Increased Risk of Meconium-Related Ileus in Extremely Premature Infants Exposed to Antenatal Magnesium Sulfate

<b><i>Introduction:</i></b> We experienced an increased incidence of meconium-related ileus (MRI) in extremely premature infants (EPIs) while adopting the antenatal magnesium sulfate (MgSO₄) protocol for fetal neuroprotection in our neonatal intensive care unit. This study aimed to test whether antenatal MgSO₄ use was associated with increased risk of MRI in EPIs. <b><i>Methods:</i></b> The incidences of complicated MRI requiring aggressive enema or surgical intervention and other intestinal complications were compared among period 1 (January 2012–December 2013, <i>n</i> = 79), before adoption of the antenatal MgSO₄ protocol for fetal neuroprotection; period 2 (January 2014–March 2016, <i>n</i> = 72), when the protocol was adopted; and period 3 (April 2016–September 2018, <i>n</i> = 75), when the protocol was temporarily withdrawn due to concern regarding intestinal complications in EPIs. <b><i>Results:</i></b> Despite similar baseline clinical characteristics among infants across the study periods, the MRI and MRI with surgical treatment incidences were higher in period 2 than those in periods 1 and 3 (13% vs. 8% and 6%, <i>p</i> = 0.391, and 11% vs. 0% and 1%, <i>p</i> = 0.001, respectively). In multivariable analysis, exposure to antenatal MgSO₄ independently increased the risk of MRI (adjusted odds ratio, 3.8; 95% confidence interval, 1.4, 10.6). <b><i>Conclusion:</i></b> Antenatal MgSO₄ may increase the risk of MRI, frequently requiring surgical intervention, in EPIs with a gestational age of 25 weeks or less.

Oxygen Saturation Index in Neonates with a Congenital Diaphragmatic Hernia: A Retrospective Cohort Study

<b><i>Introduction:</i></b> The oxygenation index (OI) is a marker for respiratory disease severity and adverse neonatal outcomes. The oxygen saturation index (OSI) is an alternative that allows for continuous noninvasive monitoring, but evidence for clinical use in critically ill neonates is scarce. The aim of this study was to evaluate the OSI as compared to the OI in term neonates with a congenital diaphragmatic hernia (CDH). <b><i>Methods:</i></b> A single-center retrospective cohort study was conducted including all live-born infants with an isolated CDH between June 2017 and December 2020. Paired values of the OI and OSI in the first 24 h after birth were collected. The relation between OI and OSI measurements was assessed, taking into account arterial pH, body temperature, and preductal versus postductal location of oxygen saturation measurement or arterial blood sampling. The predictive values for pulmonary hypertension, need for extracorporeal membrane oxygenation therapy, and survival at discharge were evaluated. <b><i>Results:</i></b> Of 33 subjects included, 398 paired values of the OI (median 5.8 [3.3–17.2]) and OSI (median 7.3 [3.6–14.4]) were collected. The OI and OSI correlated strongly (<i>r</i> = 0.77, <i>p</i> &#x3c; 0.001). The OSI values corresponding to the clinically relevant OI values (10, 15, 20, and 40) were 8.9, 10.9, 12.9, and 20.9, respectively. The predictive values of the OI and OSI were comparable for all adverse neonatal outcomes. No difference was found in the area under the receiver operating characteristic curves for the OI and the OSI for adverse neonatal outcomes. <b><i>Conclusions:</i></b> The OSI could replace the OI in clinical practice in infants with a CDH.

Evaluation of Risk Factors and Approach to Screening for Asymptomatic Neonatal Hypoglycemia

