Neonatal Outcomes After COVID-19 Vaccination in Pregnancy.

Importance: Better knowledge about neonatal adverse events after COVID-19 vaccination during pregnancy could help address concerns about vaccine safety. Objective: To evaluate the risks of neonatal adverse events after exposure to COVID-19 vaccination during pregnancy. Design, Setting, and Participants: Population-based cohort study including all infants in Sweden and Norway born from June 2021 to January 2023. Unique personal identity numbers were used to link individual information from different national registers. Exposure: Administration of any mRNA vaccine against COVID-19 during pregnancy, irrespective of previous vaccination, number of doses during pregnancy, or vaccine manufacturer. Main Outcomes and Measures: Outcomes were neonatal conditions with bleeding/thrombosis or inflammation/infection; disorders of the central nervous system; circulatory, respiratory, or gastrointestinal problems; and neonatal mortality. Statistical methods included logistic regression adjusted for characteristics of the pregnant individuals, with additional restricted and stratified analyses. Results: Of 196 470 newborn infants included (51.3% male, 93.8% born at term, 62.5% born in Sweden), 94 303 (48.0%) were exposed to COVID-19 vaccination during pregnancy. Exposed infants exhibited no increased odds of adverse neonatal outcomes, and they exhibited lower odds for neonatal nontraumatic intracranial hemorrhage (event rate, 1.7 vs 3.2/1000; adjusted odds ratio [aOR], 0.78 [95% CI, 0.61-0.99]), hypoxic-ischemic encephalopathy (1.8 vs 2.7/1000; aOR, 0.73 [95% CI, 0.55-0.96]), and neonatal mortality (0.9 vs 1.8/1000; aOR, 0.68 [95% CI, 0.50-0.91]). Subgroup analyses found a similar association between vaccination during pregnancy and lower neonatal mortality; subgroups were restricted to infants delivered by individuals unvaccinated before pregnancy, individuals vaccinated before pregnancy, individuals vaccinated after a general recommendation of vaccination during pregnancy was issued, and individuals without COVID-19 infection during pregnancy. Analyses restricted to term infants, singleton births, or infants without birth defects yielded similar results. Stratifying the analysis by vaccine manufacturer did not attenuate the association between vaccination and low neonatal mortality. Conclusions and Relevance: In this large population-based study, vaccination of pregnant individuals with mRNA COVID-19 vaccines was not associated with increased risks of neonatal adverse events in their infants.

The association between perinatal factors and cardiometabolic risk factors in children and adolescents with overweight or obesity: A retrospective two-cohort study.

BACKGROUND: Children with obesity have an increased risk of cardiometabolic risk factors, but not all children carry a similar risk. Perinatal factors, i.e., gestational age (GA) and birth weight for GA, may affect the risk for metabolic complications. However, there are conflicting data whether the association between birth size and cardiometabolic risk factors is independent among children with obesity. Moreover, differential effects of GA and birth weight for GA on cardiometabolic risk factors in pediatric obesity are still unexplored. We aimed to investigate the association between birth weight for GA and cardiometabolic risk factors in children and adolescents with overweight or obesity and to assess whether the association is modified by prematurity. METHODS AND FINDINGS: We conducted a retrospective study of 2 cohorts, using data from the world's 2 largest registers of pediatric obesity treatment-The Swedish childhood obesity treatment register (BORIS) and The Adiposity Patients Registry (APV) (1991 to 2020). Included were individuals with overweight or obesity between 2 to 18 years of age who had data of birth characteristics and cardiometabolic parameters. Birth data was collected as exposure variable and the first reported cardiometabolic parameters during pediatric obesity treatment as the main outcome. The median (Q1, Q3) age at the outcome measurement was 11.8 (9.4, 14.0) years. The main outcomes were hypertensive blood pressure (BP), impaired fasting glucose, elevated glycated hemoglobin (HbA1c), elevated total cholesterol, elevated low-density lipoprotein (LDL) cholesterol, elevated triglycerides, decreased high-density lipoprotein (HDL) cholesterol, and elevated transaminases. With logistic regression, we calculated the odds ratio (OR) and its 95% confidence interval (CI) for each cardiometabolic parameter. All the analyses were adjusted for sex, age, degree of obesity, migratory background, and register source. In total, 42,760 (51.9% females) individuals were included. Small for GA (SGA) was prevalent in 10.4%, appropriate for GA (AGA) in 72.4%, and large for GA (LGA) in 17.2%. Most individuals (92.5%) were born full-term, 7.5% were born preterm. Median (Q1, Q3) body mass index standard deviation score at follow-up was 2.74 (2.40, 3.11) units. Compared with AGA, children born SGA were more likely to have hypertensive BP (OR = 1.20 [95% CI 1.12 to 1.29], p < 0.001), elevated HbA1c (1.33 [1.06 to 1.66], p = 0.03), and elevated transaminases (1.21 [1.10 to 1.33], p < 0.001) as well as low HDL (1.19 [1.09 to 1.31], p < 0.001). On the contrary, individuals born LGA had lower odds for hypertensive BP (0.88 [0.83 to 0.94], p < 0.001), elevated HbA1c (0.81 [0.67 to 0.97], p < 0.001), and elevated transaminases (0.88 [0.81 to 0.94], p < 0.001). Preterm birth altered some of the associations between SGA and outcomes, e.g., by increasing the odds for hypertensive BP and by diminishing the odds for elevated transaminases. Potential selection bias due to occasionally missing data could not be excluded. CONCLUSIONS: Among children and adolescents with overweight/obesity, individuals born SGA are more likely to possess cardiometabolic risk factors compared to their counterparts born AGA. Targeted screening and treatment of obesity-related comorbidities should therefore be considered in this high-risk group of individuals.

