RESEARCH REPORT doi:10.1111/j.1360-0443.2007.02084.

Prenatal exposure to the 1944–45 Dutch

‘hunger winter’ and addiction later in life

Ernst J. Franzek1, Niels Sprangers1, A. Cecile J. W. Janssens2, Cornelia M. Van Duijn3 &
Ben J. M. Van De Wetering1
Bouman Mental Health Care Rotterdam, the Netherlands,1 Center for Medical Decision Sciences, Department of Public Health, Erasmus Medical Center
Rotterdam, the Netherlands2 and Genetic Epidemiology Unit, Department of Epidemiology and Biostatistics, Erasmus Medical Center Rotterdam, the Netherlands3

ABSTRACT

Aims Prenatal exposure to severe famine has been associated with an increased risk of schizophrenia and affective
disorders. We studied the relationship between prenatal exposure to famine during the Dutch hunger winter of
1944–45 and addiction later in life. Design A case–control study. Setting The Rotterdam city area during the Dutch
hunger winter lasting from mid-October 1944 to mid-May 1945. From February 1945 to mid-May 1945 the hunger
winter was characterized by a famine peak. Participants Patients are native Dutch addicted patients from the Rot-
terdam Addiction Treatment Program and controls are native Dutch inhabitants of Rotterdam, born between 1944
and 1947. Measurement Exposure to the whole hunger winter (< 1400 kcal/day) and the peak of the hunger winter
(< 1000 kcal/day) was determined for each trimester of gestation. For each trimester the exposed/unexposed ratios
were compared between patients and controls and quantified as odds ratios (OR). Findings The odds of first-trimester
gestational exposure to famine during the total hunger winter was significantly higher among patients receiving
treatment for an addictive disorder [OR = 1.34, 95% confidence interval (CI) 1.10–1.64]. Stratification by sex shows
that the odds of exposure during the first trimester was significantly higher only among men (OR = 1.34, 95% CI
1.05–1.72), but not among women (OR = 1.26, 95% CI 0.88–1.81). The odds of exposure to the peak of the hunger
winter during the first trimester of gestation were also significantly higher among addiction treatment patients
(OR = 1.61, 95% CI 1.22–2.12). We did not find any significant differences for the second and third trimesters of
gestation. Conclusion First-trimester prenatal exposure to famine appears to be associated with addiction later in life.
The study confirms the adverse influence of severe malnutrition on brain development and maturation, confirms the
influence of perinatal insults on mental health in later life and gives rise to great concern about the possible future
consequences for the hunger regions in our world.

Keywords Addiction, malnutrition, neurodevelopment, pregnancy, prenatal exposure to famine, schizophrenia.

Correspondence to: Ernst J. Franzek, Bouman Mental Health Care, PO Box 8549, 3009 AM Rotterdam, the Netherlands. E-mail: ejf@arcor.de
Submitted 5 May 2007; initial review completed 8 August 2007; final version accepted 25 October 2007

INTRODUCTION of the Netherlands was already bad but subsequently

In September 1944 the final and most dramatic episode of
World War II began to hit the Netherlands. Hoping to
capture strategic bridges over the Rhine to open a
pathway for a rapid invasion into Germany, the Allied
forces launched a parachute attack behind the Nazi forces
near the city of Arnhem. However, the operation failed
with major losses. Immediately afterwards the German
authority imposed a total embargo on occupied Nether-
lands in retaliation for the Dutch support to the Allied
forces. At that time the food situation in the western part
worsened dramatically. Although the embargo was lifted
from transports over water in early November 1944 the
famine intensified progressively because the winter was
unusually early and severe. All the waterways were
frozen and barges could not sail out. Food rations
declined to extremely low levels between February and
May 1945, resulting in an individual average daily official
ration below 1000 calories. During the weeks before lib-
eration in early May 1945 the famine reached its peak.
The normal average daily food intake is 2300 kcal for
women and 2900 kcal for men with an active life-style.

