Neonatal Intracranial Hemorrhage Research Articles

Incidence and clinical analysis of asymptomatic intracranial hemorrhage in neonates with cerebral hypoxic-ischaemic risk based on multisequence MR images

The incidence and clinical distribution of intracranial haemorrhage (ICH) in neonates at risk of cerebral hypoxia–ischaemia have not been reported in specific studies. Based on conventional magnetic resonance imaging (MRI) versus susceptibility weighted imaging (SWI), this study aimed to analyse the occurrence of asymptomatic ICH in newborns with or without risk of cerebral hypoxia–ischaemia and to accumulate objective data for clinical evaluations of high-risk neonates and corresponding response strategies. 317 newborns were included. MRI revealed that the overall incidence of ICH was 59.31%. The most common subtype was intracranial extracerebral haemorrhage (ICECH) which included subarachnoid haemorrhage (SAH) and subdural haemorrhage (SDH). ICECH accounted for 92.02% of ICH. The positive detection rate of ICECH by SWI was significantly higher than that by T1WI. The incidence of total ICH, ICECH and SAH was greater among children who were delivered vaginally than among those who underwent caesarean delivery. Asymptomatic neonatal ICH may be a common complication of the neonatal birth process, and SWI may improve the detection rate. Transvaginal delivery and a weight greater than 2500 g were associated with a high incidence of ICECH in neonates. The impact of neonatal cerebral hypoxia–ischaemia risk factors on the occurrence of asymptomatic ICH may be negligible.

Intracranial Hemorrhage in Neonates: Causes, Diagnosis, and Management

Intracranial Hemorrhage in Neonates: Causes, Diagnosis, and Management

COL4A1 gene mutations and perinatal intracranial hemorrhage in neonates: case reports and literature review.

Intracranial hemorrhage may represent a complication of the perinatal period that affects neonatal morbidity and mortality. Very poor data exist about a possible association between mutations of the type IV collagen a1 chain (COL4A1) gene and the development of intracranial hemorrhage, and only sporadic reports focus on intracerebral bleedings already developing in utero or in the neonatal period in infants with such a mutation. This study presents a case series of term neonates affected by intracranial hemorrhage, with no apparent risk factors for the development of this condition, who were carriers of COL4A1 gene variants. This study also provides a review of the most recent scientific literature on this topic, specifically focusing on the available scientific data dealing with the perinatal period.

P.048 Prevalence, type and risk factors of intracranial hemorrhage in term neonates: a systematic review and meta-analysis

Background: Intracranial hemorrhage (ICH) in newborns poses a significant challenge to wellbeing and development. In preterm neonates, germinal matrix hemorrhage is most common. In term neonates, prevalence and type of ICH has not been well elucidated. This systematic review aims to assess prevalence, type, and risk factors of ICH in term neonates. Methods: A systematic review was conducted. Inclusion criteria was ICH in neonates born at 37+ weeks gestation. Exclusion criteria was one type of ICH, one risk factor, sample size <20, text not in English, full text not accessible. Eligible studies were evaluated by two authors, data was extracted and analyzed using a predesigned template and MetaXL. Results: A total of 1226 records were initially identified and 20 studies were included in the final analysis. The overall prevalence of ICH was 9.3%. This was subdivided into an asymptomatic subgroup (5.8%) and symptomatic subgroup (29.3%). Analysis showed CT detected ICH most commonly. Extra-axial hemorrhage was most commonly detected (~30%), with subdural more common than extradural hemorrhages. The odds of having an ICH was significantly higher with instrumental delivery (3.75%). Conclusions: This shows that prevalence of ICH is relatively high in symptomatic children. Measured prevalence varies according to the type of modality used for screening.

