Extremely Premature Births During the Peak of the COVID-19 Pandemic: an International Study of the Active SafeBoosC III Departments

On the 11th of March 2020, COVID-19 was declared a pandemic by the World Health Organisation,
which led to an almost worldwide lockdown (1). During the lockdown, reductions in preterm
birth rates and very low birth weight infants have been reported in both Danish and Irish
studies. Within the SafeBoosC-III investigator group, several neonatologists concurrently
observed that the number of extremely low gestational age neonates (ELGAN) (gestational age
below 28 weeks) admitted to their respective departments, had declined during the pandemic,
while others observed no difference in the number of admitted ELGAN (oral communication).
Furthermore, despite a 60% increase in the number of hospitals open for randomisation in the
SafeBoosC-III trial from January to May, the randomisation rate has not increased as
expected. Investigators are therefore curious to evaluate if the number of admitted extremely
preterm infants has decreased in the SafeBoosC-III departments during the global lockdown,
and whether there is an association between the level of lockdown restrictions and change in
the number of ELGAN admissions. Investigators hope that this study will contribute further to
the knowledge of the COVID-19 pandemics' effect on ELGAN birth as well as its effect on
international randomised clinical trials.

This is a retrospective, observational study based on the consortium of the SafeBoosC-III
randomised clinical trial. The SafeBoosC-III trial investigates the benefit and harms of
treatment guided by cerebral near-infrared spectroscopy monitoring compared with treatment
and monitoring as usual in extremely preterm infants. All 79 neonatal intensive care units
(NICU) that are active in the consortium will be invited to participate in this study.
Primary investigators will be contacted and asked to provide the number of extremely low
gestational age neonates (ELGAN) admitted to their NICU within the most rigorous three months
of the COVID-19 pandemic as well as the number of ELGAN admitted within the same period in
2019. The most rigorous three months of the COVID-19 pandemic will be a subjective definition
by the local investigator, based on when the lockdown restrictions were strictest.
Investigators will be asked to clarify how and where the information has been obtained from.
Furthermore, investigators will be asked to classify the level of restrictions imposed upon
the public, during the lockdown period, in a Likert scale format from 1-5. Additionally,
investigators will be asked to categorize the impact of the COVID-19 lockdown on the everyday
life of a pregnant woman.

The number of ELGAN admissions during the three peak months in total, during the same months
in 2019, within each region and within each level of lockdown restriction, will be reported
as numbers. The primary outcome and the secondary outcome regarding the difference in the
number of ELGAN admissions between years and regions will be analysed by using Fisher's Exact
test for 1x2 tables. To analyse the correlation between the level of lockdown restrictions
and the change in number of ELGAN admissions, investigators will use simple linear
regression. The exploratory outcome investigating if lockdown restrictions could lead to
non-admittance of ELGAN will not undergo statistical analysis but will be reported and
discussed. For the primary outcome, an alfa level of 5% is chosen as a threshold for
significance. To correct for multiple testing in the secondary outcomes, investigators have
chosen an alfa level of 1%

In a previous funding application for the SafeBoosC-III trial, investigators estimated that
the 93 departments taking part in the application, had a total of 3000 ELGAN admissions per
year. Therefore, investigators expect participating departments on average to have had
approximately 30 admissions in 2019, i.e. approximately seven admissions in a three months
period. Therefore, if half of the NICUs (i.e. 40 departments) participate, investigators
would expect a total of 280 EP infant admissions within the 40 departments in 2019. Thus, a
16.5% change in the primary outcome is needed to show a statistical significance at a 5% alfa
level.