A STUDY ON EFFECTS OF THROMBOCYTOPENIA IN PREGNANCY AND FETOMATERNALOUTCOME

thrombocytopenic cases were followed up throughout the antenatal period, during and till 8 weeks after delivery, to record outcome and any complications like preterm labor, abruption, preeclampsia and any other morbidity. Platelet count was repeated once in the postpartum period at 8 weeks.Tests were done, if clinically indicated were antiphospholipid antibodies, antinuclear antibodies, Direct Coombs test, further investigated for LFT, KFT, peripheral smear, coagulation profile, USG abdomen. Women with fever were tested for Blood Peripheral smear for Malaria, Dengue IgM. Coagulation tests (PT, APTT, FDP and fibrinogen) was done in a patient with signs or symptoms of DIC. Platelet count of all antenatal women was done at the time of enrolment. The collection of sample was done after taking informed consent of the participant, blood specimens were withdrawn from the antecubital vein using a dry sterile disposable syringe and needle. 2ml of blood was dispensed into EDTA anticoagulant tube. The specimens were labeled with subject’s name, age, sex and C.R. number, and sent to the laboratory for platelet count estimation. Platelet count assessment was performed through automated blood count analyzer with routine antenatal haematological evaluation of the patient.Neonatal APGAR and birth weight were recorded. Neonates too were screened for thrombocytopenia and any other complications.Duration of pregnancy at the time of delivery, indication of induction and method (if required) and mode of delivery including indication for instrumental delivery or caesarean section were also recorded. Progress of labor was monitored by partograph. Methods:-Descriptive statistics will be analyzed with SPSS version 20.0 software. Continuous variables are presented as mean ± SD. Categorical variables are expressed as frequencies and percentages. The Pearson's chi-square test or Fisher’s exact test is used to determining the relationship between two categorical variables. P<0.05 is considered statistically significant.

Thrombocytopenia, defined as a platelet count of <150 x 10 9 /L, is a common hematologic abnormality during pregnancy, with an incidence of 6.6% [1] . When thrombocytopenia is detected during pregnancy, it may be a sign of complex clinical disorders that are unique to pregnancy, such as preeclampsia and HELLP (haemolysis, elevated liver enzymes, and low platelet count) syndrome. It may also be related to a pre-existing underlying disease, such as bone marrow disease, hypersplenism, or congenital platelet disorder. Furthermore, autoimmune diseases, including systemic lupus erythematosus, antiphospholipid syndrome, thrombotic thrombocytopenic purpura, haemolytic uremic syndrome, and Immune thrombocytopenia (ITP) may relapse. Nevertheless, the most common cause of pregnancy-related thrombocytopenia is gestational thrombocytopenia, which is diagnosed through exclusion when the postpartum platelet count returns to normal and also associated with uneventful pregnancy outcome.Platelets are involved in primary haemostasis by plugging sites of endothelial damage and also act as a surface for secondary haemostasis [7] .Thrombocytopenia affects 6-10% of all pregnant women and, other than anaemia, is the most common hematological disorder in pregnancy [19] . Patients with a platelet count greater than 50 x 10 9 /L /L often are asymptomatic. Patients with a count from 30 to 50x 10 9 /L rarely present with purpura, although they may have excessive bleeding with trauma. However, counts from 10 to 30 x 10 9 /L may cause bleeding with minimal trauma, and counts less than 10 x 109/L increase the risk of spontaneous bleeding, petechiae and bruising [20] .Pregnancy is associated with numerous metabolic, immunologic and other homeostatic changes that require careful consideration while attempting to define the cause of thrombocytopenia in a particular individual. There are many potential causes of pregnancy-associated thrombocytopenia; some of these are unique to pregnancy, whereas others may also occur in the non-pregnant setting [19] .Also, because therapeutic interventions used to treat thrombocytopenic disorders in pregnant womenand have toxicities unique to pregnancy, management approaches considered.
Although a number of these pregnancy-related conditions may cause morbidity or even death if not treated promptly, most instances of thrombocytopenia are benign. Severe neonatal thrombocytopenia is infrequent; however, the incidence varies according to the causes of maternal thrombocytopenia [1][2][3] . Thus, we will conduct a prospective study to evaluate maternal complications and neonatal outcomes for antenatal women who have thrombocytopenia in the Department of Obstetrics &Gynaecology, DeenDayal Upadhyay (DDU) Hospital, Hari Nagar, New Delhi.

