Foetal macrosomia — incidence, determinants and neonatal outcomes: 10-years retrospective review, 2010–2019

Objectives: Prevalence of macrosomia differs worldwide according to studied population and has been variable over last few decades. The objective of the study was to determine the trends in incidence and clinical characteristics of infants with macrosomia born in two diverse Polish neonatal centres from 2010–2019. Material and methods: Trends in the incidence of macrosomia, maternal age, delivery mode and neonatal complications were analysed over a 10 year period based on birth medical records. Results: The total number of 43 165 term neonates were analysed with macrosomia incidence of 16.63% (n = 7179). The prevalence of macrosomia was stable from 2010–2019 irrespectively of referentiality and geographical area. Mean maternal age increased over the decade with higher age of mothers of macrosomic neonates. Recognizability of gestation diabetes among pregnant women increased from 9.61% in 2010 to 15.27% in 2019 and it was comparable in mothers of macrosomic infants. The percentage of caesarean sections was higher in macrosomic neonates and gradually increased over last decade. The highest percentage of birth injuries was observed in the first grade of macrosomia (4000–4499 g). The number of neonatal complications including lower Apgar score, respiratory and cardiology symptoms correlated with severity of macrosomia, with highest morbidity in children above 5000 g. Conclusions: The prevalence of macrosomia in the studied cohort remained invariable over the last decade. Macrosomia is associated with an increased rate of caesarean sections, higher maternal age and increased neonatal morbidity. A higher macrosomia grade is related to a worse neonatal outcome. Further studies on other risk factors of macrosomia are needed

Extremely Preterm Infant Admissions Within the SafeBoosC-III Consortium During the COVID-19 Lockdown

Objective: To evaluate if the number of admitted extremely preterm (EP) infants (born before 28 weeks of gestational age) differed in the neonatal intensive care units (NICUs) of the SafeBoosC-III consortium during the global lockdown when compared to the corresponding time period in 2019. Design: This is a retrospective, observational study. Forty-six out of 79 NICUs (58%) from 17 countries participated. Principal investigators were asked to report the following information: (1) Total number of EP infant admissions to their NICU in the 3 months where the lockdown restrictions were most rigorous during the first phase of the COVID-19 pandemic, (2) Similar EP infant admissions in the corresponding 3 months of 2019, (3) the level of local restrictions during the lockdown period, and (4) the local impact of the COVID-19 lockdown on the everyday life of a pregnant woman. Results: The number of EP infant admissions during the first wave of the COVID-19 pandemic was 428 compared to 457 in the corresponding 3 months in 2019 (−6.6%, 95% CI −18.2 to +7.1%, p = 0.33). There were no statistically significant differences within individual geographic regions and no significant association between the level of lockdown restrictions and difference in the number of EP infant admissions. A post-hoc analysis based on data from the 46 NICUs found a decrease of 10.3%in the total number of NICU admissions (n = 7,499 in 2020 vs. n = 8,362 in 2019). Conclusion: This ad hoc study did not confirm previous reports of a major reduction in the number of extremely pretermbirths during the first phase of the COVID-19 pandemic. Clinical Trial Registration: ClinicalTrial.gov, identifier: NCT04527601 (registered August 26, 2020), https://clinicaltrials.gov/ct2/show/NCT04527601

Protocol for a multicenter, double-blind, randomized, placebo-controlled phase III trial of the inhaled Β2-adrenergic receptor agonist salbutamol for transient tachypnea of the newborn (the REFSAL trial)