<b><i>Introduction:</i></b> Protocols to identify asymptomatic neonatal hypoglycemia (NH) rely on the presence of established risk factors (late preterm gestation, large or small for gestational age, and infant of a diabetic mother) for inclusion. We analyzed the performance of these risk factors in identifying hypoglycemia in modern practice, and additionally evaluated the optimal duration of screening blood glucose measurements. <b><i>Methods:</i></b> We analyzed a retrospective cohort of 830 infants with 1 or more known risk factor(s) for NH admitted to the mother-baby unit of a single tertiary-care center from May 2017 to April 2018. Manual chart review was performed for data extraction and confirmation of risk factor(s). Infants were excluded if glucose measurements were obtained for any reason other than screening for asymptomatic NH. <b><i>Results:</i></b> Of the 830 included infants, 31 (3.7%) ultimately received intravenous dextrose (IVD). Most screened infants (<i>n</i> = 510, 61.4%) did not develop hypoglycemia. None of the established risk factors showed strong association with hypoglycemia. Cesarean delivery was associated with hypoglycemia, although not strongly. All infants who received IVD for feeding-refractory hypoglycemia were identified by the first 2 measurements with nearly all (30/31, 97%) identified at the initial measurement. <b><i>Conclusions:</i></b> Currently accepted risk factors are limited in their ability to identify infants who subsequently develop hypoglycemia, and as a result, most screened infants do not develop hypoglycemia. The majority of infants in our cohort who did develop hypoglycemia achieved normoglycemia with feeding-based interventions and did not require IVD. Those that received IVD were more likely to develop hypoglycemia early and to a more severe degree. Together, our data suggest further refinement of protocol duration and risk factors utilized for screening as potential areas of screening protocol optimization.

The Association between Evidence-Based Healthcare Practices and Outcomes among Preterm Births in China

<b><i>Introduction:</i></b> Very preterm infants are at high risk of early death or severe brain injury, with potential for impaired long-term neurodevelopmental function and physical health. There are evidence-based healthcare practices that can reduce the incidence. <b><i>Materials and Methods:</i></b> Infants born at 24–31⁶ weeks gestational age and admitted within 24 h to NICUs participating in the Chinese Neonatal Network in 2019 were included. We examined the association between 4 evidence-based practices: inborn (born in a tertiary hospital in the Chinese Neonatal Network), ACS (any antenatal corticosteroid), MgSO₄ (prenatal magnesium sulfate), and NT (normothermic temperature [36.0–37.5°C] at admission) and early death and/or severe brain injury in the study population. <b><i>Results:</i></b> Of 6,035 eligible infants, the incidence of early death and/or severe brain injury was 10.6%. Exposure to ACS only was associated with significant lower incidence of death and/or severe brain injury than none (aOR, 0.71; 95% CI: 0.57–0.88), but not MgSO₄ only (aOR, 0.97; 95% CI: 0.81–1.17), NT only (aOR, 0.91; 95% CI: 0.76–1.08), or inborn only (aOR, 0.91; 95% CI: 0.72–1.15). The association between number of practices and incidence of early death and/or severe brain injury is as follows: none = 23% (31/138), any 1 = 14% (84/592), any 2 = 12% (185/1,538), any 3 = 9% (202/2,285), and all 4 = 9% (140/1,482). <b><i>Discussion/Conclusion:</i></b> More comprehensive use of evidence-based practices was associated with improved survival without severe brain injury among very preterm infants born at &#x3c;32 weeks gestational age.

Course of Stress during the Neonatal Intensive Care Unit Stay in Preterm Infants

<b><i>Introduction:</i></b> Understanding the course of stress during the neonatal intensive care unit stay may provide targets for interventions. Our aim was to describe the course of stress in preterm infants during the first 28 days of life, the influence of gestational age, and associations with clinical characteristics. <b><i>Methods:</i></b> In a single centre prospective cohort study, we included infants with a gestational age &#x3c;30 weeks and/or birth weight &#x3c;1,000 g. We measured stress over the first 28 days using the Neonatal Infant Stressor Scale (NISS). We plotted daily NISS total and subcategory scores by gestational age. The subcategories were (1) nursing, (2) skin-breaking, (3) monitoring and imaging, and (4) medical morbidity-related scores. We assessed associations of cumulative NISS scores over the first 7, 14, and 28 days with clinical characteristics using regression analyses. <b><i>Results:</i></b> We included 45 infants, with a median gestational age of 27 weeks. The mean daily NISS score was 66.5 (SD 8.7), with highest scores in the first 7 days of life. Scores decreased the slowest for the lowest gestational ages, in particular for nursing scores, rather than skin-breaking, monitoring and imaging, and medical morbidity-related scores. Adjusted for gestational age, infants with lower Apgar scores, sepsis, intraventricular haemorrhages, and on mechanical ventilation had significantly higher cumulative NISS scores at 7, 14, and 28 days. <b><i>Conclusion:</i></b> NISS scores varied greatly within infants and over time, with the highest mean scores in the first week after birth. The course of declining NISS scores in the first 28 days depended on gestational age at birth.

