MRI assessed placental volume and adverse pregnancy outcomes: Secondary analysis of prospective cohort study.

INTRODUCTION: Our goal was to evaluate the potential utility of magnetic resonance imaging (MRI) placental volume as an assessment of placental insufficiency. METHODS: Secondary analysis of a prospective cohort undergoing serial placental MRIs at two academic tertiary care centers. The population included 316 participants undergoing MRI up to three times throughout gestation. MRI was used to calculate placental volume in milliliters (ml). Placental-mediated adverse pregnancy outcome (cAPO) included preeclampsia with severe features, abnormal antenatal surveillance, and perinatal mortality. Serial measurements were grouped as time point 1 (TP1) <22 weeks, TP2 22 0/7-29 6/7 weeks, and TP3 ≥30 weeks. Mixed effects models compared change in placental volume across gestation between cAPO groups. Association between cAPO and placental volume was determined using logistic regression at each TP with discrimination evaluated using area under receiver operator curve (AUC). Placental volume was then added to known clinical predictive variables and evaluated with test characteristics and calibration. RESULTS: 59 (18.7 %) of 316 participants developed cAPO. Placental volume growth across gestation was slower in the cAPO group (p < 0.001). Placental volume was lower in the cAPO group at all time points, and alone was moderately predictive of cAPO at TP3 (AUC 0.756). Adding placental volume to clinical variables had moderate discrimination at all time points, with strongest test characteristics at TP3 (AUC 0.792) with sensitivity of 77.5 % and specificity of 75.3 % at a predicted probability cutoff of 15 %. DISCUSSION: MRI placental volume warrants further study for assessment of placental insufficiency, particularly later in gestation.

Assessment of feto-placental oxygenation and perfusion in a rat model of placental insufficiency using T2* mapping and 3D dynamic contrast-enhanced MRI.

INTRODUCTION: Placental insufficiency may lead to preeclampsia and fetal growth restriction. There is no cure for placental insufficiency, emphasizing the need for monitoring fetal and placenta health. Current monitoring methods are limited, underscoring the necessity for imaging techniques to evaluate fetal-placental perfusion and oxygenation. This study aims to use MRI to evaluate placental oxygenation and perfusion in the reduced uterine perfusion pressure (RUPP) model of placental insufficiency. METHODS: Pregnant rats were randomized to RUPP (n = 11) or sham surgery (n = 8) on gestational day 14. On gestational day 19, rats imaged using a 7T MRI scanner to assess oxygenation and perfusion using T2* mapping and 3D-DCE MRI sequences, respectively. The effect of the RUPP on the feto-placental units were analyzed from the MRI images. RESULTS: RUPP surgery led to reduced oxygenation in the labyrinth (24.7 ± 1.8 ms vs. 28.0 ± 2.1 ms, P = 0.002) and junctional zone (7.0 ± 0.9 ms vs. 8.1 ± 1.1 ms, P = 0.04) of the placenta, as indicated by decreased T2* values. However, here were no significant differences in fetal organ oxygenation or placental perfusion between RUPP and sham animals. DISCUSSION: The reduced placental oxygenation without a corresponding decrease in perfusion suggests an adaptive response to placental ischemia. While acute reduction in placental perfusion may cause placental hypoxia, persistence of this condition could indicate chronic placental insufficiency after ischemic reperfusion injury. Thus, placental oxygenation may be a more reliable biomarker for assessing fetal condition than perfusion in hypertensive disorders of pregnancies including preeclampsia and FGR.

Estereología en placentas procedentes de gestaciones gemelares / Stereology in placentas from twin pregnancies

