The Effect of Gestational Diabetes Mellitus on Hearing of Neonates in a Tertiary Healthcare Centre

Abstract

Congenital hearing loss is hearing loss present in a child at birth or soon after birth. It is a debilitating condition with the potential for lifelong disability. It is thought to be multifactorial in aetiology with both genetic (autosomal and X-linked) and acquired causes (such as maternal infections, drug intake, trauma). Gestational Diabetes Mellitus (GDM) is a relatively common condition found in pregnant females but is a rather understudied risk factor in terms of congenital hearing loss. GDM is easily treatable which makes the hearing loss due to it easily preventable. (1) Determine correlation between Gestational Diabetes Mellitus and congenital hearing loss in neonates. (2) Calculate the prevalence of Gestational Diabetes Mellitus related congenital hearing loss. A two-step screening process was used for hearing evaluation of neonates with normal mothers (non-exposed) and neonates with mothers suffering from GDM (exposed) through Otoacoustic emission (OAE) and Brainstem Evoked Response Audiometry (BERA). (1) The difference of neonates diagnosed with hearing impairment in exposed and non-exposed group was statistically significant with a p-value of 0.024. OR 2.1538 95% CI 0.6120–7.5796, p < 0.05. (2) Prevalence of hearing loss in neonates of GDM mothers: 13.3%. Through rigorous exclusion of the already known risk factors for congenital hearing loss, Gestational Diabetes Mellitus has been isolated as an independent risk factor for neonatal hearing impairment. We hope to identify additional cases of congenital hearing loss early leading to a decrease in disease burden.

Introduction

According to WHO (World Health Organization), over 5% of the world’s population (430 million people) require rehabilitation for their ‘disabling’ hearing loss (432 million adults and 34 million children). WHO estimates that by 2050 over 700 million people will have disabling hearing loss. ‘Disabling’ hearing loss refers to hearing loss greater than 35 decibels (dB) in the better hearing ear [1].

Early intervention in such cases prevents delays in speech and language development and has long-lasting beneficial effects on social and emotional development and quality of life of the child.

Gestational Diabetes Mellitus (GDM) has become one of the most common comorbidities during pregnancy in India with reported prevalence being as high as 1.3%. It seems to increase with age, from 1.0% among women aged 15–19 years to 2.4% among women aged 35 years and older [2].

Mothers with GDM and their infants constitute high-risk populations for diabetes mellitus.

Prevalence of deafness in neonates of mothers with diabetes mellitus is 4.16% [3] and they (Children of Diabetic Pregnancies, CDPs) are more likely to have bilateral hearing loss (HL) (81%) and sensorineural hearing loss (SNHL) (8%) relative to children of non- diabetic pregnancies (CNDPs) (p < 0.001 and p = 0.004, respectively) [4].

GDM has high chances of being converted to overt diabetes and is much more easily preventable. However, has been largely unexplored as an independent risk factor for congenital hearing loss (CHL).

An investigation into cochlear damage in neonates of GDM mothers shows significant high-frequency hearing loss [5].

It is of great significance for mothers and infants with GDM to explore the impact of GDM on hearing screening results in newborns, strengthen the management of pregnant women with GDM, and prevent the occurrence of neonatal hearing impairment.

Hearing loss in children can be detected by Otoacoustic emission (OAE) which is usually done in neonates for early screening.

OAE measures the sound that a normal cochlea generates due to biological activity of outer hair cells with the help of a microphone placed deep in external auditory meatus.

Brainstem Evoked Response Audiometry (BERA) is a diagnostic test, usually done after attainment of 3 months of age. It is the measurement of physiological electric events occurring in response to sound stimulation in the form of complexes/ waves. It is a non-invasive, objective audiological investigation.

Aims and Objectives

1. To determine correlation between Gestational Diabetes Mellitus and Congenital Hearing Impairment in neonates by the means of a two-step screening process i.e. Otoacoustic emission and Brainstem Evoked Response Audiometry.

