Isolated non-immune-mediated second-degree atrioventricular block in the fetus: natural history and predictive factors for spontaneous recovery.

OBJECTIVES: To determine the clinical course of fetal isolated non-immune-mediated second-degree atrioventricular block (AVB) and the factors associated with spontaneous recovery in these cases. METHODS: Fetuses with isolated non-immune-mediated second-degree AVB were recruited prospectively between 2014 and 2022. These fetuses were divided into two groups: those which recovered spontaneously and those which did not. Maternal and fetal characteristics and intrauterine and postnatal outcomes were compared between the two groups. RESULTS: The study cohort included 20 fetuses with isolated non-immune-mediated second-degree AVB, diagnosed at a median gestational age of 22.0 (range, 17.0-35.0) weeks. In 12 fetuses, 1:1 atrioventricular conduction was restored spontaneously in utero and there was no recurrence during the postnatal follow-up period. In the remaining eight fetuses, second-degree AVB was maintained and, in six of these, the pregnancy was terminated on parental request. Of the two liveborn children who had persistent second-degree AVB prenatally, one had progressed to complete AVB at the latest follow-up, at the age of 34 months, but was asymptomatic, without heart enlargement or dysfunction. The other child progressed to complete AVB after delivery and was diagnosed with type-2 long QT syndrome. This infant died aged 2 months. Fetuses in the group that recovered spontaneously had earlier gestational age at diagnosis (median, 20.0 (range, 17.0-26.0) vs 24.5 (range, 18.0-35.0) weeks; P = 0.004) and higher atrial rate at diagnosis (median, 147 (range, 130-160) vs 138 (range, 125-149) bpm; P = 0.006) in comparison with the group that did not recover spontaneously. The best cut-off values for prediction of failure to recover spontaneously were 22.5 weeks' gestational age at diagnosis and 144 bpm atrial rate at diagnosis, with sensitivities of 87.5% and 75.0%, respectively, and specificities of 92.0% and 87.5%, respectively. CONCLUSIONS: The outcome of 60% of fetuses with isolated non-immune-mediated second-degree AVB was favorable. Earlier gestational age and higher atrial rate at diagnosis were associated with spontaneous reversion to normal sinus rhythm. Prenatal genetic testing should be performed in cases with persistent AVB, to exclude heritable disorders including long QT syndrome. These findings provide important information for clinical management and prenatal counseling in these cases. © 2024 International Society of Ultrasound in Obstetrics and Gynecology.

Practical Evaluation of the Fetal Cardiac Function.

The fetal heart adapts dynamically to nutrient and oxygen needs from all fetal organs. These continuous changes make it difficult to define normal/abnormal cardiac function based only on the evaluation of a few cycles. Many signs of fetal cardiac dysfunction have been suggested; however, very few can stand as true manifestations of cardiac deterioration, and none has emerged as a single reliable marker of cardiac dysfunction. It is the combination of abnormal findings that provides a more accurate assessment of the status of the fetal heart function.

Foetal cardiac function in third trimester pregnancies with reduced fetal movements.

The objective of our study was to investigate the possible relationship between poor perinatal outcome and foetal cardiac functions in pregnant women with reduced foetal movements (RFM). This cross-sectional study included 126 pregnant women with normal foetal movements (Group 1, Controls) and 42 pregnant women over 32 weeks gestation with RFM (Group 2). Group 2 was further divided into two subgroups according to their perinatal outcome: normal perinatal outcome (Group 2a) and poor perinatal outcome (Group 2b). Cardiotocography, the E/A ratio in both atrioventricular valves, myocardial performance index (MPI) and foetal tricuspid annular plane systolic excursion (f-TAPSE) were evaluated. Foetuses with poor perinatal outcome had a higher MPI (p = .003), higher tricuspid and mitral E/A (p < .001), and lower f-TAPSE values (p < .001). In regression analysis, f-TAPSE was the only parameter (p = .04) independently associated with poor perinatal outcome. In conclusion, examining f-TAPSE may predict adverse perinatal outcome in pregnancies with RFM.IMPACT STATEMENTWhat is already known on this subject? Reduced foetal movement (RFM) is associated with adverse pregnancy outcome. Cardiotocography, amniotic fluid assessment, estimated birthweight, foetal Doppler and formal foetal movement count (kick chart) are generally used in the clinical assessment of pregnancies with reduced foetal movements. These tests, we currently use to assess foetal wellbeing in women with reduced foetal movements, have limited sensitivity in predicting foetal compromise.What do the results of this study add? Foetal cardiac Doppler may potentially be used as an important adjunct to the conventional management of women with a perception of reduced foetal movements.What are the implications of these findings for clinical practice and/or further research? Foetal echocardiographic evaluation, such as f-TAPSE, may influence clinical practice by enabling improved risk stratification for poor perinatal outcome, thus allowing more timely definitive intervention. This could help to decrease the rate of stillbirth related to reduced foetal movements. The few established echocardiographically derived parameters, which can asses global right ventricle function, are not always easy to obtain, however, f-TAPSE is easily obtainable using ultrasound and it appears to be a clinically useful echocardiographic measurement of right ventricular function.

