Developmental anatomy of the thalamus, perinatal lesions, and neurological development.

The thalamic nuclei develop before a viable preterm age. GABAergic neuronal migration is especially active in the third trimester. Thalamic axons meet cortical axons during subplate activation and create the definitive cortical plate in the second and third trimesters. Default higher-order cortical driver connections to the thalamus are then replaced by the maturing sensory networks, in a process that is driven by first-order thalamic neurons. Surface electroencephalographic activity, generated first in the subplate and later in the cortical plate, gradually show oscillations based on the interaction of the cortex with thalamus, which is controlled by the thalamic reticular nucleus. In viable newborn infants, in addition to sensorimotor networks, the thalamus already contributes to visual, auditory, and pain processing, and to arousal and sleep. Isolated thalamic lesions may present as clinical seizures. In addition to asphyxia and stroke, infection and network injury are also common. Cranial ultrasound can be used to classify neonatal thalamic injuries based on functional parcelling of the mature thalamus. We provide ample illustration and a detailed description of the impact of neonatal focal thalamic injury on neurological development, and discuss the potential for neuroprotection based on thalamocortical plasticity.

Cerebral Doppler imaging in neonates: A guide for clinical application and diagnosis.

Cranial ultrasound reliably diagnoses many neonatal brain disorders. Adding Doppler imaging expands the spectrum by providing information on the status of the vasculature and haemodynamics that may guide further diagnostic and clinical management. Doppler imaging may identify neonates with congenital or acquired vascular abnormalities such as perinatal stroke, sinuvenous thrombosis, vein of Galen malformation, dural sinus malformation, sinus pericranii, and developmental venous anomaly. These entities may need further investigation with complementary imaging modalities such as magnetic resonance imaging and magnetic resonance angiography, or conventional angiography. This review aims to help clinicians to improve their Doppler sonography knowledge and skills in order to use this helpful tool in neonates with neurological symptoms or suspected cerebral vascular abnormalities admitted to the neonatal intensive care unit.

Occurrence of hyperoxia during iNO treatment for persistent pulmonary hypertension of the newborn: a cohort study.

High concentrations of oxygen are often needed to optimize oxygenation in infants with persistent pulmonary hypertension (PPHN), but this can also increase the risk of hyperoxemia. We determined the occurrence of hyperoxemia in infants treated for PPHN. Medical records of infants ≥ 34 + 0 weeks gestational age (GA) who received inhaled nitric oxide (iNO) were retrospectively reviewed for oxygenation parameters during iNO therapy. Oxygen was manually titrated to target arterial oxygen tension (PaO2) 10-13 kPa and peripheral oxygen saturation (SpO2) 92-98%. The main study outcomes were the incidence and duration of hyperoxemia and hypoxemia and the fraction of inspired oxygen (FiO2). A total of 181 infants were included. The median FiO2 was 0.43 (IQR 0.34-0.56) and the maximum FiO2 was 1.0 in 156/181 (86%) infants, resulting in at least one PaO2 > 13 kPa in 149/181 (82%) infants, of which 46/149 (31%) infants had minimal one PaO2 > 30 kPa. SpO2 was > 98% in 179/181 (99%) infants for 17.7% (8.2-35.6%) of the iNO time. PaO2 < 10 kPa occurred in 160/181 (88%) infants, of which 81/160 (51%) infants had minimal one PaO2 < 6.7 kPa. SpO2 was < 92% in 169/181 (93%) infants for 1.6% (0.5-4.3%) of the iNO time.    Conclusion: While treatment of PPHN is focused on preventing and reversing hypoxemia, hyperoxemia occurs inadvertently in most patients. What is Known: • High concentrations of oxygen are often needed to prevent hypoxemia-induced deterioration of PPHN, but this can also increase the risk of hyperoxemia. • Infants with persistent pulmonary hypertension may be particularly vulnerable to the toxic effects of oxygen, and hyperoxemia could further induce pulmonary vasoconstriction, potentially worsening the condition. What is New: • Hyperoxemia occurs in the majority of infants with PPHN during treatment with iNO. • Infants with PPHN spent a considerably longer period with saturations above the target range compared to saturations below the target range.

