Fetal and umbilical Doppler ultrasound in high-risk pregnancies

Background: Abnormal blood flow patterns in fetal circulation detected by Doppler ultrasound may indicate poor fetal prognosis. It is also possible that false positive Doppler ultrasound findings could lead to adverse outcomes from unnecessary interventions, including preterm delivery. Objectives: The objective of this review was to assess the effects of Doppler ultrasound used to assess fetal well-being in high-risk pregnancies on obstetric care and fetal outcomes. Search methods: We updated the search of Cochrane Pregnancy and Childbirth's Trials Register on 31 March 2017 and checked reference lists of retrieved studies. Selection criteria: Randomised and quasi-randomised controlled trials of Doppler ultrasound for the investigation of umbilical and fetal vessels waveforms in high-risk pregnancies compared with no Doppler ultrasound. Cluster-randomised trials were eligible for inclusion but none were identified. Data collection and analysis: Two review authors independently assessed the studies for inclusion, assessed risk of bias and carried out data extraction. Data entry was checked. We assessed the quality of evidence using the GRADE approach. Main results: Nineteen trials involving 10,667 women were included. Risk of bias in trials was difficult to assess accurately due to incomplete reporting. None of the evidence relating to our main outcomes was graded as high quality. The quality of evidence was downgraded due to missing information on trial methods, imprecision in risk estimates and heterogeneity. Eighteen of these studies compared the use of Doppler ultrasound of the umbilical artery of the unborn baby with no Doppler or with cardiotocography (CTG). One more recent trial compared Doppler examination of other fetal blood vessels (ductus venosus) with computerised CTG. The use of Doppler ultrasound of the umbilical artery in high-risk pregnancy was associated with fewer perinatal deaths (risk ratio (RR) 0.71, 95% confidence interval (CI) 0.52 to 0.98, 16 studies, 10,225 babies, 1.2% versus 1.7 %, number needed to treat (NNT) = 203; 95% CI 103 to 4352, evidence graded moderate). The results for stillbirths were consistent with the overall rate of perinatal deaths, although there was no clear difference between groups for this outcome (RR 0.65, 95% CI 0.41 to 1.04; 15 studies, 9560 babies, evidence graded low). Where Doppler ultrasound was used, there were fewer inductions of labour (average RR 0.89, 95% CI 0.80 to 0.99, 10 studies, 5633 women, random-effects, evidence graded moderate) and fewer caesarean sections (RR 0.90, 95% CI 0.84 to 0.97, 14 studies, 7918 women, evidence graded moderate). There was no comparative long-term follow-up of babies exposed to Doppler ultrasound in pregnancy in women at increased risk of complications. No difference was found in operative vaginal births (RR 0.95, 95% CI 0.80 to 1.14, four studies, 2813 women), nor in Apgar scores less than seven at five minutes (RR 0.92, 95% CI 0.69 to 1.24, seven studies, 6321 babies, evidence graded low). Data for serious neonatal morbidity were not pooled due to high heterogeneity between the three studies that reported it (1098 babies) (evidence graded very low). The use of Doppler to evaluate early and late changes in ductus venosus in early fetal growth restriction was not associated with significant differences in any perinatal death after randomisation. However, there was an improvement in long-term neurological outcome in the cohort of babies in whom the trigger for delivery was either late changes in ductus venosus or abnormalities seen on computerised CTG. Authors' conclusions: Current evidence suggests that the use of Doppler ultrasound on the umbilical artery in high-risk pregnancies reduces the risk of perinatal deaths and may result in fewer obstetric interventions. The results should be interpreted with caution, as the evidence is not of high quality. Serial monitoring of Doppler changes in ductus venosus may be beneficial, but more studies of high quality with follow-up including neurological development are needed for evidence to be conclusive

Umbilical vein blood flow: State-of-the-art

Placental blood supply to the fetus can be measured by evaluating the umbilical vein blood flow. Despite its potential application in healthcare, the umbilical vein blood flow volume is still used only in research setting. One of the reasons is a concern regarding its reproducibility, partly due to technology issues. Nowadays, technology improvements make this evaluation accurate and reproducible. The aim of this review is to refresh basic elements of the physiology of umbilical vein blood flow and its analysis. Its evaluation in normal and abnormal fetal growth is also discussed

