Tocolysis and Neurodevelopment of Children Born Very Preterm

JAMA Netw Open. 2024 Oct 1;7(10):e2442602. doi: 10.1001/jamanetworkopen.2024.42602.

Abstract

Importance: Neurodevelopmental outcomes of very preterm children exposed to tocolytics are not well described.

Objective: To investigate whether tocolysis administered after spontaneous preterm labor is associated with neurodevelopmental outcomes at 5.5 years and to assess whether the type of tocolytic drug is associated with neurodevelopmental outcomes among infants exposed.

Design, setting, and participants: This prospective, national, population-based cohort study used data from the French Etude Épidémiologique sur les Petits Âges Gestationnels-2 cohort. Children who were alive and participated in an assessment at 5.5 years and whose mothers experienced spontaneous preterm labor without an infectious context and delivered at 24 to 31 weeks were eligible for this study. Recruitment occurred from March to December 2011. Follow-up at age 5.5 years was conducted from September 2016 to December 2017. Data analysis was performed from July 2023 through April 2024.

Exposures: The primary analysis examined tocolytics (yes vs no), and the secondary analysis examined the type of tocolytic (atosiban vs calcium channel blockers [CCBs]).

Main outcome and measure: The composite outcome neurodevelopmental disabilities included cerebral palsy; visual, hearing, and cognitive deficiencies; developmental coordination disorders; or behavioral problems.

Results: A total of 1055 mothers (mean [SD] age, 29.2 [5.7] years) had preterm labor without fever and gave birth to 1320 children (704 male [weighted percentage, 53.3%; 95% CI, 50.6%-56.1%]; mean [SD] gestational age, 28.8 [2.0] weeks). Overall, 776 mothers (weighted percentage, 73.5%; 95% CI, 70.8%-76.2%) received tocolytics; 136 mothers (weighted percentage, 17.9%; 95% CI, 15.3%-20.8%) received only a CCB, and 295 mothers (weighted percentage, 37.6%; 95% CI, 34.2%-41.0%) received only atosiban. From modified Poisson regression with propensity score matching, the risk of overall neurodevelopmental disabilities (mild, moderate, or severe) at 5.5 years did not differ between preterm children exposed and not exposed to tocolytics (relative risk [RR], 1.11; 95% CI, 0.85-1.45; P = .44) or in preterm infants exposed to atosiban compared with those exposed to CCBs (RR, 0.94; 95% CI, 0.67-1.32; P = .71).

Conclusions and relevance: In this study, tocolytics were not associated with neurodevelopmental disabilities among very preterm children surviving at 5.5 years.

MeSH terms

  • Adult
  • Calcium Channel Blockers / adverse effects
  • Calcium Channel Blockers / therapeutic use
  • Child, Preschool
  • Female
  • France / epidemiology
  • Humans
  • Infant, Extremely Premature
  • Infant, Newborn
  • Male
  • Neurodevelopmental Disorders* / chemically induced
  • Neurodevelopmental Disorders* / epidemiology
  • Pregnancy
  • Prospective Studies
  • Tocolysis* / methods
  • Tocolytic Agents* / adverse effects
  • Tocolytic Agents* / therapeutic use
  • Vasotocin / analogs & derivatives
  • Vasotocin / therapeutic use

Substances

  • Tocolytic Agents
  • Vasotocin
  • atosiban
  • Calcium Channel Blockers