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Acta Psychiatr Scand 2005: 112: 2629 Copyright  2005 Blackwell Munksgaard

All rights reserved ACTA PSYCHIATRICA


DOI: 10.1111/j.1600-0447.2005.00548.x
SCANDINAVICA

Breastfeeding and risk of schizophrenia in


the Copenhagen Perinatal Cohort
Srensen HJ, Mortensen EL, Reinisch JM, Mednick SA. Breastfeeding H. J. Srensen1,2,
and risk of schizophrenia in the Copenhagen Perinatal Cohort. E. L. Mortensen2,3,
Acta Psychiatr Scand 2005: 112: 2629.  2005 Blackwell Munksgaard. J. M. Reinisch2,4,5,
S. A. Mednick2,6
Objective: The aim was to study whether early weaning from 1
Department of Psychiatry, Amager Hospital,
breastfeeding may be associated with increased risk of schizophrenia. Copenhagen University Hospital, Copenhagen, 2Danish
Method: The current sample comprises 6841 individuals from the Epidemiology Science Center, Institute of Preventive
Copenhagen Perinatal Cohort of whom 1671 (24%) had been breastfed Medicine and 3Department of Health Psychology,
for 2 weeks or less (early weaning) and 5170 (76%) had been breastfed Institute of Public Health, University of Copenhagen,
longer. Maternal schizophrenia, parental social status, single mother Copenhagen, Denmark, 4The Kinsey Institute for
status and gender were included as covariates in a multiple regression Research in Sex, Gender, and Reproduction, Indiana
analysis of the eect of early weaning on the risk of hospitalization University, Bloomington, IN, 5R2 Science
with schizophrenia. Communications, Inc., Bloomington, IN and 6Social
Science Research Center, University of Southern
Results: The sample comprised 93 cases of schizophrenia (1.4%).
California, Los Angeles, CA, USA
Maternal schizophrenia was the strongest risk factor and a signicant
association between single mother status and elevated ospring risk of Key words: schizophrenia; breastfeeding; weaning;
schizophrenia was also observed. Early weaning was signicantly single parent
related to later schizophrenia in both unadjusted and adjusted analyses Erik L. Mortensen, Department of Health Psychology,
(adjusted odds ratio 1.73 with 95% CI: 1.132.67). Copenhagen University, Blegdamsvej 3, DK-2200
Conclusion: No or <2 weeks of breastfeeding was associated with Copenhagen N, Denmark.
elevated risk of schizophrenia. The hypothesis of some protective eect E-mail: e.l.mortensen@pubhealth.ku.dk
of breastfeeding against the risk of later schizophrenia is supported by
our data. Accepted for publication February 21, 2005

acid (DHA), an important constituent of cell


Introduction
membranes in the central nervous system. Lack
A number of studies have suggested a positive of postnatal DHA intake from formula feeds could
association between breastfeeding and cognitive explain the deviant cognitive and neurological
and intellectual development (13). Schizophrenia development seen premorbidly in schizophrenia
is preceded by childhood cognitive impairment (5, 8, 11).
(4, 5) and it has been suggested that breastfeeding
may be a factor in the aetiology of schizophrenia
Aims of the study
(6). Two studies have found that breastfeeding is
less common in babies who have become schizo- The aim of the present study was to use the
phrenic in adult life (6, 7). However, in a study Copenhagen Perinatal Cohort to test the hypothe-
based on prospective data from two British sis that early weaning is associated with increased
national birth cohorts, no evidence of a protective risk of schizophrenia and that there is a protective
eect of breastfeeding against schizophrenia was eect of breastfeeding against the disease.
observed (8), and some retrospective studies have
also been unable to demonstrate that breastfeeding
is less common in babies who later develop Material and methods
schizophrenia (9, 10).
Sample
A plausible mechanism for the possible protec-
tive eect of breast milk has been suggested (8). The Copenhagen Perinatal Cohort comprises 9125
Unlike cows milk or most formula feeds, breast individuals born at the Copenhagen University
milk contains large amounts of long-chain poly- Hospital, Rigshospitalet, between October 1959
unsaturated fatty acids, especially docosahexaneoic and December 1961. When the cohort was

