Including Meconium Aspiration Syndrome Research Articles

Association Between Intrapartum Nitrous Oxide for Labor Analgesia and Short-Term Neonatal Outcomes.

To evaluate the association between intrapartum nitrous oxide use and adverse short-term neonatal outcomes. This was a retrospective cohort study of individuals with singleton gestations at 35 or more weeks who attempted labor and delivered at an academic hospital between June 1, 2015, and February 28, 2020. Data were extracted from the electronic medical record using billing and diagnostic codes. Patients were classified based on whether they received no intrapartum analgesia or received nitrous oxide only. Those who received other analgesia types were excluded. The primary outcome was neonatal intensive care unit (NICU) admission. Secondary outcomes included Apgar score less than 7 at 1 minute and 5 minutes, respiratory composite outcome (including meconium aspiration syndrome, neonatal bronchopulmonary disorders, neonatal transient tachypnea, and other neonatal respiratory distress that required NICU admission), hypoglycemia, and hyperbilirubinemia. Univariable and multivariable analyses were used to estimate the association between nitrous oxide exposure intrapartum and the selected outcomes. Of 6,047 included, 4,153 (68.7%) received no analgesia, and 1,894 (31.3%) received nitrous oxide only. In comparison with individuals who received no analgesia, those who received nitrous oxide were more likely to be nulliparous, be of Black racial identity, have noncommercial insurance, and be less likely to deliver by intrapartum cesarean. The reception of nitrous oxide, compared with the reception of no analgesia, was associated with a lower likelihood of NICU admission (6.4% vs 8.1%; adjusted odds ratio [aOR] 0.77, 95% CI, 0.62-0.96) and an increased likelihood of neonatal hyperbilirubinemia (aOR 1.23, 95% CI, 1.08-1.41). Inhaled nitrous oxide exposure, in comparison with the reception of no analgesia, was not associated with the other secondary outcomes, including Apgar score less than 7 at 1 minute (odds ratio [OR] 0.74, 95% CI, 0.50-1.10) or 5 minutes (OR 0.91, 95% CI, 0.32-2.60), respiratory composite outcome (OR 0.91, 95% CI, 0.70-1.17), and hypoglycemia (OR 0.82, 95% CI, 0.64-1.05). In this single-center retrospective cohort of low-risk patients, intrapartum inhaled nitrous oxide, compared with the reception of no analgesia, was associated with a decreased risk for NICU admission but with an increased risk for hyperbilirubinemia; other outcomes did not differ. These findings may be used to counsel patients when considering nitrous oxide for labor analgesia.

Can neonatal pneumothorax be successfully managed in regional Australia?

There is a lack of data reflecting the trend of neonatal pneumothorax in regional Australia. The aim of this study is to review the incidence and characteristics of neonates diagnosed with pneumothorax in Central Queensland, analyse outcomes in terms of the ability of local hospitals to manage this condition, and describe predictors for severe disease requiring transfer to a tertiary centre. Thus the role of regional health services in managing this condition will be reviewed. This was a retrospective observational study of all neonates born between 1 January 2008 and 31 December 2015 coded by hospital records with a diagnosis of neonatal pneumothorax in Central Queensland. Data for sex and birth gestation for all Central Queensland births of the same period were also obtained. Descriptive statistics were calculated for birth weight and gestation, and Apgar scores. Frequencies were calculated for sex, length of admission, age of diagnosis and risk factors including meconium aspiration syndrome (MAS), prolonged rupture of membranes (PROM) and positive pressure ventilation (PPV). The primary outcome measure was successful treatment at a Central Queensland hospital versus requirement for transfer to tertiary hospital or death prior to transfer. Statistical significance was calculated for binary and continuous variables. During the study period, there were 31 cases of pneumothorax amongst 17 640 deliveries recorded by three Central Queensland hospitals, with a significant bias towards males (84%) amongst pneumothorax cases (p<0.001). Median gestational age was comparable between the Central Queensland population and the pneumothorax cohort. Diagnosis of pneumothorax was usually made within 48 hours of birth (87.1%). PPV was present in two-thirds of the pneumothorax cohort whilst MAS and PROM were less common. No significant relationship was found between type of pneumothorax and gender, birth weight, MAS, PROM, caesarean section or PPV. The majority of cases were successfully treated locally (67.7%) and with oxygen alone (64.5%). Other treatment modalities included surfactant use, thoracocentesis, chest tube insertion and PPV. Patients with bilateral pneumothorax or pneumomediastinum had poorer outcomes (p=0.04). Overall local outcomes were good, with only one perinatal death prior to discharge or transfer. Neonatal pneumothorax is effectively managed in the regional hospitals studied in keeping with contributions of regional paediatricians and rural generalists. Compared with unilateral pneumothorax, bilateral pneumothorax or pneumomediastinum were associated with transfer to tertiary centre. There were no clear predictors for bilateral pneumothorax.