Introducción: La disfunción placentaria origina complicaciones fetales; de manera más frecuente, la restricción del crecimiento intrauterino y la preclampsia. Objetivo: Identificar el patrón estereológico en placentas gemelares, y su relación con la corionicidad y el peso del recién nacido. Métodos: Se realizó un estudio descriptivo en una muestra de 16 gestantes gemelares, 25 placentas y 32 recién nacidos. Se estudiaron las variables peso del recién nacido, número de vellosidades, superficie vellositaria total, área vellositaria, área de nodos, densidad óptica de fibrina en la superficie vellositaria y densidad óptica de fibrina alrededor del vaso. Resultados: Existió relación directa entre el número de vellosidades y la superficie vellositaria total. En las placentas monocoriónicas hubo predominio de recién nacidos bajo peso. Se percibe una diferencia en los resultados de área, según el tipo placentario y la región topográfica. En las placentas monocoriales se observó mayor área, tanto de la vellosidad placentaria como en los nodos sincitiales, siendo el área de la vellosidad mayor en la periferia placentaria, y el área de nodos sincitiales en la región 4 cm del cordón umbilical. Conclusiones: La estereología microscópica a nivel pericordón, a 4 cm del cordón y en la periferia del disco placentario, arrojó diferencias significativas para el área de la vellosidad y la densidad óptica de fibrina en la superficie de la vellosidad. Los valores promedio para el área de nodos sincitiales y la densidad óptica de fibrina alrededor del vaso no mostraron diferencias estadísticamente significativas. Es la corionicidad un predictor del bajo peso al nacer(AU)

Introduction: Placental dysfunction causes fetal complications; more frequently, intrauterine growth restriction and preeclampsia. Objective: To identify the stereological pattern in twin placentas, and its relationship with chorionicity and weight of the newborn. Methods: A descriptive study was carried out in a sample of 16 women with twin pregnancy, 25 placentas and 32 newborns. The variables weight of the newborn, number of villi, total villous surface, villous area, node area, optical density of fibrin on the villous surface and optical density of fibrin around the vessel were studied. Results: There was a direct relationship between the number of villi and the total villous surface. In monochorionic placentas there was a predominance of low birth weight newborns. A difference is observed in the area results according to the placental type and the topographic region. In monochorionic placentas, a greater area was observed, both in the placental villus and in the syncytial nodes, with the villus area being greater in the placental periphery and the area of syncytial nodes in the region 4 cm from the umbilical cord. Conclusions: Microscopic stereology at the perichordal level, 4 cm from the cord and at the periphery of the placental disc showed significant differences for the villus area and fibrin optical density on the villus surface. The average values for the area of syncytial nodes and the optical density of fibrin around the vessel did not show statistically significant differences. Chorionicity is a predictor of low birth weight(AU)

From Molecules to Imaging: Assessment of Placental Hypoxia Biomarkers in Placental Insufficiency Syndromes.

Placental hypoxia poses significant risks to both the developing fetus and the mother during pregnancy, underscoring the importance of early detection and monitoring. Effectively identifying placental hypoxia and evaluating the deterioration in placental function requires reliable biomarkers. Molecular biomarkers in placental tissue can only be determined post-delivery and while maternal blood biomarkers can be measured over time, they can merely serve as proxies for placental function. Therefore, there is an increasing demand for non-invasive imaging techniques capable of directly assessing the placental condition over time. Recent advancements in imaging technologies, including photoacoustic and magnetic resonance imaging, offer promising tools for detecting and monitoring placental hypoxia. Integrating molecular and imaging biomarkers may revolutionize the detection and monitoring of placental hypoxia, improving pregnancy outcomes and reducing long-term health complications. This review describes current research on molecular and imaging biomarkers of placental hypoxia both in human and animal studies and aims to explore the benefits of an integrated approach throughout gestation.

Exploring the role of a time-efficient MRI assessment of the placenta and fetal brain in uncomplicated pregnancies and these complicated by placental insufficiency.

INTRODUCTION: The development of placenta and fetal brain are intricately linked. Placental insufficiency is related to poor neonatal outcomes with impacts on neurodevelopment. This study sought to investigate whether simultaneous fast assessment of placental and fetal brain oxygenation using MRI T2* relaxometry can play a complementary role to US and Doppler US. METHODS: This study is a retrospective case-control study with uncomplicated pregnancies (n = 99) and cases with placental insufficiency (PI) (n = 49). Participants underwent placental and fetal brain MRI and contemporaneous ultrasound imaging, resulting in quantitative assessment including a combined MRI score called Cerebro-placental-T2*-Ratio (CPTR). This was assessed in comparison with US-derived Cerebro-Placental-Ratio (CPR), placental histopathology, assessed using the Amsterdam criteria [1], and delivery details. RESULTS: Pplacental and fetal brain T2* decreased with increasing gestational age in both low and high risk pregnancies and were corrected for gestational-age alsosignificantly decreased in PI. Both CPR and CPTR score were significantly correlated with gestational age at delivery for the entire cohort. CPTR was, however, also correlated independently with gestational age at delivery in the PI cohort. It furthermore showed a correlation to birth-weight-centile in healthy controls. DISCUSSION: This study indicates that MR analysis of the placenta and brain may play a complementary role in the investigation of fetal development. The additional correlation to birth-weight-centile in controls may suggest a role in the determination of placental health even in healthy controls. To our knowledge, this is the first study assessing quantitatively both placental and fetal brain development over gestation in a large cohort of low and high risk pregnancies. Future larger prospective studies will include additional cohorts.

