Vascular Malperfusion Lesions Research Articles

Identifying causes and associated factors of stillbirths using autopsy of the fetus and placenta.

The study aimed to evaluate the causes of death and associated factors in cases of stillbirth, using post-mortem examination and applying a rigorous, evidence-based holistic approach. Our retrospective observational study included cases of autopsy following stillbirth that occurred at our tertiary medical center during a period of 8 years. Detailed up-to-date criteria that incorporate clinical reports, medical history, prenatal imaging, and histopathological findings were used to evaluate the cause of death and associated factors. After applying our proposed methodology, 138 cases of stillbirth were classified into eight categories based on the causes of death. A definitive cause of death was observed in 100 (72%) cases, while 38 (28%) cases were considered unexplained. The leading cause of death was placental lesions (n = 39, 28%) with maternal vascular malperfusion (MVM) lesions being the most common (54%). Ascending infection was the second most common cause of fetal death (n = 24, 17%) and was often seen in the setting of preterm labor and cervical insufficiency. The largest category of cause of death was attributed to placental pathology. Using rigorous detailed up-to-date criteria that incorporate pathological and clinical factors may help in objectively classifying the cause of death.

Placental Histopathological Lesions and Adverse Neonatal Outcomes in Patients with Inflammatory Bowel Diseases- A retrospective Cohort Study.

Inflammatory bowel diseases (IBD) are significantly associated with adverse pregnancy and neonatal outcomes, though the pathomechanism is yet unknown. To investigate the relationship between IBD and adverse pregnancy outcomes by comparing neonatal outcomes and placental histopathology in two matched groups of patients with and without IBD. In this retrospective study, data of all patients who gave birth between 2008-2021 and were diagnosed with IBD were reviewed and compared to a control group matching two control cases for every IBD case. Neonatal outcomes and placental pathology were compared between the groups. Compared to the control group (n=76), the placentas of patients with IBD (n=36) were characterized by significantly lower placental weight (p < 0.001), and higher rates of maternal vascular malperfusion lesions (MVM, p < 0.001) and maternal and fetal inflammatory response lesions (p < 0.001). Neonates of patients with IBD were more frequently small for gestational age (SGA) (p=0.01), with increased rates of need for phototherapy (p = 0.03), respiratory morbidity and NICU admission (p < 0.001 for both outcomes). Multivariate logistic regression analyses adjusting for possible confounders (including maternal age, gestational age, chronic hypertension, smoking, and thrombophilia) confirmed the independent association between IBD and composite MVM lesions (aOR 4.31, p < 0.001), maternal inflammatory responses (aOR 40.22, p < 0.001) and SGA infants (aOR 4.31, p = 0.013). IBD is associated with increased rates of placental histopathological lesions and adverse pregnancy outcomes, including SGA infants. These novel findings imply the role of placental malperfusion and inflammatory processes in pregnancy complications of IBD patients, which should be followed accordingly. Approval of local ethics committee # WOMC-0219-20.

Postnatal Cerebral Hemodynamics and Placental Vascular Malperfusion Lesions in Neonates With Congenital Heart Disease

BackgroundNeonates with congenital heart disease (CHD) have smaller brain volume at birth. High rates of placental vascular malperfusion lesions may play a role in disrupted brain development. MethodsThis is a single-center retrospective cohort study of infants born between 2010 and 2019 who were diagnosed with a major cardiac defect requiring surgery in the first year of life. Doppler ultrasound RI of the middle cerebral artery (MCA) and anterior cerebral artery were calculated within the first 72 hours of life. Placentas were evaluated using a standardized approach. ResultsOver the study period, there were 52 patients with hypoplastic left heart syndrome (HLHS), 22 with single-ventricle right ventricular outflow tract obstruction (SV-RVOTO), 75 with a two-ventricle cardiac defect (2V), and 25 with transposition of the great arteries (TGA). MCA Doppler RI were significantly higher for all subgroups of CHD compared with control subjects (0.68 ± 0.11 in control subjects compared with 0.78 ± 0.13 in HLHS, P = 0.03; 0.77 ± 0.10 in SV-RVOTO, P = 0.002; 0.78 ± 0.13 in 2V, P = 0.03; and 0.80 ± 0.14 in TGA; P = 0.001) with the highest average MCA RI in the TGA group. In subgroup analyses, placental fetal vascular malperfusion in the 2V group was associated with higher MCA RI, but this relationship was not present in other subgroups, nor in regards to maternal vascular malperfusion. ConclusionsMajor forms of CHD are associated with significantly higher cerebral artery RI postnatally, but placental vascular malperfusion lesions may not contribute to this hemodynamic adaptation.

