Impact of antenatal corticosteroids-to-delivery interval on very preterm neonatal outcomes: a retrospective study in two tertiary centers in Japan.

BACKGROUND: Antenatal corticosteroids (ACS) are administered to prevent neonatal complications and death in women at risk of imminent preterm birth. Internationally, the optimal interval from ACS to delivery (ACS-to-delivery interval) is within seven days; however, evidence in Asian populations specifically is limited. This study aimed to investigate the association between ACS-to-delivery interval and the incidence of neonatal complications in Japan. METHODS: This retrospective observational study enrolled singleton neonates born preterm at < 32 weeks of gestational age between 2012 and 2020 at two tertiary centers. A total of 625 neonates were divided into the following four groups according to the timing of ACS (measured in days): no ACS (n = 145), partial ACS (n = 85), ACS 1-7 (n = 307), and ACS ≥ 8 (n = 88). The following outcomes were compared between the groups: treated respiratory distress syndrome (RDS), severe intraventricular hemorrhage (IVH), treated patent ductus arteriosus (PDA), necrotizing enterocolitis, sepsis, bronchopulmonary dysplasia (BPD), treated retinopathy of prematurity (ROP), periventricular leukomalacia, and death discharge. RESULTS: The ACS 1-7 group had significantly decreased adjusted odds ratios (ORs) for treated RDS (0.37 [95% confidence interval: 0.23, 0.57]), severe IVH (0.21 [0.07, 0.63]), treated PDA (0.47 [0.29, 0.75]), and treated ROP (0.50 [0.25, 0.99]) compared with the no ACS group. The ACS ≥ 8 group also showed significantly reduced adjusted ORs for RDS (0.37 [0.20, 0.66]) and treated PDA (0.48 [0.25, 0.91]) compared with the no ACS group. However, the adjusted ORs for BPD significantly increased in both the ACS 1-7 (1.86 [1.06, 3.28]) and ACS ≥ 8 groups (2.94 [1.43, 6.05]) compared to the no ACS group. CONCLUSIONS: An ACS-to-delivery interval of 1-7 days achieved the lowest incidence of several complications in preterm neonates born at < 32 weeks of gestational age. Some of the favorable effects of ACS seem to continue even beyond ≥ 8 days from administration. In contrast, ACS might be associated with an increased incidence of BPD, which was most likely to be prominent in neonates delivered ≥ 8 days after receiving ACS. Based on these findings, the duration of the effect of ACS on neonatal complications should be studied further.

Donor human milk for preventing necrotising enterocolitis in very preterm or very low-birthweight infants.

BACKGROUND: When sufficient maternal milk is not available, donor human milk or formula are the alternative forms of enteral nutrition for very preterm or very low-birthweight (VLBW) infants. Donor human milk may retain the non-nutritive benefits of maternal milk and has been proposed as a strategy to reduce the risk of necrotising enterocolitis (NEC) and associated mortality and morbidity in very preterm or VLBW infants. OBJECTIVES: To assess the effectiveness of donor human milk compared with formula for preventing NEC and associated morbidity and mortality in very preterm or VLBW infants when sufficient maternal milk is not available. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, the Maternity and Infant Care (MIC) database, and the Cumulative Index to Nursing and Allied Health Literature (CINAHL), from the earliest records to February 2024. We searched clinical trials registries and examined the reference lists of included studies. SELECTION CRITERIA: Randomised or quasi-randomised controlled trials comparing feeding with donor human milk versus formula in very preterm (< 32 weeks' gestation) or VLBW (< 1500 g) infants. DATA COLLECTION AND ANALYSIS: Two review authors evaluated the risk of bias in the trials, extracted data, and synthesised effect estimates using risk ratio, risk difference, and mean difference, with associated 95% confidence intervals. The primary outcomes were NEC, late-onset invasive infection, and all-cause mortality before hospital discharge. The secondary outcomes were growth parameters and neurodevelopment. We used the GRADE approach to assess the certainty of the evidence for our primary outcomes. MAIN RESULTS: Twelve trials with a total of 2296 infants fulfilled the inclusion criteria. Most trials were small (average sample size was 191 infants). All trials were performed in neonatal units in Europe or North America. Five trials were conducted more than 40 years ago; the remaining seven trials were conducted in the year 2000 or later. Some trials had methodological weaknesses, including concerns regarding masking of investigators and selective reporting. Meta-analysis showed that donor human milk reduces the risk of NEC (risk ratio (RR) 0.53, 95% confidence interval (CI) 0.37 to 0.76; I² = 4%; risk difference (RD) -0.03, 95% CI -0.05 to -0.01; 11 trials, 2261 infants; high certainty evidence). Donor human milk probably has little or no effect on late-onset invasive infection (RR 1.12, 0.95 to 1.31; I² = 27%; RD 0.03, 95% CI -0.01 to -0.07; 7 trials, 1611 infants; moderate certainty evidence) or all-cause mortality (RR 1.00, 95% CI 0.76 to 1.31; I² = 0%; RD -0.00, 95% CI -0.02 to 0.02; 9 trials, 2116 infants; moderate certainty evidence). AUTHORS' CONCLUSIONS: The evidence shows that donor human milk reduces the risk of NEC by about half in very preterm or VLBW infants. There is probably little or no effect on late-onset invasive infection or all-cause mortality before hospital discharge.

