Valganciclovir in Infants with Hearing Loss and Clinically Inapparent Congenital Cytomegalovirus Infection: A Nonrandomized Controlled Trial.

OBJECTIVE: To assess the efficacy of valganciclovir in infants with hearing loss and clinically inapparent congenital cytomegalovirus infection (cCMV), as there is no consensus on treatment of this group. STUDY DESIGN: A nationwide, nonrandomized controlled trial, comparing 6 weeks of oral valganciclovir to no treatment in infants with cCMV, recruited after newborn hearing screening resulted in referral to an audiologist. The choice whether to treat was left to parents of subjects. Eligible subjects were full term infants aged <13 weeks with sensorineural hearing loss and diagnosed with cCMV through dried blood spot testing. The primary outcome, measured by linear and ordinal logistic regression, was change in best-ear hearing from baseline to follow-up at 18-22 months of age. RESULTS: Thirty-seven participants were included in the final analysis, of whom 25 were in the treatment group and 12 in the control group. The majority of subjects in both groups had neuroimaging abnormalities, which were mostly mild. Hearing deterioration was more likely in the control group compared with the treatment group (common OR 0.10, 95% CI 0.02-0.45, P = .003). Mean best-ear hearing deteriorated by 13.7 dB in the control group, compared with improvement of 3.3 dB in the treatment group (difference 17 dB, 95% CI 2.6 - 31.4, P = .02). CONCLUSIONS: We investigated treatment in children with hearing loss and clinically inapparent cCMV. Although our study was nonrandomized, it is the first prospective and controlled trial in this population. Valganciclovir-treated children with hearing loss and inapparent cCMV had less hearing deterioration at 18 through 22 months of age than control subjects. EUDRACT REGISTRY NUMBER: 2013-003068-30.

Targeted screening for congenital cytomegalovirus infection: clinical, audiological and neuroimaging findings.

OBJECTIVE: To evaluate clinical, audiological and neuroimaging findings in a cohort of infants diagnosed with congenital cytomegalovirus (cCMV) infection after failure at newborn hearing screening. METHODS: A prospective observational study in the Netherlands, using the existing newborn hearing screening infrastructure for well babies. Between July 2012 and November 2016, cytomegalovirus (CMV) PCR testing of neonatally obtained dried blood spots (DBS) was offered to all infants who failed newborn hearing screening. Clinical, neuroimaging and audiological data were collected. RESULTS: DBS of 1374 infants were successfully tested and 59 were positive for CMV (4.3%). Data of 54 infants were retrieved. Three were small for gestational age and six had microcephaly. Forty-eight (89%) had sensorineural hearing loss (SNHL), of whom half had unilateral SNHL. In both unilaterally and bilaterally affected children, the majority of the impaired ears had severe or profound hearing loss. Neuroimaging abnormalities were found in 40 of 48 (83%) children who had evaluable cranial ultrasound and/or cerebral MRI. The abnormalities were mild in 34, moderate in 3 and severe in 3 infants. The degree of SNHL and the severity of neuroimaging abnormalities were found to be correlated (p=0.002). CONCLUSIONS: The yield of targeted cCMV screening following newborn hearing screening failure was eight times higher than the estimated national birth prevalence of cCMV. The majority of this cohort of infants with clinically unsuspected cCMV disease had confirmed SNHL, neuroimaging abnormalities and lower than average birth weights and head circumferences. Newborns who fail newborn hearing screening should be tested for CMV to ensure appropriate clinical, neurodevelopmental and audiological follow-up.

Specialized outpatient clinic for deaf and hard-of-hearing patients in the Netherlands: Lessons learned in an attempt to improve health care.

RATIONALE, AIMS, AND OBJECTIVE: A group of organizations and individuals in the Netherlands collaborated to attempt to improve access to health care and health education for deaf and hard of hearing (DHH) patients in the country. The outcome was the start of a specialized outpatient clinic named PoliDOSH. An independent research group was set up to evaluate the effect of this specialized clinic. Even though the initiative did not succeed and was closed after 2 years, an extensive analysis of the start-up and functioning of the whole process was made. METHODS: Structured and nonstructured questionnaires and structured interviews. RESULTS: Only a small group of DHH patients indicated that they felt a need for consultations at the PoliDOSH. It became clear that to ensure successful functioning of a specialized facility the team members should include a representative group of DHH members. All key functions should be filled by top experts in the relevant fields as well as an expert in communication and needs of the target group. CONCLUSIONS: There is a great need for facilities to collect and disseminate information to and about DHH patients. The information should be aimed at providing psycho-education for the DHH persons themselves and health care professionals, concerning the specific needs and problems of this patient group. If a similar facility is set up in the future, thorough market research prior to start up is needed to enable the facility to connect with the needs of patients. The start-up period should allow sufficient time for the project to become known and for patients to become familiar with it and trust it.

