Máximo Vento

Defining the reference range for oxygen saturation for infants after birth.

OBJECTIVE: The goal was to define reference ranges for pulse oxygen saturation (Spo2) values in the first 10 minutes after birth for infants who received no medical intervention in the delivery room. METHODS: Infants were eligible if a member of the research team was available to record Spo2 immediately after birth. Infants were excluded if they received supplemental oxygen or any type of assisted ventilation. Spo2 was measured with a sensor applied to the right hand or wrist as soon as possible after birth; data were collected every 2 seconds. RESULTS: We studied 468 infants and recorded 61650 Spo2 data points. The infants had a mean ± SD gestational age of 38 ± 4 weeks and birth weight of 2970 ± 918 g. For all 468 infants, the 3rd, 10th, 50th, 90th, and 97th percentile values at 1 minute were 29%, 39%, 66%, 87%, and 92%, respectively, those at 2 minutes were 34%, 46%, 73%, 91%, and 95%, and those at 5 minutes were 59%, 73%, 89%, 97%, and 98%. It took a median of 7.9 minutes (interquartile range: 5.0–10 minutes) to reach a Spo2 value of >90%. Spo2 values for preterm infants increased more slowly than those for term infants. We present percentile charts for all infants, term infants of ≥37 weeks, preterm infants of 32 to 36 weeks, and extremely preterm infants of <32 weeks. CONCLUSION: These data represent reference ranges for Spo2 in the first 10 minutes after birth for preterm and term infants.

Preterm Resuscitation With Low Oxygen Causes Less Oxidative Stress, Inflammation, and Chronic Lung Disease

OBJECTIVE: The goal was to reduce adverse pulmonary adverse outcomes, oxidative stress, and inflammation in neonates of 24 to 28 weeks of gestation initially resuscitated with fractions of inspired oxygen of 30% or 90%. METHODS: Randomized assignment to receive 30% (N = 37) or 90% (N = 41) oxygen was performed. Targeted oxygen saturation values were 75% at 5 minutes and 85% at 10 minutes. Blood oxidized glutathione (GSSG)/reduced glutathione ratio and urinary o-tyrosine, 8-oxo-dihydroxyguanosine, and isoprostane levels, isofuran elimination, and plasma interleukin 8 and tumor necrosis factor α levels were determined. RESULTS: The low-oxygen group needed fewer days of oxygen supplementation (6 vs 22 days; P < .01) and fewer days of mechanical ventilation (13 vs 27 days; P < .01) and had a lower incidence of bronchopulmonary dysplasia at discharge (15.4% vs 31.7%; P < .05). GSSG/reduced glutathione × 100 ratios at day 1 and 3 were significantly higher in the high-oxygen group (day 1: high-oxygen group: 13.36 ± 5.25; low-oxygen group: 8.46 ± 3.87; P < .01; day 3: high-oxygen group: 8.87 ± 4.40; low-oxygen group: 6.97 ± 3.11; P < .05). Urinary markers of oxidative stress were increased significantly in the high-oxygen group, compared with the low-oxygen group, in the first week after birth. GSSG levels on day 3 and urinary isofuran, o-tyrosine, and 8-hydroxy-2′-deoxyguanosine levels on day 7 were correlated significantly with development of chronic lung disease. CONCLUSIONS: Resuscitation of preterm neonates with 30% oxygen causes less oxidative stress, inflammation, need for oxygen, and risk of bronchopulmonary dysplasia.

Resuscitation of Newborn Infants with 21% or 100% Oxygen: An Updated Systematic Review and Meta-Analysis

Background: The issue of whether 21% O2 is more effective than 100% O2 for resuscitation of newborn infants remains controversial. Objectives: We have updated the systematic review and meta-analysis including all studies reporting resuscitation of newborn infants with 21 or 100% O2. Methods: Randomized or quasi-randomized studies of depressed newborn infants resuscitated with 21 or 100% O2 with or without masking of treatment were considered for inclusion. The outcomes of interest included neonatal mortality and hypoxic ischemic encephalopathy. Results: Ten studies fulfilled the inclusion criteria. Of these, 6 studies were identified as being strictly randomized. In total, 1,082 infants were allocated to resuscitation with 21% O2 and 1,051 infants with 100% O2. The risk of neonatal mortality was reduced in the 21% O2 group compared to the 100% O2 group both in the analysis of all studies (typical RR 0.69, 95% CI 0.54, 0.88) and in the analysis of strictly randomized studies (typical RR 0.32, 95% CI 0.12, 0.84). A trend toward a decrease in the risk of hypoxic ischemic encephalopathy stage 2 and 3 was noted with resuscitation in 21% O2 in the analysis of all studies (typical RR 0.88, 95% CI 0.72, 1.08). Conclusions: There is a significant reduction in the risk of neonatal mortality and a trend towards a reduction in the risk of severe hypoxic ischemic encephalopathy in newborns resuscitated with 21% O2.

