Annemieke J. Brouwer

Neurodevelopmental Outcome of Preterm Infants with Severe Intraventricular Hemorrhage and Therapy for Post-Hemorrhagic Ventricular Dilatation

OBJECTIVEnTo evaluate the neurodevelopmental outcome of preterm infants with a grade III or IV hemorrhage and to assess the effect of routine low-threshold therapy of post-hemorrhagic ventricular dilatation (PHVD) on neurodevelopmental outcome.nnnSTUDY DESIGNnOf the 214 preterm infants (< or = 34 weeks gestational age), 94 (44%) had a grade III intraventricular hemorrhage (IVH), and 120 (56%) had a grade IV hemorrhage. We evaluated the natural evolution of IVH, the need for intervention for PHVD, and neurodevelopmental outcome at 24 months corrected age.nnnRESULTSnPHVD developed significantly more often in the surviving infants with a grade III hemorrhage (53/68, 78%) than in infants with a grade IV hemorrhage (40/76, 53%; P = .002). Intervention for PHVD was required significantly more often in the grade III group, than in the grade IV group (P < .001). In the grade III group, cerebral palsy developed in 5 of the 68 surviving infants (7.4%), compared with 37 of the 76 infants (48.7%) with a grade IV hemorrhage (P < .001). The mean developmental quotient (DQ) in the grade III group was 99, and in the grade IV-group it was 95 at 24 months corrected age.nnnCONCLUSIONSnShort-term neurodevelopmental outcome of preterm infants with grade III or IV hemorrhage was better than reported earlier. Requiring intervention for PHVD only had a negative effect on DQ in infants with a grade IV hemorrhage. Infants with cerebral palsy had significantly lower DQs, irrespective of the severity of IVH.

Intracranial hemorrhage in full-term newborns: a hospital-based cohort study

IntroductionIn recent years, intracranial hemorrhage (ICH) with parenchymal involvement has been diagnosed more often in full-term neonates due to improved neuroimaging techniques. The aim of this study is to describe clinical and neuroimaging data in the neonatal period and relate imaging findings to outcome in a hospital-based population admitted to a level 3 neonatal intensive care unit (NICU).MethodsFrom our neuroimaging database, we retrospectively retrieved records and images of 53 term infants (1991–2008) in whom an imaging diagnosis of ICH with parenchymal involvement was made. Clinical data, including mode of delivery, clinical manifestations, neurological symptoms, extent and site of hemorrhage, neurosurgical intervention, and neurodevelopmental outcomes, were recorded.ResultsSeventeen of the 53 term infants had infratentorial ICH, 20 had supratentorial ICH, and 16 had a combination of the two. Seizures were the most common presenting symptom (71.7%), another ten infants (18.9%) presented with apneic seizures, and five infants had no clinical signs but were admitted to our NICU because of perinatal asphyxia (nu2009=u20092), respiratory distress (nu2009=u20092), and development of posthemorrhagic ventricular dilatation (nu2009=u20091). Continuous amplitude-integrated electroencephalography recordings were performed in all infants. Clinical or subclinical seizures were seen in 48/53 (90.6%) infants; all received anti-epileptic drugs. Thirteen of all 53 (24.5%) infants died. The lowest mortality rate was seen in infants with supratentorial ICH (10%). Three infants with a midline shift required craniotomy, six infants needed a subcutaneous reservoir due to outflow obstruction, and three subsequently required a ventriculoperitoneal shunt. The group with poor outcome (death or developmental quotient (DQ) <85) had a significantly lower 5-min Apgar score (pu2009=u2009.006). Follow-up data were available for 37/40 survivors aged at least 15xa0months. Patients were assessed with the Griffiths Mental Developmental Scales, and the mean DQ of all survivors was 97 (SDu2009=u200912). Six infants (17%) had a DQ below 85 [two of them had cerebral palsy (CP)]. Three infants developed CP (8.6%); one had cerebellar ataxia, and two had hemiplegia.ConclusionICH with parenchymal involvement carries a risk of adverse neurological sequelae with a mortality of 24.5% and development of CP in 8.6%. The high mortality rate could partly be explained by associated perinatal asphyxia. Infants with supratentorial ICH had a lower, although not significant, mortality rate compared with infants with infratentorial ICH and infants with a combination of supratentorial ICH and infratentorial ICH. In spite of often large intraparenchymal lesions, 30 of the 34 survivors without CP (88.2%) had normal neurodevelopmental outcome at 15xa0months.