Budesonide with surfactant decreases systemic responses in mechanically ventilated preterm lambs exposed to fetal intra-amniotic lipopolysaccharide.

BACKGROUND: Chorioamnionitis is associated with increased rates of bronchopulmonary dysplasia (BPD) in ventilated preterm infants. Budesonide when added to surfactant decreased lung and systemic inflammation from mechanical ventilation in preterm lambs and decreased the rates and severity of BPD in preterm infants. We hypothesized that the addition of budesonide to surfactant will decrease the injury from mechanical ventilation in preterm lambs exposed to intra-amniotic (IA) lipopolysaccharide (LPS). METHODS: Lambs at 126 ± 1 day GA received LPS 10 mg IA 48 h prior to injurious mechanical ventilation. After 15 min, lambs received either surfactant mixed with: (1) saline or (2) Budesonide 0.25 mg/kg, then ventilated with normal tidal volumes for 4 h. Injury markers in the lung, liver, and brain were compared. RESULTS: Compared with surfactant alone, the addition of budesonide improved blood pressures, dynamic compliance, and ventilation, while decreasing mRNA for pro-inflammatory cytokines in the lung, liver, and multiple areas of the brain. LPS caused neuronal activation and structural changes in the brain that were not altered by budesonide. Budesonide was not retained within the lung beyond 4 h. CONCLUSIONS: In preterm lambs exposed to IA LPS, the addition of budesonide to surfactant improved physiology and markers of lung and systemic inflammation. IMPACT: The addition of budesonide to surfactant decreases the lung and systemic responses to injurious mechanical ventilation preterm lambs exposed to fetal LPS. Budesonide was present in the plasma by 15 min and the majority of the budesonide is no longer in the lung at 4 h of ventilation. IA LPS and mechanical ventilation caused structural changes in the brain that were not altered by short-term exposure to budesonide. The budesonide dose of 0.25 mg/kg being used clinically seems likely to decrease lung inflammation in preterm infants with chorioamnionitis.

Fetal Hypothyroidism Impairs Aortic Vasorelaxation Responses in Adulthood: Involvement of Hydrogen Sulfide and Nitric Oxide Cross talk.

ABSTRACT: Thyroid hormones have a wide range of effects on growth, differentiation, evolution, metabolism, and physiological function of all tissues, including the vascular bed. In this study, the effect of fetal hypothyroidism on impairment of aortic vasorelaxation responses in adulthood was investigated with emphasis on possible involvement of hydrogen sulfide (H2S)/nitric oxide interaction. Two groups of female rats were selected. After mating and observation of vaginal plaque, one group received propylthiouracil (200 ppm in drinking water) until the end of pregnancy and another group had no propylthiouracil treatment during the fetal period. In adult rats, aortic relaxation responses to l-arginine and GYY4137 were assessed in the presence or absence of Nω-nitro-L-arginine methyl ester hydrochloride and dl-propargylglycine in addition to the biochemical measurement of thyroid hormones and some related factors. Obtained findings showed a lower vasorelaxation response for GYY4137 and l-arginine in the fetal hypothyroidism group, and preincubation with Nω-nitro-L-arginine methyl ester hydrochloride or dl-propargylglycine did not significantly aggravate this weakened relaxation response. In addition, aortic levels of sirtuin 3, endothelial nitric oxide synthase, cystathionine gamma-lyase, and H2S were significantly lower in the fetal hypothyroidism group. Meanwhile, no significant changes were obtained regarding serum levels of thyroid hormones including free triiodothyronine;, total triiodothyronine, free thyroxine, total thyroxine, and thyroid-stimulating hormone in adult rats. It can be concluded that hypothyroidism in the fetal period has inappropriate effects on the differentiation and development of vascular bed with subsequent functional abnormality that persists into adulthood, and part of this vascular abnormality is mediated through weakened interaction and/or cross talk between H2S and nitric oxide.

Prenatal predictors of motor function in children with open spina bifida: a retrospective cohort study.

