CX3CL1/Fractalkine as a biomarker for early pregnancy prediction of preterm premature rupture of membranes.

OBJECTIVES: The objective of our study was to evaluate serum CX3CL1/Fractalkine, a monocyte/macrophage chemoattractant expressed in cytotrophoblasts and decidual cells, as a predictive biomarker for the occurrence of preterm premature rupture of membranes (PPROM). METHODS: A case-control study of 438 pregnancies including 82 PPROM cases and 64 preterm labor with intact membranes cases with blood samples collected at first trimester, second trimester and delivery was conducted. The predictive ability of CX3CL1 and maternal risk factors for the occurrence of PPROM was assessed by receiver operating characteristic curve analysis. A second, independent cohort was prospectively constituted to confirm the case-control study results. RESULTS: First trimester CX3CL1 was significantly increased in PPROM cases when compared to matched controls. Multivariate regression analysis highlighted a significant difference for CX3CL1 measured during the first trimester (p<0.001). Alone, CX3CL1 predicts PPROM with a 90 % sensitivity and a specificity around 40 %. The area under the receiver operating characteristic curve for PPROM prediction were 0.64 (95% confidence interval: 0.57-0.71) for first trimester CX3CL1, and 0.61 (95% confidence interval: 0.54-0.68) for maternal risk factors (body mass index<18.5 kg/m2, nulliparity, tobacco use and the absence of high school diploma). The combination of CX3CL1 and maternal risk factors significantly improved the area under the curve: 0.72 (95% confidence interval: 0.66-0.79) (p<0.001). The results were confirmed on a second independent cohort. CONCLUSIONS: CX3CL1 is a promising blood biomarker in the early (first trimester) prediction of PPROM.

[Obstetrical outcome of renal transplant patients followed in a type III maternity hospital. Retrospective study from 2000 to 2020]. / Devenir obstétrical des patientes transplantées rénales suivies dans une maternité de type III. Étude rétrospective de 2000 à 2020.

AIM: To describe pregnancy outcome of kidney transplant patients till 1 year postpartum. METHODS: This retrospective, monocentric study included 15 kidney transplant patients who presented 18 pregnancies, between January 2000 and January 2020. For each of them, we searched for possible obstetrical, fetal and renal complications and we evaluated renal function before, during and after pregnancy. RESULTS: The live birth rate was 84% (16/19) with an average gestational age at delivery of 37 weeks of gestation. The rate of prematurity was 50% (8/16), gestational diabetes was 16.6% (3/18) and preeclampsia was 27.7% (5/18). Cesarean section was performed in 61.1% (11/18) of cases including, 81.8% (9/11) unplanned surgery. The average birth weight was 2635 grams and 37.5% (6/16) of the newborn were small for gestational age. All patients had stable renal function before conception of pregnancy. We noticed two acute graft rejection during pregnancy with only one resulting in graft loss. Four patients had a reduced graft function in 12months of the postpartum. CONCLUSION: Risk of maternal, fetal and renal complications remained high in kidney transplant recipients. Pregnancy should be carefully planned in transplanted women associated with adequate follow-up according to clinical guidelines (normal renal function and blood pressure without proteinuria before pregnancy, no recent graft rejection, period of one year after transplant respected and no teratogenic treatment in the month before pregnancy).

Oxytocin versus prostaglandins for labour Induction of women with an unfavourable cervix after 24 hours of cervical ripening (OPIC): protocol for an open multicentre randomised non-inferiority trial.

