Pravastatin Versus Placebo in Pregnancies at High Risk of Term Preeclampsia.

BACKGROUND: Effective screening for term preeclampsia is provided by a combination of maternal factors with measurements of mean arterial pressure, serum placental growth factor, and serum soluble fms-like tyrosine kinase-1 at 35 to 37 weeks of gestation, with a detection rate of ≈75% at a screen-positive rate of 10%. However, there is no known intervention to reduce the incidence of the disease. METHODS: In this multicenter, double-blind, placebo-controlled trial, we randomly assigned 1120 women with singleton pregnancies at high risk of term preeclampsia to receive pravastatin at a dose of 20 mg/d or placebo from 35 to 37 weeks of gestation until delivery or 41 weeks. The primary outcome was delivery with preeclampsia at any time after randomization. The analysis was performed according to intention to treat. RESULTS: A total of 29 women withdrew consent during the trial. Preeclampsia occurred in 14.6% (80 of 548) of participants in the pravastatin group and in 13.6% (74 of 543) in the placebo group. Allowing for the effect of risk at the time of screening and participating center, the mixed-effects Cox regression showed no evidence of an effect of pravastatin (hazard ratio for statin/placebo, 1.08 [95% CI, 0.78-1.49]; P=0.65). There was no evidence of interaction between the effect of pravastatin, estimated risk of preeclampsia, pregnancy history, adherence, and aspirin treatment. There was no significant between-group difference in the incidence of any secondary outcomes, including gestational hypertension, stillbirth, abruption, delivery of small for gestational age neonates, neonatal death, or neonatal morbidity. There was no significant between-group difference in the treatment effects on serum placental growth factor and soluble fms-like tyrosine kinase-1 concentrations 1 and 3 weeks after randomization. Adherence was good, with reported intake of ≥80% of the required number of tablets in 89% of participants. There were no significant between-group differences in neonatal adverse outcomes or other adverse events. CONCLUSIONS: Pravastatin in women at high risk of term preeclampsia did not reduce the incidence of delivery with preeclampsia. Registration: URL: https://www.isrctn.com; Unique identifier ISRCTN16123934.

Pregnancy Complications Lead to Subclinical Maternal Heart Dysfunction-The Importance and Benefits of Follow-Up Using Speckle Tracking Echocardiography.

Pregnancy complications such as gestational diabetes (GDM) and hypertensive disorders of pregnancy (HDP) are frequent and influence not only fetal outcomes but also the maternal cardiac function. GDM and HDP may act as a proxy for increased metabolic and cardiovascular risk later in life. Speckle tracking echocardiography (STE) is a relatively new imaging technique that provides more sensitive assessment than conventional echocardiography of the maternal cardiac function. Recent research suggests that STE can be used during pregnancy and postpartum as a useful method of early detection of subclinical maternal cardiac changes related to pregnancy complications, such as GDM and HDP, and as an indicator for future maternal cardiovascular disorders. The aim of this review was to underline the current value of STE in the follow-up protocol of high-risk pregnant women, as a mean for pre- and postpartum monitoring. A review of the literature was conducted in the PubMed database to select relevant articles regarding the association of STE changes and HDP or GDM in the prenatal and postpartum maternal evaluations. Both GDM and HDP are associated with subtle myocardial changes in shape, size and function; these preclinical cardiac changes, often missed by conventional evaluation, can be detected using STE. Left ventricular global circumferential strain might be an important predictor of maternal cardiovascular disorders and might help to define a high-risk group that requires regular monitoring later in life and timely intervention.

Diagnosis and Management of Cesarean Scar Pregnancy and Placenta Accreta Spectrum: Case Series and Review of the Literature.

With an increased cesarean delivery rate, the incidence of abnormal placentation is steadily rising, and it is estimated to be around 1.7 per 1000 pregnancies for cesarean scar pregnancy and 1 per 500 pregnancies for placenta accreta spectrum disorder. Current evidence considers cesarean scar pregnancy and placenta accreta spectrum as being the same condition, with different aspects, of the same spectrum, having higher risks with advancing gestation. We present 7 cases, diagnosed and managed in our hospital, at different gestational ages. Early diagnosis is essential for appropriate counseling and subsequent management, and an ultrasound examination is the reference standard for diagnosis. Screening for an abnormally implanted placenta in the first trimester of pregnancy might improve the perinatal outcome and reduce maternal morbidity and mortality.

