Caesarean birth in women with infertility: population‐based cohort study

Richmond, Emily; Ray, Joel G.; Pudwell, Jessica; Djerboua, Maya; Gaudet, Laura; Walker, Mark; Smith, Graeme N.; Vélez, Maria P.

doi:10.1111/1471-0528.17019

Cited by 16 publications

(12 citation statements)

References 33 publications

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“…This would contribute to the increased risk of provider-initiated preterm birth in this population, given that guidelines recommend delivery between 36þ0 and 37þ0 weeks' gestation for women presenting with uncomplicated placenta previa (30,31), and at 34þ0 to 36þ6 weeks' gestation for those with a history of vaginal bleeding or other associated risk factors for preterm delivery (30). In addition, our results support prior studies indicating an increased risk of elective prelabor cesarean delivery and labor induction (i.e., provider-initiated preterm birth without complications) in patients with infertility without treatment, or after fertility treatment, especially IVF/ICSI (32,33). Lastly, gestational diabetes, common in patients with anovulation requiring OI/IUI, increases the risk of spontaneous preterm birth and PPROM (34), as documented in our study.…”

Section: Figuresupporting

confidence: 83%

Mode of conception and risk of spontaneous vs. provider-initiated preterm birth: population-based cohort study

Wang

Ray

Pudwell

et al. 2022

Fertility and Sterility

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Section: Figuresupporting

confidence: 83%

Mode of conception and risk of spontaneous vs. provider-initiated preterm birth: population-based cohort study

Wang

Ray

Pudwell

et al. 2022

Fertility and Sterility

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“…Increasing evidence supports that infertility, independent of fertility treatment, confers an increased risk of adverse perinatal outcomes, such as preterm birth, low birthweight, small for gestational age babies and caesarean section ( Messerlian et al , 2013 ; Richmond et al , 2022 ). In the stratified analysis, the associations between infertility without fertility treatment use and childhood ADHD remained mostly significant in all strata, such as vaginal delivery or caesarean section, singleton pregnancy, term or preterm birth and those with or without adverse neonatal outcomes.…”

Section: Discussionmentioning

confidence: 99%

“…However, in a prospective cohort study of children aged 5 years, infertility was not associated with ADHD ( Bay et al , 2014 ). Infertility and fertility treatment are associated with adverse pregnancy outcomes that may predispose to ADHD, including caesarean section, multiple pregnancy and preterm birth ( Halmøy et al , 2012 ; Velez et al , 2014 ; Curran et al , 2015 ; Elias et al , 2020 ; Lodge-Tulloch et al , 2021 ; Richmond et al , 2022 ). The role of these adverse pregnancy outcomes on any possible association between infertility, fertility treatment and ADHD also warrants clarification ( Hart and Norman, 2013 ).…”

Section: Introductionmentioning

confidence: 99%

Attention-deficit hyperactivity disorder in children born to mothers with infertility: a population-based cohort study

