Risk of thrombocytopenia in neonates of thrombocytopenic mothers.

OBJECTIVE: Maternal thrombocytopenia during pregnancy may occur due to several possible etiologies, with potential neonatal impact. The aim of the present study was to investigate whether there is a correlation between maternal and neonatal platelet count among women with thrombocytopenia during pregnancy. METHODS: A cross-sectional retrospective study (2012-2019) was conducted at a tertiary medical center. Complete blood count was routinely measured in all patients on admission to the delivery ward. Thrombocytopenia was defined as a platelet count below 150 K/µL. Clinical and outcome parameters of thrombocytopenic mothers and their newborns were collected from the electronic files and analyzed by severity of maternal thrombocytopenia. RESULTS: Of 45 385 women with a documented platelet count at admission, 2841 (6.24%) had thrombocytopenia: 2623 (5.7%) mild (100-149 K/µL), 207 (0.45%) moderate (50-99 K/µL), and 11 (0.02%) severe (<50 K/µL). Eight newborns had thrombocytopenia; corresponding rates by severity of maternal thrombocytopenia were 0.11%, 1.43%, and 18.18% (P = 0.04). None of the thrombocytopenic neonates had an intraventricular hemorrhage or other bleeding complications. The correlation between maternal and neonatal platelet counts was weak (Pearson r = 0.038; P = 0.046). CONCLUSION: We suggest that although the chances of neonatal thrombocytopenia are higher with worsening maternal thrombocytopenia, actual occurrence is rare, and the correlation is poor. Therefore, maternal thrombocytopenia cannot be regarded as a significant risk factor for neonatal thrombocytopenia. Neonatal platelet count should be obtained when maternal thrombocytopenia is autoimmune or less than 100 K/µL.

Predictive effects of platelet-to-lymphocyte ratio on neonatal thrombocytopenia in primary immune thrombocytopenic mothers: a retrospective cohort study.

BACKGROUND: Primary immune thrombocytopenia (ITP) can increase the risk of neonatal thrombocytopenia (NT). This study aimed to investigate the key factors for predicting the risk of NT. METHODS: Data were retrospectively collected from all pregnant women with ITP from 2015 to 2021. Newborns were divided into two groups according to the presence or absence of NT. The parameters between the two groups were then compared. Next, the correlation between maternal platelet-to-lymphocyte ratio (PLR) and neonatal platelet count was analyzed by logistic regression and generalized additive model. Additionally, the relationships among the platelet counts of siblings were also determined. RESULTS: A total of 147 maternal cases were included. NT was observed in 46 (31.72%) neonates. A history of previous children with NT appeared to have predictive value for NT (OR 16.484, 95% CI 2.212-122.858, P < 0.001), as the nadir gestational platelet (OR 0.958, 95% CI 0.93-0.988, P < 0.001). Correlation analysis of platelet count on postnatal day 1 and the nadir platelet count in 36 sibling neonates showed a positive correlation (r=0.684, P<0.001; r=0.900, P<0.05). PLR was divided into 3 groups via tertiles, and the incidence of NT was dramatically higher in the group with lower PLR during the second and third trimesters than in the other two groups (48.5% vs 33.3% vs 22%, P<0.05; 50% vs 21.3% vs 26.7%, P<0.001). Moreover, the risk of NT was markedly higher in the first trimester (PLR < 78.51; OR 0.975, 95% CI 0.951-0.999, P<0.05) and the second trimester (PLR < 20.41; OR, 0.899, 95% CI 0.820-0.985, P<0.05) compared to the third trimester. CONCLUSION: Our findings suggest that a history of previous children with NT is a significant factor for predicting NT in subsequent pregnancies. PLR in the first, second and third trimesters can also be used as a reference to predict NT risk.

Neonatal Thrombocytopenia: Differing Characteristics of NAIT Versus Non-NAIT.

