Shoo Kim Lee

Background: Neonatal meningitis remains an important cause of mortality and health loss. We characterized temporal trends, pathogen distributions, and risk‐attributable burden in China using Global Burden of Disease (GBD) 2023 estimates. Methods: We analyzed GBD‐modeled incidence, mortality, disability‐adjusted life years, years of life lost, and years lived with disability among early (0–6 days) and late (7–27 days) neonates. Trends were assessed using estimated annual percentage change (EAPC) and segmented log‐linear regression. Log‐exponential smoothing (ETS) projected mortality through 2035, with log‐ARIMA as a sensitivity analysis. Pathogen shares and GBD‐estimated risk‐attributable burden were also assessed. Results: From 1990 to 2023, modeled incidence and mortality decreased from 715.7 and 98.0 to 79.0 and 4.5 per 100,000, respectively (EAPC = −7.6% [95% confidence interval {CI} −8.2 to −6.9] and −9.6% [95% CI −9.9 to −9.2]). Early‐neonatal mortality remained higher than late‐neonatal mortality (2023 rate ratio 1.8). Segmented regression identified 1997–2002 as the steepest decline. The 2035 log‐ETS forecasts were 4.3 (95% prediction interval [PI] 0.5–10.4), 5.5 (95% PI 0.6–12.5), and 3.9 (95% PI 0.5–9.7) per 100,000 for overall, early, and late neonates. The cumulative share of pathogen‐attributable mortality for the top five pathogens increased from 58.9% to 62.9%. Low birth weight and short gestation had the largest attributable fraction (47.7% [95% uncertainty interval 44.0%–51.1%]). Conclusions: Despite substantial reductions in burden, persistent early‐neonatal vulnerability and divergent exploratory forecasts underscore the need for clinical surveillance to validate these modeled findings and inform prevention.

Importance: The transition period from the delivery room to the neonatal intensive care unit (NICU) is critical for very preterm infants (VPIs) or very low birth weight (VLBW) infants, yet the association between physiological changes during transition period and early severe outcomes remains inadequately quantified. Objective: To investigate associations between physiological changes during transition period and early severe neonatal outcomes in VPIs or VLBW infants.Design: This cohort study utilized data from Chinese Neonatal Network (CHNN), prospectively collected from January 2019 to December 2023. Setting: National multicenter study.Participants: VPIs or VLBW infants with clear 5-minute APGAR score and the transport risk index of physiologic stability score (TRIPS) were included, and those admitted after the first day, discharged or transferred out within 7 days after birth, were excluded. Exposures: The exposure variable was a composite of the APGAR score and TRIPS. The APGAR score was analyzed as normal (7-10), low (0-6), and optimal (9-10). The TRIPS was grouped as low (0-10), intermediate (11-30), or high (>30). Main Outcome and Measures:The main outcome was a composite of early neonatal death and severe neurological injury (SNI). Adjusted odds ratios (aORs) and 95% confidence intervals (CI) were estimated using generalized estimating equation models. Results: Of the 40391 included VPIs or VLBW infants, the composite outcome occurred in 4753 (11·77%) infants, including 2326 (5·76%) early neonatal deaths and 2680 (6·64%) SNIs. Increased TRIPS was associated with elevated risks of early severe neonatal outcomes across all APGAR categories. In optimal APGAR subgroup, composite outcome incidence per 1000 infants was 52 in low-TRIPS reference group, 100 in intermediate-TRIPS group (aOR: 1·42, 95% CI: 1·12-1·80), and 211 in high-TRIPS group (aOR: 1·80, 95% CI: 1·16-2·80). The initial deterioration (intermediate-TRIPS group) was characterized by high rates of hypothermia (71·6%) and need for invasive respiratory support (37·1%), whereas hypotension was nearly absent in intermediate-TRIPS group and emerged predominantly in high-TRIPS group. Conclusions and Relevance: The quality of management during transition period was associated with early severe neonatal outcomes, thus maintenance of normothermia and effective respiratory support represent initial clinical priorities to mitigate physiological deterioration and improve clinical outcomes.

