Cumulative sum learning curve for cordocentesis among maternal-fetal medicine fellows in a low-cost simulation model.

OBJECTIVE: To determine the individual learning curves for cordocentesis in a low-cost simulator for maternal-fetal medicine (MFM) fellows. METHODS: This observational, descriptive, educational, and prospective study was performed from July through November 2022. After an introductory course based on a standardized technique for cordocentesis, each second-year MFM fellow who accepted to participate in the study performed this procedure using a low-cost simulation model, and experienced operators supervised the cordocenteses. Learning curves were then created using cumulative sum analysis (CUSUM). RESULTS: Seven second-year MFM fellows with no previous experience in cordocentesis accepted to participate in the study. A total of 2676 procedures were assessed. On average, residents performed 382 ± 70 procedures. The mean number of procedures to achieve proficiency was 369 ± 70, the overall success rate was 84.16%, and the corresponding failure rate was 15.84%. At the end of the study, all fellows were considered competent in cordocentesis. One fellow required 466 attempts to achieve competency, performing a total of 478 procedures, but the resident with the fewest attempts to reach competency required 219 procedures, completing 232 procedures. Some of the most frequent reasons for failed attempts included not reaching the indicated point for vascular access (20.99%) and being unable to retrieve the sample (69.10%). CONCLUSION: CUSUM analysis to assess learning curves, in addition to using low-cost simulation models, helped to appraise individualized learning, allowing an objective demonstration of competency for cordocentesis among MFM fellows.

Fetal Anemia: Determinants and Perinatal Outcomes according to the Method of Intrauterine Blood Transfusion.

INTRODUCTION: Fetal anemia from hemolytic disease treated by intrauterine transfusion (IUT) can be performed by intraperitoneal, intracardiac, and intravascular transfusion (IVT). Objective of our study was to compare different transfusion techniques. METHODS: Retrospective review of IUT secondary to red cell alloimmunization was conducted at eight international centers from 2012 to 2020. Severe anemia suspected if middle cerebral artery peaks systolic velocity ≥1.5 multiples of the median. Demographic, delivery, and postnatal variables were analyzed. RESULTS: Total of 344 procedures, 325 IVT and 19 other techniques (non-IVT) included. No difference in demographics, history of stillbirth (20.5 vs. 15.8%, p = 0.7), prior pregnancy IUT (25.6 vs. 31.6%, p = 0.5) or neonatal transfusion (36.1 vs. 43.8%, p = 0.5). At first IUT, non-IVT had higher hydrops (42.1% vs. 20.4%, p = 0.03), lower starting hematocrit (13.3% [±6] vs. 17.7% [±8.2], p = 0.04), and trend toward lower gestational age (24.6 [20.1-27] vs. 26.4 [23.2-29.6] weeks, p = 0.08). No difference in birthweight, neonatal phototherapy, exchange, or simple transfusion was observed. CONCLUSION: This is one of the largest studies comparing techniques to treat fetal anemia. IVT was most performed, other techniques were more likely performed in hydrops, and lower starting hematocrit was seen. Neither technique affected outcomes. This study may suggest that physician's experience may be the strongest contributor of outcomes.

A Study of the Literature on Intrauterine Treatment Options for Chronic Placental Insufficiency with Intrauterine Growth Restriction Using Intrauterine Intravascular Amino Acid Supplementation.

BACKGROUND: Intrauterine growth retardation (IUGR) is a very serious prenatal condition with 3-5% incidence of all pregnancies. It results from numerous factors, including chronic placental insufficiency. IUGR is associated with an increased risk of mortality and morbidity and is considered a major cause of fetal mortality. Currently, treatment options are significantly limited and often result in preterm delivery. Postpartum, IUGR infants also have higher risks of disease and neurological abnormalities. METHODS: The PubMed database was searched using the keywords "IUGR", "fetal growth restriction", "treatment", "management" and "placental insufficiency" for the period between 1975 and 2023. These terms were also combined together. RESULTS: There were 4160 papers, reviews and articles dealing with the topic of IUGR. In total, only 15 papers directly dealt with a prepartum therapy of IUGR; 10 of these were based on an animal model. Overall, the main focus was on maternal intravenous therapy with amino acids or intraamniotic infusion. Treatment methods have been tested since the 1970s to supplement the fetuses with nutrients lacking due to chronic placental insufficiency in various ways. In some studies, pregnant women were implanted with a subcutaneous intravascular perinatal port system, thus infusing the fetuses with a continuous amino acid solution. Prolongation of pregnancy was achieved, as well as improvement in fetal growth. However, insufficient benefit was observed in infusion with commercial amino acid solution in fetuses below 28 weeks' gestation. The authors attribute this primarily to the enormous variation in amino acid concentrations of the commercially available solutions compared with those observed in the plasma of preterm infants. These different concentrations are particularly important because differences in the fetal brain caused by metabolic changes have been demonstrated in the rabbit model. Several brain metabolites and amino acids were significantly decreased in IUGR brain tissue samples, resulting in abnormal neurodevelopment with decreased brain volume. DISCUSSION: There are currently only a few studies and case reports with correspondingly low case numbers. Most of the studies refer to prenatal treatment by supplementation of amino acids and nutrients to prolong pregnancy and support fetal growth. However, there is no infusion solution that matches the amino acid concentrations found in fetal plasma. The commercially available solutions have mismatched amino acid concentrations and have not shown sufficient benefit in fetuses below 28 weeks' gestation. More treatment avenues need to be explored and existing ones improved to better treat multifactorial IUGR fetuses.

