DOI: https://doi.org/10.18370/2309-4117.2020.54.101-109

Change of emphasis in the structure of prenatal infections, or what is SCORTCH? Literature review

Т. М. Тутченко, О. А. Бурка, О. В. Коломієць, Г. І. Іщенко, В. М. Харченко

Abstract


Prenatal infections (PI) remain an actual problem. Taking into account the epidemiological data on the increase in the incidence of syphilis in many countries, a review of modern algorithms for diagnosing this disease in pregnant women and newborns has been carried out. Universal screening for syphilis at the first prenatal examination is recommended by WHO and CDC, and is practiced in most countries. The article also presents the characteristics of modern laboratory methods of serological screening of pregnant women for syphilis and their combinations, one of which is primary screening using the treponemal test “total antibodies to syphilis” with confirmation of a positive result by immunoblotting.

Given the controversial nature of approaches to the prevention of other PI and their consequences, this review provides current recommendations for countries that screen and actively manage infections such as cytomegalovirus (CMV) and toxoplasmosis (T). Despite the proven significance of CMV as a factor in PI, universal prenatal screening, similar to screening for syphilis is not practiced in any of the countries due to the absence of prenatal treatment with proven efficacy. According to the national protocol of Germany, serostatus (titers IgG, IgM) to CMV are determined in early pregnancy. Confirmation of congenital CMV infection (HCMVI) is a positive PCR result in the amniotic fluid after 20–21 weeks of gestation. The main method of laboratory diagnostics of HCMVI in a newborn is PCR for CMV in urine. The article also presents the main approaches to the prevention of congenital toxoplasmosis, which have been practiced in France since the 90s and demonstrate effectiveness.

Thus, despite the fact that the use of effective prenatal treatment is not possible for all PI, their diagnosis using a complex of modern laboratory and instrumental methods is critical for the child’s health, since it allows the application of an appropriate algorithm for specific treatment and observation from birth

Keywords


prenatal infections; serological screening; syphilis; cytomegalovirus; toxoplasmosis; treponemal tests; nontreponemal tests; Western blotting; avidity

References


Sel, G. “Perinatal Infections.” In: Pract. Guid. to Oral Exams Obstet. Gynecol. Springer International Publishing. Cham (2020): 45–50. DOI: 10.1007/978-3-030-29669-8_7

European Centre for Disease Prevention and Control. Syphilis and congenital syphilis in Europe – A review of epidemiological trends (2007–2018) and options for response. Available from: [https://www.ecdc.europa.eu/en/publications-data/syphilis-and-congenital-syphilis-europe-review-epidemiological-trends-2007-2018], last accessed Sep 13, 2020.

Penner, J., Hernstadt, H., Burns, J.E., et al. “Stop, think SCORTCH: rethinking the traditional ‘TORCH’ screen in an era of re-emerging syphilis.” Arch Dis Child (2020). DOI: 10.1136/archdischild-2020-318841

Choudhri, Y., Miller, J., Sandhu, J., et al. “Infectious and congenital syphilis in Canada, 2010–2015.” Canada Commun Dis Rep 44 (2018): 43–48. DOI: 10.14745/ccdr.v44i02a02

Center for Disease Control and Prevention. STD surveillance 2018 (2019). DOI: 10.15620/cdc.79370

Ghanem, K.G., Ram, S., Rice, P.A. “The Modern Epidemic of Syphilis.” N Engl J Med 382 (2020): 845–54. DOI: 10.1056/NEJMra1901593

Public Health England. Addressing the increase in syphilis in England: PHE Action Plan (2019).

Mohammed, H., Mitchell, H., Sile, B., et al. “Hughes, Increase in sexually transmitted infections among men who have sex with men, England, 2014.” Emerg Infect Dis 22 (2016): 88–91. DOI: 10.3201/eid2201.151331

Sousa-Pinto, B., Freitas, A., Lisboa, C. “Syphilis hospitalisations in Portugal over the last decade.” Eur J Clin Microbiol Infect Dis 35 (2016): 169–74. DOI: 10.1007/s10096-015-2524-5

World Health Organization. WHO guideline on syphilis screening and treatment for pregnant women (2019). Available from: [http://www.who.int/reproductivehealth/publications/rtis/syphilis-ANC-screenandtreat-guidelines/en/], last accessed Aug 19, 2020.

