SARS CoV-2CRONOS-KidsNCT06968897
Neurological Development In Toddlers After Maternal SARS-CoV-2 Infection During Pregnancy
An observational study of SARS CoV-2 and Developmental Disorder, run by Philipps University Marburg at 1 site in Germany.
Trial summary
Severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) is a virus that causes neurological symptoms in a significant proportion of patients in addition to respiratory symptoms. Intrauterine exposure to the virus has been demonstrated to exert a detrimental effect on the developing nervous system. Read more about this study
- Who is it for?
- Ages 3 to 5 yearsHealthy volunteers can take part
- Conditions the study is for
- SARS CoV-2, Developmental Disorder, Pregnancy Related
- How many people
- 250 participants
- Where
- 1 siteGermany
- Study dates
- 1 Apr 2025to 30 Jun 2026
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 3 to 5 years
- All sexes
- Healthy volunteers accepted
- Child
Study population: In a pilot study intrauterine exposed toddlers are eligible for inclusion in the study if their mothers are registered in the CRONOS registry in the following five university hospitals: Marburg University Hospital, Jena University Hospital, Kiel University Hospital, Dresden University Hospital and Freiburg University Hospital. Controls, i.e. infants who have not been exposed to SARS-CoV-2, are eligible for enrolment if they live in the proximity of the recruiting hospitals.
Who may be able to join
- Toddlers (age 33 to 60 months), who were exposed (case) or not exposed (controll) with SARS-CoV-2 intrauterin.
Who cannot join
- No parental consent
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
About this study
Official title: Neurological Development in Toddlers After Maternal SARS-CoV-2 Infection During Pregnancy - A Follow-Up to the Covid-19 Related Obstetric and Neonatal Outcome Study in Germany (CRONOS) With a Dedicated Focus on Child Health
Severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) is a virus that causes neurological symptoms in a significant proportion of patients in addition to respiratory symptoms. Intrauterine exposure to the virus has been demonstrated to exert a detrimental effect on the developing nervous system. However, developmental disorders frequently remain undetected until late infancy or early childhood. Consequently, there is a paucity of published data on neurodevelopment in young children following SARS-CoV-2 infection of their pregnant mothers.
To this end, detailed data from children aged 36-60 months exposed to SARS-CoV-2 in utero will be compared with unexposed children of the same age on several clinical outcome parameters. Data in this cohort study will be adjusted for possible confounding variables, such as gestational age at birth, sex, or umbilical arterial pH, in order to investigate a relative risk of intrauterine SARS-CoV-2 infection on clinical outcomes, such as child development. Furthermore, the potential protective effect of SARS-CoV-2 vaccination during pregnancy will be investigated.
This study will provide significant data on the clinical outcomes of children exposed perinatally to SARS-CoV-2. The findings will enable healthcare providers to establish a risk score-adapted follow-up strategy for the general paediatric population of infants.
Read the detailed description
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
- Conditions
- SARS CoV-2, Developmental Disorder, Pregnancy Related
- Keywords
- SARS-CoV-2, Children, Development, pregnancy
- Medical subject headings
- Developmental Disabilities
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| Exposed intrauterine to SARS-CoV-2 | Toddlers exposed to SARS-CoV-2 (VOC alpha or delta) during their mothers' pregnancy. | |
| Not exposed to SARS-CoV-2 | Toddlers NOT exposed to SARS-CoV-2 (VOC alpha or delta) during their mothers' pregnancy. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Motoric skills
Motoric skills will be measured using the M-ABC-2 ("global rate"), as well as parental self reports in the ASQ-3 (areas: "gross motor" and "fine motor") with age-specific cut-off values.
Measured: 36 to 60 months old children
Secondary outcomes (2)
Communication
Communication will be measured using parental self reports in the ASQ-3 (area: "communication") with age-specific cut-off values.
Measured: 36 to 60 months old children
Personal-Social development
Personal-social development will be measured using parental self reports in the ASQ-3 (area: "personal-social") and self reports in the social-emotional questionaire, both with age-specific cut-off values.
Measured: 36 to 60 months old children
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 May 2025
- Study start1 Apr 2025
- Primary completion31 Dec 2025 (estimated)
- Study completion30 Jun 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for SARS CoV-2Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 250 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Philipps University Marburg
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Dr. med. Nadine Mand, Philipps University Marburg
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06968897
- Sponsor's protocol ID
- AZ 114/22
- Acronym
- CRONOS-Kids
- Status last verified
- May 2025
- First submitted
- 16 Apr 2025
- Last updated
- 13 May 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: Participants did not agree in data sharing.
