Abstract
Assisted reproductive technologies (ART), including in vitro fertilization-embryo transfer (IVF-ET) and intracytoplasmic sperm injection (ICSI), are known to contribute a higher risk of birth defects; however, studies have rarely evaluated the association between IVF-ET and diagnostic hearing loss (HL). This study aimed to evaluate the prevalence of and risk factors for HL and to clarify the association between IVF-ET and HL among twinborn infants. We enrolled 1860 live-born twin neonates born at a hospital in China from January 2017 to December 2020. After multi-step hearing screening, participants were diagnosed with HL by pediatric audiologists at 6 months of age. The prevalence of hearing loss and the adjusted odds ratios (AORs) for specific risk factors were estimated using generalized estimation equation (GEE) models in twin-born infants. Characteristics and prevalence of failure for hearing screening and HL were measured in IVF-ET twin infants. IVF-ET conception and preterm birth conferred a higher risk of hearing loss, with increased adjusted odds ratios (AOR [95% confidence intervals (CI)] IVF-ET: 2.82 [1.17–6.80], P = 0.021; preterm birth: 6.14 [2.30–16.40], P < 0.001) than the control group, respectively. Among the 1860 twin infants, more IVF-ET twins failed in dual-step hearing screening (3.26%) and were diagnosed with hearing loss (2.21%) than those conceived by spontaneous pregnancy.
Conclusion: IVF-ET conception and premature birth were associated with a higher risk of hearing impairment. Twin infants conceived by IVF-ET tended to fail in hearing screening and be diagnosed with hearing loss. These observations provide a more comprehensive approach for the prevention and management of deafness in twin-born children.
What is Known: • IVF-ET technologies conferred a higher risk of birth defects. |
What is New: • Premature birth and IVF-ET conception were associated with a higher risk of hearing loss among twin infants. • Twin infants conceived by IVF-ET tended to fail in hearing screening and diagnosed with hearing loss. |
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Data availability
The original contributions presented in the study are included in the article/supplementary material; further inquiries can be directed to the corresponding author/s.
Abbreviations
- AABR:
-
Automatic auditory brainstem evoked response
- AOR:
-
Adjusted odds ratio
- ART:
-
Assisted reproductive technologies
- C-ABR:
-
Click-evoked auditory brainstem response
- CI:
-
Confidence interval
- DPOAE:
-
Distortion product otoacoustic emission
- FGR:
-
Fetal growth restriction
- GDM:
-
Gestational diabetes mellitus
- GEE:
-
Generalized estimation equation
- HL:
-
Hearing loss
- HS:
-
Hearing screening
- ICP:
-
Intrahepatic cholestasis of pregnancy
- ICSI:
-
Intracytoplasmic sperm injection
- IVF-ET:
-
In vitro fertilization-embryo transfer
- JCIH:
-
Joint Committee of Infant Hearing
- MCDA:
-
Monochorionic-diamniotic
- NICU:
-
Neonatal intensive care unit
- OR:
-
Odds ratio
- PID:
-
Pelvic inflammatory disease
- PIH:
-
Pregnancy-induced hypertension
- PROM:
-
Premature rupture of membrane
- PTA:
-
Pure-tone average
- SNHL:
-
Sensorineural hearing loss
- T-ABR:
-
Tone burst ABR
- TEOAE:
-
Transient evoked otoacoustic emission
References
Briceag I, Costache A, Purcarea VL, Cergan R, Dumitru M, Briceag I, Sajin M, Ispas AT (2015) Fallopian tubes–literature review of anatomy and etiology in female infertility. J Med Life 8:129–131
