European Journal of Cardiovascular Medicine

33%. The global prevalence of anaemia in pregnancy is 38.2%³¹. As per National Family Health Survey 5 (2019 to 2020), the prevalence of anaemia in pregnancy in India is 52.2%. Hemoglobinopathies come under the broader classification of hemolytic anemia. Hemolytic anemia covers the burden of about 5% of all the causes of anemia. They are a group of genetic disorder. They are the most common hereditary disorders worldwide and in India. Hemoglobinopathies occur due to the defect in the synthesis of hemoglobin, the Alpha and the Beta chain. This group of anemia is caused by the inability of bone marrow to compensate for the degree of hemolysis of red cells. An estimation of about 7% of the world population carries an abnormal hemoglobin gene. The major groups are the Thalassemias and the Sickle cell syndromes.70 % of the affected births are with sickle cell syndromes, the rest are due to thalassemias. Thalassemias are common in Asian women with prevalence of 1 in 300 to 500. In India, about 3-4% of people are carriers of beta thalassemia. Sickle cell occurs in about 1 in 100 Indians. As per WHO at least 5.2% of the world population with 7% prevalence in pregnant women carries a variant of hemoglobin disorder³⁰. HbE is the most common hemoglobinopathy in north eastern states of India, with carrier frequency of around 50% in a hospital based study²⁷. The average allele frequency of HbE hemoglobinopathy is 10.9 % in North East India²⁹. According to ICMR, HbE disease prevalence in Assam is 23%.  In a study conducted by Monalisha et al²⁸ 2023, in Assam, the prevalence rate of hemoglobinopathies was 62.43% with Beta thalassemia minor (16.99%), beta thalassemia major (2.32%), HbE heterozygous (22%), HbE homozygous (6.62%), sickle cell trait (3.04%), sickle cell disease (1.69%). Patients are usually asymptomatic. They are diagnosed co-incidentally. Incidence of abortions, postpartum anaemia and urinary tract infection and intrahepatic cholestasis are increased.²¹

It is a prospective observational study, conducted for a period of 6 months from 20/3/23 to 20/9/23. Firstly, clearance from the Ethical Committee was taken. Routine antenatal investigations were sent. Patients diagnosed with anaemia were further worked up for anaemia with anaemia profile (CBC, PBS, Iron Profile, Stool for occult blood, Urine RE) and Hb typing. Sample size was calculated using openepi software version 2.3.1. with 95% confidence level and 10% absolute precision. The calculated sample size was 87. Hence, the first 87 patients with hemoglobinopathies and the babies of these patients were followed up for maternal and fetal outcomes. All the data were analysed using Microsoft excel, SPSS V 21.P value is calculated using Chi Square. P value of less than 0.05 will be considered significant.

Inclusion Criteria: 

Pregnancy with hemoglobinopathies with viable gestational period whatever the result, coming to Jorhat Medical College and hospital and the babies delivered of that mother.

Exclusion Criteria:

• Pregnancy with hemoglobinopathies who did not undergo full term follow up with the pregnancy in Jorhat Medical college and hospital.
• Who had not give consent for the study.
• Multiple gestation pregnancy was not included in the study.

The study was conducted for a total of 6 months from 20/3/23 to 20/9/23. Total number of antenatal patients admitted was 4825. Out of the total 4825 patients, 2074 (42.9%) patients were diagnosed with anemia.

Prevalence of anaemia:

Maternal age:

 83% of the patients belonged to the age group of 18-30 years. Pregnancy above 35 years was seen in 7 (8%) of the study group. One patient was under 18 years old (age 17 years).

Parity of the patients: 

55 patients (63.2 %) were Primigravida and 32 (36.8%) of them were multigravidae. 

Degree of anemia:

Out of the total admitted patients, 2074 (42.9%) patients were diagnosed with anemia. Loss to follow up among the anemic patients was 356.

In the study 68 (78.16 %) of the patients had moderate anemia that is in the range of Hb from 7 – 9 g/dl. Only 13 patients (14.94 %) of them had severe anemia. None of the patient had hemoglobin of less than 4. One of the patients presented with hemoglobin of 4.5g/dl.  Most of the patients with severe anaemia was in the HbS hemoglobinopathy group (46.15% with n = 13) as shown in table 7.

Proportion of hemoglobinopathies among the anemic patients:

Abnormal Hb typing reported was 234 (13.6%) of the total (n =1718).  Out of the total 234 patients, first 87 patients diagnosed with hemoglobinopathies were followed up.