Intrauterine Transmission of Hepatitis C Virus Concomitant with Isolated Severe Fetal Ascites.

BACKGROUND: Perinatal Hepatitis C Virus (HCV) transmission occurs in 4-7% of the cases with detectable viremia at delivery. HCV testing in pregnancy is recommended. The fetal infection was previously described as asymptomatic although there are two cases, including this one, to report the presence of isolated fetal ascites in HCV infected fetuses. CASE REPORT: A 42-year-old patient, 3G, 3P, presented in the Emergency Room for painful uterine contraction. The third-trimester ultrasound examination noted severe fetal ascites, accompanied by hyperechoic bowels and polyhydramnios. The diagnosis required a detailed ultrasound exam, invasive testing (amniocentesis, cordocentesis, and fetal paracentesis), and a complete workup. The mother tested positive for HCV antibodies, and the fetal cord blood tested positive for HCV RNA. The ascites resolved after paracentesis, and the gastrointestinal and respiratory functions markedly improved. The fetus was delivered at term in good condition. CONCLUSIONS: The etiology of isolated fetal ascites is broad. This case may indicate that intrauterine HCV transmission is a potential cause of isolated fetal ascites in the absence of other explanation, and isolated fetal ascites can be the only sign revealed on a routine examination. We suspected, having no other detected cause for ascites, the intrauterine transmission of HCV. Invasive procedures, such as paracentesis, are required for abdominal decompression to manage isolated fetal ascites, as it may be a saving procedure. A genetic investigation is needed, and a good neonatal outcome is expected in the absence of fetal structural or genetic abnormalities, as in our case.

A Rare and Challenging Case of Refractory Fetal Supraventricular Tachycardia.

Fetal supraventricular tachycardia can be difficult to manage and offers a challenging treatment course, particularly in refractory cases. The treatment course must balance maternal well-being with the health status of the fetus, all while racing against possible progression to hydrops fetalis or permanent cardiac dysfunction. We describe a case of fetal supraventricular tachycardia that demonstrates many of these concepts, as well as the importance of utilizing several treatment pathways in refractory cases.

Hemorragia materno-fetal posterior a amniocentesis y cordocentesis

Objetivo . Comparar la frecuencia y cantidad de hemorragia materno-fetal posterior a la amniocentesis y cordocentesis. Diseño . Estudio de casos y controles. Métodos . Gestantes con embarazos simples sin anomalías fetales sometidas a amniocentesis para determinación del cariotipo fetal (16 a 20 semanas de gestación) o cordocentesis (20 a 30 semanas de embarazo) en el periodo de enero de 2017 a mayo de 2022. Principales medidas de estudio. Características generales del procedimiento, resultados de la prueba de Kleihauer-Brown-Betke y concentraciones séricas de alfafetoproteína materna. Resultados . La muestra del estudio fue de 305 pacientes. La amniocentesis se realizó en 165 mujeres y la cordocentesis en 140 casos. La hemorragia materno-fetal de novo se observó en 8 pacientes (4,8%) después de la amniocentesis y en 41 pacientes (29,3%) después de la cordocentesis. Las concentraciones de alfafetoproteína sérica aumentaron en 24 casos (14,5%) después de la amniocentesis y en 55 casos (39,3%) después de la cordocentesis (p < 0,05). Luego de la cordocentesis se observó mayor volumen promedio de hemorragia maternofetal, elevación de valores individuales de volumen e incrementos significativos en la hemorragia materno-fetal severa (más de 5 mL de eritrocitos fetales) y de pérdida del volumen sanguíneo fetoplacentario total (p < 0,05). Conclusión . Estos resultados muestran que tanto la amniocentesis como la cordocentesis aumentan el riesgo de hemorragia materno-fetal. Sin embargo, la amniocentesis guiada por ecografía tiene menor riesgo de producir hemorragia y la isoinmunización Rh resultante, comparada con la cordocentesis.