Absence of Wharton's Jelly at the Abdominal Site of the Umbilical Cord Insertion. Rare Case Report and Review of the Literature.

Wharton's jelly is a specialized connective tissue surrounding and protecting umbilical cord vessels. In its absence, the vessels are exposed to the risk of compression or rupture. Because the condition is very rare and there are no available antepartum investigation methods for diagnosis, these cases are usually discovered after delivery, frequently after in utero fetal demise. We report the fortunate case of a 29-year-old nulliparous woman, with an uncomplicated pregnancy, admitted at 39 weeks in labor where a persistently abnormal cardiotocographic trace led to delivery by cesarean section of a healthy 3500 g newborn. After delivery, a Wharton's jelly anomaly was identified at the abdominal umbilical insertion (umbilical cord vessels, approximately 1 cm in length, were completely uncovered by Wharton's jelly), which required surgical thread elective ligation. In the presence of a persistently abnormal CTG trace, in a pregnancy with no clinical settings suggestive of either chronic or acute fetal hypoxemia, the absence of Wharton's jelly should be taken into consideration in the differential diagnosis.

Pregnancy Complications Can Foreshadow Future Disease-Long-Term Outcomes of a Complicated Pregnancy.

During gestation, the maternal body should increase its activity to fulfil the demands of the developing fetus as pregnancy progresses. Each maternal organ adapts in a unique manner and at a different time during pregnancy. In an organ or system that was already vulnerable before pregnancy, the burden of pregnancy can trigger overt clinical manifestations. After delivery, symptoms usually reside; however, in time, because of the age-related metabolic and pro-atherogenic changes, they reappear. Therefore, it is believed that pregnancy acts as a medical stress test for mothers. Pregnancy complications such as gestational hypertension, preeclampsia and gestational diabetes mellitus foreshadow cardiovascular disease and/or diabetes later in life. Affected women are encouraged to modify their lifestyle after birth by adjusting their diet and exercise habits. Blood pressure and plasmatic glucose level checking are recommended so that early therapeutic intervention can reduce long-term morbidity. Currently, the knowledge of the long-term consequences in women who have had pregnancy-related syndromes is still incomplete. A past obstetric history may, however, be useful in determining the risk of diseases later in life and allow timely intervention.

Platelet Changes in Pregnancies with Severe Early Fetal Intrauterine Growth Restriction.

Background and Objectives: In this study, we investigated the changes of platelet count and other platelet indices, such as mean platelet volume (MPV), in cases with severe early intrauterine fetal growth restriction (IUGR). Materials and Methods: We retrospectively analyzed all pregnancies diagnosed with severe early onset IUGR, that were followed up in our hospital between 2010 and 2015 (before implementation of screening and prophylaxis with aspirin). Pregnancies which resulted in birth of a newborn with a birthweight less than 5th percentile for gestational age, that required delivery for fetal or maternal indication before 32 weeks, were selected for the IUGR group. The IUGR cases were divided into two groups according to preeclampsia (PE) association. All cases with a complete blood count (CBC) performed within 7 days prior to delivery were included in the study, as the IUGR group. The control group included normal singleton pregnancies, delivered at term, with birthweight above 10th centile and a CBC taken at 30-32 weeks. Results: There was a significant difference in platelet count and MPV values between the IUGR group and control. Cases with IUGR presented lower platelet count and higher MPV values; there was no significant difference of these parameters when PE was associated with IUGR. Conclusions: Our results suggest that in cases of severe early IUGR, even in the absence of clinically diagnosed PE, there may be maternal endothelial damage and platelet consumption in the systemic and uteroplacental circulation. Platelet count and MPV values are simple and widely available laboratory tests that might be used as indicator of placental insufficiency; however, prospective data are required to establish the mechanistic link and to which extent these parameters are good predictors of severity or adverse perinatal outcomes.

Screening for Gestational Diabetes during the COVID-19 Pandemic-Current Recommendations and Their Consequences.

