Dr Fergus McCarthy takes a monthly look at articles just published in the area of hypertension & pre-eclampsia…

The long-term sequelae of pre-eclampsia continue to evoke interest and further research.  Vannevel et al conducted an international multicenter retrospective cohort study examining the associations between pre-eclampsia and long-term renal function in women who underwent kidney transplantation.¹ Renal function at conception, pregnancy outcomes, and short- and long-term graft outcomes were collected for women who were pregnant after renal transplantation and had transplant and obstetric care at participating centers.

Pregnancy outcomes and long-term renal outcomes were available for 52 women. Chronic hypertension was present at baseline in 27% of participants. Mean estimated glomerular filtration rate (GFR) at the start of pregnancy was 52.4±17.5 mL/min/1.73 m. Mean estimated GFR at delivery was 47.6±21.6 mL/min/1.73 m, which was significantly lower than at conception (P=.03). Twenty women (38%) developed pre-eclampsia.

Women who developed pre-eclampsia had a 10.7-mL/min/1.73 m higher drop in estimated GFR between conception and delivery than women who did not develop pre-eclampsia (P=.02). Long-term estimated GFR follow-up was obtained at a median of 5.8 years (range 1.3-27.5 years). Mean estimated GFR at last follow-up was 38±23 mL/kg/1.73 m. Seventeen women (33%) experienced graft loss over the follow-up period. The incidence of graft loss was similar in women with and without pre-eclampsia in their last pregnancy (30% and 34%, respectively; P=.99). In multivariable analysis, the decrease in estimated GFR between conception and last follow-up was similar in women who experienced pre-eclampsia during pregnancy and those who did not (difference -2.69 mL/min/1.73 m, P=.65).

While the findings suggest that pre-eclampsia commonly complicates pregnancies after renal transplantation, the changes observed were short term but reassuringly not associated with long-term renal dysfunction or graft loss.

 

Low molecular weight heparin and heparin-based pharmacological agents remain under investigation for their potential use in the prevention or treatment of pre-eclampsia. Using data and samples from the Heparin-Pre-eclampsia trial, Lecarpentier et al examined whether daily low-molecular-weight heparin (LMWH) prophylaxis during pregnancy altered the profile of circulating angiogenic factors.²

The Heparin pre-eclampsia trial was a randomized trial in pregnant women with a history of severe early-onset pre-eclampsia (<34 weeks’ gestation). In this randomised trial, all women were treated with aspirin and then randomized to receive LMWH or aspirin alone.

This mechanism of disease study measured serum levels of circulating angiogenic factors (soluble fms-like tyrosine kinase-1, placental growth factor, and soluble endoglin by immunoassay) at the following gestational windows: 10-13 6/7 weeks, 14-17 6/7 weeks, 18-21 6/7 weeks, 22-25 6/7 weeks, 26-29 6/7 weeks, 30-33 6/7 weeks, and 34-37 6/7 weeks.

Samples were available from 185 patients: LMWH and aspirin (n=92) and aspirin alone (n=93). There were no significant differences in serum levels of soluble fms-like tyrosine kinase-1, placental growth factor, and soluble endoglin in the participants who received LMWH and aspirin compared with those who received aspirin alone regardless of gestational age period. Women who developed an adverse composite outcome at less than 34 weeks of gestation demonstrated significant alterations in serum angiogenic profile as early as 10-13 6/7 weeks that was most dramatic 6-8 weeks preceding delivery.

In conclusion, prophylactic LMWH therapy taken from under 14 weeks’ gestation was not associated with an improved angiogenic profile. These findings support the lack of clinical benefit noted in clinical trials.

Finally, this month we review the study by Baca et al which evaluated the relationship between maternal 25-hydroxyvitamin D (25(OH)D) concentration and pre-eclampsia overall and by severity.³ It is estimated that up to 50% of the population are Vitamin D deficient.

The authors used a cohort of 12,861 women who had serum banked from aneuploidy screening in Pittsburgh, Pennsylvania from 1999 to 2010. A subcohort (2327 pregnancies) was randomly sampled and all remaining pre-eclampsia cases (n = 650 cases). Pre-eclampsia (defined as new-onset hypertension and proteinuria) and its mild and severe forms were identified using ICD-9 codes. Maternal serum collected at 20 weeks or less gestation was measured for 25(OH)D.

Approximately 21% of the randomly selected sample had 25(OH)D less than 50 nmol per L. The adjusted risk of pre-eclampsia declined as serum 25(OH)D increased to 50 nmol per L and then plateaued (test of nonlinearity P < .05). The adjusted pre-eclampsia risk ratios (95% confidence intervals) for 25(OH)D less than 25 nmol per L, 25 to 49.9 nmol per L, and 50 to 74.9 nmol per L were 2.4 (1.2-4.8), 1.1 (0.69-1.7), and 1.3 (0.89-1.8), respectively, compared with those with 25(OH)D 75 nmol per L and over. Similar associations were observed with severe and mild pre-eclampsia.

These results suggest that vitamin D deficiency increases the risks of severe and mild forms of pre-eclampsia.

 

References

1. Vannevel V, Claes K, Baud D, et al. Preeclampsia and Long-term Renal Function in Women Who Underwent Kidney Transplantation. Obstetrics and gynecology. 2018;131(1):57-62.
2. Lecarpentier E, Gris JC, Cochery-Nouvellon E, et al. Angiogenic Factor Profiles in Pregnant Women With a History of Early-Onset Severe Preeclampsia Receiving Low-Molecular-Weight Heparin Prophylaxis. Obstetrics and gynecology. 2018;131(1):63-69.
3. Baca KM, Simhan HN, Platt RW, Bodnar LM. Low maternal 25-hydroxyvitamin D concentration increases the risk of severe and mild preeclampsia. Ann Epidemiol. 2016;26(12):853-857 e851.