Mortality and major disease risk among migrants of the 1991-2001 Balkan wars to Sweden: A register-based cohort study.

BACKGROUND: In recent decades, millions of refugees and migrants have fled wars and sought asylum in Europe. The aim of this study was to quantify the risk of mortality and major diseases among migrants during the 1991-2001 Balkan wars to Sweden in comparison to other European migrants to Sweden during the same period. METHODS AND
FINDINGS: We conducted a register-based cohort study of 104,770 migrants to Sweden from the former Yugoslavia during the Balkan wars and 147,430 migrants to Sweden from 24 other European countries during the same period (1991-2001). Inpatient and specialized outpatient diagnoses of cardiovascular disease (CVD), cancer, and psychiatric disorders were obtained from the Swedish National Patient Register and the Swedish Cancer Register, and mortality data from the Swedish Cause of Death Register. Adjusting for individual-level data on sociodemographic characteristics and emigration country smoking prevalence, we used Cox regressions to contrast risks of health outcomes for migrants of the Balkan wars and other European migrants. During an average of 12.26 years of follow-up, being a migrant of the Balkan wars was associated with an elevated risk of being diagnosed with CVD (HR 1.39, 95% CI 1.34-1.43, p < 0.001) and dying from CVD (HR 1.45, 95% CI 1.29-1.62, p < 0.001), as well as being diagnosed with cancer (HR 1.16, 95% CI 1.08-1.24, p < 0.001) and dying from cancer (HR 1.27, 95% CI 1.15-1.41, p < 0.001), compared to other European migrants. Being a migrant of the Balkan wars was also associated with a greater overall risk of being diagnosed with a psychiatric disorder (HR 1.19, 95% CI 1.14-1.23, p < 0.001), particularly post-traumatic stress disorder (HR 9.33, 95% CI 7.96-10.94, p < 0.001), while being associated with a reduced risk of suicide (HR 0.68, 95% CI 0.48-0.96, p = 0.030) and suicide attempt (HR 0.57, 95% CI 0.51-0.65, p < 0.001). Later time period of migration and not having any first-degree relatives in Sweden at the time of immigration were associated with greater increases in risk of CVD and psychiatric disorders. Limitations of the study included lack of individual-level information on health status and behaviors of migrants at the time of immigration.
CONCLUSIONS: Our findings indicate that migrants of the Balkan wars faced considerably elevated risks of major diseases and mortality in their first decade in Sweden compared to other European migrants. War migrants without family members in Sweden or with more recent immigration may be particularly vulnerable to adverse health outcomes. Results underscore that persons displaced by war are a vulnerable group in need of long-term health surveillance for psychiatric disorders and somatic disease.

Introduction

The global population of people forced to cross national boundaries due to war, persecution, or violence reached 25.9 million at the end of 2018, representing the highest levels of external displacement ever recorded [1]. Due to this unprecedented influx of refugees and migrants to new countries, particularly from the Syrian Arab Republic, it is imperative to understand the extent of health consequences experienced by war migrant populations over the years after they arrive in a host country.

All migrants face resettlement stressors, regardless of the reason for migration, including socioeconomic adversities and accommodating to a new language and culture. Beyond these resettlement stressors, migrants of war can carry the additional burden of exposures to traumatic events such as witnessing or experiencing the threat of death, torture, violence, and persecution before or during their journey to a host country. Earlier studies have reported increased risk of psychiatric morbidity, such as post-traumatic stress disorder (PTSD), depression, and psychosis, among war migrants when compared to population natives [2,3]. However, as general stressors associated with migration are not accounted for in this comparison, we can better understand how war migration affects psychiatric morbidity if we use other migrants as a reference group. Meanwhile, few studies have assessed the risk of physical morbidity and mortality among war migrants, and results have been conflicting. Some studies indicate a decreased risk of cancer and cardiovascular disease (CVD) among migrants compared to population natives [4] while others have found migrants to be at increased risk [5,6]. To date, the majority of studies on the health of war migrants rely on comparison to population natives. This comparison is subject to the so-called healthy migrant effect, because relative to the native population, the prevalence of most frequent diseases is lower among migrants [7].

The 1991–2001 Balkan wars were marked by war crimes such as genocide, ethnic cleansing, rape, and torture. The wars are estimated to have taken 140,000 lives, and led to the displacement of approximately 4 million people [8]. During the wars, more than 100,000 adults and children migrated from the Balkans to Sweden. Extending previous research on the health impact of war migration, we here utilize the Swedish national health registries to quantify mortality and major disease risk among migrants of the Balkan wars to Sweden, as well as risk factors for adverse outcomes.

Methods

Study population and design

We conducted a historical register-based cohort study in a number of Swedish national registries, using the personal identity numbers that are uniquely assigned to every resident at birth or immigration [9]. Through the Total Population Register we identified all migrants (n = 104,770) entering Sweden from 1 January 1991 through 31 December 2001 with a country of birth registered as Albania, Bosnia-Herzegovina, Croatia, Macedonia, Slovenia, or Yugoslavia. As we had no information on individual legal status at immigration, we adhere to the United Nations Migration Agency’s definition of a migrant [10] and hereafter refer to these individuals as migrants of the Balkan wars. For comparison, we identified a cohort of all migrants from other European countries (n = 147,430) entering Sweden during the same time period with a country of birth registered as Austria, Belgium, Czech Republic, Czechoslovakia, Denmark, Finland, France, Germany, Great Britain, Greece, Hungary, Iceland, Ireland, Italy, Malta, Moldavia, the Netherlands, Norway, Poland, Portugal, Romania, Slovak Republic, Spain, or Switzerland (see S1 Table for number of migrants from each country). These countries were not at war during the specified time period.

Of the 252,200 identified migrants, 34 were excluded from analysis due to inconsistency of information concerning, for example, the date of death. The total number of migrants in the study was therefore 252,166. We followed these migrants for major disease outcomes (specified below) from the date of immigration until death, emigration out of Sweden, or end of follow-up (31 December 2010), whichever occurred first.

Ethics statement

The overarching study protocol (S1 Study Protocol) was submitted and approved by the Regional Ethics Committee in Stockholm (nr. 2016/384-31), and the study is reported as per the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) guideline (S1 Text STROBE Checklist).

Outcomes

Mortality outcomes during follow-up were identified in the Swedish Cause of Death Register and based on the International Classification of Diseases versions 9 and 10 (ICD-9 and ICD-10); we recorded overall and cause-specific mortality, including death due to CVD (ICD-9: 390–489; ICD-10: I00–I99), cancer (ICD-9: 140–209; ICD-10: C00–C99), suicide (ICD-9: 950–959; ICD-10: X60–X84), and other causes. The Swedish Cause of Death Register has been found to be a largely complete and high-quality data source [11].

The Swedish Cancer Register was utilized to obtain all newly diagnosed cancers (ICD-7: 140–209), and the Swedish National Patient Register was utilized to obtain inpatient and specialized outpatient diagnoses of CVD (ICD-9: 390–489; ICD-10: I00–199), suicide attempt (ICD 9: 950–958, 980–988; ICD 10: X60–X84, Y10–Y34), and psychiatric disorders (ICD-9: 290–319; ICD-10: F00–F99). The Swedish National Patient Register has been reported to have high validity, both for CVD and psychiatric disorders [12]. As it is likely that the migrants of the Balkan wars were exposed to multiple traumatizing events [8], we specifically looked at PTSD (ICD-9: 309B; ICD-10: F43.1). The validity of PTSD diagnoses in Swedish register data has been found to be sufficient, with a positive predictive validity of 76%–90% [13].

We conducted, ad hoc, sub-analyses on (1) smoking-related cancers, defined as buccal (ICD-7: 140–148), esophagus (ICD-7: 150), stomach (ICD-7: 151), large intestine (ICD-7: 153), pancreatic (ICD-7: 157), lung (ICD-7: 162–163), uterus (ICD-7: 171), and kidney cancer including renal pelvis (ICD-7: 180); (2) alcohol-related cancers, defined as buccal (ICD-7: 140–148), digestive (ICD-7: 150), liver (primary site) (ICD-7: 155), large intestine and rectum (ICD-7: 153–154), larynx (ICD-7: 161), and breast cancer (ICD-7: 170); and (3) other cancers, i.e., any cancer excluding the above.

Covariates

Covariates included age at immigration, sex, calendar period of immigration (1991–1994, 1995–1998, or 1999–2001), and educational attainment. The Multi-Generation Register was used to identify the number of first-degree relatives (i.e., siblings, parents, and children) also registered in Sweden at the time of immigration to the country (i.e., both migrating with the individual and already residing in Sweden).

Smoking is a major risk factor for morbidities and premature mortality, and may be unequally distributed between the migrants of the Balkan wars and other European immigrant groups. We therefore, ad hoc, obtained an estimated smoking prevalence for each migrant’s home country from the World Health Organization’s Global Health Observatory data repository for the year 2000 (S2 Table). As information was unavailable for Macedonia in the data repository, data from 2009 was used. Smoking prevalence was obtained for both sexes, for everyone 15 years and older, and was defined as daily or occasional use of tobacco, including cigarettes, cigars, pipes, or any other smoked tobacco products. When adjusting for smoking in the multivariable models, each individual received the smoking status of the country they emigrated from.

In addition, as we were concerned for differential baseline risks across populations, we subsequently adjusted for country-level cancer- and CVD-related death rates. We obtained death rates for migrants’ home countries from the WHO Global Health Observatory data repository for the year 1990 (S3 Table).

