Journal of Perinatology (2010) 30, 38–44; doi:10.1038/jp.2009.134; appear online 24 September 2009
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H Özkan1, M Çetinkaya1, N Köksal1, R Ali2, A M Güneş3, B Baytan3, F Özkalemkaş2, V Özkocaman2, T Özçelik2, Ü Günay3, A Tunali2, Y Kimya4 and C Cengiz4
Idiopathic thrombocytopenic purpura (ITP) is an autoimmune ataxia of adults and accouchement in which the patient's platelets are destroyed by autoantibodies.1,2 It is best accustomed in adolescent women during bearing age and may be associated with affectionate and fetal complications.2 Although beforehand studies appear a aerial perinatal bloodshed amount (12 to 21%), such has not been accustomed for neonatal outcomes. In addition, it is broadly accustomed that the abundance of intracranial drain is actual rare, affecting 0 to 1% at-risk babies.3,4,5 However, astringent thrombocytopenia (<20 × 109 per liter) in neonates built-in to mothers with ITP has been appear in 3 to 5% of cases.6,7 Although several studies accept been advised to ascertain affectionate characteristics for admiration the platelet akin of newborns, no alternation has been apparent amid neonatal thrombocytopenia (NT) and the affectionate platelet count, a history of beforehand splenectomy or affectionate platelet antibodies. Hence, it was adapted that a history of antecedent NT and the severity of affectionate ache ability be reliable predictors of NT.8,9,10
As alone bound and adverse abstracts are accessible on the aftereffect of affectionate ITP on neonatal outcomes, we aimed to actuate the factors associated with cast in newborns built-in to gravidas with ITP during abundance and additionally to analyze the breed with and after thrombocytopenia in acceding of affectionate and neonatal characteristics.
All of the abundant women that were followed up and advised by Hematology Department of Uludag University School Medicine Hospital in Bursa, Turkey were identified. A attendant blueprint assay was performed for all obstetric patients with ITP who were advised and delivered amid 1 January 1998 and 31 December 2008. At the aforementioned time, a agnate blueprint assay was performed for the breed built-in to these mothers with ITP. During the abstraction interval, 38 gravidas with ITP delivered 38 neonates in 38 pregnancies; however, 9 pregnancies were afar due to bereft affectionate data. Therefore, a absolute of 29 gravidas and their breed were included in this study. Admittance belief were a assay of ITP during abundance or a abundance with a antecedent history of ITP. Breed built-in to mothers with added autoimmune diseases (for example, systemic lupus erythematosus), pre-eclampsia and hemolytic anemio, animated alarmist enzymes, low platelet calculation affection were excluded. Breed with added causes of NT, such as sepsis, perinatal asphyxia, broadcast intravascular coagulation, drug-induced thrombocytopenia and ancestral forms of thrombocytopenia were additionally excluded.
ITP was diagnosed application accustomed criteria: (1) thrombocytopenia >6 months, (2) a accustomed cartilage bottom examination, (3) a accustomed white and red claret corpuscle calculation and (4) exclusion of added causes of thrombocytopenia.
The affectionate platelet calculation was bent every 3 weeks from the time of assay in abundance to commitment (more frequently in cases of astringent thrombocytopenia). Platelet counts were performed in claret samples calm in tubes absolute ethylenediamine tetraacetate application an automatic corpuscle adverse Cell-Dyn 3700 (Abbott Diagnostics, Abbott Park, IL, USA). In anniversary case, pseudothrombocytopenia was afar by analytical a borderline claret smear.
A accustomed platelet calculation was authentic as >150 × 109 per liter, balmy thrombocytopenia was authentic as a platelet calculation of 100 to 150 × 109 per liter, abstinent thrombocytopenia was authentic as a platelet calculation of 50 to 99 × 109 per liter, and astringent thrombocytopenia was authentic as a platelet calculation of <50 × 109 per liter. Affectionate circulating antiplatelet antibodies were detected by an aberrant immunofluorescence assay (IFT Euroimmun, Lübeck, Germany).
Patients with a platelet calculation <50 × 109 per liter or those with cogent signs of bleeding were accustomed assay at the time of antecedent diagnosis. Patients who had an adumbration for assay were usually accustomed prednisone (1 mg kg−1 day−1 p.o. for 3 to 4 weeks). Back a accustomed platelet calculation was achieved, steroids were cone-shaped aural several weeks. Intravenous immunoglobulin (IVIG) was acclimated at a dosage of 0.4 g kg−1 day−1 for 5 after canicule every 28 canicule for two cycles. Splenectomy was performed on patients adverse to steroids or those who became steroid-dependent to advance remission, as able-bodied as on those who bootless to acknowledge to IVIG therapy. Informed accordance was acquired in anniversary case.
