Association between childhood asthma and history of assisted reproduction techniques: a systematic review and meta-analysis

Tsabouri, Sophia; Lavasidis, Georgios; Efstathiadou, Anthoula; Papasavva, Margarita; Bellou, Vanesa; Bergantini, Helio; Priftis, Konstantinos; Ntzani, Evangelia

doi:10.1007/s00431-021-03975-7

Cited by 9 publications

(6 citation statements)

References 76 publications

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“…An increase in Th2 might also be associated with the higher prevalence of immune-related diseases in ART children. Asthma for instance has been shown to be more prevalent in children following ART ( Carson et al , 2013 ; Magnus et al , 2019 ; Tsabouri et al , 2021 ) as has atopic respiratory conditions, atopic disorders and allergies ( Halliday et al , 2014 ; Wijs et al , 2021 ) but the increased risk of asthma has not transferred into adolescence and young adulthood ( Halliday et al , 2019 ). Maternal subfertility itself has been associated with higher prevalence of asthma in the offspring ( Harju et al , 2013 ; Magnus et al , 2019 ).…”

Section: Discussionmentioning

confidence: 99%

Early childhood respiratory tract infections according to parental subfertility and conception by assisted reproductive technologies

2022

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STUDY QUESTION Are children conceived by ART or born to subfertile parents more susceptible to upper or lower respiratory tract infections (URTI, LRTI)? SUMMARY ANSWER ART-conceived children had a higher frequency of and risk of hospitalization for respiratory infections up to age 3, which was only partly explained by parental subfertility. WHAT IS KNOWN ALREADY Some studies report increased risks of infections in children conceived by ART. Results for URTIs and LRTIs are inconclusive, and the contribution of underlying parental subfertility remains unclear. STUDY DESIGN, SIZE, DURATION We included 84 102 singletons of the Norwegian Mother, Father and Child Cohort Study (MoBa) born between 1999 and 2009. Mothers reported time-to-pregnancy at recruitment and child history of, frequency of and hospitalization for, respiratory infections when the child was 6, 18 and 36 months old by questionnaires. Subfertility was defined as having taken 12 or more months to conceive. The Medical Birth Registry of Norway (MBRN) provided information on ART. URTI included throat and ear infections, while LRTI included bronchitis, bronchiolitis, respiratory syncytial virus and pneumonia. PARTICIPANTS/MATERIALS, SETTING, METHODS We used log-binomial regression to estimate risk ratios (RR) and 95% CI of any respiratory tract infection and hospitalization, and negative-binomial regression to calculate incidence rate ratios (IRR) and 95% CI for number of infections. We compared children conceived by ART, and naturally conceived children of subfertile parents, to children of fertile parents (<12 months to conceive) while adjusting for maternal age, education, BMI and smoking during pregnancy and previous livebirths. We accounted for dependency between children born to the same mother. MAIN RESULTS AND THE ROLE OF CHANCE A total of 7334 (8.7%) singletons were naturally conceived by subfertile parents and 1901 (2.3%) were conceived by ART. Between age 0 and 36 months, 41 609 (49.5%) of children experienced any URTI, 15 542 (18.5%) any LRTI and 4134 (4.9%) were hospitalized due to LRTI. Up to age 3, children conceived by ART had higher frequencies of URTI (adjusted IRR (aIRR) 1.16; 95% CI 1.05–1.28) and hospitalizations due to LRTI (adjusted RR (aRR) 1.25; 95% CI 1.02–1.53), which was not seen for children of subfertile parents. Children conceived by ART were not at higher risks of respiratory infections up to age 18 months; only at age 19–36 months, they had increased risk of any LRTI (aRR 1.16; 95% CI 1.01–1.33), increased frequency of LRTIs (IRR 1.22; 95% CI 1.02–1.47) and a higher risk of hospitalization for LRTI (aRR 1.35; 95% CI 1.01–1.80). They also had an increased frequency of URTIs (aIRR; 1.19; 95% CI 1.07–1.33). Children of subfertile parents only had a higher risk of LRTIs (aRR 1.09; 95% CI 1.01–1.17) at age 19–36 months. LIMITATIONS, REASONS FOR CAUTION Self-reported time-to-pregnancy and respiratory tract infections by parents could lead to misclassification. Both the initial participation rate and loss to follow up in the MoBa limits generalizability to the general Norwegian population. WIDER IMPLICATIONS OF THE FINDINGS ART-conceived children might be more susceptible to respiratory tract infections in early childhood. This appears to be only partly explained by underlying parental subfertility. Exactly what aspects related to the ART procedure might be reflected in these associations need to be further investigated. STUDY FUNDING/COMPETING INTEREST(S) Funding was received from the Swiss National Science Foundation (P2BEP3_191798), the Research Council of Norway (no. 262700), and the European Research Council (no. 947684). All authors declare no conflict of interest. TRIAL REGISTRATION NUMBER N/A.