OBJECTIVE: To identify predictors for intact motor function (MF) at birth and at 12 months of life in babies with prenatally versus postnatally repaired open spina bifida (OSB). DESIGN: Retrospective cohort study. SETTING: Texas Children's Hospital, 2011-2018. POPULATION: Patients who underwent either prenatal or postnatal OSB repair. METHODS: Prenatal MF of the lower extremities was evaluated by ultrasound following a metameric distribution at the time of diagnosis (US1), 6 weeks postoperatively (or 6 weeks after initial evaluation in postnatally repaired cases) (US2) and at the last ultrasound before delivery (US3). At birth and at 12 months, MF was assessed clinically. Intact MF (S1) was defined as the observation of plantar flexion of the ankle. Results from logistic regression analysis are expressed as odds ratios (95% confidence intervals, P values). RESULTS: A total of 127 patients were included: 93 with prenatal repair (51 fetoscopic; 42 open hysterotomy repair) and 34 with postnatal repair. In the prenatal repair group, predictors for intact MF at birth and at 12 months included: absence of clubfeet (OR 11.3, 95% CI 3.2-39.1, P < 0.01; OR 10.8 95% CI 2.4-47.6, P < 0.01); intact MF at US1 (OR 19.7, 95% CI 5.0-76.9, P < 0.01; OR 8.7, 95% CI 2.0-38.7, P < 0.01); intact MF at US2 (OR 22, 95% CI 6.5-74.2, P < 0.01; OR 13.5, 95% 3.0-61.4, P < 0.01); intact MF at US3 (OR 13.7, 95% CI 3.4-55.9, P < 0.01; OR 12.6, 95% CI 2.5-64.3, P < 0.01); and having a flat lesion (OR 11.2, 95% CI 2.4-51.1, P < 0.01; OR 4.1, 95% CI 1.1-16.5, P = 0.04). In the postnatal repair group, the only predictor of intact MF at 12 months was having intact MF at birth (OR 15.2, 95% CI 2.0-113.3, P = 0.03). CONCLUSIONS: The detection of intact MF in utero from mid-gestation to delivery predicts intact MF at birth and at 12 months in babies who undergo prenatal OSB repair. TWEETABLE ABSTRACT: Detection of intact motor function in utero predicts intact motor function at birth and at 1 year in fetuses who undergo prenatal OSB repair.

Fetal dural sinus thrombosis: A systematic review.

INTRODUCTION: Fetal dural sinus thrombosis (DST) is a rare condition. Although numerous case reports exist, the findings appear heterogenous and providing accurate patient counselling remains challenging. METHODS: A systematic literature review was conducted in accordance with PRISMA guidance. RESULTS: Thirty-one studies including 78 patients were included in this review. No association with maternal or neonatal coagulopathy, infection or trauma was found. The average gestational age at diagnosis was 25 weeks (range 17-34 weeks). Approximately half of foetuses affected were female (48.7%); one quarter were male (25.6%) and one quarter had no sex stated (25.6%). Termination of pregnancy was chosen in 25.6% of cases (20/78). In continuing pregnancies,10.3% (6/58) experienced a perinatal death. Antenatally, the majority of lesions either decreased in size (38.5%) or completely resolved (32.7%). The neonatal or childhood outcome was normal in 88.0% of survivors (44/50). The average age at follow up was 16.4 months, ranging from birth to 6 years. CONCLUSION: This review found that 10% of DST cases experience in-utero or neonatal death. In survivors, the majority of cases reduce in size or completely resolve in pregnancy and 85% are reported to have a good outcome. However, further evidence is needed regarding long-term neurocognitive sequelae.

Fetal Origins of Asthma: A Longitudinal Study from Birth to Age 36 Years.

Rationale: Deficits in infant lung function-including the ratio of the time to reach peak tidal expiratory flow to the total expiratory time (tptef/te) and maximal expiratory flow at FRC (V̇maxFRC)-have been linked to increased risk for childhood asthma.Objectives: To examine the individual and combined effects of tptef/te and V̇maxFRC in infancy on risk for asthma and abnormalities of airway structure into mid-adult life.Methods: One hundred eighty participants in the Tucson Children's Respiratory Study birth cohort had lung function measured by the chest-compression technique in infancy (mean age ± SD: 2.0 ± 1.2 mo). Active asthma was assessed in up to 12 questionnaires between ages 6 and 36 years. Spirometry and chest high-resolution computed tomographic (HRCT) imaging were completed in a subset of participants at age 26. The relations of infant tptef/te and V̇maxFRC to active asthma and airway structural abnormalities into adult life were tested in multivariable mixed models.Measurements and Main Results: After adjustment for covariates, a 1-SD decrease in infant tptef/te and V̇maxFRC was associated with a 70% (P = 0.001) and 55% (P = 0.005) increased risk of active asthma, respectively. These effects were partly independent, and two out of three infants who were in the lowest tertile for both tptef/te and V̇maxFRC developed active asthma by mid-adult life. Infant V̇maxFRC predicted reduced airflow and infant tptef/te reduced HRCT airway caliber at age 26.Conclusions: These findings underscore the long-lasting effects of the fetal origins of asthma, support independent contributions by infant tptef/te and V̇maxFRC to development of asthma, and link deficits at birth in tptef/te with HRCT-assessed structural airway abnormalities in adult life.

Low mortality in fetal supraventricular tachycardia: Outcomes in a 30-year single-institution experience.

