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Hearing defects in children born of mothers suffering from rubella in the first trimester of pregnancy
International Journal of Pediatric Otorhinolaryngology 54 (2000) 1 – 5 www.elsevier.com/locate/ijporl
Hearing defects in children born of mothers suffering from rubella in the first trimester of pregnancy Graz; yna Niedzielska a,*, Emilia Ka˛tska a, Dariusz Szymula b a
Department of Paediatric Otolaryngology, Phoniatry and Audiology, Medical Academy, Lublin, Poland b Department of Obstetrics and Perinatology, Medical Academy, Lublin, Poland Received 25 November 1999; received in revised form 27 March 2000; accepted 27 March 2000
Abstract The investigations concerned women that had suffered from symptomatic rubella in the first trimester of pregnancy. The presence of immunoglobulin G and immunoglobulin M antibodies in mothers and their children was detected, and the hearing organ was examined. In early childhood (up to 3 years of age), hearing loss was confirmed in 50% of the children born of mothers with rubella. © 2000 Elsevier Science Ireland Ltd. All rights reserved. Keywords: Rubella; Hearing disorders
1. Introduction Norman MacAlister Gregg’s findings in 1941 concerning the consequences of rubella in pregnant mothers resulted in the necessary development of methods reducing morbidity, especially in women in the procreative period. The attempts at virus isolation ended successfully in 1962 and since then, laboratory diagnostics have been carried out. However, despite vaccinations against rubella, it has not been completely eliminated [9,12]. Rubella morbidity in the population reached approximately 4% during the epidemic and 1.4% in the nonepidemic period. The morbidity percentage of women belonging to a procreative age group prior to vaccination reached * Corresponding author.
10–20% and after vaccination, it decreased to 2.5–10%. In Poland, due to subsequent epidemics that broke out in the past 20 years, a significant increase of morbidity has been observed (Fig. 1) [8]. In Poland, the incidence of rubella in 1986 was 1235 per 100 000 inhabitants. In Lublin district, it was even higher: 1751 per 100 000 inhabitants. The authors of publications concerning rubella rarely mentioned congenital rubella, the ethiology of which was confirmed by laboratory tests as well as the clinical examination of children at pre-school age [5]. The objective of this study was to verify the clinical diagnosis of rubella by laboratory tests and to evaluate it clinically, taking into account the hearing organ of children born of mothers with the clinical and laboratory exponent of rubella during pregnancy [5].
0165-5876/00/$ - see front matter © 2000 Elsevier Science Ireland Ltd. All rights reserved. PII: S 0 1 6 5 - 5 8 7 6 ( 0 0 ) 0 0 3 1 9 - 0
G. Niedzielska et al. / Int. J. Pediatr. Otorhinolaryngol. 54 (2000) 1–5
2
2. Material and methods From 1 March to 30 June 1986 [10], during the rubella epidemic, specific antibodies of immunoglobulin (Ig)G and IgM classes were tested with Rubazyme and Rubazyme-M sets (Abbott Company, USA). According to the producer’s instruction, the presence of antibodies is confirmed when the automatically calculated index exceeds a value of 1.0 for IgG antibodies or is equal to or higher than 1.09 for IgM antibodies [4]. Twenty pregnant women with the clinical symptoms of rubella and eight newborns of mothers with clinical symptoms of the disease were the subject of investigations. Tests were carried out in the first and tenth years of life. The data concerning body weight, height, head and chest circumference, as well as psychomotor development were obtained from questionnaires. The laryngological and audiological tests, including pure-tone audiometry and impedance audiometry as well as auditory brain stem responses (ABR), were performed.