American College of Obstetrician-Gynecologists. Guidelines for Perinatal Care, Eighth Edition Book. Available from: [https://www.acog.org/store/products/clinical-resources/guidelines-for-perinatal-care], last accessed Aug 19, 2020.

Queensland Government (Australia). Maternity and Neonatal Clinical Guideline Syphilis in pregnancy. Available from: [www.health.qld.gov.au/qcg], last accessed Sep 14, 2020.

Janier, M., Hegyi, V., Dupin, N., et al. “European guideline on the management of syphilis.” J Eur Acad Dermatology Venereol 28 (2014): 1581–93. DOI: 10.1111/jdv.12734

Pradhan, M., Jain, S. “Syphilis in Pregnancy.” J Fetal Med 7 (2020): 57–63. DOI: 10.1007/s40556-020-00242-x

Forrestel, A.K., Kovarik, C.L., Katz, K.A. “Sexually acquired syphilis: Laboratory diagnosis, management, and prevention.” J Am Acad Dermatol 82 (2020): 17–28. DOI: 10.1016/j. jaad.2019.02.074

Ortiz, D.A., Shukla, M.R., Loeffelholz, M.J. “The Traditional or Reverse Algorithm for Diagnosis of Syphilis: Pros and Cons.” Clin Infect Dis 71 (2020): S43–S51. DOI: 10.1093/cid/ciaa307

Peeling, R.W., Mabey, D., Kamb, M.L., et al. “Primer: Syphilis.” Nat Rev Dis Prim 3 (2017): 1–21. DOI: 10.1038/nrdp.2017.73

Tong, M.L., Lin, L.R., Liu, L.L., et al. “Analysis of 3 algorithms for syphilis serodiagnosis and implications for clinical management.” Clin Infect Dis 58 (2014): 1116–24. DOI: 10.1093/cid/ciu087

Chen, M.W., Akinboyo, I.C., Sue, P.K., et al. “Evaluating congenital syphilis in a reverse sequence testing environment.” J Perinatol 39 (2019): 956–63. DOI: 10.1038/s41372-019-0387-9

Silva, Â.A.O., de Oliveira, U.D., et al. “Performance of Treponema pallidum recombinant proteins in the serological diagnosis of syphilis.” PLoS One 15 (2020): e0234043. DOI: 10.1371/journal.pone.0234043

Kingston, M., French, P., Higgins, S., et al. “UK national guidelines on the management of syphilis 2015.” Int J STD AIDS 27 (2016): 421–46. DOI: 10.1177/0956462415624059

Boot, J.M., Oranje, A.P., de Groot, R., et al. “Congenital Syphilis.” Int J STD AIDS 3 (1992): 161–7. DOI: 10.1177/095646249200300302

Kamb, M.L., Newman, L.M., Riley, P.L., et al. “A Road Map for the Global Elimination of Congenital Syphilis.” Obstet Gynecol Int 2010 (2010): 1–6. DOI: 10.1155/2010/312798

Genç, M., Ledger, W.J. “Syphilis in pregnancy.” Sex Transm Infect 76 (2000): 73–9. DOI: 10.1136/sti.76.2.73

Costa, F., Mendes, M., Ferreira, M., Barroso, R. “Congenital syphilis: a revision of the cases over the last 18 years in a referral hospital in Lisbon.” J Pediatr Neonatal Individ Med 8 (2019): e080119. DOI: 10.7363/080119

Le Chevalier De Préville, M., Alessandri, J.L., Traversier, N., et al. “Evaluation of the management of pregnancies and infants at risk for congenital syphilis: La Réunion, 2008 to 2014.” J Perinatol 37 (2017): 116–21. DOI: 10.1038/jp.2016.158

Plotzker, R.E., Murphy, R.D., Stoltey, J.E. “Congenital Syphilis Prevention.” Sex Transm Dis 45 (2018): S29–S37. DOI: 10.1097/OLQ.0000000000000846

Marangoni, A., Foschi, C., Capretti, M.G., et al. “Contribution of a comparative western blot method to early postnatal diagnosis of congenital syphilis.” Clin Vaccine Immunol 23 (2016): 410–6. DOI: 10.1128/CVI.00032-16

Herremans, T., Kortbeek, L., Notermans, D.W. “A review of diagnostic tests for congenital syphilis in newborns.” Eur J Clin Microbiol Infect Dis 29 (2010): 495–501. DOI: 10.1007/s10096-010-0900-8

