Association between maternal haemoglobin concentrations and maternal and neonatal outcomes: the prospective, observational, multinational, INTERBIO-21st fetal study.

Background: Anaemia in pregnancy is a global health problem with associated maternal and neonatal morbidity and mortality. We aimed to investigate the association between maternal haemoglobin concentrations during pregnancy and the risk of adverse maternal and neonatal outcomes.

Methods: In this prospective, observational, multinational, INTERBIO-21st fetal study conducted at maternity units in Brazil, Kenya, Pakistan, South Africa, and the UK, we enrolled pregnant women (aged ≥18 years, BMI <35 kg/m², natural conception, and singleton pregnancy) who initiated antenatal care before 14 weeks' gestation. At each 5±1 weekly visit until delivery, information was collected about the pregnancy, as well as the results of blood tests taken as part of routine antenatal care, including haemoglobin values. The outcome measures were maternal (gestational diabetes, pregnancy-induced hypertension, and preterm premature rupture of membranes) and neonatal outcomes (small for gestational age, preterm birth, and acute respiratory distress syndrome).

Findings: Between Feb 8, 2012, and Nov 30, 2019, 2069 women (mean age 30·7 years [SD 5·0]) had at least one routinely haemoglobin concentration measured at 14-40 weeks' gestation, contributing 4690 haemoglobin measurements for the analysis. Compared with a haemoglobin cutoff of 110 g/L, the risk was increased more than two-fold for pregnancy-induced hypertension at haemoglobin concentrations of 170 g/L (risk ratio [RR] 2·29 [95% CI 1·19-4·39]) and higher, for preterm birth at haemoglobin concentrations of 70 g/L (RR 2·04 [95% CI 1·20-3·48]) and 165 g/L (RR 2·06 [95% CI 1·41-3·02]), and for acute respiratory distress syndrome at haemoglobin concentrations of 165 g/L (RR 2·84 [95% CI 1·51-5·35]). Trimester-specific results are also presented.

Interpretation: Our data suggests that the current WHO haemoglobin cutoffs are associated with reduced risk of adverse maternal and neonatal outcomes. The current haemoglobin concentration cutoffs during pregnancy should not only consider thresholds for low haemoglobin concentrations that are associated with adverse outcomes but also define a threshold for high haemoglobin concentrations given the U-shaped relationship between haemoglobin concentration and adverse neonatal and maternal outcomes.

Funding: Bill & Melinda Gates Foundation.