Nutrient/Antacid
PREGNANCY RECOMMENDATION: Compatible
BREASTFEEDING RECOMMENDATION: Compatible
PREGNANCY SUMMARY
Sufficient maternal calcium intake is important to ensure adequate mineralization of the fetal skeleton (1). The recommended dietary allowance (RDA) for calcium during pregnancy is based on age: 1300 mg/day for 14–18 years and 1000 mg/day for 19–50 years (2). The primary source of calcium in pregnancy is diet, but antacids and supplements containing calcium carbonate, and prenatal vitamins, also contribute. Recommended doses of calcium carbonate for heartburn relief are safe in pregnancy, but very high doses have caused milk-alkali syndrome and other toxicity. Calcium supplements, such as 1000–2000 mg/day of calcium carbonate, offer few if any benefits for pregnant women if they have adequate dietary calcium intake. However, there may be some benefits for women with low (<600 mg/day) dietary calcium intake.
FETAL RISK SUMMARY
Calcium carbonate is commonly used as a source of calcium either alone or as a component of vitamins products. It also is used as an antacid, either alone or in combination with other antacids, to neutralize stomach acid.
Calcium crosses the human placenta by active transport. The fetal concentration of calcium is related to fetal weight so that most accumulation of calcium takes place in the 3rd trimester (3).
A number of studies have evaluated calcium supplementation with calcium carbonate to prevent or reduce the risk of hypertensive disorders in pregnancy (gestational hypertension and preeclampsia), preterm birth, maternal hemodynamic dysfunction, and long-term effects on the blood pressure of offspring (4–15). Although many of these studies reported a reduction in hypertensive disorders, a large 1997 study conducted by the National Institutes of Health (NIH) did not find this outcome (16). In this study, 4589 healthy nulliparous women at 13–21 weeks’ gestation were randomized to receive daily treatment throughout their pregnancy with either 2 g of calcium carbonate or placebo. In the calcium group (N = 2295), preeclampsia occurred in 158 (6.9%), whereas in the placebo group (N = 2294), 168 (7.3%) developed preeclampsia (relative risk 0.94, 95% confidence interval 0.76–1.16). There also was no significant difference between the groups for pregnancy-associated hypertension without preeclampsia (15.3% vs. 17.3%) or all hypertensive disorders (22.2% vs. 24.6%). The mean systolic and diastolic blood pressures during pregnancy were similar in the groups. Moreover, calcium supplementation did not reduce the number of preterm births (<37 weeks; 10.8% vs. 10.0%), small-for-gestational-age infants (5.8% vs. 4.9%), or fetal and neonatal deaths (27 vs. 25 cases). In addition, calcium supplementation did not increase urolithiasis (3 vs. 4 cases) (16).
In an editorial accompanying the aforementioned NIH study, the author pointed out that whereas the investigators involved diet in the NIH study, this may not have been done in previous studies and might account for the different outcomes (17). The author also cautioned that although the NIH study clearly demonstrates that supplemental calcium 2 g/day offers no benefit for low-risk women if the desired outcome is reduced preeclampsia or improved fetal or neonatal outcome, it did not indicate that adequate or extra dietary calcium was not important (17).
A 1999 randomized, double-blind, placebo-controlled study examined the effect of calcium carbonate supplementation (≥2 g/day) during the 2nd and 3rd trimesters on fetal bone mineralization (18). A total of 256 infants (128 per group) were studied. The supplementation did increase fetal bone mineralization in women with low dietary calcium intake (<600 mg/day) compared with placebo, but in women with adequate dietary calcium intake, supplementation did not result in major improvement in this outcome (18).
The results of a multicenter, randomized, placebo- controlled, double-blind trial of calcium supplementation in low-calcium-intake pregnant women were published in 2006 (19). The trial found that calcium carbonate supplementation (1.5 g/day) did not prevent preeclampsia but did reduce its severity. Also noted was a slight, nonsignificant lowering of preterm (<37 weeks) birth (9.8% vs. 10.8%) and a significant decrease in early (<32 weeks) preterm birth (2.6% vs. 3.2%). Maternal morbidity and mortality and neonatal mortality were reduced by supplementation, but two other outcomes, low birth weight in term pregnancies and admission to intensive care units, were similar between the two groups (19).
Using data collected for the aforementioned trial, a 2010 study in Argentina evaluated the effect of calcium supplements on fetal growth in pregnant women with low calcium intake (average calcium intake <600 mg/day) (20). The women, at about 13 weeks’ gestation, were randomized to either calcium carbonate 1500 mg/day (N = 231) or placebo (N = 230). No differences between the two groups were found in serial fetal biometric measurements taken five times from 20 to 36 weeks’ gestation. Moreover, neonatal characteristics and anthropometric measurements at birth were comparable in both groups. The investigators concluded that calcium supplementation of 1500 mg/day in pregnant women with low calcium intake did not improve fetal somatic or skeletal growth (20).
Excessive consumption of calcium carbonate throughout pregnancy was suspected to be the cause of neonatal hypocalcemia, resulting in seizures (21). The mother, a healthy 24-year-old, had heartburn, which she treated with 10 to 14 extra-strength Tums daily (750 mg calcium carbonate/tablet) starting midway through the 1st trimester and continuing until the onset of labor at 39 weeks. The normal-appearing infant weighed about 3.5 kg at birth and was sent home on the second day. Generalized seizures developed at 8 days of age. Laboratory tests were normal, except for a total calcium level of 6.3 mg/dL that decreased to 6.1 mg/dL the next day (normal: 8.5–11.0 mg/dL) and a high phosphorus level (8.2 mg/dL; normal 4.0–7.0 mg/dL). The infant was treated with phenobarbital and IV calcium gluconate, and at 12 days of age, the total calcium was within the normal range, but the phosphorus level did not return to a normal range until 29 days of age. One possible mechanism proposed by the author was that the excessive maternal calcium intake had suppressed fetal parathyroid function. At 3 months of age, the infant was healthy and doing well (21).