In order to understand if suicide rates differed between the populations in the countries of the Balkan wars and other European countries, we obtained data on mean suicide rates for all studied countries for the year 1990 from Our World in Data [14] (S4 Table).

Statistical analysis

Descriptive analyses were conducted to examine baseline factors across the 2 migrant populations, including sex, age, period of immigration, educational attainment (missing information was presented in a separate category), number of first-degree relatives in Sweden, and estimated smoking prevalence for each migrant’s home country. T tests and chi-squared tests were conducted to determine if the 2 groups differed with respect to these characteristics.

Incidence rates (per 100,000 person-years) of morbidities and mortality during the time intervals 0–1, 2–4, 5–9, and 10 and more years since migration were calculated among migrants of the Balkan wars and other European migrants. Cox proportional hazard regression models were used to assess the hazard ratios (HRs) and 95% confidence intervals (CIs) of mortality and morbidities, comparing disease incidence rates and mortality rates in the 2 migrant populations. The proportionality assumption for all outcomes was not violated in any of the Cox models except for the analysis of PTSD; a model satisfying the assumption was complex but did not change the pattern of an overall high HR for PTSD. We therefore report all estimates by time intervals (0–1, 2–4, 5–9, and ≥10 years).

We present incidence rates and HRs first stratified by background characteristics (e.g., age at immigration, sex, education, period of immigration, and the number of first-degree relatives in Sweden at immigration), then age-adjusted HRs; next HRs adjusted for age at immigration, sex, education, and calendar period of immigration; and finally HRs adjusted additionally for country-specific smoking prevalence.

In tables presenting rates of morbidities and mortality by time since migration, we adjusted all models for sex, education, age at immigration, smoking (country-specific prevalence), and calendar period of immigration. Age at immigration, calendar period of immigration, and smoking were modeled as continuous variables in all tables. When assessing death due to CVD, we adjusted for the CVD-related death rate of the home country. Similarly, when assessing death due to cancer we adjusted for the cancer-related death rate of the home country. Finally, linear regression analysis was conducted to test if HRs for total mortality, CVD mortality and morbidity, psychiatric morbidity, and PTSD were higher among those with (1) late period of immigration (1999–2001) and (2) no first-degree relatives in Sweden. For the statistical analyses, we used SAS software, version 9.2 (SAS Institute).

Results

Migrants of the Balkan wars were more likely than other European migrants to be younger, to be female, and to have migrated to Sweden in an early time period (1991–1994) (p < 0.001). Mean age at immigration was slightly lower among migrants of the Balkan wars than among other European migrants, 28.02 versus 28.64 years, respectively. Median follow-up time was significantly longer for migrants of the Balkan wars (5,987 days) than for other European migrants (3,405 days). Migrants of the Balkan wars were less likely to have a university-level education and more likely to have 1 or more first-degree relatives in Sweden at the time of immigration to Sweden, compared to other European migrants (p < 0.001). The average country prevalence of smoking in the countries of the Balkan wars was higher than in the other European countries (46.55% versus 35.70%, p < 0.001) (Table 1).

Table 1

Descriptive characteristics of migrants of the Balkan wars and other European migrants to Sweden during 1991–2001.

Characteristic	War migrants	Other European migrants	p-Value*
Total	104,770	147,430
Sex female	52,337 (49.95)	70,249 (47.66)	<0.001
Age			<0.001
0–19 years	36,146 (34.50)	33,578 (22.78)
20–39 years	44,805 (42.77)	82,685 (56.10)
40–59 years	16,619 (15.86)	23,811 (16.15)
60–79 years	6,834 (6.52)	6,706 (4.55)
80 years or older	365 (0.35)	617 (0.42)
Mean age at immigration (years)	28.02	28.64
Mean number of follow-up (days)	5,987	3,405	<0.001
Period of migration			<0.001
1991–1994	70,857 (67.63)	41,592 (28.22)
1995–1998	19,625 (18.73)	42,636 (28.93)
1999–2001	14,287 (13.64)	63,169 (42.86)
Education			<0.001
Primary	39,756 (39.33)	63,104 (49.81)
Secondary	45,682 (45.20)	28,340 (22.37)
University	15,639 (15.47)	35,257 (27.82)
Missing	3,692	20,696
Number of first-degree relatives in Sweden at immigration			<0.001
0	40,689 (38.84)	87,365 (59.27)
1	32,045 (30.59)	34,252 (23.24)
2+	32,035 (30.58)	25,780 (17.49)
Smoking (%)**	46.55	35.70	<0.001

Data are given as n (percent) unless otherwise indicated.

*T test for continuous variables: age at immigration, follow-up time, smoking; chi-squared test for other (categorical) variables.

**Estimated smoking prevalence of the migrant’s home country, according to the World Health Organization’s Global Health Observatory data repository for the year 2000.

The total follow-up for mortality was 1,531,938 person-years for migrants of the Balkan wars and 1,308,877 person-years for migrants of other European countries.

Mortality

Table 2 shows mortality rates among migrants of the Balkan wars and other European migrants stratified by background characteristics as well as crude, age-adjusted, and multivariable-adjusted HRs for overall mortality, suicide, and mortality due to CVD and cancer. The crude hazard ratios varied considerably across strata of background factors without a clear pattern except across the number of first-degree relatives.

Table 2

Mortality rates in migrants of the Balkan wars compared to other European migrants, across strata of sociodemographic and lifestyle-related characteristics.