Ultrasonographic Estimation of Ventricular Volume in Infants Born Preterm with Posthemorrhagic Ventricular Dilatation: A Nested Substudy of the Randomized Controlled Early Versus Late Ventricular Intervention Study (ELVIS) Trial.

OBJECTIVE: To study the potential role of ventricular volume (VV) estimation in the management of posthemorrhagic ventricular dilatation related to the need for ventriculoperitoneal (VP)-shunt insertion and 2-year neurodevelopmental outcome in infants born preterm. STUDY DESIGN: We included 59 patients from the Early vs Late Ventricular Intervention Study from 4 participating centers. VV was manually segmented in 209 3-dimensional ultrasound scans and estimated from 2-dimensional ultrasound linear measurements in a total of 1226 ultrasounds. We studied the association of both linear measurements and VV to the need for VP shunt and 2-year neurodevelopmental outcome in the overall cohort and in the 29 infants who needed insertion of a reservoir. We used general estimating equations to account for repeated measures per individual. RESULTS: Maximum pre-reservoir VV (ß coefficient = 0.185, P = .0001) and gestational age at birth (ß = -0.338; P = .0001) were related to the need for VP shunt. The estimated optimal single VV measurement cut point of 17 cm3 correctly classified 79.31% with an area under the curve of 0.76 (CI 95% 0.74-0.79). Maximum VV (ß = 0.027; P = .012) together with VP shunt insertion (ß = 3.773; P = .007) and gestational age (ß = -0.273; P = .0001) were related to cognitive outcome at 2 years. Maximum ventricular index and anterior horn width before reservoir insertion were independently associated with the need of VP shunt and the proposed threshold groups in the Early vs Late Ventricular Intervention Study trial were associated with long-term outcome. CONCLUSIONS: Pre-reservoir VV measurements were associated with the need for VP-shunt insertion and 2-year cognitive outcome among infants born preterm with posthemorrhagic ventricular dilatation. TRIAL REGISTRATION: ISRCTN43171322.

Children Newly Diagnosed with Fetal and Neonatal Alloimmune Thrombocytopenia: Neurodevelopmental Outcome at School Age.

OBJECTIVE: To evaluate the neurodevelopmental outcome at school age in children newly diagnosed with fetal and neonatal alloimmune thrombocytopenia (FNAIT). STUDY DESIGN: This observational cohort study included children diagnosed with FNAIT between 2002 and 2014. Children were invited for cognitive and neurological testing. Behavioral questionnaires and school performance results were obtained. A composite outcome of neurodevelopmental impairment (NDI) was used, defined, and subdivided into mild-to-moderate and severe NDI. Primary outcome was severe NDI, defined as IQ <70, cerebral palsy with Gross Motor Functioning Classification System level ≥ III, or severe visual/hearing impairment. Mild-to-moderate NDI was defined as IQ 70-85, minor neurological dysfunction or cerebral palsy with Gross Motor Functioning Classification System level ≤ II, or mild visual/hearing impairment. RESULTS: In total, 44 children were included at a median age of 12 years (range: 6-17 years). Neuroimaging at diagnosis was available in 82% (36/44) of children. High-grade intracranial hemorrhage (ICH) was detected in 14% (5/36). Severe NDI was detected in 7% (3/44); two children had high-grade ICH, and one had low-grade ICH and perinatal asphyxia. Mild-to-moderate NDI was detected in 25% (11/44); one child had high-grade ICH, and eight children were without ICH, yet for two children, neuroimaging was not performed. Adverse outcome (perinatal death or NDI) was 39% (19/49). Four children (9%) attended special needs education, three of whom had severe NDI and one had mild-to-moderate NDI. Total behavioral problems within the clinical range were reported in 12%, which is comparable with 10% in the general Dutch population. CONCLUSION: Children who are newly diagnosed with FNAIT are at increased risk for long-term neurodevelopmental problems, even those without ICH. TRIAL REGISTRATION: The study was registered at ClinicalTrials.gov (Identifier: NCT04529382).

Long-term neurodevelopmental outcome in children after antenatal intravenous immune globulin treatment in fetal and neonatal alloimmune thrombocytopenia.