2. To find out the prevalence of GDM related congenital hearing loss.

Materials and Methodology

Source of Data

The study groups consisted of neonates of mothers suffering from gestational diabetes mellitus (exposed group) and neonates of non-diabetic mothers (non-exposed group) examined at Gauhati Medical College and Hospital, Guwahati.

Method of Collection of Data

A detailed history was taken from the neonates’ parents/ guardian which was followed by a clinical examination. The patient parties were clearly explained about the procedure and a written informed consent was taken. DPOAE (Distortion Product Otoacoustic Emission) test was done on the neonates before their discharge from the hospital. The neonates were then followed up after 3 months to do a subsequent BERA (Brainstem Evoked Response Audiometry) to confirm the hearing loss.

Study Design

A prospective cohort study.

Study Duration

April 2021 to March 2022.

Sample Size

Neonates in the exposed and 60 in the non-exposed group. Formula used:

$$n=\frac{\{z{}_{1-\frac{\alpha }{2}}\sqrt{[2\overline{p}(1-\overline{p})]}+z_{1-\beta }{\sqrt{[p_1(1-p_1)+p_2(1-p_2)]\}}}^2}{{(p_1-p_2)}^2}$$

Place of Study

Gauhati Medical College, Guwahati, Assam.

Inclusion Criteria

Neonates of either sex whose mothers suffer from gestational diabetes mellitus form the exposed group and whose mothers do not suffer from gestational diabetes mellitus form the non-exposed group, who are apparently symptomless on clinical examination and willing to participate in the study.

Exclusion Criteria

Mothers with any of the following:

1. Infections (Toxoplasmosis, Rubella, Cytomegalovirus).

2. Birth injuries.

3. Drug and alcohol use during pregnancy.

4. Jaundice and Rh incompatibility.

Neonates with any of the following:

1. History of treatment in a neonatal intensive care unit (NICU) or special care baby unit (SCBU) for more than 48 h.

2. Family history of early childhood deafness.

3. Craniofacial anomalies (e.g. cleft palate) associated with hearing impairment.

4. Birth Trauma.

Methodology

A total of 120 neonates was included in the study, whose mothers were admitted in Gauhati Medical College and Hospital for delivery.

Screening of mothers for GDM was performed between 24 and 28 weeks’ gestation. It was followed by a diagnostic 100-g, 3-h oral glucose tolerance test (OGTT) if screening results met or exceeded a predetermined plasma glucose concentration (135 mg/dL) [6].

The neonates were divided into exposed and non-exposed group and then clinically evaluated. An informed consent was obtained for the procedure from either of the parents. The limitations and complications of neonatal hearing screening were explained to them.

The DPOAE test was done which involved placing a small soft-tipped earpiece in the baby’s ear, after which gentle clicking sounds were played. The ear response was picked up by the screening equipment. OAE is absent when hearing loss exceeds 45–50 dB HL [7].

Two outcome categories were obtained with OAE: (a) DPOAE is absent; (b) DPOAE is clearly present and normal.

Absent DPOAE: when the DPOAE is not present at two or more f2 frequencies with sufficient signal-to-noise ratio (SNR) the absent DPOAE result usually indicates cochlear dysfunction.

Present DPOAE: (a) greater than 3–6 dB SNR at approximately 70 percent of the collected data points; and (b) appropriate absolute amplitude for the patient’s age. It is important to note that both criteria must be met to consider a response completely normal.

The Brainstem Evoked Response Audiometry (BERA) test involved placing 3 small sensors on the baby’s forehead, nape of neck and shoulder. Soft headphones were placed over the baby’s ears and gentle clicking sounds were played. If BERA test results do not show a clear response in one or both of the baby’s ears, they were labeled fail. However, if the test result showed a clear response in both the baby’s ears, it was labeled pass.