Manicklal, S., Emery, V.C., Lazzarotto, T., et al. “The ‘Silent’ global burden of congenital cytomegalovirus.” Clin Microbiol Rev 26 (2013): 86–102. DOI: 10.1128/CMR.00062-12

Morton, C.C., Nance, W.E. “Newborn hearing screening – A silent revolution.” N Engl J Med 354 (2006): 2151–64. DOI: 10.1056/NEJMra050700

Zedtwitz-Liebenstein, K., Diab-Elschahaw, M., Frass, M. “Human Cytomegalovirus Infection in Nonimmunocompromised Patients: A Retrospective Analysis and Review of the Literature.” Intervirology 59 (2016): 159–62. DOI: 10.1159/000454772

Dollard, S.C., Grosse, S.D., Ross, D.S. “New estimates of the prevalence of neurological and sensory sequelae and mortality associated with congenital cytomegalovirus infection.” Rev Med Virol 17 (2007): 355–63. DOI: 10.1002/rmv.544

Coll, O., Benoist, G., Ville, Y., et al. “Guidelines on CMV congenital infection.” J Perinat Med 37 (2009): 433–45. DOI: 10.1515/JPM.2009.127

Goderis, J., Keymeulen, A., Smets, K., et al. “Hearing in children with congenital cytomegalovirus infection: Results of a longitudinal study.” J Pediatr 172 (2016): 110–115.e2. DOI: 10.1016/j.jpeds.2016.01.024

Gabrielli, L., Bonasoni, M.P., Santini, D., et al. “Congenital cytomegalovirus infection: Patterns of fetal brain damage.” Clin Microbiol Infect 18 (2012). DOI: 10.1111/j.1469-0691.2012.03983.x

Adler, S.P., Nigro, G., Pereira, L. “Recent Advances in the Prevention and Treatment of Congenital Cytomegalovirus Infections.” Semin Perinatol 31 (2007): 10–18. DOI: 10.1053/j.semperi.2007.01.002

Ludwig, A., Hengel, H. “Epidemiological impact and disease burden of congenital cytomegalovirus infection in Europe.” Euro Surveill 14 (2009): 26–32. DOI: 10.2807/ese.14.09.19140-en

Lachmann, R., Loenenbach, A., Waterboer, T., et al. “Cytomegalovirus (CMV) seroprevalence in the adult population of Germany.” PLoS ONE 13.7 (2018): e0200267.

Picone, O., Grangeot-Keros, L., Senat, M., et al. “Cytomegalovirus non-primary infection during pregnancy. Can serology help with diagnosis?” J Matern Neonatal Med 30 (2017): 224–7. DOI: 10.3109/14767058.2016.1169521

Rawlinson, W.D., Boppana, S.B., Fowler, K.B., et al. “Congenital cytomegalovirus infection in pregnancy and the neonate: consensus recommendations for prevention, diagnosis, and therapy.” Lancet Infect Dis 17 (2017): e177–e188. DOI: 10.1016/S1473-3099(17)30143-3

Lazzarotto, T., Blázquez-Gamero, D., Delforge, M.L., et al. “Congenital Cytomegalovirus Infection: A Narrative Review of the Issues in Screening and Management From a Panel of European Experts.” Front Pediatr 8 (2020). DOI: 10.3389/fped.2020.00013

Leruez-Ville, M., Stirnemann, J., Sellier, Y., et al. “Feasibility of predicting the outcome of fetal infection with cytomegalovirus at the time of prenatal diagnosis.” Am J Obstet Gynecol 215.3 (2016): 342.e1–342.e9. DOI: 10.1016/j.ajog.2016.03.052

Britt, W., et al. “Virus entry into host, establishment of infection, spread in host, mechanisms of tissue damage.” In: Human Herpesviruses: Biology, Therapy, and Immunoprophylaxis. Chapter 41. Cambridge. Cambridge University Press (2007).

