Dyslipidemia and maternal obesity: Prematurity and neonatal prognosis / Dislipidemia e obesidade materna: prematuridade e prognóstico neonatal

Summary Objective: To identify the changes caused by dyslipidemia and obesity in pregnancy suggesting causes for premature birth, and the prognosis for the newborn. Method: Systematic review based on the Medline, Lilacs, Embase and Cochrane library databases between 1996 and 2016. The search for studies included the following keywords: "dyslipidemia, pregnancy, obesity, preterm birth." A protocol was programmed and a protocol for inclusion/exclusion of studies was implemented. Results: Of the 5,789 articles initially selected between March 1996 and July 2016, only 32 were in accordance with the established criteria. Of these, 28.12% discussed risk factors of prematurity; 37.50%, metabolic alterations and gestational dyslipidemia; 21.87%, dyslipidemic complications in preterm birth; and 12,50%, lipid metabolism, glycemic and placental transfer. Conclusion: There is a reduced adaptation of obese pregnant women to the metabolic changes of gestation. This favors dyslipidemic intercurrences in the mother, which, directly or indirectly, suggests the occurrence of premature births and high lipid transfer to the fetus. Therefore, preterm newborns, whose mothers were dyslipidemic during pregnancy, have greater risk of epicardial fat, both in early (first year of life) and in later (adult) phases of life.

Resumo Objetivo: Identificar as alterações provocadas pela dislipidemia e pela obesidade na gestação que sugerem causas de partos prematuros e o prognóstico para o recém-nascido. Método: Revisão sistemática nas bases de dados Medline, Lilacs, Embase e da biblioteca Cochrane entre os anos de 1996 e 2016. O processo de seleção ocorreu a partir dos descritores dislipidemia, gravidez, obesidade, nascimento prematuro. Um protocolo foi programado, havendo uma etapa seletiva de inclusão/exclusão das pesquisas. Resultados: Dentre os 5.789 artigos inicialmente selecionados entre março e julho de 2016, somente 32 estavam de acordo com os critérios estabelecidos. Desses, 28,12% focavam nos fatores de risco da prematuridade; 37,50%, em alterações metabólicas e dislipidemia gestacional; 21,87%, em intercorrências dislipidêmicas no parto prematuro; 12,50%, em metabolismo lipídico, glicêmico e transferências pela placenta. Conclusão: Existe uma menor adaptação da gestante obesa às mudanças metabólicas da gestação, favorecendo intercorrências dislipidêmicas na mãe, o que, direta ou indiretamente, sugere a ocorrência de partos prematuros e uma elevada transferência de lipídios para o feto. Portanto, recém-nascidos prematuros de mães dislipidêmicas durante a gravidez apresentam maior risco de desenvolver gordura epicárdica tanto na fase precoce (primeiro ano de vida) quanto na tardia (vida adulta).

Hipofosfemia en recién nacidos prematuros: un trastorno bimodal / Hypophosphatemia in preterm infants: a bimodal disorder

Las estrategias nutricionales para prematuros extremos con alto aporte de proteínas, han mostrado alteraciones metabólicas con hipofosfemia precoz, especialmente en el grupo de pacientes con restricción de crecimiento intrauterino (Rein). También se presenta hipofosfemia tardía, característica de la enfermedad metabólica ósea. En este artículo se revisan y actualizan conceptos en relación a la fisiopatología del metabolismo del fósforo en recién nacidos prematuros y uso de parenterales precoces en el contexto de enfermedad metabólica ósea. Los artículos fueron identificados en base de datos electrónicas como Pubmed y Rima. Fueron incluidos artículos en inglés y español. Fueron filtrados por título y resumen. La literatura actual propone diversas estrategias de nutrición precoz que permitan asegurar una adecuada cantidad de nutrientes para continuar con el crecimiento y desarrollo extrauterino. En pacientes con nutrición parenteral pero con diferentes aportes de fósforo, o relación calcio: fósforo inadecuada, a mayor contenido de aminoácidos, se presenta hipofosfemia, hipercalcemia, hipomagnesemia, hipokalemia e hiperglicemia, especialmente en casos de Rein. Estas alteraciones se asocian a prolongación de ventilación mecánica, mayor riesgo de displasia broncopulmonar y aumento de sepsis tardía. La hipofosfemia tardía, descrita ya hace muchos años, se presenta con normocalcemia y aumento de fosfatasas alcalinas, en la enfermedad metabólica ósea del prematuro, con alteración de la mineralización en distintos grados, secundaria a un inadecuado aporte de este mineral para los altos requerimientos de estos pacientes. Esta presentación de hipofosfemia precoz y tardía en el prematuro alerta sobre el control oportuno de fosfemia para ajustar el aporte nutricional. En el prematuro con nutrición parenteral precoz, el control en conjunto con la calcemia en la primera semana de vida, especialmente en Rein, permite tratar la hipofosfemia y prevenir sus complicaciones. En hipofosfemia tardía, el seguimiento semanal o quincenal desde las 4 semanas a los prematuros con riesgo, permite lograr un aporte óptimo de minerales.

