Neu Laxova syndrome and megacystis in the first trimester: Broadening the fetal phenotype.

Neu Laxova syndrome (NLS) is a rare and lethal congenital disorder characterized by severe intra-uterine growth retardation (IUGR), ichthyosis, abnormal facial features, limb abnormalities with arthrogryposis and a wide spectrum of severe malformations of the central nervous system (CNS). NLS is due to biallelic variants in three genes previously involved in serine-deficiency disorders (PHGDH, PSAT1 and PSPH), extending the phenotypic spectrum of these disorders.

Biochemical Screening for Fetal Trisomy 21: Pathophysiology of Maternal Serum Markers and Involvement of the Placenta.

It is now well established that maternal serum markers are often abnormal in fetal trisomy 21. Their determination is recommended for prenatal screening and pregnancy follow-up. However, mechanisms leading to abnormal maternal serum levels of such markers are still debated. Our objective was to help clinicians and scientists unravel the pathophysiology of these markers via a review of the main studies published in this field, both in vivo and in vitro, focusing on the six most widely used markers (hCG, its free subunit hCGß, PAPP-A, AFP, uE3, and inhibin A) as well as cell-free feto-placental DNA. Analysis of the literature shows that mechanisms underlying each marker's regulation are multiple and not necessarily directly linked with the supernumerary chromosome 21. The crucial involvement of the placenta is also highlighted, which could be defective in one or several of its functions (turnover and apoptosis, endocrine production, and feto-maternal exchanges and transfer). These defects were neither constant nor specific for trisomy 21, and might be more or less pronounced, reflecting a high variability in placental immaturity and alteration. This explains why maternal serum markers can lack both specificity and sensitivity, and are thus restricted to screening.

Percreta score to differentiate between placenta accreta and placenta percreta with ultrasound and MR imaging.

INTRODUCTION: The objective of this study was to assess the performance of ultrasound and magnetic resonance imaging (MRI) features in helping to classify the type of placenta accreta spectrum (PAS; accreta/increta vs percreta), alone or combined in a predictive score. MATERIAL AND METHODS: We conducted a retrospective study in 82 pregnant women with PAS who underwent ultrasound and MRI examination of the pelvis before delivery (from an initial cohort of 185 women with PAS). We estimated the sensitivity, specificity and accuracy of MRI and ultrasound in the diagnosis of the type of PAS. We analyzed cesarean and imaging features using univariable logistic regression analysis. We constructed a nomogram to predict the risk of placenta percreta and validated it with bootstrap resampling, then used receiver operating characteristic curves to assess the performance of the model in distinguishing between placenta percreta and placenta accreta/increta. RESULTS: Among the 82 patients, 29 (35%) had placenta accreta/increta and 53 (65%) had placenta percreta. The best features to discriminate between placenta accreta/increta and placenta percreta with ultrasound were increased vascularization at the uterine serosa-bladder wall interface (odds ratio [OR] 7.93; 95% confidence interval [CI] 2.78-24.99; p < 0.01) and the number of lacunae without a hyperechogenic halo (OR 1.36; 95% CI 1.14-1.67; p = 0.012). Concerning MRI markers, heterogeneous placenta (OR 12.89; 95% CI 3.05-89.16; p = 0.002), dark intraplacental bands (OR 12.89; 95% CI 3.05-89.16; p = 0.002) and bladder wall interruption (OR 15.89; 95% CI 4.78-73.33; p < 0.001) had a higher OR in discriminating placenta accreta/increta from placenta percreta. The nomogram yielded areas under the curve of 0.841 (95% CI 0.754-0.927) and 0.856 (95% CI 0.767-0.945), after bootstrap resampling, for the accurate prediction of placenta percreta. CONCLUSIONS: The nomogram we developed to predict the risk of placenta percreta among patients with PAS had good discriminative capabilities. This performance and its impact on maternal morbidity should be confirmed by future prospective studies.

Placenta percreta is associated with more frequent severe maternal morbidity than placenta accreta.

