Abstract
COVID-19 infection during pregnancy is potentially dangerous to neonatal hearing, as it is the period of organogenesis, and associated hyperthermia may cause vascular damage, disruption of cell migration, and death of the dividing neuroblasts. To investigate the possible association between neonatal hearing loss and gestational mild COVID-19 infection. A prospective case-control study was conducted at a tertiary healthcare centre in North India from March 2020 to Oct 2022. Cases included the neonates born to COVID-19-positive mothers were subjected to hearing screening at 1, 3 and 6 months using otoacoustic emission (OAE) and automated auditory brainstem response (AABR). Similar protocol was applied to controls, i.e., neonates borne to mothers with no gestational history of COVID infection. Results were analyzed statistically. Our study reported that the statistical difference between groups A (n = 942) and B (n = 942) for gestational COVID-19 infection and neonatal hearing loss was insignificant at 1 month (p-value 0.272 for OAE and p-value 0.634 for AABR) and also insignificant at 3 and 6 months (p-value 0.679 for AABR, for both). The association between gestational mild COVID-19 infection during gestation and neonatal hearing loss is statistically insignificant at initial screening as well as sequential screenings.
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Introduction
Severe acute respiratory syndrome associated with the novel Corona Virus 2 started in December 2019 in Wuhan, China, and spread to the whole world rapidly, affecting all races and ages [1]. The COVID-19 disease displayed a wide spectrum of symptoms ranging from asymptomatic carriers to severe interstitial pneumonia, and also some neurotropic symptoms such as anosmia, dysgeusia, hearing loss, tinnitus, and dizziness [2, 3].
Ministry of Health and Welfare, India has defined the mild Covid-19 disease as- the presence of symptoms of upper respiratory tract infection with or without fever, and without shortness of breath or hypoxia (respiratory rate ≤ 24/min without any breathlessness, SpO2: ≥ 94% on room air) [4]. Pregnant females were considered at high risk of acquiring the infection. The vertical transmission of COVID-19 from mother to fetus is still controversial [5]. In neonatal COVID-19 cases, the common symptoms among neonates were fever, respiratory, gastrointestinal, and neurological symptoms. As the neonate cannot be separated from the mother, it is associated with late COVID-19 infection, however, breastfeeding is not [6]. Gestational mild COVID-19 infection during the first trimester is potentially dangerous to neonatal hearing, as it is the period of organogenesis, and associated hyperthermia may cause vascular damage, disruption of cell migration, and death of the dividing neuroblasts [7]. This is also the most important and sensitive period for the development of the middle and inner ear structures [8].
Gestational mild COVID-19 infection is more commonly seen during the third trimester [9]. Few studies have suggested there is a correlation between gestational insufficiency in the medial olivocochlear efferent system which was evident on TEOAE (transient evoked otoacoustic emission) test results signifying the increased risk of congenital hearing loss [10, 11].
The implications of congenital hearing loss include impaired speech, social, and emotional development. Our study aimed to investigate the possible association between neonatal hearing loss and gestational mild COVID-19 infection.
Methods
Study Design
A prospective observational case-control study was done at a tertiary healthcare centre in North India from March 2020 to October 2022.
Participants
Group A included neonates born to mothers with a history of mild COVID-19 infection during gestation. It was made sure that mothers of neonates in group A were conservatively managed with the same treatment protocol. This protocol included the administration of paracetamol (500 mg, tablet) as per need and no other drugs were administered.
Group B constituted of an equal number of neonates (as of group A) born to mothers who had an uneventful antenatal, perinatal and postnatal history as well as laboratory proven negative results for COVID-19 infection.
Group A formed the ‘case’ cohort while group B formed the ‘control’ cohort. The neonates with low or very low birth weight, low APGAR score, maternal history of fever due to moderate to severe COVID-19 or non-COVID-19 infection, history of ototoxic drug intake during gestation, congenital anomalies, neonatal intensive care admission were excluded from the study. Written and informed consent was obtained from the parent/guardian of each participant for the publication purpose.