New nutritional approaches to treat extreme premature babies have demonstrated relevant eviden ce of metabolic disturbances with early hypophosphatemia, especially in patients with intrauterine growth restriction (IUGR). They have shown late hypophosphatemia, as well, which is characteristic in the metabolic bone disease. A sytematic search of literature describing metabolic disturbances of phosphorus in preterm newborns is presented, related to the use of early parenteral nutrition and also in the context of metabolic bone disease. The articles were gathered from electronic data bases, such as PubMed and Rima. We include articles in english and spanish which were selected by titles and abstracts. Several strategies for early nutrition have been proposed in order to ensure an adequate amount of nutrients to accomplish the development and growth of preterm babies. Patients with parenteral nutrition support with different doses of phosphate, or inadequate calcium phosphate relation, or an increased amino acid content, may present hypophosphatemia, hypercalcemia, hy pomagnesemia, hypokalemia and hyperglycemia, all of these are additionally noteworthy in the pre sence of intrauterine growth restriction. Furthermore, said alterations are associated with prolonged mechanical ventilation, as well as bronchopulmonary dysplasia and increase in late onset sepsis. The late hypophosphatemia, described several years ago, arises as normocalcemia and as an increment of alkaline phosphatases in the metabolic bone disease in preterm babies, and also with an inadequate mineralization in different grades, secondary to an inadequate supply due to high nutritional requi rements in these patients. When early or late hypophosphatemia appears in preterm babies, it shall require timely control of phosphemia and will need to adjust the nutritional intake in order to correct it. In case of preterm babies with early parenteral nutrition it will also need a control of calcemia in the first week of birth, especially if those belonging to the IUGR group. Adjustment must be made along with metabolic follow up, as well. In late hypophosphatemia, a weekly or every two weeks fo llow up will be a must for all preterm babies in risk and they should be given supplements to get an optimum mineral supply.

Factores de riesgo y marcadores bioquímicos de la enfermedad metabólica ósea del recién nacido prematuro / Risk factors and biochemical markers in metabolic bone disease of premature newborns

Introducción: La enfermedad metabólica ósea (EMO) del recién nacido prematuro (RNPT) es una complicación de origen multifactorial, que ha ido en aumento, consecuencia de la disminución progresiva de la mortalidad. El objetivo del estudio fue analizar los factores de riesgo (FR) pre y postnatales relacionados con la EMO severa y sus marcadores analíticos. Pacientes y Métodos: Estudio retrospectivo observacional, descriptivo y analítico, que incluyó RNPT nacidos con menos de 32 semanas y/o peso menor de 1.500 g entre enero de 2012 y diciembre de 2014. Se analizó la muestra en función del desarrollo de EMO severa. Resultados: 139 pacientes, con 25(OH)D3 media de 70,68 ± 25,20 nmol/l, mayor en los nacidos en primavera-verano que en otoño-invierno (80,94 ± 25,33 vs 61,13±21,07; p = 0,000). Los pacientes con EMO severa presentaron valores de 25(OH)D3 similares al resto de pacientes (65,61 ± 26,49 vs 72,07 ± 24,89; p = 0,283), y superiores de fosfatasa alcalina (FA) (1314,19 ± 506,67 vs 476,56 ± 188,85; p = 0,000). Mediante curva ROC se calculó un punto de corte de FA de 796,5 IU/l (S 95,2%, E 92,4%). Los FR más asociados al desarrollo de EMO severa fueron el crecimiento intrauterino restringido, el peso al nacimiento y la duración de ventiloterapia y nutrición parenteral. Conclusiones: Las cifras de FA son las que mejor se relacionan con el desarrollo de EMO severa. El riesgo de ésta aumenta a mayor número de factores de riesgo y menores cifras de vitamina D3. Niveles de 25(OH)D3 por encima de 70 nmol/l parecen proteger del desarrollo de EMO, incluso en pacientes con múltiples factores de riesgo.

