First-trimester diagnosis of congenital cytomegalovirus infection after maternal primary infection in early pregnancy: feasibility study of viral genome amplification by PCR on chorionic villi obtained by CVS.

OBJECTIVE: To evaluate the feasibility of amplification of the viral genome by polymerase chain reaction (PCR) analysis of trophoblast samples obtained by chorionic villus sampling (CVS) in cases of maternal primary infection (MPI) with cytomegalovirus (CMV) in early pregnancy. METHODS: This was a prospective study carried out at the Department of Obstetrics and Fetal Medicine, Hopital Necker-E.M., between October 2019 and October 2020. Following CMV serology screening in early pregnancy, CVS was offered to women at 11-14 weeks' gestation after CMV-MPI ≤ 10 weeks. Array-comparative genomic hybridization and amplification of the viral genome by PCR were performed on the trophoblasts obtained by CVS. All cases also underwent amniocentesis from 17 weeks onwards and PCR was performed on the amniotic fluid. Secondary prevention with valacyclovir was initiated as soon as MPI was diagnosed, to decrease the risk of vertical transmission. We evaluated the diagnostic performance of CMV-PCR of trophoblast obtained by CVS, using as the reference standard PCR of amniotic fluid obtained by amniocentesis. RESULTS: CVS was performed in 37 pregnancies, at a median (range) gestational age of 12.7 (11.3-14.4) weeks. CMV-PCR in chorionic villi was positive in three and negative in 34 cases. CMV-PCR following amniocentesis, performed at a median (range) gestational age of 17.6 (16.7-29.9) weeks, was positive for the three cases which were positive following CVS and, of the 34 patients with a negative finding following CVS, amniocentesis was negative in 31 and positive in three. The sensitivity of CMV-PCR analysis of trophoblast obtained by CVS for the diagnosis of CMV, using as the reference standard PCR analysis of amniotic fluid obtained by amniocentesis, was 50% (95% CI, 19-81%), specificity was 100% (95% CI, 89-100%), positive predictive value was 100% (95% CI, 44-100%) and negative predictive value was 91% (95% CI, 77-97%). CONCLUSIONS: Diagnosis of placental infection following MPI in early pregnancy can be achieved by PCR amplification of the CMV genome in chorionic villi. We propose that negative CMV-PCR in the trophoblast after 12 weeks could be used to exclude CMV-related embryopathy leading to sequelae. However, this needs to be confirmed through long-term follow-up evaluation. These findings could help to establish CVS as the diagnostic test of choice following maternal serology screening in early pregnancy. © 2021 International Society of Ultrasound in Obstetrics and Gynecology.

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.

Outcome and management of newborns with congenital cytomegalovirus infection.

Congenital cytomegalovirus (CMV) infection is the most common non-genetic cause of hearing loss and neurological disorder in children. Its overall prevalence is approximately 0.5% in Europe. In France, systematic screening during pregnancy is not recommended; screening is performed only if there are maternal or fetal symptoms suggestive of this infection. Approximately 90% of infected newborns are asymptomatic at birth, and among them the risk of neurosensory sequelae is 5-15%. By contrast, the prevalence of neurosensory impairment in symptomatic newborns at birth varies from 17% to 60%. Congenital CMV infection must be confirmed at birth before the 21st day of life by polymerase chain reaction (PCR) on saliva or urine samples. A complete clinical examination, blood tests (blood count, liver function test, CMV PCR), hearing tests, brain ultrasound and eye fundus examination should be performed. Neurological and auditory follow-up must be extended well beyond the neonatal period because the occurrence of neurosensory sequelae may be delayed. Oral valganciclovir is the recommended treatment in moderate or severe congenital CMV infections for a period of 6 weeks to 6 months; such treatment requires regular monitoring because of its possible side effects.

Refining the prognosis of fetuses infected with Cytomegalovirus in the first trimester of pregnancy by serial prenatal assessment: a single-centre retrospective study.

