Impact of early-onset preeclampsia on feeding tolerance and growth of very low birth weight infants during hospitalization / Efeito da pré-eclâmpsia precoce na tolerância alimentar e no crescimento de recém-nascidos de muito baixo peso durante a hospitalização

ABSTRACT Objective: The provision of adequate enteral nutrition to preterm infants is a great challenge, and preeclampsia (PE) may have a detrimental effect on the safety of nutrition supply. This study aims to investigate the influence of early-onset PE on preterm infants' enteral feeding tolerance and growth during hospitalization. Methods: This is a prospective study with 55 preterm infants <34 weeks born to PE mothers matched by gestational age with 55 preterm infants born to normotensive mothers from 2013 to 2016. We evaluated maternal, gestational, and neonatal clinical data. The outcomes were feeding intolerance and growth during hospitalization. Comparison between groups was performed by Student's t-test or Mann-Whitney U test, chi-square test, or Fisher's exact test. Multiple logistic regression was used to investigate whether PE was an independent risk factor for feeding intolerance. Results: The mean gestational age was 30 weeks. Preterm infants of mothers with PE had lower birth weight and were smaller at discharge. Feeding intolerance was frequent, but necrotizing enterocolitis was rare in this sample (PE=4% vs. control=2%) with no difference between groups. Preterm infants of mothers with PE had worse growth outcomes; however, PE was not an independent risk factor for feeding intolerance. The increase in gestational age was a protective factor, and being born small for gestational age (SGA) increased the risk of feeding intolerance by six times. Conclusions: Preterm infants of mothers with early-onset PE were more likely to be born SGA and had a worse growth trajectory during hospitalization. In adjusted analyses, however, low gestational age and SGA were independent predictors of feeding intolerance.

RESUMO Objetivo: A nutrição enteral adequada para recém-nascidos prematuros é um grande desafio, e a pré-eclâmpsia (PE) pode comprometer a segurança da oferta alimentar. O objetivo deste estudo é investigar a influência da PE de início precoce na tolerância alimentar e no crescimento de prematuros durante a hospitalização. Métodos: Estudo prospectivo, com 55 prematuros <34 semanas de mães com PE pareados por idade gestacional e com 55 prematuros de mães normotensas, de 2013 a 2016. Foram avaliados dados clínicos maternos, gestacionais e neonatais. Os desfechos foram intolerância alimentar e crescimento durante a hospitalização. Na comparação entre grupos, utilizaram-se teste t de Student ou de Mann-Whitney e teste qui-quadrado ou exato de Fisher. Regressão logística múltipla foi usada para investigar se a PE é fator de risco para intolerância alimentar. Resultados: A idade gestacional média foi de 30 semanas. Prematuros de mães com PE tiveram menor peso ao nascer e eram menores na alta. A intolerância alimentar foi frequente, mas a enterocolite necrosante foi rara nesta amostra (PE=4% vs. controle=2%), sem diferença entre grupos. Prematuros de mães com PE tiveram pior crescimento, mas a PE não foi fator independente de risco para intolerância alimentar. O aumento da idade gestacional foi fator de proteção, e nascer pequeno para a idade gestacional (PIG) aumentou em seis vezes o risco de intolerância alimentar. Conclusões: Prematuros de mães com PE de início precoce tiveram maior probabilidade de nascer PIG e pior trajetória de crescimento na hospitalização. Em análises ajustadas, baixa idade gestacional e PIG foram preditores independentes de intolerância alimentar.

Impact of early-onset preeclampsia on feeding tolerance and growth of very low birth weight infants during hospitalization.

OBJECTIVE: The provision of adequate enteral nutrition to preterm infants is a great challenge, and preeclampsia (PE) may have a detrimental effect on the safety of nutrition supply. This study aims to investigate the influence of early-onset PE on preterm infants' enteral feeding tolerance and growth during hospitalization. METHODS: This is a prospective study with 55 preterm infants <34 weeks born to PE mothers matched by gestational age with 55 preterm infants born to normotensive mothers from 2013 to 2016. We evaluated maternal, gestational, and neonatal clinical data. The outcomes were feeding intolerance and growth during hospitalization. Comparison between groups was performed by Student's t-test or Mann-Whitney U test, chi-square test, or Fisher's exact test. Multiple logistic regression was used to investigate whether PE was an independent risk factor for feeding intolerance. RESULTS: The mean gestational age was 30 weeks. Preterm infants of mothers with PE had lower birth weight and were smaller at discharge. Feeding intolerance was frequent, but necrotizing enterocolitis was rare in this sample (PE=4% vs. control=2%) with no difference between groups. Preterm infants of mothers with PE had worse growth outcomes; however, PE was not an independent risk factor for feeding intolerance. The increase in gestational age was a protective factor, and being born small for gestational age (SGA) increased the risk of feeding intolerance by six times. CONCLUSIONS: Preterm infants of mothers with early-onset PE were more likely to be born SGA and had a worse growth trajectory during hospitalization. In adjusted analyses, however, low gestational age and SGA were independent predictors of feeding intolerance.