Cause of death	Analysis or characteristic	IR* (95% CI) for war migrants	IR (95% CI) for other European migrants	HR (95% CI)	p-Value for HR
Overall mortality	Univariate analysis
	Crude overall HR	348.8 (339.5–358.3)	291.0 (281.9–300.4)	1.12 (1.07–1.16)	<0.001
	Age at immigration
	0–19 years	25.24 (21.39–29.79)	24.09 (19.21 30.21)	1.02 (0.76–1.35)	0.917
	20–39 years	85.75 (78.98–93.11)	64.78 (59.13–70.98)	1.19 (1.05–1.35)	0.007
	40–59 years	660.15 (628.20–693.72)	480.65 (452.58–510.46)	1.22 (1.12–1.32)	<0.001
	60–79 years	3,639.37 (3,507.27–3,776.46)	2,835.20 (2,705.39–2,971.24)	1.20 (1.13–1.27)	<0.001
	80 years or older	10,783.76 (9,560.49–12,163.54)	13,006.87 (11,874.45–14,247.29)	0.81 (0.70–0.95)	0.007
	Sex
	Male	350.23 (337.25–363.71)	315.96 (302.68–329.82)	1.03 (0.97–1.09)	0.034
	Female	347.30 (334.33–360.78)	265.69 (253.44–278.53)	1.22 (1.15–1.30)	<0.001
	Education
	Primary	686.50 (664.98–708.71)	527.75 (507.08–549.27)	1.18 (1.12–1.24)	<0.001
	Secondary	139.54 (131.13–148.48)	213.19 (198.27–229.24)	0.61 (0.55–0.67)	<0.001
	University	167.19 (151.57–184.42)	94. 33 (85.06–104.61)	1.57 (1.36–1.82)	<0.001
	Missing	555.17 (475.71–647.91)	241.88 (216.63–270.07)	2.43 (2.01–2.94)	<0.001
	Period of immigration
	1991–1994	297.96 (288.10–308.15)	356.23 (338.95–374.39)	0.82 (0.77–0.87)	<0.001
	1995–1998	639.81 (609.58–671.53)	324.51 (306.64–343.42)	1.92 (1.78–2.07)	<0.001
	1999–2001	226.53 (202.66–253.20)	210.02 (197.73–223.06)	1.07 (0.95–1.22)	0.272
	Number of first-degree relatives in Sweden
	0	653.31 (632.60–674.69)	303.49 (291.31–316.17)	2.00 (1.90–2.11)	<0.001
	1	316.71 (300.98–333.26)	439.04 (416.33–462.99)	0.67 (0.62–0.72)	<0.001
	2+	31.95 (27.35–37.32)	63.67 (54.40–74.53)	0.49 (0.39–0.61)	<0.001
	Multivariable analysis
	Adjusted for age	N/A	N/A	1.21 (1.16–1.26)	<0.001
	Adjusted for age, sex, education, and calendar period of immigration	N/A	N/A	1.17 (1.12–1.22)	<0.001
	Adjusted for age, sex, education, calendar period of immigration, and smoking**	N/A	N/A	1.20 (1.14–1.27)	<0.001
Suicide	Univariate analysis
	Crude overall HR	7.6 (6.3–9.1)	11.0 (9.3–13.0)	0.69 (0.54–0.89)	0.004
	Age at immigration
	0–19 years	2.52 (1.50–4.26)	4.82 (2.90–7.99)	0.39 (0.18–0.81)	0.012
	20–39 years	7.41 (5.61–9.81)	9.27 (7.29–11.81)	0.81 (0.56–1.18)	0.274
	40–59 years	12.26 (8.52–17.65)	23.56 (17.95–30.91)	0.54 (0.34–0.86)	0.009
	60–79 years	31.08 (20.83–46.38)	14.59 (7.59–28.04)	2.25 (1.04–4.84)	0.039
	80 years or older	0.00 incidence observed	56.19 (14.05–224.66)	N/A	N/A
	Sex
	Male	9.62 (7.66–12.09)	13.50 (10.97–16.62)	0.71 (0.52–0.98)	0.037
	Female	5.50 (4.07–7.45)	8.47 (6.50–11.03)	0.65 (0.44–0.98)	0.040
	Education
	Primary	7.25 (5.32–9.88)	1.29 (9.46–15.97)	0.65 (0.43–0.98)	0.037
	Secondary	7.58 (5.81–9.90)	14.91 (11.34–19.53)	0.48 (0.33–0.70)	<0.001
	University	5.87 (3.47–9.91)	7.09 (4.87–10.35)	0.83 (0.43–1.59)	0.572
	Missing	27.59 (13.80–55.16)	7.65 (4.12–14.23)	3.91 (1.54–9.91)	0.004
	Period of immigration
	1991–1994	7.64 (6.19–9.43)	12.15 (9.28–15.90)	0.60 (0.43–0.85)	0.004
	1995–1998	8.58 (5.65–13.03)	10.30 (7.50–14.16)	0.89 (0.52–1.50)	0.656
	1999–2001	5.12 (2.44–10.73)	10.52 (8.04–13.77)	0.49 (0.22–1.08)	0.076
	Number of first-degree relatives in Sweden
	0	11.82 (9.30–15.01)	11.25 (9.10–13.92)	1.09 (0.79–1.51)	0.594
	1	7.28 (5.20–10.18)	14.18 (10.55–19.06)	0.50 (0.32–0.78)	0.003
	2+	3.01 (1.82–5.00)	6.16 (3.71–10.22)	0.43 (0.21–0.90)	0.025
	Multivariable analysis
	Adjusted for age	N/A	N/A	0.71 (0.56–0.92)	0.008
	Adjusted for age, sex, education, and calendar period of immigration	N/A	N/A	0.63 (0.49–0.82)	<0.001
	Adjusted for age, sex, education, calendar period of immigration, and smoking**	N/A	N/A	0.68 (0.48–0.96)	0.030
Cardiovascular disease	Univariate analysis
	Crude overall HR	120.2 (114.9–125.9)	94.7 (89.6–100.2)	1.20 (1.11–1.29)	<0.001
	Age at immigration
	0–19 years	0.72 (0.27–1.92)	2.89 (1.50–5.56)	0.24 (0.07–0.81)	0.021
	20–39 years	13.76 (11.21–16.90)	6.75 (5.08–8.95)	1.69 (1.18–2.42)	0.004
	40–59 years	185.653 (169.07–203.86)	121.86 (108.13–137.33)	1.40 (1.20–1.54)	<0.001
	60–79 years	1,511.44 (1,427.16–1,600.70)	1,108.79 (1,028.73–1,195.08)	1.26 (1.15–1.39)	<0.001
	80 years or older	5,737.77 (4,864.72–6,767.51)	6,461.30 (5,677.96–7,352.71)	0.88 (0.71–1.08)	0.223
	Sex
	Male	113.15 (105.87–120.92)	100.87 (93.49–108.84)	1.06 (0.96–1.18)	0.260
	Female	127.39 (119.63–135.65)	88.51 (81.57–96.05)	1.35 (1.22–1.50)	<0.001
	Education
	Primary	270.69 (257.30–284.77)	199.03 (186.49–212.42)	1.23 (1.13–1.34)	<0.001
	Secondary	29.20 (25.49–33.45)	47.38 (40.61–55.26)	0.58 (0.47–0.72)	<0.001
	University	40.23 (32.93–49.14)	21.54 (17.35–26.75)	1.69 (1.25–2.28)	<0.001
	Missing	151.72 (112.91–203.88)	68.12 (55.34–83.86)	2.37 (1.65–3.40)	<0.001
	Period of immigration
	1991–1994	99.67 (94.03–105.64)	119.89 (110.04–130.62)	0.82 (0.74–0.91)	<0.001
	1995–1998	243.04 (224.69–262.90)	110.07 (99.87–121.31)	2.15 (1.89–2.43)	<0.001
	1999–2001	61.38 (49.56–76.02)	61.73 (55.24–68.99)	0.99 (0.78–1.26)	0.920
	Number of first-degree relatives in Sweden
	0	251.69 (238.97–265.10)	101.16 (94.24–108.60)	2.33 (2.13–2.55)	<0.001
	1	86.67 (78.62–95.53)	144.41 (131.64–158.42)	0.56 (0.49–0.64)	<0.001
	2+	2.01 (1.081–3.73)	11.50 (7.94–16.66)	0.16 (0.08–0.34)	<0.001
	Multivariable analysis
	Adjusted for age	N/A	N/A	1.35(1.26–1.46)	<0.001
	Adjusted for age, sex, education, and calendar period of immigration	N/A	N/A	1.30 (1.20–1.40)	<0.001
	Adjusted for age, sex, education, calendar period of immigration, and smoking**	N/A	N/A	1.45 (1.29–1.62) †	<0.001
Cancer	Univariate analysis
	Crude overall HR	118.7 (113.3–124.3)	81.7 (76.9–86.7)	1.36 (1.26–1.47)	<0.001
	Age at immigration
	0–19 years	5.04 (3.49–7.31)	3.21 (1.73–5.97)	1.73 (0.83–3.64)	0.145
	20–39 years	38.41 (33.97–43.44)	15.46 (12.82–18.63)	2.07 (1.65–2.60)	<0.001
	40–59 years	306.60 (285.08–329.75)	167.62 (151.38–185.60)	1.60 (1.41–1.82)	<0.001
	60–79 years	1,011.51 (943.00–1,085.00)	841.32 (771.96–916.91)	1.16 (1.03–1.30)	0.009
	80 years or older	1,220.80 (853.56–1,746.05)	1,685.56 (1,308.73–2,170.87)	0.74 (0.48–1.15)	0.175
	Sex
	Male	126.02 (118.33–134.21)	81.46 (74.85–88.65)	1.42 (1.27–1.58)	<0.001
	Female	111.27 (104.03–119.01)	81.89 (75.22–89.16)	1.29 (1.16–1.44)	<0.001
	Education
	Primary	196.22 (184.87–208.26)	130.79 (120.70–141.72)	1.41 (1.27–1.56)	<0.001
	Secondary	65.56 (59.87–71.78)	67.84 (59.66–77.16)	0.89 (0.75–1.04)	0.132
	University	82.12 (71.40–94.47)	37.57 (31.89–44.27)	1.90 (1.52–2.37)	<0.001
	Missing	248.28 (197.70–312.79)	75.01 (61.54–91.44)	3.53 (2.60–4.79)	<0.001
	Period of immigration
	1991–1994	106.70 (100.86–112.87)	101.32 (92.30–111.22)	1.03 (0.92–1.15)	0.639
	1995–1998	194.67 (178.32–212.53)	87.02 (78.01–97.08)	2.21 (1.92–2.54)	<0.001
	1999–2001	76.00 (62.71–92.10)	60.74 (54.30–67.94)	1.25 (1.00–1.56)	0.050
	Number of first-degree relatives in Sweden
	0	197.90 (186.65–209.82)	83.68 (77.41–90.47)	2.23 (2.02–2.46)	<0.001
	1	139.74 (129.42–150.88)	129.91 (117.82–143.23)	0.98 (0.86–1.11)	0.717
	2+	8.64 (6.41–11.65)	13.97 (9.98–19.55)	0.60 (0.38–0.95)	0.030
	Multivariable analysis
	Adjusted for age	N/A	N/A	1.45(1.34–1.56)	<0.001
	Adjusted for age, sex, education, and calendar period of immigration	N/A	N/A	1.43 (1.32–1.54)	<0.001
	Adjusted for age, sex, education, calendar period of immigration, and smoking**	N/A	N/A	1.27 (1.15–1.41) ††	<0.001

*Incidence rates per 100,000 person-years.

**Country-specific smoking prevalence.

†Adjusted for baseline cardiovascular disease mortality.

††Adjusted for baseline cancer mortality.

IR, incidence rate; HR, hazard ratio; N/A, not applicable.

Among migrants of the Balkan wars, having a lower number of first-degree relatives in Sweden at immigration was associated with a more pronounced risk increase for overall mortality (HR 2.00, 95% CI 1.90–2.11, p < 0.001, for no relatives; HR 0.67, 95% CI 0.62–0.72, p < 0.001, for 1 relative; HR 0.49, 95% CI 0.39–0.61, p < 0.001, for 2 or more relatives) and death due to CVD (HR 2.33, 95% CI 2.13–2.55, p < 0.001, for no relatives; HR 0.56, 95% CI 0.49–0.64, p < 0.001, for 1 relative; HR 0.16, 95% CI 0.08–0.34, p < 0.001, for 2 or more relatives) (Table 2). With a trend test, total mortality (p < 0.001) and CVD mortality (p < 0.001) decrease significantly with the number of first-degree relatives.

Compared to other European migrants, being a migrant of the Balkan wars was associated with an elevated risk of overall mortality, with risk estimates increasing in multivariable-adjusted models (HR 1.20, 95% CI 1.14–1.27, p < 0.001) compared to crude data (HR 1.12, 95% CI 1.07–1.16, p < 0.001). Similarly, being a migrant of the Balkan wars was associated with an elevated risk of CVD mortality, with risk estimates increasing in multivariable-adjusted models (HR 1.45, 95% CI 1.29–1.62, p < 0.001) compared to the crude model (HR 1.20, 95% CI 1.11–1.29, p < 0.001). Elevated risk of cancer mortality was also associated with being a migrant of the Balkan wars, with risk estimates somewhat attenuated in the multivariable-adjusted models (HR 1.27, 95% CI 1.15–1.41, p < 0.001) compared to the crude model (HR 1.36, 95% CI 1.26–1.47, p < 0.001) (Table 2).