INTRODUCTION: It remains uncertain whether the most appropriate management for women with an unfavourable cervix after 24 hours of cervical ripening is repeating the ripening procedure or proceeding directly to induction by oxytocin. No adequately powered trial has compared these strategies. We hypothesise that induction of labour with oxytocin among women who have just undergone an ineffective first ripening procedure is not associated with a higher risk of caesarean delivery than a repeated cervical ripening with prostaglandins. METHODS AND ANALYSIS: We will conduct a multicentre, non-inferiority, open-label, randomised controlled trial aimed at comparing labour induction by oxytocin with a second cervical ripening that uses prostaglandins (slow-release vaginal dinoprostone; oral misoprostol 25 µg; dinoprostone vaginal gel 2 mg). Women (n=1494) randomised in a 1:1 ratio in 10 French maternity units must be ≥18 years with a singleton fetus in vertex presentation, at a term from ≥37+0 weeks of gestation, and have just completed a 24-hour cervical ripening procedure by any method (pharmacological or mechanical) with a Bishop score ≤6. Exclusion criteria comprise being in labour, having more than 3 contractions per 10 min, or a prior caesarean delivery or a history of uterine surgery, or a fetus with antenatally suspected severe congenital abnormalities or a non-reassuring fetal heart rate. The primary endpoint will be the caesarean delivery rate, regardless of indication. Secondary outcomes concern delivery, perinatal morbidity, maternal satisfaction and health economic evaluations. The nature of the assessed procedures prevents masking the study investigators and patients to group assignment. ETHICS AND DISSEMINATION: All participants will provide written informed consent. The ethics committee 'Comité de Protection des Personnes Ile de France VII' approved this study on 2 April 2021 (No 2021-000989-15). Study findings will be submitted for publication and presented at relevant conferences. TRIAL REGISTRATION NUMBER: NCT04949633.

Tranexamic acid for the prevention of blood loss after cesarean among women with twins: a secondary analysis of the TRAnexamic Acid for Preventing Postpartum Hemorrhage Following a Cesarean Delivery randomized clinical trial.

BACKGROUND: Although prophylactic tranexamic acid administration after cesarean delivery resulted in a lower incidence of calculated estimated blood loss of >1000 mL or red cell transfusion by day 2, its failure to reduce the incidence of hemorrhage-related secondary clinical outcomes (TRAnexamic Acid for Preventing Postpartum Hemorrhage Following a Cesarean Delivery trial) makes its use questionable. The magnitude of its effect may differ in women at higher risk of blood loss, including those with multiple pregnancies. OBJECTIVE: This study aimed to compare the effect of tranexamic acid vs placebo to prevent blood loss after cesarean delivery among women with multiple pregnancies. STUDY DESIGN: This was a secondary analysis of the TRAnexamic Acid for Preventing Postpartum Hemorrhage Following a Cesarean Delivery trial data, a double-blind, randomized controlled trial from March 2018 to January 2020 in 27 French maternity hospitals, that included 319 women with multiple pregnancies. Women with a cesarean delivery before or during labor at ≥34 weeks of gestation were randomized to receive intravenously 1 g of tranexamic acid (n=160) or placebo (n=159), both with prophylactic uterotonics. The primary outcome was a calculated estimated blood loss of >1000 mL or a red blood cell transfusion by 2 days after delivery. The secondary outcomes included clinical and laboratory blood loss measurements. RESULTS: Of the 4551 women randomized in this trial, 319 had a multiple pregnancy and cesarean delivery, and 298 (93.4%) had primary outcome data available. This outcome occurred in 62 of 147 women (42.2%) in the tranexamic acid group and 67 of 152 (44.1%) receiving placebo (adjusted risk ratio, 0.97; 95% confidence interval, 0.68-1.38; P=.86). No significant between-group differences occurred for any hemorrhage-related clinical outcomes: gravimetrically estimated blood loss, provider-assessed clinically significant hemorrhage, additional uterotonics, postpartum blood transfusion, arterial embolization, and emergency surgery (P>.05 for all comparisons). CONCLUSION: Among women with a multiple pregnancy and cesarean delivery, prophylactic tranexamic acid did not reduce the incidence of any blood loss-related outcomes.

Reduced telomere length in amniocytes: an early biomarker of abnormal fetal development?

