Nonhydropic Fetuses Research Articles

Evaluation of cardiac findings using speckle tracking in fetuses with hemoglobin Bart's disease.

Hemoglobin (Hb) Bart's disease is a severe manifestation of alpha thalassemia, resulting in fetal tissue hypoxia and severe anemia. There is limited research available on assessing fetal speckle tracking analysis as a response to fetal anemia caused by Hb Bart's disease and its utility as a sonographic predictor for Hb Bart's disease. This study aimed to assess the diagnostic performance of fetal cardiac parameters derived from speckle tracking echocardiography for distinguishing between affected and unaffected fetuses in pregnancies at risk of Hb Bart's disease during the 17-24 gestational weeks. A total of 115 pregnant women at risk for fetal Hb Bart's disease, who underwent either amniocentesis or cordocentesis at Siriraj Hospital, Bangkok Thailand, were included. Speckle tracking analysis was performed on the 4-chamber view (4CV) of the fetal heart, assessing heart size, shape, ventricular contractility, and left ventricular function prior to invasive prenatal testing. Logistic regression analysis determined significant cardiac predictors and calculated the probability of a fetus having Hb Bart's disease. Among the cohort, 38 fetuses (33%) were diagnosed with Hb Bart's disease, and 9 cases (7.8%) exhibited frank hydropic signs. In comparison to the control group, affected fetuses displayed a notable enlargement of the 4CV and a more globular shape specifically in the right ventricular chamber. Additionally, there were significant differences in the left global and longitudinal contractility between affected and unaffected fetuses. However, at mid-gestation, no significant distinctions were observed in terms of transverse contractility and left ventricular function between the two groups. Based on logistic regression analysis, combined cardiac parameters derived from speckle tracking analysis as a function of head circumference, could differentiate non-hydropic fetuses with Hb Bart's disease from unaffected fetuses, achieving a maximum sensitivity of 100%, specificity of 98.7%, and overall accuracy of 99.06%. Speckle tracking echocardiography has the potential to accurately identify early fetal heart changes in individuals at risk of developing Bart's anemia during the second trimester. This not only offers a novel predictive marker for Hb Bart's disease but also helps address the question of the underlying mechanisms of heart failure associated with anemia. This article is protected by copyright. All rights reserved.

Fetal NT-proBNP levels and their course in severe anemia during intrauterine treatment

PurposeIn adults and fetuses, N-terminal pro-B-type natriuretic peptide (NT-proBNP) is a marker of cardiac failure and myocardial remodelling. We examined the effect of anemia and intrauterine transfusion (IUT) on NT-proBNP concentrations in fetuses with anemia and established gestational age-dependent reference values of a control group.MethodsWe analyzed NT-proBNP levels in anemic fetuses that underwent serial intrauterine transfusions (IUT), focusing on different causes and severity of anemia and comparing the results to a non-anemic control group.ResultsIn the control group, the average NT-proBNP concentration was 1339 ± 639 pg/ml, decreasing significantly with increasing gestational age (R = − 74.04, T = − 3.65, p = 0.001). Subjects had significantly higher NT-proBNP concentrations before initiation of IUT therapy (p < 0.001), showing fetuses with parvovirus B19 (PVB19) infection having the highest concentrations. Hydropic fetuses also showed an increased NT-proBNP concentration compared to non-hydropic fetuses (p < 0.001). During the course of therapy, NT-proBNP concentration before subsequent IUT decreased significantly from pathologically high levels, while MoM-Hb and MoM-MCA-PSV remained pathological.ConclusionNT-pro BNP levels in non-anemic fetuses are higher than in postnatal life, decreasing with ongoing pregnancy. Anemia is a hyperdynamic state and its severity correlates with circulating NT-proBNP levels. Highest concentrations occur in fetuses with hydrops and with PVB19 infection, respectively. Treatment by IUT leads to a normalisation of NT-proBNP concentrations, so the measurement of its levels may be useful in therapy monitoring.

Routine betamethasone therapy of non-hydropic fetuses with CPAM - the way to improve perinatal outcome?