Delivery Room Management of Meconium-Stained Newborns and Respiratory Support.

In this multicenter cohort study, we compare 130 nonvigorous newborns born during the retrospective 1-year period before the implementation of new NRP guidelines (October 1, 2015, to September 30, 2016) to 101 infants born during the 1-year prospective period after implementation (October 1, 2016, to September 30, 2017). Endotracheal suctioning was performed predominantly in the retrospective group compared with the prospective group (70% vs 2%), indicating the change in practice. A significantly higher proportion of newborns were admitted to the NICU for respiratory issues in the prospective group compared with the retrospective group (40% vs 22%) with an odds ratio (OR) of 2.2 (95% confidence interval [CI]: 1.2-3.9). Similarly, a significantly higher proportion of infants needed oxygen therapy (37% vs 19%) with an OR of 2.5 (95% CI: 1.2-4.5), mechanical ventilation (19% vs 9%) with an OR of 2.6 (95% CI: 1.1-5.8), and surfactant therapy (10% vs 2%) with an OR of 5.8 (95% CI: 1.5-21.8). There were no differences in the incidence of other outcomes, including meconium aspiration syndrome. The recent NRP guideline change was not associated with an increased incidence of meconium aspiration syndrome but was associated with an increased incidence of NICU admissions for respiratory issues. Also, the need for mechanical ventilation, oxygen, and surfactant therapy increased.

Hyperoxia and Hypocapnia During Pediatric Extracorporeal Membrane Oxygenation: Associations With Complications, Mortality, and Functional Status Among Survivors.

To determine the frequency of hyperoxia and hypocapnia during pediatric extracorporeal membrane oxygenation and their relationships to complications, mortality, and functional status among survivors. Secondary analysis of data collected prospectively by the Collaborative Pediatric Critical Care Research Network. Eight Collaborative Pediatric Critical Care Research Network-affiliated hospitals. Age less than 19 years and treated with extracorporeal membrane oxygenation. Hyperoxia was defined as highest PaO2 greater than 200 Torr (27 kPa) and hypocapnia as lowest PaCO2 less than 30 Torr (3.9 kPa) during the first 48 hours of extracorporeal membrane oxygenation. Functional status at hospital discharge was evaluated among survivors using the Functional Status Scale. Of 484 patients, 420 (86.7%) had venoarterial extracorporeal membrane oxygenation and 64 (13.2%) venovenous; 69 (14.2%) had extracorporeal membrane oxygenation initiated during cardiopulmonary resuscitation. Hyperoxia occurred in 331 (68.4%) and hypocapnia in 98 (20.2%). Hyperoxic patients had higher mortality than patients without hyperoxia (167 [50.5%] vs 48 [31.4%]; p < 0.001), but no difference in functional status among survivors. Hypocapnic patients were more likely to have a neurologic event (49 [50.0%] vs 143 (37.0%]; p = 0.021) or hepatic dysfunction (49 [50.0%] vs 121 [31.3%]; p < 0.001) than patients without hypocapnia, but no difference in mortality or functional status among survivors. On multivariable analysis, factors independently associated with increased mortality included highest PaO2 and highest blood lactate concentration in the first 48 hours of extracorporeal membrane oxygenation, congenital diaphragmatic hernia, and being a preterm neonate. Factors independently associated with lower mortality included meconium aspiration syndrome. Hyperoxia is common during pediatric extracorporeal membrane oxygenation and associated with mortality. Hypocapnia appears to occur less often and although associated with complications, an association with mortality was not observed.