Lowering platelet-count threshold for transfusion in preterm neonates decreases the number of transfusions without increasing severe hemorrhage events.

Thrombocytopenia is common in preterm neonates and can be associated with hemorrhage. Most platelet transfusions are prophylactic. Previously, higher platelet-count thresholds were recommended for neonates, but this recommendation has been questioned in recent studies. In the PlaNeT2 trial, mortality and serious bleeding were more frequent in neonates with the highest platelet-count threshold than in others. Following this trial, we changed our platelet transfusion practice by lowering the platelet-count threshold for prophylactic transfusion from 50,000 to 25,000/mm3. We conducted a before-after retrospective cohort study to quantify the frequency of platelet transfusions and assess the new protocol by analyzing death and serious hemorrhage events. This retrospective monocentric study included neonates born before 37 weeks of gestation with platelet count < 150,000/mm3 during the 2 years preceding the new platelet transfusion protocol (high prophylactic transfusion threshold, 50,000/mm3) and during the 2 years after the new platelet transfusion protocol (low prophylactic transfusion threshold, 25,000/mm3). The primary outcome was the proportion of neonates receiving at least one platelet transfusion in both groups. We also compared the proportion of deaths and severe hemorrhage events. A total of 707 neonates with thrombocytopenia were identified. In the high-threshold group, 99/360 (27.5%) received at least one platelet transfusion as compared with 56/347 (16.1%) in the low-threshold group (p < 0.001). The groups did not differ in proportion of deaths or severe hemorrhage events. CONCLUSIONS: A reduced platelet-count threshold for transfusion allowed for a significant reduction in the number of platelet transfusions without increasing severe hemorrhage events. WHAT IS KNOWN: • A recent randomized trial suggested that restrictive platelet-count thresholds for platelet transfusion could be beneficial for preterm neonates. WHAT IS NEW: • On lowering the platelet-count threshold for transfusion from 50,000 to 25,000/mm3, the number of transfusions significantly decreased without increasing severe hemorrhage events in a neonatal intensive care unit.

The effect of iron supplementation in preterm infants at different gestational ages.