Background: Metabolic bone disease (MBD) of prematurity is a complication of multifactorial aetiology, which has been increasing, due to progressive decrease in mortality of preterm newborns. The aim of the study was to analyze risk factors of severe MBD and its analytical markers. Patients and Method: Retrospective study involving preterm infants less than 32 weeks gestational age and/or weight less tan 1,500 g born between january 2012 and december 2014. Comparison was made according to the presence of severe MBD. Results: 139 patients were recruited. Mean value of 25(OH)D3 was 70.68 ± 25.20 nmol/L, being higher in patients born in spring-summer than in autumn-winter (80.94 ± 25.33 vs 61.13 ± 21.07; p = 0.000). Levels of 25(OH)D3 were similar in patients with severe MBD compared with the rest of patients (65.61 ± 26.49 vs 72.07 ± 24.89, P = 0.283). Higher levels of alkaline phosphatase (AP, IU/L ) (1314.19 ± 506.67 vs 476.56 ± 188.85; p = 0.000) were found in these patients. Cutoff point of AP 796.5 IU/L (S 95.2%, specificity 92.4%) was calculated by ROC curve. The risk factors most associated to severe EMO were restricted fetal growth, birth weight, duration of ventilation therapy and parenteral nutrition. Conclusions: AP levels were the best marker of severe MBD development. EMO risk increases with the number of risk factors and lower levels of 25(OH)D3. Levels of 25(OH)D3 higher than 70nmol/L appear to protect from the development of severe MBD, even in patients with multiple risk factors.

Response of oxygen saturation in preterm infants receiving rib cage stabilization with an elastic band in two body positions: a randomized clinical trial / Resposta da saturação de oxigênio no recém-nascido pré-termo com estabilização do gradil costal por meio da faixa elástica em duas posições corporais: ensaio clínico randomizado

BACKGROUND: Preterm newborns have higher thoracic compliance, providing less stability to the different forces of distortion imposed on the rib cage, leading to instability of the chest. Adequate body position may reduce this instability and facilitate respiratory work. OBJECTIVE: To assess the oxygen saturation response of preterm newborns receiving rib cage stabilization with an elastic band in two body positions. METHOD: A clinical, prospective, randomized crossover study was conducted, including sixteen newborns with a gestational age of 31 to 35 weeks (mean 32.8 weeks) at a tertiary care facility, who did not receive supplemental oxygen. The infants were placed in a sequence of prone and supine positions with and without chest stabilization with an elastic band. Respiratory rate, heart rate, and oxygen saturation were measured at 10-minute intervals, corresponding to 7 samplings of 60 minutes. Data collection was interrupted when oxygen saturation was less than 90%. RESULTS: The mean gestational age of the infants was 32.8±1.5 weeks and the mean birth weight was 1,789±255g. Better values for the variables studied were observed in the supine position with an elastic chest band compared to the supine position without the band. The positions using an elastic band resulted in lower mean respiratory rate and heart rate and higher oxygen saturation. CONCLUSION: The use of an elastic chest band improves respiratory indicators such as oxygen saturation. .

CONTEXTUALIZAÇÃO: Os recém-nascidos pré-termos possuem maior complacência torácica, oferecendo menor estabilidade às diferentes forças de distorção impostas à parede torácica, o que leva à instabilidade da caixa torácica. A posição corporal adequada pode diminuir essa instabilidade, facilitando o trabalho respiratório. OBJETIVO: Verificar a resposta da saturação de oxigênio em recém-nascido pré-termo com estabilização do gradil costal com faixa elástica em dois posicionamentos corporais. MÉTODO: Estudo com delineamento de ensaio clínico prospectivo, randomizado e tipo crossover. Foram avaliados 16 recém-nascidos com idade gestacional de 31 a 35 semanas (média 32,8 semanas) e sem oxigênio suplementar, em instituição de nível terciário. O grupo foi submetido à sequência de decúbitos posturais ventral e dorsal, alterando-os com e sem estabilização do tórax por meio da faixa elástica. Os indicadores biológicos colhidos foram frequência respiratória, frequência cardíaca e saturação de oxigênio. Os dados foram coletados de 10 em 10 minutos, totalizando 60 minutos com sete coletas. O critério de interrupção da coleta se deu pela saturação menor que 90%. RESULTADOS: O grupo estudado apresentou média de idade gestacional de 32,8±1,5 semanas e peso ao nascimento de 1.789±255g. Encontramos melhores valores das variáveis na supinação com faixa quando comparada com supinação sem faixa. Os valores médios menores da frequência respiratória e da frequência cardíaca foram alcançados no decúbito com faixa, já a saturação ...

