1. Epidemiology and Global Health
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The mother’s risk of premature death after child loss across two centuries

  1. Unnur A Valdimarsdóttir  Is a corresponding author
  2. Donghao Lu
  3. Sigrún H Lund
  4. Katja Fall
  5. Fang Fang
  6. Þórður Kristjánsson
  7. Daníel Guðbjartsson
  8. Agnar Helgason
  9. Kári Stefánsson  Is a corresponding author
  1. University of Iceland, Iceland
  2. Harvard TH Chan School of Public Health, United States
  3. Karolinska Institutet, Sweden
  4. Brigham and Women's Hospital, Harvard Medical School, United States
  5. deCODE Genetics, Iceland
  6. Örebro University, Sweden
Research Article
Cite this article as: eLife 2019;8:e43476 doi: 10.7554/eLife.43476
2 figures, 2 tables and 3 additional files

Figures

Figure 1 with 2 supplements
Hazard ratios (HRs) and 95% confidence intervals (CIs) of parental mortality after loss of a child by birth cohorts (every 20 years until 1900, 1901–1930, and 1931–1996), in the sibling cohort.

We estimated HRs from stratified Cox proportional hazards model using age as underlying time scale. We stratified by sibling groups and additionally adjusted for birth year and sex. IR, incidence rate, per 1000 person-years.

https://doi.org/10.7554/eLife.43476.004
Figure 1—figure supplement 1
Hazard ratios (HRs) and 95% confidence intervals (CIs) of parental mortality after loss of a child among all parents and parents with identifiable siblings (those subsequently included in the sibling cohort) in the population-based matched cohort.

a p-Value for difference between HRs estimated from all parents and HRs from parents with identifiable siblings in the population-based matched cohort. b p-Value for difference between HRs estimated from a subset of the population-based matched cohort of parents with siblings and HRs from the sibling cohort.

https://doi.org/10.7554/eLife.43476.005
Figure 1—figure supplement 2
Hazard ratios (HRs) and 95% confidence intervals (CIs) of parental mortality after loss of a child by birth cohorts (every 20 years until 1900, 1901–1930, and 1931–1996) in the sibling cohort, excluding parents who died on the same day as the child.

We estimated HRs from stratified Cox proportional hazards model using age as underlying time scale. We stratified by sibling groups and additionally adjusted for birth year and sex. IR, incidence rate, per 1000 person-years.

https://doi.org/10.7554/eLife.43476.006
Figure 2 with 6 supplements
Hazard ratios (HRs) and 95% confidence intervals (CIs) of parental mortality after loss of a child, by age bands at follow-up (age 14–50 and 51+) and birth cohorts (every 20 years until 1900, 1901–1930, and 1931–1996), in the sibling cohort.

We stratified by sibling groups and additionally adjusted for birth year and sex in Cox proportional hazards model. IR, incidence rate, per 1000 person-years.

https://doi.org/10.7554/eLife.43476.007
Figure 2—figure supplement 1
Hazard ratios (HRs) and 95% confidence intervals (CIs) of maternal mortality after loss of a child, by age bands at follow-up, excluding mothers dying within 1 week after giving birth, in the sibling cohort.

We stratified by sibling groups and additionally adjusted for birth year and sex in Cox proportional hazards model.

https://doi.org/10.7554/eLife.43476.008
Figure 2—figure supplement 2
Hazard ratios (HRs) and 95% confidence intervals (CIs) of parental mortality after loss of a child among parents born during 1931–1996 and followed from age 51 onward, by age at loss, in the sibling cohort.

We stratified by sibling groups and additionally adjusted for birth year and sex in Cox proportional hazards model.

https://doi.org/10.7554/eLife.43476.009
Figure 2—figure supplement 3
Hazard ratios (HRs) and 95% confidence intervals (CIs) of parental mortality after loss of a child, by age bands at follow-up (age 14–50 and 51+) and birth cohorts (every 20 years until 1900, 1901–1930, and 1931–1996), among the siblings born 5 years before or after the index parents.

