Use of Therapeutic Hypothermia in Sudden Unexpected Postnatal Collapse: A Retrospective Study.

INTRODUCTION: Sudden and unexpected postnatal collapse is a rare event with potentially dramatic consequences. Intervention approaches are limited, but hypothermia has been considered after postnatal collapse. The aim of this study was to analyse sudden and unexpected postnatal collapse cases that underwent therapeutic hypothermia in the five Portuguese hypothermia centres. MATERIAL AND METHODS: In this multicentre, retrospective and descriptive study, clinical, ultrasonography, amplitude-integrated electroencephalography and brain magnetic resonance findings of newborns with postnatal collapse that underwent therapeutic hypothermia are reported (2010 - 2018). Statistical analysis was performed by using IBM SPSS Statistics version 21. RESULTS: Twenty-two cases of sudden and unexpected postnatal collapse were referred for therapeutic hypothermia (82% outborn), all ≥ 36 weeks, with Apgar 5´ ≥ 8. Collapse occurred during the first two hours in 73% (all < 24 hours), 50% during skin-to-skin care, 55% related to feeding and 23% during co-bedding. Moderate-severe encephalopathy and severe acidosis were observed (median: Thompson score 16, pH 6.90, base deficit 22 mmol/L). Amplitude-integrated electroencephalogram was abnormal in 95% and magnetic resonance imaging showed severe brain injury in 46%. The mortality rate was 50%. A possible cause was identified in 27%. DISCUSSION: The incidence rate of 2.7 sudden cases of postnatal collapse per 100 000 births, is possibly under-estimated. All infants suffered the collapse in the first day, mostly within the first two hours, as reported before. Possible causes were identified in less than a third of cases, but multiple predisposing conditions were identified, suggesting that prevention may be possible. Newborn positioning and skin-to-skin care have been the most discussed practices. A significant proportion of infants had poor outcomes. Lower Thompson score, electroencephalogram amplitude normalization and normal magnetic resonance imaging seemed to indicate better outcomes. Although conclusive trials on therapeutic hypothermia after postnatal collapse are not available, its use has been considered individually. No severe adverse effects directly related to hypothermia were registered in this study, but the results do not allow drawing meaningful conclusions. CONCLUSION: In our national sample of 22 infants who suffered sudden and unexpected postnatal collapse and underwent therapeutic hypothermia, a significant proportion had poor outcomes. Absolute conclusions from our experience with hypothermia in postnatal collapse cannot be drawn, but systematic reporting of cases and long-term clinical evaluation would facilitate understanding of the real benefits of hypothermia. As this procedure has not been validated with clinical trials for this indication, its use should be considered on a case-by-case approach. The potentially avoidable nature of unexpected postnatal collapse is evident from its association with certain behaviours and risk factors. Surveillance practices during the first hours should be implemented, whilst the benefits of breastfeeding and skin-to-skin care should continue to be widely promoted.