Telomeres protect chromosome ends and control cell division and senescence. During organogenesis, telomeres need to be long enough to ensure the cell proliferation necessary at this stage of development. Previous studies have shown that telomere shortening is associated with growth retardation and congenital malformations. However, these studies were performed in newborns or postnatally, and data on telomere length (TL) during the prenatal period are still very limited. We measured TL using quantitative PCR in amniotic fluid (AF) and chorionic villi (CV) samples from 69 control fetuses with normal ultrasound (52 AF and 17 CV) and 213 fetuses (165 AF and 48 CV) with intrauterine growth retardation (IUGR) or congenital malformations diagnosed by ultrasound. The samples were collected by amniocentesis at the gestational age (GA) of 25.0 ± 5.4 weeks and by CV biopsy at 18.1 ± 6.3 weeks. In neither sample type was TL influenced by GA or fetal sex. In AF, a comparison of abnormal versus normal fetuses showed a significant telomere shortening in cases of IUGR (reduction of 34%, P < 10-6), single (29%, P < 10-6) and multiple (44%, P < 10-6) malformations. Similar TL shortening was also observed in CV from abnormal fetuses but to a lesser extent (25%, P = 0.0002; 18%, P = 0.016; 20%, P = 0.004, respectively). Telomere shortening was more pronounced in cases of multiple congenital anomalies than in fetuses with a single malformation, suggesting a correlation between TL and the severity of fetal phenotype. Thus, TL measurement in fetal samples during pregnancy could provide a novel predictive marker of pathological development.

Cigarette Smoke Condensate Exposure Induces Receptor for Advanced Glycation End-Products (RAGE)-Dependent Sterile Inflammation in Amniotic Epithelial Cells.

Maternal smoking is a risk factor of preterm prelabor rupture of the fetal membranes (pPROM), which is responsible for 30% of preterm births worldwide. Cigarettes induce oxidative stress and inflammation, mechanisms both implicated in fetal membranes (FM) weakening. We hypothesized that the receptor for advanced glycation end-products (RAGE) and its ligands can result in cigarette-dependent inflammation. FM explants and amniotic epithelial cells (AECs) were treated with cigarette smoke condensate (CSC), combined or not with RAGE antagonist peptide (RAP), an inhibitor of RAGE. Cell suffering was evaluated by measuring lactate dehydrogenase (LDH) medium-release. Extracellular HMGB1 (a RAGE ligand) release by amnion and choriodecidua explants were checked by western blot. NF-κB pathway induction was determined by a luciferase gene reporter assay, and inflammation was evaluated by cytokine RT-qPCR and protein quantification. Gelatinase activity was assessed using a specific assay. CSC induced cell suffering and HMGB1 secretion only in the amnion, which is directly associated with a RAGE-dependent response. CSC also affected AECs by inducing inflammation (cytokine release and NFκB activation) and gelatinase activity through RAGE engagement, which was linked to an increase in extracellular matrix degradation. This RAGE dependent CSC-induced inflammation associated with an increase of gelatinase activity could explain a pathological FM weakening directly linked to pPROM.

Human Amnion Epithelial Cells (AECs) Respond to the FSL-1 Lipopeptide by Engaging the NLRP7 Inflammasome.

Context and Objectives: Inflammation is the leading mechanism involved in both physiological and pathological rupture of fetal membranes. Our aim was to obtain a better characterization of the inflammasome-dependent inflammation processes in these tissues, with a particular focus on the nucleotide-binding oligomerization domain (NOD)-like receptor, pyrin domain containing protein 7 (NLRP7) inflammasome. Methods: The presence of NLRP7 inflammasome actors [NLRP7, apoptosis-associated speck-like protein containing a CARD domain (ASC), and caspase-1] was confirmed by reverse transcriptase-polymerase chain reaction (RT-PCR) in human amnion and choriodecidua at the three trimesters and at term. The protein concentrations were then determined by enzyme-linked immunosorbent assay in term tissues, with or without labor. The presence of Mycoplasma salivarium and Mycoplasma fermentans in human fetal membranes was investigated using a PCR approach. Human amnion epithelial cells (AECs) were treated for 4 or 20 h with fibroblast-stimulating lipopeptide-1 (FSL-1), a M. salivarium-derived ligand. Transcripts and proteins quantity was then measured by RT-quantitative PCR and Western blotting, respectively. NLRP7 and ASC colocalization was confirmed by immunofluorescence. Western blots allowed analysis of pro-caspase-1 and gasdermin D cleavage. Results: NLRP7, ASC, and caspase-1 transcripts were expressed in both sheets of human fetal membranes during all pregnancy stages, but only ASC protein expression was increased with labor. In addition, M. salivarium and M. fermentans were detected for the first time in human fetal membranes. NLRP7 and caspase-1 transcripts, as well as NLRP7, ASC, and pro-caspase-1 protein levels, were increased in FSL-1-treated AECs. The NLRP7 inflammasome assembled around the nucleus, and pro-caspase-1 and gasdermin D were cleaved into their mature forms after FSL-1 stimulation. Conclusion: Two new mycoplasmas, M. salivarium and M. fermentans, were identified in human fetal membranes, and a lipopeptide derived from M. salivarium was found to induce NLRP7 inflammasome formation in AECs.

