European Journal of Cardiovascular Medicine

Thalassemia is one of the most common hereditary hemoglobinopathies, affecting millions worldwide, particularly in South Asia, the Mediterranean, and Southeast Asia (1). It is caused by genetic mutations that result in defective haemoglobin synthesis, leading to anaemia of varying severity. While thalassemia major requires lifelong transfusions, thalassemia minor (carrier state) is often asymptomatic and diagnosed incidentally (2). However, recent research suggests that even thalassemia carriers may experience adverse pregnancy outcomes, including maternal anaemia, intrauterine growth restriction (IUGR), and low birth weight (LBW) (3).

Pregnancy itself induces physiological haemodilution and increased iron demands, which can exacerbate anaemia in thalassemia carriers, leading to potential obstetric and neonatal complications (4). Although thalassemia minor is not traditionally considered a high-risk pregnancy condition, studies indicate a higher prevalence of anaemia, increased caesarean delivery rates, and neonatal growth restriction among affected women (5). This raises concerns about the need for targeted antenatal care strategies in thalassemia carriers, including early haematological screening, iron metabolism assessment, and fetal growth monitoring (6).

Despite the known genetic basis of thalassemia, limited data exist regarding its impact on pregnancy outcomes in Indian and other South Asian populations. Most available studies focus on thalassemia major rather than the more prevalent carrier state. This study aims to fill this gap by evaluating the maternal and neonatal outcomes in pregnant women with thalassemia minor compared to non-carrier controls at a tertiary care hospital (7).

Aim and Objectives

Aim

To evaluate the impact of thalassemia minor on maternal and neonatal outcomes in pregnant women, assessing associated complications and potential risks, and determining the need for early intervention strategies to optimize pregnancy care.

Objectives

1. To assess the prevalence and severity of maternal complications in thalassemia carriers, including anaemia, gestational diabetes mellitus (GDM), hypertensive disorders, and postpartum haemorrhage (PPH).
2. To evaluate neonatal outcomes, particularly low birth weight (LBW), intrauterine growth restriction (IUGR), preterm birth, NICU admissions, and perinatal mortality in infants born to thalassemia carrier mothers.
3. To determine whether thalassemia minor significantly increases pregnancy-related risks and assess whether early intervention, prenatal monitoring, and multidisciplinary management can improve maternal and fetal outcomes.

Given the rising awareness of hemoglobinopathies in reproductive health, this study provides clinical insights into the impact of thalassemia carrier status on pregnancy. The findings will help inform prenatal screening programs and high-risk obstetric management protocols for affected women.

Study Design and Setting

This was a prospective observational study conducted at the Department of Obstetrics and Gynaecology, Nil Ratan Sircar Medical College and Hospital, a tertiary care centre in India. The study aimed to evaluate the maternal and neonatal outcomes in pregnant women with thalassemia minor and compare them with a control group of non-carrier pregnant women.

Study Population

The study included pregnant women diagnosed with the thalassemia carrier state (thalassemia minor) based on haematological and genetic screening. A control group of pregnant women without thalassemia minor was included for comparison.

Inclusion Criteria:

• Pregnant women aged 18–40 years attending antenatal care.
• Singleton pregnancies.
• Gestational age of ≥12 weeks at the time of recruitment.
• Diagnosed thalassemia minor carriers based on haemoglobin electrophoresis or high-performance liquid chromatography (HPLC).

Exclusion Criteria:

• Pregnant women with thalassemia major or intermedia.
• Women with other hemoglobinopathies (e.g., sickle cell anaemia).
• Pregnancies with known fetal congenital anomalies.
• Women with chronic medical disorders (e.g., chronic hypertension, pregestational diabetes, renal disease).
• Multiple pregnancies.

Sample Size Calculation

Based on previous studies reporting a 30–40% prevalence of maternal anaemia and fetal growth restriction in thalassemia minor pregnancies, a minimum sample size of 100 cases (thalassemia carriers) and 100 controls (non-carriers) was determined to achieve 80% power and a 5% significance level.

Data Collection and Variables Assessed

A structured data collection proforma was used to obtain demographic, haematological, obstetric, and neonatal data.