Neonatal acquiescent allowed thrombocytopenia was authentic as thrombocytopenia with a platelet calculation <150 × 109 per liter in breed built-in to gravidas with ITP. Balmy thrombocytopenia was authentic as a platelet calculation of 100 to 150 × 109 per liter, abstinent thrombocytopenia as a platelet calculation of 50 to 99 × 109 per liter and astringent thrombocytopenia as a platelet calculation of <50 × 109 per liter.11
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A bond claret platelet calculation was performed at bearing for all newborns built-in to gravidas with ITP (the aforementioned address as in the gravidas), followed by a platelet calculation by venipuncture on canicule 1, 3 and 5. All breed were evaluated for mucosal bleeding (petechiae and ecchymoses), gastrointestinal or intracranial hemorrhage. For free intracranial hemorrhage, cranial ultrasonography was performed by the aforementioned pediatric radiologist in all the 14 thrombocytopenic breed back thrombocytopenia was detected. It was additionally again account in the thrombocytopenic breed through the thrombocytopenia period. The platelet counts of all breed were evaluated through the aboriginal 3 months of activity to actuate the continuance of postnatal thrombocytopenia. Abstracts including gestational age, gender, bearing weight, Apgar scores, approach of delivery, prematurity and the platelet calculation were recorded. Breed who had thrombocytopenia were compared with those who had accustomed platelet counts in acceding of affectionate and demographic features.
Neonates with a platelet calculation of <50 × 109 per liter and/or bleeding affection were accustomed IVIG with a dosage of 1 g kg−1 day−1 for 2 days. Steroid assay (prednisolone (2 mg kg−1 day−1 p.o.)) was accustomed to cases who bootless to acknowledge to IVIG therapy. Arranged red claret beef and platelet transfusions were administered if astringent drain or astringent anemia occurred due to bleeding.
SPSS, adaptation 16.0 (SPSS Inc., Chicago, IL, USA), was acclimated for abstracts analyses. Descriptive statistics were accustomed as the mean, median, accustomed deviation, minimum, best and percentage. A χ2-test was acclimated for assay of qualitative data. A non-parametric assay was acclimated for assay of two absolute quantitative variables.
A absolute of 29 breed built-in to gravidas with ITP afore or during abundance were included in this study. Table 1 summarizes the affectionate and neonatal characteristics of 29 cases with ITP afore or during pregnancy.
A absolute of 16 gravidas (55%) were diagnosed with ITP afore abundance and 13 gravidas (45%) were diagnosed with ITP during pregnancy. Thrombocytopenia existed in 21 gravidas (72%), admitting 8 gravidas had accustomed platelet counts at the time of delivery. Thrombocytopenia was classified as mild, abstinent and astringent in 2 (7%), 11 (38%) and 8 (27.5%) thrombocytopenic gravidas, respectively. Table 1 shows the affectionate characteristics.
A absolute of 17 gravidas (59%) were administered corticosteroids because of actual low platelet counts. High-dose immunoglobulin was administered to eight gravidas (27.5%). In total, nine gravidas (31%) were accustomed platelet transfusions to access their platelet counts. Splenectomies were performed in six gravidas (20%), and afore abundance in four of the six. One accommodating underwent a splenectomy in the additional trimester due to abortion of corticosteroid and IVIG therapies.
No bleeding occurred in 27 gravidas (93%) during abundance or delivery. Epistaxis and mucosal bleeding were alone empiric in two gravidas. Neither the vaginal avenue of commitment (72%) nor cesarean commitment (28%) led to boundless bleeding in gravidas. The beggarly platelet calculation at commitment was 133±125 × 109 per liter.
Table 1 shows the characteristics of the infants. The beggarly gestational age and bearing weight of the breed were 38±1.8 weeks (range, 34 to 40 weeks) and 3114±545 g (range, 2250 to 4450 g), respectively.
Table 2 shows the characteristics of breed and gravidas with thrombocytopenia. Thrombocytopenia was classified as mild, abstinent and astringent in three (10.3%), four (13.7%), and seven (24.1%) thrombocytopenic neonates, respectively.
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Severe drain occurred in bristles breed (17%). Generalized petechiae and ecchymoses with gastrointestinal bleeding were detected in two breed with astringent thrombocytopenia, admitting mucosal bleeding occurred in three breed with abstinent or astringent thrombocytopenia.
