What are the novel findings of this work? Ophthalmic artery Doppler at 19-23 weeks' gestation improves the prediction of pre-eclampsia (PE), especially preterm PE with delivery at < 37 weeks, provided by various combinations of maternal characteristics, medical history, uterine artery pulsatility index, mean arterial pressure, serum placental growth factor and serum soluble fms-like tyrosine kinase-1. What are the clinical implications of this work? Ophthalmic artery Doppler could be incorporated into second-trimester screening for subsequent development of PE.
Objective To estimate the chorionic villus sampling (CVS)‐related risk of fetal loss in twin pregnancy after adjustment for chorionicity, nuchal translucency thickness (NT), intertwin discordance in crown–rump length (CRL), maternal demographic characteristics and serum pregnancy‐associated plasma protein‐A (PAPP‐A) and free β‐human chorionic gonadotropin (β‐hCG). Methods This was a multicenter study from eight fetal medicine units in which the leadership were trained at the Harris Birthright Research Centre for Fetal Medicine in London, UK, and in which the protocols for screening, invasive testing and pregnancy management are similar. Data were obtained prospectively from women with twin pregnancy undergoing routine ultrasound examination at 11–13 weeks' gestation. Multivariable logistic regression analysis with backward stepwise elimination was used to examine whether CVS provided a significant independent contribution to the prediction of risk of fetal loss after adjusting for maternal and pregnancy characteristics, including maternal age, racial origin and weight, method of conception, smoking status, parity, chorionicity, intertwin discordance in CRL, fetal NT ≥ 95th percentile and free β‐hCG and PAPP‐A multiples of the median. Similarly, within the CVS group, multivariable logistic regression analysis was used to investigate the effect of the number of intrauterine needle insertions and size of the needle on the risk of fetal loss. Results The study population of 8581 twin pregnancies undergoing ultrasound examination at 11–13 weeks' gestation included 316 dichorionic and 129 monochorionic twins that had CVS. First, in twin pregnancies undergoing CVS, compared to those not undergoing CVS, there was a 2‐fold increased risk of fetal loss at < 24 weeks' gestation and of loss at any stage in pregnancy. Second, the factors providing a significant independent contribution to the prediction of miscarriage or fetal loss in twin pregnancy were increased maternal weight, black racial origin, monochorionicity, and more so monoamnionicity, large intertwin discordance in CRL and increased fetal NT, and, in the case of fetal loss at any stage, there was also a contribution from assisted conception and low serum PAPP‐A. Third, after adjustment for maternal and pregnancy characteristics, CVS did not provide a significant contribution to the risk of fetal loss. Fourth, in twin pregnancies that had CVS, there was no significant contribution to fetal loss from the number of intrauterine needle insertions or needle size. Conclusion The 2‐fold increased risk of fetal loss following CVS in twin pregnancy can, to a great extent, be explained by maternal and pregnancy characteristics rather than the invasive procedure itself. © 2021 International Society of Ultrasound in Obstetrics and Gynecology.
Objective To estimate the risk of fetal loss associated with chorionic villus sampling (CVS) in twin pregnancy, using propensity score analysis. Methods This was a multicenter cohort study of women with twin pregnancy undergoing ultrasound examination at 11–13 weeks' gestation, performed in eight fetal medicine units in which the leadership were trained at the Harris Birthright Research Centre for Fetal Medicine in London, UK, and in which the protocols for screening, invasive testing and pregnancy management are similar. The risk of death of at least one fetus was compared between pregnancies that had and those that did not have CVS, after propensity score matching (1:1 ratio). This procedure created two comparable groups by balancing the maternal and pregnancy characteristics that lead to CVS being performed, similar to how randomization operates in a randomized clinical trial. Results The study population of 8581 twin pregnancies included 445 that had CVS. Death of one or two fetuses at any stage during pregnancy occurred in 11.5% (51/445) of pregnancies in the CVS group and in 6.3% (515/8136) in the non‐CVS group (P < 0.001). The propensity score algorithm matched 258 cases that had CVS with 258 non‐CVS cases; there was at least one fetal loss in 29 (11.2%) cases in the CVS group and in 35 (13.6%) cases in the matched non‐CVS group (odds ratio (OR), 0.81; 95% CI, 0.48–1.35; P = 0.415). However, there was a significant interaction between the risk of fetal loss after CVS and the background risk of fetal loss; when the background risk was higher, the risk of fetal loss after CVS decreased (OR, 0.46; 95% CI, 0.23–0.90), while, in pregnancies with a lower background risk of fetal loss, the risk of fetal loss after CVS increased (OR, 2.45; 95% CI, 0.95–7.13). The effects were statistically significantly different (P‐value of the interaction = 0.005). For a pregnancy in which the background risk of fetal loss was about 6% (the same as in our non‐CVS population), there was no change in the risk of fetal loss after CVS, but, when the background risk was more than 6%, the posterior risk was paradoxically reduced, and when the background risk was less than 6%, the posterior risk increased exponentially; for example, if the background risk of fetal loss was 2.0%, the relative risk was 2.8 and the posterior risk was 5.6%. Conclusion In twin pregnancy, after accounting for the risk factors that lead to both CVS and spontaneous fetal loss and confining the analysis to pregnancies at lower prior risk, CVS seems to increase the risk of fetal loss by about 3.5% above the patient's background risk. © 2021 International Society of Ultrasound in Obstetrics and Gynecology.
Objective To compare fetal cardiac morphology and function between pregnancies that subsequently developed pre‐eclampsia (PE) and those that remained normotensive. Methods This was a prospective observational study in 1574 pregnancies at 35–37 weeks' gestation, including 76 that subsequently developed PE. We carried out comprehensive assessment of fetal cardiac morphology and function including novel imaging modalities, such as speckle‐tracking echocardiography, and measured uterine artery pulsatility index, mean arterial pressure (MAP), serum placental growth factor (PlGF), soluble fms‐like tyrosine kinase‐1 (sFlt‐1) and cerebroplacental ratio (CPR). The findings in the group that subsequently developed PE were compared to those in pregnancies that remained normotensive. Results In fetuses of mothers who subsequently developed PE, compared to those from normotensive pregnancies, there was a more globular right ventricle, as shown by reduced right ventricular sphericity index, reduced right ventricular systolic contractility, as shown by reduced global longitudinal strain, and reduced left ventricular diastolic function, as shown by increased E/A ratio. On multivariable regression analysis, these indices demonstrated an association with PE, independent of maternal characteristics and fetal size. In pregnancies that subsequently developed PE, compared to those that remained normotensive, MAP, sFlt‐1 and the incidence of low birth weight were higher, whereas serum PlGF, CPR and the interval between assessment and delivery were lower. These findings demonstrate that, in pregnancies that develop PE, there is evidence of impaired placentation, reflected in low PlGF and reduced birth weight, placental ischemia, evidenced by increased sFlt‐1 which becomes apparent in the interval of 2–4 weeks preceding the clinical onset of PE, and consequent fetal hypoxia‐induced redistribution in the fetal circulation, reflected in the low CPR. Conclusion Although the etiology of the observed fetal cardiac changes in pregnancies that subsequently develop PE remains unclear, it is possible that the reduction in right‐heart systolic function is the consequence of high afterload due to increased placental resistance, whilst the early left ventricular diastolic changes could be due to fetal hypoxia‐induced redistribution in the fetal circulation. © 2020 International Society of Ultrasound in Obstetrics and Gynecology
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