3. Results On the basis of laboratory tests, specific antibodies IgG and IgM were found in 55.5% of women with clinical symptoms of rubella. Asymptomatic rubella was confirmed in 2% of randomly tested women. The transmission rate within the womb measured by the presence of IgM antibod-
Fig. 1. Congenital rubella in Poland in during 1966–1990.
ies in a newborn after the symptomatic rubella infection during the first trimester of pregnancy was equal to 87.5%. In two children examined in their first year of life, sensorineural hearing loss was confirmed. Congenital heart disease was diagnosed in two children. In one of them, Gregg’s syndrome was also found (Table 1). In the evaluated group, hearing loss, in each case reaching a different level of intensification, was diagnosed in four out of eight tested children. The audiological test showed bilateral deep hearing loss higher than 100 dB in two children (Gregg’s syndrome). One child suffered from asymmetric hearing loss: 80–100 dB in the right ear and 50–70 dB in the left ear. In the fourth child with congenital rubella, symmetric sensorineural hearing loss was confirmed, reaching 40–70 dB with the presence of stapedial reflex. Pure-tone audiometry and impedance audiometry did not display any deviations in four other children. On the basis of the hearing potentials from the brain stem conduction, disturbances within the stem were observed in the form of elongation of the latency of waves III and V in two children and elongation of intervals I–V in one child. In six cases, serologic tests performed on the newborns of mothers with asymptomatic rubella showed the presence of rubella antibodies (IgG, IgM). Of six naturally born children, only one newborn was examined audiologically. In our studies, we observed the discrepancy between ABR and pure-tone audiometry results: ABR showed the elongation of latency of waves III and V, while pure-tone audiometry a correct hearing. As we noticed, heart defect accompanied hearing loss in two cases. However, heart defect as a consequence of the infection occurs relatively seldom, most often when it takes place before the tenth week of pregnancy. In all children with hearing disorders, thrombocytopenia was observed in infancy. It was not observed in children diagnosed with no congenital defects. Temporary thrombocytopenia and hemorrhagic diathesis may be treated as the prognostic symptom of rubella syndrome development in children. The children of mothers with nonsymptomatic presence of IgM antibodies developed regularly.
Number
Mother Age (years)
Newborn Pregnancy period (week)
IgM
IgG
IgM
IgG
1 2 3
27 24 23
11 5 10
+ + +
+ + +
+ + +
+ + +
4 5 6 7 8
26 20 23 21 22
8 7 4 8 10
+ + + + +
+ + + + +
+ − + +/− +
+ + + + +
Clinical study
Correct Correct Heart defect, hemorrhagic diathesis, deafness, ocular damage, anemia, jaundice, hepatosplenomegalia Correct Correct Heart defect, hemorrhagic diathesis, deafness, ocular damage, anemia, jaundice Hemorrhagic diathesis, ocular damage, hearing loss, Thrombocytopenia, hemorrhagic diathesis, hearing loss
G. Niedzielska et al. / Int. J. Pediatr. Otorhinolaryngol. 54 (2000) 1–5
Table 1 Specific immunoglobulins for the rubella virus
3
4
G. Niedzielska et al. / Int. J. Pediatr. Otorhinolaryngol. 54 (2000) 1–5
The subsequent audiometric tests performed at the age of 10 confirmed the conduction disturbances within the stem, with correct results in the pure-tone audiometry in three of five children, in whom no changes were observed in the hearing organ within 1 year of life.
4. Discussion Rubella virus causes defects of the fetus during the first 3 months of pregnancy. Severe sensorineural hearing loss, being the element of Gregg syndrome, is a well-known rubella complication. Clinical tests conducted on eight newborns whose mothers had suffered from rubella during the first 3 months of pregnancy confirmed that only in one of them did the infection develop into multiorgan defects leading to Gregg syndrome. The tests on the children of mothers who had suffered from rubella had been performed for many years and concerned many aspects, such as the development of speech and psychomotor development as well as learning difficulties. Weinberger et al. observed significant speech retardation [11]. These authors suggest that the disorders may be connected with undiagnosed rubella, therefore they suggest serological screening tests of infants born during rubella epidemics. Forrest and Menser carried out tests on children with congenital rubella who had learning difficulties. The authors