Journal of Affective Disorders 171 (2015) 132–136
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Research report
Is maternal smoking during pregnancy associated with bipolar disorder in offspring? Roshan Chudal a,n, Alan S. Brown b,c, Mika Gissler a,d,e, Auli Suominen a, Andre Sourander a,b,f,g a
Department of Child Psychiatry, University of Turku, Turku, Finland Department of Psychiatry, Columbia University College of Physicians and Surgeons, New York State Psychiatric Institute, New York, USA c Department of Epidemiology, Columbia University, Mailman School of Public Health, New York, USA d Nordic School of Public Health, Gothenburg, Sweden e National Institute for Health and Welfare, Helsinki, Finland f Department of Child Psychiatry, Turku University Hospital, Turku, Finland g Regional Centre for Child and Youth Mental Health and Child Welfare, University of Tromsø, Tromso, Norway b
art ic l e i nf o
a b s t r a c t
Article history: Received 3 May 2014 Received in revised form 5 September 2014 Accepted 14 September 2014 Available online 28 September 2014
Background: Prenatal smoking exposure affects fetal growth and development and is associated with increased risk of various neurodevelopmental disorders. Only one previous study has examined the association between maternal smoking during pregnancy and the risk of bipolar disorder (BPD). Methods: In this nested case control study derived from all singleton live births in Finland between January 1st 1987 and December 31st 1998, we identified 724 children diagnosed and/or treated with BPD until 2008 and 1419 matched controls from four nationwide registers. Conditional logistic regression was used to examine the association between maternal smoking during pregnancy and BPD adjusting for potential confounding due to parental psychiatric history, maternal age and education level. Results: 18.5% of offspring were exposed to maternal smoking during pregnancy. In the unadjusted analysis, smoking during pregnancy was associated with a 1.41-fold (95% CI 1.12–1.79, P¼ 0.004) increased risk of BPD. In the final model adjusting for potential covariates, the risk was 1.14-fold (95% CI 0.88–1.49, P¼ 0.323). Limitations: The limitations of this study include: hospital based clinical diagnosis for case ascertainment, inclusion of early onset BPD cases, and lack of information on alcohol or other substance abuse during pregnancy. Conclusion: This study demonstrated that, in this sample, an increased risk of BPD among offspring of mothers who smoked during pregnancy is most likely due to confounding by familial background factors. Future studies including information on serological measures of smoking exposure in pregnancy e.g. cotinine are warranted to further clarify this association. & 2014 Elsevier B.V. All rights reserved.
Keywords: Prenatal Smoking during pregnancy Bipolar disorder
1. Introduction Prenatal smoking exposure affects fetal growth and development and is associated with adverse perinatal events, (Hofhuis et al., 2003) high blood pressure and diabetes (Blake et al., 2000; Montgomery and Ekbom, 2002). Furthermore, maternal smoking is associated with increased risk of attention-deficit/hyperactivity disorder (ADHD) (Button et al., 2005), conduct disorder (Fergusson et al., 1998) and autism spectrum disorder (ASD) (Hultman et al., 2002) as well as psychiatric morbidity (Ekblad et al., 2010). n Correspondence to: Research Centre for Child Psychiatry, Institute of Clinical Medicine, Faculty of Medicine, University of Turku Lemminkäisenkatu 3/Teutori (3rd floor), 20014 Turku. Tel.: þ358 2 333 7394; fax: þ 358 2 333 7098. E-mail address: roschu@utu.fi (R. Chudal).
http://dx.doi.org/10.1016/j.jad.2014.09.030 0165-0327/& 2014 Elsevier B.V. All rights reserved.
Bipolar disorder (BPD) has a neurodevelopmental component, the development of which involves genetic and environmental factors (Berrettini, 2000). The existing literature on the risk associated with maternal smoking during pregnancy in development of mood disorders is limited with inconsistent findings. One previous study has investigated the association specifically for BPD and showed an increased risk (Talati et al., 2013). Another study showed it to be associated with an increased risk of mood disorders (Ekblad et al., 2010), while two studies did not find any association with anxiety or major depression (Fergusson et al., 1998; Weissman et al., 1999). Based on the inconsistent findings on mood disorders, and only one previous published study on BPD, we aim to examine the association between maternal smoking during pregnancy and the risk of BPD, in this large nationwide population based epidemiological study.
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2. Materials and methods
2.4. Maternal smoking during pregnancy
2.1. Study design
Information about maternal smoking during pregnancy was obtained from FMBR. These data were collected by maternity clinic nurses during obstetric visits in the second trimester of pregnancy. This information between January 1st 1987 and September 30th 1990 was categorized as: non-smokers, smoking o10 cigarettes per day, or 410 cigarettes per day. From October 1st, 1990 to December 31st 1998, the information was available as: nonsmokers, smoking only during the first trimester and smoking throughout pregnancy. Out of the total sample, smoking information was missing for 3.6% of cases and 4.7% of controls.
This study is based on the Finnish Prenatal study of Bipolar Disorders (FIPS-B) (Chudal et al., 2014). The sampling frame of this nested case-control study with a prevalent control design, includes all singleton live born children in Finland between January 1st 1987 and December 31st 1998 (N ¼754,450). The nested design is due to selection of cases and a sample of matched controls from a defined birth cohort. Ethical approval for the study was obtained from the Institutional Ethical Review Board at Turku University Hospital, Turku University, and the Institutional Review Board of the New York State Psychiatric Institute. 2.2. National register information This study is based on data from four Finnish nationwide registers: the Finnish Medical Birth Register (FMBR), the Finnish Hospital Discharge Register (FHDR), the Finnish Central Population Register and the Register of Education at Statistics Finland. Detailed description of these registers and the study design of FIPS-B have already been reported elsewhere (Chudal et al., 2014). The FMBR, established in 1987, includes comprehensive data on the perinatal period for all newborns in Finland. The Finnish public health care system consists of both primary health care and specialized health services. Patients are typically referred by a general practitioner to specialized mental health services where the assessment is led by a child, adolescent or adult psychiatrist, depending on the patient's age. The FHDR has all medical diagnoses in hospitals in Finland since 1969 and covers all inpatient wards, in somatic and psychiatric hospitals, local health centres, military wards, prison hospitals, and private hospitals. Since 1998, it also covers the outpatient care in public specialized hospital units. In Finland, diagnostic classification is based on the International Classification of Diseases (ICD); ICD- 8 (World Health Organization, 1967) from 1968 to 1986, ICD-9 (World Health Organization, 1977) from 1987 to 1995 and ICD-10 (World Health Organization, 1992) from 1996 onwards. The Finnish Central Population Register is a computerized national register, maintained by the Population Register Centre and local register offices that contains basic information about Finnish citizens and foreign citizens residing permanently in Finland. The linkage between registers was made using the personal identity code (PIC), assigned to all residents of Finland since 1964. 2.3. Identification of study subjects The cases include all singletons diagnosed with BPD (N¼ 724) born between January 1, 1987 and December 31, 1998 and diagnosed and/or treated by December 31, 2008. They were identified from the FHDR using ICD diagnostic codes F31.x (ICD-10) and 2962A G, 2963A G, 2964A G, 2967A (ICD-9).The FMBR was established in 1987, therefore offspring born before 1987 were excluded. Controls for this study (N ¼ 1419) were offspring who were without BPD, schizophrenia or diagnoses related to these disorders (ICD-10 diagnoses: F20–29, F30, F31, F34.0, F38.0, F39, F60.0 and F60.1); ICD-9 diagnoses (2962A G, 2963A G, 2964A G, 2967A BPD, 295, 297, 298, 3010A, 3012A and 3012C). The controls were selected among the remainder of the children born during the study years and were matched to cases on selected factors (sex, date of birth (730 days) and residence in Finland on the first date of diagnosis of the matched case). Two controls for each case were identified from the Finnish Central Population Register (N ¼1448). Among 1448 control children, 29 were excluded as they belonged to a twin pair resulting in 1419 controls in the final analyses.