Maternal Outcomes Assessed:

• Haematological parameters: Haemoglobin levels, Mean Corpuscular Volume (MCV), Mean Corpuscular Haemoglobin (MCH).
• Obstetric complications:
• Anaemia (Hb <11 g/dL).
• Gestational hypertension and preeclampsia.
• Gestational diabetes mellitus (GDM).
• Hypothyroidism.
• Mode of delivery (vaginal, elective caesarean, emergency caesarean).
• Postpartum haemorrhage (PPH).

Neonatal Outcomes Assessed:

• Birth weight categories:
• Low birth weight (LBW) (<2500 g).
• Normal birth weight (2500–3500 g).
• Macrosomia (>3500 g).
• Intrauterine growth restriction (IUGR).
• Preterm births (<37 weeks gestation).
• NICU admissions.
• Stillbirths and perinatal mortality.
• Neonatal haemoglobin levels at birth.

Haematological and Biochemical Testing

• Complete blood count (CBC) with peripheral smear analysis.
• Iron studies including serum ferritin and transferrin saturation.
• Hb electrophoresis or HPLC for thalassemia screening.
• Oral Glucose Tolerance Test (OGTT) for gestational diabetes.
• Thyroid function tests (TSH, free T4) for hypothyroidism.

Statistical Analysis

• Continuous variables were expressed as mean ± standard deviation (SD) and analyzed using Student’s t-test.Categorical variables were presented as percentages and analyzed using the Chi-square test or Fisher’s exact test, where applicable.Odds ratios (OR) and relative risks (RR) with 95% confidence intervals (CI) were calculated for significant maternal and neonatal outcomes.Multivariate logistic regression was performed to adjust for confounders such as maternal age, BMI, and pre-existing anaemia.A p-value <0.05 was considered statistically significant.

The study was approved by the Institutional Ethics Committee (IEC) and Informed consent was obtained from all participants.

1. Baseline Demographic and Haematological Characteristics

The baseline characteristics of the study population are summarized in Table 1. There was no significant difference in mean maternal age between the thalassemia carrier group and the non-carrier group (29.4 ± 4.8 vs. 28.9 ± 4.5 years, p = 0.324). Similarly, the mean BMI was comparable between the two groups (24.5 ± 3.2 vs. 24.7 ± 3.5, p = 0.541).

The median gravidity and parity were similar in both groups, with no significant difference in reproductive history (p = 0.800 and p = 0.750, respectively)

However, significant differences were observed in haematological parameters. The mean haemoglobin level was significantly lower in the thalassemia carrier group compared to non-carriers (10.1 ± 1.2 g/dL vs. 11.8 ± 1.4 g/dL, p < 0.001). Additionally, mean corpuscular volume (MCV) and mean corpuscular haemoglobin (MCH) were significantly lower in thalassemia carriers (MCV: 69.8 ± 5.1 fL vs. 85.4 ± 4.3 fL, p < 0.001; MCH: 23.6 ± 3.2 pg vs. 28.2 ± 2.8 pg, p < 0.001), reflecting the characteristic microcytic hypochromic anaemia associated with thalassemia minor.

These findings confirm that thalassemia carriers exhibit significant haematological differences compared to non-carriers, particularly in terms of lower haemoglobin levels, MCV, and MCH, despite similar demographic and obstetric characteristics.

Table 1: Baseline Characteristics of Participants

2. Maternal Outcomes

This study evaluated the frequency and severity of maternal complications in pregnant women with thalassemia carrier status, comparing them with non-carrier controls. The primary maternal complications analyzed include anaemia, hypertensive disorders, gestational diabetes, postpartum haemorrhage (PPH), and mode of delivery. The results provide insights into how thalassemia minor influences pregnancy risks and the need for targeted obstetric interventions.

Table 2 summarizes the maternal complications observed in the study population.

Anaemia and Haematological Outcomes

Anaemia was significantly more prevalent among thalassemia carrier mothers (78% vs. 18%, p < 0.001), with severe anaemia (Hb <8 g/dL) occurring in 25% of carriers compared to only 5% in non-carriers (p < 0.001). The odds of developing severe anaemia were 4.52 times higher in thalassemia carriers (OR: 4.52, 95% CI: 2.1 - 9.8), confirming the increased haematological vulnerability in these pregnancies.