The effect of early-onset preeclampsia on the intestinal blood flow of preterm infants.

BACKGROUND: Preeclampsia is associated with important vascular maternal changes. However, its repercussions on newborns' circulation have hardly been reported. OBJECTIVE: To investigate whether early-onset preeclampsia is associated with altered blood flow of the superior mesenteric artery (SMA) in preterm infants. MATERIALS AND METHODS: Prospective study with 60 preterm infants of mothers with early-onset preeclampsia (PE) and 60 of normotensive mothers, paired according to the gestational age, from 2013 to 2016. Maternal, gestational, and neonatal clinical data were evaluated. The outcome of interest was the blood flow velocity in SMA, evaluated by the peak systolic velocity and end-diastolic velocity and by the resistance index and pulsatility index, through the Doppler ultrasound in the first 72 h of life. Covariance analysis was used to determine the PE effect on the SMA blood flow, controlling for possible confounding variables. RESULTS: The mean gestational age was 30 weeks. Infants of mothers with PE had significantly lower values of peak systolic and end-diastolic velocity (57.75 ± 17.49 and 12.29 ± 5.74) compared with the control group (67.17 ± 29.57 and 15.03 ± 7.52), even after control of covariates. CONCLUSION: Early-onset preeclampsia is associated with decreased blood flow of SMA in preterm infants on the first days of life.

Cord blood cytokine levels in focal early-onset neonatal infection after preterm premature rupture of membranes.

This study aimed to evaluate the levels of pro- and anti-inflammatory cytokines in umbilical cord blood of preterm neonates who developed focal early-onset infection (EOI) after preterm premature rupture of membranes (PPROM). This is a prospective study conducted on 46 preterm infants from mothers with PPROM. The cytokines were measure by flow cytometry. Newborns were classified into two groups as focal EOI (n=19) and non-infected (n=27). Interleukin (IL)-6 and IL-8 levels were higher, whereas IL-10 and IL-12 p70 levels were lower in the EOI when compared to the non-infected group. The best combination of cytokines was IL-6+IL-8, with a diagnostic accuracy of 0.97. Focal EOI after PPROM is associated with increased levels of IL-6 and IL-8 and diminished IL-10 and IL-12 in the cord blood of preterm infants. Combined assessment of IL-6 and IL-8 in cord blood may provide an additional tool for identifying preterm infants who develop EOI after PPROM.

Hypoxic-preconditioning induces neuroprotection against hypoxia-ischemia in newborn piglet brain.

Preconditioning-induced ischemic tolerance has been documented in the newborn brain, however, the signaling mechanisms of this preconditioning require further elucidation. The aims of this study were to develop a hypoxic-preconditioning (PC) model of ischemic tolerance in the newborn piglet, which emulates important clinical similarities to human situation of birth asphyxia, and to characterize some of the molecular mechanisms shown to be implicated in PC-induced neuroprotection in rodent models. One day old piglets were subjected to PC (8% O2/92% N2) for 3 h and 24 h later were exposed to hypoxia-ischemia (HI) produced by a combination of hypoxia (5% FiO2) for a period of 30 min and ischemia induced by a period of hypotension (10 min of reduced mean arterial blood pressure; ≤70% of baseline). Neuropathologic analysis and unbiased stereology, conducted at 24 h, 3 and 7 days of recovery following HI, indicated a substantial reduction in the severity of brain damage in PC piglets compared to non-PC piglets (P<0.05). PC significantly increased the mRNA expression of hypoxia-inducible factor-1α (HIF-1α) and its target gene, vascular endothelial growth factor (VEGF) at 0 h, 6h, 24 h, 3 and 7 days of recovery. Immunoblot analysis demonstrated that PC resulted in HIF-1α protein stabilization and accumulation in nuclear extracts of cerebral cortex of newborn piglet brain compared to normoxic controls. Protein levels of VEGF increased in a time-dependent manner in both cortex and hippocampus following PC. Double-immunolabeling indicated that VEGF is mainly expressed in neurons, endothelial cells and astroglia. Our study demonstrates for the first time the protective efficacy of PC against hypoxic-ischemic injury in newborn piglet model, which recapitulates many pathophysiological features of asphyxiated human neonates. Furthermore, as has been shown in rodent models of preconditioning, our results suggest that PC-induced protection in neonatal piglets may involve upregulation of VEGF.

