Accuracy of prenatal ultrasound screening to identify fetuses infected by cytomegalovirus which will develop severe long-term sequelae.

OBJECTIVES: To compare the ability of detailed routine ultrasound examination, performed without knowledge of maternal serology and fetal status, with that of targeted prenatal imaging performed in prenatal diagnostic units in cases of known fetal infection to identify cytomegalovirus (CMV)-infected fetuses that will develop long-term sequelae. METHODS: All prenatal imaging reports were collected for 255 children with congenital CMV in a registered cohort between 2013 and 2017 (NCT01923636). All women had undergone detailed routine fetal ultrasound examination at 20-24 and 30-34 weeks as part of routine antenatal care. All cases of known fetal CMV infection had also undergone targeted prenatal ultrasound examination. Postnatal structured follow-up for up to 48 months of age involved clinical, audiological and neurological assessment, including Brunet-Lezine scoring. Long-term sequelae (> 12 months) were considered to be mild in cases with isolated unilateral hearing loss and/or vestibular disorders, and severe in cases with bilateral hearing loss and/or neurological sequelae. All imaging reports were analyzed retrospectively with the knowledge of congenital CMV infection, searching for reference to findings that were, or could have been, related to fetal infection. Findings were analyzed in relation to whether the cases were diagnosed with CMV in utero or only postnatally. RESULTS: There were 237 children with complete follow-up data (> 12 months), for a median of 24 (range, 12-48) months. Of these, 30% (71/237) were diagnosed with CMV prenatally and 70% (166/237) were diagnosed within 3 weeks after birth. 72.5% (29/40) of children with long-term sequelae, including 74% (14/19) with severe long-term sequelae, were not identified in the prenatal period. Among those diagnosed prenatally, the sensitivity of prenatal imaging for predicting long-term sequelae and severe long-term sequelae was 91% and 100%, respectively, while, in the group diagnosed only postnatally, non-specific infection-related ultrasound findings had been reported without raising suspicion in 48% of cases with long-term sequelae and 64% of those with severe long-term sequelae. CONCLUSIONS: Routine detailed ultrasound examination in pregnancy is not an appropriate screening tool for congenital CMV infection that leads to long-term sequelae, in contrast with the high performance of targeted prenatal imaging in known cases of fetal infection. The non-specific nature of ultrasound features of CMV and their evolution, and a lack of awareness of caregivers about congenital CMV, are likely explanations. Awareness of the sonologist regarding congenital CMV and knowledge of the maternal serological status in the first trimester seem key to the performance of prenatal ultrasound. Copyright © 2020 ISUOG. Published by John Wiley & Sons Ltd.

The prognostic value of ultrasound abnormalities and biological parameters in blood of fetuses infected with cytomegalovirus.

OBJECTIVE: To evaluate the prognostic value of ultrasound abnormalities and of selected biological parameters in blood of fetuses infected with cytomegalovirus (CMV). DESIGN: Retrospective observational study. SETTING: Two fetal medicine units in Paris, France. POPULATION: All fetuses infected with CMV referred between 1998 and 2006. METHODS: We retrospectively analysed data collected prospectively in 73 fetuses infected by CMV with a positive CMV polymerase chain reaction in amniotic fluid. Fetal blood sampling (FBS) was performed for evaluation of platelet count, plasma levels of aminotransferases and gamma-glutamyl transpeptidases (GGT), presence of viraemia and specific fetal immunoglobulin M. Targeted ultrasound examination was performed every fortnight. Ultrasound findings were categorised into normal examination and any ultrasound abnormality, which was further grouped as ultrasound abnormality of the fetal brain and noncerebral ultrasound abnormality. MAIN OUTCOME MEASURES: A combination of histological findings after termination of pregnancy and evidence of cytomegalic inclusion disease at birth when pregnancies were continued. Clinical symptoms at birth or histological lesions attributable to CMV were considered as poor outcome. Statistical analysis was conducted to determine the value of each parameter to predict outcome. Logistic regression was used to build up a multivariate model combining the relevant parameters. RESULTS: In univariate analysis, only thrombocytopenia and the presence of any ultrasound abnormality were associated with a poor outcome (P < 10(-4) for both abnormalities). In the multivariate analysis, both thrombocytopenia and the presence of ultrasound abnormalities remained significant independent predictors of a poor outcome. Based on univariate logistic regression, odds ratio for a poor outcome were 1.24, 7.2, 22.5 and 25.5 for each 10,000/mm(3) decrease in platelet count, the presence of noncerebral, any ultrasound and cerebral ultrasound abnormalities, respectively. CONCLUSIONS: The prognosis of CMV-infected fetuses relies independently on both targeted ultrasound examination and fetal platelet count. FBS for platelet count may therefore justify FBS in infected fetuses even in the absence of ultrasound. features of brain involvement.