Placental Pathology Contributes to Impaired Volumetric Brain Development in Neonates With Congenital Heart Disease.

Neonates with congenital heart disease are at risk for impaired brain development in utero, predisposing children to postnatal brain injury and adverse long-term neurodevelopmental outcomes. Given the vital role of the placenta in fetal growth, we assessed the incidence of placental pathology in fetal congenital heart disease and explored its association with total and regional brain volumes, gyrification, and brain injury after birth. Placentas from 96 term singleton pregnancies with severe fetal congenital heart disease were prospectively analyzed for macroscopic and microscopic pathology. We applied a placental pathology severity score to relate placental abnormalities to neurological outcome. Postnatal, presurgical magnetic resonance imaging was used to analyze brain volumes, gyrification, and brain injuries. Placental analyses revealed the following abnormalities: maternal vascular malperfusion lesions in 46%, nucleated red blood cells in 37%, chronic inflammatory lesions in 35%, delayed maturation in 30%, and placental weight below the 10th percentile in 28%. Severity of placental pathology was negatively correlated with cortical gray matter, deep gray matter, brainstem, cerebellar, and total brain volumes (r=-0.25 to -0.31, all P<0.05). When correcting for postmenstrual age at magnetic resonance imaging in linear regression, this association remained significant for cortical gray matter, cerebellar, and total brain volume (adjusted R2=0.25-0.47, all P<0.05). Placental pathology occurs frequently in neonates with severe congenital heart disease and may contribute to impaired brain development, indicated by the association between placental pathology severity and reductions in postnatal cortical, cerebellar, and total brain volumes.

PO2_10. CANCELLED: Maternal vascular malperfusion lesions and preeclampsia are associated with microvascular dysfunction, worse cognition and circulating angiogenic biomarkers 8-10 after pregnancy

PO2_10. CANCELLED: Maternal vascular malperfusion lesions and preeclampsia are associated with microvascular dysfunction, worse cognition and circulating angiogenic biomarkers 8-10 after pregnancy

Pregnancy and placental outcomes according to maternal BMI in women with preeclampsia: a retrospective cohort study.

Obesity and preeclampsia share similar patho-mechanisms and can both affect placental pathology. We aimed to investigate pregnancy outcomes in correlation with placental pathology among pregnancies complicated by preeclampsia in three different maternal body mass index (BMI, kg/m2) groups. In this retrospective cohort study, medical and pathological records of patients with preeclampsia and a singleton pregnancy delivered between 2008 and 2021 at a single tertiary medical center were reviewed. Study population was divided into three BMI groups: BMI < 22.6kg/m2 (low BMI group), 22.7 ≤ BMI ≤ 28.0kg/m2 (middle-range BMI group), and BMI > 28.0kg/m2 (high BMI group). Data regarding maternal characteristics, neonatal outcomes, and placental histopathological lesions were compared. The study groups included a total of 295 patients diagnosed with preeclampsia-98, 99, and 98 in the low, middle-range, and high BMI groups respectively. Neonatal birth weight was significantly decreased in the low maternal BMI group compared to both middle and high BMI groups (p = 0.04) with a similar trend seen in placental weight (p = 0.03). Villous changes related to maternal malperfusion were more prevalent in the low and high BMI groups compared to middle-range BMI group (p < 0.01) and composite maternal vascular malperfusion lesions were also more prevalent in the groups of BMI extremities compared to the middle-range BMI group (p < 0.01). Maternal BMI might influence neonatal outcomes and placental pathology in pregnancies complicated by preeclampsia. Both extremes of BMI were associated with higher rates of placental maternal vascular malperfusion. Balanced BMI in women at risk for preeclampsia may reduce the incidence of placental lesions.

