Appropriate Management of the Nonvigorous Meconium-Stained Newborn Meconium.

Before 2015, major changes in Neonatal Resuscitation Program (NRP) recommendations not supporting previously endorsed antepartum, intrapartum and postpartum interventions to prevent meconium aspiration syndrome were based on adequately powered multicenter randomized controlled trials. The 2015 and 2020 American Heart Association guidelines and 7th and 8th edition of NRP suggest not performing routine intubation and tracheal suctioning of nonvigorous meconium-stained newborns. However, this was given as a weak recommendation with low-certainty evidence. The purpose of this review is to summarize the evidence and explore the question of appropriate delivery room management for nonvigorous meconium-stained newborns.

Evaluation for the etiology of neonatal encephalopathy and the diagnosis of FIRS.

A common disorder managed in the neonatal intensive care unit (NICU) is neonatal encephalopathy (NE). There are multiple causes of NE, including hypoxic-ischemic encephalopathy (HIE) and the fetal inflammatory response syndrome (FIRS). It is important to ascertain the specific cause of NE in an affected child, as it may affect the clinical management and will assist in prognostication. This paper discusses the background of inflammatory damage to the fetal brain, the history of FIRS as a clinical diagnosis, the characteristics of infants with FIRS, and methods to evaluate the etiology of NE.

Circumcision rates in the United States: rising or falling? What effect might the new affirmative pediatric policy statement have?

The objective of this review was to assess the trend in the US male circumcision rate and the impact that the affirmative 2012 American Academy of Pediatrics policy statement might have on neonatal circumcision practice. We searched PubMed for the term circumcision to retrieve relevant articles. This review was prompted by a recent report by the Centers for Disease Control and Prevention that found a slight increase, from 79% to 81%, in the prevalence of circumcision in males aged 14 to 59 years during the past decade. There were racial and ethnic disparities, with prevalence rising to 91% in white, 76% in black, and 44% in Hispanic males. Because data on neonatal circumcision are equivocal, we undertook a critical analysis of hospital discharge data. After correction for underreporting, we found that the percentage had declined from 83% in the 1960s to 77% by 2010. A risk-benefit analysis of conditions that neonatal circumcision protects against revealed that benefits exceed risks by at least 100 to 1 and that over their lifetime, half of uncircumcised males will require treatment for a medical condition associated with retention of the foreskin. Other analyses show that neonatal male circumcision is cost-effective for disease prevention. The benefits of circumcision begin in the neonatal period by protection against infections that can damage the pediatric kidney. Given the substantial risk of adverse conditions and disease, some argue that failure to circumcise a baby boy may be unethical because it diminishes his right to good health. There is no long-term adverse effect of neonatal circumcision on sexual function or pleasure. The affirmative 2012 American Academy of Pediatrics policy supports parental education about, access to, and insurance and Medicaid coverage for elective infant circumcision. As with vaccination, circumcision of newborn boys should be part of public health policies. Campaigns should prioritize population subgroups with lower circumcision prevalence and a higher burden of diseases that can be ameliorated by circumcision.

Veracity and rhetoric in paediatric medicine: a critique of Svoboda and Van Howe's response to the AAP policy on infant male circumcision.

In a recent issue of the Journal of Medical Ethics,Svoboda and Van Howe commented on the 2012 changein the American Academy of Pediatrics (AAP) policy on newborn male circumcision, in which the AAP stated that benefits of the procedure outweigh the risks. Svoboda and Van Howe disagree with the AAP conclusions. We show here that their arguments against male circumcision are based on a poor understanding of epidemiology,erroneous interpretation of the evidence, selective citation of the literature, statistical manipulation of data, and circular reasoning. In reality, the scientific evidence indicates that male circumcision, especially when performed in the newborn period, is an ethically and medically sound low-risk preventive health procedure conferring a lifetime of benefits to health and well-being.Policies in support of parent-approved elective newborn circumcision should be embraced by the medical,scientific and wider communities.

Circumcision and lifetime risk of urinary tract infection: a systematic review and meta-analysis.

