J Clin Nutr 2007;85:869 –76. Printed in USA. © 2007 American Society for Nutrition
by guest on May 14, 2011www.ajcn.orgDownloaded from
for familial determinants of growth and tissue distribution by
including same-sex siblings as control subjects.
SUBJECTS AND METHODS
Population source and tracing
We identified 3307 live singleton births (probands) at 3 insti-
tutions in famine-exposed cities (midwifery training schools in
Amsterdam and Rotterdam and the university hospital in Leiden)
in 1945 and early 1946 (100% sample) and in 1943 and 1947 (the
first 30 births/mo across the 3 institutions). At the time of the
famine, a large majority of deliveries (70%) in the Netherlands
were scheduled to occur at home. The client mix at the 2 mid-
wifery training schools consisted of low-risk pregnancies of
women of lower socioeconomic status whose home environment
was unsuitable for delivery. The client mix in Leiden included
such deliveries as well as women with higher-risk pregnancies
identified during prenatal care and emergency admissions
after complications of home labor. We extracted personal
identifiers, including name and maternal address, birth
weight, and other information from the admission logs and
delivery progress charts.
To trace the adult offspring, we provided the names and ad-
dresses at birth of all 3307 persons to the population register in
the municipality of birth. Of these named persons, 308 (9.3%)
were reported to have died and 275 (8.3%) to have migrated. For
294 persons (8.9%) a current address could not be located, and
the population registry in Rotterdam declined to trace 130 per-
sons born out of wedlock. Thus, a current address was obtained
for 2300 persons (70% of the institutional birth cohort).
Recruitment and examination
Traced persons were mailed a letter of invitation signed by the
current director of the institution in which they were born, a
brochure describing the study, and a response card. We mailed
one reminder letter to nonresponders. Initially, our study design
called for the recruitment of same-sex sibling pairs; hence, the
lack of an available sibling was a reason for ineligibility. We
received some reply from 1767 persons, of whom 347 (19.6%)
expressed willingness to participate together with a sibling. Of
those who declined, 67% reported not having a same-sex sibling
available for study. To increase the overall number of partici-
pants, therefore, we attempted to enroll persons who had indi-
cated ineligibility because of the lack of an available sibling.
We conducted a telephone interview, which was followed by
a clinical examination at the Leiden University Medical Center.
Most of the clinical examinations were conducted within 6 wk of
the telephone interview. All study protocols were approved by
the human subjects committees of the participating institutions,
and participants provided verbal consent at the start of the tele-
phone interview and written informed consent at the start of the
clinical examination. We obtained anthropometric measurements
from 971 subjects (437 men and 534 women): 311 proband-sibling
pairs, 2 siblings whose matching proband did not complete the
clinical examination, and 347 additional probands.
Anthropometric measures
All anthropometric measures were obtained by experienced
research nurses, who were provided specific training in the meth-
ods by one of us (HSK); only trivial differences in means or in the
variability of measures across nurses were observed. Weight was
obtained to the nearest 100 g with the participant standing on a
portable digital scale (SECA, Hamburg, Germany). Standing
height was measured to the nearest 1 mm with a portable stadi-
ometer (SECA), and seated height was obtained to the nearest 1
mm with the participant seated on a hard stool of known height
with the use of the same stadiometer. Right arm length (tip of
acromion to the distal tip of the third metacarpal bone) and waist
(at level of iliac crests, intersection with midaxillary line), hip
(buttocks at the point of maximum extension), and right midthigh
(supine with hip flexed at 45 °, between lateral inguinal crease
and proximal patella) circumferences were obtained to the near-
est 1 mm with the use of a nonextensible measuring tape
(Hoechstmass, Sulzbach, Germany). The supine sagittal abdom-
inal diameter (SAD) at the level of the iliac crests was obtained
to the nearest 1 mm with a sliding-beam caliper (Holtain, Dyfed,
Wales, United Kingdom). Tricipital, subscapular, and anterior
midthigh skinfold thicknesses were obtained to the nearest 0.2
mm with calipers with a maximal spread of 40 mm (Holtain).
These calipers were calibrated daily. A single measurement was
taken for height and weight. Two measurements were taken for
other anthropometric outcomes, and the mean was used for the
analysis. To ensure independence of the replicate measures, all
markings of measurement points were erased before the second
measure was obtained. If the first 2 measurements were not
sufficiently close (arm length, waist circumference, midthigh
circumference 1.0 cm; sagittal abdominal diameter 0.5 cm; sub-
scapular or triceps skinfold thickness 2.0 mm) a third and fourth
measure were taken and the 3 measures closest together from the
4 available measures were averaged.
Derived measures
Trunk length was calculated by subtracting the height of the
stool from seated height, and leg length was obtained by sub-
tracting trunk length from standing height. As indexes of body
proportion, we computed the ratios of the right arm to leg lengths
and the leg to trunk lengths. We computed the BMI. As additional
indexes of mass distribution, we computed the ratios of waist-
to-hip circumference, waist-to-midthigh circumference, and
SAD-to-midthigh circumference. We excluded from the analysis
individuals for whom any of the above anthropometric measures
were missing (n ҃ 12), for whom the ratio of trunk to leg length
exceeded 1.10 (n ҃ 2), and one man with polio-related atrophy
of a lower limb; the analytic sample consisted of 956 subjects.
Because several of the participants had one or more skinfold
thicknesses that exceeded the capacity of the calipers, we cate-
gorized the skinfold thicknesses into empirical quartiles. We
then developed a 3-level indicator of the relative distribution of
subcutaneous fat between the triceps and subscapular regions by
cross-tabulating the quartile distributions for these 2 regions. We
coded this indicator as Ҁ1 if the triceps value was in a higher
quartile of the distribution than was the subscapular value, as ѿ1
if the reverse was true, and 0 if both were in the same quartile.
Categorizing exposure to famine
We defined the start of each gestation by the date of the moth-
er’s last menstrual period (LMP), as noted in the original prenatal
record, unless it was missing or the resulting gestational age was
implausible (12.4%). In these cases, we approximated the date of
LMP from the unambiguous date of birth and estimates of ges-
tational age recorded on the birth record or from a gestational age
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estimate based on sex- and parity-specific birth weights of sin-
gleton live births at the Amsterdam midwives school and the
University of Amsterdam Department of Obstetrics between
1931 and 1965 at each gestation between 24 and 46 wk (20).
We characterized exposure to famine during gestation by de-
termining the weeks after the LMP during which the mother was
exposed to an official ration of 900 kcal/d (the 24 wk included
the period from 26 November 1944 to 12 May 1945). We defined
the mother as exposed in specific periods if gestational weeks
1–10, 11–20, 21–30, or 31 to delivery were entirely included in
this time window. Thus, pregnancies with an LMP between 26
November 1944 and 4 March 1945 (n ҃ 74) were considered
exposed in weeks 1–10, between 18 September 1944 and 24
December 1944 (n ҃ 124) exposed in weeks 11–20, between 10
July 1944 and 15 October 1944 (n ҃ 140) exposed between
weeks 21–30, and between 2 May 1944 and 24 August 1944
(n ҃ 128) exposed between week 31 and delivery. Because these
time windows overlap, the participants could be considered ex-
posed during one or (at most) two 10-wk periods; those exposed
in at least one 10-week period (n ҃ 350) were considered to have
some exposure to famine. In this formulation, the estimate for
the variable “any exposure to famine” is not necessarily an av-
erage of the estimates for the four 10-wk periods, because these
may have independent and additive or counteractive associa-
tions with adult size.
Statistical methods
We computed means and SDs or categorical distributions, as
appropriate. We developed independent linear regression mod-
els for all models that did not include skinfold thicknesses. Skin-
fold thicknesses and their ratios were analyzed by using logistic
regression, with the highest category compared against all others.
