Neurodevelopmental DisordersNCT06199362
Early Life Anemia and Children's Risk of Neurodevelopmental Disorders: National and Regional Register-based Studies
An observational study of Neurodevelopmental Disorders and Autism, run by Karolinska Institutet at 1 site in Sweden.
Trial summary
The overall project aim is to study children's neurodevelopmental outcomes (including diagnoses of autism, ADHD, and intellectual disability) following exposure to maternal anemia during pregnancy or anemia during the first year of life using national and regional Swedish health-data registers, and to assess… Read more about this study
- Who is it for?
- Ages 2 to 18 yearsHealthy volunteers can take part
- Conditions the study is for
- Neurodevelopmental Disorders, Autism, ADHD
- How many people
- 2,400,000 participants
- Where
- 1 siteSweden
- Study dates
- 15 Aug 2023to Dec 2024
- How long will I take part?
- 12 Years
- Phase
- Observational
- Are there results?
- None posted in the registry
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 2 to 18 years
- All sexes
- Healthy volunteers accepted
- Child, Adult
Study population: We will study the total population of children born in Sweden January 1, 1987 to December 31, 2010 (national cohort) and children born in Region Stockholm from January 1, 2007 to December 31, 2010 (Stockholm regional cohort) with maternal health and birth records available for the index pregnancy. Since records in Medical Birth Register are available for >98% of births in Sweden, we anticipate that we will need to exclude relatively few births. Children will be followed up for neurodevelopmental outcomes using Swedish health registers; the only loss to follow-up that is expected is emigration from Sweden or death of the child.
Who may be able to join
- children born in Sweden from January 1, 1987 to December 31, 2010 (national cohort)
- children born in Region Stockholm from January 1, 2007 to December 31, 2010 (Stockholm regional cohort)
Who cannot join
- Adopted children
- Children without records in the Medical Birth Registry (MBR)
Trial locations and contacts
1 site in 1 country.
About this study
The overall project aim is to study children's neurodevelopmental outcomes (including diagnoses of autism, ADHD, and intellectual disability) following exposure to maternal anemia during pregnancy or anemia during the first year of life using national and regional Swedish health-data registers, and to assess children's neurodevelopmental outcomes over the range of maternal hemoglobin levels during pregnancy.
Read the detailed description
Our overall hypothesis is that early life iron sufficiency may promote appropriate neurodevelopment and reduce risk of neurodevelopmental disorders in children. We will use Swedish register data to define a cohort of maternal-child pairs to follow from gestation through childhood. We will consider exposure to anemia during two key time periods: gestation and the first year of life. Exposure data are recorded in Swedish medical records prospectively relative to the follow-up for the outcomes.
To assess exposure to maternal anemia, we will consider maternal diagnoses of anemia during pregnancy in a national cohort of maternal-child pairs, using ICD codes recorded in pregnancy in the Swedish National Patient Register and the Swedish Medical Birth Register. In a sub-sample of mother-child pairs in Stockholm with data available from antenatal records (i.e., Obstetrix register data), we will also collect data regarding levels of maternal hemoglobin measured longitudinally over the course of pregnancy, and consider this as a continuous variable and divided into categories to reflect the full range of potential exposures from very low to very high. We will consider whether risk of the outcomes associated with exposure to anemia or decreasing hemoglobin levels vary with the time of onset during pregnancy.
To assess exposure to anemia during the first year of life, we will consider infant's diagnoses of anemia during the first year of life in a national cohort of maternal-child pairs, using ICD codes recorded during the year after birth in the Swedish National Patient Register. We will consider whether risk of the outcomes associated with exposure to anemia during vary with the time of onset during the first year of life, and whether anemia during the first year interacts with gestational age at birth.
The main outcome measures will be incidence of children's diagnoses of any of three common neurodevelopmental conditions: autism, attention-deficit/hyperactivity disorder (ADHD), and intellectual disability. Diagnoses will be ascertained using ICD codes recorded in pregnancy in the Swedish National Patient Register. For the sub-sample of mother-child pairs for children born in Stockholm, we will also ascertain outcomes in regional registers that capture further sources of outpatient treatment and care, primarily the VAL database. Secondary analyses will consider the incidence of commonly co-occurring combinations of the disorders (e.g., autism with co-occurring intellectual disability).
- Conditions
- Neurodevelopmental Disorders, Autism, ADHD, Intellectual Disability, Anemia
- Medical subject headings
- Neurodevelopmental Disorders, Autistic Disorder, Attention Deficit Disorder with Hyperactivity, Intellectual Disability, Anemia
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 |
|---|---|---|
| Swedish National Cohort | Children born in Sweden during the years 1987-2010, to be followed for diagnoses of neurodevelopmental disorders. | |
| Stockholm Regional Obstetrix Cohort | Children born in Region Stockholm during the years 2007-2010, to be followed for diagnoses of neurodevelopmental disorders. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Autism
ICD-9: 299; ICD-10: F84
Measured: Children's diagnoses of autism, with follow up beginning at 2 years of age.
