Perinatal factors influencing the neonatal hearing screening results

Background Previous studies have indicated that the majority of cases with “failed” results related to transient evoked otoacoustic emissions (OAE) test have the normal hearing. The present study aimed to assess the possible relationships between perinatal factors and the false-positive OAE results. Methods A case-control study was carried out in an Iranian Hospital in 2020. Based on the OAE results on the first day of life, newborns were divided into 2 groups; Control group included subjects with “Pass” OAE results. Every neonate with “Fail” OAE result was referred for auditory brainstem response (ABR). Neonates with bilateral fail OAE but normal ABR results (false-positive OAE) were considered as the case group. All recorded data were analyzed to assess the possible correlations between maternal/neonatal factors and the false-positive OAE results. Results One hundred and eighty-one neonates entered the study. Of all included neonates, 87 (48.1%) cases showed bilateral fail OAE and 94 (51.9%) subjects passed the OAE test. Normal ABR results (false-positive OAE) were observed in all cases with bilateral fail OAE. Comparisons of variables affecting the OAE results showed that of all perinatal factors, neonate’s sex (p = 0.046) and cesarean section (p = 0.003) were the only influencing factors that increased the risk of false-positive OAE results. Conclusion Based on the results, the cesarean section delivery and neonate’s male sex increased the risk of false-positive results related to OAE test. Implementing other screening tests such as ABR or Automated ABR as the initial screening test could be suggested for such cases.


Background
Hearing loss is one of the most frequent congenital anomalies in the neonates. It has been reported that one in every 1000 newborns suffers from congenital bilateral hearing loss [1,2]. Infants with undetected hearing loss often face significant complications related to emotional, intellectual, linguistic, speech, and social delays [3,4].
To decrease the impact of adverse effects associated with congenital hearing loss on the infant's life, early diagnosis and preventive interventions have been recommended [4]. There are different screening methods to evaluate hearing status, as soon as possible, in newborns. Recently transient evoked otoacoustic emissions (TEOAE) and auditory brain stem response (ABR) with high sensitivity and specificity are widely used as universal newborn hearing screening (UNHS) tests. However false-positive results may cause some misinterpretations and parental anxiety [4,5]. Previous studies indicated that the majority of cases with "failed" results related to screening tests have the normal hearing sense. A high rate of false-positive result ranged from 2.5 to 8% was reported regarding to use of universal newborn hearing screening tests including OAE. The results of the studies have also demonstrated that some factors including ear canal debris, ambient sound, myogenic interference, infant's position, or activity may falsely influence the results of the screening tests [5,6]. An investigation demonstrated that of 1000 screened newborns using TEOAE, 18 subjects had impaired two-step OAE results (OAE implementing on first and 10 to 15 days after neonate's birth). ABR results showed that of these subjects, 12 (1.2%) responses had been false positive [4].
Several studies have evaluated the possible associations between maternal/neonatal factors and false-positive neonatal hearing screening tests; Schwarz et al. showed that 70 newborns who failed OAE, could pass the subsequent ABR. they highlighted that of different maternal/ neonatal factors including mother's health status, age, gravida, parity, amniotic fluid index (AFI), mode of delivery, tobacco & smoking, illegal drug use, alcohol consumption, gestational age, neonate's gender, head circumference, birth weight, height, and Apgar scores, only smoking and drug use could falsely affect the results [7]. The other study demonstrated that regardless of the mode of delivery, false-positive rates related to the first (81.9%) and second (14.5%) OAE screening test were high among neonates [8]. Kepekci et al. have demonstrated a higher false-positive rate in the first OAE among newborns born by cesarean section (C/S) compared to those born by normal vaginal delivery [9].
False-positive results of hearing screening tests may interfere and postpone the accurate census associated with neonatal hearing loss or impairment. Moreover, requiring repeated screening tests may impose heavy costs on the health system and the family economy. Finally, a falsepositive hearing screen may impact some negative psychological and emotional stress on neonates' parents. Therefore, the present study was carried out to assess the possible relationships between several perinatal factors and false-positive results of the OAE test. It is supposed that by identifying such involving factors, implementing of another proper hearing screening test as the initial screening test may eliminate these parents' discomforts and mentioned complications.