Quality of life of children with hearing loss in special and mainstream education: A longitudinal study.

OBJECTIVES: To compare the quality of life (QoL) of children with hearing loss (HL) and children with normal hearing (NH) and to examine how the QoL of children with HL changes over time, considering language skills, type of hearing device, degree of HL, and type of education. METHODS AND MATERIALS: This longitudinal study included 62 children with HL and their parents. Developmental outcome data were collected at two time points, when the mean ages of the children were 4 and 11 years. The Pediatric Quality of Life (PedsQL™) questionnaire, which includes assessments of Physical, Emotional, Social, and School functioning, was completed by parents at both time points and by the children with HL at the second time point. Receptive and expressive language skills at 4 years were assessed by the Reynell Developmental Language Scale. Results were compared with a Dutch normative sample. RESULTS: The QoL of children with HL was similar to that of children with NH at both time points on two of the four QoL scales, Emotional and Physical functioning. On the other two scales, Social and School functioning, children with HL who attended special education and children who switched to mainstream education showed lower scores than children with HL who were consistently in mainstream education and lower scores than children with NH. The School QoL of children with HL decreased over time, as did the School QoL of children with NH. Social QoL of children with cochlear implants decreased over time, but this was not the case in children with hearing aids. Language skills and the degree of HL did not clinically improve the QoL over time of preschool children with HL. CONCLUSIONS: The QoL of children with HL in mainstream education and the Physical and Emotional QoL of all children with HL were satisfactory. It is essential to develop specific guidance regarding school activities for children with HL in special education and for children with HL who switch to mainstream education in order to increase their social QoL.

Concise tool based on language milestones identifies children with specific language impairment at 24-45 months of age.

AIM: This study aimed to develop a concise tool with acceptable predictive properties to identify young children with specific language impairment (SLI). METHODS: In this nested case-control study children with SLI attending two special needs schools for severe speech and language difficulties in the Netherlands were matched by date of birth and sex with control children attending mainstream education. This study analysed the predictive validity for having SLI at a mean age of eight years and three months (range 4-11 years) using combinations of six language milestones that were registered at 24, 36 and 45 months and retrieved from the children's healthcare files in 2012. RESULTS: We included 253 pairs of children with and without SLI. During a single visit, combinations of two milestones at one age achieved a specificity of at least 97% and sensitivities ranged from 32% to 64%. However, the concise tool, which combined five milestones at three different ages - 24, 36 and 45 months - had a specificity of 96% (95% confidence interval 94-99%) and a sensitivity of 71% (95% confidence interval 66-77%). CONCLUSION: Combining milestones at different ages provided a concise tool that could help to detect children with SLI at a young age.

Children with specific language impairment are more likely to reach motor milestones late.

BACKGROUND: Delayed language development without an obvious cause is considered an isolated developmental disorder and is called specific language impairment (SLI). SLI is probably the most prevalent developmental disorder in childhood with a generally cited prevalence of 7%. This study aimed to investigate whether SLI is always an isolated disorder or if children with SLI also have delayed motor development. METHODS: We used data of an earlier study with a prospective nested case-control design in which developmental data were collected from child health care files. Cases were children (4-11 years) with diagnosed SLI. They were matched by sex and date of birth with control children attending mainstream education. Data of both groups on seven gross and six fine motor milestones which had been registered in the Dutch Developmental Instrument between the ages of 15-36 months were retrieved from child health care files. McNemar tests were performed to test for differences in reaching motor milestones at the age norm between the case and control group. RESULTS: Data from 253 children in each group were available. A significant difference was found between both groups in the proportion failing to reach three of the seven investigated gross motor milestones at the age norm (p < 0.05). The proportion of children not reaching the motor milestone at the age norm was significantly higher for five of the six fine motor milestones in children with SLI compared with control children (p < 0.05). CONCLUSIONS: More children with SLI are late in reaching motor milestones than children without SLI. This means that it is debatable whether SLI can be regarded as a "specific" impairment, which is not associated with other developmental problems. A broader developmental assessment is therefore indicated when diagnosing SLI.

Accuracy of a Screening Tool for Early Identification of Language Impairment.