Authors discuss novel approach to the management of fetal congenital pulmonary cystic malformation (CPAM) and possible benefit of routine administration of betamethasone, which is currently recommended only for severe cases. The article presents authors' own experience with antenatally diagnosed CPAM and describes 4 cases of prenatally diagnosed CPAM without hydrops treated by two doses of betamethasone at 21-31 weeks of gestation with the aim of improving the perinatal prognosis by effect on not only mortality but also postnatal morbidity. Article also summarizes current knowledge on all aspects of the prenatal CPAM focusing on its treatment options. Data were obtained from the literature search based on the PubMed and Scopus database with additional search of particular articles from reference list of the selected publications.All 4 patients from the case reports showed regression of the pulmonary mass after maternal administration of betamethasone with 100 % survival rate. Even though it is not possible to say if the CPAM regression was due to the betamethasone treatment, we did not observe any complication in relation to the treatment and all cases survived until discharge. During the literature search, we did not find any data on betamethasone administration in non-hydropic fetuses with CPAM in relation to the overall perinatal and postnatal morbidity, neither data comparing the outcome between the treated versus observed only fetuses.Routine betamethasone treatment should be discussed in antenatally diagnosed CPAM cases without fetal hydrops in order to reduce the perinatal morbidity associated with CPAM (Tab. 1, Ref. 47). Keywords: betamethasone, CPAM (congenital pulmonary adenomatoid malformation), fetal therapy.

Outcome of fetuses with congenital parvovirus B19 infection: systematic review and meta-analysis.

To explore the outcome of fetuses affected by congenital parvovirus B19 (PB19) infection, with or without signs of hydrops on ultrasound. PubMed, EMBASE and CINAHL databases were searched for studies reporting on prenatal diagnosis and outcome of fetal PB19 infection. The outcomes explored were miscarriage, perinatal death (PND), intrauterine death, neonatal death, spontaneous resolution of hydrops or fetal anemia, need for intrauterine transfusion (IUT), resolution of hydrops or anemia after transfusion, fetal loss following transfusion, abnormal brain scan after birth and abnormal neurodevelopmental outcome. Outcomes were reported according to the presence or absence of signs of hydrops on ultrasound. A subgroup analysis was performed including hydropic and non-hydropic fetuses diagnosed at < 20 weeks and ≥ 20 weeks of gestation. Meta-analyses of proportions and meta-analyses using individual-data random-effects logistic regression were performed to analyze the data. Thirty-five observational studies were included, involving 611 fetuses affected by PB19 infection. The risks of miscarriage (odds ratio (OR), 11.5; 95% CI, 2.7-49.7) and PND (OR, 4.2; 95% CI, 1.6-11.0) were higher in fetuses with PB19 infection presenting, compared with those not presenting, signs of hydrops on ultrasound. In fetuses affected by hydrops, spontaneous resolution of the infection, defined as disappearance of hydrops without need for IUT, occurred in 5.2% (95% CI, 2.5-8.8%) of cases whereas, in the group of fetuses not affected by hydrops, infection resolved in 49.6% (95% CI, 20.7-78.6%) of cases. IUT was performed in 78.7% (95% CI, 66.4-88.8%) of hydropic and in 29.6% (95% CI, 6.0-61.6%) of non-hydropic fetuses affected by congenital PB19 infection and resolution of the infection after IUT occurred in 55.1% (95% CI, 34.0-75.3%) and in 100% (95% CI, 57.3-100%) of cases, respectively. The risk of fetal loss after IUT was higher in fetuses affected compared with those not affected by hydrops (OR, 9.8; 95% CI, 2.8-34.6). The prevalence of abnormal brain imaging was 9.8% (95% CI, 2.5-21.0%) in fetuses affected and 0.0% (95% CI, 0.0-7.0%) in those not affected by hydrops, whilst the corresponding figures for abnormal neurodevelopmental outcome were 9.5% (95% CI, 2.6-20.2) and 0.0% (95% CI, 0.0-7.5), respectively; however, statistical power to assess these outcomes was inadequate due to the small number of included cases. Hydrops is the main determinant of mortality and adverse perinatal outcome in fetuses with PB19 infection. Perinatal outcome in non-hydropic fetuses is generally favorable. Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd.

NT-proBNP: A Useful Biochemical Marker for Prognosis in Rh-Isoimmunized Pregnancies.