While neonatal alloimmune thrombocytopenia (NAIT) is the most common cause of severe neonatal thrombocytopenia good clinical predictors are lacking. We analyzed cases of neonatal thrombocytopenia in Schneider Children's Medical Center of Israel to pinpoint qualifiers of NAIT (NAIT+) in comparison to non-NAIT (NAIT-) thrombocytopenia. Patient and maternal data were retrospectively collected on all thrombocytopenic newborns undergoing a workup for NAIT in our tertiary center between 2001 and 2016. Among 26 thrombocytopenic neonates, the mean nadir in NAIT+ patients (25×10 9 /L) was significantly lower than NAIT- patients (64×10 9 /L) ( P <0.001). 61.5% of NAIT+ infants required treatment compared with 23% of non-NAIT ( P =0.015). NAIT+ patients also required more therapeutic modalities than infants with NAIT- thrombocytopenia. Human platelet antigen (HPA)-1a and HPA-5b alloantibodies most frequently caused NAIT. In summary, thrombocytopenia in NAIT+ was significantly more severe compared with NAIT- and more likely to require treatment. In addition, despite the varied ethnic population in Israel, the HPA alloantibodies found in our population were most similar to those common in Western countries. In the absence of rigorous prenatal screening options, we suggest platelet counts below 40 to 50×10 9 /L in a healthy newborn be considered most suggestive for NAIT and warrant urgent NAIT-specific analysis.

Risk factors for severe neonatal thrombocytopenia in cases of maternal immune thrombocytopenia.

AIM: Maternal immune thrombocytopenia (ITP) may induce neonatal thrombocytopenia (nTP), which carries a risk of neonatal haemorrhagic complications. Some risk factors for nTP have reached consensus such as maternal splenectomy and previous severe nTP, while others such as maternal platelet count have not. METHODS: We conducted a retrospective cohort study in a university hospital, including 145 neonates of mothers with ITP. We assessed the risk of severe nTP and bleeding complications. RESULTS: Severe nTP in the first 24 h after birth was more common in case of maternal splenectomy (OR = 4.4) and a previous severe nTP (OR = 46.9). Severe nTP at nadir (lowest platelet count during the initial postnatal days) was more frequent in cases of a previous neonate with severe nTP (OR = 42), maternal treatment during pregnancy (OR = 2.4) and a low maternal platelet count during pregnancy or at delivery. These risk factors were not significantly associated with an increased risk of neonatal haemorrhagic complications. CONCLUSION: In our population, we confirm the risk of severe nTP in case of maternal splenectomy or previous nTP. By monitoring the platelet count to its nadir, we identified three additional risk factors: maternal treatment during pregnancy and low maternal platelet count during pregnancy or low maternal platelet count at delivery.

Platelet CD36 deficiency is present in 2.6% of Arabian individuals and can cause NAIT and platelet refractoriness.

BACKGROUND: CD36 isoantibodies are capable of inducing neonatal alloimmune thrombocytopenia (NAIT) and platelet refractoriness. As to now the CD36 type I deficiency has been reported in East Asian and African individuals. However, it is virtually unknown in Caucasians. The aim of this study was to display the prevalence of the CD36 deficiency within parts of the Arabian population in Germany. Secondly, we are presenting the case of a newborn suffering from NAIT which was induced by CD36 antibody. METHODS: Platelet (p) CD36 was determined by flow cytometry on 1328 samples mainly from individuals of Arabian origin and a family with a neonate affected by NAIT. DNA sequencing was performed on all pCD36-negative samples. RESULTS: Thirty-five (2.64%) of all donor samples were pCD36 negative, 19 (1.43%) had a weak expression. Including only individuals from the Arabian peninsula, frequencies were 3.39% and 1.75%, respectively. CD36 type I deficiency on both platelets and monocytes combined with a CD36 isoantibody were detected in the mother of the NAIT baby. The baby was successfully transfused with two HPA-unselected platelet concentrates. In case of need, two platelet units with a weak pCD36 expression were on hand. A total of 45 different CD36 mutations were detected within pCD36-negative individuals, some being homozygous, most of them only present on one allele. CONCLUSION: The CD36-negative phenotype is present in a significant number of individuals of Arabian origin and enables CD36 isoimmunization in NAIT or refractoriness. Blood transfusion services should be aware of such cases.

Neonatal Alloimmune Thrombocytopenia: A Concise Review.

