Postgraduate Training Course in Reproductive Health/Chronic Disease

Calcium intake during pregnancy

Review prepared for the 12th Postgraduate Course in Reproductive Medicine and Biology, Geneva, Switzerland

Fernando Ariel Mahmoud M.D.
Hospital Nacional Profesor Alejandro Posadas
Buenos Aires - Argentina

See also presentation

Abstract

Objective

The objective of this review is to describe the usual calcium intake during pregnancy in different populations.

Material and Methods

The Cochrane database of systematic reviews was searched Medline (1990-2003) and Ovid-Gateway database looking for articles which describe calcium intake in pregnant women were searched.
Different types of studies were identified, 5 surveys, 2 cross-sectional, 4 randomized controlled trials and 4 longitudinal studies.

Results

Irrespective of the study design, all included articles described a low intake of calcium during pregnancy in many different parts of the world like Asia, Latin -America, Africa but also in developed countries like Canada ,USA and the UK. There was some variation between the countries, with very low intake in India (250 mg/d SD 49 to high intakes in Caucasian women in Canada 1256mg/d SD 577.

Conclusions

More research is necessary, especially in different low-income countries, to know which is the intake of calcium during pregnancy to ensure an optimal nutritional status.
Also, more investigation is needed to assess to the potentially negative effect of low calcium during pregnancy.

Introduction

Biological role of calcium

Calcium is the most abundant mineral in the body, and essentially all human biological processes require calcium. Thus, finely tuned homeostatic control mechanisms to maintain constant blood levels (extracellular) of calcium have evolved, as have complex cellular mechanisms to control the movement of intracellular calcium. When calcium levels fall, they are rapidly returned to normal by the PTH secretion from the Parathyroid gland ensuring the increased intestinal, renal tubular and bone resorption. Elevated levels of extracellular calcium inhibit the secretion of PTH and the production of calcitriol (vitamin D metabolite) and stimulate the secretion of calcitonin by the thyroid gland, thus determining a decrease in calcium absorption, increase of urinary calcium excretion and decrease of bone resorption. Adequate dietary intake of calcium is crucial to replace the calcium lost from the extracellular fluid, both in the form of losses in urine, faeces, and sweat and due to the incorporation into bone and soft tissues. Approximately 99% of body calcium is contained in bone. The calcium needed for skeletal growth comes only from dietary intake and there are not extra-skeletal reservoirs. Therefore it is likely that a decreased calcium intake can result in a reduction of calcium concentration in the extracellular fluid impairing normal bone growth and metabolism. (1)

Calcium requirements

In 1997, the Food and Nutrition board of the Institute of Medicine, National Academy of Sciences, released the new dietary reference intakes (DRIs) for calcium, magnesium, phosphorus, fluoride and vitamin D for North America. A list of the DRI values for calcium is presented in table 1. This DRI has four components: Recommended Dietary Allowances (RDA): the daily intake level that is adequate to meet the nutritional requirement of approximately 97-98% of healthy individuals at a particular life stage; Estimate Average Requirements (EAR) is the nutrient intake value to meet the requirement of 50 % of healthy individuals at a particular life stage; Adequate Intakes (AI) was set for nutrients from which there was insufficient data to calculate the EAR or RDA; Tolerable Upper Intake Levels (UL) is the maximum level of daily nutrient intake that do not cause adverse effects. The requirements were determined setting the value of intake that would promote the maximum calcium retention during growth and would minimize loss thereafter. These values were used for the first time to determine requirements for North American people. Other countries have not yet used this approach to set their requirements. (2)

Calcium requirements during life stages

During growth it is desirable to maximize calcium retention in order to maximize acquisition of peak bone mass. Maximal calcium retention occurs approximately at the onset of menarche in women. After peak bone mass has been achieved, calcium intakes required to achieve maximal retention remains at 32.5 mmol/day (1300 mg/day), but net retention decreases with age as absorption efficiency and renal tubular reabsorption efficiency decline. At the age where bone density is generally at a plateau, calcium balance is expected to be zero. Requirements after the age of 50 are higher because of declining calcium absorption with age.
Recommended calcium intake for women in North America was not increased for pregnancy and lactation, the criteria used to determine the calcium requirement was bone mineral content. Table 1 presents the Dietary Reference Intake values for calcium by life stage for US and Canada. (2)

