Severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) is a virus that causesneurological symptoms in a significant proportion of patients in addition to respiratorysymptoms. Intrauterine exposure to the virus has been demonstrated to exert a detrimentaleffect on the developing nervous system. However, developmental disorders frequentlyremain undetected until late infancy or early childhood. Consequently, there is a paucityof published data on neurodevelopment in young children following SARS-CoV-2 infection oftheir pregnant mothers.To this end, detailed data from children aged 36-60 months exposed to SARS-CoV-2 in uterowill be compared with unexposed children of the same age on several clinical outcomeparameters. Data in this cohort study will be adjusted for possible confoundingvariables, such as gestational age at birth, sex, or umbilical arterial pH, in order toinvestigate a relative risk of intrauterine SARS-CoV-2 infection on clinical outcomes,such as child development. Furthermore, the potential protective effect of SARS-CoV-2vaccination during pregnancy will be investigated.This study will provide significant data on the clinical outcomes of children exposedperinatally to SARS-CoV-2. The findings will enable healthcare providers to establish arisk score-adapted follow-up strategy for the general paediatric population of infants.
In Utero Exposure to SARS-CoV-2 - the CRONOS registry The "COVID-19 Related Obstetric and
Neonatal Outcome Study" (CRONOS) investigated the short-term effects of SARS-CoV-2
infections on mothers and their newborns during pregnancy. From April 3rd, 2020, to
February 10th, 2023, data on 8,540 women and their newborns were collected, with active
participation from 130 out of 686 (19%) German obstetric hospitals. The study was
approved by the ethics committees of the coordinating center (UKSH Kiel, AZ: D 451/20)
and each participating hospital. Information about CRONOS has been published on the
German Society of Perinatal Medicine´s website, www.dgpm-online.org, and the German
Clinical Trials Registry (DRKS00021208). About 2,000 women agreed to be contacted again
for further follow-up.
The CRONOS-Kids study focuses on child health and will study some of the
intrauterine-exposed children longitudinally. As an increased rate of placentitis with a
concomitant increased risk of stillbirth and preterm delivery has been seen in infections
with the Alpha and Delta variants, women with an SARS-CoV-2 infection between January
2021 and December 2021, initially recruited in the five participating university
hospitals, will be contacted.
Recruiting for CRONOS-Kids On each of the five research sites, women initially
participating in CRONOS will be invited via email, letter, or by phone to participate in
the CRONOS-Kids study.
Unexposed children and their parents will be invited to participate via their local
pediatricians.
All women will be able to book appointments at their respective hospitals via a dedicated
website (http://cronos-kids.de). The management of patient contact will be conducted
exclusively by non-examiners. Pseudonymization will be used.
Study instruments All children will undergo examination by personnel specifically trained
for this purpose. In order to assess potential motor and cognitive deficiencies, the
M-ABC-2 and the ASQ-3 will be utilised. Furthermore, social-emotional aspects will be
addressed using a specific SE-test.
Questions of a general nature will address the subjects of pregnancy, birth, and social
circumstances, with a view to identifying potential sources of bias with regard to
developmental delays.
Potential bias To circumvent any potential bias in the study, responsibility for patient
contact and examinations will be allocated to different members of the research team.
Personnel conducting neurodevelopmental testing will adhere to the principles of
blinding, ensuring that they remain unaware of the subjects' exposure status.
We expect a bias in the participation of highly educated and German-speaking families.
This is likely to affect both the exposed and non-exposed groups.
Statistical analysis The Marburg University research team will manage data refinement.
Analysis will control for potential confounders such as children´s sex, weeks of
gestational age at birth, asphyxia at birth and social circumstances.
To be able to measure a mean effect in an unpaired t-test with an alpha level of 0.05 and
a power of 0.8 (Cohen's d = 0.5), 64 subjects per group are required, i.e
Inclusion Criteria:
- Toddlers (age 33 to 60 months), who were exposed (case) or not exposed (controll)
with SARS-CoV-2 intrauterin.
Exclusion Criteria:
- No parental consent
Philipps University of Marburg
Marburg, Germany
Not Provided