Rh incompatibility sometimes results in life-threatening conditions in fetus like severe anemia and jaundice, leading to kernicterus and even death. Even after an uneventful intrauterine transfusion (IUT), fetus may not survive despite correction of the fetal anemia. Finding appropriate markers may help in determining the prognosis of such cases. The N-terminal prohormone of brain natriuretic peptide (NT-proBNP) suggests some degree of heart failure. Present study was planned to evaluate its role in predicting the outcome of fetus in Rh-isoimmunized pregnant woman. This prospective study consisted of total 40 pregnant patients: 10 pregnant Rh-isoimmunized women with hydropic fetuses, 10 with non-hydropic fetuses and 20 control group. If the MCA-PSV was > 1.5 MOM, cord blood sampling and IUT was done and sent for fetal hematocrit and NT-proBNP. The levels of NT-proBNP at various periods of gestation in hydropic, non-hydropic and control group fetuses showed positive correlation with the degree of fetal anemia. Correlation of high levels of NT-proBNP to fetal anemia proves that hydrops fetalis is probably due to progressive high cardiac output myocardial failure, increased capillary permeability and perhaps reduced coronary flow.

Acoustic radiation force impulse elastosonography of placenta in maternal red blood cell alloimmunization: a preliminary and descriptive study.

Maternal red blood cell alloimmunization is an important cause of fetal morbidity and mortality in the perinatalperiod, despite well-organized prophylaxis programs. The objective of the study was to evaluate placental elasticity by usingAcoustic Radiation Force Impulse (ARFI) in Rhesus (Rh) alloimmunized pregnant women with hydropic and nonhydropicfetuses and to compare those with healthy pregnant women. This case-control and descriptive studycomprised twenty-eight healthy pregnant women, 14 Rh alloimmunized pregnant women with nonhydropic fetuses, and 16 Rhalloimmunized pregnant women with hydropic fetuses in the third trimester of pregnancy. Placental elasticity measurementswere performed by ARFI elastosonography at the day of delivery. The maternal characteristics and neonatal outcomes of thepatients were also noted. The highest mean placental ARFI scores were observed in Rh alloimmunized pregnantwomen with hydropic fetuses (1.13 m/s) (p=0.001). Healthy controls and Rh alloimmunized pregnant women with nonhydropicfetuses had similar mean placenta ARFI scores (0.84 m/s, 0.88 m/s, respectively) (p<0.05). Based onthe present findings, the placenta becomes stiffer in Rh alloimmunized pregnancies complicated with hydrops fetalis. Theincreased placental ARFI scores may be a supplemental marker for adverse pregnancy outcomes, additional to Doppler evaluationof middle cerebral artery. This data should be confirmed with a large sample size and prospective studies by using serialmeasurements of ARFI elastosonography in maternal red blood cell alloimmunization.

Flecainide versus digoxin for fetal supraventricular tachycardia: Comparison of two drug treatment protocols

The optimal treatment for fetal supraventricular tachycardia (SVT) with 1:1 atrioventricular relationship is unclear. We compared the effectiveness of transplacental treatment protocols used in 2 centers. Pharmacologic treatment was used in 84 fetuses. Maternal oral flecainide was the primary therapy in center 1 (n = 34) and intravenous maternal digoxin in center 2 (n = 50). SVT mechanism was classified by mechanical ventriculoatrial (VA) time intervals as short VA or long VA. Treatment success was defined as conversion to sinus rhythm (SR), or rate control, defined as >15% rate reduction. Short VA interval occurred in 67 fetuses (80%) and long VA in 17 (20%). Hydrops was present 28 of 84 (33%). For short VA SVT, conversion to SR was 29 of 42 (69%) for digoxin and 24 of 25 (96%) for flecainide (P = .01). For long VA SVT, conversion to SR and rate control was 4 of 8 (50%) and 0 of 8, respectively, for digoxin, and 6 of 9 (67%) and 2 of 9 (cumulative 89%) for flecainide (P = .13). In nonhydropic fetuses, digoxin was successful in 23 of 29 (79%) and flecainide in 26 of 27 (96%) (P = .10). In hydrops, digoxin was successful in 8 of 21 (38%), flecainide alone in 6 of 7 (86%, P = .07 vs digoxin), and flecainide ± amiodarone in 7 of 7 (100%) (P = .01). Intrauterine or neonatal death occurred in 9 of 21 hydropic fetuses treated with digoxin (43%), compared to 0 of 7 (P = .06) treated with flecainide. Flecainide was more effective than digoxin, especially when hydrops was present. No adverse fetal outcomes were attributed to flecainide.