Because humans are sexually dimorphic and previous research
has identified associations of famine with body composition in
one or the other sex (18, 19), we tested for heterogeneity of
associations by sex using F tests. We considered a P value 0.10
to indicate an interaction and conducted sex-stratified analyses
where indicated.
We considered a set of models and regressed each outcome
variable separately on exposure to famine. Exposure to famine
was characterized by using an indicator for any gestational ex-
posure, with the reference category being no exposure, and by
using the four 10-wk intervals described, which we entered as a
set of 4 indicator variables. We used the combined population of
control subjects (unexposed births in the 3 hospitals: n ҃ 296;
siblings of the birth series: n ҃ 310) as the reference, and we
adjusted for age at examination. We used the xtreg and xtlogit
commands in STATA 8 (Stata Corp, College Station, TX) to
control for clustering within families. We assessed whether as-
sociations with exposure to famine were mediated through birth
weight or length by entering these terms and comparing the
changes in coefficients. These analyses were run on the institu-
tional birth series alone (birth weight: n ҃ 297 men and 348
women; birth length: n ҃ 278 men and 325 women; we lacked
information on size at birth for the sibling control subjects).
Estimates of the effect of exposure to famine were similar in
models that included the birth series and those that included the
birth series and the siblings.
We examined whether measurement error in seated height
because of excess adiposity in the buttocks might affect relations
by adding hip circumference to the relevant models. In practice,
this adjustment had no effect on any observed associations (data
not shown), and models without this adjustment are presented.
Models for circumferences, the SAD, and their resulting ratio
measures included a term for standing height to account for
allometric scaling; we also tested whether these associations
were affected by body proportion by including a term for the
leg-to-trunk ratio. Although the outcome measures were gener-
ally associated with both height and the leg-to-trunk ratio, addi-
tion of these terms did not alter the observed associations be-
tween the measures and exposure to famine (data not shown), and
we present results without this adjustment. Models for indexes of
mass distribution included adjustment terms describing adult
measures that might be causally related to adiposity, including
smoking status, intake of alcohol, intake of energy as estimated
from a food-frequency questionnaire, physical activity level in
the year before the examination as assessed by the SQUASH
questionnaire (21), and, for women, parity. In practice, control
for these factors did not affect the estimates (data not shown). We
did not consider these variables relevant for analyses of lengths
and body proportion because these outcomes are established by
early adulthood.
RESULTS
Differences between traced and untraced persons
The proportion of participants identified as deceased was
highest among probands born in 1943 (10.4%) and lowest among
probands born in 1947 (6.0%). Status as an emigrant or other
reasons why a current address was not found did not differ by
year of birth or period of exposure to famine. When we compared
the birth records of participants traced to a current address with
those who had either died, emigrated, or had not been located we
found no clinically significant differences in mean birth weight
(3350 compared with 3314 g) or length (50.4 compared with
50.2 cm), placental weight (601 compared with 592 g), maternal
age at delivery (28.2 compared with 27.4 y), or birth order (2.3
compared with 2.3).
Differences between interviewed and noninterviewed
persons
Of the 2300 persons who were invited to join the study, we
found no significant differences between those interviewed to
those who were not interviewed in mean birth weight (3374
compared with 3339 g) or length (50.5 compared with 50.3 cm),
placental weight (600 compared with 601 g), maternal age at
delivery (28.6 compared with 28.1 y), or birth order (2.4 com-
pared with 2.2). The response to our invitation, however, was
lower for those born in 1947 (25%) than in all others (35%).
Eleven percent of those who were interviewed lived within 5 km
of the examination site compared with 10% of those who were
not interviewed, and 34% of those interviewed lived 45 km
from the examination site compared with 29% of those who were
not interviewed.
Final sample for analysis
We analyzed anthropometric data (except for skinfold thick-
nesses) from 956 persons. On the basis of their behavior and
anthropometric measures, these persons appeared unremarkable
for Dutch populations of this age (Table 1 and Table 2).
ANTHROPOMETRIC MEASURES AFTER MATERNAL UNDERNUTRITION 871
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Exposure to famine and measures of length and body
proportions
There was no evidence of a statistical interaction by sex in the
association of maternal exposure to famine with measures of
offspring length or their ratios (data not shown). There was no
overall association between exposure to famine and these mea-
sures when famine was considered as a whole (Table 3); when
considered as 4 periods of gestation, the ratio of the arm to leg
lengths showed gestation-period—specific associations, which
increased (P 0.10) after exposure in weeks 21–30 and de-
creased (P 0.05) after exposure in weeks 31 through delivery.
Exposure to famine and indexes of mass and mass
distribution
Strong statistical evidence for interaction by sex in the asso-
ciation of any famine exposure was found for all indexes of mass
distribution (P for heterogeneity 0.001) except waist-to-hip
ratio. For men, no association between any exposure to famine
and any index was found, whether considered individually or
when the 4 periods were considered as a group (Table 4; P 0.10
for all). In contrast, all the indexes were elevated in women
exposed to famine (P 0.05 for all, except the waist-to-hip ratio,
for which P 0.10) (Table 5); when the 4 periods of exposure
were considered as a group, the associations were significant
(P 0.01) for all measures, except the ratios of the waist-to-hip
circumferences and waist to midthigh circumferences (P 0.05
for both). Inspection of the period-specific estimates suggested
similarities between men and women for the estimates for expo-
sure in gestational weeks 1–10 and substantial divergence be-
tween men and women in the estimates for exposures in later
10-wk periods.
Skinfold thicknesses
In sex-pooled analyses (Table 6), the odds of being in the
highest quartile of the subscapular skinfold thickness and the
ratio of the subscapular to tricipital skinfold thickness were mod-
estly elevated with any exposure to famine (P 0.10). The test
for interaction by sex was not significant (P 0.10 in age-
adjusted models) for any skinfold thickness. There was no strong
indication of association with specific periods of exposure to
famine.
Analyses on birth series alone
We repeated all analyses using the 645 participants with mea-
sures of birth weight and the 603 participants with measures of
birth length. Results were very consistent with those reported for
the whole sample (data not shown). In these groups, the results
did not change when birth weight or birth length were included
in the model (data not shown).
DISCUSSION
In a follow-up study of persons exposed during gestation to the
Dutch famine of 1944 –1945, we observed that maternal expo-
sure to acute famine is associated with increases in several in-
dexes of body mass and mass distribution among female off-
spring at age 59 y. We did not observe any strong independent
association of prenatal exposure to famine with adult lengths or
body proportions.
The circumstances of the Dutch famine provide a model to test
for isolated effects of undernutrition at defined stages of devel-
opment and do not speak to the situation in which inadequate
prenatal nutrition is followed by continued undernutrition, as
TABLE 1
Selected characteristics of Dutch men and women examined between 2003 and 2005
Exposed to famine during
gestation (n ҃ 350)
Time control subjects
1
(n ҃ 296)
Sibling control subjects
(n ҃ 310) P
2
Sex (% male) 45.7 46.3 41.9 NS
Age (y) 58.9 0.49
3
58.8 1.57 57.3 6.30 0.01
Birth weight (kg)
4
3.30 0.51 3.45 0.49 0.01
Birth length (cm)
4
50.3 2.3 50.8 2.2 0.05
Energy intake (kcal/d) 2247 625 2209 649 2163 630 NS
Physical activity score
5
7230 4268 7871 4936 7182 3720 NS
Current smoker (%) 25.5 24.0 22.3 NS
Alcohol consumption (%) NS
1 drink/wk 20.1 25.0 26.5
1–7 drinks/wk 37.9 33.5 31.3
8–14 drinks/wk 16.9 22.0 19.3
15–21 drinks/wk 15.5 12.2 12.9
21 drinks/wk 9.5 7.4 10.0
Number of children (%) NS
0 10.3 13.9 14.2
1 16.9 14.5 11.6
2 56.6 53.7 52.3
3 16.3 18.0 22.0
1
Born in the same institution and not exposed to famine during gestation.