Development and validation of a nomogram to predict intracranial haemorrhage in neonates

BackgroundThe aim of this study was to establish and validate a Susceptibility-weighted imaging (SWI)-based predictive model for neonatal intracranial haemorrhage (ICH). MethodsA total of 1190 neonates suspected of ICH after cranial ultrasound screening in a tertiary hospital were retrospectively enrolled. The neonates were randomly divided into a training cohort and a internal validation cohort by a ratio of 7:3. Univariate analysis was used to analyze the correlation between risk factors and ICH, and the prediction model of neonatal ICH was established by multivariate logistic regression based on minimum Akaike information criterion (AIC). The nomogram was externally validated in another tertiary hospital of 91 neonates. The performance of the nomogram was evaluated in terms of discrimination by the area under the curve (AUC), calibration by the calibration curve and clinical net benefit by the decision curve analysis (DCA). ResultsUnivariate analysis and min AIC-based multivariate logistic regression screened the following variables to establish a predictive model for neonatal ICH: Platelet count (PLT), gestational diabetes, mode of delivery, amniotic fluid contamination, 1-min Apgar score. The AUC was 0.715, 0.711, and 0.700 for the training cohort, internal validation cohort, and external validation cohort, respectively. The calibration curve showed a good correlation between the nomogram prediction and actual observation for ICH. DCA showed the nomogram was clinically useful. ConclusionWe developed and validated an easy-to-use nomogram to predict ICH for neonates. This model could support individualized risk assessment and healthcare.

Neonatal Outcomes After COVID-19 Vaccination in Pregnancy

Better knowledge about neonatal adverse events after COVID-19 vaccination during pregnancy could help address concerns about vaccine safety. To evaluate the risks of neonatal adverse events after exposure to COVID-19 vaccination during pregnancy. Population-based cohort study including all infants in Sweden and Norway born from June 2021 to January 2023. Unique personal identity numbers were used to link individual information from different national registers. Administration of any mRNA vaccine against COVID-19 during pregnancy, irrespective of previous vaccination, number of doses during pregnancy, or vaccine manufacturer. Outcomes were neonatal conditions with bleeding/thrombosis or inflammation/infection; disorders of the central nervous system; circulatory, respiratory, or gastrointestinal problems; and neonatal mortality. Statistical methods included logistic regression adjusted for characteristics of the pregnant individuals, with additional restricted and stratified analyses. Of 196 470 newborn infants included (51.3% male, 93.8% born at term, 62.5% born in Sweden), 94 303 (48.0%) were exposed to COVID-19 vaccination during pregnancy. Exposed infants exhibited no increased odds of adverse neonatal outcomes, and they exhibited lower odds for neonatal nontraumatic intracranial hemorrhage (event rate, 1.7 vs 3.2/1000; adjusted odds ratio [aOR], 0.78 [95% CI, 0.61-0.99]), hypoxic-ischemic encephalopathy (1.8 vs 2.7/1000; aOR, 0.73 [95% CI, 0.55-0.96]), and neonatal mortality (0.9 vs 1.8/1000; aOR, 0.68 [95% CI, 0.50-0.91]). Subgroup analyses found a similar association between vaccination during pregnancy and lower neonatal mortality; subgroups were restricted to infants delivered by individuals unvaccinated before pregnancy, individuals vaccinated before pregnancy, individuals vaccinated after a general recommendation of vaccination during pregnancy was issued, and individuals without COVID-19 infection during pregnancy. Analyses restricted to term infants, singleton births, or infants without birth defects yielded similar results. Stratifying the analysis by vaccine manufacturer did not attenuate the association between vaccination and low neonatal mortality. In this large population-based study, vaccination of pregnant individuals with mRNA COVID-19 vaccines was not associated with increased risks of neonatal adverse events in their infants.

Application value of cranial ultrasonography in quantitative evaluation of neonatal intracranial hemorrhage.

