Common Variable Immune Deficiency in Pregnancy: Multidisciplinary Approach to Improving Obstetrical Outcome

Common Variable Immune Deficiency in Pregnancy: Multidisciplinary Approach to Improving Obstetrical Outcome | Authorea try { document.documentElement.classList.add('js'); } catch (e) { } var _gaq = _gaq || []; _gaq.push(['_setAccount', 'G-8VDV14Y67G']); _gaq.push(['_trackPageview']); (function() { var ga = document.createElement('script'); ga.type = 'text/javascript'; ga.async = true; ga.src = ('https:' == document.location.protocol ? 'https://ssl' : 'http://www') + '.google-analytics.com/ga.js'; var s = document.getElementsByTagName('script')[0]; s.parentNode.insertBefore(ga, s); })(); Skip to main content Preprints Collections Wiley Open Research IET Open Research Ecological Society of Japan All Collections About About Authorea FAQs Contact Us Quick Search anywhere Search for preprint articles, keywords, etc. Search Search ADVANCED SEARCH SCROLL This is a preprint and has not been peer reviewed. Data may be preliminary. 6 October 2025 V1 Latest version Share on Common Variable Immune Deficiency in Pregnancy: Multidisciplinary Approach to Improving Obstetrical Outcome Authors : Fatemah AlYaqout 0009-0004-9713-4562 [email protected] , Michael Aw 0000-0002-1702-0863 , Eisa Saleh , Derek Lee , Vanessa Polito , Michael Fein , Reza Alizadehfar , Christos Tsoukas , and Genevieve Genest Authors Info & Affiliations https://doi.org/10.22541/au.175978996.62448962/v1 384 views 126 downloads Contents Abstract Information & Authors Metrics & Citations View Options References Figures Tables Media Share Abstract not-yet-known not-yet-known not-yet-known unknown Background: Pregnancy poses unique challenges for women with Common Variable Immune Deficiency (CVID), requiring tailored immunological and obstetrical management. Presently, there are no guidelines available to guide manage of such patients. Standardizing care for patients with CVID who are pregnant or contemplating pregnancy is important to optimize maternal and fetal outcomes. Methods: A systematic review of the literature was performed to guide clinical management recommendations. A retrospective chart review of women with CVID who became pregnant while receiving care at the McGill University Health Centre between 2015–2025 was conducted. Maternal, obstetrical, immunological, and immediate neonatal outcomes are described. Results: Key management principles included trimester-based immunoglobulin (IgRT) dose adjustments, regular monitoring of serum IgG, proactive management of autoimmune or infectious complications, and multidisciplinary coordination. SCIG therapy offered flexibility and stability of IgG levels. Conclusion: Pregnancy in women with CVID can result in favorable outcomes when managed with structured IgRT protocols, regular surveillance, and integrated multidisciplinary care. We propose a management algorithm based on available literature and our single center experience. This can be used as a framework for future prospective studies which are needed to refine management strategies. Title: Common Variable Immune Deficiency in Pregnancy: Multidisciplinary Approach to Improving Obstetrical Outcome Short Title: Common Variable Immune Deficiency in Pregnancy Keywords: Common variable immune deficiency, Immunoglobulin replacement therapy, Multidisciplinary care, Reproductive Immunology, Pregnancy Fatemah AlYaqout 1,2 , Michael Aw 3 , Eisa Saleh 1 , Derek Lee 4 , Vanessa Polito 1 , Michael Fein 1 , Reza Alizadehfar 1 , Christos Tsoukas 1 , Genevieve Genest 1 1 Division of Clinical Immunology and Allergy, Department of Medicine, McGill University Health Center (MUHC), Montreal, Quebec, Canada 2 Department of Internal Medicine, Mubarak Al-Kabeer Hospital, Ministry of Health, Kuwait 3 Division of Internal Medicine, Department of Medicine, McGill University Health Center (MUHC), Montreal, Quebec, Canada 4 Department of Pharmacy, McGill University Health Center (MUHC), Montreal, Quebec, Canada ORCID: Fatemah AlYaqout: https://orcid.org/0009-0004-9713-4562 Michael Aw: https://orcid.org/0000-0002-1702-0863 Michael Fein: https://orcid.org/0009-0006-2599-5763 Genevieve Genest: https://orcid.org/0000-0001-9736-1803 Corresponding Author: Fatemah AlYaqout. [email protected] (646-388-0519) not-yet-known not-yet-known not-yet-known unknown 47706 AlSalam, Ministry of Health, Jaber Al-Ahmad Hospital, Kuwait City, Kuwait Conflicts of interest statement: No author has any conflicts of interest to declare Funding: No funding was received for this manuscript. Ethics Statement: This study was approved by the McGill University Health Center (MUHC) ethics board, study number MUHC REB #2025-11526. Abbreviations: CVID: Common Variable Immune Deficiency SCIG: Subcutaneous Immunoglobulin IVF: In Vitro Fertilization FLT-4: Fms-related Tyrosine Kinase 4 NICU: Neonatal Intensive Care Unit TNFSF12: Tumor Necrosis