Prenatal Diagnosis and Evaluation of Sonographic Predictors for Intervention and Adverse Outcome in Congenital Pulmonary Airway Malformation.

ObjectiveTo describe antenatal findings and evaluate prenatal risk parameters for adverse outcome or need for intervention in fetuses with congenital pulmonary airway malformation (CPAM).MethodsIn our retrospective study all fetuses with a prenatal diagnosis of CPAM detected in our tertiary referral center between 2002 and 2013 were analyzed. Sonographic findings were noted and measurements of mass-to-thorax-ratio (MTR), congenital pulmonary airway malformation volume-ratio (CVR) and observed to expected lung-to head-ratio (o/e LHR) were conducted and correlated to fetal or neonatal morbidity and mortality and/or need for prenatal intervention.Results67 fetuses with CPAM were included in the study. Hydropic fetuses were observed in 16.4% (11/67) of cases, prenatal intervention was undertaken in 9 cases; 7 pregnancies were terminated. The survival rate of non-hydropic fetuses with conservatively managed CPAM was 98.0% (50/51), the survival rate for hydropic fetuses with intention to treat was 42.9% (3/7). 10 (18.2%) children needed respiratory assistance. Fetuses with a CVR of <0.91 were significantly less likely to experience adverse outcome or need for prenatal intervention with sensitivity, specificity and positive/negative predictive value of 0.89, 0.71, 0.62 and 0.93, respectively. A MTR (mass-to-thorax-ratio) of < 0.51 had a positive predictive value of 0.54 and a negative predictive value of 0.96 of adverse events with a sensitivity of 0.95 and a specificity of 0.63. The negative predictive value for o/e LHR of 45% was 0.84 with sensitivity, specificity and positive predictive value of 0.73, 0.68 and 0.52, respectively.ConclusionsThe majority of cases with CPAM have a favorable outcome. MTR and CVR are able to identify fetuses at risk, the o/e LHR is less sensitive.

High-dose flecainide is the most effective treatment of fetal supraventricular tachycardia

Fetal tachyarrhythmia can lead to fetal hydrops due to heart failure. Flecainide is often considered as second-line therapy when digoxin monotherapy fails, which is more likely in hydropic fetuses. Time to conversion to sinus rhythm (SR) is critical in cases presenting with hydrops. The aim of this study was to evaluate the efficacy and time to conversion to SR of transplacental treatment, especially flecainide. This is a retrospective observational study of 46 fetuses with fetal tachyarrhythmia. Treatment was either flecainide (n = 28, 60.9%), digoxin+flecainide combination (n = 4, 8.7%), or digoxin (n = 10, 21.7%). In 4 fetuses (8.7%), no treatment was necessary. In our study population, 26 of the 32 fetuses (81.2%) that were treated with flecainide as a first-line therapy (flecainide or digoxin+flecainide) converted to SR. The median time to conversion to SR was 3 days (range 1-7 days) with flecainide monotherapy and 11.5 days (range 3-14 days) with a combination therapy. Seventy-two percent (13/18) of hydropic fetuses and 90% (9/10) of nonhydropic fetuses converted to SR when treated with flecainide monotherapy. There was no statistical difference in rates of conversion to SR in hydropic and nonhydropic fetuses (P = .37) or time to conversion to SR in the 2 groups (P = .9). In the majority of the remaining fetuses, there was a partial response with decreased ventricular heart rates that were well tolerated. Flecainide is highly effective in achieving SR in hydropic and nonhydropic fetuses with supraventricular tachycardia in a median time of 3 days. In our opinion, flecainide should be considered as first-line therapy in fetal supraventricular tachycardia with and without hydrops.

Perinatal outcomes of fetal pleural effusion following thoracoamniotic shunting.

