Children Born to Mothers Enrolled in the TOCOPROM Trial
Conditions
Keywords
Prematurity, Nifedipine, Psychological assessment, Neurodevelopment, School age, Preterm prelabor rupture of membranes
Brief summary
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.
Detailed description
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.
Interventions
OTHERSelf-administered parental questionnaire
A self-administered parental questionnaire, completed online or on paper, to assess different dimension of neurodevelopment
OTHERA short psychological assessment performed online
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).
Sponsors
Assistance Publique - Hôpitaux de Paris
URC-CIC Paris Descartes Necker Cochin
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
6 Years to 78 Months
Healthy volunteers
No
Inclusion criteria
* 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
Exclusion criteria
* Major malformations and/or chromosomal aberrations evidenced after birth * Impossibility to contact the family * Opposition to participate in the follow-up
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Cerebral palsy at 6 years of age. | 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. | 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 | 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. | 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. | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Vital status at 6 years of age. | Up to 6 months after inclusion. | Whether the child is alive or not at years of age. |
| Neurodevelopmental impairment. | Up to 6 months after inclusion. | 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. |
| Survival without any neurodevelopmental impairment at 6 years of age. | Up to 6 months after inclusion. | Survival without any neurodevelopmental impairment (as defined in the primary endpoint, and then including also cognitive impairment). |
| Survival without moderate-to-severe neurodevelopmental impairment at 6 years of age. | Up to 6 months after inclusion. | 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). |
| Growth at 6 years of age. | Up to 6 months after inclusion. | Height compulsory examination in the sixth year, reported in the health book. |
| Growth at 6 years of age | Up to 6 months after inclusion | Weight. Compulsory examination in the sixth year, reported in the health book |
| Health at 6 years of age. | Up to 6 months after inclusion. | Arterial pressure. Compulsory examination in the sixth year, reported in the health book. |
| Health at 6 years of age | Up to 6 months after inclusion | chronic diseases, compulsory examination in the sixth year, reported in the health book |
| Vision at 6 years of age. | Up to 6 months after inclusion. | Visual acuity, any vision problem mentioned. Compulsory examination in the sixth year, reported in the health book. |
| Hearing at 6 years of age. | Up to 6 months after inclusion. | Hearing test. Compulsory examination in the sixth year, reported in the health book. |
| Development at 6 years of age. | Up to 6 months after inclusion. | Data reported in the health book during the compulsory examination in the sixth year. |
| Language at 6 years of age. | Up to 6 months after inclusion. | Language test. Compulsory examination in the sixth year, reported in the health book. |
| Behaviour at 6 years of age. | Up to 6 months after inclusion. | Data reported in the health book during the compulsory examination in the sixth year. |
| Cognition at 6 years of age. | Up to 6 months after inclusion. | 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). |
| Feasibility of performing an online psychological evaluation. | Up to 6 months after inclusion. | Acceptability E-Scale (adapted - 3 items), participation and completion rates, technical difficulties. |
| Parent-reported health and development. | Up to 6 months after inclusion. | 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.). |
| Parent-reported Health-Related Quality of Life. | Up to 6 months after inclusion. | 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. |
| Parent-reported school difficulties | Up to 6 months after inclusion | Ad-hoc questions |
| Maternal self-perceived health | Up to 6 months after inclusion | Minimum European Health Module - 1 item |
| Maternal mental health | Up to 6 months after inclusion | PHQ-4 (anxiety and depression) - 4 items |
| Maternal well-being | Up to 6 months after inclusion | WHO-5 Well-Being Index - 5 items |
| Maternal quality of life | Up to 6 months after inclusion | WHOQOL bref FR - 1 item |
Countries
France
Contacts
CONTACTGilles KAYEM, MD,PhD
CONTACTNelly Briand, PhD
PRINCIPAL_INVESTIGATORGilles KAYEM, MD,PhD
Université Paris Cité and Université Sorbonne Paris Nord, Paris, France. DHU Risks in Pregnancy, Paris Descartes University, Trousseau University Hospital
STUDY_DIRECTORElsa LORTHE, RM,PhD
Université Paris Cité and Université Sorbonne Paris Nord, Paris, France.
Outcome results
None listed