Preliminary assessment of the Healthy Early Life Moments (HELMS) webinars in empowering Developmental Origins of Health and Disease (DOHaD) concept among healthcare professionals - a pragmatic serial cross-sectional study.

OBJECTIVES: The Developmental Origins of Health and Disease (DOHaD) concept has gained prominence in maternal and child health (MCH), emphasizing how early-life factors impact later-life non-communicable diseases. However, a knowledge-practice gap exists in applying DOHaD principles among healthcare professionals. Healthy Early Life Moments in Singapore (HELMS) introduced webinars to bridge this gap and empower healthcare professionals. We aimed to conduct a preliminary assessment to gain early insights into the outreach and effectiveness of the educational initiative offered with the HELMS webinars. METHODS: We employed a pragmatic serial cross-sectional study approach and targeted healthcare professionals involved in MCH care. We also collected and analyzed data on webinar registration and attendance, participants' profession and organizational affiliations, and post-webinar survey responses. RESULTS: The median webinar attendance rate was 59.6 % (25th-75th percentile: 58.4-60.8 %). Nurses represented 68.6 % of attendees (n=2,589 out of 3,774). Post-webinar surveys revealed over 75 % of the participants providing positive responses to 14 out of 15 survey questions concerning content, delivery, applicability to work, and organization. CONCLUSIONS: Assessment of the HELMS webinars provided insight into the outreach and early effectiveness in enhancing healthcare professionals' knowledge and confidence in delivering DOHaD education. Bridging the knowledge-practice gap remains a crucial goal.

Associations of predominant night-eating with plasma glycemic status and continuous glucose monitoring measures among pregnant women.

BACKGROUND & AIMS: To examine whether predominant night-eating, defined as more than 50% of total daily energy intake consumed between 1900 and 0659 h, is associated with glycemic outcomes in pregnancy. METHODS: This was a prospective cohort study of 277 healthy pregnant women with complete 4-day dietary intake records at 18-24 weeks gestation, recruited from KK Women's and Children's Hospital, Singapore. Primary outcomes were fasting, 1-h, and 2-h plasma glucose after a 75-g oral glucose tolerance test at 24-28 weeks gestation. Secondary outcomes were gestational diabetes mellitus (GDM), fasting insulin, homeostasis model assessment of insulin resistance (HOMA2-IR), ß-cell function (HOMA2-%B), and continuous glucose monitoring (CGM) measures. Glucose variables in continuous form were loge-transformed before analyses. RESULTS: Predominant night-eating (11.6%) was associated with higher fasting glucose (geometric mean ratio (95% confidence interval) 1.05 (1.01, 1.08)) and 1-h glucose (1.11 (1.01, 1.21)), but not with 2-h glucose or GDM risk. Predominant night-eating women had lower fasting insulin (0.77 (0.63, 0.95)), lower HOMA2-IR (0.78 (0.64, 0.97)), and lower HOMA2-%B (0.77 (0.67, 0.89)) than their predominant day-eating counterparts. For CGM measures, predominant night-eating was associated with higher mean glucose (1.07 (1.00, 1.15)), higher glucose management indicator (1.05 (1.00, 1.10)), and higher overall glucose levels throughout 24 h (1.10 (1.02, 1.19)). All these associations were adjusted for socio-demographic, lifestyle factors, and diet composition. CONCLUSION: Predominant night-eating was mainly associated with less desirable glycemic outcomes during pregnancy. Future studies should explore dietary interventions aimed at reducing consumption of relatively more calories at night than day during pregnancy.

Perceptions and acceptance of COVID-19 vaccine among pregnant and lactating women in Singapore: A pre-vaccine rollout cross-sectional study.