Intracranial hemorrhage is a severe cranial disease in the perinatal period. We aimed to explore the feasibility and accuracy of three-dimensional (3D) ultrasonography for the quantitative evaluation of neonatal intracranial hemorrhage. A total of 374 neonates with suspected intracranial hemorrhage from January 2017 to December 2019 were selected to be primarily screened by cranial ultrasonography and then diagnosed by cranial CT scan. The examination results were compared to analyze the feasibility and accuracy of 3D ultrasonography in quantifying blood loss. CT scan showed that there were 102 cases of Papile grade I, 106 cases of grade II, 124 cases of grade III and 42 cases of grade IV. 3D ultrasonography showed that there were 108 cases of Papile grade I, 98 cases of grade II, 130 cases of grade III and 38 cases of grade IV. The diagnostic results of these two methods were not significantly different (P>0.05). The accuracies of CT scan for subventricular, intraventricular, subdural, subarachnoid and intraparenchymal hemorrhages were 47.33%, 31.24%, 94.62%, 91.73% and 91.35% respectively, and those of 3D ultrasonography were 98.74%, 96.37%, 91.51%, 90.41% and 97.64% respectively. The accuracies of 3D ultrasonography were significantly superior to those of CT scan for subependymal, intraventricular and intraparenchymal hemorrhages (P<0.05). Neonatal intracranial hemorrhage can be well diagnosed by cranial ultrasonography which timely provides evidence for clinicians, thereby elevating the cure rate and reducing the mortality rate and incidence rate of sequelae. 3D ultrasonography is feasible and accurate for the quantitative evaluation of neonatal intracranial hemorrhage, thus being of great significance to prognostic determination in clinical practice.

Construction and evaluation of neonatal respiratory failure risk prediction model for neonatal respiratory distress syndrome

BackgroundNeonatal respiratory distress syndrome (NRDS) is a common respiratory disease in preterm infants, often accompanied by respiratory failure. The aim of this study was to establish and validate a nomogram model for predicting the probability of respiratory failure in NRDS patients.MethodsPatients diagnosed with NRDS were extracted from the MIMIC-iv database. The patients were randomly assigned to a training and a validation cohort. Univariate and stepwise Cox regression analyses were used to determine the prognostic factors of NRDS. A nomogram containing these factors was established to predict the incidence of respiratory failure in NRDS patients. The area under the receiver operating characteristic curve (AUC), receiver operating characteristic curve (ROC), calibration curves and decision curve analysis were used to determine the effectiveness of this model.ResultsThe study included 2,705 patients with NRDS. Univariate and multivariate stepwise Cox regression analysis showed that the independent risk factors for respiratory failure in NRDS patients were gestational age, pH, partial pressure of oxygen (PO2), partial pressure of carbon dioxide (PCO2), hemoglobin, blood culture, infection, neonatal intracranial hemorrhage, Pulmonary surfactant (PS), parenteral nutrition and respiratory support. Then, the nomogram was constructed and verified.ConclusionsThis study identified the independent risk factors of respiratory failure in NRDS patients and used them to construct and evaluate respiratory failure risk prediction model for NRDS. The present findings provide clinicians with the judgment of patients with respiratory failure in NRDS and help clinicians to identify and intervene in the early stage.

Col4a2 Mutations Contribute to Infantile Epileptic Spasm Syndrome and Neuroinflammation.