Vander Borght M, Wyns C (2018) Fertility and infertility: definition and epidemiology. Clin Biochem 62:2–10. https://doi.org/10.1016/j.clinbiochem.2018.03.012
Jiang Z, Wang Y, Lin J, Xu J, Ding G, Huang H (2017) Genetic and epigenetic risks of assisted reproduction. Best Pract Res Clin Obstet Gynaecol 44:90–104. https://doi.org/10.1016/j.bpobgyn.2017.07.004
Davies MJ, Rumbold AR, Moore VM (2017) Assisted reproductive technologies: a hierarchy of risks for conception, pregnancy outcomes and treatment decisions. J Dev Orig Health Dis 8:443–447. https://doi.org/10.1017/s2040174417000526
Garcia JE, Rosenwaks Z (2018) Development of in vitro fertilization in the United States: a conversation between Zev Rosenwaks and Jairo E. Garcia Fertil Steril 110:14–18. https://doi.org/10.1016/j.fertnstert.2018.04.011
Goisis A, Remes H, Martikainen P, Klemetti R, Myrskylä M (2019) Medically assisted reproduction and birth outcomes: a within-family analysis using Finnish population registers. Lancet 393:1225–1232. https://doi.org/10.1016/s0140-6736(18)31863-4
Qiao J, Feng HL (2014) Assisted reproductive technology in China: compliance and non-compliance. Transl Pediatr 3:91–97. https://doi.org/10.3978/j.issn.2224-4336.2014.01.06
Berntsen S, Söderström-Anttila V, Wennerholm UB, Laivuori H, Loft A, Oldereid NB, Romundstad LB, Bergh C et al (2019) The health of children conceived by ART: ‘the chicken or the egg?’ Hum Reprod Update 25:137–158. https://doi.org/10.1093/humupd/dmz001
Davies MJ, Moore VM, Willson KJ, Van Essen P, Priest K, Scott H, Haan EA, Chan A (2012) Reproductive technologies and the risk of birth defects. N Engl J Med 366:1803–1813. https://doi.org/10.1056/NEJMoa1008095
Hansen M, Kurinczuk JJ, Milne E, de Klerk N, Bower C (2013) Assisted reproductive technology and birth defects: a systematic review and meta-analysis. Hum Reprod Update 19:330–353. https://doi.org/10.1093/humupd/dmt006
Dai P, Huang LH, Wang GJ, Gao X, Qu CY, Chen XW, Ma FR, Zhang J et al (2019) Concurrent hearing and genetic screening of 180,469 neonates with follow-up in Beijing, China. Am J Hum Genet 105:803–812. https://doi.org/10.1016/j.ajhg.2019.09.003
Fortnum HM, Summerfield AQ, Marshall DH, Davis AC, Bamford JM (2001) Prevalence of permanent childhood hearing impairment in the United Kingdom and implications for universal neonatal hearing screening: questionnaire based ascertainment study. BMJ 323:536–540. https://doi.org/10.1136/bmj.323.7312.536
Kennedy C, McCann D (2004) Universal neonatal hearing screening moving from evidence to practice. Arch Dis Child Fetal Neonatal Ed 89:F378–F383. https://doi.org/10.1136/adc.2003.034454
Duan H, Zhang D, Liang Y, Xu C, Wu Y, Tian X, Pang Z, Tan Q et al (2019) Heritability of age-related hearing loss in middle-aged and elderly Chinese: a population-based twin study. Ear Hear 40:253–259. https://doi.org/10.1097/aud.0000000000000610
(2007) Year 2007 position statement: principles and guidelines for early hearing detection and intervention programs. Pediatrics 120:898-921.https://doi.org/10.1542/peds.2007-2333
(2000) Year 2000 position statement: principles and guidelines for early hearing detection and intervention programs. Joint Committee on Infant Hearing, American Academy of Audiology, American Academy of Pediatrics, American Speech-Language-Hearing Association, and Directors of Speech and Hearing Programs in State Health and Welfare Agencies. Pediatrics 106:798–817. https://doi.org/10.1542/peds.106.4.798.
