Follow-up study to evaluate the impact of antenatal corticosteroids on late preterm births on neurodevelopment outcomes at 33 months of age
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 2,000
- 试验地点
- 6
- 主要终点
- Global neurodevelopmental status measured as development-for-age z-score (DAZ) using Global Scales for Early Development at 33 plus or minus 3 months. The GSED-DAZ is a continuous age-adjusted z-score.
研究概览
简要总结
Executive Summary:
Rationale:
Antenatal corticosteroids (ACS) are crucial for improving survival in early preterm birth (PTB). Their effects in late PTB are ambiguous, offering respiratory benefits but increasing hypoglycemia risk. The short-term effects are being investigated in a large scale WHO-coordinated study in LMICs including India. However, studies report conflicting evidence on its impact on neurodevelopment, indicating the need for a comprehensive follow-up of infants in the trial.
Novelty:
Multicenter study across India using mixed methods leveraging robust trial framework evaluating dose-related long-term neurodevelopmental and economic effects of ACS in late PTB.
Objective:
Evaluate global neurodevelopment at 33+3 months of age, as measured by the GSED-DAZ (Z-score), in children exposed antenatally to a regimen of dexamethasone (4x6mg IM q12h) or betamethasone (4x2mg IM q12h) given to their mothers during late preterm period. Generate evidence on risk of neurodevelopmental impairment, death/severe illness, equity impact, and financial risk protection with ACS use in late PTB.
Methods:
Follow-up study within robust trial (ACTION III) framework; will enroll 2000 participants from 2 sites and 5 hospitals in India. Participants are infants born to mothers at high risk of late PTB, who have received antenatal dexamethasone (4x6mg IM q12h) or betamethasone (4x2mg IM q12h) or placebo. Infants will be followed up longitudinally until 33+3 months of age to assess neurodevelopment across multiple developmental domains. The primary outcome of global neurodevelopment will be measured on a continuous scale using the General Scale of Early Development (GSED) tool. Neurodevelopmental impairment, a secondary outcome will be measured as a composite outcome of any of cognitive developmental impairment, neuro-motor impairment, hearing impairment, behavioral impairment, communication impairment, vision impairment, and epilepsy by the age of 33+3 months. The data will be collected and managed electronically and will be analyzed in an intention-to-treat analysis.
Expected outcome:
Evidence shaping clinical guidelines and policy in India regarding ACS use in late PTB, including cost analysis for intervention scaling. Contribute to global analysis and guidance on ACS for late preterm.
研究设计
- 研究类型
- Observational
入排标准
- 年龄范围
- 29.00 Day(s) 至 36.00 Month(s)（—）
- 性别
- All
入选标准
- •Children born to women enrolled in the main ACTION III trial (July 2022 to December 5 2024), who survive the first 28 days of life ACTION III trial enrolls pregnant women with high probability of late preterm birth (GA 34+0 weeks-36+6 weeks)
- •Children between 29d to 33 plus 3 months of age (the main trial is following up the mother-infant dyad for 28d post birth)
- •Parents/ caregivers willing for a 33-month follow-up of their children
- •Parents/ caregivers consent for participation of their child in the follow-up study.
排除标准
- •Children with major congenital anomaly that would preclude accurate assessment of neurodevelopment
- •Children with medical condition that would preclude accurate assessment of neurodevelopment.
结局指标
主要结局
Global neurodevelopmental status measured as development-for-age z-score (DAZ) using Global Scales for Early Development at 33 plus or minus 3 months. The GSED-DAZ is a continuous age-adjusted z-score.
时间窗: At 33 plus or minus 3 months of age
次要结局
- Hearing impairment assessed by Automated Auditory Brainstem Response (AABR) & Diagnostic BERA (if required)
- Neuromotor Impairment as assessed by Hammersmith Infant Neurological Exam (HINE)(At 12 months to 18 months)
- Global Development impairment as assessed by Bayley Scales of Infant Development (BSID IV) & Global Scales for Early Development- Short Form & Long Form (GSED SF & GSED LF)(At 33 plus or minus 3 months of age)
- Social Communication Impairment as assessed by AIIMS Modified -INCLEN Diagnostic Tool for Autism Spectrum Disorder (INDT-ASD)(At 33 plus or minus 3 months of age)
- Behavioral Impairment as assessed by Child Behavior Checklist- 1½-5 (CBCL)(At 33 plus or minus 3 months of age)
- Clinical diagnosis of Epilepsy assessed by AIIMS Modified -INCLEN Diagnostic Tool for Epilepsy (INCLEN-INDT-EPI)(At 33 plus or minus 3 months of age)
- Visual acuity as assessed by Cardiff Card Test(At 33 plus or minus 3 months of age)
- Death and severe illness requiring hospitalization(Any time after a participant dies during the study)
- Postnatal growth impairment assessed by Anthropometry: Head Circumference, Height & Weight(29d to 3 months, 12 to 18 months, 33 plus or minus 3 months of age)
- Catastrophic Healthcare Expenditure (CHE) cases averted by intervention(At 33 plus or minus 3 months of age)
- Impoverishment(At 33 plus or minus 3 months of age)
- Equity impact(At 33 plus or minus 3 months of age)
- Out of pocket expenditure averted by intervention(At 33 plus or minus 3 months of age)
- Cost per additional disability-adjusted life year (DALY) gained(At 33 plus or minus 3 months of age)
- Incremental Cost- Effectiveness Ratio (ICER) for ACS(At 33 plus or minus 3 months of age)
- Caregivers health literacy on the early child neurodevelopment(At 33 plus or minus 3 months of age)
- Impact of neurodevelopmental impaired child on family(At 33 plus or minus 3 months of age)
- Awareness among caregivers on health centre approach for neurodevelopment assessments of child(At 33 plus or minus 3 months of age)
- Experiences & challenges faced by healthcare providers on management of women delivering in late preterm period(At 33 plus or minus 3 months of age)
- Challenges among health care professionals in dealing with caregivers for early neurodevelopmental assessments(At 33 plus or minus 3 months of age)
- Compliance of referral & reporting systems to higher centers or to specialists(At 33 plus or minus 3 months of age)
- Neurodevelopment impairment assessed by clinical exam & standardized questionnaire(At 19 to 33 plus or minus 3 months)
研究者
Dr Nitya Wadhwa
Translational Health Science & Technology Institute