Morphological placental findings in women infected with SARS-CoV-2 according to trimester of pregnancy and severity of disease

IntroductionPlacental morphology findings in SARS-CoV-2 infection are considered nonspecific, although the role of trimester and severity of infection are underreported. Therefore, we aimed to investigate abnormal placental morphology, according to these two criteria. MethodsThis is an ancillary analysis of a prospective cohort study of pregnant women with suspected SARS-CoV-2 infection, managed in one maternity, from March 2020 to October 2021. Charting of clinical/obstetric history, trimester and severity of COVID-19 infection, and maternal/perinatal outcomes were done. Placental morphological findings were classified into maternal and fetal circulatory injury and acute/chronic inflammation. We further compared findings with women with suspected disease which tested negative for COVID-19. Diseases’ trimester of infection and clinical severity guided the analysis of confirmed COVID-19 cases. ResultsNinety-one placental discs from 85 women were eligible as a COVID-19 group, and 42 discs from 41 women in negative COVID-19 group. SARS-CoV-2 infection occurred in 68.2% during third trimester, and 6.6% during first; 16.5% were asymptomatic, 61.5% non-severe and 22.0% severe symptomatic (two maternal deaths). Preterm birth occurred in 33.0% (one fetal death). Global maternal vascular malperfusion (MVM) were significant in COVID-19 group whether compared with negative COVID-19 tests group; however, fetal vascular malperfusion lesions and low-grade chronic villitis were not. Three placentas had COVID-19 placentitis. Decidual arteriopathy was associated with infection in first/mid trimester, and chorangiosis in asymptomatic infections. DiscussionPlacental abnormalities after an infection by COVID-19 were more frequent after first/mid-trimester infections. Extensive placental lesions are rare, although they may be more common upon underlying medical conditions.

Placental pathology in pregnancies with late fetal growth restriction and abnormal cerebroplacental ratio

IntroductionLate fetal growth restriction (FGR) is associated with mild growth restriction and normal or mild abnormal doppler flows. The cerebroplacental ratio (CPR) has been demonstrated as more sensitive to hypoxia than its individual components in these fetuses. We hypothesized that abnormal CPR in late FGR is reflected in specific placental vascular malperfusion lesions. MethodsRetrospective cohort study of late FGR newborns between 2012 and 2022 in a tertiary hospital. Overall, 361 cases were included: 104 with pathological CPR (study group), and 257 with normal doppler flows (control group). The primary outcome was a composite of maternal vascular malperfusion lesions (MVM) and fetal vascular malperfusion lesions (FVM). Secondary outcomes were macroscopic placental characteristics and various obstetrical and neonatal outcomes. ResultsThe study group had lower birthweight compared with the normal CPR group (2063.5 ± 470.5 vs. 2351.6 ± 387.4 g. P < 0.0001), higher rates of composite adverse neonatal outcomes (34.2% vs. 22.5%, p < 0.0001), lower mean placental weight (318 ± 71.6 vs. 356.6 ± 76.5 g, p < 0.0001), as well as a higher prevalence of Vascular lesions of MVM (15.3% vs. 5.0%, p = 0.002), villous lesions of FVM (37.5% vs. 24.9%, p = 0.02), and composite FVM lesions (36.5% vs. 25.6%, p = 0.04). On multivariate regression analysis for MVM lesions and composite FVM lesions, abnormal CPR was found as an independent risk factor (aOR 2.17, 95% CI 1.63–4.19, and aOR 1.31, 95% CI 1.09–3.97, respectively). DiscussionsAbnormal CPR in late FGR is reflected in placental histopathologic vascular malperfusion lesions, and the incidence of these lesions is higher than in FGR placentas with normal CPR.