Material and methods:-
All antenatal patients attending ANC OPD in Department of Obstetrics &Gynaecology, DeenDayal Upadhyay Hospital, New Delhi. It was Prospective Descriptive study, Study period from July 2017 to May 2018, Study duration was 11 months and screening sample size 471A recent study conducted by Chauhan Vikrant et al in 2016 on Maternal and Fetal outcome among pregnant women presenting with thrombocytopenia. Taking this as our reference actual number of antenatal cases (incidence) who had thrombocytopenia, were (p)=8.4% (6), in pat ients attending OPD and with 2.5% margin of error, the minimum required sample size at 5% level of significance is 471 antenatal patients. Minimum 471 patients have to be screened for thrombocytopenia. In Inclusion criteria all pregnant women visiting antenatal OPD in the department of OBG at DDU Hospital and willing to participate in the study.After obtaining a written and informed consent all women attending antenatal OPD were enrolled in the study at first visit, irrespective of gestational age. All underwent detailed history, general, systemic and obstetric examination. All were subjected to a blood test for Hb, TLC, DLC, TPC, RBS, TSH, urine albumin and sugar, HBsAg, HIV, HCV, VDRL at their first visit irrespective of period of gestation.Over 11 months 774 women were screened, out of which 62 patients with platelet count less than 1.5 X 109 /L were included in the study, 44 antenatal women could be followed till 8 weeks postpartum. These 44 patients were included in final analysis.Women with normal platelet count before 28 weeks had a repeat platelet count at 28 weeks, 32weeks, labor. All the 1284 thrombocytopenic cases were followed up throughout the antenatal period, during and till 8 weeks after delivery, to record outcome and any complications like preterm labor, abruption, preeclampsia and any other morbidity. Platelet count was repeated once in the postpartum period at 8 weeks.Tests were done, if clinically indicated were antiphospholipid antibodies, antinuclear antibodies, Direct Coombs test, further investigated for LFT, KFT, peripheral smear, coagulation profile, USG abdomen. Women with fever were tested for Blood Peripheral smear for Malaria, Dengue IgM. Coagulation tests (PT, APTT, FDP and fibrinogen) was done in a patient with signs or symptoms of DIC. Platelet count of all antenatal women was done at the time of enrolment. The collection of sample was done after taking informed consent of the participant, blood specimens were withdrawn from the antecubital vein using a dry sterile disposable syringe and needle. 2ml of blood was dispensed into EDTA anticoagulant tube. The specimens were labeled with subject's name, age, sex and C.R. number, and sent to the laboratory for platelet count estimation. Platelet count assessment was performed through automated blood count analyzer with routine antenatal haematological evaluation of the patient.Neonatal APGAR and birth weight were recorded. Neonates too were screened for thrombocytopenia and any other complications.Duration of pregnancy at the time of delivery, indication of induction and method (if required) and mode of delivery including indication for instrumental delivery or caesarean section were also recorded. Progress of labor was monitored by partograph.

Statistical Methods:-
Descriptive statistics will be analyzed with SPSS version 20.0 software. Continuous variables are presented as mean ± SD. Categorical variables are expressed as frequencies and percentages. The Pearson's chi-square test or Fisher's exact test is used to determining the relationship between two categorical variables. P<0.05 is considered statistically significant.