Bronchopulmonary Dysplasia and Risk of Developmental Delay: An EPIPAGE-2 Cohort Study

<b><i>Background:</i></b> Overall and respiratory management of preterm children are constantly evolving, which might have changed both the pathophysiology and neurodevelopmental consequences of bronchopulmonary dysplasia (BPD). <b><i>Objectives:</i></b> The objective of this study is to determine whether the previously shown association between BPD and risk of developmental delay persists. <b><i>Methods:</i></b> The study population was children born before 32 weeks’ gestation from the French prospective cohort EPIPAGE-2. The exposure was BPD assessed at 36 weeks’ postmenstrual age. The main outcome was risk of developmental delay defined by an Age &amp; Stages Questionnaires (ASQ) score below threshold at 24 months’ corrected age. <b><i>Results:</i></b> The analyzed population included 2,706 children. Among those with available ASQ score, 196/1,587 had BPD and 671/1,587 had an ASQ score below threshold. BPD was associated with an ASQ score below threshold (odds ratio 1.52, 95% confidence interval 1.11–2.08; <i>p</i> = 0.008). <b><i>Conclusions:</i></b> BPD was strongly associated with risk of developmental delay.

Decreasing Trend in Incidence of Late Onset Culture Positive Bloodstream Infections but Not Late Onset Meningitis in Preterm Infants <33 Weeks Gestation in Canadian Neonatal Intensive Care Unit

<b><i>Introduction:</i></b> Recent studies reported decreased incidence of late onset sepsis in the neonatal intensive care unit (NICU), but it is unclear whether this is also true for late onset meningitis. Recent reports that both meningitis and intraventricular hemorrhage (IVH) are associated with systemic inflammation also raise questions about an association between the 2. <b><i>Methods:</i></b> All preterm infants &#x3c;33 weeks gestational age admitted to CNN NICUs from 2010 to 2018 were included. We compared incidence trends of late onset culture positive bloodstream infection (CPBSI) and late onset meningitis, and examined the association of meningitis and IVH (exposure), after adjustment for potential confounders. <b><i>Results:</i></b> Of 36,573 infants included, 32,198 had no infection, 3,977 had only late onset CPBSI and 398 had late onset meningitis. There was significant decrease in incidence of late onset CPBSI (14%–10%; adjusted odds ratio (AOR) = 0.93; 95% confidence interval [CI] 0.92, 0.95) but not late onset meningitis (1.6%–1.2%; AOR = 0.98; 95% CI 0.94, 1.01). Compared to infants with no IVH grade 3 or above, infants with IVH grade 3, or above had higher odds of late onset meningitis versus no infection (AOR 4.16; 95% CI 3.17, 5.44), and higher odds of late onset meningitis versus late onset CPBSI (AOR 4.11; 95% CI 3.08, 5.50). <b><i>Conclusions:</i></b> There was a decreasing trend of late onset CPBSI but not late onset meningitis. An association between late onset meningitis and IVH grade 3 or above was observed. Late onset CPBSI and meningitis may have different risk factors and require different prevention strategies.

Prevalence and Infant Mortality of Major Congenital Malformations Stratified by Birthweight