Diminished ovarian reserve is a risk factor for preeclampsia and placental malperfusion lesions

To assess obstetric outcomes and placental findings in pregnancies attained by invitro fertilization (IVF) in patients with diminished ovarian reserve (DOR). Retrospective cohort study. University-affiliated tertiary hospital. DOR, defined as an antral follicle count (AFC) of 6 or less (DOR group), compared with patients with no DOR and an antral count above 6 (control group). Live singleton births after IVF between 2009 and2017. Primary outcomes were placental findings, including anatomic, inflammatory, vascular malperfusion, and villous maturation lesions, as categorized according to the Amsterdam Placental Workshop Group Consensus. Secondary outcomes included obstetric and perinatal outcomes. A total of 110 deliveries of patients with DOR were compared with 772 controls. Maternal age was higher in the DOR group than in the control group (36.3 ± 4.4 years vs. 35.3 ± 4.1 years, P=.02). Patients with DOR were more likely to have a diagnosis of endometriosis (P=.02) and less likely to have a diagnosis of male factor (P<.001), ovulation disorder (P<.001), or tubal factor (P=.04), or a transfer of a blastocyte (P=.007). After adjustment for confounders, pregnancies in the DOR group were notable for a significantly higher rate of preeclampsia (8.1% vs. 2.7%, adjusted odds ratio: 3.05, 95% confidence interval: 1.33-6.97). On placental examination, DOR was associated with a higher rate of fetal vasculopathy (P=.01) and multiple fetal vascular malperfusion lesions (P=.03), and a lower rate of circummarginate insertion (P=.01) and intervillous thrombosis (P=.02). DOR, specifically defined as an AFC of 6 or less, is associated with a higher incidence of preeclampsia and multiple placental fetal vascular lesions.

Cumulative effect of maternal vascular malperfusion types in the placenta on adverse pregnancy outcomes

IntroductionPlacental vascular disease, characterized by Maternal Vascular Malperfusion (MVM) lesions, is considered to be the underlying cause of pregnancy complications. Aim is to evaluate the relationship between the cumulative number of MVM lesion types, and adverse pregnancy- and neonatal outcomes. MethodsThis retrospective cohort study included 272 women with singleton gestations who gave birth at a Dutch tertiary hospital between 2017 and 2018 with available placental histopathology reports. Analyzed according to the Amsterdam Placental Workshop Group Consensus Statement, placentas were divided into groups based on the cumulative number of MVM lesions: no lesions (n = 124), 1–2 types (n = 124) and 3–5 types of lesions (n = 24). ResultsThe proportion of placenta syndrome (PS) was highest (95.8%) in the 3–5 MVM lesions group (p < 0.001). The presence of MVM lesions was highly associated with PS during pregnancy (aOR 6.81, 95% CI 3.76–12.33). Furthermore, every additional type of MVM lesion corresponded with a threefold increased odds for the occurrence of PS (aOR 3.00, 95% CI 2.10–4.29). The group with 3–5 types of MVM lesions showed the highest incidence of adverse neonatal outcomes, lower mean birth weight, prolonged hospitalization, NICU admissions and neonatal deaths (aOR 6.47, 95% CI 0.33–127.68), corresponding with a fourfold increased odds for the occurrence of neonatal death for every additional MVM lesion (aOR 4.19, 95% CI 1.39–12.68). DiscussionA higher number of MVM lesion types is strongly associated with an increased incidence of adverse pregnancy- and neonatal outcomes, indicating that guidelines should focus also on the amount of MVM lesion types for the monitoring/management of subsequent pregnancies.

Placental dysfunction influences fetal monocyte subpopulation gene expression in preterm birth.

The placenta is the primary organ for immune regulation, nutrient delivery, gas exchange, protection against environmental toxins, and physiologic perturbations during pregnancy. Placental inflammation and vascular dysfunction during pregnancy are associated with a growing list of prematurity-related complications. The goal of this study was to identify differences in gene expression profiles in fetal monocytes — cells that persist and differentiate postnatally — according to distinct placental histologic domains. Here, by using bulk RNA-Seq, we report that placental lesions are associated with gene expression changes in fetal monocyte subsets. Specifically, we found that fetal monocytes exposed to acute placental inflammation upregulate biological processes related to monocyte activation, monocyte chemotaxis, and platelet function, while monocytes exposed to maternal vascular malperfusion lesions downregulate these processes. Additionally, we show that intermediate monocytes might be a source of mitogens, such as HBEGF, NRG1, and VEGFA, implicated in different outcomes related to prematurity. This is the first study to our knowledge to show that placental lesions are associated with unique changes in fetal monocytes and monocyte subsets. As fetal monocytes persist and differentiate into various phagocytic cells following birth, our study may provide insight into morbidity related to prematurity and ultimately potential therapeutic targets.

