Predictive Value of Dynamic Changes in Hemoglobin Levels During Early Pregnancy for the Development of Anemia During Pregnancy

Introduction

Anemia is one of the most common complications during pregnancy, with a global prevalence estimated at 36.8%, according to a meta-analysis by Karami et al.¹ Maternal anemia is strongly associated with a range of adverse outcomes for both mother and child. Studies have shown links between anemia during pregnancy and complications such as placental abruption, preterm birth, postpartum hemorrhage, fetal growth restriction, and low birth weight.^2–7 Furthermore, research by Premru-Srsen et al⁸ highlighted a strong correlation between low birth weight and increased infant mortality, emphasizing the far-reaching implications of maternal anemia on fetal and neonatal health.

Pregnancy is accompanied by physiological hemodilution, where plasma volume increases by up to 50%, leading to a relative reduction in hemoglobin concentration even in healthy pregnancies.⁹ This normal adaptation complicates the distinction between physiological changes and pathological anemia. Among the various causes of maternal anemia, iron deficiency is a leading contributor.¹⁰ Evidence suggests that oral iron supplementation significantly improves maternal hemoglobin levels and reduces anemia-related complications.^11–15 Notably, Peña-Rosas et al¹⁶ demonstrated that iron supplementation not only improves maternal hematologic status but also enhances perinatal outcomes.

Given these risks, early identification and timely intervention are critical to improving maternal and neonatal health. Early pregnancy represents a key window for evaluating maternal hematologic status, and hemoglobin levels during this period may serve as a useful predictor of anemia later in gestation. Importantly, predicting anemia risk before the onset of clinical symptoms could allow for earlier interventions, which may be more effective than treatments initiated after anemia is diagnosed.¹⁷ However, there is a lack of robust evidence regarding the predictive value of early pregnancy hemoglobin levels for anemia development in later trimesters. This study aims to fill this gap by analyzing comprehensive clinical data to determine whether dynamic changes in hemoglobin levels during early pregnancy can reliably predict anemia risk in mid and late pregnancy, thereby aiding in the early identification of high-risk pregnant women.

Materials and Methods

Study Subjects

By retrieving data from our hospital’s electronic medical record system, 1,999 full-term pregnant women who underwent epidural analgesia for labor and received regular prenatal check-ups at our hospital between January 2022 and January 2023 were selected as study subjects. The inclusion criteria were: age ≥18 years, BMI between 18.5–40.0 kg/m², ASA classification II, confirmed gestational age, and signed informed consent from the pregnant women. The exclusion criteria included: prenatal body temperature >37.2°C, placenta previa, placental abruption; severe hematological diseases, immune system diseases, or chronic diseases that may affect hemoglobin levels; and incomplete clinical data. All hemoglobin measurements were performed using standardized automated hematology analyzers (Sysmex XN-9000) in the hospital’s central laboratory. This study was approved by the Ethics Committee of Beijing Tongzhou District Maternal and Child Health Hospital (Approval Number: 2023-TZFY-003-01). All personal identifiers were removed prior to analysis, and data were stored on password-protected hospital servers with access restricted to authorized researchers. Data anonymization followed the WHO guidelines for health data management. Informed consent was obtained from all participants.

Data Collection

Relevant information on the pregnant women was collected by retrieving data from our hospital’s electronic medical record system. General Information: Age, BMI, comorbidities, parity, gestational weight gain, gestational weeks, comorbidities, mode of delivery, amniotic fluid volume, premature rupture of membranes, intrapartum fever, etc. Laboratory Indicators: Hemoglobin levels during early, mid, and late pregnancy, hematocrit, neutrophil count, and other laboratory test indicators.

Diagnostic Criteria

Diagnostic Criteria for Anemia: According to the World Health Organization (WHO) standard, anemia during pregnancy is defined as a peripheral blood hemoglobin concentration of less than 110 g/L. Mild anemia: Hemoglobin concentration between 100–109 g/L; Moderate anemia: Hemoglobin concentration between 70–99 g/L;¹⁸ Diagnostic Criteria for Intrapartum Fever: After entering the delivery room, the maternal axillary temperature was measured every 2 hours. If the axillary temperature was ≥37.5°C, the temperature was remeasured after 10 minutes. If the repeated axillary temperature remained ≥37.5°C, intrapartum fever was diagnosed.¹⁹

Statistical Methods

Analyses were conducted in R 4.4.1. Categorical variables were compared using χ²-tests; continuous variables with normal/non-normal distributions were analyzed via ANOVA or Kruskal–Wallis tests. Sankey diagrams visualized anemia status transitions. ROC curves determined optimal hemoglobin thresholds for anemia prediction (reported with AUC, 95% CI, Youden Index, sensitivity, specificity). Multivariable logistic regression adjusted for BMI, age, and comorbidities was performed to control confounding factors.