Clinical pharmacokinetics of vancomycin in the neonate: a review

Neonatal sepsis is common and is a major cause of morbidity and mortality. Vancomycin is the preferred treatment of several neonatal staphylococcal infections. The aim of this study was to review published data on vancomycin pharmacokinetics in neonates and to provide a critical analysis of the literature. A bibliographic search was performed using PubMed and Embase, and articles with a publication date of August 2011 or earlier were included in the analysis. Vancomycin pharmacokinetic estimates, which are different in neonates compared with adults, also exhibit extensive inter-neonatal variability. In neonates, several vancomycin dosing schedules have been proposed, mainly based on age (i.e., postmenstrual and postnatal), body weight or serum creatinine level. Other covariates [e.g., extracorporeal membrane oxygenation (ECMO), indomethacin or ibuprofen, and growth restriction] of vancomycin pharmacokinetics have been reported in neonates. Finally, vancomycin penetrates cerebrospinal fluid (range = 7-42%). Renal function drives vancomycin pharmacokinetics. Because either age or weight is the most relevant covariate of renal maturation, these covariates should be considered first in neonatal vancomycin dosing guidelines and further adjusted by renal dysfunction indicators (e.g., ECMO and ibuprofen/indomethacin). In addition to the prospective validation of available dosing guidelines, future studies should focus on the relevance of therapeutic drug monitoring and on the value of continuous vancomycin administration in neonates.

Vancomycin pharmacokinetics in preterm infants

OBJETIVE: The objective of the present study was to evaluate the kinetic disposition of vancomycin in preterm infants with emphasis on the apparent volume of distribution, biological half-life, and total body clearance as well as whether their variations cause significant modification of the trough plasma concentration of the drug, depending on the postconceptional age (PCA) and the postnatal age (PNA). MATERIAL AND METHOD: Twenty-five selected patients were distributed into 2 groups which differed significantly in terms of mean PCA (31.2-32.3 weeks in group 1, n = 13; 33.5-34.1 weeks in group 2, n = 12: CI95 percent, P < .001) and PNA (group 1, 12.0-18.5 days; group 2, 18.0-34.0 days, CI95 percent, P < .05). The parents were informed and signed a written consent for participation of the infants in the protocol that had been previously approved by the Ethics Committee of the hospital. RESULTS: Apparent volume of distribution was significantly increased in group 1 compared with patients of group 2 (0.85 vs. 0.56 L/kg, respectively; P = .01,). Additionally multiple linear regression revealed a good linear correlation (r = 0.85) of trough plasma concentration of vancomycin with the apparent volume of distribution and also with the biological half-life in patients of group 1, while a good correlation (r = 0.91) was obtained for the trough plasma concentration with total body clearance in infants of group 2. The influence of these kinetic parameters on the trough concentration of vancomycin in preterm infants seems to vary according to PCA and PNA. CONCLUSION: In conclusion, the trough plasma concentration of vancomycin depends on the pharmacokinetics, and multiple linear correlation indicates that it varies according to the postconceptional and postnatal age of preterm infants.

