OBSTETRICS Effects of calcium supplementation on uteroplacental and fetoplacental blood flow in low-calcium-intake mothers: a randomized controlled trial Guillermo Carroli, MD; Mario Merialdi, MD, PhD; Daniel Wojdyla, PhD; Edgardo Abalos, MD; Liana Campodonico, MSc; Shih-Ern Yao, MBBS; Rogelio Gonzalez, MD; Russell Deter, MD; Marshall Lindheimer, MD; Paul Van Look, MD, PhD OBJECTIVE: We postulated that calcium supplementation of calcium- deficient pregnant women would lower vascular resistance in uteropla- cental and fetoplacental circulations. STUDY DESIGN: Pulsatility index (PI) and resistance index (RI) (uterine and umbilical arteries) and presence of bilateral uterine artery diastolic notching were assessed by Doppler ultrasound between 20-36 weeks’ gestation in 510 healthy, nulliparous Argentinean women with deficient calcium intake in a randomized, placebo-controlled, double-blinded trial. RESULTS: Average umbilical and uterine artery RI and PI tended to be lower in the supplemented group at each study week. Differences be- came statistically significant for umbilical artery RI and PI from 32 and 36 weeks, respectively. Estimated probabilities of bilateral uterine ar- tery diastolic notching trended toward lower values in calcium-supple- mented women. CONCLUSION: Calcium supplementation of pregnant women with defi- cient calcium intake may affect uteroplacental and fetoplacental blood flow by preserving the vasodilation of normal gestation. Key words: calcium supplementation, Doppler velocimetry, preeclampsia Cite this article as: Carroli G, Merialdi M, Wojdyla D, et al. Effects of calcium supplementation on uteroplacental and fetoplacental blood flow in low-calcium-intake mothers: a randomized controlled trial. Am J Obstet Gynecol 2010;202:45.e1-9. H ypertensive disorders complicate approximately 9% of all pregnan- cies and are responsible for substantial morbidity and mortality in both mother and fetus with the majority of these bad outcomes due to pure or superimposed preeclampsia/eclampsia. 1 Despite recent and existing progress related to causality, the etiology and pathophysiology of pre- eclampsia remain unclear, and we are yet to develop targeted prevention strate- gies. Thus, faced with overt disease, delivery remains the only definitive treatment. There are reports that intracellular free calcium concentration is increased in women with preeclampsia. The observa- tions have been reported in platelets and lymphocytes 2-4 and interpolation of these findings to smooth muscle cells have led to the hypothesis that such changes underlie the widespread mater- nal vasoconstriction and hypertension. It has further been suggested that in- creased intracellular free calcium levels are a consequence of the increase in parathyroid hormone levels secondary to the low calcium intake, 5 a problem correctable by calcium supplementation and proposed as a preventive strategy for preeclampsia, 6 specifically among low- calcium-intake women. 7 A plausible approach toward under- standing the mechanisms linking dietary calcium intake to vasoconstriction during normal and abnormal pregnancy is to pro- spectively assess the effects of different lev- els of calcium intake on the uterine and umbilical circulations. Doppler velocim- etry allows for noninvasive estimation of blood flow characteristics in these utero- placental vessels. These are ideal vascular systems to study, as abnormal placentation has been implicated in the etiology of pre- eclampsia 8 and poor placental perfusion may be responsible for the aberrant pla- cental production of circulating maternal proteins that play a role in the preeclamp- tic process. 9 In 2006, the World Health Organiza- tion (WHO) published the results of a From Centro Rosarino de Estudios Perinatales, Rosario, Argentina (Drs Carroli, Wojdyla, and Abalos and Ms Campodonico); United Nations Development Programme (UNDP)/ United Nations Population Fund (UNFPA)/World Health Organization /World Bank Special Programme of Research, Development and Research Training in Human Reproduction, Geneva, Switzerland (Drs Merialdi, Yao, and Van Look); the Department of Obstetrics and Gynecology, Centre for Perinatal Diagnosis, Sotero del Rio Hospital, Catholic University of Chile, Santiago, Chile (Dr Gonzalez); the Department of Obstetrics and Gynecology, Baylor College of Medicine, Houston, TX (Dr Deter); and the Departments of Obstetrics and Gynecology and Medicine, Pritzker School of Medicine, University of Chicago, Chicago, IL (Dr Lindheimer). Received Feb. 4, 2009; revised June 15, 2009; accepted June 16, 2009. Reprints: Guillermo Carroli, MD, Pueyrredon 985, Rosario 2000, Santa Fe, Argentina. gcarroli@crep.com.ar. This is an ancillary study performed in parallel with the World Health Organization calcium supplementation trial among low-calcium-intake women (Am J Obstet Gynecol 2006;194:639- 49). 0002-9378/$36.00 • © 2010 Mosby, Inc. All rights reserved. • doi: 10.1016/j.ajog.2009.07.037 Research www. AJOG.org JANUARY 2010 American Journal of Obstetrics & Gynecology 45.e1