Interestingly, being a migrant of the Balkan wars was associated with a decreased mortality risk due to suicide during follow-up, with similar risk estimates in crude (HR 0.69, 95% CI 0.54–0.89, p = 0.004) and multivariable-adjusted models (HR 0.68, 95% CI 0.48–0.96, p = 0.030).

When assessing time since immigration, we found that the risk of overall mortality associated with being a migrant of the Balkan wars was elevated at 5–9 years (HR 1.20, 95% CI 1.09–1.32, p < 0.001) and ≥10 years after immigration (HR 1.35, 95% CI 1.22–1.48, p < 0.001). Being a migrant of the Balkan wars was also associated with a gradual increase in risk of death due to CVD over time (HR 1.38, 95% CI 1.05–1.82, p = 0.021, at 2 to 4 years after immigration versus HR 1.55, 95% CI 1.30–1.86, p < 0.001, at ≥10 years after immigration). The risk of death due to cancer associated with being a migrant of the Balkan wars was increased throughout follow-up. Although not statistically significant, the risk of suicide associated with being a migrant of the Balkan wars was decreased at all time points (Table 3).

Table 3

Mortality rates in migrants of the Balkan wars (exposed) compared to other European migrants (unexposed), by time since immigration.

Outcome measure	Time since immigration
	0–1 year	2–4 years	5–9 years	10+ years
Mortality (overall)
IR* (95% CI) for exposed	229.5 (209.8–251.1)	270.4 (252.6–289.5)	346.3 (330.2–363.2)	443.1 (425.5–461.4)
IR (95% CI) for unexposed	249.2 (230.8–269.0)	244.2 (227.7–262.0)	286.6 (271.4–302.6)	393.0 (370.2–417.1)
HR** (95% CI)	1.05 (0.89–1.24)	1.05 (0.92–1.20)	1.20 (1.09–1.32)	1.35 (1.22–1.48)
p-Value for HR	0.549	0.508	<0.001	<0.001
Suicide
IR (95% CI) for exposed	7.2 (4.3–11.9)	7.5 (5.0–11.3)	7.0 (5.0–9.8)	8.3 (6.2–11.2)
IR (95% CI) for unexposed	13.7 (9.9–18.9)	10.9 (7.8–15.2)	10.4 (7.8–13.9)	9.5 (6.4–13.9)
HR** (95% CI)	0.77 (0.33–1.79)	0.56 (0.27–1.15)	0.65 (0.35–1.20)	0.82 (0.41–1.64)
p-Value for HR	0.540	0.112	0.169	0.583
Death due to CVD†
IR (95% CI) for exposed	80.7 (69.4–93.9)	99.4 (88.8–111.2)	120.7 (111.3–130.8)	147.4 (137.4–158.1)
IR (95% CI) for unexposed	71.9 (62.3–82.9)	82.8 (73.4–93.4)	93.7 (85.2–103.1)	132.2 (119.3–146.5)
HR** (95% CI)	1.27 (0.91–1.77)	1.38 (1.05–1.82)	1.42 (1.16–1.73)	1.55 (1.30–1.86)
p-Value for HR	0.164	0.021	<0.001	<0.001
Death due to cancer††
IR for exposed (95% CI)	93.6 (81.4–107.7)	93.9 (83.6–105.4)	119.7 (110.4–129.8)	141.9 (132.1–152.4)
IR for unexposed (95% CI)	69.2 (59.8–80.1)	66.8 (58.5–76.4)	78.7 (70.9–87.3)	115.8 (103.8–129.3)
HR** (95% CI)	1.45 (1.09–1.93)	1.10 (0.86–1.40)	1.29 (1.08–1.55)	1.29 (1.08–1.55)
p-Value for HR	0.011	0.437	0.006	0.006

*Incidence rates per 100,000 person-years.

**Adjusting for sex, education, age at immigration, smoking (country-specific prevalence), and calendar period of immigration.

†Adjusted for baseline CVD mortality.

††Adjusted for baseline cancer mortality.

CVD, cardiovascular disease; HR, hazard ratio; IR, incidence rate.

Morbidity

Table 4 shows morbidity rates among migrants of the Balkan wars and other European migrants stratified by background characteristics as well as crude, age-adjusted, and multivariable-adjusted hazard ratios for diagnosis of psychiatric disorders, PTSD, suicide attempt, CVD, and cancer.

Table 4

Rates of morbidities in migrants of the Balkan wars compared to other European migrants, across strata of sociodemographic and lifestyle-related characteristics.

