Effectiveness and Safety of an Intravenous Immune Globulin (IVIG) Preparation in Post-exposure Prophylaxis (PEP) Against Measles in Infants

Background: Administration of measles virus (MV)-specific IgG as post-exposure prophylaxis (PEP) is known to effectively prevent measles. Since the introduction of active immunization against measles, the levels of MV-specific IgG antibodies in the population have dropped. Therefore, the concentration of MV-specific antibodies in immunoglobulin products derived from human plasma donors has declined as the proportion of vaccinated donors has increased. Literature on the effectiveness of PEP with current available immunoglobulins is limited. Here we examine the effectiveness of 400 mg/kg intravenous immunoglobulin (IVIG) (IgVena®, Kendrion) as PEP in infants during a measles outbreak in Austria, 2019.Methods: After exposure to a highly contagious measles patient, identified infants were evaluated for eligibility for IVIG PEP. Infants were tested for measles maternal antibodies, if the result was expected to be available within 72 h after exposure. IVIG was administered to eligible infants with negative maternal IgG antibody levels (n = 11), infants with protective levels but result beyond 72 h (n = 2) and infants not tested for maternal IgG antibodies (n = 52). Telephone enquiries were made asking for measles infection. Effectiveness was calculated using exact logistic regression. Samples of four out of seven used IVIG batches were tested for MV-neutralizing antibody capacity.Results: In 63 (96.9%) of 65 infants PEP with IVIG was administered. The parents of two infants declined IVIG PEP. None of the infants with IVIG PEP got measles or symptoms suggestive for measles, but both infants who did not receive PEP were infected. Effectiveness of IVIG PEP was calculated to be 99.3% (CI 95%: 88.7–100%). No serious adverse event of IVIG treatment was observed. The investigation on MV-neutralizing antibody capacity showed a geometric mean titer ranging from 10.0 to 12.7 IU/ml, resulting in a 1.57–2.26-fold higher concentration than postulated as minimum level for immunity.Conclusions: Our findings suggest that the used IVIG preparation provided an at least non-inferior protection rate compared to IVIG preparations derived from donors before the global introduction of standard active immunization against measles.

Rituximab Administration during the 2nd Trimester of Pregnancy for Systemic Lupus Erythematosus: Case Report and Review of the Literature in Rheumatic Disease

Rituximab is an anti-CD20 monoclonal antibody that is used in the treatment of many rheumatic diseases, for both licensed and unlicensed indications. Due to concerns regarding foetal B cell depletion and possible infection, there is conflicting advice about whether the drug should be administered during pregnancy, with some organizations advising administration if the potential benefit to the mother outweighs the risk to the foetus and some advising stopping rituximab six months prior to conception. Caution in particular is advised about administering rituximab in later trimesters when maternal IgG is transported across the placenta. There has been little literature thus far examining the safety of administering rituximab from the second trimester onwards in rheumatic diseases. We present a case where rituximab was used during the second trimester for the treatment of refractory systemic lupus erythematosus, without adverse effect on the neonate.

Dynamic changes of acquired maternal SARS-CoV-2 IgG in infants

At present, there are still ambiguous reports about the perinatal infection of infants born to mothers infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The dynamic characteristics of infantile serum antibodies born to mother with SARS-CoV-2 has not been well described. In this study, we analyzed the seroconversion of 27 newborns born to 26 pregnant women infected with SARS-CoV-2. The SARS-CoV-2 IgG positive rate of parturient was 80.8%, and half of their infants obtained maternal IgG. IgG transfer rates were 18.8% and 81.8% in those infants whose mother infected less and more than 2 weeks before delivery. In the first two months of life, the IgG level of infants dropped sharply to one tenth of that at birth. These results suggest that maternal SARS-CoV-2 IgG provides limited protection for infants.

