Maternal anaemia and the risk of postpartum haemorrhage: a cohort analysis of data from the WOMAN-2 trial

Background: Worldwide, more than half a billion women of reproductive age are anaemic. Each year, about 70 000 women who give birth die from postpartum haemorrhage. Almost all deaths are in low-income or middle-income countries. We examined the association between anaemia and the risk of postpartum haemorrhage. Methods: We did a prospective cohort analysis of data from the World Maternal Antifibrinolytic-2 (WOMAN-2) trial. This trial enrols women with moderate or severe anaemia giving birth vaginally in hospitals in Pakistan, Nigeria, Tanzania, and Zambia. Hospitals in each country where anaemia in pregnancy is common were identified from a network established during previous obstetric trials. Women who were younger than 18 years without permission provided by a guardian, had a known tranexamic acid allergy, or developed postpartum haemorrhage before the umbilical cord was cut or clamped were excluded from the study. Prebirth haemoglobin, the exposure, was measured after hospital arrival and just before giving birth. Postpartum haemorrhage, the outcome, was defined in three ways: (1) clinical postpartum haemorrhage (estimated blood loss ≥500 mL or any blood loss sufficient to compromise haemodynamic stability); (2) WHO-defined postpartum haemorrhage (estimated blood loss of at least 500 mL); and (3) calculated postpartum haemorrhage (calculated estimated blood loss of ≥1000 mL). Calculated postpartum haemorrhage was estimated from the peripartum change in haemoglobin concentration and bodyweight. We used multivariable logistic regression to examine the association between haemoglobin and postpartum haemorrhage, adjusting for confounding factors. Findings: Of the 10 620 women recruited to the WOMAN-2 trial between Aug 24, 2019, and Nov 1, 2022, 10 561 (99·4%) had complete outcome data. 8751 (82·9%) of 10 561 women were recruited from hospitals in Pakistan, 837 (7·9%) from hospitals in Nigeria, 525 (5·0%) from hospitals in Tanzania, and 448 (4·2%) from hospitals in Zambia. The mean age was 27·1 years (SD 5·5) and mean prebirth haemoglobin was 80·7 g/L (11·8). Mean estimated blood loss was 301 mL (SD 183) for the 8791 (83·2%) women with moderate anaemia and 340 mL (288) for the 1770 (16·8%) women with severe anaemia. 742 (7·0%) women had clinical postpartum haemorrhage. The risk of clinical postpartum haemorrhage was 6·2% in women with moderate anaemia and 11·2% in women with severe anaemia. A 10 g/L reduction in prebirth haemoglobin increased the odds of clinical postpartum haemorrhage (adjusted odds ratio [aOR] 1·29 [95% CI 1·21–1·38]), WHO-defined postpartum haemorrhage (aOR 1·25 [1·16–1·36]), and calculated postpartum haemorrhage (aOR 1·23 [1·14–1·32]). 14 women died and 68 either died or had a near miss. Severe anaemia was associated with seven times higher odds of death or near miss (OR 7·25 [95% CI 4·45–11·80]) than was moderate anaemia. Interpretation: Anaemia is strongly associated with postpartum haemorrhage and the risk of death or near miss. Attention should be given to the prevention and treatment of anaemia in women of reproductive age. Funding: The WOMAN-2 trial is funded by Wellcome and the Bill & Melinda Gates Foundation

Gliclazide in Binary and Ternary Systems Improves Physicochemical Properties, Bioactivity, and Antioxidant Activity

The poor solubility of the antidiabetic drug gliclazide (Glc) is due to its hydrophobic nature. This research is aimed at improving Glc’s solubility and drug release profile, as well as at investigating additional benefits such as bioactivity and antioxidant activity, by forming binary complexes with HPβCD at different w/w ratios (1 : 1, 1 : 2.5, 1 : 4, and 1 : 9) and ternary complexes with HPβCD and Tryp at 1 : 1 : 1, 1 : 1 : 0.27, 1 : 2.5 : 0.27, 1 : 3.6 : 3.6, 1 : 4 : 1, and 1 : 9 : 1, respectively. Complexes were prepared by the physical mixing (PM) and solvent evaporation (SE) methods. The prepared inclusion complexes were meticulously characterized by X-ray diffractometry (XRD), scanning electron microscopy (SEM), and attenuated total reflectance-Fourier transform infrared (ATR-FTIR) spectra. To verify our findings, the inclusion complexes were evaluated by equilibrium solubility, in vitro drug release profile, kinetic models, and antidiabetic and antioxidant activities in animal models. Our results demonstrated that the solubility and drug release profile were found to be enhanced through binary as well as ternary complexes. Notably, ternary complexes with a ratio of 1 : 9 : 1 showed the highest solubility and drug release profile compared to all other preparations. Data on antioxidant activity indicated that the ternary complex had the higher total antioxidant status (TAS), superoxide dismutase (SOD), and catalase (CAT) activity than the binary complex and Glc alone, in contrast to the diabetic group. In vivo antidiabetic activity data revealed a high percentage reduction in the blood glucose level by ternary complexes (49–52%) compared to the binary complexes (45–46%; p≤0.05). HPβCD and Tryp provide a new platform for overcoming the challenges associated with poorly soluble Glc by providing greater complexing and solubilizing capabilities and imparting ancillary benefits to improve the drug’s antidiabetic and antioxidant activities