Publications
Pecks U, Mand N, Kolben T, Rudiger M, Oppelt P, Zollkau J, Dempfle A; The CRONOS registry. SARS-CoV-2 Infection During Pregnancy-An Analysis of Clinical Data From Germany and Austria From the CRONOS Registry. Dtsch Arztebl Int. 2022 Sep 5;119(35-36):588-594. doi: 10.3238/arztebl.m2022.0266.
PubMed 35794736
Study at a glance
From the registry record, last updated by the sponsor on 13 May 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Neurological Development in Toddlers After Maternal SARS-CoV-2 Infection During Pregnancy - A Follow-Up to the Covid-19 Related Obstetric and Neonatal Outcome Study in Germany (CRONOS) With a Dedicated Focus on Child Health
- ClinicalTrials.gov ID
- NCT06968897
- Acronym / sponsor ID
- CRONOS-Kids / AZ 114/22
- Conditions
- SARS CoV-2, Developmental Disorder, Pregnancy Related
- Keywords
- SARS-CoV-2, Children, Development, pregnancy
- Study type
- Observational
- Recruitment status
- Enrolling by invitation
- Enrolment
- 250 participants (estimated)
- Lead sponsor
- Philipps University MarburgUniversity, hospital or other
- Study start
- 1 Apr 2025 (actual)
- Primary completion
- 31 Dec 2025 (estimated)
- Study completion
- 30 Jun 2026 (estimated)
- First posted
- 13 May 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) is a virus that causes neurological symptoms in a significant proportion of patients in addition to respiratory symptoms. Intrauterine exposure to the virus has been demonstrated to exert a detrimental effect on the developing nervous system. However, developmental disorders frequently remain undetected until late infancy or early childhood. Consequently, there is a paucity of published data on neurodevelopment in young children following SARS-CoV-2 infection of their pregnant mothers.
To this end, detailed data from children aged 36-60 months exposed to SARS-CoV-2 in utero will be compared with unexposed children of the same age on several clinical outcome parameters. Data in this cohort study will be adjusted for possible confounding variables, such as gestational age at birth, sex, or umbilical arterial pH, in order to investigate a relative risk of intrauterine SARS-CoV-2 infection on clinical outcomes, such as child development. Furthermore, the potential protective effect of SARS-CoV-2 vaccination during pregnancy will be investigated.
This study will provide significant data on the clinical outcomes of children exposed perinatally to SARS-CoV-2. The findings will enable healthcare providers to establish a risk score-adapted follow-up strategy for the general paediatric population of infants.
Detailed description
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
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Exposed intrauterine to SARS-CoV-2 | – | –Toddlers exposed to SARS-CoV-2 (VOC alpha or delta) during their mothers' pregnancy. |
| Not exposed to SARS-CoV-2 | – | –Toddlers NOT exposed to SARS-CoV-2 (VOC alpha or delta) during their mothers' pregnancy. |
Who may qualify
- Ages
- 3 to 5 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child
- Study population
- In a pilot study intrauterine exposed toddlers are eligible for inclusion in the study if their mothers are registered in the CRONOS registry in the following five university hospitals: Marburg University Hospital, Jena University Hospital, Kiel University Hospital, Dresden University Hospital and Freiburg University Hospital. Controls, i.e. infants who have not been exposed to SARS-CoV-2, are eligible for enrolment if they live in the proximity of the recruiting hospitals.
Key inclusion criteria (1 listed)
- Toddlers (age 33 to 60 months), who were exposed (case) or not exposed (controll) with SARS-CoV-2 intrauterin.
Key exclusion criteria (1 listed)
- No parental consent
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Motoric skills
Time frame: 36 to 60 months old children
Motoric skills will be measured using the M-ABC-2 ("global rate"), as well as parental self reports in the ASQ-3 (areas: "gross motor" and "fine motor") with age-specific cut-off values.
2 secondary outcomes
Communication
Time frame: 36 to 60 months old children
Personal-Social development
Time frame: 36 to 60 months old children
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 May 2025.
- Background: PubMed 35794736Pecks U, Mand N, Kolben T, Rudiger M, Oppelt P, Zollkau J, Dempfle A; The CRONOS registry. SARS-CoV-2 Infection During Pregnancy-An Analysis of Clinical Data From Germany and Austria From the CRONOS Registry. Dtsch Arztebl Int. 2022 Sep 5;119(35-36):588-594. doi: 10.3238/arztebl.m2022.0266.
- This website has been created with the express purpose of providing patients with information regarding the study.Link provided by the sponsor.
- Individual participant dataSharing planned: No. Participants did not agree in data sharing.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of SARS CoV-2 and Developmental Disorder, run by Philipps University Marburg at 1 site in Germany.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: enrolling by invitation, as of the sponsor's last update on 13 May 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Germany. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Motoric skills (time frame: 36 to 60 months old children). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT06968897, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 May 2025.