© 2008 The Authors. Journal compilation © 2008 Society for the Study of Addiction Addiction, 103, 433–438
434 Ernst J. Franzek et al.
At least 22 000 people of the 3.5 million inhabitants of
the western part of the Netherlands died because of the
famine [1].
Initially, pregnant and lactating women were entitled
to supplementary rations; however, at the peak of the
famine these extra rations could no longer be provided.
After the liberation the food situation improved very
rapidly and by June 1945 the rations had already risen to
over 2000 calories per person per day [2]. Despite the
disastrous famine, babies were still conceived and born.
Thus the circumscribed place and period of the Dutch
famine created a natural ‘experiment’ in which the indi-
viduals being conceived or having been in various states of
gestation during this period can be studied with respect to
the effects of maternal malnutrition on health in adult life.
A number of chronic somatic diseases in the offspring
in later life, such as glucose intolerance [3], high blood
pressure [4], obesity [5], heightened atherogenic lipid
profiles [6], higher risk of coronary disease [7], increased
prevalence of obstructive airways disease [8], reduced
plasma fibrinogen and factor VII concentrations [9],
microalbuminuria and higher adult mortality [10,11],
have been found to be associated with maternal famine
exposure during gestation. The same has been reported
for major psychiatric disorders such as schizophrenia
[12–14], schizophrenia spectrum disorders [15], major
affective disorders [16,17] and antisocial personality
disorder [18].
Thus, prenatal famine exposure may be a major
contributing factor for the development of a variety
of somatic, neurodevelopmental and neuropsychiatric
disorders. Modern brain research indicates that suscepti-
bility to addiction can involve neurodevelopmental abor-
malities [19,20]. We studied the association between
prenatal exposure to the Dutch hunger winter of
1944–45 in the Rotterdam area and addiction in later
life. We compared the odds of exposure/non-exposure
during each trimester of gestation between addicted
patients and inhabitants of the Rotterdam area, born
between 1944 and 1947.
METHODS
Study population
Patients included in this study are native Dutch patients
born in the period 1944–47 registered with an addiction
problem (alcohol and drug abuse) in the database of the
Dutch Mental Health Care Organization, Bouman GGZ,
based in the Rotterdam area. Controls are native Dutch
inhabitants born in the period of 1944–1947 living in
Rotterdam on 1 January 2004. Table 1 gives an overview
of the number of patients and controls included in the
study.
© 2008 The Authors. Journal compilation © 2008 Society for the Study of Addiction
Table 1 Number of addicted patients registered in the database
of Bouman GGZ and number of living native inhabitants of
Rotterdam (controls) born between 1944 and 1947.
Patients Controls
Men Women Men Women
1944 168 101 1987 2138
1945 174 67 1654 1643
1946 266 138 3197 3341
1947 270 104 2852 2877
Total 878 410 9690 9999
Definition of exposure
The Dutch hunger winter lasted from mid-October 1944
until 12 May 1945 [2]. During this period the average
daily food intake was below 1400 kcal. We defined the
period from 15 October 1944 to 12 May 1945 as the
‘whole hunger winter’. The Dutch hunger winter was
characterized by a famine peak in the months from Feb-
ruary 1945 until the end of the hunger winter. During
these months the average daily food intake was below
1000 kcal and the effects were most drastic at the end of
the hunger winter, because of the continuing starvation
process. We defined the period from 1 February 1945 to
12 May 1945 as the ‘peak of the hunger winter’.
In research studies on the effects of famine on gesta-
tion it is common to divide gestation into three trimes-
ters. A pregnancy lasts approximately 280 days; each
trimester lasts about 94 days. We assumed that all preg-
nancies lasted a full 282 days. Based on this assumption,
we obtained the dates of conception. Figure 1 shows for
each trimester of gestation the periods that define expo-
sure and non-exposure to the whole hunger winter and
the peak of the hunger winter: individuals who were
conceived within those periods were considered as
exposed for the trimester. For each individual we deter-
mined the exposure status for the first, second and third
trimesters of gestation. Individuals are considered as
exposed during a specific trimester of gestation if they
were exposed to the effects of the hunger winter for a
minimal period of 2 weeks during that trimester. Indi-
viduals are considered unexposed when they were con-
ceived during the equivalent period in the subsequent
year. We narrowed the definition of the controls explicitly
to the equivalent date of birth period in the subsequent
year because of possible confounding factors such as a
possible relationship between season of birth and addic-
tion disorders, and environmental and social effects such
as the Dutch heroin epidemic of the early 1970s
[21–26].
Figure 1 shows that there is an overlap between the
periods that define exposure/non-exposure during first-,
Addiction, 103, 433–438
 Exposure to hunger winter and addiction 435