Cytomegalovirus-related fetal brain lesions: comparison between targeted ultrasound examination and magnetic resonance imaging.

OBJECTIVE: To evaluate the relative contributions to the diagnosis of fetal brain abnormalities of targeted ultrasound examination and magnetic resonance imaging (MRI) in fetuses infected with cytomegalovirus (CMV). METHODS: This was a retrospective analysis of targeted brain ultrasound examination and fetal brain MRI performed in fetuses diagnosed with CMV infection following proven maternal primary infection. The prenatal findings were compared with findings from postnatal transfontanellar ultrasound examination during the first week following delivery or from postmortem when the pregnancy was terminated. RESULTS: Both targeted prenatal ultrasound and MRI were performed on 49 fetuses. Brain abnormalities were present in 15/49 (30.6%) cases at postnatal/post-mortem follow-up. Fetal cerebral abnormalities were observed in 19/49 (38.8%) cases by ultrasound and/or MRI. The most frequent cerebral lesions induced by CMV and seen on ultrasound and MRI, respectively, included ventricular dilatation in nine and five cases, subependymal cysts in two cases each, microcephaly in five and three cases and periventricular calcifications in five cases on ultrasound only. Termination of pregnancy was performed in 10/49 cases. Sensitivity, specificity and positive and negative predictive values for the presence of cerebral lesions were 88.9%, 93.3%, 88.9% and 93.3%, respectively, when both prenatal ultrasound and MRI findings were abnormal, 85.7%, 85.3%, 70.6% and 93.5%, respectively, for ultrasound alone, and 42.9%, 91.2%, 66.7% and 79.5%, respectively, for MRI alone. Prenatal ultrasound, MRI and postnatal or postmortem examinations were concordant with the presence of brain abnormalities in six cases; however, their conclusions were exactly concordant in only two (33.3%) of these cases. In cases without cerebral abnormality, the results of prenatal and postnatal/postmortem examinations were concordant in 28/34 cases. CONCLUSIONS: The addition of MRI to ultrasound increases the positive predictive value for the diagnosis of fetal brain abnormalities in fetuses with CMV. The two techniques appear to be complementary and should not be mutually exclusive in high-risk fetuses. Their high predictive value for the presence or absence of cerebral lesions provides a useful tool for appropriate counseling since current evaluation of the prognosis is based mainly on the presence of fetal brain lesions. The lack of concordance between ultrasound and MRI should stimulate standardization of the interpretation of both ultrasound and MRI prospectively.

[Cytomegalovirus (CMV) congenital infection]. / Infection congénitale à Cytomégalovirus (CMV).

Human Cytomegalovirus (CMV) is the main cause of mental retardation and sensorineural hearing loss related to congenital infections. Justification of systematic screening for fetal CMV infection is still controversial and is not recommended in most developed countries. This is mainly justified by the paucity of antenatal prognostic factors and the lack of established intrauterine treatment when fetal infection has been diagnosed. Our aim was to review the current state of the knowledge about the CMV congenital infection and to highlight recent advances in the diagnosis as well as in the identification of prognostic factors.

Maternal administration of valaciclovir in symptomatic intrauterine cytomegalovirus infection.

OBJECTIVES: To report early experience with treatment of intrauterine cytomegalovirus (CMV) infection using maternal oral administration of valaciclovir (VACV). DESIGN: Observational study of fetuses infected with CMV with or without treatment with valaciclovir. POPULATION: Pregnancies with confirmed fetal CMV infection were treated with oral VACV (8 g/day). MAIN OUTCOME MEASURES: Fetal viral load and drug concentration were monitored in amniotic fluid and in fetal blood. Data on the course and outcome of a group of untreated symptomatic fetuses infected with CMV are also reported. RESULTS: Therapeutic concentrations were achieved in maternal and fetal bloods. The viral load in the fetal blood (VLFB) decreased significantly after 1-12 weeks of treatment (Wilcoxon paired test P = 0.02). Twenty pregnancies including 21 fetuses were treated at 28 weeks (median, range: 22-34) for 7 weeks (median, range: 1-12). Ten infants were developing normally at between 1 and 5 years of age. Two infants (both aged 2 years) had severe isolated unilateral deafness. One neonate presented with microcephaly and severe deafness but was also diagnosed with incontinentia pigmenti. Six out of seven cases that eventually required termination of pregnancy (TOP) had evidence of in utero progression of the disease with worsening cerebral lesions. One fetus died in utero. The outcome of 14/24 (58.3%) untreated symptomatic infected fetuses was poor with either TOP, intrauterine fetal demise or severe congenital infection disease of the neonate; the remaining ten infants were healthy at follow up. CONCLUSION: Maternal oral administration of VACV leads to therapeutic concentrations in the maternal and fetal compartments, with a decrease in VLFB. Our results suggest that in cases where TOP is declined, a randomised controlled trial to study this treatment option further is indicated.