Results:-
Total 774 antenatal women who visited our antennal OPD and were subjected to platelet count during the study period, of which 62 patients with platelet count less than 1.5 X 10 9 /L were included in the study, 44 antenatal women could be followed till 8 weeks postpartum. These 44 patients were included in final analysis. In present study the incidence of maternal thrombocytopenia was 8.01% (62/774*100). most common age group age range from 21 to 25 year (50%). After applying one way ANOVA test, it was found that there was no statistically significant difference between various age groups of ANC patients and total platelet count (F(2,41) =2.966, p=0.063) [  [TABLE 9]. Pearson correlation was run to determine the relationship between 1 st visit TPC and APGAR score of the neonate. There was a strong positive correlation between 1 st visit TPC and APGAR score, which was statistically significant (r=0.558, n=44, p=0.001).A Pearson correlation was run to determine the relationship between TPC at labour and APGAR score of the neonate. There was a strong positive correlation between TPC at labour and APGAR score, which was statistically significant (r= 0.612, n=44, p=0.001).A Pearson correlation was run to determine the relationship between 28weeks TPC and APGAR score of the neonate. There was a strong positive correlation between 8 weeks postpartum TPC and APGAR score, which was statistically significant (r= 0.531, n=44, p=0.001) [

Discussion:-
In a prospective study of over 11 months all pregnant patients with thrombocytopenia with platelet count less than or equal to one lakh fifty thousand per mL were included .Their detailed history, examination findings, investigations were noted. Course of pregnancy was followed up and the maternal, obstetric and fetal outcome was noted.

Incidence:
In present study the incidence of maternal thrombocytopenia was 8.01% which is comparable to study by Dwivedi et al [7]  Thrombocytopenia in Pregnancy showed that thrombocytopenia affects 6% to 10% of all pregnant women and other than anemia is the most common hematologic disorder in pregnancy.

Distribution according to age of patient and gestational age:
Maximum incidence of cases being in 20 to 27 years age group with mean age 27.57 ± 5.64 years. According to study conducted by Singh Nisha, DhakadAmita, Singh Uma, K. Tripathi, SankhwarPushplata (Prevalence and Characterization of Thrombocytopenia in Pregnancy in Indian Women) there was no significant difference in the distribution of cases and controls according to age (P = 0.923), religion (P = 0.947) and parity (P = 0.068). According to Genovese study the mean age was 30 ± 2 years and average gestational age diagnosis was 28+3weeks. In this study 68% patients enrolled in late second trimester since most antenatal women in our population seek advice in late pregnancy or when a complication arises.

Garvidity Of Patient:
In this study 43.18% cases were primigravidas, 34% cases were gravida 2, 23% cases were gravida 3 to 5. Huparikar Anita et al stated that of 76 patients enrolled in their study 34 cases are primigravida, 28 cases 2nd gravida and 14 cases are 3rd gravid. However, this is incidental finding and has no effect on platelet count.

Severity Of Thrombocytopenia:
Out of 44 cases of thrombocytopenia, 17(38.6%) patients had mild, 22 (50%) patients had moderate and 5 (11.4%) patients had severe thrombocytopenia. In contrast Vikrant Chauhan et al stated63% of the women had mild thrombocytopenia while 35.4% and 1.5% of women were moderate and severe thrombocytopenic respectively. According to study conducted by Singh Nisha, DhakadAmita, Singh Uma ,K. Tripathi, SankhwarPushplata (Prevalence and Characterization of Thrombocytopenia in Pregnancy in Indian Women) 2012, prevalence of thrombocytopenia was 8.8%. There were 74.7% cases of mild thrombocytopenia, 17.9% of moderate thrombocytopenia and 7.4% with severe thrombocytopenia.