Clinical aspects of induced hypothermia in full term neonates with perinatal asphyxia

Moderate hypothermia is a novel neuroprotective therapy for full term neonates with severe perinatal asphyxia. Although the therapy appears to be safe, admission to a level III neonatal intensive care unit of these patients is justified. Potential complications include hypotension, tube obstruction due to sticky secretions, severe bradycardia, and thrombocytopenia. Furthermore, doses of commonly used drugs such as sedatives, anticonvulsants and antibiotics should be adjusted during hypothermia and on rewarming, and should be monitored carefully. Further studies aiming at optimizing onset, duration, and depth of hypothermia in neonates are necessary. Combination of hypothermia with drugs may further improve neuroprotection in asphyxiated full term neonates.

Effects of Posthemorrhagic Ventricular Dilatation in the Preterm Infant on Brain Volumes and White Matter Diffusion Variables at Term-Equivalent Age

OBJECTIVEnTo evaluate the differential impact of germinal matrix-intraventricular hemorrhage (GMH-IVH) and posthemorrhagic ventricular dilatation (PHVD) on brain and cerebrospinal fluid (CSF) volumes and diffusion variables in preterm born infants at term-equivalent age (TEA).nnnSTUDY DESIGNnNineteen infants (gestational age <31xa0weeks) with GMH-IVH grade II-III according to Papile etxa0al and subsequent PHVD requiring intervention were matched against 19 controls with GMH-IVH grade II but no PHVD and 19 controls without GMH-IVH. Outcome variables on magnetic resonance imaging (MRI) including diffusion weighted imaging at TEA were volumes of white matter, cortical gray matter, deep gray matter, brainstem, cerebellum, ventricles, extracerebral CSF, total brain tissue, and intracranial volume (ICV), as well as white matter and cerebellar apparent diffusion coefficients (ADCs). Effects of GMH-IVH and PHVD on TEA-MRI measurements were evaluated using multivariable regression analysis. Brain and CSF volumes were adjusted for ICV to account for differences in bodyweight at TEA-MRI and ICV between cases and controls.nnnRESULTSnPHVD was independently associated with volumes of deep gray matter (β [95% CI]: -1.4xa0cc [-2.3; -.5]), cerebellum (-2.7xa0cc [-3.8; -1.6]), ventricles (+12.7xa0cc [7.9; 17.4]), and extracerebral CSF (-11.2xa0cc [-19.2; -3.3]), and with ADC values in occipital, parieto-occipital, and parietal white matter (β: +.066-.119×10(-3)xa0mm(2)/s) on TEA-MRI (Pxa0<xa0.05). No associations were found between GMH-IVH grade II-III and brain and CSF volumes or ADC values at TEA.nnnCONCLUSIONSnPHVD was negatively related to deep gray matter and cerebellar volumes and positively to white matter ADC values on TEA-MRI, despite early intervention for PHVD in the majority of the infants. These relationships were not observed for GMH-IVH.

Early and Late Complications of Germinal Matrix-Intraventricular Haemorrhage in the Preterm Infant: What Is New?

Germinal matrix-intraventricular haemorrhage (GMH-IVH) remains a serious problem in the very and extremely preterm infant. This article reviews current methods of diagnosis, treatment and neurodevelopmental outcome in preterm infants with low-grade and severe GMH-IVH. We conclude that there is still no consensus on timing of intervention and treatment of infants with GMH-IVH, whether or not complicated by post-haemorrhagic ventricular dilatation. The discrepancies between the studies underline the need for international collaboration to define the optimal strategy for these infants.