Feto-Maternal outcomes in Intrahepatic Cholestasis in Pregnancy in a Tertiary Care Centre in Eastern Nepal

Background Intrahepatic cholestasis of pregnancy has poor feto-maternal outcomes. To date there has been sparse publications regarding impact of intrahepatic cholestasis in feto-maternal outcomes in our setting. Therefore, we aimed to study the feto-maternal outcome in patients with intrahepatic cholestasis of pregnancy.Material and Methods A hospital based prospective cross-sectional study carried out in department of Obstetrics and Gynecology of Nobel Medical College, Biratnagar, Nepal from 1st January 2014 to 30th December 2015 in women who presented with pruritus in third trimester of pregnancy and having deranged liver function tests. All the cases were followed from admission to discharge. Socio-demographic, clinico-laboratory profile and feto-maternal outcomes were recorded in a preformed structured proforma. Descriptive statistics was used to present the data.Results Among 6,780 women admitted for delivery, 80 had cholestasis of pregnancy with incidence of 1.15%. 83% were of 18-35 years and 65% were primigravida. Most distressing symptom was generalized pruritus (75.0 %). The cesarean delivery rate was 46.25% and labor induction rate was (47.5%). Fetal complications were seen in majority of cases that included meconium aspiration syndrome 26 (32.5%), intrapartum fetal distress 21 (26.25%) and requirement of: intensive care 38 (48.75%). There were 7 perinatal and 3 neonatal deaths.Conclusion Intrahepatic cholestasis of pregnancy seems fairly common among pregnant women. It may be responsible for a large number of perinatal and neonatal deaths especially after 36 weeks of gestation. A large prospective study is needed to address the problems in time.Journal of Nobel Medical College Volume 5, Number 1, Issue 8, January-July 2016, 20-25

Surfactant for meconium aspiration syndrome in term and late preterm infants.

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). To evaluate the effect of surfactant administration in the treatment of late preterm and term infants with meconium aspiration syndrome. We searched 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 handsearching, without language restrictions. We contacted study authors for additional data.We ran an updated search in November 2014 and searched the following sites for ongoing or recently completed trials: www.clinicaltrials.gov; www.controlled-trials.com; and www.who.int/ictrp. Randomised controlled trials which evaluated the effect of surfactant administration in late preterm and term infants with meconium aspiration syndrome are included in the analyses. We extracted data on 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. We conducted data analyses in accordance with the standards of the Cochrane Neonatal Review Group. Four randomised controlled trials met our inclusion criteria. The meta-analysis of four trials (326 infants) showed no statistically significant effect on mortality [typical risk ratio (RR) 0.98, 95% confidence interval (CI) 0.41 to 2.39; typical risk difference (RD) -0.00, 95% CI -0.05 to 0.05]. There was no heterogeneity for this outcome (I² = 0% for both RR and RD). The risk of requiring extracorporeal membrane oxygenation was significantly reduced in a meta-analysis of two trials (n = 208); [typical RR 0.64, 95% CI 0.46 to 0.91; typical RD -0.17, 95% CI -0.30 to -0.04; number needed to treat for an additional beneficial outcome (NNTB) 6, 95% CI 3 to 25]. There was no heterogeneity for RR (1² = 0%) but moderate heterogeneity for RD (I² = 50%). One trial (n = 40) reported a statistically significant reduction in the length of hospital stay (mean difference -8 days, 95% CI -14 to -3 days; test for heterogeneity not applicable). 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). 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.

An Update of Surfactant

In preterm infants, RDS is primarily caused by deficiency of pulmonary surfactant in an immature lung. For the past 50 years, related research and experiments with regards to surfactant replacement therapy have been encouraging and inspiring.Numerous trials have been conducted to demonstrate that surfactant plays an important role in the management of respiratory distress syndrome in preterm babies, whether it is synthetic, natural or recombinant. The use of surfactant regarding aspects of other disease has been explored as well, including meconium aspiration syndrome, congenital pneumonia and acute respiratory distress syndrome.With the advance of science, the molecular structure and function of most surfactant components has been well understood and well established. Pulmonary surfactant associated proteins (SPs) consist of a heterogeneous composition of lipids and proteins and it has been identified as SP-A, SP-B, SP-C, and SP-D.Recently, US FDA approved the first synthetic peptide-containing surfactant (Lucinactant) to treat RDS in preterm newborns. Surfactant replacement therapy has been one of the greatest achievements in the management of preterm newborns in the past few decades.