2
ANOVA or chi-square test as appropriate for comparison between categories.
3
x SD (all such values).
4
Birth series only; siblings excluded.
5
Calculated from intensity of activity by reported average duration and frequency.
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was until recently common in many developing countries. Ex-
posure to famine, as we defined it in relation to official rations, is
an ecologic measure of undernutrition; we lacked individual
dietary intake data. However, evidence of the severity of the
famine was abundant, including evidence that during the height
of the famine pregnant women actually lost weight over the second
half of their pregnancy (15). Thus, our data support the notion that
maternal undernutrition in gestation, if postnatal nutrition and in-
fections are not limiting, neither programs a person for an altered
trajectory of linear growth if it occurs in early pregnancy nor results
in unrecoverable deficits in attained length if it occurs later in ges-
tation. In women, however, the prenatal deprivation appears to have
been associated with increased weight in middle age, with more of
the increased mass deposited centrally.
Two earlier studies of persons exposed to the Dutch famine in
utero have yielded mixed results. Among men examined at age
18 y, the absolute risk of obesity (defined as 120% of the ideal
weight for height according to the Metropolitan Life Insurance
Company tables) was elevated from 1.5% to 2.8% with exposure
in midgestation (18). Our study lacked the power to detect an
effect of that small a magnitude. A study similar in design to ours
found an elevated BMI in women aged 50 y whose mothers were
exposed to the famine early in gestation, but there was no asso-
ciation with other periods of exposure to famine or among men
(19). Our results are broadly consistent with that study insofar as
we also observed a marked difference in associations between
men and women, but we did not identify early gestation as being
the critical window for effects in adulthood. A third study of the
consequences of exposure to famine, conducted among survivors
of the siege of Leningrad, did not suggest any difference in BMI
between those born before the siege commenced, born during the
siege, or born in an area not subject to the siege (22). That study
was unable to assess the timing of exposure to maternal under-
nutrition because the Leningrad siege lasted 2 y. All of the
earlier studies considered only weight and height; we examined
a wider range of anthropometric dimensions and indexes. We
observed some suggestion that the heterogeneity of associations
between famine exposure and adult body mass and mass distribution
between men and women is established only after the first 10-wk
period of gestation. This may reflect the increasing importance of
sex-specific growth factors in fetal development (23).
There is ongoing debate about the relative utility of the avail-
able indexes of body mass distribution in predicting risk for
chronic disease (24-26). Although BMI is widely used, it does
TABLE 2
Selected body measurements and ratios for Dutch men and women examined between 2003 and 2005, by famine exposure and sex
Men Women
Exposed to
famine during
gestation (n ҃ 160)
Time control
subjects
1
(n ҃ 137)
Sibling control
subjects
(n ҃ 130)
Exposed to famine
during gestation
(n ҃ 190)
Time control
subjects
1
(n ҃ 159)
Sibling control
subjects
(n ҃ 180)
Height (cm) 177.4 6.2
2
178.3 6.3 178.9 5.7 165.4 6.6 165.4 6.3 166.5 6.9
Trunk length (cm) 92.6 3.2 93.0 3.2 93.5 3.2 87.0 3.3 86.8 3.1 87.4 3.4
Leg length (cm) 84.7 4.3 85.3 4.2 85.5 4.1 78.4 4.2 78.6 4.5 79.1 4.6
Arm length (cm) 66.8 3.3 67.0 3.7 67.1 2.9 61.6 3.3 61.8 3.4 62.3 3.7
Ratio of arm to leg lengths
(҂ 100)
78.9 3.1 78.6 3.0 78.6 3.0 78.6 2.9 78.6 2.5 78.8 3.3
Ratio of leg to trunk lengths
(҂ 100)
91.5 4.5 91.7 4.2 91.5 4.7 90.1 4.2 90.7 5.2 90.6 4.8
Weight (kg) 87.6 12.1 88.8 13.4 86.0 11.6 78.7 14.9 73.6 13.4 75.3 14.1
Waist circumference (cm) 100.5 10.1 101.4 10.5 98.4 9.1 99.0 11.9 93.9 11.1 94.7 12.0
Hip circumference (cm) 102.7 6.6 103.1 6.9 101.0 5.7 108.9 12.4 104.3 9.7 105.1 10.0
Supine sagittal abdominal
diameter (cm)
23.8 3.0 23.9 3.3 23.1 2.8 23.2 3.7 21.6 3.4 21.7 3.5
BMI (kg/m
2
)
27.8 3.6 27.9 4.0 26.8 3.3 28.8 5.7 26.9 4.5 27.1 4.8
Midthigh circumference
(cm)
52.1 3.8 52.5 4.1 51.8 4.0 53.4 6.5 51.4 5.3 52.5 5.3
Ratio of waist to hip
circumferences (҂ 100)
97.7 5.5 98.3 5.5 97.3 5.7 91.0 5.4 89.9 5.8 90.0 6.0
Ratio of supine sagittal
abdominal diameter to
midthigh circumference
(҂ 100)
45.6 4.8 45.5 4.7 44.6 5.0 43.4 4.8 42.1 4.8 41.4 5.5
Ratio of waist to midthigh
circumferences (҂ 10)
19.3 1.5 19.3 1.5 19.0 1.7 18.6 1.7 18.3 1.6 18.1 1.9
Subscapular skinfold
thickness (mm)
3,4
21.0 8.3 [151] 19.0 10.3 [136] 18.7 9.6 23.1 12.0 [189] 20.6 10.7 [151] 21.4 12.0 [172]
Triceps skinfold thickness
(mm)
4
12.9 4.3 13.0 6.6 13.8 7.1 23.2 10.5 [185] 22.2 8.6 [151] 22.9 9.1 [172]
Anterior midthigh skinfold
thickness (mm)
4
14.2 7.5 [145] 15.4 12.1 [127] 15.4 7.5 [118] 31.7 앐쏜16.1 [130]
5
27.4 15.9 [105] 30.0 14.1 [135]
1
Born in the same institution and not exposed to famine during gestation.
2
x SD (all such values).
3
Sample sizes for skinfold thicknesses include subjects in whom skinfold thicknesses were measured but for whom the skinfold thickness exceeded the
caliper capacity.
4
All values are medians and interquartile intervals; n in brackets.
5
The 75th percentile for this group exceeded the maximum caliper capacity of 40 mm. The 25th percentile was 23.9 mm.