Posthaemorrhagic ventricular dilatation: when should we intervene?

Germinal matrix haemorrhage–intraventricular haemorrhage (GMH–IVH) remains a common neurological complication of preterm birth, occurring in about 10–20% of preterm infants with a gestational age (GA) below 30u2005weeks and is predictive of an adverse neurological outcome.1 About 30–50% of infants with a large IVH develop posthaemorrhagic ventricular dilatation (PHVD) and around 20–40% of infants with a severe GMH–IVH will consequently need a permanent ventriculo-peritoneal shunt.1 ,2 The presence of associated white matter injury, due to either a unilateral parenchymal haemorrhage or a more diffuse bilateral white matter damage, and development of PHVD increase the risk of an adverse neurodevelopmental outcome. Around 45–60% of infants with PHVD have marked cognitive impairment (developmental quotient equivalent of less than 70).1nnWhen to intervene with drainage of cerebrospinal fluid is a challenge for the neonatologists who care for them. In an accompanying article, Klebermass-Schrehof and colleagues address this question, when to intervene?2 As they have shown previously,3 several neurophysiological parameters may change in preterm infants with PHVD following a large IVH. Recording amplitude-integrated EEG (aEEG) and visual-evoked potentials (VEPs) before and after insertion of a ventricular reservoir, they found deterioration in aEEG background pattern and an increase in VEP latency with progressive ventricular dilatation and improvement in these parameters within a week of insertion of the reservoir. Their findings are especially interesting as most of the infants they studied showed …

Ventricular reservoir punctures performed by nurses: an improvement in quality of care.

Management strategies in the treatment of infants with posthemorrhagic ventricular dilation include the placement of a ventricular reservoir. Traditionally, ventricular punctures of these reservoirs have been performed only by physicians. In the pilot project described in this article, we taught nursing staff to perform punctures of a cerebral ventricular reservoir in neonates with hydrocephalus to give nurses more control in their daily care of these infants. All consecutive punctures performed between August 2006 and March 2007 (n = 302) were studied. The chart was reviewed for the infant’s state during the puncture, the caregiver who performed the puncture, and the timeliness of the puncture with respect to schedule and to infant state. During the day shift, there was no significant difference in timeliness, whether the puncture was performed by a physician, a nurse, a physician assistant (PA), or a nurse under the supervision of a physician. On the night shift, punctures were performed on schedule significantly more often when they were carried out by nurses (p>.001). This pilot project demonstrated that nurses can learn to perform cerebrospinal fluid removal from a ventricular reservoir. Because it increased the timeliness with which punctures were performed and gave nurses more control in planning rest periods for these infants, this policy change was judged a success.

Posthemorrhagic ventricular dilatation in preterm infants: When best to intervene?

Objective To compare neurodevelopmental outcomes of preterm infants with and without intervention for posthemorrhagic ventricular dilatation (PHVD) managed with an “early approach” (EA), based on ventricular measurements exceeding normal (ventricular index [VI] <+2 SD/anterior horn width <6 mm) with initial temporizing procedures, followed, if needed, by permanent shunt placement, and a “late approach” (LA), based on signs of increased intracranial pressure with mostly immediate permanent intervention. Methods Observational cohort study of 127 preterm infants (gestation <30 weeks) with PHVD managed with EA (n = 78) or LA (n = 49). Ventricular size was measured on cranial ultrasound. Outcome was assessed at 18–24 months. Results Forty-nine of 78 (63%) EA and 24 of 49 (49%) LA infants received intervention. LA infants were slightly younger at birth, but did not differ from EA infants for other clinical measures. Initial intervention in the EA group occurred at younger age (29.4/33.1 week postmenstrual age; p < 0.001) with smaller ventricles (VI 2.4/14 mm >+2 SD; p < 0.01), and consisted predominantly of lumbar punctures or reservoir taps. Maximum VI in infants with/without intervention was similar in EA (3/1.5 mm >+2 SD; p = 0.3) but differed in the LA group (14/2.1 mm >+2 SD; p < 0.001). Shunt rate (20/92%; p < 0.001) and complications were lower in EA than LA group. Most EA infants had normal outcomes (>−1 SD), despite intervention. LA infants with intervention had poorer outcomes than those without (p < 0.003), with scores <−2 SD in 81%. Conclusion In preterm infants with PHVD, those with early intervention, even when eventually requiring a shunt, had outcomes indistinguishable from those without intervention, all being within the normal range. In contrast, in infants managed with LA, need for intervention predicted worse outcomes. Benefits of EA appear to outweigh potential risks. Classification of evidence This study provides Class III evidence that for preterm infants with PHVD, an EA to management results in better neurodevelopmental outcomes than a LA.