Outcome measure	Analysis or characteristic	IR* (95% CI) for war migrants	IR (95% CI) for other European migrants	HR (95% CI)	p-Value for HR
Overall psychiatric morbidity	Univariate analysis
	Crude overall HR	989.8 (973.7–1,006.3)	753.2 (738.1–768.6)	1.16 (1.13–1.19)	<0.001
	Age at immigration
	0–19 years	726.24 (703.73–749.48)	16.48 (882.68–951.57)	0.67 (0.53–0.70)	<0.001
	20–39 years	1,171.83 (1,145.15–1,199.14)	648.69 (629.87–668.08)	1.59 (1.53–1.65)	<0.001
	40–59 years	1,227.00 (1,181.52–1,274.23)	879.87 (840.27–921.33)	1.30 (1.23–1.39)	<0.001
	60–79 years	686.98 (630.08–749.01)	670.58 (607.84–739.82)	0.98 (0.86–1.12)	0.811
	80 years or older	454.63 (251.77–820.93)	1,260.22 (934.63–1,699.25)	0.39 (0.20–0.75)	0.005
	Sex
	Male	907.45 (885.87–929.56)	712.89 (692.32–734.07)	1.11 (1.07–1.16)	<0.001
	Female	1,073.75 (1,050.03–1,098.01)	794.13 (772.25–816.63)	1.21 (1.17–1.25)	<0.001
	Education
	Primary	960.09 (933.89–987.01)	807.85 (781.59–834.99)	1.04 (1.00–1.09)	0.061
	Secondary	1,016.42 (992.61–1,040.80)	1,005.72 (971.42–1,041.24)	0.94 (0.90–0.98)	0.002
	University	885.36 (847.46–924.95)	524.14 (501.28–548.04)	1.51 (1.42–1.61)	<0.001
	Missing	1,813.60 (1,656.67–1,985.39)	600.94 (559.85–645.03)	3.02 (2.69–3.39)	<0.001
	Period of immigration
	1991–1994	895.41(877.76–913.42)	775.16 (748.77–802.46)	1.11 (1.07–1.16)	<0.001
	1995–1998	1,086.38 (1,045.60–1,128.75)	752.74 (724.61–781.97)	1.37 (1.30–1.45)	<0.001
	1999–2001	1,621.36 (1,552.21–1,693.59)	734.80 (711.03–759.37)	2.21 (2.09–2.33)	<0.001
	Number of first-degree relatives in Sweden
	0	1,010.76 (984.18–1,038.05)	610.54 (592.86–628.76)	1.50 (1.44–1.56)	<0.001
	1	1,282.23 (1,248.97–1,316.3)	951.89 (917.11–987.99)	1.21 (1.16–1.27)	<0.001
	2+	701.64 (678.31–725.76)	954.17 (915.00–995.02)	0.61 (0.58–0.65)	<0.001
	Multivariable analysis
	Adjusted for age	N/A	N/A	1.17 (1.14–1.20)	<0.001
	Adjusted for age, sex, education, and calendar period of immigration	N/A	N/A	1.28 (1.24–1.31)	<0.001
	Adjusted for age, sex, education, calendar period of immigration, and smoking**	N/A	N/A	1.19 (1.14–1.23)	<0.001
Post-traumatic stress disorder	Univariate analysis
	Crude overall HR	175.5 (168.9–182.2)	18.6 (16.4–21.1)	7.93 (6.95–9.06)	<0.001
	Age at immigration
	0–19 years	56.95 (51.00–63.61)	18.00 (13.85–23.39)	2.57 (1.92–3.43)	<0.001
	20–39 years	244.29(232.60–256.58)	20.11 (17.07–23.70)	9.93 (8.35–11.80)	<0.001
	40–59 years	311.92(290.03–335.48)	17.68 (12.92–24.20)	15.83 (11.45–21.87)	<0.001
	60–79 years	36.32(25.07–52.60)	8.11 (3.38–19.49)	4.03 (1.55–10.47)	0.004
	80 years or older	N/A	N/A	N/A	N/A
	Sex
	Male	180.94 (171.64–190.75)	10.93 (8.67–13.77)	13.28 (10.46–16.84)	<0.001
	Female	169.93 (160.89–179.48)	26.35 (22.68–30.61)	5.65 (4.81–6.64)	<0.001
	Education
	Primary	133.74 (124.40–143.78)	16.25 (12.94–20.41)	7.13 (5.60–9.08)	<0.001
	Secondary	190.78 (180.85–201.24)	27.53 (22.49–33.69)	6.07 (4.92–7.49)	<0.001
	University	169.45 (153.65–186.88)	13.93 (10.65–18.24)	10.10 (7.56–13.49)	<0.001
	Missing	664.25 (574.65–767.81)	16.85 (11.10–25.60)	40.01 (25.72–62.30)	<0.001
	Period of immigration
	1991–1994	143.21(136.41–150.36)	17.67 (14.13–22.09)	7.58 (6.02–9.55)	<0.001
	1995–1998	189.81(173.60–207.53)	18.45 (14.54–23.40)	9.50 (7.37–12.25)	<0.001
	1999–2001	421.90 (388.43–458.27)	19.47 (15.97–23.734)	21.87 (17.64–27.10)	<0.001
	Number of first-degree relatives in Sweden
	0	177.24 (166.57–188.60)	14.44 (11.97–17.43)	10.25 (8.40–12.51)	<0.001
	1	299.93 (284.52–316.18)	29.37 (23.92–36.07)	8.90 (7.19–11.02)	<0.001
	2+	58.03 (51.70–65.14)	17.68 (13.11–23.84)	2.52 (1.82–3.49)	<0.001
	Multivariable analysis
	Adjusted for age	N/A	N/A	8.15 (7.14–9.30)	<0.001
	Adjusted for age, sex, education, and calendar period of immigration	N/A	N/A	13.05 (11.36–14.98)	<0.001
	Adjusted for age, sex, education, calendar period of immigration, and smoking**	N/A	N/A	9.33 (7.96–10.94)	<0.001
Suicide attempt	Univariate analysis
	Crude overall HR	54.8 (51.2–58.6)	81.5 (76.7–86.5)	0.62 (0.56–0.68)	<0.001
	Age at immigration
	0–19 years	76.09 (69.14–83.73)	107.20 (96.27–119.37)	0.62 (0.54–0.72)	<0.001
	20–39 years	50.08 (44.96–55.78)	73.70 (67.64–80.30)	0.65 (0.56–0.74)	<0.001
	40–59 years	30.51 (24.21–38.43)	81.08 (70.00–93.90)	0.38 (0.29–0.50)	<0.001
	60–79 years	16.84 (9.78–29.01)	43.86 (30.08–63.96)	0.35 (0.18–0.69)	0.002
	80 years or older	40.71 (5.73–289.00)	56.21 (14.06–224.75)	0.63 (0.06–7.14)	0.711
	Sex
	Male	39.89 (35.66–44.62)	66.84 (60.87–73.39)	0.53 (0.46–0.62)	<0.001
	Female	69.78 (64.10–75.98)	96.31 (89.03–104.19)	0.68 (0.60–0.76)	<0.001
	Education
	Primary	60.53 (54.37–67.40)	86.16 (78.03–95.14)	0.58 (0.50–0.67)	<0.001
	Secondary	58.35 (52.99–64.25)	130.71(119.09–143.47)	0.44 (0.38–0.50)	<0.001
	University	24.76 (19.19–31.96)	38.72 (32.94–45.51)	0.61 (0.45–0.83)	0.002
	Missing	104.37 (72.97–149.27)	61.42 (49.33–76.46)	1.71 (1.12–2.60)	0.012
	Period of immigration
	1991–1994	48.98 (45.07–53.22)	81.99 (73.90–90.97)	0.57 (0.48–0.65)	<0.001
	1995–1998	66.58 (57.29–77.38)	86.66 (77.64–96.72)	0.74 (0.61–0.89)	0.001
	1999–2001	80.81 (67.04–97.41)	77.17 (69.85–85.25)	1.05 (0.85–1.30)	0.649
	Number of first-degree relatives in Sweden
	0	39.08 (34.25–44.58)	59.67 (54.39–65.45)	0.63 (0.53–0.74)	<0.001
	1	59.08 (52.50–66.49)	113.27(101.98–125.79)	0.48 (0.41–0.57)	<0.001
	2+	68.61 (61.69–76.31)	108.68 (96.31–122.64)	0.56 (0.47–0.66)	<0.001
	Multivariable analysis
	Adjusted for age	N/A	N/A	0.61 (0.55–0.66)	<0.001
	Adjusted for age, sex, education, and calendar period of immigration	N/A	N/A	0.58 (0.52–0.64)	<0.001
	Adjusted for age, sex, education, calendar period of immigration, and smoking**	N/A	N/A	0.57 (0.51–0.65)	<0.001
Cardiovascular disease	Univariate analysis
	Crude overall HR	1,276.3 (1,257.9–1,295.1)	873.4 (857.1–890.0)	1.37 (1.34–1.40)	<0.001
	Age at immigration
	0–19 years	341.82 (326.58–357.79)	257.99 (240.57–276.67)	1.31 (1.20–1.42)	<0.001
	20–39 years	1,013.24 (988.58–1,038.53)	506.09 (489.59–523.15)	1.72 (1.65–1.80)	<0.001
	40–59 years	3,021.10 (2,945.59–3,098.55)	1,906.94 (1,846.80–1,969.04)	1.44 (1.38–1.50)	<0.001
	60–79 years	6,776.02 (6,563.03–6,995.93)	5,400.74 (5,193.73–5,615.99)	1.23 (1.17–1.29)	<0.001
	80 years or older	9,929.82 (8,616.87–11,442.83)	12,258.48 (10,940.68–13,735.02)	0.83 (0.70–1.00)	0.051
	Sex
	Male	1,232.72 (1,207.23–1,258.76)	864.93 (842.16–888.31)	1.33 (1.28–1.38)	<0.001
	Female	1,320.38 (1,293.85–1,347.45)	882.01 (858.87–905.77)	1.41 (1.36–1.46)	<0.001
	Education
	Primary	1,650.26 (1,615.03–1,686.26)	993.14 (963.76–1,023.42)	1.65 (1.59–1.71)	<0.001
	Secondary	1,015.06 (991.23–1,039.47)	992.47 (958.519–1,027.63)	0.93 (0.92–1.01)	0.082
	University	1,237.59 (1,192.15–1,284.76)	702.53 (675.85–730.26)	1.60 (1.52–1.69)	<0.001
	Missing	1,162.28 (1,042.19–1,296.21)	661.16 (617.97–707.36)	1.76 (1.55–2.01)	<0.001
	Period of immigration
	1991–1994	1,185.02 (1,164.45–1,205.96)	980.60 (950.67–1,011.47)	1.22 (1.17–1.26)	<0.001
	1995–1998	1,714.86 (1,662.60–1,768.76)	868.24 (837.90–899.69)	1.93 (1.85–2.03)	<0.001
	1999–2001	1,229.30 (1,170.26–1,291.31)	786.70 (762.09–812.12)	1.56 (1.47–1.65)	<0.001
	Number of first-degree relatives in Sweden
	0	1,816.64 (1,780.08–1,853.94)	867.77 (846.53–889.55)	1.98 (1.92–2.05)	<0.001
	1	1,643.75 (1,605.64–1,682.76)	1,260.26 (1,219.73–1,302.14)	1.19 (1.15–1.24)	<0.001
	2+	380.83 (363.82–398.63)	420.32 (394.89–447.39)	0.87 (0.80–0.94)	<0.001
	Multivariable analysis
	Adjusted for age	N/A	N/A	1.44 (1.41–1.47)	<0.001
	Adjusted for age, sex, education, and calendar period of immigration	N/A	N/A	1.45 (1.41–1.49)	<0.001
	Adjusted for age, sex, education, calendar period of immigration, and smoking**	N/A	N/A	1.39 (1.34–1.43)	<0.001
Cancer	Univariate analysis
	Crude overall HR	233.5 (225.9–241.3)	187.4 (180.1–195.0)	1.21 (1.15–1.27)	<0.001
	Age at immigration
	0–19 years	23.30 (19.60–27.68)	16.40 (12.47–21.58)	1.30 (0.94–1.81)	0.117
	20–39 years	133.02 (124.48–142.15)	80.76 (74.41–87.66)	1.48 (1.33–1.64)	<0.001
	40–59 years	641.36 (609.43–674.96)	449.84 (422.39–479.07)	1.33 (1.22–1.44)	<0.001
	60–79 years	1,399.62 (1,316.70–1,487.76)	1,349.22 (1,257.90–1,447.18)	1.04 (0.95–1.14)	0.418
	80 years or older	1,420.80 (1,015.20–1,988.45)	1,623.98 (1,243.78–2,120.39)	0.93 (0.60–1.43)	0.733
	Sex
	Male	219.56 (209.29–230.34)	174.13 (164.30–184.55)	1.21 (1.12–1.31)	<0.001
	Female	247.56 (236.58–259.05)	200.82 (190.16–212.09)	1.21 (1.12–1.30)	<0.001
	Education
	Primary	310.46 (296.02–325.61)	234.61 (220.88–249.19)	1.35 (1.25–1.46)	<0.001
	Secondary	171.34 (161.95–181.27)	185.05 (171.11–200.13)	0.89 (0.80–0.98)	0.014
	University	241.39 (222.34–262.06)	153.85 (141.83–166.90)	1.45 (1.29–1.63)	<0.001
	Missing	235.89 (185.99–299.18)	126.84 (108.89–147.74)	1.90 (1.43–2.52)	<0.001
	Period of immigration
	1991–1994	217.40 (208.96–226.18)	214.48 (201.09–228.76)	0.97 (0.90–1.05)	0.449
	1995–1998	346.89 (324.67–370.62)	198.96 (185.00–213.97)	1.75 (1.59–1.94)	<0.001
	1999–2001	155.94 (136.30–178.41)	155.54 (144.99–166.86)	1.01 (0.87–1.18)	0.904
	Number of first-degree relatives in Sweden
	0	356.36 (341.05–372.37)	192.97 (183.27–203.18)	1.81 (1.69–1.94)	<0.001
	1	301.98 (286.52–318.27)	279.23 (261.10–298.63)	1.02 (0.93–1.11)	0.676
	2+	31.81 (27.22–37.18)	54.44 (45.90–37.18)	0.56 (0.44–0.71)	<0.001
	Multivariable analysis
	Adjusted for age	N/A	N/A	1.26 (1.19–1.32)	<0.001
	Adjusted for age, sex, education, and calendar period of immigration	N/A	N/A	1.20 (1.14–1.27)	<0.001
	Adjusted for age, sex, education, calendar period of immigration, and smoking**	N/A	N/A	1.16 (1.08–1.24)	<0.001

*Incidence rates per 100,000 person-years.