<b><i>Background:</i></b> Low birthweight and major congenital malformations (MCMs) are key causes of infant mortality. <b><i>Objectives:</i></b> The aim of this study was to explore the prevalence of MCMs in infants with low and very low birthweight and analyze the impact of MCMs and birthweight on infant mortality. <b><i>Methods:</i></b> We determined prevalence and infant mortality of 28 life-threatening MCMs in very-low-birthweight (&#x3c;1,500 g, VLBW), low-birthweight (1,500–2,499 g, LBW), or normal-birthweight (≥2,500 g, NBW) infants in a cohort of 2,727,002 infants born in Germany in 2006–2017, using de-identified administrative data of the largest statutory public health insurance system in Germany. <b><i>Results:</i></b> The rates of VLBW, LBW, and NBW infants studied were 1.3% (34,401), 4.0% (109,558), and 94.7% (2,583,043). MCMs affected 0.5% (13,563) infants, of whom &#x3e;75% (10,316) had severe congenital heart disease. The prevalence (per 10,000) of any/cardiac MCM was increased in VLBW (286/176) and LBW (244/143), as compared to NBW infants (38/32). Infant mortality rates were significantly higher in infants with an MCM, as opposed to infants without an MCM, in each birthweight group (VLBW 28.5% vs. 11.5%, LBW 16.7% vs. 0.9%, and NBW 8.6% vs. 0.1%). For most MCMs, observed survival rates in VLBW and LBW infants were lower than expected, as calculated from survival rates of VLBW or LBW infants without an MCM, and NBW infants with an MCM. <b><i>Conclusions:</i></b> Infants with an MCM are more often born with LBW or VLBW, as opposed to infants without an MCM. Many MCMs carry significant excess mortality when occurring in VLBW or LBW infants.

Does Early Cerebral Near-Infrared Spectroscopy Monitoring Predict Outcome in Neonates with Hypoxic Ischaemic Encephalopathy? A Systematic Review of Diagnostic Test Accuracy

<b><i>Introduction:</i></b> Hypoxic ischaemic encephalopathy (HIE) remains one of the top 10 contributors to the global burden of disease. Early objective biomarkers are required. Near-infrared spectroscopy (NIRS) may provide a valuable insight into cerebral perfusion and metabolism. We aimed to determine whether early NIRS monitoring (&#x3c;6 h of age) can predict outcome as defined by grade of encephalopathy, brain MRI findings, and/or neurodevelopmental outcome at 1–2 years in infants with HIE. <b><i>Methods:</i></b> We searched PubMed, Scopus, Web of Science, Embase, and The Cochrane Library databases (July 2019). Studies of infants born ≥36⁺⁰ weeks gestation with HIE who had NIRS recording commenced before 6 h of life were included. We planned to provide a narrative of all the studies included, and if similar clinically and methodologically, the results would be pooled in a meta-analysis to determine test accuracy. <b><i>Results:</i></b> Seven studies were included with a combined total of 161 infants. Only 1 study included infants with mild HIE. A range of different oximeters and probes were utilized with varying outcome measures making comparison difficult. Although some studies showed a trend towards higher cSO₂ values before 6 h in infants with adverse neurodevelopmental outcomes, in the majority, this was not significant until beyond 24 h of life. <b><i>Conclusion:</i></b> Very little data currently exists to assess the use of early NIRS to predict outcome in infants with HIE. Further studies using a standardized approach are required before NIRS can be evaluated as a potential objective assessment tool for early identification of at-risk infants.

Maternal Intrapartum Antibiotic Treatment and Gut Microbiota Development in Healthy Term Infants

<b><i>Objective:</i></b> The aim of the study was to investigate the impact of intrapartum antibiotic treatment (IAT) on the compositional development of gut microbiota in healthy term infants. <b><i>Study Design:</i></b> A case-control study of 24 infants exposed to and 24 matched infants not exposed to IAT was conducted. All subjects were born by vaginal delivery at term and breastfed. None of the infants received antibiotics during the immediate neonatal period. Fecal samples were obtained at the ages of 1 and 6 months. The composition of the intestinal microbiota was assessed by 16S rRNA gene sequencing. <b><i>Results:</i></b> IAT was associated with reduced microbial richness but not diversity at 1 month of age. Furthermore, the relative abundances of Clostridiaceae and Erysipelotrichaceae were significantly altered in infants exposed to IAT as compared to nonexposed infants at 1 month of age. The observed deviations in gut microbiota composition between infants exposed and not exposed to IAT diminished by the age of 6 months. <b><i>Conclusions:</i></b> IAT is associated with short-term perturbations in the gut microbiota development in healthy term, vaginally delivered, breastfed infants. The composition of the gut microbiota is mostly restored by the age of 6 months.