OBJECTIVES: To describe a single institutional experience managing fetuses with supraventricular tachycardia (SVT) and to identify associations between patient characteristics and fetal and postnatal outcomes. BACKGROUND: Sustained fetal SVT is associated with significant morbidity and mortality if untreated, yet the optimal management strategy remains unclear. METHODS: Retrospective cohort study including fetuses diagnosed with sustained SVT (>50% of the diagnostic echocardiogram) between 1985 and 2018. Fetuses with congenital heart disease were excluded. RESULTS: Sustained SVT was diagnosed in 65 fetuses at a median gestational age of 30 weeks (range, 14-37). Atrioventricular re-entrant tachycardia and atrial flutter were the most common diagnoses, seen in 41 and 16 cases, respectively. Moderate/severe ventricular dysfunction was present in 20 fetuses, and hydrops fetalis was present in 13. Of the 57 fetuses initiated on transplacental drug therapy, 47 received digoxin first-line, yet 39 of 57 (68%) required advanced therapy with sotalol, flecainide, or amiodarone. Rate or rhythm control was achieved in 47 of 57 treated fetuses. There were no cases of intrauterine fetal demise. Later gestational age at fetal diagnosis (odds ratio [OR], 1.1, 95% confidence interval [CI], 1.01-1.2, P = .02) and moderate/severe fetal ventricular dysfunction (OR, 6.1, 95% CI, 1.7-21.6, P = .005) were associated with postnatal SVT. Two postnatal deaths occurred. CONCLUSIONS: Fetuses with structurally normal hearts and sustained SVT can be effectively managed with transplacental drug therapy with minimal risk of intrauterine fetal demise. Treatment requires multiple antiarrhythmic agents in over half of cases. Later gestational age at fetal diagnosis and the presence of depressed fetal ventricular function, but not hydrops, predict postnatal arrhythmia burden.

Maternal and fetal thyroid dysfunction following porcine reproductive and respiratory syndrome virus2 infection.

To better understand the host response to porcine reproductive and respiratory virus-2 (PRRSV2) we evaluated circulating thyroid hormone and associated gene expression in a late gestation challenge model. Pregnant gilts were inoculated at gestation day 85 and fetal samples collected at either 12 or 21 days post-infection (dpi). A subset of fetuses was selected for analysis based on viability and viral load categorized as either uninfected-viable (UNIF), high viral load viable (HV-VIA) or high viral load meconium stained (HV-MEC) and were compared with gestational age matched controls (CON). In dams, circulating levels of total T3 and T4 decreased in the acute period following infection and rebounded by 21 dpi. A similar effect was observed in fetuses, but was largely restricted to HV-VIA and HV-MEC, with minimal decrease noted in UNIF relative to CON at 21 dpi. Gene expression in fetal heart at 12 dpi showed significant decompensatory transcription of thyroid hormone transporters (SLC16A2) and deiodinases (DIO2, DIO3), which was not observed in brain. Correspondingly, genes associated with cell cycle progression (CDK1,2,4) were downregulated in only the heart of highly infected fetuses, while expression of their inhibitor (CDKN1A) was upregulated in both tissues. Finally, expression of genes associated with cardiac stress including CAMKD and AGT were upregulated in the hearts of highly infected fetuses, and a shift in expression of MYH6 to MYH7 was observed in HV-MEC fetuses specifically. Collectively, the results suggest PRRSV2 infection causes a hypothyroid state that disproportionally impacts the fetal heart over the brain.

Mid-gestational fetal placental blood flow is diminished in the fetus with congenital heart disease.

OBJECTIVE: Data suggest fetuses with congenital heart disease (CHD) have placental abnormalities. Their abnormal placental vasculature may affect fetal placental blood flow, which has not previously been explored. METHOD: We performed a retrospective cross-sectional study comparing umbilical venous volume flow (UVVF) of single ventricle, D-transposition of the great arteries, and tetralogy of Fallot fetuses with fetuses without CHD. UVVF and combined cardiac output (CCO) were calculated from fetal echocardiography and compared using t tests, χ2 and Fisher's exact tests. RESULTS: Mean gestational age and fetal weight were greater in CHD fetuses (26.5 weeks, 1119.4 g; n = 81, P < .001) compared to controls (23.1 weeks, 675 g; n = 170, P < .001). UVVF/fetal weight was nevertheless decreased among cases (99.8 vs 115.3 mL/min/kg, P < .001). Subgroup analysis of 20- to 25-week fetuses demonstrated no significant differences in case and control baseline characteristics. In CHD fetuses (n = 31) compared to controls (n = 144), absolute UVVF (50.8 vs 62.1 mL/min, P = .006), and UVVF/fetal weight (98.8 vs 118.5 mL/min/kg, P < .001) were decreased. Findings were similar in single ventricle (n = 24) and hypoplastic left heart syndrome (n = 14). CONCLUSION: Mid-gestational placental blood flow in CHD fetuses is decreased compared to controls. Further study is needed to explore the relationship between UVVF and placental pathology, and impact on outcomes.