BACKGROUND: Neonatal alloimmune thrombocytopenia (NAIT) is defined as an uncommon platelet disorder caused by maternal alloimmunization to human-specific antigens (HPAs) that are paternally inherited, resulting in low fetal/neonatal platelet levels and debilitating effects on the newborn. The incidence of NAIT is 1 in every 1000 live births within the United States; it is the most common cause of severe thrombocytopenia (<30 × 109/L) and intracranial hemorrhage in term newborns. PURPOSE: The purpose of this article is to discuss the pathophysiology, clinical manifestations, diagnosis, and treatment of NAIT and its implications upon the lifespan of the neonate. METHODS: A literature review was conducted using PubMed, CINAHL, and Google Scholar (2014-2019). Search terms included NAIT, neonatal/fetal alloimmune thrombocytopenia, newborn platelets, and intracranial bleeding and NAIT. RESULTS: NAIT can affect first pregnancies and often goes undiagnosed until delivery. Universal screening tools with a focus on HPA-1a typing via noninvasive testing have been successfully trialed and have yielded promising results indicating a 75% reduction in risks associated with NAIT; however, none have been incorporated into practice and prophylactic treatment remains unavailable. IMPLICATIONS FOR RESEARCH: Adopting a universal screening tool and prophylaxis for NAIT would allow for early diagnosis and treatment in utero. IMPLICATIONS FOR PRACTICE: Many healthcare providers are not familiar with NAIT often focusing on other causes of thrombocytopenia as a potential diagnosis.

Neonatal Outcome of Pregnancies Complicated with Idiopathic Thrombocytopenia.

OBJECTIVE: To determine the neonatal outcome with maternal idiopathic thrombocytopenia. STUDY DESIGN: Descriptive study. PLACE AND DURATION OF STUDY: Obstetrics and Gynecology Department, Liaqat National Hospital, Karachi, from January to June 2017. METHODOLOGY: All 73 pregnant women diagnosed with idiopathic thrombocytopenia (ITP) during the study period were included. All the patients were kept under observation till birth of newborns. Neonates were assessed for thrombocytopenia, classified as mild, moderate and severe thrombocytopenia as outcome on the first post-natal day. RESULTS:  Frequency of neonatal thrombocytopenia in 73 pregnant women complicated by idiopathic thrombocytopenia was 16.44% (12 neonates). Out of 12 cases, three (25%) neonates had mild thrombocytopenia, four (33.33%) neonates had moderate thrombocytopenia and five (41.66%) neonates had severe thrombocytopenia. CONCLUSION: There are considerable chances of neonatal thrombocytopenia when mothers were suffering with idiopathic thrombocytopenia during pregnancy. These findings may be useful for the medical staff to counsel pre-pregnant or pregnant women with ITP as well as care required during delivery. Key Words: Thrombocytopenia, Idiopathic thrombocytopenia, Neonatal ITP, Pre-natal ITP.

Naitbabies - A patient organisation for families affected by foetal and neonatal alloimmune thrombocytopenia - FNAIT.

Naitbabies is a small Charitable Incorporated Organisation (CIO) (Foundation) registered in England, United Kingdom and run by families who have been diagnosed with foetal and neonatal alloimmune thrombocytopenia (FNAIT). FNAIT is a rare, life threatening bleeding disorder caused by the maternal immune response against fetal platelet antigens. Clinical research shows that approximately 1:1000 babies are affected by this disorder; of those 5-10 % will suffer internal bleeding, most particularly intracranial haemorrhage. As the only patient organisation for FNAIT, we advocate for parents worldwide; as of July 8th 2019 our Parents Support Group numbered 1250 members. We support research into FNAIT, its causes, treatment and prevention. Since 2012 we have been collaborating with scientists who have been engaged on a programme to develop a prophylactic treatment to prevent FNAIT in HPA-1a negative women. Our aim is to see routine prenatal screening for FNAIT for all pregnant women.

Epidemiology and management of fetal and neonatal alloimmune thrombocytopenia.

Fetal and neonatal alloimmune thrombocytopenia (FNAIT) is a disease in pregnancy characterized by maternal alloantibodies directed against the human platelet antigen (HPA). These antibodies can cause intracranial hemorrhage (ICH) or other major bleeding resulting in lifelong handicaps or death. Optimal fetal care can be provided by timely identification of pregnancies at risk. However, this can only be done by routinely antenatal screening. Whether nationwide screening is cost-effective is still being debated. HPA-1a alloantibodies are estimated to be found in 1 in 400 pregnancies resulting in severe burden and fetal ICH in 1 in 10.000 pregnancies. Antenatal treatment is focused on the prevention of fetal ICH and consists of weekly maternal IVIg administration. In high-risk FNAIT treatment should be initiated at 12-18 weeks gestational age using high dosage and in standard-risk FNAIT at 20-28 weeks gestational age using a lower dosage. Postnatal prophylactic platelet transfusions are often given in case of severe thrombocytopenia to prevent bleedings. The optimal threshold and product for postnatal transfusion is not known and international consensus is lacking. In this review practical guidelines for antenatal and postnatal management are offered to clinicians that face the challenge of reducing the risk of bleeding in fetuses and infants affected by FNAIT.