Etiology Of Thrombocytopenia:
Gestational thrombocytopenia was the most common etiological factor with 70.4% cases, followed by 9.09% for hypertensive disorders including HELLP syndrome, 9.09%Dengue, 6.8% Hemolytic anemia, followed by 2.27% for Malaria, 2.3% ITP. Gestational thrombocytopenia occurs in approximately 8% of all pregnancies and accounts for more than 70% of cases with thrombocytopenia in pregnancy (Usha Pereppu et al).Immune thrombocytopenia occurs in 1 in 1000-10,000 pregnancies, accounting for 3% of all thrombocytopenic gravidas. 32 56 . The HELLP syndrome is often considered to be a variant of preeclampsia. It is serious complication specific to pregnancy, affects 0.5-0.9% of all pregnancies and develops in 10% of patients with preeclampsia 43 .The major findings of our study is that thrombocytopenia points to a higher degree of severity of the primary disease, which is known to increase perinatal complications, both maternal and neonatal.Platelet counts 1286 normalize within 4-10 weeks following delivery. Burrows reported that all women with Gestational Thrombocytopenia had normal or normalizing platelet counts by the seventh postpartum day.

Mode of delivery:
The route of delivery of the 44 cases was 31(70.45%) delivered vaginally and LSCS in 13(29.54%) cases. 6 patients had pre term delivery (13.6%). Mode of delivery is not influenced by platelet count. LSCS was done for obstetric and medical conditions like previous LSCS (22.8%), failed induction (4.6%) , placenta previa (2.3%). According to study conducted in 2011 in kolkata, 91 cases delivered during the study, 61.54% had normal vaginal delivery, 36.26% had CS and 2.2% had instrumental delivery. All the cesarean sections were performed for obstetric/medical causes and none for thrombocytopenia.

Maternal Complications:
Of 44 patients, 7(15.9%) patients landed in PPH, 1(2.3%) had DIC whereas 36 (81.8%) had uncomplicated delivery. Patient with ITP landed in DIC , had platelet count as low as 7000 per ul D-dimer 0.3mg/L, FDP 16mg/L. Gum bleeding, petechiae, hematuria occurred ultimately developed sepsis. Poor perinatal outcome recorded with ICU admission in this patient. Patient had multiple blood transfusion. No mortality reported though. So according to this study, thrombocytopenia is not directly related to maternal outcome, there are also other factors which influence the maternal outcome like anemia, preeclampsia, sepsis etc. thrombocytopenia is an additional factor and not independent factor. According to study conducted by DhakadAmita (2011) incidence of PPH was 9.89% among cases. PPH was seen in 30% of medical, 15% of obstetric and only 4.92% of gestational thrombocytopenia. Incidence was significantly higher in medical thrombocytopenia (P = 0.008).Blood transfusion was done in 18 patients. Of these 4 patients required only PCV transfusion, 4 only platelets, and 7 both PCV and platelets. 3 patients needed all i.e PCV, platelet and FFP. These patients had either severe anemia, DIC or HELLP syndrome.
Neonatal Outcome: 1 neonate born to mother with ITP had platelet count less than 1 lakh , 2 had platelet count between 1lakh -1 lakh fifty thousand per ul, rest others have platelet more than 1.5lakh per ul.. Neonatal thrombocytopenia of 90,000 per ul on day-1 returned to normal on day eight. None of the babies had any bleeding complications.According to study conducted by Nisha singh in 2011 Out of the 91 newborns, platelet count assessment could be done in 75 (81.4%). All had normal platelet counts at birth except the one born to mother with ITP.This study found that mothers who gave birth to neonates with <2.5 kg weight had lower TPC as compared to mothers who gave birth to neonates with >2.5 kg weight TPC which was statistically not significant, t(42) = -1.504, p = 0.140. Vikrant Chauhan et al found mean baby weight in their study was 2.84±0.32 kg which was not related to maternal platelet count.However, APGAR Score of neonate with maternal platelet count moderate to severe was lower, which is indirectly because of underlying etiology and associated comorbid conditions rather than thrombocytopenia per se.
Neonatal Complications: 9(20.5%) babies were admitted in NICU of which 3 (6.8%) were meconium stained and 4(9%) developed Respiratory Distress Syndrome, 6 neonates (13.6%) were preterm. The association of preterm deliveries with severe thrombocytopenia was not statistically significant. Neonatal complications are not directly related to maternal platelet count. The fetal complications like birth asphyxia (6.8%), low birth weight(11.3%) and neonatal thrombocytopenia were also higher in the patients with Preeclampsia, HELLP syndrome , DIC, Dengue and Malaria. 3(33.3%) NICU admission were in neonates born to mother with Dengue 1baby had RDS with MSL, 1 had RDS while one was IUGR. 1(11.1%) admission of neonate reported in mother with ITP in which platelet count of neonate was lowest in this study 90,000ul, baby was meconium stained and developed RDS. 1(11.1) baby admitted was of mother with Eclampsia, 1(11.1) admission was in mother with malaria, 2(22.2%) in mother with hemolytic anemia in all these babies were LBW and IUGR. Only one admission was reported in patients with Gestational thrombocytopenia. The results were in concordance with the study of Burrows et al [10] and Dwivedi et al [5].This study found that neonates admitted in NICU had statistically significantly lower TPC (92,000 ± 37,718 per ul) as compared to neonates not admitted to NICU (1,02,771 ± 30,100 per ul), t (42) = -3.667, p = 0.001. However, none of the neonate had any bleeding diathesis nor any other complication due to low platelet count. Platelet count returned to normal within a week.