Antibody response to SARS-CoV-2 mRNA vaccines in pregnant women and their neonates

Pregnant women were excluded from initial clinical trials for COVID-19 vaccines1-2, thus the immunologic response to vaccination in pregnancy and the transplacental transfer of maternal antibodies are just beginning to be studied4-5. Methods: Between January 28 and March 31, 2021, we studied 122 pregnant women and their neonates at time of birth. All women had received one or both doses of a messenger RNA (mRNA)-based COVID-19 vaccine. Fifty-five women received only one dose of the vaccine and 67 women received both doses of the vaccine by time of giving birth. Eighty-five women received the Pfizer-BioNTech vaccine, while 37 women received the Moderna vaccine. All women tested negative for SARS-CoV-2 infection using reverse-transcriptase PCR on nasopharyngeal swabs, and none reported any COVID-19 symptoms at the time of admission for birth. Semi-quantitative testing for antibodies against S-Receptor Binding Domain (RBD) (ET HealthCare)3 was performed on sera of maternal peripheral blood and neonatal cord blood at the time of delivery to identify antibodies mounted against the vaccine. All women tested negative for antibodies against the Nucleocapsid Protein (NP) antigen (Roche Diagnostics EUA) to ensure that the antibodies detected were not produced in response to past SARS-CoV-2 infection. Relationship between IgG antibody levels over time was studied using ANOVA with Tukey posthoc. Relationship between maternal and neonatal IgG levels was studied using Pearson correlation analysis and linear regression on log2-scaled serological values. Relationship between IgG placental transfer ratio (neonatal/maternal) vs. time was studied using Pearson correlation analysis and linear regression on log2-scaled serological values and days. Serology levels represented as log2+1. Statistical analysis was performed using R 3.6.3, RStudio 1.1.463. The study was approved by the Weill Cornell Medicine institutional review board. Results: Pregnant women vaccinated with mRNA-based COVID-19 vaccines during pregnancy and tested at time of birth had detectable immunoglobulin (Ig)G and IgM response. Eighty-seven women tested at birth produced only an IgG response, and 19 women produced both an IgM and IgG response. Sixteen women tested at birth had no detectable antibody response, and they were all within four weeks after vaccination dose 1 (Figure 1A). There was an increase over time in the number of women that mounted an antibody response, as well as the number of women that demonstrated passive immunity to their neonates (Figure 1A). All women and their neonates, except for one neonate, had detectable IgG antibodies by 4 weeks after maternal first dose of vaccination (Figure 1A). 43.6% (24/55) of neonates born to women that received only one vaccine dose had detectable IgG, while 98.5% (65/67) of neonates born to women that received both vaccine doses had detectable IgG. The IgG levels in pregnant women increased weekly from two weeks after first vaccine dose (p=0.0047;0.019), as well as between the first and second weeks after the second vaccine dose (p=2e-07) (Figure 1B). Maternal IgG levels were linearly associated with neonatal IgG levels (R=0.89, p<2.2e-16) (Figure 2A). Placental transfer ratio correlated with the weeks that elapsed since maternal second dose of vaccine (R=0.8, p=2.6e-15) (Figure 2B). Discussion: mRNA-based COVID-19 vaccines in pregnant women lead to maternal antibody production as early as 5 days after the first vaccination dose, and passive immunity to the neonate as early as 16 days after the first vaccination dose. The increasing levels of maternal IgG over time, and the increasing placental IgG transfer ratio over time suggest that timing between vaccination and birth may be an important factor to consider in the vaccination strategies of pregnant women. Further studies are needed to understand the factors that influence transplacental transfer of IgG antibody, as well as the protective nature of these antibodies.

AB0-incompatibility of mother and fetus: the role of anti-glycan alloantibodies in the hemolytic disease of newborns

The mother and fetus incompatibility due to Rh-factor, blood group or other blood factors can lead to hemolytic disease of the fetus and newborn (HDN). HDN is a clinical disease condition of the fetus and newborn as a result of hemolysis, when maternal IgG alloantibodies cross the placenta and destroy the red blood cells of the fetus and newborn. The child disease begins in utero and can dramatically increase immediately after birth. As a result, hyperbilirubinemia and anemia develop, that can lead to abortions, serious complications, or death of the neonates in the absence of proper therapy. The range of HDN has changed significantly now compared to previous decades. Half a century ago, HDN was considered an almost complete synonym of RhD-alloimmunization, and this was a frequent problem for newborns. By now due to the high effective of Rh-conflict prevention, immunological AB0-conflicts have become the most common cause of HDN. The review aimes to one of the main causes of jaundice and anemia in neonates at present, i.e. HDN due to immunological AB0-conflict of mother and newborn (AB0-HDN). The main participants of the AВ0- incompatibility mother and child are considered, namely A- and B-glycans, as well as the corresponding anti-glycan alloantibodies. Close attention is paid to the structure features of glycan alloantigens on the red blood cells of the fetus and adult. The possible correlation of the frequency and severity of HDN with the blood group of mother and child, as well as with the titer of maternal alloantibodies, has been considered. The influence of immunoglobulin G subclasses on the AB0-HDN development has been evaluated. In most cases, AB0-HDN appear when the mother has the blood group 0, and the fetus has the group A (subgroup A1) or the group B. Other rare incidences of AB0-incompatibility with severe course are occurred. As a whole the etiology of AB0-HDN is complex and the HDN severity is influenced by many factors. The authors have analyzed statistical data, as well as the prevalence of AB0-incompatibility and AB0-HDN in various regions of the world. Current approaches to the diagnosis of AB0-HDN are discussed in addition. By now the problems of AB0- HDN occurrence and developing of ways to overcome this disease remain relevant.

