Restarting the newborn infant heart Liley, Helen G.; Haakons, Kristen
Resuscitation,
June 2024, 2024-Jun, 2024-06-00, 20240601, Letnik:
199
Journal Article
Xanthine oxidase (XO) is distributed in mammals largely in the liver and small intestine, but also is highly active in milk where it generates hydrogen peroxide (H2O2). Adult human saliva is low in ...hypoxanthine and xanthine, the substrates of XO, and high in the lactoperoxidase substrate thiocyanate, but saliva of neonates has not been examined.
Median concentrations of hypoxanthine and xanthine in neonatal saliva (27 and 19 μM respectively) were ten-fold higher than in adult saliva (2.1 and 1.7 μM). Fresh breastmilk contained 27.3 ± 12.2 μM H2O2 but mixing baby saliva with breastmilk additionally generated >40 μM H2O2, sufficient to inhibit growth of the opportunistic pathogens Staphylococcus aureus and Salmonella spp. Oral peroxidase activity in neonatal saliva was variable but low (median 7 U/L, range 2-449) compared to adults (620 U/L, 48-1348), while peroxidase substrate thiocyanate in neonatal saliva was surprisingly high. Baby but not adult saliva also contained nucleosides and nucleobases that encouraged growth of the commensal bacteria Lactobacillus, but inhibited opportunistic pathogens; these nucleosides/bases may also promote growth of immature gut cells. Transition from neonatal to adult saliva pattern occurred during the weaning period. A survey of saliva from domesticated mammals revealed wide variation in nucleoside/base patterns.
During breast-feeding, baby saliva reacts with breastmilk to produce reactive oxygen species, while simultaneously providing growth-promoting nucleotide precursors. Milk thus plays more than a simply nutritional role in mammals, interacting with infant saliva to produce a potent combination of stimulatory and inhibitory metabolites that regulate early oral-and hence gut-microbiota. Consequently, milk-saliva mixing appears to represent unique biochemical synergism which boosts early innate immunity.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
In this randomized, controlled trial, supplementation of docosahexaenoic acid in preterm infants born before 29 weeks of gestation did not result in a lower risk of bronchopulmonary dysplasia than a ...control emulsion and may have resulted in a greater risk.
Bronchopulmonary dysplasia is a serious complication of preterm birth. It is characterized by an inflammatory process causing abnormal lung development, decreased vascular and alveolar development,
1
and the need for supplemental oxygen or assisted ventilation at 36 weeks of postmenstrual age (gestational age weeks between the first day of the last menstrual period and birth plus chronological age weeks elapsed after birth).
2
Bronchopulmonary dysplasia is associated with long-term pulmonary and neurodevelopmental impairment and increased needs for health and education services.
3
,
4
Some evidence has suggested that the n−3 long-chain polyunsaturated fatty acid docosahexaenoic acid (DHA) may help protect against the development . . .
Background
Preterm birth, defined as birth between 20 and 36 completed weeks, is a major contributor to perinatal morbidity and mortality globally. Oxytocin receptor antagonists (ORA), such as ...atosiban, have been specially developed for the treatment of preterm labour. ORA have been proposed as effective tocolytic agents for women in preterm labour to prolong pregnancy with fewer side effects than other tocolytic agents.
Objectives
To assess the effects on maternal, fetal and neonatal outcomes of tocolysis with ORA for women with preterm labour compared with placebo or any other tocolytic agent.
Search methods
We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (1 December 2013).
Selection criteria
We included all randomised controlled trials (published and unpublished) of ORA for tocolysis of labour between 20 and 36 completed weeks' gestation.
Data collection and analysis
Two review authors independently evaluated methodological quality and extracted trial data. When required, we sought additional data from trial authors. Results are presented as risk ratio (RR) for categorical and mean difference (MD) for continuous data with the 95% confidence intervals (CI). Where appropriate, the number needed to treat for benefit (NNTB) and the number needed to treat for harm (NNTH) were calculated.
Main results
This review update includes eight additional studies (790 women), giving a total of 14 studies involving 2485 women.
Four studies (854 women) compared ORA (three used atosiban and one barusiban) with placebo. Three studies were considered at low risk of bias in general (blinded allocation to treatment and intervention), the fourth study did not adequately blind the intervention. No difference was shown in birth less than 48 hours after trial entry (average RR 1.05, 95% CI 0.15 to 7.43; random‐effects, (two studies, 152 women), perinatal mortality (RR 2.25, 95% CI 0.79 to 6.38; two studies, 729 infants), or major neonatal morbidity. ORA (atosiban) resulted in a small reduction in birthweight (MD ‐138.86 g, 95% CI ‐250.53 to ‐27.18; two studies with 676 infants). In one study, atosiban resulted in an increase in extremely preterm birth (before 28 weeks' gestation) (RR 3.11, 95% CI 1.02 to 9.51; NNTH 31, 95% CI 8 to 3188) and infant deaths (up to 12 months) (RR 6.13, 95% CI 1.38 to 27.13; NNTH 28, 95% CI 6 to 377). However, this finding may be confounded due to randomisation of more women with pregnancy less than 26 weeks' gestation to atosiban. ORA also resulted in an increase in maternal adverse drug reactions requiring cessation of treatment in comparison with placebo (RR 4.02, 95% CI 2.05 to 7.85; NNTH 12, 95% CI 5 to 33). No differences were shown in preterm birth less than 37 weeks' gestation or any other adverse neonatal outcomes. No differences were evident by type of ORA, although data were limited.
