International Journal of Neonatal Screening

Research

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14 pages, 894 KiB

Open AccessArticle

Droplet Digital PCR (ddPCR) Does Not Enhance the Sensitivity of Detection of Cytomegalovirus (CMV) DNA in Newborn Dried Blood Spots Evaluated in the Context of Newborn Congenital CMV (cCMV) Screening

by Nelmary Hernandez-Alvarado, Craig J. Bierle and Mark R. Schleiss

Int. J. Neonatal Screen. 2024, 10(1), 1; https://doi.org/10.3390/ijns10010001 - 20 Dec 2023

Cited by 4 | Viewed by 1814

Abstract

Congenital cytomegalovirus (cCMV) infection is a leading cause of sensorineural hearing loss (SNHL) and neurodevelopmental disabilities in children worldwide. Some regions in the United States and Canada have implemented universal newborn screening for cCMV, which requires molecular diagnostic technologies for identifying cCMV, such [...] Read more.

Congenital cytomegalovirus (cCMV) infection is a leading cause of sensorineural hearing loss (SNHL) and neurodevelopmental disabilities in children worldwide. Some regions in the United States and Canada have implemented universal newborn screening for cCMV, which requires molecular diagnostic technologies for identifying cCMV, such as PCR testing of newborn dried blood spots (DBS). This study aimed to evaluate the sensitivity of droplet digital PCR (ddPCR) compared to quantitative real-time PCR to detect CMV DNA in newborn DBS. The limit of detection of various ddPCR primer/probe combinations (singleplex UL55-HEX, singleplex UL83-FAM, and multiplex UL55-HEX/UL83-FAM) was evaluated using the National Institute of Standards and Technology’s (NIST) CMV quantitative standard. Singleplex UL55-HEX ddPCR exhibited the lowest limit of detection among the primer/probe combinations tested for ddPCR. UL55 ddPCR was then compared to real-time PCR in 49 infants with confirmed cCMV identified through newborn screening for CMV in saliva swabs and confirmed by a urine test. The results showed that ddPCR was only positive for 59% (29 out of 49) of the cCMV infants, while real-time PCR was positive for 80% (39 out of 49). Due to its lower sensitivity and throughput, ddPCR may not be suitable for cCMV newborn screening. Full article

(This article belongs to the Special Issue Newborn Screening for Congenital CMV)

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17 pages, 293 KiB

Open AccessArticle

Parental Perspectives on Communication from Health Care Providers following a Newborn Diagnosis of Congenital Cytomegalovirus Infection: A Secondary Analysis of a Qualitative Study

by Tatiana M. Lanzieri, Mary Ann K. Hall, Ashrita Rau, Holly McBride, Danie Watson, Carol Rheaume and Gail Demmler-Harrison

Int. J. Neonatal Screen. 2023, 9(3), 49; https://doi.org/10.3390/ijns9030049 - 27 Aug 2023

Cited by 2 | Viewed by 1725

Abstract

The study objective was to identify communication messages that parents of children diagnosed with congenital cytomegalovirus (cCMV) infection reported as essential and helpful. We performed a secondary analysis of focus groups and interviews conducted with 41 parents of children with cCMV who had [...] Read more.

The study objective was to identify communication messages that parents of children diagnosed with congenital cytomegalovirus (cCMV) infection reported as essential and helpful. We performed a secondary analysis of focus groups and interviews conducted with 41 parents of children with cCMV who had enrolled in a long-term follow-up cCMV study at an academic medical center. Three groups of parents who had children with cCMV participated in the study: parents with children symptomatic at birth, parents with children asymptomatic at birth who later developed sensorineural hearing loss, and parents with children asymptomatic at birth who remained asymptomatic into adulthood. Using a health marketing approach, we identified six general themes from the focus group sessions: initial diagnosis, likely health outcome(s), comfort and coping, symptom watch, resources, and prevention. Receiving the initial diagnosis was shocking for many parents, and they wanted to know how their child would or could be affected. They valued access to the information, follow-up visits for early detection of hearing loss and other developmental delays, and support from other parents. Parents wished to obtain this information from their pediatrician but felt that experts offered more up-to-date knowledge about prognosis, monitoring, and treatment. With more U.S. states implementing cCMV screening strategies which would lead to more infant diagnoses, it will be necessary for providers to meet parents’ expectations and communication needs. Full article

(This article belongs to the Special Issue Newborn Screening for Congenital CMV)