Preterm premature rupture of the membranes: Guidelines for clinical practice from the French College of Gynaecologists and Obstetricians (CNGOF).

In France, the frequency of premature rupture of the membranes (PROM) is 2%-3% before 37 weeks' gestation (level of evidence [LE] 2) and less than 1% before 34 weeks (LE2). Preterm delivery and intrauterine infection are the major complications of preterm PROM (PPROM) (LE2). Prolongation of the latency period is beneficial (LE2). Compared with other causes of preterm delivery, PPROM is associated with a clear excess risk of neonatal morbidity and mortality only in cases of intrauterine infection, which is linked to higher rates of in utero fetal death (LE3), early neonatal infection (LE2), and necrotizing enterocolitis (LE2). The diagnosis of PPROM is principally clinical (professional consensus). Tests to detect IGFBP-1 or PAMG-1 are recommended in cases of uncertainty (professional consensus). Hospitalization is recommended for women diagnosed with PPROM (professional consensus). Adequate evidence does not exist to support recommendations for or against initial tocolysis (Grade C). If tocolysis is prescribed, it should not continue longer than 48 h (Grade C). The administration of antenatal corticosteroids is recommended for fetuses with a gestational age less than 34 weeks (Grade A) and magnesium sulfate if delivery is imminent before 32 weeks (Grade A). The prescription of antibiotic prophylaxis at admission is recommended (Grade A) to reduce neonatal and maternal morbidity (LE1). Amoxicillin, third-generation cephalosporins, and erythromycin (professional consensus) can each be used individually or eythromycin and amoxicillin can be combined (professional consensus) for a period of 7 days (Grade C). Nonetheless, it is acceptable to stop antibiotic prophylaxis when the initial vaginal sample is negative (professional consensus). The following are not recommended for antibiotic prophylaxis: amoxicillin-clavulanic acid (professional consensus), aminoglycosides, glycopeptides, first- or second-generation cephalosporins, clindamycin, or metronidazole (professional consensus). Women who are clinically stable after at least 48 h of hospital monitoring can be managed at home (professional consensus). Monitoring should include checking for clinical and laboratory factors suggestive of intrauterine infection (professional consensus). No guidelines can be issued about the frequency of this monitoring (professional consensus). Adequate evidence does not exist to support a recommendation for or against the routine initiation of antibiotic therapy when the monitoring of an asymptomatic woman produces a single isolated positive result (e.g., elevated CRP, or hyperleukocytosis, or a positive vaginal sample) (professional consensus). In cases of intrauterine infection, the immediate intravenous administration (Grade B) of antibiotic therapy combining a beta-lactam with an aminoglycoside (Grade B) and early delivery of the child are both recommended (Grade A). Cesarean delivery of women with intrauterine infections is reserved for the standard obstetric indications (professional consensus). Expectant management is recommended for uncomplicated PROM before 37 weeks (Grade A), even when a sample is positive for Streptococcus B, as long as antibiotic prophylaxis begins at admission (professional consensus). Oxytocin and prostaglandins are two possible options for the induction of labor in women with PPROM (professional consensus).

Laparoscopic cervico-isthmic cerclage: About 25 cases.