Table 1. Dietary reference intake values for calcium by life stage for US and Canada

Life stage group	(mg/day)
0 to 6 months	210
6 to 12 months	270
1 – 3 years	500
4 – 8 years	800
9 – 13 years	1300
14 – 18 years	1300
19 – 30 years	1000
31 – 50 years	1000
51 – 70 years	1200
> 70 years	1200
Pregnancy
<=  18 years	1300
19 – 50 years	1000
Lactation
<= 18 years	1300
19 – 50 years	1000

Calcium and Pregnancy

Requirements
Pregnancy and lactation are periods of high calcium requirement. The skeleton of a newborn baby contains approximately 20-30 g of calcium. The bulk of fetal skeletal growth takes place from midpregnancy onwards, with maximal calcium accretion occurring during the third trimester. The total calcium accretion rate of the fetus increases from approximately 50 mg/day at 20 weeks gestation to 330 mg/day at 35 weeks. For the third trimester of pregnancy, 200 mg/day is considered the average accretion rate. (3)
The potential negative consequences of a deficiency in calcium intake during pregnancy may affect bone metabolism, may cause hypertensive disorders or affect the fetal growth.
Bone metabolism
Calcium absorption and urinary calcium excretion are higher during pregnancy than before conception or after delivery. The increase is evident in early-to-mid pregnancy and precedes the increased demand for calcium by the fetus for skeletal growth.
Bone resorption is also increased, as indicated histologically and biochemically by measurements of plasma markers such as tartrate-resistant acid phosphatase and the urinary excretion of collagen cross-links, telopeptides or hydroxyproline. The increase in absorption rate is apparent by early gestation and rises further during pregnancy. Bone formation increases similarly as indicated by plasma markers such as bone alkaline phosphatase and procollagen peptides. However, osteocalcin concentration, a commonly used plasma marker for bone formation, is lower throughout pregnancy than before conception, although concentrations in late gestation are higher than those earlier in pregnancy. This may be due to the uptake of osteocalcin by the placenta. The alterations in calcium and bone metabolism during pregnancy are accompanied by an increased concentration of the calciotropic hormone 1, 25-dihydroxyvitamin D (calcitriol) but with little alteration in parathyroid or calcitonin hormone concentrations. (4, 5, 7)
After delivery, calcium absorption and urinary calcium excretion return to pre-pregnancy values. (7)
No data showed that pregnancy causes a permanent negative effect on bone density. In fact, recent data show that human pregnancy and lactation are accompanied by physiological changes in calcium and bone metabolism that are sufficient to make calcium available for fetal growth and breast milk production without a need to increase maternal calcium intake (6). Physiological hyperabsorption of calcium occurs in pregnancy, preceding the demands of the fetus for calcium, whereas renal conservation of calcium and temporary liberation of calcium from skeleton occur during lactation period. (4, 5)

Hypertensive Disorders

Eclampsia, preeclampsia and pregnancy-induced hypertension are associated with disturbances of calcium metabolism. In particular, women with preeclampsia have a relative hypocalciuria, coupled with higher PTH concentrations and lower ionized calcium and 1, 25-dihydroxyvitamin D concentrations compared to women with normal pregnancies. Eclampsia was found to be more frequent in countries where the daily calcium intake is low. Also, the risk of pregnancy-induced hypertension in American and Canadian women is higher among women with low milk intake (<1 glass/day) than among those with a moderate intake (1–2 glasses/day). Therefore the hypothesis that dietary calcium deficiency is a primary factor in the pathogenesis of pregnancy-induced hypertension has attracted considerable interest. (8, 9)
Results of early supplementation trials were inconsistent, but they largely indicated a beneficial effect on pregnancy-induced hypertension and related complications of consuming calcium supplements that supplied an extra 1000–2000 mg/day throughout the second half of pregnancy (10, 14, 15, 23). A large randomized controlled trial, involving 4589 nulliparous pregnant women in the United States demonstrated that in a population with an average calcium intake of 1100 mg/day a calcium supplement of 2000 mg/day did not reduce the incidence of either preeclampsia or raised blood pressure (11). More recently, in a randomized controlled trial in Australia the intake of 1800-mg/day calcium supplementation showed a reduction on the incidence of preeclampsia in nulliparous women (13). In addition similar effects have been reported from randomized controlled trials in India and Ecuador. Recent systematic reviews suggest that despite the negative findings of the large trial in the United States, routine calcium supplementation may be beneficial in pregnant women with a high risk of hypertension or a low calcium intake (12). In view of the uncertainties a randomized controlled trial of calcium supplementation in women with a low calcium intake it’s now carried on to provide new evidence on this issue.