The Impact of Low-Grade Germinal Matrix-Intraventricular Hemorrhage on Neurodevelopmental Outcome of Very Preterm Infants

Background: Very preterm infants often show germinal matrix-intraventricular hemorrhage (GMH-IVH) on cranial ultrasound (cUS). Aim: To determine the impact of low-grade GMH-IVH on early neurodevelopmental outcome in very preterm infants. Methods: A retrospective case-control study in very preterm infants with and without low-grade GMH-IVH on cUS. Additional magnetic resonance imaging (MRI) was available in all infants with a gestational age (GA) <28 weeks and high-risk infants >28 weeks. Infants were seen at 2 years corrected age to assess neurodevelopment. Results: In total, 136 infants (GA 24-32 weeks) with low-grade GMH-IVH on cUS were matched with 255 controls. Outcome data was available for 342 (87%) infants. Adverse outcome (i.e., cerebral palsy [CP], neurodevelopmental delay) was present in 11 (9%) cases and 20 (9%) controls. No statistically significant differences in outcome were found between cases and controls. Additional MRI was performed in 165/391 infants (42%) and showed additional lesions in 73 (44%) infants that could explain subsequent development of CP in 2 out of 5 infants and epilepsy in 1 of 2 infants. Conclusion: Very preterm infants with low-grade GMH-IVH on cUS have a similar early neurodevelopmental outcome compared with controls. Additional MRI showed mostly subtle abnormalities that were missed with cUS, but these could not explain subsequent development of CP and developmental delay in all infants.

The Effect of Head Positioning and Head Tilting on the Incidence of Intraventricular Hemorrhage in Very Preterm Infants : A Systematic Review

Background: Despite advances in neonatal intensive care, germinal matrix-intraventricular hemorrhage (GMH-IVH) remains a frequent, serious complication of premature birth. Neutral head position and head tilting have been suggested to reduce the risk of GMH-IVH in preterm infants during the first 72 h of life. Objective: The aim of this study was to provide a systematic review of the effect of neutral head positioning and head tilting on the incidence of GMH-IVH in very preterm infants (gestational age ≤30 weeks). In addition, we reviewed their effect on cerebral hemodynamics and oxygenation. Methods: Literature was searched (June 2016) in the following electronic databases: CINAHL, Embase, Medline, SCOPUS, and several trial registers. Results: One underpowered trial studied the effect of head positioning on the incidence of GMH-IVH. This randomized controlled trial enrolled 48 preterm infants and found no effect on the occurrence of GMH-IVH. Three observational studies investigated the effect of head rotation and/or tilting on cerebral oxygenation in 68 preterm infants in total. Their results suggest that cerebral oxygenation is not significantly affected by changes in head positioning. The effect of head positioning and/or tilting on cerebral hemodynamics was described in 2 observational studies of 28 preterm infants and found no significant effect. Conclusions: There is insufficient evidence regarding the effect of head positioning and tilting on the incidence of GMH-IVH and cerebral hemodynamics and oxygenation in preterm infants. We recommend further research in this field, especially in extremely preterm and clinically unstable infants during the first postnatal days.