There are more than 70 million people worldwide living with epilepsy, with most experiencing the onset of epilepsy in childhood. Despite the availability of more than 20 anti-seizure medications, approximately 30% of epilepsy patients continue to experience unsatisfactory treatment outcomes. This situation places a heavy burden on patients' families and society. Childhood epilepsy is a significant chronic neurological disease that is closely related to genetics. Col4a2, the gene encoding the α2 chain of type IV collagen, is known to be associated with multiple diseases due to missense mutations. The Col4a2 variant of collagen type IV is associated with various phenotypes, including prenatal and neonatal intracranial hemorrhage, porencephaly, porencephaly with cataracts, focal cortical dysplasia, schizencephaly, strokes in childhood and adolescence, and sporadic delayed hemorrhagic stroke. Although epilepsy is recognized as a clinical manifestation of porencephaly, the specific mechanism of Col4a2-related epileptic phenotypes remains unclear. A total of 8 patients aged 2 years and 2 months to 18 years who were diagnosed with Col4a2-related infantile epileptic spasm syndrome were analyzed. The seizure onset age ranged from 3 to 10 months. Initial EEG results revealed hypsarrhythmia or multiple and multifocal sharp waves, spike waves, sharp slow waves, or spike slow waves. Elevated levels of the cytokines IL-1β (32.23±12.58 pg/ml) and IL-6 (45.12±16.03 pg/ml) were detected in the cerebrospinal fluid of these patients without any signs of infection. Following antiseizure treatment, decreased IL-1β and IL-6 levels in the cerebrospinal fluid were noted when seizures were under control. Furthermore, we aimed to investigate the role of Col4a2 mutations in the development of epilepsy. Through the use of immunofluorescence assays, ELISA, and Western blotting, we examined astrocyte activity and the expression of inflammatory cytokines such as IL-1β, IL-6, and TNF-α after overexpressing an unreported Col4a2 (c.1838G>T) mutant in CTX-TNA cells and primary astrocytes. We found that the levels of the inflammatory factors IL-1β, IL-6, and TNF-α were increased in both CTX-TNA cells (ELISA: p = 0.0087, p<0.001, p<0.001, respectively) and primary astrocytes (ELISA: p = 0.0275, p<0.001, p<0.001, respectively). Additionally, we conducted a preliminary investigation of the role of the JAK/STAT pathway in Col4a2 mutation-associated epilepsy. Col4a2 mutation stimulated astrocyte activation, increasing iNOS, COX-2, IL-1β, IL-6, and TNF-α levels in both CTX-TNA cells and primary astrocytes. This mutation also activated the JAK/STAT signaling pathway, leading to increased phosphorylation of JAK2 and STAT3. Treatment with the JAK/STAT inhibitor WP1066 effectively counteracted this effect in primary astrocytes and CTX-TNA cells. To date, the genes who mutations are known to cause developmental and epileptic encephalopathies (DEEs) are predominantly grouped into six subtypes according to function. Our study revealed that an unreported mutation site Col4a2Mut (c.1838G>T) of which can cause neuroinflammation, may be a type VII DEE-causing gene.

Spectrum of Fetal Intraparenchymal Hemorrhage in COL4A1/A2-Related Disorders

BackgroundCOL4A1/A2 variants affecting the alpha 1 and 2 chains of type IV collagen are increasingly recognized as a cause of fetal and neonatal intracranial hemorrhage, porencephaly, and schizencephaly. Fetal magnetic resonance imaging (MRI) findings in COL4A1/A2-related disorders are not well characterized. MethodsThis is a retrospective case series of fetal MRI findings in eight patients with intraparenchymal hemorrhage (IPH) and COL4A1/A2 variants, five of whom have postnatal imaging and clinical follow-up. ResultsIPH was multifocal and bilateral in four of eight patients. IPH involved the frontal lobes in all cases and basal ganglia in six of eight. The median maximum diameter of IPH was 16 mm (range 6 to 65 mm). All patients had ventriculomegaly, and four of eight had intraventricular hemorrhage. Prenatal IPH size correlated clinically with motor outcomes, and none had clinically symptomatic recurrent hemorrhage. ConclusionCOL4A1/A2 variants can present with a spectrum of IPH prenatally, including small and/or unifocal IPH, as well as multifocal and bilateral IPH, involving the frontal lobes and basal ganglia. Given the wide spectrum of IPH severity seen on fetal brain MRI, genetic testing for COL4A1/A2 variants should be considered in all cases of fetal IPH.

Von Willebrand Disease, Hemophilia, and Other Inherited Bleeding Disorders in Pregnancy.

