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We measured serum osteocalcin concentrations in 82 pregnant and 21 nonpregnant women. Osteocalcin values declined in the second trimester, but returned to nonpregnant levels late in the third trimester. The mean serum osteocalcin concentration in 36 women during pregnancy (mean gestation, 26 weeks) of 2.8 ng/mL was significantly lower than that in nonpregnant women (6.4 ng/mL; P less than 0.001) or term pregnant women at delivery (6.1 ng/mL; n = 46). Serum immunoreactive PTH (iPTH) levels were significantly higher during pregnancy than in nonpregnant women [97 +/- 5 vs. 56 +/- 4 ng/L (mean +/- SE); P less than 0.001]. No significant correlations were found between maternal osteocalcin concentrations and serum phosphorus, alkaline phosphatase, or iPTH, but significant negative correlations were found between osteocalcin and total calcium or total protein. Osteocalcin concentrations in midtrimester amniotic fluid were very low (mean, 0.3 +/- 0.1 ng/mL; n = 11). In 29 lactating mothers, the mean serum osteocalcin level was 9.5 +/- 1.5 ng/mL, significantly higher than in any of the other groups (P less than 0.05), but their serum calcium and iPTH levels were normal. There was no correlation between serum osteocalcin and calcium or iPTH concentrations in lactating women. These changes are compatible with a sequence in which bone turnover is reduced during early pregnancy, rebounds in the third trimester, and increases in postpartum lactating women.

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Inorganic sulfate (SO4) is an essential metabolite for the synthesis of sulfated mucopolysaccharides and steroid sulfates in the fetus and placenta. The authors' previous study of pregnant women at delivery revealed a substantial increase in serum SO4 compared with nonpregnant adults. To determine whether or not this difference was related to altered renal handling, creatinine clearance and SO4 reabsorption was measured in 43 women in the third trimester of pregnancy and in 22 nonpregnant control subjects. Serum SO4 was 32% higher in the pregnant women than in control subjects. Urinary excretion of SO4 was unchanged, but absolute reabsorption of SO4 was significantly higher. Blood pressure, serum creatinine, and serum chloride were significant predictors of serum SO4. As a group, women with hypertension (diastolic blood pressure greater than 80 mmHg) had a significantly higher serum SO4 than those with normal blood pressure. One result of the increased SO4 reabsorption by maternal kidney is that it generates a larger maternal reservoir on which the fetoplacental unit can draw for its biosynthetic needs.

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Controlled-flow ion chromatography has significantly improved the precision with which inorganic sulfate (SO4) can be measured in serum. In this study, we have shown that serum SO4 is increased in pregnancy. The increase appears to follow gestational age, resulting in a 39% higher value by the middle of the third trimester. We suggest that this increase is a natural physiological process, which enhances SO4 availability to the growing fetus and placenta.

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Inorganic sulfate is a cosubstrate for numerous sulfoconjugation reactions, including sulfation of estrogen steroids in the fetoplacental unit. It is known that the availability of inorganic sulfate can be the rate-limiting factor in these reactions, but fluxes of inorganic sulfate across the maternal-placental barrier have not been well characterized. Therefore, we measured serum inorganic sulfate in matched samples from 46 mothers and fetuses at parturition to identify any maternal-fetal gradient and explore clinical correlations. The concentration of inorganic sulfate, measured by controlled-flow anion chromatography, was significantly higher (p = 0.006) in fetal cord blood [458 +/- 10 microM; mean +/- SE] than in the maternal circulation [431 +/- 19 microM]. That a gradient was not observed for chloride ion rules out sampling artifact as a source of the difference. Maternal and fetal concentrations of inorganic sulfate were highly correlated (r = 0.84, p less than 0.001). No influence was observed for gestational history, newborn weight, sex, or Apgar scores, but values were significantly higher in those with relatively shorter (less than 36 weeks) or longer (greater than 41 weeks) gestations. We demonstrated that a small but significant fetal-to-maternal inorganic sulfate gradient exists at birth, but the origin of this gradient is not known.

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