Early pregnancy hemoglobin is a critical predictor of neonatal health, according to a massive new cohort study from Canada. The findings challenge the conventional focus solely on anaemia by revealing a U-shaped relationship between maternal haemoglobin (Hb) concentration and severe neonatal morbidity and mortality (SNM-M). This large-scale, population-based study, which included over one million births, provides crucial data for guiding antenatal care. Therefore, clinicians must re-evaluate optimal Hb targets to minimise risks.
The U-Shaped Risk Curve for Neonatal Outcomes
The study defined SNM-M as a composite measure of major neonatal conditions and critical interventions up to 27 days after birth. Researchers analysed Hb concentration in 1-g/L increments, with 125 g/L set as the reference point. Consequently, the results showed that both low and high Hb levels significantly increased the risk of SNM-M. For instance, the adjusted relative risk (aRR) of SNM-M at a haemoglobin level of 105 g/L was 1.08 (95% CI, 1.04 to 1.11), while at a more severely anaemic level of 90 g/L, the aRR climbed to 1.17 (CI, 1.10 to 1.25).
Furthermore, the risk was also elevated in mothers with relatively high Hb levels. For example, a concentration of 135 g/L yielded an aRR of 1.05 (CI, 1.03 to 1.07), and a concentration of 150 g/L resulted in an aRR of 1.20 (CI, 1.16 to 1.24). While the study was conducted in a high-income setting, similar U-shaped associations linking maternal Hb to adverse outcomes like low birth weight have been previously documented in South Asian populations, including in Bangladesh. This suggests the biological mechanism is globally relevant.
Optimising Early Pregnancy Haemoglobin
The clear association between maternal anaemia and adverse perinatal outcomes is well-established, especially in countries like India, which face a high prevalence of anaemia in pregnancy. Specifically, nearly 50% of pregnancies worldwide are affected by anaemia. This new research underscores the danger of two extremes: anaemia and relative erythrocytosis, a finding particularly significant because anaemia management often focuses only on increasing haemoglobin levels. Consequently, healthcare providers must avoid over-correction of haemoglobin in their therapeutic approach.
Furthermore, the current study highlights the need for precise clinical action. Given that the study could not account for iron replacement status before or during pregnancy, there is a recognised limitation on the observed associations. Therefore, the authors strongly recommend future randomised clinical trials (RCTs). These trials should specifically evaluate the effect of iron therapy, not just on maternal outcomes, but also on perinatal outcomes, considering the degree of haemoglobin correction. Current Indian national programs for iron-folic acid (IFA) supplementation, which often recommend 60 mg elemental iron, aim to mitigate this risk. However, some evidence supports a higher prophylactic dose of 120 mg elemental iron daily for Indian pregnant women to optimally replenish iron stores. Careful monitoring of early pregnancy hemoglobin levels is essential for balancing supplementation and avoiding the high-end risk identified in this study.
Frequently Asked Questions
Q1: What does the “U-shaped relation” mean for early pregnancy hemoglobin?
The U-shaped relation means the risk of severe neonatal morbidity and mortality (SNM-M) is lowest at an optimal hemoglobin (Hb) concentration (around 125 g/L), and the risk increases as the Hb level moves away from this optimum in either direction—both at low levels (anemia) and at high levels (relative erythrocytosis).
Q2: Why is the study’s finding on high hemoglobin important for Indian clinical practice?
While maternal anemia is highly prevalent in India, the finding that relative erythrocytosis is also associated with risk suggests that iron supplementation must be carefully monitored to prevent over-correction. Consequently, clinicians should aim for an optimal range rather than simply correcting anemia to the low end of the normal range.
References
- Shams I et al. Hemoglobin Concentration in Early Pregnancy and Severe Neonatal Morbidity and Mortality : Population-Based Cohort Study. Ann Intern Med. 2026 Feb 03. doi: 10.7326/ANNALS-25-02586. PMID: 41628471.
- Carpenter R et al. U-Shaped Association between Maternal Hemoglobin and Low Birth Weight in Rural Bangladesh. Am J Trop Med Hyg. 2021 Dec 29. doi: 10.4269/ajtmh.21-0268. PMID: 34844203.
- DrOracle.ai. Recommendations for Prophylactic Iron and Folic Acid Supplementation in Pregnancy in the Indian Setting. 2026 Jan 05.