Eight studies (1402 women) compared ORA (atosiban only) with betamimetics; four were considered of low risk of bias (blinded allocation to treatment and to intervention). No statistically significant difference was shown in birth less than 48 hours after trial entry (RR 0.89, 95% CI 0.66 to 1.22; eight studies with 1389 women), very preterm birth (RR 1.70, 95% CI 0.89 to 3.23; one study with 145 women), extremely preterm birth (RR 0.84, 95% CI 0.37 to 1.92; one study with 244 women) or perinatal mortality (RR 0.55, 95% CI 0.21 to 1.48; three studies with 816 infants). One study (80 women), of unclear methodological quality, showed an increase in the interval between trial entry and birth (MD 22.90 days, 95% CI 18.03 to 27.77). No difference was shown in any reported measures of major neonatal morbidity (although numbers were small). ORA (atosiban) resulted in less maternal adverse effects requiring cessation of treatment (RR 0.05, 95% CI 0.02 to 0.11; NNTB 6, 95% CI 6 to 6; five studies with 1161 women).
Two studies including (225 women) compared ORA (atosiban) with calcium channel blockers (CCB) (nifedipine only). The studies were considered as having high risk of bias as neither study blinded the intervention and in one study it was not known if allocation was blinded. No difference was shown in birth less than 48 hours after trial entry (average RR 1.09, 95% CI 0.44 to 2.73, random‐effects; two studies, 225 women) and extremely preterm birth (RR 2.14, 95% CI 0.20 to 23.11; one study, 145 women). No data were available for the outcome of perinatal mortality. One small trial (145 women), which did not employ blinding of the intervention, showed an increase in the number of preterm births (before 37 weeks' gestation) (RR 1.56, 95% CI 1.13 to 2.14; NNTH 5, 95% CI 3 to 19), a lower gestational age at birth (MD ‐1.20 weeks, 95% CI ‐2.15 to ‐0.25) and an increase in admission to neonatal intensive care unit (RR 1.70, 95% CI 1.17 to 2.47; NNTH 5, 95% CI 3 to 20). ORA (atosiban) resulted in less maternal adverse effects (RR 0.38, 95% CI 0.21 to 0.68; NNTB 6, 95% CI 5 to 12; two studies, 225 women) but not maternal adverse effects requiring cessation of treatment (RR 0.36, 95% CI 0.01 to 8.62; one study, 145 women). No longer‐term outcome data were included.
Authors' conclusions
This review did not demonstrate superiority of ORA (largely atosiban) as a tocolytic agent compared with placebo, betamimetics or CCB (largely nifedipine) in terms of pregnancy prolongation or neonatal outcomes, although ORA was associated with less maternal adverse effects than treatment with the CCB or betamimetics. The finding of an increase in infant deaths and more births before completion of 28 weeks of gestation in one placebo‐controlled study warrants caution. However, the number of women enrolled at very low gestations was small. Due to limitations of small numbers studied and methodological quality, further well‐designed randomised controlled trials are needed. Further comparisons of ORA versus CCB (which has a better side‐effect profile than betamimetics) are needed. Consideration of further placebo‐controlled studies seems warranted. Future studies of tocolytic agents should measure all important short‐ and long‐term outcomes for women and infants, and costs.
CONTEXT:
Current International Liaison Committee on Resuscitation recommendations on epinephrine administration during neonatal resuscitation were derived in 2010 from indirect evidence in animal or ...pediatric studies.
OBJECTIVE:
Systematic review of human infant and relevant animal studies comparing other doses, routes, and intervals of epinephrine administration in neonatal resuscitation with (currently recommended) administration of 0.01 to 0.03 mg/kg doses given intravenously (IV) every 3 to 5 minutes.
DATA SOURCES:
Medline, Embase, Cumulative Index to Nursing and Allied Health Literature, Cochrane Database of Systematic Reviews, and trial registry databases.
STUDY SELECTION:
Predefined criteria were used for selection.
DATA EXTRACTION:
Risk of bias was assessed by using published tools appropriate for the study type. Certainty of evidence was assessed by using Grading of Recommendations Assessment, Development and Evaluation.