Introdução: O colapso pós-natal súbito inesperado, apesar de raro, condiciona potenciais consequências dramáticas. As intervenções terapêuticas são limitadas, mas a hipotermia induzida tem sido considerada após estes eventos. O objetivo deste estudo foi analisar os casos de colapso pós-natal súbito inesperado submetidos a hipotermia induzida nos cinco centros portugueses que a realizam. Material e Métodos: Estudo descritivo retrospetivo multicêntrico dos recém-nascidos submetidos a hipotermia induzida após colapso pós-natal entre 2010 e 2018. Foram analisadas as variáveis clínicas, a monitorização por eletroencefalograma de amplitude integrada e imagem por ultrassonografia e a ressonância magnética cerebral. A análise estatística foi efetuada com apoio do IBM SPSS Statistics version 21. Resultados: Foram submetidos a hipotermia terapêutica por colapso súbito 22 recém-nascidos, 82% outborn, todos com 36 ou mais semanas de gestação e Apgar 5´ ≥ 8. A situação ocorreu nas primeiras duas horas de vida em 73% (todos com menos de 24 horas de vida), 50% no contacto pele-a-pele, 55% associados à amamentação e 23% durante partilha de cama. Os recém-nascidos observados apresentaram encefalopatia moderada a grave e acidose grave (mediana: Thompson 16, pH 6,90, défice bases 22 mmol/L). Entre os recém-nascidos, 95% registaram alteração no eletroencefalograma e 46% padrões graves de ressonância cerebral. A taxa de mortalidade foi de 50%. Identificaram-se possíveis causas em 27%. Discussão: Estimou-se uma incidência de 2,7 casos de colapso pós-natal súbito inesperado por cada 100 000 nascimentos, um valor possivelmente subestimado. O colapso ocorreu no primeiro dia em todas as crianças, a maioria nas primeiras duas horas, tal como descrito em publicações anteriores. Identificaram-se possíveis causas em menos de um terço dos casos, mas múltiplas condições predisponentes foram referidas, o que sugere a possibilidade de adoção de medidas preventivas. O posicionamento do recém-nascido e o contacto pele-a-pele têm sido as práticas mais discutidas. Uma proporção significativa das crianças teve uma evolução desfavorável. Um desfecho mais positivo parece ter ocorrido nos casos em que se verificaram valores inferiores na escala de Thompson, normalização do eletroencefalograma de amplitude integrada e ressonância magnética normal. Embora não estejam disponíveis ensaios conclusivos sobre a utilização da hipotermia terapêutica após o colapso pós-natal, o seu uso tem sido considerado individualmente. Nesta revisão não foram observados efeitos adversos diretamente relacionados com o procedimento, mas os resultados não permitem obter conclusões significativas. Conclusão: Na nossa amostra nacional de 22 crianças que sofreram colapso súbito pós-natal e submetidas a hipotermia terapêutica, uma proporção significativa teve uma evolução desfavorável. A nossa experiência e a raridade da entidade clínica não permitem delinear conclusões precisas sobre a aplicação da hipotermia induzida no colapso pós-natal súbito inesperado, pelo que se considera essencial a prevenção. O benefício desta terapêutica poderá ser clarificado através do registo sistemático dos casos e do seguimento a longo prazo das crianças. Embora não existam ensaios clínicos que permitam a sua validação após estes eventos, a hipotermia induzida deve ser uma opção a considerar individualmente. A associação do colapso pós-natal com determinados comportamentos e fatores de risco evidenciam a sua potencial prevenção. Devem ser implementadas estratégias de monitorização nas primeiras horas de vida que permitam simultaneamente a contínua promoção da amamentação e do contacto pele-a-pele.

Uncomplicated intraventricular hemorrhage is not associated with lower estimated cerebral volume at term age.

BACKGROUND AND AIMS: Cerebral lesions detected using cerebral ultrasound (cUS) in very preterm infants are associated with increased risk for neurodevelopmental problems. However, uncomplicated intraventricular hemorrhage (IVH) has no consistent association with poor outcome. In this study we evaluate the effect of uncomplicated IVH on estimated brain volume at term-equivalent age (TEA), using a model based on measurements made from cUS. METHODS: We studied 2 groups of preterm infants (<32 weeks' gestational age (GA)) up to and at TEA: (1) infants with uncomplicated grades 2 or 3 IVH, (2) infants with consistently normal scans. Estimated cerebral volumes at TEA were calculated using a previously described model based on linear measurements and compared between the 2 groups using independent groups t-test or the Mann-Whitney test; p-value <0.05 was considered significant. RESULTS: We assessed 95 preterm infants (18 with uncomplicated IVH and 71 with normal scans). GA and birth weight were lower in infants with uncomplicated IVH (26.8/28.7weeks, p < 0.001, 944/1082g, p < 0.05, respectively); occipital-frontal circumference at TEA was smaller in the IVH infants (34.2 vs 35.3 cm, p < 0.05). However, no significant differences at TEA were found for estimated cranial volume (383/411cc3), estimated cerebral volume (337/341cc3), Levene ventricular index (13.5/12.2 mm) or thalamo-occipital distance (21.5/20.3 mm). Statistical adjustment for the lower GA in the IVH group confirmed the absence of a significant difference in the findings. CONCLUSIONS: In summary, we found that estimated cerebral volume at TEA, based on measurements made at the bedside using cranial US, is not different between very preterm infants with consistently normal scans and those with uncomplicated grades 2 and 3 IVH.

[Morbidity in Prematurity Associated with Fetal Growth Restriction: Experience of a Tertiary Care Center]. / Morbilidade na Prematuridade Associada a Restrição do Crescimento Fetal e nos Prematuros Leves para a Idade Gestacional: Experiência de um Centro de Referência.

