Maternal and neonatal outcomes of the pregnant women with idiopathic thrombocytopenic purpura

Objective

In this study, we aimed to report the maternal and neonatal outcomes of the pregnant women with idiopathic thrombocytopenic purpura (ITP) whose gestational follow-up and delivery were carried out in our clinic.

Methods

In our study, the files of newborns and pregnant women with ITP whose gestational follow-up and delivery were carried out in the Department of Obstetrics and Gynecology, Faculty of Medicine, İnönü University between January 1, 2010 and January 1, 2017 were reviewed prospectively and the cases matching with the inclusion criteria were included in the study.

Results

During the study period, it was found that 12 (17.6%) of 68 patients followed up for ITP diagnosis were established with the diagnosis during pregnancy while 56 (82.4%) of them were established with the ITP diagnosis before the pregnancy. The use of steroids was found at a higher level, which was statistically significant, in patients whose platelet count was below 50x109/l during delivery compared to those whose platelet count was above 50x109/l (p=0.003). The history of splenectomy during pregestational period was observed in 13 (29.5%) patients in the pregnant women with ITP whose platelet count was >50x109/l and in 1 (4.2%) patients in the pregnant women whose platelet count was <50x109/l (p=0.013). In terms of newborn intense care need and newborn treatment need, there was no significant difference between the patient group whose delivery type was cesarean section and the patient group whose delivery type was vaginal delivery (p=0.889 and p=0.598, respectively). While postpartum hemorrhage was observed in 6 (8.8%) patients, 17 (25%) patients received thrombocytapheresis treatment, 5 (7.3%) patients received intravenous immunoglobulin (IVIG) treatment, and 8 (13.2%) patients received thrombocytapheresis treatment together with IVIG. No significant correlation was found between maternal platelet count during delivery and newborn platelet count during delivery (p=0.625; r=0.06).

Conclusion

Maternal and neonatal prognosis of pregnant women with ITP is usually good. Maternal platelet count below 50¥109/l during pregnancy is associated with more medical treatment needs during pregnancy and more blood product needs during delivery, yet the delivery type has no impact on perinatal outcomes.

Keywords

Idiopathic thrombocytopenic purpura, newborn thrombocytopenia, pregnancy, thrombocytopenia

Introduction

Idiopathic thrombocytopenic purpura (ITP) is an autoimmune disease in which platelets cause early degradation in the reticuloendothelial system, particularly in the spleen, as a result of the binding of autoantibodies, which were produced against platelet membrane glycoproteins, to the platelet antigens.[1] While it is seen in approximately 2 out of 1000 pregnancies, it causes roughly %5 of all thrombocytopenia cases seen during pregnancy.[2] It tends to develop especially in reproductive young women. It is well known that pregnancy affects the progress of autoimmune disorders. Unlike gestational thrombocytopenia, platelet count in ITP is either at mid-level or severely low, and it requires follow-up and treatment due to its maternal hemorrhage risk. Even slightly, newborns have thrombocytopenia risk.[3] Usually, the most common complication seen in ITP cases is caused by the increase in the hemorrhage tendency. The purpose of the treatment in pregnant patient is to prevent hemorrhage.[4] Neonatal hemorrhage occurs mostly within 24–48 hours after birth and no correlation was found with the trauma during birth.[5,6] There is limited number of studies in the literature investigating the obstetric and neonatal outcomes of pregnant women with ITP, and reporting the hemorrhage risks of these pregnant women during delivery, their treatment needs during pregnancy and the correlation between maternal platelet count during delivery and neonatal platelet count. Therefore, we aimed in our study to evaluate perinatal and neonatal outcomes of pregnant women with idiopathic thrombocytopenic purpura whose gestational follow-up and delivery were carried out in our clinic, and to compare these outcomes according to the ITP diagnosis period, platelet count during delivery and delivery type.