Hypertensive Disorders and Endocrine Complications

There was no significant difference in the incidence of gestational hypertension (12% vs. 10%, p = 0.543) or preeclampsia (5% vs. 3%, p = 0.312) between the two groups. However, hypothyroidism was significantly more frequent in thalassemia carriers (15% vs. 10%, p = 0.045), suggesting a possible association between thalassemia minor and thyroid dysfunction. The risk of hypothyroidism was 1.67 times higher in thalassemia carriers (OR: 1.67, 95% CI: 1.01 - 2.78).

Gestational diabetes mellitus (GDM) was slightly more common in thalassemia carriers (8% vs. 6%), but this difference was not statistically significant (p = 0.250, OR: 1.37, 95% CI: 0.7 - 2.5).

Postpartum Haemorrhage (PPH) and Mode of Delivery

Postpartum haemorrhage (PPH) was significantly more frequent in the thalassemia carrier group (20.4% vs. 10%, p < 0.001). The odds of experiencing PPH were 2.44 times higher in thalassemia carriers (OR: 2.44, 95% CI: 1.8 - 3.3), emphasizing the need for active third-stage labour management in these pregnancies.

Regarding mode of delivery, caesarean section (C-section) rates were significantly higher in the thalassemia carrier group (42% vs. 30%, p = 0.040). The risk of undergoing a C-section was 1.75 times higher in thalassemia carriers (OR: 1.75, 95% CI: 1.02 - 2.9). When stratified, elective C-sections were more frequent in carriers (20% vs. 12%, p = 0.080), while emergency C-sections were also slightly higher (22% vs. 18%, p = 0.050).

Vaginal delivery remained more common in non-carriers (70% vs. 58%, p = 0.040), with thalassemia carriers being less likely to have a vaginal birth (OR: 0.57, 95% CI: 0.42 - 0.89).

Table2: Maternal complications observed in the study population

Figure1: Bar chart comparing caesarean section rates between thalassemia carriers and non-carriers

Figure 1: Comparison of Caesarean Section Rates Between Thalassemia Carriers and Non-Carriers.
The bar chart illustrates the higher caesarean section rate in thalassemia carrier pregnancies (42%) compared to non-carriers (30%). The increased rate in the carrier group may be attributed to higher rates of anaemia, fetal distress, and obstetric complications.

3.Neonatal Outcomes

This study evaluated the impact of thalassemia minor on fetal growth and neonatal complications, focusing on birth weight patterns, intrauterine growth restriction (IUGR), preterm birth, NICU admissions, and neonatal health indicators. The findings reveal a significantly higher risk of fetal growth restriction and low birth weight in thalassemia carrier pregnancies, emphasizing the need for enhanced fetal surveillance and prenatal care.Table 3 summarizes the neonatal outcomes observed in the study population.

Birth Weight and Fetal Growth Patterns

The mean birth weight was significantly lower in neonates born to thalassemia carrier mothers compared to non-carriers (2718 ± 696 g vs. 2850 ± 650 g, p = 0.045). A significantly higher proportion of neonates in the thalassemia carrier group had low birth weight (LBW) (<2500 g) compared to non-carriers (38% vs. 22%, p = 0.020, OR: 2.14, 95% CI: 1.3 - 3.5), indicating an increased risk of fetal growth restriction in thalassemia pregnancies.

Conversely, the proportion of neonates with birth weight >3500 g was significantly lower in thalassemia carrier pregnancies (8% vs. 18%, p = 0.050, OR: 0.42, 95% CI: 0.2 - 0.9), suggesting that thalassemia minor pregnancies are associated with a greater likelihood of fetal growth restriction rather than macrosomia. The distribution of birth weights is visually represented in Figure 2, demonstrating the higher frequency of LBW in the carrier group.

Intrauterine Growth Restriction (IUGR) and Preterm Births

A significantly higher incidence of intrauterine growth restriction (IUGR) was observed in the thalassemia carrier group (24% vs. 10%, p = 0.010, OR: 2.88, 95% CI: 1.4 - 5.9). This finding supports the association between maternal anemia in thalassemia minor and impaired fetal growth.

Preterm birth rates were higher in thalassemia carrier pregnancies (18% vs. 12%), but the difference was not statistically significant (p = 0.100, OR: 1.62, 95% CI: 0.8 - 3.1).

