Anemia during pregnancy is a significant global health concern that affects a substantial number of women worldwide, with a prevalence rate of 30% among women of childbearing age (1). It is defined as a condition where hemoglobin levels are below average, resulting in a decreased oxygen-carrying capacity of red blood cells in tissues (2). During pregnancy, as the fetus grows, pregnant women experience metabolic changes, hormonal level fluctuations and an increase in blood volume, and the physiological demands for iron, folate, and other nutrients increase significantly to support the growth and development of the fetus, as well as to meet the expanded blood volume requirements of the mother (3–6). This heightened need often places pregnant women at a higher risk of developing anemia if these nutrients are inadequately supplied through diet or if there are underlying health conditions that interfere with nutrient absorption or utilization (7, 8). In developing countries, where access to proper nutrition and prenatal care may be limited, the rates tend to be even higher (9). This not only impacts the health and well-being of the mother but also has far-reaching implications for the pregnancy itself and the health of the newborn. Severe anemia during pregnancy can have both short-term and long-term effects on the mother, fetus and newborn, such as leading to the occurrence of adverse pregnancy outcomes like gestational hypertension, miscarriage, preterm birth and low birth weight infants (10, 11).

Despite the well-documented associations between anemia during pregnancy and these adverse outcomes, there remains some variability in the reported findings across different studies. This could be attributed to differences in the diagnostic criteria used for anemia, variations in study populations, and disparities in the methods employed to measure and assess adverse pregnancy outcomes. Furthermore, the complex interplay of multiple factors such as socioeconomic status, access to healthcare, and coexisting medical conditions makes it challenging to fully understand the precise mechanisms through which anemia leads to these adverse events. Given these uncertainties and the significant impact on both maternal and neonatal health, this study conducts a systematic review and meta-analysis of prospective and retrospective cohort studies published domestically and internationally to explore the relationship and impact degree between anemia during pregnancy and various adverse pregnancy outcomes.

Anemia is one of the common complications during pregnancy, even among pregnant women in developed countries (47). Due to the increased demand for nutrients during pregnancy, some pregnant women may experience anemia due to inadequate daily intake of nutrients or lower nutrient utilization rates (48). Chowdhury et al's (49) study indicated maternal age, BMI levels, economic status and educational level are associated with hemoglobin levels during pregnancy. Previous research has suggested that severe anemia during pregnancy, resulting in decreased hemoglobin levels and reduced oxygen-carrying capacity of the blood, can lead to various adverse pregnancy outcomes, including pregnancy-induced hypertension, miscarriage, preterm birth and LBW (50, 51).

This study found that pregnant women with anemia were at higher risk of developing pregnancy-induced hypertension, cesarean section, PROM, preterm birth, postpartum hemorrhage, neonatal asphyxia and LBW compared to non-anemic pregnant women with respective RR values of 1.33, 1.28, 1.94, 1.51, 2.76, 1.21 and 1.40. In terms of risk severity, the order from highest to lowest was postpartum hemorrhage, PROM, preterm birth, LBW, cesarean section, pregnancy-induced hypertension and neonatal asphyxia.

Our study corroborates previous research in identifying several adverse pregnancy outcomes associated with anemia. Xiong et al's (10) meta-analysis on the relationship between anemia during pregnancy and pregnancy outcomes investigated the ORs (95% CIs) of early pregnancy anemia with preterm birth, LBW, fetal growth restriction and hypertension, which were 1.32 (1.01, 1.74), 1.39 (0.70, 2.74), 1.01 (0.73, 1.38) and 0.80 (0.53, 1.20) respectively. In comparison, this study identified four adverse outcomes related to pregnancy anemia: PROM, cesarean section, postpartum hemorrhage and neonatal asphyxia. While Xiong et al' 's (10) study did not find a statistically significant association between anemia and pregnancy-induced hypertension, this study demonstrated a strong correlation between anemia during pregnancy and pregnancy-induced hypertension, with an RR value of 1.89. This difference may be attributed to the inclusion of only two relevant studies with potentially lower credibility in Xiong et al's analysis (52, 53). Our study encompassed a more comprehensive set of relevant studies, enhancing the reliability of our results. Additionally, some studies treated hypertension as a confounding factor and excluded it from their analysis, potentially influencing the results. When pregnant women have anemia, the decreased oxygen-carrying capacity of the blood leads to increased cardiovascular and peripheral vascular pressure to meet the demands for blood supply, thereby increasing the risk of hypertension (54).