ADHD
ICD-9: 314; ICD-10: F90; supplemented with methylphenidate [N06BA04] or atomoxetin [N06BA09] prescriptions registered in the Swedish Prescribed Drug Register
Measured: Children's diagnoses of ADHD, with follow up beginning at 2 years of age.
Intellectual Disability
ICD-9: 317-319 ICD-10: F70-F79
Measured: Children's diagnoses of intellectual disability, with follow up beginning at 2 years of age.
Any Neurodevelopmental Condition
Any diagnosis of Autism, ADHD, or Intellectual Disability
Measured: Children's diagnoses of neurodevelopmental conditions, with follow up beginning at 2 years of age.
Secondary outcomes (5)
Autism with Intellectual Disability
Diagnosis of both autism and intellectual disability during the follow-up period.
Measured: Children's diagnoses, with follow up beginning at 2 years of age.
Autism with ADHD
Diagnosis of both autism and ADHD during the follow-up period.
Measured: Children's diagnoses, with follow up beginning at 2 years of age.
Autism without co-morbidities (ADHD or ID)
Diagnosis of autism without a diagnosis of ADHD or intellectual disability during the follow-up period.
Measured: Children's diagnoses, with follow up beginning at 2 years of age.
ADHD without co-morbidities (ID or Autism)
Diagnosis of ADHD without a diagnosis of autism or intellectual disability during the follow-up period.
Measured: Children's diagnoses, with follow up beginning at 2 years of age.
Intellectual Disability without Autism
Diagnosis of intellectual disability without a diagnosis of autism during the follow-up period.
Measured: Children's diagnoses, with follow up beginning at 2 years of age.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Jan 2024
- Study start15 Aug 2023
- Primary completionDec 2024 (estimated)
- Study completionDec 2024 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Neurodevelopmental DisordersStudies of the same condition, open and under way.
- More trials run by Karolinska InstitutetThe sponsor's other registered studies.
- 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
- 2,400,000 participants (estimated)
- Target duration
- 12 Years
Sponsor and investigators
- Lead sponsor
- Karolinska Institutet
- Sponsor type
- University, hospital or other
- Collaborators
- The Swedish Research Council
- Responsible party
- Principal investigator, Renee Gardner, Karolinska Institutet
- Investigators
- Renee M. Gardner, PhD, Principal investigator, Karolinska Institutet
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06199362
- Sponsor's protocol ID
- VR2022-00592_1
- Other IDs
- DNR2010/1185-31/5
- Status last verified
- Dec 2023
- First submitted
- 29 Dec 2023
- Last updated
- 10 Jan 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 10 Jan 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Early Life Anemia and Children's Risk of Neurodevelopmental Disorders: National and Regional Register-based Studies
- ClinicalTrials.gov ID
- NCT06199362
- Acronym / sponsor ID
- VR2022-00592_1
- Conditions
- Neurodevelopmental Disorders, Autism, ADHD, Intellectual Disability, Anemia
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 2,400,000 participants (estimated)
- Lead sponsor
- Karolinska InstitutetUniversity, hospital or other
- Collaborators
- The Swedish Research Council
- Study start
- 15 Aug 2023 (actual)
- Primary completion
- Dec 2024 (estimated)
- Study completion
- Dec 2024 (estimated)
- First posted
- 10 Jan 2024 (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.
The overall project aim is to study children's neurodevelopmental outcomes (including diagnoses of autism, ADHD, and intellectual disability) following exposure to maternal anemia during pregnancy or anemia during the first year of life using national and regional Swedish health-data registers, and to assess children's neurodevelopmental outcomes over the range of maternal hemoglobin levels during pregnancy.
Detailed description
Our overall hypothesis is that early life iron sufficiency may promote appropriate neurodevelopment and reduce risk of neurodevelopmental disorders in children. We will use Swedish register data to define a cohort of maternal-child pairs to follow from gestation through childhood. We will consider exposure to anemia during two key time periods: gestation and the first year of life. Exposure data are recorded in Swedish medical records prospectively relative to the follow-up for the outcomes.