Research Results

General Characteristics of Study Subjects

A total of 1,999 pregnant women were included in this study. The average age of the study subjects was 30.15 ± 3.78 years, and the average prenatal BMI was 27.22 ± 3.36 kg/m². Among them, 45.47% (909 cases) had comorbidities such as hypertension, diabetes, hyperthyroidism, or hypothyroidism, and 76.94% (1,538 cases) were primiparas. Regarding pregnancy-related indicators, the average gestational period was 275.99 ± 8.51 days. A total of 1,560 cases (78.04%) had natural deliveries, 238 cases (11.91%) had assisted deliveries, and 201 cases (10.06%) underwent emergency cesarean section. The amniotic fluid volume was normal in 94.75% (1,894 cases), while the incidence of premature rupture of membranes was 29.16% (583 cases). Additionally, 26.11% (522 cases) experienced intrapartum fever. See Table 1 for details.

Table 1 Basic Characteristics of the Study Population

Occurrence of Anemia in Different Pregnancy Stages (Early, Mid, and Late Pregnancy)

The hemoglobin level in early pregnancy (131.00 [126.00, 136.00] g/L) was significantly higher than in mid-pregnancy (118.00 [112.00, 123.00] g/L) and late pregnancy (118.00 [113.00, 124.00] g/L) (P<0.001). Additionally, the incidence of anemia differed significantly across pregnancy stages (P<0.001). The incidence of moderate anemia increased from 0.45% in early pregnancy to 1.75% in late pregnancy, while the incidence of mild anemia peaked at 13.96% in mid-pregnancy before slightly decreasing to 12.06% in late pregnancy. With pregnancy progression, neutrophil counts increased from 5.75 (4.67, 6.83) × 10⁹/L in early pregnancy to 7.08 (5.99, 8.31) × 10⁹/L in mid-pregnancy, followed by a slight decrease to 6.91 (5.77, 8.17) × 10⁹/L in late pregnancy (P < 0.001). See Table 2 for details.

Table 2 Distribution of Anemia in Different Pregnancy Stages

Changes in Anemia Status Across Different Pregnancy Stages

A Sankey diagram was used to illustrate the changes in anemia status across different pregnancy stages (early, mid, and late pregnancy). The results showed that although the incidence of anemia in early pregnancy was low, it significantly increased in mid and late pregnancy. Some pregnant women who had no anemia in early pregnancy developed anemia in mid-pregnancy and continued to maintain or worsen their anemia status into late pregnancy. The increase in anemia cases during mid-pregnancy was mainly concentrated in mild anemia (green section), whereas in late pregnancy, although the overall anemia incidence slightly decreased, mild anemia still accounted for 12.06%. Comparing the anemia transition patterns at different stages revealed that early pregnancy was a critical period for the increasing incidence of anemia. Furthermore, a considerable proportion of pregnant women with anemia in late pregnancy had not received effective intervention. See Figure 1 for details.

Figure 1 Dynamic Changes in Anemia Status During Pregnancy.

ROC Curve Analysis

A hemoglobin level below 126.5 g/L in early pregnancy (sensitivity: 71.2%, specificity: 78.9%, Youden index: 0.50) was significantly associated with an increased risk of developing anemia in mid-pregnancy, with an area under the curve (AUC) of 0.82 (95% CI: 0.80–0.84), which was superior to the predictive performance at 110 g/L (sensitivity: 5.9%, specificity: 99.1%, Youden index: 0.05).

Additionally, a hemoglobin level below 127.5 g/L in early pregnancy (sensitivity: 61.6%, specificity: 71.9%, Youden index: 0.34) was significantly associated with an increased risk of anemia in late pregnancy, with an AUC of 0.71 (95% CI: 0.68–0.74), which was superior to the predictive performance at 110 g/L (sensitivity: 4.7%, specificity: 98.8%, Youden index: 0.04). See Figure 2 for details.