Inherited bleeding disorders, which comprise von Willebrand disease (VWD), hemophilia, other congenital clotting factor deficiencies, inherited platelet disorders, defects of fibrinolysis, and connective tissue disorders, have both maternal and fetal implications. Although mild platelet defects may actually be more prevalent, the most common diagnosed bleeding disorder among women is VWD. Other bleeding disorders, including hemophilia carriership, are much less common, but hemophilia carriers are unique in that they are at risk of giving birth to a severely affected male neonate. General guidance for maternal management of inherited bleeding disorders includes obtaining clotting factor levels in the third trimester, planning for delivery at a center with hemostasis expertise if factor levels do not meet the minimum threshold (eg, less than 0.50 international units/1 mL [50%] for von Willebrand factor, factor VIII, or factor IX), and using hemostatic agents such as factor concentrates, desmopressin, or tranexamic acid. General guidance for fetal management includes prepregnancy counseling, the option of preimplantation genetic testing for hemophilia, and consideration of delivery of potentially affected male neonates with hemophilia by cesarean delivery to reduce the risk of neonatal intracranial hemorrhage. In addition, delivery of possibly affected neonates should occur in a facility where there is newborn intensive care and pediatric hemostasis expertise. For patients with other inherited bleeding disorders, unless a severely affected neonate is anticipated, mode of delivery should be dictated by obstetric indications. Nonetheless, invasive procedures such as fetal scalp clip or operative vaginal delivery should be avoided, if possible, in any fetus potentially affected with a bleeding disorder.

Analysis of risk factors related to extremely and very preterm birth: a retrospective study

Background:Preterm birth is one of the main causes of perinatal morbidity and mortality and imposes a heavy burden on families and society. The aim of this study was to identify risk factors and analyze birth conditions and complications of newborns born at < 32 gestational weeks for extremely preterm (EP) and very preterm (VP) birth in the clinic to further extend the gestational period.Methods:We performed a retrospective cohort study and collected data from 1598 pregnant women and 1660 premature newborns (excluding 229 premature babies who died due to severe illness and abandonment) admitted to the Obstetrics and Gynecology Hospital Affiliated with Nanjing Medical University in China from 2016 to 2020. We compared women’s and newborns’ characteristics by t-tests and Chi-square tests for continuous and categorical variables, respectively. Multivariable logistic regression was performed to estimate the effects of risk factors on EP and VP birth.Results:We identified 3 independent risk factors for EP birth: cervical incompetency (P < 0.001); multiple pregnancy (P < 0.01), primipara (P < 0.001). Additionally, we identified 4 independent risk factors for VP birth: gestational diabetes mellitus (GDM) (P < 0.05), preterm premature rupture of membrane (PPROM) (P < 0.01), fetal intrauterine distress (P < 0.001), and hypertensive disorder complicating pregnancy (HDCP) (P < 0.001). In addition, pairwise comparisons revealed statistically significant differences in the incidence rates of neonatal pneumonia, bronchopulmonary dysplasia (BPD) and sepsis between the 28–28 + 6 and 29–29 + 6 weeks of gestation groups (P < 0.05). Compared with 28–28 + 6 weeks of gestation, neonatal complications were significantly more common at < 26 weeks of gestation (P < 0.05). The incidence rates of neonatal intracranial hemorrhage(NICH), patent ductus arteriosus(PDA), patent foramen ovale(PFO), pneumonia, BPD and sepsis were significantly higher in the 26–26 + 6 and 27–27 + 6 gestational weeks than in the 28–28 + 6 gestational weeks (P < 0.05).Conclusion:PPROM, is the most common risk factor for EP and VP birth, and cervical insufficiency, multiple pregnancy, and primipara are independent risk factors for EP birth. Therefore, during pregnancy, attention should be devoted to the risk factors for PPROM, and reproductive tract infection should be actively prevented to reduce the occurrence of PPROM. Identifying the risk factors for cervical insufficiency, actively intervening before pregnancy, and cervical cervix ligation may be considered to reduce the occurrence of EP labor. For iatrogenic preterm birth, the advantages and disadvantages should be carefully weighed, and the gestational period should be extended beyond 28 weeks to enhance the safety of the mother and child and to improve the outcomes of preterm birth.

Clinical and laboratory predictors of fetal and neonatal alloimmune thrombocytopenia.

