Epidemiology
DOI: 10.1111/1471-0528.12612 www.bjog.org
Psychosocial job strain and risk of congenital malformations in offspring—a Danish National cohort study AD Larsen,a,b H Hannerz,a AM Thulstrup,b JP Bonde,c C Obel,d KS Hougaarda a
National Research Centre for the Working Environment, Copenhagen, Denmark b Department of Occupational Medicine, Aarhus University Hospital, Aarhus, Denmark c Department of Occupational and Environmental Medicine, Copenhagen University Hospital Bispebjerg, Copenhagen, Denmark d Department of Public Health, Aarhus University, Aarhus, Denmark Correspondence: Dr AD Larsen, National Research Centre for the Working Environment, Lersoe Parkalle 105, DK-2100 Copenhagen, Denmark. Email [email protected] Accepted 20 November 2013. Published Online 5 March 2014.
Objective To investigate if maternal exposure to psychosocial
Main outcome measures Circulatory malformation,
job strain at work (high demands and low control) measured by questionnaire early in pregnancy (median week 15) is associated with malformations in the offspring.
musculoskeletal malformation or any malformation.
information on mother’s occupational status, exposure to psychosocial job strain and all covariates during pregnancy.
Results Logistic regression analyses, both crude and adjusted, indicated no associations between working under high strain and giving birth to a child with circulatory malformation (adjusted odds ratio [OR] 1.04, 95% confidence interval [95% CI] 0.75– 1.44), musculoskeletal malformation (aOR 0.88, 95% CI 0.71– 1.10) or any malformation (aOR 0.99, 95% CI 0.85–1.15). Supplementary analyses including restriction to first-borns and a stratified analysis with respect to manual and nonmanual work did not change the results.
Methods Logistic regression analysis was used to calculate
Conclusions Association between exposure to high job strain
the odds of congenital malformations as a function of job strain with adjustment for maternal age, body mass index, parity, smoking, alcohol use, manual versus nonmanual work, maternal serious disease and gestational age at interview.
during pregnancy and elevated risk of circulatory, muscle and any malformations is not supported by this study.
Design Population-based cohort study. Setting The Danish National Birth Cohort. Population A cohort of 60 386 singleton children with full
Keywords Birth cohort, cohort study, congenital malformations, high demands, influence at work, job strain.
Please cite this paper as: Larsen AD, Hannerz H, Thulstrup AM, Bonde JP, Obel C, Hougaard KS. Psychosocial job strain and risk of congenital malformations in offspring—a Danish National cohort study. BJOG 2014;121:830–839.
Introduction The number of Danish children with congenital malformations varied between 42 and 51 for every 1000 live births, in the years 1994–2005.1 The aetiology is unknown for most malformations, but maternal stress during pregnancy may be one risk factor, as it has been associated with increased risk of cleft lip and palate,2,3 and neural tube defects3,4 and heart defects.2,5 Increased production of glucocorticosteroids during stress has been proposed as a causal factor of malformations. Stressful life events have been reported to be associated with elevated maternal corticotrophin-releasing hormone and
830
corticosteroid levels during pregnancy in humans.6 A causal link between glucocorticosteroid exposure and congenital malformations is supported by studies on mothers taking corticosteroid medications during pregnancy, showing increased risk of oral clefts among the offspring.7,8 Association of maternal stress with malformations is also observed in animal studies, where maternal stress (for example by restraint of the animal) has caused birth defects.9,10 More than 12% of the women in the Danish workforce report to be stressed often in their daily life, and that workplace factors contribute significantly to this.11 Furthermore, nearly one-third of the women of childbearing age (25–44 years) in a 2005 survey reported difficulties in
ª 2014 Royal College of Obstetricians and Gynaecologists
Job strain and risk of congenital malformations in offspring
completing their work tasks within the allotted working hours and 17% of the women found that they only had limited or no influence on their work tasks.12 To our knowledge no studies have so far investigated stress specifically in pregnant women. Congenital malformations may be important contributors to mortality and morbidity in childhood as well as later in life. It is therefore important to clarify if job-related exposure to stress contributes to the incidence of malformations as these may be preventable, e.g. by interventions at the workplace, education etc. To our knowledge no previous studies have done this. We aim to test if maternal exposure to psychosocial job strain (high demands and low control) measured early in pregnancy is associated with congenital malformations in a large Danish birth cohort.