Hearing Evaluation
All neonates fulfilling the inclusion criteria were subjected to screening with Otoacoustic Emission (OAE) at 1 month. Those who failed screening (REFER) were retested with AABR (Automated Auditory Brainstem Response). Groups A and B were again subjected to screening by AABR at 3 and 6 months [12]. Those who failed the AABR test were deemed Fails and those who failed the OAE were deemed REFER. Neonates who failed at six months screening were referred to neuro-otologists for further intervention. Interacoustics Titan DPOAE Screening + ABRIS (Serial Number:1016596) machine was used for the above-mentioned screening. All the assessments were done in the audiology lab of the institute by a qualified audiologist.
Statistics
Descriptive statistics were used to analyze the demographic and clinical variables. The categorical variables were expressed as absolute values (percentage), while the continuous variables with normal distribution were described as mean ± standard deviation (SD), and those without normal distribution as median (M) and interquartile range (IQR). The results of groups A and B at 1,3 and 6 months were statistically compared using McNemar’s Chi-square test and statistical analysis was done using the SPSS (version 23) program. In all cases, the level of significance was set at a p-value < 0.05 with a confidence limit of 95%.
Results
Between March 2020 and October 2022, a total of 1248 neonates were delivered by mothers with a history of COVID-19 infection during gestation. Out of these, 942 neonates were included in Group A as per inclusion criteria while 306 neonates were excluded from the studies as per exclusion criteria. After the first screening at the age of one month, 64 neonates failed screening by OAE in group A and 54 in group B. On AABR at 1 month, 924 neonates passed while 18 failed among group A, whereas 930 passed and 12 failed among group B. However, on AABR, at 3 and 6 months, both, 928 neonates passed while 14 failed among group A, whereas 932 passed and 10 failed among group B. No change in results was noted at 3 and 6 months (Fig. 1).
We observed that the mean age for mothers at the time of delivery was 28.76 ± 4.2 years (with an IQR of 24–33 years). 168 (17.83%) mothers acquired COVID-19 infection during the first trimester, 260 (27.60%) during the second, and 514 (54.56%) during the last trimester. (Fig. 2) Male neonates were 1004 and females were 880 with male to female ratio of 1.14:1. The mean weights for groups A and B were 2938.5 g and 2868.7 g. The mean gestational age for groups A and B were 38.4 and 39.2 weeks, respectively (Table 1).
At first screening, unilateral hearing loss was seen among 14 neonates of group A and 8 neonates of group B on AABR, while at 3 as well as 6 months, 10 infants from group A and 6 from group B failed AABR test. Bilateral hearing loss was seen among 4 neonates of groups A and B, each, at 1 month of age and also at 3 and 6 months of age. Statistical analysis of our results showed that there was no significant statistical difference between case (group A) and controls (group B) concerning neonatal hearing loss (Table 2).
Discussion
Congenital hearing loss has a significant impact on the social and psychological development of an infant. Congenital hearing loss can be caused by environmental as well as genetic factors. Environmental factors include infections, ototoxicity, prematurity, and asphyxia [13]. Especially viral infections, congenital or acquired, such as cytomegalovirus, rubella virus, etc. can cause permanent or temporary hearing loss [14].
Pregnant women became infected with COVID-19 in large numbers during each wave of the pandemic. It is still unclear whether vertical transmission of COVID-19 from the infected mother to the fetus is possible [5]. A systemic review investigated the possibility of vertical transmission among neonates of COVID-19-infected mothers using nasopharyngeal swabs and IgM positivity in cord blood reported no positivity [15]. Another systemic review reported 8 COVID-19-positive neonates among 179 infected mothers [16]. The role of SARS-CoV-2 in congenital hearing loss is still debatable. The possible mechanism for maternal viral infection associated congenital hearing loss can be due to direct damage to the organ of Corti, stria vascularis, or neurons, damage to host immune response to viral antigen, indirectly decreasing the immunity and causing secondary infections, and unknown mechanisms [14].
