Clinical trial NCT06199362: Early Life Anemia and Children's Risk of Neurodevelopmental Disorders: National and Regional Register-based Studies
Official title: Early Life Anemia and Children's Risk of Neurodevelopmental Disorders: National and Regional Register-based Studies
Study type: OBSERVATIONAL
Overall status: ACTIVE_NOT_RECRUITING
Conditions: Neurodevelopmental Disorders
Autism
ADHD
Intellectual Disability
Anemia
Lead sponsor: Karolinska Institutet
Sponsor class: OTHER
Collaborators: name: The Swedish Research Council
First posted: 2024-01-10
Enrollment: 2400000
Sex: ALL
Minimum age (years): 2
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
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.

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).

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)

Primary outcomes:
measure: Autism
timeFrame: Children's diagnoses of autism, with follow up beginning at 2 years of age.
measure: ADHD
timeFrame: Children's diagnoses of ADHD, with follow up beginning at 2 years of age.
measure: Intellectual Disability
timeFrame: Children's diagnoses of intellectual disability, with follow up beginning at 2 years of age.
measure: Any Neurodevelopmental Condition
timeFrame: Children's diagnoses of neurodevelopmental conditions, with follow up beginning at 2 years of age.
Secondary outcomes:
measure: Autism with Intellectual Disability
timeFrame: Children's diagnoses, with follow up beginning at 2 years of age.
measure: Autism with ADHD
timeFrame: Children's diagnoses, with follow up beginning at 2 years of age.
measure: Autism without co-morbidities (ADHD or ID)
timeFrame: Children's diagnoses, with follow up beginning at 2 years of age.
measure: ADHD without co-morbidities (ID or Autism)
timeFrame: Children's diagnoses, with follow up beginning at 2 years of age.
measure: Intellectual Disability without Autism
timeFrame: Children's diagnoses, with follow up beginning at 2 years of age.
Other outcomes:
Locations:
city: Stockholm
country: Sweden
facility: Karolinska Institutet
Study officials:
affiliation: Karolinska Institutet
name: Renee M. Gardner, PhD
role: PRINCIPAL_INVESTIGATOR
References: