Association of assisted reproductive technology, germline de novo mutations and congenital heart defects in a prospective birth cohort study

Wang, Cheng; Lv, Hong; Ling, Xiufeng; Hong, Li; Diao, Feiyang; Dai, Juncheng; Du, Jiangbo; Chen, Ting; Xi, Qi; Zhao, Yang; Zhou, Kun; Xu, Bo; Han, Xiumei; Liu, Xiaoyu; Peng, Meijuan; Chen, Congcong; Tao, Shiyao; Huang, Lei; Liu, Cong; Wen, Mingyang; Jiang, Yangqian; Jiang, Tao; Lu, Chuncheng; Wu, Wei; Wu, Di; Chen, Minjian; Lin, Yuan; Guo, Xuejiang; Huo, Ran; Liu, Jiayin; Ma, Hongxia; Jin, Guangfu; Xia, Yankai; Sha, Jiahao; Shen, Hongbing; Hu, Zhibin

doi:10.1038/s41422-021-00521-w

Cited by 31 publications

(26 citation statements)

References 49 publications

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“…Offspring of our study conceived through assisted reproductive technology was more likely to develop CHD compared with those conceived spontaneously (20). Wang et al supported our view and explained that fetuses conceived through assisted reproductive technology carried more germline de novo mutations than those conceived spontaneously, which could affect protein-coding genes and further result in a higher risk of CHD (38).…”

Section: Discussionsupporting

confidence: 78%

How Parental Predictors Jointly Affect the Risk of Offspring Congenital Heart Disease: A Nationwide Multicenter Study Based on the China Birth Cohort

Zhang

Sun

Zhao

et al. 2022

Front. Cardiovasc. Med.

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ObjectiveCongenital heart disease (CHD) is complex in its etiology. Its genetic causes have been investigated, whereas the non-genetic factor related studies are still limited. We aimed to identify dominant parental predictors and develop a predictive model and nomogram for the risk of offspring CHD.MethodsThis was a retrospective study from November 2017 to December 2021 covering 44,578 participants, of which those from 4 hospitals in eastern China were assigned to the development cohort and those from 5 hospitals in central and western China were used as the external validation cohort. Univariable and multivariable analyses were used to select the dominant predictors of CHD among demographic characteristics, lifestyle behaviors, environmental pollution, maternal disease history, and the current pregnancy information. Multivariable logistic regression analysis was used to construct the model and nomogram using the selected predictors. The predictive model and the nomogram were both validated internally and externally. A web-based nomogram was developed to predict patient-specific probability for CHD.ResultsDominant risk factors for offspring CHD included increased maternal age [odds ratio (OR): 1.14, 95% CI: 1.10–1.19], increased paternal age (1.05, 95% CI: 1.02–1.09), maternal secondhand smoke exposure (2.89, 95% CI: 2.22–3.76), paternal drinking (1.41, 95% CI: 1.08–1.84), maternal pre-pregnancy diabetes (3.39, 95% CI: 1.95–5.87), maternal fever (3.35, 95% CI: 2.49–4.50), assisted reproductive technology (2.89, 95% CI: 2.13–3.94), and environmental pollution (1.61, 95% CI: 1.18–2.20). A higher household annual income (100,000–400,000 CNY: 0.47, 95% CI: 0.34–0.63; > 400,000 CNY: 0.23, 95% CI: 0.15–0.36), higher maternal education level (13–16 years: 0.68, 95% CI: 0.50–0.93; ≥ 17 years: 0.87, 95% CI: 0.55–1.37), maternal folic acid (0.21, 95% CI: 0.16–0.27), and multivitamin supplementation (0.33, 95% CI: 0.26–0.42) were protective factors. The nomogram showed good discrimination in both internal [area under the receiver-operating-characteristic curve (AUC): 0.843] and external validations (development cohort AUC: 0.849, external validation cohort AUC: 0.837). The calibration curves showed good agreement between the nomogram-predicted probability and actual presence of CHD.ConclusionWe revealed dominant parental predictors and presented a web-based nomogram for the risk of offspring CHD, which could be utilized as an effective tool for quantifying the individual risk of CHD and promptly identifying high-risk population.

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Section: Discussionsupporting

confidence: 78%

How Parental Predictors Jointly Affect the Risk of Offspring Congenital Heart Disease: A Nationwide Multicenter Study Based on the China Birth Cohort

Zhang

Sun

Zhao

et al. 2022

Front. Cardiovasc. Med.