Introduction: Vaccination is critical in controlling the coronavirus disease 2019 (COVID-19) pandemic. However, vaccine perception and acceptance among pregnant and lactating women is unknown in Singapore. We aimed to determine the acceptance of COVID-19 vaccination among these two groups of women in Singapore and the factors associated with vaccine acceptance. Methods: We conducted an anonymous, online survey on the perceptions of the COVID-19 vaccine and its acceptance by pregnant and lactating women at a tertiary maternal and child hospital in Singapore from 1 March to 31 May 2021. Information on their demographics and knowledge was collected. These factors were assessed for their relationship with vaccine acceptance. Results: A total of 201 pregnant and 207 lactating women participated. Vaccine acceptance rates in pregnant and lactating women were 30.3% and 16.9%, respectively. Pregnant women who were unsure or unwilling to take the vaccine cited concerns about safety of the vaccine during pregnancy (92.9%), while lactating women were concerned about its potential long-term negative effects on the breastfeeding child (75.6%). Factors that were positively associated with vaccine acceptance included a lower monthly household income or education level, appropriate knowledge regarding vaccine mechanism and higher perceived maternal risk of COVID-19. Most pregnant (70.0%) and lactating women (83.7%) were willing to take the vaccine only when more safety data during pregnancy and breastfeeding were available. Conclusion: COVID-19 vaccine acceptance was low among pregnant and lactating women in Singapore. Addressing the safety concerns when more data are available and education on the mechanism of vaccine action will likely improve acceptance among these women.

Distribution and association of interpregnancy weight change with subsequent pregnancy outcomes in Asian women.

The extent of interpregnancy weight change and its association with subsequent pregnancy outcomes among Asians remain unclear. We examined changes in maternal body mass index (BMI) between the first two deliveries and outcomes in the second delivery. Medical records of women with their first two consecutive deliveries between 2015 and 2020 at KK Women's and Children's Hospital, Singapore were retrieved. Gestational-age-adjusted BMI was determined by standardising to 12 weeks gestation and interpregnancy BMI change was calculated as the difference between both pregnancies. Pregnancy outcomes were analysed using modified Poisson regression models. Of 6264 included women with a median interpregnancy interval of 1.44 years, 40.7% had a stable BMI change within ± 1 kg/m2, 10.3% lost > 1 kg/m2, 34.3% gained 1-3 kg/m2 and 14.8% gained ≥ 3 kg/m2. Compared to women with stable BMI change, those with > 1 kg/m2 loss had higher risk of low birthweight (adjusted risk ratio [RR] 1.36; 95% confidence interval 1.02-1.80), while those with 1-3 kg/m2 gain had higher risks of large-for-gestational-age birth (1.16; 1.03-1.31), gestational diabetes (1.25; 1.06-1.49) and emergency Caesarean delivery (1.16; 1.03-1.31); these risks were higher in those with ≥ 3 kg/m2 gain. Our study strengthens the case for interpregnancy weight management to improve subsequent pregnancy outcomes.

Tranexamic acid, as an adjunct to oxytocin prophylaxis, in the prevention of postpartum haemorrhage in women undergoing elective caesarean section: A single-centre double-blind randomised controlled trial.

OBJECTIVE: To evaluate the effectiveness of tranexamic acid (TXA) in reducing blood loss during elective caesarean sections in women with and without risk factors for postpartum haemorrhage (PPH). DESIGN: A double-blind, randomised placebo-controlled trial. SETTING: An academic tertiary referral centre in Singapore. POPULATION: Multiethnic women aged 21 years or older undergoing elective caesarean section. METHODS: Randomisation to intravenous TXA or normal saline (placebo) 10 minutes before skin incision. MAIN OUTCOME MEASURES: Calculated estimated blood loss (cEBL), derived from blood volume and haematocrit levels. RESULTS: Between June 2020 and October 2021, 200 women were randomised to the placebo or TXA groups. Women who received prophylactic TXA had a significantly lower mean cEBL compared with those receiving placebo (adjusted mean difference -126.4 mL, 95% CI -243.7 to -9.1, p = 0.035). The effect was greatest in those at high risk for PPH, with a reduction in cEBL (mean difference -279.6 mL, 95% CI -454.8 to -104.3, p = 0.002) and a lower risk of cEBL ≥500 mL (risk ratio [RR] 0.54, 95% CI 0.36-0.83, p = 0.007) and cEBL ≥1000 mL (RR 0.44, 95% CI 0.20-0.98, p = 0.016). Subgroup analysis showed benefit for women with preoperative haemoglobin <10.5 g/dL (mean difference -281.9 mL, 95% CI -515.0 to -48.8, p = 0.019). There was no significant difference in need for additional medical or surgical interventions. There were no maternal or neonatal adverse outcomes. CONCLUSION: Prophylactic TXA should be considered in women with risk factors for PPH, and those most likely to benefit are those with preoperative haemoglobin <10.5 g/dL.

