In the present study, we found that high Hb(Hb ≥ 130g/L)might be a trigger for GDM in Chinese pregnant women with thalassemia minor, whereas the same phenomenon was not found in those population without thalassemia. To the best of our knowledge, it was the first time to focus on the potential effect of different Hb levels on pregnancy outcomes in the pregnant women with thalassemia of Chinese populations.
Pregnant women with thalassemia are at very high risk of thrombosis, which may be related to the following two factors: (1) pregnancy increases the risk of thrombosis three to four-fold[31]; (2) thalassemia is also a hypercoagulable state[32]. From another perspective, the hypercoagulable state can protect pregnant women from postpartum hemorrhage and improve postpartum anemia. In this paper, we did find a lower incidence of postpartum anemia in pregnant women with thalassemia. Regarding other maternal pregnancy outcomes, we found no significant differences in maternal pregnancy outcomes including GDM, PIH, cholestasis and cesarean between the two groups, which were not exactly consistent with other studies[6, 8]. A study by Veronica et. also suggested that there was no significant difference in the occurrence of GDM between the β-thalassemia minor group and control group of age and BMI-matched healthy women[6]. Nevertheless, Lao et.[8] compared the pregnancy outcomes in women with and without α-thalassemia, and they found that the presence of a-thalassemia significantly increased the likelihood of GDM, and they further indicated that although there was as yet no long-term follow-up studies on women with a-thalassemia, they were probably also at increased risk for the later development of DM. Meanwhile, they found no statistically significant differences between the two groups in maternal outcomes such as cesarean section, preeclampsia and preterm birth, which were in consistent with our findings. In terms of neonatal pregnancy outcomes, we found no significant differences in fetal pregnancy outcomes such as low birth weight, macrosomia, fetal distress, jaundice, preterm birth, hyperglycemia and pediatric attention between the two groups, which were consistently with Lao et[8]. On the contrary, some scholars suggested that neonates of women in the thalassemia group were more likely to experience neonatal jaundice or excessive weight loss after delivery[6], preterm birth and low birth weight[33]. The differences in conclusions between different studies might be related to race, number of cases, the type of thalassemia included and different standards of diagnosis. Most of the discriminant formulations described in previous literatures were individually formulated[6, 8, 34]. According to these standards, some thalassemia women probably be left out. However, in our study, the diagnostic criteria of thalassemia were based on genetic analysis. Therefore, individualized standards of diagnosis may be a core factor made different results of our study from other studies. Moreover, other scholars either focused on a-thalassemia or β-thalassemia, while we concentrated on both the most common a-thalassemia and β-thalassemia.
To date, only a few researchers have paid attention to the relationship between high maternal Hb level and pregnancy outcomes, as it has long been considered as a good signal. However, the findings are controversial. A study from China suggested that high maternal Hb level (> 130 g/dL) was significantly associated with increased risk of GDM[23]. But the findings from a meta-analysis conducted in western countries were inconsistent[35]. To our knowledge, there was not any study investigating the association between Hb concentrations of the first trimester and maternal and neonatal pregnant outcomes including GDM, PIH, caesarean and et. of pregnant women with thalassemia. In our study, we did not find significant differences between maternal and fetal pregnancy outcomes in the three different Hb concentrations subgroups of the control group, which was not the same as previous findings [22, 36]. However, the incidence of GDM in Hb ≥ 130 g/L subgroup was significantly higher comparing with Hb < 110 g/L and 110 ≤ Hb < 130 g/L subgroups in pregnant women with thalassemia minor. It indicated that high Hb concentration may be a triggered factor of GDM in thalassemia women. The mechanism of high Hb concentration on blood glucose was complex. Hb is an iron-containing metalloprotein and it is closely linked to iron levels, which means Hb is a reflection of iron load in vivo [20]. In addition, thalassemia itself is a state of iron overload[17]. Moreover, it is common that women abuse iron supplements during pregnancy. The three factors above jointly contribute to iron overload and further aggravate it. Iron overload triggers oxidative stress [37] and is β-cell toxic[38], leading to insulin resistance, excessive iron deposition in β-cell, resulting in cellular damage and diminished insulin secretion[39], which in turn lead to increased blood glucose. Therefore, in thalassemia pregnant women with high Hb concentrations, iron supplements may further aggravate iron overload and lead to adverse pregnancy outcomes. We should further explore and consider the need for iron supplementation during pregnancy in women with thalassemia, especially those with normal or high Hb levels. In addition, We found that when Hb ≥ 130g/L, fetuses of women with thalassemia were more likely to develop jaundice after birth. And, in normal Hb concentration subgroup, the proportion of fetal macrosomia in thalassemia group was significantly higher than that in control group, while low birth weight infants was significantly lower than that in the control group. This may be related to the misperception that thalassemia is a state of nutritional deficiency. Consequently, women with thalassemia probably take excessive nutrients during pregnancy. What’s more, in anemia subgroups, we found less pregnant women with thalassemia suffered from cesarean compared to pregnant women without thalassemia. Based on these findings, we indicated that the neonatal outcomes were closely linked to Hb concentration in thalassemia women. Thus, it is extremely important for pregnant women with thalassemia minor to control their Hb in an appropriate range during pregnancy, rather than blindly taking iron supplements in expectation of higher Hb concentrations. Researchers should pay more attention to the pregnancy management of thalassemia patients, especially to develop an appropriate Hb range.
Our study had several limitations. First, the number of cases in our study group was small, especially when the groups were divided into different subgroups. Second, we did not investigate the effects of iron supplementation on maternal and neonatal pregnancy outcomes. Lastly, we only evaluated the first trimester Hb levels. The second and third trimester Hb levels should be conducted in further study.
In conclusion, we found no significant differences in pregnancy outcomes between women with and without thalassemia, except for postpartum anemia. But when the two main groups were divided into three different subgroups respectively, we found that high Hb concentration(Hb ≥ 130g/L)may be an triggered factor of GDM in women with thalassemia minor, whereas we did not find the same phenomenon in the pregnant women without thalassemia in Chinese population. In addition, we suggested that in Chinese population, pregnancy complications such as jaundice, macrosomia, low birth weight and cesarean were more closely related to Hb concentration in women with thalassemia minor comparing with women without thalassemia. Therefore, much more attention should be focused on maternal iron and Hb levels during antenatal care and pregnancy management. Scholars should be further explored and considered whether iron supplements during pregnancy is necessary in women with thalassemia minor. More attention should be paid to the levels of iron and Hb in pregnant women with thalassemia minor and iron supplements should be given carefully.