PURPOSE: Urinary tract infection is common in infant males who are uncircumcised and can lead to renal parenchymal disease of the still growing pediatric kidney. Although the rate of urinary tract infection is highest in the first year of life, the cumulative incidence during the rest of the lifetime is under-recognized, but is expected to be nontrivial. Thus, any intervention that might prevent urinary tract infection would be expected to reduce suffering and medical costs. MATERIALS AND METHODS: We conducted a meta-analysis of 22 studies examining the single risk factor of lack of circumcision, then determined the prevalence and relative risk of urinary tract infection in different age groups (0 to 1, 1 to 16 and older than 16 years). From these data we estimated the lifetime prevalence. RESULTS: For age 0 to 1 year the relative risk was 9.91 (95% CI 7.49-13.1), for age 1 to 16 years RR was 6.56 (95% CI 3.26-13.2) and for older than 16 years it was 3.41-fold (95% CI 0.916-12.7) higher in uncircumcised males. We then calculated that 32.1% (95% CI 15.6-49.8) of uncircumcised males experience a urinary tract infection in their lifetime compared with 8.8% (95% CI 4.15-13.2) of circumcised males (RR 3.65, 95% CI 1.15-11.8). The number needed to treat was 4.29 (95% CI 2.20-27.2). CONCLUSIONS: The single risk factor of lack of circumcision confers a 23.3% chance of urinary tract infection during the lifetime. This greatly exceeds the prevalence of circumcision complications (1.5%), which are mostly minor. The potential seriousness of urinary tract infection supports circumcision as a desirable preventive health intervention in infant males.

A 'snip' in time: what is the best age to circumcise?

BACKGROUND: Circumcision is a common procedure, but regional and societal attitudes differ on whether there is a need for a male to be circumcised and, if so, at what age. This is an important issue for many parents, but also pediatricians, other doctors, policy makers, public health authorities, medical bodies, and males themselves. DISCUSSION: We show here that infancy is an optimal time for clinical circumcision because an infant's low mobility facilitates the use of local anesthesia, sutures are not required, healing is quick, cosmetic outcome is usually excellent, costs are minimal, and complications are uncommon. The benefits of infant circumcision include prevention of urinary tract infections (a cause of renal scarring), reduction in risk of inflammatory foreskin conditions such as balanoposthitis, foreskin injuries, phimosis and paraphimosis. When the boy later becomes sexually active he has substantial protection against risk of HIV and other viral sexually transmitted infections such as genital herpes and oncogenic human papillomavirus, as well as penile cancer. The risk of cervical cancer in his female partner(s) is also reduced. Circumcision in adolescence or adulthood may evoke a fear of pain, penile damage or reduced sexual pleasure, even though unfounded. Time off work or school will be needed, cost is much greater, as are risks of complications, healing is slower, and stitches or tissue glue must be used. SUMMARY: Infant circumcision is safe, simple, convenient and cost-effective. The available evidence strongly supports infancy as the optimal time for circumcision.

Resuscitation in the delivery room: lung protection from the first breath.

Resuscitation of newborn infants occurs in approximately 10% of the more than 100 million infants born annually worldwide. The techniques used during resuscitation, such as positive-pressure ventilation and supplemental oxygen, may revive many infants, but have the potential to harm their lungs. In recent years increasing attention has been applied to providing lung protection from the first breath. This paper reviews the currently available medical evidence concerning modifying aspects of delivery room management that are thought to mitigate lung injury. These include: F(IO(2)) < 1.0; early use of continuous positive airway pressure (CPAP) and PEEP; optimizing pressure and/or volume during ventilation; sustained inflations; need for and timing of surfactant therapy; and airway management of meconium-stained amniotic fluid. Although the evidence against 100% oxygen use is of low quality, it has been enough to alter the recommendations for oxygen use in the delivery room. It is suggested (not mandated) to use room air initially when resuscitating a term-gestation infant, and to use F(IO(2)) < 1.0 in premature infants, with F(IO(2)) adjustments depending on oximetry values. Recent studies have not indicated better outcomes in premature infants in whom CPAP or PEEP is applied in the delivery room. Optimal peak ventilatory pressure and tidal volume have yet to be delineated. Although an intriguing therapy, sustained inflations have not been shown to markedly improve outcomes. Prophylactic use of surfactant in small, premature infants remains the accepted standard. Immediate placement on CPAP after surfactant instillation has yet to demonstrate clear-cut advantages. Finally, intrapartum oropharyngeal and nasopharyngeal suctioning of meconium-stained amniotic fluid does not improve outcomes in meconium-stained infants. Moreover, routine intubation and intratracheal suctioning of apparently vigorous meconium-stained infants do not improve outcomes. In summary, although multiple therapies are touted as protecting the lungs in the delivery room "from the first breath," to date there are scant supportive data.

Protein-containing synthetic surfactant versus protein-free synthetic surfactant for the prevention and treatment of respiratory distress syndrome.