Purpose: A screening tool called the VTO Language Screening Instrument (VTO-LSI) was developed to enable more uniform and earlier detection of language impairment. This report, consisting of 2 retrospective studies, focuses on the effects of using the VTO-LSI compared to regular detection procedures. Method: Study 1 retrospectively compared VTO-LSI with regular detection procedures. Outcome measure was the detection rate of language impairment among 24-month-old children. Data were retrieved from medical records of children attending a youth health care center. Study 2 retrospectively compared the effects of VTO-LSI and regular detection procedures on the age at referral for diagnostic investigations and the influence of sex. Data were retrieved from medical records from the speech and hearing center and analyzed with multivariate analysis of variance. Results: With the VTO-LSI, significantly more cases with language impairment were identified compared with the regular detection procedure (2.4% vs. 0.4%). In regions where the VTO-LSI was used, girls were almost 2 years younger, and boys were 1 year younger when referred to diagnostic investigations than in regions with regular detection procedures. Conclusion: The VTO-LSI was more effective than regular detection procedures.

Healthcare costs attributable to congenital cytomegalovirus infection.

OBJECTIVE: Congenital cytomegalovirus infection (cCMV) can cause symptoms at birth as well as long-term impairment. This study estimates cCMV-related healthcare costs in the Netherlands in early childhood. DESIGN, SETTING AND PATIENTS: In a nationwide retrospective cohort study, 156 children with cCMV were identified by testing 31 484 neonatal dried blood spots for cCMV. Use of healthcare resources in the first 6 years of life by children with cCMV and a matched cCMV-negative control group were analysed. Mean costs per child were calculated by multiplying healthcare resource use by its reference prices. EXPOSURE: Children with cCMV were compared with cCMV-negative children. MAIN OUTCOME MEASURES: The average total healthcare costs per child were based on the average costs for hospital admissions and consultations by healthcare providers. RESULTS: Mean healthcare costs of children with cCMV (€6113, n=133) were higher than children without cCMV (€3570, n=274), although statistically not significant, with a mean difference of €2544 (95% CI €-451 to €5538). The costs of children with long-term impairment were two times higher in children with cCMV (€17 205) compared with children without cCMV (€8332). CONCLUSIONS: Children with cCMV, especially those with long-term impairment and those symptomatic at birth, accrue higher healthcare costs than cCMV-negative children in the first 6 years of life, although this is not statistically significant. This economic impact is of importance in the evaluation of preventive measures against cCMV. TRIAL REGISTRATION NUMBER: NTR3582.

Long-term impairment attributable to congenital cytomegalovirus infection: a retrospective cohort study.

AIM: This study aimed to estimate long-term impairment attributable to congenital cytomegalovirus infection (cCMV). METHOD: This nationwide cohort study retrospectively assessed cCMV in children born in 2008 in the Netherlands, testing 31 484 stored neonatal dried blood spots. Extensive medical data of cCMV-positive children (n=133) and matched cCMV-negative comparison children (n=274) up to 6 years of age were analysed. RESULTS: Moderate to severe long-term impairment was diagnosed in 24.8% (33 out of 133) of all cCMV-positive children (53.8% in symptomatic, 17.8% in asymptomatic), compared with 12.0% (33 out of 274) of cCMV-negative children. Sensorineural hearing loss was seen only in five cCMV-positive children (3.8%). Developmental delays were diagnosed more often in cCMV-positive children than cCMV-negative children: motor (12.0% vs 1.5%), cognitive (6.0% vs 1.1%), and speech-language (16.5% vs 7.3%). Long-term impairment in multiple domains was more frequent in symptomatic (19.2%) and asymptomatic (8.4%) cCMV-positive children than cCMV-negative children (1.8%). INTERPRETATION: Children with cCMV were twice as likely to have long-term impairment up to the age of 6 years, especially developmental delays and sensorineural hearing loss, than cCMV-negative comparison children, with a risk difference of 12.8%. These insights into the risk of cCMV-associated impairment can help optimize care and stimulate preventive measures. WHAT THIS PAPER ADDS: Congenital cytomegalovirus infection (cCMV) leads to impairment in 25% of cases. Fifty per cent of children with cCMV symptoms at birth have long-term impairment. The risk difference of moderate to severe long-term impairment between children with and without cCMV is 13%, attributable to cCMV. cCMV leads to motor, cognitive, and speech-language developmental delay in children.

Congenital Cytomegalovirus Infection: Child Development, Quality of Life and Impact on Daily Life.