Fetal Growth

Maternal malnutrition has a major impact on fetal growth and birth weight, and hence on skeletal mass. Poor nutrition during pregnancy may reduce neonatal bone density as well as size.
The question whether a low maternal intake of calcium can limit fetal growth or skeletal development in an otherwise healthy growing fetus has not been addressed. In an early study using radiographic densitometry, calcium supplementation of pregnant Indian women with a low calcium intake resulted in higher neonatal bone density compared to infants from mothers not receiving supplementation. There was no difference on birth weight or length between the groups. (16) Maybe the traditional anthropometric assessment of the neonate is not suitable to measure these effects. The use of sensitive absorptiometric techniques for measuring bone mineral content of small infants could be result in better outcomes.
Additional evidence of a positive effect of prenatal calcium intake comes from the studies in mothers receiving calcium supplementation as a preventive strategy to reduce preeclampsia. In a systematic review of calcium supplementation for the prevention of hypertensive disorders published in the Cochrane Library, 6 out of 9 studies reported that birth weights were higher in the intervention group compared to the control group, and in 2 of these trials the difference was statistically significant. (12)

Objective

The objective of this review is to describe the usual intake of calcium during pregnancy in different populations.

Materials and methods

Search strategy

The Cochrane database of systematic reviews was searched Medline (1990-2003) and Ovid-Gateway database looking for articles which describe calcium intake in pregnant women were searched.

Type of studies

Different types of studies were identified, 5 surveys, 2 cross-sectional, 4 randomized controlled trials and 4 longitudinal studies that described the intake of calcium in pregnant in different parts of the world. There were 12 full text articles, 2 abstracts and one personal communication of an unpublished study identified. Table 2 presents the characteristics of the included studies.

Table 2: Characteristics of the studies included

Results

The precise measurement of dietary calcium intake is difficult and is described for each study below.
Three studies conducted in pregnant women in Gambia , in Malawi and Nigeria assessed the calcium intake by weighing the food (17,18, 28). This seems to be the most accurate method, but represents great difficulties in large studies by being time consuming and the need of well trained personnel. In addition, women could modify their diet to make the weighing easy or to meet the supposed expectations of the interviewer. The authors reported a low intake of calcium in Gambia (404 mg/d) which was explained by the diet being based on cereals, groundnuts and leaves which are very low in calcium (17). In Malawi the mean intake of calcium was 813mg/d in the 2nd trimester and 640 mg/d in the 3rd trimester. These difference was explained by the seasonal influence: pregnant women used to eat more during prepares and harvest (18). In a study in Nigeria measuring the calcium intake in adolescents, the median intake was 659.1mg/d (28). There were differences in calcium intake between these three countries in Africa that could be explained by the method, costumes or self selected diet.
In Asia, the studies showed the lowest calcium intake. In India (19) calcium intake was the lowest amongst all the studies (250mg/d). The explanation could be that the participants were rural workers who based theirs meals on grains and vegetables and also described that these women ate only after every body at home had eaten their share. In Indonesian women (20) the intake of calcium was 316 mg/d with very low variation between trimesters of pregnancy. Like in India these women were rural workers with low educational level. In these last two studies the authors used the method of 24- h recall. Because of its practicality in large populations it can be used to compare nutrients intake between populations.
In a study conducted in China (29) the authors presented the results in 47.7% of RDA of the Chinese. The method of data collection was not mentioned.
In Latin -America the measured daily calcium intake was also low. In Argentina, (10) a RCT assessing calcium supplementation for the prevention of hypertensive disorders during pregnancy, identified women with a median intake of only 650 mg/d, which could be explained by the low economic resources of this population. In Brazil (23) the authors of these cross sectional study obtained a median intake of calcium in pregnant women of 500mg/d. In Ecuador there were great differences. In the first study (23) in 1989 the authors extracted data from another survey conducted in that country without mentioning the method used to measure the intake. The results were lower (mean of 292mg/d) than in the last study (15) which measured calcium intake by 24h-recall in an adolescent population and obtained a mean of 605mg/d in the placebo group and 628mg/d in the supplemented group.
In Guatemala(25) a mean of 727mg/d of calcium intake by 24-h recall was measured. In this population diet was predominantly lacto-ovo-vegetarian which could explain that deficit.
In Peru (27) the authors reported (personal communication) a calcium intake among pregnant women of 430mg/d.
Three studies were conducted in developed countries like Canada (21). In this cross sectional study the calcium intake was low, but this was more evident in the native population (Indian: mean 750mg/d, Inuit: mean 670mg/d) than in the Caucasian population (mean: 1256mg/d). An explanation would be that the native women lived in remote communities where calcium fortified foods were not affordable or available.
In USA (24) the authors assessed the calcium intake by the dietary history method in a RCT of calcium supplementation for prevention of induced hypertension in pregnant women. The mean calcium intake in the placebo group was 605mg/d and 628mg/d in the supplemented group.
In the UK (26) the authors assessed calcium intake by using two different methods, the first study used dietary history and the second a food frequency questionnaire. Table 3 presents the results by mean and SD, median and % of RDA.
Independently of the method used to measure the intake, the type of study or the country where it was conducted, all articles described a low intake of calcium during pregnancy.