Conocimientos actuales sobre la patogénesis, presentación clínica, diagnóstico y manejo de la trombocitopenia neonatal aloinmune / Current knowledge on neonatal alloimmune thrombocytopenia's pathogenesis, clinical presentation, diagnostic and management

Introducción: La trombocitopenia neonatal aloinmune es una enfermedad producida por anticuerpos maternos contra antígenos plaquetarios fetales heredados del padre. Puede ser causa de hemorragia intracraneal y conducir a la muerte o discapacidad en el feto/neonato. Aunque es la causa más grave de trombocitopenia en el neonato y la más común en los recién nacidos a término, en general ha sido poco investigada. Objetivos: Exponer los conocimientos actuales sobre la patogénesis, presentación clínica, diagnóstico y del manejo pre- y posnatal de la trombocitopenia neonatal aloinmune, Métodos: Se realizó una revisión de la literatura, en inglés y español, a través del sitio web PubMed y el motor de búsqueda Google académico de artículos publicados en los últimos 10 años. Se hizo un análisis y resumen de la bibliografía revisada. Resultados: Los anticuerpos IgG maternos son transportados a través de la placenta a la circulación fetal, opsonizan las plaquetas fetales que son removidas por fagocitosis. Los antígenos más implicados son el HPA-1a y HPA-4a. La fisiopatología de la enfermedad es muy similar a la enfermedad hemolítica perinatal, pero aún no se han implementado programas de pesquisa y el diagnóstico se realiza después del nacimiento del niño afectado de trombocitopenia, hemorragia intracraneal o muerte in útero de causa no explicada. Consideraciones finales: El impacto clínico de la trombocitopenia neonatal aloinmune y las oportunidades de tratamiento potencian la necesidad de implantar programas de pesquisa para la detección de fetos en riesgo de padecer esta enfermedad(AU)

Introduction: Neonatal alloimmune thrombocytopenia is a disease produced by maternal antibodies against fetal platelet antigens inherited from the father. It can be a cause of intracranial hemorrhage and lead to death or disability in the fetus / neonate. Although it is the most serious cause of thrombocytopenia in newborns and the most common in full-term infants, it has generally been poorly investigated. Objectives: To approximate to current knowledge about the pathogenesis, clinical presentation, diagnosis and pre- and post-natal management of neonatal alloimmune thrombocytopenia. Methods: A review of literature, in English and Spanish, through PubMed website and Google scholar search engine of articles published in the last 10 years was conducted. An analysis and summary of the reviewed bibliography was made. Results: Maternal IgG antibodies are transported through the placenta to the fetal circulation, opsonizing fetal platelets that are removed by phagocytosis. The most involved antigens are HPA-1a and HPA-4a. The pathophysiology of this disease is very similar to perinatal hemolytic disease, but research programs have not been implemented yet and diagnosis is made after birth of children affected by thrombocytopenia, intracranial hemorrhage or in uterus death by unexplained causes. Final considerations: Clinical impacts of neonatal alloimmune thrombocytopenia and treatment opportunities enhance the need to implement screening programs for the detection of fetuses at risk of suffering from this disease(AU)

Fetal and neonatal alloimmune thrombocytopenia: recommendations for evidence-based practice, an international approach.