Types of hemoglobinopathies:

 HbE disease comprising of 39 patients (44.8 %) was the most common among the hemoglobinopathies. It was followed by HbE trait 30 [34.4%], Sickle cell trait 9[10.3%], sickle cell disease 7 [8%] and Beta Thalassemia Minor 2 [9%]. This is shown in the table 6 and figure 3.

Distribution of degree of anemia among different types of hemoglobinopathies:

Out of 7 patients admitted with sickle cell disease, 3 of them had severe anemia. Most of the patients in HbE disease group (32 out of 39 patients) were with moderate anemia.

Presenting Symptoms:

83.9 % of the patients were asymptomatic. Though patients had mild and moderate anemia, they did not have any symptoms. Patients with severe anemia (14.9%) complained of generalized weakness. One patient (1.149%) was admitted with complains of pain over the joint. She was diagnosed with sickle cell disease.

Associated maternal antepartum complications:

Out of the total 87 patients, 46 (52.8%) patients had associated antepartum maternal complications as shown in table 9. Percentage is calculated with n = 87 i.e out of total patients.

Preterm labour was seen in 20 (22.9%) patients out of the total 87 patients. 8 patients had PROM (9.19%). 6 patients (6.89%) were diagnosed with FGR. Hyperbilirubinemia was seen in 4 patients (4.59%).

Significant P value (<0.05) was seen in associated maternal complications among the PPROM and hyperbilirubinemia cases as shown in table 10.

Mode of delivery:

In the study 46 [52.8%] of the patients had LSCS as the mode of delivery. 41 patients (47.1%) had undergone vaginal delivery. This is shown in table 11 and figure 7.

Indication for LSCS:

The indications for the LSCS was purely due to obstetrical indications that are shown below in table no 12. Most common cause was due to fetal distress in first stage of labour [7 out of 46 patients (15.2%)]. The second most common indication was post LSCS (10.8%) with scar tenderness and precious pregnancy (10.8%).                

Post natal Period:

Patients were followed up during the postpartum period. Those who underwent spontaneous vaginal delivery were followed up for 72 hrs and those who had LSCS were followed up for 96 hrs. At day 2 pueperium, Haemoglobin report was repeated for all the patients. 66 patients had moderate anaemia. 17 of the patients had severe anaemia in the postpartum period. 

Patients were followed up for other complications like episiotomy wound gaping, incision site wound infection. There was no wound gaping noted in the study group. Subinvolution of uterus was present among 2 patients which were managed conservatively.

One of the patients, who had abruption placenta, developed Acute Kidney Injury (AKI).

Maternal Death:

One of the patients had primary postpartum haemorrhage with an episode of sickling. Patient succumbed to death on the same day.

Neonatal outcome:

Gestational age at the time of delivery:

Table 15 shows distributions of babies according to the gestational age. 67 patients (77%) of the babies were delivered at term. 20 babies (23%) were born preterm.

Fetal growth:

Six out of 87 babies i.e 7% were with growth restrictions. 81 (93%) had normal growth.

APGAR SCORE:

Three babies (3.4 %) of the babies were born with severe depression (0 to 3). All three were admitted to NICU.  6 (7 %) were born with moderate depression (4 to 7). They were admitted in NICU.

Birth weight:                  

Table 18 and figure 13 shows the distribution of the birth weight of the baby. Sixty one babies were born with normal birth weight.  26 (29.8%) out of the total babies were delivered with low birth weight. There were no babies born with very low birth weight.

NICU admissions:

20 (22.9%) of the babies were admitted to NICU. 9 (45 %) of the babies out of n = 20 were due to preterm and 15 % were due to birth asphyxia and 15% due to LBW. Most of the babies admitted in NICU were in HbE disease group. 2 cases of neonatal death were seen. One was due to neonatal sepsis and one due to birth asphyxia. Both of them belong to sickle cell disease. There was no significant P value associated with fetal outcome.

In our study, out of the total 87 patients, 83% of them belong to the age group of 18 to 30 years indicating that most of the patients are in the early reproductive age group. This is comparable to the study conducted by Monesha et al²⁵ in 2023 where 80.5% of the pregnant women belong to the age group of 19 to 29 years.

In our study 55 (63.2%) of the patients were primigravidae. 32 (36.8%) of the patients were multigravidae. Anahita Chauhan ¹and Madhva Prasad conducted a similar study in 2018. In their study, 43.3% were primigravida and 56.7 % were multigravidae.In the Monesha et al study²⁵, 39.5% were primigravida and 60.5% patients were multigravidae.