Table 3: Results of studies

*% the RDA for Chinese Population

Discussion

In most of the 15 articles included in the review the intake is lower than recommended by the Food and Nutrition Board (2).
The results described above show some variation, going from very low intakes in India (250mg/d SD 49) to higher intakes in Caucasian women in Canada(1256mg/d SD 577). This variation may be due to inconsistencies in terms of methodology for assessment to the calcium intakes. The weighing method is the most accurate but would be biased by changes in the diet. The food frequency questionnaire has the lowest accuracy. The 24h-recall method is ideal for this kind of measure because is quick, easy, inexpensive and allows comparisons with other populations. Also, during pregnancy, diet usually changes in some countries because of myths, change in activities, appetite and self selected diet .
This low intake of calcium creates concerns for the possible risk and consequences associated.
Hypertensive disorders are more frequent in countries where the customary calcium intake is low (9). The most recent systematic review (12) suggests that routine supplementation with 2 gr/d would be beneficial for women with high risk of developing preeclampsia. Also, poor nutrition during pregnancy may reduce neonatal bone density, as well as size. But methods to access to this information, like the habitual anthropometric measures (length, cranial perimeter, etc) may not be accurate enough to detect it. More research using randomized controlled clinical trials are necessary. In fact, WHO is currently conducting a multinational calcium supplementation trial that could provide new evidence on this issue.
These studies show the calcium deficiency intake in pregnant woman among less developed countries, but in several developed countries calcium deficiency produces a great public health concern. In the last years most of national surveys in the USA reported low calcium intake in women among all age stages (30).
In a recent study (31) it was reported that in a population of women aged 22-85 in the USA the calcium intake was 591 mg/d (+- 355); half of these women were in reproductive age. In this study the principal cause of low intake was the change in diet by lowering the dairy products intake because of calories, concern about high cholesterol or costs.
The other interesting finding in this article was that women with a low intake of calcium perceived that their diet was good enough.
In another article (32) of calcium intake in adolescent (mean 13.5mg/d) and women (mean 22mg/d) in 6 European countries they found that in 3 (Italy, France and Poland) this was low.

Implications for research

More research by surveys is necessary in different low-income countries, to know which is the intake of calcium during pregnancy to ensure an optimal nutritional status.
Also, more investigation is needed to assess to the potentially negative effect of low calcium during pregnancy.

Implications for programs

If the WHO calcium trial concludes that calcium supplementation reduces preeclampsia among women with low calcium intake and that their babies have a better fetal growth, public health policymakers may start health programs that will improve the calcium intake in pregnant women.
These programs must take into account the lack of knowledge among populations about how deficient are their diets. So, if public health policymakers want to create a nutrition education program, first, they have to show women how deficient their calcium intake is.
And then, think which is the best way to improve calcium diets: a supplementation method only during the pregnancy or improving nutrition in the general population.

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