tried to find the correlation between the period of disease during pregnancy and the multiorgan disorders, such as hearing loss and central nervous system (CNS) defects [2]. Learning difficulties displayed by children with congenital rubella were mainly due to hearing loss, chorioretinopathia and CNS disorders. No correlation was found between the disease period during pregnancy and incidence of hearing and vision disorders, cardiovascular changes and CNS defects. Gregg syndrome states that hearing loss occurs as a result of the infection that takes place after the eighth week of pregnancy [2,11]. Richards describes cases of conductive hearing loss in children with congenital rubella that results from immobilization of stapes or middle ear effusion [6]. This effect may be explained by the development of the middle ear
prior to the development of the inner ear. In the case of acting virus during the sixth week of gestational age, there is a possibility of inner ear defect. Carruthers’ post-mortem pathomorphological tests proved post-rubella pathology within the cochlea and sacculus, causing Scheibe-type defect. Schall also noticed the stapes pathology of the fetus [6]. In our material, the conductive hearing loss was not observed. All our patients (except one case with Gregg syndrome) demonstrated correct development of speech, and did not have any learning difficulties. During the examinations performed at the age of 10, in 50% of the children, sensorineural hearing loss was reported, and in 38% (three children), intra-brainstem disorders were found in ABR tests. Laryngological and audiological tests were, in all cases, supplemented by logopedical tests and psychomotor evaluation. On the basis of our tests, we can assume that the consequences of rubella may appear later as the result of autoimmunizing factors activity. Appearance of diabetes, hyper or hypothyroidism in teenagers with congenital rubella was observed [1,3,7]. From the results of the tests, the following conclusions can be drawn. 1. Rubella diagnosis should be based on clinical tests supported by laboratory tests (55.5% compliance). 2. In children whose mothers had suffered from symptomatic rubella, we observed, in the majority of cases, changes in hearing organ. 3. The prognostic factor of rubella syndrome development is the hemorrhagic diathesis in infancy. 4. Children with congenital rubella should be under permanent audiological control because of possible development of defects in the future.
References [1] W.L. Clark, K.A. Shaver, G.M. Bright, A.D. Rogol, W.E. Nance, Autoimmunity in congenital rubella syndrome, J. Pediatr. 104 (3) (1984) 370 – 374. [2] J.M. Forrest, M.A. Menser, Congenital rubella in schoolchildren and adolescents, Arch. Dis. Child. 45 (1970) 63 – 69.
G. Niedzielska et al. / Int. J. Pediatr. Otorhinolaryngol. 54 (2000) 1–5 [3] F. Ginsberg-Fellner, M.E. Witt, B. Fedun, F. Taub, M.J. Dobersen, R.C. McEvoy, L.Z. Cooper, A.L. Notkins, P. Rubinstein, Diabetes mellitus and autoimmunity in patients with the congenital rubella syndrome, Rev. Inf. Dis. 7 (Suppl. 1) (1985) 170–173. [4] S. O’Shea, J. Best, J.E. Banatvala, A lymphocyte transformation assay for the diagnosis of congenital rubella, J. Virol. Methods 37 (1992) 139–143. [5] C.S. Peckham, J.A. Martin, W.C. Marshall, J.A. Dudgeon, Congenital rubella deafness: a preventable disease, Lancet 1 (8110) (1979) 258–261. [6] C.S. Richards, Middle ear changes in rubella deafness, Arch. Otolaryngol. 80 (1964) 48–59. [7] P. Rubinstein, M.E. Walker, B. Fedun, M.E. Witt, L.Z. Cooper, F. Ginsberg-Fellner, The HLA system in congenital rubella patients with and without diabetes, Diabetes 31 (12) (1982) 1088–1091.
.
5
[8] H. Rudnicka, Rozyczka — 1986 rok, Przeg. Epid. 1 (1988) 31 – 40. [9] F.J. Stanley, M. Sim, G. Wilson, S. Worthinghton, The decline in congenital rubella syndrome in Western Australia: an impact of the school girl vaccination program?, Am. J. Public Health 76 (1) (1986) 35 – 37. [10] D. Szymula, Badania obecnosci przeciwcial klasy IgG i IgM skierowanych przeciwko wirusowi ro´zyczki u pacjento´w w okresie okoloepidemicznym z wyodreˆbnieniem przypadko´w zespolu rozyczki wrodzonej. Doctor dissortation, Medical Academy, Lublin, 1994. [11] M.M. Weinberger, M.W. Masland, R.A. Asbed, J.L. Sever, Congenital rubella presenting as retarded language development, Am. J. Dis. Child. 120 (1970) 125 – 128. [12] S.M. Zakzauk, H. Al Muhaimed, Prevalence of sensorineural hearing loss due to rubella in Saudi children. ORL, J. Otorhinolaryngol. Relat. Spec. 58 (2) (1996) 74 – 77.