BACKGROUND: Abnormally invasive placentation is the leading cause of obstetric hysterectomy and can cause poor to disastrous maternal outcomes. Most previous studies of peripartum management and maternal morbidity have included variable proportions of severe and less severe cases. OBJECTIVE: The aim of this study was to compare maternal morbidity from placenta percreta and accreta. STUDY DESIGN: This retrospective study at a referral center in Paris includes all women with abnormally invasive placentation from 2003 through 2017. Placenta percreta and accreta were diagnosed histologically or clinically. When placenta percreta was suspected before birth, a conservative approach leaving the placenta in situ was proposed because of the intraoperative risk of cesarean delivery. When placenta accreta was suspected, parents were offered a choice of a conservative approach or an attempt to remove the placenta, to be followed in case of failure by hysterectomy. Maternal outcomes were compared between women with placenta percreta and those with placenta accreta/increta. The primary outcome measure was a composite criterion of severe acute maternal morbidity including at least 1 of the following: hysterectomy during cesarean delivery, delayed hysterectomy, transfusion of ≥10 U of packed red blood cells, septic shock, acute kidney injury, cardiovascular failure, maternal transfer to intensive care, or death. RESULTS: Of the 156 women included, 51 had placenta percreta and 105 placenta accreta. Abnormally invasive placentation was suspected antenatally nearly 4 times more frequently in the percreta than the accreta group (96.1% [49/51] vs 25.7% [27/105], P < .01). Among the 76 women with antenatally suspected abnormally invasive placentation (48.7%), the rate of antenatal decisions for conservative management was higher in the percreta than the accreta group (100% [49/49] vs 40.7% [11/27], P < .01). The composite maternal morbidity rate was significantly higher in the percreta than the accreta group (86.3% [44/51] vs 28/105 [26.7%], P < .001). A secondary analysis restricted to women with an abnormally invasive placentation diameter >6 cm showed similar results (86.0% [43/50) vs 48.7% [19/38), P < .01). The rate of hysterectomy during cesareans was significantly higher in the percreta than the accreta group (52.9% [27/51] vs 20.9% [22/105], P < .01) as was the total hysterectomy rate (43/51 [84.3%] vs 23.8% [25/105], P < .01). CONCLUSION: Severe maternal morbidity is much more frequent in women with placenta percreta than with placenta accreta, despite multidisciplinary planning, management in a referral center, and better antenatal suspicion.

[SMOKING CESSATION IN PREGNANCY]. / Sevrage tabagique chez la femme enceinte.

Smoking during pregnancy is the leading preventable cause of perinatal morbidity. Half of smokers are weaned during pregnancy resulting in 15% of female smokers at time of delivery. Most often, women spontaneously withdraw at the announcement of pregnancy. Thus, the action of professionals has a modest effect. But this effect is real and should encourage us to take care for patients who smoke. They should feel free with guilty. The spouse must be included in this support to create an enabling environment. Every action has its effectiveness. Nicotine prescription should be reserved for cases where it reduces consumption and keep the medicalized link. It is possible to smoke with a nicotine patch in place; the substitution then reduces the cosumption of each cigarette.

Cerebral Doppler velocimetry to predict fetal anemia after more than three intravenous fetal exchange transfusions.

BACKGROUND: We aimed to assess usefulness of the middle cerebral artery peak systolic velocity (MCA-PSV) in the prediction of fetal anemia after more than three intravenous fetal-exchange transfusions (IFET). STUDY DESIGN AND METHODS: A retrospective study was conducted over 6 years of 15 consecutive pregnancies with severe red blood cell fetomaternal alloimmunization requiring more than three IFETs. We evaluated correlation between MCA-PSV (expressed as multiples of the mean [MoM]) and pretransfusion hemoglobin (Hb) in the fetus (MoM). Analyses were also performed to assess the value of MCA-PSV to predict moderate to severe fetal anemia. RESULTS: Twenty-seven MCA-PSV measurements performed before the fourth to last IFET were coupled with pretransfusion Hb in the fetus. The median number of IFETs per fetus was five (range, four to eight). Five Hb samples found fetuses with severe (19%), seven with moderate (26%), and 15 with mild anemia (56%). There was a linear correlation between MCA-PSV(x) and Hb in the fetus(y): y = -0.21x + 0.93 (r = -0.50, p < 0.01). For the prediction of moderate to severe anemia the negative predictive value of MCA-PSV with a threshold of 1.5 MoM was 75%, positive predictive value 73%, specificity 80%, sensibility 67%, and positive likelihood ratio 3.33. The area under the receiver operating characteristic curve was 0.78 (95% confidence interval, 0.59-0.96; p < 0.001). For the prediction of severe anemia, MCA-PSV with a threshold of 1.5 MoM had 94% negative predictive value, 80% sensibility, and a positive likelihood ratio of 2.5. CONCLUSIONS: This study shows that a correlation between MCA-PSV and Hb in the fetus persists even after more than three IFETs. MCA-PSV measurements thus remain useful to monitor fetuses at risk of anemia.