Objective : To compare the frequency and amount of maternal-fetal hemorrhage following amniocentesis and cordocentesis. Design : Case-control study. Institución. Hospital Central "Dr. Urquinaona", Maracaibo, Venezuela. Methods : Pregnant women with singleton pregnancies without fetal anomalies undergoing amniocentesis for fetal karyotyping (16-20 weeks' gestation) or cordocentesis (20- 30 weeks' pregnancy) in the period January 2017-May 2022. Main study outcomes: General characteristics of the procedure, Kleihauer-Brown-Betke test results, and maternal serum alpha-fetoprotein concentrations. Results : The study sample was 305 patients. Amniocentesis was performed in 165 women and cordocentesis in 140 cases. De novo maternal-fetal hemorrhage was observed in 8 patients (4.8%) after amniocentesis and in 41 patients (29.3%) after cordocentesis, de novo maternalfetal hemorrhage was observed in 8 patients (4.8%). Serum alpha-fetoprotein concentrations increased in 24 cases (14.5%) after amniocentesis and in 55 cases (39.3%) after cordocentesis (p < 0.05). After cordocentesis, higher mean maternalfetal hemorrhage volume, elevation of individual volume values and significant increases in severe maternal-fetal hemorrhage (more than 5 mL of fetal erythrocytes) and total fetoplacental blood volume loss were observed (p < 0.05). Conclusion : These results show that both amniocentesis and cordocentesis increase the risk of maternal-fetal hemorrhage. However, ultrasound-guided amniocentesis has a lower risk of producing hemorrhage and resulting Rh isoimmunization compared to cordocentesis.

Practice patterns amongst fetal centers performing intrauterine transfusions (PACT): An international survey study.

OBJECTIVES: Fetal anemia secondary to incompatibility between maternal-fetal blood types can result in hydrops and demise. Intrauterine transfusions have improved survival in experience centers. Our objective was to determine the practice patterns amongst fetal centers. STUDY DESIGN: Thirteen fetal centers across the world were surveyed. Results from all participating centers were recorded, analyzed, and presented as ratios. Questions on the survey were related to experience of the physician, preferred methods of transfusion, fetal surveillance, and timing of delivery. RESULTS: Differences amongst centers were as follows: 54% of the centers performed transfusions in operating room, the remaining did them in a clinic room or close to the operating room; 31% did not use maternal anesthesia, 31% used oral or intravenous sedation and 38% used a combination of local with oral or intravenous sedation. The similarities include: 84% performed intravenous transfusions, while 2 centers reported intraperitoneal and intracardiac transfusions were performed for very early cases; 85% of centers performed the last transfusion at 34-35 weeks and 77% electively delivered their patients at 37 weeks. CONCLUSION: Method of transfusion and delivery timing was similar in most centers; however, differences were seen in location of procedure, anesthetic coverage, and surveillance. Further assessment is needed to determine if these differences in practice have any potential neonatal effects.

Is fetal middle cerebral artery peak systolic velocity correlated with hemoglobin levels in cases of nonimmune fetal anemia?

OBJECTIVES: To establish whether a correlation exists between the fetal middle cerebral artery peak systolic velocity (MCA PSV) and fetal hemoglobin levels before intrauterine transfusion (IUT) in cases of severe fetal anemia. METHODS: This was a single-center, retrospective study of data from 49 fetuses treated with IUT for fetal anemia between 2003 and 2018. Severe fetal anemia was suspected when MCA PSV was or exceeded 1.55 multiples of the median. RESULTS: The causes of anemia were largely idiopathic, and the overall survival rate was 57%. MCA PSV and hemoglobin were correlated in all 34 fetuses with alloimmune fetal anemia, whereas the 15 fetuses with nonimmune causes showed no correlation. Of the 15 noncorrelated cases, twin pregnancy was most common, followed by idiopathic causes. All the twin pregnancies involved monochorionic twins. Fetal hydrops, especially ascites, was significantly associated with severe anemia. CONCLUSIONS: Fetal MCA PSV may not be a reliable independent factor for the diagnosis of severe fetal anemia in nonimmune cases, and the presence of associated hydrops implies that the fetus is more likely to have severe fetal anemia than in a fetus without hydrops.

A Review of Cordocentesis: Percutaneous Umbilical Cord Blood Sampling.