Prediction of outcome in fetal autoimmune complete heart block.

Assessing cardiac function and risk stratification in a fetal anti-Sjögren syndrome type A (SSA) or anti-Sjögren syndrome type B (SSB) complete atrioventricular block (CAVB) is challenging. We aimed to evaluate the cardiovascular profile score (CVP) and its components in surveillance of fetuses with autoimmune CAVB. METHODS: Retrospective cohort review of CAVB pregnancies, excluding fetuses with significant cardiac anomalies. RESULTS: CAVBs are in 17 fetuses, diagnosed at mean gestational age of 23 ± 5 weeks. Overall mortality is 18%: 1 termination, 1 fetal demise (intrauterine fetal demise [IUFD]), and 1 postnatal death. Both mortalities had intrauterine growth restriction; IUFD had placental infarction. Presenting CVP 8.7 ± 1. No fetus had CVP <7; the score correlated with increased risk of perinatal death. The 2 mortalities had initial CVP scores of 8 and 9; both increased to 10 on subsequent exams. 30% of fetuses had low middle cerebral artery pulsatility (MCA-PI) on the last study. All had high umbilical artery pulsatility (UA-PI) throughout gestation. The 2 deaths had the lowest MCA-PI. CONCLUSION: Despite low heart rates, high CVP scores in our cohort remained high and were not predictive of mortality. Abnormalities in MCA flow reflects fetal cerebral vasodilation that may indicate altered hemodynamics and be predictive of outcomes, but data is limited. Abnormal umbilical artery (UA) flow suggests that perinatal mortality may also be related to placental disease.

Unusual Circumstances and Additional Procedures for Fetal Evaluation in Labor.

This chapter describes several circumstances in which the interpretation of the intrapartum fetal heart rate pattern falls outside the usual frame of reference. This includes a more extensive discussion of causes of tachycardia and bradycardia. Ways in which a fetal dysrhythmia may manifest itself in the context of heart rate monitoring are described. Finally, the chapter reviews technological innovations designed to clarify the fetal status when compromise is suspected from the fetal heart rate pattern.

Management of the Category II Fetal Heart Rate Tracing.

Management of the category II fetal heart rate (FHR) tracing presents a common challenge in obstetrics. Up to 80% of women will have a category II FHR tracing at some point during labor. Here we propose a management algorithm to identify specific features of the FHR tracing that correlate with risk for fetal acidemia, target interventions to address FHR decelerations, and guide clinicians about when to proceed toward operative vaginal delivery or cesarean to achieve delivery before there is a high risk for significant fetal acidemia with potential for neurological injury or death.

The Golden Hours of Fetal Heart Rate Monitoring: Systematic Approach to the Critical Times of Labor and Delivery.

The first hour after admission and the last hour before delivery are critical times for identifying and preventing hypoxic-ischemic encephalopathy. These are times of transition that require coordinated steps to identify fetuses at risk, institute effective plans for fetal heart rate monitoring, and to establish situational awareness. Interpretation and intervention based on fetal heart rate monitoring is an important part of the care provided during these crucial times. We present checklists for the first and last hour of labor for use on labor and delivery to help standardize and optimize the approach to care during these times.

Maternal Fetal Surgery: Intervention and Management.

Congenital malformations occur in about 3% of all live births and are a leading cause of perinatal morbidity and mortality. An evolving understanding of the developing human fetus, advances in imaging, availability of cutting-edge instrumentation, and enhanced understanding of fetal pathophysiology, have allowed for prenatal surgical interventions to improve fetal diseases and neonatal outcomes. Fetal surgical therapy is no longer restricted to life-threatening prenatal diagnoses and can be categorized into either open surgical techniques or minimally invasive endoscopic/ultrasound-guided techniques. Patient selection requires a thorough multidisciplinary evaluation and shared decision-making process.

Maternal biomarkers for fetal heart failure in fetuses with congenital heart defects or arrhythmias.

