Evaluating the Effects of the Supportive Parenting App on Infant Developmental Outcomes: Longitudinal Study.

BACKGROUND: Previous studies have investigated the various effects of parenting on infant developmental outcomes. In particular, parental stress and social support have been found to significantly affect the growth of the newborn. Although many parents today use mobile apps to obtain more support in parenting and perinatal care, few studies have examined how these apps could affect infant development. OBJECTIVE: This study aimed to examine the effectiveness of the Supportive Parenting App (SPA) in improving infant developmental outcomes during the perinatal period. METHODS: This study adopted a 2-group parallel prospective longitudinal design and recruited 200 infants and their parents (N=400 mothers and fathers). The parents were recruited at 24 weeks of gestation for a randomized controlled trial conducted from February 2020 to July 2022. They were randomly allocated to either the intervention or control group. The infant outcome measures included cognition, language, motor skills, and social-emotional development. Data were collected from the infants when they were aged 2, 4, 6, 9, and 12 months. Linear and modified Poisson regressions were used to analyze the data to examine between- and within-group changes. RESULTS: At 9 and 12 months post partum, the infants in the intervention group were found to have better communication and language skills than those in the control group. An analysis of motor development revealed that a larger proportion of the infants in the control group fell under the at-risk category, where they scored approximately 2 SDs below the normative scores. The control group infants scored higher on the problem solving domain at 6 months post partum. However, at 12 months postpartum, the infants in the intervention group performed better on cognitive tasks than those in the control group. Despite not being statistically significant, the intervention group infants were found to have consistently scored better on the social components of the questionnaires than the control group infants. CONCLUSIONS: Overall, the infants whose parents had received the SPA intervention tended to fare better in most developmental outcome measures than those whose parents had received standard care only. The findings of this study suggest that the SPA intervention exerted positive effects on the communication, cognition, motor, and socioemotional development of the infants. Further research is needed to improve the content and support provided by the intervention to maximize the benefits gained by infants and their parents. TRIAL REGISTRATION: ClinicalTrials.gov NCT04706442; https://clinicaltrials.gov/ct2/show/NCT04706442.

Evaluating the Effectiveness of the Supportive Parenting App on Parental Outcomes: Randomized Controlled Trial.

BACKGROUND: Adjusting to new or additional parenting responsibilities increases stress and affects parental well-being. Existing research has highlighted both parents' desire to receive more support. It has also been found that receiving sufficient social support enhances parenting outcomes. With the increasing popularity of mobile health apps, a Supportive Parenting App (SPA) intervention was developed to fulfill the support needs of parents during the perinatal period. OBJECTIVE: This study aimed to examine the effectiveness of the SPA on parental outcomes during the perinatal period. METHODS: A 2-group pretest and repeated posttest randomized controlled trial was conducted wherein 200 couples (N=400 mothers and fathers) were recruited from 2 public health care institutions in Singapore. Parents were randomly assigned to intervention (100/200, 50%) or control (100/200, 50%) groups. The SPA intervention consisted of a mobile app-based psychoeducation and peer support program to support parents from pregnancy to 6 months post partum. The outcome measures included postnatal depression, anxiety, parental bonding, parental self-efficacy, perceived social support, and parenting satisfaction. Data were collected at baseline (at >24 weeks of gestation-age of viability in Singapore) and at the first, second, fourth, sixth, ninth, and 12th month post partum. Linear mixed models were used to compare parental outcomes between the groups, and a linear mixed model for repeated measures was used to examine within-group changes. RESULTS: Parents in the intervention group mostly showed better outcomes compared with those in the control group. Parents in the intervention group had higher perceived social support than those in the control group at the first (effect size=1.59, 95% CI 0.38-2.80; Cohen standardized effect size=1.31; P=.01), second (effect size=1.98, 95% CI 1.09-2.88; Cohen standardized effect size=2.21; P=.003), and fourth (effect size=2.57, 95% CI 1.62-3.51; Cohen standardized effect size=2.72; P=.048) months post partum. However, parents in the intervention group showed significantly poorer parental bonding (effect size=1.67, 95% CI 0.24-3.11; Cohen standardized effect size=1.16; P=.02). The other parental outcomes did not differ significantly between groups. The scores of mothers and fathers also differed significantly for all outcomes except parental self-efficacy. CONCLUSIONS: Parents in the intervention group generally fared better, especially regarding perceived social support. However, the lack of statistical significance in most outcomes showed the limited effectiveness of the SPA intervention, which may be because of the COVID-19 pandemic. Parental differences in outcome scores suggest that mothers and fathers have different support needs; therefore, interventions should be tailored accordingly. Further improvements and evaluations are needed to examine the effectiveness of the SPA intervention in enhancing parental outcomes. Despite statistically insignificant results, limitations should be considered to further improve mobile health app-based interventions such as SPA, as they could serve as reliable and convenient sources of support for parents. TRIAL REGISTRATION: Clinicaltrails.gov NCT4706442; https://clinicaltrials.gov/ct2/show/NCT04706442.