ANTHROPOMETRIC MEASURES AFTER MATERNAL UNDERNUTRITION 873
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not differentiate between lean and fat tissue. The ratio of the
subscapular and tricipital skinfold thicknesses, a widely used
index of the distribution of subcutaneous fat, rather than of in-
creased visceral fat, was only weakly associated in the present
study with exposure to famine. Similarly, the waist-to-hip ratio,
a presumed correlate of ischemic heart disease (27), was mod-
estly associated with exposure in our study. We found, however,
that exposure to the famine was associated among women with
an increased ratio of SAD to the midthigh circumference—an
alternative anthropometric correlate of ischemic heart disease
(28). To date, there have been suggestions that exposure to fam-
ine in specific periods of gestation is associated with impaired
glucose tolerance (29) and with prevalent coronary heart disease
(30), inconsistently associated with blood pressure (31, 32), and
TABLE 3
Association of exposure to the Dutch famine overall or in the specified period of gestation with adult measures of length and with indexes of proportion for
956 persons examined between 2003 and 2005
1
Period of gestational exposure
Overall
(n ҃ 350)
Weeks 1–10
(n ҃ 74)
Weeks 11–20
(n ҃ 124)
Weeks 21–30
(n ҃ 140)
Week 31 to delivery
(n ҃ 128)
P
2
Estimate 95% CI Estimate 95% CI Estimate 95% CI Estimate 95% CI Estimate 95% CI
Length
Height (cm) Ҁ0.39 Ҁ1.11, 0.33 Ҁ0.30 Ҁ1.72, 1.13 Ҁ0.35 Ҁ1.51, 0.82 Ҁ1.01 Ҁ2.13, 0.11 0.51 Ҁ0.62, 1.63 NS
Trunk (cm) Ҁ0.03 Ҁ0.41, 0.35 0.11 Ҁ0.62, 0.85 Ҁ0.12 Ҁ0.73, 0.49 Ҁ0.28 Ҁ0.87, 0.30 0.17 Ҁ0.41, 0.76 NS
Leg (cm) Ҁ0.40 Ҁ0.90, 0.10 Ҁ0.47 Ҁ1.45, 0.52 Ҁ0.26 Ҁ1.07, 0.55 Ҁ0.72 Ҁ1.50, 0.06 0.29 Ҁ0.49, 1.07 NS
Arm (cm) Ҁ0.23 Ҁ0.65, 0.19 Ҁ0.41 Ҁ1.21, 0.40 Ҁ0.13 Ҁ0.80, 0.54 Ҁ0.07 Ҁ0.71, 0.57 Ҁ0.13 Ҁ0.77, 0.51 NS
Indexes of proportion
Ratio of arm to leg
lengths (҂ 100)
0.10 Ҁ0.28, 0.49 0.07 Ҁ0.65, 0.79 0.26 Ҁ0.34, 0.87 0.58 0.00, 1.16 Ҁ0.65 Ҁ1.22, Ҁ0.08 0.05
Ratio of leg to trunk
lengths (҂ 100)
Ҁ0.44 Ҁ1.00, 0.12 Ҁ0.75 Ҁ1.83, 0.34 Ҁ0.26 Ҁ1.16, 0.64 Ҁ0.53 Ҁ1.39, 0.34 0.30 Ҁ0.56, 1.17 NS
1
Values represent differences from control group (n ҃ 606). Estimates were obtained by linear regression and were adjusted for sex, age, and clustering
of siblings. Models for each specific 10-wk period of gestational exposure were also adjusted for exposure in overlapping 10-wk periods. Estimates for any
exposure may reflect additive effects of exposure in specific periods. Tests for interaction by sex were not significant (P 0.25 for each outcome).
2
Values reflect the overall test of association of all 4 periods of exposure considered as a group (Wald test, 4 df).
TABLE 4
Association of exposure to the Dutch famine overall or in the specified period of gestation with weight, circumferences, and indicators of body
composition in adulthood for 427 men measured between 2003 and 2005
1
Period of gestational exposure
Overall
(n ҃ 160)
Weeks 1–10
(n ҃ 35)
Weeks 11–20
(n ҃ 59)
Weeks 21–30
(n ҃ 69)
Week 31 to delivery
(n ҃ 59)
P
2
Estimate 95% CI Estimate 95% CI Estimate 95% CI Estimate 95% CI Estimate 95% CI
Weight and circumferences
Weight (kg) 0.98 Ҁ1.22, 3.18 3.37 Ҁ0.73, 7.46 Ҁ1.63 Ҁ5.19, 1.93 2.08 Ҁ1.31, 5.47 Ҁ1.17 Ҁ4.49, 2.16 NS
Waist circumference (cm) 0.51 Ҁ1.40, 2.42 1.82 Ҁ1.73, 5.37 Ҁ1.28 Ҁ4.37, 1.81 1.88 Ҁ1.06, 4.82 Ҁ0.37 Ҁ3.25, 2.51 NS
Hip circumference (cm) 0.73 Ҁ0.43, 1.90 1.94 Ҁ0.27, 4.15 Ҁ0.48 Ҁ2.38, 1.43 0.93 Ҁ0.89, 2.76 Ҁ0.43 Ҁ2.21, 1.36 NS
Supine sagittal abdominal
diameter (cm)
0.20 Ҁ0.38, 0.79 0.84 Ҁ0.26, 1.93 Ҁ0.42 Ҁ1.37, 0.54 0.37 Ҁ0.54, 1.28 0.01 Ҁ0.88, 0.90 NS
Midthigh circumference (cm) 0.11 Ҁ0.64, 0.87 1.04 Ҁ0.34, 2.42 0.22 Ҁ0.99, 1.43 Ҁ0.07 Ҁ1.22, 1.07 Ҁ0.73 Ҁ1.85, 0.40 NS
Indexes of mass distribution
BMI (kg/m
2
)
0.32 Ҁ0.37, 1.01 1.06 Ҁ0.23, 2.34 Ҁ0.49 Ҁ1.61, 0.63 0.66 Ҁ0.41, 1.72 Ҁ0.35 Ҁ1.40, 0.69 NS
Ratio of waist to hip
circumferences (҂ 100)
Ҁ0.27 Ҁ1.34, 0.80 0.01 Ҁ1.97, 1.98 Ҁ0.86 Ҁ2.59, 0.86 0.82 Ҁ0.82, 2.46 0.11 Ҁ1.50, 1.72 NS
Ratio of supine sagittal
abdominal diameter to
midthigh circumference
(҂ 100)
0.31 Ҁ0.61, 1.23 0.70 Ҁ1.00, 2.40 Ҁ0.86 Ҁ2.34, 0.62 0.66 Ҁ0.75, 2.06 0.76 Ҁ0.62, 2.14 NS
Ratio of waist to midthigh
circumferences (҂ 100)
0.50 Ҁ2.47, 3.47 Ҁ0.17 Ҁ5.63, 5.29 Ҁ2.91 Ҁ7.68, 1.86 3.43 Ҁ1.10, 7.96 2.20 Ҁ2.25, 6.64 NS
1
Values represent differences from control group (n ҃ 267). Estimates were obtained by linear regression and were adjusted for age, height, and clustering
of siblings. Estimates for specific 10-wk periods of gestational exposure were also adjusted for exposure in overlapping 10-wk periods. Estimates for any
exposure may reflect the additive effects of exposure in specific periods.
2
Values reflect the overall test of association of all 4 periods of exposure considered as a group (Wald test, 4 df).
874 STEIN ET AL
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not associated with overall mortality (33); all these conditions
have shown associations with adiposity. Thus, future research
needs to consider how differences in adiposity consequent to
exposure to famine during gestation, including differences in the
distribution of lean and adipose tissue throughout the body,
might mediate any effect of the famine on risk of disease.