8 pages, 434 KiB

Open AccessArticle

The Use of Saliva Samples to Test for Congenital Cytomegalovirus Infection in Newborns: Examination of False-Positive Samples Associated with Donor Milk Use

by Whitney Wunderlich, Abbey C. Sidebottom, Anna K. Schulte, Jessica Taghon, Sheila Dollard and Nelmary Hernandez-Alvarado

Int. J. Neonatal Screen. 2023, 9(3), 46; https://doi.org/10.3390/ijns9030046 - 17 Aug 2023

Cited by 4 | Viewed by 1966

Abstract

A universal screening research study was conducted in six hospitals to identify the clinical sensitivity of polymerase chain reaction (PCR) testing on newborn dried blood spots (DBSs) versus saliva specimens for the diagnosis of congenital cytomegalovirus (cCMV). CMV DNA positive results from DBSs [...] Read more.

A universal screening research study was conducted in six hospitals to identify the clinical sensitivity of polymerase chain reaction (PCR) testing on newborn dried blood spots (DBSs) versus saliva specimens for the diagnosis of congenital cytomegalovirus (cCMV). CMV DNA positive results from DBSs or saliva were confirmed with urine testing. Findings of several false-positive (FP) saliva PCR results prompted an examination of a possible association with donor milk. Documentation of the frequency of positive saliva results, including both true-positive (TP) and FP status from clinical confirmation, occurred. The frequency of donor milk use was compared for TP and FP cases. Of 22,079 participants tested between 2016 and 2022, 96 had positive saliva results, 15 were determined to be FP, 79 TP, and 2 were excluded for incomplete clinical evaluation. Newborn donor milk use was identified for 18 (19.14%) of all the positive saliva screens. Among the 15 FPs, 11 (73.33%) consumed donor milk compared to 7 of the 79 TPs (8.8%) (OR 28.29, 95% CI 7.10–112.73, p < 0.001). While milk bank Holder pasteurization inactivates CMV infectivity, CMV DNA may still be detectable. Due to this possible association, screening programs that undertake testing saliva for CMV DNA may benefit from documenting donor milk use as a potential increased risk for FP results. Full article

(This article belongs to the Special Issue Newborn Screening for Congenital CMV)

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11 pages, 1765 KiB

Open AccessArticle

Utility of Dried Blood Spots for the Diagnosis of Congenital Cytomegaloviruses within the First 21 Days of Life in a Single Center

by Ana Del Valle Penella, Jerry Miller, Ryan Rochat and Gail Demmler-Harrison

Int. J. Neonatal Screen. 2023, 9(3), 44; https://doi.org/10.3390/ijns9030044 - 4 Aug 2023

Cited by 3 | Viewed by 1890

Abstract

In this retrospective study, we aimed to evaluate the performance of dried-blood-spot (DBS) testing as a diagnostic method for the congenital cytomegalovirus (cCMV). We reviewed the medical records and DBS test results of 89 patients who had also undergone diagnostic cCMV testing within [...] Read more.

In this retrospective study, we aimed to evaluate the performance of dried-blood-spot (DBS) testing as a diagnostic method for the congenital cytomegalovirus (cCMV). We reviewed the medical records and DBS test results of 89 patients who had also undergone diagnostic cCMV testing within the first 21 days of life. The DBS test had a sensitivity of 83.9%, a specificity of 100%, a positive predictive value of 100%, and a negative predictive value of 73%. Patients with a true-positive DBS had a higher median level of CMV in blood according to PCR than those with a false-negative result. Additionally, all patients with cCMV and hearing loss had a positive DBS test, with higher median viremia levels observed in those with hearing loss compared to those without a CMV PCR blood test. These results suggest that DBS-based testing is useful in the diagnosis of cCMV, and its performance may be related to levels of CMV viremia. DBS testing accurately identified those patients with congenital/early onset hearing loss and those at risk of developing late-onset hearing loss. Full article

(This article belongs to the Special Issue Newborn Screening for Congenital CMV)

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9 pages, 764 KiB

Open AccessArticle

Identifying Clinical Criteria for an Expanded Targeted Approach to Screening for Congenital Cytomegalovirus Infection—A Retrospective Study

by Maya Heled Akiva, Hannah Hyde-De Sousa, Valerie Lamarre, Isabelle Boucoiran, Soren Gantt, Christian Renaud and Fatima Kakkar

Int. J. Neonatal Screen. 2023, 9(3), 40; https://doi.org/10.3390/ijns9030040 - 24 Jul 2023

Cited by 7 | Viewed by 1786

Abstract

Targeted screening for congenital CMV infection (cCMV), which entails CMV testing of infants who fail newborn hearing screening (NBHS), has become common practice. However, this strategy misses nearly all infected infants with normal hearing at birth who are nonetheless at high risk of [...] Read more.