Assessing the external validity and clinical relevance of umbilical doppler resistance index references in daily practice.

OBJECTIVE: To assess the external validity and clinical relevance of current references for umbilical artery resistance index (UA RI) in daily practice. METHODS: Retrospective cross-sectional single center study including all UA RI measurements between 22 and 40 gestational weeks (GW) from distinct patients between 2014 and 2022. Patients with normal pregnancies and normal neonatal outcomes that had an UA RI measurement between 2014 and 2019 were used to calculate reference ranges. The established reference for the 95th centile was compared to two current references. The clinical relevance of the established reference was tested by comparing neonatal outcomes according to the 95th percentile among the consecutive distinct patients between 2020 and 2022. RESULTS: Among the 13342 consecutive distinct patients with a singleton pregnancy that had an UA RI measurement between 22 and 40 GW between 2014 and 2022, 5298 patients were included to establish the reference ranges, and 3634 patients to validate these ranges. For each gestational age, the established references were similar to current references. Using the established references, the proportion of patients presenting an UA RI>95th percentile among the patients with normal pregnancies in the validation population was comparable to the proportion when using the two current references. Among the validation population, 268 patients (7.4 %) (95%CI[6.5-8.2]) presented an UA RI ≥ 95th percentile. Of these 268 patients, 67.9% had a SGA newborn (versus 19.2%, p<0.001) and 59% a preterm birth (versus 13.9%, p<0.001). CONCLUSIONS: The reference range obtained from daily practice is clinically relevant and similar to current references.

Prognosis and outcome of pregnancies exposed to renin-angiotensin system blockers.

OBJECTIVE: To study pregnancy outcomes and fetal renal prognosis markers in cases of exposure to renin-angiotensin system blockers. METHODS: We conducted a retrospective study of a series of 21 patients exposed to blockers of the renin-angiotensin system during pregnancy. Two markers were prenatally studied, fetal serum ß2-microglobulin and amniotic fluid volume. Poor renal prognosis evaluation was based on postnatal glomerular filtration rate or on the presence of renal histologic lesions. RESULTS: Of the 21 fetuses, only one had a normal postnatal renal function at birth (oligohydramnios regression and normal ß2-microglobulin). All fetuses with persistent oligohydramnios or ß2-microglobulin ≥ 5 mg/L presented an adverse renal outcome. CONCLUSION: Exposure to renin-angiotensin system blockers complicated by oligohydramnios is associated with a very poor outcome. We propose a prenatal management based on amniotic fluid volume monitoring and fetal serum ß2-microglobulin. However, our preliminary results have to be confirmed by a larger study.

Amniocentesis performed for karyotyping after identified ultrasonographic abnormalities: what to expect?