Modifiable Risk Factor Score and Fecundability in a Preconception Cohort in Singapore.

Importance: Although multiple modifiable risk factors have been identified for reduced fecundability (defined as lower probability of conception within a menstrual cycle), no scoring system has been established to systematically evaluate fecundability among females who are attempting to conceive. Objective: To examine the association of a risk score based on 6 modifiable factors with fecundability, and to estimate the percentage reduction in incidence of nonconception if all study participants achieved a minimal risk score level. Design, Setting, and Participants: This population-based cohort study obtained data from the S-PRESTO (Singapore Preconception Study of Long-Term Maternal and Child Outcomes) prospective cohort study. Females of reproductive age who were trying to conceive were enrolled from February 2015 to October 2017 and followed for 1 year, ending in November 2018. Data were analyzed from March to May 2022. Exposures: A reduced fecundability risk score was derived by giving participants 1 point for each of the following factors: unhealthy body mass index, unhealthy diet, smoking, alcohol intake, folic acid supplement nonuser, and older maternal age. Total scores ranged from 0 to 6 and were classified into 5 levels: level 1 (score of 0 or 1), level 2 (score of 2), level 3 (score of 3), level 4 (score of 4), and level 5 (score of 5 or 6). Main Outcomes and Measures: Fecundability, measured by time to conception in cycles, was analyzed using discrete-time proportional hazards models with confounder adjustment. Results: A total of 937 females (mean [SD] age, 30.8 [3.8] years) were included, among whom 401 (42.8%) spontaneously conceived within 1 year of attempting conception; the median (IQR) number of cycles before conception was 4 (2-7). Compared with participants with a level 1 risk score, those with level 2, 3, 4, and 5 risk scores had reductions in fecundability of 31% (adjusted fecundability ratio [FR], 0.69; 95% CI, 0.54-0.88), 41% (FR, 0.59; 95% CI, 0.45-0.78), 54% (FR, 0.46; 95% CI, 0.31-0.69) and 77% (FR, 0.23; 95% CI, 0.07-0.73), respectively. Assessment of the population attributable fraction showed that all participants achieving a minimal (level 1) risk level would be associated with a reduction of 34% (95% CI, 30%-39%) in nonconception within a year. Conclusions and Relevance: Results of this study revealed the co-occurrence of multiple modifiable risk factors for lowered fecundability and a substantially higher conception rate among participants with no or minimal risk factors. The risk assessment scoring system proposed is a simple and potentially useful public health tool for mitigating risks and guiding those who are trying to conceive.

Peritoneal autoantibody profiling identifies p53 as an autoantibody target in endometriosis.

