Translation and validation of the PVSQ and DHI-PC questionnaires for pediatric dizziness.

AIMS: Validation of the PVSQ self-report questionnaire (diagnosis) and the DHI-PC caregiver report questionnaire (Dizziness Handicap Inventory) aims to improve the management of pediatric vertigo, which is often under-diagnosed. MATERIALS AND METHODS: The PVSQ and DHI-PC questionnaires were translated according to the Forward-Backward method and presented to a group of patients consulting for dizziness in a referral center and to a control group. A retest was performed at 2weeks for both questionnaires. Statistical validation consisted in calculating discriminatory capacity, ROC curve, reproducibility and internal consistency. The main study objective was the translation and validation of the PVSQ and DHI-PC questionnaires in French. The secondary objectives were to compare results in two subgroups according to the vestibular or non-vestibular etiology of dizziness and to assess the correlation between the two questionnaires. RESULTS: In total, 112 children, in two comparable groups (53 cases and 59 controls), were included. Mean PVSQ score was 14.62 for cases and 6.55 for controls (P<0.001). Reproducibility was moderate, and internal consistency and construct validity were satisfactory. A cut-off of 11 corresponded to maximum Younden index. Mean DHI-PC score was 41.6 (cases only). Reproducibility was moderate, and internal consistency and construct validity were satisfactory. CONCLUSION: The validation of the PVSQ and DHI-PC questionnaires offers two new tools in the management of dizziness, for both screening and follow-up.

Paediatric vestibular assessment in French cochlear implant centres: Challenges and improvement areas.

OBJECTIVE: Survey of paediatric vestibular activity in all 30 French paediatric cochlear implant (CI) centres to identify challenges and areas of improvement. METHOD: All 30 French CI centres answered a 29-question questionnaire about their paediatric vestibular activity, equipment, and management in different clinical situations (e.g. vestibular assessment before a cochlear implantation or in cases of vertigo) at different ages. RESULTS: Eighteen CI centres had dedicated paediatric vestibular clinics and 12 did not. Minimum age required for vestibular testing was 3 years in eight centres. Four vestibular tests stood out: caloric tests, video Head Impulse Test (vHIT), rotating chair, vestibular evoked myogenic potentials (VEMP). Depending on the centre's experience, the use of vestibular tests in clinical routine was very heterogeneous. Expert centres mostly used vHIT and cervical VEMP (in bone conduction) for assessments before the first cochlear implantation in 1-year-old children. Dizziness assessment in 4-year children was based on the use of vHIT, cervical VEMP on bone conduction, rotatory test, and caloric test. Ocular VEMP was rarely used. CONCLUSIONS: Paediatric vestibular assessment requires specific expertise compared to adults. Due to a lack of specialised human resources, some centres may be unable to follow French paediatric CI guidelines. International recommendations could help standardise paediatric vestibular management and public health policies should be discussed to improve training and access for children.

Magnetic resonance imaging as a structural refinement to the American College of Rheumathology clinical classification criteria for knee osteoarthritis.

OBJECTIVE: To evaluate if fulfilment of the definition of osteoarthritis (OA) based on the American College of Rheumatology (ACR) clinical criteria corresponds to pathological knee findings evaluated by magnetic resonance imaging (MRI). To evaluate if any such criteria is associated with a specific MRI pattern. METHODS: Forty-six consecutive patients aged 50 years or more referred by their general practitioners (GPs) to a radiology department because of non-traumatic knee pain underwent MRI using a dedicated low field (0.2 T) machine. RESULTS: MRI results were compared against the ACR criteria for knee OA. Patients with knee pain fulfilling the ACR criteria showed more severe synovial fluid effusion (OR 6.2, 95% CI 2.02 to 19.1), cartilage lesions in the medial area (OR 2.4, 95% CI 1.2 to 5) and higher mean number of osteophytes (OR 2.3, 95% CI 1.1 to 4.5). The association between single criteria and MRI features was more difficult to establish. Nonetheless, crepitus at joint movement was associated with synovial fluid effusion (p=0.02); bone enlargement was more frequent in patients with lesions of the posterior cruciate ligament (p=0.0001); no palpable warmth was associated with cartilage lesions (p=0.02), and morning stiffness shorter than 30 minutes was associated with the surface of bone edema (p=0.02). CONCLUSIONS: The ACR clinical criteria identify patients showing the most important features of OA. The association between individual clinical ACR criteria and OA pathology depicted by MRI may be difficult to explain on the basis of anatomical changes and needs further evaluation.