BACKGROUND: Iron deficiency (ID) is the most prevalent nutritional deficiency disease in preterm infants, significantly affecting their growth and development. For preterm infants to flourish physically and neurologically, timely iron supplementation is essential. The main goals of this study were to determine whether the present iron supplementation regimen results in iron overload in late preterm infants and whether it can meet the growth requirements of early preterm infants for catch-up. METHODS: We conducted a prospective follow-up study on preterm infants at the Department of Child Health, West China Second University Hospital, Sichuan University, from January 1, 2020, to August 31, 2020. In this study, 177 preterm infants were divided into two groups based on gestational age-early preterm infants (gestational age < 34 weeks) and late preterm infants (gestational age ≥ 34 weeks and < 37 weeks)-to compare the incidence of iron deficiency, iron status, and physical growth of preterm infants receiving iron supplements (2-4 mg/kg/d). RESULTS: Iron supplementation considerably reduced the incidence of iron deficiency in preterm infants. The prevalence of iron deficiency in early preterm infants and late preterm infants was 11.3% and 5.1%, respectively, at the corrected gestational age of 3 months; at the corrected gestational age of 6 months, the prevalence was 5.3% and 6.3%, respectively. No preterm infants with iron deficiency were detected in either group at the corrected gestational age of 12 months. Ferritin was substantially lower in early preterm infants (36.87 ± 31.57 ng/ml) than in late preterm infants (65.78 ± 75.76 ng/ml) at the corrected gestational age of 3 months (p < 0.05). A multifactorial regression analysis of factors influencing iron metabolism levels in preterm infants revealed a positive relationship between log10hepcidin, birth weight, and ferritin, with higher birth weights resulting in higher ferritin levels. CONCLUSIONS: Postnatal iron supplementation at 2-4 mg/kg/d in preterm infants significantly decreases the incidence of ID. There were substantial differences in iron levels across preterm infants of varying gestational ages. A tailored iron supplementation plan based on growth, birth weight, and gestational age may be a more suitable route for iron supplementation. Although the current study found that the postnatal iron status of early preterm infants differed from that of late preterm infants, the actual mechanism of action remains unknown, and large-sample, multicenter clinical studies are required to investigate this further.

The Effect of Oral Colostrum Application on the Condition of the Mouth and Incidence of Late-Onset Sepsis Among Premature Infants: A Randomized Controlled Trial.

BACKGROUND: Premature infants have higher risks of infection due to their underdeveloped immune systems and changes to the oral cavity's normal flora colonization. PURPOSE: To assess the effect of oral colostrum application on the condition of the mouth and the incidence of late-onset sepsis (LOS) among premature infants. METHODS: In this randomized controlled trial, 70 newborn premature infants were randomly allocated to colostrum or sterile water groups. The Mouth Care Assessment Tool was used to evaluate the condition of the mouth for 5 days after oral colostrum application. The incidence of LOS was measured using clinical and laboratory indicators from 72 hours after birth until discharge. RESULTS: The condition of the mouth was significantly different on days 4 and 5, demonstrating that the colostrum group had less need for oral care ( P < .001) compared to the control group. There was no significant difference between the 2 groups in clinical symptoms and laboratory values related to LOS ( P > .05). IMPLICATIONS FOR PRACTICE: Oral colostrum application can benefit oral mucosal health and reduce the need for oral care among premature infants. It is also safe alternative oral care for premature infants who cannot breastfeed during the first few days of life. Future research should include infants of different gestational ages and mechanically ventilated infants to assess the effect of oral colostrum application on serum immune factors.

Olfactory stimulation for promoting development and preventing morbidity in preterm infants.

OBJECTIVES: This is a protocol for a Cochrane Review (intervention). The objectives are as follows: To evaluate the benefits and harms of olfactory stimulation with different odorants in the NICU for promoting development and preventing morbidity in preterm infants.

Prevention of NICU Admission Hypothermia in Moderate- and Late-Preterm Infants.

BACKGROUND: Neonatal hypothermia is a common and preventable cause of neonatal morbidity and mortality. Although hypothermia prevention has been extensively studied in infants <32 weeks' gestation, the authors of few studies have targeted moderate- and late-preterm infants (MLPIs) in the delivery room. METHODS: This quality improvement initiative was conducted from June 2019 to June 2023 at the Massachusetts General Hospital NICU and Labor and Delivery Unit. All inborn MLPIs 32 + 0/7 to 36 + 6/7 weeks' gestation admitted to the NICU were included. We expanded thermoregulatory measures typically used in protocols for infants <32 weeks' gestation, including increasing delivery room ambient temperature to 74°F and thermal mattress use. The primary outcome was hypothermia (<36.5°C) after NICU admission. The balancing measure was hyperthermia (≥38 °C). RESULTS: During the study period, there were 566 inborn MLPIs with a mean gestational age of 34 + 3/7 weeks and a mean birth weight of 2269 g. Special cause variation in neonatal hypothermia incidence was observed with a decrease from a mean baseline of 27% to 7.8% postintervention. Special cause variation was observed in hyperthermia incidence, with an increase from 1.4% to 6.2% postintervention largely initially associated with noncompliance with the protocol for thermal mattress removal. CONCLUSIONS: The expansion of several thermoregulation techniques commonly used in infants <32 weeks' gestation, particularly thermal mattress use, was associated with a decreased incidence of NICU admission hypothermia in MLPIs, with an increase in mild hyperthermia predominantly associated with concomitant polyethylene wrap use.