OBJECTIVE: To map the peritoneal autoantibody (AAb) landscape in women with endometriosis. DESIGN: Case-control laboratory study. SETTING: Academic medical and research units. PATIENT(S): Women who presented with or without endometriosis. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Using native-conformation and citrullinated modified protein arrays, proteome-wide analysis of AAbs against 1,623 proteins were profiled in peritoneal fluids (PFs) of 25 women with endometriosis and 25 women without endometriosis. RESULT(S): In women with endometriosis, the median number of AAbs detected was 4, including AAbs that targeted autoantigens involved in implantation, B-cell activation/development, and aberrant migration and mitogenicity. Forty-six percent of women with endometriosis have ≥5 peritoneal AAbs. Conversely, in women without endometriosis, the median number of detected AAbs was 1. Autoantibodies recognizing tumor suppressor protein p53 were the most commonly detected AAbs, being present in 35% of women with endometriosis, and p53 AAb was associated with a monocyte/macrophage-like PF cytokine signature. Further investigation of the global reactivity of AAbs against citrullinated PF antigens by peptidylarginine deiminase enzymes 1, 2, and 6 revealed anticitrullinated p53 as the only AAb target elevated and citrullinated by all 3 peptidylarginine deiminase isotypes. Furthermore, unsupervised hierarchical clustering and integrative pathway analysis revealed that 60% of women with endometriosis-associated infertility were positive for AAbs, which are involved in platelet-derived growth factor, transforming growth factor-ß, RAC1/PAK1/p38/MMP2 signaling, LAT2/NTAL/LAB-mediated calcium mobilization, and integrin-mediated cell adhesion. CONCLUSION(S): Together, our data identify peritoneal autoimmunity in a significant subset of women with endometriosis, with implications on infertility and disease pathophysiology. In these patients, p53 was identified as the most frequent PF AAb target, which was present in both the native and citrullinated forms.

Developmental origins of health and disease: knowledge, attitude and practice of obstetrics & gynecology residents, pediatric residents, and medical students.

Developmental Origin of Health and Disease (DOHaD) explains how the health of the mother influences the offspring's risk of non-communicable diseases in later life. However, this remains underutilized in clinical practice. This study aimed to investigate the knowledge, attitude, and practice (KAP) of medical students, Obstetrics and Gynecology (O&G) and Pediatrics residents, toward DOHaD, identify potential barriers to DOHaD counseling, and translate DOHaD concepts into clinical practice. This cross-sectional study was conducted with a multi-section digital questionnaire, rated on a five-point Likert scale (1-5), with a higher score indicating better KAP. The scores between groups were compared using ANOVA. A total of 117 participants, comprising medical students (n = 75, 64.1 percent), O&G (n = 33, 28.2 percent) and Pediatric residents (n = 9, 7.7 percent), completed the questionnaire. The mean scores for the "Knowledge," "Attitude" and "Practice" sections were 3.73 (standard deviation 0.82), 4.27 (0.59) and 3.03 (0.52), respectively. O&G residents scored higher for the "Practice" section than Pediatric residents (mean scores 3.17 vs. 2.16; p = .048). Overall, the participants demonstrated good knowledge and attitude, but poor practice toward DOHaD. Thus, there is a need to improve education and training for health care professionals, develop a structured implementation framework, and provide a transdisciplinary care continuum for mother and child.

Defects in protective cytokine profiles in spontaneous miscarriage in the first trimester.