Hearing defects in children born of mothers suffering from rubella in the first trimester of pregnancy Graz; yna Niedzielska a,*, Emilia Ka˛tska a, Dariusz Szymula b a
Department of Paediatric Otolaryngology, Phoniatry and Audiology, Medical Academy, Lublin, Poland b Department of Obstetrics and Perinatology, Medical Academy, Lublin, Poland Received 25 November 1999; received in revised form 27 March 2000; accepted 27 March 2000
Abstract The investigations concerned women that had suffered from symptomatic rubella in the first trimester of pregnancy. The presence of immunoglobulin G and immunoglobulin M antibodies in mothers and their children was detected, and the hearing organ was examined. In early childhood (up to 3 years of age), hearing loss was confirmed in 50% of the children born of mothers with rubella. © 2000 Elsevier Science Ireland Ltd. All rights reserved. Keywords: Rubella; Hearing disorders
1. Introduction Norman MacAlister Gregg’s findings in 1941 concerning the consequences of rubella in pregnant mothers resulted in the necessary development of methods reducing morbidity, especially in women in the procreative period. The attempts at virus isolation ended successfully in 1962 and since then, laboratory diagnostics have been carried out. However, despite vaccinations against rubella, it has not been completely eliminated [9,12]. Rubella morbidity in the population reached approximately 4% during the epidemic and 1.4% in the nonepidemic period. The morbidity percentage of women belonging to a procreative age group prior to vaccination reached * Corresponding author.
10–20% and after vaccination, it decreased to 2.5–10%. In Poland, due to subsequent epidemics that broke out in the past 20 years, a significant increase of morbidity has been observed (Fig. 1) [8]. In Poland, the incidence of rubella in 1986 was 1235 per 100 000 inhabitants. In Lublin district, it was even higher: 1751 per 100 000 inhabitants. The authors of publications concerning rubella rarely mentioned congenital rubella, the ethiology of which was confirmed by laboratory tests as well as the clinical examination of children at pre-school age [5]. The objective of this study was to verify the clinical diagnosis of rubella by laboratory tests and to evaluate it clinically, taking into account the hearing organ of children born of mothers with the clinical and laboratory exponent of rubella during pregnancy [5].
0165-5876/00/$ - see front matter © 2000 Elsevier Science Ireland Ltd. All rights reserved. PII: S 0 1 6 5 - 5 8 7 6 ( 0 0 ) 0 0 3 1 9 - 0
G. Niedzielska et al. / Int. J. Pediatr. Otorhinolaryngol. 54 (2000) 1–5
2
2. Material and methods From 1 March to 30 June 1986 [10], during the rubella epidemic, specific antibodies of immunoglobulin (Ig)G and IgM classes were tested with Rubazyme and Rubazyme-M sets (Abbott Company, USA). According to the producer’s instruction, the presence of antibodies is confirmed when the automatically calculated index exceeds a value of 1.0 for IgG antibodies or is equal to or higher than 1.09 for IgM antibodies [4]. Twenty pregnant women with the clinical symptoms of rubella and eight newborns of mothers with clinical symptoms of the disease were the subject of investigations. Tests were carried out in the first and tenth years of life. The data concerning body weight, height, head and chest circumference, as well as psychomotor development were obtained from questionnaires. The laryngological and audiological tests, including pure-tone audiometry and impedance audiometry as well as auditory brain stem responses (ABR), were performed.
3. Results On the basis of laboratory tests, specific antibodies IgG and IgM were found in 55.5% of women with clinical symptoms of rubella. Asymptomatic rubella was confirmed in 2% of randomly tested women. The transmission rate within the womb measured by the presence of IgM antibod-
Fig. 1. Congenital rubella in Poland in during 1966–1990.