Placental vascular malperfusion lesions in fetal congenital heart disease

Fetuses with congenital heart disease are at increased risk of perinatal morbidity and mortality, which is highly influenced by their prenatal health. Placental function is vital for the health of the fetus, but increased rates of pathologic lesions of the placenta have been observed in pregnancies complicated by fetal congenital heart disease. This study aimed to determine the prevalence of both gross and histologic placental pathologies in a cohort of pregnancies complicated by fetal congenital heart disease vs healthy controls using the Amsterdam Placental Workshop Group Consensus Statement sampling and definitions of placental lesions. This single-center retrospective cohort study included placental examinations from pregnancies diagnosed prenatally with fetal congenital heart disease between 2010 and 2019; moreover, control placentas were collected from pregnancies without maternal or fetal complications. Placentas were sampled and evaluated according to the Amsterdam Placental Workshop Group Consensus Statement and gross and histopathologic diagnoses determined. Approximately 80% of fetuses diagnosed with congenital heart disease (n=305) had a placental examination for comparison with controls (n=40). Of note, 239 placentas (78%) in the group with fetal congenital heart disease had at least 1 gross or histopathologic lesion compared with 11 placentas (28%) in the control group (P<.01). One-third of placentas complicated by fetal congenital heart disease met the criteria for small for gestational age, and 48% of placentas had one or more chronic lesions, including maternal vascular malperfusion (23% vs 0%; P<.01), villitis of unknown etiology (22% vs 0%; P<.01), fetal vascular malperfusion (20% vs 0%; P<.01), and other chronic lesions (16% vs 0%; P<.01). Acute inflammation was equally present in both the group with fetal congenital heart disease and the control group (28% vs 28%; P=1.00). Although gestational age and birthweight z score were similar between the 2 groups, birth head circumference was 1.5 cm less in pregnancies complicated by fetal congenital heart disease with a significantly lower z score compared with the control group (-0.52±1.22 vs 0.06±0.69; P<.01). Vascular malperfusion lesions and chronic forms of inflammation occur at markedly higher rates in placentas complicated by fetal congenital heart disease, which may contribute to the decreased head circumference at birth. Further work in neuroplacentology is needed to explore connections among cardiac defects, placental vascular malperfusion lesions, and fetal brain development.

Is there a difference in placental pathology in pregnancies complicated with gestational diabetes A2 versus gestational diabetes A1, versus one abnormal value, on 100 gr glucose tolerance test?

The objective of the study was to investigate pregnancy outcome and placental pathology lesions among patients with gestational diabetes mellitus (GDM) versus patients with one abnormal value (OAV), in the oral glucose tolerance test (OGTT). A prospective study was performed from 2016 to 2019. All participants performed an OGTT between 24 and 28 weeks. Included patients who delivered at term (>37 weeks) with the diagnosis of GDMA2 (treated with insulin), GDMA1 (controlled with diet) and those with OAV. Maternal characteristics, pregnancy outcomes, and placental histopathology reports were compared between the GDMA2, GDMA1, and OAV groups. Placental lesions were classified according to "Amsterdam" criteria to maternal and fetal vascular malperfusion (MVM, FVM) lesions, and inflammatory lesions. The GDMA2 group (n=59) was characterized by higher maternal BMI (p<0.001), increased rate of chronic hypertension (p<0.01), cesarean delivery (CD) (p<0.001), adverse neonatal outcomes (p<0.001) and prolonged hospitalization (p<0.001) as compared to the GDMA1 (n=73) and the OAV group (n=124). Average placental weight in the GDMA2 group were higher (p=0.004). There were no between groups differences in the rate of placental MVM or inflammatory lesions. The OAV and GDMA1 groups were characterized by an increased rate of FVM lesions, as compared to the GDMA2 group (p=0.02). GDMA2 is associated with increased rate of CD and adverse neonatal outcome. The similar rate of placental MVM lesions among the study groups, and the increased rate of FVM lesions observed among the OAV group, implies of impaired placental function among the OAV group as in GDM pregnancies.