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Breastfeeding and schizophrenia

established, demographic, socioeconomic, prena-


Psychiatric hospitalization with schizophrenia
tal, and postnatal medical data were recorded
prospectively during pregnancy, at delivery, and at Written approval to conduct a registry-based
a 1-year examination (12, 13). The mothers were psychiatric follow-up was obtained by the regional
mainly residents in Copenhagen, but some were scientic and ethics committee. The Danish Psy-
admitted on obstetrical indications or because of chiatric Central Register has been computerized
single mother status. A total of 8400 infants since 1 April 1969 (14). The register contains data
survived the rst month after birth. on all admissions to Danish psychiatric in-patient
facilities. The diagnostic system in use when the
Danish Psychiatric Central Register was compu-
Breastfeeding
terized was the International Classication of
A physician had interviewed the mother at the Diseases, 8th Revision (ICD-8) (15). The cohort
1-year examination and collected information on and their parents were followed in the Danish
duration of breastfeeding. Data on duration of Psychiatric Central Register to identify all admis-
breastfeeding was available for 6841 cohort mem- sions with a diagnosis of schizophrenia (ICD-8
bers (3485 males and 3356 females) who were code 295 or ICD-10 code F20) until December
registered as citizens of Denmark by 1 April 1969, 1999. In ICD-8, schizophrenia is dened by pro-
and identiable in the Danish Psychiatric Register. totypic descriptions of symptoms, such as bizarre
Duration of breastfeeding was originally recorded delusions, delusions of control, abnormal aect,
on a 111 point scale (from 12 weeks to autism, hallucinations, and disorganized thinking.
>12 months). It was not possible to include a In 1994, the more operational ICD-10 criteria were
separate category for children who were never implemented (16). The cohort and their parents
breastfed as they had been coded as 12 weeks or were categorized with a history of schizophrenia
less. Thus, we were unable to use the categorization (ICD-8 code 295 or ICD-10 code F20) if they had
bottle-fed, breastfed <1 month, and breastfed ever been admitted with one of these diagnoses. It
>1 month used in previous studies (8). For has previously been shown that paternal hospital-
sample size considerations and to facilitate com- ization with schizophrenia is not a signicant
parison with previous studies, we dichotomized the predictor of ospring risk of schizophrenia in this
sample in an early weaning category (12 weeks; cohort (17).
n 1671 or 24%) and a late weaning category
(>2 weeks, n 5170 or 76%).
Statistical analysis
Logistic regression analysis was used to estimate
Single mother status
ospring risk (odds ratio, OR with 95% condence
Information on maternal marital status was limits) of schizophrenia associated with i) early
recorded at the time of delivery. Data were weaning (2 weeks duration of breastfeeding or no
missing for 29 individuals in the study population breastfeeding), ii) single mother status, and iii)
(0.4%). For this study, subjects were divided into maternal hospitalization with schizophrenia. These
two groups: ospring of single mothers (n estimates were subsequently adjusted for gender
2570) and ospring of mothers who were not and parental social class. The third model estima-
single (n 4242). ted the joint inuences of all three variables
adjusted for gender and social class.
Parental social status
Results
Information on parental social status was obtained
from an interview with the mother when the child Ninety-three subjects (1.4%) (61 males and 32
was 1 year old. The 18 point socioeconomic status females) were identied as cases with schizophre-
index was based on information about the bread- nia. Table 1 shows that the cumulative incidence of
winners occupation, breadwinners education, schizophrenia in the early weaning category was
type of income (wage/salary) and quality of hous- 2.0% (95% CI: 1.52.8), whereas the cumulative
ing. Sucient data for classication was available incidence in the later weaning category was 1.1%
for only 6025 individuals (88.1% of the study (95% CI: 0.91.5).
sample). The overall social status mean was sub- Table 2 shows the OR of ospring developing
stituted for missing data and a dummy variable schizophrenia in relation to duration of breast-
included to indicate missing data on social status in feeding, maternal schizophrenia, and single mother
the logistic regression analysis. status. The ORs presented in the rst column were

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Srensen et al.