Newborn eye examination is a painful procedure. Untreated pain experiences in infants have both short-term and long-term consequences, and pain control is essential. Unfortunately, non-pharmacological pain strategies are usually ineffective for complex and protracted procedures, whereas many pharmacologic agents have adverse effects. Magnetic auricular acupuncture (MAA) is a new method of pain relief that is potentially safe and effective. The objective of this study was to conduct a large definitive triple blinded randomized controlled trial of MAA for reducing pain in neonates undergoing ophthalmic examination. The trial was registered at the Chinese Clinical Trial Registry (ID number ChiCTR1900027474) on November 14, 2019. This was a multi-center randomized controlled trial conducted at 16 tertiary hospitals in the People’s Republic of China. Infants were eligible for participation if they were born at 26 to 42 weeks gestational age (GA) and admitted to participating NICUs during the study enrollment period, and scheduled to receive an eye examination for the first time at <44 weeks’ corrected GA. Written informed consent was obtained from parents. Infants who were critically ill, dying or receiving sedatives were excluded. Infants randomized to the intervention (MAA) group received magnetic stickers applied prior to the ophthalmic procedure. Control group infants received placebo stickers with the magnets removed. We compared the primary outcome of Premature Infant Pain Profile (PIPP) score during the procedure between the two groups. A total of 408 patients were randomized, but 14 patients in each of the placebo and intervention groups did not receive ophthalmic examination; leaving 190 patients in control group and 190 in intervention group. Infant characteristics were similar in the two groups, mean PIPP scores during eye exam were significantly lower in the intervention group compared to the control group (median (IQR): 10.00 (5.00,13.00) v 12.00 (7.00,14.00), p = 0.038). MAA may offer an alternative or adjunct to current non-pharmacologic and pharmacologic interventions to alleviate neonatal pain. Future studies should assess combinations of pain interventions and long term outcomes.

Background Previous studies suggest that birth timing may impact the prognosis of extremely premature infants, increasing early mortality and the risk of intensive resuscitation, asphyxia, or sIVH. The aim of this study was to investigate the relationship between birth timing and outcomes of very preterm infants (VPIs) in China. Methods This multicenter retrospective study used CHNN 2019–2021 data on preterm infants born at 24⁰ to 31⁶ weeks’ GA. Exposure included birth timing (daytime, evening, night) on weekdays and non-weekdays. The primary outcome was in-hospital mortality rate. Secondary outcomes included delivery room outcomes and morbidities. Results The study included 17,670 VPIs and found increased mortality during both daytime-evening shifts and night shifts on weekdays, primarily affecting infants born at 24⁰ to 27⁶ weeks’ GA. Among weekday births, evening shifts were associated with 5-minute Apgar scores ≤7 (aOR 1.22, 95% CI 1.07–1.39) and sIVH (aOR 1.30, 95% CI 1.08–1.57), while nighttime shifts were linked to hypothermia (aOR 1.13, 95% CI 1.02–1.24). In infants born at 28⁰ to 29⁶ weeks’ GA, night shifts were associated with intensive resuscitation (aOR 1.23, 95% CI 1.02–1.48), and evening shifts with 5-minute Apgar scores ≤7 (aOR 1.38, 95% CI 1.11–1.71). For infants born at 30⁰ to 31⁶ weeks’ GA, the evening shift significantly increased the risk of sIVH (aOR 1.78, 95% CI 1.27–2.48). Conclusion Mortality increased for infants born during daytime handovers and nighttime, especially at 24⁰ to 27⁶ weeks’ GA. Infants at 28⁰ to 31⁶ weeks’ GA faced higher risks of asphyxia, hypothermia, or sIVH during off-peak hours.

Neonatal vascular air embolism is a rare but often fatal condition. The literature comprises mostly case reports and a few dated systematic reviews. Our objective was to review all case reports of neonatal vascular air embolism to date and provide up-to-date information about patient characteristics, clinical presentations, outcomes, pathogenesis, diagnosis, prevention, treatment, and prognosis. We searched the literature for case reports of neonatal vascular air embolism, using MEDLINE, CINAHL, and EMBASE, and the keywords “neonates” and “vascular air embolism.” Results were summarized. There were 117 cases of neonatal vascular air embolism, with a mean gestational age of 30.4 weeks (range: 23–40), mean birth weight of 1,422 g (range 830–3,844), and median age of occurrence of 2 days (range: 1–540) after birth. The majority were preterm (75.2%), male (62.7%), on assisted respiratory support (90.5%), and had air leak syndrome (52.9%). The most common clinical presentation was sudden acute clinical deterioration, sometimes accompanied by crying, cardiac rhythm abnormalities, skin discoloration, and a decrease in end-tidal carbon dioxide concentration. Incidence of mortality and adverse neurological sequelae among survivors was 73.9 and 16.6%, respectively, overall, but significantly (p < 0.05) higher among preterm infants (81.8 and 31.2%, respectively) and lower among surgical infants (23.8 and 0%, respectively). Diagnosis included visualizing air in infusion lines or retinal vessels, a decrease in the end-tidal carbon dioxide levels, and radiographic, doppler ultrasound, transesophageal echocardiography, or computed tomography (CT) imaging. The prognosis for neonatal air embolism is poor, especially for preterm infants requiring mechanical ventilation. Prevention is key and treatment is supportive.