**Country specific prevalence.

HR, hazard ratio; IR, incidence rate.

Stratified analyses revealed that the elevated risk of CVD and cancer as well as the reduced risk of suicide attempt associated with being a migrant of the Balkan wars were fairly similar across strata of sex, age, and education. However, being male was associated with stronger risk elevations for PTSD (HR 13.28, 95% CI 10.46–16.84, p < 0.001, for males versus HR 5.65, 95% CI 4.81–6.64, p < 0.001, for females). Being a young or middle-aged migrant of the Balkan wars was also associated with a more pronounced risk increase for PTSD (HR 9.93, 95% CI 8.35–11.80, p < 0.001, for individuals aged 20–39 years; HR 15.83, 95% CI 11.45–21.87, p < 0.001, for individuals aged 40–59 years) (Table 4).

As compared to earlier immigration (in 1991–1994), later immigration (1999–2001) was associated with stronger risk elevations for both PTSD (HR 7.58, 95% CI 6.02–9.55, p < 0.001, for earlier migration versus HR 21.87, 95% CI 17.64–27.10, p < 0.001, for late immigration) and CVD morbidity (HR 1.22, 95% CI 1.17–1.26, p < 0.001, for earlier immigration versus HR 1.56, 95% CI 1.47–1.65, p < 0.001, for late immigration) (Table 4). With a trend test, overall psychiatric disorders (p < 0.001), PTSD (p < 0.001), and CVD (p = 0.005) increase significantly with the period of immigration.

Similarly, having a lower number of first-degree relatives in Sweden at immigration was associated with a more pronounced risk increase in overall psychiatric disorders (HR 1.50, 95% CI 1.44–1.56, p < 0.001, for no relatives; HR 1.21, 95% CI 1.16–1.27, p < 0.001, for 1 relative; HR 0.61, 95% CI 0.58–0.65, p < 0.001, for 2 or more relatives), PTSD (HR 10.25, 95% CI 8.40–12.51, p < 0.001, for no relatives; HR 8.90, 95% CI 7.19–11.02, p < 0.001, for 1 relative; HR 2.52, 95% CI 1.82–3.49, p < 0.001, for 2 or more relatives), and CVD (HR 1.98, 95% CI 1.92–2.05, p < 0.001, for no relatives; HR 1.19, 95% CI 1.15–1.24, p < 0.001, for 1 relative; HR 0.87, 95% CI 0.80–0.94, p < 0.001, for 2 or more relatives) (Table 4). With a trend test, overall psychiatric disorders (p < 0.001), PTSD (p < 0.001), and CVD (p < 0.001) decrease significantly with the number of first-degree relatives in Sweden.

Being a migrant of the Balkan wars was associated with a higher risk of psychiatric disorders compared to other European migrants during follow-up, with similar risk estimates in crude (HR 1.16, 95% CI 1.13–1.19, p < 0.001) and multivariable-adjusted models (HR 1.19, 95% CI 1.14–1.23, p < 0.001). Having been diagnosed with PTSD was also associated with being a migrant of the Balkan wars, with risk estimates increasing in multivariable-adjusted models (HR 9.33, 95% CI 7.96–10.94, p < 0.001) compared to the crude model (HR 7.93, 95% CI 6.95–9.06, p < 0.001). In contrast, being a migrant of the Balkan wars was associated with an overall reduced risk of suicide attempt, with similar risk estimates in crude (HR 0.62, 95% CI 0.56–0.68, p < 0.001) and multivariable-adjusted models (HR 0.57, 95% CI 0.51–0.65, p < 0.001) (Table 4).

Compared to other European migrants, being a migrant of the Balkan wars was further associated with an elevated risk of a clinical diagnosis of CVD, with similar risk estimates in crude (HR 1.37, 95% CI 1.34–1.40, p < 0.001) and multivariable-adjusted models (HR 1.39, 95% CI 1.34–1.43, p < 0.001). In addition, being a migrant of the Balkan wars was associated with an increased risk of cancer diagnosis, with relative risk estimates somewhat similar in the multivariable adjusted models (HR 1.16, 95% CI 1.08–1.24, p < 0.001) and the crude model (HR 1.21, 95% CI 1.15–1.27, p < 0.001) (Table 4).

Finally, both smoking-related cancer malignancies (overall HR 1.24, 95% CI 1.09–1.42, p = 0.001) and cancer malignancies not related to alcohol or smoking (overall HR 1.19, 95% CI 1.07–1.32, p = 0.001) were associated with being a migrant of the Balkan wars (S5 Table).

Sensitivity analysis excluding individuals with missing educational attainment had little influence on our main results (S6 Table).

When assessing time since migration, we found that the risk of overall psychiatric disorders was consistently increased among migrants of the Balkan wars throughout the follow-up period, with the risk of PTSD highly elevated during the first year (HR 30.98, 95% CI 17.51–50.83, p < 0.001) as well as 2–4 years after immigration (HR 18.93, 95% CI 12.16–29.46, p < 0.001). The risk of suicide attempt was decreased among migrants of the Balkan wars 5–9 years (HR 0.58, 95% CI 0.48–0.71, p < 0.001) and ≥10 years after immigration (HR 0.44, 95% CI 0.36–0.53, p < 0.001). Being a migrant of the Balkan wars was associated with a consistently increased risk of CVD throughout the follow-up period. Risk of cancer diagnosis was increased at all time points, although non-significant at 2–4 years after immigration (HR 1.13, 95% CI 0.96–1.33, p < 0.001) (Table 5).

Table 5

Rates of morbidities in migrants of the Balkan wars (exposed) compared to other European migrants (unexposed), by time since immigration.

Outcome measure	Time since immigration
	0–1 year	2–4 years	5–9 years	10+ years
Psychiatric disorders (overall)
IR* (95% CI) for exposed	554.2 (523.0–587.3)	504.7 (479.9–530.8)	946.9 (919.3–975.2)	1,525.3 (1,490.6–1,560.7)
IR (95% CI) for unexposed	556.7 (528.7–586.2)	566.8 (541.0–593.8)	747.4 (722.0–773.8)	1,202.1 (1,159.7–1,245.9)
HR** (95% CI)	1.23 (1.11–1.37)	1.29 (1.18–1.42)	1.34 (1.26–1.43)	1.10 (1.04–1.16)
p-Value for HR	<0.001	<0.001	<0.001	<0.001
Post-traumatic stress disorder
IR (95% CI) for exposed	90.9 (78.8–104.9)	83.4 (73.7–94.3)	150.4 (139.8–161.7)	286.2 (272.0–301.1)
IR (95% CI) for unexposed	6.1 (3.7–9.9)	9.7 (6.8–13.8)	20.4 (16.6–25.0)	38.0 (31.3–46.0)
HR** (95% CI)	30.98 (17.51–50.83)	18.93 (12.16–29.46)	9.73 (7.42–12.76)	5.43 (4.31–6.83)
p-Value for HR	<0.001	<0.001	<0.001	<0.001
Suicide attempt
IR (95% CI) for exposed	14.9 (10.5–21.2)	51.7 (44.3–60.5)	61.1 (54.5–68.4)	66.5 (59.9–73.8)
IR (95% CI) for unexposed	48.7 (41.0–57.9)	69.2 (60.6–78.9)	84.0 (75.9–92.9)	123.3 (110.7–137.2)
HR** (95% CI)	0.84 (0.52–1.35)	0.89 (0.68–1.17)	0.58 (0.48–0.71)	0.44 (0.36–0.53)
p-Value for HR	0.468	0.418	<0.001	<0.001
Cardiovascular diseases
IR (95% CI) for exposed	1,258.8 (1,211.2–1,308.3)	848.2 (815.6–882.1)	1,171.2 (1,140.2–1,203.0)	1,659.6 (1,622.9–1,697.1)
IR (95% CI) for unexposed	740.9 (708.5–774.8)	719.2 (690.0–749.7)	849.4 (822.2–877.6)	1,249.2 (1,205.8–1,294.2)
HR** (95% CI)	1.44 (1.32–1.56)	1.27 (1.17–1.37)	1.52 (1.43–1.61)	1.37 (1.30–1.45)
p-Value for HR	<0.001	<0.001	<0.001	<0.001
Cancer
IR (95% CI) for exposed	238.3 (218.2–260.2)	188.4 (173.6–204.5)	236.3 (223.0–250.4)	255.3 (242.0–269.4)
IR (95% CI) for unexposed	171.7 (156.5–188.3)	165.0 (151.5–179.7)	190.0 (177.6–203.2)	224.7 (207.5–243.4)
HR** (95% CI)	1.18 (1.00–1.40)	1.13 (0.96–1.33)	1.16 (1.03–1.31)	1.26 (1.11–1.43)
p-Value for HR	0.055	0.142	0.016	<0.001

*Incidence rates per 100,000 person-years.