Fine

Dayan

Djerboua³

et al. 2022

Human Reproduction

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STUDY QUESTION Is the risk of attention-deficit hyperactivity disorder (ADHD) increased in children born to mothers with infertility, or after receipt of fertility treatment, compared to mothers with unassisted conception? SUMMARY ANSWER Infertility itself may be associated with ADHD in the offspring, which is not amplified by the use of fertility treatment. WHAT IS KNOWN ALREADY Infertility, and use of fertility treatment, is common. The long-term neurodevelopmental outcome of a child born to a mother with infertility, including the risk of ADHD, remains unclear. STUDY DESIGN, SIZE, DURATION This population-based cohort study comprised all singleton and multiple hospital births in Ontario, Canada, 2006–2014. Outcomes were assessed up to June 2020. PARTICIPANTS/MATERIALS, SETTING, METHODS Linked administrative datasets were used to capture all hospital births in Ontario, maternal health and pregnancy measures, fertility treatment and child outcomes. Included were all children born at ≥24 weeks gestation between 2006 and 2014, and who were alive at age 4 years. The main exposure was mode of conception, namely (i) unassisted conception (reference group), (ii) infertility without fertility treatment (history of an infertility consultation with a physician within 2 years prior to conception but no fertility treatment), (iii) ovulation induction (OI) or intrauterine insemination (IUI) and (iv) IVF or intracytoplasmic sperm injection (ICSI). The main outcome was a diagnosis of ADHD after age 4 years and assessed up to June 2020. Hazard ratios (HRs) were adjusted for maternal age, income quintile, rurality, immigration status, smoking, obesity, parity, any drug or alcohol use, maternal history of mental illness including ADHD, pre-pregnancy diabetes mellitus or chronic hypertension and infant sex. In addition, we performed pre-planned stratified analyses by mode of delivery (vaginal or caesarean delivery), infant sex, multiplicity (singleton or multiple), timing of birth (term or preterm <37 weeks) and neonatal adverse morbidity (absent or present). MAIN RESULTS AND THE ROLE OF CHANCE The study included 925 488 children born to 663 144 mothers, of whom 805 748 (87%) were from an unassisted conception, 94 206 (10.2%) followed infertility but no fertility treatment, 11 777 (1.3%) followed OI/IUI and 13 757 (1.5%) followed IVF/ICSI. Starting at age 4 years, children were followed for a median (interquartile range) of 6 (4–8) years. ADHD occurred among 7.0% of offspring in the unassisted conception group, 7.5% in the infertility without fertility treatment group, 6.8% in the OI/IUI group and 6.3% in the IVF/ICSI group. The incidence rate (per 1000 person-years) of ADHD was 12.0 among children in the unassisted conception group, 12.8 in the infertility without fertility treatment group, 12.9 in the OI/IUI group and 12.2 in the IVF/ICSI group. Relative to the unassisted conception group, the adjusted HR for ADHD was 1.19 (95% CI 1.16–1.22) in the infertility without fertility treatment group, 1.09 (95% CI 1.01–1.17) in the OI/IUI group and 1.12 (95% CI 1.04–1.20) in the IVF/ICSI group. In the stratified analyses, these patterns of risk for ADHD were largely preserved. An exception was seen in the sex-stratified analyses, wherein females had lower absolute rates of ADHD but relatively higher HRs compared with that seen among males. LIMITATIONS, REASONS FOR CAUTION Some mothers in the isolated infertility group may have received undocumented OI oral therapy, thereby leading to possible misclassification of their exposure status. Parenting behaviour, schooling and paternal mental health measures were not known, leading to potential residual confounding. WIDER IMPLICATIONS OF THE FINDINGS Infertility, even without treatment, is a modest risk factor for the development of ADHD in childhood. The reason underlying this finding warrants further study. STUDY FUNDING/COMPETING INTEREST(s) This study was made possible with funding from the Canadian Institutes of Health Research, Grant number PJT 165840. The authors report no conflict of interest. TRIAL REGISTRATION NUMBER N/A.

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“…The study exposure was mode of conception as recorded in BORN, namely (1) unassisted conception (reference group); (2) subfertility, defined as a history of an infertility consultation with a physician within 2 years before conception, identified by Ontario Health Insurance Plan (OHIP) billing code 628 from the International Classification of Diseases, Ninth Revision (ICD-9) in the absence of fertility treatment, (3) OI or IUI; and (4) IVF or ICSI. 29,30,37,38…”

