Maternal calcium metabolic stress and fetal growth

Am J Clin Nutr. 2014 Apr;99(4):918-25. doi: 10.3945/ajcn.113.076034. Epub 2014 Feb 5.


Background: Suboptimal maternal calcium intake and vitamin D status may or may not adversely influence fetal growth.

Objective: It was hypothesized that maternal calcium metabolic stress in early pregnancy, rather than suboptimal calcium intake or insufficient vitamin D, influences the risk of small-for-gestational-age (SGA) births and other aspects of fetal growth. Stress to calcium metabolism was defined as elevated intact parathyroid hormone (PTH) (>62 pg/mL) accompanied by a very low calcium intake [<60% of the Estimated Average Requirement (EAR)] or insufficient 25-hydroxyvitamin D [25(OH)D] (<20 ng/mL).

Design: This was a prospective cohort study of 1116 low-income and minority gravidae at entry to care of 13.8 ± 5.6 wk (mean ± SD).

Results: The PTH concentration depended on circulating 25(OH)D and total calcium intake. When 25(OH)D was insufficient, even a high calcium intake (which equaled or exceeded the Recommended Dietary Allowance) was unable to maintain PTH or to moderate the proportion of patients with an elevated PTH. When examined one at a time, very low calcium intake (<60% of EAR), very low 25(OH)D (<12 ng/mL), and elevated PTH (>62 pg/mL) each had a small but significant association with birth weight. Elevated PTH was also related to birth length and risk of SGA birth. Elevated PTH accompanied by insufficient 25(OH)D or very low calcium intake was associated with a 2- to 3-fold increased risk of SGA birth and a significantly lower birth weight, birth length, and head circumference, even after women who developed preeclampsia were excluded. Infants born to gravidae with insufficient 25(OH)D or very low calcium intake without elevated PTH or with elevated PTH alone were unaffected.

Conclusion: Maternal calcium metabolic stress, rather than low calcium intake or insufficient vitamin D, has an adverse influence on fetal growth. This trial was registered at as NIH 0320070046.

Trial registration: NCT02032459.

Publication types

  • Clinical Trial
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adolescent
  • Adult
  • Calcifediol / blood
  • Calcium / deficiency*
  • Cohort Studies
  • Female
  • Fetal Development*
  • Fetal Growth Retardation / epidemiology
  • Fetal Growth Retardation / etiology*
  • Humans
  • Hyperparathyroidism / blood
  • Hyperparathyroidism / physiopathology
  • Infant, Newborn
  • Infant, Small for Gestational Age
  • Male
  • Maternal Nutritional Physiological Phenomena*
  • New Jersey / epidemiology
  • Parathyroid Hormone / blood
  • Pregnancy
  • Pregnancy Complications / blood
  • Pregnancy Complications / physiopathology
  • Prospective Studies
  • Risk
  • Vitamin D Deficiency / blood
  • Vitamin D Deficiency / physiopathology*
  • Young Adult


  • PTH protein, human
  • Parathyroid Hormone
  • Calcifediol
  • Calcium

Associated data