Congenital cytomegalovirus (cCMV) infection is the most common congenital infection worldwide and can lead to long-term impairments such as developmental delay. It is currently unknown how this affects the daily life of children and their parents. Children For this study, children with cCMV were identified by testing stored dried blood spots of 31,484 five-year-old children born in 2008 in the Netherlands. Parents of 133 children with cCMV and 274 children without cCMV participated and filled in questionnaires on the child's development, the child's and parents' quality of life, care provided for the children and consequences of cCMV on daily life. School performance reports at 6 years of age were also investigated. Children with cCMV had delays in general and expressive language development more often, and they attended physical therapists more frequently than children without cCMV. School performance of children with cCMV and symptoms at birth was poorer than that of cCMV-negative children with similar symptoms at birth. The quality of life of children with long-term impairment was lower in children with cCMV than those without cCMV. Parents of children with cCMV and long-term impairments reported more physical and concentration problems than parents of children without cCMV. These findings indicate that cCMV has a considerable impact not only on the child's development and school performance but also on the daily life of children and their parents. The care for children with cCMV should therefore include support for motor and speech-language development as well as family-centered care.

Can You Hear What I Think? Theory of Mind in Young Children With Moderate Hearing Loss.

OBJECTIVES: The first aim of this study was to examine various aspects of Theory of Mind (ToM) development in young children with moderate hearing loss (MHL) compared with hearing peers. The second aim was to examine the relation between language abilities and ToM in both groups. The third aim was to compare the sequence of ToM development between children with MHL and hearing peers. DESIGN: Forty-four children between 3 and 5 years old with MHL (35 to 70 dB HL) who preferred to use spoken language were identified from a nationwide study on hearing loss in young children. These children were compared with 101 hearing peers. Children were observed during several tasks to measure intention understanding, the acknowledgement of the other's desires, and belief understanding. Parents completed two scales of the child development inventory to assess expressive language and language comprehension in all participants. Objective language test scores were available from the medical files of children with MHL. RESULTS: Children with MHL showed comparable levels of intention understanding but lower levels of both desire and belief understanding than hearing peers. Parents reported lower language abilities in children with MHL compared with hearing peers. Yet, the language levels of children with MHL were within the average range compared with test normative samples. A stronger relation between language and ToM was found in the hearing children than in children with MHL. The expected developmental sequence of ToM skills was divergent in approximately one-fourth of children with MHL, when compared with hearing children. CONCLUSION: Children with MHL have more difficulty in their ToM reasoning than hearing peers, despite the fact that their language abilities lie within the average range compared with test normative samples.

Comparing policies for children of parents attending hospital emergency departments after intimate partner violence, substance abuse or suicide attempt.

To improve identification of child maltreatment, a new policy ('Hague protocol') was implemented in hospitals in The Netherlands, stating that adults attending the hospital emergency department after intimate partner violence, substance abuse or a suicide attempt should be asked whether they care for children. If so, these children are referred to the Reporting Center for Child Abuse and Neglect (RCCAN), for assessment and referrals to support services. An adapted, hospital-based version of this protocol ('Amsterdam protocol') was implemented in another region. Children are identified in the same manner, but, instead of a RCCAN referral, they are referred to the pediatric outpatient department for an assessment, including a physical examination, and referrals to services. We compared results of both protocols to assess how differences between the protocols affect the outcomes on implementation, detection of child maltreatment and referrals to services. Furthermore, we assessed social validity and results of a screening physical examination. We included 212 families from the Amsterdam protocol (cohort study with reports by pediatric staff and parents) and 565 families from the Hague protocol (study of RCCAN records and telephone interviews with parents). We found that the RCCAN identified more maltreatment than pediatric staff (98% versus at least 51%), but referrals to services were similar (82% versus 80% of the total sample) and parents were positive about both interventions. Physical examination revealed signs of maltreatment in 5%. We conclude that, despite the differences, both procedures can serve as suitable methods to identify and refer children at risk for maltreatment.

Failure to meet language milestones at two years of age is predictive of specific language impairment.

AIM: This study established predictive properties of single language milestones for specific language impairment (SLI) after the age of four, as these had not previously been reported in the literature. METHODS: In this nested case-control study, children attending special needs schools for severe speech and language difficulties were matched with children attending mainstream schools. Data covering the ages of zero to four years were retrieved from well-child care clinics and the outcomes of 23 language milestones in the Dutch Developmental Instrument were analysed. The predictive properties were expressed as positive likelihood ratios, sensitivity and specificity. RESULTS: We included 253 pairs of children with and without SLI, aged from four to 11 years. The mean age was eight years and three months, and 77% were boys. From the age of 18 months, cases and controls differed significantly on all milestones (p < 0.01). After 24 months, the language milestones had positive likelihood ratios that ranging from 6 to 108. In general, language milestones had a high specificity (range 77-100%), but the sensitivity was relatively low (range 0-68%). CONCLUSION: Failure to meet language milestones from the age of 24 months was predictive of SLI, but the use of separate milestones had limited value due to low sensitivity.