The mechanisms underlying the adverse pregnancy outcomes in anemic pregnant women are multifactorial and biologically plausible. The decreased oxygen-carrying capacity of the blood due to anemia leads to compensatory physiological responses (55, 56). For instance, the increased cardiovascular and peripheral vascular pressure to meet the oxygen demands of the fetus can precipitate hypertension (57, 58). Postpartum hemorrhage is a significant cause of maternal mortality. Omotayo et al's (59) study showed that severe anemia during pregnancy increases the risk of postpartum hemorrhage, and there is no significant correlation between mild to moderate anemia and postpartum hemorrhage. The mechanism behind this may be related to iron deficiency anemia and increased secretion of nitric oxide. During pregnancy, trophoblasts and placental cells secrete nitric oxide through paracrine action, which then binds with nitric oxide synthase in the uterine muscle layer. This process plays a crucial role in maintaining the stability of the uterus. In the case of anemia, this process is intensified, leading to a decrease in the contraction function of uterine smooth muscles, thereby causing uterine muscle weakness and increasing the risk of postpartum uterine bleeding (60). Nur et al (61). also confirmed in a case-control study that anemia is a significant risk factor for postpartum hemorrhage.

Fetal hypoxia, a consequence of maternal anemia, is a key contributor to neonatal asphyxia. Maternal anemia causes a reduction in hemoglobin levels in the maternal blood, decreasing the blood's capacity to carry oxygen and affecting the fetus's ability to obtain sufficient oxygen in the uterus. When the fetus experiences hypoxia in the maternal uterus, it may result in asphyxia (62, 63). Additionally, this study demonstrates a strong association between maternal anemia during pregnancy and LBW and preterm birth with RR values of 1.40 and 1.51, respectively. Allen's (64) research suggests that placental insufficiency in anemic patients leading to hypoxia is considered one of the mechanisms causing LBW. Maternal anemia is often accompanied by inadequate nutrient intake and insufficient placental blood supply. Due to the lack of essential nutrients, the metabolic capacity of pregnant women's cells decreases, affecting fetal development and growth, leading to LBW (65). Furthermore, when the immune system function of newborns is immature, there is an increased risk of complications such as respiratory infections, indirectly raising the likelihood of neonatal asphyxia (66).

In general, maternal anemia during pregnancy impacts fetal oxygen supply and overall health, potentially leading to inadequate uterine contractions that can affect fetal growth and development. This condition may trigger preterm birth or delivery complications such as placental abruption, PROM, among others (67–69). Apart from oxidative damage, another known biological mechanism indicates that anemia and iron deficiency stimulate the synthesis of corticotropin-releasing hormone (CRH), leading to stress responses in both the mother and the fetus (70). Elevated levels of CRH are major risk factors for preterm birth, gestational hypertension, preeclampsia and PROM (64, 71). This study did not find an association between maternal anemia during pregnancy and gestational diabetes, puerperal infections, fetal distress, etc., which may be related to unpublished negative study results or differences in literature diagnostic criteria. Further, future high-quality research and relevant data are needed for supplementation and improvement.

The high heterogeneity observed in our meta-analysis, as indicated by the I² values, warrants further exploration. Subgroup analyses based on factors such as country income levels, study design, and sample size have provided valuable insights. For example, income levels influenced the risk of postpartum hemorrhage, preterm birth, and cesarean section. In high-income countries, the risk of postpartum hemorrhage was higher, potentially due to differences in healthcare utilization and management practices. Study design also emerged as a significant source of heterogeneity, with retrospective studies often showing different results compared to prospective ones. This could be attributed to differences in data collection methods, recall bias in retrospective studies, and the ability to control for confounding factors. Sample size differences further contributed to heterogeneity, particularly in outcomes like preterm birth and LBW. Smaller studies may be more susceptible to sampling variability and less likely to capture the full spectrum of associations.

The strength of this study lies in focusing solely on the pregnancy outcomes of singleton anemic women. This is because twin or multiple pregnancies carry a higher risk of adverse perinatal outcomes. If there were a significant number of multiple pregnancies in the anemic group, it would lead to selection bias and magnify the impact of anemia on adverse pregnancy outcomes. Our study also has several limitations that should be considered when interpreting the results. On the one hand, the reliance on publicly available Chinese and English literature may have introduced selection bias, potentially overlooking relevant studies in other languages or unpublished research. The exclusion of specific types of anemia, such as aplastic anemia and thalassemia, limits the generalizability of our findings. On the other hand, while we standardized certain factors like singleton pregnancies, the lack of control for other confounding variables such as parity and BMI may have affected the accuracy of our estimates. Future studies should expand the literature search to include non-English and non-Chinese databases and grey literature sources more comprehensively. Collaborations with international research groups could also help in accessing a broader range of studies. In addition, future researchs can specifically investigate the impact of different types of anemia on pregnancy outcomes. This could involve conducting separate meta-analyses for each major type of anemia or including detailed subgroup analyses within a comprehensive study.

Maternal anemia is associated with an increased risk of adverse pregnancy outcomes. Anemia during pregnancy poses significant risks, not only leading to poor health conditions for pregnant women, premature rupture of membranes and postpartum hemorrhage but also being detrimental to fetal development, resulting in outcomes such as low birth weight, preterm birth and neonatal asphyxia. For pregnant women, special attention should be paid to supplementing iron. Adopting excellent nutritional management measures plays an essential supportive role in preventing the occurrence of pregnancy-induced anemia and avoiding the worsening of anemia.