The simplified French Matrix. A tool for evaluation of speech intelligibility in noise.

INTRODUCTION: In audiology, the usual tests of speech perception in silence are non-predictive of intelligibility in noise. The French Matrix was developed to assess intelligibility in noise in adults with normal cognitive capacity. A simplified adaptive version, FRA-SIMAT, was derived for use with children and elderly persons with diminished memory span. The aim of the present study was to apply this adaptive procedure to determine signal-to-noise ratio (SNR) according to percentage intelligibility. METHODS: Twenty normal-hearing adults and 60 normal-hearing children aged 5-6 years (G1), 7-8 years (G2) and 9-10 years (G3) were included. FRA-SIMAT uses groups of 3 words, to limit memory demand. RESULTS: In adults, SNR for 50% (SNR-50) and 80% intelligibility (SNR-80) was respectively -7.1±1.4dB and -3.7±1.6dB. In children, SNR-50 was -4.2±1.3dB in G1, -4.6±1.2dB in G2, and -5.5±1.5dB in G3. CONCLUSION: The FRA-SIMAT test of speech perception in noise was validated in adults and children of different ages, and can be implemented as a diagnostic and rehabilitation tool in clinical practice.

Outcome for bilateral cochlear implantation in patients with congenital Cytomegalovirus infection.

OBJECTIVES: To analyze the impact of bilateral cochlear implantation (CI) on perceptual and linguistic development in hearing-impaired children with congenital Cytomegalovirus (CMV) infection. PATIENTS AND METHOD: A retrospective study was performed for the period 1991-2016 in a pediatric CI reference center. Closed Set Word (CSW) recognition scores, Categories of Auditory Performance (CAP) and linguistic level on the MT Lenormand scale (MTL) were compared between bilateral (Bi) and unilateral (Uni) groups 12, 24 and 36 months after first CI (CI-1). RESULTS: 84 patients with congenital CMV infection who underwent CI were included, in 2 groups: sequential or simultaneous bilateral CI (Bi) (N=20), and unilateral CI (Uni) (N=64). Twelve, 24 and 36 months after CI-1, CSW scores were 35.56%, 64.52% and 82.93% in Uni and 60.3%, 85% (P=0.0084*), and 100% (P=0.00085*) in Bi. CAP scores 12, 24 and 36 months after CI-1 were 2.57, 3.85 and 4.3 in Uni and 3.91 (P=0.0068*), 5.00 (p=0.029*) and 5.50 (P=0.051*) in Bi. MTL linguistic level scores at 12, 24 and 36 months were 0.72, 1.25 and 1.65 in Uni, and 1.72, 3 (P=0.033) and 3.11 (P=0.045) in Bi. These significantly better scores in Bi at 24 and 36 months after CI-1 were also found on analysis of subgroups with no associated neurologic disorder (P=0.046* and P=0.032*), no associated psychiatric pathology (P=0.0055* and P=0.0073*), and no other associated disorder (P=0.0018* and P=0.035*), and for all subgroups together (P=0.0036 and P=0.037). CONCLUSION: Bilateral CI is a faster way than unilateral CI for patients with congenital CMV infection to achieve structured fluent oral language. 50% of the series showed cerebral abnormalities on MRI, without difference between groups. This was not in itself predictive of poor progression of oral communication, unless associated with major neurologic disorder. Some children made little or no use of their CI in the medium term.

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.

Hearing impairment and osteogenesis imperfecta: Literature review.