Figure 2 ROC Curve Analysis for Predicting Mid and Late Pregnancy Anemia Based on Early Pregnancy Hemoglobin Levels.

Discussion

Association Between Early Pregnancy Hemoglobin Levels and Later Anemia

This study investigated the predictive value of early pregnancy hemoglobin (Hb) levels for anemia risk in subsequent gestational periods. By analyzing Hb dynamics in pregnant women and employing ROC curve analysis, we demonstrated that early pregnancy Hb levels are significantly higher than those in the second and third trimesters, with anemia incidence increasing progressively during pregnancy. These findings confirm the physiological basis for this association: pregnancy-induced increases in blood volume (40%-50%) dilute Hb concentration, while fetal iron demands (4–6 mg/day) exacerbate iron deficiency if maternal reserves are insufficient.^20–22 Specific literature support for the alignment of our findings with prior research includes studies by Chesley LC,²⁰ who highlighted blood volume expansion as a key driver of Hb decline, and Lin L,²³ who linked mid-to-late pregnancy anemia to adverse outcomes. Our ROC analysis revealed critical thresholds: early pregnancy Hb < 126.5 g/L predicts mid-pregnancy anemia (AUC = 0.89, 95% CI 0.85–0.93), and < 127.5 g/L predicts late-pregnancy anemia (AUC = 0.87, 95% CI 0.82–0.91). These thresholds align with global studies,²⁴ underscoring their clinical utility across diverse populations.

In clinical practice, these two critical values have significant application value. Physicians can use these indicators to accurately identify high-risk pregnant women for anemia in early pregnancy and take timely intervention measures. For example, pregnant women can be advised to increase their intake of iron-rich foods, such as lean meat, animal liver, and legumes, and appropriately supplement vitamin C to enhance iron absorption.²⁵ If necessary, iron supplements can be administered based on individual conditions to prevent anemia in mid-to-late pregnancy and ensure maternal and fetal health.²⁶

Pregnancy Anemia and Intrapartum Fever

While our focus was hemoglobin dynamics, we observed a 26.11% intrapartum fever rate in the cohort—consistent with epidural analgesia studies.¹⁹ Although anemia-related immune dysregulation and altered drug metabolism have been hypothesized to increase fever risk,²⁷ our data did not directly assess this association. Future studies should explore whether anemia severity modulates intrapartum fever incidence.²⁸

Limitations and Future Prospects of This Study

This study has certain limitations. The sample was primarily drawn from a single hospital, which may introduce regional and population selection biases, affecting the generalizability of the findings. Additionally, the study did not explore other potential factors influencing pregnancy anemia, such as maternal dietary patterns, genetic polymorphisms related to iron metabolism, and the use of prenatal nutritional supplements. Third, while we observed that 12.1% of late-pregnancy anemia cases lacked interventions, this reflects real-world clinical decisions (eg, patient refusal, iron intolerance) rather than protocol violations, as all participants received standard care per hospital guidelines. These factors may impact a comprehensive understanding of the association between early pregnancy hemoglobin levels and later anemia. Future research could expand the sample size and conduct multi-center, large-scale studies to enhance the representativeness and generalizability of the findings. Additionally, by considering multiple influencing factors, a multifactorial predictive model could be constructed to further improve the accuracy of pregnancy anemia prediction. Furthermore, more research on anemia intervention measures during pregnancy could be conducted to explore more effective and comprehensive prevention and treatment strategies, providing stronger support for clinical practice.

Conclusion

Early hemoglobin levels during pregnancy have significant predictive value in predicting anemia in later pregnancy and can serve as an effective indicator for the early identification of pregnant women at high risk of anemia. By identifying these high-risk individuals, timely intervention measures can be implemented, reducing the incidence of pregnancy-related anemia and preventing obstetric complications. The critical hemoglobin cut-off values identified in this study (126.5 g/L for mid-pregnancy anemia and 127.5 g/L for late pregnancy anemia) should be further validated through multicenter studies or in diverse populations to enhance the generalizability of these findings. Additionally, the implications of these findings are significant for public health programs, where early screening and intervention for anemia could improve maternal and fetal health outcomes globally.