1 / 68

Should EHDI Programs Be Concerned about Cytomegalovirus (CMV)?

Should EHDI Programs Be Concerned about Cytomegalovirus (CMV)?. Karen B. Fowler, DrPH Department of Pediatrics University of Alabama at Birmingham. Faculty Disclosure Information.

symona
Download Presentation

Should EHDI Programs Be Concerned about Cytomegalovirus (CMV)?

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. Should EHDI Programs Be Concerned about Cytomegalovirus (CMV)? Karen B. Fowler, DrPH Department of Pediatrics University of Alabama at Birmingham

  2. Faculty Disclosure Information In the last 12 months, I have not had a significant financial interest or other relationship with the manufacturer(s) of the product(s) or provider(s) of the service(s) that will be discussed in my presentation This presentation will not include discussion of pharmaceuticals or devices that have not been approved by the FDA.

  3. Brief Review of Congenital CMV Infection • Characteristics of Populations at Increased Risk for Congenital CMV Infections • Congenital CMV Infection & Sensorineural Hearing Loss (SNHL) • NIDCD Study • What should EHDI programs know about CMV?

  4. Cytomegalovirus (CMV) is a herpesvirus that may be transmitted from mother to fetus anytime during gestation and may or may not cause any apparent damage to the fetus (Congenital CMV Infection)

  5. Human CMV may be transmitted through either direct or indirect person-to-person contact Sources of Virus: urine semen tears blood oropharyngeal secretions cervical & vaginal secretions

  6. Human CMV may be transmitted through either direct or indirect person-to-person contact CMV is not very contagious and the spread of virus requires close or intimate contact with infected secretions

  7. Clinical evidence alone will not identify most congenital CMV infections Diagnosis of Congenital CMV Infection • Saliva or urine • Within the first 2 weeks of life • Virus isolation (culture) or identification (immunofluorescence test-DEAFF) of virus

  8. Symptoms of congenital CMV infection petechiae hyperbilirubinemia (jaundice) hepatosplenomegaly (enlarged spleen or liver) thrombocytopenia seizures intracranial calcifications microcephaly (< 5%tile)

  9. 90% of the infants with congenital CMV infection will have no clinical evidence (symptoms) of infection during the newborn period Only 10% of the infants with congenital CMV infection will have clinical evidence or symptoms of infection during the newborn period

  10. The expected 10% symptomatic estimate is based on studies of infants screened for congenital CMV infection where the investigators have reviewed their medical records for specific symptoms and categorized them accordingly. However, in our data about 2/3 of infants we classified as symptomatic were not identified by the medical staff while in the hospital as having CMV infection. This suggests unless routine CMV screening takes place, < 5% of infants with CMV infection are identified.

  11. Sequelae of congenital CMV infection Sensorineural hearing loss 19% Mental retardation (IQ < 70) 19% Retinitis 6% Cerebral Palsy 4% Neurologic problems/Seizures 6% Based on UAB data

  12. Summary Review of Congenital CMV infection • CMV is a common virus although not easily spread person to person • Diagnosis needs to be made in the first 2 weeks of life • Clinical observation of infection in the newborn period identifies < 5% of all infants with congenital CMV infection • Long term sequelae may occur following infection with sensorineural hearing loss being the most common

  13. Characteristics of Populations at Increased Risk for Congenital CMV Infections

  14. Congenital CMV Infection is the most common intrauterine infection in humans • Incidence estimates of congenital CMV infection range from 0.2% – 2.2%. • US estimates of congenital CMV infection range from 0.5% – 1.0%.

  15. The incidence of congenital CMV infection varies: • by geography • the underlying CMV seroprevalence in the maternal population • The incidence of congenital CMV infection is higher in populations where the underlying CMV seroprevalence or pre-existing immunity is higher in the mothers.