Identifying neonatal adverse events in preterm and term infants using a paediatric trigger tool.

AIM: To explore the incidence and characteristics of inpatient neonatal adverse events in a Swedish setting. METHODS: A retrospective record review, using a trigger tool, performed by registered nurses and a neonatologist, at a University Hospital. The identified adverse events were categorised by, for example, preventability, severity and time of occurrence. RESULTS: A random selection of 150 admissions representing 3531 patient days were reviewed (mean [SD] birthweight 2620 [1120]g). Three hundred and sixty adverse events were identified in 78 (52.0%) infants, and 305 (84.7%) of these were assessed as being preventable. The overall adverse event rate was 240 per 100 admissions and 102.0 per 1000 patient days. Preterm infants had a higher rate than term infants (353 versus 79 per 100 admissions, p = 0.001); however, with regard to the length of stay, the rates were similar. Most adverse events were temporary and less severe (n = 338/360, 93.9%) and the most common type involved harm to skin, tissue or blood vessels (n = 163/360, 45.3%). Forty percent (n = 145) of adverse events occurred within the first week of admission. CONCLUSION: Adverse events were common in neonatal care, and many occurred during the first days of treatment. Characterisation of adverse events may provide focus areas for improvements in patient safety.

Preterm birth in the Nordic countries-Capacity, management and outcome in neonatal care.

AIM: Organisation of care, perinatal and neonatal management of very preterm infants in the Nordic regions were hypothesised to vary significantly. The aim of this observational study was to test this hypothesis. METHODS: Information on preterm infants in the 21 greater healthcare regions of Denmark, Finland, Iceland, Norway and Sweden was gathered from national registers in 2021. Preterm birth rates, case-mix, perinatal interventions, neonatal morbidity and survival to hospital discharge in very (<32 weeks) and extremely preterm infants (<28 weeks of gestational age) were compared. RESULTS: Out of 287 642 infants born alive, 16 567 (5.8%) were preterm, 2389 (0.83%) very preterm and 800 (0.28%) were extremely preterm. In very preterm infants, exposure to antenatal corticosteroids varied from 85% to 98%, live births occurring at regional centres from 48% to 100%, surfactant treatment from 28% to 69% and use of mechanical ventilation varied from 13% to 77% (p < 0.05 for all comparisons). Significant regional variations within and between countries were also seen in capacity in neonatal care, case-mix and number of admissions, whereas there were no statistically significant differences in survival or major neonatal morbidities. CONCLUSION: Management of very preterm infants exhibited significant regional variations in the Nordic countries.

International Variation in the Management of Patent Ductus Arteriosus and Its Association with Infant Outcomes: A Survey and Linked Cohort Study.

