Calcium is considered a critical nutrient during pregnancy with at least a twofold increase in requirements observed. Its metabolism during gestation significantly changes from as early as 12 weeks, with doubling of both absorption and excretion, followed by additional losses through lactation, which can account for reductions in maternal bone mineral content of 3-10% (Prentice 2003). While it is clear that general supplementation would be necessary in those women with poor preconception calcium levels, it is suggested that for healthy women the metabolic compensation evident in pregnancy should be sufficient to guarantee adequate fetal
Prevention of pre-eclampsia Epidemiological evidence illustrates an inverse relationship between calcium status and the prevalence of pre-eclampsia (Frederick et al 2005, Lopez-Jaramillo et al 2001 ) and recent studies confirm abnormalities in markers of calcium metabolism and status in a pre-eclamptic population compared to controls, including low urinary and serum calcium levels (Ingec et al 2006, Sukonpan & Phupong 2005). Trials that included a 1996 meta-analysis of studies involving calcium and hypertension in pregnancy have shown a substantial mean reduction in both SBP and DBP, which was also confirmed by more recent reviews (Atallah et al 2002, Bûcher et al 1996).
Positive correlations demonstrated in original smaller trials between calcium supplementation and reduced prevalence of pre-eclampsia, involving over 400 women, were put into question when the Calcium for Prevention of Pre-eclampsia study (CPEP), the largest trial to date, found no effect on the incidence or severity of the condition (Levine et al 1997). However, the CPEP study, involving over 4000 healthy nulliparous women, is not a replication of the existing trials. While the original studies used populations with a low calcium intake to ascertain the connection between correction of this deficiency and prevalence of pre-eclampsia, this more recent trial represented a 'pharmacological intervention in women with a normal calcium intake' (Lopez-Jaramillo et al 2001 ). Further reviews of all the evidence have supported calcium's preventative role and researchers have concluded that calcium supplementation should be recommended for those women with a low calcium intake who are at risk of developing gestational hypertension (Crowther et al 1999, Hofmeyr et al 2003).
A 2003 review of calcium and the prevention of pre-eclampsia concluded that while considerable evidence from observational and experimental studies links calcium intake and hypertension during pregnancy, there is currently no satisfactory Calcium 153
explanation of the mechanisms (Villar et al 2003). One possible explanation may be the antagonistic relationship between calcium and lead (Sowers et al 2002).
A small number of studies have investigated the effects of calcium in combination with other nutrients, including antioxidant and omega-3 oils in this population. One randomised, placebo-controlled, double-blind study involving a sample of 48 primigrávidas, using a combination of 600 mg/day calcium and 450 mg/day of conjugated linoleic acid (CLA) from weeks 18-22 until delivery, resulted in a significantly reduced incidence of pregnancy-induced hypertension (8% vs 42% of the control group) (Herrera et al 2005). Further studies are warranted to elicit the individual impact of both nutrients and to determine the superiority of sole or combination treatment.
Leg cramps Calcium supplements are commonly prescribed in pregnancy when leg cramps are a problem. A Cochrane review of five trials involving 352 women taking various supplements for the treatment of leg cramps in pregnancy included only one placebo-controlled trial of calcium. From this, researchers concluded that any improvement in cramps in those groups treated solely with calcium was likely due to a placebo effect, with significant findings limited to the groups taking other nutrients (Young & Jewell 2002).
Fetal growth The greatest period of fetal mineral accretion has been identified as the gestational period of 20-33 weeks, with daily needs escalating from 50 mg/day to 330 mg/day at its peak. The average newborn contains about 20-30 g calcium, and one study of 256 women in their second trimester showed that supplementation in women with poor calcium status significantly increased neonatal bone mineral content, as determined by X-ray absorptiometry measurements at 1 week postpartum (Koo et al 1999). However, the full relationship between maternal calcium intake and fetal growth, particularly in non-deficient women, has yet to be elucidated (Prentice 2003). One suggested effect of gestational mineral intake has been the determination of calcium concentration in the mother's breastmilk, while it has been established that this concentration is not the result of calcium intake postpartum (Prentice et al 1999).
Lead toxicity Increased blood lead levels are commonly a result of bone resorption during pregnancy and are considered a potential risk to fetal and infant health. Lead can be transferred to the fetus and infant via cord blood and breastmilk. Several studies suggest a low placental barrier to lead, with 79% of the mobilised lead from maternal bone passed to the infant (Dorea & Donangelo 2005). While a number of studies have indicated lead levels in the breastmilk of Australian women appear to be Calcium 154
well within a safe range, recent data from a study conducted by Ettinger et al
revealed that even low lead content In human milk appears to be highly Influential on the lead levels of infants in their first month of life (2004). A separate review published in 2005 discussed additional related trends such as increased lead concentrations in cord blood during winter months, because of lower vitamin D status (Dorea 2004).
A RCT of 617 lactating women supplemented with high-dose calcium carbonate found that the women in the calcium group showed significant reductions in blood lead levels. Those subjects who showed improved compliance and also had baseline higher bone lead content produced an overall reduction of 16.4% (Hernandez-Avila et al 2003). Similar positive findings came from a study in Mexico of 367 lactating women; however, the maximal reduction in lead concentrations reached only 10% (Ettinger et al 2006). Nevertheless, when considered together these results suggest that calcium supplementation may represent an important interventional strategy, albeit with a modest effect, for reducing infant lead exposure. Neonatal benefits Calcium supplementation during pregnancy has been postulated to have prolonged benefits in the offspring, as indicated in a study of nearly 600 children aged 5-9 years whose mothers had previously participated in a calcium trial during their pregnancy. The children demonstrated reduced SBP, compared with the children whose mothers had taken placebo, with significance reached particularly for those in the upper BMI bracket (Belizan et al 1997).
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