The goal is to clarify the epidemiology of hearing loss in patients with osteogenesis imperfecta (OI), so as to improve management. A literature review analyzed data from 15 patient series. Hearing loss prevalence in OI varied widely, from 2% to 94.1%. Typically, hearing loss was conductive in young patients and sensorineural in older patients. Prevalence increased with age, but after 50 years the increase was slight, and seldom became total. Hearing loss was usually bilateral, but not necessarily symmetrical. There were no correlations between type of mutation (COL1A1 or COL1A2), prevalence, type or severity of hearing loss, or age of symptom onset; there was intra-familial variability. There was also no correlation between mutated gene, type of mutation and auditory phenotype. Frequency, type and severity of hearing loss were unrelated to other clinical parameters. Hearing loss prevalence depended on type of OI: higher in type I and lower in type IV. Incidence of otitis media was higher in children with OI, related to the associated craniofacial dysmorphia. Hearing screening before 5 years of age with long-term follow-up are recommended.

Sequential bilateral cochlear implants in children and adolescents: Outcomes and prognostic factors.

OBJECTIVES: Cochlear implants (CI) have enabled an increasing proportion of deaf children to develop oral communication. Despite the well-known benefits of bilateral implantation, many of these children and teenagers have only a unilateral implant. The aim of this study was to evaluate the benefits of sequential bilateral CI and the influence of relevant factors on outcome. MATERIAL AND METHODS: A single-center retrospective study included 109 children and adolescents who received a second sequential CI between 2008 and 2016. Subjects were evaluated before sequential implantation and subsequently at 3, 12 and 24 months, on Speech Intelligibility Rating and speech perception tests: Categories of Auditory Performance, word and sentence recognition in silence and in noise. The influence of inter-implant interval and performance with the first CI were analyzed. RESULTS: In the majority of patients, sequential CI provided significant improvement in speech and intelligibility perception. These benefits were seen not only for short but also for long inter-implant intervals. Some subjects with poor performance with their first implant showed significant progression after sequential bilateral implantation. CONCLUSION: In view of the benefits of sequential bilateral CI, we suggest that a second CI should be proposed to all unilaterally implanted children and adolescents, regardless of inter-implant interval and initial performance with the first CI. Further studies need to be conducted to identify prognostic factors for success in sequential contralateral implantation.

Pediatric cochlear reimplantation: Decision-tree efficacy.

OBJECTIVES: The context leading to pediatric cochlear reimplantation (CreI) can be complex. The objectives of this study were to define initial CreI indications, analyze final diagnosis and draw up a decision-tree. METHODS: A retrospective study included patients undergoing CreI between 2005 and 2015. Demographic characteristics, CreI circumstances and technical reports were collected. Circumstances indicating CreI were classified in 3 groups: performance decrement, suspected device failure, or medical. After CreI, final diagnoses were classified in 2 groups: confirmed failure (DFail) or medical (DMed). RESULTS: 69 out of 734 cochlear implantation surgeries were for CreI (8%). Manufacturers' reports were available in 64 cases (93%). Two principal causes were found: trauma and infection. Initial indications were: performance decrement: 27%; device failure: 56%; and medical: 17%. Final diagnoses were: DFail: 72%; and DMed: 28%. Initial indication and final diagnosis were similar in 86% of cases. The majority of the 14% initial indication errors belonged to the "performance decrement" group. Traumatic causes correlated with risk of initial indication error (P=0.039). CONCLUSION: Apart from spontaneous device failure, the two causes of CreI were infection and trauma. Using the present decision algorithm, half of the complex cases were resolved after CreI.

Patología apendicular: de lo frecuente a lo infrecuente / Appendicular pathology: from frequent to infrequent

La apendicitis aguda es la patología más común en el apéndice y la causa principal del abdomen quirúrgico. Aproximadamente 300,000 personas se someten a apendicectomía cada año en los Estados Unidos. El riesgo estimado de presentar un cuadro de apendicitis aguda en algún momento de la vida está estimado en un 7%. El uno por ciento de las apendicectomías corresponde a tumores apendiculares. Los tumores malignos se confirman por análisis patológico en 0,9 al 1.4% de todas las apendicetomías realizadas.Objetivos. Evaluar incidencia de patología apendicular benigna, analizar la incidencia de tumores apendiculares, determinar sobrevida y mortalidad de tumores apendiculares a 5 años. (AU)

The acute appendicitis is the most common pathology in the appendix and the main cause of the surgical abdomen. Approximately 300,000 people undergo appendectomy each year in the United States. The life-time risk of acute appendicitis is around 7%. One percent of the appendicectomies correspond to appendicular tumors. Malignant tumors are confirmed by pathological analysis in 0.9­1.4% of all appendectomies performed. Objectives To evaluate the incidence of benign appendicular pathology, to analyze the incidence of appendicular tumors, to determine survival and mortality of appendicular tumors at 5 years. (AU)

Choroidal excavation in choroidal osteoma complicated by choroidal neovascularization.

