6-year Follow-up of Children Born to Mothers Exposed to Nifedipine vs Placebo After Preterm Prelabor Rupture of Membranes at 22 to 33 Weeks of Gestation
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 480
- 试验地点
- 1
- 主要终点
- Cerebral palsy at 6 years of age.
研究概览
简要总结
The purpose of this study is to evaluate the neurodevelopment at age 6 of children born to women with preterm prelabor rupture of membranes at 22 to 33 weeks of gestation, after antenatal exposure to nifedipine vs placebo.
详细描述
Preterm prelabor rupture of membranes (PPROM) complicates 3% of pregnancies and accounts for one-third of preterm births. It is a leading cause of neonatal mortality and morbidity and increases the risk of maternal infectious morbidity. In cases of early PPROM (22 to 33 completed weeks' gestation), expectant management is recommended in the absence of labor, chorioamnionitis or fetal distress. Antenatal steroids and antibiotics administration are recommended by international guidelines. However, there is no recommendation regarding tocolysis administration in the setting of PPROM. In theory, reducing uterine contractility should delay delivery and reduce the risks of prematurity and neonatal adverse consequences. Likewise, a prolongation of gestation may allow administering a corticosteroids complete course that is associated with a two-fold reduction of morbidity and mortality. However, tocolysis may prolong fetal exposure to inflammation and be associated with higher risk of materno-fetal infection, potentially associated with neonatal death or long-term sequelae, including cerebral palsy.
The investigators implemented the TOCOPROM randomized clinical trial to assess whether short-term (48 hr) tocolysis reduces perinatal morti-morbidity in cases of PPROM at 22-33 weeks. However, both short- and long-term outcomes should be taken into account to define the optimal treatment strategy. There are currently no data allowing to evaluate the impact of a short course of nifedipine versus placebo on neurodevelopmental outcomes in school-aged children born after PPROM. Therefore, following-up children born to mothers enrolled in the TOCOPROM trial, through a new study, the TOCOKIDS cohort, is a unique and timely opportunity to advance scientific knowledge and adapt clinical practices in France and worldwide.
The assessment at 6 years of age will consist in:
- A self-administered parental questionnaire, completed online or on paper
- Data collected from the health book, in particular the 6-year consultation
- A short psychological assessment (45 minutes), performed remotely by a psychologist through video conference.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 年龄范围
- 6 Years 至 78 Months（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •All children born to mothers enrolled in the TOCOPROM trial who consented to participate in the 2-year follow-up and who agreed to be contacted for the 6-year follow-up
- •Alive at 6 years
- •Internet access, including access to a good-quality video-conference system (only for the psychological evaluation)
- •Non opposition of the holders of the exercise of parental authority
排除标准
- •Major malformations and/or chromosomal aberrations evidenced after birth
- •Impossibility to contact the family
- •Opposition to participate in the follow-up
研究组 & 干预措施
Nifedipine
Exposure during pregnancy to Oral Nifedipine 20 mg LP (between 22 to 33 weeks of gestation): Loading dose at T0 and T0.5 (i.e. 30 min), total=2x20 mg Maintenance dose:
Oral Nifedipine 20 mg LP at T3, then 1 pill every 8 hours for 48 hours (i.e. T11, T19, T27, T35 and T43, total=6x20 mg)
干预措施: Self-administered parental questionnaire (Other)
Placebo
Exposure during pregnancy to oral placebo of nifedipine (between 22 to 33 weeks of gestation) at T0, T0.5, T3, T11, T19, T27, T35 and T43
干预措施: A short psychological assessment performed online (Other)
结局指标
主要结局
Cerebral palsy at 6 years of age.
时间窗: Up to 6 months after inclusion.
Cerebral palsy assessed using the Gross Motor Function Classification System (GMFCS), a five-level classification based on the child's current gross motor abilities, limitations in gross motor function, and need for assistive technology and wheeled mobility. Severe/moderate cerebral palsy (GMFCS≥2). Mild cerebral palsy (GMFCS-1).
Developmental Coordination Disorder at 6 years of age.
时间窗: Up to 6 months after inclusion.
Measured using the Developmental Coordination Disorder Questionnaire - European French (DCDQ-FE), a brief parent questionnaire (15 items) designed to screen for gross and fine motor skills and coordination disorders in children, aged 5 to 15 years. Total score=15-56: indication of a risk of DCD or suspected of a risk of DCD. Total score=57-75: probably no DCD.
Language at 6 years of age
时间窗: Up to 6 months after inclusion.
Language assessed using the verbal communication subscale (4 items) of the 5-15R scale, covering comprehension, expressive language skills and verbal communication, with an extra question on the impact of language and communication difficulties on daily activities. Mean (SD). Reference to cut-off scores in relation to the 90 and 98 percentiles (%).
Behavior at 6 years of age.
时间窗: Up to 6 months after inclusion.
Behavior assessed using the Strengths and Difficulties Questionnaire (SDQ), a brief behavioral screening questionnaire (25 items), designed to screen for symptoms of hyperactivity inattention, emotional, conduct, and peer problems among 2-17 year olds. Mean (SD). Abnormal: \>90th percentile. Mildly abnormal: 80-90 percentile.
Executive functions at 6 years of age.
时间窗: Up to 6 months after inclusion.
Executive functions measured using the Childhood Executive Functioning Inventory (CHEXI), a rating instrument (24 items) for parents that was developed for measuring executive functioning in children age 4-12. It includes four different subscales tapping working memory, planning, regulation and inhibition, combined into two global scales: working memory (working memory and planning subscales) and inhibition (inhibition and regulation subscales). Normative data are not yet available. Abnormality will be defined considering a cut-off or deviation compared to the mean score, depending on the literature.
次要结局
- Vital status at 6 years of age.(Up to 6 months after inclusion.)
- Neurodevelopmental impairment.(Up to 6 months after inclusion.)
- Survival without any neurodevelopmental impairment at 6 years of age.(Up to 6 months after inclusion.)
- Survival without moderate-to-severe neurodevelopmental impairment at 6 years of age.(Up to 6 months after inclusion.)
- Growth at 6 years of age.(Up to 6 months after inclusion.)
- Growth at 6 years of age(Up to 6 months after inclusion)
- Health at 6 years of age.(Up to 6 months after inclusion.)
- Vision at 6 years of age.(Up to 6 months after inclusion.)
- Hearing at 6 years of age.(Up to 6 months after inclusion.)
- Development at 6 years of age.(Up to 6 months after inclusion.)
- Language at 6 years of age.(Up to 6 months after inclusion.)
- Behaviour at 6 years of age.(Up to 6 months after inclusion.)
- Cognition at 6 years of age.(Up to 6 months after inclusion.)
- Feasibility of performing an online psychological evaluation.(Up to 6 months after inclusion.)
- Parent-reported health and development.(Up to 6 months after inclusion.)
- Parent-reported Health-Related Quality of Life.(Up to 6 months after inclusion.)
- Parent-reported school difficulties(Up to 6 months after inclusion)
- Maternal self-perceived health(Up to 6 months after inclusion)
- Maternal mental health(Up to 6 months after inclusion)
- Maternal well-being(Up to 6 months after inclusion)
- Maternal quality of life(Up to 6 months after inclusion)
- Health at 6 years of age(Up to 6 months after inclusion)