Fertility and pregnancy

Individuals with PI benefit from having a healthcare team that understands their condition and can partner with them throughout pregnancy. Many OB/Gyn providers are not familiar with PI. It is important to communicate early and clearly with your OB/Gyn about your PI diagnosis because closer monitoring will set you up for success.

You may want to find a maternal-fetal medicine (MFM) specialist or a high-risk OB and connect them with your immunologist and other relevant providers. Involving an immunologist and ensuring good communication with the obstetric team can help support safe and coordinated care for both you and your baby.

Pregnant individuals who are carriers of PI may also need to educate their OB/Gyn providers and/or seek out specialized MFM or high-risk OB providers. This is especially important if you are a symptomatic carrier for conditions like X-linked chronic granulomatous disease (CGD) or Wiskott-Aldrich syndrome (WAS).

A survey of pregnant women on immunoglobulin (Ig) replacement therapy found that, although they had a good experience with prenatal care, they felt marginalized and unheard when discussing their PI and the need for Ig replacement therapy [11]. Ig replacement therapy, either subcutaneous (SCIG) or intravenous (IVIG), is generally safe in pregnancy. In fact, all babies rely on the protective IgG antibodies transferred through the placenta from their mothers during their first several months of life. Because of this, Ig replacement therapy for a pregnant person with antibody deficiency is critical for both the mother and child.

IgG antibodies move from the mother’s bloodstream to the developing baby’s bloodstream across the placenta, starting as early as 13 weeks of pregnancy. This IgG transfer increases as pregnancy progresses, with the largest amount transferred from mother to baby in the third trimester [12]. Studies of pregnant women without PI show that the baby receives all subclasses of IgG and IgG that protects against a wide variety of infections. Other classes of antibodies, such as IgA, are not transferred to the developing baby. By week 36 of pregnancy, the baby’s IgG levels are equal to, if not slightly higher, than the mother’s.

In the 2015 survey, the majority of women did not report changes in Ig dosing during pregnancy: 25% received a dose increase, 13% received Ig more often, and 1% reported a dose reduction [1]. However, healthcare providers should consider increasing the dose or frequency of Ig replacement therapy because:

1. As the pregnant person’s weight and blood volume increase, they will need a higher dose of Ig or more frequent infusions to maintain protective antibody levels.
2. Transport of IgG through the placenta means the pregnant person needs higher doses or more frequent infusions to provide protective antibody levels to the baby.

If you are using SCIG and become pregnant, you and your healthcare provider should discuss whether to continue SCIG or switch to IVIG. Many women on SCIG continue safely throughout pregnancy, especially if they infuse in their thighs, hips, or upper arms instead of the abdomen. The decision should be guided by your immunologist and Ob/Gyn, the size and location of your infusion sites, your comfort, and whether vein access or your volume/dose needs to change during pregnancy.

Healthcare providers should test Ig levels throughout the pregnancy, especially in the third trimester, to watch for trends and adjust the amount of Ig or frequency of infusions so that the mother feels her best.

Many individuals with PI take medications other than Ig that are essential to treating their condition. The American College of Obstetricians and Gynecologists (ACOG) classifies medications in terms of their risk of causing birth defects in a baby (teratogenicity) or other complications in a pregnancy [13]. However, the potential harmful effects of newer medications available to treat PI may not be known.

Many people with PI are on additional medications to prevent infections. These include preventative antimicrobials such as antibiotics, antivirals, or antifungals or medications that boost elements of the immune system, like interferon gamma-1b (trade name Actimmune) or granulocyte-colony stimulating factor (G-CSF). Healthcare providers, the person with PI, and their loved ones need to consider the safety of these medications in pregnancy.

Some people with PI take medications that suppress or adjust certain parts of the immune system (immunosuppressants or immunomodulators) to prevent widespread, damaging immune dysregulation, such as inflammation, autoimmunity, or overgrowth of white blood cells (lymphoproliferation). While some of these medications are linked with potential harm to the developing baby, it is important to also consider their ability to keep a pregnant individual's immune system under control. Uncontrolled immune dysregulation has just as much potential, if not more, to harm the baby.

Note that some medications are potentially more harmful in the first trimester of pregnancy, but can be safely restarted later on. Others should be stopped or healthcare providers should consider other alternatives.

One recent review looked at outcomes for pregnant individuals with chronic inflammatory conditions (such as FMF or cryopyrin-associated periodic syndromes (CAPS)), which are linked with higher risk for pregnancy complications, who were treated with anakinra and/or canakinumab during their pregnancies [14]. Anakinra and canakinumab are immunosuppressants that stop inflammation by blocking chemical signals to the IL-1 protein. Of the 88 pregnancies, 57 (65%) resulted in healthy, full-term deliveries without complications. Twelve of the pregnancies (14%) resulted in preterm births and one pregnancy resulted in stillbirth. The review concluded that treatment with IL-1 blocking medications during pregnancy does not increase the risk of poor outcomes in people with these otherwise high-risk conditions.