It is possible that participation bias may have led to our find-
ings if heavy women with famine exposure were more likely to
TABLE 5
Association of exposure to the Dutch famine overall or in the specified period of gestation with weight, circumferences, and indexes of adiposity in
adulthood for 529 women measured between 2003 and 2005
1
Period of gestational exposure
Overall
(n ҃ 190)
Weeks 1–10
(n ҃ 39)
Weeks 11–20
(n ҃ 65)
Weeks 21–30
(n ҃ 71)
Week 31 to delivery
(n ҃ 69)
P
2
Estimate 95% CI Estimate 95% CI Estimate 95% CI Estimate 95% CI Estimate 95% CI
Weight and circumferences
Weight (kg) 4.83
3
2.51, 7.14 3.98 Ҁ0.53, 8.48 3.71 0.04, 7.39 3.53 0.02, 7.05 2.75 Ҁ0.77, 6.26 0.01
Waist circumference (cm) 4.69
3
2.66, 6.72 1.96 Ҁ1.93, 5.85 2.83 0.64, 7.02 3.88 0.83, 6.93 2.50 Ҁ0.53, 5.53 0.01
Hip circumference (cm) 4.37
3
2.58, 6.15 2.86 Ҁ0.66, 6.38 3.81 0.96, 6.66 3.27 0.54, 6.00 2.56 Ҁ0.18, 5.30 0.01
Supine sagittal abdominal
diameter (cm)
1.52
3
0.91, 2.13 1.00 Ҁ0.18, 2.18 1.13 0.17, 2.10 0.84 Ҁ0.08, 1.77 1.34 0.42, 2.26 0.01
Midthigh circumference
(cm)
1.61
3
0.65, 2.57 1.01 Ҁ0.86, 2.88 1.40 Ҁ0.12, 2.92 1.64 0.18, 3.09 0.56 Ҁ0.90, 2.01 0.01
Indexes of mass distribution
BMI (kg/m
2
)
1.85
3
1.01, 2.69 1.44 Ҁ0.21, 3.09 1.45 0.11, 2.80 1.34 0.06, 2.62 1.08 Ҁ0.20, 2.37 0.01
Ratio of waist to hip
circumferences (҂ 100)
0.89
4
Ҁ0.15, 1.83 0.09 Ҁ1.80, 1.99 0.33 Ҁ1.22, 1.88 1.09 Ҁ0.04, 2.57 0.17 Ҁ1.31, 1.64 NS
Ratio of supine sagittal
abdominal diameter to
midthigh circumference
(҂100)
1.54
3
0.69, 2.39 1.28 Ҁ0.35, 2.91 0.90 Ҁ0.44, 2.23 0.33 Ҁ0.94, 1.61 2.09 0.82, 3.36 0.01
Ratio of waist to midthigh
circumferences (҂ 100)
3.34
5
0.38, 6.29 1.84 Ҁ3.82, 7.50 1.79 Ҁ2.85, 6.44 2.28 Ҁ2.16, 6.72 2.71 Ҁ1.70, 7.13 NS
1
Values represent differences from control group (n ҃ 339). Estimates were obtained by linear regression and were adjusted for age, height, and clustering
of siblings. Estimates for specific 10-wk periods of gestational exposure were also adjusted for exposure in overlapping 10-wk periods. Estimates for any
exposure may reflect the additive effects of exposure in specific periods.
2
Values reflect the overall test of association of all 4 periods of exposure considered as a group (Wald test, 4 df).
3
P 0.01.
4
P 0.10.
5
P 0.05.
TABLE 6
Association of exposure to the Dutch famine overall or in the specified period of gestation with selected skinfold thicknesses in adulthood for persons
measured between 2003 and 2005
1
Period of gestational exposure
P
2
Overall Weeks 1–10 Weeks 11–20 Weeks 21–30
Week 31 to
delivery
Odds
ratio 95% CI
Odds
ratio 95% CI
Odds
ratio 95% CI
Odds
ratio 95% CI
Odds
ratio 95% CI
Subscapular
(n ҃ 929)
3
1.38
4
0.95, 1.99 0.87 0.43, 1.76 1.35 0.77, 2.37 1.09 0.64, 1.88 1.42 0.82, 2.44 NS
Tricipital (n ҃ 935)
3
1.30 0.89, 1.89 1.50 0.75, 3.00 1.16 0.64, 2.07 1.09 0.63, 1.91 1.37 0.79, 2.38 NS
Anterior midthigh
(n ҃ 760)
3
1.21 0.80, 1.81 1.18 0.57, 2.47 1.10 0.59, 2.06 1.35 0.73, 2.52 0.84 0.45, 1.58 NS
Ratio of subscapular to
tricipital (n ҃ 916)
5
1.55
6
1.08, 2.22 1.07 0.55, 2.08 1.67 0.96, 2.92 1.46 0.86, 2.49 1.09 0.63, 1.87 0.10
1
Estimates were obtained by logistic regression and were adjusted for sex, age, height, and clustering of siblings. Tests for interaction by sex were not
significant (P 0.10). Estimates for specific 10-wk periods of gestational exposure were also adjusted for exposure in overlapping 10-wk periods.
2
Values reflect the overall test of association of all 4 periods of exposure considered as a group (Wald test, 4 df).
3
Odds ratios are for the highest quartile compared with all others.
4
P 0.10.
5
Odds ratios are for the group in which the subscapular skinfold is in a higher quartile than is the tricipital skinfold compared with all others.
6
P 0.05.
ANTHROPOMETRIC MEASURES AFTER MATERNAL UNDERNUTRITION 875
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participate in our study than were heavy women with no famine
exposure. We have no method to test for this potential bias,
however. We note that participation rates did not differ by sex or
by distance from the examination site. It is also possible that
parental characteristics associated with offspring adiposity dif-
fered by period of maternal exposure to famine. The effect of
such bias was minimized in our study because we selected con-
trol subjects from among siblings born outside of the famine
period (thus controlling for genetic sources of variation in adult
adiposity) and among births in the same institutions (thus minimiz-
ing social class differences between exposed and unexposed per-
sons). Adjustment for several variables that are themselves predic-
tors of adiposity, including measures of energy balance and, in
women, parity, did not affect our measures of association between
famine exposure and body mass distribution of the offspring.
In conclusion, exposure to the Dutch famine was strongly asso-
ciated with a wide range of indexes of body mass distribution in
middle-age women, and it was not associated with these indexes in
men or with measures of length or body proportions in either men or
women. These data suggest sex-specific, long-lasting effects of ma-
ternal undernutrition during pregnancy.
We thank the Vroedvrouwenscholen of Amsterdam and Rotterdam and
the Obstetrics Department of the Leiden University Medical Center for their
help in accessing their archives. The clinical examinations were carried out
at the study center of Gerontology & Geriatrics, Leiden University Medical
Center, under supervision of L de Man (head of study center).
LHL, ADS, and HSK developed the study hypothesis and study protocols,
designed the study, and developed and coordinated all data collection activ-
ities. LHL obtained the major funding. ADS conducted the data analysis and
wrote the initial drafts of the manuscript. LHL and HSK participated in the
data interpretation. KvdP participated in the development of the data collec-
tion protocols and initial data management and in data interpretation. PAZ
managed the files and data cleaning and participated in the data interpreta-
tion. AR participated in the data analysis and interpretation. All authors
reviewed and approved the final version of the manuscript. None of the
authors declared any financial conflict of interest.
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... However, this association was not present in girls at the same age 15 . Overall, human observations show that female offspring are more likely to develop adiposity in response to maternal undernutrition 16 . In contrast, maternal overnutrition is more likely to increase adiposity risk in the male offspring 17 . ...
... There is growing evidence for sexual dimorphism in the way epigenetic marks are acquired during cell differentiation 77 . Before the formation of the gonads, sex-related epigenetic dissimilarities 16 -Obesity (human) 16 Maternal overnutrition -Increased adipocyte size at P70 (mouse) 145 -Increased gonadal fat pad weights (mouse) 178 -Adipose inflammation (mouse) 179 -Obesity (human) 17 -Increased adiposity (mouse) 35 Paternal overnutrition -Increased gonadal and retroperitoneal fat pad weights in F1 (mouse) 146 Overview of sexual dimorphism in the function of key metabolic organs in human and sexual dimorphic intergenerational programming effects observed in male (non-italic) and female (italic) offspring in human and animal models (species are indicated in parentheses). ...
... There is growing evidence for sexual dimorphism in the way epigenetic marks are acquired during cell differentiation 77 . Before the formation of the gonads, sex-related epigenetic dissimilarities 16 -Obesity (human) 16 Maternal overnutrition -Increased adipocyte size at P70 (mouse) 145 -Increased gonadal fat pad weights (mouse) 178 -Adipose inflammation (mouse) 179 -Obesity (human) 17 -Increased adiposity (mouse) 35 Paternal overnutrition -Increased gonadal and retroperitoneal fat pad weights in F1 (mouse) 146 Overview of sexual dimorphism in the function of key metabolic organs in human and sexual dimorphic intergenerational programming effects observed in male (non-italic) and female (italic) offspring in human and animal models (species are indicated in parentheses). ...