OBJECTIVE: To study differences in cytokine expression profiles between women with ongoing pregnancy and those experiencing spontaneous miscarriage, among women who presented with threatened miscarriage before week 16 of gestation. DESIGN: Prospective cohort study. SETTING: Academic hospital. PATIENT(S): In this prospective cohort study, 155 pregnant women, comprising normal pregnant women recruited from antenatal clinics (n = 97) and women with threatened miscarriage recruited from an emergency walk-in clinic (n = 58). INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Sixty-five serum cytokines quantified using multiplex immunoassay correlated with miscarriage outcomes. RESULT(S): Among women presenting with threatened miscarriage, those who eventually miscarried had significantly lower levels of interleukin (IL)-2, IL-12p70, IL-17A, B-cell-activating factor, B lymphocyte chemoattractant, basic nerve growth factor, interferon-γ, tumor necrosis factor-related apoptosis-inducing ligand, thymic stromal lymphopoietin, and tumor necrosis factor-α and higher levels of vascular endothelial growth factor A, IL-21, and stromal cell-derived factor 1α than those with ongoing pregnancy. Comparisons between normal pregnancies and women with threatened miscarriage who eventually miscarried revealed significant differences across 7 cytokines: B-cell-activating factor; B lymphocyte chemoattractant; basic nerve growth factor; IL-17A; fractalkine/CX3CL1; vascular endothelial growth factor A; and CCL22. Vascular endothelial growth factor A exhibited a negative correlation with the progesterone level (r = -0.270). The cluster of significant cytokines alludes to T cell proliferation, B-cell proliferation, natural killer cell-mediated cytotoxicity, and apoptosis as important pathways that determine pregnancy outcomes. Bioinformatic analysis further revealed alteration of the suppressor of cytokine signaling proteins family of Janus kinase-signal transducer and activator of transcription signaling axis by cytokines as a plausible key molecular mechanism in spontaneous miscarriage. CONCLUSION(S): This study demonstrates that the regulated balance between the proinflammatory and anti-inflammatory pathways is crucial to maintaining pregnancy. A better understanding of the cytokines associated with immunomodulatory effects may lead to novel targets for the prediction and treatment of spontaneous miscarriage.

The Effect of Vitamin D Supplementation in Pregnant Women with Overweight and Obesity: A Randomised Controlled Trial.

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.

Decreased Innate Migration of Pro-Inflammatory M1 Macrophages through the Mesothelial Membrane Is Affected by Ceramide Kinase and Ceramide 1-P.

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-1ß, TNF-α, TNF-ß, 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.

Effects of an integrated mobile health lifestyle intervention among overweight and obese women planning for pregnancy in Singapore: protocol for the single-arm healthy early life moments in Singapore (HELMS) study.

INTRODUCTION: Changes in social and lifestyle factors have led to increasing rates of metabolic and mental health problems. We hypothesise that a transformation of the current maternal and child health system is required to deliver interventions that effectively promote a good start to life in populations at risk of metabolic and mental health problems. We describe a single-arm implementation study 'Healthy Early Life Moments in Singapore', which aims to examine whether an integrated lifestyle intervention initiated at preconception and continuing throughout pregnancy and postpartum periods can improve the metabolic and mental health of overweight and obese women, and improve early child growth. METHODS AND ANALYSIS: This single-centre implementation trial is conducted at KK Women's and Children's Hospital, Singapore. The trial aims to recruit 500 women, aged 21-40 years with a body mass index of 25-40 kg/m2 who plan to get pregnant, with interventions delivered before conception, until 18 months postdelivery. Primary outcomes comprise pregnancy rate, maternal metabolic and mental health status. Secondary outcomes include maternal reproductive health, pregnancy outcomes and offspring growth. The intervention will be delivered using a mobile health application, to provide anticipatory guidance, raise awareness and guide goal-setting on lifestyle behaviours that include diet, physical activity, mental wellness and sleep hygiene from preconception to postpartum. Women who conceive within 1 year of recruitment will be followed through pregnancy and studied with their infants at six-time points during the first 18 months of life. Questionnaires, anthropometric measurements and multiple biosamples will be collected at each visit. ETHICS AND DISSEMINATION: The study has been approved by the Centralised Institutional Review Board of SingHealth (2021/2247). Written informed consent will be obtained from all participants. The findings will be published in peer-reviewed journals and disseminated to national and international policy makers. TRIAL REGISTRATION NUMBER: NCT05207059.

Dietary Supplement Intake and Fecundability in a Singapore Preconception Cohort Study.

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.

A Golden Thread approach to transforming Maternal and Child Health in Singapore.

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.

Nocturnal Lifestyle Behaviours and Risk of Poor Sleep during Pregnancy.

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 (ß 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.

Developing a lifestyle intervention program for overweight or obese preconception, pregnant and postpartum women using qualitative methods.