Placental Pathology in Maternal Ornithine Transcarbamylase Deficiency.

Ornithine transcarbamylase (OTC) deficiency is the most common urea cycle disorder, inherited in an X-linked manner. Males are severely affected. Female phenotypes vary from asymptomatic to severe, and symptoms may be triggered by high metabolic states like childbirth. Literature on OTC deficiency in pregnancy and placental pathology is limited. Pathology records were searched at a single referral center from 2000-2020 and identified three placental cases from two mothers heterozygous for OTC deficiency. Placental pathology and maternal and neonatal history were reviewed in detail. The placenta from one symptomatic mother carrying an affected male fetus showed widespread high-grade fetal vascular malperfusion (FVM) lesions of varying age. These lesions were not seen in the two placentas from the asymptomatic mother. In cases of symptomatic maternal OTC deficiency, our findings highlight the need for placental examination. Since thrombotic events in the placenta have the potential to associate with fetal and neonatal endothelial damage, a high index of suspicion for neonatal thrombosis may be warranted.

Maternal Vascular Lesions in the Placenta Predict Vascular Impairments a Decade After Delivery.

Women with adverse pregnancy outcomes later experience excess hypertension and cardiovascular disease, but how the events are linked is unknown. Examination of the placenta may provide clues to vascular impairments after delivery. Maternal vascular malperfusion lesions (MVMs) were abstracted from clinical reports, validated and characterized using clinical guidelines and severity score. A total of 492 women (170 with MVMs and 322 without MVMs) participated in a study visit 8 to 10 years after delivery to assess blood pressure, cardiometabolic factors, and sublingual microvascular features using sidestream dark field imaging. Covariates included age, race, adverse pregnancy outcomes (preeclampsia, small for gestational age, and preterm birth), and health behaviors. Women with versus without MVM had a distinct sublingual microvascular profile comprised of (1) lower microvascular density (-410 μm/mm2, P=0.015), (2) higher red blood cell filling as a marker of perfusion (2%, P=0.004), and (3) smaller perfused boundary region (-0.07 µm, P=0.025) as a measure of glycocalyx integrity, adjusted for covariates including adverse pregnancy outcomes. Women with MVM also had higher adjusted diastolic blood pressure (+2.6 mm Hg, P=0.021), total and LDL (low-density lipoprotein)-cholesterol (+11.2 mg/dL, P=0.016; +8.7 mg/dL, P=0.031). MVM associations with subsequent cardiovascular measures did not vary by type of adverse pregnancy outcome, except among women with preterm births where blood pressure was higher only among those with MVM. Results were similar when evaluated as MVM severity. A decade after delivery, women with placental vascular lesions had an adverse cardiovascular profile comprised of microvascular rarefaction, higher blood pressure and more atherogenic lipids. Placental histopathology may reveal a woman's early trajectory toward subsequent vascular disease.

Placental pathology in a pregnant woman with severe COVID-19 and successful ECMO treatment: a case report