Fetal and neonatal alloimmune thrombocytopenia (FNAIT) is the most common cause of intracranial hemorrhage (ICH) in thrombocytopenic term infants. We investigated clinical and laboratory predictors of severe FNAIT in a tertiary care referral center. Retrospective cohort study over a 30-year period. We defined FNAIT as recurrence of neonatal thrombocytopenia in a subsequent pregnancy; and severe outcomes as any of: (1) a birth platelet count below 20 × 109 /L; (2) ICH or (3) fetal death. We used a generalized estimating equations analysis and classification tree analysis to identify risk factors for severe FNAIT in a subsequent pregnancy. During index pregnancies (n=135 in 131 mothers), 71 infants (52.6%) had severe outcomes including a platelet count <20 × 109 /L (n=45), fetal or neonatal ICH (n=32), or fetal death (n=4). During subsequent pregnancies (n=72), 15 infants (20.8%) had severe outcomes including birth platelets <20 × 109 /L (n=10), ICH (n=2), or death (n=3). Forty-two women (58.3%) received antenatal intravenous immune globulin (IVIG) during subsequent pregnancies. Eight mothers (n=9 infants) had severe FNAIT outcomes despite receiving antenatal IVIG. Maternal antibodies to human platelet antigens (HPA) was the only independent predictor of severe FNAIT in a subsequent pregnancy (OR=25.3, p=.004). Nevertheless, one of 43 infants from antibody-negative mothers had a severe outcome. The presence of anti-HPA is highly indicative of the diagnosis of severe FNAIT; however, we observed one infant who had severe FNAIT recurrence, defined using strict clinical criteria, without a maternal antibody. Improved diagnostic and therapeutic strategies are needed to prevent severe FNAIT in high-risk mothers.

Intracranial Hemorrhage in Term and Late-Preterm Neonates: An Institutional Perspective.

Distribution of intracranial hemorrhage in term and late-preterm neonates is relatively unexplored. This descriptive study examines the MR imaging-detectable spectrum of intracranial hemorrhage in this population and potential risk factors. Prevalence and distribution of intracranial hemorrhage in consecutive term/late-preterm neonates who underwent brain MR imaging between January 2011 to August 2018 were assessed. MRIs were analyzed to determine intracranial hemorrhage distribution (intraventricular, subarachnoid, subdural, intraparenchymal, and subpial/leptomeningeal), and chart review was performed for potential clinical risk factors. Of 725 term/late-preterm neonates who underwent brain MR imaging, intracranial hemorrhage occurred in 63 (9%). Fifty-two (83%) had multicompartment intracranial hemorrhage. Intraventricular and subdural were the most common hemorrhage locations, found in 41 (65%) and 39 (62%) neonates, respectively. Intraparenchymal hemorrhage occurred in 33 (52%); subpial, in 19 (30%); subarachnoid, in 12 (19%); and epidural, in 2 (3%) neonates. Twenty infants (32%) were delivered via cesarean delivery, and 5 (8%), via instrumented delivery. Cortical vein thromboses were present in 34 (54%); periventricular or medullary vein thromboses, in 37 (59%); and cerebral venous sinus thrombosis, in 5 (8%). Thirty-seven (59%) had elevated markers of coagulopathy (international normalized ratio > 1.2, fibrinogen level < 234), 9 (14%) had a clinically meaningful elevation in the international normalized ratio (>1.4), and 3 (5%) had a clinically meaningful decrease in the fibrinogen level (<150). Three (5%) neonates had thrombocytopenia (platelet count < 100 × 103/μL). While relatively infrequent, there was a wide distribution of intracranial hemorrhage in term and late-preterm infants; intraventricular and subdural hemorrhages were the most common types. We report a high prevalence of venous congestion or thromboses accompanying neonatal intracranial hemorrhage.

