Healthy Pregnancy With AIHA Is Possible But Carries Risks: Study

Fetal complications are about 4 times more common in women with AIHA

Lindsey Shapiro, PhD avatar

by Lindsey Shapiro, PhD |

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Fetal complications are about four times more common in pregnant women with autoimmune hemolytic anemia (AIHA), including cold agglutinin disease (CAD), than in those without the autoimmune condition, according to a small study.

Still, maternal complications occurred at similar rates, and most were directly linked to AIHA relapses, or events characterized by red blood cell destruction (hemolysis). All hemolytic events recorded were severe enough to require treatment, but were also responsive to therapy.

The findings overall offer “insight into pregnancy outcomes in AIHA, suggesting that the occurrence of AIHA does not preclude the ability to carry a healthy pregnancy, provided close monitoring, prompt therapy, and awareness of potential maternal and fetal complications,” researchers wrote.

The study, “Autoimmune Hemolytic Anemia During Pregnancy And Puerperium: An International Multi-Center Experience,” was published in Blood.

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Some women develop antibodies against red blood cells during pregnancy

AIHA refers to a group of conditions in which the body’s immune system produces self-reactive antibodies that wrongly attack red blood cells, resulting in too few red blood cells (anemia) and poor oxygen transport throughout the body.

CAD is a type of AIHA in which disease-driving antibodies, called cold agglutinins, attack red blood cells at low temperatures. In other forms of AIHA, self-reactive antibodies are active at warm temperatures or across a range of temperatures.

Pregnancy can cause substantial changes to the functioning of the immune system. It’s been reported that in some cases, women develop antibodies against red blood cells during pregnancy, but these antibodies don’t always lead to overt symptoms of AIHA.

It’s possible that AIHA may pose risks to a pregnant mother or developing fetus, but reports of new or relapsing AIHA in pregnancy are rare, and therefore little is known about its presentation, management, and outcomes.

To examine the effects of AIHA on pregnancy, an international team of researchers analyzed medical records from women with new or relapsing AIHA during pregnancy or shortly after who were seen across 12 hematology centers in Italy, Denmark, France, the Netherlands, the U.K., the U.S., and Spain from 1997 to 2022.

The analysis included 45 pregnancies occurring in 33 women, 20 of whom had an AIHA diagnosis before pregnancy, nine developed AIHA during pregnancy, and four had AIHA onset in the months after giving birth. Two women had a CAD diagnosis.

All 20 women with a prior AIHA diagnosis required at least one line of treatment, and 13 used two or more treatments, such as rituximab, cell death-promoting immunosuppressants, or surgical removal of the spleen. Eight of them were on active treatment at the time of pregnancy.

… the occurrence of AIHA does not preclude the ability to carry a healthy pregnancy, provided close monitoring, prompt therapy, and awareness of potential maternal and fetal complications.

Half of the women with AIHA had a relapse during or shortly after pregnancy

Half of these women with existing AIHA experienced a relapse, occurring during pregnancy in eight patients and during the months after giving birth in two women.

Two women who developed AIHA during the first months after a first pregnancy subsequently relapsed during a second pregnancy.

In total, 24 AIHA relapses, or hemolytic events, were reported in 23 women during pregnancy or in the first weeks after giving birth, all of which required treatment.

Management of these events included steroid-based immunosuppressive therapy (96%), blood transfusions (58%), and intravenous immunoglobulins (IVIG; 29%). IVIG delivers specific antibodies purified from healthy people to neutralize self-reactive antibodies in the patient’s bloodstream and block the abnormal production of these antibodies.

All patients responded to treatment in a median of 14 days, with a complete response seen in 65% of cases.

Preventive medication for blood clots, including heparin or aspirin, were given to eight patients. For nine women who experienced a relapse during pregnancy, hemolysis continued after giving birth, which was managed with steroids in addition to rituximab, erythropoietin, or the immunosuppressant cyclosporine.

Maternal complications occurred in seven pregnancies (15.6%), five of which (71.4%) happened during a hemolytic event. These complications included premature rupture of membranes protecting the fetus, placental detachment from the uterus, preeclampsia, severe COVID-19 infection during immunosuppressive therapy, infection after delivery, and biliary colic (abdominal pain caused by a gallstone blockage).

Preeclampsia is a condition characterized by high blood pressure and signs of liver or kidney damage during pregnancy.

A total of six early miscarriages were reported (13.3%), five of which occurred in a woman with treatment-resistant AIHA, and one in a woman who developed AIHA while pregnant.

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Fetal complications more frequent and severe in women with AIHA

A total of 10 fetal complications were reported, including growth restriction, preterm birth (before 37 weeks of gestation), epilepsy, AIHA in the newborn, and two stillbirths (death after 28 weeks of gestation).

Notably, rates of maternal complications were comparable between women with AIHA and a control group of 56 pregnant women without AIHA (15% vs. 18%). However, fetal complications were significantly more frequent and more severe in AIHA pregnancies compared with controls (22% vs. 5%).

Findings overall demonstrate that AIHA during pregnancy or in the following months “is a severe event,” the researchers wrote, adding that “severe maternal and fetal complications occurred in a significant proportion of cases and were associated with active hemolysis.”

Since hemolytic events occurred in half of the women diagnosed with AIHA before pregnancy, these patients should be more closely monitored, the team wrote.

Still, treatments were overall effective and safe, and “should not be delayed, especially in case of fetal distress,” the researchers concluded.