Endometriosis is a common inflammatory gynecological disorder which causes pelvic scarring, pain, and infertility, characterized by the implantation of endometrial-like lesions outside the uterus. The peritoneum, ovaries, and deep soft tissues are the commonly involved sites, and endometriotic lesions can be classified into three subphenotypes: superficial peritoneal endometriosis (PE), ovarian endometrioma (OE), and deep infiltrating endometriosis (DIE). In 132 women diagnosed laparoscopically with and without endometriosis (n = 73, 59 respectively), and stratified into PE, OE, and DIE, peritoneal fluids (PF) were characterized for 48 cytokines by using multiplex immunoassays. Partial-least-squares-regression analysis revealed distinct subphenotype cytokine signatures—a six-cytokine signature distinguishing PE from OE, a seven-cytokine signature distinguishing OE from DIE, and a six-cytokine-signature distinguishing PE from DIE—each associated with different patterns of biological processes, signaling events, and immunology. These signatures describe endometriosis better than disease stages (p < 0.0001). Pathway analysis revealed the association of ERK1 and 2, AKT, MAPK, and STAT4 linked to angiogenesis, cell proliferation, migration, and inflammation in the subphenotypes. These data shed new insights on the pathophysiology of endometriosis subphenotypes, with the potential to exploit the cytokine signatures to stratify endometriosis patients for targeted therapies and biomarker discovery.

Maternal and child health (MCH) in Singapore is entering a new phase, with challenges different to those faced 50 years ago. The advancement of medical technologies and access to MCH resources have led to a dramatic fall in maternal and infant mortality rates. However, there has been a steep rise in the rates of obesity and related metabolic diseases. Alongside this is an emerging mental wellness challenge, with one in ten women experience depression across pre-, during and post-pregnancy. Maternal obesity and mental disorders before and during pregnancy not only increase a woman’s risk of pregnancy complications, but also result in increased risks in the offspring of childhood obesity, behavioral disorders and later life metabolic disease, catalyzing vicious cycles of disease. Thus, there is a pressing need to transform the current MCH system to address a burgeoning metabolic and mental health challenge for Singapore. Initiating interventions during preconception and continuing into the postpartum has the potential to confer long-term maternal-child benefits, promoting virtuous cycles of health. However, the current MCH system emphasizes antenatal care and lacks focus on the equally, if not more important, preconception, postpartum and inter-pregnancy stages. We describe a new model-of-care framework that integrates a life-course approach to health across preconception, pregnancy and postpartum phases, with the social-ecological model comprising individual, interpersonal, institutional, community and policy as the major targets for health promotion interventions. This “golden thread” approach is being established at the Singapore KK Women’s and Children’s Hospital (KKH), to address both metabolic and mental health challenges to achieve the goal of a thriving, healthy nation. This new model-of-care is set up in KKH as a pilot program known as Healthy Early Life Moments in Singapore (HELMS). HELMS will reach out to women planning to conceive through coordinated interventions across preconception, pregnancy and postpartum periods. A mobile health platform is being developed to facilitate interventions and engage participants in the program through a digital, personalized and interactive approach. This new model-of-care is designed to secure a population with healthy life cycles, by influencing each life-course, early-in-life, to provide the best start for generations to come.

The impact of vitamin D supplementation on 25-hydroxyvitamin D (25OHD) levels, metabolic status, and pregnancy outcomes in pregnant women with overweight and obesity (OW/OB) is uncertain. This study aimed to examine whether administrating 800 IU of vitamin D3 orally would improve maternal serum 25OHD levels, lipid profile, and pregnancy outcomes compared to 400 IU. This was a two-arm, parallel, non-blinded randomised controlled trial involving 274 pregnant women recruited from KK Women’s and Children’s Hospital, with a body mass index of ≥25 kg/m² within 16 weeks gestation. The participants were randomly assigned to receive 800 IU/day (intervention group) or 400 IU/day (control group) of oral vitamin D3 supplements. The primary outcomes were maternal serum 25OHD and lipid levels at 24–28 weeks gestation. The secondary outcomes included maternal and birth outcomes. Compared with controls (n = 119), the intervention group (n = 112) exhibited higher 25OHD levels at 24–28 weeks gestation (adjusted mean difference 6.52 nmol/L; 95% confidence interval 2.74, 10.31). More women in the intervention group achieved sufficient 25OHD levels (77.7% vs. 55.5%; p < 0.001). No differences were observed in lipid profiles or maternal or birth outcomes between the groups. An additional 400 IU of oral vitamin D3 supplementation increased serum 25OHD levels but did not impact lipid profiles or pregnancy outcomes.