Factor Superfamily Member 12 UNG: Uracil DNA Glycosylase MODY: Maturity-Onset Diabetes of the Young TNFRSF13B: Tumor Necrosis Factor Receptor Superfamily Member 13B HNF4A: Hepatocyte Nuclear Factor 4 Alpha Acknowledgements: We would like to thank the Montreal General Hospital Foundation for their financial support for this project. All illustrations were created with Biorender. During the preparation of this work the authors used ChatGTP to assist with grammatical corrections and occasional sentence structuring. After using this tool, the authors reviewed and edited the content as needed and take full responsibility for the content of the publication. Abstract: Background: Pregnancy poses unique challenges for women with Common Variable Immune Deficiency (CVID), requiring tailored immunological and obstetrical management. Presently, there are no guidelines available to guide manage of such patients. Standardizing care for patients with CVID who are pregnant or contemplating pregnancy is important to optimize maternal and fetal outcomes. Methods : A systematic review of the literature was performed to guide clinical management recommendations. A retrospective chart review of women with CVID who became pregnant while receiving care at the McGill University Health Centre between 2015–2025 was conducted. Maternal, obstetrical, immunological, and immediate neonatal outcomes are described. Results : Key management principles included trimester-based immunoglobulin (IgRT) dose adjustments, regular monitoring of serum IgG, proactive management of autoimmune or infectious complications, and multidisciplinary coordination. SCIG therapy offered flexibility and stability of IgG levels. Conclusion : Pregnancy in women with CVID can result in favorable outcomes when managed with structured IgRT protocols, regular surveillance, and integrated multidisciplinary care. We propose a management algorithm based on available literature and our single center experience. This can be used as a framework for future prospective studies which are needed to refine management strategies. Introduction : Common Variable Immune Deficiency (CVID) is the most common symptomatic primary immune deficiency (1). Advances in diagnosis and immunoglobulin replacement therapy (IgRT) have enabled many women with CVID to contemplate pregnancy (2). However, pregnancy introduces unique immunological, infectious, and obstetrical challenges requiring individualized management (3). There is a paucity of literature describing pregnancy outcomes in CVID patients; no guidelines detailing optimal management currently exist. We performed a systematic review of the available literature on pregnancy outcomes of patients with CVID to identify a general approach to care. We then retrospectively reviewed the outcomes of pregnant CVID patients treated at the McGill University Health Centre Immune Deficiency Treatment Center (IDTC) (2015–2025), a quaternary center specializing in the diagnosis and management of immune-deficiency diseases. Here, we propose an algorithm for the management of such patients incorporating pre-pregnancy planning and multidisciplinary care. Methods : Systematic Review: We conducted a systematic literature search to identify studies on the management of pregnancy in patients with CVID (Figure 1). The review adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA)(4). MEDLINE and Embase electronic databases were reviewed for articles published between April 2005 and April 2025. The search was limited to articles published since 2005, as immunoglobulin replacement therapy preparations have been relatively standardized since this time and differ from preparations used prior. The search strategy included the following key components: CVID Terms: ”Common Variable Immunodeficiency,” ”CVID,” ”Hypogammaglobulinemia,” ”Antibody Deficiency,” and related variations. Pregnancy Terms: ”Pregnancy,” ”Pregnant,” ”Gestation,” ”Maternal,” ”Antenatal,” ”Prenatal,” ”Perinatal,” ”Obstetric,” ”Delivery,” ”Childbirth,” ”Postpartum,” and related terms. Management Terms: ”Disease Management,” ”Treatment,” ”Therapy,” ”Care,” ”Monitoring,” ”Protocol,” ”Guideline,” ”Immunoglobulin,” ”IVIG,” ”SCIG,” ”Prophylaxis,” ”Antibiotic,” ”Antimicrobial,” and related terms. Inclusion criteria encompassed articles describing women with a confirmed diagnosis of CVID who had completed pregnancy with reporting of maternal and or fetal/neonatal outcomes. Abstract-only publications, conference proceedings, editorials, opinion pieces, or narrative reviews without patient-level data, animal studies or in vitro studies, and non-English language publications without accessible translations were excluded from analysis. Extracted data included study characteristics (study ID, title, author information, journal, publication year, study type and design, years of data collection, sample size, and funding sources) and population