Prediction of fetal and neonatal outcomes after preterm manifestations of placental insufficiency: systematic review of prediction models.

OBJECTIVES: To identify all prediction models for fetal and neonatal outcomes in pregnancies with preterm manifestations of placental insufficiency (gestational hypertension, pre-eclampsia, HELLP syndrome or fetal growth restriction with its onset before 37 weeks' gestation) and to assess the quality of the models and their performance on external validation. METHODS: A systematic literature search was performed in PubMed, Web of Science and EMBASE. Studies describing prediction models for fetal/neonatal mortality or significant neonatal morbidity in patients with preterm placental insufficiency disorders were included. Data extraction was performed using the CHARMS checklist. Risk of bias was assessed using PROBAST. Literature selection and data extraction were performed by two researchers independently. RESULTS: Our literature search yielded 22 491 unique publications. Fourteen were included after full-text screening of 218 articles that remained after initial exclusions. The studies derived a total of 41 prediction models, including four models in the setting of pre-eclampsia or HELLP, two models in the setting of fetal growth restriction and/or pre-eclampsia and 35 models in the setting of fetal growth restriction. None of the models was validated externally, and internal validation was performed in only two studies. The final models contained mainly ultrasound (Doppler) markers as predictors of fetal/neonatal mortality and neonatal morbidity. Discriminative properties were reported for 27/41 models (c-statistic between 0.6 and 0.9). Only two studies presented a calibration plot. The risk of bias was assessed as unclear in one model and high for all other models, mainly owing to the use of inappropriate statistical methods. CONCLUSIONS: We identified 41 prediction models for fetal and neonatal outcomes in pregnancies with preterm manifestations of placental insufficiency. All models were considered to be of low methodological quality, apart from one that had unclear methodological quality. Higher-quality models and external validation studies are needed to inform clinical decision-making based on prediction models. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Third-trimester uterine artery Doppler for prediction of adverse outcome in late small-and adequate for-gestational-age fetuses.

Fetal growth restriction includes all those fetuses that do not reach their own growth potential due to placental insufficiency and therefore at higher risk of adverse perinatal outcomes. Identification and follow-up of these fetuses is essential to decrease this additional risk. Although estimated fetal weight under the 3rd centile and pathological cerebroplacental ratio are the most accepted predictive criteria, some evidence suggests that abnormal uterine artery Doppler may be a useful prognostic parameter in late-onset growth restriction fetuses at the moment of diagnosis. However, its prediction capacity as a standalone parameter is limited. In that context, integrated models of biometric and hemodynamic ultrasound parameters including uterine Doppler have been proposed as an effective approach to stratify the risk and improve perinatal outcomes. Moreover, an association of abnormal uterine artery Doppler and histological findings of placental underperfusion due to vascular obstruction has been described. Finally, it has also been suggested that the evaluation of uterine artery Doppler at third trimester in appropriate-for-gestational-age fetuses could identify cases of subclinical placental insufficiency, but further evidence is needed to define such predictive strategies.

Postnatal genetic and neurodevelopmental assessment in infants born at term with severely low birth weight of non-placental origin.