BACKGROUND: Diagnosis of fetal heart failure depends primarily on fetal ultrasonography assessment. Our recent study demonstrated that plasma natriuretic peptide levels in umbilical cord blood were correlated with the severity of heart failure in fetuses with congenital heart defects or arrhythmias. However, percutaneous umbilical blood sampling is an invasive procedure, and therefore, less or noninvasive biomarkers reflecting fetal heart failure are required. OBJECTIVE: The aim of this study was to investigate the possibility of whether maternal serum biomarkers can diagnose fetal heart failure in fetuses with congenital heart defects or arrhythmias. STUDY DESIGN: This exploratory cross-sectional study was conducted at a tertiary pediatric cardiac center. A total of 50 singletons with fetal congenital heart defects or arrhythmias and 50 controls who were registered in the National Cerebral and Cardiovascular Center Biobank from 2013 to 2016 were included. Maternal serum samples obtained during the third trimester were analyzed for 2 hormones and 36 cytokines using the Bio-Plex Pro Human Cancer Biomarker panels 1 and 2. We comprehensively analyzed the association between maternal serum biomarkers and ultrasonography findings or fetal arrhythmia status. Fetal heart failure was defined as a cardiovascular profile score ≤7. RESULTS: Of 37 fetuses with congenital heart defects, heart failure was found in 1 case of tricuspid valve dysplasia with moderate tricuspid regurgitation. Of 13 fetuses with arrhythmias, 5 had heart failure at 28-33 weeks of gestation. Maternal serum cytokine and hormone concentrations were compared between patients with and without fetal heart failure at 28-33 weeks of gestation (n = 6 and n = 61, respectively). Sixty-one fetuses without heart failure consisted of 10 with congenital heart defect, 6 with arrhythmia, and 45 controls. Maternal serum concentrations of tumor necrosis factor-α, interleukin-6, soluble Fas ligand, transforming growth factor-α, and vascular endothelial growth factor-D were significantly higher when fetuses had heart failure than when they did not (P < .05), whereas maternal serum concentrations of heparin-binding epidermal growth factor-like growth factor were significantly lower when fetuses had heart failure than when they did not (P < .05). Multivariate analysis showed that maternal serum concentrations of tumor necrosis factor-α, vascular endothelial growth factor-D, and heparin-binding epidermal growth factor-like growth factor were independently associated with fetal heart failure. The cutoff values were as follows: tumor necrosis factor-α, 68 pg/mL (sensitivity of 50.0%, specificity of 93.4%, positive likelihood ratio of 7.6, negative likelihood ratio of 0.5); vascular endothelial growth factor-D, 1156 pg/mL (sensitivity of 50.0%, specificity of 93.4%, positive likelihood ratio of 7.6, negative likelihood ratio of 0.5); and heparin-binding epidermal growth factor-like growth factor, 90 pg/mL (sensitivity of 83.3%, specificity of 83.6%, positive likelihood ratio of 5.1, negative likelihood ratio of 0.2). The combination of these 3 cytokines showed sensitivity of 100%, specificity of 80.3%, positive likelihood ratio of 5.1, and negative likelihood ratio of 0. In the absence of fetal heart failure, concentrations of all maternal serum cytokines and hormones were similar in cases of fetal congenital heart defects and controls, while maternal serum soluble CD40 ligand concentrations were increased only in fetal arrhythmias. CONCLUSION: Maternal serum concentrations of tumor necrosis factor-α, vascular endothelial growth factor-D, and heparin-binding epidermal growth factor-like growth factor were associated with fetal heart failure.

Performance of fetal middle cerebral artery peak systolic velocity for prediction of anemia in untransfused and transfused fetuses: systematic review and meta-analysis.

OBJECTIVE: To evaluate the performance of fetal middle cerebral artery peak systolic velocity (MCA-PSV) ≥ 1.5 multiples of the median (MoM) for the prediction of moderate-severe anemia, in untransfused and transfused fetuses. METHODS: A systematic search was performed to identify relevant observational studies reported in the period 2008-2018 that evaluated the performance of MCA-PSV, using a threshold of 1.5 MoM for the prediction of fetal anemia. Diagnosis of fetal anemia by blood sampling was the reference standard. A hierarchical summary receiver-operating characteristics (hSROC) curve was constructed using random-effects modeling. Subgroup and meta-regression analyses, according to the number of previous intrauterine transfusions, were performed. RESULTS: Twelve studies and 696 fetuses were included in the meta-analysis. The area under the hSROC curve (AUC) for moderate-severe anemia was 83%. Pooled sensitivity and specificity (95% CI) were 79% (70-86%) and 73% (62-82%), respectively, and positive and negative likelihood ratios were 2.94 (95% CI, 2.13-4.00) and 0.272 (95% CI, 0.188-0.371). When considering only untransfused fetuses, prediction improved, achieving an AUC of 87%, sensitivity of 86% (95% CI, 75-93%) and specificity of 71% (95% CI, 49-87%). A decline in sensitivity for the prediction of moderate-severe anemia by MCA-PSV ≥1.5 MoM was observed (estimate, -5.5% (95% CI, -10.7 to -0.3%), P = 0.039) as the number of previous transfusions increased. CONCLUSIONS: MCA-PSV ≥ 1.5 MoM for the prediction of moderate-severe anemia in untransfused fetuses shows moderate accuracy (86% sensitivity and 71% specificity), which declines with increasing number of intrauterine transfusions. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.

