OBJECTIVE: 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.

This study aimed to evaluate the incidence and risk factors associated with refeeding syndrome (RFS) in preterm infants (≤32 weeks gestational age) during their first week of life. Infants (gestational age ≤ 32 weeks; birth weight < 1500 g) who were admitted to the neonatal intensive care unit (NICU), level III, and received parenteral nutrition between January 2015 and April 2024 were retrospectively evaluated. Modified log-Poisson regression with generalized linear models and a robust variance estimator was applied to adjust the relative risk of risk factors. Of the 760 infants identified, 289 (38%) developed RFS. In the multivariable regression analysis, male, intraventricular hemorrhage (IVH), and sodium phosphate significantly affected RFS. Male infants had significantly increased RFS risk (aRR1.31; 95% CI 1.08-1.59). The RFS risk was significantly higher in infants with IVH (aRR 1.71; 95% CI 1.27-2.13). However, infants who received higher sodium phosphate in their first week of life had significantly lower RFS risk (aRR 0.67; 95% 0.47-0.98). This study revealed a notable incidence of RFS among preterm infants aged ≤32 gestational weeks, with sex, IVH, and low sodium phosphate as significant risk factors. Refined RFS diagnostic criteria and targeted interventions are needed for optimal management.

Preterm infants, especially those of lower gestational age (GA), are at high risk of hospital readmission in the early years.
OBJECTIVE: To describe the frequency and characteristics of readmissions in preterm infants younger than 32 weeks of GA or weighing less than 1500 g (< 32w/< 1500 g) at 2 years post-discharge from neonatology.
METHODS: Retrospective observational study of a cohort of newborns < 32w/< 1500 g discharged from a public health care center (2009-2017). The frequency, time of occurrence, risk factors, causes, and severity of hospital readmissions were analyzed. The respective perinatal characteristics and subsequent readmissions were described. The Ethics Committee approved the data collection protocol.
RESULTS: 989 newborns < 32w/< 1500 g were included; 410 (41.5%) were readmitted at least once before the age of 2 years, equivalent to 686 episodes (1.7/child); 129 children (31.4%) were admitted to the Pediatric Intensive Care Unit (PICU), with a mean length of stay of 7.7 days. The greatest risk for hospital readmission was during the first 6 months post-discharge. The main cause was respiratory (70%) and respiratory syncytial virus was the most frequent germ. The risk factors associated with readmission due to respiratory causes were bronchopulmonary dysplasia (BPD) (OR: 1.73; 95%CI: 1.26-2.37) and number of siblings (OR: 1.18; 95%CI: 1.04-1.33).
CONCLUSIONS: Newborns < 32s/< 1500 g are at high risk of hospital readmission due to respiratory causes and PICU admission in the first months post-discharge; BPD and number of siblings were the main risk factors.

Some systemic inflammatory indices have been reported to be associated with intracerebral hemorrhage in adults. However, the relationship between systemic inflammatory indices and intraventricular hemorrhage (IVH) in premature neonates is still not completely understood.
OBJECTIVE: To evaluate the relationship between systemic inflammatory indices obtained on the first day of life in premature infants and the development of severe IVH.
METHODS: Premature newborns < 32 weeks of gestational age were included. Eligible patients were divided into 2 groups: Group 1: without IVH or grade I and II hemorrhage, and Group 2: grade III and IV HIV. Demographic characteristics, clinical outcomes, monocyte-to-lymphocyte ratio (MLR), neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), systemic immune inflammation index (SII), pan-immune inflammation value (PIV), and Systemic inflammation response index (SIRI) were compared between groups.
RESULTS: A total of 1176 newborns were included in the study, 1074 in Group 1 and 102 premature babies in Group 2. There was no difference between the groups in terms of the count of leukocytes, neutrophils, monocytes, lymphocytes and platelets (p > 0.05). The values of NLR, MLR, PLR, PIV, SII and SIRI were similar in both groups (p > 0.05).
CONCLUSIONS: While the relationship between inflammation, hemodynamics and IVH is still under discussion, our results show that systemic inflammatory indices have no predictive value for IVH.