Results and Observation

Blood Glucose Level (Oral Glucose Tolerance Test) Wise Ditribution

The mean blood glucose level [by oral glucose tolerance testing (OGTT), 100-g, 3-h] of mothers of neonates examined was 168 mg/dl with a standard deviation of 15 mg/dl among the exposed and 105 mg/dl with a standard deviation of 18 mg/dl among the non-exposed (Fig. 1). The increased prevalence of hearing loss among the neonates of mothers with a higher OGTT proved to be of statistical significance with a p-value of 0.0001.

Fig. 1.

Consort diagram

Distribution According to Fasting Blood Glucose (FBS) Levels of Mothers

The mean FBS level of mothers of neonates examined was 97.64 mg/dl with a standard deviation of 18.25 mg/dl among the exposed and 81.22 mg/dl with a standard deviation of 8.85 mg/dl among the non-exposed. The increased prevalence of hearing loss among the neonates of mothers with a higher mean FBS level proved to be of statistical significance with a p-value of 0.0001.

Distribution According to Random Blood Glucose (RBS) Levels of Mothers

The mean RBS level of mothers of neonates examined was 154.84 mg/dl with a standard deviation of 10.1 mg/dl among the exposed and 169.75 mg/dl with a standard deviation of 19.27 mg/dl among the non-exposed. The increased prevalence of hearing loss among the neonates of mothers with a higher mean RBS level proved to be of statistical significance with a p-value of 0.0001.

Otoacoustic Emission Testing

Among the exposed, 81.7% neonates showed a positive OAE test and 18.3% neonates showed a negative OAE test. Among the non-exposed, 86.7% neonates showed a positive OAE test and 13.3% showed a negative OAE test. The difference of negative OAE test results was statistically significant between the 2 groups with a p-value of 0.0043.

Brainstem Evoked Response Audiometry (Bera)

Among the exposed, 86.7% neonates showed a PASS and hence were diagnosed with NO HEARING IMPAIRMENT whereas 13.3% neonates showed a FAIL and hence were diagnosed with IMPAIRED HEARING. Among the non-exposed, 93.3% neonates showed a PASS (i.e. NO HEARING IMPAIRMENT) and 6.7% showed a FAIL (i.e. IMPAIRED HEARING). The difference of FAIL test results was statistically significant between the 2 groups with a p-value of 0.024.

Discussion

The increased prevalence of hearing loss among the neonates of mothers with a higher mean blood glucose level (OGTT) (Table 1), higher FBS (Table 2) and a higher RBS (Table 3) proved to be of statistical significance with a p-value of 0.0001 each (Table 4).

Table 1.

Blood glucose level (OGTT) wise ditribution

	Exposed		Non-exposed		Total		p-value
	Mean	SD	Mean	SD	Mean	SD
Blood Glucose (OGTT) (mg/dL)	168	15	105	18	136	36	0.0001

Table 2.

Distribution according to fasting blood glucose (FBS) levels of mothers

	Exposed		Non-exposed		Total		p-value
	Mean	SD	Mean	SD	Mean	SD
FBS (mg/dL)	97.64	18.25	81.22	8.85	89.43	16.49	0.0001

Table 3.

Distribution according to random blood glucose (RBS) levels of mothers

	Case		Control		Total		p-value
	Mean	SD	Mean	SD	Mean	SD
RBS (mg/dL)	154.84	10.01	169.75	19.27	162.29	17.02	0.0001

Table 4.

Otoacoustic emission testing results

	Exposed		Non-exposed		Total		p-value
	Count	Column N %	Count	Column N %	Count	Column N %
Otoacoustic emission
Absent	11	18.3	8	13.3	19	15.8	0.0043
Present	49	81.7	52	86.7	101	84.2

This study was conducted to evaluate the effect of Gestational Diabetes Mellitus (GDM) on hearing impairments of neonates. It was observed that in the exposed group (with GDM), 13.3% neonates were diagnosed with impaired hearing and 86.7% neonates were diagnosed with no hearing impairment. In the non-exposed group, 6.7% neonates were diagnosed with impaired hearing and 93.3% neonates were diagnosed with no hearing impairment. The difference of neonates diagnosed with hearing impairment in the exposed and non-exposed groups was statistically significant with a p-value of 0.024. The Odds Ratio (OR) was observed to be 2.1538, 95% CI 0.6120–7.5796, p < 0.05 (Tables 5, 6).