Rendimiento de la velocidad sistólica máxima de la arteria cerebral media fetal para la predicción de la anemia en fetos sometidos a transfusión y no sometidos: revisión sistemática y metaanálisis OBJETIVOS: Estimar las diferencias en la frecuencia del diagnóstico del útero septo mediante tres definiciones diferentes y determinar si estas diferencias son significativas en la práctica clínica, y examinar la relación entre el diagnóstico del útero septo, por medio de cada una de las tres definiciones, y la infertilidad o el aborto espontáneo previo, así como con el costo de la recomendación de cirugía. MÉTODOS: Este estudio fue un análisis secundario de los datos de un estudio prospectivo de 261 mujeres en edad reproductiva que asisten de forma consecutiva a una clínica privada especializada en el diagnóstico y tratamiento de las malformaciones congénitas del útero. El nuevo análisis de los conjuntos de datos se realizó de acuerdo con tres maneras diferentes de definir el útero septo: siguiendo las recomendaciones de la Sociedad Americana de Medicina Reproductiva (ASRM, por sus siglas en inglés), una actualización de 2016 de las de la Sociedad Americana de la Fertilidad de 1988 (ASRM-2016: profundidad de la hendidura interna del fondo uterino ≥1,5 cm, ángulo de la hendidura interna <90o y profundidad de la hendidura externa <1 cm); con base en las recomendaciones de la Sociedad Europea para la Reproducción Humana y Embriología/Sociedad Europea de Endoscopía Ginecológica (ESHRE/ESGE, por sus siglas en inglés), publicadas en 2013 y revisadas en 2016 (ESHRE/ESGE-2016: profundidad de la hendidura interna del fondo uterino >50% del espesor de la pared uterina y profundidad de la hendidura externa <50% del espesor de la pared uterina, cuando se mide el espesor de la pared uterina por encima de la línea interostial/intercornual); y utilizando una definición publicada el año pasado que se basaba en la decisión tomada con mayor frecuencia por un grupo de expertos (Malformación Uterina Congénita según los Expertos; CUME, por sus siglas en inglés) (CUME-2018: profundidad de la hendidura interna del fondo uterino ≥1 cm y profundidad de la hendidura externa del fondo uterino <1cm). Se comparó la tasa de diagnóstico del útero septo utilizando cada una de estas tres definiciones y, para cada una, se estimó la relación entre el diagnóstico y la infertilidad y/o el aborto espontáneo previo, y se anticiparon los costos asociados con su implementación mediante un método de estimación conjetural. RESULTADOS: Aunque el 32,6% (85/261) de las mujeres cumplieron con los criterios de una de las tres definiciones de útero septo, sólo el 2,7% (7/261) de ellas se pudieron definir como con útero septo de acuerdo con las tres definiciones. Significativamente, se diagnosticaron más casos de útero septo usando los criterios de ESHRE/ESGE-2016 que usando los de ASRM-2016 (31% vs 5%, riesgo relativo (RR)=6,7, P<0.0001) o de CUME-2018 (31% vs 12%, RR=2,6, P<0.0001). También se observaron casos frecuentes que no pudieron ser clasificados definitivamente por ASRM-2016 (zona gris: ni normal/arcuado ni septo; 6,5%). No hubo diferencias significativas (P>0,05) en la prevalencia de útero septo en mujeres con infertilidad vs mujeres fértiles, según ASRM-2016 (5% vs 4%), ESHRE/ESGE-2016 (35% vs 28%) o CUME-2018 (11% vs 12%). El diagnóstico del útero septo fue significativamente más frecuente en mujeres con aborto espontáneo previo, según los criterios de ASRM-2016 (11% vs 3%; P=0,04) y de CUME-2018 (22 vs 10%; P=0,04), pero no según los criterios de ESHRE/ESGE-2016 (42% vs 28%; P=0,8). Los cálculos mostraron que los costos globales para el sistema de salud dependerían en gran medida de los criterios utilizados desde el punto de vista clínico para definir el útero septo, siendo los costos asociados con la definición de ESHRE/ESGE-2016 potencialmente de 100-200 mil millones de dólares adicionales durante 5 años, en comparación con los asociados a las definiciones ASRM-2016 y CUME-2018. CONCLUSIONES: La prevalencia del útero septo según las definiciones de ESHRE/ESGE-2016, ASRM-2016 y CUME-2018 difiere considerablemente. Una limitación importante de la clasificación ASRM, que debe ser abordada, es la alta proporción de casos no clasificables originalmente denominados, por nosotros, como en la 'zona gris'. La alta tasa de sobrediagnóstico del útero septo en función de ESHRE/ESGE-2016 puede llevar a un uso innecesario de la cirugía y, por lo tanto, a un riesgo innecesario en estas mujeres y puede imponer una carga financiera considerable a los sistemas sanitarios. Se deben fomentar los esfuerzos para definir criterios clínicamente significativos y aplicables de forma universal para el diagnóstico del útero septo.

Perinatal changes in fetal cardiac geometry and function in diabetic pregnancy at term.