PurposeTo describe multimodal imaging features of choroidal osteoma (CO) complicated by choroidal neovascularization (CNV) and focal choroidal excavation (FCE).MethodsPatients presenting with CO and CNV between January and October 2016 were considered for this study. Diagnosis of CO was confirmed by ultrasound examination. All patients underwent multimodal imaging including optical coherence tomography (OCT), swept-source OCT angiography (DRI OCT Triton, Topcon, Inc., Tokyo, Japan) and fluorescein angiography (Spectralis HRA+OCT; Heidelberg Engineering, Heidelberg, Germany).ResultsTwo patients (one with bilateral CO) were included in the study. OCT showed a FCE in two eyes of two patients (one in correspondence of the CNV and the other adjacent to the CNV). OCT-A demonstrated presence of microvascular flow within neovascular network of the CNVs. Decalcification of the tumor was noted in correspondence of one eye with FCE.ConclusionsFCE may be found in eyes with choroidal osteoma and CNV. OCT-A was a valuable tool for detection of CNV complicating choroidal osteoma. Decalcification of choroidal osteoma may represent a common pathogenic pathway for development of FCE and CNV in choroidal osteoma.

Optical coherence tomography analysis of evolution of Bruch's membrane features in angioid streaks.

PurposeTo describe optical coherence tomography (OCT) features in the Bruch's membrane (BM) of eyes with angioid streaks (AS) and evaluate their evolution over the follow-up.Patients and methodsPatients with AS presenting between March 2016 and September 2016 at two tertiary referral centers were consecutively recruited in this study. Eligibility criteria included prior spectral domain (SD)-OCT images, taken at least 3 months before at the same referral center, with automated eye tracking and image alignment modules. Alterations of BM were described and compared to previous scans over the follow-up. Multimodal imaging was used to identify alteration of retinal pigment epithelium (RPE) and choroid.ResultsThirty-two eyes of 16 consecutive patients with AS were included. BM undulations, mostly observed around the optic nerve head, were found in 19 (59.4%) of 32 eyes. BM breaks were found in 31 (96.9%) out of 32 eyes. Evolution of BM undulations into BM breaks was observed in 5 eyes (15.6%). Choroidal neovascularization (CNV) was observed in 12 eyes (37.5%) during follow-up, typically in areas of BM interruption.ConclusionsBM undulations, probably caused by high stretching forces exerted on the BM around the optic nerve head, seem to precede some BM breaks. BM interruptions may be a preferred way for the growth of CNV, which was identified in one-third of our cases.

Childhood psychogenic hearing loss: Identification and diagnosis.

Psychogenic hearing loss, formerly known as functional or non-organic hearing loss, is a classic cause of consultation in infantile audiology. Risk factors include female gender, and age 8 or 12 years. Onset is relatively sudden, without impact on schooling or voice quality. Audiometric signs comprise non-superimposable audiometric thresholds (variable audiometric results), bilaterality, flat mean audiometric curve, and discrepancy between pure-tone and speech audiometry. The child needs reassuring during audiometric examination: attention-diversion techniques may be effective. Objective audiometry allows positive diagnosis, followed by rehabilitation and psychological care.

How to perform ABR in young children.

The diagnosis of hearing loss, especially in the context of newborn hearing screening, is mostly based on auditory brainstem response (ABR). According to the official CCAM nomenclature, ABR consists of recording early auditory evoked potentials to detect thresholds, study conduction times and measure amplitudes (corresponding to codes CDQP006 when performed without general anesthesia, and CDQP014 when performed with general anesthesia). ABR must be rigorously performed and interpreted, always in combination with a complete ENT examination and behavioral audiometry as soon as possible. In order to obtain good quality recordings, ABR must be performed with the infant totally immobile, during a nap. Several protocols can be used according to the child's age in order to obtain good quality sleep. ABR contribute to a precise hearing diagnosis, allowing early management by the first months of life.