BACKGROUND: Respiratory distress syndrome (RDS) is a significant cause of morbidity and mortality in preterm infants. RDS is caused by a deficiency, dysfunction, or inactivation of pulmonary surfactant. Numerous surfactants of either animal extract or synthetic design have been shown to improve outcomes. New surfactant preparations that include peptides or whole proteins that mimic endogenous surfactant protein have recently been developed and tested. OBJECTIVES: To assess the effect of administration of synthetic surfactant containing surfactant protein mimics compared to protein free synthetic surfactant on the risk of mortality, chronic lung disease, and other morbidities associated with prematurity in preterm infants at risk for or having RDS. SEARCH STRATEGY: Standard search methods of the Cochrane Neonatal Review Group were used. The search included MEDLINE (1966 - March 2009) and the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library) in all languages. SELECTION CRITERIA: Randomized and quasi-randomized controlled clinical trials were considered for this review. Studies that enrolled preterm infants or low birth weight infants at risk for or having RDS who were treated with either a synthetic surfactant containing surfactant protein mimics or a protein free synthetic surfactant were included for this review. Studies of treatment or prevention of respiratory distress syndrome were included. DATA COLLECTION AND ANALYSIS: Data regarding mortality, chronic lung disease and multiple secondary outcome measures were abstracted by the review authors. Statistical analysis was performed using Review Manager software. Categorical data were analyzed using relative risk, risk difference, and number needed to treat. 95% confidence intervals reported. A fixed effects model was used for the meta-analysis. Heterogeneity was assessed using the I(2) statistic. MAIN RESULTS: One study was identified that compared protein containing synthetic surfactants (PCSS) to protein free synthetic surfactants. Infants who received protein containing synthetic surfactant compared to protein free synthetic surfactant did not demonstrate significantly different risks of prespecified primary outcomes: mortality at 36 weeks postmenstrual age (PMA) [RR 0.89 (95% CI 0.71, 1.11)], chronic lung disease at 36 weeks PMA [RR 0.89 (95% CI 0.78, 1.03)], or the combined outcome of mortality or chronic lung disease at 36 weeks PMA [RR 0.88 (95% CI 0.77, 1.01)]. Among the secondary outcomes, a decrease in the incidence of respiratory distress syndrome at 24 hours of age was demonstrated in the group that received PCSS [RR 0.83 (95% CI 0.72, 0.95). AUTHORS' CONCLUSIONS: In the one trial comparing protein containing synthetic surfactants compared to protein free synthetic surfactant for the prevention of RDS, no statistically different clinical differences in death and chronic lung disease were noted. Clinical outcomes between the two groups were generally similar although the group receiving protein containing synthetic surfactants did have decreased incidence of respiratory distress syndrome. Further well designed studies comparing protein containing synthetic surfactant to the more widely used animal derived surfactant extracts are indicated.

Drug therapies in bronchopulmonary dysplasia: debunking the myths.

Bronchopulmonary dysplasia (BPD), also known as chronic lung disease (CLD), is one of the most challenging complications in premature infants. The incidence of BPD has been increasing over the past two decades in parallel with an improvement in the survival of this population. Furthermore, the clinical characteristics and the natural history of infants affected by BPD have changed considerably, and newer definitions to clarify the term 'BPD' have also evolved since its first description more than four decades ago. Several drug therapies have also evolved, either to manage these infants' respiratory distress syndrome with an aim to prevent BPD or to manage the established condition. Although there is good evidence to support the 'routine' use of some therapies, many other therapies currently used in relation to BPD remain individual- or institution-specific, depending on beliefs and myths that we have adopted. In this article, we discuss the importance of defining BPD more objectively and the support--or lack thereof--for the drug therapies used in relation to BPD.

Adjunctive therapies in chronic lung disease: examining the evidence.

Chronic lung disease (CLD) or bronchopulmonary dysplasia (BPD) is one of the most common long-term complications in very premature infants. The incidence of CLD has been increasing over the past two decades in parallel with an improvement in the survival of this population. We have witnessed a revolution in the therapies that are used, either to manage these infants' respiratory distress syndrome (RDS) with an aim to prevent CLD or to manage the established condition. Several devices and strategies have been developed to provide respiratory support with minimal risk of lung injuries. Multiple adjunctive agents have also been used either to reduce the risk of CLD or to mitigate its course. There is considerable evidence supporting the use of exogenous surfactant, but unfortunately many other therapies currently used for CLD, either preventative or as a treatment, are based on very little or no evidence. The gold standard to assess a given therapy is the randomised controlled trial (RCT), designed to look at clinically meaningful outcomes and long-term safety. In this context, we discuss the support - or lack thereof - for the adjunctive therapies used in relation to CLD. Many of the therapies have been examined as systematic reviews by the Cochrane Neonatal Review Group. These reviews are noted in the references and can be easily accessed at the following website sponsored by the National Institute of Child Health and Human Development: www.nichd.nih.gov/cochrane/default.cfm.

