In this review, we discuss the potential use of antimalarial drugs as an adjuvant therapy for preeclampsia, focusing on the mechanisms of action of this class of drugs in the context of preeclampsia. In particular, hydroxychloroquine has been shown to have various beneficial effects on patients with systemic lupus erythematosus. There are several pathways targeted by the antimalarial drugs that are similar to the pathophysiology of preeclampsia and hence offering opportunities to develop novel therapies to treat the disease. Given the safety profile of hydroxychloroquine in pregnancy, there is merit in exploring the efficacy of this drug as an adjuvant therapy in women with early onset preeclampsia.
In preeclampsia, widespread maternal endothelial dysfunction is often secondary to excessive generation of placental-derived anti-angiogenic factors, including soluble fms-like tyrosine kinase-1 (sFlt-1) and soluble endoglin (sEng), along with proinflammatory cytokines such as tumour necrosis factor-α (TNF-α) and activin A, understanding of which offers potential opportunities for the development of novel therapies. The antimalarial hydroxychloroquine is an anti-inflammatory drug improving endothelial homeostasis in lupus. It has not been explored as to whether it can improve placental and endothelial function in preeclampsia. In this in vitro study, term placental explants were used to assess the effects of hydroxychloroquine on placental production of sFlt-1, sEng, TNF-α, activin A, and 8-isoprostane after exposure to hypoxic injury or oxidative stress. Similarly, human umbilical vein endothelial cells (HUVECs) were used to assess the effects of hydroxychloroquine on in vitro markers of endothelial dysfunction. Hydroxychloroquine had no effect on the release of sFlt-1, sEng, TNF-α, activin A, or 8-isoprostane from placental explants exposed to hypoxic injury or oxidative stress. However, hydroxychloroquine mitigated TNF-α-induced HUVEC production of 8-isoprostane and Nicotinanamide adenine dinucleotide phosphate (NADPH) oxidase expression. Hydroxychloroquine also mitigated TNF-α and preeclamptic serum-induced HUVEC monolayer permeability and rescued the loss of zona occludens protein zona occludens 1 (ZO-1). Although hydroxychloroquine had no apparent effects on trophoblast function, it may be a useful endothelial protectant in women presenting with preeclampsia.
Gestational diabetes mellitus (GDM) is associated with maternal and neonatal complications. We aimed to evaluate the relationship between the abnormalities of the oral glucose tolerance test (OGTT) and adverse pregnancy outcomes. This was a retrospective study of GDM patients over a five-year period in a Malaysian tertiary center. The diagnosis of GDM was based on the National Institute for Health and Care Excellence (NICE) guideline. The data on patients’ demographics, OGTT results, GDM treatment, and pregnancy outcomes were analyzed. A total of 1105 women were included in the final analysis. The percentage of women with isolated abnormal fasting glucose, isolated two-hour abnormality, and both abnormal values were 4.8%, 87.1%, and 8.1%, respectively. Women with both OGTT abnormalities had a higher risk of preeclampsia (odds ratio (OR) 4.73; 95% confidence interval (CI) 1.45–15.41) and neonatal hypoglycemia (OR 8.78; 95% CI 1.93–39.88). Isolated postprandial abnormality was associated with an 80% lesser risk of neonatal hypoglycemia (OR 0.19; 95% CI 0.04–0.87). Both isolated fasting and multiple OGTT abnormalities were associated with insulin therapy. Multiple OGTT abnormalities were a positive predictor of adverse pregnancy outcomes, while isolated postprandial abnormality was associated with a lesser risk of neonatal complication. Further prospective study is essential to validate these findings.
Pregnant women are susceptible to COVID-19 complications due to gestation-related physiological changes. We aimed to evaluate the level of maternal knowledge, perception, and practice during the pandemic. A cross-sectional study was conducted during the Malaysian Movement Control Order (MCO) between April and June 2020. A self-administered electronic questionnaire that included the knowledge and practice domains was distributed. A newly designed set of questions was used to evaluate (1) women’s perception of MCO and (2) maternal experience, which was subdivided into clinical care provision and maternal anxiety. The survey response rate was 93% with the final number for analysis of 415. The majority of women (95%) demonstrated an adequate level of knowledge on COVID-19, whilst 99% had a good practice. We found that tertiary education (p < 0.001), employment status (p = 0.03), higher household income (p < 0.001), and multiple sources of information (p < 0.001) were independent predictors of adequate maternal knowledge on COVID-19. Women with adequate knowledge also reported a more positive perception of MCO (p < 0.001) and better obstetric care experience (p = 0.037), as did those of Malay ethnicity. Younger (p < 0.001) and nulliparous (p = 0.01) women demonstrated greater anxiety levels. The majority of our women reported good practice and adequate knowledge, which contributed to a positive perception of MCO and better maternal obstetric experience. First-time mothers may benefit from extra support and reassurance during the pandemic to alleviate maternal anxiety.
Pap smear screening can detect cervical cancer early, but is underutilized. Motivational factors play a role in ensuring that women undergo Pap smear screening. This study was conducted to validate the adapted instrument, which was based on the protection motivation theory (PMT), into the Malay language to evaluate the motivational factors for Pap smear screening among women. The original 26-item PMT scale was developed based on seven constructs of the PMT framework. The adaptation involved translation by bilingual experts (n = 4), followed by synthesis (n = 6). Subsequently, we performed content validation (content validation index, CVI) among the health experts (n = 5) and face validation (face validation index, FVI) among women (n = 11). Reliability testing for internal consistency was determined via the confirmatory factor analysis (CFA) of women aged between 21 and 65 years (n = 150). One item was deleted based on the expert consensus, leaving a total of 25 items after the adaptation. The validation yielded a good CVI and FVI. Prior to CFA reliability testing, one item was deleted due to very low factor loading. The CFA indicated a good fit for 24 items. The factor loading (range: 0.45–0.98), average variance extracted (range: 0.44–0.90), and composite reliability (range: 0.69–0.97) indicated that the convergent validity for each construct was acceptable, except for the perceived vulnerability. However, the perceived vulnerability construct was accepted based on expert verification. We confirmed that the translation, cross-cultural, adaptation, and validation of the Malay-version PMT scale were valid and reliable. The scale contains 24 items that represent the seven constructs of the PMT framework.