Maternal hemodynamics : a method to classify hypertensive disorders of pregnancy

BACKGROUND: The classification of hypertensive disorders of pregnancy is based on the time at the onset of hypertension, proteinuria, and other associated complications. Maternal hemodynamic interrogation in hypertensive disorders of pregnancy considers not only the peripheral blood pressure but also the entire cardiovascular system, and it might help to classify the different clinical phenotypes of this syndrome. OBJECTIVE: This study aimed to examine cardiovascular parameters in a cohort of patients affected by hypertensive disorders of pregnancy according to the clinical phenotypes that prioritize fetoplacental characteristics and not the time at onset of hypertensive disorders of pregnancy. STUDY DESIGN: At the fetal-maternal medicine unit of Ziekenhuis Oost-Limburg (Genk, Belgium), maternal cardiovascular parameters were obtained through impedance cardiography using a noninvasive continuous cardiac output monitor with the patients placed in a standing position. The patients were classified as pregnant women with hypertensive disorders of pregnancy who delivered appropriate- and small-for-gestational-age fetuses. Normotensive pregnant women with an appropriate-for-gestational-age fetus at delivery were enrolled as the control group. The possible impact of obesity (body mass index 6530 kg/m2) on maternal hemodynamics was reassessed in the same groups. RESULTS: Maternal age, parity, body mass index, and blood pressure were not significantly different between the hypertensive disorders of pregnancy/appropriate-for-gestational-age and hypertensive disorders of pregnancy/small-for-gestational-age groups. The mean uterine artery pulsatility index was significantly higher in the hypertensive disorders of pregnancy/small-for-gestational-age group. The cardiac output and cardiac index were significantly lower in the hypertensive disorders of pregnancy/small-for-gestational-age group (cardiac output 6.5 L/min, cardiac index 3.6) than in the hypertensive disorders of pregnancy/appropriate-for-gestational-age group (cardiac output 7.6 L/min, cardiac index 3.9) but not between the hypertensive disorders of pregnancy/appropriate-for-gestational-age and control groups (cardiac output 7.6 L/min, cardiac index 4.0). Total vascular resistance was significantly higher in the hypertensive disorders of pregnancy/small-for-gestational-age group than in the hypertensive disorders of pregnancy/appropriate-for-gestational-age group and the control group. All women with hypertensive disorders of pregnancy showed signs of central arterial dysfunction. The cardiovascular parameters were not influenced by gestational age at the onset of hypertensive disorders of pregnancy, and no difference was observed between the women with appropriate-for-gestational-age fetuses affected by preeclampsia or by gestational hypertension with appropriate-for-gestational-age fetuses. Women in the obese/hypertensive disorders of pregnancy/appropriate-for-gestational-age and obese/hypertensive disorders of pregnancy/small-for-gestational-age groups showed a significant increase in cardiac output, as well as significant changes in other parameters, compared with the nonobese/hypertensive disorders of pregnancy/appropriate-for-gestational-age and nonobese/hypertensive disorders of pregnancy/small-for-gestational-age groups. CONCLUSION: Significantly low cardiac output and high total vascular resistance characterized the women with hypertensive disorders of pregnancy associated with small for gestational age due to placental insufficiency, independent of the gestational age at the onset of hypertension. The cardiovascular parameters were not significantly different in the women with appropriate-for-gestational-age or small-for-gestational-age fetuses affected by preeclampsia or gestational hypertension. These findings support the view that maternal hemodynamics may be a candidate diagnostic tool to identify hypertensive disorders in pregnancies associated with small-for-gestational-age fetuses. This additional tool matches other reported evidence provided by uterine Doppler velocimetry, low vascular growth factors in the first trimester, and placental pathology. Obesity is associated with a significantly higher cardiac output and outweighs other determinants of hemodynamics in pregnancy; therefore, in future studies on hypertensive disorders, obesity should be studied as an additional disease and not simply as a demographic characteristic

Reduced fetal growth velocity and weight loss are associated with adverse perinatal outcome in fetuses at risk of growth restriction.