Ultimately, decisions about medication changes in pregnancy are personal and should be made together with your medical team. Your immunologist and Ob/Gyn providers can help review the risks and benefits, discuss different options, and support you in choosing what feels right for you and your family.

Pregnant individuals with PI should receive all vaccines routinely recommended in pregnancy by the American College of Obstetricians and Gynecologists (ACOG) to protect themselves from infections and to support the baby’s growing immune system [15,16].

These immunizations are safe and recommended even in individuals on Ig replacement therapy or immunosuppressants. First, Ig products generally do not protect against current seasonal virus strains, such as the newest influenza or COVID-19 variants because of the time it takes to manufacture them. Second, patients with antibody deficiencies may still make T cell responses to vaccines that provide some protection against severe infection [17]. Finally, if the mother makes any IgG antibodies in response to vaccines, they will be transferred through the placenta to the baby. Since newborn babies cannot make their own antibodies (even if they don’t have PI) until they are 4-6 months of age, these transferred antibodies are an important layer of protection for them in early life.

There are increased risks during pregnancy in individuals with PI that need to be clearly communicated to OB/Gyn or MFM providers. These risks depend on the type of PI the pregnant person has and may include infections, bleeding (or, conversely, clotting), and flares of autoimmune or autoinflammatory symptoms.

Individuals with PI are at risk for recurrent, long-lasting, severe, and difficult-to-treat infections. These infections may include ear infections, sinus infections, or pneumonia but can also include skin and soft tissue infections like cellulitis, central nervous system infections like meningitis and encephalitis, gut infections, bone and joint infections, and infections of other organs. People with PI are also at risk for infections involving large parts of the body (systemic or disseminated infections). Specific to pregnancy, chorioamnionitis, which is an infection of the amniotic fluid and the membranes surrounding the baby, can also happen in people with PI [18]. Depending on the type of PI, viruses, bacteria, and fungi can all cause these infections.

OB/Gyn and MFM providers should be aware that individuals with PI may not have classic symptoms of infection, such as a fever, so they need to watch for subtle signs of infection as well. Providers should test and evaluate the pregnant individual for an infection if they feel unwell, even if there is no fever. If a pregnant person with PI does have signs or symptoms of an infection, they need to be seen in a hospital emergency room right away. Providers should not hesitate to prescribe antibiotics or other antimicrobials.

Many people with PI have low blood cells or platelets, so their hemoglobin and platelet counts need to be monitored carefully during pregnancy through a complete blood count (CBC) with differential tests. This is especially important for individuals who have had episodes of autoimmune hemolytic anemia (AIHA) or immune thrombocytopenic purpura (ITP) as part of their PI. These complications are most often triggered by physiological stress, of which pregnancy and childbirth are clear examples.

Hemoglobin and platelet counts are not routinely checked in pregnant individuals without PI. Experts recommend checking these levels at least once every trimester in individuals with PI, and even more frequently in the final month of pregnancy. It is also critical to monitor these counts at least once during labor and childbirth and within the first weeks after childbirth. Experts recommend that the pregnant individual see their OB/Gyn provider for a CBC with differential test within the first two weeks after delivery.

Pregnancy increases the risk of blood clots, even in people who don’t have PI. However, individuals with PI, especially those with autoinflammatory disorders or PIRDs, are at even higher risk for blood clots, especially if they have stopped their medications during pregnancy. Clots can block blood flow, causing damage to organs and tissues, like the legs (deep vein thrombosis), lungs (pulmonary embolism), or brain (ischemic stroke). Signs of these conditions, like swelling or pain in the legs, chest pain, or slurred speech, are medical emergencies that need immediate emergency room attention with ultrasound or imaging tests.

Many people with PI fear that they will experience flares of autoimmune or autoinflammatory symptoms during pregnancy. The physiological stress of pregnancy can trigger flares of the underlying PI. If the person stopped immunosuppressants prior to pregnancy, a flare is even more likely. Your OB/Gyn or MFM provider needs to work with your immunologist or rheumatologist to carefully follow you and manage your care in this case.

If a flare occurs, your healthcare providers may restart you on a lower dose of immunosuppressant or prescribe an alternative medication. Your provider may recommend immediate delivery of your baby if a life-threatening flare happens.

Because some individuals with PI have a higher risk of infection or complications during delivery, experts recommend planning for a hospital delivery. Midwives and doulas can still be important members of the care team, but it is safest to deliver in a facility that can quickly address complications if needed. Experts do not recommend home births, hospital-based deliveries where midwives or doulas serve as the only medical provider, or alternative birthing plans for pregnant individuals with PI. These recommendations are aimed at protecting the safety of both the delivering mother and the newborn child.

When possible, individuals with PI should deliver vaginally, because it generally has a lower risk of infection and complications than a Cesarean section (C-section). Pregnant individuals with PI should undergo C-section based on standard medical/obstetric guidelines, rather than solely because of PI.