Subfertility is a global problem affecting millions worldwide, with declining total fertility rates. Preconception dietary supplementation may improve fecundability, but the magnitude of impact remains unclear. This prospective cohort study aimed to examine the association of preconception micronutrient supplements with fecundability, measured by time to pregnancy (TTP). The study was conducted at KK Women’s and Children’s Hospital, Singapore, between February 2015 and October 2017, on 908 women aged 18-45 years old, who were trying to conceive and were enrolled in the Singapore PREconception Study of long-Term maternal and child Outcomes (S-PRESTO). Baseline sociodemographic characteristics and supplement intake were collected through face-to-face interviews. The fecundability ratio (FR) was estimated using discrete-time proportional hazard modelling. Adjusting for potentially confounding variables, folic acid (FA) (FR 1.26, 95% confidence interval 1.03–1.56) and iodine (1.28, 1.00–1.65) supplement users had higher fecundability compared to non-users. Conversely, evening primrose oil supplement users had lower fecundability (0.56, 0.31–0.99) than non-users. In this study, preconception FA and iodine supplementation were associated with shortened TTP, while evening primrose oil use was associated with longer TTP. Nonetheless, the association between supplement use and the magnitude of fecundability changes will need to be further confirmed with well-designed randomised controlled trials.

The extent to which lifestyle practices at night influence sleep quality in pregnant women remains unknown. This study aimed to examine whether nocturnal behaviours were associated with poor sleep during pregnancy. We performed a cross-sectional analysis of a prospective cohort of pregnant women at 18–24 gestation weeks recruited from KK Women’s and Children’s Hospital, Singapore, between 2019 and 2021. Nocturnal behaviours were assessed with questionnaires, and sleep quality was measured using the Pittsburgh Sleep Quality Index (PSQI) with a global score ≥5 indicative of poor sleep quality. Modified Poisson regression and linear regression were used to examine the association between nocturnal behaviour and sleep quality. Of 299 women, 117 (39.1%) experienced poor sleep. In the covariate-adjusted analysis, poor sleep was observed in women with nocturnal eating (risk ratio 1.51; 95% confidence interval [CI] 1.12, 2.04) and nocturnal artificial light exposure (1.63; 1.24, 2.13). Similarly, nocturnal eating (β 0.68; 95% CI 0.03, 1.32) and light exposure (1.99; 1.04, 2.94) were associated with higher PSQI score. Nocturnal physical activity and screen viewing before bedtime were not associated with sleep quality. In conclusion, reducing nocturnal eating and light exposure at night could potentially improve sleep in pregnancy.

The retrograde flow of endometrial tissues deposited into the peritoneal cavity occurs in women during menstruation. Classically (M1) or alternatively (M2) activated macrophages partake in the removal of regurgitated menstrual tissue. The failure of macrophage egress from the peritoneal cavity through the mesothelium leads to chronic inflammation in endometriosis. To study the migration differences of macrophage phenotypes across mesothelial cells, an in vitro model of macrophage egress across a peritoneal mesothelial cell monolayer membrane was developed. M1 macrophages were more sessile, emigrating 2.9-fold less than M2 macrophages. The M1 macrophages displayed a pro-inflammatory cytokine signature, including IL-1α, IL-1β, TNF-α, TNF-β, and IL-12p70. Mass spectrometry sphingolipidomics revealed decreased levels of ceramide-1-phosphate (C1P), an inducer of migration in M1 macrophages, which correlated with its poor migration behavior. C1P is generated by ceramide kinase (CERK) from ceramide, and blocking C1P synthesis via the action of NVP231, a specific CERK chemical inhibitor, prohibited the emigration of M1 and M2 macrophages up to 6.7-fold. Incubation with exogenously added C1P rescued this effect. These results suggest that M1 macrophages are less mobile and have higher retention in the peritoneum due to lower C1P levels, which contributes to an altered peritoneal environment in endometriosis by generating a predominant pro-inflammatory cytokine environment.