Poster Presentation & Flash Talk 46th Annual Meeting of the Fetal and Neonatal Physiological Society 2019

Conflicting effects of fetal growth restriction on blood pressure between human and animal offspring: a systematic review and meta-analysis (#120)

Fieke Terstappen 1 2 , Judith Kooiman 2 , Lilian van Wagensveld 2 , Arie Franx 2 , Kimberley E. Wever 3 , Tessa J. Roseboom 4 , Jaap A. Joles 5 , Hendrik Gremmels 5 , A. Titia Lely 2
  1. Department for Developmental Origins of Disease, Wilhelmina Children's Hospital and UMC Utrecht Brain Center, Utrecht, The Netherlands
  2. Department of Obstetrics, Wilhelmina Children's Hospital Birth Center, Utrecht University , Utrecht, The Netherlands
  3. SYstematic Review Center for Laboratory animal Experimentation (SYRCLE), Department for Health Evidence, Radboud university medical center, Nijmegen, The Netherlands
  4. Department of Clinical Epidemiology, Biostatistics and Bioinformatics, Obstetrics and Gynecology, Amsterdam Public Health Research Institute, Amsterdam Reproduction and Development Research Institute,Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands
  5. Department of Nephrology and Hypertension, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands

Background: Low birth weight is associated with increased risk of adult hypertension. Low birth weight often results from fetal growth restriction (FGR) or prematurity. FGR is postulated to impact adult blood pressure by epigenetic programming, yet observational studies show contradictory effects. This systematic review and meta-analysis studies the effect of FGR, compared with normal-growth on blood pressure in human and animal offspring.

Methods: Pubmed and Web of Science were searched for studies reporting on blood pressure after FGR compared with normal growth controls. Primary outcome was mean absolute difference (MD) in blood pressure with 95% confidence intervals (ΔBP mmHg [95%CI]). Meta-analysis was performed using a random effects model. Subgroup-analyses were performed on species, sex and age.

Results: 41 human and 31 animal studies were included. 87% of animal studies was conducted in rats. Due to large interspecies heterogeneity, analyses were performed separately for all the human studies and the 27 rat studies. Meta-analysis of human studies showed no blood pressure difference between FGR and controls (-0.6 [-1.7, 0.6]; p=0.34; I2=91%). Subgroup analysis on sex or age showed no evidence for interaction. Human studies were hampered by varying FGR definitions, heterogeneous populations, and generally a mild FGR phenotype. In rats, mean blood pressure was 12.0 mmHg ([8.8, 15.2]; p<0.001; I2=81%) higher in FGR offspring versus controls. This difference was more pronounced in FGR males (13.6 [10.3, 17.0] versus 9.1 [5.3, 12.8] in FGR females; p<0.01;I2=80%). Subgroup analyses on age showed no interaction.

Conclusions: This meta-analysis showed no blood pressure difference between human FGR offspring and normal-growth peers. In contrast, blood pressure was higher in rat FGR offspring. High quality studies with less heterogeneity in severe and well-defined FGR populations are needed before FGR effects on blood pressure in humans can be discarded.

 

 

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