Comparison of Obstetric and Neonatal Outcomes According to Oral Glucose Challenge Test in Korean Pregnant Women

Purpose : The purpose of the study was to compare obstetric and perinatal outcomes according to glucose challenge test (GCT) in a single institution. Methods : One thousand six women, who were underwent antepartum gestational diabetes mellitus (GDM) screening by a GCT in mid-pregnancy and delivered at National Health Service between January 1, 2007 and July 31, 2012, were included in the study. The medical records of patients were analyzed retrospectively. The Subjects were categorized into three groups according to the results of 50 g oral GTC and 100 g oral GTC; normal glucose tolerance (NGT, n=826), less than 140 mg/dL; gestational impaired glucose tolerance (GIGT, n=128), more than 140 mg/dL but non-GDM ; gestational diabetes mellitus (GDM, n=52). Pre-existed maternal DM or hypertension and twin pregnancy were excluded. Obstetric and perinatal outcomes were compared among the three groups. Result : Maternal age, parity, and pre-pregnancy body mass index were higher in the GDM. The preterm delivery and gestational hypertension increased across the groups from NGT to GIGT to GDM (13.9% vs. 18.8% vs. 25.0%, P<0.01, and 1.9% vs.5.5% vs. 13.5%, P<0.01, respectively). Large for gestational age (LGA) and Neonatal Intensive Care Unit admission rate were higher in order in NGT, GIGT, and GDM (6.2% vs. 15.6% vs. 15.4%, P<0.01, and 12.3% vs. 24.2% vs. 38.5%, P<0.01), but other complications requiring intensive care were not different among the groups, including meconium aspiration syndrome and birth asphyxia. Conclusion : GDM was a risk factor of cesarean section, preterm delivery, and gestational hypertension. In addition, GIGT was positively correlated with gestational hypertension, preterm labor, cesarean section rate, and LGA. This study suggests that there is a need to develop a guideline for Korean pregnant women who were diagnosed with GIGT.

Respiratory Distress Including Meconium Aspiration Syndrome in Vigorous Neonates Born Through Meconium Stained Amniotic Fluid: Incidence, Onset, Severity and Predictors at Birth

This study aimed to find out incidence, predictors, onset and severity of respiratory distress including meconium aspiration syndrome (MAS) among vigorous neonates born through meconium stained amniotic fluid (MSAF), which may or may not be evident at birth. Two hundred ninety vigorous neonates were studied. Data were collected on perinatal risk factors, clinical course and development of respiratory distress. Predictors of respiratory distress were identified by logistic regression and a score based on adjusted OR was assigned for each. Diagnostic performance of the score (0-24) was assessed on another 247 vigorous neonates using receiver operator characteristic analysis (ROC). Respiratory distress developed in 97(33.4 %) infants, MAS in 75(25.9 %). The distress appeared within 12 h in 97.9 %, was severe in only 21.7 %. Of 10 risk factors significantly associated with respiratory distress, seven entered in regression analysis. Fetal distress(adj OR = 11.8; 95%CI = 6.2-22.5), prolonged labor(adj OR = 5.2; 95%CI = 2.5-10.7), and absent/poor cry(adj OR = 5.6; 95%CI = 2.4-13.3) were identified as independent predictors; each assigned a score of 12, 6 and 6, respectively. To predict respiratory distress, a cut-off score of 9 points had sensitivity-74.1 % (95%CI = 63.3 %-82.7 %), specificity-84.6 % (95 % CI = 77.9 %-89.6 %), positive predictive value- 71.6 % (95%CI = 60.8 %-80.4 %), negative predictive value- 86.2 % (95 % CI = 79.6 %-90.9 %), likelihood ratio (LR) + ve 4.8(95%CI = 3.3-7.0) and LR-ve 0.3(95%CI = 0.2-0.4). Respiratory distress occurred in one third neonates, mostly had onset within 12 h of birth, and it was mild to moderate in majority. Fetal distress, prolonged labor, and absent/poor cry predicted respiratory distress and were validated. However, larger studies in different settings are required to confirm its utility.

Overcoming surfactant inhibition with polymers

Inhibition of the function of pulmonary surfactant in the alveolar space is an important element of the pathophysiology of many lung diseases, including meconium aspiration syndrome, pneumonia and acute respiratory distress syndrome. The known mechanisms by which surfactant dysfunction occurs are (a) competitive inhibition of phospholipid entry into the surface monolayer (e.g. by plasma proteins), and (b) infiltration and destabilization of the surface film by extraneous lipids (e.g. meconium-derived free fatty acids). Recent data suggest that addition of non-ionic polymers such as dextran and polyethylene glycol to surfactant mixtures may significantly improve resistance to inhibition. Polymers have been found to neutralize the effects of several different inhibitors, and can produce near-complete restoration of surfactant function. The anti-inhibitory properties of polymers, and their possible role as an adjunct to surfactant therapy, deserve further exploration.