OBJECTIVES: The aim of this study was to evaluate the relative risk of identifying fetal chromosomal anomalies after finding ultrasonographic (US) abnormalities in a high-risk population who underwent amniocentesis. METHODS: A retrospective review of a cohort of patients with single pregnancies who underwent genetic amniocentesis was undertaken. Univariate and multivariate analysis were used to determine the best correlations between US findings and chromosomal abnormalities. RESULTS: Overall, 191 chromosomal abnormalities were found in 5,604 fetuses (3.4%). Multivariate analysis showed chromosomal abnormalities were significant ly associated with anomalies of the central nervous system (OR = 4.4, 95% CI 2.2-8.7), face and neck (OR = 15.7, 95% CI 9.2-26.8), heart (OR = 5.4, 95% CI 2.6-11.2), abdomen (OR = 5.6, 95% CI 2.9-10.9), extremities (OR = 5.7, 95% CI 2.4-13.4), an increased nuchal fold (OR = 5.2, 95% CI 3.3-8.1), an intrauterine growth restriction (OR = 3.6, 95% CI 1.6-7.9) and a short femur (OR = 4.1, 95% CI 1.4-12.1). CONCLUSIONS: Our results confirm the validity of specific US markers in detecting chromosomal abnormalities in the fetus.

Fetopathologic examination for early termination of pregnancy: dogma or necessity?

OBJECTIVE: Our objective was assessment of fetopathological examination after termination of pregnancy (TOP) for fetal anomalies with normal karyotype <17 weeks of gestation. STUDY DESIGN: This was a multicenter retrospective study. Records of TOP for fetal anomalies with normal karyotype were analyzed. Primary outcomes were modifications of genetic counseling and management of next subsequent pregnancies. Medical TOPs were compared with surgical TOPs. RESULTS: In all, 59 pregnancies were included (30 aspirations, 29 inductions). Fetopathological examination modified genetic counseling for 22 patients: 62% for the medical induction group vs 13% in the vacuum aspiration group (P < .001). Management of subsequent pregnancies was modified in 17% in the medical induction group vs 3% in the aspiration group (P = .06). CONCLUSION: Fetopathological examination for early TOP with normal karyotype is relevant, especially when an intact fetus is examined. Thanks to it, genetic counseling is often modified, as is management of the next pregnancy. Medical procedures should be preferred to surgical procedures.

Amniotic Aaquaporins (AQP) in Normal and Pathological Pregnancies: Interest in Polyhydramnios.

Polyhydramnios is a common feature diagnosed by ultrasound in the second half of pregnancy. Biochemical analysis of amniotic fluid can be useful when suspecting Bartter syndrome or digestive atresia but in most of cases, no etiology of polyhydramnios is found because of the complex regulation of amniotic fluid. Aquaporins (AQP) are transmembrane channel proteins contributing to water transfers. Some of them are expressed in fetal membranes and placenta. Their expression has been shown to be disrupted in some pathological conditions such as maternal diabetes, often associated with polyhydramnios. AQP-1, 3 and 8 levels in amniotic fluid were retrospectively measured in patients suffering from polyhydramnios (n=21) from 23 weeks of gestation (WG). They were compared to the levels observed in control subjects (n=96) and their relationship with maternal factors and neonatal issues was analyzed. AQP-1, 3, 8 levels were physiologically fluctuating, AQP-1 levels always being the lowest and AQP-3 the highest, with a significant decrease at the end of pregnancy. AQPs/AFP ratios increased about 8 folds during pregnancy, their kinetic profiles reflecting physiological dynamic evolution of amniotic fluid volume. In polyhydramnios, AQP-3 level tended to be decreased whereas AQP-8 level was decreased from mid-gestation whatever the etiology of polyhydramnios. No significant relationship was found between AQPs levels and either the fetal prematurity degree or macrosomia. No specific pattern was observed in idiopathic polyhydramnios, limiting the interest of AQPs dosage in amniotic fluid in the management of those complicated pregnancies.

Megacystis in the first trimester of pregnancy: Prognostic factors and perinatal outcomes.