NICU Admissions and Neonatal Health Indicators

NICU admissions were more frequent in neonates born to thalassemia carrier mothers (15% vs. 8%), but the difference did not reach statistical significance (p = 0.080, OR: 1.99, 95% CI: 0.9 - 3.8). Similarly, the proportion of neonates with an APGAR score <7 at 5 minutes was slightly higher in the carrier group (10% vs. 6%), but this difference was not statistically significant (p = 0.120, OR: 1.72, 95% CI: 0.6 - 3.2).

These findings indicate that while thalassemia minor is associated with a higher risk of fetal growth restriction and LBW, it does not significantly increase the risk of severe neonatal distress or NICU admissions.

Table 3: Neonatal Outcomes

Figure 2: Birth Weight Distribution Among Thalassemia Carriers and Non-Carriers

The above bar chart illustrates the distribution of birth weight categories, complementing Table 3. Low birth weight (LBW) was significantly more frequent in the thalassemia carrier group (38% vs. 22%, p = 0.020), while the proportion of neonates with birth weight >3500 g was lower in carriers (8% vs. 18%, p = 0.050). These findings underscore the increased risk of fetal growth restriction and impaired fetal nutrition in pregnancies complicated by thalassemia minor.

4.Stratified Neonatal Outcomes by Birth Weight

Neonatal outcomes were further analyzed based on birth weight categories, as summarized in Table 4. This stratification highlights the differential impact of thalassemia carrier status on fetal growth and neonatal complications.

NICU Admissions and Neonatal Morbidity

NICU admissions were significantly higher in low birth weight (LBW) neonates born to thalassemia carrier mothers compared to LBW neonates in the non-carrier group (52% vs. 45%, p = 0.040). Among neonates with normal birth weight, NICU admission rates remained higher in the carrier group (8% vs. 5%), though this difference was not statistically significant.

APGAR scores <7 at 5 minutes were more frequent in LBW neonates of thalassemia carriers (18% vs. 12%), but the difference was not statistically significant (p = 0.060). In neonates with normal birth weight, APGAR scores <7 were observed in 4% of carrier group neonates vs. 2% in non-carriers.

Intrauterine Growth Restriction (IUGR) and Birth Weight-Related Findings

The incidence of IUGR was significantly higher in LBW neonates from thalassemia carrier pregnancies (42% vs. 25%, p = 0.012). Among normal birth weight neonates, IUGR was also more frequent in thalassemia carriers (12% vs. 7%), indicating that fetal growth restriction may occur even in neonates with birth weight ≥2500g, though to a lesser extent.

These findings reinforce the association between thalassemia minor and restricted fetal growth, particularly in cases where maternal anaemia and microcytosis were more severe.

Summary of Stratified Neonatal Risks in Thalassemia Carrier Pregnancies

• Significantly higher NICU admission rates among LBW neonates (p = 0.040).
• Higher incidence of IUGR in both LBW and normal birth weight neonates, with significant risk in the LBW subgroup (p = 0.012).
• No statistically significant difference in APGAR scores, though lower scores were observed in LBW neonates of thalassemia carriers.

Figure3:Comparison of Birth Weight Distribution Between Thalassemia Carriers and Non-Carriers

Summary of Stratified Neonatal Risks in Thalassemia Carrier Pregnancies

• Significantly higher NICU admission rates among LBW neonates (p = 0.040).
• Higher incidence of IUGR in both LBW and normal birth weight neonates, with significant risk in the LBW subgroup (p = 0.012).
• No statistically significant difference in APGAR scores, though lower scores were observed in LBW neonates of thalassemia carriers.

5. Logistic Regression and Risk Analysis

Logistic regression analysis was performed to assess the risk of significant maternal and neonatal complications associated with thalassemia carrier status (Table 5).

• Caesarean section risk was significantly higher in carriers (OR = 1.75, p = 0.040), though after adjustment for confounders, the association weakened (Adjusted OR = 1.58).
• Anaemia and severe anaemia showed the strongest association, with ORs of 3.24 and 4.52, respectively (p < 0.001), remaining highly significant after adjustment.
• IUGR risk was nearly three times higher in thalassemia carrier pregnancies (OR = 2.88, p = 0.010), maintaining significance post-adjustment (Adjusted OR = 2.62).
• NICU admissions showed a trend towards increased risk (OR = 1.99, p = 0.080) but were not statistically significant.
• GDM was not significantly different between groups (p = 0.250).

