Kenny A Rodriguez-Wallberg1, Frida E Lundberg2, Sara Ekberg3, Anna L V Johansson4, Jonas F Ludvigsson5, Catarina Almqvist6, Sven Cnattingius3, Anastasia N Iliadou4. 1. Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden; Department of Reproductive Medicine, Division of Gynecology and Reproduction, Karolinska University Hospital, Stockholm, Sweden. Electronic address: kenny.rodriguez-wallberg@ki.se. 2. Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden; Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden. 3. Division of Clinical Epidemiology, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden. 4. Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden. 5. Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden; Department of Pediatrics, Örebro University Hospital, Örebro, Sweden. 6. Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden; Astrid Lindgren Children's Hospital, Karolinska University Hospital, Stockholm, Sweden.
Abstract
OBJECTIVE: To assess infant (<1 year) and childhood (1-18 years) mortality in singletons conceived through assisted reproductive techniques (ART) versus naturally conceived singletons. DESIGN: Nationwide prospective study. SETTING: Sweden. PATIENT(S): All singleton liveborn infants born from 1983 to 2012 in Sweden identified using the Medical Birth Register (N = 2,847,108), of whom 43,506 were conceived through ART treatments including in vitro fertilization with and without intracytoplasmic sperm injection. INTERVENTION(S): None. MAIN OUTCOME MEASURES(S): Infant (<1 year) and childhood (1-18 years) mortality. RESULT(S): Data on ART treatment and covariates were retrieved from population-based registers using the unique personal identity number assigned to all permanent residents in Sweden. Cox proportional hazards models estimated the hazard ratios (HRs) with 95% confidence intervals (CIs) as measures of association between ART treatments and death. The analyses were adjusted for maternal characteristics, infertility, child sex, and birth cohort and were restricted to individuals with complete information on covariates for fully adjusted analysis. Compared with naturally conceived singletons, higher infant mortality risks were seen in infants conceived through ART (adjusted HR 1.45; 95% CI, 1.19-1.77), especially after transfer of cryopreserved embryos (adjusted HR 2.30; 95% CI, 1.46-3.64). Early neonatal mortality risk (deaths during the first week) was increased in children born after transfer of blastocysts (HR 2.40; 95% CI, 1.05-5.48). No increased mortality risk was observed between the ages of 1 and 18 years. CONCLUSION(S): Singletons conceived through ART had an increased risk of infant mortality from birth up to 1 year of life, predominantly in the early neonatal period and in pregnancies after transfer of frozen and thawed embryos.
OBJECTIVE: To assess infant (<1 year) and childhood (1-18 years) mortality in singletons conceived through assisted reproductive techniques (ART) versus naturally conceived singletons. DESIGN: Nationwide prospective study. SETTING: Sweden. PATIENT(S): All singleton liveborn infants born from 1983 to 2012 in Sweden identified using the Medical Birth Register (N = 2,847,108), of whom 43,506 were conceived through ART treatments including in vitro fertilization with and without intracytoplasmic sperm injection. INTERVENTION(S): None. MAIN OUTCOME MEASURES(S): Infant (<1 year) and childhood (1-18 years) mortality. RESULT(S): Data on ART treatment and covariates were retrieved from population-based registers using the unique personal identity number assigned to all permanent residents in Sweden. Cox proportional hazards models estimated the hazard ratios (HRs) with 95% confidence intervals (CIs) as measures of association between ART treatments and death. The analyses were adjusted for maternal characteristics, infertility, child sex, and birth cohort and were restricted to individuals with complete information on covariates for fully adjusted analysis. Compared with naturally conceived singletons, higher infantmortality risks were seen in infants conceived through ART (adjusted HR 1.45; 95% CI, 1.19-1.77), especially after transfer of cryopreserved embryos (adjusted HR 2.30; 95% CI, 1.46-3.64). Early neonatal mortality risk (deaths during the first week) was increased in children born after transfer of blastocysts (HR 2.40; 95% CI, 1.05-5.48). No increased mortality risk was observed between the ages of 1 and 18 years. CONCLUSION(S): Singletons conceived through ART had an increased risk of infantmortality from birth up to 1 year of life, predominantly in the early neonatal period and in pregnancies after transfer of frozen and thawed embryos.