BackgroundInfection with SARS-CoV-2 during pregnancy can lead to a severe condition in the patient, which is challenging for obstetricians and anaesthesiologists. Upon severe COVID-19 and a lack of improvement after multidrug therapy and mechanical ventilation, extracorporeal membrane oxygenation (ECMO) is introduced as the last option. Such treatment is critical in women with very preterm pregnancy when each additional day of the intrauterine stay is vital for the survival of the newborn.Case presentationWe report a case of a 38-year-old woman at 27 weeks of gestation treated with multidrug therapy and ECMO. The woman was admitted to the intensive care unit (ICU) with increasing fever, cough and dyspnoea. The course of the pregnancy was uncomplicated. She was otherwise healthy. At admission, she presented with severe dyspnoea, with oxygen saturation (SpO2) of 95% on passive oxygenation, heart rate of 145/min, and blood pressure of 145/90. After confirmation of SARS-CoV-2 infection, she received steroids, remdesivir and convalescent plasma therapy. The foetus was in good condition. No signs of an intrauterine infection were visible. Due to tachypnea of 40/min and SpO2 of 90%, the woman was intubated and mechanically ventilated. Due to circulatory failure, the prothrombotic activity of the coagulation system, further saturation worsening, and poor control of sedation, she was qualified for veno-venous ECMO. An elective caesarean section was performed at 29 weeks on ECMO treatment in the ICU. A preterm female newborn was delivered with an Apgar score of 7 and a birth weight of 1440 g. The newborn had no laboratory or clinical evidence of COVID-19. The placenta showed the following pathological changes: large subchorionic haematoma, maternal vascular malperfusion, marginal cord insertion, and chorangioma.ConclusionsThis case presents the successful use of ECMO in a pregnant woman with acute respiratory distress syndrome in the course of severe COVID-19. Further research is required to explain the aetiology of placental disorders (e.g., maternal vascular malperfusion lesions or thrombotic influence of COVID-19). ECMO treatment in pregnant women remains challenging; thus, it should be used with caution. Long-term assessment may help to evaluate the safety of the ECMO procedure in pregnant women.

SARS-CoV-2 and Placental Pathology: Malperfusion Patterns Are Dependent on Timing of Infection During Pregnancy.

The extent to which severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection at different points in the pregnancy timeline may affect maternal and fetal outcomes remains unknown. We sought to characterize the impact of SARS-CoV-2 infection proximate and remote from delivery on placental pathology. We performed a secondary analysis of placental pathology from a prospective cohort of universally tested SARS-CoV-2 positive women >20 weeks gestation at 1 institution. Subjects were categorized as having acute or nonacute SARS-CoV-2 based on infection <14 or ≥14 days from delivery admission, respectively, determined by nasopharyngeal swab, symptom history, and serologies, when available. A subset of SARS-CoV-2 negative women represented negative controls. Placental pathology was available for 90/97 (92.8%) of SARS-CoV-2 positive women, of which 26 were from women with acute SARS-CoV-2 infection and 64 were from women with nonacute SARS-CoV-2. Fetal vascular malperfusion lesions were significantly more frequent among the acute SARS-CoV-2 group compared with the nonacute SARS-CoV-2 group (53.8% vs. 18.8%; P=0.002), while frequency of maternal vascular malperfusion lesions did not differ by timing of infection (30.8% vs. 29.7%; P>0.99). When including 188 SARS-CoV-2 negative placentas, significant differences in frequency of fetal vascular malperfusion lesions remained between acute, nonacute and control cases (53.8% vs. 18.8% vs. 13.2%, respectively; P<0.001). No differences were noted in obstetric or neonatal outcomes between acutely and nonacutely infected women. Our findings indicate timing of infection in relation to delivery may alter placental pathology, with potential clinical implications for risk of thromboembolic events and impact on fetal health.

Passively inhaled tobacco smoke - pregnancy and neonatal outcomes in correlation with placental histopathology

IntroductionWe aimed to investigate the effect of maternal passive smoking (MPS) during pregnancy-on placental pathology and pregnancy outcomes. MethodsA prospective case-control study. We recruited low-risk laboring women at 37+0–41 + 0 weeks between 9/2019–7/2020. MPS was defined as exposure to in-house spouse tobacco smoking of >20 cigarettes/day in the absence of maternal active-smoking. In attempt to “purify” the effect of MPS on placental pathology-we excluded cases with preeclampsia, diabetes, suspected fetal growth restriction (FGR), preterm labor, and illicit drug use. Maternal characteristics, pregnancy outcomes, and placental pathology were compared between the MPS group and a control group matched for gestational age, maternal age, and delivery date. Placental lesions were classified according to the “Amsterdam” criteria. The study was powered to detect a 33% difference in placental malperfusion lesions. Multivariable regression was performed to identify independent associations with placental malperfusion lesions. ResultsIn labor, the MPS group (n = 115) had higher rates of meconium stained amniotic fluid (MSAF, p < 0.001) and non-reassuring fetal heart-rate (NRFHR,p = 0.006), compared to controls (n = 115). Neonates in the MPS group had higher rates of undiagnosed FGR (p = 0.01) and NICU admissions (p = 0.004). The MPS group had higher rates of placental-hypoplasia (p = 0.02) and fetal vascular malperfusion (FVM) lesions (p = 0.04). In regression analysis MPS was associated with FVM lesions independent of background confounders (aOR = 1.24 95% CI 1.10–2.65). DiscussionIn otherwise low-risk pregnancies, MPS was associated with higher rates of MSAF, NRFHR, undiagnosed FGR, and NICU admissions, probably mediated via placental FVM. These worrisome findings mandate patient counseling and further investigation in larger population-based studies.