Platelet and arranged red corpuscle transfusions were administered to two breed with gastrointestinal bleeding. No intraventricular drain was bent in infants. Thrombocytopenia persisted for an boilerplate of 13±16 canicule (range, 4 to 60 days) in breed with thrombocytopenia. Thrombocytopenia lasted best than 30 canicule in four infants, three of whom had mothers with absolute antiplatelet antibodies and astringent thrombocytopenia compared with the added mothers. Table 3 shows the affectionate characteristics of breed with thrombocytopenia. Although three mothers had abundance access ITP with abrogating autoantibodies and accustomed platelet counts at delivery, they had ITP assay at the aftereffect according to the analytic ITP criteria. They were additionally accustomed adapted therapies for ITP at the follow-up.
Table 4 shows the allegory of characteristics of breed with and after thrombocytopenia. The age of the mothers accepting breed with thrombocytopenia was decidedly higher, best of the breed (71%) were males (P<0.05).
Infants with and after thrombocytopenia were additionally compared with account to affectionate characteristics. Overall, 64% of mothers in the thrombocytopenic baby accumulation and 46% of the mothers in the non-thrombocytopenic baby accumulation were diagnosed with ITP (Table 5, P>0.05). In total, 9 of 14 mothers (64%) with thrombocytopenic breed had a history of platelet transfusions during pregnancy, admitting 13% of mothers with non-thrombocytopenic breed appropriate an antepartum platelet admixture (Table 5, P<0.05). Splenectomy afore abundance was performed on four mothers in the thrombocytopenic baby accumulation and one mother in the non-thrombocytopenic baby group. In addition, splenectomy was performed on one mother in the additional trimester and this baby had thrombocytopenia at birth. There were no cogent differences in acceding of affectionate splenectomy amid the two groups of infants. The beggarly platelet counts of mothers at commitment were decidedly lower in the thrombocytopenic baby accumulation compared with those in the non-thrombocytopenic accumulation (Table 5, P<0.05).
A absolute of seven breed built-in to eight mothers with astringent thrombocytopenia during commitment (87.5%) had thrombocytopenia at bearing (Table 6, P<0.05). Table 6 shows the affiliation amid affectionate platelet counts and baby platelet counts at birth.
Neonatal thrombocytopenia accessory to transplacental access of affectionate platelet autoantibodies occurs in neonates built-in to gravidas with ITP or systemic lupus erythematosus. In this attendant study, 48% of neonates built-in to gravidas with ITP had thrombocytopenia at birth. Affectionate age and macho gender were apparent to be accident factors for the development of thrombocytopenia. Astringent affectionate thrombocytopenia, ceremony during abundance and platelet admixture during abundance were additionally associated with thrombocytopenia in infants.
Maternal ache severity and/or platelet calculation during abundance or the accident of astringent thrombocytopenia in a antecedent adolescent accept been appear as the best able indicators for admiration the likelihood of cogent fetal and NT complicating the accustomed pregnancy.12 A contempo attendant abstraction that included a aerial admeasurement of thrombocytopenic gravidas showed a college accident of afflicted neonates, 25% of whom had thrombocytopenia, 9% of whom had a platelet calculation of <50 × 109 per liter, 15% of whom accustomed assay for bleeding in affiliation with thrombocytopenia and two fetuses died (one with all-encompassing hemorrhage).13 In added studies, development of astringent thrombocytopenia (<50 × 109 per liter) and added astringent thrombocytopenia (<20 × 109 per liter) in breed built-in to mothers with ITP were appear to be 6 to 10% and 1 to 5%, respectively.9,10,14,15
In our study, 50% of breed had platelet counts <150 × 109 per liter. Rates of severe, abstinent and balmy thrombocytopenia were detected in 24, 14 and 10%, respectively. This award was agnate to a antecedent abstraction performed in our institute,16 and was constant with the address of Nisaratanaporn and Sukcharoen,17 who begin that 24% of breed built-in to gravidas with ITP accept astringent thrombocytopenia at birth. Borna et al.18 appear thrombocytopenia in 20 breed (67%) built-in to 30 gravidas with ITP and the arrangement was additionally in acceptable accordance with the abstracts appear in this study. On the added hand, adverse abstracts abide on the aftereffect of severity of affectionate thrombocytopenia on neonatal outcomes. In this study, 87.5% of breed built-in to gravidas with astringent thrombocytopenia were thrombocytopenic at birth, with 70% accepting abstinent or astringent thrombocytopenia. However, 50% of breed built-in to gravidas with accustomed platelet counts during commitment additionally had thrombocytopenia at birth. Therefore, we advance that the severity of thrombocytopenia during commitment may affect the neonatal platelet calculation and may be associated with the severity of NT. This antecedent was accurate by allegation appear by Valat et al.9 who detected astringent thrombocytopenia at bearing in 57% of breed who were built-in to gravidas with astringent thrombocytopenia. Similarly, astringent affectionate thrombocytopenia has been adapted to be awful predictive of thrombocytopenia in infants.19,20 In contrast, some studies accept appear no alternation amid affectionate and neonatal platelet counts.9,13,21,22 These differences may be due to the differences in cardinal of patients, affectionate and neonatal admittance criteria, affectionate and neonatal platelet appraisal time, abridgement of abstracts and the abeyant of misdiagnosis.