Antenatal intravenous immunoglobulins in pregnancies at risk of fetal and neonatal alloimmune thrombocytopenia: comparison of neonatal outcome in treated and nontreated pregnancies

Maternal alloantibodies to human platelet antigen-1a can cause severe intracranial hemorrhage in a fetus or newborn. Although never evaluated in placebo-controlled clinical trials, most Western countries use off-label weekly administration of high-dosage intravenous immunoglobulin in all pregnant women with an obstetrical history of fetal and neonatal alloimmune thrombocytopenia. In Norway, antenatal intravenous immunoglobulin is only recommended in pregnancies wherein a previous child had intracranial hemorrhage (high-risk) and is generally not given in other human platelet antigen-1a alloimmunized pregnancies (low-risk). To compare the frequency of anti-human platelet antigen-1a-induced intracranial hemorrhage in pregnancies at risk treated with intravenous immunoglobulin vs pregnancies not receiving this treatment as a part of a different management program. This was a retrospective comparative study wherethe neonatal outcomes of 71 untreated human platelet antigen-1a-alloimmunized pregnancies in Norway during a 20-year period was compared with 403 intravenous-immunoglobulin-treated pregnancies identified through a recent systematic review. We stratified analyses on the basis of whether the mothers belonged to high- or low-riskpregnancies. Therefore, only women who previously had a childwith fetal and neonatal alloimmune thrombocytopenia were included. Two neonates with brain bleeds were identified from 313 treated low-risk pregnancies (0.6%; 95% confidence interval, 0.2-2.3). There were no neonates born with intracranial hemorrhage of 64 nontreated, low-risk mothers (0.0%; 95% confidence interval, 0.0-5.7). Thus, no significant difference was observed in the neonatal outcome between immunoglobulin-treated and untreated low-risk pregnancies. Among high-risk mothers, 5 of 90 neonates from treated pregnancies were diagnosed with intracranial hemorrhage (5.6%; 95% confidence interval, 2.4-12.4) compared with 2 of 7 neonates from nontreated pregnancies (29%; 95% confidence interval, 8.2-64.1; P=.08). The most reliable data hitherto for the evaluation of intravenous immunoglobulins treatment in low-risk pregnancies is shown herein. We did not find evidence that omitting antenatal intravenous immunoglobulin treatment in low-risk pregnancies increases the risk of neonatal intracranial hemorrhage.

Study on the Application of Cranial B-ultrasound and MRI in the Diagnosis of Neonatal Intracranial Hemorrhage

Study on the Application of Cranial B-ultrasound and MRI in the Diagnosis of Neonatal Intracranial Hemorrhage

Noninvasive prenatal diagnosis of congenital factor XIII deficiency in Iran

Congenital factor (F) XIII deficiency is a rare coagulation factor deficiency that is inherited in an autosomal recessive manner. FXIII deficiency presents various clinical manifestations, such as intracranial hemorrhage (ICH), which is the most common cause of morbidity and mortality. As ICH can occur in the neonatal period, prenatal diagnosis (PND) is an effective way to reduce neonatal ICH and its associated fatal consequences. In this study, we investigated a noninvasive prenatal diagnosis (NIPD) method, cell-free fetal DNA (cffDNA), for PND in FXIII deficiency. This study was conducted on seven pregnant women in the first trimester. After extraction of cffDNA from maternal plasma, PCR-restriction fragment length polymorphism (PCR-RFLP) was performed to find the underlying F13A gene mutations previously identified in the family members. PCR-RFLP was also performed on postnatal DNA samples. Sanger sequencing was performed to confirm the results. Four cases were heterozygous for F13A gene mutations, whereas three were unaffected. PCR- RFLP results for cffDNA and postnatal DNA samples were identical, and Sanger sequencing confirmed the results. cffDNA is a noninvasive and effective method for PND in congenital FXIII deficiency.