characteristics (number of CVID women, number of pregnancies, diagnostic criteria, age, comorbidities, and baseline IgG levels). Information on CVID-associated complications was also collected, including interstitial lung disease, gastrointestinal manifestations, autoimmune diseases, and other complications, as well as pre-pregnancy infection history. Intervention details captured the type of immunoglobulin replacement (IVIG, SCIG, or fSCIG), dosing regimen, timing and adjustments during pregnancy, prophylaxis use (antibacterial, antiviral, or antifungal), indications, trimester of initiation, and adverse effects. Maternal outcomes assessed included IgG levels during pregnancy, infection occurrence, obstetric complications, and hospitalizations. Neonatal outcomes included live birth rates, gestational age at delivery, birth weight, neonatal IgG levels, and neonatal complications. Post-partum follow-up was recorded, focusing on maternal IgG monitoring and continuation of immunoglobulin therapy. Finally, special considerations were noted, such as multidisciplinary care involvement, IgRT dosing strategies, and lessons learned. Data extraction was independently performed by three reviewers using a standardized, pre-piloted extraction form within Covidence(5) . Discrepancies in extracted data were resolved by discussion among the reviewers or adjudicated by a senior team member when required. The study selection process is detailed in Figure 1. not-yet-known not-yet-known not-yet-known unknown Retrospective Chart Review: We retrospectively reviewed the management strategies as well as maternal and fetal outcomes for all patients with CVID who experienced pregnancy while receiving care at McGill University Health Centre’s IDTC clinic). Eligible participants included pregnant patients with a confirmed diagnosis of CVID (6). Criteria for CVID diagnosis included significantly reduced serum immunoglobulin levels (IgG, IgA, and/or IgM levels ≥2 standard deviations below age-specific means), impaired vaccine antibody responses, and exclusion of alternative causes of hypogammaglobulinemia. The study period included patients who experienced pregnancy while under care at MUHC’ IDTC clinic between January 2015 and January 2025. Patients with other documented immunodeficiencies were excluded from analysis. Ethics approval was obtained from the McGill University Health Center Research Ethics Board (Study number 2025-11526). Individual consent was waived for this study. Results : Systematic Review: Immunoglobulin Replacement Therapy Immunoglobulin replacement therapy was the cornerstone of pregnancy management across all included studies (2, 7-12). Both intravenous immunoglobulin (IVIG) and subcutaneous immunoglobulin (SCIG) therapies were utilized. IVIG was the most used treatment modality, and dosing adjustments were frequently required during pregnancy, particularly during the third trimester to maintain IgG levels (2, 12). Facilitated SCIG (fSCIG) administration was used in a subset of patients and reported in registry data as a safe and effective option without significant maternal or neonatal adverse events (13). Overall, no differences in maternal or neonatal infection rates were reported between IVIG, SCIG or fSCIG users. Monitoring frequency varied across studies, with most employing monthly or trimester-based IgG measurements (12, 14). Studies that employed regular monitoring reported fewer infectious complications during pregnancy. (10, 14). Antimicrobial prophylaxis was selectively employed across studies, typically in patients with recurrent infections or underlying bronchiectasis (2, 12). In the PREPI study, anti-infective prophylaxis was associated with higher live birth rates among women with primary immunodeficiency (82% vs 63% without optimal prophylaxis) (2). Common prophylactic agents included azithromycin and trimethoprim-sulfamethoxazole (15). Prophylaxis was generally initiated during the second trimester and was not associated with major adverse events. No standardized protocols for prophylaxis initiation or duration were identified across studies (See Figure 2 for trimester-specific antibiotic management options). Maternal infection rates during pregnancy were low among women who maintained adequate IgG levels. Mild respiratory infections were the most frequently reported complications. No maternal mortalities or severe sepsis events were reported. Obstetric complications, including preeclampsia and preterm labor, were reported in some cases but were not consistently linked to CVID (9). Overall, live birth rates were generally high across studies with gestational ages at delivery consistently term deliveries (37–40 weeks). Neonatal outcomes were largely favorable, with normal birth weights predominating. Cord blood IgG levels were within or near normal reference ranges when reported (2, 10, 12). NICU admissions were infrequent and largely unrelated