OBJECTIVE: To determine the frequency of genetic syndromes and childhood neurodevelopmental impairment in non-malformed infants born at term with severely low birth weight and no evidence of placental insufficiency. METHODS: This case series was constructed from the data of infants delivered at term between 2013 and 2018 with severely low birth weight, defined as birth weight more than 2.5 SD below the mean, with normal maternal and fetal Doppler (umbilical artery, fetal middle cerebral artery, cerebroplacental ratio and uterine artery) and no maternal hypertensive disorder during pregnancy or fetal structural anomaly on prenatal ultrasound examination. Clinical exome sequencing and copy number variation (CNV) analysis were performed using DNA extracted from the children's saliva. Cognitive and psychomotor development was evaluated using the Bayley Scales of Infant and Toddler Development, 3rd edition or the Wechsler Intelligence Scale for Children, 5th edition tests, according to the child's age at testing. RESULTS: Among the 36 405 infants born within the study period, 274 (0.75%) had a birth weight below -2.5 SD, of whom 98 met the inclusion criteria. Among the 63 families contacted, seven (11%) reported a postnatal diagnosis of a genetic syndrome and a further 18 consented to participate in the study. Median gestational age at delivery was 38.0 (interquartile range (IQR), 37.3-38.5) weeks and median birth weight was 2020 (IQR, 1908-2248) g. All 18 children showed a normal result on clinical exome sequencing and CNV analysis, but six (33%) obtained a low score on neurodevelopmental testing. CONCLUSION: Non-malformed severely small term infants with no clinical or Doppler signs of placental insufficiency present a high rate of genetic syndromes and neurodevelopmental impairment during childhood. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Placental functional assessment and its relationship to adverse pregnancy outcome: comparison of intravoxel incoherent motion (IVIM) MRI, T2-relaxation time, and umbilical artery Doppler ultrasound.

BACKGROUND: Early identification of placental insufficiency can lead to appropriate treatment selections and can improve neonates' outcomes. Possible contributions of magnetic resonance imaging (MRI) have been suggested. PURPOSE: To evaluate the prognostic capabilities of placental intravoxel incoherent motion (IVIM) parameters and T2-relaxation time, and their correlation with fetal growth and adverse outcomes, comparing umbilical artery (UmA) pulsatility index (PI). MATERIAL AND METHODS: A total of 68 singleton pregnancies at 24-40 weeks of gestation underwent placental MRI and were reviewed retrospectively. UmA-PI was measured using Doppler ultrasound by obstetricians. IVIM parameters (Dfast, Dslow, and f) were calculated with a Bayesian model fitting. First, the associations between gestational age (GA) with placental IVIM parameters, T2-relaxation time, and placental thickness (PT) were evaluated. Second, IVIM parameters, T2 value (Z-score), PT (Z-score), and UmA-PI (Z-score) were compared between ( 1) those delivering small for gestational age (SGA) and appropriate for gestational age (AGA) neonates, ( 2) emergency cesarean section (ECS), and non-ECS, and ( 3) preterm birth and full-term birth. RESULTS: Low birth weight was observed in 15/68 cases (22%). GA was significantly associated only with T2-relaxation time and PT. SGA was significantly associated with T2 value (Z-score), f, and UmA-PI (Z-score). In the ECS groups, T2 value (Z-score), f, and Dfast were significantly lower than those in non-ECS groups. All IVIM parameters and T2 values (Z-score) showed significantly lower scores in the preterm birth group. CONCLUSION: Placental f and T2 value (Z-score) had significant associations with low birth weight and clinical adverse outcomes and could be potential imaging biomarkers of placental insufficiency.

Femur development in fetal growth restriction as observed on prenatal magnetic resonance imaging.

OBJECTIVE: To investigate human femur development in fetal growth restriction (FGR) by analyzing femur morphometrics and distal epimetaphyseal features on prenatal magnetic resonance imaging (MRI). METHODS: This was a retrospective study of 111 fetuses (mean gestational age (GA), 27 + 2 weeks (range, 19-35 weeks)) with FGR associated with placental insufficiency without other major abnormalities and 111 GA-matched normal controls. On 1.5-Tesla echoplanar MRI, femur morphometrics, including diaphyseal length, epiphyseal length and epiphyseal width, were assessed. Using a previously reported grading system, epimetaphyseal features, including cartilaginous epiphyseal shape, metaphyseal shape and epiphyseal ossification, were analyzed qualitatively. To compare FGR cases and controls, the paired t-test was used to assess morphometrics, generalized estimating equations were used for epimetaphyseal features and time-to-event analysis was used to assess the visibility of epiphyseal ossification. RESULTS: There were significant differences in femur morphometrics between FGR cases and controls (all parameters, P < 0.001), with bone shortening observed in FGR. No significant differences were found in the distribution of epimetaphyseal features between FGR cases and controls (epiphyseal shape, P = 0.341; metaphyseal shape, P = 0.782; epiphyseal ossification, P = 0.85). Epiphyseal ossification was visible at a median of 33.6 weeks in FGR cases and at 32.1 weeks in controls (P = 0.008). CONCLUSIONS: On prenatal MRI, cases with FGR associated with placental insufficiency exhibit diaphyseal and epiphyseal shortening of the femur. However, FGR cases and normal controls share similarly graded distal epimetaphyseal features. Consequently, these features may not be appropriate MRI characteristics for the identification of FGR. © 2022 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Dynamic contrast enhanced magnetic resonance imaging: A review of its application in the assessment of placental function.

