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1.  Early life bereavement and childhood cancer: a nationwide follow-up study in two countries 
BMJ Open  2013;3(5):e002864.
Objective
Childhood cancer is a leading cause of child deaths in affluent countries, but little is known about its aetiology. Psychological stress has been suggested to be associated with cancer in adults; whether this is also seen in childhood cancer is largely unknown. We investigated the association between bereavement as an indicator of severe childhood stress exposure and childhood cancer, using data from Danish and Swedish national registers.
Design
Population-based cohort study.
Setting
Denmark and Sweden.
Participants
All live-born children born in Denmark between 1968 and 2007 (n=2 729 308) and in Sweden between 1973 and 2006 (n=3 395 166) were included in this study. Exposure was bereavement by the death of a close relative before 15 years of age. Follow-up started from birth and ended at the first of the following: date of a cancer diagnosis, death, emigration, day before their 15th birthday or end of follow-up (2007 in Denmark, 2006 in Sweden).
Outcome measures
Rates and HRs for all childhood cancers and specific childhood cancers.
Results
A total of 1 505 938 (24.5%) children experienced bereavement at some point during their childhood and 9823 were diagnosed with cancer before the age of 15 years. The exposed children had a small (10%) increased risk of childhood cancer (HR 1.10; 95% CI 1.04 to 1.17). For specific cancers, a significant association was seen only for central nervous system tumours (HR 1.14; 95% CI 1.02 to 1.28).
Conclusions
Our data suggest that psychological stress in early life is associated with a small increased risk of childhood cancer.
doi:10.1136/bmjopen-2013-002864
PMCID: PMC3664350  PMID: 23793702
Childhood cancer; bereavement; psychological stress; risk factor; follow up
2.  The paternal role in pre-eclampsia and giving birth to a small for gestational age infant; a population-based cohort study 
BMJ Open  2012;2(4):e001178.
Objective
To estimate the effect of partner change on risks of pre-eclampsia and giving birth to a small for gestational age infant.
Design
Prospective population study.
Setting
Sweden.
Participants
Women with their first and second successive singleton births in Sweden between 1990 and 2006 without pregestational diabetes and/or hypertension (n=446 459).
Outcome measures
Preterm (<37 weeks) and term (≥37 weeks) pre-eclampsia, and giving birth to a small for gestational age (SGA) infant. Risks were adjusted for interpregnancy interval, maternal age, body mass index, height and smoking habits in second pregnancy, years of involuntary childlessness before second pregnancy, mother's country of birth, years of formal education and year of birth. Further, when we calculated risks of SGA we restricted the study population to women with non-pre-eclamptic pregnancies.
Results
In women who had a preterm pre-eclampsia in first pregnancy, partner change was associated with a strong protective effect for preterm pre-eclampsia recurrence (OR 0.24; 95% CI 0.07 to 0.88). Similarly, partner change was also associated with a protective effect of recurrence of SGA birth (OR 0.75; 95% CI 0.67 to 0.84). In contrast, among women without SGA in first birth, partner change was associated with an increased risk of SGA in second pregnancy. Risks of term pre-eclampsia were not affected by partner change.
Conclusions
There is a paternal effect on risks of preterm pre-eclampsia and giving birth to an SGA infant.
doi:10.1136/bmjopen-2012-001178
PMCID: PMC3432846  PMID: 22936817
3.  Cause-specific infant mortality in a population-based Swedish study of term and post-term births: the contribution of gestational age and birth weight 
BMJ Open  2012;2(4):e001152.
Objective
To investigate infant mortality and causes of infant death in relation to gestational age (GA) and birth weight for GA in non-malformed term and post-term infants.
Design
Observational, retrospective nationwide cohort study.
Setting
Sweden 1983–2006.
Participants
2 152 738 singleton non-malformed infants born at 37 gestational weeks or later.
Main outcome measures
Infant, neonatal and postneonatal mortality and causes of infant death.
Results
Infant mortality rate was 0.12% (n=2687). Compared with infants born at 40 weeks, risk of infant mortality was increased among early term infants (37 weeks, adjusted OR 1.70, 95% CI 1.43 to 2.02). Compared with infants with normal birth weight for GA, very small for gestational age (SGA; <3rd percentile) infants faced a doubled risk of infant mortality (adjusted OR 2.13, 95% CI 1.80 to 2.53), and corresponding risk was also increased among moderately SGA infants (3rd to <10th percentile; adjusted OR 1.46, 95% CI 1.26 to 1.68). Sudden infant death syndrome (SIDS) was the most common cause of death, accounting for 39% of all infant mortality. Compared with birth at 40 weeks, birth at 37 weeks was associated with increased risks of death by infections, cardiovascular disorders, SIDS and malignant neoplasms. Very and moderately SGA were associated with increased risks of death by neonatal respiratory disorders, infections, cardiovascular disorders, SIDS and neuromuscular disorders. High birth weight for GA was associated with increased risks of death by asphyxia and malignant neoplasms.