Methods

The approval of the Committee of Scientific Investigation and Publication Ethics (Health Sciences, İnönü University) was obtained for the study, and the investigators complied with the Declaration of Helsinki by World Medical Association (including the amendments made in 2008) and the Good Clinical Practices (GCP) guidelines put into effect on December 29, 1995 as the annex to the Circular Note No. 51748 by the Turkish Ministry of Health (Ethics Committee’s Approval No. 2016/10-8). The files of newborns and pregnant women with idiopathic thrombocytopenic purpura who were followed up until delivery were carried out in the Department of Obstetrics and Gynecology, Faculty of Medicine, İnönü University between January 1, 2010 and January 1, 2017 were reviewed prospectively and the cases matching with the inclusion criteria were included in the study. All pregnant women included in the study due to idiopathic thrombocytopenic purpura were followed up together with Hematology Clinic of Internal Diseases Department. After the delivery, neonatal platelet count was checked as a routine practice, and Neonatology Clinic were consulted for all newborns.

Inclusion criteria

1. 18–39 years old
2. Presence of singleton live pregnancy
3. Getting the diagnosis of ITP before or during pregnancy
4. Other thrombocytopenia reasons being ruled out (infection, medication, hematological malignancies, disseminated intravascular coagulopathy, HELLP syndrome, gestational thrombocytopenia, and systemic lupus erythematosus)
5. Carrying out gestational follow-up and delivery in our clinic

Exclusion criteria

1. Multiple pregnancies
2. Major fetal anomalies (fatal anomalies or the anomalies requiring prenatal and postnatal surgical intervention), chromosomal anomalies and genetic syndromes
3. Intrauterine fetal death

The diagnosis of ITP was established in all patients by performing normal leukocyte and erythrocyte counts by Hematology Clinic of Internal Diseases Department (Faculty of Medicine, İnönü University) as well as identifying thrombocytopenia complying with standard criteria associated with normal bone marrow findings and ruling out all other reasons causing thrombocytopenia. Bone marrow examination was done in suspicious ITP cases who had anomalies in complete blood count and peripheral blood smear except thrombocytopenia (and microcytic anemia potentially attributed with chronic hemorrhage). Maternal platelet count was obtained by analyzing the venous blood samples collected into EDTA (ethylenediaminetetraacetic acid) tubes via automatic cell count device. Peripheral blood smear was performed in all patients to rule out the pseudothrombocytopenia.
The following parameters of all patients included in the study were recorded: age, gravida, parity, diagnosis period (before pregnancy, during pregnancy), platelet count before pregnancy, platelet count during pregnancy, platelet count during delivery, postpartum 24-h platelet count, treatment during pregnancy, splenectomy history, blood product required during delivery, anesthesia type if delivery type was cesarean section, maternal complication, week of gestation during delivery, delivery type, cesarean indication, birth weight, sex, neonatal platelet count, pH of cord blood, neonatal complication (hemorrhage, intraventricular bleeding), intense care need of newborn, and treatment parameters performed on newborns.
Statistical Package for the Social Sciences (SPSS) version 22.0 (SPSS Inc., Chicago, IL, USA) was used for statistical analysis. Basic data in study and control groups were defined as median and minimum - maximum values, and constant data were defined as mean and standard deviation. For statistical comparison of the cases, the normality distribution of the data obtained from the patients was analyzed by Shapiro-Wilk test. While t-test was used for the data complying with normal distribution, the noncompliant data were compared and analyzed by Mann-Whitney U test. The categorical variables were summarized by numbers and percentages, and Pearson’s exact chi-square and chi-square with correction for continuity were used for the comparisons. The correlation between maternal and neonatal platelet counts was analyzed by Spearman’s correlation test. In all analyses, 0.05 was considered as the significance level.