Selection of a probiotic to prevent necrotizing enterocolitis for preterm infants in a French neonatology department.

Very premature and/or low-birth-weight infants are at risk of developing necrotizing ulcerative enterocolitis (NEC). Prophylactic use of probiotics would change the composition of the gut microbiota and thus reduce the risk of NEC. In order to choose a probiotic at the local level, international recommendations were compared, and the available specialties were listed. Discrepancies between the different recommendations appeared, and the great variability of infant specialties available, as well as their status, did not allow us to select one. The local objective will therefore be to participate in the discussion of this subject at a national level.

Quality Improvement Interventions to Prevent Intraventricular Hemorrhage: A Systematic Review.

OBJECTIVES: Quality improvement may reduce the incidence and severity of intraventricular hemorrhage in preterm infants. We evaluated quality improvement interventions (QIIs) that sought to prevent or reduce the severity of intraventricular hemorrhage. METHODS: PubMed, CINAHL, Embase, and citations of selected articles were searched. QIIs that had reducing incidence or severity of intraventricular hemorrhage in preterm infants as the primary outcome. Paired reviewers independently extracted data from selected studies. RESULTS: Eighteen quality improvement interventions involving 5906 infants were included. Clinical interventions in antenatal care, the delivery room, and the NICU were used in the QIIs. Four of 10 QIIs reporting data on intraventricular hemorrhage (IVH) and 9 of 14 QIIs reporting data on severe IVH saw improvements. The median Quality Improvement Minimum Quality Criteria Set score was 11 of 16. Clinical intervention heterogeneity and incomplete information on quality improvement methods challenged the identification of the main reason for the observed changes. Publication bias may result in the inclusion of more favorable findings. CONCLUSIONS: QIIs demonstrated reductions in the incidence and severity of intraventricular hemorrhage in preterm infants in some but not all settings. Which specific interventions and quality improvement methods were responsible for those reductions and why they were successful in some settings but not others are not clear. This systematic review can assist teams in identifying potentially better practices for reducing IVH, but improvements in reporting and assessing QIIs are needed if systematic reviews are to realize their potential for guiding evidence-based practice.

Infection in preterm infants receiving topical emollient oil massage: a systematic review and meta-analysis of randomised control trials.

BACKGROUND: Preterm infants are highly susceptible to infections, which significantly contribute to morbidity and mortality. This systematic review and meta-analysis investigated the effectiveness of topical emollient oil application in preventing infections among preterm infants. METHODS: A comprehensive search was conducted across multiple electronic databases (PubMed, Cochrane, Scopus, Clinical trials, Epistemonikos, HINARI and Global Index Medicus) and other sources. A total of 2185 articles were identified and screened for eligibility. The quality of included studies was assessed using the Cochrane Risk of Bias Tool for randomised controlled trials. Data analysis was performed using StataCrop MP V.17 software. Heterogeneity among the studies was evaluated using the I2 and Cochrane Q test statistics. Sensitivity and subgroup analyses were conducted. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses checklist guided the presentation of the results. RESULTS: Of 2185 retrieved articles from initial searches, 11 met eligibility criteria and were included in the final analysis. A random effects meta-analysis revealed that infants who received massages with emollient oils had a 21% reduced risk of infection (risk ratio=0.79, 95% CI 0.64 to 0.97, I2=0.00%). Subgroup analyses indicated that preterm babies who received topical emollient oil massages with coconut oil, administered twice a day for more than 2 weeks, had a lower likelihood of acquiring an infection compared with their non-massaged counterparts. CONCLUSION: It is quite evident from this analysis that topical emollient oil application in preterm neonates is most likely effective in preventing infection. However, further studies, particularly from the African continent, are warranted to support universal recommendations.

Evidence on the benefits of probiotics for preterm infants.

