The global prevalence of thalassemia ranges from 2.5–25.0%, with a gene carrier rate of 1.7%. In China, Guangdong, Guangxi, Hainan and Sichuan are areas with a high prevalence of thalassemia, of which Guangxi has one of the highest rates of thalassemia carriage, up to 25%. Wang Liang et al. showed that α-thalassemia is currently the most common type of thalassemia within Guangxi. [5–6] The following deletion types of α-thalassemia genes have been identified in the population: -α3.7, -α4.2, -α2.7, --SEA, --THAI, --FIL, --HW, --11.1. However, the common nondeletion types of α-thalassemia genes are Hb CS, Hb QS, Hb WS. α-Thalassemia is clinically classified according to the number of defects in the α-genes. There are four types of α-thalassemia: carrier, minor, intermediate (HBH disease) and severe (hemoglobin Bart’s hydrops fetalis). Among them, α-thalassemia major leads to Bart′s edema in the fetus, which often results in intrauterine death in the middle or late stages of pregnancy or a few hours after delivery. [7–8] Therefore, there are no patients with alpha-thalassemia major in the population.
The distribution of the type of thalassemia, a common hereditary disease, has regional and ethnic differences. Understanding the characteristics of the genotype distribution in the region where it is located is beneficial to the prevention and control of thalassemia and genetic counseling work in the region. In this study, the α-thalassemia mothers were overrepresented by the Han and Zhuang ethnic groups, which is in line with the distribution of the local population in Guangxi by ethnicity. We detected a total of 25 genotypes, the most common of which were -SEA/ααα (673 cases, 49.2%), -α3.7/ααα (273 cases, 20.0%) and αCSα/ααα (153 cases, 11.2%). This is consistent with the findings of Wang Liang [6], Lu Heng [9] and Wei Shuai [10] on the distribution of α-thalassemia genotypes in Guangxi.
In pregnant women with thalassemia, the maternal circulating blood volume increases during pregnancy, forming gestational anemia. At the same time, due to the increased demand for various nutritional elements, such as iron and protein, for fetal growth and development, maternal hemolytic anemia will become serious. The high iron load in the body is high due to chronic hemolysis and the fact that anemia leads to a decrease in hepatic iron-regulating hormone levels, which increases intestinal iron absorption and further aggravates the iron load[11]. This causes serum ferritin levels to be higher in affected pregnant women than in non-affected pregnant women, but maternal serum ferritin levels still decrease with increasing gestational weeks as the fetal demand increases. In our study, the hemoglobin level in the experimental group was lower than that in the control group regardless of the gestational period, with the lowest hemoglobin level occurring in the intermediate group; however, the serum ferritin level showed a rise. For both indicators, the decrease with gestation was also most significant in the intermediate group. This may be related to the fact that pregnancy may induce the hemolytic mechanism of thalassemia, thus aggravating anemia. In particular, thalassemia carriers should theoretically be no different from normal people; however, our results showed that there was no significant difference between the carrier group and the control group in the first and second trimesters, but the anemia condition of the carrier group in the third trimester was heavier than that of the control group. We speculate that pregnancy is in a chronic inflammatory immune state, and inflammatory cytokines may affect iron metabolism, inhibit the proliferation of red blood cells, shorten the life span of red blood cells, and eventually lead to the aggravation of anemia. Therefore, it has been suggested that pregnancy status may be one of the factors changing the phenotype of thalassemia. All of this suggests that we should pay special attention to the hemoglobin and serum ferritin levels of pregnant women with thalassemia and routinely recommend supplementation with folic acid and vitamin B12, as well as administration of blood transfusions when necessary in patients with severe anemia, recurrent infections, splenomegaly and fetal growth restriction.