Characterization of neural stem/progenitor cells expressing VEGF and its receptors in the subventricular zone of newborn piglet brain.

Neural stem/progenitor cell (NSP) biology and neurogenesis in adult central nervous system (CNS) are important both towards potential future therapeutic applications for CNS repair, and for the fundamental function of the CNS. In the present study, we report the characterization of NSP population from subventricular zone (SVZ) of neonatal piglet brain using in vivo and in vitro systems. We show that the nestin and vimentin-positive neural progenitor cells are present in the SVZ of the lateral ventricles of neonatal piglet brain. In vitro, piglet NSPs proliferated as neurospheres, expressed the typical protein of neural progenitors, nestin and a range of well-established neurodevelopmental markers. Upon dissociation and subculture, piglet NSPs differentiated into neurons and glial cells. Clonal analysis demonstrates that piglet NSPs are multipotent and retain the capacity to generate both glia and neurons. These cells expressed VEGF, VEGFR1, VEGFR2 and Neuropilin-1 and -2 mRNAs. Real time PCR revealed that SVZ NSPs from newborn piglet expressed total VEGF and all VEGF splice variants. These findings show that piglet NSPs may be helpful to more effectively design growth factor based strategies to enhance endogenous precursor cells for cell transplantation studies potentially leading to the application of this strategy in the nervous system disease and injury.

The newborn pain cry: descriptive acoustic spectrographic analysis.

INTRODUCTION: Study the characteristics of pain vocal emission of newborns during venepuncture through acoustic analysis and relate it to NIPS pain scale and some variables of the newborns. METHODS: Emissions of 111 healthy term newborns were recorded, whose lifetime varied from 24 to 72 h. The acoustic analysis was realized with GRAM 5.7 software verifying the occurrence of tense strangled voice quality, sounds, concentration of acoustic energy, breaks, double harmonic breaks and frequency instability, type of phonation, vocal attack and cough. The NIPS scale was realized during venepuncture and descriptive statistical analysis and correlation through Spearman test. RESULTS: Hundred percent of the emissions had guttural sounds, vowels, hard vocal attack, frequency, breaks, double harmonic breaks and tense strangled voice quality; 34.2% higher fundamental frequency; 62.2% periods of emission absence and 100% occurrence of tracing instability, concentration of acoustic energy, inspiratory and expiratory phonation. The cough occurred in 14.4%. The signs of vocal tract constriction associated with all the parameters. There was a negative correlation between the higher fundamental frequencies and the weight of newborns and positive correlation between cough and NIPS score. CONCLUSIONS: The newborn pain emission is tense and strident, the modifications of frequency and spectrographic tracing and the presence of sounds show laryngeal and vocal tract participation. The smaller the newborn weight, the bigger the presence of higher fundamental frequency with tense strangled voice quality and the bigger the NIPS score, the more frequent the cough. Such characteristics make pain crying peculiar, helping in the evaluation of pain during a procedure.

Cistos subependimários diagnosticados pelo ultra-som transfontanelar / Diagnosis of subependymal cysts by brain ultrasound

Objetivos: avaliar a evolução ultra-sonográfica de cistos subependimários (CSE) do ângulo externo dos ventrículos laterais, e a evolução clínica dos pacientes. Comparar os pacientes com CSE isolados e os com CSE associados a outras lesões.Métodos: foram diagnosticados um a vários cistos no ângulo externo de um ou de ambos os ventrículos laterais, por meio de ultra-som transfontanelar (US) de rotina, realizado nos primeiros dias de vida, caracterizando os CSE. Durante o período de 1981-2000, 66recém-nascidos tiveram CSE evidenciados na UTI neonatal doHospital de Port-Royal. Foram constituídos dois grupos: G-I, com CSE isolados (n=21), e G-Il, com CSE associados a outras lesões (n=45).Resultados: os recém-nascidos do GI apresentaram maior maturidade, melhores condições de nascimento e menor morbidade respiratória em relação a GIl. A incidência de mal formações congênitas foi elevada em ambos os grupos. Houve baixa taxa de infecção bacteriana e ausência de infecção congênita. Os CSE foram uni ou bilaterais, únicos ou múltiplos (colar de pérolas), sem diferença entre os grupos estudados, e predominaram à esquerda. US seriados foram realizados em 49/66 pacientes (74por cento), mostrando aumento no tamanho do cisto em 21/49 (45por cento), no primeiro mês de vida, enquanto 12CSE (24por cento) desapareceram. O óbito ocorreu em dez recém-nascidos com lesões neurológica graves (quatro leucomalâcias periventriculares, cinco hemorragias peri e intraventriculares), e somente um com hérnia diafragmâtica não apresentava outras lesões ao US transfontanelar.Conclusões: as características dos CSE não diferiram quando esses estavam associados a outras lesões. O nítido predomínio no lado esquerdo sugere um etiologia vascular. Foi encontrada uma alta taxa de malformações associadas, alertando para a possibilidade de uma etiologia malformativa. Ambas hipóteses sugerem um desvio de desenvolvimento, e não de uma fetopatia viral