Long term results after cochlear implantation: Schooling and social insertion of teenagers and young adults.

INTRODUCTION: To analyse the long-term impact of cochlear implantation (CI) in deaf patients on perception and language, and on schooling and social insertion. METHOD: A total of 131 profoundly deaf patients that had unilateral CI, aged at follow up 16 to 26 years old and with 5 years minimum of follow up were included for the study. 84 of them had profound congenital deafness (Gc) and 47 had progressive deafness (Gp). In Gc, the mean age at CI was 5 years (3-16), the mean FU was 15 years. In Gp, the mean age at CI was 9 years (3-17 years), the mean FU was 11 years. The perceptive scores (open set sentences (OSS), word in open set sentences (WSS)), the intelligibility rate (SIR), the lexical scores (EVIP) were analysed and compared to the Schooling Status (SS) & Social Insertion (SSSI) (University/Working/Handicapped environment) and Classified as (Mainstream or Specialized). Both groups were compared. RESULTS: The mean results for Gc and Gp respectively were for the OSS score: 67.1% and 80.7% (P=0.009) and the SIR: 4.5 and 4.8 (P=0.049). EVIP scores were: in Gc, 56% of patients had normal or≥+1 SD; in Gp 72% of patients had normal or≥+1 SD. The SSSI: 63% in Gc and 83% in Gp were in Mainstream Schooling. Low level of EVIP scores were linked to Specialized environment in both groups (P=0.01, P=0.04). DISCUSSION: Long-term results show that differences have to be expected whether implanted children had congenital or progressive deafness. In both groups, strong correlations remain between perceptive results, lexical scores and the SSSI. CONCLUSION: On the long term the lexical level remains a relevant tool to assess the evolution of implantees. For those who do not reach a near to normal lexical level, impact on the schooling and the social insertion has to be expected.

Pseudorabies Virus US3 Protein Kinase Protects Infected Cells from NK Cell-Mediated Lysis via Increased Binding of the Inhibitory NK Cell Receptor CD300a.

UNLABELLED: Several reports have indicated that natural killer (NK) cells are of particular importance in the innate response against herpesvirus infections. As a consequence, herpesviruses have developed diverse mechanisms for evading NK cells, although few such mechanisms have been identified for the largest herpesvirus subfamily, the alphaherpesviruses. The antiviral activity of NK cells is regulated by a complex array of interactions between activating/inhibitory receptors on the NK cell surface and the corresponding ligands on the surfaces of virus-infected cells. Here we report that the US3 protein kinase of the alphaherpesvirus pseudorabies virus (PRV) displays previously uncharacterized immune evasion properties: it triggers the binding of the inhibitory NK cell receptor CD300a to the surface of the infected cell, thereby providing increased CD300a-mediated protection of infected cells against NK cell-mediated lysis. US3-mediated CD300a binding was found to depend on aminophospholipid ligands of CD300a and on group I p21-activated kinases. These data identify a novel alphaherpesvirus strategy for evading NK cells and demonstrate, for the first time, a role for CD300a in regulating NK cell activity upon contact with virus-infected target cells. IMPORTANCE: Herpesviruses have developed fascinating mechanisms to evade elimination by key elements of the host immune system, contributing to their ability to cause lifelong infections with recurrent reactivation events. Natural killer (NK) cells are central in the innate antiviral response. Here we report that the US3 protein kinase of the alphaherpesvirus pseudorabies virus displays a previously uncharacterized capacity for evasion of NK cells. Expression of US3 protects infected cells from NK cell-mediated lysis via increased binding of the inhibitory NK cell receptor CD300a. We show that this US3-mediated increase in CD300a binding depends on aminophospholipids and on cellular p21-activated kinases (PAKs). The identification of this novel NK cell evasion strategy may contribute to the design of improved herpesvirus vaccines and may also have significance for other PAK- and CD300a-modulating viruses and cancer cells.

Placental programmed cell death: insights into the role of aquaporins.