The Epidemiology of Respiratory Failure in Neonates Born at an Estimated Gestational Age of 34 Weeks or More

The auth describes a prospective study of 1011 newborn infan who had reached a gestational age of at least 34 weeks. They were inubated for respiratory support within 72 hours f birth and were expected to require ventilation for longer than 6 hours. A single healthcare team attended each infant fr m birth to age 72 hours. The mean gestational age in this series was 37 weeks, and the mean birth weight was 2.9 kg. More than 60% of infants were males, and 69% were delivered by cesarean section. Chronic lung disease was defined as the need for supplemental oxygen at age 30 days. The most common condition necessitating assisted ventilation, diagnosed in 43% of cases, was respiratory distress syndrome. A variety of other conditions were encountered, including meconium aspiration syndrome, pneumonia/sepsis, transient tachypnea, idiopathic persistent pulmonary hypertension, and aspiration of blood or amniotic fluid. Approximately one fifth of infants had major congenital anomalies, the most common being gastroschisis, congenital diaphragmatic hernia, and tracheoesophageal fistula. A large majority of infants, 85% of the group, received at least one adjunctive treatment, and 52% required 2 or more adjunctive treatments. Surfactant was used in 55% of infants, vasopressors in 35%, high-frequency ventilation in 20%, inhaled nitric oxide in 17%, and neuromuscular blockade in 17%. Extra volume was administered to 60% of infants, most often using normal saline. Seventy-three infants (7%) were eligible to receive extracorporeal membrane oxygenation, and 36 of them actually received this treatment for a median time of 6 days. The most prominent risk factor associated with chronic lung disease or death was the presence of a major congenital anomaly. Excluding infants with hypoxic-ischemic encephalopathy or a major neurologic anomaly, adverse neurologic events occurred in 6% of cases. On multivariate logistic regression analysis, the risk of death was increased by a major anomaly, a 5-minute Apgar score less than 5, extracorporeal membrane oxygenation, and treatment with inhaled nitric oxide. Chronic lung disease was associated with pulmonary hypoplasia, major congenital anomaly, inhaled nitric oxide, surfactant treatment, and treatment with vasopressors. Risk factors for adverse neurologic events included a major neurologic anomaly, a primary diagnosis of hypoxic-ischemic encephalopathy, extracorporeal membrane oxygenation, vasopressor treatment, and a 5-minute Apgar score less than 5. Adverse neurologic events were less frequent when infants received surfactant.

Lucinactant: a novel synthetic surfactant for the treatment of respiratory distress syndrome

Lucinactant (Surfaxin®, Discovery Laboratories) is a synthetic surfactant, which contains the novel peptide, sinapultide, a surfactant-associated proteinB mimic. Randomised clinical trials suggest that this compound is a safe and effective treatment for respiratory distress syndrome in preterm infants. It is also being actively investigated for other indications, including meconium aspiration syndrome, treatment of bronchopulmonary dysplasia in neonates, acute respiratory distress syndrome and asthma. A novel aerosol formulation administered with nasal continuous positive airway pressure is also under development for treatment of respiratory insufficiency in neonates. Its non-animal origin may make it an attractive alternative to present animal-derived surfactants by eliminating the risks of infection and immunogenicity related to the latter.

ECMO for neonatal respiratory failure

Extracorporeal membrane oxygenation (ECMO) has been offered as a life-saving technology to newborns with respiratory and cardiac failure refractory to maximal medical therapy. ECMO has been used in treatment of neonates with a variety of cardio-respiratory problems, including meconium aspiration syndrome (MAS), persistent pulmonary hypertension of the neonate (PPHN), congenital diaphragmatic hernia (CDH), sepsis/pneumonia, respiratory distress syndrome (RDS), air leak syndrome, and cardiac anomalies. For this group of high-risk neonates with an anticipated mortality rate of 80% to 85%, ECMO has an overall survival rate of 84%, with recent data showing nearly 100% survival in many diagnostic groups. This article reviews the current selection criteria for ECMO and the clinical management of neonates on ECMO, and discusses the long-term outcome of neonates treated with ECMO.

Pulmonary surfactant for neonatal respiratory disorders.