OBJECTIVE: To assess whether treating patients with a presymptomatic patent ductus arteriosus (PDA), based on early routine echocardiography, performed regardless of clinical signs, improved outcomes. STUDY DESIGN: This multicenter, survey-linked retrospective cohort study used an institutional-level questionnaire and individual patient-level data and included infants of <29 weeks of gestation born in 2014-2016 and admitted to tertiary neonatal intensive care units (NICUs) of 9 population-based national or regional neonatal networks. Infants in NICUs receiving treatment of presymptomatic PDA identified by routine echocardiography and those not were compared for the primary composite outcome (early death [≤7 days after birth] or severe intraventricular hemorrhage) and secondary outcomes (any in-hospital mortality and major morbidities). RESULTS: The unit survey (response rates of 86%) revealed a wide variation among networks in the treatment of presymptomatic PDA (7%-86%). Among 246 NICUs with 17 936 infants (mean gestational age of 26 weeks), 126 NICUs (51%) with 7785 infants treated presymptomatic PDA. The primary outcome of early death or severe intraventricular hemorrhage was not significantly different between the NICUs treating presymptomatic PDA and those who did not (17% vs 21%; aOR 1.00, 95% CI 0.85-1.18). The NICUs treating presymptomatic PDA had greater odds of retinopathy of prematurity treatment (13% vs 7%; aOR 1.47, 95% CI 1.01-2.12); however, it was not significant in a sensitivity analysis excluding Japanese data. CONCLUSIONS: Treating presymptomatic PDA detected by routine echocardiography was commonplace but associated with no significant benefits. Well-designed trials are needed to assess the efficacy and safety of early targeted PDA treatment.

Implementation of a revised classification for intrapartum fetal heart rate monitoring and association to birth outcome: A national cohort study.

INTRODUCTION: A revised intrapartum cardiotocography (CTG) classification was introduced in Sweden in 2017. The aims of the revision were to adapt to the international guideline published in 2015 and to adjust the classification of CTG patterns to current evidence regarding intrapartum fetal physiology. This study aimed to investigate adverse neonatal outcomes before and after implementation of the revised CTG classification. MATERIAL AND METHODS: A before-and-after design was used. Cohort I (n = 160 210) included births from June 1, 2014 through May 31, 2016 using the former CTG classification, and cohort II (n = 166 558) included births from June 1, 2018 through May 31, 2020 with the revised classification. Data were collected from the Swedish Pregnancy and Neonatal Registers. The primary outcome was moderate to severe neonatal hypoxic ischemic encephalopathy (HIE 2-3). Secondary outcomes were birth acidemia (umbilical artery pH <7.05 and base excess < -12 mmol/L or pH <7.00), A-criteria for neonatal hypothermia treatment, 5-min Apgar scores <4 and <7, neonatal seizures, meconium aspiration, neonatal mortality and delivery mode. Logistic regression was used (period II vs period I), and results are presented as adjusted odds ratios (aORs) with 95% confidence intervals (95% CIs). RESULTS: There were no statistically significant differences in HIE 2-3 (aOR 1.27; 95% CI 0.97-1.66), proportion of neonates meeting A-criteria for hypothermia treatment (aOR 0.96; 95% CI 0.89-1.04) or neonatal mortality (aOR 0.68; 95% CI 0.39-1.18) between the cohorts. Birth acidemia (aOR 1.36; 95% CI 1.25-1.48), 5-min Apgar scores <7 (aOR 1.27; 95% CI 1.18-1.36) and <4 (aOR 1.40; 95% CI 1.17-1.66) occurred more often in cohort II. The absolute risk difference for HIE 2-3 was 0.02% (95% CI 0.00-0.04). Operative delivery (vacuum or cesarean) rates were lower in cohort II (aOR 0.82; 95% CI 0.80-0.85 and aOR 0.94; 95% CI 0.91-0.97, respectively). CONCLUSIONS: Although not statistically significant, a small increase in the incidence of HIE 2-3 after implementation of the revised CTG classification cannot be excluded. Operative deliveries were fewer but incidences of acidemia and low Apgar scores were higher in the latter cohort. This warrants further in-depth analyses before a full re-evaluation of the revised classification can be made.

Perinatal risk factors for mortality in very preterm infants-A nationwide, population-based discriminant analysis.

AIM: To assess the strength of associations between interrelated perinatal risk factors and mortality in very preterm infants. METHODS: Information on all live-born infants delivered in Sweden at 22-31 weeks of gestational age (GA) from 2011 to 2019 was gathered from the Swedish Neonatal Quality Register, excluding infants with major malformations or not resuscitated because of anticipated poor prognosis. Twenty-seven perinatal risk factors available at birth were exposures and in-hospital mortality outcome. Orthogonal partial least squares discriminant analysis was applied to assess proximity between individual risk factors and mortality, and receiver operating characteristic (ROC) curves were used to estimate discriminant ability. RESULTS: In total, 638 of 8,396 (7.6%) infants died. Thirteen risk factors discriminated reduced mortality; the most important were higher Apgar scores at 5 and 10 min, GA and birthweight. Restricting the analysis to preterm infants <28 weeks' GA (n = 2939, 16.9% mortality) added antenatal corticosteroid therapy as significantly associated with lower mortality. The area under the ROC curve (the C-statistic) using all risk factors was 0.86, as determined after both internal and external validation. CONCLUSION: Apgar scores, gestational age and birthweight show stronger associations with mortality in very preterm infants than several other perinatal risk factors available at birth.