BACKGROUND: Children with fetal and neonatal alloimmune thrombocytopenia face increased risk of intracranial hemorrhage potentially leading to developmental impairment. To prevent intracranial hemorrhage, pregnant women with alloantibodies against fetal platelets are often treated with intravenous immunoglobulin. Intravenous immunoglobulin seems effective in vastly reducing the risk of fetal or neonatal bleeding complications. However, information on long-term neurodevelopment of these children is lacking. OBJECTIVE: This study aimed to evaluate long-term neurodevelopmental outcome in children with fetal and neonatal alloimmune thrombocytopenia who were treated with intravenous immunoglobulin antenatally. STUDY DESIGN: An observational cohort study was performed, including children of mothers treated with intravenous immunoglobulin during pregnancy because a previous child was diagnosed with fetal and neonatal alloimmune thrombocytopenia. Children were invited for a follow-up assessment including standardized cognitive and neurologic tests. The parents were asked to complete a behavioral questionnaire and school performance reports. The primary outcome was severe neurodevelopmental impairment, defined as severe cognitive impairment (intelligence quotient <70), cerebral palsy with Gross Motor Function Classification System Level ≥3, bilateral blindness, and/or bilateral deafness (requiring amplification). The secondary outcome was mild to moderate neurodevelopmental impairment, defined as either mild to moderate cognitive impairment (intelligence quotient <85), cerebral palsy with Gross Motor Function Classification System Level ≤2, minor neurologic dysfunction, vision loss, and/or hearing loss. RESULTS: Between 2003 and 2017, 51 children were live-born after antenatal intravenous immunoglobulin treatment. One family moved abroad and was therefore not eligible for inclusion. In total, 82% (41/50) of the eligible cases were included for neurodevelopmental assessment at a median age of 9 years and 8 months. Severe neurodevelopmental impairment was not detected. The incidence of mild to moderate neurodevelopmental impairment was 14% (6/41; 95% confidence interval, 6%-29%). The children's mean cognitive score, behavioral scores, and academic achievement were not different from those observed in the Dutch norm groups. Neuroimaging was performed in 90% (37/41) of cases. Severe intracranial hemorrhage was diagnosed in 2 cases (5%), one antenatally before the start of intravenous immunoglobulin and the other case 1 day after birth. Both cases had a normal neurodevelopmental outcome. CONCLUSION: The risk of neurodevelopmental impairment in children whose mothers were treated for fetal and neonatal alloimmune thrombocytopenia with antenatal intravenous immunoglobulin is comparable to that reported in the general population.

Mammillary body injury in neonatal encephalopathy: a multicentre, retrospective study.

BACKGROUND: The mammillary bodies (MBs) have repeatedly been shown to be critical for memory, yet little is known about their involvement in numerous neurological conditions linked to memory impairments, including neonatal encephalopathy. METHODS: We implemented a multicentre retrospective study, assessing magnetic resonance scans of 219 infants with neonatal encephalopathy who had undergone hypothermia treatment in neonatal intensive care units located in the Netherlands and Italy. RESULTS: Abnormal MB signal was observed in ~40% of infants scanned; in half of these cases, the brain appeared otherwise normal. MB involvement was not related to the severity of encephalopathy or the pattern/severity of hypoxic-ischaemic brain injury. Follow-up scans were available for 18 cases with abnormal MB signal; in eight of these cases, the MBs appeared severely atrophic. CONCLUSIONS: This study highlights the importance of assessing the status of the MBs in neonatal encephalopathy; this may require changes to scanning protocols to ensure that the slices are sufficiently thin to capture the MBs. Furthermore, long-term follow-up of infants with abnormal MB signal is needed to determine the effects on cognition, which may enable the use of early intervention strategies. Further research is needed to assess the role of therapeutic hypothermia in MB involvement in neonatal encephalopathy. IMPACT: The MBs are particularly sensitive to hypoxia in neonates. Current hypothermia treatment provides incomplete protection against MB injury. MB involvement is likely overlooked as it can often occur when the rest of the brain appears normal. Given the importance of the MBs for memory, it is necessary that this region is properly assessed in neonatal encephalopathy. This may require improvements in scanning protocols.

Combining advanced MRI and EEG techniques better explains long-term motor outcome after very preterm birth.