Surfactant therapy has revolutionized neonatal care and is used routinely for preterm infants with respiratory distress syndrome. Recent investigation has further elucidated the function of surfactant-associated proteins and their contribution toward surfactant and lung immune defense functions. As the field of neonatology moves away from intubation and mechanical ventilation of preterm infants at birth toward more aggressive use of nasal continuous positive airway pressure, the optimal timing of exogenous surfactant therapy remains unclear. Evidence suggests that preterm neonates with bronchopulmonary dysplasia and prolonged mechanical ventilation also experience surfactant dysfunction; however, exogenous surfactant therapy beyond the first week of life has not been well studied. Surfactant replacement therapy has been studied for use in other respiratory disorders, including meconium aspiration syndrome and pneumonia. Commercial surfactant preparations currently available are not optimal, given the variability of surfactant protein content and their susceptibility to inhibition. Further progress in the treatment of neonatal respiratory disorders may include the development of "designer" surfactant preparations.

Overcoming surfactant inhibition with polymers.

Inhibition of the function of pulmonary surfactant in the alveolar space is an important element of the pathophysiology of many lung diseases, including meconium aspiration syndrome, pneumonia and acute respiratory distress syndrome. The known mechanisms by which surfactant dysfunction occurs are (a) competitive inhibition of phospholipid entry into the surface monolayer (e.g. by plasma proteins), and (b) infiltration and destabilization of the surface film by extraneous lipids (e.g. meconium-derived free fatty acids). Recent data suggest that addition of non-ionic polymers such as dextran and polyethylene glycol to surfactant mixtures may significantly improve resistance to inhibition. Polymers have been found to neutralize the effects of several different inhibitors, and can produce near-complete restoration of surfactant function. The anti-inhibitory properties of polymers, and their possible role as an adjunct to surfactant therapy, deserve further exploration.

ECMO in the newborn.

Since the first use in neonates in 1974, extracorporeal membrane oxygenation (ECMO) has been a life-saving technology for newborns with respiratory and cardiac failure. ECMO has been used to treat a variety of cardio-respiratory problems, including meconium aspiration syndrome (MAS), persistent pulmonary hypertension of the neonate (PPHN), congenital diaphragmatic hernia (CDH), sepsis, and cardiac anomalies. For this group of high-mortality neonates, ECMO has produced a survival of 76% in all newborns treated. This review article will examine the current selection criteria for ECMO, the clinical management of neonates on ECMO and discuss the long-term outcome of neonates treated with ECMO.

The impact of a policy of amnioinfusion for meconium-stained amniotic fluid

To evaluate the impact of an amnioinfusion (AI) policy for thick or moderate meconium-stained amniotic fluid (AF) on neonatal outcome, specifically meconium-aspiration syndrome and its complications. We reviewed maternal and neonatal charts of 937 vertex, singleton pregnancies complicated by moderate or thick meconium-stained AF during a 3-year period. The patients were divided into groups according to whether AI was performed. Demographic characteristics, risk factors, mode of delivery, pregnancy outcome, and neonatal complications, including meconium-aspiration syndrome, were analyzed. Four hundred forty patients (47%) received AI (AI group); 497 (53%) did not, for the following reasons: imminent delivery (310 patients), occult meconium (141), or emergency cesarean delivery (46) (no-AI group). Our study did not show any reduction in the incidence of 5-minute Apgar scores of 7 or less (8 versus 7%), meconium below the vocal cords (28 versus 29%), meconium aspiration syndrome (4.5 versus 3.8%), ventilation requirement (4.3 versus 2.4%), or neonatal death (0.7 versus 0.2%) in the AI and no-AI groups, respectively. The AI group had a higher incidence of fetal heart rate abnormalities in labor (48 versus 31%, P < .05), instrumental delivery (15 versus 8%, P < .05), cesarean delivery (28 versus 17%, P < .001), and endometritis (21 versus 13%, P = .004). With the policy of routine AI for moderate or thick meconium-stained AF, AI was not clinically feasible in 53% of the cases. We were unable to demonstrate any improvement in neonatal outcome in those who received AI for moderate or thick meconium.

