Impaired placental perfusion and major fetal cardiac defects

Objectives: To investigate the relationship between fetal congenital heart defects (CHD) and placental perfusion assessed by uterine artery pulsatility index (UtA-PI) in relation to development of preeclampsia (PE). Methods: This was a prospective screening study in singleton pregnancies at 19-24 weeks’ gestation. Transvaginal ultrasound was used to measure the UtA-PI and the values were converted into multiples of the normal median (MoM). Median MoM values in pregnancies with fetuses with isolated major CHD were compared to those without CHD in relation to development of PE. Results: The 91,407 singleton pregnancies fulfilling the entry criteria included 206 (0.23%) with isolated major fetal CHD and 91,201 without CHD. The prevalence of PE was 4.4% in those with CHD and 2.7% in those without CHD (RR 1.6, 95% CI 0.84-3.04; p=0.150); the respective values for preterm-PE, with delivery at <37 weeks’ gestation, were 2.4% and 0.7%, (RR 3.4, 95% CI 1.42-8.09; p=0.006). In the total population, the median UtA-PI MoM was significantly higher in those that developed PE compared to those without PE (1.22, IQR 0.94-1.57 vs. 1.00, IQR 0.84-1.19; p<0.0001) and in the PE group the median UtA-PI MoM was inversely related to gestational age at delivery (r=-0.458; p<0.0001). The same pattern of inverse relationship between UtA-PI MoM and gestational age at delivery with PE was observed in pregnancies with and without CHD, but in the CHD group, compared to those without CHD, UtA-PI was significantly higher both in pregnancies with and in those without PE. Conclusions: In both pregnancies with and without fetal CHD that develop PE impedance to flow in the uterine arteries is increased and this increase is particularly marked in those with preterm-PE. The prevalence of preterm-PE is more than 3 times higher in pregnancies with than without fetal major CHD and the prevalence of major CHD in pregnancies with preterm-PE is also more than 3 times higher than in those without PE. However, >97% of pregnancies with fetal CHD do not develop preterm-PE and >99% of pregnancies with preterm-PE are not associated with fetal CHD

IONA test for first-trimester detection of trisomies 21, 18 and 13

OBJECTIVE: To assess the potential performance of screening for fetal trisomies 21, 18 and 13 by cell-free DNA (cfDNA) analysis of maternal blood using the IONA\uae test. METHODS: This was a nested case-control study of cfDNA analysis of maternal plasma using the IONA test. Samples were obtained at 11-13 weeks' gestation, before chorionic villus sampling, from 201 euploid pregnancies, 35 with trisomy 21, four with trisomy 18 and two with trisomy 13. Laboratory personnel were blinded to the fetal karyotype. RESULTS: Probability scores for trisomies 21, 18 and 13 were given for 241/242 samples analyzed. No probability score was provided for one (0.5%) euploid pregnancy because of low fetal fraction. In all 35 cases of trisomy 21 the probability score for trisomy 21 was > 95% and the scores for trisomies 18 and 13 were 64 0.0001%. In all four cases of trisomy 18, the probability score for trisomy 18 was > 77% and the scores for trisomies 21 and 13 were 64 0.0001%. In the two cases of trisomy 13, the probability score for trisomy 13 was > 59% and the scores for trisomies 21 and 18 were 64 0.0001%. In the 200 euploid pregnancies with a test result, the probability score was < 0.08% for trisomy 21, < 0.001% for trisomy 18 and < 0.002% for trisomy 13. Therefore, the IONA test detected 100% of all three trisomies, with a false-positive rate of 0%. CONCLUSION: The IONA test successfully differentiated all cases of trisomies 21, 18 and 13 from euploid pregnancies

Fetal major cardiac defects and placental dysfunction at 11-13 weeks' gestation

Objectives: To investigate the relationship between fetal major cardiac defects and markers of placental perfusion and function. Methods: This was a prospective screening study in singleton pregnancies at 11-13 weeks’ gestation. Uterine artery pulsatility index (UTPI), serum pregnancy associated plasma protein-A (PAPP-A) and placental growth factor (PLGF) were measured and the values were converted into multiples of the normal median (MoM). Median MoM values in fetuses with isolated major cardiac defects were compared to those in fetuses without major defects. Results: The 50,094 singleton pregnancies fulfilling the entry criteria included 49,898 pregnancies with a normal cardiac anatomy and 196 (0.39%) with major congenital cardiac defects; 73 (37.2%) with conotruncal defects, 63 (32.1%) with left ventricular outflow tract (LVOT) defects and 60 (30.6%) with valvular defects. In the group of cardiac defects, compared to controls, there was lower median PAPP-A MoM (0.81 vs 1.00, p<0.0001) and PLGF MoM (0.78 vs 1.00, p<0.0001) but no significant difference in UTPI MoM (1.01 vs 1.00, p=0.162). Conclusions: In pregnancies with isolated major cardiac defects there is evidence of placental dysfunction in the absence of impaired placental perfusion

Current practice in the diagnosis and management of fetal growth restriction: An international survey