The aim is to evaluate perinatal outcomes of fetal pleural effusion after thoracoamniotic shunting. This was a retrospective study of 68 singleton pregnancies with massive fetal pleural effusion that underwent thoracoamniotic shunting between 1999 and 2012 at Asan Medical Center, Seoul, Korea. Through a review of medical records, we investigated perinatal outcomes according to the presence of fetal hydrops and identified prognostic factors by stepwise multivariate logistic regression analysis. Of the 68 pregnancies, three were lost to follow-up and two fetuses died in utero. The median gestational age at shunting was 28.3 weeks (range, 18.5-34.1 weeks). Of the 65 fetuses, 50 (76.9%) were hydropic, of which hydrops resolved following shunting in 29 fetuses (58.0%). Among the 63 live births, the median gestational age at delivery was 33.6 weeks (range, 26.2-40.0 weeks), with 36 fetuses (57.1%) delivered preterm. The overall survival rate was 75.4% (49/65), and in a subgroup analysis, the survival rate was highest for non-hydropic fetuses (14/15, 93.3%), followed by fetuses whose hydrops resolved (25/29, 86.2%) and remained after shunting (10/21, 47.6%). Thoracoamniotic shunting can be helpful for fetuses with massive pleural effusion. While fetal hydrops can occur in such cases, perinatal outcomes can be improved by successful shunting.

Correlation of maternal flecainide concentrations and therapeutic effect in fetal supraventricular tachycardia.

Transplacental flecainide is an established therapy for fetal supraventricular tachycardia (SVT), but there is a paucity of data regarding the dose-response relationship. The purpose of this study was to investigate the relationship between maternal flecainide concentrations, arrhythmia control, and adverse fetal effects in fetal SVT. Fetuses with SVT treated with transplacental flecainide at our tertiary fetal cardiology unit between 1997 and 2012 were retrospectively studied. The maternal trough flecainide concentrations throughout treatment were collated, and clinical notes were reviewed to ascertain the response to therapy and fetal outcome. Thirty-three fetuses were treated at a median (range) gestation of 28 weeks (20-38 weeks). Median fetal heart rate was 250/min (range 207-316/min). One patient was lost to follow-up, and this fetus was excluded from further analysis. In total, 25 of 32 fetuses (78%) converted to sinus rhythm. Median time to conversion to sinus rhythm was 3 days (range 2-12 days). Median flecainide concentration was 460 μg/L (range 250-866 μg/L) at conversion to sinus rhythm. Flecainide concentrations were not significantly different between responders and nonresponders (P = .849). Twelve of 14 hydropic and 13 of 18 nonhydropic fetuses converted to sinus rhythm with similar flecainide concentrations (P = .316). No fetus achieved cardioversion with a maternal serum flecainide concentration <250 μg/L. No fetus died while being treated with flecainide. The clinical response to flecainide appears good, even in hydropic fetuses. Trough maternal flecainide concentrations, once therapeutic, do not predict cardioversion in the fetus with SVT. Flecainide therapy appears both safe and effective for the fetus when monitored appropriately.

Antenatal Maternal Serum IAT Titer and Fetal Outcome in Rh Isoimmunized Pregnancies.

The incidence of Rh negativity in India is about 1-5% and the rate of Rh sensitization to be approximately 0.79% of live births. This study evaluated the role of antenatal maternal serum Indirect Antiglobulin Test (IAT) titre in predicting the feto-neonatal outcome. The study was conducted from Jan 2007 to Dec 2012 at our centre in Pune, Maharashtra, India. This study reports our experience with 75 IUTs carried out for 42 cases of severe Rh isoimmunization. IAT was performed by ID gel cards and test tube method was utilized for titration. Results were analysed by odds ratio (OR) with 95% Confidence Interval. IAT titre was found to have a direct correlation with the maternal parity, requirement of number of IUT's and adverse fetal outcome. Of the 42 cases of severe Rhisoimmunization who underwent IUT, 11 (26.2%) had hydropic fetus resulting in 08 (73%) live babies, two intrauterine and one neonatal death. The remaining 31 (73.8%) non-hydropic fetuses who received IUT, one intrauterine and one neonatal death were observed. In the 11 hydropic cases, who received IUTs, two intrauterine and one neonatal death were observed in which the IAT titre was ≥512, which was found statistically significant with OR of 9.77 & P value of 0.05. The overall survival rate was 37/42 (88.1%). Severity and fetal outcome in Rh isoimmunized pregnancies, showed a significant association with antenatal maternal serum IAT titre. More the antibody titre more would be the fetal and/or neonatal severity with respect to immune hemolytic anemia. Requirement of multiple IUTs are also associated with high antenatal serum IAT titre.

