Maternal vitamin D status in preeclampsia: seasonal changes are not influenced by placental gene expression of vitamin D metabolizing enzymes.

Preeclampsia, a hypertensive disorder in pregnancy develops in 2-8% of pregnancies worldwide. Winter season and vitamin D deficiency have been associated with its onset.To investigate the influence of season on maternal vitamin D status and placental vitamin D metabolism.25-OH vitamin D and 1,25-(OH)2 vitamin D were measured in maternal serum obtained during the winter or summer months from 63 pregnant women at delivery (43 healthy, 20 preeclampsia). In a subgroup, mRNA expression of CYP24A1 (24-hydroxylase), CYP27B1 (1α-hydroxylase) and VDR (vitamin D receptor) were quantified by real time PCR in placental samples of 14 women with normal pregnancies and 13 with preeclampsia.In patients with preeclampsia,25-OH vitamin D levels were lower, but differed significantly from controls only in summer (18.21±17.1 vs 49.2±29.2 ng/mL, P<0.001), whereas 1,25-(OH)2 vitamin D levels were significantly lower only in winter (291±217 vs 612.3±455 pmol/mL, P<0.05). A two-factorial analysis of variance produced a statistically significant model (P<0.0001) with an effect of season (P<0.01) and preeclampsia (P = 0.01) on maternal 25-OH vitamin D levels, as well as a significant interaction between the two variables (P = 0.02). Placental gene expression of CYP24A1, CYP27B1, and VDR did not differ between groups or seasons. A negative correlation between placental gene expression of CYP24A1 and CYP27B1 was observed only in healthy controls (r = -0.81, P<0.0001).Patients with preeclampsia displayed lower vitamin D serum levels in response to seasonal changes.The regulation of placental CYP24A1, but not of the VDR or CYP27B1 might be altered in preeclampsia

mRNA expression of placental CYP24A1, CYP27B1 and VDR (mean ± SD and (range) do not differ between patients with preeclampsia and healthy controls.

<p>mRNA expression of placental CYP24A1, CYP27B1 and VDR (mean ± SD and (range) do not differ between patients with preeclampsia and healthy controls.</p

mRNA expression of placental CYP24A1, CYP27B1 and VDR (mean ± SD and (range) do not differ between patients with preeclampsia and healthy controls.

<p>mRNA expression of placental CYP24A1, CYP27B1 and VDR (mean ± SD and (range) do not differ between patients with preeclampsia and healthy controls.</p

Boxplots showing the smallest observation (lower bar), lower and upper quartile (box), median (line in the box) and largest observation (upper bar) of a) maternal 25-OH vitamin D serum levels (ng/mL) in winter (grey box) and summer (open box).

<p>Maternal 25-OH vitamin D levels differ between patients with preeclampsia and healthy controls in the summer (** p<0.01). b) Maternal 1,25-(OH)₂ vitamin D (pmol/mL) serum levels are similar in both groups, but significantly lower during winter months in patients with preeclampsia (** p<0.01).</p

Patient characteristics (mean + SD and (range)) for age, pre-pregnancy BMI, maternal calcium, 25- OH vitamin D, 1,25-(OH)₂ vitamin D levels in serum, systolic (SBP) and diastolic (DBP) blood pressure on admission to the hospital, as well as child length, weight, and BMI standard deviation scores (SDS) at birth.

<p>In patients with preeclampsia, maternal 25-OH vitamin D levels are significantly lower than in healthy controls. * differs from healthy controls (*<i>P</i><0.05, ** <i>P</i><0.01) ^#blood pressure obtained on admission to hospital was below the criterion for preeclampsia in one patient, despite preeclampsia with proteinuria and elevated blood pressure readings before and after admission.</p

Correlation of placental mRNA expression of CYP24A1 (x-axis) and a) CYP27B1 or b) maternal 25-OH vitamin D (ng/ml) in healthy controls (black circles) and patients with preeclampsia (transparent circles).

<p>a) Placental gene expression of CYP24A1 correlates negatively with CYP27B1 expression in healthy controls (r = −0.81, <i>P</i><0.0001, solid line) but not in the patients with preeclampsia (dotted line). b) CYP24A1 correlates negatively with maternal 25-OH vitamin D levels (r = −0.76, <i>P</i> = 0.01) in patients with preeclampsia (dotted line).</p