The association between maternal placental growth factor and placental maternal vascular malperfusion lesions

IntroductionPlacental Growth Factor (PlGF) is used for the prediction of preeclampsia (PE), a syndrome associated with maternal vascular malperfusion (MVM). Our goal is to determine the correlation between PlGF and MVM. Material and methodsWe performed a secondary analysis of the PEARL study that included nulliparous women with PE (cases), and low-risk nulliparous women recruited in early pregnancy (controls). All participants provided blood samples at diagnosis of PE (cases), or between 26 and 34 weeks (controls) for measurement of PlGF (B·R·A·H·M·S plus KRYPTOR automated assays), that was transformed into multiple of median (MoM). Placental examination was performed for the diagnosis of MVM based on the Amsterdam Placental Workshop Group Consensus Statement. Nonparametric tests and receiver operating characteristic (ROC) curves were used to compare PlGF in pregnancies with, and without PE, stratified by the presence of MVM. ResultsThird trimester PlGF was lower in PE cases with MVM (N = 20; median: 0.04 MoM; interquartile: 0.03–0.09; p<0.0001), and in controls with MVM (N = 4; 0.30MoM; 0.07–0.52; p = 0.002) compared to controls without MVM (N = 29; 0.99 MoM; 0.67–1.52). PlGF in PE cases without MVM (N = 5; 0.18 MoM; 0.17–1.64) was not significantly different than in controls without MVM but the sample size was small. ROC curve demonstrated a greater predictability of PlGF for PE with MVM than PE without MVM (AUC: 0.99 vs. 0.38; p<0.0001). DiscussionThird trimester PlGF is a better predictor of PE associated with MVM than a predictor of PE without MVM. We hypothesize that PlGF is a stronger marker of MVM than PE.

Effects of ‘rescue’ dose of antenatal corticosteroids on placental histopathology in preterm births

IntroductionAntenatal corticosteroids (ACS) are frequently used to reduce neonatal morbidity in preterm births (PTBs). A ‘rescue’ dose of ACS can be administer, if the risk of PTB remains. Some reports indicated that repeated doses of ACS might impact placental histology and possibly its function. We aimed to study whether repeated doses of ACS effect placental histopathology and pregnancy outcome. MethodsThe medical files and placental reports of all PTB, at 24-336/7 weeks, between Nov 2008–Dec 2019, were reviewed. The study population was divided into three groups; no-ACS (PTBs without ACS treatment), one-ACS (PTBs after a full or partial ACS course), and rescue-ACS (PTBs after a ‘rescue’ course of ACS). Placental lesions were classified according to “Amsterdam” criteria into maternal and fetal vascular malperfusion lesions, maternal and fetal inflammatory responses and chronic villitis. Placental lesions and pregnancy outcome were compared between the study groups. ResultsThe no-ACS group (n = 58) was characterized by increased rates of PTB<28 weeks (p = 0.003), perinatal death (p < 0.001) and composite neonatal infectious morbidity (p = 0.022), as compared to the one-ACS group (n = 331) and the rescue-ACS group (n = 53). Placental MIR lesions were more common among the rescue-ACS group, compared to the one- and no-ACS groups (p = 0.022). Other placental lesions did not differ between the groups. On multivariate logistic regression analysis, MIR lesions were independently associated with rescue-ACS treatment (aOR 3.00, 95% CI 1.10–8/17, p = 0.031). DiscussionRescue course of ACS is associated with increased rate of placental maternal inflammatory response. These findings probably result from maternal stress stimuli without an adverse impact on early neonatal outcome.