We discuss the current indications, technical variation and procedure-related complications of percutaneous umbilical cord blood sampling (PUBS). The term PUBS is commonly used in the United States. Cordocentesis and funipuncture are equivalent terms. A needle guided by ultrasound is introduced into a blood vessel (usually the vein) of the umbilical cord to collect fetal specimen in PUBS. We conducted a literature search in PubMed indexed journals and analyzed all related articles on PUBS and cordocentesis. We chose this subject because it is a relatively new but convenient method that has both diagnostic and therapeutic value in fetal medicine. At present the only procedure that provides direct access to fetal circulation is PUBS. The most common clinical indication for PUBS is suspected fetal anemia. Other major indications for PUBS are the diagnosis of congenital infections, cytogenetic analysis, metabolic disorders, fetal growth restriction and hematologic disorders. Therapeutic applications of cordocentesis or puncture of the umbilical cord are in utero transfusions for rhesus alloimmunization and medication administration. PUBS also provides a direct assessment of fetal thyroid function diagnosing fetal thyroid disorders and helps administer therapy in utero.  Literature demonstrates a low incidence of complications associated with percutaneous umbilical blood sampling. For PUBS, the true complication rate related to the method of sampling remains unclear. A few cases reported complications conducted PUBS for therapeutic purposes which naturally has a higher accident rate compared to diagnostic purposes. Although life-threatening complications are rare, there are potential risks that include bleeding from the puncture site, fetal bradycardia, vertical transmission of maternal infection. Therefore, PUBS should be performed at perinatal care centers by experienced physicians and the best time is between 17 to 40 weeks of gestation. There are three methods used to approach the umbilical cord that includes direct, indirect and free puncture. Anteriorly placed placenta allows an easier approach to the umbilical cord. The danger of abruption of placenta must be kept in mind while using this technique. The number of punctures should be limited to a maximum of 3 to reduce complications. According to a case series report, the mean time required for the procedure was 4 minutes with a fall in duration seen with increased experience. In conclusion, percutaneous blood sampling allows direct access to fetal circulation thus opening up new areas of prenatal diagnosis and therapy. PUBS is now a well-codified procedure. It is clear from our literature review that risks directly related to the technique are small. The indication of the procedure must be carefully chosen as the risk of complications of umbilical cord puncture is directly related to the severity of the condition. Complications such as bleeding and hematoma formation are related to duration and number of punctures which are operator-dependent. Thus, only highly trained personnel should conduct the procedure. The list of indications is extensive and growing. Nevertheless, this technique shows potential to open up new realms in the area of fetal medicine.

Non-immune hydrops fetalis: Two case reports.

BACKGROUND: Fetal hydrops is a serious condition difficult to manage, often with a poor prognosis, and it is characterized by the collection of fluid in the extravascular compartments. Before 1968, the most frequent cause was the maternal-fetal Rh incompatibility. Today, 90% of the cases are non-immune hydrops fetalis. Multiple fetal anatomic and functional disorders can cause non-immune hydrops fetalis and the pathogenesis is incompletely understood. Etiology varies from viral infections to heart disease, chromosomal abnormalities, hematological and autoimmune causes. CASE SUMMARY: A 38-year-old pregnant woman has neck lymphoadenomegaly, fever, cough, tonsillar plaques at 14 wk of amenorrhea and a rash with widespread itching. At 27.5 wk a fetal ultrasound shows signs of severe anemia and hydrops. Cordocentesis is performed with confirmation of severe fetal anemia and subsequent fetal transfusion. The karyotype is 46, XX, array-comparative genome hybridization (CGH) negative, and infectious tests are not conclusive. In the following days there is a progressive improvement of the indirect signs of fetal anemia. At 33.6 wk, for relapse of severe fetal anemia, further fetal transfusions are necessary and an urgent cesarean section is performed. On the day 12 of life, for the detection of anemia, the newborn is subjected to transfusion of concentrated red blood cells and begins treatment with erythropoietin. Later there is a normalization of blood chemistry values and the baby does not need new transfusions. A 29-year-old pregnant woman, with Sjogren's syndrome and positive Anti-Ro/SSA antibodies, is subjected to serial fetal ecocardio for branch block. At 26.5 wk there is a finding of fetal ascites. Infectious disease tests on amniotic fluid are negative as well as quantitative fluorescent polymerase chain reaction, Array CGH. At cordocentesis Hb is 1.3 mmol/L, consequently fetal transfusion is performed. Also in this case, due to continuous episodes of relapse of fetal anemia with consequent transfusions, at 29.4 wk a cesarean section is performed. On day 9 of life, a treatment with erythropoietin is started in the newborn, but the baby needs three blood transfusions. The search for autoantibodies in the baby found SS-A Ro60 positive, SSA-Ro52 positive and SS-B negative. The hemoglobin values normalized after the disappearance of maternal autoantibodies. CONCLUSION: An attempt to determine the etiology of hydrops should be made at the time of diagnosis because the goal is to treat underlying cause, whenever possible. Even if the infectious examinations are not conclusive, but the pregnancy history is strongly suggestive of infection as in the first case, the infectious etiology must not be excluded. In the second case, instead, transplacental passage of maternal autoantibodies caused hydrops fetalis and severe anemia. Finally, obstetric management must be aimed at fetal support up to an optimal timing for delivery by evaluating risks and benefits to increase the chances of survival without sequelae.