2.5. Covariates The covariates initially considered in the analyses were: parental psychiatric history, maternal age and education level, place of birth and weight for gestational age (WGA). These covariates have been shown to be associated with maternal smoking (Matthews, 2001; Ventura et al., 2000; Jaakkola et al., 2001; Jaakkola and Gissler, 2004; Maughan et al., 2004) and BPD (Frans et al., 2008; Laursen et al., 2005; Chudal et al., 2014) in previous studies. Maternal age data obtained from the Medical Birth Register was classified as: o20, 20–24, 25–29, 30–34 and Z35 years. Data from the FHDR was used to classify a father or mother as having a psychiatric history (Yes/No), if he/she had any mental disorder of F10–99, based on the ICD-10 classification, or corresponding diagnoses based on the ICD-9 (291–316) and the ICD-8 (291–308). Diagnoses related to mental retardation (ICD-10: F70–79, ICD-9: 317–319, ICD-8: 310–315) were excluded. Maternal educational level data obtained from Statistics Finland were classified into three categories: 1) university degree, 2) secondary school graduate and 3) basic education (comprehensive school). The birth municipality information for cases and controls obtained from the Population Register Centre was used to categorize birthplace into four categories (southern Finland, northern Finland, western Finland, and eastern Finland). The calculation of birth weight for gestational age [(small for gestational age (SGA)/ appropriate for gestational age (AGA) and large for gestational age (LGA)] was done according to national sex-specific weight distributions standards at a given gestational age. The growth curves were derived from data on 75 061 singleton children, with a gestational age of 24–43 weeks, born between 1979 and 1983 in Helsinki University maternity hospitals in Uusimaa, Finland (Pihkala et al., 1989). WGA was categorized into three groups: SGA:o2 standard deviations (SD) below the mean; AGA: between 2 SDs and þ2 SDs and LGA: 2 SDs above the mean. 2.6. Statistical analyses Initially, bivariate analyses were conducted (using Pearson's chi squared test for dichotomous variables with statistical significance at po0.1) to test the significance of association between covariates (maternal age, paternal psychiatric history, maternal psychiatric history, maternal education level, place of birth and weight for gestational age (WGA)) and maternal smoking among controls as well as between covariates and BPD (Appendix A: Supplementary material). Conditional logistic regression models were used to examine the association between maternal smoking during pregnancy and BPD. Initially, smoking was examined as a binary variable (yes/no) for the total sample. Unadjusted odds ratios (OR) and 95% confidence intervals (CI) were calculated. Maternal smoking was then adjusted in sequential models for maternal age, educational level and maternal and paternal psychiatric history. In the final model, we calculated ORs adjusting for all the above mentioned covariates.
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We also calculated ORs adjusting for a combination of any two of these covariates. Maternal smoking during pregnancy was subsequently classified into two separate categories based on definitions of smoking exposure. We calculated unadjusted ORs and 95% CI and ORs adjusting for maternal age, and education level and parental psychiatric history. Maternal smoking during pregnancy was subsequently classified into two separate categories based on different definitions of smoking exposure used, i.e. offspring born between January 1st 1987 and September 30st 1990, and offspring born between October 1st 1990 and December 31st 1998. We calculated both unadjusted odds ratios (OR) and 95% confidence intervals (CI) and odds ratios (OR) adjusting for maternal age, and education level and parental psychiatric history. In all analyses, a two-sided P-value of o0.05 was considered statistically significant. Statistical analyses were performed with SAS statistical software (SAS Version 9.3; SAS Institute Inc., Cary, NC).
3. Results The mean age at diagnosis of cases was 17.4 years (SD: 2.6, Range: 5–21 years). Table 1 shows the descriptive of cases and controls in the study. In the total sample, 18.5% of offspring were exposed to maternal smoking. Among the covariates, paternal psychiatric history, maternal age, psychiatric history and education
level were significantly associated with both maternal smoking during pregnancy and BPD (Appendix A). However, birth province was significantly associated only with BPD, and WGA was not associated with both maternal smoking during pregnancy and BPD. Therefore, adjustment was made only for paternal psychiatric history, maternal age, psychiatric history and education level in the final analysis. In the unadjusted analysis, smoking during pregnancy in the total sample was associated with a 1.41- fold (95% CI 1.12–1.79, P¼ 0.004) increased risk of BPD (Table 2). In the final model adjusting for potential confounders, the risk was 1.14-fold (95% CI 0.88–1.49, P ¼0.323). There were no significant differences in the risk based on sex (P ¼0.28). There were no significant associations following adjustment for any two confounders: maternal age and psychiatric history, OR ¼1.22, 95% CI 0.95–1.56, maternal age and educational level, OR ¼1.25, 95% CI 0.97–1.59,maternal age and paternal psychiatric history, OR¼ 1.24, 95% CI 0.97–1.60, maternal educational level and paternal psychiatric history OR¼1.23, 95% CI 0.95–1.59, maternal educational level and psychiatric history OR¼ 1.21, 95% CI 0.94–1.56, and maternal and paternal psychiatric history OR¼ 1.24, 95%CI 0.96–1.60. Being exposed to 410 cigarettes/day was associated with greater risk OR¼1.29, 95% CI 0.87–1.92, than those smoking o 10 cigarettes/ day OR¼ 1.02, 95%CI 0.69–1.51 (Table 3).