It is important to develop a better understanding of placental insufficiency given its role in common maternofetal complications such as preeclampsia and fetal growth restriction. Functional magnetic resonance imaging offers unprecedented techniques for exploring the placenta under both normal and pathological physiological conditions. Dynamic contrast-enhanced magnetic resonance imaging (DCE MRI) is an established and very robust method to investigate the microcirculatory parameters of an organ and more specifically its perfusion. It is currently a gold standard in the physiological and circulatory evaluation of an organ. Its application to the human placenta could enable to access many microcirculatory parameters relevant to the placental function such as organ blood flow, fractional blood volume, and permeability surface area, by the acquisition of serial images, before, during, and after administration of an intravenous contrast agent. Widely used in animal models with gadolinium-based contrast agents, its application to the human placenta could be possible if the safety of contrast agents in pregnancy is established or they are confirmed to not cross the placenta.

MRI based morphological examination of the placenta.

Ultrasound is widely used as the initial diagnostic imaging modality during pregnancy with both high spatial and temporal resolution. Although MRI in pregnancy has long focused on the fetus, its use in placental imaging has greatly increased over recent years. In addition to the possibilities of evaluating function, MRI with a wide field of view and high contrast resolution allows characterization of placental anatomy, particularly in situations that are difficult to specify with ultrasound, especially for suspected placenta accreta. MRI also appears to be a particularly useful examination for the anatomical evaluation of the placenta independent of maternal body habitus or fetal position. Indeed, surprisingly little attention is paid to the placenta in MRI when the indication for the examination is fetal. Thus, some aspects of the placenta seem to us to be important to be recognized by the radiologist and to be described on the MRI report. In this review, we will describe MRI sequences used for, and common features seen in, imaging of i) the normal placenta, ii) abnormal aspects of the placenta that should be identified on MRI performed for fetal reason, and iii) placental anomalies for which placental MRI may be indicated.

Chronic hypoxia in pregnant mice impairs the placental and fetal vascular response to acute hypercapnia in BOLD-MRI hemodynamic response imaging.

INTRODUCTION: Brief hypercapnic challenge causes acute placental hypoperfusion with fetal brain sparing on BOLD-MRI. We hypothesize that this non-invasive imaging strategy can distinguish between normal pregnancy and chronic placental hypoperfusion (using the maternal hypoxia model). METHODS: Eighteen pregnant female ICR mice were randomized to three groups: normoxia, late-onset hypoxia (12%O2;E13.5-17.5) and early-onset hypoxia (12%O2;E10.5-17.5). On E17.5, animals were imaged in a 4.7-T Bruker-Biospec MRI scanner. Fast coronal True-FISP was performed to identify organs of interest (placenta and fetal heart, liver and brain). BOLD-MRI was performed at baseline and during a 4-min hypercapnic challenge (5%CO2). %-change in placental and fetal signal was analyzed from T2*-weighted gradient echo MR images. Following MRI, fetuses and placentas were harvested, weighed and immuno-stained. RESULTS: In normoxic mice, hypercapnia caused reduction in BOLD-MRI signal in placenta (-44% ± 7%; p < 0.0001), fetal liver (-32% ± 7%; p < 0.0001) and fetal heart (-54% ± 12%; p < 0.002), with relative fetal brain sparing (-12% ± 5%; p < 0.0001). These changes were markedly attenuated in both hypoxia groups. Baseline fetal brain/placenta SI ratio was highest in normoxic mice (1.14 ± 0.017) and reduced with increasing duration of hypoxia (late-onset hypoxia: 1.00 ± 0.026; early-onset hypoxia: 0.91 ± 0.016; p = 0.02). Both hypoxic groups exhibited fetal growth restriction with prominent placental glycogen-containing cells, particularly in early-onset hypoxia. There was increased fetal neuro- and intestinal-apoptosis in early-onset hypoxia only. CONCLUSIONS: BOLD-MRI with brief hypercapnic challenge distinguished between normoxia and both hypoxia groups, while fetal neuroapoptosis was only observed after early-onset hypoxia. This suggests that BOLD-MRI with hypercapnic challenge can identify chronic fetal asphyxia before the onset of irreversible brain injury.