Prevención de enfermedad hemolítica perinatal severa con inmunoglobulina intravenosa en paciente altamente sensibilizada / Prevention of severe perinatal hemolytic disease with intravenous immunoglobulin in a highly sensitized patient

RESUMEN La enfermedad hemolítica perinatal es infrecuente hoy por la prevención que de ella se hace. Sin embargo, existen casos de madres altamente sensibilizadas que desean tener un hijo, lo que obliga a que ese embarazo deseado sea controlado de manera especial y sometido a procedimientos invasivos no exentos de morbimortalidad fetal. El uso prenatal de inmunoglobulina humana en la madre puede representar una alternativa terapéutica. Se presenta un caso en que su uso impidió el desarrollo de enfermedad intrauterina y favoreció la buena evolución neonatal a pesar de que el pronóstico inicial era muy adverso.

ABSTRACT Perinatal Hemolytic Disease is uncommon today due to its prevention. However, there are cases of highly sensitized mothers who wish to have a child, that forces this desired pregnancy to be controlled in a special way and be subjected to invasive procedures not exempt from fetal morbidity and mortality. Prenatal use of human inmunoglobulin in the mother may represent a therapeutic alternative. We present a case in which its use prevented the development of intrauterine disease and favored a good neonatal evolution despite the fact that the initial prognosis was very adverse.

Time advantage of HemoCue versus traditional complete blood count during cordocentesis.

OBJECTIVES: During cordocentesis, a significant risk factor for adverse outcome is procedure length. One of the greatest contributors to total procedure length is the time that elapses between obtaining a fetal sample and receiving the results of the complete blood count (CBC) from the hospital laboratory. We aimed to evaluate whether there is an advantage to using a point of care hemoglobinometer (HemoCue) compared with traditional CBC during cordocentesis, measured in time elapsing between obtaining fetal sample, and available result. Secondarily we aimed to compare accuracy of HemoCue in relation to traditional CBC. METHODS: A prospective cohort study was conducted on women undergoing cordocentesis and fetal transfusion for suspected fetal anemia from July 2016 to July 2018 at an urban academic medical center. Fetal blood samples were obtained during cordocentesis, and concurrently sent for traditional CBC, as well as immediately analyzed at bedside using a HemoCue machine. The time elapsing between the obtained fetal sample and availability of results with HemoCue versus traditional CBC were recorded. Primary outcome was time elapsed between obtaining fetal sample and result available for HemoCue versus traditional CBC. Secondary outcome was comparison of HemoCue and CBC hemoglobin values for accuracy. RESULTS: Forty-five fetal samples were compared using CBC and HemoCue. Sixteen cordocentesis procedures were performed on 10 patients during the study period. Use of HemoCue was associated with a significantly shorter time to yield a fetal hemoglobin result, compared to traditional CBC (1.5 versus 5.5 min, p = .0001). Results yielded by the HemoCue highly correlated to those yielded by traditional CBC (R = 0.96). CONCLUSIONS: Use of HemoCue during cordocentesis is associated with a 4-min time advantage over traditional CBC. Hemoglobin results yielded by HemoCue and traditional CBC are highly correlated.KEY MESSAGEUse of a point-of-care hemoglobinometer is associated with a time advantage of 4 min over traditional complete blood count during cordocentesis. This represents a potentially modifiable risk factor for procedure length, and thus procedure complications.

Effects of peripheral and umbilical cord blood sampling on transfusion and complications in very low birth weight infants during hospitalization / 中华围产医学杂志