Evidence-based use of adjunctive therapies to ventilation.

Respiratory distress is the most common reason for admission to newborn intensive care units. Over the past two decades, we have witnessed a revolution in the therapies that are used to manage neonates who have pulmonary disorders. Multiple adjunctive agents have also been used in an attempt to mitigate the course of neonatal lung disease. The disorders we discuss include respiratory distress syndrome, chronic lung disease/bronchopulmonary dysplasia, persistent pulmonary hypertension of the newborn, meconium aspiration syndrome, and transient tachypnea of the newborn. We review the evidence that either supports or refutes the use of adjunctive therapies for these disorders.

RACP's policy statement on infant male circumcision is ill-conceived.

OBJECTIVE: To conduct a critical peer-review of the 2004 Policy Statement on routine male circumcision produced by the Royal Australasian College of Physicians (RACP). METHOD: Comprehensive evaluation in the context of the research field. RESULTS: We find that the current Statement downplays the wide-ranging life-long benefits of circumcision in prevention of urinary tract infections (UTIs), penile and cervical cancer, genital herpes and chlamydia in women, HIV infection, phimosis, and various penile dermatoses, and at the same time overstates the complication rate. We highlight the many errors in the RACP Statement and note that it sidesteps making a conclusion based on circumcision's well-documented prophylactic health benefits by instead referring to the status of the foreskin at birth. In the era of preventative medicine we view this as irresponsible. CONCLUSION: The RACP's Statement on routine male circumcision is not evidence-based and should be retracted. IMPLICATIONS: In the interests of public health and individual well-being an extensive, comprehensive, evidence-based revision should be conducted so as to provide scientifically accurate, balanced information on the advantages, and also the low rate of mostly minor complications, associated with this simple procedure, which for maximum benefits and minimal risk should ideally be performed in the neonatal period.

Histological chorioamnionitis and the risk of early intraventricular hemorrhage in infants born < or =28 weeks gestation.

OBJECTIVE: To test the hypothesis that histological chorioamnionitis (CA) is not associated with increased risk of early onset intraventricular hemorrhage (IVH). STUDY DESIGN: Clinical data were prospectively collected for 62 consecutive neonates born before 28 weeks of gestation. Placental histology for CA was performed by a pathologist unaware of the head ultrasound scan (HUS) results. The first HUS was obtained by 30 minutes of life. Follow-up HUS were performed before 24 hours and again at 48 to 72 postnatal hours of life. An IVH (grade I to IV) at less than 72 hours of life was deemed an early hemorrhage. RESULTS: Nine of the 62 (14.5%) infants had early onset IVH. In all, 29 infants were born to women with histological evidence of CA; 33 infants did not have CA. Infants did not differ in birth weight, gestational age, sex, cord blood pH, 5-minute Apgar score of <7, cesarean delivery, prenatal use of steroids, administration of tocolytics, need for resuscitation, presence of pneumothorax, platelet count at birth, or use of surfactant. Early IVH rates (3/29 in CA vs 6/33 in non-CA) were similar (p=0.48). Two infants in each group with early IVH died before 2 weeks of age. Five additional infants from the CA group developed IVH at more than 72 postnatal hours of life (late onset IVH), and two of those infants progressed to develop periventricular leukomalacia (PVL). In contrast, only three non-CA infants had late IVH and none developed PVL. Logistic regression confirmed that no perinatal variables including CA were associated with early onset IVH. CONCLUSION: Chorioamnionitis is not associated with increased risk of early IVH.

A multicenter, randomized, controlled trial of lucinactant versus poractant alfa among very premature infants at high risk for respiratory distress syndrome.