Article
Strong evidence suggests that early-life exposures to suboptimal environmental factors, including those in utero, influence our long-term metabolic health. This has been termed developmental programming. Mounting evidence suggests that the growth and metabolism of male and female fetuses differ. Therefore, sexual dimorphism in response to pre-conception or early-life exposures could contribute to known sex differences in susceptibility to poor metabolic health in adulthood. However, until recently, many studies, especially those in animal models, focused on a single sex, or, often in the case of studies performed during intrauterine development, did not report the sex of the animal at all. In this review, we (a) summarize the evidence that male and females respond differently to a suboptimal pre-conceptional or in utero environment, (b) explore the potential biological mechanisms that underlie these differences and (c) review the consequences of these differences for long-term metabolic health, including that of subsequent generations. Ozanne and colleagues discuss the evidence of sex differences in the response to suboptimal pre-conceptual and in utero environments, detail the biological mechanisms underlying the intergenerational inheritance of metabolic traits, and show how these sex differences can manifest as metabolic disease in adults.
... Previous famine studies have provided a number of evidences supporting the association between early famine exposure and adulthood anthropometric profile [23][24][25][26][27][28][29][30][31][32][33][34][35]. Yet, the findings were not always consistent. ...
... Yet, the findings were not always consistent. For example, positive associations of early life famine exposure with obesity [23,27,34] and adult height [26,31,35] were found in China and Dutch famine studies, but not in Leningrad studies [30,36] and another Chinese study [35]. Two previous systematic review and meta-analysis reported the association between early life famine and the risks of obesity and overweight later in life [37,38]. ...
... The remaining 20 studies [23-26, 28-34, 45-56] have been included in the current systematic review. Of these, 12 studies were included in the metaanalysis to estimate the relationship between early-life exposure to famine and BMI [23-25, 29, 31, 33, 53], waist circumference [24,29,45,49,52,53] and height [24,26,27,31,33,53] in adulthood. The detailed characteristics of the studies have been shown in Table 1. ...
Article
Full-text available
Background Previous famine studies reported the association between early life famine exposure and adulthood anthropometric profile. However, the findings were variable. Thus, a systematic review and meta-analysis was conducted to clarify the association of famine exposure in early life with the anthropometric profiles in adults. Methods Potentially relevant studies were searched through Scopus, Medline, Google Scholar and Google for gray literature and reference lists of previous studies. The random effects model (REM) and I² test was used to adapt the pooling method and assess heterogeneity, respectively. Results Prenatal famine exposure was associated with increased risk of body mass index [SMD = 0.10 (95% CI: 0.02, 0.18)], waist circumference [SMD = 0.21 (95% CI: 0.11, 0.31)] in adults. Likewise, famine exposure during prenatal life was associated with decreased adult height [SMD) = − 0.26 (95% CI: − 0.44, − 0.09)]. Moreover, famine exposure during early childhood was associated with increased risk of waist circumference [SMD = 0.09 (95% CI: 0.01, 0.16)] and decreased adult height [SMD = − 0.16 (95% CI: − 0.27, − 0.04)]. Conclusion Our finding indicates that exposure to famine during early life was associated with the anthropometric profile of adults. In terms of public health significance, the results of the study further underscore the importance of improving the nutritional status of mothers and children to prevent adulthood diseases in the long run. Systematic review registration number PROSPERO CRD42020168424
... The phenotypes of the mTOR-KO Placenta mice are consistent with rodent females with increased adiposity and disrupted glucose homeostasis because of exposure to in utero undernutrition (26). The current data are also consistent with increased body mass index (BMI), waist circumference, and adiposity and disrupted lipid profile (increased cholesterol and triglycerides) seen in women and not in men (32)(33)(34)(35)(36). In maternal undernutrition/FGR in humans, increased BMI and adiposity have been observed in female offspring (32,33). ...
... The current data are also consistent with increased body mass index (BMI), waist circumference, and adiposity and disrupted lipid profile (increased cholesterol and triglycerides) seen in women and not in men (32)(33)(34)(35)(36). In maternal undernutrition/FGR in humans, increased BMI and adiposity have been observed in female offspring (32,33). In rat and mouse models of FGR by maternal low-protein diet during the third trimester of pregnancy, male offspring develop insulin resistance associated with insufficient β cell mass compensation (37,38). ...
Article
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Fetal growth restriction, or low birthweight is a strong determinant for eventual obesity and Type 2 diabetes. Clinical studies suggest placental mechanistic target of rapamycin (mTOR) signaling regulate fetal birthweight and the metabolic health trajectory of the offspring. In the current study, we used genetic model with loss of placental mTOR function (mTORKOPlacenta) to test the direct role of mTOR signaling on birthweight and the metabolic health in the adult offspring. mTORKOPlacenta animals displayed reduced placental area and total weight, as well as fetal bodyweight at embryonic day (e) 17.5. Birthweight and serum insulin levels were reduced; however, β-cell mass was normal in mTORKOPlacenta newborns. Adult mTORKOPlacenta offspring, under a metabolic high-fat challenge, displayed exacerbated obesity and metabolic dysfunction compared to littermate controls. Subsequently, we tested whether enhancing placental mTOR complex 1 (mTORC1) signaling, via genetic ablation of TSC2, in utero would improve glucose homeostasis in the offspring. Indeed, increased placental mTORC1 conferred protection from a diet-induced obesity in the offspring. In conclusion, placental mTORC1 serves as a mechanistic link between placental function and programming of obesity and insulin resistance in the adult offspring.
... Obesity is associated with a higher risk of developing impaired glucose tolerance (IGT), type 2 diabetes mellitus (T2DM), dyslipidemia, hypertension, cardiovascular disease (CVD), and obstructive sleep apnea (OSA) [55]. In fact, increased adipose tissue alone has been uniformly documented to increase CVD-related mortality after controlling for BMI [56]. ...
... Les (Goodman et Martin, 2002). Les stress endurés au début de la vie peuvent augmenter le risque de développer certaines maladies ou des problèmes chroniques dans le futur, comme : des problèmes cardiaques, de l'hypertension, des diabètes type 2, des problèmes de développement cognitif, des risques d'infection, de l'obésité (Araújo et al., 2016 ;Barker et al., 1989 ;Finer et al., 2016 ;France Portrait, Teeuwiszen et Dorly Deeg, 2011 ;Rotar et al., 2015 ;Aryeh D. Stein et al., 2007 (Larsen, 2015). L'analyse des squelettes fournit de nombreuses informations sur les modes de vie des populations du passé, sur leur santé, leur alimentation, les violences et les traumatismes endurés, sur leurs activités professionnelles, la démographie, les impacts d'une colonisation, mais 13 aussi sur les inégalités sociales, y compris de genre. ...