4. Discussion Table 1 Descriptive of BPD cases and controls in the study. BPD cases (n¼ 724), n (%)
Controls (N¼ 1419), n (%)
Sex Male Female
n¼ 724 230 (31.8) 494 (68.2)
n¼ 1419 453 (31.9) 966 (68.1)
Mother’s age (years) Mean (SD) Range
n¼ 724 28.4 (5.9) 15–47
n¼ 1419 28.6(5.1) 16–45
Maternal smoking during pregnancy No Yes
n¼ 698
n¼ 1352
546 (78.2) 152 (21.8)
1125 (83.2) 227 (16.8)
Mother’s psychiatric history No Yes
n¼ 724 504(69.6) 220 (30.4)
n¼ 1419 1250 (88.1) 169 (11.9)
Father’s psychiatric history No Yes
n¼ 706 513 (72.7) 193 (27.3)
n¼ 1400 1222(87.3 178 (12.7)
Mother’s educational level University degree Secondary school graduate Basic education
n¼ 724 118(16.3) 418 (57.7) 188 (26.0)
n¼ 1419 294 (20.7) 841 (59.3) 284 (20.0)
This study has several methodological strengths including ascertainment of cases and matched controls from nationwide hospital registers; maternal smoking information collected by midwives during antenatal care and information on several potential confounders. This study demonstrated that, in this sample, an increased risk of BPD among offspring of mothers who smoked during pregnancy was most likely due to confounding by familial background factors. Mothers who continue to smoke despite being pregnant are different from non-smokers, including having vulnerability to BPD which becomes transmitted from the mother to child (Maj, 2013). As seen in previous studies (Matthews, 2001; Ventura et al., 2000), our study sample showed that mothers who smoked during pregnancy were younger, had lower educational level and had more often a history of some psychiatric illness. Several previous studies (D'Onofrio et al., 2012a, 2012b) have suggested that the association between maternal smoking during pregnancy and offspring behavioral problems and substance use is confounded by familial background factors. This study failed to replicate the findings seen in a previously published study showing an association between maternal smoking during pregnancy and BPD (Talati et al., 2013). The inconsistent findings between the two studies may be accounted for by the fact that the birth cohort of Talati et al. (2013) was based on pregnancies from 1959 to 1966, when
Table 2 Smoking during pregnancy and risk of BPD in the total samplea. Odds ratio
95% confidence interval
P-value
Maternal smoking during pregnancy (unadjusted)
1.41
1.12–1.79
0.004
Maternal smoking during pregnancy adjusting for: Maternal age Maternal educational level Maternal psychiatric history Paternal psychiatric history Maternal smoking during pregnancy (adjusting for all potential confounders)n
1.32 1.28 1.30 1.32 1.14
1.04–1.67 1.01–1.64 1.02–1.66 1.03–1.69 0.88–1.49
0.024 0.044 0.037 0.026 0.323
n
a
Adjusting for maternal age, maternal and paternal psychiatric history and maternal education level. Statistical significance at P o0.05. Born between January 1st 1987 and December 31st 1998.
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Table 3 Smoking during pregnancy and risk of BPD in two sub samples. Frequencies
OR (95% CI)
P-value
OR1 (95% CI)
P-value
Casesc
Controlsd
Sub-sample (1987–1990)a No smoking Smoking o10 cigs/day Smoking 410 cigs/day
(N ¼531) (%) 422 (79.5) 55 (10.4) 54 (10.2)
(N¼ 1021) (%) 848 (83.1) 97 (9.5) 76 (7.4)
Ref 1.14 (0.79–1.64) 1.47 (1.01–2.13)
0.502 0.044
Ref 1.02 (0.69–1.51) 1.29 (0.87–1.92)
0.933 0.206
Sub sample (1990–1998)b No smoking Smoking only in first trimester Continued smoking after first trimester
(N ¼167) (%) 124 (74.3) 2 (1.2) 41 (24.6)
(N¼ 331) (%) 277 (83.7) 8 (2.4) 46 (13.9)
Ref 0.63 (0.13–3.06) 2.14 (1.29–3.55)
0.567 0.033
Ref 0.38 (0.07–2.04) 1.38 (0.78–2.43)
0.260 0.268
OR ¼ Odds Ratios, OR1: Adjusted for maternal age, maternal and paternal psychiatric history and maternal education level; Statistical significance at Po 0.05. a Born between January 1st 1987 and September 30th 1990. b Born between October 1st 1990 and December 31st 1998. c Smoking data missing for cases: 3.6%. d Smoking data missing for controls: 4.7%.
smoking was considered to be a more normative behavior and less likely to be associated with maternal psychiatric disorders.
highest risk for continued smoking during pregnancy (Jaakkola et al., 2001; Dejin-Karlsson et al., 1996).
5. Limitations
Conflict of interest The authors report no conflicts of interest.
The limitations in this study need to be considered in the interpretation of results. First, the data on smoking were acquired by maternal self-report during pregnancy with no information available on post-natal tobacco exposure. Self-report of maternal smoking during pregnancy is known to underestimate the actual smoking trends (Ford et al., 1997). However, the validity of the FMBR data on maternal smoking has been shown to be excellent (Jaakkola et al., 2001). Second, information on alcohol or other substance use during pregnancy as well as paternal smoking data was not available in the registers. Third, the diagnoses in the FHDR are not based on standardized interviews, but are hospital-based clinical diagnoses. However, the validity of the FHDR has been found to be good for the diagnosis of mental disorders in general (Keskimäki and Aro, 1991) and particularly for BPD (Kieseppä et al., 2000; Perälä et al., 2007). Fourth, the children with BPD included in this study were aged r21 years, and thus the findings or lack thereof, may be specific to early onset cases. Fifth, despite having a moderate sample size, it is possible that the lack of sufficient statistical power could have resulted in failure to detect significant associations. Lastly, our study sample includes only cases utilizing specialized mental health services and we assume that it represents rather well more severe cases of BPD in the population. Children having less severe BPD may not utilize specialized mental health services and therefore are missing in the nationwide registers. However, the health care services in Finland are universal, financed by the state and municipalities and the overall health coverage is good. Thus, BPD cases missing due to lack of access to health services is expected to be small.
6. Conclusions Future studies aimed at further clarifying this association include serologically documented measure of smoking exposure in pregnancy such as cotinine, a nicotine metabolite. Furthermore, availability of a larger sample size, thereby increasing the statistical power and including later onset BPD cases are warranted. A high prevalence of smoking during pregnancy (Martin et al., 2009; Ward et al., 2007) despite existing smoking cessation strategies calls for population based preventive measures, with increased focus on women with low psychosocial resources who are at the
Funding disclosure This work was supported by grants from NARSAD Independent Investigator Award, USA (A.S), the Sigrid Juselius Foundation, Finland (A.S), NIMH 5K02-MH65422 (A.S.B.) and the University of Turku Graduate School funding (UTUGS) (RC).
Contributors Authors RC, ASB, MG, AS and AS designed the study. Author RC managed the literature searches and analyses. Authors AS undertook the statistical analysis, and author RC wrote the first draft of the manuscript. All authors contributed to and have approved the final manuscript. Acknowledgments The study was conducted at the University of Turku, Finland. We thank the study investigators and staff at medical centers involved in this research. Specifically we would like to thank the members involved in the data collection process including: Juha-Pekka Virtanen, Pyry Kantanen, Kristiina Saanakorpi, Tanja Sarlin, Jarna Lindroos and Lauri Sillanmäki from Research Centre for Child Psychiatry, University of Turku.
Appendix A. Supporting information Supplementary data associated with this article can be found in the online version at http://dx.doi.org/10.1016/j.jad.2014.09.030. References Berrettini, W.H., 2000. Genetics of psychiatric disease. Annu. Rev. Med. 51, 465–479. Blake, K.V., Gurrin, L.C., Evans, S.F., Beilin, L.J., Landau, L.I., Stanley, F.J., Newnham, J.P., 2000. Maternal cigarette smoking during pregnancy, low birth weight and subsequent blood pressure in early childhood. Early Hum. Dev. 57, 137–147. Button, T.M., Thapar, A., McGuffin, P., 2005. Relationship between antisocial behaviour, attention-deficit hyperactivity disorder and maternal prenatal smoking. Br. J. Psychiatry 187, 155–160. Chudal, R., Sucksdorff, D., Suominen, A., Lehti, V., Hinkka-Yli-Salomäki, S., Huttunen, J., Ristkari, T., Gissler, M., McKeague, I.W., Brown, A.S., Sourander, A., 2014. Finnish Prenatal Study of Bipolar Disorders (FIPS-B): overview, design and description of the sample. Nord. J. Psychiatry 68, 169–179.