Introduction The aim of this survey was to evaluate the current practice in respect of diagnosis and management of fetal growth restriction among obstetricians in different countries. Material and methods An e-questionnaire was sent via REDCap with "click thru" links in emails and newsletters to obstetric practitioners in different countries and settings with different levels of expertise. Clinical scenarios in early and late fetal growth restriction were given, followed by structured questions/response pairings. Results A total of 275 participants replied to the survey with 87% of responses complete. Participants were obstetrician/gynecologists (54%; 148/275) and fetal medicine specialists (43%; 117/275), and the majority practiced in a tertiary teaching hospital (56%; 153/275). Delphi consensus criteria for fetal growth restriction diagnosis were used by 81% of participants (223/275) and 82% (225/274) included a drop in fetal growth velocity in their diagnostic criteria for late fetal growth restriction. For early fetal growth restriction, TRUFFLE criteria were used for fetal monitoring and delivery timing by 81% (223/275). For late fetal growth restriction, indices of cerebral blood flow redistribution were used by 99% (250/252), most commonly cerebroplacental ratio (54%, 134/250). Delivery timing was informed by cerebral blood flow redistribution in 72% (176/244), used from >= 32 weeks of gestation. Maternal biomarkers and hemodynamics, as additional tools in the context of early-onset fetal growth restriction (<= 32 weeks of gestation), were used by 22% (51/232) and 46% (106/230), respectively. Conclusions The diagnosis and management of fetal growth restriction are fairly homogeneous among different countries and levels of practice, particularly for early fetal growth restriction. Indices of cerebral flow distribution are widely used in the diagnosis and management of late fetal growth restriction, whereas maternal biomarkers and hemodynamics are less frequently assessed but more so in early rather than late fetal growth restriction. Further standardization is needed for the definition of cerebral blood flow redistribution

Intrauterine versus post-mortem magnetic resonance in second trimester termination of pregnancy for central nervous system abnormalities

Objective: To evaluate if limiting factors of intrauterine magnetic resonance imaging (iuMRI) performed in the early second trimester of pregnancy (19\u201323 weeks) affect its accuracy in comparison to post-mortem MRI (pmMRI) in fetuses that underwent termination of pregnancy (TOP) for central nervous system (CNS) defects. Study design: This is a secondary analysis of a 10 years prospective observational study. Cases of TOP < 23 weeks for CNS malformation that had undergone neurosonography (NSG), iuMRI, pmMRI and autopsy were included. The agreement between iuMRI and pmMRI was calculated. The autopsy represented the gold-standard. Results: Overall, 143 TOPs for fetal congenital anomaly underwent the post-mortem diagnostic protocol. Of these, 31 cases underwent iuMRI and pmMRI for CNS abnormality. Three cases were excluded due to brain autolysis at autopsy. Corpus callosum defects were the most represented (16/28; 57 %). In only one case of posterior fossa defect, pmMRI identified the presence of vermian hypoplasia not diagnosed at iuMRI. In 2 cases (7%), iuMRI added clinically relevant additional findings to NSG, that were posteriorly confirmed by pmMRI. Conclusions: The study shows that, at 19\u201323 weeks and for CNS defects, limiting factors that might influence the performance of iuMRI have little influence on iuMRI accuracy. This finding is particularly important for professionals who work in countries with legal bound for TOP in the early second trimester

Ultrasound prediction of adverse outcome and perinatal complications at diagnosis of late-onset fetal growth restriction: a cohort study

Background: Abnormal umbilical, cerebral and uterine artery Doppler findings and fetal biometry below the 3rd percentile have been proposed as risk factors for perinatal complications in late-onset fetal growth restriction (FGR). Recent evidence has allowed to reach a consensus on the clinical use of Doppler ultrasound for the monitoring and timing of delivery in early-onset FGR, however there is limited data on the relationship between abnormal Doppler and severity of the growth restriction and adverse outcome when a diagnosis of late-onset FGR is made. Objective: To evaluate the relationship between the ultrasound parameters measured at diagnosis and perinatal adverse outcome within a cohort of late-onset FGR fetuses. Methods: This is a multicentre retrospective study between 2014 and 2019 including non-anomalous singleton pregnancies complicated by late-onset FGR, which was defined either by abdominal circumference (AC), estimated fetal weight (EFW) &lt;10th percentile for the gestation or by a reduction of the longitudinal growth of the AC by over 50 percentiles compared to an ultrasound scan performed between 18 and 32 weeks of gestation. Sonographic findings at diagnosis were compared between fetuses with and without adverse outcomes including stillbirth, obstetric intervention due to intrapartum distress, neonatal acidaemia, transfer to neonatal intensive care unit (NICU) and composite adverse perinatal outcome (CAO), which was defined by either stillbirth or the combination of at least two adverse perinatal outcomes. Results: Overall, 468 cases with full biometry and umbilical, middle cerebral, and uterine artery (UtA) Doppler data were included, among whom CAO was recorded in 53 (11.3%). At logistic regression analysis, only the EFW percentile proved to be independently associated with CAO (p=0.01) and NICU admission (p&lt;0.01), while the mean UtA pulsatility index (PI) MoM &gt;95th percentile at diagnosis proved to be independently associated with obstetric intervention due to intrapartum distress (p&lt;0.01). The model including baseline pregnancy characteristics and the EFW percentile was associated with an area under the curve of 0.889, 95%CI (0.813-0.966), p&lt;0.001 for CAO. A cut-off value corresponding to the 3.95th percentile was found to better discriminate between cases with and without CAO yielding a 58.5% sensitivity [95% confidence interval (CI) (44.1-71.9)], a 69.6% specificity [95%CI (65.0-74.0)], a 19.8% positive predictive value [95%CI (13.8-26.8)], and a 92.9% negative predictive value [95%CI (89.5-95.5)]. Conclusions: Retrospective data on a large cohort of late-onset FGR fetuses shows that at diagnosis the EFW is the only sonographic parameter independently associated with the occurrence of adverse perinatal outcomes, while a mean UtA PI MoM &gt;95th percentile at diagnosis is independently associated with intrapartum distress leading to obstetric intervention. This article is protected by copyright. All rights reserved