Another important award of this abstraction was that macho neonates built-in to gravidas with ITP had decidedly added astringent thrombocytopenia compared with changeable neonates. This award is additionally constant with the abstraction of Mortensen et al.20 who appear macho gender as a accident agency for perinatal thrombocytopenia. As bound abstracts are accessible on the aftereffect of a neonate's gender on the accident of perinatal thrombocytopenia, added investigations are warranted.
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We begin in this abstraction that affectionate age is an important accident agency for astringent thrombocytopenia in breed built-in to gravidas with ITP, as affectionate age was decidedly college in breed with thrombocytopenia. Our abstraction is the aboriginal to address abstracts on the aftereffect of affectionate age on NT. Therefore, this accountable should be accurate in approaching studies.
Antiplatelet antibodies were absolute in 55% of 29 gravidas. Boehlen et al.23 adapted that antiplatelet antibodies were not associated with the severity of NT and that affectionate antiplatelet antibodies could not be acclimated for admiration the accident of NT. However, in our study, we begin that thrombocytopenia persisted in breed built-in to mothers with absolute antiplatelet autoantibodies compared with those defective these antibodies.
Splenectomy was appear to be the distinct important accident agency for astringent NT in one study,21 which included 52 gravidas and 54 infants. A added contempo and beyond calibration abstraction from Japan including 284 gravidas with ITP and 286 neonates appear that breed built-in to splenectomized mothers had added astringent thrombocytopenia compared with those built-in to mothers who had not undergone a splenectomy.22 Although agnate abstracts accept been begin in this study, the aberration was not statistically significant, acceptable due to the baby sample size.
Corticosteroids with or after immunoglobulins were accustomed to gravidas if indicated. Although breed built-in to gravidas who accustomed neither steroids nor immunoglobulins had added astringent thrombocytopenia, the aberration was not statistically significant. This award is additionally constant with the literature.22 NT was decidedly college in breed built-in to gravidas who had accustomed a platelet beverage during pregnancy. Affectionate history of alternate ITP and bleeding during abundance were additionally associated with NT. As bound abstracts are accessible on the aftereffect of affectionate appearance on the severity of NT, we advance that all of these appearance may be associated with the severity of ITP in abundance and charge be advised in approaching studies.
The approach of commitment in gravidas with ITP is a arguable issue. It is about accustomed that neonates built-in to mothers with ITP may be delivered vaginally unless a cesarean commitment is adumbrated for obstetrical reasons.1,2,13,16,24 In our study, eight gravidas (28%) underwent cesarean commitment for obstetrical break and the actual gravidas (72%) were delivered vaginally. No complications occured either in the mother or the fetus due to the avenue of delivery. This award is additionally in acceptable acceding with antecedent studies.1,6,11,13,16,25
Although 14 breed presented with thrombocytopenia (3 mild, 4 abstinent and 7 severe) in this study, none of them had intracranial hemorrhages. This award is additionally in acceptable acceding with antecedent studies that appear a actual low accident of 0 to 2% for astringent thrombocytopenia intracranial bleeding.3,4,5,9,11,13,16,25
As a result, affectionate age and macho gender were the capital accident factors associated with added NT in breed built-in to mothers with ITP. Astringent affectionate disease, ceremony during abundance and platelet admixture during abundance were additionally associated with astringent NT. Breed built-in to mothers with astringent ITP ability accept risks for NT and the continuance of thrombocytopenia ability be best in breed built-in to mothers with absolute antiplatelet antibodies. As these accident factors were not mentioned in antecedent studies, approaching -to-be studies, including a college cardinal of gravidas and breed are acceptable for anxiously free the aftereffect of affectionate ITP on neonatal morbidity.
The authors acknowledge no battle of interest.
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