Early-onset sepsis (EOS) poses a substantial risk to very preterm infants, necessitating the prevalent administration of empirical antibiotics in the neonatal intensive care unit (NICU). Puopolo et al¹ reported that more than one-third of the extremely preterm infants in their study were categorized as low risk for EOS, with an incidence of 0.5%. In these low-risk groups, prolonged empirical antibiotic treatment (≥5 days) was observed in approximately 35% of cases.¹ Recent studies^1-3 have suggested a potential association of prolonged antibiotic therapy with both increased mortality and a higher incidence of adverse neonatal outcomes, including bronchopulmonary dysplasia (BPD), within this vulnerable population. However, these studies often relegated BPD as a secondary outcome, lacking comprehensive consideration of relevant confounding factors. Moreover, the literature has reported inconsistent results in this domain.^4-6 The reported association may be influenced by factors such as culture-proven sepsis bacteremia, illness severity, and early respiratory disease.

The objective of this study was to assess the relationship of ACS with neonatal outcomes among very preterm infants born to mothers with clinical chorioamnionitis in China. This was a multicenter retrospective cohort study. Study participants included infants born at <32 weeks’ gestation with clinical chorioamnionitis and registered in the Chinese Neonatal Network from 1 January 2019 to 31 December 2020. Infants were divided into two groups: any amount of ACS or no administration of ACS. Multivariable generalized linear models using generalized estimating equations were used to assess the association between ACS and neonatal outcomes among the study population. We identified 2193 infants eligible for this study; 1966 (89.6%) infants had received ACS therapy, and 227 (10.4%) had not received any ACS therapy. Among very preterm infants born to mothers with clinical chorioamnionitis, any ACS usage was significantly associated with decreased risks of early death (aRR 0.56, 95% CI 0.32, 0.99) and severe ROP (aRR 0.51, 95% CI 0.28, 0.93) after adjustment for maternal hypertension, gestational age at birth, Caesarean section, being inborn, and administration of systemic antibiotics to the mother within 24 h before birth. In addition, out of the 2193 infants, the placentas of 1931 infants underwent pathological examination with recorded results. Subsequently, 1490 of these cases (77.2%) were diagnosed with histological chorioamnionitis. In 1490 cases of histologic chorioamnionitis, any ACS usage was significantly related to decreased risks of overall mortality (aRR 0.52, 95% CI 0.31, 0.87), severe ROP (aRR 0.47, 95% CI 0.25, 0.97), and respiratory distress syndrome (aRR 0.52, 95% CI 0.31, 0.87). We concluded that any ACS was associated with reduced risks for neonatal early death and severe ROP among very preterm infants born to mothers with clinical chorioamnionitis.

Editorial National neonatal networks around the world history, organization, function and research Shoo K. Lee, Prakesh S. Shah

Introduction: Sepsis and intraventricular hemorrhage (IVH) are associated with poorer long-term neurodevelopmental outcomes in very preterm infants (VPIs), but less is known about the long-term effect of meningitis and the combined impact of both meningitis and IVH. Our objective was to examine the long-term neurodevelopmental outcomes of VPIs with late onset sepsis and meningitis, with and without IVH, in Canada. Methods: We conducted a retrospective cohort study of all infants <29 weeks GA who were admitted to 26 tertiary-level neonatal intensive care units in the Canadian Neonatal Network (CNN) and Canadian Neonatal Follow-Up Network (CNFUN) databases, from January 1, 2010, to December 31, 2016. Results: Of the 6,322 infants in the cohort, 4,575 had no infection, 1,590 had late onset culture-positive bloodstream infection (CPBSI) only, and 157 had late onset meningitis. There was a significant (p < 0.05) trend of increasing rates of significant neurodevelopmental delay (sNDI) when comparing infants with no infection (sNDI rate 15.0%), late onset CPBSI (sNDI rate 22.9%), and late onset meningitis (sNDI rate 32.0%), even after adjustment for infant characteristics. Similar trends were observed for neurodevelopmental impairment, cerebral palsy, and individual Bayley-III scores <85 for cognitive, language, and motor development. There was an additive effect of IVH in all infant categories, but there was no multiplicative effect between IVH and late onset meningitis. Conclusion: There was an increasing trend of adverse neurodevelopmental outcomes when infants with no infection, late onset CPBSI and late onset meningitis are compared. IVH had an additive effect.