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“…Emerging evidence has suggested the increased risk of congenital disabilities, including chromosome abnormalities and development disorders, in fetuses conceived with ART methods (Chen and Heilbronn, 2017;Sammel et al, 2018;Yu et al, 2018;Luke et al, 2020;Wen et al, 2020;Luke et al, 2021;Wang et al, 2021). The results from our case report indicate that IVF-ET pregnancies need more attention and careful prenatal screening.…”

Section: Discussionmentioning

confidence: 59%

Case Report: Twin Pregnancy Gives Birth to a Girl with Partial Trisomy 21 Mosaicism after in vitro Fertilization and Embryo Transfer

Guo

Kang

et al. 2022

Front. Genet.

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Objective: To report a rare case in which an IVF-ET twin pregnancy gave birth to a partial trisomy 21 chimera girl.Design: Case report.Setting: University hospital.Patient: A girl with partial trisomy 21 mosaicism after in vitro fertilization and embryo transfer.Interventions:In vitro fertilization (IVF) and embryo transfer (ET).Main Outcome Measure: Karyotype analysis, Copy Number Variation sequencing (CNV-seq), stLFR-WGS, and Short Tandem Repeat (STR) analysis.Results: Being assisted with IVF and EF technology, the couple successfully gave birth to twin sisters at 37 weeks of gestational age. The NonInvasive Prenatal Testing (NIPT) and Nuchal Translucency (NT) examination showed no detectable genetic abnormalities during pregnancy. However, the younger infant displayed growth retardation and feeding difficulties after birth, which was not observed in her twin sister. Further genetic counseling and diagnosis suggested that she is a Chimera with complex partial trisomy 21. The stLFR-WGS assay showed multiple CNV variations in Chr21 and STR analysis confirmed the paternal origin of the additional fragments.Conclusion: It is rare for IVF-ET-assisted twin pregnancy to give birth to a girl with a complex combination of abnormal Chr21, which might result from paternal chromosome rearrangement during meiosis and mitosis.

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“…From 1980 to 2014, the rate of twin pregnancy in the United States increased by 79% [ 1 , 2 ], which is mainly related to the increase in assisted reproductive technology (ART) applications [ 3 ]. Although ART has enabled many infertile couples to have a baby, numerous studies have demonstrated that the risk associated with ART is clearly higher than without ART and includes not only twin or multiple pregnancies but also adverse perinatal outcomes, such as hypertensive disorders, postpartum hemorrhage, preterm birth, and birth defects [ 4 , 5 , 6 , 7 , 8 , 9 ]. Finding out the relationship between ART and pregnancy complications of twin pregnancy is of great significance to avoid adverse pregnancy outcomes and improve the quality of offspring.…”

Section: Introductionmentioning

confidence: 99%

The Maternal–Neonatal Outcomes of Twin Pregnancies with Preeclampsia and Their Association with Assisted Reproductive Technology: A Retrospective Study

Lyu

Zhao

et al. 2022

Diagnostics

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Objective: This study aimed to investigate the maternal–neonatal outcomes of twin pregnancies of mothers with preeclampsia and their association with assisted reproductive technology (ART). Methods: A retrospective study on the clinical and maternal–neonatal outcome data of 698 women with twin pregnancies who delivered in our hospital from December 2013 to September 2021 was conducted. Continuous variables were analyzed using a Student’s t-test or Wilcoxon rank-sum test. Categorical variables were analyzed using the Chi-square test. The risk factors of twin pregnancies with preeclampsia were analyzed by logistic regression. Results: The rate of twin pregnancy complicated by preeclampsia was 17.62% (123/698). Logistic regression analysis showed that ART increased the risk of preeclampsia in twin pregnancies (AOR: 1.868, 95% CI: 1.187–2.941). Mothers with preeclampsia carrying twins conceived with ART had a higher rate of delivery at gestational week <34 (29.9% vs. 12.5%) and asphyxia of the neonate at 5 min after delivery (13.4% vs. 1.8%) than those with preeclampsia conceived without ART (p < 0.05). Conclusions: ART increases the risk of preeclampsia in twin pregnancies and the rate of adverse maternal–neonatal outcomes for twin pregnancies with preeclampsia. The policy of single embryo transfer is a method to reduce the adverse pregnancy outcomes of ART.

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Association of assisted reproductive technology, germline de novo mutations and congenital heart defects in a prospective birth cohort study

Cited by 31 publications

References 49 publications

How Parental Predictors Jointly Affect the Risk of Offspring Congenital Heart Disease: A Nationwide Multicenter Study Based on the China Birth Cohort

How Parental Predictors Jointly Affect the Risk of Offspring Congenital Heart Disease: A Nationwide Multicenter Study Based on the China Birth Cohort

Case Report: Twin Pregnancy Gives Birth to a Girl with Partial Trisomy 21 Mosaicism after in vitro Fertilization and Embryo Transfer

The Maternal–Neonatal Outcomes of Twin Pregnancies with Preeclampsia and Their Association with Assisted Reproductive Technology: A Retrospective Study

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