These findings confirm that thalassemia carrier pregnancies have a significantly higher risk of anaemia, severe anaemia, caesarean section, and fetal growth restriction, necessitating closer antenatal monitoring.

Table 5: Logistic Regression and Risk Analysis

* Adjusted ORs were calculated after controlling for maternal BMI, gestational age, and anaemia severity.

Pregnancy Outcomes in Women with Thalassemia Carrier State

This study evaluated the maternal and neonatal outcomes in pregnant women with thalassemia minor compared to non-carrier controls, highlighting the increased risk of anaemia, caesarean section, and fetal growth restriction. Our findings contribute to the growing body of evidence on the impact of thalassemia carrier status on pregnancy, aligning with previous studies while offering region-specific insights.

Maternal Outcomes and Pregnancy Complications

The most striking finding in our study was the significantly higher prevalence of anaemia in thalassemia carriers (78% vs. 18%, p < 0.001). This is consistent with Ismael et al., who reported anaemia as the most prevalent complication in β-thalassemia minor pregnancies【8】. Furthermore, severe anaemia (Hb <8 g/dL) was four times more likely in carriers (OR = 4.52, p < 0.001), underscoring the need for early iron status monitoring and supplementation strategies.

While gestational diabetes (GDM) rates were comparable between the groups (8% vs. 6%, p = 0.25), our study found a slightly higher prevalence of hypothyroidism in carriers (15% vs. 10%, p = 0.045). This aligns with Lao et al., who highlighted the potential link between thalassemia trait and thyroid dysfunction【9】. Postpartum haemorrhage (PPH) was significantly more common in carriers (20.4% vs. 10%, p < 0.001), necessitating careful intrapartum and postpartum haemostatic monitoring.

Mode of delivery analysis revealed a significantly higher caesarean section rate in thalassemia carriers (42% vs. 30%, p = 0.040), with a notable increase in elective C-sections. This finding is supported by Soni-Trinidad et al., who documented an increased likelihood of operative delivery in pregnancies complicated by beta-thalassemia minor【10】.

Neonatal Outcomes and Fetal Growth Patterns

A significant proportion of thalassemia carrier pregnancies resulted in fetal growth restriction (IUGR, 24% vs. 10%, p = 0.01), with a nearly threefold increased risk (OR = 2.88, p = 0.010). Similar trends were reported by Charoenboon et al., where thalassemia minor was associated with an increased risk of IUGR and low birth weight (LBW) neonates【11】.

Low birth weight was significantly more common in carrier pregnancies (38% vs. 22%, p = 0.020), while the proportion of macrosomic (>3500 g) neonates was lower (8% vs. 18%, p = 0.050). This suggests a strong link between maternal anaemia and fetal growth restriction, reinforcing findings by Al-Riyami et al., who reported a higher incidence of LBW among thalassemia carrier pregnancies【12】.

Preterm birth rates were higher in thalassemia carriers (18% vs. 12%), though not statistically significant (p = 0.100). NICU admissions were more frequent among carrier neonates (15% vs. 8%), but this difference did not reach statistical significance (p = 0.080), aligning with Wu et al., who observed a similar trend in NICU admissions for neonates born to thalassemia carrier mothers【13】.

Logistic Regression Analysis and Risk Adjustment

Multivariate regression analysis adjusted for maternal BMI, gestational age, and anaemia severity confirmed that thalassemia minor was an independent risk factor for anaemia, severe anaemia, and IUGR.

• Anaemia remained the most significantly associated complication (Adjusted OR = 3.00, p < 0.001).
• IUGR risk remained high after adjustment (Adjusted OR = 2.62, p = 0.010).
• Caesarean section risk was slightly attenuated after adjustment (Adjusted OR = 1.58, p = 0.040), suggesting that fetal growth concerns and obstetrician preference contribute to the higher C-section rate rather than thalassemia alone.

Clinical Implications and Recommendations

Our findings reinforce the necessity for closer haematological monitoring and multidisciplinary management for thalassemia carrier pregnancies.