Early identification: Language skills and social functioning in deaf and hard of hearing preschool children.

OBJECTIVE: Permanent childhood hearing impairment often results in speech and language problems that are already apparent in early childhood. Past studies show a clear link between language skills and the child's social-emotional functioning. The aim of this study was to examine the level of language and communication skills after the introduction of early identification services and their relation with social functioning and behavioral problems in deaf and hard of hearing children. STUDY DESIGN: Nationwide cross-sectional observation of a cohort of 85 early identified deaf and hard of hearing preschool children (aged 30-66 months). METHODS: Parents reported on their child's communicative abilities (MacArthur-Bates Communicative Development Inventory III), social functioning and appearance of behavioral problems (Strengths and Difficulties Questionnaire). Receptive and expressive language skills were measured using the Reynell Developmental Language Scale and the Schlichting Expressive Language Test, derived from the child's medical records. RESULTS: Language and communicative abilities of early identified deaf and hard of hearing children are not on a par with hearing peers. Compared to normative scores from hearing children, parents of deaf and hard of hearing children reported lower social functioning and more behavioral problems. Higher communicative abilities were related to better social functioning and less behavioral problems. No relation was found between the degree of hearing loss, age at amplification, uni- or bilateral amplification, mode of communication and social functioning and behavioral problems. CONCLUSION: These results suggest that improving the communicative abilities of deaf and hard of hearing children could improve their social-emotional functioning.

Missed cases in the detection of child abuse based on parental characteristics in the emergency department (the Hague Protocol).

INTRODUCTION: We aimed to assess the number of "missed cases" in the detection of child abuse based on the Hague Protocol. This protocol considers 3 parental characteristics of ED adult patients to identify child abuse: (1) domestic violence, (2) intoxication, and (3) suicide attempt or auto-mutilation. METHODS: This study focuses on parents whose children should have been referred to the Reporting Centre for Child Abuse and Neglect (RCCAN) in the Hague, the Netherlands, according to the guidelines of the Hague Protocol. Data were collected from all referrals by the Medical Centre Haaglanden (Medisch Centrum Haaglanden) to the RCCAN in the Hague between July 1 and December 31, 2011. The hospital's database was searched to determine whether the parents had visited the emergency department in the 12 months before their child's referral to the RCCAN. RESULTS: Eight missed cases out of 120 cases were found. The reasons for not referring were as follows: forgetting to ask about children and assuming that it was not necessary to refer children if parents indicated that they were already receiving some form of family support. DISCUSSION: Barriers to identifying missing cases could be relatively easy to overcome. Regular training of emergency nurses and an automated alert in the electronic health record to prompt clinicians and emergency nurses may help prevent cases being missed in the future.

Detecting child abuse based on parental characteristics: does the Hague Protocol cause parents to avoid the emergency department?

OBJECTIVES: The Hague Protocol is used by professionals at the adult Emergency Departments (ED) in The Netherlands to detect child abuse based on three parental characteristics: (1) domestic violence, (2) substance abuse or (3) suicide attempt or self-harm. After detection, a referral is made to the Reporting Center for Child Abuse and Neglect (RCCAN). This study investigates whether implementing this Protocol will lead parents to avoid medical care. METHOD: We compared the number of patients (for whom the Protocol applied) who attended the ED prior to implementation with those attending after implementation. We conducted telephone interviews (n = 14) with parents whose children were referred to the RCCAN to investigate their experience with the procedure. RESULTS: We found no decline in the number of patients, included in the Protocol, visiting the ED during the 4 year implementation period (2008-2011). Most parents (n = 10 of the 14 interviewed) were positive and stated that they would, if necessary, re-attend the ED with the same complaints in the future. CONCLUSION: ED nurses and doctors referring children based on parental characteristics do not have to fear losing these families as patients.

What parental characteristics can predict child maltreatment at the Emergency Department? Considering expansion of the Hague Protocol.

The Hague Protocol considers three parental characteristics of Emergency Department adult patients to identify child abuse: (a) domestic violence, (b) intoxication, and (c) suicide attempt or auto mutilation. This study investigated whether additional parental characteristics could be included to improve the chance of detection. Using a nested case-control design, we compared parents identified as child abusers who were missed by the Protocol with a matched group of nonabusing parents. The parental characteristics used were, among others, all physical injuries possibly resulting from domestic violence, psychological, or mental complaints that might indicate elevated domestic stress levels and the number of Emergency Department visits during the previous year. None of the characteristics were statistically significantly associated with child abuse. The Hague Protocol will not be improved by adding one or more of the characteristics that were investigated.