Recombinant ADAMTS13 for Hereditary Thrombotic Thrombocytopenic Purpura

New England Journal of Medicine, Год журнала: 2022, Номер 387(25), С. 2356 - 2361

Опубликована: Дек. 21, 2022

A 27-year-old patient with a history of severe obstetrical complications and arterial thrombosis received diagnosis hereditary thrombotic thrombocytopenic purpura (TTP) due to ADAMTS13 deficiency when she presented an acute episode in the 30th week her second pregnancy. When TTP became plasma-refractory fetal death was imminent, weekly injections recombinant at dose 40 U per kilogram body weight were initiated. The patient's platelet count normalized, growth fetus stabilized. At 37 weeks 1 day gestation, small-for-gestational-age boy delivered by cesarean section. time this report, son well, continued receive every 2 weeks. (Funded Swiss National Science Foundation.).

Язык: Английский

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Placental pathology and neonatal encephalopathy

International Journal of Gynecology & Obstetrics, Год журнала: 2022, Номер 160(1), С. 22 - 27

Опубликована: Июнь 13, 2022

Neonatal encephalopathy (NE) is an important cause of neonatal morbidity and mortality worldwide; however, there remain gaps in our knowledge about its pathogenesis. The placenta has been implicated the pathogenesis this disease but conclusive evidence related to placental factors that influence it sparse. This review aims outline current on role with particular attention NE as a consequence hypoxia-ischemia. A total 26 original articles/review papers were used compile review. Three themes identified from these publications: fetal vascular malperfusion including umbilical cord pathology, inflammatory changes placenta, maternal weight. These features being significant development NE. Advancing understanding relationship between pathology may facilitate additional antenatal screening better identify at-risk fetuses. We highlight areas for further research through histology.

Язык: Английский

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

Journal of the American Heart Association, Год журнала: 2024, Номер 13(5)

Опубликована: Фев. 29, 2024

Background Neonates with congenital heart disease are at risk for impaired brain development in utero, predisposing children to postnatal injury and adverse long‐term neurodevelopmental outcomes. Given the vital role of placenta fetal growth, we assessed incidence placental pathology explored its association total regional volumes, gyrification, after birth. Methods Results Placentas from 96 term singleton pregnancies severe were prospectively analyzed macroscopic microscopic pathology. We applied a severity score relate abnormalities neurological outcome. Postnatal, presurgical magnetic resonance imaging was used analyze injuries. Placental analyses revealed following abnormalities: maternal vascular malperfusion lesions 46%, nucleated red blood cells 37%, chronic inflammatory 35%, delayed maturation 30%, weight below 10th percentile 28%. Severity negatively correlated cortical gray matter, deep brainstem, cerebellar, volumes ( r =−0.25 −0.31, all P <0.05). When correcting postmenstrual age linear regression, this remained significant volume (adjusted R 2 =0.25–0.47, Conclusions occurs frequently neonates may contribute development, indicated by between reductions cortical, volumes.

Язык: Английский

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Behind the Curtain of Abnormal Placentation in Pre-Eclampsia: From Molecular Mechanisms to Histological Hallmarks

International Journal of Molecular Sciences, Год журнала: 2024, Номер 25(14), С. 7886 - 7886

Опубликована: Июль 18, 2024

Successful human pregnancy needs several highly controlled steps to guarantee an oocyte’s fertilization, the embryo’s pre-implantation development, and its subsequent implantation into uterine wall. The placenta development ensures adequate fetal nutrition oxygenation, with trophoblast being first cell lineage differentiate during this process. sustains growth of fetus by providing it oxygen nutrients removing waste products. It is not surprising that issues early can lead common disorders, such as recurrent miscarriage, restriction, pre-eclampsia, stillbirth. Understanding normal essential for recognizing contextualizing any pathological aberrations may occur. effects these become apparent until later in pregnancy, mid or advanced stages. This review discusses process embryo phase, molecular mechanisms involved, abnormalities those are thought contribute pre-eclampsia. also covers histological hallmarks pre-eclampsia found examination placental tissue from patients.

Язык: Английский

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Pathologic placental lesions in early and late fetal growth restriction

Acta Obstetricia Et Gynecologica Scandinavica, Год журнала: 2019, Номер 98(12), С. 1585 - 1594

Опубликована: Авг. 1, 2019

The purpose of the study was to evaluate differences in individual histopathologic placental lesions pregnancies complicated by early-onset (<32 weeks at diagnosis) and late-onset (≥32 fetal growth restriction (FGR).A cohort 440 singleton FGR, diagnosed according standard ultrasonographic criteria, followed up delivered same institution between 2010 2016. Placental were classified Amsterdam Workshop Consensus Criteria. Pathologic examination placentas from 113 healthy term served as controls. Binary multinomial logistic regression models used independent association with type FGR.In our prevalences early late FGR 37.3% (164/440) 62.7% (276/440), respectively. overall rates preeclampsia (69/164 vs 59/276, P < 0.01) absent/reversed umbilical artery pulsatility indices (61/164 14/276, 0.001) higher among than FGR. characteristics differed mainly regard maternal vascular malperfusion scores rather scores, found be a cofactor modulating severity associated lesions. In binary analysis, recent infarcts (OR 2.44, 95% CI 1.2-5), distal villous hypoplasia 1.8, 1.0-3.2), atherosis 2.71, 1.35-5.47), persistent endovascular trophoblasts 1.67, 1.03-2.7), reduced fetal/placental weight score 0.27, 0.2-0.38) independently an increased likelihood compared sensitivity, specificity, area under curve model 60% (95% 51.2-66.2), 89.1% 84.9-92.3), 0.81 0.77-0.85), respectively, suggesting fair good predictive value.Individual suggestive ischemia, defective remodeling spiral arteries, peripheral hypoxia interfering villus development, efficiency significantly more common