The time period before, during and after pregnancy represents a unique opportunity for interventions to cultivate sustained healthy lifestyle behaviors to improve the metabolic health of mothers and their offspring. However, the success of a lifestyle intervention is dependent on uptake and continued compliance. To identify enablers and barriers towards engagement with a lifestyle intervention, thematic analysis of 15 in-depth interviews with overweight or obese women in the preconception, pregnancy or postpartum periods was undertaken, using the integrated-Promoting Action on Research Implementation in Health Services framework as a guide to systematically chart factors influencing adoption of a novel lifestyle intervention. Barrier factors include time constraints, poor baseline knowledge, family culture, food accessibility, and lack of relevant data sources. Enabling factors were motivation to be healthy for themselves and their offspring, family and social support, a holistic delivery platform providing desired information delivered at appropriate times, regular feedback, goal setting, and nudges. From the findings of this study, we propose components of an idealized lifestyle intervention including (i) taking a holistic life-course approach to education, (ii) using mobile health platforms to reduce barriers, provide personalized feedback and promote goal-setting, and (iii) health nudges to cultivate sustained lifestyle habits.

Abdominal heterotopic pregnancy post-IVF double embryo transfer.

Uterosacral ligament (USL) is an uncommon site of implantation for abdominal ectopic pregnancies. This is the first case of USL heterotopic pregnancy post invitro fertilisation (IVF). The patient presented 6 weeks after a double embryo transfer with acute onset abdominal pain and was diagnosed with a suspected live tubal ectopic pregnancy with a viable intrauterine pregnancy on ultrasound. A diagnostic laparoscopy revealed an ectopic pregnancy implanted on the left USL which was resected and confirmed on histology. The patient was discharged well on postoperative day 2 with a viable intrauterine pregnancy. This case highlights the importance of considering non-tubal heterotopic pregnancies in the context of risk factors including IVF with double embryo transfer presenting with abdominal pain.

Maternal meal irregularities during pregnancy and lifestyle correlates.

Meal regularity can influence metabolic health. However, habits of skipping and delaying meals are rarely studied among pregnant women. This study examined the incidence of maternal meal skipping and meal delaying, and their associated lifestyle patterns during pregnancy. Pregnant women in the second trimester (18-24 weeks' gestation; n = 90) were recruited from the antenatal clinics in KK Women's and Children's Hospital, Singapore, 2019-2020. Data on sociodemographic, lifestyle and dietary habits were collected. Firstly, principal component analysis was used to identify lifestyle patterns. Subsequently, multiple logistic regression model was used to examine the association of lifestyle patterns with meal skipping and delaying. In total, 32 (35.6%) women had irregular meals, in which 25 (27.8%) and 26 (28.9%) women reported meal skipping and meal delaying for at least 3 times a week, respectively. Women with 'poor sleep and emotion' pattern as characterized by higher scores for poor sleep, depression, anxiety, and stress symptoms were associated with higher odds of meal skipping (OR 1.99; 95% CI 1.13, 3.53) and meal delaying (2.50; 1.31, 4.79). 'Sedentary' pattern, as characterized by greater daily time spent on television and screen electronic devices, and 'weight and inactivity' pattern, as characterized by higher BMI and physical inactivity level, were not associated with meal regularity. In this study, almost one-third of women reporting meal irregularities during pregnancy. 'Poor sleep and emotion' pattern is associated with a higher incidence of meal skipping and delaying. These findings suggest the need to address sleep and emotional health in interventions promoting healthy nutrition specifically regular eating in pregnancy.

Metabolic health status and fecundability in a Singapore preconception cohort study.