In our study the prevalence of undiagnosed hemoglobinopathy was 99%.  Only one multigravida case (1%) was aware of her hemoglobinopathy status which was diagnosed during her first pregnancy. In a study conducted by Sumedha et al³² in 2021, the prevalence of undiagnosed hemoglobinopathy carriers was up to 6.3%. In their study the prevalence of undiagnosed beta thalassemia carriers was 3.3% and undiagnosed sickle cell carriers was 1.7% and of undiagnosed HbE carriers was 1.4%. This shows that the awareness among the pregnant women on the existence of hemoglobinopathies in our study is extremely poor.

The range of haemoglobin level in our study is between 4.5g/dl-9.4 g/dl. The mean haemoglobin of HbE homozygous is 8.3g/dl in our study .The lowest haemoglobin recorded was 4.5 g/dl, which belonged to a patient with sickle cell trait. In Anahita et al¹ 2018, the haemoglobin ranged from 5.7 g/dl to 13g/dl, with an average of 9.2g/dl. Similarly in the study conducted by Monesha et al²⁵ in 2023, the average haemoglobin was 8.9 g/dl. In the study conducted by Sirichotikakul et al¹³ in 2016, the average haemoglobin was 10.03g/dl. The mean hemoglobin level of our study is the lowest among all the other studies.

In our study, 68 (78.16%) of the total 87 patients had moderate anemia with Hb between 7-<9 g/dl. It is followed by severe anemia in 13 patients (14.94%) with Hb of less than 7g/dl and mild anemia (Hb between 9-10.9g/dl) in 6 patients (6.89%). In Monesha et al²⁵ in 2023,109 (54.5%) had moderate anemia, 17(8.5%) had severe anemia and 74 (37%) had mild anemia. There is higher percentage of patients with moderate and severe anaemia in our study. This might be due to the varied distribution of anaemia according to the different regions. In the Upper Assam where our study was conducted, there is higher number of patients coming from tea gardens. They are genetically prone to hemoglobinopathies and also to poor nutrition and health care facilities.

 HbE disease was the most common hemoglobinopathy observed in our study making up to 44.8% of the study patients. This is similar to the result of the study done by Monesha et al² in 2023 with where HbE disease comprised of 39% of the patients with hemoglobinopathies out of the total 200 patients. In the study by Anahita et al¹in 2018, Beta thalassemia trait was the most common hemoglobinopathies with 81.66% of the study population. The difference in the distribution in the type of hemoglobinopathies is due to the difference in the demographical difference in our study and Monesha et al ²⁵study which is based in Assam compared to the Anahita et al¹ study n 2018 which is based in Mumbai.

In our study 13 patients was diagnosed with severe anaemia. Out of the 13 patients, 6 patients had HbS hemoglobinopathy (Sickle cell trait and sickle cell disease), 4 had HbE disease, 2 had HbE trait and 1 had Beta thalassemia minor. In the Monesha et al study²⁵, among the 17 patients with severe anaemia group, 8 patients had HbE with Beta thalassemia, 4 patients had HbE disease, 2 had Beta thalassemia homozygous, 2 had HbE trait and 1 had Beta thalassemia trait. There is similar distribution of patients in both the studies with maximum of the patients with severe anaemia among the HbS hemoglobinopathy.

In our study 46 (52.8%) of the patients had associated antepartum complications. Similarly in the study by Monesha et al, 133 patients (66.5%) had maternal complications and 33.3% had no associated maternal complications. The slightly lower number of maternal complications in our study is mostly due to smaller number of sample size.

PROM and PPROM were seen in 8 (9.1%) in our study. Out of 8 patients with PROM in our study 4 patients belong to HbE trait. There is statistically significant association between PROM and HbE trait with P value of less than 0.05in our study. In Monesha et al²⁵ study 2023, PROM and PPROM comprised of 48 (24%) out of 200 patients. This indicates that the etiological factors are less prevalent in Upper Assam area then in the lower Assam area. 4 (4.59%) cases in our study had maternal hyperbilirubinemia. All the cases associated with hyperbilirubinemia were seen in sickle cell disease and one in sickle cell trait. There is statistically significant association between maternal hyperbilirubinemia and hemoglobinopathies with P value of less than 0.05. In Monesha et al²⁵ study 2023, out of 18 patients with coexisting HbE disease and beta thalassemia hemoglobinopathy, 6 (3%) had maternal hyperbilirubinemia.