INTRODUCTION: Prematurity and low birth weight have been associated with increased neonatal morbidity and mortality. This study aimed to evaluate possible risk factors for prematurity associated with fetal growth restriction and being small for gestational age and to determine the incidence of morbidity in these two groups of infants. MATERIAL AND METHODS: Retrospective case-control study of newborns with gestational age of less than 32 weeks, with obstetric diagnosis of fetal growth restriction and with the clinical diagnosis of small for gestational age, admitted to the Neonatal Intensive Care Unit of a tertiary hospital for a period of six years. RESULTS: A total of 356 newborns were studied, with an incidence of 11% of fetal growth restriction and 18% of small for gestational age. Pre-eclampsia was the risk factor for gestation with higher statistical significance (47% vs 16%, p < 0.001) in small for gestational age newborns. There was also a higher incidence of mild bronchopulmonary dysplasia (66% vs 38%, p = 0.005), late sepsis (59% vs 37%, p = 0.003), retinopathy of prematurity (58% vs 26%, p = 0.003) and necrotizing enterocolitis (20% vs 9%, p = 0.005). Mortality was similar in all three groups. DISCUSSION: There were fewer newborn males diagnosed with fetal growth restriction during pregnancy compared to women. Significant differences were observed in the group of these infants regarding the occurrence of chorioamnionitis and pre-eclampsia in comparison to the control group. Newborns with fetal growth restriction and small for age had higher scores on clinical risk indices compared to the control group. In general, small for gestational age newborns had a higher incidence of morbidity than infants with fetal growth restriction and the control group. CONCLUSION: Advances in neonatal intensive care decreased mortality in preterm infants. However, there are still significant differences in the incidence of morbidity in newborns with growth compromise. The collaboration between obstetricians and neonatologists provides the basis for a correct clinical evaluation, early signaling and global intervention on these newborns, with a significant impact on short and long-term prognosis.

Introdução: A prematuridade e o baixo peso ao nascer têm sido associados a maior morbilidade e mortalidade neonatais. Este estudo teve como objetivo avaliar possíveis fatores de risco para a prematuridade associada a restrição do crescimento fetal e a recém-nascidos leves para a idade gestacional e determinar a incidência da morbilidade nestes dois grupos de recém-nascidos.Material e Métodos: Estudo caso-controlo retrospetivo dos recém-nascidos com idade gestacional inferior a 32 semanas, com o diagnóstico obstétrico de restrição do crescimento fetal e com o diagnóstico clínico de leves para a idade gestacional, internados na Unidade de Cuidados Intensivos Neonatais de um hospital terciário, durante um período de seis anos.Resultados: Foram estudados 356 recém-nascidos, observando-se uma incidência de 11% de restrição do crescimento fetal e 18% de leves para a idade gestacional. A pré-eclâmpsia foi o fator de risco da gestação com maior significado estatístico (47% vs 16%, p < 0,001) nos recém-nascidos leves para a idade gestacional. Observou-se também, nestes recém-nascidos, maior incidência de displasia broncopulmonar ligeira (66% vs 38%, p = 0,005), de sépsis tardia (59% vs 37%, p = 0,003), de retinopatia da prematuridade (58% vs 26%, p = 0,003) e de enterocolite necrotizante (20% vs 9%, p = 0,005). A mortalidade foi idêntica nos três grupos.Discussão: Encontraram-se menos recém-nascidos do sexo masculino diagnosticados com restrição do crescimento fetal durante a gravidez comparativamente ao sexo feminino. Observaram-se diferenças significativas no grupo destes recém-nascidos, quanto à ocorrência de corioamnionite e de pré-eclâmpsia, face ao grupo controlo. Tanto os recém-nascidos com restrição do crescimento fetal como os leves para a idade gestacional apresentaram uma pontuação mais elevada nos índices de risco clínico comparativamente ao grupo controlo. De forma global, os recém-nascidos leves para a idade gestacional tiveram maior incidência de morbilidade que os recém-nascidos com restrição do crescimento fetal e que o grupo controlo.Conclusão: Os avanços nos cuidados intensivos neonatais diminuíram a mortalidade nos recém-nascidos prematuros. Contudo, observam-se ainda diferenças significativas na incidência da morbilidade nos recém-nascidos com compromisso do crescimento. A colaboração entre obstetras e neonatalogistas constitui a base para uma correta avaliação clínica, sinalização precoce e intervenção global sobre estes recém-nascidos, com impacto significativo no prognóstico a curto e longo prazo.

Persistent periventricular echogenicities in preterms are not related to smaller brains at term-equivalent age.

BACKGROUND: Periventricular white matter (PWM) is particularly vulnerable in very preterm infants. Non-cystic white matter injury, known as non-cystic periventricular leukomalacia (ncPVL), is the commonest 'lesion' affecting the preterm brain. There is no consensus about whether ncPVL can be reliably identified from cerebral ultrasound (cUS) or whether there is any reliable correlate of ncPVL on cUS at term-equivalent age (TEA). OBJECTIVE: To compare brain volumes and linear measures at TEA in infants with and without a diagnosis of ncPVL. METHODS: Preterm infants of ≤32 weeks' gestation without major lesions were serially assessed using cUS. ncPVL was defined as PWM echogenicity comparable to the choroid plexus on two scans at least 2 weeks apart after the first postnatal week. At TEA, infants were scanned for the estimation of brain volume and ventricular and tissue dimensions. Head circumference was measured. The data were compared between those with/without ncPVL. Observer agreement was assessed using kappa statistic. RESULTS: Of 63 eligible infants 29% had ncPVL. Significant differences were found between those with/without ncPVL for 5 min Apgar score, CRIB score, invasive ventilation rates and chronic lung disease but not for other relevant clinical data. No significant differences were found for estimated brain volume, ventricular size, corpus callosum length/thickness or central grey matter width. Intra-observer reliability was moderate (kappa = 0.51-0.56); inter-observer reliability was poor (kappa = 0.20-0.32). CONCLUSIONS: This study indicates that an ultrasound diagnosis of ncPVL should not be used as a sole predictor of lower brain growth detectable at TEA.