In pregnant women with thalassemia, prolonged anemia and iron overload due to hemolysis can affect the function of various systems and organs. If iron is deposited in myocardial cells causing cellular damage, this can lead to heart failure and arrhythmias [13–14], while chronic anemia can also lead to myocardial ischemia and electrocardiographic changes [15–16]. Excess iron can also mediate islet β-cell damage and alter insulin synthesis and secretion, leading to insulin resistance [17–18] and ultimately abnormal glucose metabolism [19]. Several studies [20–23] found that severe anemia and serum ferritin levels were significantly associated with the incidence of hypertensive disorders, and Wang Yanxia et al [24] also indicated that high iron load causes the body to experience oxidative stress and increased vasoconstriction, leading to the development of hypertensive disorders of pregnancy. If a large amount of iron is deposited in the thyroid gland, chronic fibrotic changes in its substance can occur, and free iron can catalyze the formation of highly reactive oxygen radicals, leading to cytotoxicity and thyroid functional impairment [25–26]. Although the majority of pregnant women without comorbidities have normal liver biochemical parameters [27], the abnormal nucleoprotein chain in thalassemic women leads to damage to the body's red blood cells and increases production of bilirubin, causing hyperbilirubinemia, which in turn affects the patient's liver function [28]. In this study, we found that the incidence of pregnancy comorbidities was higher in both the observation and control groups, which is consistent with the results of previous studies. It has therefore been suggested that pregnancy should not recommended for women with iron overload. Pregnant women with thalassemia should be monitored in the early stages of pregnancy by means of regular tests of cardiac and liver function and thyroid function and close monitoring of blood glucose and blood pressure, especially for patients who require multiple transfusions. In particular, pregnant women with thalassemia who are severely anemic should still be alerted to a decline in cardiac reserve after delivery, as well as to outbreaks of liver or thyroid abnormalities.
In terms of delivery outcome, it can be concluded from the results that the rates of cesarean section, preterm labor, and postpartum hemorrhage were all higher in the observation group than in the control group, and the most common causes of cesarean section were fetal distress and abnormal labor, which may be due to long-term chronic anemia and insufficient blood circulation to the uterus and placenta, which affects the contraction of the uterine muscles and leads to postpartum hemorrhage [29]. This is consistent with the results of a study by Luo Li and Liang Xu Xia [30]. It has also been reported that anemia in pregnancy can result in inadequate production of antibodies in pregnant women[31], reducing their immune function and predisposing them to infections. Thalassemia is not a surgical indication for cesarean section, and the choice of delivery method for pregnant women with combined thalassemia should be individualized, with clear obstetric indications for cesarean section.
The effects of anemia during pregnancy on the fetus have been shown to cause intrauterine ischemia and hypoxia, restricted growth and development due to inadequate nutrient supply, and increased incidence of low birth weight. A study by Pang Ting and Guo Xuefeng et al.[32] showed that maternal comorbidities with minor alpha-thalassemia may increase the risk of lower birth weight in newborns. A study by Huang Xiaochun and Qiu Xiaoqiang et al. [33] also showed that the presence of thalassemia in both or either parent increased the risk of low birth weight in newborns. This is consistent with the results of our study showing that the neonatal weight was lower in the observation group than in the control group. The neonatal Apgar scores are usually assessed clinically, with the 1-minute Apgar score being more representative of the status of the newborn in utero. Several studies have suggested that the degree of maternal anemia affects the Apgar score of the newborn, with more severe anemia leading to a higher risk of neonatal asphyxia. In this study, the 1-min Apgar scores were slightly but significantly lower in the carrier and minor groups than in the control group. The fetus receives all the iron it needs for growth and development from the mother through the placenta. When the pregnant woman has different degrees of anemia and insufficient iron reserves, the hematopoiesis and iron reserves of the fetus are also affected to varying degrees, manifesting as a decrease in hemoglobin and serum ferritin in the newborn [34]. Recent studies have also shown [35] that both iron and iron saturation in the cord blood of newborns are reduced in maternal anemia. Women with thalassemia in combination with pregnancy are more anemic during pregnancy than anemic women without thalassemia, so theoretically, newborns delivered by women with thalassemia should have lower hemoglobin levels, which is also consistent with the comparative results of the hemoglobin of newborns delivered in this study at 24 hours of life.
In this study, we suggest that the pregnancy status, delivery outcomes and neonatal outcomes of pregnant women with thalassemia are somewhat different from those of normal pregnant women; however, this study is a retrospective study, and the different dietary habits of different pregnant women may affect their pregnancy status to some extent. In addition, due to the low incidence of intermediate α-thalassemia, there were only 39 pregnant women with intermediate thalassemia in this study, so this group had a smaller sample size than the other groups, which may lead to bias and certain limitations in the results. In future studies, the sample size should be further increased to draw more objective and accurate conclusions.