to CVID or maternal immunodeficiency management. Of note, Mallart et al. identified a history of severe maternal infections as a risk factor for poor obstetrical and neonatal outcomes compared to the general population (aOR 0.33, 95% CI 0.12-0.90, p=0.031) (2). Retrospective Review: In total, four patients were identified from retrospective chart review. A detailed summary of their clinical course, management and gestational outcomes are described in supplemental Table 1. not-yet-known not-yet-known not-yet-known unknown Case 1: A 35 yo G7P4A3 presented with recurrent miscarriages prior to her CVID diagnosis. Her first pregnancy (age 30) was a term pregnancy complicated by fetal intra-uterine growth restriction and maternal thrombocytopenia. Her son was born by C-section at 2900g (10th percentile), with pathologic evidence of placental vascular malperfusion. She then had two first trimester miscarriages and two therapeutic abortions at 28- and 20-weeks’ gestation (GW) for multiple congenital malformations. Her partner was found to have a pathogenic FLT-4 mutation, and the couple underwent IVF for pre-implantation genetic screening for monogenic disorders (PGT-M). She subsequently miscarried a euploid non-affected embryo and failed two euploid, unaffected embryo transfers. During her son’s integration to daycare, she developed recurrent sinopulmonary infections. Workup revealed low IgG (3.37 g/l), low IgA levels (0.33 g/l), low/absent serum IgG titers to Diphtheria, Tetanus, Hemophilus influenzae and Streptococcus pneumoniae, as well as mild splenomegaly and thrombocytopenia. Her 7th pregnancy was unplanned. Hizentra® 6g/week (0.4 g/kg), low dose aspirin and Tinzaparin 4500 units daily were started at GW6. She was treated for an episode of sinusitis at GW10 and Hizentra® was increased to 8g/week (0.6 g/kg). At GW28, Hizentra® was increased to 10g/week (0.8g/kg) to maintain IgG levels \(\geq\)10g/L and she received influenza, Tdap, and RSV vaccines. She had an uncomplicated pregnancy and a term vaginal delivery of a healthy male (3040g). Postpartum, Hizentra® was decreased to 6 g/week, and she breastfed without complications. not-yet-known not-yet-known not-yet-known unknown Case 2: A 37-year-old (G2P2) was diagnosed with CVID after her first pregnancy which was complicated by pre-term premature rupture of membranes at 34 weeks. She delivered a small for gestation age boy (1810g, 12th percentile), who required a 2-week hospitalization in the neonatal intensive care unit (NICU). Post partum, the patient developed an empyema requiring IV antibiotics and surgical drainage; subsequently presenting with recurrent sinopulmonary infections. Investigations revealed IgG 4.07 g/L, IgA <0.05 g/L, and poor pneumococcal vaccine response. Genetic testing demonstrated a likely pathogenic variant in TNFSF12 and UNG. She was maintained on Hizentra® 4 g/week (0.3 g/kg) weekly prior to her second pregnancy with stable IgG levels \(\geq\)10 g/L. Influenza vaccination was given at GW 16. By GW 23, IgG levels decreased to 7.8 g/L and Hizentra® was increased to 6 g weekly (0.6 g/kg). Pregnancy was complicated by immune thrombocytopenia at GW 28 with good response to steroids. She required an urgent C-section at GW 34 for pre-term labor and thrombocytopenia, delivering a healthy boy who did not require NICU admission. The infant did not have any infectious complications. Case 3: A 26-year-old G3P1A2 was diagnosed with CVID at age 5 (heterozygous TNFRSF13B mutation), Maturity-Onset Diabetes of the Young (MODY) diabetes (HNF4A mutation), liver cirrhosis (glycogen storage disease), and Fanconi syndrome. Her first two pregnancies were miscarriages (age 17 and 22 with different partners; she was not compliant with Hizentra ® and had recurrent infections at the time). Her 3 rd pregnancy was unplanned while on Hizentra ® 6g weekly (0.4 g/kg) with a stable IgG of 9.67 g/L. During pregnancy, she developed worsening proteinuria; Hizentra ® was increased to 8g/week at GW 10, 10g at GW 25, and ultimately 12g weekly at GW 32, IgG peaked at 7.29 g/L despite dose escalation. She received appropriate vaccinations during pregnancy (Tdap at GW 24, influenza at GW 25, and COVID-19 at GW 28), but contracted COVID-19 at GW 31.5 and developed pre-term labor (PTL). She was hospitalized for 48h and treated with tocolytics, Sotrovimab ® , amoxicillin and betamethasone for fetal lung maturity. At GW 34, she went into PTL and had an uneventful vaginal delivery of a 3680g baby girl. Her daughter was hospitalized in the NICU for 3 weeks for ongoing hypoglycemia but is currently doing well. There were no neonatal infectious complications. not-yet-known not-yet-known not-yet-known unknown Case 4: A 30-year-old woman (G2P2) with long-standing CVID and stable SCIG therapy experienced two uncomplicated term pregnancies without infectious or neonatal complications. She remained clinically stable for