076 DETERMINING THE OPTIMAL THERAPY FOR FETAL SUPRAVENTRICULAR TACHYCARDIA (SVT): A COMPARISON OF TWO DRUG TREATMENT PROTOCOLS

<h3>Introduction</h3> The best treatment for sustained fetal SVT with 1:1 atrio ventricular relationship is not known. We compared two treatment protocols. <h3>Methods</h3> 155 consecutive fetuses with supraventricular tachyarrhythmia presented 2000–2012. 127 had SVT with 1:1 atrio-ventricular conduction. 86 received drug treatment according to one of two protocols: first-line maternal intravenous digoxin (n=52, centre 2), or maternal oral flecainide (n=34, centre 1). Treatment success was defined as live birth after conversion to sinus rhythm, or rate reduction by &gt;15%. <h3>Results</h3> Short ventriculo-atrial (VA) interval occurred in 69 and long VA in 17. Age at treatment start was median 31 weeks gestation in each centre. Hydrops was present in 30/86 (35%). Digoxin was successful in 23/28 (82%) and flecainide in 26/27 (96%, p 0.19) of non-hydropic fetuses, compared to 8/21 (38%) and 6/7 (86%, p 0.07) respectively when hydrops was present. For short VA SVT, conversion to sinus rhythm and rate control was 31/44 (70%) and 0/44 for digoxin, and 23/25 (92%) and 1/25 (cumulative 96%, p 0.01) for flecainide. For long VA SVT, conversion to sinus rhythm and rate control was 4/8 (50%) and 0/8 for digoxin, and 5/9 (55%) and 2/9 (cumulative 78%, p 0.3) for flecainide. Second line drug treatment was added to digoxin in 19/52 (37%), and to flecainide in 2/34 (6%, p 0.002). Intrauterine or neonatal death occurred in 9/21 (43%, including 1 termination) hydropic fetuses treated with digoxin compared to 0/9 (p 0.03) of those treated with flecainide. <h3>Conclusions</h3> Flecainide was more effective than digoxin in short VA SVT, especially when hydrops was present. Additional treatment was used more often in the digoxin protocol. No adverse fetal outcomes were attributed to flecainide.

Fetal lung lesions: can we start to breathe easier?

The purpose of this study was to develop a simple and accurate approach for risk stratification of fetal lung lesions that are associated with respiratory compromise at birth. We conducted a retrospective review of 64 prenatal lung lesions that were managed at a single fetal care referral center (2001-2011). Sonographic data were analyzed and correlated with perinatal outcomes. Hydrops occurred in only 4 cases (6.3%). Among fetuses without hydrops, the congenital pulmonary airway malformation volume ratio (CVR) was the only variable that was associated significantly with respiratory compromise and the need for lung resection at birth (P < .01). Based on a maximum CVR >1.0, the sensitivity, specificity, positive predictive value, and negative predictive value for respiratory morbidity were 90%, 93%, 75%, and 98%, respectively. Nonhydropic fetuses with a maximum CVR >1.0 are a subgroup of patients who are at increased risk for respiratory morbidity and the need for surgical intervention. These patients should be delivered at a tertiary care center with pediatric surgery expertise to ensure optimal clinical outcomes.

