Current Status of the Workforce and Training at Fetal Therapy Centers in North America.

INTRODUCTION: We sought to characterize the current workforce and training for fetal intervention procedures at fetal centers in North America. METHODS: An anonymous electronic survey was developed to query the 34 centers in the North American Fetal Treatment Network regarding the demographics and training of their faculty. Telephone surveys were conducted with directors of known fetal intervention fellowships. RESULTS: More than 50% of maternal-fetal medicine (MFM) faculty at fetal centers were female; more than two-thirds of pediatric surgical faculty were male. Most of the training of faculty was undertaken by visiting more experienced centers or having new faculty work with more experienced ones at the same center. Current fetal intervention fellowships appear to achieve levels of competency for intrauterine transfusions and laser therapy for twin-twin transfusion syndrome. Two-thirds of centers stated that they would be able to offer a position to an MFM who completed a formal fellowship in fetal intervention. CONCLUSION: A collaborative effort should be undertaken to establish formal fellowships in fetal medicine and intervention.

Validation and development of models using clinical, biochemical and ultrasound markers for predicting pre-eclampsia: an individual participant data meta-analysis.

BACKGROUND: Pre-eclampsia is a leading cause of maternal and perinatal mortality and morbidity. Early identification of women at risk is needed to plan management. OBJECTIVES: To assess the performance of existing pre-eclampsia prediction models and to develop and validate models for pre-eclampsia using individual participant data meta-analysis. We also estimated the prognostic value of individual markers. DESIGN: This was an individual participant data meta-analysis of cohort studies. SETTING: Source data from secondary and tertiary care. PREDICTORS: We identified predictors from systematic reviews, and prioritised for importance in an international survey. PRIMARY OUTCOMES: Early-onset (delivery at < 34 weeks' gestation), late-onset (delivery at ≥ 34 weeks' gestation) and any-onset pre-eclampsia. ANALYSIS: We externally validated existing prediction models in UK cohorts and reported their performance in terms of discrimination and calibration. We developed and validated 12 new models based on clinical characteristics, clinical characteristics and biochemical markers, and clinical characteristics and ultrasound markers in the first and second trimesters. We summarised the data set-specific performance of each model using a random-effects meta-analysis. Discrimination was considered promising for C-statistics of ≥ 0.7, and calibration was considered good if the slope was near 1 and calibration-in-the-large was near 0. Heterogeneity was quantified using I2 and τ2. A decision curve analysis was undertaken to determine the clinical utility (net benefit) of the models. We reported the unadjusted prognostic value of individual predictors for pre-eclampsia as odds ratios with 95% confidence and prediction intervals. RESULTS: The International Prediction of Pregnancy Complications network comprised 78 studies (3,570,993 singleton pregnancies) identified from systematic reviews of tests to predict pre-eclampsia. Twenty-four of the 131 published prediction models could be validated in 11 UK cohorts. Summary C-statistics were between 0.6 and 0.7 for most models, and calibration was generally poor owing to large between-study heterogeneity, suggesting model overfitting. The clinical utility of the models varied between showing net harm to showing minimal or no net benefit. The average discrimination for IPPIC models ranged between 0.68 and 0.83. This was highest for the second-trimester clinical characteristics and biochemical markers model to predict early-onset pre-eclampsia, and lowest for the first-trimester clinical characteristics models to predict any pre-eclampsia. Calibration performance was heterogeneous across studies. Net benefit was observed for International Prediction of Pregnancy Complications first and second-trimester clinical characteristics and clinical characteristics and biochemical markers models predicting any pre-eclampsia, when validated in singleton nulliparous women managed in the UK NHS. History of hypertension, parity, smoking, mode of conception, placental growth factor and uterine artery pulsatility index had the strongest unadjusted associations with pre-eclampsia. LIMITATIONS: Variations in study population characteristics, type of predictors reported, too few events in some validation cohorts and the type of measurements contributed to heterogeneity in performance of the International Prediction of Pregnancy Complications models. Some published models were not validated because model predictors were unavailable in the individual participant data. CONCLUSION: For models that could be validated, predictive performance was generally poor across data sets. Although the International Prediction of Pregnancy Complications models show good predictive performance on average, and in the singleton nulliparous population, heterogeneity in calibration performance is likely across settings. FUTURE WORK: Recalibration of model parameters within populations may improve calibration performance. Additional strong predictors need to be identified to improve model performance and consistency. Validation, including examination of calibration heterogeneity, is required for the models we could not validate. STUDY REGISTRATION: This study is registered as PROSPERO CRD42015029349. FUNDING: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 24, No. 72. See the NIHR Journals Library website for further project information.