Birth outcomes between 22 and 26 weeks' gestation in national population-based cohorts from Sweden, England and France.

AIM: We investigated the timing of survival differences and effects on morbidity for foetuses alive at maternal admission to hospital delivered at 22 to 26 weeks' gestational age (GA). METHODS: Data from the EXPRESS (Sweden, 2004-07), EPICure-2 (England, 2006) and EPIPAGE-2 (France, 2011) cohorts were harmonised. Survival, stratified by GA, was analysed to 112 days using Kaplan-Meier analyses and Cox regression adjusted for population and pregnancy characteristics; neonatal morbidities, survival to discharge and follow-up and outcomes at 2-3 years of age were compared. RESULTS: Among 769 EXPRESS, 2310 EPICure-2 and 1359 EPIPAGE-2 foetuses, 112-day survival was, respectively, 28.2%, 10.8% and 0.5% at 22-23 weeks' GA; 68.5%, 40.0% and 23.6% at 24 weeks; 80.5%, 64.8% and 56.9% at 25 weeks; and 86.6%, 77.1% and 74.4% at 26 weeks. Deaths were most marked in EPIPAGE-2 before 1 day at 22-23 and 24 weeks GA. At 25 weeks, survival varied before 28 days; differences at 26 weeks were minimal. Cox analyses were consistent with the Kaplan-Meier analyses. Variations in morbidities were not clearly associated with survival. CONCLUSION: Differences in survival and morbidity outcomes for extremely preterm births are evident despite adjustment for background characteristics. No clear relationship was identified between early mortality and later patterns of morbidity.

Maternal Obesity and Risk of Early-onset Neonatal Bacterial Sepsis: Nationwide Cohort and Sibling-controlled Studies.

BACKGROUND: Maternal overweight and obesity are related to risks of pregnancy and delivery complications that, in turn, are associated with newborn infections. We examined the associations between early pregnancy body mass index (BMI; kg/m2) and risk of early-onset neonatal bacterial sepsis (EOS). METHODS: We conducted a nationwide population-based retrospective cohort study of 1 971 346 live singleton infants born in Sweden between 1997 and 2016. Outcome was a culture-confirmed EOS diagnosis. We estimated hazard ratios (HR) of EOS according to BMI using proportional hazard models, and identified potential mediators. Among term infants, we conducted sibling-controlled analyses. RESULTS: EOS risk per 1000 live births was 1.48; 0.76 in term and 15.52 in preterm infants. Compared with infants of normal-weight mothers (BMI, 18.5-24.9), the adjusted HR (95% confidence interval [CI]) of EOS for BMI categories <18.5, 25.0-29.9, 30.0-34.9, 35.0-39.9, and ≥40.0 were, respectively, 1.07 (.83-1.40), 1.19 (1.08-1.32), 1.70 (1.49-1.94), 2.11 (1.73-2.58), and 2.50 (1.86-3.38). Maternal overweight and obesity increased the risk of EOS by group B Streptococcus, Staphylococcus aureus, and Escherichia coli. Half of the association was mediated through preeclampsia, cesarean section delivery, and preterm delivery. A dose-response association was consistently apparent in term infants only. In sibling-controlled analyses, every kilogram per meter squared interpregnancy BMI change was associated with a mean 8.3% increase in EOS risk (95% CI, 1.7%-15.3%; P = .01). CONCLUSIONS: Risk of EOS increases with maternal overweight and obesity severity, particularly in term infants.

Variations in Neonatal Length of Stay of Babies Born Extremely Preterm: An International Comparison Between iNeo Networks.