OBJECTIVE: To define the predictive value (PV) of known prognostic factors of fetal infection with Cytomegalovirus following maternal primary infection <14 weeks of gestation, at different time points of pregnancy: the end of the second trimester; following prenatal magnetic resonance imaging (MRI) at 32 weeks of gestation; and using all ultrasound scans performed in the third trimester (US3rdT). DESIGN: A retrospective study. SETTING: Reference fetal medicine unit. POPULATION: Sixty-two fetuses infected <14 weeks of gestation. METHODS: We defined second-trimester assessment (STA) as the combination of ultrasound findings <28 weeks of gestation and fetal platelet count at cordocentesis. Three groups were defined: normal, extracerebral, and cerebral STA. MAIN OUTCOME MEASURES: For each group, the PV of STA alone, STA + MRI, and STA + US3rdT were assessed retrospectively. Outcome at birth and at follow-up were reported. RESULTS: The STA was normal, and with extracerebral and cerebral features, in 43.5, 42.0, and 14.5%, respectively. The negative PV of normal STA and MRI for moderate to severe sequelae was 100%. The residual risk was unilateral hearing loss in 16.7% of cases. Of pregnancies with cerebral STA, 44% were terminated. Following extracerebral STA, 48% of neonates were symptomatic and 30% had moderate to severe sequelae. In those cases, the positive and negative PV of MRI for sequelae were 33 and 73%, respectively. STA + US3rdT had a lower negative PV than MRI for symptoms at birth and for moderate to severe sequelae. Any false-positive findings at MRI were mostly the result of hypersignals of white matter. CONCLUSIONS: Serial assessment in the second and third trimesters by ultrasound and MRI is necessary to predict the risk of sequelae occurring in 35% of pregnancies following fetal infection in the first trimester of pregnancy. TWEETABLE ABSTRACT: Serial ultrasound prognostic assessment following fetal CMV infection in the 1st trimester is improved by MRI at 32 weeks.

Recent actuality about Bacillus cereus and human milk bank: a new sensitive method for microbiological analysis of pasteurized milk.

Three cases of Bacillus cereus infection or colonization occurred in the same region in France, and milk from the milk bank was suspected as a possible common source of contamination. All Batches delivered to the three cases complied with the requirements of the bacteriological reference method recommended by good practices guidelines. Still, a retrospective analysis with a more sensitive method showed one batch to contain B. cereus, however straincomparison revealed no epidemiological link betweenisolates from patients and those from the milk. Consequently, in accordance with the precautionary principle, we developed a new sensitive method for the screening of pasteurized milk for pathogenic bacteria. From January 1 to August 31, 2017, 2526 samples of pasteurized milk were prospectively included in the study. We showed that a 20 mL sample of pasteurized milk incubated for 18 h at 37 °C under aerobic conditions was favoring the detection of B. Cereus. The nonconformity rate was 6.3% for the reference method and 12.6% for the improved method (p < 0.0001). Nonconformity was due to the presence of B. cereus in 88.5% of cases for the improved method and 53% of cases for the reference method (p < 0.0001). Thus our new method is improves the microbiological safety of the product distributed and only moderately increases the rate of bacteriological nonconformity .

Preterm premature rupture of membranes is a collateral effect of improvement in perinatal outcomes following fetoscopic coagulation of chorionic vessels for twin-twin transfusion syndrome: a retrospective observational study of 1092 cases.

OBJECTIVES: Preterm premature rupture of membranes (PPROM) is a leading complication following fetoscopic laser coagulation (FLC) for twin-twin transfusion syndrome (TTTS). Our primary objective was to describe the impact of improvements in surgical technique on survival and rate of PPROM over time. The secondary objective was to assess potential risk factors for PPROM. DESIGN AND SETTING: Single-centre retrospective observational study. POPULATION: 1092 consecutive cases of TTTS operated by FLC between 2000 and 2016, with a 6.8% rate of loss to follow up. METHODS: The incidence of PPROM and potential risk factors were analysed using competing risks models. MAIN OUTCOME MEASURES: PPROM, neonatal survival and neurological damage at 28 days. RESULTS: PPROM <32 weeks increased from 15 to 40% between 2000 and 2016 along with an overall improvement of perinatal outcomes: dual survival rose from 42 to 66% whereas dual losses dropped two-fold, from 19 to 9%. Gestational age at surgery at <17 weeks was a significant risk-factor for PPROM, with an additional risk of 10% within the first week of surgery. Although early PPROM at <20 weeks carried a 56% risk of miscarriage, the occurrence of PPROM at >20 weeks did not affect survival, despite an increase in preterm birth at <32 weeks. CONCLUSIONS: With significant improvement in perinatal outcomes, possibly related to improvements in surgical technique, postoperative complications have shifted to non-lethal obstetric complications such as PPROM, with rather reassuring postnatal outcomes, despite an increase in preterm birth and, potentially, morbidity. Early surgeries (<17 weeks) are at higher risk of postoperative PPROM. TWEETABLE ABSTRACT: Following laser/TTTS, rates of PPROM increased with perinatal survival; surgeries at <17 weeks are at highest risk.

