Linköping University Post Print
Preterm birth or foetal growth impairment and
psychiatric hospitalization in adolescence and
early adulthood in a Swedish population-based
W Monfils Gustafsson, Ann Josefsson, Katarina Ekholm and Gunilla Sydsjö
N.B.: When citing this work, cite the original article.
The definitive version is available at www.blackwell-synergy.com:
W Monfils Gustafsson, Ann Josefsson, Katarina Ekholm and Gunilla Sydsjö , Preterm birth
or foetal growth impairment and psychiatric hospitalization in adolescence and early
adulthood in a Swedish population-based birth cohort, 2009, ACTA PSYCHIATRICA
SCANDINAVICA, (119), 1, 54-61.
Copyright: Blackwell Publishing Ltd
Postprint available at: Linköping University Electronic Press
Preterm birth or foetal growth impairment and psychiatric hospitalization
in adolescence and early adulthood in a Swedish population-based birth
Monfils Gustafsson Wiktor BSc, Ekholm Selling Katarina MA, Josefsson Ann
MD, Sydsjö Gunilla PhD
Division of Obstetrics and Gynaecology, Dept. of Clinical and Experimental Medicine
Faculty of Health Sciences
SE-581 85 Linköping, Sweden
Dr. Gunilla Sydjsö
Division of Obstetrics and Gynaecology
University Hospital, SE-581 85 Linköping
Phone +46 13 22 20 00 Fax +46 13 14 81 56
Word count for text only (exclusive of title, abstract, acknowledgements, references, and
Context: Preterm birth and restricted foetal growth are related to symptoms of psychiatric
disorder in childhood and early adulthood. However, psychiatric hospitalization has only
been studied to a limited extent.
Objective: To investigate possible relations between being born preterm and/or small for
gestational age (SGA) and later psychiatric hospitalization.
Design: A population-based registry study of psychiatric hospitalization. Registries allowed
for inclusion of parental socioeconomic characteristics, pregnancy and delivery complications
in the analyses. Preterm birth was defined as <37 weeks of gestation and SGA as a birth
weight <-2.01 SD of the Swedish standard. Logistic regression was used to calculate adjusted
odds ratios (OR) and 95% confidence intervals (CI95%).
Settings: Public hospitals in Sweden.
Participants: 155,994 males and 148,281 females born in Sweden 1973-1975, registered in
the Swedish Medical Birth Register.
Main outcome measures: Incidence and duration of all psychiatric hospitalization during the
Results: The risk of hospitalization for all mental disorders was increased for: preterm SGA
males (OR 2.19, CI95% 1.49-3.21); at term SGA males (OR 1.55, CI95% 1.34-1.79); at term
SGA females (OR 1.31, CI95% 1.15-1.50). Similarly, child psychiatric disorders and mental
retardation were overrepresented among preterm males, preterm SGA males, at term SGA
males, and at term SGA females. At term SGA males and females also suffered increased
risk for anxiety and adjustment disorders (OR 1.70, CI95% 1.18-2.45 and OR 1.49, CI95% 1.14-
1.94). For the males substance-related disorders were more common as well (OR 1.37, CI95%
1.11-1.71). Preterm, SGA males were also at risk for personality disorders (OR 3.30, CI95%
1.16-9.41) and psychotic disorders (OR 4.36, CI95% 1.85-10.30). SGA males were
overrepresented in all hospitalization durations.
Conclusions: The results show a relationship between being born SGA and later psychiatric
hospitalization, where preterm birth and male gender seem to increase the risk.
Preterm birth and/or fetal growth impairment have recently been subjects for research
concerning mental illness. Low birth weight has been related to both psychiatric symptoms
and psychiatric disorders (1-4), and in those born preterm there is some evidence of an
increased mental burden (5,6). It has also recently been shown amongst a sample of
individuals born preterm and small for gestational age (SGA) that symptoms of anxiety and
depression were more frequent (7). By linking medical birth registries to those of
hospitalization further relations have been shown. Examples of these are between low birth
weight (8) or SGA (9) and hospitalization because of schizophrenia in late adolescence and
adulthood; very preterm birth and SGA and hospitalization because of anorexia nervosa (10);
SGA and suicide (11). Linking such registries, results have also shown relations between low
birth weight children of 14 years or younger and mental retardation, Asperger´s Syndrome,
learning disorders, and eating disorders among others (12). In general SGA works as the ideal
marker of foetal growth impairment, however, it is still lesser studied than low birth weight.