Perinatal support for couples during COVID-19: A descriptive qualitative study.

AIMS AND OBJECTIVES: To explore the perspectives of parents during the perinatal period amid the COVID-19 pandemic and explore the experiences of Singaporean parents receiving perinatal support via the Supportive Parenting App (SPA). BACKGROUND: The stressors accompanying parenting responsibilities often affect the overall well-being of the family unit. With the emergence of the COVID-19 pandemic, Singaporean parents are forced to shoulder childcare responsibilities with minimal support due to safety restrictions. The Supportive Parenting Application (SPA) was introduced to parents during the start of the pandemic to offer timely additional support. It is a mobile health application-based educational support for parents across the perinatal period, consisting of features such as peer support, expert advice and discussion forums. DESIGN: Descriptive qualitative study. METHODS: Semi-structured one-to-one interviews were conducted with 33 parents (16 from the control group, 17 from the intervention group) in an ongoing randomised controlled trial between June 2021 and February 2022. The COREQ checklist was used to guide the reporting of the data. RESULTS: Four themes with 10 subthemes describing the perinatal experiences of parents were identified. The themes include 'Ups and downs' of parenting experiences; Perinatal care from 'best care' to 'flying blind'; What kept couples going and Use of technology-a way forward. CONCLUSION: Although COVID-19 negatively affected parents' availability of care and support, most could still access other support sources to help them. Additionally, the SPA was found to be a dependable information source for the intervention group parents. Future research could work on improving technology-based support based on the feedback given to offer better quality perinatal care for parents. RELEVANCE TO CLINICAL PRACTICE: Technology-based support provided by healthcare professionals helps provide reliable perinatal information and support for parents. More efforts should be directed towards developing quality informational resources and support to improve perinatal care. PATIENT OR PUBLIC CONTRIBUTION: Patients/members of the public contributed to the data collected and were involved in member checking to ensure the rigour of the study. CLINICAL TRIAL REGISTRATION NUMBER: NHG DSRB: 2019/00875.

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.

Risk score to stratify miscarriage risk levels in preconception women.

Spontaneous miscarriage is one of the most common complications of pregnancy. Even though some risk factors are well documented, there is a paucity of risk scoring tools during preconception. In the S-PRESTO cohort study, Asian women attempting to conceive, aged 18-45 years, were recruited. Multivariable logistic regression model coefficients were used to determine risk estimates for age, ethnicity, history of pregnancy loss, body mass index, smoking status, alcohol intake and dietary supplement intake; from these we derived a risk score ranging from 0 to 17. Miscarriage before 16 weeks of gestation, determined clinically or via ultrasound. Among 465 included women, 59 had miscarriages and 406 had pregnancy ≥ 16 weeks of gestation. Higher rates of miscarriage were observed at higher risk scores (5.3% at score ≤ 3, 17.0% at score 4-6, 40.0% at score 7-8 and 46.2% at score ≥ 9). Women with scores ≤ 3 were defined as low-risk level (< 10% miscarriage); scores 4-6 as intermediate-risk level (10% to < 40% miscarriage); scores ≥ 7 as high-risk level (≥ 40% miscarriage). The risk score yielded an area under the receiver-operating-characteristic curve of 0.74 (95% confidence interval 0.67, 0.81; p < 0.001). This novel scoring tool allows women to self-evaluate their miscarriage risk level, which facilitates lifestyle changes to optimize modifiable risk factors in the preconception period and reduces risk of spontaneous miscarriage.

