Cerebral palsy (CP) is the most common motor disability in childhood. This syndrome is the manifestation of intrauterine pathologies, intrapartum complications and post-natal sequel, especially among preterm neonates. A double hit model theory is proposed suggesting that an intrauterine condition along with intrapartum or postnatal insult lead to the development of CP. Recent reports demonstrated that treatment during the process of preterm birth like magnesium sulfate and post-natal modalities such as cooling may prevent or reduce the prevalence of this syndrome. Moreover, animal model demonstrated that post-natal treatment with anti-inflammatory drugs coupled with nanoparticles may affect the course of the disease in pups with neuroinflammation. The current review would describe the changes in the epidemiology of this disease, the underlying prenatal mechanisms, and possible treatments that may reduce the prevalence of CP and alter the course of disease.

The objectives of this study were: 1) To determine the component needed to generate a validated DIC score during pregnancy. 2) To validate such scoring system in the identification of patients with clinical diagnosis of DIC. This is a population based retrospective study, including all women who gave birth at the ‘Soroka University Medical Center’ during the study period, and have had blood coagulation tests including complete blood cell count, prothrombin time (PT)(seconds), partial thromboplastin time (aPTT), fibrinogen, and D-dimers. Nomograms for pregnancy were established, and DIC score was constructed based on ROC curve analyses. 1) maternal plasma fibrinogen concentrations increased during pregnancy; 2) maternal platelet count decreased gradually during gestation; 3) the PT and PTT values did not change with advancing gestation; 4) PT difference had an area under the curve (AUC) of 0.96 (p<0.001), and a PT difference ≥1.55 had an 87% sensitivity and 90% specificity for the diagnosis of DIC; 5) the platelet count had an AUC of 0.87 (p<0.001), an 86% sensitivity and 71% specificity for the diagnosis of DIC; 6) fibrinogen concentrations had an AUC of 0.95 (p<0.001) and a cutoff point ≤3.9 g/L had a sensitivity of 87% and a specificity of 92% for the development of DIC; and 7) The pregnancy adjusted DIC score had an AUC of 0.975 (p<0.001) and at a cutoff point of ≥26 had a sensitivity of 88%, a specificity of 96%, a LR(+) of 22 and a LR(−) of 0.125 for the diagnosis of DIC. We could establish a sensitive and specific pregnancy adjusted DIC score. The positive likelihood ratio of this score suggests that a patient with a score of ≥26 has a high probability to have DIC.

Obstetrical hemorrhage and especially DIC (disseminated intravascular coagulation) is a leading cause for maternal mortality across the globe, often secondary to underlying maternal and/or fetal complications including placental abruption, amniotic fluid embolism, HELLP syndrome (hemolysis, elevated liver enzymes and low platelets), retained stillbirth and acute fatty liver of pregnancy. Various obstetrical disorders can present with DIC as a complication; thus, increased awareness is key to diagnosing the condition. DIC patients can present to clinicians who may not be experienced in a variety of aspects of thrombosis and hemostasis. Hence, DIC diagnosis is often only entertained when the patient already developed uncontrollable bleeding or multi-organ failure, all of which represent unsalvageable scenarios. Beyond the clinical presentations, the main issue with DIC diagnosis is in relation to coagulation test abnormalities. It is widely believed that in DIC, patients will have prolonged prothrombin time (PT) and partial thromboplastin time (PTT), thrombocytopenia, low fibrinogen, and raised D-dimers. Diagnosis of DIC can be elusive during pregnancy and requires vigilance and knowledge of the physiologic changes during pregnancy. It can be facilitated by using a pregnancy specific DIC score including three components: 1) fibrinogen concentrations; 2) the PT difference – relating to the difference in PT result between the patient’s plasma and the laboratory control; and 3) platelet count. At a cutoff of ≥ 26 points, the pregnancy specific DIC score has 88% sensitivity, 96% specificity, a positive likelihood ratio (LR) of 22, and a negative LR of 0.125. Management of DIC during pregnancy requires a prompt attention to the underlying condition leading to this complication, including the delivery of the patient, and correction of the hemostatic problem that can be guided by point of care testing adjusted for pregnancy.

Purpose: To determine whether previously established mRNA signatures are predictive of early preeclampsia when evaluated by maternal cellular transcriptome analysis in samples collected before clinical manifestation. Materials and methods: We profiled gene expression at exon-level resolution in whole blood samples collected longitudinally from 49 women with normal pregnancy (controls) and 13 with early preeclampsia (delivery <34 weeks of gestation). After preprocessing and removal of gestational age-related trends in gene expression, data were converted into Z-scores based on the mean and standard deviation among controls for six gestational-age intervals. The average Z-scores of mRNAs in each previously established signature considered herein were compared between cases and controls at 9–11, 11–17, 17–22, 22–28, 28–32, and 32–34 weeks of gestation. Results: (1) Average expression of the 16-gene untargeted cellular mRNA signature was higher in women diagnosed with early preeclampsia at 32–34 weeks of gestation, yet more importantly, also prior to diagnosis at 28–32 weeks and 22–28 weeks of gestation, compared to controls (all, p < .05). (2) A combination of four genes from this signature, including a long non-protein coding RNA [H19 imprinted maternally expressed transcript (H19)], fibronectin 1 (FN1), tubulin beta-6 class V (TUBB6), and formyl peptide receptor 3 (FPR3) had a sensitivity of 0.85 (0.55–0.98) and a specificity of 0.92 (0.8–0.98) for prediction of early preeclampsia at 22–28 weeks of gestation. (3) H19, FN1, and TUBB6 were increased in women with early preeclampsia as early as 11–17 weeks of gestation (all, p < .05). (4) After diagnosis at 32–34 weeks, but also prior to diagnosis at 11–17 weeks, women destined to have early preeclampsia showed a coordinated increase in whole blood expression of several single-cell placental signatures, including the 20-gene signature of extravillous trophoblast (all, p < .05). (5) A combination of three mRNAs from the extravillous trophoblast signature (MMP11, SLC6A2, and IL18BP) predicted early preeclampsia at 11–17 weeks of gestation with a sensitivity of 0.83 (0.52–0.98) and specificity of 0.94 (0.79–0.99). Conclusions: Circulating early transcriptomic markers for preeclampsia can be found either by untargeted profiling of the cellular transcriptome or by focusing on placental cell-specific mRNAs. The untargeted cellular mRNA signature was consistently increased in early preeclampsia after 22 weeks of gestation, and individual mRNAs of this signature were significantly increased as early as 11–17 weeks of gestation. Several single-cell placental signatures predicted future development of the disease at 11–17 weeks and were also increased in women already diagnosed at 32–34 weeks of gestation.