BACKGROUND: Preterm born children are at high risk for adverse motor neurodevelopment. The aim of this study was to establish the relationship between motor outcome and advanced magnetic resonance imaging (MRI) and electroencephalography (EEG) measures. METHODS: In a prospective cohort study of 64 very preterm born children, the motor outcome was assessed at 9.83 (SD 0.70) years. Volumetric MRI, diffusion tensor imaging (DTI), and EEG were acquired at 10.85 (SD 0.49) years. We investigated associations between motor outcome and brain volumes (white matter, deep gray matter, cerebellum, and ventricles), white matter integrity (fractional anisotropy and mean, axial and radial diffusivity), and brain activity (upper alpha (A2) functional connectivity and relative A2 power). The independence of associations with motor outcome was investigated with a final model. For each technique, the measure with the strongest association was selected to avoid multicollinearity. RESULTS: Ventricular volume, radial diffusivity, mean diffusivity, relative A2 power, and A2 functional connectivity were significantly correlated to motor outcome. The final model showed that ventricular volume and relative A2 power were independently associated with motor outcome (B = -9.42 × 10-5, p = 0.027 and B = 28.9, p = 0.007, respectively). CONCLUSIONS: This study suggests that a lasting interplay exists between brain structure and function that might underlie motor outcome at school age. IMPACT: This is the first study that investigates the relationships between motor outcome and brain volumes, DTI, and brain function in preterm born children at school age. Ventricular volume and relative upper alpha power on EEG have an independent relation with motor outcome in preterm born children at school age. This suggests that there is a lasting interplay between structure and function that underlies adverse motor outcome.

Associations between Neonatal Magnetic Resonance Imaging and Short- and Long-Term Neurodevelopmental Outcomes in a Longitudinal Cohort of Very Preterm Children.

OBJECTIVE: To assess associations between neonatal brain injury assessed by magnetic resonance imaging and cognitive, motor, and behavioral outcomes at 2 and 10 years of age, in a longitudinal cohort of children born very preterm. STUDY DESIGN: There were 112 children born at <32 weeks of gestation who participated in a longitudinal prospective study on brain injury and neurodevelopmental outcome. Using the Kidokoro score, neonatal brain injury and altered brain growth in white matter, cortical and deep gray matter, and the cerebellum were assessed. Cognitive, motor, and behavioral outcomes were assessed during follow-up visits at both 2 (corrected) and 10 years of age. RESULTS: After adjusting for perinatal factors and level of maternal education, the global brain abnormality score was associated with cognition (B = -1.306; P = .005), motor skills (B = -3.176; P < .001), and behavior (B = 0.666; P = .005) at 2 years of age, but was not associated with cognition at 10 years of age. In the subgroup of children with a moderate-severe global brain abnormality score, magnetic resonance imaging was independently associated with cognitive impairment at 10 years of age. For children with milder forms of brain injury, only birth weight and level of maternal education were associated with cognitive outcomes. CONCLUSIONS: Neonatal brain injury, assessed by a standardized scoring system, was associated with short-term neurodevelopmental outcomes, but only with motor skills and behavior in childhood. Environmental factors, such as level of maternal education, become more important for cognitive development as children grow older, especially for children with relatively mild neonatal brain injury.

Intracerebral hemorrhage in a neonate with an intragenic COL4A2 duplication.

Intracerebral hemorrhage is rare in term born neonates. Besides several non-genetic risk factors, pathogenic variants in COL4A1 and COL4A2 have been described to play a role in the pathophysiology of neonatal intracerebral hemorrhage. To the best of our knowledge, no intragenic COL4A2 duplications have been reported in humans to date. We report a neonate with intracerebral hemorrhage and a de novo intragenic COL4A2 duplication. Although it is not clear yet whether this genetic factor fully explains the clinical phenotype, it may have contributed at least as a risk factor for cerebral hemorrhage. Screening for intragenic COL4A1 and COL4A2 duplications as part of collagen IV diagnostics should be considered as part of the fetal and neonatal work-up for unexplained cerebral hemorrhages and to collect more evidence of the pathogenicity of this genetic mechanism.

The road to zero nosocomial infections in neonates-a narrative review.