Cortical Auditory-Evoked Responses in Preterm Neonates: Revisited by Spectral and Temporal Analyses.

Characteristic preterm EEG patterns of "Delta-brushes" (DBs) have been reported in the temporal cortex following auditory stimuli, but their spatio-temporal dynamics remains elusive. Using 32-electrode EEG recordings and co-registration of electrodes' position to 3D-MRI of age-matched neonates, we explored the cortical auditory-evoked responses (AERs) after 'click' stimuli in 30 healthy neonates aged 30-38 post-menstrual weeks (PMW). (1) We visually identified auditory-evoked DBs within AERs in all the babies between 30 and 33 PMW and a decreasing response rate afterwards. (2) The AERs showed an increase in EEG power from delta to gamma frequency bands over the middle and posterior temporal regions with higher values in quiet sleep and on the right. (3) Time-frequency and averaging analyses showed that the delta component of DBs, which negatively peaked around 550 and 750 ms over the middle and posterior temporal regions, respectively, was superimposed with fast (alpha-gamma) oscillations and corresponded to the late part of the cortical auditory-evoked potential (CAEP), a feature missed when using classical CAEP processing. As evoked DBs rate and AERs delta to alpha frequency power decreased until full term, auditory-evoked DBs are thus associated with the prenatal development of auditory processing and may suggest an early emerging hemispheric specialization.

Prenatal factors associated with neonatal survival of infants with congenital chylothorax.

OBJECTIVES: Congenital chylothorax is a rare disease and prognostic factors are key element in properly informing parents. This study aimed at determining the prenatal factors associated with neonatal survival in a cohort of liveborn infants with congenital chylothorax. STUDY DESIGN: Observational monocentric cohort study including all liveborn neonates consecutively admitted for congenital chylothorax. RESULTS: Neonatal mortality was 32% (16/50). Prematurity (or birth weight), persistence of hydrops at birth and the absence of thoracoamniotic shunt procedure were significantly associated with mortality, whereas prenatal diagnosis of pleural effusion, side of pleural effusion, hydrops fetalis and amniodrainage were not. In case of prenatal diagnosis of hydrops fetalis, the reversal in utero of hydrops fetalis was significantly associated with survival (P=0.001). In case of thoracoamniotic shunting, the interval between thoracoamniotic shunting intervention and delivery was significantly longer for patients who survived (P=0.03). CONCLUSIONS: Thoracoamniotic shunting and reversal of hydrops significantly improves survival, whereas prematurity worsened outcome of liveborn infants with congenital chylothorax. Our data also suggest that the interval between thoracoamniotic shunting and birth appears to be crucial; the longer the interval, the more likely is the reversal of antenatal hydrops and neonatal survival.

[Prenatal discovery of Joubert syndrome associated with small bowel volvulus]. / Découverte anténatale d'un syndrome de Joubert associé à un volvulus du grêle.

Joubert syndrome and prenatal volvulus are difficult to diagnose during pregnancy. Joubert syndrome and related diseases should be considered in case of prenatal abnormal features of the fourth ventricle. Small bowel volvulus is also a surgical emergency because of the risk of intestinal necrosis before or after delivery. This type of condition justifies the transfer of pregnant women to a specialized hospital where the newborn may receive appropriate care. We report the case of a 31-week and 4-day gestational-age fetus in whom intrauterine growth retardation and small-bowel volvulus were diagnosed. Additional imaging revealed associated Joubert syndrome. This highlights the need for regular ultrasound monitoring during pregnancy and the comanagement of obstetricians and pediatricians to provide appropriate care before and after delivery.