**Adjusting for sex, education, age at immigration, smoking (country-specific prevalence), and calendar period of immigration.

HR, hazard ratio; IR, incidence rate.

Discussion

This comprehensive follow-up study of more than 100,000 migrants of the Balkan wars to Sweden shows that compared to other European migrants to Sweden, being a war migrant is associated with considerable elevations in risks of cardiovascular- and cancer-related morbidities and mortality, as well as elevation in the risk of psychiatric disorders, specifically PTSD. Migration during the last years of the Balkan wars was associated with even greater risk elevations, as was having no first-degree relatives in Sweden at immigration.

Limitations of the study include lack of information about health status at the time of immigration. It is plausible that war migrants’ health was worse at the time of immigration, as indicated by their increased risk of CVD during the first year of follow-up. It is also possible that war migrants diagnosed with late stage cancer opted to stay in Sweden for healthcare access rather than returning to the home country, causing bias in hazard rates. We also lack information about what populations immigrated from the countries of the Balkan wars at different time points. It is possible, for example, that soldiers immigrated later than civilians. Furthermore, we were not able to control for behavioral factors possibly contributing to increased risk of morbidity and mortality such as alcohol consumption, physical exercise, BMI, and diet. We also lack individual smoking history information, a known risk factor for many outcomes under study, and therefore derived prevalence estimates from national statistics from the country of emigration. In addition, the Swedish National Patient Register does not include psychiatric diagnoses made in primary care. Importantly, findings of this study apply to migrants of the Balkan wars, and caution must therefore be taken in generalizing our results to other migrant populations.

This large-scale epidemiological study with virtually complete register data on health outcomes of migrants of the Balkan wars immigrating to Sweden contributes to existing work by assessing mortality and major disease risk among both child and adult migrants from the same war-exposed geographic area. This study expands previous research with its extensive follow-up and by utilizing other migrants as a comparison group. Examining war migrants’ health status compared to other migrants, rather than the native population, offers a unique opportunity to examine the health consequences of additional stressors brought on by war exposure.

Our results of greater risk of psychiatric morbidity among migrants of the Balkan wars extends previous research on the mental health of refugees compared to native populations in the host country [15,16], as our methodology included other European migrants as the comparison group, addressing the confounder of general migration-related stress. This permits firmer conclusions to be drawn about the effects of migration from a country affected by war. Our study also broadens earlier studies showing that war migrants have worse self-reported mental health [17] and more psychotropic drug prescriptions than other migrants [18]. The greater risk of psychiatric morbidity, specifically PTSD, found among war migrants in our study is likely explained by greater exposure to war-related traumatic events.

Interestingly, migrating during the last years of the Balkan wars, an indicator of longer war exposure duration and shorter time of follow-up, was associated with an increased risk of psychiatric morbidity, compared to migrating during the earlier years of the wars. Cumulative trauma exposure pre-migration [3] and longer duration of exposure to threat [19] have previously been associated with adverse mental health problems such as PTSD and depression among migrants.

This is, to our knowledge, the largest systematic investigation of major disease risk among a war-exposed cohort utilizing other migrants as the comparison group. Our findings gain support from studies showing similar results among samples of male refugees from various countries of origin in Sweden [6] and Finns who were forced to migrate from their home country after the Second World War [5]. We further found that later time period of migration was associated with greater risk increase of CVD compared to earlier migration, indicating that longer duration of exposure to war trauma may be associated with more elevated CVD risk. These results are in line with a recent study finding that exposure to traumatic events increases the risk of endothelial dysfunction, a hallmark of CVD [20]. The increased risk of CVD events and CVD mortality among migrants of the Balkan wars is possibly explained by the cumulative physiological strain caused by residing in war-stricken areas. Indeed, during the 1991 Balkan war in Croatia, the incidence of and mortality from acute myocardial infarction increased greatly among civilians who remained there [21].

We further found that being a migrant of the Balkan wars was associated with an overall increased risk of being diagnosed with or dying from cancer. Migrants have in general been found to have lower cancer mortality rates compared to native populations, leading to the healthy migrant hypothesis [22]. Few studies, however, have focused specifically on migrants of war, relative to other migrants. The increased cancer risk in our data is possibly explained by different lifestyles, greater stressor exposure among migrants of the Balkan wars compared to other European migrants, or both. Exposure to high levels of psychological stress as well as repeated exposure over a long period of time have both been linked to weakening of the immune system [23]. However, to date, no consensus has been reached on whether stress also affects the incidence of cancer [24]. Psychological stress and trauma can also impact cancer and CVD risk indirectly through behaviors such as smoking and alcohol consumption [25]. Sub-analysis by cancer type, however, revealed that cancer risk was evident for both smoking-related cancers and cancers not related to tobacco or alcohol consumption. As smoking is a dominant risk factor for CVD, migrants’ country-level smoking prevalence was also controlled for. We further compared cancer- and CVD-related death rates among residents of the countries of the Balkan wars and the other European countries under study. We found that while cancer mortality rates were similar, CVD rates were on average higher in the countries of the Balkan wars in 1990 (S3 Table). It is therefore possible that the increased CVD risk among migrants of the Balkan wars is partly explained by risk factors attributable to the country of origin.

Not having any first-degree relatives in Sweden at immigration was associated with greater risk elevations for CVD and psychiatric disorders, particularly PTSD, among migrants of the Balkan wars. Previous research has found social support, family connectedness, and allegiances to one’s original culture to be sources of resilience for war migrants [26]. Among refugees and asylum seekers, loneliness has also been found to be associated with risk of PTSD and other severe mental illnesses [27]. Previous research has also found unaccompanied refugee children to be at greater risk of psychiatric morbidity and inpatient care than children who settle with their families [16]. The increased risk of morbidity among the migrants of the Balkan wars could be because they lack social support but also because they have lost relatives in the war; bereavement is indeed an established risk factor for psychiatric morbidity [3]. This increased risk might also reflect the additional stress migrants of war are faced with knowing their family members are residing in areas of conflict.

Despite war-related traumatic experiences being an established risk factor for suicidal behavior [28], with rates increasing in Serbia and Montenegro among males during the wars [29], we found that being a migrant of the Balkan wars was associated with a decreased risk of suicide compared to other migrants. Previous studies on risk of suicide among migrants compared to population controls have found conflicting results, with some studies finding war migrants to be at increased suicide risk [5] and others finding substantially lower risk [30,31]. As rates of suicide among migrants have been found to be strongly linked with country-of-origin suicide rates [30], we retrieved the risk patterns of suicide in the countries of the Balkan wars under study, and found them to be, on average, similar to those in the home countries of the other European migrants (S4 Table). A possible explanation for the decreased suicide risk among migrants of the Balkan wars is that those experiencing mental health problems, such as depression, at the time of the wars were less likely to migrate. Conversely, those who migrated from war could represent individuals who maintained a high drive for survival despite adversity. It is also possible that lower rates of suicide among war migrants are due to increased surveillance, such as more frequent health check-ups, among the war migrant group.

More people than ever are affected by forced displacement as a result of atrocities such as war and human rights violations. Our results underscore that war migrants are a particularly vulnerable group in need of long-term health surveillance and treatment for psychiatric and somatic disorders, particularly those with extended stay in war-stricken areas and those immigrating alone. Policy makers should assess possible barriers war migrants face in accessing treatment and enhance both the availability and accessibility of social services to war migrants, particularly those who are alone in the host country.

(DOC)

Click here for additional data file.

Number of migrants with regard to whether they are migrants of the Balkan wars (exposed) or other European migrants (unexposed).

(DOCX)

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Prevalence of smoking in the year 2000 in Balkan war countries (exposed) and other European countries (unexposed) among individuals that were 15 years or older.

(DOCX)

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Cancer- and cardiovascular-disease-related death rates in the year 1990 (age-standardized rates per 100,000 inhabitants) in Balkan war countries (exposed) versus other European countries (unexposed).

(DOCX)

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Mean suicide rate (age-adjusted rate of suicide per 100,000 inhabitants) in the year 1990 in the Balkan war countries (exposed) and other European countries (unexposed).

(DOCX)

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Smoking- and alcohol-related cancer incidence among migrants of the Balkan wars (exposed) versus other European migrants (unexposed).

(DOCX)

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Mortality and morbidity rates among migrants of the Balkan wars (exposed) compared to other European migrants (unexposed), with regard to whether individuals with missing education level are included.

(DOCX)

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(DOCX)

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20 Apr 2020

Dear Dr. Thordardottir,

Thank you very much for submitting your manuscript "Mortality and major disease risk among migrants of the 1991-2001 Balkan wars to Sweden" (PMEDICINE-D-19-03629) for consideration at PLOS Medicine.

