Neonatology最新文献

Introduction: The concept of male disadvantage regarding the prognosis of premature newborns was introduced more than half a century ago, and it has been corroborated over time. However, the influence of the sex of one twin on the outcomes of the other has yielded contradictory results.

Objective: The aim of the study was to determine if, in twin pregnancies of VLBW infants, the outcomes of one twin are modified by the sex of the co-twin.

Methods: A multicentre retrospective study of a cohort of infants admitted to the collaborating units of the Spanish SEN1500 neonatal network was conducted. Liveborn VLBW twin infants, from 23+0 to 31+6 weeks of gestational age (GA), admitted from 2011 to 2020 were included. Outborn patients, infants with major congenital anomalies, and cases with only one twin admitted were excluded. The main outcomes were survival until first hospital discharge, survival without moderate or severe bronchopulmonary dysplasia (BPD), survival without major brain damage (MBD), and survival without major morbidity. Incidence rate ratios (IRR) and 95% confidence intervals (CI) were calculated.

Results: 2,111 twin pairs were included. Male infants exhibited worse outcomes than females (IRR; 95% CI) regarding survival (0.96; 0.94, 0.98), survival without moderate or severe BPD (0.89; 0.86, 0.93), survival without MBD (0.94; 0.91, 0.97), and survival without major morbidity (0.87; 0.81, 0.93). Differences disappeared when the co-twin was a female infant: survival (1.00; 0.97, 1.03), survival without moderate or severe BPD (0.96; 0.91, 1.01), survival without MBD (0.99; 0.95, 1.04), and survival without major morbidity (0.94; 0.85, 1.03). Results for female infants did not change significantly with co-twin sex.

Conclusions: Among VLBW twins from 23+0 to 31+6 weeks of GA, male infants have higher risk of morbidity and mortality overall. In cases of pregnancies with different-sex foetuses, males seem to improve their results, while these do not change for females. The underlying mechanism of this influence deserves further investigation.

Introduction: Preterm birth represents the leading cause of neonatal mortality. Pathophysiological pathways, or endotypes, leading to prematurity can be clustered into infection/inflammation and dysfunctional placentation. We aimed to perform a systematic review and meta-analysis exploring the association between these endotypes and risk of mortality during first hospital admission Methods: PROSPERO ID: CRD42020184843. PubMed and Embase were searched for observational studies examining infants with gestational age (GA) ≤34 weeks. Chorioamnionitis represented the infectious-inflammatory endotype, while dysfunctional placentation proxies were hypertensive disorders of pregnancy (HDP) and small for GA (SGA)/intrauterine growth restriction (IUGR). A random-effects model was used to calculate odds ratios (ORs) and 95% confidence intervals. Heterogeneity was studied using random-effects meta-regression analysis.

Results: Of 4,322 potentially relevant studies, 150 (612,580 infants) were included. Meta-analysis showed positive mortality odds for chorioamnionitis (OR: 1.43, 95% confidence interval: 1.25-1.62) and SGA/IUGR (OR: 1.68, 95% confidence interval: 1.38-2.04) but negative mortality odds for HDP (OR 0.74, 95% confidence interval: 0.64-0.86). Chorioamnionitis was associated with a lower GA, while HDP and SGA/IUGR were associated with a higher GA. Meta-regression showed a significant correlation between these differences in GA and mortality odds.

Conclusion: Our data suggest that the infectious/inflammatory endotype of prematurity has a greater overall impact on mortality risk as it is the most frequent endotype in the lower GAs. However, when the endotype of placental dysfunction is severe enough to induce growth restriction, it is strongly associated with higher mortality rates even though newborns are more mature.

Introduction: Our objective was to evaluate the temporal trend of systemic postnatal steroid (PNS) receipt in infants of 24-28 weeks' gestational age, identify characteristics associated with PNS receipt, and correlate PNS receipt with the incidence of bronchopulmonary dysplasia (BPD) and BPD/death from an international cohort included in the iNeo network.

Methods: We conducted a retrospective study using data from 2010 to 2018 from seven international networks participating in iNeo (Canada, Finland, Israel, Japan, Spain, Sweden, and Switzerland). Neonates of 24 and 28 weeks' gestational age who survived 7 days and who received PNS were included. We assessed temporal trend of rates of systemic PNS receipt and BPD/death.

Results: A total of 47,401 neonates were included. The mean (SD) gestational age was 26.4 (1.3) weeks and birth weight was 915 (238) g. The PNS receipt rate was 21% (12-28% across networks) and increased over the years (18% in 2010 to 26% in 2018; p < 0.01). The BPD rate was 39% (28-44% across networks) and remained unchanged over the years (35.2% in 2010 to 35.0% in 2018). Lower gestation, male sex, small for gestational age status, and presence of persistent ductus arteriosus (PDA) were associated with higher rates of PNS receipt, BPD, and BPD/death.

