Inflammatory and oxidative stress airway markers in premature newborns of hypertensive mothers

Although oxidative stress and inflammation are important mechanisms in the pathophysiology of preeclampsia and preterm diseases, their contribution to the respiratory prognosis of premature infants of hypertensive mothers is not known. Our objective was to determine the levels of oxidative stress and inflammation markers in the airways of premature infants born to hypertensive and normotensive mothers, in the first 72 h of life, and to investigate whether they are predictors of bronchopulmonary dysplasia (BPD)/death. This was a prospective study with premature infants less than 34 weeks’ gestation on respiratory support who were stratified into 2 groups: 32 premature infants of hypertensive mothers and 41 of normotensive women, with a mean gestational age of 29 weeks. Exclusion criteria were as follows: diabetes mellitus, chorioamnionitis, malformation, congenital infection, and death within 24 h after birth. The outcome of interest was BPD/death. Malondialdehyde (MDA), nitric oxide (NO), and interleukin 8 (IL-8) were measured in airway aspirates from the first and third days of life and did not differ between the groups. Univariate and multivariate statistical analyses were performed. The concentrations of MDA, NO, and IL-8 were not predictors of BPD/death. Premature infants who developed BPD/death had higher levels of IL-8 in the first days of life. The gestational age, mechanical ventilation, and a small size for gestational age were risk factors for BPD/death. In conclusion, the biomarkers evaluated were not increased in premature infants of hypertensive mothers and were not predictors of BPD/death.

Hipertensión arterial en la mujer adulta / Hypertension in women

The present review examines the types of hypertension that women may suffer throughout life, their physiopathological characteristics and management. In early life, the currently used low-dose oral contraceptives seldom cause hypertension. Pregnancy provokes preeclampsia, its main medical complication, secondary to inadequate transformation of the spiral arteries and the subsequent multisystem endothelial damage caused by deportation of placental factors and microparticles. Hypertension in preeclampsia is an epiphenomenon which needs to be controlled at levels that reduce maternal risk without impairing placental perfusion. The hemodynamic changes of pregnancy may unmask a hypertensive phenotype, may exacerbate a chronic hypertension, or may complicate hypertension secondary to lupus, renovascular lesions, and pheochromocytoma. On the other hand a primary aldosteronism may benefit from the effect of progesterone and present as a postpartum hypertension. A hypertensive pregnancy, especially preeclampsia, represents a risk for cardiac, vascular and renal disease in later life. Menopause may mimic a pheochromocytoma, and is associated to endothelial dysfunction and salt-sensitivity. Among women, non-pharmacological treatment should be forcefully advocated, except for sodium restriction during pregnancy. The blockade of the renin-angiotensin system should be avoided in women at risk of pregnancy; betablockers could be used with precautions during pregnancy; diuretics, ACE inhibitors and angiotensin receptor antagonists should not be used during breast feeding. Collateral effects of antihypertensives, such as hyponatremia, cough and edema are more common in women. Thus, hypertension in women should be managed according to the different life stages.

Alterações do fluxo sanguíneo em artéria umbilical na síndrome hipertensiva gestacional e suas implicações nos resultados neonatais / Changes of blood flow in the umbilical artery in hypertensive pregnancy and the implications in the neonatal outcomes