ies in a newborn after the symptomatic rubella infection during the first trimester of pregnancy was equal to 87.5%. In two children examined in their first year of life, sensorineural hearing loss was confirmed. Congenital heart disease was diagnosed in two children. In one of them, Gregg’s syndrome was also found (Table 1). In the evaluated group, hearing loss, in each case reaching a different level of intensification, was diagnosed in four out of eight tested children. The audiological test showed bilateral deep hearing loss higher than 100 dB in two children (Gregg’s syndrome). One child suffered from asymmetric hearing loss: 80–100 dB in the right ear and 50–70 dB in the left ear. In the fourth child with congenital rubella, symmetric sensorineural hearing loss was confirmed, reaching 40–70 dB with the presence of stapedial reflex. Pure-tone audiometry and impedance audiometry did not display any deviations in four other children. On the basis of the hearing potentials from the brain stem conduction, disturbances within the stem were observed in the form of elongation of the latency of waves III and V in two children and elongation of intervals I–V in one child. In six cases, serologic tests performed on the newborns of mothers with asymptomatic rubella showed the presence of rubella antibodies (IgG, IgM). Of six naturally born children, only one newborn was examined audiologically. In our studies, we observed the discrepancy between ABR and pure-tone audiometry results: ABR showed the elongation of latency of waves III and V, while pure-tone audiometry a correct hearing. As we noticed, heart defect accompanied hearing loss in two cases. However, heart defect as a consequence of the infection occurs relatively seldom, most often when it takes place before the tenth week of pregnancy. In all children with hearing disorders, thrombocytopenia was observed in infancy. It was not observed in children diagnosed with no congenital defects. Temporary thrombocytopenia and hemorrhagic diathesis may be treated as the prognostic symptom of rubella syndrome development in children. The children of mothers with nonsymptomatic presence of IgM antibodies developed regularly.
Number
Mother Age (years)
Newborn Pregnancy period (week)
IgM
IgG
IgM
IgG
1 2 3
27 24 23
11 5 10
+ + +
+ + +
+ + +
+ + +
4 5 6 7 8
26 20 23 21 22
8 7 4 8 10
+ + + + +
+ + + + +
+ − + +/− +
+ + + + +
Clinical study
Correct Correct Heart defect, hemorrhagic diathesis, deafness, ocular damage, anemia, jaundice, hepatosplenomegalia Correct Correct Heart defect, hemorrhagic diathesis, deafness, ocular damage, anemia, jaundice Hemorrhagic diathesis, ocular damage, hearing loss, Thrombocytopenia, hemorrhagic diathesis, hearing loss
G. Niedzielska et al. / Int. J. Pediatr. Otorhinolaryngol. 54 (2000) 1–5
Table 1 Specific immunoglobulins for the rubella virus
3
4
G. Niedzielska et al. / Int. J. Pediatr. Otorhinolaryngol. 54 (2000) 1–5
The subsequent audiometric tests performed at the age of 10 confirmed the conduction disturbances within the stem, with correct results in the pure-tone audiometry in three of five children, in whom no changes were observed in the hearing organ within 1 year of life.
4. Discussion Rubella virus causes defects of the fetus during the first 3 months of pregnancy. Severe sensorineural hearing loss, being the element of Gregg syndrome, is a well-known rubella complication. Clinical tests conducted on eight newborns whose mothers had suffered from rubella during the first 3 months of pregnancy confirmed that only in one of them did the infection develop into multiorgan defects leading to Gregg syndrome. The tests on the children of mothers who had suffered from rubella had been performed for many years and concerned many aspects, such as the development of speech and psychomotor development as well as learning difficulties. Weinberger et al. observed significant speech retardation [11]. These authors suggest that the disorders may be connected with undiagnosed rubella, therefore they suggest serological screening tests of infants born during rubella epidemics. Forrest and Menser carried out tests on children with congenital rubella who had learning difficulties. The authors tried to find the correlation between the period of disease during pregnancy and the multiorgan disorders, such as hearing loss and central nervous system (CNS) defects [2]. Learning difficulties displayed by children with congenital rubella were mainly due to hearing loss, chorioretinopathia and CNS disorders. No correlation was found between the disease period during pregnancy and incidence of hearing and vision disorders, cardiovascular changes and CNS defects. Gregg syndrome states that hearing loss occurs as a result of the infection that takes place after the eighth week of pregnancy [2,11]. Richards describes cases of conductive hearing loss in children with congenital rubella that results from immobilization of stapes or middle ear effusion [6]. This effect may be explained by the development of the middle ear