We stratified on sibling groups and additionally adjusted for birth year and sex in Cox proportional hazards model. IR, incidence rate, per 1000 person-years.

https://doi.org/10.7554/eLife.43476.010
Figure 2—figure supplement 4
Hazard ratios (HRs) and 95% confidence intervals (CIs) of parental mortality after loss of a child, by age bands at follow-up (age 14–50 and 51+) and birth cohorts (every 20 years until 1900, 1901–1930, and 1931–1996), by restricting to same-sex siblings.

We stratified by sibling groups and additionally adjusted for birth year and number of alive children at the matching in Cox proportional hazards model. IR, incidence rate, per 1000 person-years.

https://doi.org/10.7554/eLife.43476.011
Figure 2—figure supplement 5
Hazard ratios (HRs) and 95% confidence intervals (CIs) of parental mortality after loss of a child, by age bands at follow-up (age 14–50 and 51+) and birth cohorts (every 20 years until 1900, 1901–1930, and 1931–1996), in the sibling cohort with additional adjustment for number of alive children at matching.

We stratified by sibling groups and additionally adjusted for birth year, sex, and number of alive children at the matching in Cox proportional hazards model. IR, incidence rate, per 1000 person-years.

https://doi.org/10.7554/eLife.43476.012
Figure 2—figure supplement 6
Hazard ratios (HRs) and 95% confidence intervals (CIs) of parental mortality after loss of a child, by age bands at follow-up (age 14–50 and 51+) and birth cohorts (every 20 years until 1900, 1901–1930, and 1931–1996), by restricting to unexposed siblings who were already parents at the same age as when the index parents lost a child.

We stratified by sibling groups and additionally adjusted for birth year, sex, and number of alive children at the matching in Cox proportional hazards model. IR, incidence rate, per 1000 person-years.

https://doi.org/10.7554/eLife.43476.013

Tables

Table 1
Descriptive characteristics of parents born from 1800 to 1996 who lost a child by death during their life course, and their siblings who did not lose a child, N (%).
https://doi.org/10.7554/eLife.43476.002
Parents with lossParents without lossP for difference
Total number47 711126 342-
Sex
Female25 125 (53)63 328 (50)3.65e-21
Male22 586 (47)63 014 (50)
Total number of children276 819531 736-
Number of children, mean (SD)5.80 (3.19)4.21 (2.71)0
Number of children
11775 (4)16 012 (13)0
2–417 766 (37)64 908 (51)
5–921 947 (46)39 019 (31)
10+6223 (13)6403 (5)
Age at first child birth, mean (SD)25.55 (5.09)27.16 (6.11)0
Age at matching*, mean (SD)38.76 (15.39)37.35 (14.60)8.84e-67
Age at matching*
13–3017 963 (38)52 434 (42)1.84e-70
31–5019 980 (42)51 348 (41)
51–758123 (17)19 480 (15)
76+1645 (3)3080 (2)
Age of deceased child, mean (SD)9.44 (14.95)--
Length of follow-up, mean (SD)31.79 (18.36)25.45 (18.03)0
Age at death70.81 (16.66)71.80 (16.20)1.40e-21
  1. * Age at loss of first child for parents who lost a child; the same age for their siblings who did not lose a child or the age when the siblings became parents, whichever came later.

Table 2
Hazard ratios (HRs) and 95% confidence intervals (CIs) of premature mortality after loss of a child among young parents followed up to age 50, by time since loss and demographic characteristics, compared to their siblings.