WHAT IS THE PROBLEM?: Pre-eclampsia, a condition in pregnancy that results in raised blood pressure and protein in the urine, is a major cause of complications for the mother and baby. WHAT IS NEEDED?: A way of accurately identifying women at high risk of pre-eclampsia to allow clinicians to start preventative interventions such as administering aspirin or frequently monitoring women during pregnancy. WHERE ARE THE RESEARCH GAPS?: Although over 100 tools (models) have been reported worldwide to predict pre-eclampsia, to date their performance in women managed in the UK NHS is unknown. WHAT DID WE PLAN TO DO?: We planned to comprehensively identify all published models that predict the risk of pre-eclampsia occurring at any time during pregnancy and to assess if this prediction is accurate in the UK population. If the existing models did not perform satisfactorily, we aimed to develop new prediction models. WHAT DID WE FIND?: We formed the International Prediction of Pregnancy Complications network, which provided data from a large number of studies (78 studies, 25 countries, 125 researchers, 3,570,993 singleton pregnancies). We were able to assess the performance of 24 out of the 131 models published to predict pre-eclampsia in 11 UK data sets. The models did not accurately predict the risk of pre-eclampsia across all UK data sets, and their performance varied within individual data sets. We developed new prediction models that showed promising performance on average across all data sets, but their ability to correctly identify women who develop pre-eclampsia varied between populations. The models were more clinically useful when used in the care of first-time mothers pregnant with one child, compared to a strategy of treating them all as if they were at high-risk of pre-eclampsia. WHAT DOES THIS MEAN?: Before using the International Prediction of Pregnancy Complications models in various populations, they need to be adjusted for characteristics of the particular population and the setting of application.

Ductus venosus Doppler in the assessment of fetal cardiovascular health: an updated practical approach.

The ductus venosus has a central role in the distribution of highly oxygenated umbilical venous blood to the heart. Its waveform is related to the pressure-volume changes in the cardiac atria and it is therefore important in the monitoring of any fetal condition that may affect forward cardiac function. The cardiovascular parameters that can influence forward cardiac function include afterload, myocardial performance and preload. Decreased forward flow during atrial systole (a-wave) is the most sensitive and ubiquitous finding when any of these parameters is affected. In contrast, decreased forward velocities during end-systolic relaxation (v-wave) are more specifically related to myocardial performance. The ductus venosus pulsatility index alone does not accurately reflect cardiac function, and in cases of suspected fetal cardiac dysfunction, echocardiography is required to identify the underlying mechanism. The role of ductus venosus Doppler in the assessment of fetal growth restriction, supraventricular tachycardia, fetal hydrops, complicated monochorionic twins and congenital heart disease is discussed with these considerations in mind.

Uterine and fetal blood flow indexes and fetal growth assessment after chronic estrogen suppression in the second half of baboon pregnancy.

Although estrogen regulates important aspects of maternal cardiovascular physiology, the role of estrogen on uteroplacental and fetal blood flow is incompletely understood. This study tested the hypothesis that chronically suppressing endogenous estrogen production during the second half of baboon pregnancy alters uterine and fetal blood flow dynamics assessed by ultrasonography. Pregnant baboons were untreated or treated daily with the aromatase inhibitor letrozole or letrozole plus estradiol on days 100-160 of gestation (term = 184 days). Blood flow dynamics were determined by Doppler ultrasonography on day 60 and longitudinally between days 110 and 160 of gestation. Letrozole decreased maternal serum estradiol and estrone concentrations by 95% (P < 0.001). Fetal growth biometrical parameters increased (P < 0.001) between days 110 and 160 of gestation and were similar in untreated and letrozole-treated animals. Uterine, umbilical, and fetal middle cerebral artery pulsatility index and resistance index declined (P < 0.01) by 30-50% and uterine artery volume flow increased sixfold (P < 0.001) between days 60 and 160, but values were similar in untreated, letrozole-treated, and letrozole plus estradiol-treated baboons. Thus uterine and fetal artery blood flow indexes, uterine artery volume flow, and fetal growth were maintained at normal levels despite chronic estrogen suppression in the second half of baboon pregnancy. This suggests that elevated levels of endogenous estrogen are not required to maintain low impedance blood flow within the uteroplacental vascular bed during the second half of nonhuman primate pregnancy.

Comprehensive assessment of fetal wellbeing: which Doppler tests should be performed?

PURPOSE OF REVIEW: Doppler applications in pregnancy are expanding exponentially. Flow velocity waveforms provide important information 12 weeks to term, from maternal vessels, placental circulation and fetal systemic vessels, with implications for both mother and fetus. As applications proliferate, awareness of the complexity of fetal and placental circulations, in normal pregnancy and in sequential responses to compromise, has also grown. The necessary data are now available to establish core values in Doppler evaluation for at-risk pregnancies. RECENT FINDINGS: Uterine arteries depict maternal vascular effects of the invading placenta, predicting the frequency and severity of pre-eclampsia and intrauterine growth restriction. New evidence suggests early treatment based on this principle, significantly reduces these impacts. Umbilical artery Doppler reflects downstream placental vascular resistance, strongly correlated with intrauterine growth restriction and the multisystem effects of placental deficiency. Abnormalities are progressive, with reduction, loss, and finally a reversal of diastolic flow. When umbilical arteries become abnormal, the differentiation of fetal status requires Doppler information from systemic vessels. Middle cerebral artery changes begin when the redistribution of cardiac output reflects rising placental resistance, demonstrating 'brain sparing' when cerebrovascular dilation occurs. In the compromised intrauterine growth retarded fetus, precordial veins illustrate fetal cardiac function, changing as the respiratory status declines. This Doppler information is combined with biophysical profile scoring to determine the need for and timing of intervention. SUMMARY: Doppler evaluation of at-risk pregnancies provides crucial prognostic and diagnostic detail about placentation and fetal adaptation. What has been research detail is now becoming the standard of care, in comprehensive fetal-maternal assessment.