Calcium Metabolism In Pregnancy Research Articles

A Case of Pseudohypoparathyroidism Type 1b in Pregnancy

Introduction: Pseudohypoparathyroidism (PHP) type 1b is characterized by target organ resistance to PTH leading to hypocalcemia and hyperphosphatemia in the setting of elevated PTH due to abnormal imprinting that affects the regulatory elements of GNAS1. It poses challenges in management during pregnancy and lactation. We report the case of a patient who was diagnosed with PHP type 1b while pregnant. Case Presentation: A 30 year old woman, 16 weeks pregnant was referred for the evaluation of hypocalcemia. She had a history of traumatic fracture of her lower extremity and hypothyroidism treated with levothyroxine. She was noted to have hypocalcemia 1 year prior during routine labs. Family history was significant for hypothyroidism in her sister. On physical examination, she did not have phenotypic features of Albright hereditary osteodystrophy except for short stature. Before pregnancy her labs were significant for Ca 8.1 mg/dL(8.6–10.2), iCa 4.2 mg/dL(4.8–5.6), iPTH 289 pg/mL (14–64), creatinine 0.6 mg/dL(0.8–1.2), 25 vitamin D 22 ng/mL and 24 hr urine Ca 80 mg/24 hr (65-250mg). She was started on a combination of calcium citrate and carbonate 600 mg daily and vitamin D 1000 units daily. Labs while pregnant showed Ca 8.1 mg/dL, iCa 4.1 mg/dL, iPTH 184 pg/mL, PO4 4.9 mg/dL(2.5–3.5), 1,25 Vitamin D 53 pg/mL(18–72) and 25 Vitamin D 38 ng/mL. She had mild paresthesia and muscle cramps. Calcium supplements were increased to 1800 mg daily. While the urine Ca increased to 315 mg/24 hr, other biochemical parameters did not improve. Given her low Ca, high iPTH, high PO4, normal GFR and 25 vitamin D, PHP was suspected. Genetic testing showed loss of methylation at GNAS locus down to 5% (NL >43%) Diagnosis of PHP type 1b was made. Her Ca decreased the next months to a nadir of 7.9 mg/dL despite increased doses of calcium up to 1200 mg BID. Calcitriol 0.25 mcg BID was added. The rest of her pregnancy the serum Ca stayed between 8.1–8.6 mg/dL. She delivered a boy. At birth his Ca was 8.0 mg/ dL and PTH 81pg/mL. Genetic testing showed 41% methylation of GNAS. While breast feeding her Ca was 9.4 mg/dL, her calcitriol and calcium supplements were decreased. She continues to do well on calcium 630 mg daily and calcitriol 0.25 mcg daily with serum Ca between 8.5–8.8 mg/dL. Conclusion: The literature on PHP in pregnancy is scarce due to its rarity and the management is challenging due to altered calcium and vitamin D metabolism during pregnancy and lactation. The fetus draws calcium from maternal circulation and predisposes mother to hypocalcemia. Some patients may become normocalcemic during pregnancy due to placental secretion of 1,25 Vitamin D and PTHrp. There is also increased demand for calcium with lactation. There are genetic implications on the baby as it is inherited in an autosomal dominant mode. It is important to monitor calcium levels closely as there are multiple factors that could influence calcium metabolism in pregnancy.

Calcium metabolism in pregnancy and lactation.

Homeostatic adaptation to maternal calcium metabolism is a prerequisite for optimal delivery of sufficient calcium to the fetus and neonate during pregnancy and lactation, respectively. This article outlines the major adaptations known to occur and the physiological regulators likely to be principally involved. Importantly, different adaptive responses are used in pregnancy and lactation. The rarity of calcium disorders in pregnancy underscores the successful implementation of these adaptations in most women. For those few women with either pre-existing or pregnancy-acquired disorders of calcium metabolism, a knowledge of normal physiology is essential to understand the implications for managing these disorders in pregnant women.