Gestational age-specific normative values and determinants of serum progesterone through the first trimester of pregnancy.

Progesterone is a steroid hormone that is critical for implantation and maintenance of pregnancy, and low levels are associated with higher miscarriage risk. However, little is known about its trajectory during early pregnancy. We sought to determine the gestational age-specific normative values of serum progesterone on a week-by-week basis, and its associated maternal and fetal factors, during the first trimester of a viable low-risk pregnancy. A cross-sectional study was conducted at KK Women's and Children's Hospital from 2013 to 2018. 590 women with a single viable intrauterine low-risk pregnancy, between gestational weeks 5 and 12, were recruited. Serum progesterone showed an increasing trend during the first trimester, with a transient decline between gestational weeks 6-8, corresponding to the luteal-placental shift. Lowest levels were seen at week 7. Maternal age, BMI, parity, gestational age and outcome of pregnancy at 16 weeks' gestation were found to be associated with progesterone levels. Normative values of serum progesterone for low-risk pregnancies would form the basis for future work on pathological levels of serum progesterone that may increase risk of miscarriage. Larger studies are required to validate these normative values, and personalize them to account for maternal age, BMI, parity and gestational age.

Development of a Supportive Parenting App to Improve Parent and Infant Outcomes in the Perinatal Period: Development Study.

BACKGROUND: The transition to parenthood can be challenging, and parents are vulnerable to psychological disorders during the perinatal period. This may have adverse long-term consequences on a child's development. Given the rise in technology and parents' preferences for mobile health apps, a supportive mobile health intervention is optimal. However, there is a lack of a theoretical framework and technology-based perinatal educational intervention for couples with healthy infants. OBJECTIVE: The aim of this study is to describe the Supportive Parenting App (SPA) development procedure and highlight the challenges and lessons learned. METHODS: The SPA development procedure was guided by the information systems research framework, which emphasizes a nonlinear, iterative, and user-centered process involving 3 research cycles-the relevance cycle, design cycle, and rigor cycle. Treatment fidelity was ensured, and team cohesiveness was maintained using strategies from the Tuckman model of team development. RESULTS: In the relevance cycle, end-user requirements were identified through focus groups and interviews. In the rigor cycle, the user engagement pyramid and well-established theories (social cognitive theory proposed by Bandura and attachment theory proposed by Bowlby) were used to inform and justify the features of the artifact. In the design cycle, the admin portal was developed using Microsoft Visual Studio 2017, whereas the SPA, which ran on both iOS and Android, was developed using hybrid development tools. The SPA featured knowledge-based content, informational videos and audio clips, a discussion forum, chat groups, and a frequently asked questions and expert advice section. The intervention underwent iterative testing by a small group of new parents and research team members. Qualitative feedback was obtained for further app enhancements before official implementation. Testing revealed user and technological issues, such as web browser and app incompatibility, a lack of notifications for both administrators and users, and limited search engine capability. CONCLUSIONS: The information systems research framework documented the technical details of the SPA but did not take into consideration the interpersonal and real-life challenges. Ineffective communication between the health care research team and the app developers, limited resources, and the COVID-19 pandemic were the main challenges faced during content development. Quick adaptability, team cohesion, and hindsight budgeting are crucial for intervention development. Although the effectiveness of the SPA in improving parental and infant outcomes is currently unknown, this detailed intervention development study highlights the key aspects that need to be considered for future app development.

Epidemiology of pregnancy-associated pulmonary embolism in South Asian multi-ethnic country: Mortality trends over the last four decades.