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Dejin-Karlsson, E., Hanson, B.S., Ostergren, P.O., Ranstam, J., Isacsson, S.O., Sjöberg, N.O., 1996. Psychosocial resources and persistent smoking in early pregnancy–a population study of women in their first pregnancy in Sweden. J. Epidemiol. Community Health 50, 33–39. D'Onofrio, B.M., Rickert, M.E., Langström, N., Donahue, K.L., Coyne, C.A., Larsson, H., Ellingson, J.M., Van Hulle, C.A., Iliadou, A.N., Rathouz, P.J., Lahey, B.B., Lichtenstein, P., 2012a. Familial confounding of the association between maternal smoking during pregnancy and offspring substance use and problems. Arch. Gen. Psychiatry 69, 1140–1150. D’Onofrio, B.M., Van Hulle, C.A., Goodnight, J.A., Rathouz, P.J., Lahey, B.B., 2012b. Is maternal smoking during pregnancy a causal environmental risk factor for adolescent antisocial behavior? Testing etiological theories and assumptions. Psychol. Med. 42, 1535–1545. Ekblad, M., Gissler, M., Lehtonen, L., Korkeila, J., 2010. Prenatal smoking exposure and the risk of psychiatric morbidity into young adulthood. Arch. Gen. Psychiatry 67, 841–849. Fergusson, D.M., Woodward, L.J., Horwood, L.J., 1998. Maternal smoking during pregnancy and psychiatric adjustment in late adolescence. Arch. Gen. Psychiatry 55, 721–727. Ford, R.P., Tappin, D.M., Schluter, P.J., Wild, C.J., 1997. Smoking during pregnancy: how reliable are maternal self-reports in New Zealand? J. Epidemiol. Community Health 51, 246–251. Frans, E.M., Sandin, S., Reichenberg, A., Lichtenstein, P., Långström, N., Hultman, C.M., 2008. Advancing paternal age and bipolar disorder. Arch. Gen. Psychiatry 65, 1034–1040. Hofhuis, W., De Jongste, J.C., Merkus, P.J., 2003. Adverse health effects of prenatal and postnatal tobacco smoke exposure on children. Arch. Dis. Child. 88, 1086–1109. Hultman, C.M., Sparén, P., Cnattingius, S., 2002. Perinatal risk factors for infantile autism. Epidemiology 13, 417–423. Jaakkola, N., Jaakkola, M.S., Gissler, M., Jaakkola, J.J., 2001. Smoking during pregnancy in Finland: determinants and trends, 1987–1997. Am. J. Public Health 91, 284–286. Jaakkola, J.J., Gissler, M., 2004. Maternal smoking in pregnancy, fetal development, and childhood asthma. Am. J. Public Health 94, 136–140. Keskimäki, I., Aro, S., 1991. Accuracy of data on diagnoses, procedures and accidents in the Finnish Hospital Discharge Register. Int. J. Health. Sci. 2, 15–21. Kieseppä, T., Partonen, T., Kaprio, J., Lönnqvist, J., 2000. Accuracy of register-and record-based bipolar I diagnoses in Finland—a study of twins. Acta Neuropsychiatr. 12, 106–109.
Laursen, T.M., Labouriau, R., Licht, R.W., Bertelsen, A., Munk-Olsen, T., Mortensen, P.B., 2005. Family history of psychiatric illness as a risk factor for schizoaffective disorder. Arch. Gen. Psychiatry 62, 841–848. Maj, M., 2013. The association between maternal smoking during pregnancy and bipolar disorder in the offspring: alternative interpretations. Am. J. Psychiatry 170, 1090–1092. Martin, J.A.,Hamilton,B.E.,Sutton,P.D.,Ventura,S.J.,Menacker,F.,Kirmeyer,S.,Mathews,T.J., 2009. Births:Final Data for 2006. National Vital Statistics Reports; 57,7. 〈http:// www.cdc.gov/nchs/data/nvsr/nvsr57/nvsr57_07.pdf〉. (accessed: 12 05 13). Matthews, T.J., 2001. Smoking During Pregnancy in the 1990s. National Vital Statistics Reports.49,7. 〈http://www.cdc.gov/nchs/data/nvsr/nvsr49/nvsr49_07. pdf〉. (accessed: 25.06.13). Maughan, B., Taylor, A., Caspi, A., Moffitt, T.E., 2004. Prenatal smoking and early childhood conduct problems: testing genetic and environmental explanations of the association. Arch. Gen. Psychiatry 61, 836–843. Montgomery, S.M., Ekbom, A., 2002. Smoking during pregnancy and diabetes mellitus in a British longitudinal birth cohort. BMJ 324, 26–27. Pihkala, J., Hakala, T., Voutilainen, P., Raivio, K, 1989. Uudetsuomalaisetsikiönk as vukäyrät (Characteristics of recent fetal growth curves in Finland, in Finnish) Duodecim 105, 1540–1560. Perälä, J., Suvisaari, J., Saarni, S.I., Kuoppasalmi, K., Isometsä, E., Pirkola, S., Partonen, T., Tuulio-Henriksson, A., Hintikka, J., Kieseppä, T., Härkänen, T., Koskinen, S., Lönnqvist, J., 2007. Lifetime prevalence of psychotic and bipolar I disorders in a general population. Arch. Gen. Psychiatry 64, 19–28. Talati, A., Bao, Y., Kaufman, J., Shen, L., Schaefer, C.A., Brown, A.S., 2013. Maternal smoking during pregnancy and bipolar disorder in offspring. Am. J. Psychiatry 170, 1178–1185. Ventura, S., Martin, J., Curtin, S., Mathews,T.J., Park, M.M., 2000. Births: Final Data for 1998. National Vital Statistics Reports. 48:3. 〈http://www.cdc.gov/nchs/data/ nvsr/nvsr48/nvs48_03.pdf〉. (accessed: 25 06 13). Ward, C., Lewis, S., Coleman, T., 2007. Prevalence of maternal smoking and environmental tobacco smoke exposure during pregnancy and impact on birth weight: retrospective study using Millennium Cohort. BMC Public Health 7, 81. Weissman, M.M., Warner, V., Wickramaratne, P.J., Kandel, D.B., 1999. Maternal smoking during pregnancy and psychopathology in offspring followed to adulthood. J. Am. Acad. Child. Adolesc. Psychiatry 38, 892–899. World Health Organization. 1967. International Classification of Diseases, Eighth Revision (ICD-8). Geneva, Switzerland. World Health Organization. 1977. International Classification of Diseases, Ninth Revision (ICD-9). Geneva, Switzerland. World Health Organization.1992. International Classification of Diseases, 10th Revision (ICD-10). Geneva, Switzerland.