Introduction: This article reviews the evidence for the use of different strains of probiotics in the prevention of prevalent pathologies in premature neonates. A systematic review was conducted of the use of probiotics in neonates with less than 37 weeks of gestational age, based on a search for systematic reviews and observational and experimental studies performed during the period from January 2014 to February 2021. For this purpose, the PubMed, MEDLINE and Cochrane Library databases were consulted. The aim of this article was to review the existing data on the relationship between the administration of probiotics (with different strains and doses) and the risk of necrotising enterocolitis, mortality, late sepsis and other disease parameters in premature infants. The literature search obtained 240 articles, of which we selected 16, representing a total sample of over 200,000 premature infants. Analysis of the data obtained reveals statistical evidence that the combined administration of probiotics (especially of Lactobacillus and Bifidobacterium strains) reduces the incidence of grade II or higher necrotising enterocolitis, all-cause mortality, late sepsis, length of hospital stay and time until complete enteral nutrition is achieved. However, no benefits were apparent with respect to alleviating bronchopulmonary dysplasia, retinopathy of prematurity or intraventricular haemorrhage. Further research is needed to determine the most appropriate strains, doses and treatment duration for preterm infants to achieve the health benefits identified.

Introducción: En este artículo se revisa la evidencia del uso de las diferentes cepas de probióticos en la prevención de diversas patologías prevalentes en recién nacidos prematuros. Se ha realizado una revisión sistemática sobre el uso de probióticos en recién nacidos de menos de 37 semanas de edad gestacional, realizando una búsqueda de revisiones sistemáticas, estudios observacionales y experimentales desde enero de 2014 hasta febrero de 2021. Para ello se han utlizado motores de búsqueda como PubMed, MEDLINE y la biblioteca Cochrane. El objetivo de este artículo fue revisar los datos existentes sobre la relación entre la administración de probióticos (con diferentes cepas y dosis) y el riesgo de enterocolitis necrotizante, mortalidad, sepsis tardía, y otros parámetros de enfermedad en prematuros. En la búsqueda se obtuvieron 240 artículos, de los que seleccionamos 16, obteniendo más de 200.000 recién nacidos prematuros como muestra. En esta revisión se muestra con evidencia estadística, que la administración combinada de probióticos (espcialmente cepas de Lactobacillus y Bifidobacterium) reducen la incidencia de NEC en grado II o mayor, mortalidad por todas las causas, sepsis tardía, días de estancia hospitalaria y tiempo en lograr nutrición enteral completa. No se han podido evidenciar beneficios en cuanto a la displasia broncopulmonar, retinopatía de la prematuridad y hemorragia intraventricular. Se precisan nuevos estudios para conocer las cepas, dosis y tiempo de tratamiento más adecuados en neonatos prematuros para lograr beneficios en salud.

Exclusive Human Milk Diets and the Reduction of Necrotizing Enterocolitis.

BACKGROUND: Necrotizing enterocolitis (NEC) is common in preterm infants, especially infants less than 32 weeks gestation. Mortality from NEC is 7% and occurs in 1 out of 1000 preterm infants. Studies have shown the efficacy of an exclusive milk from mother diet in decreasing rates of NEC and associated mortality. PURPOSE: To evaluate the effectiveness of an existing exclusive human milk diet (EHMD) protocol on the incidence of NEC in extremely premature infants. EHMD, for the purposes of this project is defined as breast milk of mother, with or without human milk-based fortifier. METHODS: A single-center retrospective quasi-experimental study. The sample included 201 infants born less than 32 weeks gestation, weighing less than 1250 grams, small for gestational age (SGA) and with low Apgar scores. Outcomes measured included incidences of NEC, mortality, and co-morbidities in infants pre- and postinitiation of an EHMD protocol. RESULTS: Just 4.8% of the EHMD group had a NEC diagnosis compared to 10.5% of the bovine-based (BOV) group. There was a 1% mortality rate of the EHMD group as compared to 6% in the BOV group. The EHMD group had a statistically significant greater weight gain during hospitalization as compared to infants fed BOV ( P = < .05). IMPLICATIONS FOR PRACTICE AND RESEARCH: Neonatal intensive care units should consider EHMDs for use in this infant population. Future research is needed to support dissemination of the use of EHMD as standard of practice.

Strategies for cessation of caffeine administration in preterm infants.