Your paper was evaluated by a senior editor and discussed among all the editors here. It was also discussed with an academic editor with relevant expertise, and sent to independent reviewers, including a statistical reviewer. The reviews are appended at the bottom of this email and any accompanying reviewer attachments can be seen via the link below:

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In light of these reviews, I am afraid that we will not be able to accept the manuscript for publication in the journal in its current form, but we would like to consider a revised version that addresses the reviewers' and editors' comments. Obviously we cannot make any decision about publication until we have seen the revised manuscript and your response, and we plan to seek re-review by one or more of the reviewers.

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*As the study is observational, it isn't straight forward to infer causality; in most of the manuscript text, this is appropriately presented but there are a few places where the authors mention "elevated/increased risk" or "reduced risk" which does seem to imply the association is causal and the language could be fine-tuned in such instances (ie "associated with increased risk").

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Comments from the reviewers:

Reviewer #1: I confine my remarks to statistical aspects of this paper.

One big issue is the use of linear regression. Since there are a lot of people from each of a bunch of countries, the assumption of independent errors that linear regression makes will be violated. One method of dealing with this is a multilevel model. In addition, this allows clearer use of both individual and country-level variables.

In addition,

Line 106-7 Do not categorize independent variables. In *Regression Modeling Strategies* Frank Harrell lists 11 problems with doing this and sums up "Nothing could be more disastrous". I wrote a blog post illustrating some of the problems : https://medium.com/@peterflom/what-happens-when-we-categorize-an-independent-variable-in-regression-77d4c5862b6c

Peter Flom

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Reviewer #2: The paper addresses a relevant health problem and the data used together with the analytic strategy adds to the literature. The topic as well as the data-set itself is very complex and this is a good attempt to attack the issues at hand. To this reviewer's mind, there are some points that could be sharpened in the paper. Comments:

The background and the conclusion in the abstract should - as the methods part does - make clear that this is a comparison between different groups of immigrants.

The authors present complex models first and then later return to stratified analyses (but also there we see only adjusted models). I would much have preferred to from the beginning see more presentation of the crude data, e.g. starting with something like table 4 displaying incidence rates, HR:s in unadjusted and then adjusted models in strata as in table 4. Then proceed to the multivariate models.

Likewise, it would be easier to understand the data and follow the line of interpretation if we in the modeling could see what happens in different steps of the adjustment. This need not be covariate by covariate, but could be in "chunks" of co-variates. The present results-section does not convince the reader that the models presented are the adequate ones and does not permit assessment of effect-modification and alike phenomena.

Persons with missing data on education is an extreme group judging from table 4. It is not clear in the methods part how the missing category was handled and if the choice of method here influence the results in a major way. Have the authors considered an imputation here or some more advanced strategy to find out what is happening?

The tables are very unclear about what a "rate" is. E.g. table 4 shows hazard ratios, not rates, the other tables show both incidence rates and hazard ratios. It is very difficult to find out the enumeration of the denominators for the rates.

It is very good that we for many tables see both incidence rates and the hazard ratio. This in turn could lead to a part in the discussion to show what the absolute health impact is likely to be in say 1000 individuals during five years of observation.

The discussion could be better structured. The study, say the authors, "offers a unique opportunity to examine the health consequences of additional stressors brought on by war exposure". The critical question is then if the design, data, analysis and results reflect a causal pathway for this, or if the findings are a result of other things such as data handling, selection of who migrates, or exposures in the home-country. Some of the hazard ratios are quite low and could be the result of bias rather than causal. The discussion enters this discussion but only partly and fragmented. Mostly, the authors use a rather strong "causal language" - which admittedly could be used around psychiatric disorders but is more questionable for e.g. cancer. A clearer structure could probably also lead to a shortening, which would put the message across clearer.

In the conclusion, line 315-321 is a repetition of the main findings and unnecessary. What comes after are consequences of the findings and the interpretation, which is a good final note. Could more of this be "transplanted" to the abstract?

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Reviewer #3: Comments to author

This is an important and well-performed register-based investigation on the risk of mortality and major disease risk among migrants of the 1991-2001 Balkan wars to Sweden compare to migrants from other European counties to Sweden during the same period. The strengths of the study includes the use of comprehensive registers and careful statistical analyses. The manuscript is well written and easy to read.

I have only minor comments:

METHODS

1. They authors should describe any work/effort validating the information source. How accurate is the information in this database, how complete are the data; are they equally complete throughout the study period?

2. Line 85, ICD-10 for CVD diagnosis is I00-I99, not 100-199

3. Line 94 and Line 97, ICD-7 code of 150 is "esophagus"

4. Line 95, ICD-7 code for lung cancer 162-163, code 161 is a diagnosis of larynx, the author has defined it as a separate subtype (Line 98).

5. Line 97, ICD-7 code for liver cancer are 155 and 156

6. Line 107-108, please indicate first degree relatives in the methods; as the authors have mentioned in Table 4, siblings, parents, and children.

7. Please clarify how the rate of morbidities and mortalities was calculated, it was for per 100 000 inhabitants or per 100 000 person years.

RESULTS

8. Please add a footnote to indicate incidence rates (IR) in Table 1, 2 and Supplementary Table 5, for per 100 000 inhabitants, or per 100 000 person years.

DISCUSSIONS AND CONCLUSION

9. It should be noted that cancer survival in Sweden overall is internationally favorable. The findings that some groups with low cancer incidence may have even a more favorable survival. Even the study has controlled by the variable of residence time and country-level cancer and related rates, the possibility of immigrants diagnosed with a cancer in the earlier stage may move back to their home country, while severely ill patients stay in host country, causing bias in Hazard rates.

10. Suggest how your findings are useful for health care workers (or policy makers)? What might they do with this information?

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Any attachments provided with reviews can be seen via the following link:

[LINK]

Submitted filename: Comments to author.docx

Click here for additional data file.

20 Jun 2020

Submitted filename: Response_to_Reviewers.DOCX

Click here for additional data file.

25 Aug 2020

Dear Dr. Thordardottir,

Thank you very much for re-submitting your manuscript "Mortality and major disease risk among migrants of the 1991-2001 Balkan wars to Sweden: A register-based cohort study" (PMEDICINE-D-19-03629R1) for consideration at PLOS Medicine.

I have discussed the paper with editorial colleagues and it was also seen again by two reviewers. I am pleased to tell you that, provided the remaining editorial and production issues are fully dealt with, we expect to be able to accept the paper for publication in the journal.

The remaining issues that need to be addressed are listed at the end of this email. Any accompanying reviewer attachments can be seen via the link below. Please take these into account before resubmitting your manuscript:

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Requests from Editors:

Noting the comments from our academic editor (below), we ask you to give some thought to how study participants are described in the text (including the title and abstract). In particular, the term "war migrants" seems unusual, and "displaced persons" or "persons displaced by war" would be preferred. We suggest explaining the legal status of study participants in Sweden early in your article, and then using a standard term throughout the text - one possibility would be to use an abbreviation (e.g., "asylum seekers/refugees", "AS/R").

To your data statement, please non-author contact details to the two sources mentioned for readers interested in inquiring about access to study data.

Please add a sentence, say, to your abstract quoting aggregate demographic details for study participants.

At line 26, please begin the sentence "Our findings indicate that ..." or similar.

Early in the methods section of your main text, please state whether or not the study had a protocol or prespecified analysis plan, and if so attach the relevant document as a supplementary file, referred to in the text. Please highlight analyses that were not prespecified.

Noting "p<0.0001" at line 203 and elsewhere, please quote exact p values or "p<0.001" throughout the article.

Please remove the information on funding and competing interests from the end of the main text. In the event of publication, this information will appear in the article metadata, via information provided in the submission form.

Throughout the paper, please add p values alongside 95% CI, where available.

Are you able to add a URL, and accessed date, to reference 9?

Please move the STROBE checklist to a separate attached file and refer to this in the methods section of your main text (i.e., "See S1_STROBE_Checklist" or similar).

Comments from academic editor:

a. Definitions: I would suggest using the terms asylum seekers, refugees and (economic) migrants.

i. I believe all displaced persons from the Balkan war would be considered asylum seekers while some may have received refugee status during their time in Sweden. However, the authors need to clarify whether Sweden gave the Balkan ‘refugees’ a special status until the war was done and then they had to return (I am not sure if this is the case, but Germany did).

ii. Displaced persons from other countries (they may be asylum seekers, refugees or migrants).

b. I also agree with the referee who said “I would much have preferred to from the beginning see more presentation of the crude data, e.g. starting with something like table 4 displaying incidence rates, HR:s in unadjusted and then adjusted models in strata as in table 4. Then proceed to the multivariate models.”

Comments from Reviewers:

***Reviewer #1:

The authors have addressed my concerns and I now recommend publication.

*** Reviewer #3:

Comments:

The authors have satisfactorily responded to all my questions and made the necessary changes to the manuscript. I have no additional comments.

***

Any attachments provided with reviews can be seen via the following link:

[LINK]

Submitted filename: Comments to authorXL2.docx

Click here for additional data file.

29 Oct 2020

Dear Dr. Thordardottir,

On behalf of my colleagues and the academic editor, Dr. Paul Spiegel, I am delighted to inform you that your manuscript entitled "Mortality and major disease risk among migrants of the 1991-2001 Balkan wars to Sweden: A register-based cohort study" (PMEDICINE-D-19-03629R2) has been accepted for publication in PLOS Medicine.

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Thank you again for submitting the manuscript to PLOS Medicine. We look forward to publishing it.

Best wishes,

Richard Turner, PhD

Senior Editor

PLOS Medicine

plosmedicine.org