OBJECTIVE: To determine the cumulative incidence, time of occurrence and risk factors of pregnancy-associated pulmonary embolism (PE) in Singapore, and to review the maternal mortality ratio of PE over the last four decades. STUDY DESIGN AND SETTING: In this retrospective epidemiology review, women with pregnancy-associated PE were identified via International Classification of Diseases codes and included if they had been objectively diagnosed on imaging with PE during pregnancy or within 6 weeks postpartum from 2004 to 2016 at KK Women's and Children's Hospital (KKH) and Singapore General Hospital (SGH) in Singapore. The medical records were reviewed and the time of occurrence of confirmed PE cases and risk factors for PE were noted. RESULTS: There were 18 PE cases out of 174 708 deliveries, of which two were fatal, giving a cumulative incidence of PE at 1.03 per 10 000 deliveries and a mortality rate of 11.1%. The maternal mortality ratio is 1.14 per 100 000 deliveries, the lowest compared to that of the previous three decades (2.5-4.9 per 100 000 deliveries). Majority of PE (66.7%) occurred during the first 2 weeks postpartum. Cumulative incidence of postpartum PE was four times more in caesarean section compared to vaginal delivery at 1.58 per 10 000 deliveries and 0.40 per 10 000 deliveries, respectively. CONCLUSION: Although the cumulative incidence of pregnancy-associated PE in Singapore is low, it is comparable to the United Kingdom (UK) and United States (US). Risk assessment and thromboprophylaxis have decreased PE mortality significantly during this period.

Risk factors for pregnancy-associated venous thromboembolism in Singapore.

OBJECTIVES: Pregnancy-associated venous thromboembolism (VTE), including deep venous thrombosis (DVT) and pulmonary embolism (PE), is associated with increased risk of maternal mortality and morbidity. This study aimed to assess potential risk factors for pregnancy-associated VTE. METHODS: In this case-control study, women with pregnancy-associated VTE were identified via International Classification of Diseases codes and included if they had been objectively diagnosed with VTE during pregnancy or within six weeks postpartum, from 2004 to 2016, at KK Women's and Children's Hospital or Singapore General Hospital in Singapore. Controls, i.e. pregnant women without VTE, were selected from a prospective longitudinal study. The odds ratio (OR) for VTE was computed for a range of maternal and obstetric factors. RESULTS AND CONCLUSIONS: From 2004 to 2016, 89 cases of pregnancy-associated VTE and 926 controls were identifed and analysed using logistic regression. The most significant risk factors for pregnancy-associated VTE were smoking (OR 5.44, p=0.0002) and preterm delivery (OR 5.06, p=0.023). Malay race, multiparity, non-O blood group and caesarean section, were also identified to be of higher risk. These risk factors should be useful in the development of thromboprophylaxis strategies for pregnancy and the postpartum period, especially in Singapore.

Novel approach using serum progesterone as a triage to guide management of patients with threatened miscarriage: a prospective cohort study.

Threatened miscarriage is a common gynaecological emergency, with up to 25% of women eventually progressing to spontaneous miscarriage. The uncertainty of pregnancy outcomes results in significant anxiety. However, there is currently no acceptable framework for triaging patients presenting with threatened miscarriage. We aim to evaluate the efficacy and safety of a novel clinical protocol using a single serum progesterone level to prognosticate and guide management of patients with threatened miscarriage. 1087 women presenting with threatened miscarriage were enrolled in the study. The primary outcome was spontaneous miscarriage by 16 weeks' gestation. Among the 77.9% (847/1087) of study participants with serum progesterone ≥ 35 nmol/L who were not treated with oral dydrogesterone, the miscarriage rate was 9.6% (81/847). This did not differ significantly from the 8.5% (31/364) miscarriage rate observed in our prior studies; p = 0.566. Among women with serum progesterone < 35 nmol/L who were treated with dydrogesterone, the miscarriage rate was 70.8% (170/240). Our novel clinical triage protocol using a single serum progesterone level allowed both effective risk stratification and a reduction in progestogen use with no significant adverse pregnancy outcomes. This protocol, based on a single serum progesterone cutoff, can be readily adapted for use in other healthcare institutions.

Retrospective study on the efficacy and prognostic factors of conservative versus drainage of tubo-ovarian abscesses.