[The noninvasive prenatal testing for Down's Syndrome. Retrospective study of 8821 patients]. / Le dépistage prénatal non invasif de la trisomie 21. Étude rétrospective à propos de 8821 patientes.

OBJECTIVE: To demonstrate the decrease in intrauterine invasive procedures through analysis of DNA fetoplacental free circulating in maternal blood: Non Invasive Prenatal Test (NIPT), in Prenatal Diagnosis Center of American Hospital of Paris (AHP). MATERIALS AND METHODS: Retrospective descriptive study of 8821 patients in Prenatal Diagnosis Center at the AHP between 01/01/2012 and 09/25/2014. The NIPT is available to patients since 1st January 2013. RESULTS: The number of invasive procedures decreased significantly (P<0.0001) between 2012 (n=1177, i.e. 42 % of the global activity of the Prenatal Diagnosis Center at the AHP in 2012) and 2013 (n=987 or 28.5 %) and between 2013 and 2014 (n=599 or 23.4 %). The NIPT calculated performance statistics are: sensitivity≥99.9 %; specificity=99.8 %; Positive Predictive Value=90.4 %; Negative Predictive Value≥99.9 %; False Positives=3. While the actual screening statistic values are: sensitivity≥95.4 %; specificity=82.5 %; Positive Predictive Value=6.5 %; Negative Predictive Value=99.9 %; False Positives=1197. The NIPT has reduced the number of invasive procedures at the Prenatal Diagnosis Center at the AHP. The NIPT performances are superior to those of the actual screening.

[Parkinson disease and pregnancy. Apropos of a case]. / Maladie de Parkinson et grossesse. A propos d'un cas.

Parkinson's disease is a neurological condition associated with neuronal degeneration in the corpora nigra with a drop in the level of dopamine in the striatum. It is rarely encountered in women of reproductive age. Treatment is by giving levodopa. We report a case of pregnancy in a woman of 34 years of age who was suffering from severe Parkinson's disease treated with levodopa. We have assessed this case in the light of viewing the literature which confirms that there is no effect on the pregnancy or on the fetus although the symptoms of Parkinson's disease are made worse. Levodopa seems to be quite innocuous as far as the fetus is concerned. There is no teratogenicity although in animal experiments high doses teratogenic effects have been noted.

[Contribution of kidney echography to upper urinary tract infection in pregnancy]. / Apport de l'échographie rénale dans les infections urinaires hautes au cours de la grossesse.

The authors carried out a prospective study and also looked at the literature in order to assess the contribution ultrasound makes in the diagnosis of the aetiology of upper urinary tract infections in pregnancy. They studied two matched series (patients and controls). They note that ultrasound is reliable in the aetiological diagnosis of upper urinary tract infections without complications and they discuss its place and the contribution it can make as compared with more invasive investigations of infections of the upper urinary tract in pregnancy (such as I.V.U. and C.T. scanning).

[Prenatal echographic study of esophageal duplication. A case report]. / Aspect échographique anténatal d'une duplication oesophagienne. A propos d'un cas.

We report a case of abdomino-thoracic oesophageal duplication revealed by prenatal ultrasonography as a liquid mass in the posterior mediastinum, responsible for a major chylothorax. Tow our knowledge, this is the first thoroughly documented case occurring in the prenatal period. The various possible ultrasonographic diagnoses and the possibility of therapeutic drainage of pleural effusions are discussed in the light of anatomy, embryogenesis and ultrasonographic images of the lesion.

[RU 486 and sulprostone in pregnancy termination in the 2nd and 3rd trimesters]. / RU 486 et sulprostone dans le cadre des interruptions médicales de la grossesse aux 2e et 3e trimestres.