OBJECTIVE: To determine whether bladder size is associated with an unfavorable neonatal outcome, in the case of first-trimester megacystis. MATERIALS AND METHODS: This was a retrospective observational study between 2009 and 2019 in two prenatal diagnosis centers. The inclusion criterion was an enlarged bladder (> 7 mm) diagnosed at the first ultrasound exam between 11 and 13+6 weeks of gestation. The main study endpoint was neonatal outcome based on bladder size. An adverse outcome was defined by the completion of a medical termination of pregnancy, the occurrence of in utero fetal death, or a neonatal death. Neonatal survival was considered as a favorable outcome and was defined by a live birth, with or without normal renal function, and with a normal karyotype. RESULTS: Among 75 cases of first-trimester megacystis referred to prenatal diagnosis centers and included, there were 63 (84%) adverse outcomes and 12 (16%) live births. Fetuses with a bladder diameter of less than 12.5 mm may have a favorable outcome, with or without urological problems, with a high sensitivity (83.3%) and specificity (87.3%), area under the ROC curve = 0.93, 95% CI (0.86-0.99), p< 0.001. Fetal autopsy was performed in 52 (82.5%) cases of adverse outcome. In the 12 cases of favorable outcome, pediatric follow-up was normal and non-pathological in 8 (66.7%). CONCLUSION: Bladder diameter appears to be a predictive marker for neonatal outcome. Fetuses with smaller megacystis (7-10 mm) have a significantly higher chance of progressing to a favorable outcome. Urethral stenosis and atresia are the main diagnoses made when first-trimester megacystis is observed. Karyotyping is important regardless of bladder diameter.

Non-random, individual-specific methylation profiles are present at the sixth CTCF binding site in the human H19/IGF2 imprinting control region.

Expression of imprinted genes is classically associated with differential methylation of specific CpG-rich DNA regions (DMRs). The H19/IGF2 locus is considered a paradigm for epigenetic regulation. In mice, as in humans, the essential H19 DMR--target of the CTCF insulator--is located between the two genes. Here, we performed a pyrosequencing-based quantitative analysis of its CpG methylation in normal human tissues. The quantitative analysis of the methylation level in the H19 DMR revealed three unexpected discrete, individual-specific methylation states. This epigenetic polymorphism was confined to the sixth CTCF binding site while a unique median-methylated profile was found at the third CTCF binding site as well as in the H19 promoter. Monoallelic expression of H19 and IGF2 was maintained independently of the methylation status at the sixth CTCF binding site and the IGF2 DMR2 displayed a median-methylated profile in all individuals and tissues analyzed. Interestingly, the methylation profile was genetically transmitted. Transgenerational inheritance of the H19 methylation profile was compatible with a simple model involving one gene with three alleles. The existence of three individual-specific epigenotypes in the H19 DMR in a non-pathological situation means it is important to reconsider the diagnostic value and functional importance of the sixth CTCF binding site.

Factors associated with regular cervical cancer screening.

OBJECTIVE: To identify the factors associated with regular cervical screening (CS) in the French female population. METHODS: Face-to-face interviews with 5354 randomly selected French women were carried out in this population-based, observational, cross-sectional study. The variables found significant by univariate analysis were entered in a stepwise analysis. A multivariate logistic model constructed with these variables permitted to identify which were significantly related to women undergoing regular CS. RESULTS: A significant relationship was found between regular CS and previous screening for HIV infection, being professionally active, fear of cervical cancer, level of education, and having had a gynecologic check-up in the past 5 years. CONCLUSION: Since the study sample was known to be representative of the female adult population, most of our observations may have important public health implications in France, where information on HPV infection and its possible consequences need to be improved.

[Prevention of human papillomavirus (HPV)-induced infections: access of adolescent girls to health care. A population-based, cross-sectional observational study]. / Prévention des infections à papillomavirus humains (HPV): accès des jeunes filles aux circuits de soins. Etude observationnelle transversale en population générale féminine.

