Obstetrical Use of Intravenous Immunoglobulin at a Tertiary Care Canadian Center: A 14-Year Retrospective Study
Authors: Khalife Roy , Niu Bonnie T , Perelman Iris , El-Chaar Darine , Fergusson Dean , Karovitch Alan , Mack Johnathan P. , Tokessy Melanie , Webert Kathryn Elizabeth , Tinmouth Alan T. 
Published: December 2023

Introduction:
Intravenous immunoglobulin (IVIG) has gained widespread acceptance for the treatment of various medical conditions. However, its availability is limited, it incurs substantial costs, and reports of shortages have raised concerns regarding patient access. Additionally, adverse events with IVIG use underscore the need for prudent administration. While IVIG is approved for specific indications, its off-label use remains significant. Prior studies have addressed the general use of IVIG use and called for measures to ensure its appropriate application, research specific to the obstetrical use of IVIG is lacking. Understanding how IVIG is used in pregnancy could guide future research endeavours and shape policies aimed at optimizing patient care, minimizing unwarranted exposure, and containing healthcare costs. The objectives of this study are three-fold: (1) to assess the frequency, volume, and indications of IVIG use in pregnancy, (2) to assess the congruent use of IVIG with the approved Canadian indications and the approved conditions by the Ontario Immunoglobulin Utilization Management Guidelines, and (3) to compare the volume of IVIG used in pregnancy to the total volumes of IVIG use.
Methods:
This retrospective cohort study used administrative data and chart reviews to analyze all pregnant individuals between 2007 and 2020 who received IVIG during their pregnancy and delivered at a large tertiary care academic center with high-risk obstetrical care in Ontario, Canada. Data were collected on IVIG volumes, administration regimens, indications, and timing of administration during pregnancy. A descriptive analysis was performed to present the findings.
Results:
The study cohort comprised 122 pregnant patients, accounting for 136 deliveries. The cumulative volume of IVIG used across all obstetrical patients amounted to 41,107.50 grams, representing 1.6% of the total consumption of IVIG (2,575,766.50 grams) at our center. Among the indications for IVIG administration during pregnancy (Table 1), the most prevalent were maternal thrombocytopenia (77/136 deliveries, 56.6%) and antenatal therapy for Fetal/Neonatal Alloimmune Thrombocytopenia (F/NAIT) (22/136 deliveries, 16.2%). The highest IVIG consumption was observed in F/NAIT, with a total of 26,435 grams (64.3%) used in all pregnancies and a median of 1015 grams per pregnancy (IQR = 542.5, 1938.75). Maternal thrombocytopenia followed, accounting for a total of 6,952.50 grams (16.9%) used in all pregnancies and a median of 70 grams per pregnancy (IQR = 40, 90). We observed an overall increase in the trend of IVIG use in pregnancy and average volumes per delivery, but this remains a small proportion of total IVIG use (Figure 1). In terms of congruent use of IVIG, 38.2% of deliveries (52/136) did not meet the Canadian licensed indications for IVIG use, accounting for a large amount (33,025 grams, 80.3% of total volume used). However, 17.6% of deliveries (24 out of 136) did not adhere to the Ontario guidelines' indications for IVIG use, which constituted a total of 5,475 grams (13% of total volume used).
Conclusions:
The obstetrical use of IVIG represents a minor proportion of the total volume used at a large Canadian tertiary care center. Hematologic conditions, particularly F/NAIT and maternal thrombocytopenia, are the predominant drivers of IVIG administration during pregnancy. Recent reports on IVIG use in the general population demonstrated similarly high prescribing patterns of IVIG among hematologists, but also neurologists. Rational prescribing and dose minimization are important strategies to improve judicious and cost-effective use of IVIG. However, implementation of such strategies for obstetrical use of IVIG may be limited as evidence generally stems from small, retrospective, observational studies, and reaching a consensus among various specialists may sometimes prove difficult. There is a pressing need for prospective multicenter studies in pregnant individuals, particularly for conditions with high IVIG consumption. These studies would help to examine the efficacy and safety of IVIG during pregnancy and provide essential guidance for appropriate IVIG use in this unique patient population.