Thesis
Ce travail évalue l’impact de crises démographiques de différentes natures au sein d’une société, en prenant comme exemple la ville de Martigues (Bouches-du-Rhône) au XVIIIe siècle. Cette ville a été touchée par la dernière grande épidémie de peste en France, la peste dite de Marseille, qui a affecté la Provence et le Haut Languedoc entre 1720 et 1722, tuant près du quart des habitants. Cette épidémie intervient après une succession de crises (problèmes climatiques, guerres, famines et/ou épidémies) qui ont contribué à affaiblir la population. Considérant les effets que les famines, les épidémies et la malnutrition chronique peuvent avoir sur le développement et la santé des individus, nous avons cherché à mesurer l’impact des difficultés alimentaires et/ou épidémiques qui ont affecté les habitants de Martigues à différents moments de leur cycle de vie, et à évaluer le rôle des inégalités socio-économiques et de genre dans la présence des marqueurs de stress sur les individus observés. Nous accordons une attention particulière à la situation des femmes, tant d’un point de vue sanitaire qu’historique. Notre étude s’appuie sur un corpus des squelettes de victimes de la peste de 1720, à Martigues. Une telle collection ostéologique est bien adaptée à notre problématique car elle est composée d’individus contemporains entre eux, décédés dans un laps de temps très court (moins d’un an), qui ont connu les mêmes contraintes environnementales et qui ont vécu selon les mêmes règles sociales. L’observation des stress vécus repose sur l’analyse de marqueurs de stress physiologiques (cribra orbitalia, hyperostose poreuse de la voûte crânienne, hypoplasie linéaire de l’émail dentaire et stature). L’analyse du corpus a nécessité la mise en œuvre de nouveaux outils méthodologiques, tant pour mieux mesurer l’intensité des stress vécus par la population à différents âges, que pour implémenter une analyse intersectionnelle en bioanthropologie. Ces données ont été enrichies par les informations historiques contextualisant l’état sanitaire de la population étudiée, ce qui nous a permis de démontrer la représentativité de l’échantillon par rapport aux victimes de la peste et par rapport à la population vivante (distribution par sexe et par âge et composition sociale). Cela nous a aussi permis de relier les stress observés dans certaines classes d’âge aux crises démographiques connues par les textes. Les résultats, validés statistiquement, ont été analysés en recourant à des concepts issus de la sociologie (tels que l’approche intersectionnelle et biosociale) que nous avons adaptés à l’archéologie et à la bioanthropologie. Analyser les marqueurs de stress sans le filtre d’une distribution préétablie, par sexes ou par groupes d’âge par exemple, permet de mettre en lumière l’impact des rapports sociaux sur le développement biologique des individus. Notre étude a ainsi mis en évidence un lien entre une naissance dans les années de crises et l’observation d’une proportion plus élevée de marqueurs de stress physiologiques chez les individus immatures. Nous n’avons pas observé le même phénomène chez les adultes, qui ont été affectés par les stress de façon plus uniforme. Nous remarquons néanmoins que le nombre des crises traversées et leur intensité ont un impact plus important sur l’état sanitaire des individus que leur appartenance à l’un ou l’autre sexe ou à tel ou tel groupe d’âge. Les nouveaux outils méthodologiques développés à l’occasion de ce cette recherche doctoral pourront être appliqués à d’autres études. Le contexte exceptionnel de cette étude, à la fois en termes de représentativité de la collection ostéologique et de diversité des données historiques disponibles, nous a permis d’apporter ces contributions originales en bioanthropologie.
... Detailed food records were kept in The Netherlands which provides basis for experiments investigating the effect of early life famine exposure on disease riskin later life. The studies found that exposure to famine during the early life environment was associated with an increased risk of disease in adulthood, furthermore the timing of the exposure had differential effects on the disease risk[205][206][207][208][209][210] (Figure 1.16). ...
Thesis
Osteoporosis is a systemic skeletal disease which affects the ageing population and results in an increased risk of developing fractures, for example at the wrist, hip and spine. Peak bone mass in early adulthood has been shown to predict the risk of developing osteoporosis in later life and studies have shown that the early life environment might influence the bone health trajectory, through epigenetic processes such as DNA methylation. DNA methylation can be measured in suitable candidate genes to potentially act as a biomarker for predicting bone health in later life, and to guide interventions aimed at improving the accrual of bone mass during growth. Studies within the SWS cohort have identified two candidate biomarkers, RXRA and CDKN2A, of which DNA methylation has been shown to be associated with bone measures in later childhood. Whether DNA methylation is causally involved in bone outcomes is unknown therefore, randomised controlled trials provide an opportunity to investigate these associations further and to determine the possibility of a causal relationship. Within this thesis, DNA methylation of four genes, RXRA, CDKN2A, Osterix and Runx2, were measured within the MAVIDOS trial, a randomised, controlled, double blind study where pregnant mothers were recruited and received either 1000 IU/d cholecalciferol or placebo daily from 14 weeks gestation until delivery. Infants born during the winter months to cholecalciferol supplemented mothers had greater bone measures at birth compared to the placebo group. The results showed that infants born to cholecalciferol supplemented mothers had lower methylation of RXRA and Osterix CpG loci and higher methylation at CDKN2A CpG loci. Furthermore, DNA methylation of Osterix and Runx2 was positively associated with bone measures at birth. Next, the functional importance of the RXRA CpGs of interest was investigated in osteosarcoma cell lines to provide a mechanistic insight into the interactions between vitamin D and RXRA methylation. The results showed that site directed mutagenesis upstream of the RXRA promoter impaired luciferase expression within osteosarcoma cell lines, both in the presence and absence of vitamin D supplementation. In humans, the measurement of DNA methylation in tissues central to the pathogenesis of osteoporosis is difficult, so DNA methylation of several key genes was measured in adult tibiae from mice exposed to a prenatal vitamin D deficient diet. The results showed that a prenatal vitamin D deficient diet altered tibial DNA methylation and suggests a link between prenatal vitamin D deficiency, mechanical loading and DNA methylation within tibiae. These observations provide insight into candidate biomarkers of bone health that respond accordingly to a dietary intervention of maternal vitamin D supplementation within the MAVIDOS trial, and provide insight into the mechanisms and functional importance that altered DNA methylation of these genes could have on bone phenotype.
... Differences in DNA methylation also suggest that fetal deaths may be increased by prenatal famine exposure [29]. With regard to other outcomes, studies of coronary artery disease in men and women followed through middle age after prenatal exposure to the Dutch famine present conflicting findings [30,31]. The men in the current study exposed in early gestation show a 10% increase in mortality; however, at age 63 no increase in deaths reported from cardiovascular disease [10,11]. ...
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Background Weight for height has been used in the past as an indicator of obesity to report that prenatal exposure to the Dutch famine of 1944–1945 determined subsequent obesity. Further evaluation is needed as unresolved questions remain about the possible impact of social class differences in fertility decline during the famine and because being overweight is now defined by a Body Mass Index (BMI: kg/m ² ) from 25 to <30 and obesity by a BMI of 30 or more. Methods We studied heights and weights of 371,100 men in the Netherlands born between 1943 and 1947 and examined for military service at age 19. This group includes men with and without prenatal exposure to the Dutch famine. Results There was a 1.3-fold increase in the risk of being overweight or obese in young adults at age 19 after prenatal famine exposure in early gestation. The increase was only seen in sons of manual workers born in the large cities of Western Netherlands and not among those born in smaller cities or rural areas in the West. Social class differentials in fertility decline during the famine did not bias study results. Conclusions The long-term adverse impact of prenatal famine on later life type 2 diabetes and mortality through age 63 is already showing at age 19 in this population as a significant increase in overweight risk.
Chapter
The overall aim of this chapter is to investigate the possibility that environmental factors are driving the obesity pandemic by causing epigenetic changes during development and throughout life. A background on the role of epigenetics in variable obesity predisposition is provided, covering obesity-associated diseases (Prader Willi syndrome and Angelman syndrome) and imprinted genes such as IGF2/H19. Several human-based studies assessing potential contributing environmental factors are then discussed, including investigations into possible mechanisms by which they alter epigenetic profiles to promote obesity and obesity associated diseases such as T2D. The effects of parental exposure, aging, and lifestyle on obesity epigenetics is also extensively evaluated. The chapter finishes with an overview on the potential for using epigenetic treatments to combat obesity, particularly looking at how physical activity can reverse obesity-associated epigenetic marks.