Experimental treatment of bilateral fetal chylothorax using in‐utero pleurodesis

To assess the use and efficacy of in-utero pleurodesis for experimental treatment of bilateral fetal chylothorax. This was a study of 78 fetuses with bilateral pleural effusion referred to three tertiary referral centers in Taiwan between 2005 and 2009. Fetuses were karyotyped following amniocentesis and the lymphocyte ratio in the pleural effusion was determined following thoracocentesis. Forty-nine (62.8%) fetuses had a normal karyotype and were recognized to have fetal chylothorax; of these, 45 underwent intrapleural injection of 0.1KE OK-432 per side per treatment. We evaluated clinical (hydrops vs. no hydrops) and genetic (mutations in the reported lymphedema-associated loci: VEGFR3, PTPN11, FOXC2, ITGA9) parameters, as well as treatment outcome. Long-term survival was defined as survival to 1 year of age. The overall long-term survival rate (LSR) was 35.6% (16/45); the LSR for non-hydropic fetuses was 66.7% (12/18) and for hydropic fetuses it was 14.8% (4/27). If we included only fetuses with onset of the condition in the second trimester, excluding those with onset in the third trimester, the LSR decreased to 29.4% (10/34). Notably, 29.6% (8/27) of hydropic fetuses had mutations in three of the four loci examined. OK-432 pleurodesis appeared to be an experimental alternative to the gold-standard technique of thoracoamniotic shunting in non-hydropic fetal chylothorax. In hydropic fetuses, pleurodesis appeared less effective.

Intrauterine Fetal Death Due To Cardiac Rhabdomyomas

A 21-year-old patient, in her first and regularly controlled uneventful pregnancy, was admitted to hospital due to lower leg edema, hypertension, proteinuria, and weight gain. Fetal death occurred the next day and a female nonhydropic fetus, 40 cm CH, 1460 grams, at 29-week gestation was delivered. An autopsy showed no visible gross abnormalities except in the heart. The heart was enlarged, with five intramural and subendocardial nodules, 0.3 to 1 cm in size, three in the left ventricular free wall, and one in the right ventricle and right atrium, sharply demarcated, reddish-gray, moderately firm, with the typical appearance of rhabdomyoma.

Early intrauterine transfusion in severe red blood cell alloimmunization

To determine perinatal outcome in pregnancies with early severe red blood cell (RBC) alloimmunization. This was a retrospective analysis of 30 patients requiring their first intrauterine transfusion (IUT) at < 22 weeks of gestation. Timing of the first IUT was based on evaluation of either the middle cerebral artery peak systolic velocity (MCA-PSV) or development of ascites. Thirty-three per cent of the patients had experienced a previous intrauterine fetal death as a result of RBC alloimmunization. Of these alloimmunized pregnancies, 26 (87%) were associated with anti-D, four (13%) with anti-Kell and 12 had more than one antibody type involved. The antibody titers before the first IUT ranged from 1:128 to 1:8024. All fetuses were severely anemic before the first IUT with a median hemoglobin (Hb) level of 37 (range, 3-81) g/L. The nine hydropic fetuses had a lower Hb level compared with non-hydropic fetuses (median 15 g/L vs. 42 g/L, P = 0.016). However, 15 (71%) non-hydropic fetuses had an Hb level of < 50 g/L before the first IUT. The median gestational age at the first IUT was 20.4 (range, 16-22) weeks, and between one and nine transfusions were needed during pregnancy. Transfusion was via the intrahepatic vein (IHV) (n = 19), umbilical vein (n = 6) or umbilical artery (n = 2), or was intracardiac (n = 2) or intraperitoneal (n = 1). Overall perinatal survival rate was 80% and did not differ between hydropic and non-hydropic fetuses. Median gestation at delivery, after exclusion of six intrauterine fetal deaths, was 36.7 (range, 27.8-38.4) weeks. In early severe RBC alloimmunization, fetuses can be severely anemic without hydrops, and prognosis cannot be predicted by the presence or absence of hydrops. Early IUT followed by serial transfusions is associated with a perinatal survival rate of about 80%.

Haemoglobin level, proportion of haemoglobin Bart's and haemoglobin Portland in fetuses affected by homozygous α0‐thalassemia from 12 to 40 weeks' gestation