AIM: Nosocomial infections (NI) in neonates are associated with prolonged hospitalisation, adverse neurodevelopmental outcome and high mortality. Over the past decade, numerous prevention strategies have resulted in significant reductions in NI rates. In this review, we aim to provide an overview of current NI rates from large, geographically defined cohorts. METHODS: PubMed, Web of Science, EMBASE and Cochrane Library were searched for evidence regarding epidemiology and prevention of NI in neonates. Extracted studies were synthesised in a narrative form with experiential reflection. RESULTS: Despite the abundance of geographically defined incidence proportions, an epidemiological overview of NI is difficult to provide, given the lack of consensus definition for neonatal NI and different baseline populations being compared. Successful prevention efforts have focused on implementing evidence-based practices while eliminating outdated strategies. The most promising model for reduction in infection rates is based on quality improvement (QI) collaboratives and benchmarking, involving identification and implementation of best practices, selection of measurable outcomes and fostering a sense of community and transparency. CONCLUSION: The preventative rather than curative approach forms the new paradigm for reducing the burden of neonatal infections. Despite progress achieved, continued work towards improved prevention practices is required in the strive towards zero NIs.

Randomized Controlled Early versus Late Ventricular Intervention Study in Posthemorrhagic Ventricular Dilatation: Outcome at 2 Years.

OBJECTIVE: To compare the effect of intervention at low vs high threshold of ventriculomegaly in preterm infants with posthemorrhagic ventricular dilatation on death or severe neurodevelopmental disability. STUDY DESIGN: This multicenter randomized controlled trial reviewed lumbar punctures initiated after either a low threshold (ventricular index of >p97 and anterior horn width of >6 mm) or high threshold (ventricular index of >p97 + 4 mm and anterior horn width of >10 mm). The composite adverse outcome was defined as death or cerebral palsy or Bayley composite cognitive/motor scores <-2 SDs at 24 months corrected age. RESULTS: Outcomes were assessed in 113 of 126 infants. The composite adverse outcome was seen in 20 of 58 infants (35%) in the low threshold group and 28 of 55 (51%) in the high threshold (P = .07). The low threshold intervention was associated with a decreased risk of an adverse outcome after correcting for gestational age, severity of intraventricular hemorrhage, and cerebellar hemorrhage (aOR, 0.24; 95% CI, 0.07-0.87; P = .03). Infants with a favorable outcome had a smaller fronto-occipital horn ratio (crude mean difference, -0.06; 95% CI, -0.09 to -0.03; P < .001) at term-equivalent age. Infants in the low threshold group with a ventriculoperitoneal shunt, had cognitive and motor scores similar to those without (P = .3 for both), whereas in the high threshold group those with a ventriculoperitoneal shunt had significantly lower scores than those without a ventriculoperitoneal shunt (P = .01 and P = .004, respectively). CONCLUSIONS: In a post hoc analysis, earlier intervention was associated with a lower odds of death or severe neurodevelopmental disability in preterm infants with progressive posthemorrhagic ventricular dilatation. TRIAL REGISTRATION: ISRCTN43171322.

State-of-the-art neonatal cerebral ultrasound: technique and reporting.

In the past three decades, cerebral ultrasound (CUS) has become a trusted technique to study the neonatal brain. It is a relatively cheap, non-invasive, bedside neuroimaging method available in nearly every hospital. Traditionally, CUS was used to detect major abnormalities, such as intraventricular hemorrhage (IVH), periventricular hemorrhagic infarction, post-hemorrhagic ventricular dilatation, and (cystic) periventricular leukomalacia (cPVL). The use of different acoustic windows, such as the mastoid and posterior fontanel, and ongoing technological developments, allows for recognizing other lesion patterns (e.g., cerebellar hemorrhage, perforator stroke, developmental venous anomaly). The CUS technique is still being improved with the use of higher transducer frequencies (7.5-18 MHz), 3D applications, advances in vascular imaging (e.g. ultrafast plane wave imaging), and improved B-mode image processing. Nevertheless, the helpfulness of CUS still highly depends on observer skills, knowledge, and experience. In this special article, we discuss how to perform a dedicated state-of-the-art neonatal CUS, and we provide suggestions for structured reporting and quality assessment.