Table 5.

Brainstem evoked response audiometry (BERA) testing results

	Exposed		Non-exposed		Total		p-value
	Count	Column N %	Count	Column N %	Count	Column N %
BERA
Fail	8	13.3	4	6.7	12	10.0	0.024
Pass	52	86.7	56	93.3	108	90.0

Table 6.

Comparison of results with prior studies

Studies	Prevalence of Hearing impaired in GDM	Odd’s Ratio	No. of Patients
Our Study	13.3%	2.1538	11 (out of 60 GDM pregnancies)
Padmadasan et al.[3]	3.06%	7 (approx.)	4 (out of 120 diabetic mothers)
Joshua A Lee et al. [4]	71.1% in Children of diabetic pregnancies	1.66	221 (out of 311 CDPs)
Jun-Hong Zhou et al.[11]	4.35%	3.8312	3 (out of 69 GDM pregnancies)
Susan Sabbagh et al.[12]	8.9%	3.6358	17 (out of 190 GDM pregnancies)
Fatih Mehmet Hanege et al. [14]	0%	1.4056	0 (out of 71 GDM pregnancies)
Gangadhara et al.[15]	13.63%	1.7876	6 (out of 44 GDM pregnancies)

The present findings of this study also found that the newborns of mothers with GDM were at a higher risk of hearing loss. Padmadasan and his colleagues [3] reported the prevalence of deafness in neonates of mothers with diabetes mellitus was 7 times higher than the prevalence of this loss in neonates without any risk-factor.

However, a systematic review reported contradictory results regarding neonatal hearing loss in the presence of gestational diabetes during pregnancy [8]. Because of the high energy utilization of the inner ear and due to microangiopathic processes that follow glucoprotein deposition caused by hyperglycemia, it is possible that gestational diabetes affects the auditory system [9].

Lee JA et al. [4] observed that the Children of diabetic pregnancies were at significant risk for the development of hearing loss (OR 1.66, 95%CI 1.28–2.17). Clear distinction between gestational diabetes and prediabetes was not made in their study.

Maternal diabetes was identified as one of the potential risk factors for hearing impairment in the baby by Kountakis et al. [10].

In a matched case–control study done by A. Selcuk et al. [5] there were no significant differences in average pure tone air-bone hearing thresholds between the groups (p > 0.05). However, evaluation of high-frequency hearing thresholds indicated significantly increased auditory thresholds at 10 kHz and 12 kHz for right ears and at 8, 10, 12 and 14 kHz for left ears in the gestational diabetes group (p < 0.001).

In a study by Jun-Hong Zhou et al. [11], a significant difference was seen in the result of hearing screening between babies born to GDM and non GDM mothers and it was concluded that GDM increases the incidence of abnormal hearing in newborns.

In an analytical case–control study by Susan Sabbagh et al. [12], several risk factors proved out to be statistically significant including, GDM (p-value = 0.01); Low Birth Weight (p-value = 0.01) and exposure to ototoxic drugs (p-value = 0.001).

In a study by Angeli C. Carlos-Hiceta et al. [13] it was found that the odds of having a ‘refer’ result in the initial hearing screening test (transient evoked otoacoustic emissions) of a baby born to a diabetic mother is 2 × higher when compared with the results of a baby born to a non-diabetic mother. This finding is similar to the observations of the present study.

A retrospective study was conducted by Fatih Mehmet Hanege et al. [14], there was no difference between the hearing screening (OAE) results of infants born to healthy women and women with GDM..

In a prospective institutional based study by Gangadhara K. S. et al. [15], 6 neonates born out of 44 GDM pregnancies failed the screening test, however this result was not significant statistically when compared to the controls. (p-value = 0.181).