Gestational diabetes mellitus (GDM) is recognized as one of the most common medical complications of pregnancy that can lead to significant short-term and long-term risks for the mother and the fetus if not detected early and treated appropriately. Current evidence suggests that, with the use of appropriate screening programs for GDM, those women diagnosed and treated have reduced perinatal morbidity. It has been implied that, when screening for GDM, there should be uniformity in the testing used and in further management. This paper summarizes and compares current screening strategies proposed by international bodies and discusses application in the context of the COVID-19 pandemic.

Fatal Association of Mirror and Eisenmenger Syndrome during the COVID-19 Pandemic.

Mirror syndrome (MS) or Ballantyne's syndrome is a rare maternal condition that can be life-threatening for both mother and fetus. The condition is characterized by maternal signs and symptoms similar to those seen in preeclampsia in the setting of fetal hydrops. Despite recent advances in the field of maternal-fetal medicine, the etiopathogenesis of MS remains elusive. For patients and doctors, the COVID-19 pandemic has become an extra hurdle to overcome. The following case illustrates how patients' non-compliance associated with mirror syndrome and SARS-CoV-2 infection led to the tragic end of a 19-year-old patient. Therefore, knowledge of the signs and symptoms of mirror syndrome should always be part of the armamentarium of every obstetrician.

Heterotopic Quadruplet Pregnancy. Literature Review and Case Report.

Heterotopic pregnancy is the condition where both intrauterine and ectopic pregnancy are present. It rarely occurs after natural conception, but is more common with assisted reproductive techniques, when more than one embryo is transferred. Quadruplet heterotopic pregnancy is exceedingly rare. METHODS: A literature review was conducted aiming to highlight the diagnosis difficulties and the management options in heterotopic quadruplet pregnancies. RESULTS: Nine relevant studies were identified by researching PubMed up to 2021 for "heterotopic quadruplet pregnancy", "quadruplet intrauterine and ectopic pregnancy", "synchronous intrauterine and ectopic pregnancy". CONCLUSIONS: In this paper, we present a case of heterotopic quadruplet pregnancy and address the difficulty in diagnosing this condition and make formal recommendations.

Fetal Surveillance in Pregnancies with Myasthenia Gravis.

Myasthenia gravis (MG) is an autoimmune condition, that commonly impacts adult women of reproductive age. Myasthenia gravis in pregnancy is rare, but the incidence is higher in different geographical areas. Pregnancies in mothers with MG can have an unfortunate outcome. Acetylcholine receptor antibodies may pass into the fetal circulation and can affect the fetal neuromuscular junction, generating transient MG or even fetal arthrogryposis. The 2016 and 2021 International Consensus Guidance for Management of Myasthenia Gravis issued by Myasthenia Gravis Foundation of America is lacking in recommendation for fetal surveillance for pregnancies in women with MG. The aim of this paper is to highlight fetal and neonatal complications in mothers with MG and to offer antenatal care insights. Close maternal and pregnancy monitoring can improve pregnancy outcome. Patients with MG should be encouraged to conceive, to avoid triggers for exacerbations of the disease during pregnancy and a multidisciplinary team should be established to ensure the optimal support and therapy.

Severe Neonatal Anemia Due to Spontaneous Massive Fetomaternal Hemorrhage at Term: An Illustrative Case with Suspected Antenatal Diagnosis and Brief Review of Current Knowledge.

Fetomaternal hemorrhage is defined as transfer of fetal blood into placental circulation and therefore into maternal circulation during pregnancy, and represents an important contributor to intrauterine fetal demise and neonatal death. The condition is rarely diagnosed prenatally because clinical findings are often nonspecific, and it is unpredictable. In this paper we present an illustrative case of massive spontaneous fetomaternal hemorrhage where the diagnosis was highly suspected antenatally based on maternal reported reduced fetal movements, abnormal suggestive cardiotocographic trace, and increased peak systolic velocity in the fetal middle cerebral artery. We discuss obstetrical and neonatal management and review the current knowledge in the literature. Maintaining a high index of suspicion for this condition allows the obstetrician to plan for adequate diagnostic tests, arrange intrauterine treatment or delivery, and prepare the neonatal team.

Routine assessment of cerebroplacental ratio at 35-37 weeks' gestation in the prediction of adverse perinatal outcome.

