title: Association Between the Birth of an Infant With Major Congenital Anomalies and Subsequent Risk of Mortality in Their Mothers.
abstract: Giving birth to a child with a major birth defect is a serious life event for a woman, yet little is known about the long-term health consequences for the mother.
  
  
  
  To assess whether birth of an infant born with a major congenital anomaly was associated with higher maternal risk of mortality.
  
  
  
  This population-based cohort study (n = 455 250 women) used individual-level linked Danish registry data for mothers who gave birth to an infant with a major congenital anomaly (41 508) between 1979 and 2010, with follow-up until December 31, 2014. A comparison cohort (413 742) was constructed by randomly sampling, for each mother with an affected infant, up to 10 mothers matched on maternal age, parity, and year of infant's birth.
  
  
  
  Live birth of an infant with a major congenital anomaly as defined by the European Surveillance of Congenital Anomalies classification system.
  
  
  
  Primary outcome was all-cause mortality. Secondary outcomes included cause-specific mortality. Hazard ratios (HRs) were adjusted for marital status, immigration status, income quartile (since 1980), educational level (since 1981), diabetes mellitus, modified Charlson comorbidity index score, hypertension, depression, history of alcohol-related disease, previous spontaneous abortion, pregnancy complications, smoking (since 1991), and body mass index (since 2004).
  
  
  
  Mothers in both groups were a mean (SD) age of 28.9 (5.1) years at delivery. After a median (IQR) follow-up of 21 (12-28) years, there were 1275 deaths (1.60 per 1000 person-years) among 41 508 mothers of a child with a major congenital anomaly vs 10 112 deaths (1.27 per 1000 person-years) among 413 742 mothers in the comparison cohort, corresponding to an absolute mortality rate difference of 0.33 per 1000 person-years (95% CI, 0.24-0.42), an unadjusted HR of 1.27 (95% CI, 1.20-1.35), and an adjusted HR of 1.22 (95% CI, 1.15-1.29). Mothers with affected infants were more likely to die of cardiovascular disease (rate difference, 0.05 per 1000 person-years [95% CI, 0.02-0.08]; adjusted HR, 1.26 [95% CI, 1.04-1.53]), respiratory disease (rate difference, 0.02 per 1000 person-years [95% CI, 0.00-0.04]; adjusted HR, 1.45 [95% CI, 1.01-2.08]), and other natural causes (rate difference, 0.11 per 1000 person-years [95% CI, 0.07-0.15]; adjusted HR, 1.50 [95% CI, 1.27-1.76]).
  
  
  
  In Denmark, having a child with a major congenital anomaly was associated with a small but statistically significantly increased mortality risk in the mother compared with women without an affected child. However, the clinical importance of this association is uncertain.
authors.affiliation: Department of Pediatrics, The Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada2Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus, Denmark3Institute of Health Policy, Management, and Evaluation, University of Toronto, Toronto, Ontario, Canada4Center for Primary Care and Outcomes Research, Stanford University, Stanford, California5Clinical Excellence Research Center, Stanford University School of Medicine, Stanford, California.
authors.forename: Eyal
authors.initials: E
authors.lastname: Cohen
authors.affiliation: Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus, Denmark.
authors.forename: Erzsébet
authors.initials: E
authors.lastname: Horváth-Puhó
authors.affiliation: Institute of Health Policy, Management, and Evaluation, University of Toronto, Toronto, Ontario, Canada6St Michael's Hospital Department of Medicine, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Joel G
authors.initials: JG
authors.lastname: Ray
authors.affiliation: Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus, Denmark.
authors.forename: Lars
authors.initials: L
authors.lastname: Pedersen
authors.affiliation: Center for Health and Community, University of California-San Francisco School of Medicine.
authors.forename: Nancy
authors.initials: N
authors.lastname: Adler
authors.affiliation: Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus, Denmark.
authors.forename: Anne Gulbech
authors.initials: AG
authors.lastname: Ording
authors.affiliation: Center for Primary Care and Outcomes Research, Stanford University, Stanford, California.
authors.forename: Paul H
authors.initials: PH
authors.lastname: Wise
authors.affiliation: Clinical Excellence Research Center, Stanford University School of Medicine, Stanford, California.
authors.forename: Arnold
authors.initials: A
authors.lastname: Milstein
authors.affiliation: Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus, Denmark8Division of Epidemiology, Department of Health Research and Policy, Stanford University, Stanford, California.
authors.forename: Henrik Toft
authors.initials: HT
authors.lastname: Sørensen
mesh_terms: D000328:Adult; D002423:Cause of Death; D015331:Cohort Studies; D000013:Congenital Abnormalities / Q000453:epidemiology*; D003718:Denmark / Q000453:epidemiology; D005260:Female; D006801:Humans; D007223:Infant; D008875:Middle Aged; D009026:Mortality / Q000639:trends*; D009035:Mothers / Q000706:statistics & numerical data*; D011247:Pregnancy; D012042:Registries; D012306:Risk