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Updated: Dec 30, 2025
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Published on: June 29, 2013
Conflicting Effects of Fetal Growth Restriction on Blood Pressure Between Human and Rat Offspring: A Meta-Analysis
Judith Kooiman1, Fieke Terstappen1,2, Lilian van Wagensveld1
1From the Department of Obstetrics (J.K., F.T., L.v.W., A.F., A.T.L.), University Medical Center Utrecht, the Netherlands.
Insights
Fetal growth restriction (FGR) is linked to higher blood pressure in rat offspring, but human studies show no significant difference. This suggests potential species-specific effects or limitations in human observational data regarding FGR and hypertension.
Area of Science:
- Developmental programming
- Cardiovascular health
- Perinatal medicine
Background:
- Low birth weight, often due to fetal growth restriction (FGR), is associated with hypertension.
- FGR is hypothesized to influence offspring blood pressure (BP) through developmental programming.
- Understanding this link is crucial for long-term cardiovascular health assessment.
Purpose of the Study:
- To systematically review and meta-analyze studies on blood pressure in human and animal offspring following FGR.
- To compare BP differences between FGR and control groups across species.
- To investigate potential factors influencing heterogeneity in study results.
Main Methods:
- Systematic literature search of PubMed and Web of Science for studies on placental insufficiency-induced FGR and offspring BP.
- Meta-analysis using random-effects models to determine mean absolute BP difference (ΔBP).
- Separate analyses for human (n=41) and animal (rat, n=27) studies, with subgroup analyses on various factors.
Main Results:
- Human studies showed a non-significant ΔBP of -0.6 mm Hg (95% CI, -1.7 to 0.6) between FGR and control offspring.
- Rat studies revealed significantly higher BP in FGR offspring (mean ΔBP = 12.0 mm Hg; 95% CI, 8.8-15.2).
- In rats, higher BP differences were observed in males and under restrained conditions during BP measurement.
Conclusions:
- Rat models strongly support a link between FGR and elevated offspring BP, particularly in males and under stress.
- Human observational studies did not confirm this association, possibly due to study design limitations or absence in humans.
- Further research is needed to elucidate the discrepancies and confirm FGR's impact on human cardiovascular health.
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]; I2=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]; I2=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.
