Tinzaparin for the treatment of foetal growth retardation: An open-labelled randomized clinical trial

Abstract

Objective: Foetal growth retardation (FGR) is a leading cause of perinatal death and long-term harms at survivors. Placental infarction plays a role in FGR, yet, no trials have evaluated whether low molecular weight heparins increase birth weight in ongoing FGR pregnancies.

Methods: An open-labelled randomized trial in Denmark during 2011-2016, including singleton pregnant women with FGR (estimated foetal weight < 2.3 percentile) diagnosed before gestational weeks 32. Participants were randomly assigned using sealed, blinded envelopes 1:1 to tinzaparin (4500 IU daily until 37 gestational weeks) or no tinzaparin. The primary outcomes were the observed birthweight relative to the expected for gestational age and gender, and foetal growth rates in the two trial groups evaluated by an intention to treat analysis.

Results: We enrolled 53 women. The mean gestational age was 261 days in the tinzaparin group and 246 days in the no treatment group. The mean birth weight was 2229 g in the tinzaparin group compared to 1968 g in the no treatment group. However, the birth weight relative to the expected from gestational age and gender was only 2.5 percentage points higher in the tinzaparin group [-5.1 to 10.0] (p = 0.51). The foetal growth rate during follow-up was 124 g/week in the tinzaparin group and 119 g/week in the no treatment group, a difference of 5 g/week [-19 to 29] (p = 0.67). Two perinatal deaths both occurred in the no treatment group.

Conclusion: We found no evidence of a tinzaparin effect on the foetal growth rate or the birth weight after adjustment for gestational age.

Keywords: Birth weight; Foetal growth retardation; Heparin, low molecular weight; Placenta, thrombosis; Randomized controlled trial.