OBJETIVO: O objetivo do presente estudo foi investigar a farmacocinética da vancomicina em neonatos pretermo, considerando a idade pós-conceptual e também a idade pós-natal para determinar se as alterações no volume aparente de distribuição, meia-vida biológica e depuração plasmática causam variação significativa no vale plasmático da vancomicina. MATERIAL E MÉTODO: Os vinte e cinco pacientes selecionados foram distribuídos em dois grupos, que diferiram significativamente em termos de idade pós-conceptualgrupo 1, n=13: 31,2-32,3 semanas; grupo 2, n=12: 33,5-34,1 semanas, IC95 por cento, p<0,0001) e idade pós-natalgrupo 1: 12,0-18,5 dias; grupo 2: 18,0-34,0 dias, p<0,05). Todos os responsáveis foram informados sobre os detalhes do estudo e assinaram o termo de consentimento livre e esclarecido. O protocolo foi submetido e aprovado previamente pelo Comitê de Ética em Pesquisa do hospital. RESULTADO: O volume aparente de distribuição se mostrou significativamente aumentado no grupo 1 comparado aos pacientes do grupo 2 0,85 vs 0,56 L/kg, p=0,01). Adicionalmente, o teste de regressão linear múltipla mostrou boa correlação linear: 0,85) da concentração plasmática de vale com o volume aparente de distribuição, e também com a meia-vida biológica nos pacientes do grupo 1. Nas crianças do grupo 2 evidenciou-se boa correlação(r: 0,91) entre o vale e a depuração plasmática. A influência desses parâmetros farmacocinéticos sobre o vale nos prematuros parece variar de acordo com a idade pós-conceptual e a idade pós-natal. CONCLUSÃO: Concluindo, a concentração de vale para a vancomicina depende da farmacocinética e a correlação múltipla varia de acordo com a idade pós-conceptual e a idade pós-natal dos recém-nascidos pré-termos.

Amniotic fluid interleukin-6 and the risk of Early-Onset sepsis among preterm infants

Background. High concentrations of interleukin-6 (IL-6) have been demonstrated in amniotic fluid (AF) from women with intra-amniotic infection. Recent studies have reported that IL-6 levels in AF were related to a increase in neonatal morbidity; moreover, higher Il-6 plasma levels have been observed in neonates with sepsis. Methods. A cohort study was carried out at the National Institute of Perinatology in Mexico City. Inclusion criteria were the following: 1) preterm singleton pregnancy; 2) intact membranes at time of enrollment, and 3) written informed consent. Women with other complications of pregnancy were excluded. Newborn sepsis during the first 72 h was defined as early-onset sepsis. Amniotic fluid was obtained at the moment of delivery. Amniotic fluid Il-6 (Af IL-6) was determined by enzyme-linked immunoassays. Results. Ninety-three women met the criteria for enrolment in the study and 31 (33 percent) of their newborns had early-onset neonatal sepsis. The mean AF IL-6 in mothers of septic newborns was 5779 ñ 2804 pg/ml compared to 729 ñ 382 pg/ml in mothers with noninfected neonates (p<0.001). AF IL-6 concentrations higher than 1250 pg/ml were significantly associated with early-onset sepsis (OR 33.3: 95 percent CI 9.4-117.3) (p< 0.001). Gestational age under 32 weeks was also associated with neonatal sepsis (OR 2.56; 95 percent CI 1.2-9) (p = 0.002). Women whose infants developed neonatal sepsis had a higher frequency of clinical choriamnionitis (p = 0.02). Conclusions. IL-6 determination in AF may be a useful indicator to identifity neonates with higher risk of in utero bacterial infection

Farmacocinética de ceftazidima en neonatos / Pharmacokinetics of ceftazidime in newborn infants

A pharmacokinetic study of ceftazidime was performed in newborn children. Six premature infants with a body weight up to 2000 g and with symptoms of pneumonia (Table 1) were treated with ceftazidime (50 mg/kg body weight) by endovenous route. Plasma concentrations of the antibiotic (Fig. 1) were determined by HPLC. A kinetic behavior was described through a compartment model independent analysis. The calculated parameters were as follows: half-life (T1/2z = 4.05 +/- 0.81 h) apparent volume of distribution (Vz = 686.0 +/- 258.6 ml/kg), elimination rate constant (lambda z = 0.18 +/- 0.04h-1), area under curve (AUC = 464.4 +/- 139.1 mu gh/ml, mean residence time (MRT = 5.2 +/- 1.3 h), and total clearance (CI = 114.9 +/- 30.0 ml/h. kg) (Table 2). Good correlation was observed (r = 0.83, p < 0.05 between lambda z = and Vz). The loading and maintenance doses calculated for enterobacteria and P. aeruginosa were 15 and 13 mg/kg i.v. respectively each 12 h.