OBJECTIVE: To compare length of stay (LOS) in neonatal care for babies born extremely preterm admitted to networks participating in the International Network for Evaluating Outcomes of Neonates (iNeo). STUDY DESIGN: Data were extracted for babies admitted from 2014 to 2016 and born at 24 to 28 weeks of gestational age (n = 28 204). Median LOS was calculated for each network for babies who survived and those who died while in neonatal care. A linear regression model was used to investigate differences in LOS between networks after adjusting for gestational age, birth weight z score, sex, and multiplicity. A sensitivity analysis was conducted for babies who were discharged home directly. RESULTS: Observed median LOS for babies who survived was longest in Japan (107 days); this result persisted after adjustment (20.7 days more than reference, 95% CI 19.3-22.1). Finland had the shortest adjusted LOS (-4.8 days less than reference, 95% CI -7.3 to -2.3). For each week's increase in gestational age at birth, LOS decreased by 12.1 days (95% CI -12.3 to -11.9). Multiplicity and male sex predicted mean increases in LOS of 2.6 (95% CI 2.0-3.2) and 2.1 (95% CI 1.6-2.6) days, respectively. CONCLUSIONS: We identified between-network differences in LOS of up to 3 weeks for babies born extremely preterm. Some of these may be partly explained by differences in mortality, but unexplained variations also may be related to differences in clinical care practices and healthcare systems between countries.

Association between travel time to delivery unit and unplanned out-of-hospital birth, infant morbidity and mortality: A population-based cohort study.

INTRODUCTION: Over the last decade, a number of delivery units have been closed in Sweden, justified by both economic incentives and patient safety issues. However, concentrating births to larger delivery units naturally increases travel time for some parturient women, which may lead to unintended negative consequences. We aimed to investigate the association between travel time to delivery unit and unplanned out-of-hospital birth, and subsequent infant morbidity and mortality. MATERIAL AND METHODS: We performed a population-based cohort study including 365 604 women in the Swedish Pregnancy Register, giving birth between 2014 and 2017. Modified Poisson regression was used to investigate the association between travel time from home address to actual delivery unit, based on geographic information system analysis, and risk of an unplanned out-of-hospital birth. Analyses were stratified by parity and urban/rural residence. Lastly, the associations between an unplanned out-of-hospital birth and severe infant morbidity, stillbirth, peripartum, perinatal and neonatal mortality were investigated. RESULTS: Of those with an unplanned out-of-hospital birth (n = 2159), 65% had a travel time up to 30 minutes. A travel time between 31 and 60 minutes was associated with a doubled risk of unplanned out-of-hospital birth (adjusted risk ratio [RR] 1.96, 95% confidence interval [CI] 1.74-2.22) and women with a travel time of more than 1 hour had an adjusted RR of 3.19 (95% CI 2.64-3.86), compared with those with a travel time of <30 minutes. No difference in results was seen when stratified for parity and urban/rural residence. No association was found between unplanned out-of-hospital birth and severe infant morbidity. Significant associations were found in crude analyses for stillbirth (RR 1.85, 95% CI 1.09-3.13), peripartum (RR 1.93, 95% CI 1.18-3.16), perinatal (RR 2.03, 95% CI 1.28-3.23) and neonatal mortality (RR 3.08, 95% CI 1.27-7.46), although neonatal mortality was very rare (2.3/1000 out-of-hospital births). Similar effect estimates were found in the adjusted analyses, though no longer significant. CONCLUSIONS: Although the majority of unplanned out-of-hospital births occurred in the group of women with a travel time of 0-30 minutes, increasing travel time to a delivery unit is associated with unplanned out-of-hospital birth, which may increase the risk of mortality.

The type and timing of patent ductus arteriosus treatment was associated with neurodevelopment when extremely preterm infants reached 6.5 years.

AIM: This study investigated patent ductus arteriosus (PDA) treatment and neurodevelopmental outcomes when extremely preterm born children reached 6.5 years. METHOD: Our cohort was 435 children with neonatal PDA treatment data and neurodevelopmental follow-up data, born in 2004-2007, who participated in the Extremely Preterm Infants in Sweden Study. Pharmacological or surgical PDA treatment and the age at PDA treatment, were investigated in relation to the risks of moderate to severe neurodevelopmental impairment (NDI) and full-scale intelligence quotient (FSIQ) at 6.5 years. RESULTS: The children who received PDA drug treatment, including those who also had surgery, had the same risk of moderate to severe NDI or lower FSIQ as untreated children. However, children who had primary PDA surgery faced increased risks of NDI, with an adjusted incidence rate ratio of 1.62 (95% confidence interval [CI] 1.28-2.06) and a lower adjusted mean difference FSIQ of -7.1 (95% CI -11 to -3.2). Surgery at less than 10 days of life was associated with a significantly increased risk of moderate to severe NDI and lower FSIQ than surgery after 20 days. CONCLUSION: Drug treatment followed by deferred surgery appeared to be a safer option for extremely preterm infants severely affected by PDA.

