In extremely low birth weight (ELBW) infants, systemic hypotension is associated with poor neurological outcomes as a result of cerebral hypoperfusion. Treatment with arginine vasopressin (AVP) has been shown to increase blood pressure (BP) and urine output in ELBW infants suffering from refractory hypotension. The purpose of this study was to clarify whether low doses of AVP increased renal blood flow (RBF) in ELBW infants. We retrospectively analyzed data from the medical charts describing nine AVP infusions at 0.3-0.8 mU/kg/min in four ELBW infants. The median gestational age was 23 (22.5-23.5, interquartile range) weeks, and the median birth weight was 466 (414-563) g. Changes in the heart rate, BP, urine output, and RBF velocity patterns in response to the AVP infusions were compared using statistical analyses. The AVP infusion caused significant increases in systolic BP from 44 (41.0-47.0) to 50 (42.5-55.5) mmHg, diastolic BP from 17 (15.0-26.5) to 31 (28.5-33.0) mmHg, mean BP from 26 (24.5-30.5) to 36 (34.5-40.5) mmHg, and urine output from 1.4 (0.2-2.5) to 2.8 (1.0-8.6) mL/kg/hr. We also observed significant decreases in the resistance index from 1.0 (0.96-1.0) to 0.8 (0.71-0.91) and peak systolic flow velocity in the renal artery from 40 (27.2-50.6) to 28 (16.0-28.9) cm/s after AVP infusions. AVP infusions at 0.3-0.8 mU/kg/min in ELBW infants appeared to significantly increase the RBF by inducing renal vascular dilation and increasing the BP. Increasing the RBF most likely induces an increase in the glomerular filtration rate, resulting in the diuretic effect of AVP.
Patent ductus arteriosus (PDA) is a common problem among preterm infants. The standard of care for PDA has been to attempt to close the PDA by pharmacological treatment or surgical ligation. Recently, conservative approach for PDA (i.e., infants receive no treatment for PDA unless it is necessary for rescue) is gaining interest. However, when PDA is persisted under the conservative approach, there is a concern about the neurodevelopmental problems caused by decreased cerebral oxygenation. Our objective was to examine the risk of neurodevelopmental impairment in preterm infants, when PDA remained persistently open under conservative approach for PDA. We retrospectively analyzed data from the medical charts in 72 included infants (gestational age < 29 weeks, birth weight < 1,250 g). Under our conservative approach for PDA, we divided infants by their ductal patency: a closed ductus group (ductus closure within 14 days after birth, n = 52) and a persistent patent ductus arteriosus group (ductus closure after 14 days, n = 20). We compared the clinical parameters and neurodevelopmental outcomes assessed with the Kaufman Assessment Battery for Children (K-ABC) at 5 years of corrected age in two groups. Among the children who completed the K-ABC test, there were no significant differences in neurodevelopmental scores between a closed ductus group (n = 44) and a persistent patent ductus arteriosus group (n = 17). A conservative approach for PDA, even in the case of prolonged PDA, does not increase the risk of neurodevelopmental impairment at 5 years of corrected age in preterm infants.
The molecular mechanisms of pre-eclampsia are being increasingly clarified in animals and humans. With the uncovering of these mechanisms, preventive therapy strategies using chronic infusion of adrenomedullin, vascular endothelial growth factor-121 (VEGF-121), losartan, and sildenafil have been proposed to block narrow spiral artery formation in the placenta by suppressing related possible factors for pre-eclampsia. However, although such preventive treatments have been partly successful, they have failed in ameliorating fetal growth restriction and carry the risk of possible side-effects of drugs on pregnant mothers. In this study, we attempted to develop a new symptomatic treatment for pre-eclampsia by directly rescuing placental ischemia with artificial oxygen carriers (hemoglobin vesicles: HbV) since previous data indicate that placental ischemia/hypoxia may alone be sufficient to lead to pre-eclampsia through up-regulation of sFlt-1, one of the main candidate molecules for the cause of pre-eclampsia. Using a rat model, the present study demonstrated that a simple treatment using hemoglobin vesicles for placental ischemia rescues placental and fetal hypoxia, leading to appropriate fetal growth. The present study is the first to demonstrate hemoglobin vesicles successfully decreasing maternal plasma levels of sFlt-1 and ameliorating fetal growth restriction in the pre-eclampsia rat model (p < 0.05, one-way ANOVA). In future, chronic infusion of hemoglobin vesicles could be a potential effective and noninvasive therapy for delaying or even alleviating the need for Caesarean sections in pre-eclampsia.