Results

While the mean age of the patients followed up with the diagnosis of ITP at pregnancy during the study period was 29.79±5.57, 21 (30.8%) of the patients were nulliparous. While 12 (17.6%) of 68 patients who were followed up with ITP diagnosis were established the diagnosis during the pregnancy, 56 (82.4%) of them were established ITP diagnosis during the pregnancy. Bone marrow analysis was performed in 1 (8.3%) patient established with ITP diagnosis during the pregnancy and in 19 (33.9%) patients established with ITP diagnosis before the pregnancy. Mean platelet count of the patients during pregnancy (first trimester) was 94.86±100.95x109/l while it was 100.35±96.39x109/l during delivery. Maternal and neonatal outcomes of the patients followed up with ITP diagnosis are shown in Table 1.
Fourteen (20.6%) of the patients had splenectomy history before the pregnancy, and it was found that 39 (57.4%) of the patients used steroid (oral prednisolone) during the pregnancy. The use of steroids was found at a higher level, which was statistically significant, in patients whose platelet count was below 50x109/l during delivery compared to those whose platelet count was above 50x109/l [20 (83.3%) and 19 (43.2%), respectively; p=0.003]. The history of splenectomy during pregestational period was observed in 13 (29.5%) patients in the pregnant women with ITP whose platelet count was >50x109/l and in 1 (4.2%) patients in the pregnant women whose platelet count was <50x109/l (p=0.013). The prenatal outcomes of pregnant women with platelet count below 50x109/l and those with platelet count above 50x109/l during delivery are shown in Table 2.
While 13.2% (9/68) of the patients had preterm labor, median week of delivery was 38 (mean: 38.32, range: 33 to 41). The delivery type was cesarean section in 38 (55.9%) patients and the most common cesarean indication was the elective cesarean section (42.1%) due to the cesarean history. Splenectomy history in the patients whose delivery type was cesarean section was lower than those who had normal delivery, and this difference was statistically significant [4 (10.5%) and 10 (33.3%), respectively; p=0.045]. In terms of neonatal platelet count, newborn intense care need and newborn treatment need, there was no significant difference between the patient group whose delivery type was cesarean section and the patient group whose delivery type was vaginal delivery (p=0.248, p=0.889, and p=0.598, respectively). Maternal and neonatal outcomes of the pregnant women with ITP diagnosis who had cesarean section and vaginal delivery are shown in Table 3.
While postpartum hemorrhage was observed in 6 (8.8%) patients, 17 (25%) patients received thrombocytapheresis treatment, 5 (7.3%) patients received intravenous immunoglobulin (IVIG) treatment, and 8 (13.2%) patients received thrombocytapheresis treatment together with IVIG. Thirty-three (48.6%) of the patients did not require any treatment during the delivery. Mean birth weight of newborns was 3065.57±408.44 g, and 21 (30.9%) newborns needed newborn intense care. The median platelet count of the newborns was 192.5 (mean: 189.04, range: 19 to 588) x109/l, it was found that 11 (16.2%) newborns received IVIG treatment and 4 (5.9%) newborns received phototherapy. Hemorrhagic complication or intraventricular bleeding was not observed in any newborn. No significant correlation was found between maternal platelet count during delivery and newborn platelet count during delivery (p=0.625; r=0.06). Neonatal platelet count in those with pregestational ITP diagnosis was higher than those diagnosed with ITP during pregnancy, and this difference was statistically significant [200.50 (range: 19.0 to 588.0) and 117.0 (range: 29.0 to 244.0), respectively; p=0.047]. Maternal and neonatal outcomes of the pregnant women who were established with ITP diagnosis before and during pregnancy are shown in Table 4.