Mode of delivery and adverse short- and long-term outcomes in vertex-presenting very preterm born infants: a European population-based prospective cohort study.

OBJECTIVES: To compare mortality, morbidity and neurodevelopment by mode of delivery (MOD) for very preterm births with low prelabour risk of caesarean section (CS). METHODS: The study was a population-based prospective cohort study in 19 regions in 11 European countries. Multivariable mixed effects models and weighted propensity score models were used to estimate adjusted odds ratios (aOR) by observed MOD and the unit's policy regarding MOD. Population: Singleton vertex-presenting live births at 24 + 0 to 31 + 6 weeks of gestation without serious congenital anomalies, preeclampsia, HELLP or eclampsia, antenatal detection of growth restriction and prelabour CS for fetal or maternal indications. RESULTS: Main outcome measures: A composite of in-hospital mortality and intraventricular haemorrhage (grade III/IV) or periventricular leukomalacia. Secondary outcomes were components of the primary outcome, 5 min Apgar score <7 and moderate to severe neurodevelopmental impairment at two years of corrected age. The rate of CS was 29.6% but varied greatly between countries (8.0-52.6%). MOD was not associated with the primary outcome (aOR for CS 0.99; 95% confidence interval [CI] 0.65-1.50) when comparing units with a systematic policy of CS or no policy of MOD to units with a policy of vaginal delivery (aOR 0.88; 95% CI 0.59-1.32). No association was observed for two-year neurodevelopment impairment for CS (aOR 1.15; 95% CI 0.66-2.01) or unit policies (aOR 1.04; 95% CI 0.63-1.70). CONCLUSIONS: Among singleton vertex-presenting live births without medical complications requiring a CS at 24 + 0 to 31 + 6 weeks of gestation, CS was not associated with improved neonatal or long-term outcomes.

Association of Maternal SARS-CoV-2 Infection in Pregnancy With Neonatal Outcomes.

Importance: The outcomes of newborn infants of women testing positive for SARS-CoV-2 in pregnancy is unclear. Objective: To evaluate neonatal outcomes in relation to maternal SARS-CoV-2 test positivity in pregnancy. Design, Setting, and Participants: Nationwide, prospective cohort study based on linkage of the Swedish Pregnancy Register, the Neonatal Quality Register, and the Register for Communicable Diseases. Ninety-two percent of all live births in Sweden between March 11, 2020, and January 31, 2021, were investigated for neonatal outcomes by March 8, 2021. Infants with malformations were excluded. Infants of women who tested positive for SARS-CoV-2 were matched, directly and using propensity scores, on maternal characteristics with up to 4 comparator infants. Exposures: Maternal test positivity for SARS-CoV-2 in pregnancy. Main Outcomes and Measures: In-hospital mortality; neonatal resuscitation; admission for neonatal care; respiratory, circulatory, neurologic, infectious, gastrointestinal, metabolic, and hematologic disorders and their treatments; length of hospital stay; breastfeeding; and infant test positivity for SARS-CoV-2. Results: Of 88 159 infants (49.0% girls), 2323 (1.6%) were delivered by mothers who tested positive for SARS-CoV-2. The mean gestational age of infants of SARS-CoV-2-positive mothers was 39.2 (SD, 2.2) weeks vs 39.6 (SD, 1.8) weeks for comparator infants, and the proportions of preterm infants (gestational age <37 weeks) were 205/2323 (8.8%) among infants of SARS-CoV-2-positive mothers and 4719/85 836 (5.5%) among comparator infants. After matching on maternal characteristics, maternal SARS-CoV-2 test positivity was significantly associated with admission for neonatal care (11.7% vs 8.4%; odds ratio [OR], 1.47; 95% CI, 1.26-1.70) and with neonatal morbidities such as respiratory distress syndrome (1.2% vs 0.5%; OR, 2.40; 95% CI, 1.50-3.84), any neonatal respiratory disorder (2.8% vs 2.0%; OR, 1.42; 95% CI, 1.07-1.90), and hyperbilirubinemia (3.6% vs 2.5%; OR, 1.47; 95% CI, 1.13-1.90). Mortality (0.30% vs 0.12%; OR, 2.55; 95% CI, 0.99-6.57), breastfeeding rates at discharge (94.4% vs 95.1%; OR, 0.84; 95% CI, 0.67-1.05), and length of stay in neonatal care (median, 6 days in both groups; difference, 0 days; 95% CI, -2 to 7 days) did not differ significantly between the groups. Twenty-one infants (0.90%) of SARS-CoV-2-positive mothers tested positive for SARS-CoV-2 in the neonatal period; 12 did not have neonatal morbidity, 9 had diagnoses with unclear relation to SARS-CoV-2, and none had congenital pneumonia. Conclusions and Relevance: In a nationwide cohort of infants in Sweden, maternal SARS-CoV-2 infection in pregnancy was significantly associated with small increases in some neonatal morbidities. Given the small numbers of events for many of the outcomes and the large number of statistical comparisons, the findings should be interpreted as exploratory.