Objective:To analyze the effects of different blood sampling methods on the incidence of iatrogenic blood loss, anemia, transfusion, and complications in very low birth weight infants (VLBWI) during hospitalization.Method:A retrospective analysis was performed on VLBWIs (birth weight <1 500 g) admitted to the neonatal intensive care unit of the Second Hospital of Yangtze University, Jingzhou Central Hospital, Hubei province, from January 2014 to December 2018. According to the first blood sampling method, these infants were subjected to the umbilical cord blood and peripheral blood groups. Blood sampling, transfusion, complications, and outcomes were compared between the two groups. Independent samples t-test, rank-sum test, and Chi-square (or Fisher's exact) test were used for statistical analysis. Results:(1) Totally 240 neonates enrolled, including 104 cases in the umbilical cord blood group and 136 in the peripheral blood group. There was no statistical significance in the general information and blood test results for the first time between the two groups. (2)The blood volume collected in the first week in the umbilical cord blood group was lower than that in the peripheral blood group [6.5 ml (1-23 ml) and 10 ml (1-30 ml), Z=－4.706, P<0.01]. Differences between the two groups in the blood volume at 2-9 weeks were insignificant (all P>0.05). The number of blood collection procedures in each of the first four weeks after birth in the umbilical cord blood group was less than that in the peripheral blood group ( Z value was－9.124,－2.272,－4.688, and－2.017, respectively, all P<0.05), but no statistical difference was found at the fifth week ( P>0.05). The time of the first red blood cell transfusion (RBCT) in the umbilical cord blood group was later than that in the peripheral blood group [4 weeks (1-7 weeks) vs 3 weeks (1-5 weeks), Z=－2.839, P<0.05]. The proportion of infants who have received RBCT twice or more times in the umbilical cord blood group was lower than that in the peripheral blood group [39.7% (25/63) vs 56.8% (50/88), χ2=4.312, P<0.05]. The rate of RBCT during the first three weeks in the umbilical cord blood group was lower than that in the peripheral blood group [34.9% (22/63) vs 59.1% (52/88), χ2=8.583, P<0.05]. There were no significant differences in the volume of RBCT per time, adverse reactions after transfusion, and the erythrocyte count, hemoglobin, and hematocrit before and after the first RBCT between the two groups. (3) The incidence of neonatal respiratory distress syndrome, neonatal necrotizing enterocolitis, bronchopulmonary dysplasia, retinopathy of prematurity, and intraventricular hemorrhage (grade Ⅲ-Ⅳ) and their outcomes were similar between the two groups (all P>0.05). Conclusion:Blood sampling methods show no significant effect on the total incidence of anemia and RBCT in VLBWIs during hospitalization. Umbilical cord blood sampling may delay the first RBCT time of VLBWIs and reduce the rate of RBCT in the first three weeks, but do not affect the incidence of complications.

Prenatal Diagnosis for Primary Immunodeficiency Disorders-An Overview of the Indian Scenario.

Prenatal Diagnosis (PND) forms an important part of primary preventive management for families having a child affected with primary immunodeficiency. Although individually sparse, collectively this group of genetic disorders represents a significant burden of disease. This paper discusses the prenatal services available for affected families at various centers across the country and the challenges and ethical considerations associated with genetic counseling. Mutation detection in the index case and analysis of chorionic villous sampling or amniocentesis remain the preferred procedures for PND and phenotypic analysis of cordocentesis sample is reserved for families with well-characterized index case seeking PND in the latter part of the second trimester of pregnancy. A total of 112 families were provided PND services in the last decade and the presence of an affected fetus was confirmed in 32 families. Post-test genetic counseling enabled the affected families to make an informed decision about the current pregnancy.

Conservative in utero treatment of fetal dyshormonogenetic goiter with levothyroxine, a systematic literature review.

Fetal goitrous hypothyroidism is a rare condition associated with important obstetrical, neonatal complications, and neurodevelopmental impairments. Prenatal treatment remains controversial, and the risk to benefit ratio must be accurately assessed and considered for individualized management. The objective of this review was to evaluate the feasibility, safety, and effectiveness of the conservative in utero treatment of fetal goitrous hypothyroidism. In total, 25 reports that met our inclusion criteria were selected and the management of 38 cases was analyzed. Prenatal diagnosis consisted mainly of ultrasonographic findings. Fetal thyroid status was assessed by cordocentesis. Prenatal treatment varied widely in terms of levothyroxine (LT4) route of administration, dosage, number of injections, and frequency. Although different regimens and routes of administration were proposed, they seem to have similar results regarding fetal goiter reduction and thyroid status at birth. At birth, most babies had hypothyroidism, but the long-term follow-up indicated a normal psycho-neuromotor development. Our data confirm the feasibility of conservative treatment with LT4 for fetal goitrous hypothyroidism. Further studies are needed to determine the optimal management of this disorder.

Evaluation of chromosomal abnormalities and copy number variations in late trimester pregnancy using cordocentesis.

