Long term effect of calcium supplementation during pregnancy on the blood pressure of offspring: follow up of a randomised controlled trial

Belizán, José M.; Villar, José; Bergel, Eduardo; Pino, AV; Fulvio, Sabrina Di; Galliano, Sebastián; Kattan, Clarisse

doi:10.1136/bmj.315.7103.281

Cited by 163 publications

(155 citation statements)

References 24 publications

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“…These findings are in agreement with findings of our previous study on children and provide support to our statement that the effect of maternal calcium intake during pregnancy on blood pressure of the offspring could be amplified throughout later life and could contribute to hypertension on adulthood 8 . On the other hand a dietary calcium intake much higher than the recommended levels showed no further benefits.…”

Section: Discussionsupporting

confidence: 83%

“…In 1987 our group performed a large, randomised, placebo controlled trial of calcium supplementation during pregnancy 7 in a population with low calcium intake, and seven years later we conducted the follow up of children born from these mothers 8 . This study showed that the offspring of calcium supplemented mothers had a lower incidence of high blood pressure than offspring of mothers receiving placebo, suggesting a role of fetal calcium restriction on the genesis of hypertension in later life.…”

Section: Introductionmentioning

confidence: 99%

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A deficient maternal calcium intake during pregnancy increases blood pressure of the offspring in adult rats

Bergel¹

2002

BJOG: An International Journal of Obstetrics and Gynaecology

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Objective To assess in an animal model the effect of maternal dietary calcium intake during pregnancy on the blood pressure of offspring. Design Randomised controlled trial.Sample Ninety-eight 20-week-old female Wistar-Kyoto rats, giving birth to a total of 119 pups that were included in the follow up study. Methods Rats were randomised to a calcium deficient diet, a diet with the recommended calcium levels, or a diet with calcium content much higher than the recommended levels. After one month on the experimental diet they were bred. After birth, systolic blood pressure in the offspring was measured monthly till 52 weeks of age. Main outcome measures Blood pressure of the offspring.Results The difference in blood pressure of the offspring between the normal and low maternal calcium group increased 0.49 mmHg per month (95% CI 0.18 to 0.84), 0.38 (0.07 to 0.68) between the low and high calcium group, and 0.12 (À0.20 to 0.43) between the normal and high calcium group. At the end of the follow up (52 weeks of age) blood pressure of the offspring in the deficient calcium group was 12.1 mmHg (95% CI 8.8 to 15.4, P < 0.0001) higher than in the normal calcium group and 7.5 mmHg (95% CI 4.4 to 10.5, P < 0.001) higher than the high calcium group. Blood pressure of the offspring in the high calcium group was 4.3 mmHg (95% CI 1.0 to 7.5, P ¼ 0.01) higher than in the normal calcium group. In a multiple regression model maternal calcium intake during pregnancy was the strongest predictor of blood pressure of the offspring during adulthood. Conclusions This experiment supports previous studies in humans suggesting a link between calcium intake during pregnancy and blood pressure in the offspring, and provides an animal model to explore the mechanisms involved in such association.

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Section: Discussionsupporting

confidence: 83%

Section: Introductionmentioning

confidence: 99%

A deficient maternal calcium intake during pregnancy increases blood pressure of the offspring in adult rats

Bergel¹

2002

BJOG: An International Journal of Obstetrics and Gynaecology

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“…Parallel to this increase, a higher number of exposed children exceeded the expected normal range of systolic blood pressure. Nutritional factors [48][49][50] and maternal smoking during pregnancy 51 may contribute to increased blood pressure in children. These parameters would be unlikely to explain the associations found, because stunting was of negligible importance, and only a few women smoked at all during pregnancy.…”

Section: Discussionmentioning

confidence: 99%

Pesticide Exposure and Stunting as Independent Predictors of Neurobehavioral Deficits in Ecuadorian School Children

Harari²,

et al. 2006

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OBJECTIVES. To examine possible effects on blood pressure, neurological function, and neurobehavioral tests in school-aged children with and without prenatal pesticide exposure in an area where stunting is common.METHODS. In a community of Northern Ecuador with intensive floriculture and a high female employment rate, we invited 79 children attending the 2 lowest grades of a public school for clinical examinations. In addition to a thorough physical examination, we administered simple reaction time, Santa Ana dexterity test, Stanford-Binet copying, and Wechsler Intelligence Scale for Children-Revised Digit Spans forward. Maternal interview included detailed assessment of occupational history to determine pesticide exposure during pregnancy. Recent and current pesticide exposure was assessed by erythrocyte acetylcholine esterase activity and urinary excretion of organophosphate metabolites.RESULTS. All eligible children participated in the study, but 7 children were excluded from data analysis due to other disease or age Ͼ9 years. A total of 31 of the remaining 72 children were classified as stunted based on their height for age. Maternal occupational history revealed that 37 children had been exposed to pesticides during development. After confounder adjustment, prenatal pesticide exposure was associated with a higher systolic blood pressure than in the controls. On neurological examination, 14 exposed children and 9 controls showed Ն1 abnormalities. Of 5 neurobehavioral tests, the Stanford-Binet copying test showed a lower drawing score for copying designs in exposed children than in controls. Stunting was associated with a lower score on this test only, and both risk factors remained statistically significant in a multiple regression analysis with adjustment for demographic and social confounders. Increased excretion of dimethyl and diethyl metabolites of organophosphates was associated with increased reaction time and no other outcomes.CONCLUSION. Prenatal pesticide exposure may cause lasting neurotoxic damage and add to the adverse effects of malnutrition in developing countries. The effects differ from those due to acute pesticide exposure. T HE DEVELOPING BRAIN is particularly susceptible to adverse effects of environmental toxicants and nutritional deficiencies. 1 During fetal development, the placenta offers some protection against unwanted compounds, but it is not an effective barrier against environmental neurotoxicants. 2 Furthermore, the blood-brain barrier, which protects the adult brain from many toxic agents, is not completely formed until ϳ6 months after birth 3 and, therefore, provides no protection during sensitive developmental stages. At the same time, the brain depends on appropriate supplies of essential nutrients, and malnutrition, as apparent from stunted growth, may result in delayed neurobehavioral development. [4][5][6][7][8][9] The vulnerability of the brain originates from the combination of immaturity and ongoing development. 10 For optimal brain development to occur, a numb...

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“…Maternal and early postnatal micronutrients related to development of cardiovascular risk factors in childhood and adulthood seem to be calcium and sodium. Prospective cohort studies showed inverse associations of maternal calcium intake with blood pressure in childhood [26][27][28][29]. However, results seem not to be consistent.…”

Section: Fetal Nutritionmentioning

confidence: 45%

Fetal nutritional origins of adult diseases: challenges for epidemiological research

Jaddoe

2008

Eur J Epidemiol

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Long term effect of calcium supplementation during pregnancy on the blood pressure of offspring: follow up of a randomised controlled trial

Cited by 163 publications

References 24 publications

A deficient maternal calcium intake during pregnancy increases blood pressure of the offspring in adult rats

A deficient maternal calcium intake during pregnancy increases blood pressure of the offspring in adult rats

Pesticide Exposure and Stunting as Independent Predictors of Neurobehavioral Deficits in Ecuadorian School Children

Fetal nutritional origins of adult diseases: challenges for epidemiological research

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