To assess exposure to maternal anemia, we will consider maternal diagnoses of anemia during pregnancy in a national cohort of maternal-child pairs, using ICD codes recorded in pregnancy in the Swedish National Patient Register and the Swedish Medical Birth Register. In a sub-sample of mother-child pairs in Stockholm with data available from antenatal records (i.e., Obstetrix register data), we will also collect data regarding levels of maternal hemoglobin measured longitudinally over the course of pregnancy, and consider this as a continuous variable and divided into categories to reflect the full range of potential exposures from very low to very high. We will consider whether risk of the outcomes associated with exposure to anemia or decreasing hemoglobin levels vary with the time of onset during pregnancy.
To assess exposure to anemia during the first year of life, we will consider infant's diagnoses of anemia during the first year of life in a national cohort of maternal-child pairs, using ICD codes recorded during the year after birth in the Swedish National Patient Register. We will consider whether risk of the outcomes associated with exposure to anemia during vary with the time of onset during the first year of life, and whether anemia during the first year interacts with gestational age at birth.
The main outcome measures will be incidence of children's diagnoses of any of three common neurodevelopmental conditions: autism, attention-deficit/hyperactivity disorder (ADHD), and intellectual disability. Diagnoses will be ascertained using ICD codes recorded in pregnancy in the Swedish National Patient Register. For the sub-sample of mother-child pairs for children born in Stockholm, we will also ascertain outcomes in regional registers that capture further sources of outpatient treatment and care, primarily the VAL database. Secondary analyses will consider the incidence of commonly co-occurring combinations of the disorders (e.g., autism with co-occurring intellectual disability).
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Target follow-up
- 12 Years
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Swedish National Cohort | – | –Children born in Sweden during the years 1987-2010, to be followed for diagnoses of neurodevelopmental disorders. |
| Stockholm Regional Obstetrix Cohort | – | –Children born in Region Stockholm during the years 2007-2010, to be followed for diagnoses of neurodevelopmental disorders. |
Who may qualify
- Ages
- 2 to 18 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child, Adult
- Study population
- We will study the total population of children born in Sweden January 1, 1987 to December 31, 2010 (national cohort) and children born in Region Stockholm from January 1, 2007 to December 31, 2010 (Stockholm regional cohort) with maternal health and birth records available for the index pregnancy. Since records in Medical Birth Register are available for >98% of births in Sweden, we anticipate that we will need to exclude relatively few births. Children will be followed up for neurodevelopmental outcomes using Swedish health registers; the only loss to follow-up that is expected is emigration from Sweden or death of the child.
Key inclusion criteria (2 listed)
- children born in Sweden from January 1, 1987 to December 31, 2010 (national cohort)
- children born in Region Stockholm from January 1, 2007 to December 31, 2010 (Stockholm regional cohort)
Key exclusion criteria (2 listed)
- Adopted children
- Children without records in the Medical Birth Registry (MBR)
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
Autism
Time frame: Children's diagnoses of autism, with follow up beginning at 2 years of age.
ICD-9: 299; ICD-10: F84
ADHD
Time frame: Children's diagnoses of ADHD, with follow up beginning at 2 years of age.
ICD-9: 314; ICD-10: F90; supplemented with methylphenidate [N06BA04] or atomoxetin [N06BA09] prescriptions registered in the Swedish Prescribed Drug Register
Intellectual Disability
Time frame: Children's diagnoses of intellectual disability, with follow up beginning at 2 years of age.
ICD-9: 317-319 ICD-10: F70-F79
Any Neurodevelopmental Condition
Time frame: Children's diagnoses of neurodevelopmental conditions, with follow up beginning at 2 years of age.
Any diagnosis of Autism, ADHD, or Intellectual Disability
5 secondary outcomes
Autism with Intellectual Disability
Time frame: Children's diagnoses, with follow up beginning at 2 years of age.
Autism with ADHD
Time frame: Children's diagnoses, with follow up beginning at 2 years of age.
Autism without co-morbidities (ADHD or ID)
Time frame: Children's diagnoses, with follow up beginning at 2 years of age.
ADHD without co-morbidities (ID or Autism)
Time frame: Children's diagnoses, with follow up beginning at 2 years of age.
Intellectual Disability without Autism
Time frame: Children's diagnoses, with follow up beginning at 2 years of age.
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Jan 2024.
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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. This study is not recruiting at the moment.
Renee M. Gardner, PhD principal investigator
Karolinska Institutet
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 Neurodevelopmental Disorders and Autism, run by Karolinska Institutet at 1 site in Sweden.
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 2 inclusion and 2 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: status not confirmed, as of the sponsor's last update on 10 Jan 2024. 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 Sweden. 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?
Results are not available in the source record.
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?
Autism (time frame: Children's diagnoses of autism, with follow up beginning at 2 years of age.). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 10 Jan 2024; AzTrials last refreshed its copy on 8 Nov 2026.