暂无摘要。

BACKGROUND: Hypothermia is an important cause of morbidity and mortality among preterm and low-birth-weight neonates. In resource-constrained settings, limited referral infrastructure and technologies for temperature control potentiate preterm hypothermia. While there is some documentation on point-of-admission hypothermia from single center studies, there are limited multicenter studies on the occurrence of hypothermia among preterm infants in resource-limited-settings. Therefore, we conducted a multicenter study to determine the prevalence and risk factors for hypothermia at the time of admission and during the first 72 h after admission in northern Nigeria.
METHODS: We carried out a prospective cohort study on preterm infants admitted to four referral hospitals in northern Nigerian between August 2020 and July 2021. We documented temperature measurements at admission and the lowest and highest temperatures in the first 72 h after admission. We also collected individual baby-level data on sociodemographic and perinatal history data. We used the World Health Organization classification of hypothermia to classify the babies\' temperatures into mild, moderate, and severe hypothermia. Poisson regression analysis was used to identify risk factors for moderate-severe hypothermia.
RESULTS: Of the 933 preterm infants enrolled, 682 (72.9%) had hypothermia at admission although the prevalence of hypothermia varied across the four hospitals. During the first 24 h after admission, 7 out of every 10 babies developed hypothermia. By 72 h after admission, between 10 and 40% of preterm infants across the 4 hospitals had at least one episode of moderate hypothermia. Gestational age (OR = 0.86; CI = 0.82-0.91), birth weight (OR = 8.11; CI = 2.87-22.91), presence of a skilled birth attendant at delivery (OR = 0.53; CI = 0.29-0.95), place of delivery (OR = 1.94 CI = 1.13-3.33) and resuscitation at birth (OR = 1.79; CI = 1.27-2.53) were significant risk factors associated with hypothermia.
CONCLUSIONS: The prevalence of admission hypothermia in preterm infants is high and hypothermia is associated with low-birth-weight, place of delivery and presence of skilled birth attendant. The prevalence of hypothermia while in care is also high and this has important implications for patient safety and quality of patient care. Referral services for preterm infants need to be developed while hospitals need to be better equipped to maintain the temperatures of admitted small and sick newborns.

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.
OBJECTIVE: To evaluate the effects of early versus late discontinuation of caffeine administration in preterm infants.
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.
METHODS: 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.
METHODS: 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.
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.
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.

BACKGROUND: Intestinal obstruction secondary to the use of fortified milk is a rare cause in pre-term patients.
METHODS: We present the case of a female pre-term newborn admitted as a result of abdominal distension and rectal bleeding, which mimicked necrotizing enterocolitis. On abdominal X-ray, she had an obstruction pattern, and on ultrasonography, echogenic masses at the distal ileum were observed. Given the lack of improvement with conservative management, urgent exploratory laparotomy was decided upon. At surgery, compact milk masses at the level of the distal ileum were identified as the cause of intestinal obstruction. Appendicostomy and lavage with saline solution through the ileocecal valve were performed. This allowed milk masses to come out towards the colon, and a great amount of acholic stools to be expelled.
CONCLUSIONS: The increase in \"milk curd syndrome\" cases should lead us to consider this cause in the differential diagnosis of intestinal obstruction in pre-term newborns fed with fortified milk.
BACKGROUND: La obstrucción intestinal secundaria al uso de leche fortificada es una causa infrecuente descrita en pacientes prematuros.
METHODS: Presentamos el caso de una recién nacida prematura que ingresa por distensión abdominal y rectorragia, simulando una enterocolitis necrotizante. En la radiografía abdominal presenta patrón obstructivo y en ecografía se identifican masas ecogénicas en íleon distal. Dada la no mejoría con manejo conservador, se decide laparotomía exploradora urgente. En la intervención se detectan masas compactas de leche a nivel de íleon distal como causa de la obstrucción intestinal. Se realiza apendicostomía y lavado con suero fisiológico a través de la válvula ileocecal, permitiendo salida de moldes hacia colon y expulsión de gran cantidad de heces acólicas.
CONCLUSIONS: El repunte de casos de “milk curd syndrome” nos obliga a considerar esta causa en el diagnóstico diferencial de obstrucción intestinal en prematuros alimentados con leche fortificada.