Hyde, T.B., Schmid, D.S., Cannon, M.J. “Cytomegalovirus seroconversion rates and risk factors: Implications for congenital CMV.” Rev Med Virol 20 (2010): 311–26. DOI: 10.1002/rmv.659

Vauloup-Fellous, C., Picone, O., Cordier, A.G., et al. “Does hygiene counseling have an impact on the rate of CMV primary infection during pregnancy? Results of a 3-year prospective study in a French hospital.” J Clin Virol 46 (2009). DOI: 10.1016/j.jcv.2009.09.003

Revello, M.G., Tibaldi, C., Masuelli, G., et al. “Prevention of Primary Cytomegalovirus Infection in Pregnancy.” EBioMedicine 2 (2015): 1205–10. DOI: 10.1016/j.ebiom.2015.08.003

Buxmann, H., Hamprecht, K., Meyer-Wittkopf, M., Friese, K. “Primary human cytomegalovirus (HCMV) infection in pregnancy.” Dtsch Arztebl Int 114 (2017): 45–52. DOI: 10.3238/arztebl.2017.0045

Picone, O., Vauloup-Fellous, C., Cordier, A.G., et al. “A series of 238 cytomegalovirus primary infections during pregnancy: Description and outcome.” Prenat Diagn 33 (2013): 751–8. DOI: 10.1002/pd.4118

Enders, G., Daiminger, A., Bäder, U., et al. “Intrauterine transmission and clinical outcome of 248 pregnancies with primary cytomegalovirus infection in relation to gestational age.” J Clin Virol 52 (2011): 244–6. DOI: 10.1016/j.jcv.2011.07.005

Faure-Bardon, V., Magny, J.F., Parodi, M., et al. “Sequelae of Congenital Cytomegalovirus Following Maternal Primary Infections Are Limited to Those Acquired in the First Trimester of Pregnancy.” Clin Infect Dis 69 (2019): 1526–32. DOI: 10.1093/cid/ciy1128

Exler, S., Daiminger, A., Grothe, M., et al. “Primary cytomegalovirus (CMV) infection in pregnancy: Diagnostic value of CMV PCR in saliva compared to urine at birth.” J Clin Virol 117 (2019): 33–6. DOI: 10.1016/j.jcv.2019.05.015

Dubey, J.P. Toxoplasmosis of Animals and Humans. CRC Press (2016). DOI: 10.1201/9781420092370

Khan, K., Khan, W. “Congenital toxoplasmosis: An overview of the neurological and ocular manifestations.” Parasitol Int 67 (2018): 715–21. DOI: 10.1016/j.parint.2018.07.004

Berger, F., Goulet, V., Le Strat, Y., Desenclos, J.C. “Toxoplasmosis among pregnant women in France: Risk factors and change of prevalence between 1995 and 2003.” Rev Epidemiol Sante Publique 57 (2009): 241–8. DOI: 10.1016/j.respe.2009.03.006

Picone, O., Fuchs, F., Benoist, G., et al. “Toxoplasmosis screening during pregnancy in France: Opinion of an expert panel for the CNGOF.” J Gynecol Obstet Hum Reprod (2020): 101814. DOI: 10.1016/j.jogoh.2020.101814

De Oliveira Azevedo, C.T., et al. “Performance of Polymerase chain reaction analysis of the amniotic fluid of pregnant women for diagnosis of congenital toxoplasmosis: A systematic review and meta-analysis.” PLoS One 11 (2016). DOI: 10.1371/journal.pone.0149938

Peyron, F., L’ollivier, C., Mandelbrot, L., et al. “Maternal and congenital toxoplasmosis: Diagnosis and treatment recommendations of a French multidisciplinary working group.” Pathogens 8 (2019). DOI: 10.3390/pathogens8010024


GOST Style Citations


1.      Sel, G. “Perinatal Infections.” In: Pract. Guid. to Oral Exams Obstet. Gynecol. Springer International Publishing. Cham (2020): 45–50. DOI: 10.1007/978-3-030-29669-8_7

2.      European Centre for Disease Prevention and Control. Syphilis and congenital syphilis in Europe – A review of epidemiological trends (2007–2018) and options for response. Available from: [https://www.ecdc.europa.eu/en/publications-data/syphilis-and-congenital-syphilis-europe-review-epidemiological-trends-2007-2018], last accessed Sep 13, 2020.