PURPOSE: Management of tubo-ovarian abscesses (TOA) is often complex and may include antibiotics, image-guided drainage via interventional radiology (IR) or surgery. We aim to (i) identify clinical factors that prognosticate primary drainage and (ii) compare outcomes of each treatment regimen. METHODS: This is a retrospective analysis on patients with TOA, admitted to KK Hospital, a tertiary women's hospital in Singapore from June 2016 to June 2017. Pregnant patients or patients who were discharged against medical advice were excluded. 102 patients were included in this study. RESULTS: 85.3% patients received antibiotics only, while 14.7% patients received antibiotics with IR drainage or surgery (primary drainage) as initial treatment. Subsequently, 20.7% failed antibiotic treatment and required IR drainage or surgery (secondary drainage). Patients aged above 40 years, TOA diameter of larger than 7 cm and presence of fever were found to be predictive of antibiotic failure, requiring secondary drainage. However, patients with primary drainage had a longer length of stay by 2.69 days (95% CI 1.44-3.94, p value < 0.001), compared to patients successfully managed conservatively. CONCLUSION: Patients who are above 40 years, febrile and have a larger TOA are at a higher risk of medical treatment failure, and should, therefore, be recommended for primary drainage at presentation. Further prospective studies should be conducted with a larger sample size to compare the outcomes of conservative management versus drainage of TOA.

Characterisation of serum progesterone and progesterone-induced blocking factor (PIBF) levels across trimesters in healthy pregnant women.

Progesterone-induced blocking factor (PIBF), which plays an important role in maintaining healthy pregnancies, has shown great promise as a prognostic biomarker for threatened miscarriage. To better characterise the physiological trends of progesterone and PIBF, we analysed serum progesterone and PIBF concentrations in healthy non-pregnant and pregnant women across trimesters. We saw increasing concentrations of progesterone and PIBF in pregnant women with advancing trimesters. The serum progesterone and PIBF percentiles across gestational age in healthy pregnancies can be used as a guide for the formulation of reference ranges. We also demonstrated a significant positive correlation between progesterone and PIBF levels. This study demonstrates increasing progesterone and PIBF concentrations in later trimesters and underscores the importance of progesterone and PIBF in healthy pregnancies. Characterisation of progesterone and PIBF across gestational age in healthy pregnant women may help to prognosticate pregnancy viability and support further research into the importance of progesterone and PIBF in the maintenance of healthy pregnancies.

Multiplex Surface-Enhanced Raman Scattering Identification and Quantification of Urine Metabolites in Patient Samples within 30 min.

Successful translation of laboratory-based surface-enhanced Raman scattering (SERS) platforms to clinical applications requires multiplex and ultratrace detection of small biomarker molecules from a complex biofluid. However, these biomarker molecules generally exhibit low Raman scattering cross sections and do not possess specific affinity to plasmonic nanoparticle surfaces, significantly increasing the challenge of detecting them at low concentrations. Herein, we demonstrate a "confine-and-capture" approach for multiplex detection of two families of urine metabolites correlated with miscarriage risks, 5ß-pregnane-3α,20α-diol-3α-glucuronide and tetrahydrocortisone. To enhance SERS signals by 1012-fold, we use specific nanoscale surface chemistry for targeted metabolite capture from a complex urine matrix prior to confining them on a superhydrophobic SERS platform. We then apply chemometrics, including principal component analysis and partial least-squares regression, to convert molecular fingerprint information into quantifiable readouts. The whole screening procedure requires only 30 min, including urine pretreatment, sample drying on the SERS platform, SERS measurements, and chemometric analyses. These readouts correlate well with the pregnancy outcomes in a case-control study of 40 patients presenting threatened miscarriage symptoms.

Immunological observations and transcriptomic analysis of trimester-specific full-term placentas from three Zika virus-infected women.

OBJECTIVES: Effects of Zika virus (ZIKV) infection on placental development during pregnancy are unclear. METHODS: Full-term placentas from three women, each infected with ZIKV during specific pregnancy trimesters, were harvested for anatomic, immunologic and transcriptomic analysis. RESULTS: In this study, each woman exhibited a unique immune response with raised IL-1RA, IP-10, EGF and RANTES expression and neutrophil numbers during the acute infection phase. Although ZIKV NS3 antigens co-localised to placental Hofbauer cells, the placentas showed no anatomic defects. Transcriptomic analysis of samples from the placentas revealed that infection during trimester 1 caused a disparate cellular response centred on differential eIF2 signalling, mitochondrial dysfunction and oxidative phosphorylation. Despite these, the babies were delivered without any congenital anomalies. CONCLUSION: These findings should translate to improve clinical prenatal screening procedures for virus-infected pregnant patients.

Coverage and determinants of influenza vaccine among pregnant women: a cross-sectional study.