several years on Hizentra® 6 g/week, before conceiving her first planned pregnancy at age 28, which proceeded uneventfully without dose adjustments and IgG levels >10 g/L. She delivered a term boy (3410g) without complications. In her second pregnancy at age 30, her IgG dropped to 7.26 g/L at GW 28, prompting an increase in Hizentra® to 9 g/week. She again had an uncomplicated term delivery of a 3570g boy. Discussion : Review of the pregnancy course of 4 patients with CVID highlights physiologic changes of pregnancy, the importance of regular monitoring, and the protective maternal and infantile benefit of IgRT. Preserved maternal humoral immunity promotes a tolerogenic environment for the developing fetus and maternal immunoglobulin transfer, in the third trimester, provides passive fetal immunity(16). Dysregulation, such as in CVID, increase gestational complications and post-partum infections (2, 9). In the last 5 years, we have seen an increase in the number of women with CVID contemplating pregnancy. Based on our review of literature and clinical experience (Table 1, Figure 1, Supplemental Table 1), we have identified several key components in the clinical management of such patients (Figure 3). Preconception consultation: Pregnancy should be discussed with all CVID patients of reproductive age . In patients with IgG levels <8 g/L, active infection, or recent recurrent infections, pregnancy should be delayed until disease stability is achieved. Patients should be reassured that IgRT is safe in pregnancy and that compliance with IgRT is paramount to ensure maternal and fetal protection from infection (17). Other medications such as prophylactic antibiotics need to be tailored for pregnancy (Figure 3). Patients with known penicillin allergy should be assessed for de-labelling prior to pregnancy. Patients with co-existing auto-immune disease should achieve disease stability at least three months prior to pregnancy; teratogenic medications must be replaced with pregnancy safe alternatives prior to conception attempts. In patients with known monogenic disease mutations, risk of transmission to the fetus should be discussed. A referral to a fertility specialist for IVF with PGT-M or to a Geneticist for peri-natal screening should be offered. Immunoglobulin replacement therapy: IgRT is safe, well tolerated and is indicated for CVID management during pregnancy (18). Subcutaneous immunoglobulin (scIg) has been shown to be as safe and effective as intravenous immunoglobulin (IVIg) in the treatment of CVID patients (1, 13). ScIg must be given special consideration in pregnancy due to the flexibility of administration and more consistent serum IgG levels (17). Alternatively, fSCIG (HyQvia®), enables higher-volume delivery with less frequent dosing compared to conventional scIg. This reduces injection burden and should be considered (8). Due to increased circulating volume, increased IgG catabolism during pregnancy (9), as well as IgG transplacental transfer in the third trimester (19, 20), we recommend dosing serum IgG once per trimester with appropriate IgRT adjustment to maintain serum IgG levels >8 g/L. In our experience, dose escalation of 20–50% were typically required during the second and third trimesters, consistent with available literature (Table 1, supplemental Table 1). Of note, two of our patients had multiple miscarriages prior IgRT compliance or CVID diagnosis. Following initiation of IgRT, successful birth of two healthy children was achieved, which supports the role of IgRT. Similarly, a retrospective (n=50) Czech study found higher rates of pre-term labour, small gestational weight and stillbirths compared to the general population (9). The number of unsuccessful pregnancies were greater among those with untreated; however, IgRT did not significantly affect obstetrical outcomes. Overall, this highlights the possibility that appropriate CVID management may improve reproductive outcomes (18). High risk pregnancy: CVID pregnancies should be considered high-risk and managed as such. A normal immune response to the semi-allogenic embryo/fetus is required to promote tolerance to the conceptus and ensure a complication free pregnancy (21). Immune dysregulation, as is the case in CVID, may lead to an increase in maternal and fetal complications as well as post-partum infections (2, 9). Indeed, a retrospective study found higher rates of pre-term labor, small gestational weight, and stillbirths in mothers with CVID compared to the general population (9). We recommend that all CVID patients be referred to a high-risk obstetric unit; in CVID patients with autoimmune comorbidities (specifically cytopenia or endocrinopathies), co-management by Obstetric Medicine should also be considered. Since CVID patients are at high risk of infection, a rapid access plan for care must be available should any infectious symptoms arise. Severe maternal infections