Conflicting Effects of Fetal Growth Restriction on Blood Pressure Between Human and Rat Offspring: A Meta-Analysis

Kooiman, J. and Terstappen, F. and van Wagensveld, L. and Franx, A. and Wever, K. E. and Roseboom, T. J. and Joles, J. A. and Gremmels, H. and Lely, A. T.

Hypertension (2020) 75: 806–818

DOI: 10.1161/hypertensionaha.119.14111

Abstract

Low birth weight is associated with hypertension. Low birth weight can result from fetal growth restriction (FGR) or prematurity. FGR is postulated to impact blood pressure (BP) by developmental programming. This systematic review and meta-analysis studies BP in human and animal offspring following FGR. Pubmed and Web of Science were searched for studies reporting on BP after placental insufficiency induced FGR compared with normal growth controls. Primary outcome was mean absolute BP difference (ΔBP mm Hg [95% CI]). Meta-analysis was performed using random-effects models. Subgroup analyses were executed on species, sex, age, pregnancy duration, and stress during BP readings. Due to large interspecies heterogeneity, analyses were performed separately for human (n=41) and animal (n=31) studies, the latter restricted to rats (n=27). Human studies showed a ΔBP between FGR and controls of -0.6 mm Hg ([95% CI, -1.7 to 0.6]; I(2)=91%). Mean ΔBP was -2.6 mm Hg (95% CI, -5.7 to 0.4) in women versus -0.5 mm Hg (95% CI, -3.7 to 2.7) in men. Subgroup analyses did not indicate age, gestational age, and stress during measurements as sources of heterogeneity. In rats, mean BP was 12.0 mm Hg ([95% CI, 8.8-15.2]; I(2)=81%) higher in FGR offspring. This difference was more pronounced in FGR males (13.6 mm Hg [95% CI, 10.3-17.0] versus 9.1 mm Hg [95% CI, 5.3-12.8]). Subgroup analyses on age showed no statistical interaction. BP readings under restrained conditions resulted in larger BP differences between FGR and control rats (15.3 mm Hg [95% CI, 11.6-18.9] versus 5.7 mm Hg [95% CI, 1.1-10.3]). Rat studies confirm the relation between FGR and offspring BP, while observational studies in humans do not show such differences. This may be due to the observational nature of human studies, methodological limitations, or an absence of this phenomenon in humans. Clinical Trial Registration URL: http://www.clinicaltrials.gov. Unique identifier: CRD42018091819.

Citation

Kooiman, J., Terstappen, F., van Wagensveld, L., Franx, A., Wever, K. E., Roseboom, T. J., Joles, J. A., Gremmels, H., & Lely, A. T. (2020). Conflicting Effects of Fetal Growth Restriction on Blood Pressure Between Human and Rat Offspring: A Meta-Analysis. Hypertension, 75(3), 806–818. https://doi.org/10.1161/hypertensionaha.119.14111 Animals, Male, Rats, Female, Humans, Birth Weight, Pregnancy, Animals, Newborn, Species Specificity, Infant, Newborn, *placental insufficiency, Observational Studies as Topic, Infant, Low Birth Weight, *Blood Pressure, *fetal growth restriction, *gestational age, *hypertension, Fetal Growth Retardation/etiology/*physiopathology, Hypertension/*epidemiology/etiology/physiopathology, Placental Insufficiency/physiopathology, Restraint, Physical/adverse effects

Keywords

• Animals
• Male
• Rats
• Female
• Humans
• Birth Weight
• Pregnancy
• Animals
• Newborn
• Species Specificity
• Infant
• Newborn
• *placental insufficiency
• Observational Studies as Topic
• Infant
• Low Birth Weight
• *Blood Pressure
• *fetal growth restriction
• *gestational age
• *hypertension
• Fetal Growth Retardation/etiology/*physiopathology
• Hypertension/*epidemiology/etiology/physiopathology
• Placental Insufficiency/physiopathology
• Restraint
• Physical/adverse effects