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.

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.

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.

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.

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.

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.

A Rare Case of Allantoic Cyst with Patent Urachus in Fetus with a Microdeletion in 1q21.1q21.2 Region.

An allantoic cyst is a rare malformation with a frequency of 3 in 1,000,000 that may be seen antenatally by ultrasound assessment when the connection between the cloaca (future bladder) and the allantois fails to regress. A patent urachus that presents as a cyst (allantoic) is usually considered not to be associated with chromosomal abnormalities, but if it is not repaired after birth this leads to complications such as urinary tract infections and stone formation. We present a case of a fetus diagnosed with allantoic cyst at the first trimester ultrasound assessment at 12 weeks gestation. The follow up scans showed a decrease in size of the allantoic cyst with no other obvious major defects and, when invasive testing (amniocentesis with microarray analysis) was performed, a rare microdeletion, 1q21.1q21.2 was identified (1.82 Mb deletion).

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.

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.

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.

Ultrasound Patterns in the First Trimester Diagnosis of Congenital Heart Disease.

Congenital heart disease (CHD) is the most common birth defect, with a reported prevalence of 5-12 per 1000 live births. Very recently, the American Institute of Ultrasound in Medicine published a guideline recommending the use of the four-chamber and the three-vessel and trachea views to screen for CHD in the first trimester of pregnancy. Our aim is to present abnormal image patterns that are seen in the four-chamber, three-vessel, and trachea views of the fetal heart in the first trimester and to describe their association with specific CHD types. We used a total of 29 cases of CHD from the archives of Filantropia Hospital and the Maternal and Child Health Institute (INSMC) fetal medicine units. We selected cases with a clear and well-documented diagnosis of the CHD type. We identified a series of repeating color doppler flow patterns seen in the four-chamber, three-vessel, and trachea views of the studied cases. Our observations could be developed into a diagnosis algorithm to orientate the examiner to the most likely type of CHD in individual cases.

Treatment of Fetal Arrhythmias.

Fetal arrhythmias are mostly benign and transient. However, some of them are associated with structural defects or can cause heart failure, fetal hydrops, and can lead to intrauterine death. The analysis of fetal heart rhythm is based on ultrasound (M-mode and Doppler echocardiography). Irregular rhythm due to atrial ectopic beats is the most common type of fetal arrhythmia and is generally benign. Tachyarrhythmias are diagnosed when the fetal heart rate is persistently above 180 beats per minute (bpm). The most common fetal tachyarrhythmias are paroxysmal supraventricular tachycardia and atrial flutter. Most fetal tachycardias can be terminated or controlled by transplacental or direct administration of anti-arrhythmic drugs. Fetal bradycardia is diagnosed when the fetal heart rate is slower than 110 bpm. Persistent bradycardia outside labor or in the absence of placental pathology is mostly due to atrioventricular (AV) block. Approximately half of fetal heart blocks are in cases with structural heart defects, and AV block in cases with structurally normal heart is often caused by maternal anti-Ro/SSA antibodies. The efficacy of prenatal treatment for fetal AV block is limited. Our review aims to provide a practical guide for the diagnosis and management of common fetal arrythmias, from the joint perspective of the fetal medicine specialist and the cardiologist.

Asthma in Pregnancy. Review of Current Literature and Recommendations.

Background:Asthma is the most common respiratory disorder affecting women during pregnancy. Although it is a reversible disease, it may adversely affect maternal quality of life and perinatal outcomes, especially in severe and inappropriately managed cases. Conversely, pregnancy influences the course of asthma through the physiological respiratory, hormonal, and immune system changes. Exacerbations are a key feature of asthma, representing a significant problem if severe, requiring aggressive medical intervention, hospital and even ICU admission. Purpose: The purpose of this article is to summarize the current knowledge and to provide a comprehensive overview of asthma in pregnancy. We also want rising awareness among patients and clinicians on the importance of proper asthma management during pregnancy. Data sources: A comprehensive literature search in PubMed, Medline, and Taylor& Francis was performed. We have searched for review articles as well as prospective and retrospective studies published in English, investigating the bilateral relationship between asthma and pregnancy, using the key words mentioned bellow. Manual search through both national and international guidelines as well as relevant journals and publications on the topic has been also conducted. Conclusion:Optimal asthma control, preventing, detecting, and treating the exacerbations are of the utmost importance to minimize the adverse effects for both the mother and fetus/neonate. Guidelines recommend active asthma management during pregnancy. Strong support prior and throughout the pregnancy and individualized treatment, guided by a multidisciplinary team, is suggested. Education on the importance of anti-asthmatic therapy, avoiding triggers, frequent and accurate monitoring are essential for good asthma management. Considering the pandemic, we are facing and the potential impact of COVID-19 on asthma, Global Initiative for Asthma (GINA) guideline recommendations for physicians are mentioned in the present article.

Fetal Skeletal Dysplasias that Involve the Face: Binder Syndrome and Nager Syndrome.

Binder syndrome and Nager syndrome are part of the spectrum of skeletal dysplasias. Although exceedingly rare, both syndromes are amenable to prenatal diagnosis because they present with features that can be detected by prenatal ultrasound. Genetic prenatal diagnosis is sometimes possible but remains difficult if the etiology of the disease is not homogenous. In cases of severe skeletal dysplasias, the prognosis is unfavorable irrespectively of the genetic defect. In cases with only mild structural anomalies, prenatal counselling is especially difficult. We present cases of Binder syndrome and Nager syndrome diagnosed by us prenatally. We elaborate on the etiology of Binder syndrome and discuss the current classification of facial dysostoses.

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.

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.

Early Ultrasound Identification of Cord Entanglement in Monochorionic Monoamniotic Twin Pregnancy.

Monochorionic monoamniotic pregnancy are considered high risk gestations and the fetal outcome is at times unpredictable. Correct diagnosis and counselling are extremely important, especially regarding the risk of unexpected fetal demise. We present the rare case of a monochorionic monoamniotic twin pregnancy with early identification of cord entanglement and the characteristic ultrasound findings in the first trimester of pregnancy.

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.