Baseline population N = 100 418 Not working, not pregnant N = 36 679 N = 63 739 Multitons N = 1962 N = 61 777 Missing exposure N = 209 N = 61 568
Methods We combined data from the Danish National Birth Cohort (DNBC)13 with data from national registers. DNBC is a nationwide Danish longitudinal survey, established in 1996. It includes prospective interview data of more than 100 000 pregnancies in Denmark. The original cohort protocol of the DNBC included four computer-assisted telephone interviews: two before birth, at 12–16 and 30–32 weeks of gestation, and two postnatal interviews. Information on the mother’s psychosocial work environment during pregnancy was obtained from the initial interview (median week 15). Data on covariates were available the DNBC interviews together with exposure information from the first DNBC interview. Data on congenital malformations were extracted from the Danish Medical Birth Register14 by use of the personal identification number given to every Danish child at birth, which allows combination of DNBC with national registers. The structure, aim and details of DNBC can be found at www.dnbc.dk and have been described in a previous paper.13 A total of 100 418 pregnancies were included in the DNBC from 1996 to 2002. The first criterion for inclusion in this study was that the woman was still pregnant and working at baseline (first interview), which resulted in 63 739 pregnancies. We included only singletons (n = 61 777) as multiple gestations have higher risk of congenital malformation for reasons unrelated to occupational job strain.15,16 An additional 209 children were excluded from the study population because of lack of answer to the questions regarding exposure to psychosocial job strain. Finally, information on covariates was missing for 1182 pregnancies; the final study population therefore included 60 386 liveborn children; the flowchart is shown in Figure 1. In accordance with Guidelines for Good Epidemiological Practice for Occupational and Environmental Epidemiologic
ª 2014 Royal College of Obstetricians and Gynaecologists
Missing covariates N = 1182 Final study population N = 60 386 Figure 1. Flowchart describing inclusion and exclusion criteria for the study population.
Research,17 a protocol outlined the methods to be used in the study before analysis.
Exposure The psychosocial work environment was assessed by self-report in the first telephone interview from the DNBC data collection (6–21 weeks of gestation, median 15 weeks) and had the response categories: often, sometimes and seldom: A172: Do you have too many tasks at your work? (Demand dimension) A173: Do you have the opportunity to influence your tasks and working conditions? (Control dimension). These questions allowed for assessment of psychosocial load in the working environment according to the dimensions of the Demand Control Model (Job Strain Model18), which has previously been used in DNBC to discuss effects of work-related stress.19,20 The primary interest was the combination of high demands and low control because it predicts mental strain according to the Job Strain Model.21 Four job categories were constructed from the answers to A172 and A173 related to the dimensions of demand and control: low strain (low demands, high control), active (high demands, high control), passive (low demands, low control) and high strain (high demands, low control). To ensure the highest possible contrast in exposure, the high strain group was defined as those women answering
831
Larsen et al.
‘often’ to demands and ‘seldom’ to the question relating to control. The low strain group served as reference, defined by the answering of ‘sometimes’ or ‘seldom’ to high demands and ‘often’ or ‘sometimes’ to high control. The active and passive groups were also included in the analysis to allow for interpretation of the control and the demand dimension. For an illustration of the grouping see fig. 2 in ref. 22, where this grouping was also used.
does the power exceed 70%, and we could therefore not expect to see any reliable results. This also holds true for the remaining organ systems that present with even lower incidences of malformations (data not presented). Based on the power calculations the present study includes malformations in the circulatory system (n = 582), the musculoskeletal system (n = 1555), and any system (all malformations included, n = 3059).
Outcomes
Statistical analysis
The following types of congenital malformations are recorded in the Danish Medical Birth Register according to the International Classification of Disease, 10th revision (ICD-10): congenital malformations of the nervous system (Q00–Q07), eye, ear, face and neck (Q10–Q18), the circulatory system (Q20–Q28), the respiratory system (Q30–Q34), cleft lip and cleft palate (Q35–Q37), the digestive system (Q38–Q45), genital organs (Q50–Q56), the urinary system (Q60–Q64), the musculoskeletal system (Q65–Q79), other congenital malformations (Q80–Q89) and chromosomal abnormalities (Q90–Q99). Power calculations with a statistical significance level of 0.05% focused on the contrast between high and low strain (Figure 2). For example with an odds ratio of 1.3 or higher, the analysis will have an 87% probability of identifying a statistically significant association between high strain and musculoskeletal malformations compared with low strain. The corresponding numbers for any malformation, malformations in the circulatory and in the nervous system are 98%, 52% and 17%, respectively. The low power for nervous system malformations is the result of the low incidence of this type of malformation. It is evident from Figure 2 that low power precludes study of malformations in the nervous system. Not even with an odds ratio of 2.0
We used logistic regression models to estimate prevalence odds ratios with 95% confidence intervals for any congenital malformations as a function of the following maternal baseline variables. All covariates were chosen a priori based on a screening of the scientific literature.