Maternal SARS-CoV-2 IgG provides limited protection for their infants

At present, there are still many ambiguous reports about the perinatal infection of infants born to mothers infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)1-3. The dynamic characteristics of infantile serum antibodies born to mother with SARS-CoV-2 has not been well described4-6. In this study, we analyzed the seroconversion of 27 newborns born to 26 pregnant women infected with SARS-CoV-2. The SARS-CoV-2 IgG positive rate of parturients was 80.8%, and half of their infants obtained maternal IgG. IgG transfer rates were 18.8% and 81.8% in those infants whose mother infected less and more than 2 weeks before delivery respectively. In the first two months of life, the IgG level of infants dropped sharply to one tenth of that at birth. The IgM was confirmed positive in 53.8% of mothers and negative in all infants. These results suggest that maternal IgG has limited protection for infants, which may help us to improve vaccination strategies in future.

“APS pregnancy – The offspring”

Background Antiphospholipid antibody syndrome (APS) is an autoimmune disease that affects women in childbearing age. In recent years, great improvements were achieved in the management of pregnancies in these women. Prematurity could be an issue in these pregnancies, mainly due to the direct pathogenic effect of antiphospholipid antibodies (aPL) on the placental surface. Maternal IgG aPL can cross the placenta and theoretically interact with the growing fetus; it could reach the fetal brain because of the incompleteness of the fetal blood-brain barrier: whether this can have an effect on brain development is still debated. Neonatal thrombosis episodes have been described in children positive for aPL, not always associated with maternal antibody positivity, suggesting the hypothesis of a possible aPL de novo synthesis in fetus and neonates. Methods A keyword-based literature search was conducted. We also described a case of neonatal catastrophic antiphospholipid syndrome (CAPS). Results Offspring of patients with APS are generally healthy but the occurrence of neonatal thrombosis or minor neurological disorders were reported. Conclusions The limited number of the available data on this sensitive issue supports the need for further studies. Clinical follow-up of children of mothers with APS seems to be important to exclude, in the neonatal period, the occurrence of aPL associated pathological events such as thrombosis, and in the long-term, impairment in learning skills or behavioral problems.

Blocked-D phenomenon in hemolytic disease of fetus and newborn with multiple maternal antirhesus antibodies

Background: The blocking of D antigen sites of RBC membrane of the fetus by the passively transferred IgG anti-D in cases of Hemolytic Disease of fetus and new born (HDFN) is called blocked- D phenomenon. The coating of maternal IgG type of anti-D prevents the agglutination of the Rh-(D) antigen positive red blood cells (RBC) by the IgM D-antigen typing reagents. We are reporting two cases of Rh-(D) HDFN which were falsely typed as Rh (D) antigen negative with routine typing reagents and had multiple allo-antibodies in the maternal serum. Aims: To rule out HDFN and to confirm the Rh-(D) status of baby, to detect the presence of other allo-antibodies in the maternal serum that can complicate future transfusions in mother. Materials: After routine blood grouping, sample of baby was subjected to adsorption-elution studies and maternal serum was used for antibody screening and identification Results: In both the cases, blocked-D phenomenon got detected and there were multiple anti-rhesus antibodies other than anti-D in the maternal serum. Conclusion: Antibody identification in antenatal women is important in the case management of HDFN to protect future pregnancies and to avoid the risk of mismatched transfusions.