BACKGROUND: Pregnant women are at increased risk of influenza-related complications. The World Health Organisation recommends influenza vaccination to this high-risk population as highest priority. However, achieving high influenza vaccine coverage among pregnant women remains challenging. We conducted a cross-sectional survey to estimate the coverage and determinants of influenza vaccination among pregnant women in Singapore. METHODS: Between September and November 2017, pregnant women aged ≥21 years were recruited at two public hospitals in Singapore. Participants completed an anonymous, self-administered online questionnaire assessing participants' influenza vaccination uptake, knowledge of and attitudes towards influenza and the influenza vaccine, vaccination history, willingness to pay for the influenza vaccine, and external cues to vaccination. We estimated vaccine coverage and used multivariable Poisson models to identify factors associated with vaccine uptake. RESULTS: Response rate was 61% (500/814). Only 49 women (9.8, 95% Confidence Interval (CI): 7.3-12.7%) reported receiving the vaccine during their current pregnancy. A few misconceptions were identified among participants, such as the belief that influenza can be treated with antibiotics. The most frequent reason for not being vaccinated was lack of recommendation. Women who were personally advised to get vaccinated against influenza during pregnancy were 7 times more likely to be vaccinated (prevalence ratio (PR) = 7.11; 95% CI: 3.92-12.90). However, only 12% of women were personally advised to get vaccinated. Other factors associated with vaccine uptake were vaccination during a previous pregnancy (PR = 2.51; 95% CI: 1.54-4.11), having insurance to cover the cost of the vaccine (PR = 2.32; 95% CI: 1.43-3.76), and higher vaccine confidence (PR = 1.62; 95% CI: 1.30-2.01). CONCLUSIONS: Influenza vaccination uptake among pregnant women in Singapore is low. There is considerable scope for improving vaccination coverage in this high-risk population through vaccination recommendations from healthcare professionals, and public communication targeting common misconceptions about influenza and influenza vaccines.

Macronutrient composition and food groups associated with gestational weight gain: the GUSTO study.

PURPOSE: To examine the associations of energy, macronutrient and food intakes with GWG on 960 pregnant women from the Growing Up in Singapore Towards healthy Outcomes (GUSTO) mother-offspring cohort. METHODS: Dietary intake was assessed at 26-28 weeks' gestation with a 24-hour recall and 3-day food diary. GWG z-scores were calculated from first (4-13 weeks' gestation) and last (30-40 weeks gestation) measured weights; inadequate and excessive GWG were defined using the Institute of Medicine recommendations based on weights between 15 and 35 weeks' gestation. Associations were examined using substitution models for macronutrient composition, with linear or multinomial logistic regressions. RESULTS: Mean ± SD daily energy intake was 1868 ± 598 kcal, and percentage energy intakes were 51.8 ± 8.9% from carbohydrate, 15.7 ± 3.9% from protein and 32.6 ± 7.7% from fat. Higher energy intake (per 500 kcal increment) was associated with 0.18 SD higher GWG. In isocaloric diets, higher-carbohydrate and lower-fat intakes (at 5% energy substitution) were associated with 0.07 SD higher GWG, and 14% higher likelihood of excessive GWG. Concordantly, the highest tertile of carbohydrate-rich foods intake was associated with 0.20 SD higher GWG, but the highest tertile of fruit and vegetable intake was independently associated with 60% lower likelihood of inadequate GWG. Additionally, the highest tertile of dairy intake was associated with 0.18 SD lower GWG; and the highest tertile of plant-based protein foods intake was associated with 60% and 34% lower likelihood of inadequate and excessive GWG. CONCLUSIONS: Balancing the proportions of carbohydrates and fat, and a higher intake of plant-based protein foods may be beneficial for achieving optimal GWG.

Serum progesterone distribution in normal pregnancies compared to pregnancies complicated by threatened miscarriage from 5 to 13 weeks gestation: a prospective cohort study.