Section: Exposure Statusmentioning

confidence: 99%

“…Next, we performed causal mediation analysis to describe the mediating role of 6 adverse pregnancy outcomes that have been reported to be associated with infertility and fertility treatments: preeclampsia, cesarean delivery, multifetal pregnancy, preterm birth at less than 37 weeks' gestation, and severe neonatal morbidity (eFigure 2 in Supplement 1). [28][29][30][31][32]41 Causal mediation analysis is based on a counterfactual framework 42 and used herein to disentangle the association between mode of conception and ASD (ie, total effect) into the natural direct effect (ie, the association between each mode of conception and ASD in the absence of the mediator) and the natural indirect effect (ie, the association operating through each of the 6 respective mediators mentioned above). We then estimated the proportion of the total effect between mode of conception and ASD mediated through each of the 6 adverse pregnancy outcomes (eFigure 2 in Supplement 1).…”

Section: Causal Mediation Analysismentioning

confidence: 99%

Infertility and Risk of Autism Spectrum Disorder in Children

Velez,

Dayan,

Shellenberger

et al. 2023

JAMA Netw Open

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ImportancePrevious studies on the risk of childhood autism spectrum disorder (ASD) following fertility treatment did not account for the infertility itself or the mediating effect of obstetrical and neonatal factors.ObjectiveTo assess the association between infertility and its treatments on the risk of ASD and the mediating effect of selected adverse pregnancy outcomes on that association.Design, Setting, and ParticipantsThis was a population-based cohort study in Ontario, Canada. Participants were all singleton and multifetal live births at 24 or more weeks’ gestation from 2006 to 2018. Data were analyzed from October 2022 to October 2023.ExposuresThe exposure was mode of conception, namely, (1) unassisted conception, (2) infertility without fertility treatment (ie, subfertility), (3) ovulation induction (OI) or intrauterine insemination (IUI), or (4) in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI).Main Outcome and MeasuresThe study outcome was a diagnosis of ASD at age 18 months or older. Cox regression models generated hazard ratios (HR) adjusted for maternal and infant characteristics. Mediation analysis further accounted for the separate effect of (1) preeclampsia, (2) cesarean birth, (3) multifetal pregnancy, (4) preterm birth at less than 37 weeks, and (5) severe neonatal morbidity.ResultsA total of 1 370 152 children (703 407 male [51.3%]) were included: 1 185 024 (86.5%) with unassisted conception, 141 180 (10.3%) with parental subfertility, 20 429 (1.5%) following OI or IUI, and 23 519 (1.7%) following IVF or ICSI. Individuals with subfertility or fertility treatment were older and resided in higher-income areas; the mean (SD) age of each group was as follows: 30.1 (5.2) years in the unassisted conception group, 33.3 (4.7) years in the subfertility group, 33.1 (4.4) years in the OI or IUI group, and 35.8 (4.9) years in the IVF or ICSI group. The incidence rate of ASD was 1.93 per 1000 person-years among children in the unassisted conception group. Relative to the latter, the adjusted HR for ASD was 1.20 (95% CI, 1.15-1.25) in the subfertility group, 1.21 (95% CI, 1.09-1.34) following OI or IUI, and 1.16 (95% CI, 1.04-1.28) after IVF or ICSI. Obstetrical and neonatal factors appeared to mediate a sizeable proportion of the aforementioned association between mode of conception and ASD risk. For example, following IVF or ICSI, the proportion mediated by cesarean birth was 29%, multifetal pregnancy was 78%, preterm birth was 50%, and severe neonatal morbidity was 25%.Conclusions and RelevanceIn this cohort study, a slightly higher risk of ASD was observed in children born to individuals with infertility, which appears partly mediated by certain obstetrical and neonatal factors. To optimize child neurodevelopment, strategies should further explore these other factors in individuals with infertility, even among those not receiving fertility treatment.

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Caesarean birth in women with infertility: population‐based cohort study

Cited by 16 publications

References 33 publications

Mode of conception and risk of spontaneous vs. provider-initiated preterm birth: population-based cohort study

Mode of conception and risk of spontaneous vs. provider-initiated preterm birth: population-based cohort study

Attention-deficit hyperactivity disorder in children born to mothers with infertility: a population-based cohort study

Infertility and Risk of Autism Spectrum Disorder in Children

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