Bone marker status in mothers and their newborns in Iran

Objectives. The contribution of maternal skeletal calcium metabolism in pregnancy is evidenced in changes in the markers of bone formation and bone resorption. Changes in maternal bone markers could affect fetal bone mineralization. The aim of this study was to determine the association between maternal and cord blood bone markers.Methods. Five hundred and fifty-two pregnant women were recruited from Tehran University educating hospitals in the winter of 2002. Maternal and cord blood samples were taken at delivery. The serum was assayed for osteocalcin and crosslaps, calcium, and parathyroid hormone.Results. There was significant correlation between maternal and cord blood serum osteocalcin and crosslaps levels, and the mean cord blood levels of osteocalcin and crosslaps were significantly higher at about 1.59- and 1.62-fold maternal levels, respectively. Serum calcium levels strongly correlated with osteocalcin and crosslaps in mothers (r = 0.21, p = 0.001 and r = 0.25, p = 0.001, respectively).Conclusions. Skeletal calcium release may play a major role in calcium homeostasis during pregnancy. Because of this, calcium supplements could have an important role in pregnant women in decreasing the risk of subsequent complications such as osteoporosis.

Postpartum abnormalities of carbohydrate and cellular calcium metabolism in pregnancy induced hypertension.

We have previously reported that young, primigravid, African-American women who developed preeclampsia exhibited insulin resistance (elevated fasting insulin:glucose ratios) and abnormal intracellular free calcium ([Ca2+]i) metabolism as early as the second trimester of pregnancy. To determine if these abnormalities persist postpartum (suggesting a genetic link), we evaluated the effects of an oral glucose load (50 g) on plasma and glucose insulin, basal platelet [Ca2+]i and platelet [Ca2+]i responses to arginine vasopressin (AVP). The study population consisted of nine, young, primigravid, African-American women at 43 +/- 12 weeks postpartum from pregnancy induced hypertensive (PIH) gestations and 10 age- and weight-matched African-American women who were 29 +/- 7 weeks postpartum from normal pregnancies. The PIH group consisted of five subjects who were preeclamptic and four subjects with gestational hypertension. Baseline fasting body weights, body mass indices, plasma glucose, plasma insulin, basal platelet [Ca2+]i, and platelet [Ca2+]i responses to AVP were similar in the postpartum PIH and control groups. The oral glucose load had no effect on basal platelet [Ca2+]i levels in either group. However, plasma glucose and insulin and platelet [Ca2+]i responses to AVP were accentuated at 30 min following an oral glucose load suggesting a subtle abnormality of carbohydrate and [Ca2+]i metabolism that persists in individuals with pregnancy induced hypertension. Long term studies involving African-American populations will be necessary to determine if these metabolic abnormalities are associated with an increased propensity to hypertension.

Calcium metabolism in pregnancy

During pregnancy and lactation there are many changes in maternal calcium physiology which maintain homeostasis in the face of greatly altered calcium balance. In the course of fetal growth and development, 30g of calcium is incorporated into the fetus by term, an amount derived wholly from the maternal system. Most of this accumulates in the latter half of pregnancy, representing a net transfer of 200mg calcium/day (5mmoles). The fact that this is not achieved at the expense of the maternal skeleton is testimony to the conservative and protective adjustments that are seen in calcium metabolism in pregnancy. Furthermore, the changes must persist both in the puerperium and later when lactation presents a source of continuing maternal calcium loss to the suckling infant. The calcium content of human breast milk s i 6–9mmols calcium/l, two to three times the maternal serum level. In the course of one week a normal breast-fed at term infant takes two to three litres of milk, containing 10–30mmols of calcium. The maternal daily calcium intake recommended by the World Health Organization s i 1.25g (30mmol) of which only 25% is absorbed. Thus calcium loss from mother to baby is significant and may not be replaced by diet in many parts of the world.

Calcium metabolism in pregnancy and in the newborn.

SummaryVarious aspects of calcium metabolism were studied in Negro, Caucasian and Asian mothers and their infants. There was an increase in circulating parathyroid hormone in pregnancy and umbilical cord plasma levels were usually as high as those in maternal plasma at delivery indicating that parathyroid hormone crossed the placental barrier. This increase in circulating parathyroid hormone probably reflects calcium depletion of the mother by the fetus and was most marked in women whose diet had a low vitamin D, low calcium and high phytic acid phosphorus content. Transient neonatal hypocalcaemia was most common in the infants of Asian women, even when these were breast fed, and it was these women whose antenatal serum calcium, phosphorus and heat labile alkaline phosphatase values suggested that they had maximum parathyroid stimulation. Bakwin (1937) suggested that high circulating levels of parathyroid hormone cause hypoplasia of the fetal parathyroid glands with a fall of serum calcium in the neonatal period; our results support this theory.