Elevated immunoreactive endothelin-1 levels in newborn infants with persistent pulmonary hypertension

To study the potential role of endothelin-1, a potent endothelium-derived vasoconstrictor peptide, in the pathophysiology of persistent pulmonary hypertension of the newborn (PPHN), we measured arterial concentrations of immunoreactive endothelin-1 (irET-1) in 24 neonates with PPHN. Secondary diagnoses included meconium aspiration syndrome (13 patients), sepsis (2), congenital diaphragmatic hernia (1), asphyxia (1), pulmonary hemorrhage (1), aspiration of blood (1), and respiratory distress syndrome (1). Compared with irET-1 levels in umbilical cord blood in normal infants (15.1 +/- 4.1 pg/ml; mean +/- SEM) and in newborn infants with hyaline membrane disease who were supported by mechanical ventilation (11.8 +/- 1.2 pg/ml), infants with PPHN had markedly elevated circulating irET-1 levels (27.6 +/- 3.6 pg/ml; p < 0.01 vs cord blood, hyaline membrane disease). Infants with severe PPHN requiring extracorporeal membrane oxygenation (ECMO) therapy had higher irET-1 levels than infants with milder disease (31.0 +/- 4.7 for ECMO-treated infants vs 21.2 +/- 2.0 for non-ECMO-treated infants; p < 0.05). In patients treated without ECMO, irET-1 progressively decreased during the following 3 to 5 days, paralleling clinical improvement. In contrast, irET-1 concentrations remained elevated in infants with severe PPHN during ECMO therapy. We conclude that circulating irET-1 levels are elevated in newborn infants with PPHN, are positively correlated with disease severity, and decline with resolution of disease in patients who do not require ECMO therapy. Whether endothelin-1 contributes directly to the pathophysiology of PPHN or is simply a marker of disease activity remains speculative.

Clinical responses to prolonged treatment of persistent pulmonary hypertension of the newborn with low doses of inhaled nitric oxide

We studied the efficacy of low-dose nitric oxide inhalation in nine consecutive patients with severe persistent pulmonary hypertension of the newborn (PPHN) who were candidates for extracorporeal membrane oxygenation (ECMO). All patients had marked hypoxemia despite aggressive ventilator management and echocardiographic evidence of pulmonary hypertension. Associated diagnoses included meconium aspiration syndrome (3 patients), sepsis (3 patients), and congenital diaphragmatic hernia (2 patients). Infants were initially treated with inhaled nitric oxide at 20 ppm for 4 hours and then at 6 ppm for 20 hours. In all infants, oxygenation promptly improved (arterial/alveolar oxygen ratio, 0.077 +/- 0.016 at baseline vs 0.193 +/- 0.030 at 4 hours; p < 0.001) without a decrease in systemic blood pressure. Sustained improvement in oxygenation was achieved in eight patients treated with inhaled nitric oxide for 24 hours at 6 ppm (arterial/alveolar oxygen ratio, 0.270 +/- 0.053 at 24 hours; p < 0.001 vs baseline). One patient with overwhelming sepsis had an initial improvement of oxygenation with nitric oxide but required ECMO for multiorgan and cardiac dysfunction. We conclude that low doses of nitric oxide cause sustained clinical improvement in severe PPHN and may reduce the need for ECMO. However, immediate availability of ECMO is important in selected cases of PPHN complicated by severe systemic hemodynamic collapse.

Possible Causes Linking Asphyxia, Thick Meconium and Respiratory Distress

The cause of fetal distress and neonatal respiratory distress (RD) in association with meconium-stained liquor is not always clear. To clarify this, a prospective study was undertaken in a tertiary referral maternity hospital for 1 year. In all infants born after meconium-stained liquor who developed RD, evidence was sought for 1) fetal distress (from the cardiotocograph (CTG), the cord blood pH, the Apgar score and the asphyxial complications in the neonate) 2) causes of fetal distress (including maternal risk factors, fetal infection and fetal malnutrition) 3) causes of respiratory distress (including meconium aspiration syndrome (MAS), persistent pulmonary hypertension of the newborn (PPHN) and infection). Of 4,026 livebirths, 717 (17.8%) had meconium-stained liquor and 44 term and 5 preterm infants developed RD. In the 44 term infants, there was frequent evidence of fetal distress possibly caused by previously unrecognized factors such as fetal malnutrition with reduced neonatal skinfold thickness in 35% triceps and 41% subscapular measurements, and histological chorioamnionitis (CA) in 74%. The cause for respiratory distress was identified in only 48% of infants, and included clinical evidence of PPHN (41%), MAS (16%) and infection (2%). However in preterm infants, 80% had definite or suspected infection. The findings indicate that fetal distress is common in infants who develop respiratory distress after meconium-stained liquor. A role for histological CA and reduced nutrition in the fetus, as factors contributing to the vulnerability of the term infant to intrapartum fetal distress, is suggested.