Neurobehavioral Development in Toddlers and Preschoolers in Relation to Prenatal Exposure of Mild Analgesics (NeuroToP - a COPANA Follow up)

Condition(s) studied

Study summary

Fundamental aspects of both neurological and reproductive function are established in fetal life, and there is a present increased awareness of the potential effects of fetal exposures on neurodevelopmental and reproductive health of offspring. Experimental and epidemiological research studies strongly suggest that paracetamol and NSAID are endocrine disruptive in the fetus, which could increase the risks of some neurodevelopmental, reproductive, and urogenital disorders. In recent years, there has been an increasing rate of neurodevelopmental disorders such as ADHD and autism. The original cohort, the Copenhagen Analgesic Study (COPANA), is the first prospective human study designed primarily to assess the effect of fetal exposure to mild analgesics on male and female reproductive function. If the same children are examined with relevant neurobehavioral testing during mid-childhood, the study design allows the investigators to assess the effect of mild analgesics as well as other EDCs on neurodevelopmental health.

Eligibility

Primary outcome measure(s)

• Behavior Rating Inventory of Executive Function-Preschool Version (BRIEF-P) (male and female children) — 2-5 years of age
  Parents will complete the BRIEF-P to assess their child's executive functioning, and the Global Executive Composite score will be used in the analysis.
• BRIEF-P Global Executive Composite (GEC) (male and female children) — 2-5 years of age
  The Global Executive Composite (GEC) score is derived from the BRIEF-P questionnaire, which includes 63 items assessing executive functioning in preschool-aged children. The GEC score reflects the overall level of executive function difficulties and is calculated from the five clinical subscales: Inhibit, Shift, Emotional Control, Working Memory, and Plan/Organize.
• BRIEF-P Emergent Metacognition Index (male and female children) — 2-5 years
  The EMI score reflects the child's ability to sustain ideas and activities in working memory and to plan and organize problem-solving approaches. It is composed of the Working Memory and Plan/Organize subscales and is critical for developing systematic metacognitive strategies.
• Child Behavioral and Emotional Functioning - Child Behavior Checklist (CBCL) - (male and female children) — 2-5 years of age
  Behavioral and emotional functioning will be assessed using the Child Behavior Checklist (CBCL), a validated parent-report questionnaire. The CBCL provides a Total Score as well as multiple subscale scores reflecting specific behavioral and emotional domains. The questionnaire is completed electronically by the child's mother or father when the child is between 2 and 4 years of age. Unit of Measure: CBCL standardized score (T-score)
• CBCL Total Problem Score (TPS) (male and female children) — 2-5 years of age
  The Total Problem Score (TPS) from the Child Behavior Checklist for Ages 1½-5 (CBCL/1½-5) is derived by summing responses of all items. The possible TPS ranges from 0 to 200, with higher scores representing more severe behavioral and emotional problems. According to standardized CBCL norms. Raw scores are converted to age- and sex-adjusted T-scores for interpretation.
• CBCL Internalizing Score (male and female children) — 2-5 years of age
  The Internalizing Score is based on 24 items assessing emotional symptoms such as anxiety, depression, and withdrawal. The score range is 0-48.
• CBCL Externalizing Score (male and female children) — 2-5 years of age
  The Externalizing Score is based on 36 items assessing behaviors such as aggression and rule-breaking. The score range is 0-72.
• Danish MacArthur-Bates Communicative Development Inventories (MB-CDI) (male and female children) — 2-4 years
  Using the validated Danish MacArthur-Bates Communicative Development Inventories (MB-CDI) "Words and Sentences", which consists of a vocabulary check list (part I) and questions regarding sentences and grammar (part II). Distributed electronically to the mother of the child at age 2-4 years.
• MB-CDI Vocabulary Size (Words Understood and Produced) (male and female children) — 2-4 years
  Assessed using Part I of the validated Danish version of the MacArthur-Bates Communicative Development Inventories (MB-CDI) "Words and Sentences". This section consists of a vocabulary checklist completed by the child's mother. Unit of Measure: Number of words understood and/or produced
• MB-CDI Sentence and Grammar Use (male and female children) — 2-4 years of age
  Assessed using Part II of the Danish MB-CDI "Words and Sentences", which includes questions about the child's use of sentences and grammatical structures. The questionnaire is distributed electronically to the mother. Unit of Measure: Parental report of sentence complexity and grammatical usage (qualitative and/or categorical scoring)
• Preschool Activities Inventory - Gender-typical behavior (male and female children) — 3-5 years
  Using the "Preschool Activities Inventory "(PSAI). This includes 24 items about the child's toy and activity preferences. The inventory holds 12 typical masculine and 12 typical feminine activities. The parents will score each activity on a likert scale which creates a composite score on the childs preferences.
• Attention deficit hyperactivity disorder (ADHD) symptom load - Measured by the ADHD Rating Scale (male and female children) — At 5 years of age
  The ADHD Rating Scale (ADHD-RS) assesses ADHD symptom severity based on 26 items rated on a 4-point scale (0 = never, 3 = very often). The total score ranges from 0 to 78, with higher scores indicating greater symptom severity. The total score is calculated by summing all item scores.
• Inattention symptom load - Measured by the ADHD Rating Scale (male and female children) — 5 years of age
  The ADHD Rating Scale Inattention Subscore is based on 9 items rated on a 4-point scale (0 = never, 3 = very often). Scores range from 0 to 27, with higher scores indicating greater severity of inattention symptoms.
• Hyperactivity/Impulsivity symptom load - Measured by the ADHD Rating Scale (male and female children) — 5 years of age
  The ADHD Rating Scale Inattention Subscore is based on 9 items rated on a 4-point scale (0 = never, 3 = very often). Scores range from 0 to 27, with higher scores indicating greater severity of inattention symptoms.
• Total Difficulties Score derived from the "Strengths and Difficulties Questionnaire" (SDQ) (male and female children) — 2-5 years
  The Strengths and Difficulties Questionnaire (SDQ) is a 25-item behavioral screening tool that assesses emotional and behavioral problems in children. The Total Difficulties Score is calculated by summing four subscales: Emotional Symptoms, Conduct Problems, Hyperactivity-Inattention, and Peer Problems (20 items in total). The Total Difficulties Score ranges from 0 to 40, with higher scores indicating greater emotional and behavioral difficulties. According to standardized norms, scores can be interpreted depending on age- and sex-specific cutoffs. The SDQ also includes a separate Prosocial Behavior subscale, which is not included in the Total Difficulties Score.

Trial sites (1)

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