The primary aim of this study was to explore the extent of relations between being born
preterm and/or SGA and later psychiatric hospitalization for a wide range of mental disorders.
As most studies until now have focused on a small selection of mental disorders, this
investigation would provide a comprehensive knowledge of the possible relations within the
whole spectrum of psychiatric hospitalization, and indirectly the extent of more severe
psychiatric sequelae related to preterm birth and/or fetal growth impairment. Moreover, as
most studies on the subject have used low birth weight as a proxy of foetal growth
impairment, this study defined SGA by an external standard providing strength to its
definition of SGA. Presuming that there were relations, would they differ by gender, and/or
remain after adjustments made for medical events of pregnancy and delivery or parental
Materials and Methods
Since 1973 the Swedish Medical Birth Register (MBR) has gathered information on maternal,
antenatal and perinatal data (13). The register continuously receives information on births
including identity, social factors, pregnancy, delivery and infant variables including birth
weight and gestational length. Today the register covers approximately 99 percent of all
births. During the period of pregnancy and delivery of the cohort (1973-1975) studied,
diagnoses in the MBR were made according to the eighth revision of the World Health
Organization (WHO) International Classification of Disease (ICD-8) (14). The Swedish
Hospital Discharge Register (HDR) has been in use since 1964. From 1987 on it covers all
public hospitalization in Sweden (15). The register continuously receives information on
patient-, hospital-, and administration data, including a main diagnosis. During the studied
period _ 1987 until 1996 _ diagnoses of mental disorder in the register were made according to
the Swedish version of the ninth revision of the WHO International Classification of Disease
Identifying the subjects within the cohort and their parents involved multiple registries: the
Total Population Register (TPR) made it possible to retrieve information on marital status,
births, deaths and migration including country of origin for parents and cohort (17); the
Causes of Death Register revealed data on deceased individuals (18); the Multi-generation
Register allowed for identification of the parents (19); and the Population and Housing
Census 1970 was used to retrieve the educational level of the parents (20). The unique
personal identification number assigned all Swedish citizens allowed for cross-reference of all
The cohort consisted of males and females born in Sweden during the years 1973, 1974 and
1975 registered in the MBR and the TPR. Of all registered births only those alive and living
in Sweden by age thirteen were included. Because of missing values on birth weight and/or
gestational length 1,161 males and 1,029 females were excluded, as were 167 males and 126
females with extremely high birth weights compared to their length of gestation. The mother
and/or the father of 1,161males and 1,003 females could not be identified, thus these males
and females were also excluded. The final number consisted of 148,281 females and 155,994
males. The exclusion-process has been described more thoroughly previously (21). During
the study period, 0.9 percent of the males emigrated and 0.5 percent were deceased. The
corresponding percentages among the females were 1.7 and 0.2.
The relation with the following categories of preterm birth, or markers of foetal growth
impairment on psychiatric hospitalization care were investigated: preterm birth defined as less
than 37 completed weeks of gestation, and SGA defined as a birth weight less than two
standard deviations (SD) below the mean birth weight according to Swedish external
standards from 1996 (22). SGA births were also stratified into those born at term SGA,
preterm SGA, moderately SGA (MSGA - being within 3.00 to 2.01 SD below mean birth
weight), and very SGA (VSGA - those below 3.00 SD).
Adjustments were made for various background variables. Medical diagnoses related to
pregnancy or delivery of the cohort were grouped together on a three-digit basis according to
the ICD-8, allowing for adjustment of these events (Table 1). Also a number of background
variables served as estimations of the early socioeconomic environment for the infants:
maternal age classified as 13-19, 20-26, 27-33 and > 34 years of age; parity of mother as
previous or no previous children; parental educational level, classified according to the
Swedish educational system as 9-10, 11-13 and > 14 years; marital status of mothers at time
of birth as married, divorced/widow or unmarried; and parental country of origin.
Table 1. Complications of pregnancy- and delivery for males and females born 1973-75.
n=148281 Complication Category ICD-8#
during pregnancy 401, 637 13101 12118
Preterm rupture of the
645.95, 661.0 1806 1553
655 3978 3514
delivery - 8281 5829
Cesarean section - 10103 9071
Apgar score at 1 minute
- 149130 142885
0-6 scores - 6864 5396
775 1069 975
Outcome variables for the cohort were hospital discharge with a main diagnosis of mental
disorder according to ICD-9. For the study period of 1987 until 1996 the overall cumulative
incidence of hospital discharge with a main diagnosis of mental disorder was investigated;
that is, hospitalization one or more times versus no hospitalization. For further analysis the
diagnosis codes of the Swedish version of ICD-9, chapter V mental disorders were divided
into nine diagnostic subcategories: substance-related disorders; mood disorders; personality
disorders; psychotic disorders; anxiety and adjustment disorders; somatoform and
dissociative disorders; eating disorders; child psychiatric disorders and mental retardation;
and other disorders (Table 2). For each subcategory the cumulative incidence of the study
period was investigated. Duration of hospitalization with a main diagnosis of mental disorder
was also investigated. The total number of days of psychiatric hospitalization during 1987-
1996 was classified into six subgroups: 1-7 days; 8-14 days; 15-30 days; 31-60 days; 61-120
days; and >120 days. For the study period the cumulative incidence of total number of days
of psychiatric hospitalization for each of these subgroups was investigated.
Table 2. Diagnostic subcategories and number of hospitalizations of males and females born
1973-1975 during the period of 1987-1996.
All mental disorders
Substance-related disorders 291, 292, 303-305 1475 882
Mood disorders 296, 300E, 301B, 311 257 474
Personality disorders 301A, 301C, 301E,301F,
301G, 301H, 301J, 301W,
Psychotic disorders 295, 297, 298 335 254
Anxiety and adjustment
300A, 300C, 300D,
300W, 300X, 308, 309
Somatoform and dissociative
300B, 300F, 300G, 300H,
Eating disorders 307B, 307F 37 533
Child psychiatric disorders
and mental retardation
299, 312-315, 317-319 581 661
Other disorders 290, 293, 294, 302, 307A,
307C-E, 307G, 307H,
Analyses were performed separately for the studied males and females and all variables in the
analyses were treated as categorical. Multiple logistic regression analysis was used to
estimate the effects of socioeconomic variables, delivery and pregnancy on subsequent overall
risk (cumulative incidence) of psychiatric hospitalization. Year of birth of the males and
females studied as well as ‘twin birth’ were also included in the analyses. The relations
between preterm birth, SGA and SGA-subgroups to subsequent risk for psychiatric
hospitalization were also estimated through logistic regression analysis. Both the crude odds
ratios (OR) and the ORs adjusted for the background variables were calculated; however, only
adjusted ORs are presented. The dependent variables were the overall cumulative incidence of
psychiatric hospitalization according to mental disorders of ICD-9 during the study period, as
well as the cumulative incidence of being hospitalized according to each diagnostic
subcategory. In order to find any differences on the character of hospitalization, each length-
of-stay subgroup was also used as a dependent variable, although restricted to the overall
cumulative incidence of psychiatric hospitalization.
This study was approved by the Human Research Ethics Committee; Faculty of Health
Sciences, Linköping University.
During the years 1973 to 1975, 7467 males and 6071 females were born preterm. In total
7461 males and 7942 females were born SGA. The total number of hospitalizations for
mental disorders for males and females born 1973-1975 are presented in Table 2.
For all mental disorders males born at term SGA, and in particular males born SGA and
preterm, were at an increased risk of hospitalization (Table 3). This was also true for females
born at term SGA. The only statistically significant increased risk for males born preterm was
within the subcategory of child psychiatric disorders and mental retardation.
Correspondingly, there was a weak tendency, although not statistically significant, in the
same subcategory for preterm females. Both males and females born at term SGA were at
increased risk of hospitalization within the subcategories of anxiety and adjustment disorders
and also child psychiatric disorders and mental retardation. Males born at term SGA;
however, differed from their female peers by also being at an increased risk for hospitalization
within the subcategory of substance-related disorders. Preterm SGA males were also at
increased risks for hospitalizations within the subcategories of: personality disorders;
psychotic disorders; child psychiatric disorders and mental retardation; and other disorders.
Data also implied an increased risk for mood disorders. In general the risks of hospitalization
within these subcategories were at a higher level for preterm SGA males, as compared to
those born at term SGA.
As primary analysis deemed SGA to be the one marker most strongly related to psychiatric
hospitalization, further analysis was initiated to reveal any possible differences among those
born SGA. Males and females born SGA were subdivided into MSGA, and VSGA, of which
1103 males, and 1155 females had a birth weight below 3.00 SD´s. Risks were equal to or
Table 3. Adjusted odds ratios for the cumulative incidence of psychiatric hospitalization according to subcategories of disorders amongst males and females
born as either preterm, SGA or both.
Subcategories of disorders OR*,†,‡ 95% CI
Substance-related disorders 1.11 0.89-1.40
Mood disorders 1.26 0.76-2.10
Personality disorders 1.43 0.84-2.42
Psychotic disorders 1.15 0.71-1.87
Anxiety and adjustment disorders 1.05 0.67-1.64
Somatoform and dissociative disorders 0.88 0.34-2.30
Eating disorders 0.57 0.07-4.37
Child psychiatric disorders and mental retardation 1.50 1.10-2.06
Other disorders 1.17 0.59-2.30
All mental disorders 1.14 0.97-1.33
Substance-related disorders 1.19 0.87-1.64
Mood disorders 1.33 0.88-2.02
Personality disorders 1.28 0.78-2.09
Psychotic disorders 1.12 0.62-2.03
Anxiety and adjustment disorders 1.12 0.80-1.56
Somatoform and dissociative disorders 1.42 0.84-2.41
Eating disorders 1.23 0.82-1.83
Child psychiatric disorders and mental retardation 1.30 0.92-1.83
Other disorders 1.01 0.52-1.95
All mental disorders 1.13 0.96-1.33
Abbreviations: OR=odds ratio, CI= confidence intervals, SGA=small for gestational age
Logistic regression analysis. † Adjusted for socioeconomic and pregnancy- or delivery related variables. ‡ Not adjusted for birth weight.
At term and SGA
OR*,† 95% CI
Preterm and SGA
OR*,† 95% CI
higher for males born MSGA or VSGA for all diagnostic subcategories as compared to the
females, with the exception of eating disorders (Table 4). Both SGA subgroups of males and
females were at a statistically significant increased risk of hospitalization for all mental
disorders, but risks were stronger for males and those born VSGA. For males born MSGA
increased risks were also observed for: substance-related disorders; anxiety and adjustment
disorders; and child psychiatric disorders and mental retardation. In comparison, VSGA
males also suffered an increased risk for: substance-related disorders; mood disorders;
psychotic disorders; anxiety and adjustment disorders; child psychiatric disorders and mental
retardation; and other disorders. All risks were at a higher level for these diagnostic
subcategories among the VSGA males as compared to those born MSGA. The only increased
risk within the diagnostic subcategories for MSGA females were for anxiety and adjustment
disorders and child psychiatric disorders and mental retardation. The VSGA females did not
follow the pattern observed among the VSGA males, and the only indication of a possibly
increased risk among the diagnostic subcategories was for anxiety and adjustment disorders.
Preterm males and females differed very little from those born at term with regards to total
duration of hospitalization for the studied period (Figure 1). For preterm females a positive
trend was observed with increased risks for hospitalizations of longer durations. However,
increased risks were only found statistically significant for hospitalizations of > 60 days OR
1.45 (CI95% 1.07-1.98, p=0.02). In males born preterm the risk for a total hospitalization
duration of 31-60 days was somewhat increased, OR 1.87 (CI95% 1.21- 2.89, p=0.005). In
contrast, SGA males suffered statistically significant increased risks for hospitalization
durations of all lengths as compared to those born appropriate for gestational age, with
increasing risk for hospitalizations of longer duration (Figure 2). In females born SGA a
negative trend was observed with increasing risks for hospitalizations of shorter duration,
although the only significant increased risk was for a hospitalization of 1-7 days, OR 1.41
(CI95% 1.16-1.70, p<0.001).
Table 4. Adjusted odds ratios for cumulative incidence of psychiatric hospitalization according to
subcategories of disorders amongst males and females born as MSGA or VSGA.
Subcategories of disorders OR*, † 95% CI
Substance-related disorders 1.34 1.07-1.68
Mood disorders 1.17 0.67-2.07
Personality disorders 1.31 0.74-2.31
Psychotic disorders 1.30 0.81-2.11
Anxiety and adjustment disorders 1.66 1.13-2.44
Somatoform and dissociative
disorders 1.82 0.83-3.96
Eating disorders 0.00 0.00-
Child psychiatric disorders and
mental retardation 1.94 1.43-2.62
Other disorders 1.51 0.79-2.89
All mental disorders 1.51 1.30-1.75
Substance-related disorders 1.11 0.83-1.50
Mood disorders 0.90 0.57-1.41
Personality disorders 1.15 0.72-1.84
Psychotic disorders 0.97 0.54-1.74
Anxiety and adjustment disorders 1.39 1.05-1.85
Somatoform and dissociative
disorders 1.44 0.89-2.33
Eating disorders 0.85 0.55-1.30
Child psychiatric disorders and
mental retardation 1.77 1.34-2.35
All mental disorders 1.25 1.09-1.45
Abbreviations: OR=odds ratio, CI=confidence interval, MSGA= moderately small for gestational age,
VSGA=very small for gestational age
* Logistic regression analysis.
† Adjusted for socioeconomic- and, pregnancy- or, delivery related
Figure 1. Adjusted odds ratios of total hospitalization duration 1987-1996 for preterm males
and females, as compared to full term males and females.
Figure 2. Adjusted odds ratios of total hospitalization duration 1987-1996 for small for
gestational age males and females, as compared to appropriate for gestational age males and
We believe that this study provides unique evidence of a relation between being born SGA
and hospitalization during late adolescence and early adulthood for the following groups of
disorders: substance-related; mood; anxiety and adjustment; personality; child psychiatric
and mental retardation; and other disorders. In this population-based register-study it was
shown that males within the study cohort who were born preterm suffered a very modest
increased risk of psychiatric hospitalization in late adolescence and early adulthood. In
comparison, subgroups of males born SGA and, to a lesser degree also females born SGA had
a higher risk of psychiatric hospitalization, especially males born SGA and preterm, or within
the VSGA subgroup. This was seen both for the total cumulative incidence of mental
disorder, and within several diagnostic subcategories. These increased risks were observed
after adjustments made for childhood socioeconomic characteristics and complications during
pregnancy and delivery. The evidence that those born SGA was at a greater risk was further
supported by the fact that SGA males were over-represented within all hospitalization-
duration subcategories. In conclusion, this indicates that there is a relationship between being
born SGA and later psychiatric hospitalization, which seems to be stronger when SGA birth is
combined with preterm birth and male gender. Preterm birth on its own, on the other hand,
was to a minor degree related to psychiatric hospitalization. It should be noticed that for
several of the risk increases the confidence intervals approached one, implying that the real
effect could be modest.
Lack of national registries on birth-data and mental hospitalization can limit the potential for
doing studies to determine if there is increased psychopathology amongst those born preterm
and/or SGA because samples may be limited in size and selection, for example if only
hospital-based samples are available. We were able to access population-based registries in
our study, which also allowed for adjustment for pregnancy, delivery, and socioeconomic
variables. It has been recognized that these are significant factors contributing to the
multifactor etiology of mental disorder (23,24). An earlier finding by Eaton et al. (12) showed
that children 14 years or younger who were born preterm and/or with signs of fetal growth
impairment were at an increased risk of hospitalization for a range of mental disorders. This
could, to some extent, be compared with our results. However, their sub-grouping of
gestational age, birth weight, and diagnoses, as well as the adjustments made for possible
confounders, differed very much from ours, making a comparison difficult. We were unable
to find an increased risk of hospitalization with a diagnosis of anorexia nervosa amongst
preterm females, as was done by Cnattingius et al. (10). These females were; however, born
very preterm, and the study included all live-birth females in Sweden during the years 1973 to
1984. Today there is some evidence of an increased psychopathology amongst children born
preterm. Still, this study showed only a limited increase in risk for psychiatric hospitalization
among the males born preterm, and none among the females born preterm (5,6). Earlier
studies have found that SGA (9) and low birth weight or low birth weight combined with
preterm birth (8) is associated with an increased risk of hospitalization with a diagnosis of
schizophrenia. Restricted to males our findings seem to be in accordance with this, however
we chose to analyze the sub-diagnostic category of psychotic disorders, which beside
schizophrenia also includes reactive psychosis and paranoid states.