BACKGROUND Although fetal size is associated with adverse perinatal outcome, the relationship between fetal growth velocity and adverse perinatal outcome is unclear. OBJECTIVE This study aimed to evaluate the relationship between fetal growth velocity and signs of cerebral blood flow redistribution, and their association with birthweight and adverse perinatal outcome. STUDY DESIGN This study was a secondary analysis of the TRUFFLE-2 multicenter observational prospective feasibility study of fetuses at risk of fetal growth restriction between 32+0 and 36+6 weeks of gestation (n=856), evaluated by ultrasound biometry and umbilical and middle cerebral artery Doppler. Individual fetal growth velocity was calculated from the difference of birthweight and estimated fetal weight at 3, 2, and 1 week before delivery, and by linear regression of all available estimated fetal weight measurements. Fetal estimated weight and birthweight were expressed as absolute value and as multiple of the median for statistical calculation. The coefficients of the individual linear regression of estimated fetal weight measurements (growth velocity; g/wk) were plotted against the last umbilical-cerebral ratio with subclassification for perinatal outcome. The association of these measurements with adverse perinatal outcome was assessed. The adverse perinatal outcome was a composite of abnormal condition at birth or major neonatal morbidity. RESULTS Adverse perinatal outcome was more frequent among fetuses whose antenatal growth was <100 g/wk, irrespective of signs of cerebral blood flow redistribution. Infants with birthweight <0.65 multiple of the median were enrolled earlier, had the lowest fetal growth velocity, higher umbilical-cerebral ratio, and were more likely to have adverse perinatal outcome. A decreasing fetal growth velocity was observed in 163 (19%) women in whom the estimated fetal weight multiple of the median regression coefficient was <-0.025, and who had higher umbilical-cerebral ratio values and more frequent adverse perinatal outcome; 67 (41%; 8% of total group) of these women had negative growth velocity. Estimated fetal weight and umbilical-cerebral ratio at admission and fetal growth velocity combined by logistic regression had a higher association with adverse perinatal outcome than any of those parameters separately (relative risk, 3.3; 95% confidence interval, 2.3-4.8). CONCLUSION In fetuses at risk of late preterm fetal growth restriction, reduced growth velocity is associated with an increased risk of adverse perinatal outcome, irrespective of signs of cerebral blood flow redistribution. Some fetuses showed negative growth velocity, suggesting catabolic metabolism

Placental Chorangiocarcinoma a Specific Histological Pattern of Uncertain Incidence and Clinical Impact: Systematic Review of the Literature

Chorangiocarcinoma is a very rare and misdiagnosed placental neoplasm. The unique morphologic features of the lesion distinguish it from other trophoblastic tumors and vascular abnormalities. We present a systematic review of the literature to provide clarity on chorangiocarcinoma entity and biology. A literature search was carried out in December 2022 using the keywords "Placental chorangiocarcinoma", "Chorangioma", "Placenta", and "Throphoblast proliferation". Articles published from 1988 to 2022 were obtained from Scopus, Google Scholar, and PUBMED. In our review, we examined maternal age, gestational age at the time of delivery, parity, type of pregnancy, placental weight, ultrasound features of the placenta, macroscopic examination and tumor size, microscopic examination, immunostaining, maternal beta-human chorionic gonadotropin, fetal and maternal outcome. Eight manuscripts were detected. They are all case reports. The macroscopic characteristics of the lesions were represented by the presence of a grey-yellow-white color well-demarcated round nodule. Microscopically, all the authors described typical aspects of malignancy as a high rate of mitosis, nuclear atypia and necrotic areas. In some cases, the presence of AE1/AE3 cytoplasmic positivity, p63 nuclear staining, and beta-human chorionic gonadotropin (BHCG) were reported. A good fetal outcome was reported in all cases of newborns with normal birth weight, except one with fetal growth restriction. Maternal outcome was good in all cases except one with maternal lung metastasis three months after delivery. The clinical course has probably underestimated the real incidence of the pathology. Only greater knowledge of its histology and its clinical course will allow us to evaluate the real prevalence of the disease

The Bacterial DNA Profiling of Chorionic Villi and Amniotic Fluids Reveals Overlaps with Maternal Oral, Vaginal, and Gut Microbiomes

The in utero microbiome hypothesis has been long debated. This hypothesis will change our comprehension of the pioneer human microbiome if proved correct. In 60 uncomplicated pregnancies, we profiled the microbiome of chorionic villi (CV) and amniotic fluids (AF) in relation to maternal saliva, rectum, and vagina and the soluble cytokines cascade in the vagina, CV and AF. In our series, 12/37 (32%) AF and 10/23 (44%) CV tested positive for bacterial DNA. CV and AF harbored bacterial DNA of Streptococcus and Lactobacillus, overlapping that of the matched oral and vaginal niches, which showed a dysbiotic microbiome. In these pregnant women, the immune profiling revealed an immune hyporesponsiveness in the vagina and a high intraamniotic concentration of inflammatory cytokines. To understand the eventual role of bacterial colonization of the CV and AF and the associated immune response in the pregnancy outcome, further appropriate studies are needed. In this context, further studies should highlight if the hematogenous route could justify the spread of bacterial DNA from the oral microbiome to the placenta and if vaginal dysbiosis could favor the likelihood of identifying CV and AF positive for bacterial DNA

CARE 1000: randomized controlled trial for the evaluation of the effectiveness of a mHealth app for supporting the first 1000 days of life