BACKGROUND: Available therapeutic surfactants are either animal-derived or non-protein-containing synthetic products. Animal-derived surfactants contain variable amounts of surfactant apoproteins, whereas the older-generation synthetic products contain only phospholipids and lack surfactant proteins (SPs). Both decrease morbidity and mortality rates associated with respiratory distress syndrome (RDS) among preterm infants, compared with placebo. However, excess mortality rates have been observed with non-protein-containing synthetic surfactants, compared with the animal-derived products. Evidence suggests that synthetic surfactants consisting solely of phospholipids can be improved with the addition of peptides that are functional analogs of SPs. Lucinactant is a new synthetic peptide-containing surfactant that contains sinapultide, a novel, 21-amino acid peptide (leucine and lysine repeating units, KL4 peptide) designed to mimic human SP-B. It is completely devoid of animal-derived components. OBJECTIVE: We hypothesized that the outcomes for premature infants treated with lucinactant and poractant alfa would be similar. Therefore, we compared lucinactant (Surfaxin; Discovery Laboratories, Doylestown, PA) with porcine-derived, poractant alfa (Curosurf; Chiesi Farmaceutici, Parma, Italy) in a trial to test for noninferiority. METHODS: A total of 252 infants born between 24 and 28 weeks of completed gestation, with birth weights between 600 and 1250 g, were assigned randomly in a multicenter, multinational, noninferiority, randomized, controlled study to receive either lucinactant (n = 124) or poractant alfa (n = 128) within 30 minutes of life. The primary outcome was the incidence of being alive without bronchopulmonary dysplasia (BPD) through 28 days of age. Key secondary outcomes included death at day 28 and 36 weeks postmenstrual age (PMA), air leaks, neuroimaging abnormalities, and other complications related to either prematurity or RDS. An independent, international, data and safety monitoring committee monitored the trial. RESULTS: The treatment difference between lucinactant and poractant alfa for survival without BPD through 28 days was 4.75% (95% confidence interval [CI]: -7.3% to 16.8%) in favor of lucinactant, with the lower boundary of the 95% CI for the difference, ie, -7.3%, being greater than the prespecified noninferiority margin of -14.5%. At 28 days, 45 of 119 infants given lucinactant were alive without BPD (37.8%; 95% CI: 29.1-46.5%), compared with 41 of 124 given poractant alfa (33.1%; 95% CI: 24.8-41.3%); at 36 weeks PMA, the rates were 64.7% and 66.9%, respectively. The corresponding mortality rate through day 28 for the lucinactant group was lower than that for the poractant alfa group (11.8% [95% CI: 6.0-17.6%] vs 16.1% [95% CI: 9.7-22.6%]), as was the rate at 36 weeks PMA (16% and 18.5%, respectively). There were no differences in major dosing complications. In addition, no significant differences were observed in the incidences of common complications of prematurity, including intraventricular hemorrhage (grades 3 and 4) and cystic periventricular leukomalacia (lucinactant: 14.3%; poractant alfa: 16.9%). CONCLUSIONS: Lucinactant and poractant alfa were similar in terms of efficacy and safety when used for the prevention and treatment of RDS among preterm infants. The ability to enhance the performance of a synthetic surfactant with the addition of a peptide that mimics the action of SP-B, such as sinapultide, brings potential advantages to exogenous surfactant therapy.

Oropharyngeal and nasopharyngeal suctioning of meconium-stained neonates before delivery of their shoulders: multicentre, randomised controlled trial.

BACKGROUND: Meconium aspiration syndrome (MAS) is a life-threatening respiratory disorder in infants born through meconium-stained amniotic fluid (MSAF). Although anecdotal data concerning the efficacy of intrapartum oropharyngeal and nasopharyngeal suctioning of MSAF are conflicting, the procedure is widely used. We aimed to assess the effectiveness of intrapartum suctioning for the prevention of MAS. METHODS: We designed a randomised controlled trial in 11 hospitals in Argentina and one in the USA. 2514 patients with MSAF of any consistency, gestational age at least 37 weeks, and cephalic presentation were randomly assigned to suctioning of the oropharynx and nasopharynx (including the hypopharynx) before delivery of the shoulders (n=1263), or no suctioning before delivery (n=1251). Postnatal delivery-room management followed Neonatal Resuscitation Program guidelines. The primary outcome was incidence of MAS. Clinicians diagnosing the syndrome and designating other study outcomes were masked to group assignment. An informed consent waiver was used. Analysis was by intention to treat. FINDINGS: 18 infants in the suction group and 15 in the no suction group did not meet entry criteria after random assignment. 87 in the suction group were not suctioned, and 26 in the no suction group were suctioned. No significant difference between treatment groups was seen in the incidence of MAS (52 [4%] suction vs 47 [4%] no suction; relative risk 0.9, 95% CI 0.6-1.3), need for mechanical ventilation for MAS (24 [2%] vs 18 [1%]; 0.8, 0.4-1.4), mortality (9 [1%] vs 4 [0.3%]; 0.4, 0.1-1.5), or in the duration of ventilation, oxygen treatment, and hospital care. INTERPRETATION: Routine intrapartum oropharyngeal and nasopharyngeal suctioning of term-gestation infants born through MSAF does not prevent MAS. Consideration should be given to revision of present recommendations.