Study design
A case-control study was carried out in Yas Women Hospital affiliated to Tehran University of Medical Sciences (Tehran-Iran) between January and June 2020. The population study was single birth neonates with gestational age > 34 weeks who attended for hearing screening test by OAE (Maico Diagnostics Universal Neonatal Hearing Screening; Germany) on the first day of life. Based on the OAE results, newborns were divided into 2 groups. The control group included subjects with "Pass" results when there was OAE response to the stimulus at > 35 dB Hearing Level (dBHL) [10]. Every neonate with Fail result (no response to the stimulus) was referred for auditory brainstem response (using ABR; The Interacoustics Eclipse; USA) the next day. Neonates with bilateral Fail OAE but normal ABR results (false-positive OAE) were considered as the case group. Both automated OAE and ABR tests were done by an expert audiologist. The case and control groups were matched regarding to age and sex. Newborns with failed both OAE and ABR tests as well as having the risk factors associated with hearing loss (Maternal infections, Hyperbilirubinemia, congenital head and neck abnormalities or syndromes) were also excluded from the study.
Demographic data related to all neonates and their mothers including maternal age, level of education, parity, gravid, type of delivery, prenatal corticosteroid administration, prenatal complications and underlying diseases, amniotic fluid index (AFI), gestational age, the first and fifth minutes Agar scores, anthropometric measures, and history of hospitalization were extracted from medical records and recorded.
All recorded data related to the results of hearing screening tests as well as maternal/ neonatal data were analyzed to assess the possible correlations between some maternal-neonatal factors and false positive OAE result.

Ethical considerations
Ethics approval was obtained from the institutional review board of Tehran University of Medical Sciences according to Helsinki declaration (IR.TUMS.VCR.REC.1398.061). All participants' parents gave written consent before enrollment. Participants' data were considered confidential and no extra cost was imposed on our participants.

Sample size
Schwarz et al. [7] in a study (determining the affecting factors on false positive OAE test) showed 10% of false positive OAE in newborns were associated with maternal variables like drug usage, while this rate among the control group was 1.3%. Based on these parameters, using formula for estimation of a proportion between two independent groups with a power of 80% and an alpha error of 0.05, 94 subjects in each group (for achieving the effective factor on false positive OAE) were included.

Discussion
In the present study, possible relationships between several perinatal factors and false-positive results related to the OAE test were assessed. By identifying such influencing factors, initially using a more advanced screening test like ABR can eliminate the defect associated with OAE screening test.
Our results showed that of all perinatal factors, neonate's sex was a significant influencing factor on the false-positive OAE test; the majority of the cases were male (67.1% vs. 32.9%). We suppose that this sex-related discrepancy may arise from differences in male and female's skull bones as well as skull structures. A former study has reported that the amplitudes of the otoacoustic emissions for female neonates are greater and more perceptible than their male counterparts [11]. Other studies have also shown that the failed results related to NHS tests were more frequent in male subjects; Lima et al. have reported that 12% of participants in their study failed the NHS test; of them 55.27% were male [12]. Other investigation showed that of 88 screened neonates, 39.77% failed the NHS while the numbers of male subject were significantly higher than females (62.86% vs. 51.43%) [13]. In accordance with our finding da-Silva Reis et al. demonstrated that the fail results associated with the first hearing screening test were significantly frequent among male newborns compared to the females (n = 34; male: 28.3% vs. female: 11.7%, p = 0.0128). Of all these 34 cases, more male neonates passed the rescreening ABR test than the females (17.6% vs. 14.7%) [14].
The results in the current study have also indicated that there was a significant difference between case and control groups regarding to type of delivery; more neonates with false-positive OAE results had been born by cesarean section. The reason may correlate to accumulation of wax or amniotic fluid in the external and middle ear in the cesarean cases. Unlike the OAE test, the ABR test is not affected by such factors [4,15]. In addition, it is supposed that in the cesarean cases, anesthesia and the time of screening after that may affect the OAE results [16]. According to such findings, we suggest the implementing of ABR test as the first screening test for neonates born by cesarean section. By using this test, rescreenining might be avoided. Compatible to our findings, Xiao  The authors indicated that although false-positive results in the cesarean group were higher than the normal vaginal delivery group; the difference between two groups was not significant [18]. Güven also did not find any significant association between false-positive hearing screening result and the mode of delivery, however the author showed that after fluid resorption in the ear, success rate related to the first OAE was significantly increased [8]. Tabrizi et al. have also noted that for higher success rate, the first OAE test after cesarean delivery should be postponed [19]. In contrast to our finding, Farahani et al. have demonstrate that false-positive OAE results in the vaginal delivery group was significantly higher than the cesarean group (15.5% vs. 9.5%) [20].
According to the results, we could not find any significant relationships between false-positive OAE results and other perinatal factors. However further studies with larger sample size, implementing of different screening methods in variable postnatal times may provide more beneficial data.

Conclusion
In summary based on the results, the cesarean section delivery and neonate's male sex increased the risk of false-positive results related to OAE test. Implementing other screening tests such as ABR or Automated ABR as the initial screening test could be suggested for such cases. Using these methods as the first screening tool may be cost effective by avoiding of rescreenining and also reduces parents' anxiety related to false-positive results. Moreover, with regard to high rates of falsepositive rates in the implementing of OAE test, the performing the second screening modality for the failed OAE cases should be considered.