OBJECTIVE: To evaluate the effect of diabetes in pregnancy on fetal and neonatal cardiac geometry and function around the time of delivery. METHODS: This was a prospective study of 75 pregnant women delivering at term, comprising 54 normal pregnancies and 21 with a diagnosis of pregestational or gestational diabetes mellitus. Fetal and neonatal conventional and spectral tissue Doppler and two-dimensional speckle-tracking echocardiography were performed a few days before and within hours after delivery. Fetal and neonatal cardiac geometry, global myocardial deformation and performance, diastolic and systolic function and left ventricular (LV) torsion were compared between normal pregnancies and those with diabetes, and perinatal changes within the diabetes group were assessed. RESULTS: Compared with normal pregnancies, diabetic pregnancies demonstrated significant differences in fetal ventricular geometry, myocardial deformation and cardiac function (right ventricular (RV) sphericity index, 0.56 vs 0.65; LV torsion, 2.1 °/cm vs 5.6 °/cm; LV isovolumetric relaxation time, 101 ms vs 115 ms; and RV isovolumetric contraction time, 107 ms vs 119 ms; P < 0.001 for all). Compared with normal pregnancies, diabetic pregnancies demonstrated significant differences in neonatal cardiac parameters (mean RV sphericity index, 0.43 vs 0.55; mean LV torsion, 1.30 °/cm vs 2.78 °/cm; median LV myocardial performance index (MPI'), 0.39 vs 0.51; median RV-MPI', 0.34 vs 0.40; P < 0.01 for all). Paired comparison between fetal and neonatal cardiac indices in diabetic pregnancies demonstrated that delivery resulted in a significant improvement in some, but not all, cardiac indices (mean RV sphericity index, 0.65 vs 0.55; mean LV torsion, 5.60 °/cm vs 2.78 °/cm; median RV-MPI', 0.51 vs 0.40; P < 0.01 for all). CONCLUSIONS: Compared with normal term fetuses and neonates, those of diabetic women exhibit cardiac indices indicative of myocardial impairment, reflecting a response to a relatively hyperglycemic intrauterine environment with alteration in fetal loading conditions (LV preload deprivation and increased RV afterload) and adaptation to subsequent acute changes in hemodynamic load at delivery. Elucidating mechanisms that contribute to the alterations in perinatal cardiac function in diabetic pregnancy could help in refining management and developing better therapeutic strategies to reduce the risk of adverse pregnancy outcomes. Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd.

Fetal cardiac findings and hemodynamic changes associated with severe lower urinary tract obstruction in utero.

OBJECTIVES: To describe fetal echocardiographic findings associated with lower urinary tract obstruction (LUTO) and to compare anatomic and hemodynamic measurements between fetuses with LUTO and gestational age (GA)-matched controls, with an emphasis on quantitative indices of diastolic function and cardiac output. METHODS: This was a retrospective cohort study of fetuses diagnosed with severe LUTO with giant bladder, which underwent at least one fetal echocardiogram at our center between January 2005 and June 2018. Fetuses with major congenital heart disease were excluded. Control fetuses did not have any structural or functional abnormalities and were GA-matched to the LUTO fetuses based on the time of the first fetal echocardiogram. Cardiac anatomy and hemodynamic measurements were compared between fetuses with LUTO and controls. In infants with LUTO, serial fetal and postnatal echocardiographic data were assessed, when available, and clinical outcomes were reviewed. RESULTS: Twenty-six fetuses with LUTO and at least one fetal echocardiogram available were identified, one of which was excluded due to hypoplastic left heart syndrome, leaving 25 LUTO fetuses in the final cohort. The mean GA at the first fetal echocardiogram was 25.4 ± 5.1 weeks in the LUTO group and 25.3 ± 5.0 weeks in the control group. Common findings in fetuses with LUTO included cardiomegaly (40%), pericardial effusion (44%), right ventricular (RV) hypertrophy (64%) and left ventricular (LV) hypertrophy (48%). Compared with GA-matched controls, LUTO fetuses had lower ascending aorta Z-score (-0.10 ± 0.94 vs -0.93 ± 1.03; P = 0.02) and aortic isthmus Z-score (-0.14 ± 0.86 vs -1.62 ± 1.11; P < 0.001), shorter mitral valve inflow time indexed to cardiac cycle length (0.46 ± 0.04 vs 0.41 ± 0.06; P = 0.002), and worse (increased) LV myocardial performance index (0.39 ± 0.03 vs 0.44 ± 0.04; P < 0.001). In addition, the ratio of RV to LV cardiac index was higher in LUTO fetuses compared with controls (1.62 ± 0.13 vs 1.33 ± 0.11; P < 0.001). Of the 25 LUTO pregnancies, two were lost to follow-up, three underwent elective termination of pregnancy and three ended in intrauterine fetal demise. Four (16%) patients had mildly hypoplastic left-heart structures, comprising two with aortic arch hypoplasia and two with mitral and aortic stenosis. CONCLUSION: In addition to presenting with cardiomegaly, pericardial effusion and ventricular hypertrophy, fetuses with LUTO demonstrate LV diastolic dysfunction and appear to redistribute cardiac output as compared to control fetuses, which may contribute to the development of left-heart hypoplasia. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.