IVIG during pregnancy found to ease MG symptoms in newborn

Fetal disorder called FARAD may occur in women asymptomatic for MG

Margarida Maia, PhD avatar

by Margarida Maia, PhD |

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Treatment with intravenous immunoglobulin (IVIG) during pregnancy may have helped ease symptoms of a fetal disorder in a girl born to a mother with myasthenia gravis (MG), according to a report from Germany.

The woman’s firstborn had developed severe FARAD (or fetal acetylcholine receptor antibody-related disorder), which occurs when MG-causing antibodies are passed on to the baby while in the womb. The mother showed no symptoms of MG, but tested positive for self-reactive antibodies against the acetylcholine receptor (AChR), which can cause the disease.

The report highlights that doctors should consider a diagnosis of FARAD in babies with muscle weakness and hypotonia (low muscle tone), even if the mothers are asymptomatic, or show no symptoms of MG.

For women who are pregnant or planning to become pregnant, “IVIG treatment seems to have a positive impact on the clinical severity of FARAD highlighting its important clinical implications for future pregnancies,” researchers wrote.

The report, “Maternal immunoglobulin treatment can reduce severity of fetal acetylcholine receptor antibody-associated disorders (FARAD),” was published as a letter to the editor in the journal Neurological Research and Practice.

MG is an autoimmune disease where self-reactive antibodies attack and disrupt the normal communication between nerves and muscles, resulting in episodes of muscle weakness and fatigue.

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Women with MG can pass on self-reactive antibodies through placenta

Babies may be born with transient neonatal MG, which occurs when a mother with MG passes on her self-reactive antibodies through the placenta, causing a similar autoimmune response in the baby.

Symptoms typically appear shortly after birth and include muscle weakness and hypotonia, impaired suckling or swallowing, and a weak cry or trouble breathing. They usually disappear within a few weeks with supportive treatment.

However, because symptoms of transient neonatal MG can differ in severity and duration, it has been suggested that this type of MG may be part of a full spectrum disorder, coined FARAD.

Now, a team of researchers in Germany described the case of a woman, showing no symptoms of MG herself, who had two daughters with FARAD.

“Our case demonstrates that diagnosing FARAD is notably challenging when the mother does not suffer from MG but shows exclusively elevated AChR antibodies,” the researchers wrote.

The older daughter was born without complications, but experienced hypotonia and trouble breathing soon after birth. She was taken to the intensive care unit and placed on a ventilator mask to help with breathing. She also was fed through a tube.

At 3 months of age, the girl was admitted to the hospital due to reduced facial expression and muscle weakness in the head and upper trunk. Physical examination also revealed a tent-shaped mouth.

After excluding other neuromuscular diseases, doctors suspected the mother may have MG. They tested her blood for the presence of disease-causing antibodies, and the results came back positive for anti-AChR antibodies. A diagnosis of FARAD was then made.

At 5 months old, the baby had a feeding tube placed due to her persistent feeding problems. She was also started on salbutamol, a medication usually used to widen the airways, to help with breathing. This “improved swallowing and reduced vomiting.”

By 3 years old, the girl could sit, walk, and speak three-word sentences, though her speech was low in volume and slurred. She also had normal muscle strength, head control, and hearing.

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Woman started treatment at 12 weeks during second pregnancy

When the woman became pregnant again, she was started on IVIG, a pool of antibodies from donated plasma that are thought to help neutralize and eliminate the self-reactive antibodies that drive MG.

Treatment was started when the woman was 12 weeks pregnant.

“The patient received a total seven infusions and IVIG was well tolerated,” the researchers wrote.

Soon after birth, the second baby girl was placed on a ventilator to help with breathing for four hours. She had hypotonia and muscle weakness in her neck. While “head control was poor in the beginning,” she didn’t require help with feeding.

Her symptoms eased within the first two months, and she reached her developmental milestones within the normal timeframe, such as turning around at 4 months, sitting without support at 7 months, walking unaided at 14 months, and saying her first words at 12 months.

“Overall, her symptoms were much less severe compared to the first-born sister,” the researchers wrote. “IVIG treatment of the mother resulted in a positive impact on the following clinical course of the child.”