Achievement of Targeted Saturation Values in Extremely Low Gestational Age Neonates Resuscitated With Low or High Oxygen Concentrations: A Prospective, Randomized Trial

OBJECTIVE. Extremely low gestational age neonates have very low oxygen saturation in utero and an immature antioxidant defense system. Abrupt increases in oxygen saturation after birth may cause oxidative stress. We compared achievement of a targeted oxygen saturation of 85% at 10 minutes of life when resuscitation was initiated with low or high fractions of inspired oxygen and levels were adjusted according to preductal pulse oxygen saturation values. METHODS. A prospective, randomized, clinical trial was performed in 2 level III neonatal referral units. Patients of ≤28 weeks of gestation who required active resuscitation were randomly assigned to the low-oxygen group (fraction of inspired oxygen: 30%) or the high-oxygen group (fraction of inspired oxygen: 90%). Every 60 to 90 seconds, the fraction of inspired oxygen was increased in 10% steps if bradycardia occurred (<100 beats per minute) or was decreased in similar steps if pulse oxygen saturation reached values of >85%. Preductal pulse oxygen saturation was continuously monitored. RESULTS. The fraction of inspired oxygen in the low-oxygen group was increased stepwise to 45% and that in the high-oxygen group was reduced to 45% to reach a stable pulse oxygen saturation of ∼85% at 5 to 7 minutes in both groups. No differences in oxygen saturation in minute-to-minute registers were found independent of the initial fraction of inspired oxygen used 4 minutes after cord clamping. No differences in mortality rates in the early neonatal period were detected. CONCLUSIONS. Resuscitation can be safely initiated for extremely low gestational age neonates with a low fraction of inspired oxygen (∼30%), which then should be adjusted to the infants needs, reducing the oxygen load to the neonate.

Resuscitation of depressed newborn infants with ambient air or pure oxygen: a meta-analysis.

Background: It is discussed whether depressed newborn infants should be resuscitated with room air or 100% O2. Objective: To perform a systematic review and meta-analysis including studies that report resuscitation of depressed newly born infants with 21 or 100% O2. Methods: Inclusion criterion was randomized or pseudo-randomized, blinded or not, studies of depressed newborn infants resuscitated with either 21 or 100% O2. The literature was searched in Medline/Pubmed/EMBASE and The Cochrane library databases. All identified studies were included. Results: Five studies fulfilled the inclusion criterion in which 881 infants were resuscitated with 21% O2 and 856 with 100% O2. Neonatal mortality was 8.0 vs. 13.0% in the 21 and 100% O2 groups respectively, OR 0.57, 95% CI 0.42–0.78. In term infants neonatal mortality was 5.9% in the 21% O2 group and 9.8% in the 100% O2 group, OR 0.59, 95% CI 0.40–0.87. The figures for the premature infants were very similar. In infants with 1-min Apgar score <4, OR for neonatal mortality was 0.81 (95% CI 0.54–1.21). Apgar score at 5 min and heart rate at 90 s were significantly higher, and time to first breath significantly earlier in infants given 21% O2 compared with 100% O2. Conclusions: A systematic review and meta-analysis demonstrated that neonatal mortality is significantly reduced when depressed newly born infants are resuscitated with ambient air instead of pure oxygen. For infants with low 1-min Apgar score (<4), no significant difference in neonatal mortality was found. Recovery was faster in infants resuscitated with 21% O2 than 100% O2.

Microbial ecology and host-microbiota interactions during early life stages

The role of human microbiota has been redefined during recent years and its physiological role is now much more important than earlier understood. Intestinal microbial colonization is essential for the maturation of immune system and for the developmental regulation of the intestinal physiology. Alterations in this process of colonization have been shown to predispose and increase the risk to disease later in life. The first contact of neonates with microbes is provided by the maternal microbiota. Moreover, mode of delivery, type of infant feeding and other perinatal factors can influence the establishment of the infant microbiota. Taken into consideration all the available information it could be concluded that the exposure to the adequate microbes early in gestation and neonatal period seems to have a relevant role in health. Maternal microbial environment affects maternal and fetal immune physiology and, of relevance, this interaction with microbes at the fetal-maternal interface could be modulated by specific microbes administered to the pregnant mother. Indeed, probiotic interventions aiming to reduce the risk of immune-mediated diseases may appear effective during early life.