are associated with fetal demise in primary immunodeficiency and timely management is crucial to reduce adverse pregnancy outcomes (2, 22). Vaccinations: All pregnant CVID patients should receive trimester-specific and season appropriate vaccinations. While IgRT contain protective antibodies to viruses to which the population has developed herd immunity, it will not protect against emerging viral strains (COVID, influenza, RSV). Additionally, despite RSV vaccination, CVID mothers may not be able to mount a protective antibody response. We recommend neonates receive RSV prophylaxis (ex: Palivisumab, Nirsevimab) at birth. In alignment with these recommendations, we have developed a clinician’s checklist to facilitate pregnancy planning and management for patients with CVID (Supplemental Figure 1). Given the small sample size, our results may not be broadly generalizable and should not be assumed to represent all patients with CVID. Unfortunately, literature on CVID management during pregnancy remains limited, with most evidence derived from case reports and small observational series. Despite generally favorable outcomes, prospective studies with larger sample sizes are needed to establish standardized management protocols, refine prophylaxis strategies, and optimize vaccination practices in this unique population (1, 20). Conclusion: In conclusion, pregnancy in women with CVID is feasible with favorable outcomes when managed with individualized IgRT protocols, infection surveillance, and coordinated multidisciplinary care. We believe that a standardized approach as well as enhanced reporting and registry studies will help improve maternal and fetal outcomes for this vulnerable population. References: 1. Zhang S, Cunningham-Rundles C. Primary Antibody Immunodeficiency and the Pregnant Patient. Immunol Allergy Clin North Am. 2023;43(1):133-44.2. Mallart E, Francoise U, Driessen M, Blanche S, Lortholary O, Lefort A, et al. Pregnancy in primary immunodeficiency diseases: The PREPI study. J Allergy Clin Immunol. 2023;152(3):760-70.3. Gundlapalli AV, Scalchunes C, Boyle M, Hill HR. Fertility, pregnancies and outcomes reported by females with common variable immune deficiency and hypogammaglobulinemia: results from an internet-based survey. J Clin Immunol. 2015;35(2):125-34.4. Page MJ, McKenzie JE, Bossuyt PM, Boutron I, Hoffmann TC, Mulrow CD, et al. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. BMJ. 2021;372:n71.5. Innovation VH. Covidence systematic review software. Melbourne, Australia: Veritas Health Innovation; 2025.6. Ameratunga R, Gillis D, Steele R. Diagnostic criteria for common variable immunodeficiency disorders. J Allergy Clin Immunol Pract. 2016;4(5):1017-8.7. Manson AL, Zaheri S, Kelleher P, Wakelin S, Nelson-Piercy C, Seneviratne SL, et al. Management of granulomatous common variable immunodeficiency diagnosed in pregnancy: a case report. J Perinatol. 2012;32(5):387-9.8. Danieli MG, Moretti R, Pettinari L, Gambini S. Management of a pregnant woman with common variable immunodeficiency and previous reactions to intravenous IgG administration. BMJ Case Rep. 2012;2012.9. Kralickova P, Kurecova B, Andrys C, Krcmova I, Jilek D, Vlkova M, et al. Pregnancy Outcome in Patients with Common Variable Immunodeficiency. J Clin Immunol. 2015;35(6):531-7.10. Marasco C, Venturelli A, Rao L, Vacca A, Carratù MR. Management of common variable immunodeficiency by subcutaneous IgG self-administration during pregnancy - a case report. Clin Case Rep. 2017;5(8):1309-11.11. Sheikhbahaei S, Sherkat R, Camacho-Ordonez N, Khoshnevisan R, Kalantari A, Salehi M, et al. Pregnancy, child bearing and prevention of giving birth to the affected children in patients with primary immunodeficiency disease; a case-series. BMC Pregnancy Childbirth. 2018;18(1):299.12. Egawa M, Kanegane H, Imai K, Morio T, Miyasaka N. Intravenous immunoglobulin (IVIG) efficiency in women with common variable immunodeficiency (CVID) decreases significantly during pregnancy. J Matern Fetal Neonatal Med. 2019;32(18):3092-6.13. Borte M, Raffac S, Hrubisko M, Jahnz-Rozyk K, Garcia E, McCoy B, et al. Long-term safety of facilitated subcutaneous immunoglobulin treatment in pregnant women with primary immunodeficiency diseases: results from a registry study. Immunotherapy. 2022;14(8):609-16.14. Gardulf A, Andersson E, Lindqvist M, Hansen S, Gustafson R. Rapid subcutaneous IgG replacement therapy at home for pregnant immunodeficient women. J Clin Immunol. 2001;21(2):150-4.15. Bonilla FA, Barlan I, Chapel H, Costa-Carvalho BT, Cunningham-Rundles C, de la Morena MT, et al. International Consensus Document (ICON): Common Variable Immunodeficiency Disorders. J Allergy Clin Immunol Pract. 2016;4(1):38-59.16. Abu-Raya B, Michalski C, Sadarangani M, Lavoie PM. Maternal Immunological Adaptation During Normal Pregnancy. Front Immunol. 