Discussion

ITP management during pregnancy is complicated due to the wide distribution in maternal and fetal platelet counts.[7] These pregnant women should be followed up closely during pregnancy by a medical team consisting of hematologist, obstetrician, anesthetist and neonatologist. Although different pharmacological agents are used in the treatment, there is no standard treatment approach used for pregnant women with ITP.[8,9] In this study, we showed that more than 80% of the pregnant women with ITP whose platelet count was <50x109/l used steroid (oral prednisolone) during pregnancy, and the medical treatment need was significantly high in these pregnant women compared to the pregnant women with platelet count >50x109/l. Moreover, compared to the pregnant women with platelet count <50x109/l, the history of splenectomy before pregnancy was significantly higher in the pregnant women with ITP whose platelet count was >50x109/l. While short-term corticosteroid (prednisolone 1 mg/kg) or IVIG treatment is recommended as a major treatment option in cases with maternal ITP whose maternal platelet count is <20x109/l, the effects of these treatment options on maternal and neonatal outcomes were found similar.[10] Although there are different practices, it is recommended to conduct IVIG treatment as the primary treatment in cases having adverse effects associated with the use of corticosteroids or during the first trimester of pregnancy where potential teratogenic effects of corticosteroids are concerned.[11] It was reported that treatment is not required until delivery in cases whose platelet count is >20x109/l.[12] On the other hand, there are studies which recommend keeping platelet count at 50x109/l at least during second and third trimesters due to the cesarean section risk which may be necessary without planning.[13] The mechanism of action of the corticosteroids was associated with the decrease of autoantibody production as well as the phagocytosis inhibition of platelets that autoantibodies are attached.[14] In their cohort study, Care et al. evaluated the treatment strategies for the pregnant women with severe primary autoimmune thrombocytopenia, and reported that more than 50% of the patients received treatment during pregnancy in order to reach targeted platelet count during delivery although they were asymptomatic.[15] For patients with chronic ITP who have severe or persistent hemorrhage and are not responding to treatment, splenectomy is the secondary treatment option. In line with our study, Rezk et al. compared maternal and fetal outcomes of the pregnant women with ITP who underwent medical treatment and pregestational splenectomy, and reported that the patients who underwent medical treatment had severe thrombocytopenia, hemorrhage episodes and postpartum hemorrhage compared to the patients with the history of splenectomy.[16] It seems that performing splenectomy before pregnancy to the patients with chronic ITP who are planning pregnancy and have poor response to medical treatment may have beneficial effects on the obstetric outcomes.
Antiplatelet antibodies may pass through the placenta and induce thrombocytopenia in fetus. Although the development mechanism of fetal thrombocytopenia cannot be understand well, it depends on many factors such as the maturation of fetal reticuloendothelial system, and it cannot be predicted by using available clinical or laboratory parameters.[11] In this study, we could not identify any correlation between maternal platelet count and neonatal platelet count during delivery, but we showed that newborns did not have severe hemorrhagic complication or intraventricular bleeding. In parallel with our study, a retrospective study analyzing neonatal outcomes of the pregnant women with ITP did not show a statistically significant correlation between maternal platelet count and neonatal platelet count.[17] While there was no significant correlation between the severity of neonatal thrombocytopenia and maternal thrombocytopenia, the neonatal thrombocytopenia was not correlated with maternal platelet-related immunoglobulin, splenectomy history and many other parameters, either.[18] Distinctively, we found neonatal platelet count significantly low in the patient group who were established with ITP diagnosis during pregnancy. Although maternal characteristics becoming insufficient to predict neonatal thrombocytopenia brought up fetal scalp sampling at labor or invasive tests such as cordocentesis in order to determine fetal platelet count, the general opinion is to allow labor without determining fetal platelet count since severe thrombocytopenia or hemorrhage complication is rarely seen in newborns.[19] However, independent from the delivery type, it is recommended to send cord platelet count from all newborns during delivery and to monitor platelet count daily as it may decrease within 4–5 days after delivery. Treatment for immune thrombocytopenia is recommended for newborns developing thrombocytopenia during this period.[20]
ITP is not an indication for cesarean section. Delivery type should be determined completely by considering obstetric indications. Although cesarean section was recommended for the pregnant women with ITP in the past believing that it might decrease fetal intracranial hemorrhage risk during labor, the recent studies show that this belief is incorrect.[21] In this study, we showed that the delivery type had no effect on neonatal outcomes in the pregnant women with ITP, but we found that the need for blood products was significantly higher in the patients who had cesarean section than the pregnant women who delivered vaginally. In their retrospective study where they exhibited their 11 years of experience on pregnant women with ITP, Webert et al. reported vaginal delivery rate 82.4%, platelet suspension need at birth 5%, and erythrocyte suspension need 1.7%. On the other hand, they showed that hemorrhagic complications are quite rare and the complications observed are not correlated with the severity of thrombocytopenia.[22] The authors recommended that the decision to use operative labor techniques such as forceps or vacuum extraction, which increases fetal hemorrhage risk during delivery, should be made by the obstetrician considering the obstetric indications.[23]

Conclusion

In conclusion, maternal and neonatal prognosis of pregnant women with ITP is usually good. Maternal platelet count below 50x109/l during pregnancy is associated with more medical treatment needs during pregnancy and more blood product needs during delivery, yet the delivery type has no impact on perinatal outcomes. These pregnant women should be managed with a multidisciplinary approach by hematology, neonatology and anesthesia departments.

References

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	File/Dsecription
	Table 1. Maternal and neonatal outcomes of the patients followed up with ITP diagnosis.
	Table 2. The maternal and neonatal outcomes of pregnant women with platelet count below 50x109/l and those with platelet count above 50x109/l during delivery.
	Table 3. Maternal and neonatal outcomes of the pregnant women with ITP diagnosis who had cesarean section and vaginal delivery.
	Table 4. Maternal and neonatal outcomes of the pregnant women who were established with ITP diagnosis before and during pregnancy.