• Early iron metabolism assessment and targeted nutritional interventions could help mitigate the high risk of anaemia.
• Frequent fetal growth monitoring using ultrasound biometry is essential in carrier pregnancies to detect IUGR early.
• High-risk obstetric care strategies, including individualized delivery planning, are crucial to reduce unnecessary cesarean sections while ensuring optimal neonatal outcomes.

Additionally, genetic counselling remains vital for at-risk couples, particularly in regions with high thalassemia carrier prevalence, as suggested by Virot et al.【14】

This study confirms that pregnancies in thalassemia carriers are associated with significantly higher rates of anaemia, IUGR, and caesarean deliveries. However, with proper prenatal monitoring and multidisciplinary management, adverse maternal and neonatal outcomes can be minimized. Further prospective, multicentric studies are needed to refine screening, management, and intervention strategies for thalassemia minor in pregnancy.

1. Piel FB, Weatherall DJ. The prevalence and management of hemoglobin disorders. Nat Rev Dis Primers.2017;3:17015.
2. Galanello R, Origa R. Beta-thalassemia. Orphanet J Rare Dis.2010;5:11.
3. Chaudhuri S, Chatterjee S. Maternal and perinatal outcomes in pregnancies complicated by beta-thalassemia minor. Indian J Hematol Blood Transfus. 2015;31(3):378-83.
4. Rodríguez-Morales AJ, Sánchez-Duque JA. Anemia in pregnancy and adverse perinatal outcomes: A systematic review. BMC Pregnancy Childbirth.2021;21:403.
5. Lukens JN. The thalassemias and related disorders: Quantitative disorders of hemoglobin synthesis. Wintrobe’s Clinical Hematology.2009;12:1325-65.
6. Origa R, Sollaino MC, Giagu N, et al. Pregnancy in β-thalassemia trait: Evidence for an increased risk of gestational diabetes. 2010;117(4):471-4.
7. Pavord S, Daru J, Prasannan N, et al. UK guidelines on the management of iron deficiency in pregnancy. Br J Haematol. 2019;188(6):819-30.
8. Thompson AA, Kim HY, Singer ST, Vichinsky E, Eile J, Yamashita R, et al. Pregnancy outcomes in women with thalassemia in North America and the United Kingdom. Am J Hematol. 2013;88(9):771-3.
9. Voskaridou E, Balassopoulou A, Boutou E, Komninaka V, Christoulas D, Dimopoulou M, et al. Pregnancy in beta‐thalassemia intermedia: 20‐year experience of a Greek thalassemia center. Eur J Haematol. 2014;93(6):492-9.
10. Soni-Trinidad C, Vázquez-García RE, Soni-Gallardo J, Rodríguez-Infante LI, Velasco-Cárdenas DF, Sosa-González CK. Pregnancy with beta-thalassemia minor and development of low-frequency irregular alloantibody. GinecolObstet Mex. 2022;90(01):90-5.
11. Charoenboon C, Jatavan P, Traisrisilp K, Tongsong T. Pregnancy outcomes among women with beta-thalassemia trait. Arch Gynecol Obstet.2016;293:771-4.
12. Al-Riyami N, Suleiman A, Al-Lawati T, Al-Khabori M, Daar S. Pregnancy outcomes in women with beta-thalassemia in Oman. Oman Med J. 2014;29(3):178-83.
13. Wu Y, Han L, Chen X, He J, Fan X, Dai J, et al. Effects of thalassemia on pregnancy outcomes of women with gestational diabetes mellitus. J Obstet Gynaecol Res. 2022;48(5):1132-40.
14. Virot E, Thuret I, Jardel S, Herbrecht R, Lachenal F, Lionnet F, et al. Pregnancy outcome in women with transfused beta-thalassemia in France. Ann Hematol. 2022:1-8.
15. Lao TT. Obstetric care for women with thalassemia. Best Pract Res Clin Obstet Gynaecol.2017;39:89-100.
16. Ismael EM, Shamdeen MY. The pregnancy outcome in patients with minor β-thalassemia. Med J Babylon. 2019;16(3):229-33.
17. Akıncı B, Yaşar AŞ, Karadaş NÖ, Siviş ZÖ, Özdemir HH, Karapınar DY, et al. Fertility in patients with thalassemia and outcome of pregnancies: A Turkish experience. Turk J Hematol. 2019;36(4):274.