Early Life Anemia and Children's Risk of Neurodevelopmental Disorders: National and Regional Register-based Studies

NCT ID: NCT06199362

Last Updated: 2024-01-10

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Total Enrollment: 2400000 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2023-08-15
• Study Completion Date: 2024-12-31

Brief 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 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).

Conditions

Neurodevelopmental Disorders; Autism; ADHD; Intellectual Disability; Anemia

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Study Groups

Swedish National Cohort

Children born in Sweden during the years 1987-2010, to be followed for diagnoses of neurodevelopmental disorders.

No interventions assigned to this group

Stockholm Regional Obstetrix Cohort

Children born in Region Stockholm during the years 2007-2010, to be followed for diagnoses of neurodevelopmental disorders.

No interventions assigned to this group

Eligibility Criteria

Inclusion Criteria

• 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)

Exclusion Criteria

• Adopted children
• Children without records in the Medical Birth Registry (MBR)

• Minimum Eligible Age: 2 Years
• Maximum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

The Swedish Research Council

OTHER_GOV

Sponsor Role: collaborator

Karolinska Institutet

OTHER

Sponsor Role: lead

Responsible Party

Renee Gardner

Principal Researcher

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Renee M. Gardner, PhD

Role: PRINCIPAL_INVESTIGATOR

Karolinska Institutet

Locations

Karolinska Institutet

Stockholm, , Sweden

Countries

Sweden

Other Identifiers

DNR2010/1185-31/5

Identifier Type: OTHER

Identifier Source: secondary_id

VR2022-00592_1

Identifier Type: -

Identifier Source: org_study_id