Month of conception

May-44

May-45

May-46
Aug-44
Sep-44

Nov-44
Dec-44

Aug-45
Sep-45

Nov-45
Dec-45
Feb-44
Mar-44

Feb-45
Mar-45

Feb-46
Mar-46
Jan-44

Jun-44

Jan-45

Jun-45

Jan-46

Jun-46
Apr-44

Oct-44

Apr-45

Oct-45

Apr-46
Jul-44

Jul-45
Exposed UnExposed
First Trimester Exposed UnExposed

Exposed UnExposed
Second Trimester Exposed UnExposed

Third Trimester Exposed UnExposed

Exposed UnExposed

= Exposed during whole hunger winter

= Exposed during peak hunger winter
= Total hunger winter (< 1400 kcal/day) and peak of the hunger winter (1000 < kcal/day)

Figure 1 Definition of exposure and non-exposure to the whole hunger winter and peak of the hunger winter for the first, second and third
trimesters of gestation

Month of conception
May-44

May-45

May-46
Aug-44

Sep-44

Nov-44

Dec-44

Aug-45

Sep-45

Nov-45

Dec-45
Feb-45

Mar-45

Feb-46

Mar-46
Jun-44

Jan-45

Jun-45

Jan-46

Jun-46
Oct-44

Apr-45

Oct-45

Apr-46
Jul-44

Jul-45
First trimester Exposed UnExposed
Second trimester Exposed UnExposed
Third trimester Exposed UnExposed

Minimal overlap 3rd only 2nd & 3rd 2nd 1st & 2nd 1st only 3rd only 2nd & 3rd 2nd 1st & 2nd 1st only

= Peak of the hunger winter (< 1000 kcal/day)

Figure 2 Definition of exposure and non-exposure to the peak of the hunger winter for the first, second and third trimesters of gestation
and for exposure during two trimesters (first and second, or second and third)

second- and third-trimester exposure, i.e. some of the of exposure during the first trimester was significantly
subjects are exposed during two trimesters. For exposure higher only among men (OR = 1.34, 95% CI 1.05–1.72;
to the peak of the hunger winter, we therefore stratified P < 0.05), but not in women (OR = 1.26, 95% CI 0.88–
the population additionally into five groups: exposure to 1.81). There were no significant differences between the
the first, second or third trimesters, to the first and second odds of exposure to second- and third-trimester gesta-
trimesters and to the second and third trimesters tional famine (<1400 kcal/day) of patients and controls.
(see Fig. 2). Table 3 shows the results of gestational exposure to
the peak of the hunger winter with an average food
Data analysis intake of less than 1000 kcal/day. The odds of exposure
during the first trimester of gestation was significantly
For each trimester we calculated odds ratios (OR) and
higher among patients (OR = 1.61, 95% CI 1.22–2.12;
95% confidence intervals (CI) as the exposed/unexposed
P < 0.001). Stratification by sex again shows that the
ratio in patients divided by the exposed/unexposed ratio
odds of exposure differ significantly only in men: the OR
in controls. Using Pearson’s c2 test we tested whether the
in men was 1.63 (95% CI 1.16–2.27; P < 0.01) com-
exposed/unexposed ratios were different between patients
pared to an OR of 1.40 (95% CI 0.85–2.33; P > 0.05) in
and controls (P < 0.05, two-tailed).
women. There were no significant differences between
the odds of exposure in patients and controls during the
RESULTS
second and third trimesters of gestation.
Table 2 shows the number of exposed and unexposed Finally, Table 4 presents the ORs for the stratification
patients and controls for each trimester of gestation. The during five periods of exposure. The table shows that the
odds of first-trimester gestational exposure to the famine odds of exposure to famine during the first trimester
effects of the total hunger winter (< 1400 kcal/day) remains significantly higher only among male patients
among patients was significantly higher than the odds of than among male controls (OR = 1.82, CI 1.18–2.80;
exposure among controls (OR = 1.34, 95% CI 1.10– P < 0.01). None of the other comparisons yielded a
1.64; P < 0.01). Stratification by sex shows that the odds statistically significant difference.

