Medulloblastoma Presenting as Severe Headache during Pregnancy: A Case Report and Review of the Literature.

Headache is a common complaint during pregnancy and the puerperium. The differentiation between a benign headache and a headache that has an underlying more endangering cause, such as an intracranial tumor, can be difficult and often requires diagnostic procedures and brain imaging techniques. We report the case of an 18-year-old female patient who developed clinical symptoms-persistent headache followed by neurological deficit-in the last part of her pregnancy. A medulloblastoma (MB) was diagnosed and treated after delivery. We review 11 other cases of MB in pregnancy reported in the literature. The most common clinical manifestation at diagnosis was headache followed by neurological deficits. We discuss the association of brain tumor growth with physiological changes during pregnancy. We conclude that clinical features of intracranial tumors can be misinterpreted as pregnancy-related symptoms and should not be dismissed.

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.

Myelomeningocele Surgery over the 10 Years Following the MOMS Trial: A Systematic Review of Outcomes in Prenatal versus Postnatal Surgical Repair.

Background and Objectives: Myelomeningocele is the most severe form of spina bifida, a congenital neural tube defect arising from an incomplete neural tube closure during early development with damage worsening with advancing gestational age. The Management of Myelomeningocele Study (MOMS) Trial proved that surgery performed before 26 weeks of gestation significantly improved the prognosis, significantly changing treatment paradigms. This article aims to provide a review of the changes and updates in spina bifida repair over the 10-year period following the MOMS Trial. Material and methods: We performed a systematic review in the PubMed and Cochrane databases as well as a hand-search of high-impact journals using the reference list of all identified articles, searching for randomized controlled trials and observational studies. Results: We identified 27 articles published between 2011 and 2021 that fulfilled the inclusion criteria and review them in the present study. Conclusions: With growing experience and with the improvement of prenatal open and fetoscopic techniques, the outcome of SB-associated conditions could be improved and the risks to both the mother and the fetus reduced. A continuous follow-up of the treated infants and further randomized trials are essential to study the complications and advantages or disadvantages of any given treatment strategy.

Spatial Configuration of the Uterine Artery Cervical Segment in 3-Dimensional Reconstruction at 11 to 14 Weeks' Gestation.

Uterine artery blood flow measurement is an important component of preeclampsia screening in the first trimester. Transabdominal measurement of the uterine artery pulsatility index has been reported to have relatively low interobserver reproducibility, mainly because the uterine artery is not sampled in the same place every time. We assessed the uterine artery pathway using 3-dimensional power Doppler reconstruction. We found that the artery always forms a loop at the level of the uterine cervix, with anterior descending and posterior ascending segments. The loop spatial position and the appearance of its segments vary according to the parity. In nullipara, the loop is most times regular, with some variations in orientation. It has an anteroposterior position above or at the level of the internal os, and it represents the most inferior point of the uterine artery at this level. In multipara, the loop is almost always rotated; its segments are tortuous and more elongated. The loop is often not the most inferior point of the uterine artery, and its anterior afferent segment sometimes descends below to the level of the loop. Three-dimensional reconstruction can clearly show the appearance of the uterine artery at the level of the cervix. Understanding the spatial arrangement of the uterine artery could enhance the performance of pulsatility index measurement.

Diagnosis of Fetal Structural Anomalies at 11 to 14 Weeks.

OBJECTIVES: To assess the performance of first-trimester ultrasound (US) in identifying major fetal structural abnormalities in an unselected population. METHODS: We conducted a retrospective analysis of all pregnancies that underwent the 11- to 14-week scan in the Fetal Medicine Department of Filantropia Hospital in Bucharest, which were prospectively examined within our screening program. The purpose of the first-trimester US was to evaluate the risk for chromosomal abnormalities and to conduct fetal anatomic examination using a detailed protocol. RESULTS: Our population consisted of 7480 pregnant patients (7576 fetuses). The follow-up was completed for 6045 patients (6114 fetuses). The prevalence of major structural anomalies was 1.89%. In the first trimester, we identified 79% of all major structural anomalies. The highest detection rates were achieved for abdominal wall defects (100%), major central nervous system anomalies (88%), cardiac defects (74%), and skeletal anomalies (71%). The nuchal translucency was increased in 35% of the cases with structural anomalies, and 95% of these were diagnosed in the first trimester. Seventy percent of the patients who presented with structural anomalies and a normal nuchal translucency were diagnosed in the first trimester. CONCLUSIONS: Our results emphasize the importance of performing a detailed US examination at 11 to 14 weeks' gestation in identification of fetal structural defects.