prior to the development of the inner ear. In the case of acting virus during the sixth week of gestational age, there is a possibility of inner ear defect. Carruthers’ post-mortem pathomorphological tests proved post-rubella pathology within the cochlea and sacculus, causing Scheibe-type defect. Schall also noticed the stapes pathology of the fetus [6]. In our material, the conductive hearing loss was not observed. All our patients (except one case with Gregg syndrome) demonstrated correct development of speech, and did not have any learning difficulties. During the examinations performed at the age of 10, in 50% of the children, sensorineural hearing loss was reported, and in 38% (three children), intra-brainstem disorders were found in ABR tests. Laryngological and audiological tests were, in all cases, supplemented by logopedical tests and psychomotor evaluation. On the basis of our tests, we can assume that the consequences of rubella may appear later as the result of autoimmunizing factors activity. Appearance of diabetes, hyper or hypothyroidism in teenagers with congenital rubella was observed [1,3,7]. From the results of the tests, the following conclusions can be drawn. 1. Rubella diagnosis should be based on clinical tests supported by laboratory tests (55.5% compliance). 2. In children whose mothers had suffered from symptomatic rubella, we observed, in the majority of cases, changes in hearing organ. 3. The prognostic factor of rubella syndrome development is the hemorrhagic diathesis in infancy. 4. Children with congenital rubella should be under permanent audiological control because of possible development of defects in the future.
References [1] W.L. Clark, K.A. Shaver, G.M. Bright, A.D. Rogol, W.E. Nance, Autoimmunity in congenital rubella syndrome, J. Pediatr. 104 (3) (1984) 370 – 374. [2] J.M. Forrest, M.A. Menser, Congenital rubella in schoolchildren and adolescents, Arch. Dis. Child. 45 (1970) 63 – 69.
G. Niedzielska et al. / Int. J. Pediatr. Otorhinolaryngol. 54 (2000) 1–5 [3] F. Ginsberg-Fellner, M.E. Witt, B. Fedun, F. Taub, M.J. Dobersen, R.C. McEvoy, L.Z. Cooper, A.L. Notkins, P. Rubinstein, Diabetes mellitus and autoimmunity in patients with the congenital rubella syndrome, Rev. Inf. Dis. 7 (Suppl. 1) (1985) 170–173. [4] S. O’Shea, J. Best, J.E. Banatvala, A lymphocyte transformation assay for the diagnosis of congenital rubella, J. Virol. Methods 37 (1992) 139–143. [5] C.S. Peckham, J.A. Martin, W.C. Marshall, J.A. Dudgeon, Congenital rubella deafness: a preventable disease, Lancet 1 (8110) (1979) 258–261. [6] C.S. Richards, Middle ear changes in rubella deafness, Arch. Otolaryngol. 80 (1964) 48–59. [7] P. Rubinstein, M.E. Walker, B. Fedun, M.E. Witt, L.Z. Cooper, F. Ginsberg-Fellner, The HLA system in congenital rubella patients with and without diabetes, Diabetes 31 (12) (1982) 1088–1091.
.
5
[8] H. Rudnicka, Rozyczka — 1986 rok, Przeg. Epid. 1 (1988) 31 – 40. [9] F.J. Stanley, M. Sim, G. Wilson, S. Worthinghton, The decline in congenital rubella syndrome in Western Australia: an impact of the school girl vaccination program?, Am. J. Public Health 76 (1) (1986) 35 – 37. [10] D. Szymula, Badania obecnosci przeciwcial klasy IgG i IgM skierowanych przeciwko wirusowi ro´zyczki u pacjento´w w okresie okoloepidemicznym z wyodreˆbnieniem przypadko´w zespolu rozyczki wrodzonej. Doctor dissortation, Medical Academy, Lublin, 1994. [11] M.M. Weinberger, M.W. Masland, R.A. Asbed, J.L. Sever, Congenital rubella presenting as retarded language development, Am. J. Dis. Child. 120 (1970) 125 – 128. [12] S.M. Zakzauk, H. Al Muhaimed, Prevalence of sensorineural hearing loss due to rubella in Saudi children. ORL, J. Otorhinolaryngol. Relat. Spec. 58 (2) (1996) 74 – 77.