6.89 % of the total babies were FGR in our study comparable to the findings in Anahita et al¹ study where the percentage of FGR delivery was 6.66%. Most of the babies with FGR, 62.1% of the babies delivered belong to the mothers with Hb E disease. This is due to higher number of patients falling among Hb E disease group in our study. In the study conducted by Hanprasertpong et al¹⁵in 2013, FGR was seen in 1.8% of hemoglobinopathy associated pregnancy. Similarly in other studies like Kasparek et al ²¹ in 2021, 5.1% of the patients had FGR pregnancy.

In our study, 23% babies were born preterm. Monesha et al²⁵ study in 2023 had similar results with 23.5% of patients undergoing preterm delivery. 1.66 % babies were born preterm in Anahita et al¹ study in 2018. This indicates higher number of preterm delivery in our study compared to other group.

LSCS was the most common mode of termination in our study (53%) which is comparable to the study by Anahita et al¹ where 50% of the patients underwent LSCS. 36.9% of the patients underwent LSCS in the study by Monesha et al²⁵.In our study, the most common indication of LSCS was due to MSL with fetal distress in first stage of labour (19.56% with n = 46).This is similar to the study conducted by Anahita et al¹ [33.3%] and Monesha et al²⁵ [66.1%]. In all the studies indicate that fetal distress in first stage of labour is very common among pregnant women with hemoglobinopathies.

Postpartum Haemorrhage was seen in one patient (1.14%) in our study. It was a case of sickle cell disease with an episode of sickling.  Charoenboon et al⁵ study in 2016 reported PPH in 3.5% of Beta Thalassemia trait and the study by Luewan  S et al¹⁹ in 2009 reported 5.6% of PPH in their study patients. Sirichotiyakul et al¹³ in 2016 reported PPH in 2.5% HbE homozygous and 3.2% in HbE trait. This indicates that PPH may be a concern for pregnancy with hemoglobinopathies.

In our study, 6 had severe anaemia. The cause of severe anaemia was due to Sickle cell disease. All of them were given blood transfusion. In our study it was seen that patients with beta thalassemia and sickle cell had higher requirement of blood transfusion, followed by beta thalassemia trait and HbE trait.

In the study conducted by Monesha et al²⁵, there was statistical significant association between blood transfusion and types of hemoglobinopathies with P value <0.001.

In our study there was one (1.14%) mortality due to PPH with an episode of sickling in a patient with sickle cell disease. There were 2 (3.3%) maternal mortality in Anahita et al¹ study. Both of the patients belonged to sickle cell disease.

Regarding babies, Low birth weight baby comprised of 26 (29.8%) of the total babies delivered. FGR comprised of 6 (23.0%), Preterm 15 (57.6%) of the total babies delivered with low birth weight. In Monesha et al²⁵ study, 105 (54.6%) of baby were born with low birth weight. 12.5% of the total patients in Kasparek et al²¹ study 2021, had low birth weight babies. In the study conducted by Hanprasertpong et al¹⁵, LBW was seen in 6% of the pregnant women. The higher number of low birth weight babies in our study compared to the other referred studies might be due to poor health seeking behaviour, poor nutrition and socioeconomic condition of the people 20 (22.9%) babies were admitted to NICU. In our study 15% of the indication for NICU admission was due to LBW and 10% was due to neonatal hyperbilirubinemia. In Monesha et al study²¹ in 2023, 44.7% babies were admitted in NICU and the most common cause of NICU admission was due to neonatal hyperbilirubinemia (62.4%). NICU admissions were seen in 1.6% in Hanprasertpong et al^l5study in 2013and 10.4% in Kasparek et al²¹ study in 2021. Higher incidence of NICU was seen more in my study due to increased preterm and FGR babies. There was no still birth in my study. Similarly there was no still birth in the study conducted by Monesha et al²⁵ 2023. One still birth was seen in Anahita et al¹ study2018. In our study, it has been seen that hemoglobinopathy has a direct role in the birth weight of the baby which increases the neonatal morbidity.

In our study there were two neonatal deaths due to neonatal sepsis and severe birth asphyxia. Both belonged to sickle cell disease.

• Most of the patients are in the early reproductive age group in our study.
• Our study shows that the awareness among the pregnant women on the existence of hemoglobinopathies is extremely poor.
• HbE disease was the most common hemoglobinopathy observed in our study.
• There is statistically significant association between maternal hyperbilirubinemia and hemoglobinopathies.
• Most of the patients visit small centers where HPLC is not available, hence the late diagnosis and treatment.
• There is high number of FGR, low birth weight Due to poor socio-economic condition and poor nutritional status, harsher working atmosphere and late health seeking behaviour of the patients in our region.
• Since the incidence of hemoglobinopathy is very high in our region, haemoglobin less than 8 should undergo Hb typing.

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