Intrapartum hypoxic events (“birth asphyxia”) may result in stillbirth, neonatal or postneonatal mortality, and impairment. Systematic morbidity estimates for the burden of impairment outcomes are currently limited. Neonatal encephalopathy (NE) following an intrapartum hypoxic event is a strong predictor of long-term impairment. Linear regression modeling was conducted on data identified through systematic reviews to estimate NE incidence and time trends for 184 countries. Meta-analyses were undertaken to estimate the risk of NE by sex of the newborn, neonatal case fatality rate, and impairment risk. A compartmental model estimated postneonatal survivors of NE, depending on access to care, and then the proportion of survivors with impairment. Separate modeling for the Global Burden of Disease 2010 (GBD2010) study estimated disability adjusted life years (DALYs), years of life with disability (YLDs), and years of life lost (YLLs) attributed to intrapartum-related events. In 2010, 1.15 million babies (uncertainty range: 0.89–1.60 million; 8.5 cases per 1,000 live births) were estimated to have developed NE associated with intrapartum events, with 96% born in low- and middle-income countries, as compared with 1.60 million in 1990 (11.7 cases per 1,000 live births). An estimated 287,000 (181,000–440,000) neonates with NE died in 2010; 233,000 (163,000–342,000) survived with moderate or severe neurodevelopmental impairment; and 181,000 (82,000–319,000) had mild impairment. In GBD2010, intrapartum-related conditions comprised 50.2 million DALYs (2.4% of total) and 6.1 million YLDs. Intrapartum-related conditions are a large global burden, mostly due to high mortality in low-income countries. Universal coverage of obstetric care and neonatal resuscitation would prevent most of these deaths and disabilities. Rates of impairment are highest in middle-income countries where neonatal intensive care was more recently introduced, but quality may be poor. In settings without neonatal intensive care, the impairment rate is low due to high mortality, which is relevant for the scale-up of basic neonatal resuscitation.

/pdf/intrapartum-related-neonatal-encephalopathy-incidence-and-49thar3l9s.pdf

Intrapartum-related neonatal encephalopathy incidence and impairment at regional and global levels for 2010 with trends from 1990

Asphyxia remains one of the main causes of later disability in term infants. Despite many publications identifying possible predictors of outcome in this population of interest, little is known of the long-term developmental outcome of asphyxiated term neonates. Observational studies have largely focused on short-term outcomes, with an emphasis on significant neurologic sequelae and intellectual impairments. This article reviews the literature that has described the developmental outcome of asphyxiated term newborns. As part of this review, we have also highlighted the evolution of the definition of asphyxia and delineated appropriate markers that should be used in future research on this population.

Long-term developmental outcome of asphyxiated term neonates.

Objective. Infants with meconium aspiration syndrome (MAS) have marked surfactant dysfunction. Airways and alveoli of affected neonates contain meconium, inflammatory cells, inflammatory mediators, edema fluid, protein, and other debris. The objective of this study was to compare treatment with bronchoalveolar lavage using dilute Surfaxin with standard therapy in a population of newborn infants with MAS. Methods. Inclusion criteria were 1) gestational age ≥35 weeks, 2) enrollment within 72 hours of birth, 3) diagnosis of MAS, 4) need for mechanical ventilation, and 5) an oxygenation index ≥8 and ≤25. Subjects were randomized to either lavage with Surfaxin or standard care (2:1 proportion). In lavaged infants, a volume of 8 mL/kg dilute Surfaxin (2.5 mg/mL) was instilled into each lung over approximately 20 seconds followed by suctioning after 5 ventilator breaths. The procedure was repeated twice. The third and final lavage was with a more concentrated solution (10 mg/mL) of Surfaxin. Results. Twenty-two infants were enrolled (15 Surfaxin and 7 control). Demographic characteristics were similar. There were trends (not significant) for Surfaxin-lavaged infants to be weaned from mechanical ventilation earlier (mean of 6.3 vs 9.9 days, respectively), as well as to have a more rapid decline in their oxygenation indexes compared with control infants, the latter difference persisting for the 96-hour-long study period. The therapy was safe and generally well tolerated by the infants. Conclusions. Dilute Surfaxin lavage seems to be a safe and potentially effective therapy in the treatment of MAS. Data from this investigation support future prospective, controlled clinical trials of bronchoalveolar lavage with Surfaxin in neonates with MAS.

A multicenter, randomized, controlled trial comparing Surfaxin (Lucinactant) lavage with standard care for treatment of meconium aspiration syndrome.

A review of developmental outcomes of term infants with post-asphyxia neonatal encephalopathy

