Corticosteroid use in pregnancy doubles risk of severe VOC: Study

Can be given to promote fetal development in women at risk of preterm birth

Andrea Lobo, PhD avatar

by Andrea Lobo, PhD |

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A pregnant woman cradles her abdomen with one hand while holding a stuffed toy with the other.

Corticosteroids taken during pregnancy are a risk factor for more severe vaso-occlusive crises (VOCs) in women with sickle cell disease (SCD), according to a study in France.

Particularly, this risk was higher in women with a more severe SCD type and evidence of more severe disease. Newborns exposed to corticosteroids also were more likely to be born prematurely and have complications.

These findings indicate that corticosteroids “should be used only after a multidisciplinary benefit/risk assessment and decision with the patient, when there is a crucial risk of very preterm delivery,” the researchers wrote.

The study, “Impact of prenatal corticosteroid therapy on sickle cell disease in pregnant women,” was published in the International Journal of Gynecology & Obstetrics.

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Pregnancy with SCD is known to carry risks, with complications leading to fetal or maternal death found in about 1% of all pregnancies in high-resource countries despite improved treatment, the researchers noted.

Maternal complications include VOCs, acute chest syndrome, pre-eclampsia (high blood pressure accompanied by organ damage), blood clotting problems, and infections. Fetal complications primarily are preterm (premature) birth, growth restriction in the uterus, and death.

VOCs occur when red blood cells block blood flow, depriving tissues of oxygen and causing inflammation and pain. Acute chest syndrome is a serious complication caused by blood vessel obstruction in the lungs that’s marked by fever, chest pain, and difficulty breathing.

In women at high risk of giving birth prematurely, before 34 weeks of pregnancy (gestation), the use of corticosteroids is recommended to aid fetal lung maturation. But corticosteroid treatment also may trigger a VOC, leading some experts to consider resorting to preventive blood transfusions instead.

However, “there has been no study to date and no guideline, so corticosteroid use differs between countries and centers,” the researchers wrote.

To determine whether an association between corticosteroid therapy and serious VOCs — one requiring emergency hospital care — exists in pregnant patients, researchers conducted a retrospective, observational study of maternity units associated with reference SCD centers in France and Martinique.

Data covered 410 pregnancies in patients who gave birth at 23 weeks of gestation or longer between January 2009 and June 2020. For woman with more than one eligible pregnancy, researchers included either the first pregnancy or the first in which corticosteroids were used.

Most women (60.5%) had mutations in both copies of the beta-globin gene resulting in the production hemoglobin S — the faulty version of hemoglobin found in SCD patients — and a history of severe disease (51.9%). During pregnancy, 189 women (46.1%) received scheduled transfusions.

Among SCD complications during pregnancy, VOCs were the most common, with one or more occurring in 56.8% of the patients. Also, 15.1% had pulmonary or kidney infections, 10.2% were treated for acute chest syndrome, and 2.7% had blood clotting complications (deep vein thrombosis or pulmonary embolism).

Pregnancy-related complications were reported in 37.5% of the patients, and included fetal growth restriction (13.2%), pre-eclampsia (12.9%), and infection of the placenta and amniotic fluid (1.7%).

Severe VOC twice as likely in pregnant sickle cell patients given a corticosteroid

Most deliveries were by cesarean section (59.5%). A total of 34 babies, all born prematurely, had neonatal complications, mainly respiratory distress syndrome, a condition requiring oxygen support and help to breathe.

All the women were hospitalized due to a high risk of premature birth, and 40 (9.8%) received corticosteroids while pregnant.

No significant difference was seen in the incidence of VOCs requiring hospital care between pregnant women given corticosteroids and those who were not (62.5% vs. 57.9%).

However, a severe VOC was twice as likely in corticosteroid-treated patients than in the others, with more of these pregnant women requiring intensive hospital care (25% vs. 12.9%), emergency blood transfusions (44.7% vs. 22.7%), and having acute chest syndrome (22.5% vs. 8.9%).

After adjusting for SCD severity and type, women who received corticosteroids during pregnancy were 2.73 times more likely to be admitted to intensive care for a VOC, and 4.15 times more likely of having acute chest syndrome. VOCs occurred a mean of 1.2 days following corticosteroid administration.

“Two of the patients in the group who received corticosteroids had non-severe VOC before administration; both of them became severe within a few hours and required transfer to intensive care on day 1 and day 2, respectively,” the researchers noted.

Over half of the women receiving corticosteroids delivered before 34 weeks of pregnancy (57.5%), mostly by emergency cesarean section (72.5%). Among those without such treatment, preterm delivery was 6.8%. Postpartum maternal intensive care was required in 25% of the women with corticosteroid treatment, mainly for a severe VOC or acute chest syndrome.

Babies exposed to corticosteroids were more likely to be born prematurely and to have more neonatal complications than those who were not exposed to them (33.3% vs 4.4%).

Additional analyses found that transfusions or other types of preventive treatment did not reduce a VOC occurrence after corticosteroid use.

“[Prenatal corticosteroids] are a risk factor for more severe VOC in patients with SCD, especially in S/S SCD and severe baseline characteristics,” the researchers concluded.

“The present study was the first to study the impact of prenatal corticosteroids on sickle cell disease. They were associated with more severe VOC, suggesting that steroids should be avoided in these women,” they added.