OBJETIVO: Avaliar as características antropométricas, a morbidade e mortalidade de recém-nascidos (RN) prematuros nascidos vivos de mães hipertensas em função da presença ou não de diástole zero (DZ) ou reversa (DR) na doplervelocimetria arterial umbilical. MÉTODOS: Estudo prospectivo, envolvendo RN prematuros nascidos vivos de gestantes hipertensas, com idade gestacional entre 25 e 33 semanas, submetidas à doplervelocimetria da artéria umbilical nos 5 dias que antecederam o parto, realizado no Hospital do Distrito Federal, entre 1º de novembro de 2009 e 31 de outubro de 2010. Os RN foram estratificados em dois grupos, conforme o resultado da doplervelocimetria da artéria umbilical: Gdz/dr=presença de diástole zero (DZ) ou diástole reversa (DR) e Gn=doplervelocimetria normal. Medidas antropométricas ao nascimento, morbidades e mortalidade neonatal foram comparadas entre os dois grupos. RESULTADOS: Foram incluídos 92 RN, assim distribuídos: Gdz/dr=52 RN e Gn=40 RN. No Gdz/dr a incidência de RN pequenos para idade gestacional foi significativamente maior, com risco relativo de 2,5 (IC95% 1,7‒3,7). No grupo Gdz/dr os RN permaneceram mais tempo em ventilação mecânica mediana 2 (0‒28) e no Gn mediana 0,5 (0‒25), p=0,03. A necessidade de oxigênio aos 28 dias de vida foi maior no Gdz/dr do que no Gn (33 versus10%; p=0,01). A mortalidade neonatal foi maior em Gdz/dr do que em Gn (36 versus 10%; p=0,03; com risco relativo de 1,6; IC95% 1,2 - 2,2). Nessa amostra a regressão logística mostrou que a cada 100 gramas a menos de peso ao nascer no Gdz/dr a chance de óbito aumentou 6,7 vezes (IC95% 2,0 - 11,3; p<0,01). CONCLUSÃO: Em RN prematuros de mães hipertensas com alteração na doplervelocimetria da artéria umbilical a restrição do crescimento intrauterino é frequente e o prognóstico neonatal pior, sendo elevado o risco de óbito relacionado ao peso ao nascimento.

PURPOSE: To evaluate the anthropometric characteristics of morbidity and mortality of premature newborns (NB) of hypertensive mothers according to the presence or absence of flow (DZ) or reverse (DR) diastolic flow in the dopplervelocimetry of the umbilical artery. METHODS: A prospective study was conducted on preterm newborns of pregnant women with hypertension between 25 and 33 weeks of gestational age, submitted to umbilical artery Doppler study during the five days before delivery. Delivery occurred at Hospital Regional da Asa Sul, Brasília - Federal District, between November 1st, 2009 and October 31st, 2010. The infants were stratified into two groups according to the results of Doppler velocimetry: Gdz/dr=absent end-diastolic velocity waveform or reversed end-diastolic velocity waveform, and Gn=normal Doppler velocimetry. Anthropometric measurements at birth, neonatal morbidity, and mortality were compared between the two groups. RESULTS: We studied 92 infants, as follows: Gdz/dr=52 infants and Gn=40 infants. In Gdz/dr, the incidence of infants small for gestational age was significantly greater, with a relative risk of 2.5 (95%CI 1.7 - 3.7). In Gdz/dr, infants remained on mechanical ventilation for a longer time: median 2 (0‒28) and Gn median 0.5 (0‒25) p=0.03. The need for oxygen at 28 days was higher in G dz/dr comparing to Gn (33 versus 10%; p=0.01). Neonatal mortality was higher in Gdz/dr compared to Gn (36 versus 10%; p=0.03; relative risk of 1.6; 95%CI 1.2‒2.2). Logistic regression showed that, with each 100 grams lower birth weight, the chance of death increased 6.7 times in G dz/dr (95%CI 2.0 - 11.3; p<0.01). CONCLUSION: In preterm infants of mothers with hypertensive changes in Doppler velocimetry of the umbilical artery, intrauterine growth restriction and neonatal prognosis are often worse, with a high risk of death related to birth weight.

Adenosin deaminasa como molécula coestimuladora y marcador de inmunidad celular / Adenosine deaminase as costimulatory molecule and marker of cellular immunity

La adenosin deaminasa (ADA), es una enzima del metabolismo de las purinas que ha sido objeto de mucho interés debido a que el defecto congénito de esta enzima causa el síndrome de inmunodeficiencia combinada severa. Una de las tres isoformas de la enzima (ecto-ADA) es capaz de unirse a la glicoproteína CD26 y a los receptores de adenosina A1 y A2B. La interacción ADA-CD26 produce una señal coestimuladora en los eventos de activación de las células T y en la secreción de IFN-g, TNF-a e IL-6. Durante dicha activación la actividad de la enzima está regulada de manera positiva por IL-2 e IL-12 y negativamente por IL-4, basado en un mecanismo de translocación. Diversos estudios señalan que los niveles séricos y plasmáticos de ADA se elevan en algunas enfermedades causadas por microorganismos que infectan principalmente a los macrófagos; así como en trastornos hipertensivos, lo cual podría representar un mecanismo compensatorio como consecuencia de la elevación de los niveles de adenosina y la liberación de mediadores hormonales e inflamatorios estimulados por la hipoxia.

