Perinatal Arterial Ischemic Stroke in Fetal Vascular Malperfusion: A Case Series and Literature Review.

Fetal vascular malperfusion includes a continuum of placental histologic abnormalities increasingly associated with perinatal brain injury, namely arterial ischemic stroke. Here, we describe the clinical-neuroimaging features of 5 neonates with arterial ischemic stroke and histologically proved fetal vascular malperfusion. All infarcts involved the anterior territories and were multiple in 2 patients. In 2 neonates, there were additional signs of marked dural sinus congestion, thrombosis, or both. A mixed pattern of chronic hypoxic-ischemic encephalopathy and acute infarcts was noted in 1 patient at birth. Systemic cardiac or thrombotic complications were present in 2 patients. These peculiar clinical-radiologic patterns may suggest fetal vascular malperfusion and should raise the suspicion of this rare, underdiagnosed condition carrying important implications in patient management, medicolegal actions, and future pregnancy counseling.

Neonatal Developmental Venous Anomalies: Clinicoradiologic Characterization and Follow-Up.

BACKGROUND AND PURPOSE: Although developmental venous anomalies have been frequently studied in adults and occasionally in children, data regarding these entities are scarce in neonates. We aimed to characterize clinical and neuroimaging features of neonatal developmental venous anomalies and to evaluate any association between MR imaging abnormalities in their drainage territory and corresponding angioarchitectural features. MATERIALS AND METHODS: We reviewed parenchymal abnormalities and angioarchitectural features of 41 neonates with developmental venous anomalies (20 males; mean corrected age, 39.9 weeks) selected through a radiology report text search from 2135 neonates who underwent brain MR imaging between 2008 and 2019. Fetal and longitudinal MR images were also reviewed. Neurologic outcomes were collected. Statistics were performed using χ2, Fisher exact, Mann-Whitney U, or t tests corrected for multiple comparisons. RESULTS: Developmental venous anomalies were detected in 1.9% of neonatal scans. These were complicated by parenchymal/ventricular abnormalities in 15/41 cases (36.6%), improving at last follow-up in 8/10 (80%), with normal neurologic outcome in 9/14 (64.2%). Multiple collectors (P = .008) and larger collector caliber (P < .001) were significantly more frequent in complicated developmental venous anomalies. At a patient level, multiplicity (P = .002) was significantly associated with the presence of ≥1 complicated developmental venous anomaly. Retrospective fetal detection was possible in 3/11 subjects (27.2%). CONCLUSIONS: One-third of neonatal developmental venous anomalies may be complicated by parenchymal abnormalities, especially with multiple and larger collectors. Neuroimaging and neurologic outcomes were favorable in most cases, suggesting a benign, self-limited nature of these vascular anomalies. A congenital origin could be confirmed in one-quarter of cases with available fetal MR imaging.

Bacterial invasive infections in a neonatal intensive care unit: a 13 years microbiological report from an Italian tertiary care centre.

INTRODUCTION: To evaluate the aetiology of neonatal invasive diseases (positive cultures from blood or cerebrospinal fluid, CSF) due to bacteria other than coagulase-negative staphylococci in a large tertiary care centre and compare with results of surveillance cultures. METHODS: Retrospective analysis of microbiological data of children admitted in neonatal intensive care unit (NICU) of a large tertiary care centre from 2005 to 2018. RESULTS: 230 bacterial strains, 223 from blood and 7 from CSF, respectively, were detected as cause of invasive infections, while 152 were detected in surveillance cultures. Methicillin-susceptible Staphylococcus aureus (MSSA) was the most frequently isolated pathogen both in invasive infections (18%) and colonizations (23%) followed by Escherichia coli (16% on invasive disease and 20% of colonizations). Other common bacteria include Enterococcus faecalis and Streptococcus agalactiae for invasive disease and methicillin-resistant Staphylococcus aureus in colonizations. Invasive infection was due to a pathogen detected in surveillance cultures in 33% of cases. In more than 50% of invasive diseases the identified pathogen was not present in surveillance cultures. CONCLUSIONS: The high percentage of invasive infections due to bacteria not previously identified in surveillance cultures raises doubts about the efficiency of this procedure and highlights the need to search for alternative infection sources. This finding and the high prevalence of invasive infections due to nosocomial pathogens such as Staphylococcus aureus could be the result of horizontal transmission between patients through the hands of health care professionals, emphasizing once again the importance of applying stringent hand hygiene procedures and isolation standards.

Congenital chylothorax: Current evidence-based prenatal and post-natal diagnosis and management.

Congenital chylothorax is an uncommon condition but represents the main cause of congenital pleural effusion during the neonatal period. It usually appears before birth, both as an isolated disorder or in association with hydrops fetalis, negatively affecting the subsequent neonatal outcome. Prenatal treatment is usually considered to ensure a satisfactory lung development in case of moderate to severe pleural effusion or in the presence of hydrops, although consensus on treatment timing and modalities has not been reached to date. Both medical and surgical therapeutic strategies are available to treat this condition and novel treatment options have been recently attempted with acceptable results in both prenatal and post-natal setting. The heterogeneous clinical presentation of congenital chylothorax together with its rarity, its numerous etiologies and the absence of a highly effective treatment renders the diagnostic and therapeutic approach difficult to standardize. In addition, adequate visualization of the lymphatic system is complex, especially in small neonates, although new promising techniques have been developed lately and may contribute to improved management of this serious but infrequent condition. This review focuses on the current evidence base for the diagnosis and treatment options for congenital chylothorax, suggesting a rational diagnostic and therapeutic approach both in the prenatal and in the neonatal period.

Behaviours monitoring and infection control in neonatal intensive care unit: how to improve ourselves?

INTRODUCTION: Healthcare-associated infections are important events in neonatal intensive care unit.Hand hygiene is considered one of the most important procedures to control these complications. METHODS: Healthcare workers procedures for patient's approaching were directly monitored from February to April 2018 in the Neonatal Intensive Care Unit of Istituto Giannina Gaslini, Genoa, Italy.Number and type of total contacts with patients or "patient unit" (e.g.: ventilator, monitor, isolette) were recorded as well as errors related to lack of hand hygiene after and before performing procedures. RESULTS: A total of 1,040 actions were observed on patient or patient unit: 560 actions by nursing staff, 240 by residents and 240 by consultants. The most common misbehaviour was the "double touch" in nursing staff (30%), "glasses, hair or nose" in residents (35%), and "double touch" and "glasses hair or nose" in consultants (25% and 23% respectively). CONCLUSIONS: Extemporaneous contact is the more frequent potential "high risk" moment for transmission of healthcare associated infections in NICU.

The CHOPIn Study: a Multicenter Study on Cerebellar Hemorrhage and Outcome in Preterm Infants.

Cerebellar hemorrhage (CBH) is a frequent complication of preterm birth and may play an important and under-recognized role in neurodevelopment outcome. Association between CBH size, location, and neurodevelopment is still unknown. The main objective of this study was to investigate neurodevelopmental outcome at 2 years of age in a large number of infants with different patterns of CBH. Of preterm infants (≤ 34 weeks) with known CBH, perinatal factors, neuro-imaging findings, and follow-up at 2 years of age were retrospectively collected. MRI scans were reassessed to determine the exact size, number, and location of CBH. CBH was divided into three groups: punctate (≤ 4 mm), limited (> 4 mm but < 1/3 of the cerebellar hemisphere), or massive (≥ 1/3 of the cerebellar hemisphere). Associations between pattern of CBH, perinatal factors, and (composite) neurodevelopmental outcome were assessed. Data of 218 preterm infants with CBH were analyzed. Of 177 infants, the composite outcome score could be obtained. Forty-eight out of 119 infants (40%) with punctate CBH, 18 out of 35 infants (51%) with limited CBH, and 18 out of 23 infants (78%) with massive CBH had an abnormal composite outcome score. No significant differences were found for the composite outcome between punctate and limited CBH (P = 0.42). The risk of an abnormal outcome increased with increasing size of CBH. Infants with limited CBH have a more favorable outcome than infants with massive CBH. It is therefore important to distinguish between limited and massive CBH.

Early fetal hydropic changes are associated with moderate dilatation of the brain ventricular system: A clue to a possible link between cervical lymphatic engorgement and ventricular dilatation?