Most of the mothers showed COVID-19 positivity in the third trimester (54.56%) in our study. A study by Yildiz et al. [17] also showed maximum COVID-19 positivity among mothers during the third trimester (47%). Ghiselli et al. [18] also reported maximum COVID-19 positivity among mothers in the third trimester (63.5%). Conversely, another study by Alan et al. [11] observed maximum COVID-19 positivity among mothers in the first trimester (78.8%). Our study reported an insignificant relationship between gestational COVID-19 infection and neonatal hearing loss at 1 month (p-value 0.272 for OAE and p-value 0.634 for AABR) and 3 and 6 months (p-value 0.679 for AABR, for both). Our study showed bilateral REFER results in 14 patients (1.4%) and 50 (5.30%) unilateral REFER results for group A, while REFER results for group B were 6 bilateral (0.63%) and 48 unilateral (5.09%), at 1 month. Alan et al. [11] reported that 31.4% of COVID-19 group infants had bilateral REFER results. However, AABR results were statistically not significant for these infants. Mostafa et al. [19] recently reported that 18% of neonates failed at 1 month and 2.9% on AABR. They observed higher failure rates only during primary screening. Kaplan et al. [20] found that 12.4% of neonates failed the first screening and 1.3% failed the second screening. They observed no statistically significant difference between cases and controls. Kosmidou et al. [21] reported that 21.87% of neonates failed the first screening while all these neonates cleared the second screening. A study by Tanyeri Toker et al. reported no significant association between COVID-19 infection during different trimesters and congenital hearing loss. Furthermore, similar to our study they have suggested that gestational COVID-19 infection is not associated with permanent congenital hearing loss [22].
Our study was monocentric. This serves as a limitation as our study’s results may not apply to a different population. Thus, we propose that the further studies should be multicentric. Also, the lack of prolonged follow-up was another limitation.
Conclusion
We found that the statistical difference between groups A and B concerning neonatal hearing loss was insignificant at 1, 3 and 6 months. This implicated that there is no significant association between gestational COVID-19 and neonatal hearing loss. Thus, we propose multicentric studies with long-term follow-up to detect the late effects of gestational mild COVID-19 infection on neonatal hearing.
Abbreviations
- TEOAE:
-
Transient evoked otoacoustic emission
- DPOAE:
-
Distortion product otoacoustic emission
- AABR:
-
Automated auditory brainstem response
- OAE:
-
Otoacoustic emission
References
Huang C, Wang Y, Li X, Ren L, Zhao J, Hu Y et al (2020) Clinical features of patients infected with 2019 novel coronavirus in Wuhan China. Lancet 395:497–506. https://doi.org/10.1016/S0140-6736(20)30183-5
Romana GC, Spencerc PS, Reisd J, Buguete A, El Alaoui FM, Katrakg SM et al (2020) The neurology of COVID-19 revisited: a proposal from the environmental neurology specialty Group of the World Federation of neurology to implement international neurological registries. J Neurol Sci 414:116884. https://doi.org/10.1016/j.jns.2020.116884
Jafari Z, Kolb BE, Mohajerani MH (2022) Hearing loss, tinnitus, and dizziness in COVID-19: a systematic review and meta-analysis. Can J Neurol Sci 49(2):184–195. https://doi.org/10.1017/cjn.2021.63
Ministry of Health and Family Welfare, India: Revised guidelines for Home Isolation of mild /asymptomatic COVID-19 cases. [Dated 5th January, 2022]. https://old.iitr.ac.in/safety/Covid%20Guidelines%202022/MoHFW_Revised%20Home%20Isolation%20Guidelines_05-01-2022.pdf
Yang Z, Liu Y (2020) Vertical transmission of severe acute respiratory syndrome coronavirus-2: a systemic review. Am J Perinatol 37:1055–1060. https://doi.org/10.1055/s-0040-1712161
Raschetti R, Vivanti AJ, Vauloup-Fellous C, Loi B, Benachi A, De Luca D (2020) Synthesis and systematic review of reported neonatal SARS-CoV-2 infections. Nat Commun 11:5164. https://doi.org/10.1038/s41467-020-18982-9