BACKGROUND: Transient tachypnea of the newborn (TTN), which results from inadequate absorption of fetal lung fluid, is the most common cause of neonatal respiratory distress. Stimulation of β-adrenergic receptors enhances alveolar fluid absorption. Therefore, the β2-adrenergic receptor agonist salbutamol has been proposed as a treatment for TTN. This study aims to evaluate the efficacy and safety of salbutamol as supportive pharmacotherapy together with non-invasive nasal continuous positive airway pressure (NIV/nCPAP) for the prevention of persistent pulmonary hypertension of the newborn (PPHN) in infants with TTN. METHODS AND ANALYSIS: This multicenter, double-blind, phase III trial will include infants with a gestational age between 32 and 42 weeks who are affected by respiratory disorders and treated in eight neonatal intensive care units in Poland. A total of 608 infants within 24 h after birth will be enrolled and randomly assigned (1:1) to receive nebulized salbutamol with NIV or placebo (nebulized 0.9% NaCl) with NIV. The primary outcome is the percentage of infants with TTN who develop PPHN. The secondary outcomes are the severity of respiratory distress (assessed with the modified TTN Silverman score), frequency of need for intubation, duration of NIV and hospitalization, acid–base balance (blood pH, partial pressure of O(2) and CO(2), and base excess), and blood serum ionogram for Na(+), K(+), and Ca(2+). DISCUSSION: The Respiratory Failure with Salbutamol (REFSAL) study will be the first clinical trial to evaluate the efficacy and safety of salbutamol in the prevention of persistent pulmonary hypertension in newborns with tachypnea, and will improve short term outcomes. If successful, the study will demonstrate the feasibility of early intervention with NIV/nCPAP together with nebulized salbutamol in the management of TTN. ETHICS AND DISSEMINATION: The study protocol was approved by the Bioethics Committee of the Medical University of Warsaw, Warsaw, Poland on November 16, 2020 (decision number KB/190/2020). All procedures will follow the principles of the Declaration of Helsinki. The results of the study will be submitted for knowledge translation in peer-reviewed journals and presented at national and international pediatric society conferences. CLINICAL TRIAL REGISTRATION: It is registered at ClinicalTrials.gov NCT05527704, EudraCT 2020-003913-36; Protocol version 5.0 from 04/01/2022

Assessment of an optimized manufacturing process for inactivated quadrivalent influenza vaccine: a phase III, randomized, double-blind, safety and immunogenicity study in children and adults

Abstract Background GSK has modified the licensed monovalent bulk manufacturing process for its split-virion inactivated quadrivalent influenza vaccine (IIV4) to harmonize the process among different strains, resulting in an increased number of finished vaccine doses, while compensating for the change from inactivated trivalent influenza vaccine (IIV3) to IIV4. To confirm the manufacturing changes do not alter the profile of the vaccine, a clinical trial was conducted to compare IIV4 made by the currently licensed process with a vaccine made by the new (investigational) process (IIV4-I). The main objectives were to compare the reactogenicity and safety of IIV4-I versus IIV4 in all age groups, and to demonstrate the non-inferiority of the hemagglutination-inhibition (HI) antibody responses based on the geometric mean titer ratio of IIV4-I versus IIV4 in children. Methods The Phase III, randomized, double-blind, multinational study included three cohorts: adults (18–49 years; N = 120), children (3–17 years; N = 821), and infants (6–35 months; N = 940). Eligible subjects in each cohort were randomized 1:1 to receive IIV4-I or IIV4. Both vaccines contained 15 μg of hemagglutinin antigen for each of the four seasonal virus strains. Adults and vaccine-primed children received one dose of vaccine, and vaccine-unprimed children received two doses of vaccine 28 days apart. All children aged ≥9 years were considered to be vaccine-primed and received one dose of vaccine. Results The primary immunogenicity objective of the study was met in demonstrating immunogenic non-inferiority of IIV4-I versus IIV4 in children. The IIV4-I was immunogenic against all four vaccine strains in each age cohort. The reactogenicity and safety profile of IIV4-I was similar to IIV4 in each age cohort, and there was no increase in the relative risk of fever (≥38 °C) with IIV4-I versus IIV4 within the 7-day post-vaccination period in infants (1.06; 95% Confidence Interval: 0.75, 1.50; p = 0.786). Conclusions The study demonstrated that in adults, children, and infants, the IIV4-I made using an investigational manufacturing process was immunogenic with a reactogenicity and safety profile that was similar to licensed IIV4. These results support that the investigational process used to manufacture IIV4-I is suitable to replace the current licensed process. Trial registration ClinicalTrials.gov: NCT02207413; trial registration date: August 4, 2014

Additional file 2: of Assessment of an optimized manufacturing process for inactivated quadrivalent influenza vaccine: a phase III, randomized, double-blind, safety and immunogenicity study in children and adults

Serious adverse events in infants (6–35 months), children (3–17 years), and adults (18–49 years) during the entire study (total vaccinated cohort). (PDF 362 kb

Additional file 1: of Assessment of an optimized manufacturing process for inactivated quadrivalent influenza vaccine: a phase III, randomized, double-blind, safety and immunogenicity study in children and adults

Solicited oculorespiratory syndrome–like symptoms within the 3-day post vaccination period in infants (6–35 months), children (3–17 years), and adults (18–49 years) (total vaccinated cohort). (PDF 378 kb