Pregnant Women Should Monitor Serum Calcium Levels, Researchers Say

Maintaining serum calcium levels within the low normal reference range, checking them closely, and assuring a coordinated approach among health professionals are among the recommendations for pregnant women with hypoparathyroidism, according to a review study.

The study, “Hypoparathyroidism in Pregnancy: Review and Evidence Based Recommendations for Management,” appeared in the European Journal of Endocrinology.

Hypoparathyroidism is a rare disorder caused by low levels of the parathyroid hormone (PTH) in the body. Normally, PTH is produced when the levels of calcium in the blood are low, to trigger its increase. Therefore, one of the consequences of low PTH levels is a marked decrease in calcium in the blood.

To evaluate calcium homeostasis (its equilibrium within the body) in pregnancy and provide recommendations for the management of hypoparathyroidism during pregnancy, researchers conducted a literature review of studies published between 2000 and April 2018 using three online databases. Sixty-five studies were included.

A reduction in albumin — the most abundant protein in plasma — during pregnancy leads to a decrease in the total amount of albumin-bound calcium. Also, levels of PTH, which are affected by maternal calcium intake and vitamin D levels, is lowered in the first trimester, but later rises to the mid-normal reference range. In turn, the synthetic vitamin D analog calcitriol rises to twice or three times its level by term, increasing intestinal calcium absorption and suppressing PTH.

Increased levels of serum calcitonin — a hormone secreted by the thyroid that lowers blood calcium — during pregnancy have also been observed, although evidence has been contradictory.

Thyroid C-cells, the breast and the placenta have been proposed as the main contributors to this rise in the amount of calcitonin. Other studies have suggested that increases in estrogen and in parathyroid hormone-related protein (PTHrP) — attributed to the placenta and breast — are associated with this elevation in calcitonin levels.

Pregnant women with hypoparathyroidism require close monitoring of serum calcium — every three or four weeks, researchers recommend. However, if a change in doses of calcium or calcitriol are advised, the team recommends repeating the lab profile with serum calcium corrected for albumin in a week or two.

Adjusting the dose of calcium and calcitriol may be necessary to avoid insufficient (hypocalcemia) or exaggerated (hypercalcemia) levels of calcium. Inadequate calcium intake in the first trimester may be detrimental to fetus development in the last trimester. Variable levels of PTHrP and calcitriol may also lead to different dose requirements during pregnancy.

Delivery of calcium, phosphate and magnesium via the placenta is essential for fetal skeleton mineralization. Women with severe hypoparathyroidism and severe hypocalcemia may generate a fetus that also has hypocalcemia. This stimulates the fetal parathyroid glands and results in hyperparathyroidism and demineralization of the skeleton, potentially leading to intrauterine rib and limb fractures, low birth weight, and spontaneous abortion.

In turn, calcium transfer to the fetus is increased in pregnant women with hypercalcemia, resulting in suppression of the fetal parathyroid glands. If untreated, hypoparathyroidism may increase the risk for abortion. “Therefore, it is important to maintain serum calcium in the low normal reference range during pregnancy and monitor closely to ensure that both hypocalcemia and hypercalcemia are avoided,” researchers said.

Also recommended during pregnancy — though scientists caution that the quality of evidence is very low — is to maintain serum phosphate, magnesium, 25 hydroxyvitamin D (the major circulating form of vitamin D) and 24-hour urinary calcium levels within the low normal reference range.

Supplements of calcium, calcitriol and vitamin D are safe during pregnancy. The safety of PTH has not been sufficiently evaluated and the team recommends stopping replacement therapy with PTH (1-84) and PTH (1-34). Thiazide diuretics should be discontinued.

Researchers also say patients should be educated on symptoms of hypercalcemia and hypocalcemia, as well as the importance of checking serum calcium levels. “Optimal care outcomes for both the mother and baby are achieved with coordinated care among the endocrinologist, obstetrician as well as the pediatrician,” researchers stated.

Close calcium monitoring is also advised after the baby’s birth, as the impact of changed calcitriol and estradiol levels during pregnancy is variable. However, the team cautioned not to adjust doses of calcitriol and calcium supplements too often, given the potential wide fluctuations in serum calcium.

Measurements of serum albumin and ionized calcium levels are recommended as soon as the first week post-partum. If breastfeeding, the authors advise to verify calcium levels once a month.

The target should again be the low normal reference range, which also avoids increases in renal calcium excretion. However, biochemical tests may not be needed if calcium levels are well-controlled during pregnancy and the newborn develops well.