Article
Background & aims: The double burden of malnutrition (DBM) in China resulted in high prevalence of diet-related non-communicable diseases. The aim of this study was to analyze the moderation of economic conditions on the association between early famine exposure and metabolic dysfunction associated fatty liver disease (MAFLD) in adulthood. Methods: 10190 participants in the SPECT-China study enrolled from 2014 to 2016 were included in this study. Participants with fetal famine exposure (birth year 1959-1962) or early-childhood famine exposure (birth year 1955-1958) formed the exposure group. The associations with MAFLD were assessed via regression analyses. Results: In men, economic status could not moderate the association between early-life famine and MAFLD after adjusting for age, excess alcohol drinking, current smokers, famine severity, waist circumference, diabetes, hypertension, and dyslipidemia (P for interaction=0.52). However, in women and in the total population, economic status could moderate the association between early-life famine and MAFLD after adjusting for the above confounders (P for interaction=0.01). In the total population and in women, early life famine exposure was associated with MAFLD in both low economic status and high economic status. However, in men, early-life famine exposure was not associated with MAFLD in low economic status, while in high economic status, early-childhood famine-exposure was associated with MAFLD. Conclusions: Economic status could moderate the association between early-life famine exposure and MAFLD in total population and in women.
Article
Nutrition during adolescence, pregravid and postpartum is a major public health challenge, as it affects not only the health of adolescents and women, but also the health of future generations. Therefore, the International Federation of Gynaecology and Obstetrics' guidelines aim to address a number of nutritional concerns for adolescents and young women before, during and after pregnancy. Health care providers should think about nutrition first, with a focus on optimizing the nutrition and health of adolescents and mothers from the pre-conception period. This approach will help to achieve significant positive results in ensuring the health of women and their children, as well as in ensuring the health, life expectancy and well-being of future generations. The main findings on the use of micronutrients (vitamins and minerals) are presented. It is known that the number of calories required for the development of a child during pregnancy does not increase significantly, while the requirements for vitamins and minerals increase significantly. Therefore, pregnant women should focus on increasing their micronutrient intake and try to limit their intake of empty calorie foods.
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Background: It was shown that men who were conceived during the Dutch famine of 1944–1945 had higher rates of obesity at age 19 y than those conceived before or after it. Objective: Our objective was to study the effects of prenatal exposure to the Dutch famine on obesity in women and men at age 50 y. Design: We measured the body size of 741 people born at term between November 1943 and February 1947 in Amsterdam. We compared people exposed to famine in late, mid, or early gestation (exposed participants) with those born before or conceived after the famine period (nonexposed participants). Results: The body mass index (BMI; in kg/m²) of 50-y-old women exposed to famine in early gestation was significantly higher by 7.4% (95% CI: 0.7%, 14.5%) than that of nonexposed women. BMI did not differ significantly in women exposed in mid gestation (−2.1%; −7.0%, 3.1%) or in late gestation (−1.3%; −6.3%, 3.9%). In 50-y-old men, BMI was not significantly affected by exposure to famine during any stage of gestation: BMI differed by 0.4% (−3.5%, 4.5%) in men exposed to famine in late gestation, by −1.2% (−5.5%, 3.3%) in those exposed in mid gestation, and by 0.5% (−4.6%, 6.0%) in those exposed in early gestation compared with nonexposed men. Conclusions: Maternal malnutrition during early gestation was associated with higher BMI and waist circumference in 50-y-old women but not in men. These findings suggest that pertubations of central endocrine regulatory systems established in early gestation may contribute to the development of abdominal obesity in later life.
Article
Background: Body mass index (BMI; in kg/m²) is considered a poor indicator of overall and abdominal obesity in the elderly. Objectives: Our goal was to determine which simple anthropometric measurements [BMI, waist-to-hip ratio (WHR), waist circumference (WC), percentage body fat (%BF), or fat mass (FM)] are most closely associated with metabolic risk factors and insulin resistance in elderly men. Design: This was a cross-sectional study of 2924 men aged 60–79 y with no history of coronary heart disease, stroke, or diabetes who were drawn from general practices in 24 British towns. Results: BMI and WC were the measures most strongly associated with the metabolic syndrome (≥3 of the following: hypertension, low HDL cholesterol, high triacylglycerols, or high blood glucose) and insulin resistance. For a 1-SD increase in BMI, WC, WHR, %BF, and FM, the odds ratios (95% CIs) of having the metabolic syndrome after adjustment for age, socioeconomic status, smoking status, and physical activity were as follows: BMI, 1.61 (1.44, 1.79); WC, 1.65 (1.48, 1.81); WHR, 1.49 (1.34, 1.66); %BF, 1.41 (1.25, 1.59); and FM, 1.53 (1.38, 1.70). For insulin resistance, the odds ratios (95% CIs) were as follows: 2.48 (2.22, 2.77), 2.46 (2.19, 2.65), 1.75 (1.59, 1.93), 1.79 (1.60, 2.00), and 2.10 (1.88, 2.34), respectively. In normal-weight (BMI < 25) and overweight (BMI 25–29.9) men, the presence of the metabolic syndrome and insulin resistance increased with increasing WC; this did not occur in obese men. Conclusions: BMI and WC are the simple measures of adiposity most strongly associated with metabolic abnormalities in elderly men. Our findings suggest that WC can be used as a complementary measurement to identify health risks in normal-weight and overweight elderly persons.
Article
OBJECTIVE To assess the effect of prenatal exposure to maternal malnutrition on coronary heart disease in people born around the time of the Dutch famine, 1944–45.DESIGNHistorical cohort study.SETTINGCommunity study.PATIENTSSingletons born alive between November 1943 and February 1947 for whom detailed birth records were available.DESIGNThe prevalence of coronary heart disease was compared between those exposed to famine in late gestation (n = 120), in mid-gestation (n = 108), or in early gestation (n = 68), and those born in the year before the famine or those conceived in the year after the famine (non-exposed subjects, n = 440).MAIN OUTCOME MEASURESPrevalence of coronary heart disease, defined as the presence of angina pectoris according to the Rose questionnaire, Q waves on the ECG, or a history of coronary revascularisation.RESULTSThe prevalence of coronary heart disease was higher in those exposed in early gestation than in non-exposed people (8.8% v 3.2%; odds ratio adjusted for sex 3.0, 95% confidence interval (CI) 1.1 to 8.1). The prevalence was not increased in those exposed in mid gestation (0.9%) or late gestation (2.5%). People with coronary heart disease tended to have lower birth weights (3215 g v 3352 g, p = 0.13), and smaller head circumferences at birth (32.2 cmv 32.8 cm, p = 0.05), but the effect of exposure to famine in early gestation was independent of birth weight (adjusted odds ratio 3.2, 95% CI 1.2 to 8.8).CONCLUSIONS Although the numbers are very small, this is the first evidence suggesting that maternal malnutrition during early gestation contributes to the occurrence of coronary heart disease in the offspring.
Article
In a case-control study of 217 hospitalized incident cases of ischemic heart disease and 261 controls we compared various anthropometric indices for the strength of their associations to the outcome event. The ratio of supine sagittal abdominal diameter to midthigh girth (“abdominal diameter index”; ADI) was the simple index that best discriminated cases from controls for both men (standardized difference, 0.65; p < 0.0001) and women (standardized difference, 0.95; p < 0.0001). The waist-to-thigh ratio of girths (WTR) (standardized difference, 0.57 and 0.90; p < 0.0001) was nearly as strong as the ADI and stronger than the traditional waist-to-hip ratio (standardized difference, 0.34 and 0.68; p < 0.005). After adjustments for age and race, the men's odds ratio for ischémic heart disease (tertile 3 vs. tertile 1) was 5.5 (95% CI, 2.9–10) using ADI and 5.1 (2.6–10) using the WTR. The women's odds ratio was 6.3 (1.9–20) using ADI and 8.7 (2.3–33) using the WTR. Further adjustments for body mass index and cardiovascular risk factors did not substantially change these risk estimates. Similar odds ratios were estimated by analyses restricted to 169 neighborhood-matched case-control pairs. In contrast, increased midthigh girth and subcutaneous fat mass (sum of three skinfolds) were associated with a protective effect against ischemic heart disease. Anthropometry using the ADI or WTR could offer a low-cost, noninvasive method for the clinical or epidemiologic evaluation of ischemic heart disease risk.