The aim of this study is to assess whether early cervical lymphatic obstruction is associated with a sonographically detectable dilatation of the ventricular system in the 1st trimester of pregnancy. In particular, the objective is to assess whether fetuses with non-immune hydrops fetalis (NIHF), cystic hygroma, or enlarged nuchal translucency (NT) have a greater atrial width/biparietal diameter (AW/BPD) ratio than normal at time of the combined first trimester screening scan. This retrospective study included 96 first trimester fetuses (33 normal and 63 with various degree of cervical lymphatic engorgement). Inclusion criteria were CRL in the 45-84 mm range and availability of one or more three-dimensional volume datasets of the fetal head, acquired from the BPD plane. Each three-dimensional volume dataset was opened and multiplanar correlation employed to align the three orthogonal planes. The ratio between the atrial width and the BPD (AW/BPD ratio) was used to evaluate the possible presence of increased amount of cerebrospinal fluid. Abnormal cases were placed into 4 categories: 1) enlarged non-septated NT 2.5-3.9 mm, no hydrops; 2) grossly enlarged non-septated NT / edema >3.9 mm; 3) cystic hygroma and/ or NIHF; 4) major anomalies with NT <2.5 mm. Presence of dilatation of the laterocervical jugular lymphatic sacs, karyotype and presence of congenital anomalies were also recorded. The One-way ANOVA test was used to compare means. Intra- and inter-observer variability were also assessed. The AW/BPD ratio was found to be significantly higher in fetuses with grossly enlarged NT/nuchal edema and NIHF/septated cystic hygroma than in normal (p <0.05 and p <0.01, respectively). Also, the AW/BPD ratio was significantly higher in NIHF/septated cystic hygroma than in enlarged NT 2.5-3.9 mm (p <0.05). In case of enlarged NT (2.5-3.9 mm), the AW/BPD ratio is significantly higher in presence of JLS (p <0.01). At the end of the first trimester, presence of cervical lymphatic engorgement, in terms of grossly enlarged NT, nuchal edema, septated cystic hygroma, and NIHF, is statistically associated with a moderate dilatation of the ventricular system. Of note, among fetuses with moderately enlarged NT, those with evidence of dilatation of the JLS show a statistically significant increase in the AW/BPD ratio.

Brain lymphatic drainage system in fetus and newborn: Birth of a new era of exploration.

A peculiar brain lymphatic drainage system has been recently fully recognized in animals and humans. It comprises different draining pathways, including the lymphatic system, the perivascular drainage pathway, and the cerebrospinal fluid (CSF) drainage routes. Although scant data are available about its function during the neonatal period, it may play a role in neonatal brain diseases. In this review, we focus on the actual knowledge of brain lymphatic drainage system, and we hypothesize potential implications of its impairment and dysfunction in major neonatal neurological diseases.

Variability of Cerebral Deep Venous System in Preterm and Term Neonates Evaluated on MR SWI Venography.

BACKGROUND AND PURPOSE: The anatomy of the deep venous system is characterized by a great variability that might play an important role in the pathogenesis of brain lesions in the preterm brain. The aim of this study was to compare the anatomy of cerebral subependymal veins evaluated on SWI venography in 3 groups of neonates with normal brain MR imaging (very preterm [gestational age <32 weeks], moderate-to-late preterm [gestational age ≥32 to ≤37 weeks], and term neonates [gestational age >37 weeks]) and to evaluate the influence of preterm birth on development of subependymal veins. MATERIALS AND METHODS: SWI venographies of 84 very preterm, 31 moderate-to-late preterm, and 50 term neonates were retrospectively evaluated. Subependymal vein anatomy was classified into 6 different patterns: type 1 represented the classic pattern and types 2-6 were considered anatomic variants. A χ2 test was used to evaluate differences between the distributions of subependymal vein patterns. RESULTS: A significant difference (P = .011) was noticed between the 6 patterns based on gestational age. Type 1 was more frequent in term neonates (68%) than in both very preterm (41.7%) and moderate-to-late preterm neonates (56.5%). Anatomic variants were more common in very preterm neonates (66%) than in both moderate-to-late preterm (41%) and term neonates (36%). Interhemispheric asymmetry was more frequent in very preterm (59.5%) and moderate-to-late preterm neonates (51.6%) than in term neonates (34%; P = .017). Sex and monozygotic twin birth did not significantly affect the frequency of subependymal vein patterns (P = .0962). CONCLUSIONS: The deep venous system of the neonatal brain shows a large spectrum of anatomic variants with higher variability of subependymal vein anatomy in preterm than term neonates, likely related to the influence of the preterm birth and epigenetic factors on subependymal vein development.

Congenital Chylothorax of the Newborn: Diagnosis and Treatment in Three Pictures.

There is general agreement regarding the evident need for an international, multicenter trial including long-term follow-up to establish the correct criteria for diagnosing and managing congenital chylothorax. In an attempt to identify these criteria, which could then be used to draft a prospective multicenter trial, we propose three flow-charts showing three algorithms that could be used to: 1) obtain a definitive diagnosis of pleural chylous effusion; 2) specifically focus on chyle leakage evolution and etiology of chylothorax; and 3) focus on the management of congenital chylothorax. The aim of the algorithms we propose is to build the basis on which a strongly needed multicenter trial might be structured.

Inguinal hernia in neonates and ex-preterm: complications, timing and need for routine contralateral exploration.