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Journal of Affective Disorders journal homepage: www.elsevier.com/locate/jad
Research report
Is maternal smoking during pregnancy associated with bipolar disorder in offspring? Roshan Chudal a,n, Alan S. Brown b,c, Mika Gissler a,d,e, Auli Suominen a, Andre Sourander a,b,f,g a
Department of Child Psychiatry, University of Turku, Turku, Finland Department of Psychiatry, Columbia University College of Physicians and Surgeons, New York State Psychiatric Institute, New York, USA c Department of Epidemiology, Columbia University, Mailman School of Public Health, New York, USA d Nordic School of Public Health, Gothenburg, Sweden e National Institute for Health and Welfare, Helsinki, Finland f Department of Child Psychiatry, Turku University Hospital, Turku, Finland g Regional Centre for Child and Youth Mental Health and Child Welfare, University of Tromsø, Tromso, Norway b
art ic l e i nf o
a b s t r a c t
Article history: Received 3 May 2014 Received in revised form 5 September 2014 Accepted 14 September 2014 Available online 28 September 2014
Background: Prenatal smoking exposure affects fetal growth and development and is associated with increased risk of various neurodevelopmental disorders. Only one previous study has examined the association between maternal smoking during pregnancy and the risk of bipolar disorder (BPD). Methods: In this nested case control study derived from all singleton live births in Finland between January 1st 1987 and December 31st 1998, we identified 724 children diagnosed and/or treated with BPD until 2008 and 1419 matched controls from four nationwide registers. Conditional logistic regression was used to examine the association between maternal smoking during pregnancy and BPD adjusting for potential confounding due to parental psychiatric history, maternal age and education level. Results: 18.5% of offspring were exposed to maternal smoking during pregnancy. In the unadjusted analysis, smoking during pregnancy was associated with a 1.41-fold (95% CI 1.12–1.79, P¼ 0.004) increased risk of BPD. In the final model adjusting for potential covariates, the risk was 1.14-fold (95% CI 0.88–1.49, P¼ 0.323). Limitations: The limitations of this study include: hospital based clinical diagnosis for case ascertainment, inclusion of early onset BPD cases, and lack of information on alcohol or other substance abuse during pregnancy. Conclusion: This study demonstrated that, in this sample, an increased risk of BPD among offspring of mothers who smoked during pregnancy is most likely due to confounding by familial background factors. Future studies including information on serological measures of smoking exposure in pregnancy e.g. cotinine are warranted to further clarify this association. & 2014 Elsevier B.V. All rights reserved.
Keywords: Prenatal Smoking during pregnancy Bipolar disorder
1. Introduction Prenatal smoking exposure affects fetal growth and development and is associated with adverse perinatal events, (Hofhuis et al., 2003) high blood pressure and diabetes (Blake et al., 2000; Montgomery and Ekbom, 2002). Furthermore, maternal smoking is associated with increased risk of attention-deficit/hyperactivity disorder (ADHD) (Button et al., 2005), conduct disorder (Fergusson et al., 1998) and autism spectrum disorder (ASD) (Hultman et al., 2002) as well as psychiatric morbidity (Ekblad et al., 2010). n Correspondence to: Research Centre for Child Psychiatry, Institute of Clinical Medicine, Faculty of Medicine, University of Turku Lemminkäisenkatu 3/Teutori (3rd floor), 20014 Turku. Tel.: þ358 2 333 7394; fax: þ 358 2 333 7098. E-mail address: roschu@utu.fi (R. Chudal).
http://dx.doi.org/10.1016/j.jad.2014.09.030 0165-0327/& 2014 Elsevier B.V. All rights reserved.
Bipolar disorder (BPD) has a neurodevelopmental component, the development of which involves genetic and environmental factors (Berrettini, 2000). The existing literature on the risk associated with maternal smoking during pregnancy in development of mood disorders is limited with inconsistent findings. One previous study has investigated the association specifically for BPD and showed an increased risk (Talati et al., 2013). Another study showed it to be associated with an increased risk of mood disorders (Ekblad et al., 2010), while two studies did not find any association with anxiety or major depression (Fergusson et al., 1998; Weissman et al., 1999). Based on the inconsistent findings on mood disorders, and only one previous published study on BPD, we aim to examine the association between maternal smoking during pregnancy and the risk of BPD, in this large nationwide population based epidemiological study.
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2. Materials and methods
2.4. Maternal smoking during pregnancy
2.1. Study design
Information about maternal smoking during pregnancy was obtained from FMBR. These data were collected by maternity clinic nurses during obstetric visits in the second trimester of pregnancy. This information between January 1st 1987 and September 30th 1990 was categorized as: non-smokers, smoking o10 cigarettes per day, or 410 cigarettes per day. From October 1st, 1990 to December 31st 1998, the information was available as: nonsmokers, smoking only during the first trimester and smoking throughout pregnancy. Out of the total sample, smoking information was missing for 3.6% of cases and 4.7% of controls.
This study is based on the Finnish Prenatal study of Bipolar Disorders (FIPS-B) (Chudal et al., 2014). The sampling frame of this nested case-control study with a prevalent control design, includes all singleton live born children in Finland between January 1st 1987 and December 31st 1998 (N ¼754,450). The nested design is due to selection of cases and a sample of matched controls from a defined birth cohort. Ethical approval for the study was obtained from the Institutional Ethical Review Board at Turku University Hospital, Turku University, and the Institutional Review Board of the New York State Psychiatric Institute. 2.2. National register information This study is based on data from four Finnish nationwide registers: the Finnish Medical Birth Register (FMBR), the Finnish Hospital Discharge Register (FHDR), the Finnish Central Population Register and the Register of Education at Statistics Finland. Detailed description of these registers and the study design of FIPS-B have already been reported elsewhere (Chudal et al., 2014). The FMBR, established in 1987, includes comprehensive data on the perinatal period for all newborns in Finland. The Finnish public health care system consists of both primary health care and specialized health services. Patients are typically referred by a general practitioner to specialized mental health services where the assessment is led by a child, adolescent or adult psychiatrist, depending on the patient's age. The FHDR has all medical diagnoses in hospitals in Finland since 1969 and covers all inpatient wards, in somatic and psychiatric hospitals, local health centres, military wards, prison hospitals, and private hospitals. Since 1998, it also covers the outpatient care in public specialized hospital units. In Finland, diagnostic classification is based on the International Classification of Diseases (ICD); ICD- 8 (World Health Organization, 1967) from 1968 to 1986, ICD-9 (World Health Organization, 1977) from 1987 to 1995 and ICD-10 (World Health Organization, 1992) from 1996 onwards. The Finnish Central Population Register is a computerized national register, maintained by the Population Register Centre and local register offices that contains basic information about Finnish citizens and foreign citizens residing permanently in Finland. The linkage between registers was made using the personal identity code (PIC), assigned to all residents of Finland since 1964. 2.3. Identification of study subjects The cases include all singletons diagnosed with BPD (N¼ 724) born between January 1, 1987 and December 31, 1998 and diagnosed and/or treated by December 31, 2008. They were identified from the FHDR using ICD diagnostic codes F31.x (ICD-10) and 2962A G, 2963A G, 2964A G, 2967A (ICD-9).The FMBR was established in 1987, therefore offspring born before 1987 were excluded. Controls for this study (N ¼ 1419) were offspring who were without BPD, schizophrenia or diagnoses related to these disorders (ICD-10 diagnoses: F20–29, F30, F31, F34.0, F38.0, F39, F60.0 and F60.1); ICD-9 diagnoses (2962A G, 2963A G, 2964A G, 2967A BPD, 295, 297, 298, 3010A, 3012A and 3012C). The controls were selected among the remainder of the children born during the study years and were matched to cases on selected factors (sex, date of birth (730 days) and residence in Finland on the first date of diagnosis of the matched case). Two controls for each case were identified from the Finnish Central Population Register (N ¼1448). Among 1448 control children, 29 were excluded as they belonged to a twin pair resulting in 1419 controls in the final analyses.
