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.
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.
Study Type
OBSERVATIONAL
Enrollment
480
A self-administered parental questionnaire, completed online or on paper, to assess different dimension of neurodevelopment
NEMI-3: an intelligence test administered by a psychologist measuring a fluid and crystallised intelligence. The test consists of 117 spoken and visual questions, for a total administration time of 45 min. Results are expressed in the form of standard indices (mean 100, standard deviation 15) that facilitate comparisons with the results obtained on other intelligence scales. Results will be classified as normal, mild delay (between 1 and \<2 standard deviation \[SD\] below the mean) or severe delay (≥2 SD).
Trousseau University Hospital
Paris, France, France
RECRUITINGCerebral palsy at 6 years of age.
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).
Time frame: Up to 6 months after inclusion.
Developmental Coordination Disorder at 6 years of age.
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.
Time frame: Up to 6 months after inclusion.
Language at 6 years of age
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 (%).
Time frame: Up to 6 months after inclusion.
Behavior at 6 years of age.
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.
Time frame: Up to 6 months after inclusion.
Executive functions at 6 years of age.
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.
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Time frame: Up to 6 months after inclusion.
Vital status at 6 years of age.
Whether the child is alive or not at years of age.
Time frame: Up to 6 months after inclusion.
Neurodevelopmental impairment.
Moderate-to-severe impairment (severe/moderate cerebral palsy, and/or abnormal SDQ score, and/or NEMI-3 ≥2 SD below the mean, and/or blindness, and/or deafness), mild impairment (mildly abnormal scores or mild impairment) vs no neurodevelopmental impairment.
Time frame: Up to 6 months after inclusion.
Survival without any neurodevelopmental impairment at 6 years of age.
Survival without any neurodevelopmental impairment (as defined in the primary endpoint, and then including also cognitive impairment).
Time frame: Up to 6 months after inclusion.
Survival without moderate-to-severe neurodevelopmental impairment at 6 years of age.
Survival without moderate-to-severe neurodevelopmental impairment (i.e. severe/moderate cerebral palsy, and/or abnormal SDQ score, and/or NEMI-3 ≥2 SD below the mean, and/or blindness, and/or deafness).
Time frame: Up to 6 months after inclusion.
Growth at 6 years of age.
Height compulsory examination in the sixth year, reported in the health book.
Time frame: Up to 6 months after inclusion.
Growth at 6 years of age
Weight. Compulsory examination in the sixth year, reported in the health book
Time frame: Up to 6 months after inclusion
Health at 6 years of age.
Arterial pressure. Compulsory examination in the sixth year, reported in the health book.
Time frame: Up to 6 months after inclusion.
Health at 6 years of age
chronic diseases, compulsory examination in the sixth year, reported in the health book
Time frame: Up to 6 months after inclusion
Health at 6 years of age
oral health. Compulsory examination in the sixth year, reported in the health book
Time frame: Up to 6 months after inclusion
Vision at 6 years of age.
Visual acuity, any vision problem mentioned. Compulsory examination in the sixth year, reported in the health book.
Time frame: Up to 6 months after inclusion.
Hearing at 6 years of age.
Hearing test. Compulsory examination in the sixth year, reported in the health book.
Time frame: Up to 6 months after inclusion.
Development at 6 years of age.
Data reported in the health book during the compulsory examination in the sixth year.
Time frame: Up to 6 months after inclusion.
Language at 6 years of age.
Language test. Compulsory examination in the sixth year, reported in the health book.
Time frame: Up to 6 months after inclusion.
Behaviour at 6 years of age.
Data reported in the health book during the compulsory examination in the sixth year.
Time frame: Up to 6 months after inclusion.
Cognition at 6 years of age.
NEMI-3: an intelligence test administered by a psychologist measuring a fluid and crystallised intelligence. The test consists of 117 spoken and visual questions, for a total administration time of 45 min. Results are expressed in the form of standard indices (mean 100, standard deviation 15) that facilitate comparisons with the results obtained on other intelligence scales. Results will be classified as normal, mild delay (between 1 and \<2 standard deviation \[SD\] below the mean) or severe delay (≥2 SD).
Time frame: Up to 6 months after inclusion.
Feasibility of performing an online psychological evaluation.
Acceptability E-Scale (adapted - 3 items), participation and completion rates, technical difficulties.
Time frame: Up to 6 months after inclusion.
Parent-reported health and development.
Self-reported. Perceived health and development of the child, parental concerns about health and development, and professional diagnoses of health conditions (e.g., asthma, respiratory problems, etc.).
Time frame: Up to 6 months after inclusion.
Parent-reported Health-Related Quality of Life.
PedsQL Short Form - 15 items. All items will be added up and linearly transformed on a scale between 0 and 100, a higher score indicating a better HRQoL. Physical and psychosocial functioning will be further assessed using the corresponding subscales. Poor HRQoL, physical or psychosocial functioning will be defined using thresholds compatible with a severe health condition.
Time frame: Up to 6 months after inclusion.
Parent-reported school difficulties
Ad-hoc questions
Time frame: Up to 6 months after inclusion
Maternal self-perceived health
Minimum European Health Module - 1 item
Time frame: Up to 6 months after inclusion
Maternal mental health
PHQ-4 (anxiety and depression) - 4 items
Time frame: Up to 6 months after inclusion
Maternal well-being
WHO-5 Well-Being Index - 5 items
Time frame: Up to 6 months after inclusion
Maternal quality of life
WHOQOL bref FR - 1 item
Time frame: Up to 6 months after inclusion