© 2008 The Authors. Journal compilation © 2008 Society for the Study of Addiction Addiction, 103, 433–438
436 Ernst J. Franzek et al.

Table 2 Exposure to the whole hunger winter (< 1400 kcal/day) in addicted patients and controls.

Controls Patients OR (95% CI)

First trimester
All Exposed 2048 154 1.34 (1.10–1.64)*
Unexposed 5152 289
Men Exposed 1038 109 1.34 (1.05–1.72)**
Unexposed 2493 195
Women Exposed 1010 45 1.26 (0.88–1.81)
Unexposed 2659 94
Second trimester
All Exposed 2679 184 1.14 (0.94–1.37)
Unexposed 5319 321
Men Exposed 1330 133 1.21 (0.97–1.52)
Unexposed 2599 214
Women Exposed 1349 51 0.96 (0.68–1.35)
Unexposed 2720 107
Third trimester
All Exposed 3148 224 1.06 (0.89–1.28)
Unexposed 4123 276
Men Exposed 1572 158 1.09 (0.87–1.36)
Unexposed 2048 189
Women Exposed 1576 66 1.00 (0.72–1.38)
Unexposed 2075 87

CI = confidence interval; OR = odds ratio. *P < 0.01, **P < 0.05.

Table 3 Exposure to the peak of the hunger winter (<1000 kcal/day) in addicted patients and controls.

Controls Patients OR (95% CI)

First trimester
All Exposed 917 81 1.61 (1.22–2.12)***
Unexposed 2879 158
Men Exposed 484 59 1.63 (1.16–2.27)**
Unexposed 1387 104
Women Exposed 433 22 1.40 (0.85–2.33)
Unexposed 1492 54
Second trimester
All Exposed 1343 87 1.16 (0.89–1.51)
Unexposed 3229 180
Men Exposed 663 61 1.15 (0.83–1.58)
Unexposed 1545 124
Women Exposed 680 26 1.15 (0.72–1.85)
Unexposed 1684 56
Third trimester
All Exposed 1915 134 1.15 (0.92–1.43)
Unexposed 3453 211
Men Exposed 954 98 1.24 (0.95–1.63)
Unexposed 1692 140
Women Exposed 961 36 0.93 (0.62–1.40)
Unexposed 1761 71

CI = confidence interval; OR = odds ratio. **P < 0.01, ***P < 0.001.

DISCUSSION discussing the implications of our study, some method-

ological issues need to be addressed. First, we cannot
Our study is the first to show an association between pre- exclude potential misclassification of addiction. Control
natal exposure to famine and addiction in later life. Before data of the inhabitants of the Rotterdam city area were

© 2008 The Authors. Journal compilation © 2008 Society for the Study of Addiction Addiction, 103, 433–438
 Exposure to hunger winter and addiction 437

Table 4 Prenatal exposure to the peak of the hunger winter (< 1000 kcal/day) in addicted patients and controls, with minimal
overlap between birth cohorts

Controls Patients OR (95% CI)

Only 1st trimester

Men Exposed 273 38 1.82 (1.18–2.80)**
Unexposed 772 59
Women Exposed 245 13 1.32 (0.69–2.55)
Unexposed 823 33
1st and 2nd trimesters
Men Exposed 211 21 1.36 (0.80–2.34)
Unexposed 615 45
Women Exposed 188 9 1.53 (0.69–3.40)
Unexposed 669 21
Only 2nd trimester
Men Exposed 69 7 1.14 (0.46–2.89)
Unexposed 203 18
Women Exposed 101 4 0.77 (0.24–2.49)
Unexposed 215 11
2nd and 3rd trimesters
Men Exposed 383 33 1.03 (0.66–1.60)
Unexposed 727 61
Women Exposed 391 13 1.11 (0.56–2.20)
Unexposed 800 24
Only 3rd trimester
Men Exposed 571 65 1.39 (0.99–1.96)
Unexposed 965 79
Women Exposed 570 23 0.83 (0.50–1.37)
Unexposed 961 47

CI = confidence interval; OR = odds ratio. **P < 0.01.

obtained from the municipal statistics department and
these data do not contain information about the health
status of the inhabitants. It is therefore possible that the
control population also included inhabitants who are
addicted and perhaps even inhabitants who were regis-
tered in our database. If, however, misclassification of
diagnosis had affected the results, it would probably lead
to an underestimation of the effect. Secondly, we were
unable to ascertain if all patients and controls were born
in the Rotterdam area, and hence were exposed to the
hunger winter. Because this problem holds for both
patients and controls, we do not expect that the results
were biased by this. Thirdly, although our study included
1288 patients and 19 689 controls, this sample may not
have been large enough to demonstrate subgroup effects.
The effect of malnutrition is probably underestimated,
because patients were already in their 60s and there may
have been excess mortality among this group during the
preceding 20–30 years. Finally, because we had no data
on comorbidity, we were unable to assess whether famine
during gestation led to addiction, or whether this was an
indirect effect explained by other psychiatric disorders
such as schizophrenia [12–15]. One could argue that the
effect found in this study is confounded by the presence of
comorbidity. However, the prevalence of these disorders
in the population of Bouman GGZ is low and it is very
unlikely that this can explain the reported associations.
Although we found a statistically significant associa-
tion only with exposure during the first trimester of ges-
tation, we also cannot rule out an effect of famine during
all trimesters. All ORs in men and most ORs in women
were higher than 1. Moreover, among men the OR for
exposure during the third trimester was 1.39 and border-
line statistically significant (Table 4). This could mean
that exposure to prenatal food rationing leads to a higher
risk of addiction in all trimesters, and that the risk is
strongest for exposure to famine during the first trimester.
A related issue is the presence of a dose–effect rela-
tionship: is greater exposure to famine during gestation
associated with a higher risk of addiction later in life? On
one hand, we found that the association was stronger for
first-trimester exposure during the peak of the hunger
winter compared to exposure to the total hunger winter.
On the other hand, the effect of gestational exposure to
the first trimester only was larger than exposure to the
first and second trimesters. Thus, longer exposure to
famine did not result in a higher risk of addiction. This
supports the view that the first trimester is crucial in the

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438 Ernst J. Franzek et al.
development of the reward system in the human brain
that is involved mainly in addictive behaviour [20].
In conclusion, we have found for the first time an asso-
ciation between famine during gestation and participat-
ing in treatment for addiction in adulthood. Further
studies are needed to confirm these findings and to inves-
tigate other possible relationships between addiction
and prenatal development, such as the influence of an
unbalanced diet, influenza and other stressors.
Acknowledgements
We would like to express our gratitude to the ‘Centrum
voor Onderzoek en Statistiek van de gemeente Rotterdam’
(Centre of Research and Statistics of the Municipality of
Rotterdam) for their excellent service and for providing
the birth dates of the native Dutch inhabitants.
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