Obliterated cavum septi pellucidi: Clinical significance and role of fetal magnetic resonance

Introduction: The objective of this study was to describe a cohort of fetuses with an ultrasound prenatal diagnosis of obliterated cavum septi pellucidi (oCSP) with the aim to explore the rate of associated malformations, the progression during pregnancy and the role of fetal magnetic resonance imaging (MRI).Material and methods: This was a retrospective multicenter international study of fetuses diagnosed with oCSP in the second trimester with available fetal MRI and subsequent ultrasound and/or fetal MRI follow-up in the third trimester. Where available, postnatal data were collected to obtain information on neurodevelopment.Results: We identified 45 fetuses with oCSP at 20.5 weeks (interquartile range 20.1-21.1). oCSP was apparently isolated at ultrasound in 89% (40/45) and fetal MRI found additional findings in 5% (2/40) of cases, including polymicrogyria and microencephaly. In the remaining 38 fetuses, fetal MRI found a variable amount of fluid in CSP in 74% (28/38) and no fluid in 26% (10/38). Ultrasound follow-up at or after 30 weeks confirmed the diagnosis of oCSP in 32% (12/38) while fluid was visible in 68% (26/38). At follow-up MRI, performed in eight pregnancies, there were periventricular cysts and delayed sulcation with persistent oCSP in one case. Among the remaining cases with normal follow-up ultrasound and fetal MRI findings, the postnatal outcome was normal in 89% of cases (33/37) and abnormal in 11% (4/37): two with isolated speech delay, and two with neurodevelopmental delay secondary to postnatal diagnosis of Noonan syndrome at 5 years in one case and microcephaly with delayed cortical maturation at 5 months in the other.Conclusions: Apparently isolated oCSP at mid-pregnancy is a transient finding with the visualization of the fluid later in pregnancy in up to 70% of cases. At referral, associated defects can be found in around 11% of cases at ultrasound and 8% at fetal MRI indicating the need for a detailed evaluation by expert physicians when oCSP is suspected

Current practice in the diagnosis and management of fetal growth restriction: An international survey

Introduction The aim of this survey was to evaluate the current practice in respect of diagnosis and management of fetal growth restriction among obstetricians in different countries. Material and methods An e-questionnaire was sent via REDCap with “click thru” links in emails and newsletters to obstetric practitioners in different countries and settings with different levels of expertise. Clinical scenarios in early and late fetal growth restriction were given, followed by structured questions/response pairings. Results A total of 275 participants replied to the survey with 87% of responses complete. Participants were obstetrician/gynecologists (54%; 148/275) and fetal medicine specialists (43%; 117/275), and the majority practiced in a tertiary teaching hospital (56%; 153/275). Delphi consensus criteria for fetal growth restriction diagnosis were used by 81% of participants (223/275) and 82% (225/274) included a drop in fetal growth velocity in their diagnostic criteria for late fetal growth restriction. For early fetal growth restriction, TRUFFLE criteria were used for fetal monitoring and delivery timing by 81% (223/275). For late fetal growth restriction, indices of cerebral blood flow redistribution were used by 99% (250/252), most commonly cerebroplacental ratio (54%, 134/250). Delivery timing was informed by cerebral blood flow redistribution in 72% (176/244), used from ≥32 weeks of gestation. Maternal biomarkers and hemodynamics, as additional tools in the context of early-onset fetal growth restriction (≤32 weeks of gestation), were used by 22% (51/232) and 46% (106/230), respectively. Conclusions The diagnosis and management of fetal growth restriction are fairly homogeneous among different countries and levels of practice, particularly for early fetal growth restriction. Indices of cerebral flow distribution are widely used in the diagnosis and management of late fetal growth restriction, whereas maternal biomarkers and hemodynamics are less frequently assessed but more so in early rather than late fetal growth restriction. Further standardization is needed for the definition of cerebral blood flow redistribution