1.0 0.9 0.8
Power
0.7 0.6 0.5 0.4
Parity Most epidemiological studies on congenital malformations include parity.3,24 Medical parity is the number of times a woman has given birth—so delivering twins/triplets only count as one birth, as do stillbirths.25 The parity variable was categorised into: 0, 1, ≥2 births. Smoking Some studies find a positive association between maternal smoking and congenital malformations.26,27 Based on questions in the DNBC three categories were constructed: (1) not smoked during pregnancy; (2) smoked during pregnancy but not every day (at the time of interview); and (3) smokes every day. Cross-tabulation of the smoking variable from the first and the second interview during pregnancy shows that 89% of the women who smoked daily in the first part of the pregnancy also smoked daily during the latter part of the pregnancy. The smoking variable is therefore based on information from the interview during early pregnancy.
Nervous syst.
0.3
Circulatory syst.
0.2
Musculoskeletal
0.1
All
0.0
1.0
1.1
1.2
1.3
1.4 1.5 1.6 Odds ratio
1.7
1.8
1.9
2.0
Figure 2. Power curves for congenital malformations in any organ system as well as the nervous, circulatory and musculoskeletal system by focusing on the contrast between high strain and low strain.
832
Maternal age Women above 35 years have an elevated risk of giving birth to children with congenital malformations, e.g. hypospadias.23 Information about mother’s age at birth was collected from the Danish Medical Birth Register. Age was divided into four categories: 35 years.
Alcohol A large alcohol intake during pregnancy increases the risk of congenital malformations, e.g. fetal alcohol syndrome.28 The categorisation of the alcohol-variable is: 0, 2 units of alcohol per week. Maternal body mass index (BMI) prepregnancy Maternal overweight and obesity are known risk factors for giving birth to children with congenital malformations.29
ª 2014 Royal College of Obstetricians and Gynaecologists
Job strain and risk of congenital malformations in offspring
In accordance with the WHO, BMI were classified as: underweight (15 ≤ BMI
DOI: 10.1111/1471-0528.12612 www.bjog.org
Psychosocial job strain and risk of congenital malformations in offspring—a Danish National cohort study AD Larsen,a,b H Hannerz,a AM Thulstrup,b JP Bonde,c C Obel,d KS Hougaarda a
National Research Centre for the Working Environment, Copenhagen, Denmark b Department of Occupational Medicine, Aarhus University Hospital, Aarhus, Denmark c Department of Occupational and Environmental Medicine, Copenhagen University Hospital Bispebjerg, Copenhagen, Denmark d Department of Public Health, Aarhus University, Aarhus, Denmark Correspondence: Dr AD Larsen, National Research Centre for the Working Environment, Lersoe Parkalle 105, DK-2100 Copenhagen, Denmark. Email [email protected] Accepted 20 November 2013. Published Online 5 March 2014.
Objective To investigate if maternal exposure to psychosocial
Main outcome measures Circulatory malformation,
job strain at work (high demands and low control) measured by questionnaire early in pregnancy (median week 15) is associated with malformations in the offspring.
musculoskeletal malformation or any malformation.
information on mother’s occupational status, exposure to psychosocial job strain and all covariates during pregnancy.
Results Logistic regression analyses, both crude and adjusted, indicated no associations between working under high strain and giving birth to a child with circulatory malformation (adjusted odds ratio [OR] 1.04, 95% confidence interval [95% CI] 0.75– 1.44), musculoskeletal malformation (aOR 0.88, 95% CI 0.71– 1.10) or any malformation (aOR 0.99, 95% CI 0.85–1.15). Supplementary analyses including restriction to first-borns and a stratified analysis with respect to manual and nonmanual work did not change the results.
Methods Logistic regression analysis was used to calculate
Conclusions Association between exposure to high job strain
the odds of congenital malformations as a function of job strain with adjustment for maternal age, body mass index, parity, smoking, alcohol use, manual versus nonmanual work, maternal serious disease and gestational age at interview.
during pregnancy and elevated risk of circulatory, muscle and any malformations is not supported by this study.
Design Population-based cohort study. Setting The Danish National Birth Cohort. Population A cohort of 60 386 singleton children with full
Keywords Birth cohort, cohort study, congenital malformations, high demands, influence at work, job strain.