[Virological tools for the diagnosis, the prognosis and the surveillance of congenital cytomegalovirus infections]. / Utilisation des tests virologiques pour le diagnostic, le pronostic et la surveillance des infections congénitales à cytomégalovirus.

Cytomegalovirus (CMV) infection is the main cause of congenital infection in industrialized countries. The virological tools used for the diagnosis of congenital CMV are serology for diagnosis of primary infection in the mother, CMV PCR in amniotic fluid for diagnosis of fetal infection, PCR in urine or saliva for neonatal diagnosis and PCR in dried blood spots on Guthrie cards for retrospective diagnosis in young children. The prognostic value of viral load in amniotic fluid, fetal blood and neonatal blood will be discussed. The performance of the virological tests for antenatal or postnatal screening of congenital CMV will also be discussed.

[The Paris cell for collecting preoccupying information (la CRIP 75): an organization at the heart of child protection]. / La cellule de recueil des informations préoccupantes de Paris, la CRIP 75 : un dispositif au cœur de la protection de l'enfance.

Within the objective of coordinating actions of the different partners whose mission involves childhood protection measures, and to allow convergence of preoccupying information toward a centralized unit, law n(o) 2007-293 of 5 March 2007 reforming child protection requires the creation of a departmental cell for the collection, processing, and assessment of preoccupying information (cellule départementale, de recueil, de traitement, et d'évaluation des informations préoccupantes, CRIP) on the circumstances of a minor in danger or at risk of being so. The CRIP 75 is a multidisciplinary cell comprising an administrative pole, a socio-educational pole, and a medical health officer. Its mission is to participate in assessing preoccupying information and directing it appropriately, with a preference toward treating situations within an administrative framework and in accordance with the parents. The public prosecutor is only called in when the recommended measures have not provided an adequate response to the danger. Situations that are a matter for prosecution as a criminal offence are transmitted directly to the public prosecutor's office, as are situations for which the social or medico social services are unable to make an assessment.

[HTLV and "donating" milk]. / HTLV-1 et don de lait maternel.

In France, the screening for human T-cell leukemia/ lymphoma virus type 1 and 2 (HTLV-1 and HTLV-2) during the donation of human milk has been carried out from 1992 with the application of the circular DGS 24 November 1992. The screening for antibodies against these viruses is regulated and done systematically during every donation of milk. Breast feeding being the main mode of transmission of the HTLV-1, the last ministerial decree of 25 August 2010 has made the screening test compulsory for the anonymous donation and for the personalized donation (of a mother for her own child) from all women including those affected by the infection. The milk delivered by milk banks is pasteurized (62.5 °C for 30 minutes) before freezing at -18 °C, which inactivates the pathogens. This double means of prevention of the transmission of the HTLV-1 paradoxically seems disproportionate in the absence of any precautionary measure in the case of direct breast-feeding and the use of mother's raw milk. Indeed, in most neonatal intensive care units in maternity hospitals, unpasteurized milk is administered to the neonates without any systematic preliminary testing of the serological HTLV-1 status of the mother. An increased sensitization of the community of the obstetricians, midwives and neonatologists by the Association of the Milk Banks of France (ADLF) and the Société de pathologie exotique could address the issue of screening for HTLV-1 in "donated" milk and breast-feeding.

[New in light of immune modulation by probiotics bacteria and increase IL10 producing regulatory T cells]. / Un nouvel éclairage physiopathologique de la modulation de la réponse immune par les lactobacilles.

Studies on probiotics had found a benefit in their use. That was attributed to a barrier effect at the intestinal mucosa. We tried a new immunephysiological explanation supported by murine works and in humans. Immune modulation by probiotic bacteria and induce IL10 producing regulatory T cells. Receptors DCSIGN and Toll dendrites cells interfere in the copresentation of antigens and generate an immune response modulation by regulatory T cells and their inhibitory cytokines TGFß, IL10.

[Pregnancy care of visual deficient women: what specificity?]. / Prise en charge des grossesses chez les femmes aveugles ou amblyopes: quelles spécificités?