INTRODUCTION: The purpose of this study is to report on our experience of laparoscopic cervico-isthmic cerclage. MATERIAL AND METHOD: A monocentric retrospective study covering a 13-year period during which 25 cases of laparoscopic cerclage outside of pregnancy were performed, using the technique described by Dubuisson, at the University Hospital of Clermont-Ferrand. Individual patient data included pregnancy outcomes before and after cerclage and the characteristics of surgery. RESULTS: The mean age of the patients was 33.9 (±4.6) years. A total of 68 pregnancies were recorded before cerclage, including 31 late miscarriages, 11 premature deliveries, with only 9 pregnancies attaining full-term. The average time of surgery was 54 (±17.5) minutes with a hospital stay of 24h. 3 minor intraoperative complications (12%) with hemorrhage <300cc were noted and managed intraoperatively. In some cases laparoscopy allowed treatment of associated pathologies (septum resection, adhesiolysis, endometriosis, ovarian drilling, tube assessment). 21 pregnancies (68% of patients) were recorded post cerclage including 5 early miscarriages and 16 cesarean deliveries with an average time taken to conceive of 11.8 months. The overall neonatal survival rate after cerclage was 76.2% versus 16.20% before surgery (p<0.0001), with a 100% neonatal survival rate beyond the 1st trimester as compared to 21.6% before cerclage (p<0.0001).

Retinoic acid and tracheal occlusion for diaphragmatic hernia treatment in rabbit fetuses.

INTRODUCTION: Lung hypoplasia and pulmonary arterial hypertension in congenital diaphragmatic hernia lead to a high perinatal mortality. Although sustained fetoscopic tracheal occlusion (TO) improves lung development, a major side effect is abnormal pneumocyte differentiation. This study evaluated the potential ability of intratracheal retinoic acid (RA) administration to reduce adverse effects of sustained TO in a rabbit model of diaphragmatic hernia. METHODS: A left diaphragmatic defect was created on day 23 in time-dated pregnant rabbits. On day 28, the same rabbits underwent sham surgery or TO, with an injection of empty or RA-loaded liposomes. On day 30, the fetuses were harvested, and the lungs were processed for histology, immunohistochemistry, and gene expression quantification. RESULTS: A tracheal RA injection at the time of TO had no effect on the lung-to-body-weight ratio, radial alveolar count or lung connective tissue composition. Retinoic acid plus TO had synergic effects on vascular measurements, proportional medial thickness, and endothelin-1 receptor type-A gene expression. The most noticeable effect was recovery of normal pneumocyte differentiation. CONCLUSION: Retinoic acid plus TO prevented abnormal pneumocyte differentiation and seemed to have a beneficial effect on pulmonary vascularization.

Cigarette smoke condensate affects the retinoid pathway in human amnion.

INTRODUCTION: The preterm premature rupture of membranes (PPROM) is a frequent pathology responsible of more than 30% of preterm births. Tobacco smoking is one of the most frequently described risk factors identified and contributes to the pre term weakening of fetal membranes. As previously demonstrated, all-trans retinoic acid (atRA) regulates several genes involved in the extracellular matrix dynamics, an essential actor in fetal membrane ruptures. We hypothesized that cigarette smoke may affect this pathway in human amnion. METHODS: Amnion was obtained from full-term fetal membranes collected from non-smoking women after cesarean births and used either as explants or for the isolation of derived epithelial cells. The pro-healing and transcriptomic effects of atRA were studied by a scratch assay experiment and quantitative RT-PCR, respectively, after treatment with dimethyl sulfoxyde (DMSO), atRA, DMSO + cigarette smoke condensate (CSC), or atRA + CSC. RESULTS: Our results show a strong alteration of the retinoid pathway after CSC treatment on amnion-derived epithelial cells and explants. We first demonstrated that CSC inhibits the activity of the RARE reporter gene in amnion-derived epithelial cells. Then, atRA's effects on both the transcription of its target genes and wound healing were demonstrated to be inhibited or at least decreased by the CSC in human amnion epithelial cells. DISCUSSION: Here, we demonstrated that CSC altered the retinoid signal, already known to have roles in fetal membrane physiopathology. These results highlight a potential negative action of maternal smoking on the retinoid pathway in human amnion and more generally on pregnancy.

All-trans retinoic acid promotes wound healing of primary amniocytes through the induction of LOXL4, a member of the lysyl oxidase family.

Thirty percent of preterm births directly result from preterm premature rupture of fetal membranes (PPROM). Clinical management currently proposes using a collagen plug to mechanically stop loss of amniotic fluid. Vitamin A and its active metabolite (retinoic acid) have well-known pro-healing properties and could thus make good candidates as a proposable adjuvant to this mechanical approach. Here we investigate the molecular mechanisms involved in the pro-healing properties of all-trans retinoic acid (atRA) in fetal membranes via an approach using an in vitro primary amniocyte wound model and transcriptomics. The results demonstrate that atRA promotes migration in primary amniocytes, improving wound healing in vitro by up to 90%. This effect is mediated by the induction of LOXL4, which plays a crucial role in the dynamics of the extracellular matrix by regulating collagen reticulation. This new insight into how atRA exerts its pro-healing properties prompts us to propose using atRA as a candidate strategy to help prevent future PPROM.