Background Surfactant replacement therapy has been proven beneficial in the prevention and treatment of neonatal respiratory distress syndrome (RDS). The deficiency of surfactant or surfactant dysfunction may contribute to respiratory failure in a broader group of disorders, including meconium aspiration syndrome (MAS). Objectives To evaluate the effect of surfactant administration in the treatment of term/near-term infants with MAS. Search strategy Searches were made using The Cochrane Library (Issue 4, 2006), MEDLINE and EMBASE (1985 to December 2006), previous reviews including cross-references, abstracts, conference and symposia proceedings, expert informants, and journal hand searching. No language restrictions were applied. Authors were directly contacted to provide additional data. Selection criteria Randomised controlled trials which evaluated the effect of surfactant administration in term infants with meconium aspiration syndrome are included in the analyses. Data collection and analysis Data regarding clinical outcomes including mortality, treatment with extracorporeal membrane oxygenation (ECMO), pneumothorax, duration of assisted ventilation, duration of supplemental oxygen, intraventricular haemorrhage (any grade and severe IVH), and chronic lung disease, and were excerpted from the reports of the clinical trails by the review authors. Data analyses were done in accordance with the standards of the Cochrane Neonatal Review Group. Main results Four randomised controlled trials met inclusion criteria. The meta-analysis of 4 trials enrolling 326 infants showed no statistically significant effect on mortality (typical relative risk 0.98 (95% CI 0.41, 2.39), typical risk difference 0.00 (95% CI -0.05, 0.05). The risk of requiring extracorporeal membrane oxygenation was significantly reduced in a meta-analysis of two trials (n = 208); (typical relative risk 0.64, 95% CI 0.46, 0.91; typical risk difference -0.17, 95% CI -0.30, -0.04); number needed to treat to benefit 6 (95% CI 3, 25). One trial (n = 40) reported a statistically significant reduction in the length of hospital stay [mean difference - 8 days (95% CI -14, -3 days)]. There were no statistically significant reductions in any other outcomes studied (duration of assisted ventilation, duration of supplemental oxygen, pneumothorax, pulmonary interstitial emphysema, air leaks, chronic lung disease, need for oxygen at discharge or intraventricular haemorrhage). Authors' conclusions In infants with MAS, surfactant administration may reduce the severity of respiratory illness and decrease the number of infants with progressive respiratory failure requiring support with ECMO. The relative efficacy of surfactant therapy compared to, or in conjunction with, other approaches to treatment including inhaled nitric oxide, liquid ventilation, surfactant lavage and high frequency ventilation remains to be tested.

Surfactant for meconium aspiration syndrome in full term/near term infants.

Objective. Meconium aspiration syndrome (MAS) is a major cause of respiratory morbidity and mortality in term infants. We reported our pilot experience on the use of diluted bovine lung surfactant lipid extract solution (Survanta [Ross Laboratories, Ohio, USA]) as a tracheobronchial lavage fluid for the treatment of infants with severe MAS. Our goal was to establish the safety and the effectiveness of this procedure before organizing a randomized controlled trial. Method. Six infants with severe MAS necessitating mechanical ventilation with an oxygen index of ≥15 within 6 hours of life recruited consecutively during a 1½-year period were treated with tracheobronchial lavage with 15 mL/kg of diluted surfactant solution (Survanta) at a phospholipid concentration of 5 mg/mL administered in 2-mL aliquots. The outcome of treatment was assessed by comparison with 6 consecutive historic control infants with equally severe MAS of similar inclusion criteria retrospectively. Results. The mean oxygen index, mean airway pressure, fraction of inspired oxygen, and arterial/alveolar oxygen tension ratio improved significantly within the first 48 hours after treatment in the lavage group. The duration of ventilation (mean ± SEM, 55.3 ± 4.6 hours vs 131 ± 60 hours) and oxygen therapy (mean ± SEM, 4.1 ± 0.5 days vs 20.8 ± 8.2 days) were also significantly reduced in the lavage-treated group compared with the control group. All 6 patients in the lavage group survived without sequelae whereas there were 2 deaths in the control group. The process of administering the surfactant lavage was well tolerated with no air leak complications. Conclusions. Our experience suggested that surfactant lavage seems to be an effective and safe method for treatment of severe MAS. A multicenter randomized control trial is indicated to further study the efficacy of this treatment.

Surfactant lavage for meconium aspiration syndrome: a pilot study.

We evaluated the effect of tracheobronchial lavage with diluted surfactant solution (bovine lipid extract surfactant, bLES) in a rabbit model of meconium aspiration. All animals were anaesthetized, tr

Surfactant tracheobronchial lavage for the management of a rabbit model of meconium aspiration syndrome.

Meconium aspiration syndrome (MAS) continues to be a major cause of morbidity and mortality in newborn infants. Recent studies on the pathophysiology of MAS showed that the meconium is more potent and toxic than we had previously appreciated. On the basis of animal experiences and a clinical pilot study, we propose that early tracheobronchial lavage with diluted surfactant is an effective and safe method for treatment of severe MAS.

Surfactant lavage for the management of severe meconium aspiration syndrome.

The perinatal events of 40 term newborn infants who had severe birth asphyxia were reviewed and correlated with the neurological outcome at a mean age of 2 1/2 years. Severe birth asphyxia was defined as an Apgar Score of less than or equal to 3 at 1 min. The majority (68.5%) of the babies had an abnormal fetal heart pattern before delivery. Persistent fetal bradycardia was most frequently associated with poor outcome. The neurological staging, the need for assisted ventilation for more than 24 hours and severe renal impairment were the best predictors of neonatal death or subsequent poor neurological outcome. The overall mortality was 10% and 15% of the surviving babies had varying degrees of neurological handicap.

Perinatal features of birth asphyxia and neurologic outcome.

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Surfactant lavage for meconium aspiration syndrome: a pilot study.

Surfactant tracheobronchial lavage for the management of a rabbit model of meconium aspiration syndrome.

Surfactant lavage for the management of severe meconium aspiration syndrome.

Perinatal features of birth asphyxia and neurologic outcome.