INTRODUCTION: The human papillomavirus (HPV) is the most common cause of sexually transmitted infections worldwide, and its prevalence is highest among young women aged 17-25 years. It is the principal risk factor for cervical cancer. Systematic vaccination of adolescent girls should significantly reduce the incidence of this disease and its related mortality. AIM: One of the objectives of the Enjeux study, a population-based survey, was to identify the place of young girls within the French health care system to help assess the optimal conditions for implementing anti-HPV vaccination. METHODS: Data came from 5354 interviews of women aged 18-70 years, 320 of whom provided information about daughters aged 11-14 years and 406 about daughters aged 15-17 years. Among the latter, 318 were also interviewed and 294 completed a self-administered questionnaire. RESULTS: The results showed that sexual activity was reported by approximately one third of the girls aged 15-17 years. At-risk behaviors in these girls included insufficient contraception (only 51% use condoms). Data on the medical management of the population of 11-17 year-old girls indicate that they have access to - and are integrated into - the health care system, with frequent medical visits. They see the general practitioner (GP) most frequently, followed by the school doctor. The frequency of general practice visits is similar in both age groups; more than 50% of the girls visit their GP more than twice a year. Vaccination is a frequent reason for these visits; gynecologic reasons are less frequent. CONCLUSION: The results of this survey underline the central place of the GP in the health management of young girls aged 11 to 17 years.

Early surgical management for giant omphalocele: Results and prognostic factors.

OBJECTIVES: Giant omphalocele often represents a major surgical challenge and is reported with high mortality and morbidity rates. The aim of this study was to assess the outcome of neonates with giant omphalocele managed with early operative surgical treatment, and subsequently to identify possible factors that could alter the prognosis. METHODS: We reviewed the medical records of 29 consecutive newborns with prenatally diagnosed giant omphalocele. In these cases one of two procedures had been performed: either staged closure after silo, or immediate closure with a synthetic patch. The cases were separated into 2 groups: Isolated giant omphalocele (IO group) and giant omphalocele associated with malformation (NIO group). RESULTS: Infants in the IO group had a lower size of the omphalocele (p<0,001), a shorter hospital stay (95 days [45-915] vs. 41.5 days [10-110] p= 0, 02), and a shorter median ventilation length (10 days [1-33] vs. 27, 5 [6-65] p = 0, 05). In the NIO group, 5 cases displayed a significantly more difficult course than the others. They were compared to the remaining cases for prenatal and anatomic features. Four factors associated with greater morbidity were identified: CONCLUSIONS: Isolated omphalocele, even containing the whole liver, has a very good prognosis with early surgical treatment. Without associated anomalies, 95% of giant omphaloceles can be discharged with a median of 41.5 days in hospital. However, associated anomalies (especially cardiopathies) may burden the prognosis and should be both carefully assessed during pregnancy and taken into account in parental information. TYPE OF STUDY: Retrospective Study LEVEL OF EVIDENCE: Level I.

[Labour in women with scarred uterus in the Democratic Republic of the Congo: trial of scar and factors influencing the outcome]. / Accouchements sur utérus cicatriciel en République Démocratique du Congo: épreuve utérine et facteurs déterminants de l'issue.

OBJECTIVE: Our study aims to identify risks factors associated with failed trial of scar and to set a predictive score of labour in women with scarred uterus in the Democratic Republic of the Congo. METHODS: We conducted a multicenter cross-sectional analytic study of patients with scarred uterus in four maternity units in the Democratic Republic of the Congo (DRC) from 1 January to 31 December 2013. Logistic regression model was used to identify factors associated with failed trial of scar. We set a predictive score based on this model in order to predict trial of scar failure in maternity units in the DRC. ROC curve was used to assess the ability of the set score to identify patients at risk for trial of scar failure. The cut off point for the predictive score was determined on the basis of the Youden-index-based optimal sensitivity and specificity. All the tests in our study were carried out by using a significance threshold of α=0.05. RESULTS: Two explanatory factors in trial of scar failure were retained. They were the socio-demographic factor (maternal age) and three obstetric factors (fundal height, fetal presentation and premature rupture of membranes). Predictive score was set to predict trial of scar failure. This score was determined based on four elements: maternal age, evaluation of the gestational sac on admission, fundal height and fetal presentation. The minimum score was set at 4 and the maximum score was set at 16. The threshold value was set at 7. A total score greater than or equal to 7 reflects a risk of trial of scar failure. CONCLUSION: We set a predictive score to predict trial of scar failure. This score was determined based on four elements: maternal age, evaluation of the gestational sac on admission, fundal height and fetal presentation. A total score greater than or equal to 7 reflects a risk of trial of scar failure.