Please cite this paper as: Larsen AD, Hannerz H, Thulstrup AM, Bonde JP, Obel C, Hougaard KS. Psychosocial job strain and risk of congenital malformations in offspring—a Danish National cohort study. BJOG 2014;121:830–839.
Introduction The number of Danish children with congenital malformations varied between 42 and 51 for every 1000 live births, in the years 1994–2005.1 The aetiology is unknown for most malformations, but maternal stress during pregnancy may be one risk factor, as it has been associated with increased risk of cleft lip and palate,2,3 and neural tube defects3,4 and heart defects.2,5 Increased production of glucocorticosteroids during stress has been proposed as a causal factor of malformations. Stressful life events have been reported to be associated with elevated maternal corticotrophin-releasing hormone and
830
corticosteroid levels during pregnancy in humans.6 A causal link between glucocorticosteroid exposure and congenital malformations is supported by studies on mothers taking corticosteroid medications during pregnancy, showing increased risk of oral clefts among the offspring.7,8 Association of maternal stress with malformations is also observed in animal studies, where maternal stress (for example by restraint of the animal) has caused birth defects.9,10 More than 12% of the women in the Danish workforce report to be stressed often in their daily life, and that workplace factors contribute significantly to this.11 Furthermore, nearly one-third of the women of childbearing age (25–44 years) in a 2005 survey reported difficulties in
ª 2014 Royal College of Obstetricians and Gynaecologists
Job strain and risk of congenital malformations in offspring
completing their work tasks within the allotted working hours and 17% of the women found that they only had limited or no influence on their work tasks.12 To our knowledge no studies have so far investigated stress specifically in pregnant women. Congenital malformations may be important contributors to mortality and morbidity in childhood as well as later in life. It is therefore important to clarify if job-related exposure to stress contributes to the incidence of malformations as these may be preventable, e.g. by interventions at the workplace, education etc. To our knowledge no previous studies have done this. We aim to test if maternal exposure to psychosocial job strain (high demands and low control) measured early in pregnancy is associated with congenital malformations in a large Danish birth cohort.
Baseline population N = 100 418 Not working, not pregnant N = 36 679 N = 63 739 Multitons N = 1962 N = 61 777 Missing exposure N = 209 N = 61 568
Methods We combined data from the Danish National Birth Cohort (DNBC)13 with data from national registers. DNBC is a nationwide Danish longitudinal survey, established in 1996. It includes prospective interview data of more than 100 000 pregnancies in Denmark. The original cohort protocol of the DNBC included four computer-assisted telephone interviews: two before birth, at 12–16 and 30–32 weeks of gestation, and two postnatal interviews. Information on the mother’s psychosocial work environment during pregnancy was obtained from the initial interview (median week 15). Data on covariates were available the DNBC interviews together with exposure information from the first DNBC interview. Data on congenital malformations were extracted from the Danish Medical Birth Register14 by use of the personal identification number given to every Danish child at birth, which allows combination of DNBC with national registers. The structure, aim and details of DNBC can be found at www.dnbc.dk and have been described in a previous paper.13 A total of 100 418 pregnancies were included in the DNBC from 1996 to 2002. The first criterion for inclusion in this study was that the woman was still pregnant and working at baseline (first interview), which resulted in 63 739 pregnancies. We included only singletons (n = 61 777) as multiple gestations have higher risk of congenital malformation for reasons unrelated to occupational job strain.15,16 An additional 209 children were excluded from the study population because of lack of answer to the questions regarding exposure to psychosocial job strain. Finally, information on covariates was missing for 1182 pregnancies; the final study population therefore included 60 386 liveborn children; the flowchart is shown in Figure 1. In accordance with Guidelines for Good Epidemiological Practice for Occupational and Environmental Epidemiologic
ª 2014 Royal College of Obstetricians and Gynaecologists
Missing covariates N = 1182 Final study population N = 60 386 Figure 1. Flowchart describing inclusion and exclusion criteria for the study population.
Research,17 a protocol outlined the methods to be used in the study before analysis.
Exposure The psychosocial work environment was assessed by self-report in the first telephone interview from the DNBC data collection (6–21 weeks of gestation, median 15 weeks) and had the response categories: often, sometimes and seldom: A172: Do you have too many tasks at your work? (Demand dimension) A173: Do you have the opportunity to influence your tasks and working conditions? (Control dimension). These questions allowed for assessment of psychosocial load in the working environment according to the dimensions of the Demand Control Model (Job Strain Model18), which has previously been used in DNBC to discuss effects of work-related stress.19,20 The primary interest was the combination of high demands and low control because it predicts mental strain according to the Job Strain Model.21 Four job categories were constructed from the answers to A172 and A173 related to the dimensions of demand and control: low strain (low demands, high control), active (high demands, high control), passive (low demands, low control) and high strain (high demands, low control). To ensure the highest possible contrast in exposure, the high strain group was defined as those women answering
831
Larsen et al.