Neonatal Intensive Care Unit-Level Patent Ductus Arteriosus Treatment Rates and Outcomes in Infants Born Extremely Preterm.

OBJECTIVES: To assess associations between neonatal intensive care unit (NICU)-level patent ductus arteriosus (PDA) treatment rates (pharmacologic or surgical) and neonatal outcomes. STUDY DESIGN: This cohort study included infants born at 24-28 weeks of gestation and birth weight <1500 g in 2007-2015 in NICUs caring for ≥100 eligible infants in 6 countries. The ratio of observed/expected (O/E) PDA treatment rates was derived for each NICU by estimating the expected rate using a logistic regression model adjusted for potential confounders and network. The primary composite outcome was death or severe neurologic injury (grades III-IV intraventricular hemorrhage or periventricular leukomalacia). The associations between the NICU-level O/E PDA treatment ratio and neonatal outcomes were assessed using linear regression analyses including a quadratic effect (a square term) of the O/E PDA treatment ratio. RESULTS: From 139 NICUs, 39 096 infants were included. The overall PDA treatment rate was 45% in the cohort (13%-77% by NICU) and the O/E PDA treatment ratio ranged from 0.30 to 2.14. The relationship between the O/E PDA treatment ratio and primary composite outcome was U-shaped, with the nadir at a ratio of 1.13 and a significant quadratic effect (P<.001). U-shaped relationships were also identified with death, severe neurologic injury, and necrotizing enterocolitis. CONCLUSIONS: Both low and high PDA treatment rates were associated with death or severe neurologic injury, whereas a moderate approach was associated with optimal outcomes.

Family Rooms in Neonatal Intensive Care Units and Neonatal Outcomes: An International Survey and Linked Cohort Study.

OBJECTIVES: To evaluate the proportion of neonatal intensive care units with facilities supporting parental presence in their infants' rooms throughout the 24-hour day (ie, infant-parent rooms) in high-income countries and to analyze the association of this with outcomes of extremely preterm infants. STUDY DESIGN: In this survey and linked cohort study, we analyzed unit design and facilities for parents in 10 neonatal networks of 11 countries. We compared the composite outcome of mortality or major morbidity, length of stay, and individual morbidities between neonates admitted to units with and without infant-parent rooms by linking survey responses to patient data from 2015 for neonates of less than 29 weeks of gestation. RESULTS: Of 331 units, 13.3% (44/331) provided infant-parent rooms. Patient-level data were available for 4662 infants admitted to 159 units in 7 networks; 28% of the infants were cared for in units with infant-parent rooms. Neonates from units with infant-parent rooms had lower odds of mortality or major morbidity (aOR, 0.76; 95% CI, 0.64-0.89), including lower odds of sepsis and bronchopulmonary dysplasia, than those from units without infant-parent rooms. The adjusted mean length of stay was 3.4 days shorter (95%, CI -4.7 to -3.1) in the units with infant-parent rooms. CONCLUSIONS: The majority of units in high-income countries lack facilities to support parents' presence in their infants' rooms 24 hours per day. The availability vs absence of infant-parent rooms was associated with lower odds of composite outcome of mortality or major morbidity and a shorter length of stay.

Cross-sectional study identifying high-alert substances in medication error reporting among Swedish paediatric inpatients.