3.      Penner, J., Hernstadt, H., Burns, J.E., et al. “Stop, think SCORTCH: rethinking the traditional ‘TORCH’ screen in an era of re-emerging syphilis.” Arch Dis Child (2020). DOI: 10.1136/archdischild-2020-318841

4.      Choudhri, Y., Miller, J., Sandhu, J., et al. “Infectious and congenital syphilis in Canada, 2010–2015.” Canada Commun Dis Rep 44 (2018): 43–48. DOI: 10.14745/ccdr.v44i02a02

5.      Center for Disease Control and Prevention. STD surveillance 2018 (2019). DOI: 10.15620/cdc.79370

6.      Ghanem, K.G., Ram, S., Rice, P.A. “The Modern Epidemic of Syphilis.” N Engl J Med 382 (2020): 845–54. DOI: 10.1056/NEJMra1901593

7.      Public Health England. Addressing the increase in syphilis in England: PHE Action Plan (2019).

8.      Mohammed, H., Mitchell, H., Sile, B., et al. “Hughes, Increase in sexually transmitted infections among men who have sex with men, England, 2014.” Emerg Infect Dis 22 (2016): 88–91. DOI: 10.3201/eid2201.151331

9.      Sousa-Pinto, B., Freitas, A., Lisboa, C. “Syphilis hospitalisations in Portugal over the last decade.” Eur J Clin Microbiol Infect Dis 35 (2016): 169–74. DOI: 10.1007/s10096-015-2524-5

10.    World Health Organization. WHO guideline on syphilis screening and treatment for pregnant women (2019). Available from: [http://www.who.int/reproductivehealth/publications/rtis/syphilis-ANC-screenandtreat-guidelines/en/], last accessed Aug 19, 2020.

11.    American College of Obstetrician-Gynecologists. Guidelines for Perinatal Care, Eighth Edition Book. Available from: [https://www.acog.org/store/products/clinical-resources/guidelines-for-perinatal-care], last accessed Aug 19, 2020.

12.    Queensland Government (Australia). Maternity and Neonatal Clinical Guideline Syphilis in pregnancy. Available from: [www.health.qld.gov.au/qcg], last accessed Sep 14, 2020.

13.    Janier, M., Hegyi, V., Dupin, N., et al. “European guideline on the management of syphilis.” J Eur Acad Dermatology Venereol 28 (2014): 1581–93. DOI: 10.1111/jdv.12734

14.    Pradhan, M., Jain, S. “Syphilis in Pregnancy.” J Fetal Med 7 (2020): 57–63. DOI: 10.1007/s40556-020-00242-x

15.    Forrestel, A.K., Kovarik, C.L., Katz, K.A. “Sexually acquired syphilis: Laboratory diagnosis, management, and prevention.” J Am Acad Dermatol 82 (2020): 17–28. DOI: 10.1016/j. jaad.2019.02.074

16.    Ortiz, D.A., Shukla, M.R., Loeffelholz, M.J. “The Traditional or Reverse Algorithm for Diagnosis of Syphilis: Pros and Cons.” Clin Infect Dis 71 (2020): S43–S51. DOI: 10.1093/cid/ciaa307

17.    Peeling, R.W., Mabey, D., Kamb, M.L., et al. “Primer: Syphilis.” Nat Rev Dis Prim 3 (2017): 1–21. DOI: 10.1038/nrdp.2017.73

18.    Tong, M.L., Lin, L.R., Liu, L.L., et al. “Analysis of 3 algorithms for syphilis serodiagnosis and implications for clinical management.” Clin Infect Dis 58 (2014): 1116–24. DOI: 10.1093/cid/ciu087

19.    Chen, M.W., Akinboyo, I.C., Sue, P.K., et al. “Evaluating congenital syphilis in a reverse sequence testing environment.” J Perinatol 39 (2019): 956–63. DOI: 10.1038/s41372-019-0387-9

20.    Silva, Â.A.O., de Oliveira, U.D., et al. “Performance of Treponema pallidum recombinant proteins in the serological diagnosis of syphilis.” PLoS One 15 (2020): e0234043. DOI: 10.1371/journal.pone.0234043

21.    Kingston, M., French, P., Higgins, S., et al. “UK national guidelines on the management of syphilis 2015.” Int J STD AIDS 27 (2016): 421–46. DOI: 10.1177/0956462415624059

22.    Boot, J.M., Oranje, A.P., de Groot, R., et al. “Congenital Syphilis.” Int J STD AIDS 3 (1992): 161–7. DOI: 10.1177/095646249200300302