Infecção do trato urinário na criança - estudo retrospectivo / Urinary infection in child-retrospective study

A infecção urinária é patologia freqüente em crianças e sua importância está na existência do risco de complicações em pacientes com anomalias congênitas e refluxo vesico-ureteral com dilatação, que, associados à repetição da infecção urinária, podem levar ao desenvolvimento de cicatrizes renais, com conseqüente presença de hipertensão arterial e/ou insuficiência renal. Objetivo: Relatar casuística retrospectiva de 155 crianças com infecção urinária. Métodos: Os dados foram obtidos por meio do preenchimento de protocolos de crianças de 1 a 122 meses de idade, média de 45,2 meses, atendidas durante o período de janeiro de 1989 a dezembro de 2000. Resultados: Observamos que 71 por cento foram do sexo feminino e 41,9 por cento com idade inferior a 2 anos. Cento e doze pacientes (72,2 por cento) apresentaram febre, 14,2 por cento disúria e 13,5 por cento dor abdominal. O agente etiológico foi a E. coli em 73,5 por cento dos pacientes. Dilatação da pelvis renal (20,4 por cento) e refluxo vésico-ureteral (38,1 por cento) foram as alterações mais freqüentes observadas nos estudos por imagem. Sessenta e um pacientes (39,4 por cento) apresentaram o trato urinário normal. Sessenta e oito pacientes (43,9 por cento) apresentaram infecção de repetição e o agente foi a E. coli em 47,5 por cento e Proteus em 22,8 por cento. Das 68 crianças com infecção de repetição, 42 (61,7 por cento) apresentaram anormalidades do trato urinário. Conclusão: A infecção urinária foi observada em maior porcentagem em crianças do sexo feminino; na faixa etária até 2 anos; tendo como principal quadro clínico febre, constatando-se anormalidades do trato urinário associadas à presença de recidivas da infecção.

[Diagnosis of subependymal cysts by brain ultrasound]. / Cistos subependimários diagnosticados pelo ultra-som transfontanelar.

OBJECTIVE: The aim of this study was to describe the clinical data and sonographic evolution of subependymal cysts (SEC) and to compare alone SEC versus SEC combined with other brain abnormalities. METHODS: The diagnosis of SEC relied on the discovery of one/several cysts at the outer angle of one/both lateral ventricles detected by routine brain ultrasound tests in the first days of life. During the 1981-2000 period, 66 neonates had evidence of SEC in Port-Royal Department of Neonatal Medicine. The cases were divided into two groups: G-I, alone SEC; G-II, SEC combined with other brain abnormalities. Hospital charts were reviewed for gestational and delivery data and ultrasound scans were analyzed according to a preset list of items (dates, measurements, other findings). RESULTS: Patients with alone SEC had a higher gestational and birthweight, better birth conditions, and less respiratory morbidity. High rates of associated congenital anomalies were observed in both groups (19% in G-I, 13% in G-II, NS). Rare pre/perinatal infections did not show any association with SEC. SEC were uni or bilateral, single or multiple (string), with no difference between G-I and G-II. Unilateral SEC predominated in the left side (26/28, P<0.01). Serial examinations were carried out in 49/66 (74%), showing an increase in size of SEC in 21/49 (45%) in the first month of life, while 12 SEC (24%) disappeared. The 11 deaths occurred in neonates with other severe brain injuries (five peri-intraventricular hemorrhages, four periventricular leukomalacias) except one (diaphragmatic hernia). CONCLUSIONS: Alone SEC and SEC combined with other brain abnormalities follow the same morphologic pattern and evolution. The striking predominance in the left side may suggest another etiology. Both are in favor of a developmental deviation and not a viral fetopathy.