Adenosine deaminase (ADA) is an enzyme of purine metabolism which has been the subject of much interest because the congenital defect of this enzyme causes severe combined immunodeficiency syndrome. One of the three isoforms of the enzyme (ecto-ADA) is capable of binding to the glycoprotein CD26 and adenosine receptors A1 and A2B. ADA-CD26 interaction produces a costimulatory signal in the events of T cell activation and secretion of IFN-g, TNF-a and IL-6. During this activation, the enzyme activity is regulated positively by IL-2 and IL-12 and negatively by IL-4, based on the mechanism of translocation. Diverse studies suggest that seric and plasmatic levels of ADA rise in some diseases caused by microorganisms infecting mainly the macrophages and in hypertensive disorders, which may represent a compensatory mechanism resulting from increased adenosine levels and the release of hormones and inflammatory mediators estimulated by hipoxia.

Resultados clínicos y perinatales de los embarazos con hipertensión arterial en un hospital de referencia de la VIII Región de Chile / Clinical and perinatal outcomes associated with hypertension syndrome in pregnancy

Objetivo: Conocer los resultados clínicos, bioquímicos y perinatales asociados al síndrome de hipertensión del embarazo (SHE) en el Hospital Herminda Martín de Chillan. Métodos: Se realizó un estudio retrospectivo de registros clínicos (n=416) con diagnóstico de SHE en el periodo 2006 a 2008. Los registros disponibles fueron divididos en tres grupos de acuerdo al nivel de presión arterial: Grupo I (n=124) <140/90 mmHg; Grupo II (n=98) ³ 140-159/³ 90-109 mmHg y Grupo III (n=41)³ 160/110 mmHg. Adicionalmente, un subgrupo (n=85) fue dividido considerando el percentil de distribución del nivel de ácido úrico materno en: SHE con niveles bajos (p75). Se analizaron y compararon los grupos estudiados y se correlacionó las variables estudiadas con los resultados perinatales. Resultados: La prevalence de SHE fue de 3,8 por ciento. Las mujeres del grupo II y III muestran peores resultados clínicos y neonatales que las mujeres del grupo I. El índice de masa corporal (IMC), la presión arterial materna y el nivel de ácido úrico están relacionados negativamente con la antropometría neonatal. Además, la antropometría neonatal fue menor en las mujeres con niveles más altos de ácido úrico, situación que no obedece a la severidad de la hipertensión o el IMC materno. Conclusión: La presencia de SHE esta asociada a mayor morbilidad materna y neonatal. Este estudio permitió detectar deficiencias (e.L, falta de cumplimiento en criterio diagnóstico) y hacer recomendaciones sobre probables marcadores de riesgo perinatal (e.L, nivel de ácido úrico).

Aims: To know the clinical and biochemical spectra and perinatal outcomes associated with syndrome of hypertension in pregnancy (HP) in the Herminda Martin Hospital from Chilian. Methods: It is a retrospective study using clinical records with HP diagnosis (N=416) during 2006 to 2008. The available records were divided in three different groups according with arterial blood pressure: Group I (n=124) <140/90 mmHg; Group II (n=98) ³ 140-159/³ 90-109 mmHg and Group III (n=41)³ 160/110 mmHg. Additionally, a subset (n=85) was divided considering the percentile of the uric acid level in the mother as: HP with low (p75th) uric acid levels. The studied groups were analyzed and compared each other and quantitative variables were correlated with perinatal outcomes. Results: The prevalence of HP was 3.8 percent. Women in the groups II and III showed worse clinical and neonatal outcomes compared with women in the group I. Body mass index (BMI), maternal blood pressure and uric acid levels were negatively correlated with neonatal anthropometry. Moreover, neonatal anthropometry was lower in women with high uric acid levels, a situation that was independent of maternal hypertension or BMI. Conclusion: Hypertension in pregnancy was associated with high maternal and neonatal morbidity. This study allowed identifies some weaknesses (e.i., lack of compliance in diagnosis criteria) as well as suggest the potential role of perinatal risk markers (e.i., uric acid levels).