23.    Kamb, M.L., Newman, L.M., Riley, P.L., et al. “A Road Map for the Global Elimination of Congenital Syphilis.” Obstet Gynecol Int 2010 (2010): 1–6. DOI: 10.1155/2010/312798

24.    Genç, M., Ledger, W.J. “Syphilis in pregnancy.” Sex Transm Infect 76 (2000): 73–9. DOI: 10.1136/sti.76.2.73

25.    Costa, F., Mendes, M., Ferreira, M., Barroso, R. “Congenital syphilis: a revision of the cases over the last 18 years in a referral hospital in Lisbon.” J Pediatr Neonatal Individ Med 8 (2019): e080119. DOI: 10.7363/080119

26.    Le Chevalier De Préville, M., Alessandri, J.L., Traversier, N., et al. “Evaluation of the management of pregnancies and infants at risk for congenital syphilis: La Réunion, 2008 to 2014.” J Perinatol 37 (2017): 116–21. DOI: 10.1038/jp.2016.158

27.    Plotzker, R.E., Murphy, R.D., Stoltey, J.E. “Congenital Syphilis Prevention.” Sex Transm Dis 45 (2018): S29–S37. DOI: 10.1097/OLQ.0000000000000846

28.    Marangoni, A., Foschi, C., Capretti, M.G., et al. “Contribution of a comparative western blot method to early postnatal diagnosis of congenital syphilis.” Clin Vaccine Immunol 23 (2016): 410–6. DOI: 10.1128/CVI.00032-16

29.    Herremans, T., Kortbeek, L., Notermans, D.W. “A review of diagnostic tests for congenital syphilis in newborns.” Eur J Clin Microbiol Infect Dis 29 (2010): 495–501. DOI: 10.1007/s10096-010-0900-8

30.    Manicklal, S., Emery, V.C., Lazzarotto, T., et al. “The ‘Silent’ global burden of congenital cytomegalovirus.” Clin Microbiol Rev 26 (2013): 86–102. DOI: 10.1128/CMR.00062-12

31.    Morton, C.C., Nance, W.E. “Newborn hearing screening – A silent revolution.” N Engl J Med 354 (2006): 2151–64. DOI: 10.1056/NEJMra050700

32.    Zedtwitz-Liebenstein, K., Diab-Elschahaw, M., Frass, M. “Human Cytomegalovirus Infection in Nonimmunocompromised Patients: A Retrospective Analysis and Review of the Literature.” Intervirology 59 (2016): 159–62. DOI: 10.1159/000454772

33.    Dollard, S.C., Grosse, S.D., Ross, D.S. “New estimates of the prevalence of neurological and sensory sequelae and mortality associated with congenital cytomegalovirus infection.” Rev Med Virol 17 (2007): 355–63. DOI: 10.1002/rmv.544

34.    Coll, O., Benoist, G., Ville, Y., et al. “Guidelines on CMV congenital infection.” J Perinat Med 37 (2009): 433–45. DOI: 10.1515/JPM.2009.127

35.    Goderis, J., Keymeulen, A., Smets, K., et al. “Hearing in children with congenital cytomegalovirus infection: Results of a longitudinal study.” J Pediatr 172 (2016): 110–115.e2. DOI: 10.1016/j.jpeds.2016.01.024

36.    Gabrielli, L., Bonasoni, M.P., Santini, D., et al. “Congenital cytomegalovirus infection: Patterns of fetal brain damage.” Clin Microbiol Infect 18 (2012). DOI: 10.1111/j.1469-0691.2012.03983.x

37.    Adler, S.P., Nigro, G., Pereira, L. “Recent Advances in the Prevention and Treatment of Congenital Cytomegalovirus Infections.” Semin Perinatol 31 (2007): 10–18. DOI: 10.1053/j.semperi.2007.01.002

38.    Ludwig, A., Hengel, H. “Epidemiological impact and disease burden of congenital cytomegalovirus infection in Europe.” Euro Surveill 14 (2009): 26–32. DOI: 10.2807/ese.14.09.19140-en

39.    Lachmann, R., Loenenbach, A., Waterboer, T., et al. “Cytomegalovirus (CMV) seroprevalence in the adult population of Germany.” PLoS ONE 13.7 (2018): e0200267.