Placental chemical elements concentration in small fetuses and its relationship with Doppler markers of placental function.

INTRODUCTION: In this study, we aimed at quantifying placental concentrations of 22 chemical elements in small fetuses (SGA) as compared with normally grown fetuses (AGA), and to assess the relationship with Doppler markers of placental function. METHODS: Prospective cohort study, including 71 SGA fetuses (estimated fetal weight < 10th percentile) and 96 AGA fetuses (estimated fetal weight > 10th percentile), recruited in the third trimester of gestation. The placental concentration of 22 chemical elements was determined by inductively coupled plasma optical emission spectrophotometer (ICP-OES, ICAP 6500 Duo Thermo): aluminum (Al), beryllium (Be), bismuth (Bi), calcium (Ca), cadmium (Cd), cobalt (Co), chrome (Cr), copper (Cu), magnesium (Mg), manganese (Mn), molybdenum (Mo), nickel (Ni), phosphorus (P), lead (Pb), rubidium (Rb), sulfur (S), strontium (Sr), titanium (Ti), thallium (Tl), antimony (Sb), selenium (Se), and zinc (Zn). Placental function was assessed by measuring the following fetal-maternal parameters: Uterine artery Pulsatility Index (UtA PI), Umbilical artery Pulsatility Index (UA PI) and Middle Cerebral artery Pulsatility Index (MCA PI). The association between the chemical elements concentration and study group and the association with Doppler measures were evaluated. RESULTS: SGA was associated with significantly (p < 0.05) lower concentrations of Al (AGA 21.14 vs SGA 0.51 mg/kg), Cr (AGA 0.17 vs SGA 0.12 mg/kg), Cu (AGA 0.89 vs SGA 0.81 mg/kg), Mg (AGA 0.007 vs SGA 0.006 g/100g), Mn (AGA 0.60 vs SGA 0.47 mg/kg), Rb (AGA 1.68 vs SGA 1.47 mg/kg), Se (AGA 0.02 vs SGA 0.01 mg/kg), Ti (AGA 0.75 vs SGA 0.05 mg/kg) and Zn (AGA 9.04 vs SGA 8.22 mg/kg). Lower placental concentrations of Al, Cr, Mn, Se, Ti were associated with abnormal UtA, UA and MCA Doppler. DISCUSSION: Lower placental concentrations of Al, Cr, Cu, Mn, Rb, Se, Ti and Zn are associated with SGA fetuses and abnormal fetal-maternal Doppler results. Additional studies are required to further understand how chemical elements affect fetal growth and potentially find strategies to prevent SGA.

Abnormal Fetal Growth: Small for Gestational Age, Fetal Growth Restriction, Large for Gestational Age: Definitions and Epidemiology.

Abnormal fetal growth (growth restriction and overgrowth) is associated with perinatal morbidity, mortality, and lifelong risks to health. To describe abnormal growth, "small for gestational age" and "large for gestational age" are commonly used terms. However, both are statistical definitions of fetal size below or above a certain threshold related to a reference population, rather than referring to an abnormal condition. Fetuses can be constitutionally small or large and thus healthy, whereas fetuses with seemingly normal size can be growth restricted or overgrown. Although golden standards to detect abnormal growth are lacking, understanding of both pathologic conditions has improved significantly.

Evaluation and Management of Suspected Fetal Growth Restriction.

Impaired fetal growth owing to placental insufficiency is a major contributor to adverse perinatal outcomes. No intervention is available that improves outcomes by changing the pathophysiologic process. Monitoring in early-onset fetal growth restriction (FGR) focuses on optimizing the timing of iatrogenic preterm delivery using cardiotocography and Doppler ultrasound. In late-onset FGR, identifying the fetus at risk for immediate hypoxia and who benefits from expedited delivery is challenging. It is likely that studies in the next decade will provide evidence how to best integrate different monitoring variables and other prognosticators in risk models that are aimed to optimize individual treatment strategies.

How to define late fetal growth restriction.

