Pregnant Women at Low Risk of Having a Child with Fetal and Neonatal Alloimmune Thrombocytopenia Do Not Require Treatment with Intravenous Immunoglobulin

Fetal and neonatal alloimmune thrombocytopenia (FNAIT) is a rare condition in which maternal alloantibodies to fetal platelets cause fetal thrombocytopenia that may lead to intracranial hemorrhage (ICH). Off-label intravenous immunoglobulin (IVIg) has for 30 years been the standard of care for pregnant women who previously have had a child with FNAIT. The efficacy of this treatment has never been tested in a placebo-controlled clinical trial. Although IVIg treatment may improve the neonatal outcome in women who previously have had a child with FNAIT-associated ICH, the question is whether IVIg is necessary for all immunized pregnant women at risk of having a child with FNAIT. The results from some recent publications suggest that antenatal IVIg treatment is not necessary for women who are (1) HPA-1a-immunized and HLA-DRB3*01:01-negative, (2) HPA-1aimmunized with a previous child with FNAIT but without ICH or (3) HPA-5b-immunized. If IVIg is not used for these categories of pregnant women, the amount of IVIg used in pregnant women with platelet antibodies would be reduced to less than 1/4 of today’s use. This is important because IVIg is a scarce resource, and the collection of plasma for the treatment of one pregnant woman is not only extremely expensive but also requires tremendous donor efforts

Risk factors for anxiety and depression among pregnant women during COVID-19 pandemic-Results of a web-based multinational cross-sectional study

Objective To assess risk factors for anxiety and depression among pregnant women during the COVID-19 pandemic using Mind-COVID, a prospective cross-sectional study that compares outcomes in middle-income economies and high-income economies. Methods A total of 7102 pregnant women from 12 high-income economies and nine middle-income economies were included. The web-based survey used two standardized instruments, General Anxiety Disorder-7 (GAD-7) and Patient Health Questionnaire-9 (PHQ-9). Result Pregnant women in high-income economies reported higher PHQ-9 (0.18 standard deviation [SD], P < 0.001) and GAD-7 (0.08 SD, P = 0.005) scores than those living in middle-income economies. Multivariate regression analysis showed that increasing PHQ-9 and GAD-7 scales were associated with mental health problems during pregnancy and the need for psychiatric treatment before pregnancy. PHQ-9 was associated with a feeling of burden related to restrictions in social distancing, and access to leisure activities. GAD-7 scores were associated with a pregnancy-related complication, fear of adverse outcomes in children related to COVID-19, and feeling of burden related to finances. Conclusions According to this study, the imposed public health measures and hospital restrictions have left pregnant women more vulnerable during these difficult times. Adequate partner and family support during pregnancy and childbirth can be one of the most important protective factors against anxiety and depression, regardless of national economic status

Old tools revisited give hope - new treatment option for families with a history of severe FNAIT complications.

Accepted manuscript version. Published version at http://doi.org/10.1111/aogs.12842

Fetal and neonatal alloimmune thrombocytopenia - The Norwegian management model

In Norway, the management strategy for fetal and neonatal alloimmune thrombocytopenia (FNAIT) has for more than two decades differed from most other countries. The focus of this paper is to describe and discuss the Norwegian FNAIT management program. We recommend antenatal IVIg to women who previously have had a child with FNAIT-induced ICH, and usually not to HPA-1a alloimmunized pregnant women where a previous child had FNAIT, but not ICH. When deciding management strategy, we use not only the obstetric history but also the antenatal anti-HPA-1a antibody level as a tool for risk stratification. The Norwegian National Unit for Platelet Immunology (NNUPI) at the University Hospital of North Norway in Tromsø provides diagnostic and consulting service for the clinicians and the blood banks all over the country, and serves as a national reference laboratory for FNAIT investigations

Current perspectives on fetal and neonatal alloimmune thrombocytopenia - Increasing clinical concerns and new treatment opportunities

Differences in platelet type between the fetus and the mother can lead to maternal immunization and destruction of the fetal platelets, a condition named fetal and neonatal alloimmune thrombocytopenia (FNAIT). FNAIT is reported to occur in ~1 per 1,000 live born neonates. The major risk is intracranial hemorrhage in the fetus or newborn, which is associated with severe neurological complications or death. Since no countries have yet implemented a screening program to detect pregnancies at risk, the diagnosis is typically established after the birth of a child with symptoms. Reports on broader clinical impact have increased clinical concern and awareness. Along with new treatment options for FNAIT, the debate around antenatal screening to detect pregnancies at risk of FNAIT has been revitalized

A combined effect of anti-HPA-1a and anti-HLA Class I in pregnancy?

Background - Maternal anti–human leukocyte antigen (HLA) Class I is commonly detected alongside anti–human platelet antigen (HPA)-1a in fetal and neonatal alloimmune thrombocytopenia (FNAIT). Little is known regarding whether the presence of anti-HLA Class I may exert an additive effect on the risk and severity of FNAIT. Methods and Materials - We reanalyzed samples originally collected as part of a large Norwegian screening study on FNAIT during 1995-2004. This study identified and managed 170 pregnancies where the mother was HPA-1a negative and had detectable anti-HPA-1a during pregnancy. Maternal samples from 166 of these pregnancies were rescreened for anti-HLA Class I, revealing 111 (67%) that were antibody positive. Various regression models were used to assess if and how maternal anti-HLA Class I influenced the neonatal platelet count. Results and Conclusions - Unadjusted neonatal platelet counts and the frequency of neonatal thrombocytopenia was not significantly affected by the presence of anti-HLA Class I alongside anti–HPA-1a, but results from regression analyses revealed a possible increased risk when the mother was nulliparous. These results warrant further investigation

Fetal exposure to maternal human platelet antigen-1a does not induce tolerance. An analytical observational study

Fetal and neonatal alloimmune thrombocytopenia (FNAIT) is a disease that may cause severe bleeding complications with risk of perinatal death or lifelong disability. The main cause of FNAIT is maternal antibodies against human platelet antigen (HPA)-1a. Both fetomaternal bleeding and transplacental trafficking of fetal cells during pregnancy could be the cause of alloimmunization. Persistence of fetal cells in the mother (fetal microchimerism) and maternal cells in the child (maternal microchimerism) are well-recognized phenomena. Thus, it could be envisaged that fetal exposure to the HPA-1a antigen could tolerize an HPA-1a negative female fetus and prevent production of anti-HPA-1a antibodies later in life if she becomes pregnant with an HPA-1a positive fetus. The objective of the current study was to assess if the risk of producing anti-HPA-1a antibodies and the severity of neonatal thrombocytopenia in HPA-1a negative women with HPA-1a positive mothers (i.e. the mother is HPA-1a/b), was lower than in HPA-1a negative women with HPA-1a negative mothers. HPA-1a negative women with HPA-1a antibodies, identified from a Norwegian screening study (1996–2004), where HPA-1 genotype of their mothers was available, were included in the study. The frequency of HPA-1a positive mothers to HPA-1a immunized daughters were compared to the calculated frequency in the general population. We did not find any difference in the frequency of HPA-1ab among mothers to daughters with HPA-1a antibodies as compared with the general population. Furthermore, acknowledging sample-size limitations, we neither found an association between the mothers’ HPA type and their daughters’ anti-HPA-1a antibody levels or any difference between the two groups of mothers (HPA-1ab vs HPA-1bb), with respect to frequency of thrombocytopenia in the children of their daughters with HPA-1a antibodies. Hence, there was no indication of tolerance against fetal HPA-1a antigen in HPA-1bb women who had been exposed to HPA-1a antigen during fetal development