2.5. Covariates The covariates initially considered in the analyses were: parental psychiatric history, maternal age and education level, place of birth and weight for gestational age (WGA). These covariates have been shown to be associated with maternal smoking (Matthews, 2001; Ventura et al., 2000; Jaakkola et al., 2001; Jaakkola and Gissler, 2004; Maughan et al., 2004) and BPD (Frans et al., 2008; Laursen et al., 2005; Chudal et al., 2014) in previous studies. Maternal age data obtained from the Medical Birth Register was classified as: o20, 20–24, 25–29, 30–34 and Z35 years. Data from the FHDR was used to classify a father or mother as having a psychiatric history (Yes/No), if he/she had any mental disorder of F10–99, based on the ICD-10 classification, or corresponding diagnoses based on the ICD-9 (291–316) and the ICD-8 (291–308). Diagnoses related to mental retardation (ICD-10: F70–79, ICD-9: 317–319, ICD-8: 310–315) were excluded. Maternal educational level data obtained from Statistics Finland were classified into three categories: 1) university degree, 2) secondary school graduate and 3) basic education (comprehensive school). The birth municipality information for cases and controls obtained from the Population Register Centre was used to categorize birthplace into four categories (southern Finland, northern Finland, western Finland, and eastern Finland). The calculation of birth weight for gestational age [(small for gestational age (SGA)/ appropriate for gestational age (AGA) and large for gestational age (LGA)] was done according to national sex-specific weight distributions standards at a given gestational age. The growth curves were derived from data on 75 061 singleton children, with a gestational age of 24–43 weeks, born between 1979 and 1983 in Helsinki University maternity hospitals in Uusimaa, Finland (Pihkala et al., 1989). WGA was categorized into three groups: SGA:o2 standard deviations (SD) below the mean; AGA: between 2 SDs and þ2 SDs and LGA: 2 SDs above the mean. 2.6. Statistical analyses Initially, bivariate analyses were conducted (using Pearson's chi squared test for dichotomous variables with statistical significance at po0.1) to test the significance of association between covariates (maternal age, paternal psychiatric history, maternal psychiatric history, maternal education level, place of birth and weight for gestational age (WGA)) and maternal smoking among controls as well as between covariates and BPD (Appendix A: Supplementary material). Conditional logistic regression models were used to examine the association between maternal smoking during pregnancy and BPD. Initially, smoking was examined as a binary variable (yes/no) for the total sample. Unadjusted odds ratios (OR) and 95% confidence intervals (CI) were calculated. Maternal smoking was then adjusted in sequential models for maternal age, educational level and maternal and paternal psychiatric history. In the final model, we calculated ORs adjusting for all the above mentioned covariates.
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We also calculated ORs adjusting for a combination of any two of these covariates. Maternal smoking during pregnancy was subsequently classified into two separate categories based on definitions of smoking exposure. We calculated unadjusted ORs and 95% CI and ORs adjusting for maternal age, and education level and parental psychiatric history. Maternal smoking during pregnancy was subsequently classified into two separate categories based on different definitions of smoking exposure used, i.e. offspring born between January 1st 1987 and September 30st 1990, and offspring born between October 1st 1990 and December 31st 1998. We calculated both unadjusted odds ratios (OR) and 95% confidence intervals (CI) and odds ratios (OR) adjusting for maternal age, and education level and parental psychiatric history. In all analyses, a two-sided P-value of o0.05 was considered statistically significant. Statistical analyses were performed with SAS statistical software (SAS Version 9.3; SAS Institute Inc., Cary, NC).
3. Results The mean age at diagnosis of cases was 17.4 years (SD: 2.6, Range: 5–21 years). Table 1 shows the descriptive of cases and controls in the study. In the total sample, 18.5% of offspring were exposed to maternal smoking. Among the covariates, paternal psychiatric history, maternal age, psychiatric history and education
level were significantly associated with both maternal smoking during pregnancy and BPD (Appendix A). However, birth province was significantly associated only with BPD, and WGA was not associated with both maternal smoking during pregnancy and BPD. Therefore, adjustment was made only for paternal psychiatric history, maternal age, psychiatric history and education level in the final analysis. In the unadjusted analysis, smoking during pregnancy in the total sample was associated with a 1.41- fold (95% CI 1.12–1.79, P¼ 0.004) increased risk of BPD (Table 2). In the final model adjusting for potential confounders, the risk was 1.14-fold (95% CI 0.88–1.49, P ¼0.323). There were no significant differences in the risk based on sex (P ¼0.28). There were no significant associations following adjustment for any two confounders: maternal age and psychiatric history, OR ¼1.22, 95% CI 0.95–1.56, maternal age and educational level, OR ¼1.25, 95% CI 0.97–1.59,maternal age and paternal psychiatric history, OR¼ 1.24, 95% CI 0.97–1.60, maternal educational level and paternal psychiatric history OR¼1.23, 95% CI 0.95–1.59, maternal educational level and psychiatric history OR¼ 1.21, 95% CI 0.94–1.56, and maternal and paternal psychiatric history OR¼ 1.24, 95%CI 0.96–1.60. Being exposed to 410 cigarettes/day was associated with greater risk OR¼1.29, 95% CI 0.87–1.92, than those smoking o 10 cigarettes/ day OR¼ 1.02, 95%CI 0.69–1.51 (Table 3).