BACKGROUND/PURPOSE: Aim of this study was to present a series of neonates and ex-preterm babies who underwent inguinal hernia repair focusing on complications and possible indication to perform routine contralateral groin exploration. METHODS: This is a retrospective study of a series of consecutive patients weighing less than 5 kg who underwent inguinal hernia repair between January 2007 and December 2012. Only the affected side was treated. Patients have been routinely followed up postoperatively. We resorted to available outpatients' charts and admission notes to record demographic data, surgical details, complications and the occurrence of metachronous hernias. A questionnaire was administered to all patients' relatives to confirm the long-term outcome. RESULTS: One hundred fifty-four patients were operated for a total of 184 herniotomies (88 right sided, 36 left sided and 30 bilateral). Median length of follow-up was 42 months (range 6 months-7.5 years). Thirteen patients (13/124 = 10.5 %) developed metachronous hernia that proved to be significantly more frequent in patients weighing less than 1,500 g at birth (p < 0.05). We observed 10 % of complications, including 2.7 % testicular atrophy and 4.5 % recurrence. Atrophy proved to occur more frequently in patients who experienced preoperative incarceration (p < 0.05). No other risk factors were identified. CONCLUSIONS: The results of our series demonstrated that, though technically demanding, herniotomy in the neonate and ex-preterm is associated with a relatively low incidence of complications. Based on our results and in accordance with literature data, we do not advocate routine contralateral exploration in case of unilateral hernia but surgery to be performed only on the symptomatic side, as soon as possible after initial diagnosis. Very low birth weight patients should be followed with care in the early postoperative period due to the higher likelihood of developing a metachronous hernia.

Dynamics of pleural fluid effusion and chylothorax in the fetus and newborn: role of the lymphatic system.

Pleural fluid effusion particularly chylothorax is a relatively rare occurrence in the newborn, but when it occurs it is often life-threatening. In this article, we describe and illustrate the morphologic features of the visceral and parietal pleura including pleural lymphatics and the physiology and pathophysiology of pleural fluid balance. The role and function of the lymphatic system in controlling the volume and composition of pleural liquid are detailed and a conceptual scheme presented. Finally, the crucial role of inadequate lymphatic drainage (either functional overload from an imbalance in Starling forces or mechanical insufficiency from lymphatic dysplasia) is emphasized.

Neonatal stroke.

Neonatal stroke encompasses a range of focal and multifocal ischaemic and haemorrhagic tissue injuries. This review will concentrate on focal brain injury that occurs as a consequence of arterial infarction, most frequently the left middle cerebral artery, or more rarely as a consequence of cerebral sinus venous thrombosis (CSVT). Both conditions are multifactorial in origin. The incidence of both acquired and genetic thrombophilic disorders in both mothers and infants is high although rarely causal in isolation. Neurodevelopmental morbidity occurs in over 50% of children. Specific therapy in the form of anticoagulation is currently only recommended in CSVT and needs to be carefully monitored in the presence of haemorrhage.

Deep medullary vein involvement in neonates with brain damage: an MR imaging study.

BACKGROUND AND PURPOSE: Different and specific MR imaging patterns of lesions involving WM are widely defined in neonatal encephalopathy. The aim of this study was to describe a novel MR imaging pattern of damage characterized by the abnormal prominence of DMVs in premature and full-term neonates. MATERIALS AND METHODS: Twenty-one (11 premature and 10 full-term) neonates with MR imaging evidence of linear radially oriented fan-shaped lesions in the periventricular WM and without dural venous thrombosis were enrolled in this retrospective study. A total of 37 MR imaging examinations were performed at ages ranging from day 0 to 24 months. RESULTS: According to the appearance of linear anomalies on T2-weighted images, we identified 2 main patterns: T2 hypointense lesions without WM cavitations and T2 hypointense lesions associated with linear cysts. The first pattern was found in 17 examinations performed between 0 and 44 days of life; the second pattern was found in another 14 examinations performed between 6 days and 4 months of life. Five examinations performed between 9 and 24 months of life showed a reduction in volume and hyperintense signal intensity of the periventricular WM on T2-weighted and FLAIR images. CONCLUSIONS: Subtle linear WM lesions with the same anatomic distribution of DMVs may be evident in premature and full-term neonates without signs of major venous thrombosis, both in the acute and subacute phases. Their appearance and evolution suggest that transient DMV engorgement/thrombosis may be responsible for WM damage that can lead to a PVL-like pattern.

Neonatal stroke.

