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Primary maternal cytomegalovirus infections: accuracy of fetal ultrasound to predict sequelae in offspring

Published:October 22, 2016DOI:https://doi.org/10.1016/j.ajog.2016.10.025
      To the Editors:
      We thank Leyder et al
      • Leyder M.
      • Vorsselmans A.
      • Done E.
      • et al.
      Primary maternal cytomegalovirus infections: accuracy of fetal ultrasound for predicting sequelae in offspring.
      for their contribution that addresses the important and challenging issue of predicting outcome when cytomegalovirus infection is diagnosed prenatally. Their group in Brussels has a long-standing experience in this field. The study confirms findings by us
      • Picone O.
      • Vauloup-Fellous C.
      • Cordier A.G.
      • et al.
      A series of 238 cytomegalovirus primary infections during pregnancy: description and outcome.
      and others that the time of maternal infection is a prognostic factor, because all cases with a poor outcome had an infection before 15 weeks of gestation (2 cases with unknown timing). The other major factor to be associated with poor outcome is the presence of ultrasound abnormalities.
      Leyder et al conclude that, of 38 fetuses with normal ultrasound results, more than one- of them half had cytomegalovirus-related anomalies at clinical follow up or at autopsy in case of pregnancy termination, which led them to state that prenatal ultrasound findings are correlated poorly with postnatal outcomes.
      This conclusion may be overstated for several reasons, in addition to the number lost to follow up. First, the paper fails to mention when the ultrasound examinations were performed. This is important because it has been shown that ultrasound signs may take several weeks or months to appear.
      • Picone O.
      • Vauloup-Fellous C.
      • Cordier A.G.
      • Grangeot-Keros L.
      • Frydman R.
      • Senat M.V.
      Late onset of ultrasound abnormalities in a case of periconceptional congenital cytomegalovirus infection.
      Second, the autopsy findings must be interpreted with caution. It is impossible to determine whether microscopic lesions would have resulted in neurologic impairment had the child lived, but the presence of cytomegalovirus inclusions in the placenta, lungs, or abdomen does not lead necessarily to neurologic impairment. Furthermore, since microscopic lesions may precede visible abnormalities by many weeks, ongoing surveillance with serial ultrasound examinations would have been likely to detect the most severe evolving lesions, microcephaly for instance. Third, regarding the liveborn children, of 23 children with normal prenatal ultrasound scans, 1 child had had mild developmental delay, and 1 child had mild neurologic sequelae, thus a negative predictive value of 91% to exclude neurologic problems. Of course, ultrasound scans cannot detect hearing loss, which much be discussed with the couple.
      Thus, the negative predictive value is underestimated in this article. Furthermore, more complete evaluation may be considered with fetal blood sampling for platelet count and magnetic resonance imaging. This is important with regards to the high proportion of pregnancies that were terminated, despite normal ultrasound findings. Lack of confidence in favorable prognostic elements and serial follow-up evaluations can lead to distress leading to termination of pregnancy.
      Thanks to the better knowledge of the natural history of the disease, we now can establish with good reliability which fetuses will go on to be asymptomatic neonates with a low risk of neurologic sequelae.
      • Picone O.
      • Vauloup-Fellous C.
      • Cordier A.G.
      • et al.
      A series of 238 cytomegalovirus primary infections during pregnancy: description and outcome.
      • 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.
      Of course, the prediction is not perfect, and we cannot exclude the occurrence of hearing loss. We strongly agree with Leyder et al that further longitudinal studies are required. Management of these cases must be performed with experts on fetal ultrasound scanning and cytomegalovirus disease.

      References

        • Leyder M.
        • Vorsselmans A.
        • Done E.
        • et al.
        Primary maternal cytomegalovirus infections: accuracy of fetal ultrasound for predicting sequelae in offspring.
        Am J Obstet Gynecol. 2016; 215: 638.e1-638.e8
        • Picone O.
        • Vauloup-Fellous C.
        • Cordier A.G.
        • et al.
        A series of 238 cytomegalovirus primary infections during pregnancy: description and outcome.
        Prenat Diagn. 2013; 33: 751-758
        • Picone O.
        • Vauloup-Fellous C.
        • Cordier A.G.
        • Grangeot-Keros L.
        • Frydman R.
        • Senat M.V.
        Late onset of ultrasound abnormalities in a case of periconceptional congenital cytomegalovirus infection.
        Ultrasound Obstet Gynecol. 2008; 31: 481-483
        • 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. 2016; 215: 342.e1-342.e9

      Linked Article

      • Primary maternal cytomegalovirus infections: accuracy of fetal ultrasound for predicting sequelae in offspring
        American Journal of Obstetrics & GynecologyVol. 215Issue 5
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          Cytomegalovirus infection is the most common perinatal viral infection that can lead to severe long-term medical conditions. Antenatal identification of maternal cytomegalovirus infections with proven fetal transmission and potential postnatal clinical sequelae remains a major challenge in perinatology. There is a need to improve the prenatal counseling offered to patients and guide future clinical management decisions in cases of proven primary cytomegalovirus infection.
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        American Journal of Obstetrics & GynecologyVol. 216Issue 3
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          We thank Picone and Mandelbrot for their interesting comments. In Belgium, 3 prenatal ultrasound scans are refunded by the Federal Institute for Health Insurance (1st, 2nd, and 3rd trimester ultrasound examinations). As mentioned in our article, pregnant patients with primary cytomegalovirus infections were invited for targeted additional ultrasound scans to be performed every 4 weeks until delivery. Dates of the ultrasound scans and gestational ages for every included patient were registered (data not shown) as well as fetal and placental findings.
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