Targeted screening for congenital CMV infection (cCMV), which entails CMV testing of infants who fail newborn hearing screening (NBHS), has become common practice. However, this strategy misses nearly all infected infants with normal hearing at birth who are nonetheless at high risk of subsequent hearing loss and would benefit from timely cCMV diagnosis. The objective of this study was to identify expanded criteria predictive of cCMV to increase the scope and utility of targeted newborn CMV screening. In this retrospective study, 465 newborns were tested for cCMV at a single tertiary care center with a targeted screening program between 2014 and 2018. Twenty-two infants were diagnosed with cCMV, representing 0.2% of the 12,189 births over this period and 4.7% of the infants tested. The highest prevalence of cCMV infection was among infants tested because of primary maternal CMV infection (8/42, 19%), followed by failed initial NBHS (10/88, 11.4%), maternal HIV infection (3/137, 2.2%), and clinical suspicion alone (5/232, 2.2%). The symptoms with the highest prevalence of infection among all infants tested included an enlarged liver and/or spleen (33.3%) (3/9), followed by petechiae (33.3%), microcephaly (9.4%), direct hyperbilirubinemia (7.7%), thrombocytopenia (6%), and growth impairment (4.3%). In addition to CMV screening of newborns who fail the NBHS, these data suggest that certain clinical signs of cCMV—in particular: thrombocytopenia, growth impairment, and HIV exposure in pregnancy—should be additional criteria for expanded targeted newborn CMV screening, where universal screening is not yet the standard of care. Full article

(This article belongs to the Special Issue Newborn Screening for Congenital CMV)

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10 pages, 1359 KiB

Open AccessArticle

A Qualitative Assessment of Clinical Practice Guidelines and Patterns for Congenital Cytomegalovirus in the United States

by Stephanie Kalb, John Diaz-Decaro, Harout Tossonian, Andrew Natenshon, Lori Panther, James Mansi and Laura Gibson

Int. J. Neonatal Screen. 2023, 9(3), 37; https://doi.org/10.3390/ijns9030037 - 30 Jun 2023

Viewed by 2260

Abstract

Cytomegalovirus (CMV) infection during pregnancy may result in long-term health problems for children with congenital CMV (cCMV). Currently, no prevention or treatment interventions are approved by the Food and Drug Administration for a cCMV indication. Healthcare provider and public awareness is low, and [...] Read more.

Cytomegalovirus (CMV) infection during pregnancy may result in long-term health problems for children with congenital CMV (cCMV). Currently, no prevention or treatment interventions are approved by the Food and Drug Administration for a cCMV indication. Healthcare provider and public awareness is low, and formal clinical practice guidelines and local practice patterns vary. A pilot study of eight cCMV experts was performed using qualitative semi-structured interviews to better understand clinical practice guidelines and patterns in the United States. Results from participant interviews highlighted the need for better prenatal diagnostic techniques, broader neonatal screening opportunities, and more robust evidence supporting intervention strategies. Healthcare provider and public partnerships are essential for advancing cCMV guidelines and improving care delivery. Our results provide a preliminary knowledge base and framework for developing a consensus cCMV research agenda to address evidence gaps that limit the revision of clinical practice guidelines. The changes in clinical practice patterns that may arise as a result of further research have the potential to reduce risk during pregnancy and improve care for children with cCMV infection. Full article

(This article belongs to the Special Issue Newborn Screening for Congenital CMV)

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9 pages, 1022 KiB

Open AccessArticle

Comparison of Overall Sensitivity and Specificity across Different Newborn Screening Algorithms for Congenital Cytomegalovirus

by Mark R. Schleiss, Lori Panther, Sandeep Basnet, Meklit Workneh and John Diaz-Decaro

Int. J. Neonatal Screen. 2023, 9(2), 33; https://doi.org/10.3390/ijns9020033 - 14 Jun 2023

Cited by 6 | Viewed by 3095

Abstract

Screening newborns for congenital cytomegalovirus (cCMV) infection is critical for early detection and prompt diagnosis of related long-term consequences of infection, such as sensorineural hearing loss and neurodevelopmental delays. The objective of this study was to describe the validity of different newborn cCMV [...] Read more.