The perinatal ischemic stroke is defined as "a group of heterogenous conditions with a focal disruption of cerebral flow secondary to an arterial or a venous thrombosis or embolization between the 20 week of foetal life through the 28 post-natal day". Three subgroups are identified: arterial ischemic stroke (AIS), cerebral sinovenous thrombosis (CSVT) and haemorragic infarct. Many strokes are detected in the neonatal period due to early onset seizures, although symptoms can be more subtle leading to a significant delay in the diagnosis. MRI-DWI remains the best tool for a correct diagnosis, extension of the lesion and suggestion of timing. Lesions detected in utero or at early neonatal imaging with signs of tissue loss are considered "foetal stroke". The "neonatal stroke", with the symptoms in the first 4 days, shows the typical abnormalities of the acute phase evolving later in a white matter loss. The AIS shows the ischemic area of restriction at the early DWI in a arterial territory, mainly the middle cerebral artery. The MR-Venogram is useful in the CVST to detect the thrombus in a sinovenous vessel and the potentially associated lesion, such as intraventricular haemorrage and parenchymal oedema. The extension of the lesion and the involvement of the basal ganglia and thalami have a negative prognostic value for the development of hemiplegia especially in the presence of abnormal PLIC. An early diagnosis.

Diagnosis of perinatal stroke II: mechanisms and clinical phenotypes.

INTRODUCTION: Here (and in an accompanying article dealing with definitions, differential diagnosis and registration), a structured sequential diagnostic flow is proposed to discern clinical phenotypes for perinatal stroke, including arterial ischaemic stroke (AIS), cerebral sinovenous thrombosis (CSVT) and haemorrhagic stroke. MATERIAL AND RESULTS: For neonatal AIS, the diagnostic sequence is infection, trauma, embolism, arteriopathy, other, primary thrombosis and unclassifiable; for neonatal CSVT, the sequence is infection, trauma, venopathy, other, primary thrombosis and unclassifiable. The proposed hierarchical diagnostic flows are an initial step towards a standard for registration of the causes of neonatal stroke. Such standardization should guide attempts at prevention and intervention. An extensive literature search and study of a retrospective cohort of 134 newborn infants with stroke suggest that embolism is the most common identifiable cause for stroke in general (25%), preceding trauma (10%) and infection (8%). Other causes, such as asphyxia, acute blood loss, extracorporeal membrane oxygenation, genetic disorders or prothrombotic conditions, are seen in <5% of cases. For neonatal AIS, the presence of an embolic phenotype is 33% in this cohort. The designation unclassifiable scored 34% for the entire stroke group and 25% for neonatal AIS. Complex arterial stroke with multiple arteries involved is often seen when the underlying cause is infection, cranial trauma or embolism. One important conclusion is that a means of prevention is avoidance of embolism from thrombosis outside the brain. CONCLUSION: To prevent the occurrence and recurrence of neonatal ischaemic stroke, clinicians must develop a standardized diagnostic approach that results in characterization of the clinical phenotype.

Diagnosis of perinatal stroke I: definitions, differential diagnosis and registration.

INTRODUCTION: Perinatal stroke can be divided into three subtypes: ischaemic stroke, either arterial or sinovenous and haemorrhagic stroke. For the sake of universal registration and to perform intervention studies, we propose a detailed diagnostic registration system for perinatal stroke taking 10 variables into account. These variables are discussed here and in the accompanying article. MATERIAL AND RESULTS: Differentiation is needed from focal brain changes as a result of disorders other than stroke, whereby accurate timing is possible only when early neonatal imaging is available. Detailed templates are presented for arterial and venous vascular classification. AIS is further subdivided into single territory and complex infarction and some stratification is proposed in the complicated stroke group. This registration system has been applied to a retrospective cohort of 134 newborns with stroke (single-centre observation from 1999 to 2007) and the results are compared with published data. By applying this registration system, intervention studies for one homogeneous stroke type (e.g. complete middle cerebral artery stroke) may be facilitated. CONCLUSION: Ten variables may be sufficient to register a perinatal stroke. These include gestational age, birthweight, gender, delivery mode, time of detection, presentation, type of stroke, vessel affected or type of cavity, imaging method at detection and clinical context.

Thrombophilia and fetal germinal matrix-intraventricular hemorrhage: does it matter?

Germinal matrix-intraventricular hemorrhage (GMH-IVH) in the fetus is very rare and the role of thrombophilia in its pathogenesis is unclear. We report on the prenatal diagnosis by magnetic resonance imaging of GMH-IVH in a 24-week fetus. The newborn presented posthemorrhagic ventriculomegaly and was found to be heterozygous for two thrombophilic patterns, factor V Leiden and methylenetetrahydrofolate reductase mutation. The combination of this hypercoagulable state and prenatal GMH-IVH is discussed together with the opportunity of testing these infants for thrombophilia.