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The fetal origins of hypertension: a systematic review and meta-analysis of the evidence from animal experiments of maternal undernutrition

Van Abeelen, Annet F.M.a,b,*; Veenendaal, Marjolein V.E.a,*; Painter, Rebecca C.c; De Rooij, Susanne R.a; Thangaratinam, Shakilad; Van Der Post, Joris A.M.c; Bossuyt, Patrick M.M.a; Elias, Sjoerd G.b; Uiterwaal, Cuno S.P.M.b; Grobbee, Diederick E.b; Saade, George R.e; Mol, Ben Willem J.c; Khan, Khalid S.f; Roseboom, Tessa J.a,c

doi: 10.1097/HJH.0b013e3283588e0f

Objective: Numerous experiments in animals have been performed to investigate the effect of prenatal undernutrition on the development of hypertension in later life, with inconclusive results. We systematically reviewed animal studies examining the effects of maternal undernutrition on SBP, DBP, and mean arterial blood pressure (BP) in offspring.

Methods: A search was performed in Medline and Embase to identify articles that reported on maternal undernutrition and hypertension in experimental animal studies. Summary estimates of the effect of undernutrition on SBP, DBP, and mean arterial BP were obtained through meta-analysis.

Results: Of the 6151 articles identified, 194 were considered eligible after screening titles and abstracts. After detailed evaluation, 101 met the inclusion criteria and were included in the review. Both maternal general and protein undernutrition increased SBP [general undernutrition: 14.5 mmHg, 95% confidence interval (CI) 10.8–18.3; protein undernutrition: 18.9 mmHg, 95% CI 16.1–21.8] and mean arterial BP (general undernutrition: 5.0 mmHg, 95% CI 1.4–8.6; protein undernutrition: 10.5 mmHg, 95% CI 6.7–14.2). There was substantial heterogeneity in the results. DBP was increased by protein undernutrition (9.5 mmHg, 95% CI 2.6–16.3), whereas general undernutrition had no significant effect.

Conclusion: The results of this meta-analysis generally support the view that in animals, maternal undernutrition – both general and protein – results in increased SBP and mean arterial BP. DBP was only increased after protein undernutrition. The results depended strongly on the applied measurement technique and animal model.

aDepartment of Clinical Epidemiology, Biostatistics and Bioinformatics, Academic Medical Center, University of Amsterdam, Amsterdam

bJulius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht

cDepartment of Obstetrics and Gynaecology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands

dDepartment of Obstetrics and Gynaecology and Clinical Epidemiology, University of Birmingham, Birmingham, UK

eDivision of Maternal-Fetal Medicine, The University of Texas Medical Branch, Galveston, Texas, USA

fBarts and the London School of Medicine, London, UK

*Annet F.M. Van Abeelen and Marjolein V.E. Veenendaal contributed equally to the writing of this article.

Correspondence to Annet F.M. Van Abeelen, Academic Medical Center, Meibergdreef 9, 1105 AZ Amsterdam, Post Office Box 22660, 1100 DD Amsterdam, The Netherlands. Tel: +31 20 56 65810; fax: +31 20 69 12683; e-mail:

Abbreviation: BP, blood pressure; CI, confidence interval

Received 22 December, 2011

Revised 21 May, 2012

Accepted 25 July, 2012

© 2012 Lippincott Williams & Wilkins, Inc.