Modern medical imaging techniques have made it possible to study in detail the morphology
of the brain. In this way it has been shown that differences in cerebral white matter are present
amongst samples of children and adolescents born preterm with low birth weights (<1500
grams)(25,26). Inder et al. (27) have, in addition, shown that a sample of preterm infants
(mean birth weight 1040 grams) also differed from their full term peers at term in morphology
of cerebral ventricles and cortical grey matter. The same study also showed that major
predictors of altered cerebral volumes were gestational age and white matter injury. In a
sample of preterm infants, Tolsa et al. (28) showed that those who suffered from intrauterine
growth retardation _ both at time of birth and at term _ had significantly lower cerebral cortical
grey volumes compared to those born preterm and appropriate for gestational age. Although
there are limitations to the conclusions that can be made from these findings, it remains
tempting to make the assumption that among them are to be found plausible explanations for
an increased mental morbidity.
Earlier quality control of the MBR has implied that “hard” data like birth weight are relatively
reliable. The quality of information on gestational length and birth weight has been found
“acceptable” and “good” (29). This is a general conclusion, and it should be understood that
the risk of incorrectly entered data increases when handling extreme values as, for example,
low birth weights. It should also be understood that diagnoses in the registry are made on a
basis of various diagnostic criteria in clinical practice. The same holds true for the HDR
which, on the matter of mental disorders, deserves its own discussion when one considers the
fact that psychiatric care had the highest number of missing main diagnoses within the HDR
in a recent evaluation of the registry (16). In the year 2004 approximately nine percent were
missing. During the past ten years the average number has been seven percent. The reasons
for this still remain unanswered.
Keeping in mind the numerous studies on increased symptoms of psychiatric disorder
amongst children born preterm and/or with sign of fetal growth restriction, one must
remember that this study measured hospitalization and not morbidity. If preterm and/or SGA
birth is associated with later adverse psychiatric outcome then it can be assumed that we only
measured the most extreme outcome. It could be that this group of individuals is prone to
information-bias when it comes to reporting symptoms of psychiatric disorder. Even so, our
study shows that the anthropometrical variables of SGA and to a minor extent preterm birth
are significantly related to psychiatric hospitalization care. Thus the knowledge that these
individuals are prone to psychopathology severe enough to cause increased risk of psychiatric
hospitalization in late adolescence and early adulthood could necessitate early recognition and
support, and add insight into the etiology of mental illness.
Author contributions: All authors had full access to data through Katarina Ekholm Selling,
whom takes full responsibility for the integrity of the data and the accuracy of the data
Study concepts and design: Monfils Gustafsson, Ekholm Selling, Sydsjö
Acquisition of the data: Monfils Gustafsson, Ekholm Selling, Sydsjö
Analysis and interpretation of data: Monfils Gustafsson, Ekholm Selling, Josefsson, Sydsjö
Drafting the manuscript: Monfils Gustafsson, Ekholm Selling, Sydsjö
Critical revision of the manuscript for important intellectual content: Monfils Gustafsson,
Ekholm Selling, Josefsson, Sydsjö
Statistical analysis: Monfils Gustafsson, Ekholm Selling
Obtaining funding: Sydsjö
Administrative, technical, or material support: Ekholm Selling, Josefsson, Sydsjö
Supervision: Ekholm Selling, Sydsjö
Conflicts of interest: None
Financial disclosure: None.
Funding/Support: This study was supported by grants from the Swedish Council for
Working Life and Social Research (FAS) and the Medical Research Council of Southeast
Role of the sponsors: FAS and FORSS had no role in the design or conduct of the study;
collection, management, analysis, or interpretation of the data; or in preparation, review or
approval of the manuscript.
Acknowledgements: The authors would like to thank the Swedish National Board of Health
and Welfare and Statistics Sweden for access to the registries.
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