Fetal and neonatal alloimmune thrombocytopenia (FNAIT) may result in severe bleeding, particularly fetal and neonatal intracranial haemorrhage (ICH). As a result, FNAIT requires prompt identification and treatment; subsequent pregnancies need close surveillance and management. An international panel convened to develop evidence-based recommendations for diagnosis and management of FNAIT. A rigorous approach was used to search, review and develop recommendations from published data for: antenatal management, postnatal management, diagnostic testing and universal screening. To confirm FNAIT, fetal human platelet antigen (HPA) typing, using non-invasive methods if quality-assured, should be performed during pregnancy when the father is unknown, unavailable for testing or heterozygous for the implicated antigen. Women with a previous child with an ICH related to FNAIT should be offered intravenous immunoglobulin (IVIG) infusions during subsequent affected pregnancies as early as 12 weeks gestation. Ideally, HPA-selected platelets should be available at delivery for potentially affected infants and used to increase the neonatal platelet count as needed. If HPA-selected platelets are not immediately available, unselected platelets should be transfused. FNAIT studies that optimize antenatal and postnatal management, develop risk stratification algorithms to guide management and standardize laboratory testing to identify high risk pregnancies are needed.

[Polymorphism of human platelet antigens in Tunisian population: Clinical and anthropological interests]. / Polymorphisme des antigènes plaquettaires humains dans la population tunisienne : intérêt clinique et anthropologique.

OBJECTIVES: Human Platelet Antigens (HPA) are of considerable interest in obstetric transfusion medicine and anthropological genetics. This study aims to provide clinicians with a detailed database of HPA antigenic variants, which allows them to estimate the probability of allo-immunisation of each antigen. In addition, it aims to make an interethnic comparison of the Tunisian population with other populations. METHODS: The target population consists of 324 healthy and unrelated Tunisian blood donors recruited from the National Blood Transfusion Center in Tunis. DNA extraction was performed by the Salting Out method and molecular genotyping was performed by the PCR-SSP technique. The statistical analysis was performed using two approaches: manual calculation and computerized calculation. Phylogenetic trees were constructed through the use of Standard Genetic Distances that were calculated from allelic frequencies. RESULTS: With the exception of the HPA-4 system, statistical analysis showed that all HPA systems are polymorphic especially the two systems HPA-3 and HPA-15. The inter-ethnic analysis showed that Tunisians are closer to North Africans and Caucasians than Sub-Saharan and Asian populations, which shows genetic mixing between Tunisians, Arabs, Europeans and Africans. CONCLUSION: The results of this study could be exploited to prepare a ready-to-use genotyping plate dedicated to HPA antigens, with the aim of ensuring better management, especially for polytransfused patients.

[FETAL/NEONATAL ALLOIMMUNE THROMBOCYTOPENIA (F/NAIT) - THE PREVALENCE VERSUS AWARENESS OF A LIFE-THREATENING CLINICAL CONDITION].

AIMS: To determine the prevalence and incidence of HPA antigens and antibodies in the Israeli population and to evaluate the degree of awareness to F/NAIT in Israel. BACKGROUND: In fetal/neonatal alloimmune thrombocytopenia (F/NAIT) the fetus suffers from thrombocytopenia mediated by maternal IgG antibodies directed against fetal platelets leading to intracranial hemorrhage (ICH) in about 20% of cases. The antibodies are directed against Human Platelet Antigens (HPA). Diagnosis of F/NAIT is essential because thrombocytopenia may recur and worsen in subsequent pregnancies; hence awareness of F/NAIT is crucial. METHODS: We conducted a retrospective analysis of cases referred to the platelet immunology laboratory between the years 2011-2015 and medical records of newborns born at Rambam Medical Center during 2010-2015. RESULTS: Of the 322 cases studied, 175 (54.35%) had anti-platelet antibodies. The most common antibody was anti-HPA1a (41.85%) followed by anti-HPA5b (28.75%). The prevalence of HPA antigens was similar to that of the Caucasian population. About 80% of the cases were referred due to neonatal thrombocytopenia, found in a random blood count or after bleeding, and 13% of cases were referred due to suspected ICH during pregnancy. In only 22.6% of cases, the diagnosis was made immediately after birth, and 18.7% of the suspected cases were referred only during the subsequent pregnancy. About 84% of infants with severe thrombocytopenia were not referred to F/NAIT diagnosis. CONCLUSIONS: The prevalence of platelet antigens in the Israeli population is similar to that of the Caucasian population. The paucity of referrals points to the need to establish diagnostic guidelines and raise awareness among caregivers.

Maternal HPA-1a antibody level and its role in predicting the severity of Fetal/Neonatal Alloimmune Thrombocytopenia: a systematic review.