Ingestion of calcium carbonate has been associated with three published cases of milk-alkali syndrome in pregnancy (22–24). The first case involved a 34-year-old woman in her second pregnancy (22). She had excessive vomiting and took large quantities (amount not specified) of calcium carbonate, milk, and cheese. She was admitted to the hospital at 23 weeks’ gestation with dehydration and a 3-day history of abdominal pain, nausea, vomiting, and diarrhea. Laboratory tests revealed hypercalcemia (14.3 mg/dL), and acute renal insufficiency (serum creatinine 2.1 mg/dL; blood urea nitrogen 52 mg/dL). The hypercalcemia was caused by the milk-alkali syndrome and resulted in pancreatitis and azotemia. Aggressive IV hydration, 5 L of isotonic saline over 12 hours, resulted in a normal calcium level and renal function and her abdominal pain resolved in 4 days. She was discharged home in good health. At 37 weeks, she gave birth to a stillborn fetus. The fetus had short limbs and low-set ears but a normal chromosome analysis. An autopsy revealed no evidence of tissue calcification (22).
A 31-year-old woman at 36 weeks’ gestation presented with a 3-day history of disorientation, ataxia, nausea, and vomiting (23). Over the previous 2 weeks she had daily ingested 5 glasses of milk and about 30 antacid tablets, each containing 500 mg calcium carbonate. Her total calcium level was 22.5 mg/mL. Because acute severe hypercalcemia (≥15 mg/dL) can be life-threatening and may result in intractable nausea, vomiting, polyuria, dehydration, coma, cardiac arrhythmias, and circulatory arrest, she was aggressively treated with IV therapy and furosemide, followed by hemodialysis. The fetal condition was normal with external monitoring. An ultrasound examination revealed normal amniotic fluid volume but no fetal breathing, body motion, or tone. Four weeks later, the woman gave birth to a 2950-g normal male infant who was doing well at 1 year of age (23).
A third case of the milk-alkali syndrome in pregnancy secondary to excessive ingestion of calcium carbonate was reported in 2004 (24). A 32-year-old woman at 16 weeks’ gestation, who had taken an antacid (Tums; 6–10 tablets/day) for gastroesophageal reflux, presented with severe hypercalcemia (total and ionized calcium 22 mg/dL and 12.16 mg/ dL, respectively), alkalosis, and acute renal insufficiency. The normal ranges for total and ionized calcium were 8.5–10.5 and 4.65–5.20 mg/dL, respectively. At admission, she was treated with IV isotonic saline, furosemide, and a 600-mg dose of IV etidronate. On day 5, symptoms of bisphosphonate-induced hypocalcemia were noted (tingling of the extremities and a positive Chvostek sign). Her symptoms were relieved with IV calcium gluconate and she was started on calcium carbonate. Her low concentrations of total and ionized calcium (7.4–8.0 and 4.00–4.56 mg/dL, respectively) normalized in about 2 weeks. No information was provided on the eventual pregnancy outcome (24).
BREASTFEEDING SUMMARY
The RDA for calcium during lactation is based on age: 1300 mg/day for 14–18 years and 1000 mg/day for 19–50 years (2).
In a small 1994 study, the calcium needed for milk production appeared to be met by decreased urinary excretion and increased bone resorption and not by increased absorption (25). A 1995 study found that calcium carbonate supplements (1000 mg) 5 days each week in Gambian women consuming a low-calcium diet had no effect on breast milk calcium concentration or on maternal bone mineral content. The investigators concluded that physiologic mechanisms worked to furnish calcium for breast milk production (26).
In a 2006 study, pregnant women in Gambia were randomized to calcium carbonate supplementation (1500 mg/day) (N = 61) or placebo (N = 62) from 20 weeks’ gestation to delivery (27). Breast milk levels of calcium were analyzed at 2, 13, and 52 weeks after delivery. No differences between subjects and controls in the calcium or phosphorus concentrations in breast milk were noted. Moreover, calcium supplementation had no effect on infant birth weight, growth, or bone mineral status (27).
In Mexican lactating women with high lead levels (mean blood lead 8.5 mcg/mL), a 2003 study measured the effect of calcium carbonate supplementation (1200 mg/day) compared with placebo (28). The supplements resulted in a small decline (0.29 mcg/dL) of blood lead levels. A greater reduction (1.16 mcg/dL) was observed in women who were compliant with supplement use and had high bone lead levels (patella bone lead ≥5 mcg/g bone) (28).
A 1997 study evaluated the effect of calcium carbonate supplementation (1 g/day) compared with placebo on the bone density of the maternal lumbar spine (29). In lactating women, the lumbar spine bone density decreased by 4.2% in the supplement group compared with a 4.9% decrease in the placebo group. In nonlactating women, calcium supplements increased lumbar spine bone density by 2.2% vs. 0.4% with placebo. There was no effect of lactation or supplementation on bone density in the forearm and supplementation did not increase the calcium concentration in breast milk (29). An accompanying editorial supported the findings of the study. The author noted that nursing mothers provide an average of 200–250 mg/day of calcium to their infants and recommended that they increase their calcium intake by 400–800 mg/day (30).
References
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