OBJECTIVES: Maternity has been denied to blind women for a long time, and is still often criticized or not understood in a very demanding social environment for the future mothers. Our objective is to describe the follow-up of the pregnancies and the childbirth of the visual handicapped women within the framework of a dedicated network of care liking with the Maternal and Infant Protection Unit and the paediatric ward. PATIENTS AND METHOD: We studied a retrospective series of 18 women blind or amblyopic followed up at the at the institut de puériculture et périnatologie (Paris, France) from 2001 to 2006. We report the social and morphological characteristics women, the characteristics of the monitoring of their pregnancy and childbirth and the approach of antenatal care. The results were compared with the data of the average French population studied in the perinatal investigation of 2003. RESULTS: The pregnancies proceeded without particular obstetrical complications and lead to the birth of 20 healthy children. The population of the women is older than the French average, of higher initial weight. There is no increase in the number of consultation and ultrasound scans. The characteristics of the follow-up are discussed. DISCUSSION AND CONCLUSION: Each maternity team should be able to follow and deliver women with a visual defect. Some specificity however needs to be helped along for these future mothers. The training of the professionals, the work within a dedicated network and the adjusting of our methodologies not only come to improve the pregnancies but also to enrich our practices.

[Retrospective diagnosis of congenital CMV infection in DBS from Guthrie cards: French experience]. / Le diagnostic rétrospectif de l'infection congénitale à cytomégalovirus sur le sang séché des cartes de Guthrie: l'expérience en France.

Systematic screening for cytomegalovirus congenital infection is not performed in France. For children with hearing loss or other neurological CMV compatible symptoms, retrospective diagnosis is possible by PCR detection of CMV DNA in dried blood spot of neonatal Guthrie cards. We report here the results obtained with this technique in the French national reference laboratory for cytomegalovirus.

[Extreme prematurity: comparison of outcome at 5 years depending on gestational age below or above 26 weeks]. / Extrême prématurité : comparaison du devenir à 5 ans en fonction de l'âge gestationnel inférieur ou supérieur à 26 semaines d'aménorrhée.

OBJECTIVE: Is it reasonable to care for children born under 26 gestational weeks (GW)? To answer this question, we compared outcome at 5 years of 2 groups of children:less or equal to 25 GW+6 days (group 1) and 26-27 GW+6 days (group 2). METHOD: Retrospective study on extremely preterm children hospitalized in our center between 1999 and 2001. Perinatal data were obtained from medical reports. Five-year outcome was evaluated by questionnaire sent to Centers for Early Medicosocial Intervention, pediatricians or the child's parents. The children were classified according to their disability: none, minor or major. Progression was considered favorable if the child survived with or without minor disability and unfavorable if the child had died or had major disability. RESULTS: One hundred and sixty-six preterm babies were recorded. In group 1 (n=63), mortality was higher (58% vs 29%; p=0.0002), a neurologic cause was often responsible for death (36% vs 19%; p=0.018), a high level of intracranial hemorrhage was more frequent (35% vs 19%; p=0.002), and a decision to stop healthcare more often made (35% vs 18%; p=0.01) than in group 2 (n=103). Among the 99 survivors, 78 were being followed up at 5 years of age. In terms of disability, no difference was observed between group 1 (n=21) and group 2 (n=57). Including deaths, the risk for unfavorable progression was higher in group 1 (64% vs 41%; p=0.008). CONCLUSION: The progression of under 26-GW preterm babies is more often unfavorable than the progression of babies born 26-27 GW+6 days. However, given the low number of patients, no significant difference was made concerning the prognosis at 5 years between the survivors of the 2 groups.

[Persistent central diabetes insipidus in a very low birth weight infant]. / Diabète insipide central idiopathique chez un très grand prématuré

Central diabetes insipidus (DI) is extremely rare during the neonatal period. Most cases of central DI are secondary to a known aetiology. Substitutive treatment with desmopressin is effective with nasal or oral preparation, but doses are variable and must be tailored individually. We report on a case in a very low birth weight infant with an idiopathic central DI during the first month of life. He was successfully treated with oral desmopressin. The treatment was maintained after discharge with low doses desmospressin.