Changes in heart rate in the first minutes after birth

The normal range of heart rate (HR) in the first minutes after birth has not been defined. Objective To describe the HR changes of healthy newborn infants in the delivery room (DR) detected by pulse oximetry. Study Design All inborn infants were eligible and included if a member of the research team attended the birth. Infants were excluded if they received any form of medical intervention in the DR including supplemental oxygen, or respiratory support. HR was measured using a pulse oximeter (PO) with the sensor applied to the right hand or wrist immediately after birth. PO data (oxygen saturation, HR and signal quality) were downloaded every 2 sec and analysed only when the signal had no alarm messages (low IQ signal, low perfusion, sensor off, ambient light). Results Data from 468 infants with 61 650 data points were included. Infants had a mean (range) gestational age of 38 (25–42) weeks and birth weight 2970 (625–5135) g. At 1 min the median (IQR) HR was 96 (65–127) beats per min (bpm) rising at 2 min and 5 min to 139 (110–166) bpm and 163 (146–175) bpm respectively. In preterm infants, the HR rose more slowly than term infants. Conclusions The median HR was <100 bpm at 1 min after birth. After 2 min it was uncommon to have a HR <100 bpm. In preterm infants and those born by caesarean section the HR rose more slowly than term vaginal births.

In Utero Exposure to Mycophenolate Mofetil : A Characteristic Phenotype?

Mycophenolate mofetil (MMF) is a widely prescribed immunosuppressive agent after solid organ transplantation. Potential teratogenic effects after in utero exposure to MMF in experimental studies and clinical observations in humans has been postulated in recent literature. However, a specific pattern of malformation has not been identified yet. We present a newborn patient, born to a recipient of renal transplantation, who became pregnant while taking MMF as immunosuppressive therapy. The newborn exhibited cleft lip and palate, bilateral microtia and atretic external auditory canals, chorioretinal coloboma, hypertelorism, and micrognathia. An extensive review of the literature documented six other cases with similar malformations after in utero exposure to MMF. A consistent pattern of malformations comprising cleft lip and palate, microtia and external auditory canals could be observed in five of the six cases. A different malformative pattern observed in one of the patients could be attributed to a different agent rather than MMF. The possible teratogenic effects of other immunosuppressive drugs, such as tacrolimus and prednisone, to which this patient was also exposed, are discussed herein. In addition, the differential diagnosis with other dysmorphic syndromes that can present with a similar phenotype, such as CHARGE syndrome, 18q deletion and hypertelorism‐microtia‐clefting (HMC) syndrome, is presented. We conclude that in utero exposure to MMF can cause a characteristic phenotype and propose the existence of a mycophenolate‐associated embryopathy whose main features are: cleft lip and palate, microtia with atresia of external auditory canal, micrognathia and hypertelorism. Ocular anomalies, corpus callosum agenesis, heart defects, kidney malformations, and diaphragmatic hernia may be part of the phenotypic spectrum of MMF embryopathy. The human teratogenicity of MMF is reinforced by this report, and the current contraceptive recommendations about its use in fertile women are stressed.

The First Golden Minutes of the Extremely-Low-Gestational-Age Neonate: A Gentle Approach

An increasing body of evidence has revealed that interventions performed during resuscitation of extremely-low-gestational-age neonates (ELGANs) may have a direct influence on the immediate survival and also on long-term morbidity. It has been proposed that interventions in the delivery room and/or hypothermia could trigger changes constitutive of chronic lung disease. New approaches in the first minutes of life using more gentle parameters of intervention are being studied. Thus, titrating inspiratory fraction of oxygen, the use of non-invasive ventilation to reduce trauma to the lung, the use of polyethylene/polyurethane wrapping to avoid hypothermia and delaying cord clamping altogether constitute promising initiatives. The first minutes of life are a valuable window for intervention. However, whilst these practice changes make sense and there are emerging data to support them, further evidence including long-term follow up is needed to definitively change resuscitation procedures in ELGANs.

European Consensus Guidelines on the Management of Respiratory Distress Syndrome - 2016 Update.

Advances in the management of respiratory distress syndrome (RDS) ensure that clinicians must continue to revise current practice. We report the third update of the European Guidelines for the Management of RDS by a European panel of expert neonatologists including input from an expert perinatal obstetrician based on available literature up to the beginning of 2016. Optimizing the outcome for babies with RDS includes consideration of when to use antenatal steroids, and good obstetric practice includes methods of predicting the risk of preterm delivery and also consideration of whether transfer to a perinatal centre is necessary and safe. Methods for optimal delivery room management have become more evidence based, and protocols for lung protection, including initiation of continuous positive airway pressure and titration of oxygen, should be implemented from soon after birth. Surfactant replacement therapy is a crucial part of the management of RDS, and newer protocols for surfactant administration are aimed at avoiding exposure to mechanical ventilation, and there is more evidence of differences among various surfactants in clinical use. Newer methods of maintaining babies on non-invasive respiratory support have been developed and offer potential for greater comfort and less chronic lung disease. As technology for delivering mechanical ventilation improves, the risk of causing lung injury should decrease although minimizing the time spent on mechanical ventilation using caffeine and if necessary postnatal steroids are also important considerations. Protocols for optimizing the general care of infants with RDS are also essential with good temperature control, careful fluid and nutritional management, maintenance of perfusion and judicious use of antibiotics all being important determinants of best outcome.