Ultrasound of acquired posterior fossa abnormalities in the newborn.

Neonatal brain sonography is part of routine clinical practice in neonatal intensive care units, but ultrasound imaging of the posterior fossa has gained increasing attention since the burden of perinatal acquired posterior fossa abnormalities and their impact on motor and cognitive neurodevelopmental outcome have been recognized. Although magnetic resonance imaging (MRI) is often superior, posterior fossa abnormalities can be suspected or detected by optimized cranial ultrasound (CUS) scans, which allow an early and bed-side diagnosis and monitoring through sequential scans over a long period of time. Different ultrasound appearances and injury patterns of posterior fossa abnormalities are described according to gestational age at birth and characteristics of the pathogenetic insult. The aim of this review article is to describe options to improve posterior fossa sequential CUS image quality, including the use of supplemental acoustic windows, to show standard views and normal ultrasound anatomy of the posterior fossa, and to describe the ultrasound characteristics of acquired posterior fossa lesions in preterm and term infants with effect on long-term outcome. The limitations and pitfalls of CUS and the role of MRI are discussed.

Rotavirus-Induced Neonatal Epileptic Encephalopathy-A Disease Spectrum Illustrated by Monochorionic Twins.

Rotavirus has been associated with neonatal seizures and specific white matter magnetic resonance imaging (MRI) abnormalities. We describe monochorionic twins who not only tested positive for rotavirus with these white matter MRI abnormalities but who also showed an electroencephalogram (EEG) pattern characteristic of early infantile epileptic encephalopathy (EIEE), which has so far solely been described in epileptic encephalopathies with a poor prognosis. This report suggests that rotavirus infection must be added to the list of causes of EIEE EEG, and that the outcome then is likely more favorable. As MRI and EEG signs of rotavirus encephalopathy were present in one twin with only subtle neurologic symptoms, rotavirus may well cause insidious central nervous system complications more often. We suggest considering rotavirus infection in neonates presenting with seizures, and to add rotavirus infection to the differential diagnosis of EIEE.

Putting genome-wide sequencing in neonates into perspective.

PURPOSE: Several studies have reported diagnostic yields up to 57% for rapid exome or genome sequencing (rES/GS) as a single test in neonatal intensive care unit (NICU) patients, but the additional yield of rES/GS compared with other available diagnostic options still remains unquantified in this population. METHODS: We retrospectively evaluated all genetic NICU consultations in a 2-year period. RESULTS: In 132 retrospectively evaluated NICU consultations 27 of 32 diagnoses (84.4%) were made using standard genetic workup. Most diagnoses (65.6%) were made within 16 days. Diagnostic ES yield was 5/29 (17.2%). Genetic diagnoses had a direct effect on clinical management in 90.6% (29/32) of patients. CONCLUSIONS: Our study shows that exome sequencing has a place in NICU diagnostics, but given the associated costs and the high yield of alternative diagnostic strategies, we recommend to first perform clinical genetic consultation.

Correction: Putting genome-wide sequencing in neonates into perspective.

The original version of this Article contained an error in the spelling of the author Pleuntje J. van der Sluijs, which was incorrectly given as Eline (P. J.) van der Sluijs. This has now been corrected in both the PDF and HTML versions of the Article.

Assessment of Brain Injury and Brain Volumes after Posthemorrhagic Ventricular Dilatation: A Nested Substudy of the Randomized Controlled ELVIS Trial.