Conclusion: The use of PNS in extremely preterm neonates increased, but there was no correlation between increased use and the BPD rate. Research is needed to determine the optimal timing, dose, and indication for PNS use in preterm neonates.

Introduction: Interleukin (IL)-33 and its receptor ST2L play key roles in the IL-33/ST2 signaling pathway. Soluble ST2 (sST2) inhibits the proper function of IL-33. sST2 levels are increased in patients with several neurological diseases, but in infants with hypoxic-ischemic encephalopathy (HIE), IL-33 and sST2 levels have not been studied. This study aimed to investigate whether serum levels of IL-33 and sST2 are useful as biomarkers of HIE severity and prognostic factors for infants with HIE.

Methods: Twenty-three infants with HIE and 16 controls (gestational age ≥36 weeks and ≥1,800 g birth weight) were enrolled in this study. Serum levels of IL-33 and sST2 were measured at <6 h, 1-2, 3, and 7 days of age. Hydrogen-1 magnetic resonance spectroscopy was performed, and ratios of peak integrals of lactate/N-acetylaspartate (Lac/NAA) were calculated as objective indicators of brain damage.

Results: In the moderate and severe HIE, serum sST2 concentrations were increased and there was a good correlation between serum sST2 and HIE severity on days 1-2, whereas no variation was observed in serum IL-33. Serum sST2 levels were positively correlated with Lac/NAA ratios (Kendall's rank correlation coefficient = 0.527, p = 0.024), and both sST2 and Lac/NAA ratios were significantly higher in HIE infants with neurological impairment (p = 0.020 and <0.001, respectively).

Conclusions: sST2 may be a useful predictor of severity and later neurological outcomes in infants with HIE. Further investigation is required to elucidate the relationship between the IL-33/ST2 axis and HIE.

Introduction: We evaluate the accuracy of postnatal biochemical and lung function tests performed within 3 h from birth for predicting surfactant need in preterm infants ≤34 weeks' gestation receiving noninvasive respiratory support for respiratory distress syndrome (RDS).

Methods: We systematically searched MEDLINE, Embase, The Cochrane Library, PROSPERO, and clinicaltrials.gov databases for studies published from 2000 to November 10, 2021, cross-referencing relevant literature and contacting experts. We included diagnostic accuracy studies and systematic reviews of biochemical or lung function tests identifying the need for surfactant in preterm neonates ≤34 weeks' with RDS not intubated at birth. The authors individually assessed the risk of bias following a tailored QUADAS-2 tool.

Results: Eight studies, including 810 infants, met the inclusion criteria. Four tests were included: the click test, the stable microbubble test, the lamellar body count on gastric aspirates, and the forced oscillation technique. The reference standards were transparent criteria for distinguishing the infants according to oxygen requirement, which reflected the current criteria for surfactant therapy. The risk of bias was judged high because of the population selection and exclusion of participants from the analysis. There were no serious concerns regarding blinding and applicability. The individual study sensitivity and specificity range from 0.60 to 1 and from 0.51 to 0.91, respectively. It was not appropriate to combine the accuracy estimates in a meta-analysis because of the heterogeneity of the study characteristics.

Conclusions: Current evidence is insufficient to recommend biochemical and lung function tests for tailoring surfactant therapy.

Introduction: Predicting impairment in preterm children is challenging. Our aim is to explore the association between MRI at term-equivalent age (TEA) and neurocognitive outcomes in late childhood and to assess whether the addition of EEG improves prognostication.

Methods: This prospective observational study included forty infants with gestational age 24 + 0-30 + 6. Children were monitored with multichannel EEG for 72 h after birth. Total absolute band power for the delta band on day 2 was calculated. Brain MRI was performed at TEA and scored according to the Kidokoro scoring system. At 10-12 years of age, we evaluated neurocognitive outcomes with Wechsler Intelligence Scale for Children 4th edition, Vineland adaptive behavior scales 2nd edition and Behavior Rating Inventory of Executive Function. We performed linear regression analysis to examine the association between outcomes and MRI and EEG, respectively, and multiple regression analysis to explore the combination of MRI and EEG.

Results: Forty infants were included. There was a significant association between global brain abnormality score and composite outcomes of WISC and Vineland test, but not the BRIEF test. The adjusted R2 was 0.16 and 0.08, respectively. For EEG, adjusted R2 was 0.34 and 0.15, respectively. When combining MRI and EEG data, adjusted R2 changed to 0.36 for WISC and 0.16 for the Vineland test.