BACKGROUND: Apnea and intermittent hypoxemia (IH) are common developmental disorders in infants born earlier than 37 weeks' gestation. Caffeine administration has been shown to lower the incidence of these disorders in preterm infants. Cessation of caffeine treatment is based on different post-menstrual ages (PMA) and resolution of symptoms. There is uncertainty about the best timing for caffeine discontinuation. OBJECTIVES: To evaluate the effects of early versus late discontinuation of caffeine administration in preterm infants. SEARCH METHODS: We searched CENTRAL, PubMed, Embase, and three trial registries in August 2023; we applied no date limits. We checked the references of included studies and related systematic reviews. SELECTION CRITERIA: We included randomized controlled trials (RCTs) in preterm infants born earlier than 37 weeks' gestation, up to a PMA of 44 weeks and 0 days, who received caffeine for any indication for at least seven days. We compared three different strategies for caffeine cessation: 1. at different PMAs, 2. before or after five days without symptoms, and 3. at a predetermined PMA versus at the resolution of symptoms. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methods. Primary outcomes were: restarting caffeine therapy, intubation within one week of treatment discontinuation, and the need for non-invasive respiratory support within one week of treatment discontinuation. Secondary outcomes were: number of episodes of apnea in the seven days after treatment discontinuation, number of infants with at least one episode of apnea in the seven days after treatment discontinuation, number of episodes of intermittent hypoxemia (IH) within seven days of treatment discontinuation, number of infants with at least one episode of IH in the seven days after of treatment discontinuation, all-cause mortality prior to hospital discharge, major neurodevelopmental disability, number of days of respiratory support after treatment discontinuation, duration of hospital stay, and cost of neonatal care. We used GRADE to assess the certainty of evidence for each outcome. MAIN RESULTS: We included three RCTs (392 preterm infants). Discontinuation of caffeine at PMA less than 35 weeks' gestation versus PMA equal to or longer than 35 weeks' gestation This comparison included one single completed RCT with 98 premature infants with a gestational age between 25 + 0 and 32 + 0 weeks at birth. All infants had discontinued caffeine treatment for five days at randomization. The infants received either an oral loading dose of caffeine citrate (20 mg/kg) at randomization followed by oral maintenance dosage (6 mg/kg/day) until 40 weeks PMA, or usual care (controls), during which caffeine was stopped before 37 weeks PMA. Early cessation of caffeine administration in preterm infants at PMA less than 35 weeks' gestation may result in an increase in the number of IH episodes in the seven days after discontinuation of treatment, compared to prolonged caffeine treatment beyond 35 weeks' gestation (mean difference [MD] 4.80, 95% confidence interval [CI] 2.21 to 7.39; 1 RCT, 98 infants; low-certainty evidence). Early cessation may result in little to no difference in all-cause mortality prior to hospital discharge compared to late discontinuation after 35 weeks PMA (risk ratio [RR] not estimable; 98 infants; low-certainty evidence). No data were available for the following outcomes: restarting caffeine therapy, intubation within one week of treatment discontinuation, need for non-invasive respiratory support within one week of treatment discontinuation, number of episodes of apnea, number of infants with at least one episode of apnea in the seven days after discontinuation of treatment, or number of infants with at least one episode of IH in the seven days after discontinuation of treatment. Discontinuation based on PMA versus resolution of symptoms This comparison included two RCTs with a total of 294 preterm infants. Discontinuing caffeine at the resolution of symptoms compared to discontinuing treatment at a predetermined PMA may result in little to no difference in all-cause mortality prior to hospital discharge (RR 1.00, 95% CI 0.14 to 7.03; 2 studies, 294 participants; low-certainty evidence), or in the number of infants with at least one episode of apnea within the seven days after discontinuing treatment (RR 0.60, 95% CI 0.31 to 1.18; 2 studies; 294 infants; low-certainty evidence). Discontinuing caffeine based on the resolution of symptoms probably results in more infants with IH in the seven days after discontinuation of treatment (RR 0.38, 95% CI 0.20 to 0.75; 1 study; 174 participants; moderate-certainty evidence). No data were available for the following outcomes: restarting caffeine therapy, intubation within one week of treatment discontinuation, need for non-invasive respiratory support within one week of treatment discontinuation, or number of episodes of IH in the seven days after treatment discontinuation. Adverse effects In the Rhein 2014 study, five of the infants randomized to caffeine had the caffeine treatment discontinued at the discretion of the clinical team, because of tachycardia. The Pradhap 2023 study reported adverse events, including recurrence of apnea of prematurity (15% in the short and 13% in the regular course caffeine therapy group), varying severities of bronchopulmonary dysplasia, hyperglycemia, extrauterine growth restriction, retinopathy of prematurity requiring laser treatment, feeding intolerance, osteopenia, and tachycardia, with no significant differences between the groups. The Prakash 2021 study reported that adverse effects of caffeine therapy for apnea of prematurity included tachycardia, feeding intolerance, and potential neurodevelopmental impacts, though most were mild and transient. We identified three ongoing studies. AUTHORS' CONCLUSIONS: There may be little or no difference in the incidence of all-cause mortality and apnea in infants who were randomized to later discontinuation of caffeine treatment. However, the number of infants with at least one episode of IH was probably reduced with later cessation. No data were found to evaluate the benefits and harms of later caffeine discontinuation for: restarting caffeine therapy, intubation within one week of treatment discontinuation, or need for non-invasive respiratory support within one week of treatment discontinuation. Further studies are needed to evaluate the short-term and long-term effects of different caffeine cessation strategies in premature infants.

