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Study of the effect of calcium supplementation during pregnancy on the risk of preterm birth or low birthweight infants is inconclusive
  1. Winston Koo
  1. Correspondence to Winston Koo
    Department of Pediatrics, Neonatology, Lousiana State University, 1501 King's Hwy, Shreveport, LA 71130, USA; wkoo{at}lsuhsc.edu

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Context

Multiple compensatory mechanisms including increased absorption, decreased excretion and altered metabolism played key roles in maintaining calcium homeostasis during pregnancy and lactation. Under normal circumstances, the loss of bone mass in the maternal skeleton during pregnancy and lactation appears to be reversible. Thus dietary reference intake for calcium remains age specific and no additional calcium is recommended for pregnancy or lactation at least in USA.1 However, the role of calcium supplementation in relation to overall maternal nutritional status is not well defined.

Methods

This is a systematic review with meta-analysis of randomised control trials of pregnant women who received calcium supplementation (vs placebo or no supplement) on maternal (other than hypertension), fetal and neonatal outcomes. Data from a literature search of three databases and selected journals were analysed according to criteria outlined in http://www.cochrane-handbook.org (accessed 14 March 2012). Primary maternal outcome was preterm birth (<37 weeks or <34 weeks depending on the study), and fetal outcome was low birth weight (<2500 g). Multiple secondary outcomes included maternal muscular skeletal, serious morbidity and death; perinatal mortality and fetal growth and skeletal development. Adverse outcomes focused on maternal gastrointestinal, renal and hepatic systems and anaemia.

Findings

Substantial heterogeneity exists among studies with no significant difference in the primary outcomes for preterm labour or low birth weight or in most secondary outcomes. Few secondary outcome measures reached statistical significance. These included an increased mean birth weight of 64.66 g (95% CI 15.75 to 113.58 g; τ2=7080, I2=78% random effects model); and a skewed data set with greater bone density of the radius and ulna of neonates from mothers who received either 300 mg or 600 mg of elemental calcium supplement daily.2 No significant increase in adverse outcomes was observed up to 2 g elemental calcium supplement daily for >20 weeks of pregnancy.

Commentary

Buppasiri et al concluded that there is no benefit from calcium supplementation to reduce preterm deliveries and low -birthweight neonates. However, lack of evidence of effect is not the same as evidence of lack of effect. They illustrated the difficulties in interpreting narrowly defined outcomes from data with severe heterogeneity in design, patient population and other biases. Mean birth weight increase of 65 g in gestational matured neonates is unlikely to have any clinical significance. However, increased neonatal regional2 or total body3 ,4 bone mass from maternal calcium supplement is consistent with the premise of a positive influence on fetal skeletal mineralisation from calcium supplement in mothers with low-dietary calcium intake2 ,3 or as a component of better overall dietary intake.4 In women who had adequate overall nutrient intake, the threshold for maternal dietary calcium intake that may affect fetal bone mineralisation appears to be <600 mg/day.3

In contrast, one report of women in Gambia, West Africa with an average calcium intake of ∼350 mg/day receiving 1500 mg elemental calcium or placebo/day from 20 weeks of pregnancy showed no significant benefit on total body, radius and ulna bone mass in the neonate and throughout infancy.5 In the same study, calcium supplementation had no effect on maternal bone mass at delivery but revealed a greater decrease in maternal lumbar spine and total body bone mass between 13 and 52 weeks of lactation.6 Unfortunately, longitudinal bone mass over three time points were measured in <35%5 and <41%6 of the recruited subjects. Few maternal–infant dyads have complete series of bone measurements.5 ,6 This population also has seasonal variations in food supply resulting in marked differences in pregnancy weight gain, birth weight and infant growth.5 ,6 However, in Brazilian women with normal prepregnancy body mass index and gestational weight gain but low-habitual calcium intake (average 463 mg/day, up to ∼1 g/day), a longitudinal dual stable isotope kinetics study showed improved bone calcium balance with increasing dietary calcium intake during pregnancy and lactation.7

It is not surprising that calcium supplementation alone may not improve bone mineralisation since many nutrients are needed in this process. Even in developed countries, low-dietary calcium is often associated with multiple nutrient deficiencies.8 Benefits of maternal calcium supplementation during pregnancy exist but only as part of the diet to achieve an adequate overall dietary intake.

References

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Footnotes

  • Competing interests None.