Conclusion: There was a small association between TEA MRI and neurocognitive outcomes in late childhood. Adding EEG to the model improved the explained variance. Combining EEG and MRI data did not have any additional benefit over EEG alone.

Background: There is increasing concern that infants with mild hypoxic-ischaemic encephalopathy (HIE) may develop seizures and progress to moderate HIE beyond the therapeutic window for cooling.

Objective: The aim of this study was to examine the effect of therapeutic hypothermia on magnetic resonance imaging (MRI) biomarkers and neurological outcomes in infants with mild HIE and seizures within 24 h after birth.

Methods: This study shows an observational cohort study on 366 (near)-term infants with mild HIE and normal amplitude-integrated electroencephalography background.

Results: Forty-one infants showed progression (11.2%); 29/41 (70.7%) were cooled. Infants with progression showed cerebral metabolite perturbations and higher white matter injury scores compared to those without in both cooled and non-cooled groups (p = 0.001, p = 0.02). Abnormal outcomes were seen in 5/12 (42%) non-cooled and 7/29 (24%) cooled infants with progression (p = 0.26).

Conclusions: Early biomarkers are needed to identify infants with mild HIE at risk of progression. Mild HIE infants with progression showed a higher incidence of brain injury and abnormal outcomes.

Introduction: High-end cutoffs of thyroid-stimulating hormone (TSH) have been emphasized for hypothyroidism therapy in extremely preterm infants, but the significance of low TSH levels remains unknown. This study hypothesized that the spectrum of TSH levels by newborn screening after birth signifies specific morbidities in extremely preterm neonates.

Methods: The multicenter population cohort analyzed 434 extremely preterm neonates receiving TSH screening at 24-96 h of age in 2008-2019. Neonates were categorized by blood TSH levels into group 1: TSH <0.5 µU/mL, group 2: 0.5 ≤ TSH <2 µU/mL, group 3: 2 ≤ TSH <4 µU/mL, and group 4: TSH ≥4 µU/mL. Neonatal morbidities were categorized using the modified Neonatal Therapeutic Intervention Scoring System.

Results: The four groups differed in gestational age, birth weight, and the postnatal age at blood sampling so did the proportions of mechanical ventilation usage (p = 0.01), hypoxic respiratory failure (p = 0.005), high-grade intraventricular hemorrhage (p = 0.007), and periventricular leukomalacia (p = 0.048). Group 1 had higher severity scores for respiratory distress syndrome (RDS; effect size 0.39 [95% confidence interval [CI]: 0.18-0.59]) and brain injury (0.36 [0.15-0.57]) than group 2, which remained significant after adjusting for gestational age, birth weight, dopamine usage, and the postnatal age at TSH screening (RDS: mean + 0.45 points [95% CI: 0.11-0.79]; brain injury: +0.32 [0.11-0.54]).

Conclusions: Low TSH levels in extremely preterm neonates are associated with severe RDS and brain injuries. Studies recruiting more neonates with complete thyroid function data are necessary to understand central-peripheral interactions of the hypothalamic-pituitary-thyroid axis.

Introduction: The partial oxygen pressure in the air decreases with increasing altitude. This study was designed to compare the pulse oxygen saturation (SpO2) among well full-term neonates at different altitudes during their first 2 h after birth and to establish cutoff values of SpO2 identifying hypoxemia between 30 and 120 min after birth.

Methods: A multisite prospective cohort study was conducted at five participating hospitals from the Chinese High Altitude Neonatal Medicine Alliance. Healthy full-term infants were recruited and divided into four groups based on the altitude. Preductal SpO2 was recorded at 10 min, 10-30 min, and 30-120 min after birth. The 2.5th percentile of the SpO2 distribution range was considered as the cutoff for identifying hypoxemia at each altitude.

Results: A total of 727 infants were eligible for analysis. The SpO2 of neonates at different altitudes increased with the time after birth. A higher altitude was associated with lower SpO2, especially Shangri-La (3,509 m) and Yushu (4,360 m). The cutoff SpO2 for identifying hypoxemia during 30-120 min after birth were 94% in Xishuangbanna (847 m), 92% in Kunming (1,983 m), 89% in Shangri-La (3,509 m), and 83% in Yushu (4,360 m).

Conclusion: An increase in altitude, especially Shangri-La (3,509 m) and Yushu (4,360 m), had a significant impact on SpO2 among healthy full-term neonates during their first 2 h of life. Establishing the cutoff value of SpO2 for identifying hypoxemia during the early postnatal period serves to optimize the oxygen therapy at different altitudes.