BACKGROUND: Third-trimester studies in selected high-risk pregnancies have reported that low cerebroplacental ratio, due to high pulsatility index in the umbilical artery, and or decreased pulsatility index in the fetal middle cerebral artery, is associated with increased risk of adverse perinatal outcomes. OBJECTIVE: To investigate the predictive performance of screening for adverse perinatal outcome by the cerebroplacental ratio measured routinely at 35-37 weeks' gestation. STUDY DESIGN: This was a prospective observational study in 47,211 women with singleton pregnancies undergoing routine ultrasound examination at 35+6 to 37+6 weeks' gestation, including measurement of umbilical artery-pulsatility index and middle cerebral artery-pulsatility index. The measured umbilical artery-pulsatility index and middle cerebral artery-pulsatility index and their ratio were converted to multiples of the median after adjustment for gestational age. Multivariable logistic regression analysis was used to determine whether umbilical artery-pulsatility index, middle cerebral artery-pulsatility index, and cerebroplacental ratio improved the prediction of adverse perinatal outcome that was provided by maternal characteristics, medical history, and obstetric factors. The following outcome measures were considered: (1) adverse perinatal outcome consisting of stillbirth, neonatal death, or hypoxic-ischemic encephalopathy grades 2 and 3; (2) presence of surrogate markers of perinatal hypoxia consisting of umbilical arterial or venous cord blood pH ≤7 and ≤7.1, respectively, 5-minute Apgar score <7, or admission to the neonatal intensive care unit for >24 hours; (3) cesarean delivery for presumed fetal compromise in labor; and (4) neonatal birthweight less than the third percentile for gestational age. RESULTS: First, the incidence of adverse perinatal outcome, presence of surrogate markers of perinatal hypoxia, and cesarean delivery for presumed fetal compromise in labor was greater in pregnancies with small for gestational age neonates with birthweight <10th percentile compared with appropriate for gestational age neonates; however, 80%-85% of these adverse events occurred in the appropriate for gestational age group. Second, low cerebroplacental ratio <10th percentile was associated with increased risk of adverse perinatal outcome, presence of surrogate markers of perinatal hypoxia, cesarean delivery for presumed fetal compromise in labor, and birth of neonates with birthweight less than third percentile. However, multivariable regression analysis demonstrated that the prediction of these adverse outcomes by maternal demographic characteristics and medical history was only marginally improved by the addition of cerebroplacental ratio. Third, the performance of low cerebroplacental ratio in the prediction of each adverse outcome was poor, with detection rates of 13%-26% and a false-positive rate of about 10%. Fourth, the detection rates of adverse outcomes were greater in small for gestational age than in appropriate for gestational age babies and in pregnancies delivering within 2 weeks rather than at any stage after assessment; however, such increase in detection rates was accompanied by an increase in the false-positive rate. Fifth, in appropriate for gestational age neonates, the predictive accuracy of cerebroplacental ratio was low, with positive and negative likelihood ratios ranging from 1.21 to 1.82, and 0.92 to 0.98, respectively; although the accuracy was better in small for gestational age neonates, this was also low with positive likelihood ratios of 1.31-2.26 and negative likelihood ratios of 0.69-0.92. Similar values were obtained in fetuses classified as small for gestational age and appropriate for gestational age according to the estimated fetal weight. CONCLUSIONS: In pregnancies undergoing routine antenatal assessment at 35-37 weeks' gestation, measurement of cerebroplacental ratio provides poor prediction of adverse perinatal outcome in both small for gestational age and appropriate for gestational age fetuses.

Prediction of small for gestational age neonates: screening by maternal factors, fetal biometry, and biomarkers at 35-37 weeks' gestation.