Abu-Amara J, Szpecht D, Al-Saad SR, Karbowski LM (2021) Contracting COVID-19 in the first and second trimester of pregnancy: what we know - a concise qualitative systematic review. Arch Med Sci 17:1548–1557. https://doi.org/10.5114/aoms/133121
Lavigne-Rebillard M, Dechesne C, Pujol R, Sans A, Escudero P (1985) Development of the internal ear during the 1st trimester of pregnancy. Differentiation of the sensory cells and formation of the 1st synapses (Article in French). Ann Otolaryngol Chir Cervicofac 102:493–8
Kotlyar AM, Grechukhina O, Chen A, Popkhadze S, Grimshaw A, Tal O et al (2021) Vertical transmission of coronavirus disease 2019: a systematic review and meta-analysis. Am J Obstet Gynecol 224:35-53.e3. https://doi.org/10.1016/j.ajog.2020.07.049
Celik T, Simsek A, Koca CF, Aydin S, Yasar S (2021) Evaluation of cochlear functions in infants exposed to SARS-CoV-2 intrauterine. Am J Otolaryngol 42:102982. https://doi.org/10.1016/j.amjoto.2021.102982
Alan MA, Alan C (2021) Hearing screening outcomes in neonates of SARS-CoV-2 positive pregnant women. Int J Ped Otorhinolaryngol 146:110754. https://doi.org/10.1016/j.ijporl.2021.110754
American Academy of Pediatrics, Joint Committee on Infant Hearing (2007) Year 2007 position statement: principles and guidelines for early hearing detection and intervention programs. Pediatrics 120(4):898–921. https://doi.org/10.1542/peds.2007-2333
Smith RJH, Bale JR, White KR (2005) Sensorineural hearing loss in children. Lancet 365(9462):879–890
Cohen BE, Durstenfeld A, Roehm PC (2014) Viral causes of hearing loss: a review for hearing health professionals. Trends Hear 18:2331216514541361
Huntley BJF, Huntley ES, Di Mascio D, Chen T, Berghella V, Chauhan SP (2020) Rates of maternal and perinatal mortality and vertical transmission in pregnancies complicated by severe acute respiratory syndrome coronavirus 2 (SARS-Co-V-2) infection: a systematic review. Obstet Gynecol 136(2):303–312. https://doi.org/10.1097/AOG.0000000000004010. (PMID: 32516273)
Egloff C, Vauloup-Fellous C, Picone O, Mandelbrot L, Roques P (2020) Evidence and possible mechanisms of rare maternal-fetal transmission of SARS-CoV-2. J Clin Virol 128:104447. https://doi.org/10.1016/j.jcv.2020.104447
Yıldız G, Kurt D, Mat E, Yıldız P, Basol G, Gündogdu EC et al (2022) Hearing test results of newborns born from the coronavirus disease 2019 (COVID-19) infected mothers: a tertiary center experience in Turkey. J Obstet Gynaecol Res 48(1):113–118
Ghiselli S, Laborai A, Biasucci G, Carvelli M, Salsi D, Cuda D (2022) Auditory evaluation of infants born to COVID19 positive mothers. Am J Otolaryngol 43(2):103379. https://doi.org/10.1016/j.amjoto.2022.103379
Mostafa BE, Mostafa A, Fiky LME, Omara A, Teaima A (2022) Maternal COVID-19 and neonatal hearing loss: a multicentric survey. Eur Arch Otorhinolaryngol 279:3435–3438. https://doi.org/10.1007/s00405-021-07098-5
Oskovi-Kaplan ZA, Ozgu-Erdinc AS, Buyuk GN, Sert-Dinc UY, Ali-Algan C, Demir B et al (2022) Newborn hearing screening results of infants born to mothers who had COVID-19 disease during pregnancy: a retrospective cohort study. Ear Hear 43(1):41–44. https://doi.org/10.1097/AUD.0000000000001167. (PMID:34812792;PMCID:PMC8693928)
Kosmidou P, Karamatzanis I, Tzifas S, Vervenioti A, Gkentzi D, Dimitriou G (2022) Hearing outcomes of infants born to mothers with active COVID-19 infection. Cureus 14(6):e25571. https://doi.org/10.7759/cureus.25571. (PMID: 35784961; PMCID: PMC9249119)
Tanyeri Toker G, Kumbul YC, Centikol AE, Aslan H, Baba P, Oncel MY (2023) Is gestational COVID-19 a risk factor for congenital hearing loss? Otol Neurotol 44(2):115–120. https://doi.org/10.1097/MAO.0000000000003761
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Rajanna, L.B., Raina, S., Bhatia, R. et al. Gestational Mild COVID-19 Infection Associated Neonatal Hearing Loss: A Case-Control Study from North India. Indian J Otolaryngol Head Neck Surg 75, 1847–1852 (2023). https://doi.org/10.1007/s12070-023-03786-2
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DOI: https://doi.org/10.1007/s12070-023-03786-2