Hyperglycosylated-hCG: Its Role in Trophoblast Invasion and Intrauterine Growth Restriction.

Human chorionic gonadotropin (hCG) is produced by the placenta and its roles have been studied for over a century, being the first known pregnancy-related protein. Although its main role is to stimulate the production of progesterone by corpus luteal cells, hCG does not represent just one biologically active molecule, but a group of at least five variants, produced by different cells and each with different functions. The hyperglycosylated variant of hCG (H-hCG) plays a key role in trophoblast invasion, placental development and fetal growth. During trophoblast invasion, H-hCG promotes extravillous cytotrophoblast cells to infiltrate the decidua, and also to colonize and remodel the spiral arteries in to low resistance, larger-diameter vessels. As fetal growth is heavily reliant on nutrient availability, impaired trophoblast invasion and remodeling of the uterine arteries, leads to a defective perfusion of the placenta and fetal growth restriction. Understanding the function of H-hCG in the evolution of the placenta might unveil new ways to manage and treat fetal growth restriction.

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.

Operator experience impact on the evaluation of still images of a first trimester cardiac assessment protocol.

OBJECTIVE: Congenital heart disease (CHD) is the most common birth defect and represents the leading cause for mortality and morbidity in infants and young adults. Early fetal echocardiography is usually considered a highly specialized scan. The goal of this study is to evaluate the impact of operator's experience in assessing still images of the 4-chamber view and 3-vessels view and to evaluate the feasibility and the performance of a first trimester screening protocol for CHD. METHODS: An online questionnaire consisting of still images of the 4-camber view and 3-vessel view from 50 normal and abnormal cases was reviewed by an expert group made of seven obstetricians specialized in fetal medicine and a nonexpert group made of 13 obstetricians that are certified in ultrasound. After individually visualizing each image set made of the 4-chamber view and 3-vessel view, they had to conclude if the case was normal or abnormal and what images were abnormal. RESULTS: A total of 50 image sets of both normal and abnormal fetal hearts were examined by the 20 reviewers, resulting in 1000 evaluations. The expert group achieved a detection rate of 97.1% with a false positive rate of 5.7%. The nonexpert group achieved also a good detection rate of 91.3% but with a much higher false positive rate of 33.9%. The most frequently missed CHD involved the great arteries and had a normal 4-chamber view. In the majority of false positive cases the 3-vessel view was incorrectly interpreted as abnormal. CONCLUSIONS: A screening protocol for CHD, based on the 4-chamber view and 3-vessel view alone can offer a good detection rate for CHD with a small false positive rate, but only if it is implemented by highly specialized sonographers.

Placental volume at 11-13 weeks' gestation in the prediction of birth weight percentile.

OBJECTIVE: To determine the value of placental volume measured by 3D ultrasound at 11-13 weeks' gestation in combination with maternal characteristics and serum pregnancy-associated plasma protein-A (PAPP-A) in the prediction of small and large for gestational age (SGA and LGA) neonates. METHODS: Maternal serum PAPP-A and placental volume were measured at 11-13 weeks in 3,104 singleton pregnancies. Regression analysis was used to examine the contribution of maternal characteristics, placental volume and PAPP-A in the prediction of SGA and LGA neonates. RESULTS: There was a significant association between placental volume and PAPP-A (r = 0.268, p < 0.0001). Median placental volume and PAPP-A, expressed as multiples of the median (MoM) in appropriate for gestational age (AGA) neonates, were reduced in the SGA group (placental volume 0.88 MoM, vs. 1.00 MoM in AGA, p < 0.0001; PAPP-A 0.92 MoM vs. 1.00 MoM in AGA, p = 0.019) and increased in the LGA group (placental volume 1.09 MoM vs. 1.00 MoM in AGA, p < 0.0001; PAPP-A 1.15 MoM vs. 1.00 MoM in AGA, p = 0.015). Maternal characteristics with either placental volume or PAPP-A detected about 30% of the SGA or LGA neonates, at a false positive rate of 10%. CONCLUSION: Measurement of placental volume and serum PAPP-A can improve the prediction of SGA or LGA neonates provided by maternal characteristics alone.

