Gestational hypercalcemia is associated with an increased risk of maternal, fetal and neonatal morbidity and mortality. Hypercalcemia may develop during pregnancy in individuals who were previously asymptomatic. The increased sensitivity during pregnancy may be related to physiological, gestational alterations in vitamin D and calcium metabolism and may be influenced by gene variants. The prevalence is unknown. We investigated the prevalence of hypercalcemia in trimester 3 (T3) in a population representative prospective cohort study (n = 1832) in South-West Sweden. Women with serum albumin (Alb) adjusted calcium (CaAlb) ≥ 2.65 mmol/L in T3 (n = 30) were matched to normo-calcemic controls, and markers of calcium and vitamin D metabolism were investigated in trimester 1 (T1) and T3. Serum concentrations of Ca, phosphate (P), Magnesium (Mg), Alb and creatinine (Cr), parathyroid hormone (PTH; T3 only), vitamin D metabolites (total 25(OH)D, 1,25(OH)2D, 24,25(OH)2D, and free 25(OH)D) were analysed in T1 and T3. CaAlb (Payne; inter-laboratory difference: UEA = 0.15 + 0.9*UGOT; UEA 2.54 = UGOT 2.65) and estimated glomerular filtration rate (eGFR; modified 4-variable MDRD) and vitamin D metabolites ratios (VMR) were calculated. Normally and non-normally distributed data were presented as mean (SD) or median (95 %CI). Group differences in relationships between vitamin D metabolites and with PTH were investigated with multiple regression analyses. Hypercalcemia in T3 was found in 1.7 % of women. PTH concentrations suggestive of primary hyperparathyroidism was found in 1 woman and none had 25(OH)D or 24,25(OH)2D concentrations in the toxicity range or suggestive of mutations in the CYP24A1 gene. CaAlb was significantly higher in hypercalcemic cases compared to controls in T1 (2.44 (2.30-2.80) vs 2.37 (2.25-2.49) mmol/L) and T3 (2.63 (2.52-2.78) vs 2.46 (2.31-2.58) mmol/L). Serum P was higher among cases than controls in T3 (1.12 (0.16) vs 1.07 (0.18) mmol/L) but not in T1 (1.12 (0.18) and 1.12 (0.16) mmol/L). PTH in T3 was lower in cases (1.6 (1.6-2.8) vs 2.3 (2.1-2.8) pmol/L) but 1,25(OH)2D concentrations were similar. There were no significant group differences in serum 25(OH)D, free 25(OH)D, 24,25(OH)2D, Mg, Alb, Cr and eGFR. Regression analyses did not show significant differences between cases and controls in relationships between vitamin D metabolites and with PTH, except for the free 25(OH)D-PTH relationship and a higher free:total 25(OH)D ratio in cases at T1. In conclusion, most common causes of hypercalcemia were excluded in the majority of women. Hypercalcemic women had a relatively high serum 1,25(OH)2D concentration despite an appropriately suppressed PTH, suggestive of abnormal gestational adaptions.

中文翻译：

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妊娠期高钙血症：患病率和生化特征。

妊娠期高钙血症与孕产妇，胎儿和新生儿的发病率和死亡风险增加有关。以前无症状的人在怀孕期间可能会发生高钙血症。怀孕期间敏感性的提高可能与维生素D和钙代谢的生理，妊娠改变有关，并可能受到基因变异的影响。患病率未知。我们在瑞典西南部的一项具有人口代表性的前瞻性队列研究（n = 1832）中调查了妊娠中期（T3）高钙血症的患病率。在T3（n = 30）中血清白蛋白（Alb）调整的钙（CaAlb）≥2.65 mmol / L的妇女与正常血钙对照相匹配，并且在孕期1（T1）和T3中研究了钙和维生素D代谢的指标。血清中Ca，磷酸盐（P），镁（Mg），Alb和肌酐（Cr），甲状旁腺激素（PTH;仅T3），维生素D代谢产物（总计25（OH）D，1,25（OH）2D，24,25（OH）2D和游离25（OH）D ）在T1和T3中进行了分析。计算CaAlb（Payne；实验室间差异：UEA = 0.15 + 0.9 * UGOT； UEA 2.54 = UGOT 2.65），并估算肾小球滤过率（eGFR；修饰的4变量MDRD）和维生素D代谢物比率（VMR）。正态和非正态分布的数据表示为平均值（SD）或中位数（95％CI）。通过多元回归分析研究了维生素D代谢物与PTH之间关系的群体差异。1.7％的女性发现T3中的高钙血症。在1名女性中发现提示原发性甲状旁腺功能亢进的PTH浓度，但均未发现25（OH）D或24（OH）D，毒性范围内浓度为25（OH）2D，或提示CYP24A1基因突变。高钙血症病例中的CaAlb明显高于对照组，T1（2.44（2.30-2.80）vs 2.37（2.25-2.49）mmol / L）和T3（2.63（2.52-2.78）vs 2.46（2.31-2.58）mmol / L） 。T3组患者血清P高于对照组（1.12（0.16）vs 1.07（0.18）mmol / L），而T1组（1.12（0.18）和1.12（0.16）mmol / L）高。病例中T3中的PTH较低（1.6（1.6-2.8）vs 2.3（2.1-2.8）pmol / L），但是1,25（OH）2D浓度相似。血清25（OH）D，游离25（OH）D，24,25（OH）2D，Mg，Alb，Cr和eGFR的组间无显着差异。回归分析未显示维生素D代谢物与PTH之间的关系与病例和对照之间的显着差异，除了游离的25（OH）D-PTH关系和较高的游离：在T1时，总25（OH）D比率。总之，大多数妇女排除了高钙血症的最常见原因。高钙血症女性尽管PTH受到适当抑制，但血清中1,25（OH）2D浓度相对较高，提示异常的妊娠适应。