When More Is Not Better: A Balanced View of Haemoglobin Concentrations During Pregnancy

The relationship between maternal haemoglobin concentration and pregnancy outcomes has long challenged clinicians and researchers. While anaemia in pregnancy remains a major global public health concern, increasing evidence suggests that higher haemoglobin concentrations may also signal elevated risk [1]. This has shifted the conversation from identifying a single threshold for anaemia to understanding the full spectrum of haemoglobin concentrations associated with optimal maternal and neonatal health. In this issue of Paediatric and Perinatal Epidemiology, Yu and colleagues make an important contribution to this evolving literature by examining haemoglobin concentrations in a large cohort of pregnant women in China and proposing trimester‐specific haemoglobin ranges [2].

Using data from nearly 42,000 singleton live births and more than 120,000 haemoglobin measurements, the authors observed predominantly U‐shaped associations between maternal haemoglobin concentration and adverse outcomes, including preeclampsia, postpartum haemorrhage, preterm birth, small‐for‐gestational‐age birth, and neonatal asphyxia. Taken together, the authors conclude that concentrations between approximately 10.5 and 12.5 g/dL during the second and third trimesters may represent an optimal target range.

The study arrives at a particularly important time. Despite decades of research on maternal anaemia, uncertainty persists regarding the lower and upper limits of healthy haemoglobin concentrations during pregnancy. Current clinical practice often emphasises identifying and treating anaemia, while elevated haemoglobin concentrations receive comparatively little attention, partly because there is no clearly defined cutoff value of elevated haemoglobin during pregnancy that clinicians can use. Yet accumulating evidence suggests that inadequate plasma volume expansion, reflected in persistently high haemoglobin concentrations, is associated with placental dysfunction and adverse pregnancy outcomes [3]. By simultaneously evaluating risks of both low and high haemoglobin concentrations, Yu et al. move the field forward, beyond a simple anaemia versus no anaemia framework.

Several aspects of the study deserve recognition. First, the sample size is exceptionally large, providing sufficient statistical power to examine U‐shaped associations between haemoglobin concentrations and pregnancy outcomes. Second, modelling haemoglobin concentration as a continuous exposure using restricted cubic splines avoids the limitations of arbitrary categorisation and allows more nuanced identification of risk patterns. Lastly, the authors assessed multiple clinically important maternal and neonatal outcomes by trimester, including rarer outcomes that are often understudied due to sample size limitations. This helps address the call to action from a systematic review I conducted with colleagues, in which we noted a need for more data examining the association between maternal haemoglobin and rare birth outcomes, such as preterm birth, by trimester [4]. This approach also better reflects the reality faced by clinicians, who must balance risks across competing outcomes.

However, several important questions remain before these proposed haemoglobin ranges can be translated into clinical guidance. The first challenge concerns the interpretation of haemoglobin itself. Maternal haemoglobin concentrations naturally decline during mid‐pregnancy because plasma volume expands more rapidly than red blood cell mass. This haemodilution is generally considered a normal adaptation that supports placental perfusion and fetal growth [5], but complicates the definition of optimal haemoglobin ranges. Additionally, haemoglobin concentration is not a direct measure of iron status, nutritional adequacy, or plasma volume expansion. Rather, it reflects a complex combination of physiological and pathological processes. Low haemoglobin may indicate iron deficiency, inflammation, haemoglobinopathies, micronutrient deficiencies, or other conditions. Similarly, elevated haemoglobin concentrations may result from inadequate plasma volume expansion, dehydration, chronic disease, or other factors. Thus, identifying an optimal haemoglobin range has limited utility in clinical practice, as it does not reveal the causal factor for those that fall outside of the optimal range. This distinction is particularly important because interventions and clinicians target causes rather than haemoglobin concentrations themselves. Future studies incorporating biomarkers of iron status and inflammation could help disentangle these pathways and provide greater insight.

It is also important to remain mindful of issues related to generalizability. The study was conducted using data from a single hospital in China, and the authors appropriately acknowledge this limitation. Haemoglobin distributions vary substantially across populations due to differences in genetics, altitude, nutritional status, infection burden, healthcare access, and obstetric practices. For example, research my colleagues and I conducted examining associations between haemoglobin and biomarkers of iron status among pregnant women in Ghana and Malawi found that the associations differed by country [6]. The optimal range identified in this cohort may therefore not be directly applicable to populations in other settings. This concern is especially relevant given the growing interest in revisiting global anaemia thresholds during pregnancy. Before new clinical cut‐points are considered, similar analyses should be replicated across diverse geographic and demographic populations.

Perhaps the most provocative aspect of the study is its challenge to conventional thinking about the anaemia threshold in the third trimester. Currently, the World Health Organisation defines anaemia as haemoglobin concentrations below 10.5 g/dL in the second trimester and below 11 g/dL in the third trimester [7]. However, Yu et al. present results that challenge this standard and make a compelling argument supported by their data for a cut‐point of 10.5 g/dL to define anaemia for both the second and third trimester. Likewise, although there is no agreed‐upon definition of high haemoglobin during pregnancy, clinicians and researchers typically use a range of 13–14 g/dL to define elevated haemoglobin. However, Yu et al. suggest that the cutoff should be 12.5 g/dL. This will be a useful study to consider as the field works towards a definition of elevated haemoglobin.

Ultimately, the greatest contribution of this study may not be the specific haemoglobin range it proposes, but rather the framework it offers for evaluating maternal haemoglobin across the full distribution of risk. By emphasising that both low and high concentrations deserve attention, Yu and colleagues encourage a more balanced understanding of maternal haemoglobin concentrations during pregnancy. Future research should focus on validating these findings in diverse populations and integrating biomarkers that clarify underlying mechanisms. Such work will be essential for the field to have well‐grounded definitions for both anaemia and elevated haemoglobin.

Author Contributions

The author takes full responsibility for this article.

Funding

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Disclosure

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Conflicts of Interest

The author declares no conflicts of interest.

Linked Articles

This article is linked to Yu et al. manusctipt. To view this article, visit https://doi.org/10.1111/ppe.70142.

Data Availability Statement

The author has nothing to report.