BACKGROUND: Small for gestational age (SGA) neonates are at increased risk for perinatal mortality and morbidity; however, the risks can be substantially reduced if the condition is identified prenatally, because in such cases close monitoring and appropriate timing of delivery and prompt neonatal care can be undertaken. The traditional approach of identifying pregnancies with SGA fetuses is maternal abdominal palpation and serial measurements of symphysial-fundal height, but the detection rate of this approach is less than 30%. A higher performance of screening for SGA is achieved by sonographic fetal biometry during the third trimester; screening at 30-34 weeks' gestation identifies about 80% of SGA neonates delivering preterm but only 50% of those delivering at term, at a screen-positive rate of 10%. There is some evidence that routine ultrasound examination at 36 weeks' gestation is more effective than that at 32 weeks in predicting birth of SGA neonates. OBJECTIVE: To investigate the potential value of maternal characteristics and medical history, sonographically estimated fetal weight (EFW) and biomarkers of impaired placentation at 35+0- 36+6 weeks' gestation in the prediction of delivery of SGA neonates. MATERIALS AND METHODS: A dataset of 19,209 singleton pregnancies undergoing screening at 35+0-36+6 weeks' gestation was divided into a training set and a validation set. The training dataset was used to develop models from multivariable logistic regression analysis to determine whether the addition of uterine artery pulsatility index (UtA-PI), umbilical artery PI (UA-PI), fetal middle cerebral artery PI (MCA-PI), maternal serum placental growth factor (PlGF) and soluble fms-like tyrosine kinase-1 (sFLT) would improve the performance of maternal factors and EFW in the prediction of delivery of SGA neonates. The models were then tested in the validation dataset to assess performance of screening. RESULTS: First, in the training dataset, in the SGA group, compared to those with birthweight in ≥10th percentile, the median multiple of the median (MoM) values of PlGF and MCA-PI were reduced, whereas UtA-PI, UA-PI, and sFLT were increased. Second, multivariable regression analysis demonstrated that in the prediction of SGA in <10th percentile there were significant contributions from maternal factors, EFW Z-score, UtA-PI MoM, MCA-PI MoM, and PlGF MoM. Third, in the validation dataset, prediction of 90% of SGA neonates delivering within 2 weeks of assessment was achieved by a screen-positive rate of 67% (95% confidence interval [CI], 64-70%) in screening by maternal factors, 23% (95% CI, 20-26%) by maternal factors, and EFW and 21% (95% CI, 19-24%) by the addition of biomarkers. Fourth, prediction of 90% of SGA neonates delivering at any stage after assessment was achieved by a screen-positive rate of 66% (95% CI, 65-67%) in screening by maternal factors, 32% (95% CI, 31-33%) by maternal factors and EFW and 30% (95% CI, 29-31%) by the addition of biomarkers. CONCLUSION: The addition of biomarkers of impaired placentation only marginally improves the predictive performance for delivery of SGA neonates achieved by maternal factors and fetal biometry at 35+0-36+6 weeks' gestation.

Prediction of imminent preeclampsia at 35-37 weeks gestation.

BACKGROUND: In the weeks preceding the clinical onset of preeclampsia, the maternal serum level of the angiogenic placental growth factor is decreased and that of the antiangiogenic factor soluble fms-like tyrosine kinase-1 is increased. Women presenting at specialist clinics with signs or symptoms of hypertensive disorders have been stratified according to concentrations of placental growth factor or the ratio of concentrations of soluble fms-like tyrosine kinase-1 and placental growth factor to determine clinical management for the subsequent 1-4 weeks. An alternative approach for the prediction of preeclampsia is use of the competing risks model, a Bayes' theorem based method, to derive patient-specific risk for preeclampsia by various combinations of maternal characteristics and medical history with multiples of the median values of biomarkers. OBJECTIVE: The purpose of this study was to compare the performance of screening for delivery with preeclampsia at ≤2 and ≤4 weeks after assessment at 35+0-36+6 weeks gestation between the use of percentile cut-offs in placental growth factor alone or the soluble fms-like tyrosine kinase-1/placental growth factor ratio and the competing risks model. STUDY DESIGN: This was a prospective observational study in women who attended a routine hospital visit at 35+0-36+6 weeks gestation in 2 maternity hospitals in England. The visits included the recording of maternal demographic characteristics and medical history and the measurement of serum placental growth factor and soluble fms-like tyrosine kinase-1 and mean arterial pressure. The areas under the receiver operating characteristics curves were used to compare the predictive performance for preeclampsia with delivery at ≤2 and ≤4 weeks from assessment of screening by placental growth factor alone and the soluble fms-like tyrosine kinase-1/placental growth factor ratio with that of a previously developed competing risks model with a combination of maternal factors, placental growth factor, soluble fms-like tyrosine kinase-1, and mean arterial pressure (triple test). RESULTS: First, the study population of 15,247 pregnancies included 326 pregnancies (2.1%) that subsequently experienced preeclampsia. Second, in the screening for delivery with preeclampsia at ≤2 and ≤4 weeks from assessment, the performance of the triple test was superior to that of placental growth factor alone or the soluble fms-like tyrosine kinase-1/placental growth factor ratio. The area under the receiver operating characteristics curves for preeclampsia at ≤2 weeks in screening by the triple test (0.975; 95% confidence interval, 0.964-0.985) was higher than that of placental growth factor alone (0.900; 95% confidence interval, 0.866-0.935; P<.0001) and the soluble fms-like tyrosine kinase-1/placental growth factor ratio (0.932; 95% confidence interval, 0.904-0.960; P=.0001). Similarly, the areas under the receiver operating characteristics curves for preeclampsia at ≤4 weeks in screening by the triple test (0.907; 95% confidence interval, 0.886-0.928) was higher than that of placental growth factor alone (0.827; 95% confidence interval, 0.800-0.854; P<.0001) or the soluble fms-like tyrosine kinase-1/placental growth factor ratio (0.857; 95% confidence interval, 0.830-0.883; P<.0001). Third, at most, screen-positive rates of 2-30% the detection rate of delivery with preeclampsia at ≤2 and ≤4 weeks that was achieved by the triple test was approximately 10% higher than that of the soluble fms-like tyrosine kinase-1/placental growth factor ratio and 20% higher than that of placental growth factor alone; the negative predictive value was similar for the 3 tests. CONCLUSION: At 35+0-36+6 weeks gestation, the performance of screening for imminent delivery with preeclampsia by the competing risks model is superior to that of placental growth factor alone or the soluble fms-like tyrosine kinase-1/placental growth factor ratio.