Table 1. Cumulative incidence of schizophrenia according to breastfeeding cate- gender, and parental social status (adjusted OR
gory in the Copenhagen Perinatal Cohort
1.53 with 95% CI: 1.002.32).
No. of cases Cumulative incidence
Duration of with of schizophrenia (%)
Breastfeeding breastfeeding schizophrenia* with 95% CI Discussion

Early weaning (n 1671) 2 weeks 34 2.0 (1.52.8) This study showed a 1.7-fold higher risk of
Later weaning (n 5170) >2 weeks 59 1.1 (0.91.5) schizophrenia in ospring of mothers who did
Entire sample (n 6841) 93 1.4 (1.11.7) not breastfeed or stopped breastfeeding within
*Schizophrenia identified on the basis of Danish Psychiatric Central Register
2 weeks, when compared with ospring of mothers
records of hospitalization with a diagnosis of schizophrenia (ICD-8 code 295 or ICD- who breastfed longer. This eect remained signi-
10 code F20) until end of 1999. cant after adjustment for gender, social status,
maternal schizophrenia, and single mother status
Table 2. Multiple logistic regression analysis predicting schizophrenia in members when the child was born. A weaker predictive eect
of the Copenhagen Perinatal Cohort of early weaning was observed when 1 month
Odds ratio (95% CI) duration of breastfeeding was used as cuto.
It is an advantage of our prospective study that
Variable Unadjusted Model 1* Model 2 the mothers were interviewed about the duration of
Breastfeeding category breastfeeding by a physician when the child was
>2 weeks (Ref.) 1.00 1.00 1.00 1 year, and that cases of schizophrenia were
2 weeks 1.80 (1.182.75) 1.75 (1.142.68) 1.73 (1.132.67) identied in a national registry independently of
Covariates
Mother 9.42 (4.3820.22) 9.69 (4.4820.93) 10.46 (4.8122.77)
information collected when the Perinatal Cohort
schizophrenia was established. Cohort members were followed
Single mother 1.94 (1.292.92) 1.90 (1.222.94) 1.84 (1.182.85) through most of the risk period for schizophrenia
and the registered cases were eectively incident
*Model outputs were adjusted for gender of the cohort member and parental
social status at 1 year of age. cases. As pointed out elsewhere, this does not lead
Outputs for a model that included breastfeeding, maternal hospitalization with to bias towards chronic illness (8).
schizophrenia, single mother status and also adjusted for gender of the cohort The psychiatric diagnoses in the present study
members and parental social status.
Schizophrenia identified on the basis of Danish Psychiatric Central Register
were clinical diagnoses according to ICD-8 or
records of hospitalization with a diagnosis of schizophrenia (ICD-8 code 295 or ICD- ICD-10. The ICD-8 diagnosis of schizophrenia was
10 code F20) until end of 1999. used conservatively in Denmark, and previous
studies have shown that almost all patients with a
unadjusted, while those presented in the second diagnosis of schizophrenia meet the DSM-III-R
column were adjusted for gender and parental criteria for schizophrenia (18). The rather narrow
social class. The eect of early weaning, adjusted concept of schizophrenia according to ICD-8 is
for maternal schizophrenia, single mother status, likely to have led to diagnostic caution rather than
gender of the cohort member, and parental social over-inclusiveness before the diagnostic system was
status, is shown in the third column of the table. changed in 1994.
Early weaning from breastfeeding was associ- Being ospring of a single mother was associated
ated with increased risk in the unadjusted analysis both with elevated risk of schizophrenia and with
(OR 1.80 with 95% CI: 1.182.75). The eect short duration of breastfeeding. The confounding
remained signicant after adjustment for gender eect of maternal marital status may not have been
and parental social status and was also statistically considered in other studies of the association
signicant when all covariates were analysed between breastfeeding and risk of schizophrenia.
together (OR 1.73 with 95% CI: 1.132.67). Our nding of a robust more than twofold increase
Additional analyses showed no signicant interac- in the risk of schizophrenia of children born to
tion between gender and early weaning with single mothers is compatible with a large popula-
respect to schizophrenia. The association between tion-based cohort study that observed a twofold
single mother status at birth and ospring risk of increase in the risk of schizophrenia in individuals
schizophrenia remained signicant in the adjusted with unknown fathers (19). It is possible that
analysis (OR 1.84 with 95% CI: 1.182.85). growing up in a family without a father is an
Analyses identical to those presented in Table 2 independent risk factor, but it is also possible that
were conducted with early weaning dened as single mother status correlates with other risk
1 month. The association between early weaning factors such as genetic liability for schizophrenia in
and risk of schizophrenia was only marginally the father, prenatal stress, or maternal depression.
signicant for the model that included adjustment It is of interest that the predictive eect of early
for maternal schizophrenia, single mother status, weaning was stronger when the cuto for early

