Mortality from infancy to adolescence in singleton children conceived from  assisted reproductive techniques versus naturally conceived singletons in Sweden

Kenny A Rodriguez-Wallberg; Frida E Lundberg; Sara Ekberg; Anna L V Johansson; Jonas F Ludvigsson; Catarina Almqvist; Sven Cnattingius; Anastasia N Iliadou

doi:10.1016/j.fertnstert.2019.10.018

Assisted Reproduction Safety and Risks

Mortality from infancy to adolescence in singleton children conceived from assisted reproductive techniques versus naturally conceived singletons in Sweden

Rodriguez-Wallberg KA, Lundberg FE, Ekberg S, Johansson ALV, Ludvigsson JF, Almqvist C, Cnattingius S, Iliadou AN

Published March 2020 Fertility and Sterility, 113(3), 524-532

DOI 10.1016/j.fertnstert.2019.10.018 PMID 32081362

RRM Academy Synopsis

Singletons conceived by ART had higher infant mortality in Sweden

In a Swedish cohort of 2,847,108 singleton births, children conceived through assisted reproductive techniques (ART) had higher infant mortality. Researchers followed 43,506 ART-conceived children and found no increased mortality between ages 1 and 18 years.

Key Findings

Infant mortality before age 1 was higher in ART-conceived singletons than in naturally conceived singletons (adjusted HR 1.45; 95% CI, 1.19-1.77).
After transfer of frozen-thawed embryos, adjusted infant mortality was higher still (adjusted HR 2.30; 95% CI, 1.46-3.64).
Early neonatal mortality, deaths during the first week, was increased after blastocyst transfer in the 2002-2012 birth cohort (adjusted HR 2.40; 95% CI, 1.05-5.48).
Mortality from age 1 to 18 years showed no increase after ART conception (adjusted HR 0.99; 95% CI, 0.70-1.39).
The analysis included 2,813,731 children with complete covariate information, 43,320 of them conceived through ART, with a median follow-up of 15.9 years.

Interpretation

The study is a nationwide register-based cohort. It reports an association between ART conception and infant mortality, and an observational design does not establish cause. The authors note that the frozen-thawed embryo and blastocyst findings rest on small numbers. The authors also could not account for how long couples had been infertile, and they state that the source of the excess risk remains unknown: the technique, unmeasured maternal characteristics, or the underlying infertility. The absolute risk for each individual is very small.

RRM Context

Restorative reproductive medicine looks for the reasons a couple has not conceived and treats them, so that pregnancy can begin in the couple's own cycle. The authors cite earlier work linking infertility itself, even when it resolved without treatment, to higher risks around birth. That finding points to the cause of infertility.

Our editorial summary of this paper, not the article's abstract.

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.

Patients

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.

Interventions

None.

Main Outcome Measures

Infant (<1 year) and childhood (1-18 years) mortality.

Results

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.

Conclusions

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.

Topics

Assisted Reproduction

Safety and Risks Long Term Child Outcomes

Assisted Reproduction › Safety and Risks › Long Term Child Outcomes

Kenny A Rodriguez-Wallberg, Frida E Lundberg, Sara Ekberg, Anna L V Johansson, Jonas F Ludvigsson, Catarina Almqvist, Sven Cnattingius, Anastasia N Iliadou

K Rodriguez-Wallberg, F Lundberg, S Ekberg, A Johansson, J Ludvigsson, C Almqvist, S Cnattingius, A Iliadou

PMID 32081362 32081362 DOI 10.1016/j.fertnstert.2019.10.018 10.1016/j.fertnstert.2019.10.018 Rodriguez-Wallberg et al. 2020, Rodriguez-Wallberg 2020

Mortality from infancy to adolescence in singleton children conceived from assisted reproductive techniques versus naturally conceived singletons in Sweden

Singletons conceived by ART had higher infant mortality in Sweden

Key Findings

Interpretation

RRM Context

Abstract

Topics

By this author

Parenthood in a Swedish prospective cohort of 1,378 adolescents and young adults banking semen for fertility preservation at time of cancer diagnosis

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