Pregnancy shortly after an acute episode of severe acquired thrombotic thrombocytopenic purpura.

Thrombotic thrombocytopenic purpura (TTP) is a rare but potentially fatal condition. In women with a previous history of TTP there is increased risk of recurrence during pregnancy and the puerperium. There is some evidence that the risk of relapse during pregnancy is increased if the interval between the event and conception is short. We present a case in which pregnancy was achieved a few days after full recovery from an acute episode of severe acquired TTP (ADAMTS13 activity <0.1%) which was successfully treated with four courses of plasma exchange. There was no relapse of TTP during pregnancy and a healthy baby was delivered at term; the puerperium was uneventful.

Space filling of ß-cyclodextrin and ß-cyclodextrin derivatives by volatile hydrophobic guests.

The inclusion of volatile derivatives of benzene and cyclohexane in ß-cyclodextrin (ß-CD), hydroxypropyl-ß-CD, and hydrophilic ß-CD-thioethers was investigated by static headspace gas chromatography (HS-GC) and molecular modelling. The obtained binding constants strongly increase with the amount of space filling of the CD cavity and the salt concentration. ß-CD thioethers show a 3-10 times higher binding potential than native ß-CD.

Prenatal Ultrasound Diagnosis of Klippel-Trenaunay Syndrome.

Klippel-Trenaunay syndrome (KTS) is a very rare vascular malformation syndrome also referred to as a capillary-lymphatic-venous malformation with unknown aetiology. The aim of our paper is to highlight interesting images, regarding a rare case of foetal Klippel-Trenaunay syndrome diagnosed prenatally in our department and confirmed postnatally with a favourable evolution during the gestation and neonatal periods. This case was diagnosed at 26 weeks gestation and characterised through ultrasound by the presence of superficial multiple cystic structures of different sizes spreading over the left leg with hemihypertrophy and reduced mobility. The cystic lesions were spreading to the left buttock and the pelvic area. The right leg and upper limbs had normal appearance with good mobility. There were no signs of hyperdynamic circulation or foetal anaemia, but mild polyhydramnios was associated. The ultrasound findings were confirmed postnatally, the left leg presented multiple cystic lesions and port wine stains, and there was hypertrophy and fixed position, with favourable evolution at 6 months of life, when the size of the lesions began to decrease and the mobility of the leg improved.

Skeletal Dysplasia: A Case Report.