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Breastfeeding and schizophrenia

weaning was set at 2 weeks than when the cuto 5. Jones P, Rodgers B, Murray R, Marmot M. Child develop-
was set at 1 month. It is possible that this relatively ment risk factors for adult schizophrenia in the British
1946 birth cohort. Lancet 1994;344:13981402.
modest variation in risk estimates may be the result 6. McCreadie RG. The Nithsdale Schizophrenia Surveys. 16.
of stochastic variation. However, it is an intriguing Breast-feeding and schizophrenia: preliminary results and
possibility that as little as 1-month exposure to hypotheses. Br J Psychiatry 1997;170:334337.
maternal milk may have a protective eect against 7. Peet M, Poole J, Laugharne J. Infant feeding and the
the development of schizophrenia. Consequently, development of schizophrenia. Schizophr Res
1997;24:255256.
we nd that further studies are needed, and that it 8. Leask SJ, Done DJ, Crow TJ, Richards M, Jones PB. No
may be too early to dismiss the hypothesis that association between breast-feeding and adult psychosis in
breastfeeding might have a protective eect against two national birth cohorts. Br J Psychiatry 2000;177:218
the development of schizophrenia. Because of the 221.
prevalence of early weaning as an exposure in the 9. Amore M, Balista C, McCreadie RG et al. Can breast-
feeding protect against schizophrenia? Biol Neonate
general population, it would be of public health 2003;83:97101.
interest, if independent studies were to replicate the 10. Sasaki T, Okazaki Y, Akaho R et al. Type of feeding during
ndings presented here. infancy and later development of schizophrenia. Schizophr
Res 2000;42:7982.
11. Done J, Johnstone EC, Frith CD, Golding J, Shepherd PM,
Acknowledgements Crow TJ. Complications of pregnancy and delivery in
relation to psychosis in adult life: data from the British
Supported by Sygekassernes Helsefond (Health Insurance Perinatal Mortality Survey Sample. BMJ 1991;302:1576
Foundation) grant to Srensen, grants HD-17655 and HD- 1580.
20263 from the National Institute of Child Health and Human 12. Zachau-Christiansen B, Ross EM. Babies: human develop-
Development to Reinisch, grant from the National Institute of ment during the rst year. New York: John Wiley & Sons,
Drug Abuse to Reinisch, grant 9700093 from the Danish 1975.
Research Council to Mortensen, and grant 1400/2-4-1997 from 13. Reinisch, JM, Mortensen, EL, Sanders, SA. The prenatal
the Danish National Board of Health to Mortensen. Thanks development project. Acta Psychiatr Scand Suppl 1993;
are due to Vibeke Munk, BA, for help with the manuscript and 370:5461.
critical comments. 14. Munk-Jrgensen P, Mortensen PB. The Danish Psychiatric
Central Register. Dan Med Bull 1997;44:8284.
15. WHO. Manual of the international statistical classication
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