A Broader Perspective on the Prenatal Diagnosis of Cornelia de Lange Syndrome: Review of the Literature and Case Presentation.

Cornelia de Lange syndrome (CDLS) is caused by pathogenic variants in genes which are structural or regulatory components of the cohesin complex. The classical Cornelia de Lange (CDLS) phenotype is characterized by distinctive facial features, growth retardation, upper limb reduction defects, hirsutism, and developmental delay. Non-classical phenotypes make this condition heterogeneous. Although CDLS is a heterogeneous clinical and genetic condition, clear diagnostic criteria have been described by specialist consensus. Many of these criteria refer to features that can be seen on prenatal ultrasound. The aim of this paper is twofold: to present the ultrasound findings in fetuses affected by CDLS syndrome; to discuss the recent advances and the limitations in the ultrasound and genetic prenatal diagnosis of CDLS. Our review aims to offer, apart from the data needed to understand the genetics and the prenatal presentation of the disease, a joint perspective of the two specialists involved in the prenatal management of this pathology: the fetal medicine specialist and the geneticist. To better illustrate the data presented, we also include a representative clinical case.

The outcome of structural heart defects diagnosed in the first trimester of pregnancy.

PURPOSE: We present the results of a detailed protocol of fetal heart examination in the first trimester, in a fetal medicine unit in Romania. METHODS: Since October 2009, in Filantropia Hospital in Bucharest, we have systematically assessed pregnancies at 11-14 weeks to screen for aneuploidies and for major fetal structural defects. The fetal anatomy examination protocol included the detailed assessment of the fetal heart. This was performed using the same principles as for the second trimester examination, in the entire cohort. RESULTS: Our population consisted of 7693 patients and 7816 embryos. The protocol for the ultrasound evaluation of the fetal heart was completed for 7597 embryos (97.2%). The outcome is known for 6912 cases (90.9%). We diagnosed 39 heart defects - 30 in the first trimester, seven in the second trimester, two postnatally. Twenty of the 39 heart defects were isolated cardiac malformations. Twelve of the isolated heart defects were diagnosed in the first trimester. The sensitivity of the first trimester ultrasound in identifying major heart defects was 76.92%. The overall survival in cases of isolated congenital heart disease diagnosed in the first trimester was significantly lower than the survival in the cases diagnosed in the second trimester. CONCLUSIONS: Many (76.92%) of the significant heart defects can be diagnosed by ultrasound examination, in the first trimester. Our study is an argument for developing the multidisciplinary approach needed for the management of early detected structural heart disease.

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.

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.

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.

Maternal plasma inhibin A at 11-13 weeks of gestation in hypertensive disorders of pregnancy.

OBJECTIVE: To investigate the potential value of maternal plasma inhibin A in first-trimester screening for preeclampsia (PE). METHOD: The concentration of inhibin A at 11-13 weeks was measured in samples from 121 pregnancies that developed PE, 87 cases of gestational hypertension (GH) and 208 normal controls. The distributions of inhibin A multiple of median (MoM) in the control and hypertensive groups were compared. Logistic regression analysis was used to derive algorithms for the prediction of hypertensive disorders. RESULTS: The maternal plasma inhibin A MoM was significantly higher in the early and late PE groups (1.55 MoM and 1.24 MoM, respectively; p < 0.0083), compared to the controls (0.98 MoM), but not in GH. Significant contributions for the prediction of PE were provided by maternal factors, plasma inhibin A and uterine artery pulsatility index (PI) and with combined screening the detection rates for early and late PE were 88% and 42%, respectively, for a false positive rate of 10%. CONCLUSION: The proposed combined screening test could be used to identify women at high risk for PE and intensive monitoring in such patients would lead to earlier identification of the disease which could potentially improve pregnancy outcome.

Differential Diagnosis of Polyhydramnios in a Patient with Gestational Diabetes and Structurally Abnormal Fetus.