This paper presents a rare case of fetal hydrops detected at just 23 weeks of gestation in a 22-year-old woman's first pregnancy. The fetal ultrasound revealed severe skeletal anomalies, craniofacial deformities, and thoracic abnormalities, suggesting a complex and severe skeletal dysplasia, potentially type IA Achondrogenesis-a lethal autosomal recessive condition marked by ossification delay. This case highlights the significance of advanced genetic testing, such as next-generation sequencing (NGS) and whole-genome sequencing (WGS), in diagnosing and understanding skeletal dysplasias. Skeletal dysplasias represent a group of genetic disorders that affect osteogenesis. The prevalence of this condition is 1 in 4000 births. Sadly, 25% of affected infants are stillborn, and around 30% do not survive the neonatal period. There is a wide range of rare skeletal dysplasias, each with its own specific recurrence risk, dysmorphic expression, and implications for neonatal survival and quality of life. When skeletal dysplasia is incidentally discovered during routine ultrasound screening in a pregnancy not known to be at risk of a specific syndrome, a systematic examination of the limbs, head, thorax, and spine is necessary to reach the correct diagnosis. Prenatal diagnosis of skeletal dysplasia is crucial for providing accurate counselling to future parents and facilitating the proper management of affected pregnancies. An accurate diagnosis can be a real challenge due to the wide spectrum of clinical presentations of skeletal dysplasia but advances in imaging technologies and molecular genetics have improved accuracy. Additionally, some of these skeletal dysplasias may present clinical overlap, making it especially difficult to distinguish. After the 11th revision of genetic skeletal disorder nosology, there are 771 entities associated with 552 gene mutations. The most common types of skeletal dysplasia are thanatophoric dysplasia, osteogenesis imperfect, achondroplasia, achondrogenesis, and asphyxiating thoracic dystrophy.

Risk of vertical transmission of chronic viral infections after invasive prenatal procedures.

OBJECTIVES: Invasive prenatal procedures including amniocentesis, chorionic villus sampling (CVS) can be prenatally indicated for diagnostic purposes. Chronic viral infections with Human Immunodeficiency Virus (HIV), hepatitis C virus (HCV), hepatitis B virus (HBV) are not uncommon in women of reproductive age. The aim of this narrative literature review is to provide guidance on the best clinical practice in antenatal invasive testing and fetal surveillance in pregnancies with HIV, HCV, HBV and treponema pallidum infected women. MATERIAL AND METHODS: A review of the literature was conducted in the database of PubMed to select full-length articles published in peer-reviewed journals between 1990 and 2020. The keywords along with respective combinations included in the search strategy were invasive testing, prenatal diagnosis, amniocentesis, chorionic villus sampling, cordocentesis, fetoscopy, chronic viral infections, hepatitis B, hepatitis C, HIV, treponema pallidum, syphilis, vertical transmission, MTCT. RESULTS: For patients with hepatitis B infection, it is important to assess the HBeAg status and HBV DNA levels and for those patients with high viral load, antiviral therapy (Tenofovir) for a few weeks may be needed to reduce the viral load prior to the invasive procedure. In women positive for HCV, the viral load and HIV status should be assessed to establish the risk of vertical transmission; while for patients with HIV, highly active antiretroviral therapy administration and low viral load are predictive for reduced vertical transmission even after performing an invasive procedure. In all cases invasive procedure should be replaced by non-invasive prenatal testing if this is a feasible alternative and when invasive testing is indeed required, transplacental passage should be avoided.

The Potential Benefit of Hydroxychloroquine in Chronic Placental Inflammation of Unknown Etiology Associated with Adverse Pregnancy Outcomes.

The placenta is the site of connection between maternal and fetal circulation, and the liaison is established early in pregnancy. A large variety of pregnancy complications such as preterm birth, fetal growth restriction, or pregnancy loss have placental expression and can be accompanied in some cases of acute or chronic identifiable placental inflamatory lesions. Chronic placental inflammatory (CPI) lesions include chronic villitis of unknow etiology (CVUE), chronic intervillositis of unknown etiology, CIUE (also described as chronic histiocytic intervillositis, CHI), and chronic deciduits. Hydroxychloroquine (HCQ) has been prescribed with good results during pregnancy to prevent adverse perinatal outcomes in maternal autoimmune conditions. Its success has paved the way to its use in CPI as CIUE/CHI; however, to date, there are no prospective, informatively designed, controlled studies on its value in these setting. This review aims to explore the potential role of HCQ in CPI of unknown etiology. Ideally, properly designed, probably multicentric studies should be undertaken to fully understand HCQ's role for prevention of adverse pregnancy outcomes after a chronic placental inflammation.