BACKGROUND AND OBJECTIVES: In Caucasians, fetal/neonatal alloimmune thrombocytopenia (FNAIT) is most commonly due to maternal HPA-1a antibodies. HPA-1a typing followed by screening for anti-HPA-1a antibodies in HPA-1bb women may identify first pregnancies at risk. Our goal was to review results from previous published studies to examine whether the maternal antibody level to HPA-1a could be used to identify high-risk pregnancies. MATERIALS AND METHODS: The studies included were categorized by recruitment strategies: screening of unselected pregnancies or samples analyzed from known or suspected FNAIT patients. RESULTS: Three prospective studies reported results from screening programmes, and 10 retrospective studies focused on suspected cases of FNAIT. In 8 studies samples for antibody measurement, performed by the monoclonal antibody immobilization of platelet antigen (MAIPA) assay, and samples for determining fetal/neonatal platelet count were collected simultaneously. In these 8 studies, the maternal antibody level correlated with the risk of severe thrombocytopenia. The prospective studies reported high negative predictive values (88-95%), which would allow for the use of maternal anti-HPA-1a antibody level as a predictive tool in a screening setting, in order to identify cases at low risk for FNAIT. However, due to low positive predictive values reported in prospective as well as retrospective studies (54-97%), the maternal antibody level is less suited for the final diagnosis and for guiding antenatal treatment. CONCLUSION: HPA-1a antibody level has the potential to predict the severity of FNAIT.

Clinical characteristics, neonatal risk and recurrence rate of gestational thrombocytopenia with platelet count <100 × 109/L.

OBJECTIVE: Gestational thrombocytopenia (GT) accounts for 75% of cases of thrombocytopenia in pregnancy. In most cases of GT, thrombocytopenia is mild (100-150 × 109/L) and has no consequences for either the mother or the fetus. We aimed to investigate the characteristics, neonatal risk and recurrence rate of GT with a platelet count <100 × 109/L. STUDY DESIGN: We reviewed the records of women who delivered during 2006-2016 at a large tertiary care university hospital, and who had platelet count <100 × 109/L during pregnancy. RESULTS: Of 97 pregnancies in which platelet count lower than 100 × 109/L was encountered, 66 (68%) were diagnosed as GT and 31 (32%) as new-onset immune-thrombocytopenic purpura (ITP). The proportions of women with onset of thrombocytopenia in early pregnancy (P = 0.004) and a lower maternal nadir platelet count (P = 0.01) were higher among those with new-onset ITP than GT. There was no difference in the rate of neonatal thrombocytopenia (<100 × 109/L) between those with newly diagnosed ITP and GT (16.1% vs. 10.6%, P = 0.51). Among women with GT, the rate of neonatal thrombocytopenia was higher in those who experienced antepartum bleeding (P = 0.009) and in whom the onset of thrombocytopenia was in early pregnancy (P = 0.002). Of 40 subsequent pregnancies, a recurrence of GT (<100 × 109/L) was encountered in 22 (55%), with similar maternal and perinatal outcomes compared to the initial pregnancy. CONCLUSION: The risk of neonatal thrombocytopenia was substantial, with no difference found between those with GT and new-onset ITP. The recurrence rate of GT was high in subsequent pregnancies.

A Prospective Study on the Incidence and Outcomes of Neonatal Thrombocytopenia at a Tertiary Care Facility in Central Saudi Arabia.

BACKGROUND: The incidence of neonatal thrombocytopenia is low, yet highly dependent on the populations studied. PURPOSE: To assess the incidence of neonatal thrombocytopenia and identify factors associated with its outcomes, namely time to disease onset, recovery duration, and platelet count. METHODS: A prospective observational study was conducted between May and October 2013 at a large tertiary care facility in Saudi Arabia. Neonates with a platelet count of fewer than 150,000/µL of blood were followed up until their recovery or death. RESULTS: The period incidence of neonatal thrombocytopenia was 84/4379 (1.9%). The mortality rate associated with the condition was 68/100,000 births. The male-female ratio of neonates with thrombocytopenia was 2.4:1. The mean (standard deviation) time to disease onset was 1.83 (1.29) days, whereas that of recovery duration was 15.35 (18.46) days. The mean (standard deviation) platelet count at onset was 109,543 (32,826)/µL of blood, whereas that of the increase in platelet count from onset to recovery was 121,876 (78,218)/µL of blood. Treatment comprised monitoring/spontaneous recovery (n = 52, 64.2%) or platelet transfusion (n = 9, 11.1%), immunoglobulins (n = 8, 9.9%), or a combination of both (n = 12, 14.8%). Neonates with a higher gestational age (ß = 8061, t = 2.456) and late disease onset (ß = 26,178, t = 3.969) were more likely to have a larger increase in platelet count from onset to recovery than those with a lower gestational age (adjusted P = .017) and earlier disease onset (adjusted P < .001). IMPLICATIONS: The high incidence of neonatal thrombocytopenia in this Middle Eastern setting indicates that it may be dependent on the population studied. Special attention should be focused on neonates of lower gestational ages and with an early disease onset, because their platelet count recovery may be slower than that of the countergroup.