Effects of vanilla odor on hypoxia-related periodic breathing in premature newborns: A pilot study.

BACKGROUND: Periodic breathing (PB)-related intermittent hypoxia can have long-lasting deleterious consequences in preterm infants. Olfactory stimulation using vanilla odor is beneficial for apnea of prematurity in the first postnatal days/weeks. We aimed to determine for the first time whether vanilla odor can also decrease PB-related intermittent hypoxia. METHOD: This pilot study was a balanced crossover clinical trial including 27 premature infants born between 30 and 33+6 weeks of gestation. We performed 12-h recordings on two nights separated by a 24-h period. All infants were randomly exposed to vanilla odor on the first or second study night. The primary outcome was the desaturation index, defined as the number per hour of pulse oximetry (SpO2) values <90 % for at least 5 s, together with a drop of ≥5 % from the preceding value. Univariate mixed linear models were used for the statistical analysis. RESULTS: Overall, exposure to vanilla odor did not significantly decrease the desaturation index (52 ± 22 events/h [mean ± SD] on the intervention night vs. 57 ± 26, p = 0.2); furthermore, it did not significantly alter any secondary outcome. In a preliminary post hoc subgroup analysis, however, the effect of vanilla odor was statistically significant in infants with a desaturation index of ≥70/h (from 86 ± 12 to 65 ± 23, p = 0.04). CONCLUSION: In this pilot study, vanilla odor overall did not decrease PB-related intermittent hypoxia in infants born at 30-33+6 weeks of gestation, which is when they are close to term. Preliminary results suggesting a beneficial effect in infants with the highest desaturation index, however, justify further studies in the presence of PB-related intermittent hypoxia as well as in infants born more prematurely.

Association of different doses of antenatal corticosteroids exposure with early major outcomes and early weight loss percentage in extremely preterm infants or extremely low birthweight infants: a multicentre cohort study.

OBJECTIVES: To determine the dose-dependent associations between antenatal corticosteroids (ANS) exposure and the rates of major morbidities, and the early weight loss percentage (EWLP) in hospital among extremely preterm infants (EPI) or extremely low birthweight infants (ELBWI). METHODS: A multicentre, retrospective cohort study of EPI or ELBWI born between 2017 and 2018 was conducted. Infants were classified into no ANS, partial ANS and complete ANS exposure group; three subgroups were generated by gestational age and birth weight. Multiple logistic regression and multiple linear regression were performed. RESULTS: There were 725 infants included from 32 centres. Among no ANS, partial ANS and complete ANS exposure, there were significant differences in the proportions of bronchopulmonary dysplasia (BPD) (24.5%, 25.4% and 16.1%), necrotising enterocolitis (NEC) (6.7%, 2.0% and 2.0%) and death (29.6%, 18.5% and 13.5%), and insignificant differences in the proportions of intraventricular haemorrhage (IVH) (12.5%, 13.2% and 12.2%), and extrauterine growth restriction (EUGR) (50.0%, 56.6% and 59.5%). In the logistic regression, compared with no ANS exposure, complete ANS reduced the risk of BPD (OR 0.58, 95% CI 0.37 to 0.91), NEC (OR 0.21, 95% CI 0.08 to 0.57) and death (OR 0.36, 95% CI 0.23 to 0.56), and partial ANS reduced the risk of NEC (OR 0.23, 95% CI 0.07 to 0.72) and death (OR 0.54, 95% CI 0.34 to 0.87). Compared with partial ANS exposure, complete ANS decreased the risk of BPD (OR 0.58, 95% CI 0.37 to 0.91). There were insignificant associations between ANS exposure and IVH, EUGR. In the multiple linear regression, partial and complete ANS exposure increased EWLP only in the ≥28 weeks (w) and <1000 g subgroup (p<0.05). CONCLUSIONS: Different doses of ANS (dexamethasone) exposure were protectively associated with BPD, NEC, death in hospital, but not EUGR at discharge among EPI or ELBWI. Beneficial dose-dependent associations between ANS (dexamethasone) exposure and BPD existed. ANS exposure increased EWLP only in the ≥28 w and<1000 g subgroup. ANS administration, especially complete ANS, is encouraged before preterm birth. TRIAL REGISTRATION NUMBER: NCT06082414.