To determine haematological parameters in fetuses affected by homozygous α(0)-thalassemia. This was a cross-sectional retrospective study reviewing 546 blood samples (268 fetal and 278 neonatal cord) being collected between 1993 and 2006, from 12 weeks' gestation onwards for any indication, including the prenatal diagnosis of homozygous α(0)-thalassemia, other haematological disorders, hydrops or aneuploidy. The proportion of haemoglobin (Hb) fractions was determined by electrophoresis of haemolysate on cellulose acetate in all samples. There were significant differences in the haematological parameters between homozygous α(0)-thalassemia (n = 183) and control (n = 363) which were either heterozygous α(0)-thalassemia (alpha thalassemia trait) or normal. In homozygous α(0)-thalassemia, the median Hb level, proportion of Hb Bart's (γ(4)) and Hb Portland 1(ζ(2)γ(2)) were 6.4 g/dL, 77.5% and 22.5%, respectively. While the Hb level and the proportion of Hb Bart's increased significantly with gestation, the proportion of Hb Portland 1 decreased. The Hb level contributed by Hb Portland 1 remained around 1.4 g/dL throughout gestation. The proportion of mild, moderate and severe anaemia in the affected fetuses was 27.5, 32.7 and 39.8%, respectively. There was no significant difference in these proportions across different gestation (P = 0.231). There were no differences in the haematological parameters between hydropic and non-hydropic fetuses. Although the degree of anaemia is mild in around one-quarter of the affected fetuses, the contribution by Hb Portland 1 (ζ(2)γ(2)) to the Hb level was very low throughout gestation, and the affected fetuses may therefore be at risk for hypoxia.

Perinatal outcome following fetal chest shunt insertion for pleural effusion

To evaluate perinatal outcome of fetuses with primary pleural effusions following pleuroamniotic shunting. This was a retrospective study of 88 fetuses with large pleural effusions referred to a tertiary fetal medicine unit between 1991 and 2008 which, after a thorough work-up, underwent pleuroamniotic shunting. At presentation, 59 (67.0%) fetuses were hydropic and 67 (76.1%) had bilateral effusions. In 17 (19.3%) fetuses, pleural fluid was aspirated prior to shunting and in 71 (80.7%), shunts were inserted directly as the first procedure. Mean gestational age at shunting was 27.6 (range, 18-37) weeks and at delivery 34.2 (range, 19-42) weeks. Seventy-four (84.1%) babies were born alive, of whom 52 (70.3%) survived the neonatal period. Of 59 hydropic fetuses, 10 (16.9%) died @ in utero and 18 neonates (30.5%) died, resulting in perinatal survival of 52.5%, whereas of 29 non-hydropic fetuses, perinatal survival was 72.4%. Hydrops resolved following shunting in 28 fetuses, of whom 71% survived, compared to 35% survival in 31 fetuses where hydrops persisted (P = 0.006). Of 22 neonatal deaths, seven were related to pulmonary hypoplasia, five to genetic syndromes, two to aneuploidy and one to a congenital anomaly (truncus arteriosus). Overall 13 (14.8%) were diagnosed with a chromosomal, genetic or other condition, several of which could not have been diagnosed antenatally. Carefully selected fetuses with primary pleural effusions can benefit from pleuroamniotic shunting, allowing hydrops to resolve with a survival rate of almost 60%.

Current Status of Fetal Cardiac Intervention

The potential benefits of fetal cardiac intervention (FCI) have been realized for many years. In 1975, Eibschitz et al1 reported intrapartum treatment of fetal ventricular tachycardia by administering propranolol to the mother, and as early as 1986, in utero pacing was attempted for complete heart block in a human fetus.2 Recently, however, interest in FCI has accelerated.3–18 As with other fetal interventions,19,20 FCI can only become a highly useful clinical tool if it is applied to conditions in which a feasible mode of therapy is available and either the fetus is at risk for demise as a result of the condition or intervention may alter the evolution of the condition such that the severity of the postnatal disease is substantially reduced (Table 1). For conditions in which the fetus is at high risk for prenatal or neonatal death, the rationale for FCI is obvious, to improve survival. If death is not imminent but the disease is likely to have major lifelong morbidity, the rationale is that FCI will modify the course of cardiac growth, function, and/or development in utero sufficiently to alter postnatal outcome and justify the potential risks of the procedure. Prenatal intervention may also allow the fetus to recover in the supportive in utero environment, during a developmental period when there is enhanced wound healing and the capacity for myocyte proliferation.21,22 View this table: Table 1. Congenital Cardiovascular Anomalies Potentially Amenable to FCI This construct rightfully emphasizes death or significant morbidity as therapeutic targets. FCI can entail substantial short-term risk to the fetus, uncertain long-term risk to the fetus and child, and at least some risk to the mother. There are no known medical benefits to the mother. With that risk profile, FCI will not be embraced by the maternal-fetal medicine and cardiology communities unless it …