Because the numbers of detected fetal abnormalities increase as gestation progresses, we evaluated the safety and efficacy of cordocentesis for single nucleotide polymorphism (SNP) analysis tests in 754 women during third trimester pregnancy. Conventional karyotyping was performed on all fetuses, and Affymetrix CytoScan HD was used for SNP-array testing. In addition to the 24 cases with chromosomal abnormalities detected with conventional karyotyping analysis, the SNP-array test identified 56 (7.4%) cases with normal karyotypes but abnormal copy number variations (CNVs). Of those, 24 were pathogenic CNVs and 32 were of uncertain clinical significance. In 742 of the cases, there were abnormal sonographic findings, and cytogenetic abnormalities were detected in 76 cases (10.2%). The largest number of abnormalities involved multiple malformations (21.7%), followed by defects in the lymphatics or effusion (19.0%) or urogenital system (15.3%). The use of SNP-array test fully complemented chromosome karyotype analysis after late cordocentesis. It also improved the detection rate for fetal chromosomal abnormalities and was effective for preventing and controlling the occurrence of birth defects.

Prediction of Fetal Anemia in Subsequent Transfusions: Is There a Need to Change the Threshold of the Peak Systolic Velocity of the Middle Cerebral Artery?

INTRODUCTION: Peak systolic velocity (PSV) of the middle cerebral artery (MCA) shows 100% sensitivity for predicting fetal anemia before the first intrauterine transfusion (IUT). However, its ability to predict subsequent transfusions has remained mostly controversial. OBJECTIVES: To assess if there is a need to change the threshold of MCA-PSV from 1.5 to 1.69 multiples of the median (MoM) to predict fetal anemia and the need for subsequent IUT. METHODS: This is a retrospective audit, wherein case records of mothers who underwent IUT at the Bangalore Fetal Medicine Centre between April 2008 and May 2017 were reviewed; 86 cases were included, and the data were analyzed using MS Excel. The MCA-PSV and pretransfusion Hb were converted into MoM. 40 fetuses that had more than 1 IUT were included in the analysis. -Results: 31/40 fetuses that had >1 IUT had an MCA-PSV >1.5 MoM, of which 29 were anemic according to the post-IUT Hb MoM. 20/29 (69%) had an MCA-PSV >1.69, whereas 9/29 (31%) had an MCA-PSV between 1.5 and 1.69 MoM. Our study shows that changing the MCA-PSV threshold from 1.5 to 1.69 MoM will reduce the detection of fetal anemia and hence the need for repeat IUT by 31%. CONCLUSIONS: Increasing the fetal MCA-PSV threshold from 1.5 to 1.69 will miss out one-third of the fetuses that will require a 2nd, 3rd, or 4th IUT. This is more relevant in geographical areas where the parents must travel long distances for IUTs, which are performed in tertiary fetal care centers.

Cytogenetic analysis of 3387 umbilical cord blood in pregnant women at high risk for chromosomal abnormalities.

BACKGROUND: Cordocentesis in our practice is most commonly indicated for rapid karyotyping in the second or third trimester and is regarded as the gold standard for foetal chromosomal aberration diagnosis in pregnancies at high risk for chromosomal abnormalities. In this study, we investigated 3387 umbilical cord blood samples for karyotyping from pregnant women who underwent cordocentesis and explored the pregnancy outcomes of foetal sex chromosome mosaicism and chromosomal polymorphism. RESULTS: Out of the 3387 samples, 182 abnormal karyotypes were detected. Ultrasound soft markers were the most common prenatal diagnostic indication, but the detection rate of abnormal karyotypes was 2.02%, while it was 46.97% in the genome-wide NIPT-positive group. The rate of aneuploidy was lower in the soft marker group than in the other groups. Out of 16 cases with sex chromosome mosaicism, three pregnant women with foetuses with a lower proportion of sex chromosome mosaicism delivered healthy foetuses; the foetus with karyotype 46,X,i(Y)(q10)[20]/45,X[6] showed unclear genitals. Three foetuses with chromosomal polymorphisms had postnatal disorders. CONCLUSIONS: NIPT should not be recommended as the first-tier screening for chromosomal aberration for pregnancies with ultrasound soft markers or pathological ultrasound findings, but NIPT can be considered an acceptable alternative for pregnancies with contraindications to cordocentesis or the fear of procedure-related foetal loss. Mosaicism found in amniotic fluid cell culture requires further cordocentesis for karyotype confirmation, and the continuation of pregnancy is safe when a normal karyotype is identified in foetal blood culture. Further genetic testing and parental karyotype analysis are needed for foetal chromosomal polymorphisms.

Cordocentesis-associated fetal loss and risk factors: single-center experience with 6650 cases.