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Section: Discussionmentioning

confidence: 99%

Early childhood respiratory tract infections according to parental subfertility and conception by assisted reproductive technologies

2022

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“…concluded that the data on the risk of asthma and allergies among ART conceived are inconsistent [236]. Otherwise, a number of population-based studies as well as systematic reviews and meta-analyses have demonstrated an increased risk of atopy among ART-conceived children [237,238]. A subgroup analysis on singletons and multiple births showed a statistically significant linkage with the risk of asthma only for the former group [238].…”

Section: Art and Altered Immune Functionsmentioning

confidence: 99%

Long-Term Effects of ART on the Health of the Offspring

Ahmadi,

Aghebati-Maleki,

Rashidiani

et al. 2023

IJMS

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Assisted reproductive technologies (ART) significantly increase the chance of successful pregnancy and live birth in infertile couples. The different procedures for ART, including in vitro fertilization (IVF), intracytoplasmic sperm injection (ICSI), intrauterine insemination (IUI), and gamete intrafallopian tube transfer (GIFT), are widely used to overcome infertility-related problems. In spite of its inarguable usefulness, concerns about the health consequences of ART-conceived babies have been raised. There are reports about the association of ART with birth defects and health complications, e.g., malignancies, high blood pressure, generalized vascular functional disorders, asthma and metabolic disorders in later life. It has been suggested that hormonal treatment of the mother, and the artificial environment during the manipulation of gametes and embryos may cause genomic and epigenetic alterations and subsequent complications in the health status of ART-conceived babies. In the current study, we aimed to review the possible long-term consequences of different ART procedures on the subsequent health status of ART-conceived offspring, considering the confounding factors that might account for/contribute to the long-term consequences.

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“…Contrasting data exist in the literature with respect to the prevalence of asthma in children born from ART, and the data may be confounded, or the outcomes mediated, by the prevalence of maternal asthma, smoking, neonatal morbidity, preterm birth, and low birth weight. Two systematic reviews have reported a mild increased risk of asthma in ART-conceived offspring in comparison to their naturally conceived counterparts, with studies on allergies being limited and less conclusive ( 18 , 19 ).…”

Section: The Longer-term Influences Of Art On the Offspringmentioning

confidence: 99%

“…Of particular relevance, several studies have reported differences between ART-conceived and naturally conceived offspring with regard to mental health outcomes, reporting a potentially higher prevalence of depression, autism spectrum disorder, attention-deficit disorder, and behavioural differences ( 15 – 17 ). Furthermore, there are conflicting reports as to whether asthma and allergies are more prevalent in the offspring of ART ( 18 , 19 ).…”

Section: Introductionmentioning

confidence: 99%

The longer-term effects of IVF on offspring from childhood to adolescence

Hart

Wijs²

2022

Front. Reprod. Health

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It is well established that there are increased pregnancy-related complications for a woman who conceives through assisted reproductive treatment (ART). Furthermore, it is known that the risk to the child born is greater, believed to be related to prematurity and growth restriction. Studies have also reported epigenetic changes in the DNA of offspring conceived through ART. In addition, it is believed that they have a greater risk of congenital malformations, although some of these risks may relate to underlying infertility, rather than the ART treatment per se. As a result, it may be expected that there is a greater risk to the longer-term health of the child who is born from ART; however, evidence about the long-term health of children conceived through ART is reassuring. Even though, it is recognised that many of the studies in this field come with limitations. Low numbers of participants is one of the major limitations, which makes subgroup analyses for diverse types of ART, or diverse types of infertility, not feasible. Furthermore, studies are often limited by short follow-up periods because of the difficulty and costs involved in longitudinal study designs. In addition, the rapid changes over time in ART limit the generalisability and significance of long-term findings. Well-designed studies investigating the long-term health outcomes of ART-conceived offspring and the potential influences of various aspects of the ART procedure, as well as studies of the potential underlying epigenetic mechanisms, are imperative. Furthermore, conclusions from childhood hospitalisation data from the United Kingdom, the long-term follow-up and quality of life study from researchers in Melbourne, and the data published from the Western Australian Growing Up Healthy Study will go a long way to help reassure current and prospective parents who may require ART to conceive.

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Association between childhood asthma and history of assisted reproduction techniques: a systematic review and meta-analysis

Cited by 9 publications

References 76 publications

Early childhood respiratory tract infections according to parental subfertility and conception by assisted reproductive technologies

Early childhood respiratory tract infections according to parental subfertility and conception by assisted reproductive technologies

Long-Term Effects of ART on the Health of the Offspring

The longer-term effects of IVF on offspring from childhood to adolescence

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