Background Recent developments in eHealth and mobile health (mHealth), as well as the introduction of information and communication technology innovations in clinical practice, such as telemedicine, telemonitoring, and remote examinations, are already changing the current scenario and will continue to generate innovations in the coming decades. The widespread use of mobile devices, with an estimated nearly 30 billion devices and more than 325,000 apps worldwide, will provide various opportunities for people to take control of their own health. Already in 2017, most of the apps available were focused on pregnancy support, more than any other medical field. There have been some reported experiences with social media and mHealth that could benefit the promotion of maternal physical and mental health during pregnancy. However, many apps targeting the first 1000 days of a child's life do not consider the continuity between the prenatal and postnatal periods and their joint impact on maternal and child health. The aim of this study is to evaluate the effectiveness of this mHealth app to support women during the first 1000 days (from conception to 24 months of age) and to improve health prevention behaviours such as immunizations during pregnancy, weight gain during pregnancy, abstinence from smoking and alcohol consumption, and adherence to the routine childhood immunization schedule. In addition, the study aims to understand the level of appreciation of this mHealth app as a tool to overcome information and communication gaps between patients and institutions. MethodsConduction of a randomized controlled trial. DiscussionOur results will be relevant for improving this mHealth app to promote health and prevention and to support the first 1000 days of life for both mother and child. Our results will be relevant to the future expansion of such an mHealth app to promote positive health-related outcomes in patients and co-user satisfaction and to support the organization of health services

Hypertensive Disorders of Pregnancy and Fetal Growth Restriction: Clinical Characteristics and Placental Lesions and Possible Preventive Nutritional Targets

Background: The purpose of this study was to describe the placental lesions in pregnancies complicated by hypertensive disorders (HDP) and/or fetal growth restriction (FGR) and in uneventful control pregnancies. Methods: This is a case control study that included singleton pregnancies with HDP and normally grown fetus (HDP-AGA fetus), with HDP and FGR, early FGR, late FGR, and uneventful pregnancies. Feto-placental Doppler velocimetry and sFlt-1/PlGF ratio were performed. Placental histology was evaluated blinded according to the Amsterdam Consensus criteria. Results: Placental lesions with maternal vascular malperfusion (MVM) were significantly more frequent in HDP-FGR and early FGR (92% and 83%). MVM were significantly associated with abnormal feto-placental Doppler parameters, especially in early FGR. Delayed villous maturation (DVM) was associated with late FGR (83%). HDP-AGA fetus cases presented a heterogeneous pattern of placental lesions, including 60% of cases with MVM, but were not associated with abnormal Doppler feto-placental velocimetry. Conclusions: We found a prevalence of placental maternal vascular malperfusion in HDP-FGR and early FGR groups. These lesions were also associated with abnormal, anti-, and angiogenic markers. Conversely HDP-AGA fetus and late FGR presented more heterogeneous placental lesions not severe enough to cause feto-placental Doppler anomalies. These conditions are likely associated with different etiologies, such as maternal pre-pregnancy risk factors for metabolic syndrome. These findings suggest a possible preventive nutritional approach in addition to low-dose aspirin in pregnant women with predisposing factors for HDP-AGA fetuses and late FGR

Case Report: Two cases of apparent discordance between non-invasive prenatal testing (NIPT) and amniocentesis resulting in feto-placental mosaicism of trisomy 21. Issues in diagnosis, investigation and counselling

The sequencing of cell-free fetal DNA in the maternal plasma through non-invasive prenatal testing (NIPT) is an accurate genetic screening test to detect the most common fetal aneuploidies during pregnancy. The extensive use of NIPT, as a screening method, has highlighted the limits of the technique, including false positive and negative results. Feto-placental mosaicism is a challenging biological issue and is the most frequent cause of false positive and negative results in NIPT screening, and of discrepancy between NIPT and invasive test results. We are reporting on two cases of feto-placental mosaicism of trisomy 21, both with a low-risk NIPT result, identified by ultrasound signs and a subsequent amniocentesis consistent with a trisomy 21. In both cases, after the pregnancy termination, cytogenetic and/or cytogenomic analyses were performed on the placenta and fetal tissues, showing in the first case a mosaicism of trisomy 21 in both the placenta and the fetus, but a mosaicism in the placenta and a complete trisomy 21 in the fetus in the second case. These cases emphasize the need for accurate and complete pre-test NIPT counselling, as well as to identify situations at risk for a possible false negative NIPT result, which may underestimate a potential pathological condition, such as feto-placental mosaicism or fetal trisomy. Post-mortem molecular autopsy may discriminate between placental, fetal and feto-placental mosaicism, and between complete or mosaic fetal chromosomal anomalies. A multidisciplinary approach in counselling, as well as in the interpretation of biological events, is essential for the clarification of complex cases, such as feto-placental mosaicisms