4. Discussion Table 1 Descriptive of BPD cases and controls in the study. BPD cases (n¼ 724), n (%)
Controls (N¼ 1419), n (%)
Sex Male Female
n¼ 724 230 (31.8) 494 (68.2)
n¼ 1419 453 (31.9) 966 (68.1)
Mother’s age (years) Mean (SD) Range
n¼ 724 28.4 (5.9) 15–47
n¼ 1419 28.6(5.1) 16–45
Maternal smoking during pregnancy No Yes
n¼ 698
n¼ 1352
546 (78.2) 152 (21.8)
1125 (83.2) 227 (16.8)
Mother’s psychiatric history No Yes
n¼ 724 504(69.6) 220 (30.4)
n¼ 1419 1250 (88.1) 169 (11.9)
Father’s psychiatric history No Yes
n¼ 706 513 (72.7) 193 (27.3)
n¼ 1400 1222(87.3 178 (12.7)
Mother’s educational level University degree Secondary school graduate Basic education
n¼ 724 118(16.3) 418 (57.7) 188 (26.0)
n¼ 1419 294 (20.7) 841 (59.3) 284 (20.0)
This study has several methodological strengths including ascertainment of cases and matched controls from nationwide hospital registers; maternal smoking information collected by midwives during antenatal care and information on several potential confounders. This study demonstrated that, in this sample, an increased risk of BPD among offspring of mothers who smoked during pregnancy was most likely due to confounding by familial background factors. Mothers who continue to smoke despite being pregnant are different from non-smokers, including having vulnerability to BPD which becomes transmitted from the mother to child (Maj, 2013). As seen in previous studies (Matthews, 2001; Ventura et al., 2000), our study sample showed that mothers who smoked during pregnancy were younger, had lower educational level and had more often a history of some psychiatric illness. Several previous studies (D'Onofrio et al., 2012a, 2012b) have suggested that the association between maternal smoking during pregnancy and offspring behavioral problems and substance use is confounded by familial background factors. This study failed to replicate the findings seen in a previously published study showing an association between maternal smoking during pregnancy and BPD (Talati et al., 2013). The inconsistent findings between the two studies may be accounted for by the fact that the birth cohort of Talati et al. (2013) was based on pregnancies from 1959 to 1966, when
Table 2 Smoking during pregnancy and risk of BPD in the total samplea. Odds ratio
95% confidence interval
P-value
Maternal smoking during pregnancy (unadjusted)
1.41
1.12–1.79
0.004
Maternal smoking during pregnancy adjusting for: Maternal age Maternal educational level Maternal psychiatric history Paternal psychiatric history Maternal smoking during pregnancy (adjusting for all potential confounders)n
1.32 1.28 1.30 1.32 1.14
1.04–1.67 1.01–1.64 1.02–1.66 1.03–1.69 0.88–1.49
0.024 0.044 0.037 0.026 0.323
n
a
Adjusting for maternal age, maternal and paternal psychiatric history and maternal education level. Statistical significance at P o0.05. Born between January 1st 1987 and December 31st 1998.
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Table 3 Smoking during pregnancy and risk of BPD in two sub samples. Frequencies
OR (95% CI)
P-value
OR1 (95% CI)
P-value
Casesc
Controlsd
Sub-sample (1987–1990)a No smoking Smoking o10 cigs/day Smoking 410 cigs/day
(N ¼531) (%) 422 (79.5) 55 (10.4) 54 (10.2)
(N¼ 1021) (%) 848 (83.1) 97 (9.5) 76 (7.4)
Ref 1.14 (0.79–1.64) 1.47 (1.01–2.13)
0.502 0.044
Ref 1.02 (0.69–1.51) 1.29 (0.87–1.92)
0.933 0.206
Sub sample (1990–1998)b No smoking Smoking only in first trimester Continued smoking after first trimester
(N ¼167) (%) 124 (74.3) 2 (1.2) 41 (24.6)
(N¼ 331) (%) 277 (83.7) 8 (2.4) 46 (13.9)
Ref 0.63 (0.13–3.06) 2.14 (1.29–3.55)
0.567 0.033
Ref 0.38 (0.07–2.04) 1.38 (0.78–2.43)
0.260 0.268
OR ¼ Odds Ratios, OR1: Adjusted for maternal age, maternal and paternal psychiatric history and maternal education level; Statistical significance at Po 0.05. a Born between January 1st 1987 and September 30th 1990. b Born between October 1st 1990 and December 31st 1998. c Smoking data missing for cases: 3.6%. d Smoking data missing for controls: 4.7%.
smoking was considered to be a more normative behavior and less likely to be associated with maternal psychiatric disorders.
highest risk for continued smoking during pregnancy (Jaakkola et al., 2001; Dejin-Karlsson et al., 1996).
5. Limitations
Conflict of interest The authors report no conflicts of interest.
The limitations in this study need to be considered in the interpretation of results. First, the data on smoking were acquired by maternal self-report during pregnancy with no information available on post-natal tobacco exposure. Self-report of maternal smoking during pregnancy is known to underestimate the actual smoking trends (Ford et al., 1997). However, the validity of the FMBR data on maternal smoking has been shown to be excellent (Jaakkola et al., 2001). Second, information on alcohol or other substance use during pregnancy as well as paternal smoking data was not available in the registers. Third, the diagnoses in the FHDR are not based on standardized interviews, but are hospital-based clinical diagnoses. However, the validity of the FHDR has been found to be good for the diagnosis of mental disorders in general (Keskimäki and Aro, 1991) and particularly for BPD (Kieseppä et al., 2000; Perälä et al., 2007). Fourth, the children with BPD included in this study were aged r21 years, and thus the findings or lack thereof, may be specific to early onset cases. Fifth, despite having a moderate sample size, it is possible that the lack of sufficient statistical power could have resulted in failure to detect significant associations. Lastly, our study sample includes only cases utilizing specialized mental health services and we assume that it represents rather well more severe cases of BPD in the population. Children having less severe BPD may not utilize specialized mental health services and therefore are missing in the nationwide registers. However, the health care services in Finland are universal, financed by the state and municipalities and the overall health coverage is good. Thus, BPD cases missing due to lack of access to health services is expected to be small.
6. Conclusions Future studies aimed at further clarifying this association include serologically documented measure of smoking exposure in pregnancy such as cotinine, a nicotine metabolite. Furthermore, availability of a larger sample size, thereby increasing the statistical power and including later onset BPD cases are warranted. A high prevalence of smoking during pregnancy (Martin et al., 2009; Ward et al., 2007) despite existing smoking cessation strategies calls for population based preventive measures, with increased focus on women with low psychosocial resources who are at the
Funding disclosure This work was supported by grants from NARSAD Independent Investigator Award, USA (A.S), the Sigrid Juselius Foundation, Finland (A.S), NIMH 5K02-MH65422 (A.S.B.) and the University of Turku Graduate School funding (UTUGS) (RC).
Contributors Authors RC, ASB, MG, AS and AS designed the study. Author RC managed the literature searches and analyses. Authors AS undertook the statistical analysis, and author RC wrote the first draft of the manuscript. All authors contributed to and have approved the final manuscript. Acknowledgments The study was conducted at the University of Turku, Finland. We thank the study investigators and staff at medical centers involved in this research. Specifically we would like to thank the members involved in the data collection process including: Juha-Pekka Virtanen, Pyry Kantanen, Kristiina Saanakorpi, Tanja Sarlin, Jarna Lindroos and Lauri Sillanmäki from Research Centre for Child Psychiatry, University of Turku.
Appendix A. Supporting information Supplementary data associated with this article can be found in the online version at http://dx.doi.org/10.1016/j.jad.2014.09.030. References Berrettini, W.H., 2000. Genetics of psychiatric disease. Annu. Rev. Med. 51, 465–479. Blake, K.V., Gurrin, L.C., Evans, S.F., Beilin, L.J., Landau, L.I., Stanley, F.J., Newnham, J.P., 2000. Maternal cigarette smoking during pregnancy, low birth weight and subsequent blood pressure in early childhood. Early Hum. Dev. 57, 137–147. Button, T.M., Thapar, A., McGuffin, P., 2005. Relationship between antisocial behaviour, attention-deficit hyperactivity disorder and maternal prenatal smoking. Br. J. Psychiatry 187, 155–160. Chudal, R., Sucksdorff, D., Suominen, A., Lehti, V., Hinkka-Yli-Salomäki, S., Huttunen, J., Ristkari, T., Gissler, M., McKeague, I.W., Brown, A.S., Sourander, A., 2014. Finnish Prenatal Study of Bipolar Disorders (FIPS-B): overview, design and description of the sample. Nord. J. Psychiatry 68, 169–179.