STUDY HYPOTHESIS: Are the placental aquaporins (AQPs) involved in the apoptosis of human trophoblast? STUDY FINDING: The general blocking of placental AQPs with HgCl2 and, in particular, the blocking of AQP3 activity with CuSO4 abrogated the apoptotic events of human trophoblast cells. WHAT IS KNOWN ALREADY: Although apoptosis of trophoblast cells is a natural event involved in the normal development of the placenta, it is exacerbated in pathological processes, such as pre-eclampsia, where an abnormal expression and functionality of placental AQPs occur without alterations in the feto-maternal water flux. Furthermore, fluctuations in O2 tension are proposed to be a potent inducer of placental apoptotic changes and, in explants exposed to hypoxia/reoxygenation (H/R), transcellular water transport mediated by AQPs was undetectable. This suggests that AQPs might be involved in processes other than water transport, such as apoptosis. STUDY DESIGN, SAMPLES/MATERIALS, METHODS: Explants from normal term placentas were maintained in culture under conditions of normoxia, hypoxia and H/R. Cell viability was determined by assessing 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide incorporation. For the general or specific inhibition of AQPs, 0.3 mM HgCl2, 5 mM CuSO4, 0.3 mM tetraethylammonium chloride (TEA) or 0.5 mM phloretin were added to the culture medium before explants were exposed to each treatment. Oxidative stress parameters and apoptotic indexes were evaluated in the presence or absence of AQPs blockers. AQP3 expression was confirmed by western blot and immunohistochemistry. MAIN RESULTS AND THE ROLE OF CHANCE: First, we observed that in H/R treatments cell viability decreased by 20.16 ± 5.73% compared with those explants cultured in normoxia (P = 0.009; n = 7). Hypoxia did not modify cell viability significantly. Both hypoxia and H/R conditions induced oxidative stress. Spontaneous chemiluminescence and thiobarbituric acid reactive substance levels were significantly increased in explants exposed to hypoxia (n = 6 per group, P = 0.0316 and P = 0.0009, respectively) and H/R conditions (n = 6 per group, P = 0.0281 and P = 0.0001, respectively) compared with those cultured in normoxia. Regarding apoptosis, H/R was a more potent inducer of trophoblast apoptosis than hypoxia alone. Bax expression and the number of apoptotic nuclei were significantly higher in explants cultured in H/R compared with normoxia and hypoxia conditions (n = 12, P = 0.0135 and P = 0.001, respectively). DNA fragmentation was only observed in H/R and, compared with normoxia and hypoxia, the activity of caspase-3 was highest in explants cultured in H/R (n = 12, P = 0.0001). In explants exposed to H/R, steric blocking of AQP activity with HgCl2 showed that DNA degradation was undetectable (n = 12, P = 0.001). Bax expression and caspase-3 activity were drastically reduced (n = 12, P = 0.0146 and P = 0.0001, respectively) compared with explants cultured in H/R but not treated with HgCl2. Similar results were observed in explants exposed to H/R when we blocked AQP3 activity with CuSO4. DNA degradation was undetectable and the number of apoptotic nuclei and caspase-3 activity were significantly decreased compared with explants cultured in H/R but not treated with CuSO4 (n = 12, P = 0.001 and P = 0.0001, respectively). However, TEA and phloretin treatments, to block AQP1/4 or AQP9, respectively, failed in abrogate apoptosis. In addition, we confirmed the expression and localization of AQP3 in explants exposed to H/R. LIMITATIONS, REASONS FOR CAUTION: Our studies are limited by the number of experimental conditions tested, which do not fully capture the variability in oxygen levels, duration of exposure and alternating patterns of oxygen seen in vivo. WIDER IMPLICATIONS OF THE FINDINGS: Our results suggest that any alteration in placental AQP expression might disturb the equilibrium of the normal apoptotic events and may be an underlying cause in the pathophysiology of placental gestational disorders such as pre-eclampsia. Furthermore, the dysregulation of placental AQPs may be one of the crucial factors in triggering the clinical manifestations of pre-eclampsia. LARGE SCALE DATA: n/a. STUDY FUNDING AND COMPETING INTERESTS: This study was supported by UBACyT 20020090200025 and 20020110200207 grants and PIP-CONICET 11220110100561 grant, and the authors have no conflict of interest to declare.