Neonatal and obstetric risk factors are associated with the increased risk of neonatal intracranial hemorrhage

BackgroundIn newborns, intracranial hemorrhage (ICH) is an acquired lesion with a high risk of morbidity, mortality, and long-term neurodevelopmental outcomes. Despite major improvements in newborn care and greater preterm infant survival in recent decades, ICH remains a serious concern. This study aimed to determine the prevalence of ICH in newborns and the various obstetric and neonatal risk factors linked to ICH development. This case–control study was conducted throughout the period from June 2017 to December 2017.Patients and methodsThis case–control research involved 240 infants admitted to Cairo University's Obstetrics and Gynecology Hospital's Neonatal Intensive Care Unit (NICU). We took detailed history, such as the maternal, obstetric, and delivery circumstances, laying stress on maternal and obstetric ICH risk factors. The general condition was assessed at 1 and 5 min using the Apgar score. Ballard score was used to determine gestational age. The birth weight was measured. A thorough clinical examination with a focus on neurological evaluation in accordance with the Sarnat phases was performed. The authors used cranial ultrasonography for imaging (CUS).ResultsOf 240 neonates, 78 neonates developed ICH (32.5%). Overall, 42.9% were males and 21.1% were females. Intraventricular hemorrhage was the commonest one (24.2%), and grade one intraventricular hemorrhage represented 13.4%. The prevalence of asymptomatic cases with ICH was 66.7%. The neonatal risk factors associated with increased ICH risk were prematurity, representing 67.4%; pneumothorax, representing 76.9%; and trauma, representing 77.3%. The sensitivity of CUS for detection of ICH was 84.6%, and the specificity of CUS was higher, representing 97.5%. Overall, 41.03% of ICH cases appeared on the first day of life and 76.9% on the third day by CUS.ConclusionThe prevalence of asymptomatic cases with ICH was 66.7%. Certain neonatal risk factors are associated with increased risk of ICH such as birth weight, sex, gestational age, mode of delivery, and obstetric risk factors. CUS can be considered as a specific and sensitive indicator for the occurrence of ICH.

Clinical efficacy of mouse nerve growth factor plus nimodipine in neonatal intracranial hemorrhage and its effect on plasma PAF, CNP, MMP-2, and neurological function.

To investigate the clinical efficacy of combination of mouse nerve growth factor (NGF) and nimodipine in the treatment of neonatal intracranial hemorrhage (NICH) and its effect on plasma platelet-activating factor (PAF), C-type natriuretic peptide (CNP), matrix metalloproteinase-2 (MMP-2), and neurological function. A total of 90 infants with severe ICH admitted to our hospital from December 2016 to December 2018 were enrolled for retrospective study. According to different treatment schemes, they were assigned into 2 groups: group A (n=40) treated with mouse NGF plus nimodipine; group B (n=50) treated with nimodipine. The recovery time, serum indexes (PAF, MMP-2, CNP), neurological function (neonatal behavioral neurological assessment (NBNA) score), complications, and total effective rate of patients were recorded, and the satisfaction degree of family members was statistically analyzed. Patients in group A showed shorter recovery time, down-regulated PAF and MMP-2, evidently up-regulated CNP, and significantly increased NBNA score after one/two weeks of treatment, as well as fewer complications, higher total effective rate and higher satisfaction of family members. To sum up, the combination of mouse NGF and nimodipine achieves good clinical efficacy in NICH, which down-regulates plasma PAF and MMP-2, up-regulates CNP, and improves neurological function. Therefore, it is suitable for clinical promotion.

Asparagine Synthetase Deficiency with Intracranial Hemorrhage Can Mimic Molybdenum Cofactor Deficiency.

Here we report a consanguineous Egyptian family with two siblings presented with congenital microcephaly, early-onset epileptic encephalopathy, feeding difficulties, and early lethality. The condition was initially diagnosed as molybdenum cofactor deficiency as the brain imaging for one of them showed brain edema and intracranial hemorrhage in addition to the hypoplastic corpus callosum, vermis hypoplasia, and small-sized pons. Subsequently, whole exome sequencing identified a novel homozygous missense variant in exon 4 of ASNS gene c.397_398GT > CA (p.Val133Gln) confirming the diagnosis of asparagine synthetase deficiency syndrome. No discernible alternative cause for the intracranial hemorrhage was found. Our patient is the second to show asparagine synthetase deficiency and intracranial hemorrhage, thus confirming the involvement of ASNS gene. As such, it is important to consider asparagine synthetase deficiency syndrome in patients with microcephaly, brain edema, and neonatal intracranial hemorrhage.