We stratified by sibling groups and additionally adjusted for birth year and sex. IR, incidence rate, per 1000 person-years.

https://doi.org/10.7554/eLife.43476.003
OverallWomenMen
N (Crude IR)HR (95% CI)N (Crude IR)HR (95% CI)N (Crude IR)HR (95% CI)
Time since loss
0–4 years1711 (10.2)1.19 (1.11–1.27)907 (10.3)1.52 (1.35–1.71)804 (10.0)0.96 (0.85–1.07)
0–4 years*1595 (9.5)1.10 (1.03–1.18)832 (9.4)1.40 (1.24–1.58)763 (9.5)0.89 (0.80–1.01)
5–9 years1145 (7.9)1.13 (1.05–1.23)508 (6.5)1.22 (1.06–1.41)637 (9.5)1.02 (0.90–1.16)
10–19 years1654 (8.2)1.15 (1.07–1.23)764 (6.7)1.33 (1.18–1.50)890 (10.0)1.09 (0.97–1.22)
20–39 years388 (6.2)1.12 (0.98–1.29)214 (5.3)1.28 (1.03–1.59)174 (7.9)1.16 (0.91–1.48)
Child’s age at loss
03357 (8.9)1.14 (1.08–1.20)1672 (8.0)1.43 (1.31–1.57)1685 (9.9)0.94 (0.86–1.03)
1–52016 (9.4)1.16 (1.09–1.24)964 (8.1)1.26 (1.13–1.41)1052 (11.0)1.12 (1.00–1.25)
6–17269 (6.7)1.17 (0.99–1.38)130 (5.6)1.31 (0.99–1.74)139 (8.3)1.32 (1.00–1.73)
18+66 (5.4)1.44 (1.05–1.97)22 (2.8)0.96 (0.54–1.71)44 (10.3)1.99 (1.24–3.20)
Number of alive children at loss
02390 (9.7)1.20 (1.13–1.28)1135 (8.3)1.39 (1.24–1.56)1255 (11.4)1.15 (1.04–1.28)
1–32793 (8.4)1.12 (1.06–1.18)1379 (7.5)1.37 (1.25–1.51)1414 (9.5)0.98 (0.89–1.07)
4+525 (8.1)1.12 (0.99–1.26)274 (7.3)1.18 (0.97–1.44)251 (9.1)0.94 (0.77–1.14)
Sex of the lost child
Female3075 (8.6)1.14 (1.08–1.20)1483 (7.5)1.29 (1.17–1.41)1592 (10.0)1.06 (0.97–1.16)
Male2633 (9.2)1.17 (1.10–1.24)1305 (8.2)1.44 (1.30–1.59)1328 (10.4)1.01 (0.92–1.11)
Age at loss
13–303459 (8.5)1.13 (1.08–1.19)1815 (7.5)1.33 (1.22–1.45)1644 (10.1)1.02 (0.93–1.12)
31–401945 (9.5)1.19 (1.12–1.27)873 (8.7)1.43 (1.27–1.61)1072 (10.2)1.04 (0.93–1.15)
41–50304 (8.7)1.14 (0.98–1.32)100 (6.1)1.11 (0.81–1.52)204 (11.0)1.12 (0.90–1.40)
Age at first childbirth
13–21988 (6.0)1.20 (1.09–1.32)653 (5.4)1.29 (1.13–1.47)335 (7.7)1.15 (0.95–1.40)
22–241507 (8.5)1.09 (1.01–1.17)829 (8.0)1.27 (1.12–1.44)678 (9.2)0.97 (0.84–1.11)
25–271520 (10.3)1.20 (1.11–1.30)665 (9.5)1.35 (1.17–1.56)855 (11.1)1.08 (0.96–1.23)
28+1693 (10.8)1.16 (1.08–1.24)641 (9.9)1.55 (1.34–1.80)1052 (11.3)1.01 (0.91–1.13)
  1. * A sensitivity analysis excluding parents dying on the same day as their child.

Additional files

Source code 1

R script used for the primary analyses.

https://doi.org/10.7554/eLife.43476.014
Supplementary file 1

Descriptive characteristics of parents born from 1800 to 1996 who lost a child by birth cohorts in the population-based matched cohort, N (%).

https://doi.org/10.7554/eLife.43476.015
Transparent reporting form
https://doi.org/10.7554/eLife.43476.016

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