Gestational diabetes is a metabolically heterogeneous disorder. Various studies have shown that the cochlear system may be altered in diabetic patients; about 24 per cent of diabetic patients have impaired hearing [16].

Many clinical trials have revealed a relationship between hearing loss and diabetes. A recent meta-analysis showed type 2 diabetic patients to have a significantly higher incidence of at least mild hearing loss [17].

In a study by Ozel et al., hearing thresholds at all frequencies (except 0.5 kHz for bone conduction) and speech recognition scores values were significantly lower in patients with diabetes mellitus than in control participants [18].

Biurrun et al. [19] identified 11 cases (23.9 per cent) of mild SNHL, mostly at high frequencies, with no associated auditory complaints.

These studies have established inner-ear vessel involvement and alterations to vascular striae in diabetic patients, strongly suggesting a causative link between diabetes and hearing loss. The auditory system requires high glucose levels because of the high energy utilization of its complex signal processing activity.

Hearing loss in the context of type 2 diabetes may result from microangiopathic processes that follow glucoprotein deposition caused by hyperglycaemia in small blood vessels, which affects neurological function [20].

Vascular and neurological aetiologies, including effects of diabetes on the central nervous system, in addition to mitochondrial abnormalities and genetic causes have been proposed to explain the link between hearing loss and type 2 diabetes [20, 21].

While many studies have reported distinct effects of type 2 diabetes on the auditory system, none have investigated the effects of gestational diabetes on the auditory system. Recognized maternal complications of gestational diabetes include an increased risk of developing type 2 diabetes, metabolic syndrome and cardiovascular diseases [22, 23].

Altered glucose metabolism in pregnancy may influence inner ear physiology to resemble that seen in diabetic patients. Gestational diabetes may result in hearing loss to a similar extent to that seen in diabetes mellitus. However, a robust evaluation of hearing loss associated with gestational diabetes requires larger study populations and additional research focusing on the mechanism of the pathology.

Conclusion

The birth of a child is a universal cause for celebration that transcends race, ethnicity, and culture. However, a diagnosis of Gestational diabetes mellitus for expectant, wishful mothers can be devastating news. Apart from the already known complications of GDM, it still remains an unchartered territory when it comes to the less known complications. One such complication is hearing impairment in the neonate. Through our rigorous exclusion of the already known risk factors (such as NICU stay, positive family history, craniofacial deformities, overt diabetes), we have tried to isolate GDM as an independent risk factor for neonatal hearing impairment. Neonatal hearing impairment has the ability to cause immense burden on the lives of the families involved in terms of money, child care and a lifelong disability. Through this study, we hope to provide a basis on which a neonatal hearing screening program can be created in order to detect the cases early and therefore provide some assistance in early intervention, creating awareness among mothers and help in decreasing the disease burden.

Author Contributions

All authors contributed to the study conception and design. Material preparation, data collection and analysis were performed by NM, KS and RK. The first draft of the manuscript was written by NM and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript. Conceptualization: KS, NM and RK; Methodology: KS, NM and RK; Formal analysis and investigation: KS, NM and RK; Writing—original draft preparation: NM; Writing—review and editing: NM; Funding acquisition: NM; Supervision: KS and RK.

Funding

The research leading to these results received funding from the Indian Council Of Medical Research (ICMR) under Grant Agreement No.3/2/Dec-2021/PG-Thesis-HRD (01).

Declarations

Conflict of interest

The authors declare no conflict of interest during the making of this manuscript.

Ethical Approval.

Ethical clearance was taken prior to conducting the study from the institutional ethics committee of Srimanta Sankaradeva University of Health Sciences (No. MC/190/2007/Pt.II/April-2021/TH-1) and the study was performed in accordance with the ethical standards as laid down in the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards.

Informed Consent

A well-documented, written and informed consent was taken from the parents of all the neonates participating in the study.