[Prevention of prematurity's complications]. / Prévention des complications de la prématurité.

Prematurity remains a leading cause of mortality and morbidity in neonates and children. Prevention of preterm birth and of its complications is a major public health issue. From before conception to long term follow up, many health actors are engaged in this preventive strategy with the same goal : to give the best quality of life for these vulnerable young patients. We will review different preventive aspects during antenatal and perinatal period, during NICU (Neonatal Intensive Care Unit) stay and after discharge. Prevention of prematurity's complications requires a global approach including respiratory, nutritional and infectious aspects among others. Neuroprotective strategies are a key point of this global approach.

La prématurité reste une cause majeure de mortalité et morbidité néonatales et infantiles. La prévention des naissances prématurées et de leurs complications est donc un enjeu majeur de santé publique. De la période pré-conceptionnelle au suivi à long terme de ces enfants, nombreux sont les acteurs impliqués dans un même objectif : offrir la meilleure qualité de vie à ces jeunes patients vulnérables. Nous reverrons ici différents aspects préventifs en période anténatale, périnatale, lors du séjour en néonatologie et lors du suivi après la sortie. La prévention des complications de la prématurité nécessite une prise en charge globale intégrée incluant, notamment, des aspects ventilatoires, nutritionnels, infectieux, néphrologiques et métaboliques. La neuroprotection est au centre des préoccupations et guide l'ensemble de l'approche.

No differences were observed in the prevention of necrotizing enterocolitis and late-onset sepsis among preterm infants who received either single-species or multi-species probiotics.

BACKGROUND: Probiotic prophylaxis has been suggested to reduce the incidence of necrotizing enterocolitis (NEC) and late-onset sepsis (LOS) in very preterm newborns. However, choosing the optimal probiotic is difficult due to variations in strain-specific effects and interactions facilitated by the use of combination species. AIMS: To compare clinical outcomes of very preterm infants receiving multi or single-species probiotics. STUDY DESIGN: Retrospective, single-center, cohort study. SUBJECTS: Very preterm infants (<32 weeks' gestation) born between 2019 and 2022 at a tertiary perinatal center received either a multi-species (Lactobacillus rhamnosus 45 %, Lactobacillus casei 15 %, Lactobacillus acidophilus 15 %, Bifidobacterium infantis 15 %, Bifidobacterium bifidum 10 %; n = 228) or a single-species (Bifidobacterium breve BR03 and B632; n = 227) probiotic formulation. MAIN OUTCOME MEASURES: NEC, LOS, and mortality. RESULTS: The overall incidence of NEC and LOS was 3.1 % and 13.8 %, respectively. There were no differences between the multi-species and single-species probiotic groups in the rate of NEC (3.5 % vs 2.6 %; p = 0.787), LOS (15.4 % vs 12.3 %; p = 0.416), mortality (0.9 % vs 1.8 %; p = 0.449), or composite outcome (NEC, LOS and/or death; 16.7 % vs 12.8 %; p = 0.290). CONCLUSION: The clinical outcomes of very preterm newborns receiving multi vs. single-species probiotic formulations were similar in our study. In view of the sample size and low baseline rate of NEC in our unit, further trials are warranted to investigate the effects of specific probiotics for prevention of serious neonatal morbidities.