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Dejin-Karlsson, E., Hanson, B.S., Ostergren, P.O., Ranstam, J., Isacsson, S.O., Sjöberg, N.O., 1996. Psychosocial resources and persistent smoking in early pregnancy–a population study of women in their first pregnancy in Sweden. J. Epidemiol. Community Health 50, 33–39. D'Onofrio, B.M., Rickert, M.E., Langström, N., Donahue, K.L., Coyne, C.A., Larsson, H., Ellingson, J.M., Van Hulle, C.A., Iliadou, A.N., Rathouz, P.J., Lahey, B.B., Lichtenstein, P., 2012a. Familial confounding of the association between maternal smoking during pregnancy and offspring substance use and problems. Arch. Gen. Psychiatry 69, 1140–1150. D’Onofrio, B.M., Van Hulle, C.A., Goodnight, J.A., Rathouz, P.J., Lahey, B.B., 2012b. Is maternal smoking during pregnancy a causal environmental risk factor for adolescent antisocial behavior? Testing etiological theories and assumptions. Psychol. Med. 42, 1535–1545. Ekblad, M., Gissler, M., Lehtonen, L., Korkeila, J., 2010. Prenatal smoking exposure and the risk of psychiatric morbidity into young adulthood. Arch. Gen. Psychiatry 67, 841–849. Fergusson, D.M., Woodward, L.J., Horwood, L.J., 1998. Maternal smoking during pregnancy and psychiatric adjustment in late adolescence. Arch. Gen. Psychiatry 55, 721–727. Ford, R.P., Tappin, D.M., Schluter, P.J., Wild, C.J., 1997. Smoking during pregnancy: how reliable are maternal self-reports in New Zealand? J. Epidemiol. Community Health 51, 246–251. Frans, E.M., Sandin, S., Reichenberg, A., Lichtenstein, P., Långström, N., Hultman, C.M., 2008. Advancing paternal age and bipolar disorder. Arch. Gen. Psychiatry 65, 1034–1040. Hofhuis, W., De Jongste, J.C., Merkus, P.J., 2003. Adverse health effects of prenatal and postnatal tobacco smoke exposure on children. Arch. Dis. Child. 88, 1086–1109. Hultman, C.M., Sparén, P., Cnattingius, S., 2002. Perinatal risk factors for infantile autism. Epidemiology 13, 417–423. Jaakkola, N., Jaakkola, M.S., Gissler, M., Jaakkola, J.J., 2001. Smoking during pregnancy in Finland: determinants and trends, 1987–1997. Am. J. Public Health 91, 284–286. Jaakkola, J.J., Gissler, M., 2004. Maternal smoking in pregnancy, fetal development, and childhood asthma. Am. J. Public Health 94, 136–140. Keskimäki, I., Aro, S., 1991. Accuracy of data on diagnoses, procedures and accidents in the Finnish Hospital Discharge Register. Int. J. Health. Sci. 2, 15–21. Kieseppä, T., Partonen, T., Kaprio, J., Lönnqvist, J., 2000. Accuracy of register-and record-based bipolar I diagnoses in Finland—a study of twins. Acta Neuropsychiatr. 12, 106–109.
Laursen, T.M., Labouriau, R., Licht, R.W., Bertelsen, A., Munk-Olsen, T., Mortensen, P.B., 2005. Family history of psychiatric illness as a risk factor for schizoaffective disorder. Arch. Gen. Psychiatry 62, 841–848. Maj, M., 2013. The association between maternal smoking during pregnancy and bipolar disorder in the offspring: alternative interpretations. Am. J. Psychiatry 170, 1090–1092. Martin, J.A.,Hamilton,B.E.,Sutton,P.D.,Ventura,S.J.,Menacker,F.,Kirmeyer,S.,Mathews,T.J., 2009. Births:Final Data for 2006. National Vital Statistics Reports; 57,7. 〈http:// www.cdc.gov/nchs/data/nvsr/nvsr57/nvsr57_07.pdf〉. (accessed: 12 05 13). Matthews, T.J., 2001. Smoking During Pregnancy in the 1990s. National Vital Statistics Reports.49,7. 〈http://www.cdc.gov/nchs/data/nvsr/nvsr49/nvsr49_07. pdf〉. (accessed: 25.06.13). Maughan, B., Taylor, A., Caspi, A., Moffitt, T.E., 2004. Prenatal smoking and early childhood conduct problems: testing genetic and environmental explanations of the association. Arch. Gen. Psychiatry 61, 836–843. Montgomery, S.M., Ekbom, A., 2002. Smoking during pregnancy and diabetes mellitus in a British longitudinal birth cohort. BMJ 324, 26–27. Pihkala, J., Hakala, T., Voutilainen, P., Raivio, K, 1989. Uudetsuomalaisetsikiönk as vukäyrät (Characteristics of recent fetal growth curves in Finland, in Finnish) Duodecim 105, 1540–1560. Perälä, J., Suvisaari, J., Saarni, S.I., Kuoppasalmi, K., Isometsä, E., Pirkola, S., Partonen, T., Tuulio-Henriksson, A., Hintikka, J., Kieseppä, T., Härkänen, T., Koskinen, S., Lönnqvist, J., 2007. Lifetime prevalence of psychotic and bipolar I disorders in a general population. Arch. Gen. Psychiatry 64, 19–28. Talati, A., Bao, Y., Kaufman, J., Shen, L., Schaefer, C.A., Brown, A.S., 2013. Maternal smoking during pregnancy and bipolar disorder in offspring. Am. J. Psychiatry 170, 1178–1185. Ventura, S., Martin, J., Curtin, S., Mathews,T.J., Park, M.M., 2000. Births: Final Data for 1998. National Vital Statistics Reports. 48:3. 〈http://www.cdc.gov/nchs/data/ nvsr/nvsr48/nvs48_03.pdf〉. (accessed: 25 06 13). Ward, C., Lewis, S., Coleman, T., 2007. Prevalence of maternal smoking and environmental tobacco smoke exposure during pregnancy and impact on birth weight: retrospective study using Millennium Cohort. BMC Public Health 7, 81. Weissman, M.M., Warner, V., Wickramaratne, P.J., Kandel, D.B., 1999. Maternal smoking during pregnancy and psychopathology in offspring followed to adulthood. J. Am. Acad. Child. Adolesc. Psychiatry 38, 892–899. World Health Organization. 1967. International Classification of Diseases, Eighth Revision (ICD-8). Geneva, Switzerland. World Health Organization. 1977. International Classification of Diseases, Ninth Revision (ICD-9). Geneva, Switzerland. World Health Organization.1992. International Classification of Diseases, 10th Revision (ICD-10). Geneva, Switzerland.