OBJECTIVE: To compare the effect of early and late intervention for posthemorrhagic ventricular dilatation on additional brain injury and ventricular volume using term-equivalent age-MRI. STUDY DESIGN: In the Early vs Late Ventricular Intervention Study (ELVIS) trial, 126 preterm infants ≤34 weeks of gestation with posthemorrhagic ventricular dilatation were randomized to low-threshold (ventricular index >p97 and anterior horn width >6 mm) or high-threshold (ventricular index >p97 + 4 mm and anterior horn width >10 mm) groups. In 88 of those (80%) with a term-equivalent age-MRI, the Kidokoro Global Brain Abnormality Score and the frontal and occipital horn ratio were measured. Automatic segmentation was used for volumetric analysis. RESULTS: The total Kidokoro score of the infants in the low-threshold group (n = 44) was lower than in the high-threshold group (n = 44; median, 8 [IQR, 5-12] vs median 12 [IQR, 9-17], respectively; P < .001). More infants in the low-threshold group had a normal or mildly increased score vs more infants in the high-threshold group with a moderately or severely increased score (46% vs 11% and 89% vs 54%, respectively; P = .002). The frontal and occipital horn ratio was lower in the low-threshold group (median, 0.42 [IQR, 0.34-0.63]) than the high-threshold group (median 0.48 [IQR, 0.37-0.68], respectively; P = .001). Ventricular cerebrospinal fluid volumes could be calculated in 47 infants and were smaller in the low-threshold group (P = .03). CONCLUSIONS: More brain injury and larger ventricular volumes were demonstrated in the high vs the low-threshold group. These results support the positive effects of early intervention for posthemorrhagic ventricular dilatation. TRIAL REGISTRATION: ISRCTN43171322.

Perinatal Outcome and Long-Term Neurodevelopment after Intracranial Haemorrhage due to Fetal and Neonatal Alloimmune Thrombocytopenia.

OBJECTIVES: To evaluate the perinatal and long-term neurodevelopmental outcome in a cohort of children with intracranial haemorrhage (ICH) due to fetal and neonatal alloimmune thrombocytopenia (FNAIT) and to clearly outline the burden of this disease. SUBJECTS AND METHODS: We performed an observational cohort study and included all consecutive cases of ICH caused by FNAIT from 1993 to 2015 at Leiden University Medical Centre. Neurological, motor, and cognitive development were assessed at a minimum age of 1 year. The primary outcome was adverse outcome, defined as perinatal death or severe neurodevelopmental impairment (NDI). Severe NDI was defined as any of the following: cerebral palsy (Gross Motor Function Classification System [GMFCS] level ≥II), bilateral deafness, blindness, or severe motor and/or cognitive developmental delay (<-2 SD). RESULTS: In total, 21 cases of ICH due to FNAIT were included in the study. The perinatal mortality rate was 10/21 (48%). Long-term outcome was assessed in 10 children (n = 1 lost to follow-up). Severe and moderate NDI were diagnosed in 6/10 (60%) and 1/10 (10%) of the surviving children. The overall adverse outcome, including perinatal mortality or severe NDI, was 16/20 (80%). CONCLUSIONS: The risk of perinatal death or severe NDI in children with ICH due to FNAIT is high. Only screening and effective preventive treatment can avoid this burden.

Persistent pulmonary hypertension of the newborn after fetomaternal hemorrhage.

BACKGROUND: Newborns with anemia are at increased risk of persistent pulmonary hypertension of the newborn (PPHN), yet reports on the association between fetomaternal hemorrhage (FMH) and PPHN are rare. To optimize care for pregnancies complicated by FMH, clinicians should be aware of the risks of FMH and the possible diagnostic and therapeutic options. To increase the current knowledge, the incidence of PPHN and short-term neurologic injury in FMH cases were studied. STUDY DESIGN AND METHODS: We included all FMH cases (≥30 mL fetal blood transfused into the maternal circulation) admitted to our neonatal unit between 2006 and 2018. First, we evaluated the incidence of PPHN and short-term neurologic injury. Second, we studied the potential effect of intrauterine transfusion (IUT). RESULTS: PPHN occurred in 37.9% of newborns (11 of 29), respectively, 14.3% (one of seven) and 45.5% (10 of 22) in the IUT group and no-IUT group (p = 0.20). The mortality rate was 13.8% (4 of 29). Severe brain injury occurred in 34.5% (10 of 29), respectively, and 14.3% (one of seven) and 40.9% (nine of 22) in the IUT group and no-IUT group (p = 0.37). CONCLUSION: Awareness should be raised among perinatologists and neonatologists about the possible life-threatening consequences of FMH, as more than one-third of neonates with anemia due to FMH experience PPHN and suffer from severe brain injury. Antenatal treatment with IUT seems to reduce these risks. Specialists should therefore always consider fetal anemia in FMH cases and refer patients to a fetal therapy center. If anemia is present at birth, it should be corrected promptly and neonatologists should be aware of signs of PPHN.