OBJECTIVE: Describe our experience with the RU 486 (mifepristone) in case of pregnancy termination induced by sulprostone. METHOD: Prospective non controlled study in the department of Fetal Medicine of the "Institut de Puériculture de Paris". 158 women undergoing termination of pregnancy during the second and third trimester received a single dose of 600 mg of RU 486, 36 hours prior to infusion of 100 micrograms/hour of sulprostone. MAIN OUTCOME MEASURES: Delay between sulprostone therapy and diagnosis of labour duration of delivery. Prostaglandin doses used and frequency of secondary effects. RESULTS: The mean time between sulprostone administration and diagnosis of labour (146.5 +/- 106 minutes) as well delay of delivery (592.2 +/- 504 minutes) corresponded to the results reported in the literature. The primigravid women needed higher doses of prostaglandin and consequently experienced more secondary effects. No severe secondary effects were observed in this study. CONCLUSION: RU 486 is a satisfactory treatment for pregnancy termination during the second or third trimester.

[Periodic disease and pregnancy]. / Maladie périodique et grossesse.

The authors report a case of familial Mediterranean fever in a pregnant woman treated with Colchicine. She delivered normally at term. A review of the literature shows that colchicine does not have a teratogenic effect which it was long thought to have. All the same it is best to carry out fetal karyotype examination using early amniocentesis. Furthermore, colchicine improves fertility which is disturbed in these patients and pregnancy has a good effect on the disease.

[The treatment of obstetrical uterine inversion. Apropos of 3 cases]. / Les traitements des inversions utérines obstétricales. A propos de trois observations.

Uterine inversion is exceptional and spectacular, although treatment is simple if diagnosed early. Three cases are reported with a review of possible obstetrical procedures for reduction. Manual repositioning by central pressure is emphasised. General anesthesia is generally needed because of associated state of shock. The three principal steps of manual reduction are: intra-abdominal repositioning of the uterus, removal of placenta, intramural injection of ocytocine to avoid immediate relapse. Ideally, obstetrical procedure should be carried out within one-half hour after inversion.

[Management of persistent posterior occipital presentation. 253 extractions by forceps]. / Conduite à tenir devant une présentation en occipito-postérieure persistante. A propos de 253 extractions par forceps.

A retrospective study of the notes of 253 deliveries was carried out in the two maternity units attached to the University of Rennes between 1980 and 1985. This followed a review of the literature on delivery of babies presenting with a persistent occipito posterior position. Tarnier's forceps were used in each case with full rotation of the presenting part carried out or else delivery in the occipito posterior position. There were five cases of failed forceps. We have not been able to show that there was a significant statistical difference as far as the neonatal state of the babies was, because to the methods of delivery. On the other hand, there was a greater frequency of urinary-vaginal lesions after full rotation. We therefore suggest that a trial of forceps delivery should be carried out in the operating theatre when the optimal obstetrical conditions have been fulfilled, so long as the manoeuvres are carried out technically easily and so long as Caesarean section is resorted to if all the obstetrical conditions are not fulfilled, or if it seems difficult to deliver the baby with a forceps.

[Intrahepatic arteriovenous fistula. Prenatal diagnosis, physiopathological study and neonatal management]l. / Fistule artério-veineuse intrahépatique. Diagnostic anténatal, étude physiopathologique et prise en charge néonatale.

A case of arteriovenous fistula of the liver diagnosed at 30 weeks of gestation is reported. The etiologies of an hypoechogenic structure in the fetal liver are discussed showing the contribution of pulsed wave Doppler and color Doppler to the diagnosis. The clinical evolution towards heart failure led us to examine the pathophysiology of such a lesion. The prenatal management of this arteriovenous malformation is exposed.

[Toxoplasmosis in pregnancy. Diagnosis and new therapeutic possibilities]. / Toxoplasmose au cours de la grossesse. Diagnostic et nouvelles possibilités thérapeutiques.

Congenital toxoplasmosis results from contamination of the foetus by Toxoplasma gondii during pregnancy. It is a frequent and severe condition calling for close surveillance of mothers at risk. During the last few years, numerous advances have been made in the diagnosis and treatment of toxoplasmosis. Its diagnosis in the mother is now more reliable due to improvements in serological techniques, while in the foetus the use of foetal vascular techniques has made it possible to detect those who are infected. Owing to a new and effective therapeutic method certain foetuses can now be treated successfully in utero, so that induced abortion is reserved to cases with severe and early toxoplasmosis. The contribution of new molecular biology techniques to advances in this ever moving field is explained.

[Digestive endometriosis. Apropos of 5 cases of intestinal involvement and resection]. / L'endométriose digestive. A propos de 5 localisations intestinales réséquées.

The authors report 5 cases of intestinal endometriosis which required resection. They review the pathological characteristics and attempt to define the while accepting that the indications for resection should be extremely limited from both gynecological and intestinal viewpoints.