OBJECTIVES: To identify procedural risk factors associated with fetal loss following cordocentesis and to determine the rate of cordocentesis-related fetal loss associated with the current cordocentesis protocol used in our institution. METHODS: This was a retrospective cohort study of pregnancies that underwent midpregnancy cordocentesis in a single center (a tertiary hospital, teaching school), between 1992 and 2018, based on data retrieved from our prospective database. All consecutive cases were validated to retrieve those meeting the eligibility criteria, which included: singleton pregnancy without underlying maternal disease, normal fetus (no structural or chromosomal abnormality or severe disorder), gestational age between 16 and 24 weeks at the time of the procedure and availability of pregnancy outcome. Cases that resulted in termination of pregnancy were excluded. We assessed the effect of prior cordocentesis model training on the fetal-loss rate and procedure-related complications, and evaluated potential risk factors of fetal loss secondary to cordocentesis, including procedure difficulty, placenta penetration, prolonged bleeding, fetal bradycardia, puncture site and early gestational age at procedure. Pregnancy outcomes were compared between the study group and a control group of women, who did not undergo cordocentesis, selected randomly at a 1:1 ratio from our obstetric database. RESULTS: A total of 10 343 procedures were performed during the study period, of which 6650 met the eligibility criteria and were included in the analysis. The fetal-loss rate in the first 60 procedures (early practice) of six operators (n = 360 procedures), who did not have prior model training, was significantly higher than that during the early practice of 18 operators (n = 1080 procedures) with prior model training (6.9% vs 1.6%; P < 0.001); whereas the fetal-loss rate in the next 60 procedures of practice was comparable between the two groups. After excluding the first 360 procedures of the groups without prior model training, the overall fetal-loss rate in pregnancies that underwent cordocentesis was significantly higher than that in the control group (1.6% vs 1.0%; P < 0.001). Considering the fetal-loss rate in the normal controls as background loss, the incremental cordocentesis-associated fetal-loss rate was 0.6%. Penetration of the placenta (odds ratio (OR), 2.65 (95% CI, 1.71-4.10)), prolonged bleeding from the puncture site (OR, 10.85 (95% CI, 5.27-22.36)) and presence of fetal bradycardia (OR, 3.32 (95% CI, 1.83-6.04)) during cordocentesis were independent risk factors associated with fetal loss. CONCLUSIONS: Cordocentesis model training markedly reduces fetal loss during the early learning curve of practice. Thus, cordocentesis practice without prior model training should not be acceptable. Significant procedural risk factors for fetal loss secondary to cordocentesis are placental penetration, prolonged bleeding and fetal bradycardia. Cordocentesis-related fetal loss may be only 0.6%, much lower than the rate reported previously. Copyright © 2020 ISUOG. Published by John Wiley & Sons Ltd.

Refining the prognosis of fetuses infected with Cytomegalovirus in the first trimester of pregnancy by serial prenatal assessment: a single-centre retrospective study.

OBJECTIVE: To define the predictive value (PV) of known prognostic factors of fetal infection with Cytomegalovirus following maternal primary infection <14 weeks of gestation, at different time points of pregnancy: the end of the second trimester; following prenatal magnetic resonance imaging (MRI) at 32 weeks of gestation; and using all ultrasound scans performed in the third trimester (US3rdT). DESIGN: A retrospective study. SETTING: Reference fetal medicine unit. POPULATION: Sixty-two fetuses infected <14 weeks of gestation. METHODS: We defined second-trimester assessment (STA) as the combination of ultrasound findings <28 weeks of gestation and fetal platelet count at cordocentesis. Three groups were defined: normal, extracerebral, and cerebral STA. MAIN OUTCOME MEASURES: For each group, the PV of STA alone, STA + MRI, and STA + US3rdT were assessed retrospectively. Outcome at birth and at follow-up were reported. RESULTS: The STA was normal, and with extracerebral and cerebral features, in 43.5, 42.0, and 14.5%, respectively. The negative PV of normal STA and MRI for moderate to severe sequelae was 100%. The residual risk was unilateral hearing loss in 16.7% of cases. Of pregnancies with cerebral STA, 44% were terminated. Following extracerebral STA, 48% of neonates were symptomatic and 30% had moderate to severe sequelae. In those cases, the positive and negative PV of MRI for sequelae were 33 and 73%, respectively. STA + US3rdT had a lower negative PV than MRI for symptoms at birth and for moderate to severe sequelae. Any false-positive findings at MRI were mostly the result of hypersignals of white matter. CONCLUSIONS: Serial assessment in the second and third trimesters by ultrasound and MRI is necessary to predict the risk of sequelae occurring in 35% of pregnancies following fetal infection in the first trimester of pregnancy. TWEETABLE ABSTRACT: Serial ultrasound prognostic assessment following fetal CMV infection in the 1st trimester is improved by MRI at 32 weeks.