RESULTS:
Only 2 of 4 eligible cohort studies among 593 unique retrieved records yielded data allowing comparisons. There were no differences between IV and endotracheal epinephrine for the primary outcome of death at hospital discharge (risk ratio = 1.03 95% confidence interval 0.62 to 1.71) or for failure to achieve return of spontaneous circulation, time to return of spontaneous circulation (1 study; 50 infants), or proportion receiving additional epinephrine (2 studies; 97 infants). There were no differences in outcomes between 2 endotracheal doses (1 study). No human infant studies were found in which authors addressed IV dose or dosing interval.
LIMITATIONS:
The search yielded sparse human evidence of very low certainty (downgraded for serious risk of bias and imprecision).
CONCLUSIONS:
Administration of epinephrine by endotracheal versus IV routes resulted in similar survival and other outcomes. However, in animal studies, researchers continue to suggest benefit of IV administration using currently recommended doses.
To evaluate the safety of an aerosolised surfactant, SF-RI 1, administered via nasal continuous positive airway pressure (nCPAP) and a prototype breath synchronisation device (AeroFact), to preterm ...infants with respiratory distress syndrome (RDS).
Multicentre, open-label, dose-escalation study with historical controls.
Newborn intensive care units at Mater Mothers' Hospital, Brisbane, and Royal Hospital for Women, Sydney, Australia.
Infants 26 weeks through 30 weeks gestation who required nCPAP 6-8 cmH
O and fraction of inspired oxygen (FiO
) <0.30 at <2 hours of age.
In part 1, infants received a single dose of 216 mg/kg of aerosolised surfactant. In part 2, infants could receive up to four doses of aerosolised surfactant. Three historical control infants were matched for each enrolled infant.
Treatment failure was defined as Respiratory Severity Score (FiO
×cmH
O nCPAP) >2.4, nCPAP >8 cmH
O, arterial carbon dioxide >65 mm Hg, pH <7.20 or three severe apnoeas within 6 hours during the first 72 hours of life. Other outcomes included tolerance of the AeroFact treatment and complications of prematurity.
10 infants were enrolled in part 1 and 21 in part 2 and were compared with 93 historical controls. No safety issues were identified. In part 2, 6 of 21 (29%) AeroFact-treated infants compared with 30 of 63 (48%) control infants met failure criteria. Kaplan-Meier analysis of patients in part 2 showed a trend towards decreased rate of study failure in the AeroFact-treated infants compared with historical controls (p=0.10).
The AeroFact system can safely deliver aerosolised surfactant to preterm infants with RDS who are on nCPAP.
ACTRN12617001458325.
Preterm birth and multiple gestation are independently associated with adverse neurodevelopmental outcomes. The objective of this study was to describe risks of screening positive for ...attention-deficit/hyperactivity disorder (ADHD), autism spectrum disorder (ASD), and anxiety in preterm-born twin children by zygosity (monozygotic, dizygotic) and birth order (first-born, second-born).
Caregivers of 349 preterm-born twin pairs (42% monozygotic) aged 3-18 years reported child behavioral outcomes on Strengths and Weaknesses of ADHD Symptoms and Normal Behavior; Social Responsiveness Scale, Second Edition; and Preschool Anxiety Scale or Screen for Child Anxiety and Related Emotional Disorders.
Concordance for behavioral outcomes in twin pairs ranged from 80.06 to 89.31% for ADHD, 61.01 to 84.23% for ASD, and 64.76 to 73.35% for anxiety. Monozygotic twins had a greater risk than dizygotic of screening positive for inattention (risk ratio = 2.91, 95% CI = 1.48-5.72) and social anxiety (1.79, 1.23-2.61). Relative to first-born, second-born twins had a greater risk of screening positive for hyperactivity/impulsivity (1.51, 1.06-2.16); overall ASD (2.38, 1.62-3.49); difficulties with social awareness (2.68, 1.94-3.71), social cognition (4.45, 3.06-6.46), and social communication (2.36, 1.56-3.57); restricted/repetitive behavior (1.91, 1.30-2.81); overall anxiety (1.34, 1.10-1.64); generalized anxiety (1.34, 1.11-1.60); and social anxiety (1.32, 1.06-1.64).
The current findings emphasize considering zygosity and birth order in preterm and multiple birth outcomes research, and highlight clinical implications for discharge planning, neurodevelopmental surveillance, and facilitating parenting and family support.
Zygosity and birth order are important determinants of behavioral and socioemotional outcomes in preterm-born twins. Among 349 preterm-born twin pairs aged 3-18 years (42% monozygotic), 61-89% demonstrated concordance for behavioral and socioemotional outcomes. Monozygosity had greater risks than dizygosity for positive screening of inattention and social anxiety. Second-born twins had greater risks than first-born for hyperactivity/impulsivity, social difficulties (awareness, cognition, communication), restricted/repetitive behavior, and anxiety (generalized, social). These findings have implications for discharge planning, neurodevelopmental surveillance, and facilitating parenting and family support.
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