Intracranial hemorrhages in neonates born from 32 weeks of gestation-low frequency of associated fetal and neonatal alloimmune thrombocytopenia: a register-based study.

BACKGROUND: Fetal and neonatal alloimmune thrombocytopenia (FNAIT) is a rare condition, with an estimated incidence of one in 1000 to 2000 live births. Predominantly, FNAIT is due to maternal alloantibodies that target paternally derived human platelet antigen (HPA) 1a. The most feared complication is an intracranial hemorrhage (ICH). The aim of this study was to determine the frequency of associated maternal platelet (PLT) alloimmunization in a population of neonates born from 32 weeks of gestation and diagnosed with an ICH. STUDY DESIGN AND METHODS: The Swedish Neonatal Quality (SNQ) register was used to identify neonates diagnosed with an ICH born between 2003 and 2012. Mothers were invited to donate peripheral blood, to investigate their HPA-1a antigen status, and test for anti-HPA and anti-HLA Class I alloantibodies. Clinical data for the neonates were retrieved from the SNQ register and available clinical records. RESULTS: Of 286 registered neonates, 278 mothers were contacted. Of 105 analyzed maternal samples, two (1.9%) were HPA-1a antigen negative. Antibody analyses revealed in total three (2.9%) mothers with anti-HPA: one mother (0.94%) with anti-HPA-1a and two mothers (1.9%) with anti-HPA-5b, of whom one had concurrent anti-HPA-15a. Twenty-four percent tested positive for anti-HLA Class I antibodies. A total of 8.5% of neonates (5/59) with PLT counts available in clinical records were severely thrombocytopenic, with PLT counts of less than 50 × 109 /L. CONCLUSIONS: This retrospective cohort revealed a wide range of factors associated with ICH in neonates born from 32 weeks of gestation and suggests PLT alloimmunization to be a less common contributor than anticipated.

Neonatal alloimmune thrombocytopenia caused by anti-HPA antibodies in pregnant Chinese women: a study protocol for a multicentre, prospective cohort trial.

BACKGROUND: Neonatal alloimmune thrombocytopenia (NAIT), caused by maternal antibodies raised against alloantigens carried on foetal platelets, is a very common haematological abnormality in newborns worldwide. However, baseline data on NAIT in China are lacking. Therefore, this study seeks to explore the incidence of alloantibody against the human platelet antigen (HPA) in pregnant women and its associations with NAIT in China. METHODS: A multicentre, prospective cohort study design will be used, and 55,497 pregnant women will be recruited for the first screening of the anti-HPA antibody at 12 to 28 weeks of gestational age. Subjects who are positive in the first screening for the anti-HPA antibody will be included in the exposure group. Re-tests of the antibody titre, antigen-specificity and genotyping of HPA and HLA will be conducted during admission. A ratio of 1:1 paired individuals with the same ethnicity and parity but testing negative for the anti-HPA antibody will be randomly selected to be included in the non-exposure group. NAIT will be diagnosed in the newborns on day one of the birth. The HPA of the neonates in the exposure group will also be genotyped by sequencing. Associations of maternal HLA with the occurrence of the anti-HPA antibody and correlation of the severity of NAIT with the titre of the anti-HPA antibody will be further analysed. DISCUSSION: The study is expected to provide baseline data on NAIT in China. Besides, we hope to find out a population who expresses particular HLA molecules has significant higher risk of HPA alloimmunization in Chinese individuals. We also hope to find a Chinese-specific cut-off antibody titre for the prediction of the severity of NAIT and to provide a means to evaluate the necessity of antenatal treatment. TRIAL REGISTRATION: ClinicalTrials.gov: NCT02934906 (date registered: 13.10.2016).