2020;11:575197.17. D’Mello RJ, Hsu CD, Chaiworapongsa P, Chaiworapongsa T. Update on the Use of Intravenous Immunoglobulin in Pregnancy. Neoreviews. 2021;22(1):e7-e24.18. Banjar S, Kadour E, Khoudja R, Ton-Leclerc S, Beauchamp C, Beltempo M, et al. Intravenous immunoglobulin use in patients with unexplained recurrent pregnancy loss. Am J Reprod Immunol. 2023;90(2):e13737.19. Pavan-Ramos T, Willy-Fabro AP, Rozalem AC, Lessa Mazzucchelli JT, Carvalho BC. IgG serum levels in CVID patients during pregnancy. World Allergy Organization Journal. 2015;8:A157-A.20. Palmeira P, Quinello C, Silveira-Lessa AL, Zago CA, Carneiro-Sampaio M. IgG placental transfer in healthy and pathological pregnancies. Clin Dev Immunol. 2012;2012:985646.21. Genest G, Banjar S, Almasri W, Beauchamp C, Benoit J, Buckett W, et al. Immunomodulation for unexplained recurrent implantation failure: where are we now? Reproduction. 2023;165(2):R39-R60.22. Pradhan J, Mallick S, Mishra N, Tiwari A, Negi VD. Pregnancy, infection, and epigenetic regulation: A complex scenario. Biochim Biophys Acta Mol Basis Dis. 2023;1869(7):166768. Tables and Figures Manson 2012 (7) Case Report Retrospective Year of study not specified United Kingdom 1 patient 2 pregnancies 2 live births 34-year-old patient diagnosed with granulomatous CVID 24 GW of second pregnancy (low Ig levels, impaired vaccine response to Tetanus, recurrent respiratory tract infections since childhood) IVIg (type not specified), started 15 g/month (0.27g/kg) at 26 GW, increased to 22g (0.4g/kg) at 32 weeks and to 30 g (0.54g/kg) at 37GW The patient had an uncomplicated term pregnancy prior to CVID diagnosis. Second pregnancy complicated by Deep vein thrombosis and pseudomonas bacteremia at 24 GW. IVIg started at 26 GW. Cholestasis of pregnancy 37 weeks Urgent C-section for placental abruption, post partum hemorrhage requiring uterine artery embolization. Healthy male infant Consider CVID pregnancies high risk. Increase IgRT dose to maintain stable IgG levels Danieli 2012 (8) Case Report Retrospective 01/2011 – 02/2012 Italy 1 patient 2 pregnancies 1 live birth 1 miscarriage 42-year-old patient with CVID (longstanding recurrent upper respiratory tract infections, pan-hypogammaglobulinemia, impaired tetanus vaccine response) 10% liquid IVIg; then Privigen\(®\), (0.6g/kg/month) Patient had one spontaneous miscarriage at 8 weeks while on IVIg. Post miscarriage: recurrent infusion reaction to IVIg and discontinuation of therapy. Second pregnancy: Alternative IgRT (Privigen® 10%; 0.6 g/kg/month) started at 18 GW with premedication and slow infusion rate; IgG levels maintained >10 mg/dL Term, healthy boy (40GW), breast fed Privigen decreased to 0.4 g/month post partum Privigen\(®\) preparation is well tolerated in patients with adverse reactions to IVIg IVIg is necessary to prevent maternal/fetal infections Dose increased must be considered in pregnancy Kralockova 2015 (9) Cohort study Retrospective Year of study not specified Czech Republic 50 patients 115 pregnancies 88 live births (92 children, 2 sets of twins) 12 miscarriages 3 stillbirths 11 pregnancy terminations (9 by choice, 2 for congenital anomalies) 1 ectopic pregnancy Group A (n=85): pregnancies occurring before CVID manifestations Group B (n=14): pregnancies occurring after first CVID symptoms but before IgRT Group C (n=16): Pregnancies occurring in women with established CVID and on IgRT Not specified Higher rates of preterm labor, eclampsia and preeclampsia, low birth weight offspring and stillbirths in CVID patients compared to the general population Higher rates of antibiotic use during pregnancy in Group B Higher rates of antibiotic administration to offspring 0-12 months in Group B IVIg and scIg was equally effective in preventing infectious complications Consider CVID pregnancies high risk pregnancies Continue IgRT during pregnancy Increase IgRT dose to maintain stable trough IgG levels Marasco 2017 (10) Case Report Retrospective 2008-2012 Italy 1 patient 2 pregnancies 2 live births I 36-year-old patient diagnosed with CVID after second pregnancy (recurrent respiratory infections, pan-hypogammaglobulinemia, impaired tetanus vaccine response) Hizentra® 20% 8g/week (0.4g/kg/month) started at CVID diagnosis, increased to 10g/week at 28 weeks until delivery First pregnancy complicated by ITP prior to CVID diagnosis Later diagnosis of CVID (recurrent respiratory infections, low immunoglobulin levels, impaired tetanus vaccine response) Second pregnancy on SCIG uncomplicated, term birth, healthy girl. Increase IgRT dose during 3 rd trimester to maintain stable IgG levels SCIG is safe during pregnancy Sheikhbahaei 2018 (11) Case Series Retrospective Year of study not specified Iran 3 patients 3 live births 9 patients with PID 3 pregnant âtients with CVID patients with CVID IgRT not specified One patient on 0.4g/kg/3week IVIg had ITP and increased to 0.8g/kg/3week in 2 nd trimester. Term, healthy child. Patient with CVID and autoimmune hepatitis, off