AIM: The aims were to characterise paediatric medication errors and to identify the prevalence of known high-alert substances in these errors. METHODS: All paediatric drug-related incident reports and complaints nationally reported to the Health and Social Care Inspectorate in Sweden 2011-2017 regarding inpatients were characterised by context and modal details. In addition, drug use at a university hospital was matched to local incident reports. Drug substances were classified using three high-alert lists. RESULTS: On a national level, there were 160 reports (2.5 per 10 000 patients) in which the three high-alert lists were found in different degrees (17/35/47%). Morphine (n = 12), vancomycin (n = 11) and potassium (n = 7) were most frequently involved. Eighty per cent of the reports concerned patients aged 0-6 years. Intravenous was the most common route of administration (66%). On a university hospital level, the prevalence of all types of drug incidents reports was 1.7% among all inpatients. The prevalence of local incident reports involving high-alert substances was almost double that of non-alert substances. CONCLUSION: Existing high-alert drug lists are relevant for paediatric inpatients. A higher awareness and usage of such lists among hospital staff prescribing, dispensing and administering drugs to children may have the potential to reduce medication errors.

Lung function and pulmonary vascular resistance are not associated in 6-year-old children born extremely preterm.

AIM: Children born preterm are at increased risk of reduced lung function. The aim was to test whether lung function was associated with pulmonary vascular resistance. METHODS: Participants were recruited from a population-based cohort born in 2004-2007. Lung function was assessed with spirometry after administration of a beta2-agonist. Forced vital capacity (FVC) and forced expiratory volume in one second (FEV1 ) were determined. Estimations of pulmonary vascular resistance, arterial dimensions, right ventricular wall thickness, sphericity, and systolic (TAPSE) and diastolic functions were performed with echocardiography. Adjusted regression analyses were used to study associations. RESULTS: Sixty-six children (33 boys) born at 22-26 weeks of gestational age (birthweights 460-1134 g) were assessed at a mean age of 6.7 years. Despite large variations in lung function with FVC z-scores ranging from -4.6 to +2.8, there were no associations between lung function and pulmonary arterial pressure, right ventricular structure or function. Children with higher FVC z-scores (r = .52, ß = .55 mm, P = .015) and higher FEV1 z-scores (r = .58, ß = .73 mm, P = .001) exhibited larger pulmonary arteries. CONCLUSION: In children born extremely preterm, lung function was not associated with pulmonary vascular resistance. Routine echocardiographic evaluation of extremely preterm children may not be indicated at age 6.5 years.

Survey shows marked variations in approaches to redirection of care for critically ill very preterm infants in 11 countries.

AIM: We surveyed care practices for critically ill very preterm infants admitted to neonatal intensive care units (NICUs) in the International Network for Evaluating Outcomes in Neonates (iNeo) to identify differences relevant to outcome comparisons. METHODS: We conducted an online survey on care practices for critically ill very preterm infants and infants with severe intracranial haemorrhage (ICH). The survey was distributed in 2015 to representatives of 390 NICUs in 11 countries. Survey replies were compared with network incidence of death and severe ICH for infants born between 230/7 and 286/7  weeks of gestation from January 1, 2015, to December 31, 2015. RESULTS: Most units in Israel, Japan and Tuscany, Italy, favoured withholding care when care was considered futile, whereas most units in other networks favoured redirection of care. For infants with bilateral grade 4 ICH, redirection of care was very frequently (≥90% of cases) offered in the majority of units in Australia and New Zealand and Switzerland, but rarely in other networks. Networks where redirection of care was frequently offered for severe ICH had lower rates of survivors with severe ICH. CONCLUSION: We identified marked inter-network differences in care approaches that need to be considered when comparing outcomes.

Review of guidelines and recommendations from 17 countries highlights the challenges that clinicians face caring for neonates born to mothers with COVID-19.

AIM: This review examined how applicable national and regional clinical practice guidelines and recommendations for managing neonates born to mothers with COVID-19 mothers were to the evolving pandemic. METHODS: A systematic search and review identified 20 guidelines and recommendations that had been published by May 25, 2020. We analysed documents from 17 countries: Australia, Brazil, Canada, China, France, India, Italy, Japan, Saudi Arabia, Singapore, South Africa, South Korea, Spain, Sweden, Switzerland, the UK and the United States. RESULTS: The documents were based on expert consensus with limited evidence and were of variable, low methodological rigour. Most did not provide recommendations for delivery methods or managing symptomatic infants. None provided recommendations for post-discharge assimilation of potentially infected infants into the community. The majority encouraged keeping mothers and infants together, subject to infection control measures, but one-third recommended separation. Although breastfeeding or using breastmilk was widely encouraged, two countries specifically prohibited this. CONCLUSION: The guidelines and recommendations for managing infants affected by COVID-19 were of low, variable quality and may be unsustainable. It is important that transmission risks are not increased when new information is incorporated into clinical recommendations. Practice guidelines should emphasise the extent of uncertainty and clearly define gaps in the evidence.