Nuclear retinoid receptors and pregnancy: placental transfer, functions, and pharmacological aspects.

Animal models of vitamin A (retinol) deficiency have highlighted its crucial role in reproduction and placentation, whereas an excess of retinoids (structurally or functionally related entities) can cause toxic and teratogenic effects in the embryo and foetus, especially in the first trimester of human pregnancy. Knock-out experimental strategies-targeting retinoid nuclear receptors RARs and RXRs have confirmed that the effects of vitamin A are mediated by retinoic acid (especially all-trans retinoic acid) and that this vitamin is essential for the developmental process. All these data show that the vitamin A pathway and metabolism are as important for the well-being of the foetus, as they are for that of the adult. Accordingly, during this last decade, extensive research on retinoid metabolism has yielded detailed knowledge on all the actors in this pathway, spurring the development of antagonists and agonists for therapeutic and research applications. Natural and synthetic retinoids are currently used in clinical practice, most often on the skin for the treatment of acne, and as anti-oncogenic agents in acute promyelocytic leukaemia. However, because of the toxicity and teratogenicity of retinoids during pregnancy, their pharmacological use needs a sound knowledge of their metabolism, molecular aspects, placental transfer, and action.

Postpartum hemorrhage: guidelines for clinical practice from the French College of Gynaecologists and Obstetricians (CNGOF): in collaboration with the French Society of Anesthesiology and Intensive Care (SFAR).

Postpartum haemorrhage (PPH) is defined as blood loss ≥500mL after delivery and severe PPH as blood loss ≥1000mL, regardless of the route of delivery (professional consensus). The preventive administration of uterotonic agents just after delivery is effective in reducing the incidence of PPH and its systematic use is recommended, regardless of the route of delivery (Grade A). Oxytocin is the first-line prophylactic drug, regardless of the route of delivery (Grade A); a slowly dose of 5 or 10 IU can be administered (Grade A) either IV or IM (professional consensus). After vaginal delivery, routine cord drainage (Grade B), controlled cord traction (Grade A), uterine massage (Grade A), and routine bladder voiding (professional consensus) are not systematically recommended for PPH prevention. After caesarean delivery, placental delivery by controlled cord traction is recommended (grade B). The routine use of a collector bag to assess postpartum blood loss at vaginal delivery is not systematically recommended (Grade B), since the incidence of severe PPH is not affected by this intervention. In cases of overt PPH after vaginal delivery, placement of a blood collection bag is recommended (professional consensus). The initial treatment of PPH consists in a manual uterine examination, together with antibiotic prophylaxis, careful visual assessment of the lower genital tract, a uterine massage, and the administration of 5-10 IU oxytocin injected slowly IV or IM, followed by a maintenance infusion not to exceed a cumulative dose of 40IU (professional consensus). If oxytocin fails to control the bleeding, the administration of sulprostone is recommended within 30minutes of the PPH diagnosis (Grade C). Intrauterine balloon tamponade can be performed if sulprostone fails and before recourse to either surgery or interventional radiology (professional consensus). Fluid resuscitation is recommended for PPH persistent after first line uterotonics, or if clinical signs of severity (Grade B). The objective of RBC transfusion is to maintain a haemoglobin concentration (Hb) >8g/dL. During active haemorrhaging, it is desirable to maintain a fibrinogen level ≥2g/L (professional consensus). RBC, fibrinogen and fresh frozen plasma (FFP) may be administered without awaiting laboratory results (professional consensus). Tranexamic acid may be used at a dose of 1 g, renewable once if ineffective the first time in the treatment of PPH when bleeding persists after sulprostone administration (professional consensus), even though its clinical value has not yet been demonstrated in obstetric settings. It is recommended to prevent and treat hypothermia in women with PPH by warming infusion solutions and blood products and by active skin warming (Grade C). Oxygen administration is recommended in women with severe PPH (professional consensus). If PPH is not controlled by pharmacological treatments and possibly intra-uterine balloon, invasive treatments by arterial embolization or surgery are recommended (Grade C). No technique for conservative surgery is favoured over any other (professional consensus). Hospital-to-hospital transfer of a woman with a PPH for embolization is possible once hemoperitoneum is ruled out and if the patient's hemodynamic condition so allows (professional consensus).