BACKGROUND: Pulmonary vascular disease (PVD) and pulmonary hypertension (PH) is a significant disorder affecting prognosis of extremely preterm infants. However, there is still a lack of a consensus on the definition and optimal treatments of PH, and there is also a lack of research comparing these conditions with persistent pulmonary hypertension of newborn (PPHN), early PH, and late PH. To investigate PH in extremely preterm infants, this study compared the baseline characteristics, short-term outcomes, and treatment duration, categorized by the timing of requiring PH treatment.
METHODS: This study retrospectively analyzed extremely preterm infants admitted to a single tertiary center. Between 2018 and 2022, infants with clinical or echocardiographic diagnosis of PH who required treatment were divided into three groups based on the timing of treatment initiation: initial 3 days (extremely early-period), from day 4 to day 27 (early-period), and after day 28 (late-period). The study compared the outcomes, including mortality rates, bronchopulmonary dysplasia (BPD) severity, PH treatment duration, and oxygen therapy duration, among the three groups.
RESULTS: Among the 157 infants, 67 (42.7%) were treated for PH during their stay. Of these, 39 (57.3%) were treatment in extremely early, 21 (31.3%) in early, and seven (11.4%) in late periods. No significant differences were observed in maternal factors, neonatal factors, or morbidity between the three groups. However, infants who received extremely early-period treatment had a higher mortality rate, but shorter duration of noninvasive respiratory support, oxygen therapy, and PH medication use. On the other hand, the late-period treatment group received longer durations of respiratory support and treatment.
CONCLUSIONS: This study revealed differences in mortality rates, respiratory outcomes, and treatment duration between the three groups, suggesting varying pathophysiologies over time in extremely preterm infants.

BACKGROUND: Necrotizing enterocolitis (NEC) is a life-threatening disease that affects premature infants. However, the role of inflammatory biomarkers in identifying surgical/death NEC without pneumoperitoneum remains elusive.
OBJECTIVE: We aimed to verify the value of platelet-to-lymphocyte ratio (PLR) and the combination of white blood cell (WBC), absolute neutrophil count (ANC), absolute lymphocyte count (ALC), neutrophil lymphocyte ratio (NLR), PLR, C reactive protein (CRP) and procalcitonin (PCT) in predicting the severity of NEC, and to construct a model to differ surgically NEC from non-surgically NEC.
METHODS: A retrospective analysis was performed on 191 premature infants with NEC. Based on the inclusion and exclusion criteria, 90 infants with Stage II and IIIA NEC were enrolled in this study, including surgical/death NEC (n = 38) and medical NEC (n = 52). The values of inflammatory biomarkers were collected within 24 h of onset.
RESULTS: The univariate analysis revealed that the values of WBC (p = 0.040), ANC (p = 0.048), PLR (p = 0.009), CRP (p = 0.016) and PCT (p < 0.01) in surgical/death NEC cohort were significantly higher than medical NEC cohort. Binary multivariate logistic regression analysis indicates that ANC, PLR, CRP, and PCT are capable of distinguishing infants with surgical/death NEC, and the AUC of the regression equation was 0.79 (95% CI 0.64-0.89; sensitivity 0.63; specificity 0.88), suggesting the equation has a good discrimination.
CONCLUSIONS: Elevated PLR is associated with severe inflammation in surgical/death NEC patients. The prediction modelling of combination of ANC, PLR, CRP and PCT can differentiate surgical/death NEC from infants with medical NEC, which may improve risk awareness and facilitate effective communication between nurses and clinicians. However, multicentre research is needed to verify these findings for better clinical management of NEC.