Язык: Английский

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Disorders of placental villous maturation in fetal death

Journal of Perinatal Medicine, Год журнала: 2020, Номер 0(0)

Опубликована: Апрель 1, 2020

Objective The aims of this study were to ascertain the frequency disorders villous maturation in fetal death and also delineate other placental histopathologic lesions death. Methods This was a retrospective observational cohort deaths occurring among women between January 2004 2016 at Hutzel Women's Hospital, Detroit, MI, USA. Cases comprised fetuses with beyond 20 weeks' gestation. Fetal congenital anomalies multiple gestations excluded. Controls included pregnant without medical/obstetrical complications delivered singleton, term (37-42 weeks) neonate 5-min Apgar score ≥7 birthweight 10th 90th percentiles. Results Ninety-two percent (132/143) placentas showed histologic lesions. associated (1) higher [44.0% (64/143) vs. 1.0% (4/405), P < 0.0001, prevalence ratio, 44.6; delayed maturation, 22% (31/143); accelerated 20% (28/143); arrest, 4% (5/143)]; (2) maternal vascular malperfusion [75.5% (108/143) 35.7% (337/944), 2.1] [88.1% (126/143) 19.7% (186/944), 4.5]; (3) patterns suggestive hypoxia [59.0% (85/143) 9.3% (82/942), 6.8]; (4) chronic inflammatory [53.1% (76/143) 29.9% (282/944), 0.001, ratio 1.8]. Conclusion demonstrates that 44 times more likely present compared those normal pregnancy. suggests burden is substantial.

Язык: Английский

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Magnetic resonance imaging measurement of placental perfusion and oxygen saturation in early‐onset fetal growth restriction

BJOG An International Journal of Obstetrics & Gynaecology, Год журнала: 2020, Номер 128(2), С. 337 - 345

Опубликована: Июнь 30, 2020

We hypothesised that a multi-compartment magnetic resonance imaging (MRI) technique is sensitive to fetal blood oxygenation would identify changes in placental volume and pregnancies complicated by early-onset growth restriction (FGR).Case-control study.London, UK.Women with uncomplicated (estimated weight [EFW] >10th centile for gestational age [GA] normal maternal Doppler ultrasound, n = 12) or FGR (EFW <3rd without abnormal ultrasound <32 weeks GA, were studied.All women underwent MRI examination. Using technique, we quantified feto-placental oxygenation.Disease severity was stratified according pulsatility index the relationship parameters investigated, including influence of GA at scan.The group (mean 27+5 weeks, range 24+2 33+6 weeks) had significantly lower EFW compared control 29+1 weeks; -705 g, 95% CI -353 -1057 g). MRI-derived oxygen saturation higher controls (75 ± 9.6% versus 56 16.2%, P 0.02, 7.8-30.3%). Feto-placental estimation correlated strongly scan (r -0.83).Using novel multimodal protocol demonstrated reduced FGR. The degree abnormality disease defined findings. Gestational age-dependent also present pregnancies.MRI reveals differences between pregnancy associated severity.

Язык: Английский

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SARS-CoV-2 and Placental Pathology

The American Journal of Surgical Pathology, Год журнала: 2021, Номер 46(1), С. 51 - 57

Опубликована: Июль 26, 2021

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

Язык: Английский

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Maternal and fetal vascular lesions of malperfusion in the placentas associated with fetal and neonatal death: results of a prospective observational study

American Journal of Obstetrics and Gynecology, Год журнала: 2021, Номер 225(6), С. 660.e1 - 660.e12

Опубликована: Июнь 8, 2021

Язык: Английский

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Modeling preeclampsia using human induced pluripotent stem cells

Scientific Reports, Год журнала: 2021, Номер 11(1)

Опубликована: Март 15, 2021

Abstract Preeclampsia (PE) is a pregnancy-specific hypertensive disorder, affecting up to 10% of pregnancies worldwide. The primary etiology considered be abnormal development and function placental cells called trophoblasts. We previously developed two-step protocol for differentiation human pluripotent stem cells, first into cytotrophoblast (CTB) progenitor-like then both syncytiotrophoblast (STB)- extravillous trophoblast (EVT)-like showed that it can model normal differentiation. have now applied this induced (iPSC) derived from placentas with or without PE. While there were no differences in CTB induction EVT formation, PE-iPSC-derived defect syncytialization, as well blunted response hypoxia. RNAseq analysis defects STB formation hypoxia; however, DNA methylation changes minimal, corresponding only Overall, PE-iPSC recapitulated multiple associated dysfunction, including lack decreased oxygen tension. This emphasizes the importance maternal microenvironment placentation, highlights potential pathways targeted diagnosis therapy, while absence marked suggests other regulatory mechanisms mediate these alterations.

Язык: Английский

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