‘often’ to demands and ‘seldom’ to the question relating to control. The low strain group served as reference, defined by the answering of ‘sometimes’ or ‘seldom’ to high demands and ‘often’ or ‘sometimes’ to high control. The active and passive groups were also included in the analysis to allow for interpretation of the control and the demand dimension. For an illustration of the grouping see fig. 2 in ref. 22, where this grouping was also used.
does the power exceed 70%, and we could therefore not expect to see any reliable results. This also holds true for the remaining organ systems that present with even lower incidences of malformations (data not presented). Based on the power calculations the present study includes malformations in the circulatory system (n = 582), the musculoskeletal system (n = 1555), and any system (all malformations included, n = 3059).
Outcomes
Statistical analysis
The following types of congenital malformations are recorded in the Danish Medical Birth Register according to the International Classification of Disease, 10th revision (ICD-10): congenital malformations of the nervous system (Q00–Q07), eye, ear, face and neck (Q10–Q18), the circulatory system (Q20–Q28), the respiratory system (Q30–Q34), cleft lip and cleft palate (Q35–Q37), the digestive system (Q38–Q45), genital organs (Q50–Q56), the urinary system (Q60–Q64), the musculoskeletal system (Q65–Q79), other congenital malformations (Q80–Q89) and chromosomal abnormalities (Q90–Q99). Power calculations with a statistical significance level of 0.05% focused on the contrast between high and low strain (Figure 2). For example with an odds ratio of 1.3 or higher, the analysis will have an 87% probability of identifying a statistically significant association between high strain and musculoskeletal malformations compared with low strain. The corresponding numbers for any malformation, malformations in the circulatory and in the nervous system are 98%, 52% and 17%, respectively. The low power for nervous system malformations is the result of the low incidence of this type of malformation. It is evident from Figure 2 that low power precludes study of malformations in the nervous system. Not even with an odds ratio of 2.0
We used logistic regression models to estimate prevalence odds ratios with 95% confidence intervals for any congenital malformations as a function of the following maternal baseline variables. All covariates were chosen a priori based on a screening of the scientific literature.
1.0 0.9 0.8
Power
0.7 0.6 0.5 0.4
Parity Most epidemiological studies on congenital malformations include parity.3,24 Medical parity is the number of times a woman has given birth—so delivering twins/triplets only count as one birth, as do stillbirths.25 The parity variable was categorised into: 0, 1, ≥2 births. Smoking Some studies find a positive association between maternal smoking and congenital malformations.26,27 Based on questions in the DNBC three categories were constructed: (1) not smoked during pregnancy; (2) smoked during pregnancy but not every day (at the time of interview); and (3) smokes every day. Cross-tabulation of the smoking variable from the first and the second interview during pregnancy shows that 89% of the women who smoked daily in the first part of the pregnancy also smoked daily during the latter part of the pregnancy. The smoking variable is therefore based on information from the interview during early pregnancy.
Nervous syst.
0.3
Circulatory syst.
0.2
Musculoskeletal
0.1
All
0.0
1.0
1.1
1.2
1.3
1.4 1.5 1.6 Odds ratio
1.7
1.8
1.9
2.0
Figure 2. Power curves for congenital malformations in any organ system as well as the nervous, circulatory and musculoskeletal system by focusing on the contrast between high strain and low strain.
832
Maternal age Women above 35 years have an elevated risk of giving birth to children with congenital malformations, e.g. hypospadias.23 Information about mother’s age at birth was collected from the Danish Medical Birth Register. Age was divided into four categories: 35 years.
Alcohol A large alcohol intake during pregnancy increases the risk of congenital malformations, e.g. fetal alcohol syndrome.28 The categorisation of the alcohol-variable is: 0, 2 units of alcohol per week. Maternal body mass index (BMI) prepregnancy Maternal overweight and obesity are known risk factors for giving birth to children with congenital malformations.29
ª 2014 Royal College of Obstetricians and Gynaecologists
Job strain and risk of congenital malformations in offspring
In accordance with the WHO, BMI were classified as: underweight (15 ≤ BMI