BACKGROUND: Obesity compromises metabolic health and female fertility, yet not all obese women are similar in metabolic status. The extent to which fecundability is influenced by the metabolic health status of women who are overweight or obese before conception is unknown. OBJECTIVE: This study aimed to: (1) determine the metabolic health status, and (2) examine the association between metabolic health status and fecundability of overweight and obese women trying to conceive in the Singapore PREconception Study of long-Term maternal and child Outcomes cohort study. STUDY DESIGN: We conducted a prospective preconception cohort study of Asian women (Chinese, Malay, and Indian) aged 18 to 45 years trying to conceive who were treated from 2015 to 2017 in KK Women's and Children's Hospital in Singapore (n=834). We defined women to have metabolically unhealthy status if they: (1) met 3 or more modified Joint Interim Statement metabolic syndrome criteria; or (2) had homeostasis model assessment-insulin resistance index ≥2.5. Body mass index was categorized as normal (18.5-22.9 kg/m2), overweight (23-27.4 kg/m2), or obese (≥27.5 kg/m2) on the basis of cutoff points for Asian populations. Fecundability was measured by time to pregnancy in menstrual cycles within a year of enrolment. Discrete-time proportional hazards models were used to estimate fecundability odds ratios, with adjustment for confounders and accounting for left truncation and right censoring. RESULTS: Of 232 overweight women, 28 (12.1%) and 25 (10.8%) were metabolically unhealthy by metabolic syndrome ≥3 criteria and homeostasis model assessment-insulin resistance ≥2.5, respectively. Of 175 obese women, 54 (30.9%) and 93 (53.1%) were metabolically unhealthy by metabolic syndrome ≥3 criteria and homeostasis model assessment-insulin resistance ≥2.5, respectively. Compared with metabolically healthy normal-weight women, lower fecundability was observed in metabolically unhealthy overweight women on the basis of metabolic syndrome criteria (fecundability odds ratios, 0.38 [95% confidence interval, 0.15-0.92]) and homeostasis model assessment-insulin resistance (fecundability odds ratios, 0.68 [95% confidence interval, 0.33-1.39]), with metabolic syndrome criteria showing a stronger association. Metabolically unhealthy obese women showed lower fecundability than the healthy normal-weight reference group by both metabolic syndrome (fecundability odds ratios, 0.35; 95% confidence interval, 0.17-0.72) and homeostasis model assessment-insulin resistance criteria (fecundability odds ratios, 0.43; 95% confidence interval, 0.26-0.71). Reduced fecundability was not observed in overweight or obese women who showed healthy metabolic profiles by either definition. CONCLUSION: Overweight or obesity was not synonymous with having metabolic syndrome or insulin resistance. In our preconception cohort, metabolically unhealthy overweight and obese women showed reduced fecundability, unlike their counterparts who were metabolically healthy. These findings suggest that metabolic health status, rather than simply being overweight and obese per se, plays an important role in fecundability.

Development and Validation of a Lifestyle Behavior Tool in Overweight and Obese Women through Qualitative and Quantitative Approaches.

There is a paucity of effective intervention tools for overweight/obese women to assess, guide and monitor their eating behavior. This study aimed to develop a lifestyle intervention tool, assess its acceptability and usefulness, and verify its construct validity in overweight/obese women. The 6P tool (Portion, Proportion, Pleasure, Phase, Physicality, Psychology) was developed and 15 women with a body mass index (BMI) ≥ 25 kg/m2 were interviewed to assess its perceived acceptability and usefulness. Subsequently, the revised 6P tool was tested in 46 women with a BMI ≥ 25 kg/m2. The Three-Factor Eating Questionnaire (TFEQ), International Physical Activity Questionnaire-Short (IPAQ), and weight were measured at baseline and one-month. Most participants were satisfied with the presentation of the 6P tool (86.8%), and agreed it was useful in guiding healthy eating (81.6%) and raising awareness of eating behavior (97.4%). There were significant improvements in cognitive restraint (p = 0.010) and disinhibition (p = 0.030) (TFEQ), portion size (P1), pleasure behaviors (P3), and total composite 6P score (p < 0.001). However, there was no significant reduction in weight or increase in physical activity. The 6P tool is acceptable and presents with good validity for assessing lifestyle behaviors.