Congenital diaphragmatic hernia may be associated with 17q12 microdeletion syndrome.

Microdeletions of 17q12 encompassing TCF2 are associated with maturity-onset of diabetes of the young type 5, cystic renal disease, pancreatic atrophy, Mullerian aplasia in females and variable cognitive impairment. We report on a patient with a de novo 17q12 microdeletion, 1.8 Mb in size, associated with congenital diaphragmatic hernia (CDH). The 5-year-old male patient presented multicystic renal dysplasia kidneys, minor facial dysmorphic features and skeletal anomalies, but neither developmental delay nor behavioral abnormalities. CDH has been previously associated with the 17q12 microdeletion syndrome only in one prenatal case. The present study reinforces the hypothesis that CDH is part of the phenotype for 17q12 microdeletion and that 17q12 encompasses candidate(s) gene(s) involved in diaphragm development. We suggest that PIGW, a gene involved in an early step of GPI biosynthesis, could be a strong candidate gene for CDH.

Prenatal ultrasound findings observed in the Wolf-Hirschhorn syndrome: data from the registry of congenital malformations in Auvergne.

BACKGROUND: Wolf-Hirschhorn syndrome (WHS) is associated with facial dysmorphism including high forehead, high nasal bridge, hypertelorism and severe mental retardation. WHS results from a 4p16.3 deletion. Only a small number of reports have been made on the prenatal ultrasound findings observed in WHS. CASES: Here we report our experience on 10 cases of WHS ascertained prenatally between 1983 and 2009 through the CEMC-Auvergne registry of congenital malformations. CONCLUSION: The assumption that a "Greek warrior helmet" facies is pathognomonic of WHS could lead to misdiagnosis. Other clinical findings such as severe and early onset intrauterine growth retardation, facial dysmorphism (high forehead, high nasal bridge, low-set ears, micrognathia, hypertelorism), atrial or ventricular septal defect, and renal dysplasia should help obstetricians to suspect the diagnosis of WHS prenatally.

Placenta percreta: urologic complication after successful conservative management by uterine arterial embolization: a case report.

We report a case of placenta accreta that was managed conservatively by uterine arterial embolization and subsequently was complicated by hematuria. Ultrasound revealed a calcified mass at the posterior bladder wall. A careful resection under cystoscopy was carried out without hemorrhagic complication. Pathologic examination showed placental tissue that confirmed placenta percreta.

Hyperechoic congenital lung lesions in a non-selected population: from prenatal detection till perinatal management.

OBJECTIVE: To present longitudinal observations of hyperechoic lung lesions (HLL) in a non-selected population from the time of prenatal diagnosis by ultrasound (US) until postnatal surgery. METHODS: We conducted a retrospective study of all fetuses diagnosed with an HLL between 1990 and 2005 in our Fetal Medicine Unit. RESULTS: We observed 21 cases of HLL. Among the 17 fetuses with unilateral lesion, two cyst punctures were attempted on fetuses with signs of fetal compromise. Termination of pregnancy (TOP) was performed on seven fetuses. Fourteen fetuses were followed till birth. First Chest X-ray was abnormal in ten cases, while delayed CT scans revealed a lung lesion in 12 cases. Two neonates required emergency surgery and died post operatively. Surgery was successfully performed in all other cases (n = 10). Pathological examination revealed congenital high airway obstruction syndrome, CHAOS (n = 4), lower airway stenosis (n = 2), bronchogenic cyst (n = 1), congenital lobar emphysema (n = 1), and congenital cystic adenomatoid malformation, CCAM (n = 11) including two cases associated with a sequestration. CONCLUSION: HLL cover a wide spectrum of lung abnormalities of various severities. Post natal management should always include an early chest X-ray and CT scan to allow appropriate selection for surgery.