Preterm cerebellum at term age: ultrasound measurements are not different from infants born at term.

BACKGROUND: Reduced supratentorial brain growth has been shown in preterm-born infants at term-equivalent age (TEA), but cerebellar growth may be preserved in the absence of supratentorial injury. Our study aims to compare cerebellar size assessed using cerebral ultrasound (cUS) at TEA between preterm infants and term-born controls. METHODS: Cerebellar dimensions (including transverse cerebellar diameter (TCD), cerebellar vermis height, anteroposterior vermis diameter (APVD), and cerebellar vermis area (CVA)) were measured using Image Arena software (TomTec Imaging Systems, Unterschleissheim, Germany) in 71 infants <32-wk gestation without significant scan abnormality at TEA and in 58 term-born control infants. Intra- and interobserver agreement were evaluated. RESULTS: In comparison with controls, preterms at TEA had smaller TCDs (4.9 vs. 5.2 cm; P < 0.001) but larger CVAs (4.7 vs. 4.3 cm(2); P < 0.005) and APVDs (2.4 vs. 2.2 cm; P < 0.001); however, these differences were no longer seen after accounting for head shape. In <28-wk gestational age infants, CVA was statistically similar to controls, as were for small-for-gestational-age infants. CONCLUSION: Our data support neonatal sparing of preterm cerebellar growth that is measureable using cUS, and this includes the most immature and small-for-gestational-age infants. We suggest cUS can be used to assess cerebellar size at TEA, with measures of both width and height being taken into account, and thus may be a useful tool for detecting infants with poorer cerebellar growth who are at increased risk of disability.

Cerebral volume at term age: comparison between preterm and term-born infants using cranial ultrasound.

BACKGROUND AND AIMS: Very preterm infants are at particular risk of neurodevelopmental impairments. This risk can be anticipated when major lesions are seen on cerebral ultrasound (cUS). However, most preterm infants do not have such lesions yet many have a relatively poor outcome. Our study aims were to describe a tri-dimensional cUS model for measuring cranial and brain volume and to determine the range of brain volumes found in preterm infants without major cUS lesions at term equivalent age (TEA) compared to term-born control infants. We also aimed to evaluate whether gestational age (GA) at birth or being small for gestational age (SGA) influenced estimated brain size. METHODS: We scanned a cohort of very preterm infants at TEA and term-born controls. Infants with major cerebral lesions were excluded. Measurements of intracranial diameters (bi-parietal, longitudinal, cranial height), brain structures, ventricles and extracerebral space (ECS) were made. A mathematical model was built to estimate from the cUS measurements the axial area and volumes of the cranium and brain. Appropriate statistical methods were used for comparisons; a p-value under 0.05 was considered significant. SGA infants from both groups were analysed separately. RESULTS: We assessed 128 infants (72 preterms and 56 controls). The preterms' head was longer (11.5 vs. 10.5 cm, p < 0.001), narrower (7.8 vs. 8.4 cm, p < 0.001) and taller (8.9 vs. 8.6 cm, p < 0.01) than the controls'. Estimated intracranial volume was not statistically different between the groups (411 vs. 399 cm(3), NS), but preterms had larger estimated ECS volume (70 vs. 22 cm(3), p < 0.001), lateral ventricular coronal areas (33 vs. 12 mm(2), p < 0.001) and thalamo-occipital distances (20 vs. 16 mm, p < 0.001), but smaller estimated cerebral volume (340 vs. 377 cm(3), p < 0.001). Smaller brain volumes were associated with being of lower gestational age and birth weight and being small-for-gestational age. CONCLUSIONS: We have developed a model using cranial ultrasound for measuring cranial and brain volumes. Using this model our data suggest that even in the absence of major cerebral lesions, the average extrauterine cerebral growth of very preterm infants is compromised. Our model can help in identifying those preterm infants with smaller brains. Later follow-up data will determine the neurodevelopmental outcome of these preterm infants in relation to their estimated brain volumes.