Polyhydramnios is frequently seen in patients with diabetes in pregnancy, as well as in cases of fetal malformations. The aim of our paper is to present a rare case of a fetus with anomalies of the precordial veins (absent ductus venosus, intracardiac drainage of the umbilical vein, persistent left superior vena cava) and upper intestinal tract obstruction. The mother developed gestational diabetes and polyhydramnios, in this case. The 29-year-old patient was admitted to our hospital at 35 weeks of gestation with ruptured membranes. Cesarean section was performed. A live baby boy, 2400 g, with multiple congenital abnormalities (including esophageal atresia) was delivered. Our case illustrates the diagnostic approach to polyhydramnios and the difficulty to prenatally diagnose esophageal atresia, in the context of a fetus with multiple malformations.

Ultrasound prenatal diagnosis of typical megacystis, microcolon, intestinal hypoperistalsis syndrome.

In the presence of megacystis in the second half of pregnancy, with increased amniotic fluid, especially in a female fetus, the most likely diagnostic result is megacystis, microcolon, intestinal hypoperistalsis syndrome, MMIHS. In these cases, the diagnosis of MMIHS should be strongly considered instead of lower urinary tract obstruction.

Prenatal Genetic Testing for Dopa-Responsive Dystonia - Clinical Judgment in the Context of Next Generation Sequencing.

We present a family in which the first child was diagnosed with dopa-responsive dystonia based on biochemical findings only. Dopa-responsive dystonia is a severe heterogeneous genetic disease. The possibly involved genes are GCH1 and TH. In their second pregnancy, the parents came for genetic counseling and prenatal diagnosis late, at 12 weeks of gestation. Genetic testing in the affected child was performed, but the results were difficult to interpret. The identified mutations were classified as VOUS - variants of unknown clinical significance. Although possibly causative, a homozygous variant in the TH gene was not reported before in children with dopa-responsive dystonia. Due to limited time, establishing the fetal prognosis was challenging. Our report emphasizes the importance of a multidisciplinary approach in the context of new diagnostic techniques, such as Next Generation Sequencing. We illustrate the fact that behind any laboratory result remains sophisticated clinical judgment. We also describe a previously not reported variant of the TH gene in a child with severe, early-onset dystonia.

The first trimester combined test for aneuploidies - a single center experience.

PURPOSE: We present the results of the systematic application of the first trimester combined test for aneuploidies, in a Romanian center. METHODS: Since October 2009, in Filantropia Hospital in Bucharest, we have systematically been using the FMF (Fetal Medicine Foundation) combined first trimester test to screen for common aneuploidies at 11 to 13 + 6 weeks of gestation. We assessed the crown to rump length (CRL), nuchal translucency, fetal heart rate as well as PAPP-A, and free ß-hCG in maternal serum. We evaluated additional first trimester ultrasound markers in most of the cases. The individual risk for aneuploidies was calculated using the FMF algorithm. RESULTS: Pregnancy outcome is known for 6030 euploid fetuses and 42 aneuploid fetuses from our screening population. The detection rate for trisomy 21 of the combined test was 87.5% for a screen positive rate of 1.96%. All of the trisomy 18 and trisomy 13 cases were detected prenatally. Some of the trisomy 18 cases proved not to be symptomatic in the first trimester. CONCLUSIONS: Our results are similar to those of the main studies on the FMF method of first trimester screening for aneuploidies. Our numbers are small because of limited availability of the very specialized resources involved.

Maternal plasma P-selectin at 11 to 13 weeks of gestation in hypertensive disorders of pregnancy.

OBJECTIVE: To determine if development of preeclampsia is preceded by altered maternal plasma P-selectin and if the levels are related with uterine artery pulsatility index. METHODS: Plasma P-selectin and uterine artery pulsatility index were measured at 11-13 weeks in 121 cases that subsequently developed preeclampsia, 87 cases that developed gestational hypertension and 208 unaffected controls. RESULTS: In the preeclampsia group the median multiple of the median in controls (MoM) P-selectin and uterine artery PI were significantly increased (1.2 MoM and 1.3 MoM). There was no significant association between P-selectin and uterine artery pulsatility index in either the preeclampsia or control group. CONCLUSION: In pregnancies that develop preeclampsia there is evidence of platelet activation from the first trimester. However, there is no direct link between the degree of impaired placentation and platelet activation.