Vasario E, Borgarello V, Bossotti C, Libanori E, Biolcati M, Arduino S, Spinelli R, Delle Piane L et al (2010) IVF twins have similar obstetric and neonatal outcome as spontaneously conceived twins: a prospective follow-up study. Reprod Biomed Online 21:422–428. https://doi.org/10.1016/j.rbmo.2010.04.007
Mallen JR, Hunter JB, Auerbach C, Wexler L, Vambutas A (2018) Characterization of newborn hearing screening failures in multigestational births. Int J Pediatr Otorhinolaryngol 105:158–162. https://doi.org/10.1016/j.ijporl.2017.12.017
Kim SY, Choi BY, Jung EY, Park H, Yoo HN, Park KH (2018) Risk factors for failure in the newborn hearing screen test in very preterm twins. Pediatr Neonatol 59:586–594. https://doi.org/10.1016/j.pedneo.2018.01.014
Carlin JB, Gurrin LC, Sterne JA, Morley R, Dwyer T (2005) Regression models for twin studies: a critical review. Int J Epidemiol 34:1089–1099. https://doi.org/10.1093/ije/dyi153
Iachina M, Jørgensen B, Christensen K, Iachine I (2002) Analysis of functional abilities for elderly Danish twins using GEE models. Twin Res 5:289–293. https://doi.org/10.1375/13690520260186489
Lieu JEC, Kenna M, Anne S, Davidson L (2020) Hearing loss in children: a review. JAMA 324:2195–2205. https://doi.org/10.1001/jama.2020.17647
Hille ET, van Straaten HI, Verkerk PH (2007) Prevalence and independent risk factors for hearing loss in NICU infants. Acta Paediatr 96:1155–1158. https://doi.org/10.1111/j.1651-2227.2007.00398.x
Van Kerschaver E, Boudewyns AN, Declau F, Van de Heyning PH, Wuyts FL (2013) Socio-demographic determinants of hearing impairment studied in 103,835 term babies. Eur J Public Health 23:55–60. https://doi.org/10.1093/eurpub/cks010
Jeong J, Youk TM, Oh J, Eo TS, Choi HS (2021) Neonatal and maternal risk factors for hearing loss in children based on population-based data of Korea. Int J Pediatr Otorhinolaryngol 147:110800. https://doi.org/10.1016/j.ijporl.2021.110800
Thangavelu K, Martakis K, Fabian S, Venkateswaran M, Roth B, Beutner D, Lang-Roth R (2019) Prevalence and risk factors for hearing loss in high-risk neonates in Germany. Acta Paediatr 108:1972–1977. https://doi.org/10.1111/apa.14837
Yasemin Sert U, Kansu Celik H, Canpolat FE, Sımsek GK, Engin Ustun Y (2020) Hearing screening test results of newborns conceived by intracytoplasmic sperm injection: a retrospective study of tertiary referral center. Fetal Pediatr Pathol 39:288–296. https://doi.org/10.1080/15513815.2019.1651804
Smith RJ, Bale JF Jr, White KR (2005) Sensorineural hearing loss in children. Lancet 365:879–890. https://doi.org/10.1016/s0140-6736(05)71047-3
Korver AM, Smith RJ, Van Camp G, Schleiss MR, Bitner-Glindzicz MA, Lustig LR, Usami SI, Boudewyns AN (2017) Congenital hearing loss. Nat Rev Dis Primers 3:16094. https://doi.org/10.1038/nrdp.2016.94
Snoeckx RL, Huygen PL, Feldmann D, Marlin S, Denoyelle F, Waligora J, Mueller-Malesinska M, Pollak A et al (2005) GJB2 mutations and degree of hearing loss: a multicenter study. Am J Hum Genet 77:945–957. https://doi.org/10.1086/497996
Moore JK, Linthicum FH Jr (2007) The human auditory system: a timeline of development. Int J Audiol 46:460–478. https://doi.org/10.1080/14992020701383019
Acknowledgements
We thank the families who participated in this project.
Funding
This study was funded by the National Natural Science Foundation of China (No. 81903221), the Natural Science Foundation of Changsha (No. kq2202033), and the Scientific Research Program of Health Commission of Hunan province (No. D202307019683).
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Jinghua Yin drafted the manuscript, carried out the analyses, critically reviewed the manuscript for important intellectual content. Yu Su and LinPeng Siyuan designed the data collection instruments, collected data, carried out the initial analyses, and reviewed and revised the manuscript. Fei Yin coordinated and supervised data collection and reviewed and revised the manuscript. Weidong Wang, Fengliang Deng, and Taosha Wang conceptualized and designed the study and reviewed and revised the manuscript. All authors approved the final manuscript as submitted and agree to be accountable for all aspects of the work.
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The study was approved by the Changsha Hospital for Maternal & Child Health Care in China (registration number 2022025) and complied with national regulations of data protection and consent.
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Yin, J., Su, Y., Siyuan, L. et al. Association between in vitro fertilization-embryo transfer and hearing loss: risk factors for hearing loss among twin infants in a cohort study. Eur J Pediatr 182, 1289–1297 (2023). https://doi.org/10.1007/s00431-022-04767-3
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DOI: https://doi.org/10.1007/s00431-022-04767-3