40.    Picone, O., Grangeot-Keros, L., Senat, M., et al. “Cytomegalovirus non-primary infection during pregnancy. Can serology help with diagnosis?” J Matern Neonatal Med 30 (2017): 224–7. DOI: 10.3109/14767058.2016.1169521

41.    Rawlinson, W.D., Boppana, S.B., Fowler, K.B., et al. “Congenital cytomegalovirus infection in pregnancy and the neonate: consensus recommendations for prevention, diagnosis, and therapy.” Lancet Infect Dis 17 (2017): e177–e188. DOI: 10.1016/S1473-3099(17)30143-3

42.    Lazzarotto, T., Blázquez-Gamero, D., Delforge, M.L., et al. “Congenital Cytomegalovirus Infection: A Narrative Review of the Issues in Screening and Management From a Panel of European Experts.” Front Pediatr 8 (2020). DOI: 10.3389/fped.2020.00013

43.    Leruez-Ville, M., Stirnemann, J., Sellier, Y., et al. “Feasibility of predicting the outcome of fetal infection with cytomegalovirus at the time of prenatal diagnosis.” Am J Obstet Gynecol 215.3 (2016): 342.e1–342.e9. DOI: 10.1016/j.ajog.2016.03.052

44.    Britt, W., et al. “Virus entry into host, establishment of infection, spread in host, mechanisms of tissue damage.” In: Human Herpesviruses: Biology, Therapy, and Immunoprophylaxis. Chapter 41. Cambridge. Cambridge University Press (2007).

45.    Hyde, T.B., Schmid, D.S., Cannon, M.J. “Cytomegalovirus seroconversion rates and risk factors: Implications for congenital CMV.” Rev Med Virol 20 (2010): 311–26. DOI: 10.1002/rmv.659

46.    Vauloup-Fellous, C., Picone, O., Cordier, A.G., et al. “Does hygiene counseling have an impact on the rate of CMV primary infection during pregnancy? Results of a 3-year prospective study in a French hospital.” J Clin Virol 46 (2009). DOI: 10.1016/j.jcv.2009.09.003

47.    Revello, M.G., Tibaldi, C., Masuelli, G., et al. “Prevention of Primary Cytomegalovirus Infection in Pregnancy.” EBioMedicine 2 (2015): 1205–10. DOI: 10.1016/j.ebiom.2015.08.003

48.    Buxmann, H., Hamprecht, K., Meyer-Wittkopf, M., Friese, K. “Primary human cytomegalovirus (HCMV) infection in pregnancy.” Dtsch Arztebl Int 114 (2017): 45–52. DOI: 10.3238/arztebl.2017.0045

49.    Picone, O., Vauloup-Fellous, C., Cordier, A.G., et al. “A series of 238 cytomegalovirus primary infections during pregnancy: Description and outcome.” Prenat Diagn 33 (2013): 751–8. DOI: 10.1002/pd.4118

50.    Enders, G., Daiminger, A., Bäder, U., et al. “Intrauterine transmission and clinical outcome of 248 pregnancies with primary cytomegalovirus infection in relation to gestational age.” J Clin Virol 52 (2011): 244–6. DOI: 10.1016/j.jcv.2011.07.005

51.    Faure-Bardon, V., Magny, J.F., Parodi, M., et al. “Sequelae of Congenital Cytomegalovirus Following Maternal Primary Infections Are Limited to Those Acquired in the First Trimester of Pregnancy.” Clin Infect Dis 69 (2019): 1526–32. DOI: 10.1093/cid/ciy1128

52.    Exler, S., Daiminger, A., Grothe, M., et al. “Primary cytomegalovirus (CMV) infection in pregnancy: Diagnostic value of CMV PCR in saliva compared to urine at birth.” J Clin Virol 117 (2019): 33–6. DOI: 10.1016/j.jcv.2019.05.015

53.    Dubey, J.P. Toxoplasmosis of Animals and Humans. CRC Press (2016). DOI: 10.1201/9781420092370

54.    Khan, K., Khan, W. “Congenital toxoplasmosis: An overview of the neurological and ocular manifestations.” Parasitol Int 67 (2018): 715–21. DOI: 10.1016/j.parint.2018.07.004

55.    Berger, F., Goulet, V., Le Strat, Y., Desenclos, J.C. “Toxoplasmosis among pregnant women in France: Risk factors and change of prevalence between 1995 and 2003.” Rev Epidemiol Sante Publique 57 (2009): 241–8. DOI: 10.1016/j.respe.2009.03.006

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