  16. Maternal Seroprevalence (%) Rate of Congenital CMV Infection (%)

  17. Similar maternal and socio-demographic factors have been associated with delivering an infant with congenital CMV infection in studies of different populations

  18. Rates of Congenital CMV Infection

  19. Caucasian (origin in any of the original people of Europe, the Middle East or North Africa)

  20. Central/South America (Hispanic-Cuban, Mexican, Puerto Rican, South or Central American, or other Spanish culture or origin, regardless of race)

  21. African or African American (origins in any of the black racial groups of Africa) *Fowler, unpublished data

  22. Asian (origins in any of the original peoples of the Far East, Southeast Asia or the Indian subcontinent) *S Broor, personal communication

  23. Incidence of Congenital CMV Infection by Racial/Ethnic Categories *Fowler, meta analysis, unpublished

  24. Prevalence of Congenital CMV Infection by Maternal Age for Newborns Screened at UAB Hospital (n=46,095) & a Private Hospital (n=9,892) Per 1000 births Maternal Age at Delivery Fowler, et. al. JID1993 & Fowler, et. al. submitted

  25. Prevalence of Congenital CMV Infection Teen MothersScreened at UAB Hospital, 1980 - 2000 African American Caucasian Per 1000 births Maternal Age at Delivery Fowler, unpublished data

  26. Summary Review of Congenital CMV Infection Rates • Congenital CMV infection will be more common in populations with high (> 70%) maternal CMV seroprevalances • African Americans and Hispanic delivery populations will have higher rates of congenital CMV infection than primarily Caucasian and Asian delivery populations • Delivery populations with large numbers of teens will have the highest rates of congenital CMV infection

  27. Congenital CMV Infection & Sensorineural Hearing Loss (SNHL)

  28. CMV Infection & Hearing Loss 1960s-CID or Symptomatic CMV Infection & HL was first reported. Medearis, 1964 McCracken, et al. 1969 1970s-Inapparent or Asymptomatic CMV Infection & HL was first reported Reynolds, et al. 1974 & Dahle, et al. 1974 Hanshaw, et al. 1976 Stagno, et al. 1977

  29. CMV Infection & Hearing Loss 1970s & 1980s-Progression and Delayed Onset Hearing Loss were first described Dahle, et al. 1979 Pass, et al. 1980 Williamson, et al. 1982

  30. Population Based Longitudinal Studies Delayed Onset Loss Symptoms N SNHL N (%) Progressive Loss Fluctuating Loss Hamilton, Canada 3 Sx 1 (33) N Y N Saigal, et. al. 198238 ASx 6 (16) Malmö, Sweden 9 Sx 2 (22) N N N Ahlfors, et. al. 198434 ASx 2 (6) London, England 3 Sx 1 (33) Y N N Preece, et. al. 198447 ASx 4 (8)

  31. Population Based Longitudinal Studies Delayed Onset Loss Symptoms N SNHL N (%) Progressive Loss Fluctuating Loss Cleveland, US 17 ASx 4 (23) N N Y Kumar, et. al. 1984 Houston, US 17 Sx 11 (65) Y N Y Williamson, et al. 1982 59 ASx 9 (15) Williamson, et al. 1992 Birmingham, US 209 Sx 85 (41) Y Y Y Dahle, et al. 2000651 ASx 48 (7) Sapporo, Japan 17 ASx 2 (12) N N Y Numazaki, et al. 2004

  32. Summarizing from these studies: • 22 – 65% Symptomatic children will have hearing loss • 6-23% Asymptomatic children will have hearing loss • Sensorineural hearing loss following congenital CMV infection may be present at birth or delayed • Progression (audiometric threshold > 10 dB deterioration) and fluctuation of hearing loss may occur in children with SNHL due to congenital CMV infection

  33. In the 1990s & 2000s, multiple studies have further characterized HL due to congenital CMV infection UAB Cohort-the largest cohort to date Characteristics of CMV related HL

  34. UAB Longitudinal Study of HL Asymptomatic Symptomatic Total Number of Children 651 209 SNHL 48 (7.4%) 85 (40.7%) Unilateral 25 (52.1%) 28 (32.9%) Bilateral 23 (47.9%) 57 (67.1%) High-Frequency Only 18 (37.5%) 11 (12.9%) (4000-8000 Hz) Dahle, et. al., 2000

  35. UAB Longitudinal Study of HL Asymptomatic Symptomatic Total Number of Children 651 209 Degree of Loss % % Mild (21-45 dB HL) 17.0 11.8 Moderate (46-70 dB HL) 14.9 13.4 Severe (71-90 dB HL) 17.0 30.7 Profound (> 90 dB HL) 51.1 44.1 Dahle, et. al., 2000

  36. UAB Longitudinal Study of HL Asymptomatic Symptomatic Total Number of Children 651 209 Delayed Onset Loss 18 (37.5%) 23 (27.1%) Median age (range) of Delayed Onset 44 mo (24-182) 33 mo (6-197) Dahle, et. al., 2000

  37. UAB Longitudinal Study of HL Asymptomatic Symptomatic Total Number of Children 651 209 Progressive Loss 26 (54.2%) 46 (54.1%) Median age (range) of First Progression 51 mo (3-186) 26 mo (2-209) Fluctuating Loss 26 (54.1%) 25 (29.4%) Improvement of Loss 23 (47.9%) 18 (21.2%) Dahle, et. al., 2000

  38. Timing of HL due to CMV

  39. Cumulative incidence of SNHL in 388 children with congenital CMV infection Age of Child SNHL > 20 dB SNHL > 30 dB < 1 month 5.2% 3.9% 3 months 6.5% 5.3% 12 months 8.4% 6.8% 24 months 9.9% 7.2% 36 months 10.8% 7.6% 60 months 12.4% 7.6% 72 months 15.4% 8.3% Fowler, et. al., 1999

  40. Cumulative incidence of SNHL in 388 children with congenital CMV infection Symptomatic n=53 Asymptomatic n=335 Age of Child < 1 month 16.5% 2.9% 3 months 22.8% 4.0% 72 months 36.4% 11.3% Fowler, et. al., 1999

  41. Disseminated infection at birth with or without CNS involvement is associated with HL in symptomatic infants Rivera, et al. 2002 Maternal and perinatal factors do not predict hearing loss in children with asymptomatic congenital CMV infection Fowler, unpublished data Possible Other factor Contributing to HL due to CMV

  42. Possible Other factor Contributing to HL due to CMV Children with asymptomatic congenital CMV infection with higher amounts of infectious CMV in their urine and CMV DNA in their blood during early infancy are more likely to have SNHL Boppana, et al. 2005

  43. Viral Burden in Infancy & HL in Asymptomatic Infants Hearing Loss N=4 Normal Hearing N=54 Mean duration of follow-up, mos 39.3 ± 23.9 33.5 ± 17.6 Median number of hearing evals 7 (2-14) 6 (2-13) Mean amount of CMV in urine 1.6 x 105± 2.1 x 105 2.9 x 104± 7.8 x 104 (pfu/ml ± SD)* Mean PB blood virus burden 8.7 x 105± 1.6 x 106 1.1 x 104± 1.5 x 104 (ge/ml± SD)* *p < 0.05 Boppana, et al. 2005

  44. Impact of Universal Newborn Screening on the Detection of HL due to CMV

  45. Risk criteria based neonatal auditory screening was not successful in identifying HL due to congenital CMV infection Only 17.6% of children with SNHL due to congenital CMV infection were identified by risk criteria based neonatal auditory screening at UAB between 1985-1998

  46. SNHL in infants with congenital CMV infection according to results of risk criteria based neonatal auditory screening, 1985-1998 Audiology Newborn Hearing N Follow-up SNHL Failed 15 15 8 (53.3) Inconclusive 3 3 1 (33.3) Passed 55 50 4 (8.0) Not Tested 321 287 38 (13.2) Hicks, et al., 1993 Fowler, unpublished data

  47. SNHL in infants with congenital CMV infection since universal newborn hearing screening, 1998-2002 Audiology Newborn Hearing N Follow-up SNHL Failed 8 8 3 (37.5) Passed 34 32 4 (11.8) Not Tested 42 42 5 (11.9) Fowler, unpublished data

  48. Overall, 3/12 (25%) of the children with SNHL due to congenital CMV infection were identified in the newborn period by universal screening 3/5 not tested had documented delayed onset loss 7/12 (58%) of children with SNHL had delayed onset loss 3/5 (60%) of children with SNHL at birth were identified by universal screening

  49. Summary Review of SNHL due to CMV • ~50% of the loss is bilateral • ~ 65% is severe to profound loss • ~50% of the loss is progressive • ~50% to 60% is delayed onset (occurring in the first years of life) • Fluctuating and high frequency loss also occur

More Related