Conclusion
Early term birth and very to moderately low birth weight for GA are independent risk factors for infant mortality among non-malformed term infants.
Article summary
Article focus
Term infants (born at 37 gestational weeks or more) contribute with 30% to all neonatal mortality. Infants born at 37 and 38 weeks have higher rates of infant mortality than infants born at 40 weeks. Little is known about the interplay between GA and birth weight for GA and its effect on infant mortality.
Key messages
This study adds detailed analyses of the relationships between GA and birth weight for GA and risks of neonatal and postneonatal mortality and causes of infant death. We conclude that induced deliveries before 39 weeks gestation should be avoided when possible and that extra caution should be taken in term pregnancies with suspected severe or moderate intrauterine growth restriction.
Strengths and limitations of this study
The main strengths of this study are related to sample size and to the large number of predefined risk factors and confounders. Limitations were that some malformations may not have been detected, causing a theoretical selection bias, and that time trends may have influenced the outcome.
doi:10.1136/bmjopen-2012-001152
PMCID: PMC3391369  PMID: 22763662
4.  Population-based trends in pregnancy hypertension and pre-eclampsia: an international comparative study 
BMJ Open  2011;1(1):e000101.
Objective
The objective of this study was to compare international trends in pre-eclampsia rates and in overall pregnancy hypertension rates (including gestational hypertension, pre-eclampsia and eclampsia).
Design
Population data (from birth and/or hospital records) on all women giving birth were available from Australia (two states), Canada (Alberta), Denmark, Norway, Scotland, Sweden and the USA (Massachusetts) for a minimum of 6 years from 1997 to 2007. All countries used the 10th revision of the International Classification of Diseases, except Massachusetts which used the 9th revision. There were no major changes to the diagnostic criteria or methods of data collection in any country during the study period. Population characteristics as well as rates of pregnancy hypertension and pre-eclampsia were compared.
Results
Absolute rates varied across the populations as follows: pregnancy hypertension (3.6% to 9.1%), pre-eclampsia (1.4% to 4.0%) and early-onset pre-eclampsia (0.3% to 0.7%). Pregnancy hypertension and/or pre-eclampsia rates declined over time in most populations. This was unexpected given that factors associated with pregnancy hypertension such as pre-pregnancy obesity and maternal age are generally increasing. However, there was also a downward shift in gestational age with fewer pregnancies reaching 40 weeks.
Conclusion
The rate of pregnancy hypertension and pre-eclampsia decreased in northern Europe and Australia from 1997 to 2007, but increased in Massachusetts. The use of a different International Classification of Diseases coding version in Massachusetts may contribute to the difference in trend. Elective delivery prior to the due date is the most likely explanation for the decrease observed in Europe and Australia. Also, the use of interventions that reduce the risk of pregnancy hypertension and/or progression to pre-eclampsia (low-dose aspirin, calcium supplementation and early delivery for mild hypertension) may have contributed to the decline.
Article summary
Article focus
The population prevalence of factors associated with increased and decreased risk of pregnancy hypertension and pre-eclampsia has changed over time, but the impact of these changes is unknown.
International comparisons of absolute population rates of pregnancy hypertension and pre-eclampsia are hindered by different diagnostic criteria and methods of data collection.
Comparing trends between countries overcomes the difficulties in comparing absolute rates.
Key message
Pregnancy hypertension and/or pre-eclampsia rates declined over time in northern Europe and Australia, but not Massachusetts (USA).
Declining hypertension rates were accompanied by a downward shift in gestational age with fewer pregnancies reaching term, the time when the pregnancy hypertension and pre-eclampsia are most likely to occur.
Strengths and limitations of this study
Strengths include numerous validation studies indicating that the hypertensive disorders are reliably reported in the population data sets used for the study and the consistency of trends across most countries.
Limitations include a different International Classification of Diseases coding version in Massachusetts and lack of available information on clinical interventions.
doi:10.1136/bmjopen-2011-000101
PMCID: PMC3191437  PMID: 22021762
Trends; pregnancy; pre-eclampsia; gestational hypertension; international classification of diseases; maternal medicine; obstetrics; hypertension; epidemiology; statistics; epidmiology; delivery; birth; infant mortality; information; public health; health economics; health policy; international health services; quality in healthcare; health and socio-economic inequalities; maternal and child health; statistics and research methods; parturition; preterm birth

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