A fraction of third-trimester small fetuses does not achieve their endowed growth potential mainly due to placental insufficiency, usually not evident in terms of impaired umbilical artery Doppler, but severe enough to increase the risk of perinatal adverse outcomes and long-term complications. The identification of those fetuses at higher-risk helps to optimize their follow-up and to decrease the risk of intrauterine demise. Several parameters can help in the identification of those fetuses at higher risk, defined as fetal growth restricted (FGR) fetuses. Severe smallness and the cerebroplacental ratio are the most consistent parameters; regarding uterine artery Doppler, although some evidence in favour has been published, there is currently no consensus about its use. Thirty-two weeks of gestation is the accepted cut-off to define late FGR. The differentiation with early FGR is necessary as these two entities have different clinical maternal manifestations, and different associated short-term and long-term neonatal outcomes. The use of angiogenic factors is promising but more research is needed on this field.

Diagnostic accuracy of fetal growth charts for placenta-related fetal growth restriction.

INTRODUCTION: The choice of fetal growth chart to be used in antenatal screening for fetal growth restriction (FGR) has an important impact on the proportion of fetuses diagnosed as small for gestational age (SGA), and on the detection rate for FGR. We aimed to compare diagnostic accuracy of SGA diagnosed using four different common fetal growth charts [Hadlock, Intergrowth-21st (IG21), World Health Organization (WHO), and National Institute of Child Health and Human Development (NICHD)], for abnormal placental pathology. METHODS: A secondary analysis of data from a prospective cohort study in low-risk nulliparous women. The exposure was SGA (birthweight <10th centile for gestational age) using each of the four charts. The outcomes were one of three types of abnormal placental pathology associated with fetal growth restriction: maternal vascular malperfusion (MVM), chronic villitis, and fetal vascular malperfusion. RESULTS: A total of 742 nulliparous women met the study criteria. The proportion of SGA was closest to the expected rate of 10% using the Hadlock chart (12.7%). The detection rates (DR) and false positive rates (FPR) for MVM pathology were similar for the Hadlock (DR = 53.1%, FPR = 10.8%), WHO (DR = 59.4%, FPR = 14.2%), and NICHD (DR = 53.1%, FPR = 12.3%) charts, and each was superior when compared to the IG21 chart (DR = 34.4%, FPR = 3.8%, p < 0.001). The diagnosis of SGA was associated with increased risks of preeclampsia and preterm birth for all four charts. DISCUSSION: The selection of fetal growth chart to be used in screening programs for FGR has important implications with regard to the false positive and detection rate for FGR.

Maternal and fetal effects of COVID-19 virus on a complicated triplet pregnancy: a case report.

BACKGROUND: Coronavirus disease 2019 (COVID-19), the global pandemic that has spread throughout the world, is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Given the limited scientific evidence on the manifestations and potential impact of this virus on pregnancy, we decided to report this case. CASE PRESENTATION: The patient was a 38 year-old Iranian woman with a triplet pregnancy and a history of primary infertility, as well as hypothyroidism and gestational diabetes. She was hospitalized at 29 weeks and 2 days gestational age due to elevated liver enzymes, and finally, based on a probable diagnosis of gestational cholestasis, she was treated with ursodeoxycholic acid. On the first day of hospitalization, sonography was performed, which showed that biophysical scores and amniotic fluid were normal in all three fetuses, with normal Doppler findings in two fetuses and increased umbilical artery resistance (pulsatility index [PI] > 95%) in one fetus. On day 4 of hospitalization, she developed fever, cough and myalgia, and her COVID-19 test was positive. Despite mild maternal symptoms, exacerbated placental insufficiency occurred in two of the fetuses leading to the rapid development of absent umbilical artery end-diastolic flow. Finally, 6 days later, the patient underwent cesarean section due to rapid exacerbation of placental insufficiency and declining biophysical score in two of the fetuses. Nasopharyngeal swab COVID-19 tests were negative for the first and third babies and positive for the second baby. The first and third babies died 3 and 13 days after birth, respectively, due to collapsed white lung and sepsis. The second baby was discharged in good general condition. The mother was discharged 3 days after cesarean section. She had no fever at the time of discharge and was also in good general condition. CONCLUSIONS: This was a complicated triplet pregnancy, in which, after maternal infection with COVID-19, despite mild maternal symptoms, exacerbated placental insufficiency occurred in two of the fetuses, and the third fetus had a positive COVID-19 test after birth. Therefore, in cases of pregnancy with COVID-19 infection, in addition to managing the mother, it seems that physicians would be wise to also give special attention to the possibility of acute placental insufficiency and subsequent fetal hypoxia, and also the probability of vertical transmission.