Conclusion:-
Thrombocytopenia affects 6% to 10% of all pregnant women and other than anemia is the most commo n hematologic disorder in pregnancy.Most common cause of moderate to severe thrombocytopenia in pregnancy is 1287 mainly Gestational Thrombocytopenia, while ITP, preeclampsia, and HELLP syndrome, Dengue, Malaria are less common. Patients with Gestational Thrombocytopenia have favorable maternal and perinatal outcomes. Mode of delivery does not depend upon platelet count, but is guided by obstetric and medical indications. Platelet count of neonates has no relation with maternal platelet count. However, patients with moderate to severe thrombocytopenia alongwith other comorbid condition associated needed NICU admission due to RDS, asphyxia, LBW, preterm delivery. Proper diagnosis and risk evaluation in the antenatal period are essential. It help for developing specific plans for any antenatal interventions and for management of delivery and the postpartum periods, and also very helpful for neonate. In developing countries like India, diseases like Malaria and Dengue which are uncommonin other parts of the world, add to the morbidity of the condition and prove to be challenging and pose a management dilemma. Careful observation is required for these pregnancies in high-risk patient for early detection and treatment of possible complications, in order to try to reduce maternal and neonatal morbidities. Further future studies among these high-risk populations with moderate to severe thrombocytopenia should investigate, make early diagnosis and to make the efficacy of possible surveillance programs. Most common gravida are G1. After applying one way ANOVA test, it was found that there was no statistically significant difference between the parity of ANC patients and total platelet count (F(3,40) =1.892, p=0.146).   Maximum incidence is of gestational thrombocytopenia 31(70.5%), pre eclampsia/eclampsia with HELLP together account for 4(9%), malaria 1(2.3%), dengue 4(9%), hemolytic anemias 3(6.9%),ITP 1(2.3%).     (2-tailed) .000 N 44 44 Correlation is significant at the 0.01 level (2-tailed).
Pearson correlation was run to determine the relationship between 1 st visit TPC and APGAR score of the neonate. There was a strong positive correlation between 1 st visit TPC and APGAR score, which was statistically significant (r=0.558, n=44, p=0.001).  (2-tailed) .000 N 44 44 Correlation is significant at the 0.01 level (2-tailed).

Correlations
A Pearson correlation was run to determine the relationship between TPC at labour and APGAR score of the neonate. There was a strong positive correlation between TPC at labour and APGAR score, which was statistically significant (r= 0.612, n=44, p=0.001).  (2-tailed) .000 N 44 44 1290 Correlation is significant at the 0.01 level (2-tailed).

Descriptive Statistics
A Pearson correlation was run to determine the relationship between 28weeks TPC and APGAR score of the neonate. There was a strong positive correlation between 8 weeks postpartum TPC and APGAR score, which was statistically significant (r= 0.531, n=44, p=0.001) Only 9(20.5%) neonates required NICU admission, mostly belong to mothers with moderate to severe thrombocytopenia alongwithother comorbidity.