Screening newborns for congenital cytomegalovirus (cCMV) infection is critical for early detection and prompt diagnosis of related long-term consequences of infection, such as sensorineural hearing loss and neurodevelopmental delays. The objective of this study was to describe the validity of different newborn cCMV infection screening approaches and compare the expected number of cCMV cases detected across targeted and universal screening algorithms. The overall sensitivity (OSn) of targeted screening algorithms that required failure of auditory brain stem response and transient evoked otoacoustic emissions (TOAE; two-fail serial testing) or TOAE only (one-fail serial testing) before diagnostic CMV testing using saliva and urine PCR tests was 79% and 88%, respectively. The OSn for two-fail serial testing with diagnostic CMV testing using dried blood spot (DBS) was 75%. In contrast, OSn was 90% for universal screening (saliva and urine PCR tests) and 86% for universal screening with DBS testing alone. Overall, specificities were 100% across all algorithms. Universal screening using DBS testing and universal screening using saliva and urine testing can potentially detect 312 and 373 more cCMV cases per 100,000 live births, respectively, than two-fail serial testing. Overall, implementing universal cCMV newborn screening would improve cCMV detection, ultimately leading to better health outcomes. Full article

(This article belongs to the Special Issue Newborn Screening for Congenital CMV)

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13 pages, 932 KiB

Open AccessArticle

A Cross-Sectional Survey of Pediatric Infectious Disease Physicians’ Approach to Congenital Cytomegalovirus Infection

by Chieko Hoki, Michelle White, Megan H. Pesch, Ann J. Melvin and Albert H. Park

Int. J. Neonatal Screen. 2023, 9(2), 17; https://doi.org/10.3390/ijns9020017 - 24 Mar 2023

Cited by 5 | Viewed by 2501

Abstract

Congenital cytomegalovirus (cCMV) continues to be a major public health care issue due to its high prevalence throughout the world. However, there is a paucity of studies evaluating how providers manage this infection. This study surveyed North American Pediatric Infectious Disease (PID) physicians [...] Read more.

Congenital cytomegalovirus (cCMV) continues to be a major public health care issue due to its high prevalence throughout the world. However, there is a paucity of studies evaluating how providers manage this infection. This study surveyed North American Pediatric Infectious Disease (PID) physicians to elicit their approach towards the evaluation and treatment of this condition. Thirty-two PID physicians responded to this survey. Institutional testing and screening for cCMV were infrequently reported. The respondents in general agreed upon most laboratory and diagnostic testing except for neuroimaging. For those tests, there was a disparity in indications for head ultrasound versus brain MRI imaging. Most (68.8%) agreed with the clinical practice of starting valganciclovir in an infant less than 1 month of age with one sign or symptom of disease, and 62.5% would do so for an infant with isolated sensorineural hearing loss. However, only 28.1% would treat cCMV-infected infants older than 1 month of age. In conclusion, few healthcare institutions represented by PID physicians in this cohort had a cCMV screening or testing initiative, yet most respondents would test at a much higher level based on their clinical practice. While there is general consensus in evaluation and treatment of these children, there are disparities in practices regarding neuroimaging and indications for antiviral treatment with respect to age and severity of disease. There is a great need for an evidence based policy statement to standardize cCMV workup and treatment. Full article

(This article belongs to the Special Issue Newborn Screening for Congenital CMV)

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10 pages, 237 KiB

Open AccessArticle

Congenital Cytomegalovirus Screening in Massachusetts Birth Hospitals: A Statewide Survey

by Cheryl K. Glovsky, Kendall Carroll, Naomi Clark, Peter Colleran, Vanessa Colleran, Shayne Gaffney, Margaret Kenna, Evelyn Kuhns-Rankin, Tracy Evans Luiselli, Talia Mango, Barbara Morris, Charlotte Mullen, Matthew Stenerson, Laura Gibson and Michael S. Cohen

Int. J. Neonatal Screen. 2022, 8(4), 65; https://doi.org/10.3390/ijns8040065 - 13 Dec 2022

Cited by 2 | Viewed by 2842

Abstract

This study sought to assess the current state of screening for congenital cytomegalovirus infection in newborns among birth hospitals and newborn nurseries in the state of Massachusetts. A survey assessing hospital protocols for cytomegalovirus testing in newborns was distributed to all birth hospitals [...] Read more.