IgRT (allergy), stopped Cellcept® and prednisone at diagnosis of pregnancy (with normalization of liver enzymes). Eclampsia at 24 weeks, conservatively managed with delivery at 38 GW One patient with CVID had previous pregnancy prior to diagnosis, which was complicated by recurrent pneumonia and severe dyspnea thoughout pregnancy Untreated CVID can increase risk of adverse maternal and fetal outcomes (infections, ITP, eclampsia) Increase IgRT dose during pregnancy Egawa 2019 (12) Case Series Retrospective 01/2007-12/2026 Japan 4 patients 9 pregnancies 8 live births 1 miscarriage Pregnant patients with CVID on IgRT ‘10% liquid IVIg’ (Japan Blood Products Organization) And/or Hizentra\(®\) 20% Target IgG Target IgG level \(\geq\) 10 mg/dL One patient had a 12-week miscarriage and 3 healthy pregnancies Patients with IgG levels <10 mg/dL had more recurrent infections No other adverse obstetrical or perinatal adverse events Increase IgG dose during pregnancy: IVIg: shorten interval to every 2 weeks from 28-35 weeks and weekly from 36 weeks to delivery scIg: shorten dosing interval to twice per week after 28 weeks until delivery, add IVIg in patients not maintaining target IgG levels Mallart 2023 (2) Retrospective observational, monocentric study 1966-2022 France 51 patients with ‘primarily antibody deficiency’ 119 pregnancies 82 live births 27 miscarriages 2 ectopic pregnancies 2 pregnancy losses >20 weeks 7 voluntary pregnancy terminations, 1 medical termination of pregnancy Patients with ‘primarily antibody deficiency’ 31 patients became pregnant while on IgRT Not specified Better outcomes in pregnancies treated with IgRT 68/78 (87%) term birth 10/78 (17%) pre-term birth (32-37 weeks 7/78 (3%) Extreme pre-term birth (<32 weeks) 16% low birth weight (<10 th percentile) 7/69 (10%) infection during neonatal period Trimester-specific and season specific vaccination Multidisciplinary care Discontinue teratogenic medication and substitute when possible Increase IgRT during pregnancy if IgG levels are ‘low’ not-yet-known not-yet-known not-yet-known unknown Table 1: Summary of available studies available on CVID and pregnancy . Abbreviations: CVID: Common variable immunodeficiency; IgRt: immunoglobulin replacement therapy; IVIg: intravenous immunoglobulin therapy; SCIg: subcutaneous immunoglobulin therapy; GW: gestational week; ITP: idiopathic thrombocytopenia purpura. Figure 1: Systematic review of pregnancy outcomes in patients with CVID . PRISMA flow diagram summarizing the study selection process for the systematic review of pregnancy management in women with CVID. not-yet-known not-yet-known not-yet-known unknown Figure 2: Antibiotic recommendations in CVID pregnancy. * SMX/TMP: Sulfamethoxazole 800 mg/Trimethoprim 160 mg - avoid in 1st trimester due to neural tube defect risk Abbreviations PO: per os (oral administration); IV: intravenous; IVIG: intravenous immunoglobulin; BID: twice daily; QID: four times daily; TMP-SMX: trimethoprim-sulfamethoxazole; MRSA: methicillin-resistant staphylococcus aureus; ID: infectious disease specialist; IgG: immunoglobulin G; CVID: common variable immunodeficiency. Mg: Milligrams; 3x weekly: Three times per week; Daily = Once per day. Figure 3: Management of CVID during pregnancy . Multidisciplinary management of CVID in pregnancy requires coordinated care between immunology, obstetrics, genetics, and neonatology. Monthly IgG monitoring with mid-pregnancy dose adjustments and pre-implantation genetic screening options are critical components to optimize maternal and fetal outcomes throughout pregnancy and postpartum. Information & Authors Information Version history V1 Version 1 06 October 2025 Copyright This work is licensed under a Non Exclusive No Reuse License. Keywords clinical immunology education immune deficiencies prevention Authors Affiliations Fatemah AlYaqout 0009-0004-9713-4562 [email protected] McGill University Department of Medicine View all articles by this author Michael Aw 0000-0002-1702-0863 McGill University Department of Medicine View all articles by this author Eisa Saleh McGill University Department of Medicine View all articles by this author Derek Lee McGill University Health Centre View all articles by this author Vanessa Polito McGill University Department of Medicine View all articles by this author Michael Fein McGill University Department of Medicine View all articles by this author Reza Alizadehfar McGill University Department of Medicine View all articles by this author Christos Tsoukas McGill University Department of Medicine View all articles by this author Genevieve Genest McGill University Department of Medicine View all articles by this author Metrics & Citations Metrics Article Usage 384 views 126 downloads .FvxKWukQNSOunydq8rnd { width: 100px; } Citations Download citation Fatemah AlYaqout, Michael Aw, Eisa Saleh, et al. 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