TOCOKIDS

Scientific justification:

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.

Principal objectif :

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.

Secondary objectives :

• Assess the impact of antenatal exposure to nifedipine vs. placebo after RPMAT on other dimensions of health and functioning in children and parents.
• Assess the feasibility of online psychological assessment in a population of school-aged children, including many premature infants.
• Assess children’s neurological development in relation to other antenatal complications, such as intrauterine infection.

Target population :

All children born to mothers who participated in the TOCOPROM trial may be included in the TOCOKIDS cohort.

Number of subjects required :

The sample size will be determined by the number of participants in the original trial (n=850 pregnant women). In March 2024, we recorded 5.6% stillbirths, pregnancy terminations, or neonatal deaths. This would correspond to a total of 45 to 50 children ineligible for the 6-year follow-up. Of these 800 children, we expect a participation rate of 60%. We therefore plan to include 480 children in the TOCOKIDS cohort.

Number of centers :

1 center because all study procedures will be performed centrally by the research team

Duration of the studie:

Participation time: 30 minutes (psychological assessment) + approximately 20 to 30 minutes to complete the online questionnaire (at age 6, maximum age 6 years and 6 months)
Total duration: 84 months (October 2025-September 2032)

Progress report

The study is scheduled to begin at the end of 2025.