This study sought to assess the current state of screening for congenital cytomegalovirus infection in newborns among birth hospitals and newborn nurseries in the state of Massachusetts. A survey assessing hospital protocols for cytomegalovirus testing in newborns was distributed to all birth hospitals and newborn nurseries in Massachusetts from November 2020 to February 2021. 73.3% of hospitals responded to at least one survey question. Of these, fewer than half (48.5%) had any established approach for neonatal cytomegalovirus screening. Salivary polymerase chain reaction was the most common testing modality. Most hospitals did not perform confirmatory testing for positive test results. Most respondents (87.9%) did not know or did not answer how results of cCMV screening were reported to families and who was responsible for coordinating care for cCMV-infected infants. We conclude that congenital cytomegalovirus screening protocols are absent or incomplete in most Massachusetts birth hospitals and newborn nurseries. A cohesive strategy involving standardized education and screening guidelines is needed to reduce the incidence and burden of congenital cytomegalovirus disease on children and their families. Full article

(This article belongs to the Special Issue Newborn Screening for Congenital CMV)

13 pages, 938 KiB

Open AccessArticle

Inconsistent Provider Testing Practices for Congenital Cytomegalovirus: Missed Diagnoses and Missed Opportunities

by Kate L. Wilson, Kimi Shah and Megan H. Pesch

Int. J. Neonatal Screen. 2022, 8(4), 60; https://doi.org/10.3390/ijns8040060 - 14 Nov 2022

Cited by 8 | Viewed by 2390

Abstract

Newborn congenital cytomegalovirus (cCMV) screening programs have been found to increase the rates of early diagnosis and treatment. In North America, newborn cCMV screening programs have not been widely implemented, leaving healthcare providers to rely on clinical suspicion alone to prompt testing. This [...] Read more.

Newborn congenital cytomegalovirus (cCMV) screening programs have been found to increase the rates of early diagnosis and treatment. In North America, newborn cCMV screening programs have not been widely implemented, leaving healthcare providers to rely on clinical suspicion alone to prompt testing. This study sought to examine healthcare providers’ cCMV testing practices at a quaternary children’s hospital. A retrospective review of the electronic health record was completed for eligible infants over a six-year period. Bivariate calculations and analyses were performed. Between 2014 and 2019, a total of 40,091 infants were cared for at the study institution, of which 178 were tested for cCMV and 10 infants were diagnosed with cCMV. Isolated small-for-gestational age was the most common indication (53/178) to prompt testing. Overall, the cCMV testing rate was 4.5 tests per 1000 infants, with a resulting diagnostic prevalence of 0.2 cases per 1000 infants, which is 15-fold lower than the expected prevalence. Providers relying on clinical suspicion alone are infrequently testing infants for cCMV, resulting in missed diagnoses and missed opportunities for treatment. Systematic cCMV screening practices may improve diagnosis, treatment, and childhood outcomes. Full article

(This article belongs to the Special Issue Newborn Screening for Congenital CMV)

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Review

Jump to: Research

13 pages, 314 KiB

Open AccessReview

The Psychosocial Impact of Congenital Cytomegalovirus on Caregivers and Families: Lived Experiences and Review of the Literature

by Michelle P. Zappas, Amanda Devereaux and Megan H. Pesch

Int. J. Neonatal Screen. 2023, 9(2), 30; https://doi.org/10.3390/ijns9020030 - 26 May 2023

Cited by 6 | Viewed by 2915

Abstract

Caring for a child with congenital cytomegalovirus (cCMV) can be costly for families, not only in terms of out-of-pocket expenses, but also in terms of caregiver time, relationships, career trajectories, and mental health. These additional burdens are sometimes referred to as “spillover effects”. [...] Read more.

Caring for a child with congenital cytomegalovirus (cCMV) can be costly for families, not only in terms of out-of-pocket expenses, but also in terms of caregiver time, relationships, career trajectories, and mental health. These additional burdens are sometimes referred to as “spillover effects”. As parents of children with cCMV, we, the authors of this article, discuss the impact that cCMV has had on our families. While multiple studies have reported on the epidemiology, prevention, screening, diagnosis, and management of cCMV, there has been minimal research regarding the possible impact on the family unit. In this narrative review, we discuss the various areas of the lives of families and caregivers that may be impacted by raising a child with cCMV. Whether children are minimally or severely affected by the sequelae of cCMV, they and their families merit the progression of awareness of the virus and governmental policies to help end cCMV. As the existing cCMV-specific literature is limited, we correlate studies of other childhood disabilities and find the mutuality experienced by families affected by cCMV. Full article

(This article belongs to the Special Issue Newborn Screening for Congenital CMV)

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