BACKGROUND: Progesterone is a critical hormone in early pregnancy. A low level of serum progesterone is associated with threatened miscarriage. We aim to establish the distribution of maternal serum progesterone in normal pregnancies compared to pregnancies complicated by threatened miscarriage from 5 to 13 weeks gestation. METHODS: This is a single centre, prospective cohort study of 929 patients. Women from the Normal Pregnancy [NP] cohort were recruited from antenatal clinics, and those in the Threatened Miscarriage [TM] cohort were recruited from emergency walk-in clinics. Women with multiple gestations, missed, incomplete or inevitable miscarriage were excluded from the study. Quantile regression was used to characterize serum progesterone levels in the NP and TM cohorts by estimating the 10th, 50th and 90th percentiles from 5 to 13 weeks gestation. Pregnancy outcome was determined at 16 weeks of gestation. Subgroup analysis within the TM group compared progesterone levels of women who subsequently miscarried with those who had ongoing pregnancies at 16 weeks of gestation. RESULTS: Median serum progesterone concentration demonstrated a linearly increasing trend from 57.5 nmol/L to 80.8 nmol/L from 5 to 13 weeks gestation in the NP cohort. In the TM cohort, median serum progesterone concentration increased from 41.7 nmol/L to 78.1 nmol/L. However, median progesterone levels were uniformly lower in the TM cohort by approximately 10 nmol/L at every gestation week. In the subgroup analysis, median serum progesterone concentration in women with ongoing pregnancy at 16 weeks gestation demonstrated a linearly increasing trend from 5 to 13 weeks gestation. There was a marginal and non-significant increase in serum progesterone from 19.0 to 30.3 nmol/L from 5 to 13 weeks gestation in women who eventually had a spontaneous miscarriage. CONCLUSIONS: Serum progesterone concentration increased linearly with gestational age from 5 to 13 weeks in women with normal pregnancies. Women with spontaneous miscarriage showed a marginal and non-significant increase in serum progesterone. This study highlights the pivotal role of progesterone in supporting an early pregnancy, with lower serum progesterone associated with threatened miscarriage and a subsequent complete miscarriage at 16 weeks gestation.

The randomised controlled trial of micronised progesterone and dydrogesterone (TRoMaD) for threatened miscarriage.

There has not been conclusive evidence in literature on the efficacy of progestogen in the treatment of threatened miscarriage, although some studies showed benefits. In our centre, threatened miscarriage is treated with either micronised progesterone (MP) or dydrogesterone (DYD). OBJECTIVE: The aim of this study is to compare clinical outcomes of miscarriage, extent of vaginal bleeding at follow-up and side effects between treatment groups. STUDY DESIGN: This study was a prospective parallel-group, open-label, randomized controlled trial. 141 women presenting with threatened miscarriage were randomised to either MP or DYD of which 118 were included in the analysis. Baseline maternal demographics and serum progesterone levels were collected at presentation. Post-treatment bleeding pattern and self-reported side effects were recorded at the follow-up visit (on day 4-10 of treatment). The occurrence of spontaneous miscarriage was ascertained at week 16 of gestation. RESULTS: The population with miscarriage and resolution of bleeding were not statistically different between MP and DYD groups. A significantly higher percentage of women treated with MP reported drowsiness (p = 0.003). After stratification into low and high serum progesterone levels, a significantly higher miscarriage rate was found in the low progesterone group, regardless of treatment type. CONCLUSION: In conclusion, extent of bleeding at day 4-10 and subsequent miscarriage rates were comparable between MP and DYD groups. However, fewer patients treated with DYD reported drowsiness and giddiness. The finding of significantly higher miscarriage rates in women with low progesterone levels despite treatment is an important factor to consider in counselling and prognosticating pregnancy outcomes.

Threatened miscarriage and depressive and anxiety symptoms among women and partners in early pregnancy.

BACKGROUND: Antenatal depression has been associated with poor maternal and fetal outcomes, and threatened miscarriage is often seen clinically to impact adversely on maternal wellbeing, notwithstanding the limited research evidence. Our study aims to examine the link between threatened miscarriage and antenatal depression and anxiety in an Asian obstetric population. METHODS: We recruited 121 women and 68 partners facing threatened miscarriage, and 241 women and 180 partners experiencing uncomplicated pregnancies from a tertiary maternity hospital in Singapore. All participants completed a Patient Information Questionnaire and the Edinburgh Postnatal Depression Scale (EPDS). RESULTS: The proportion of women with major depressive and anxiety symptomatology was significantly higher among women facing threatened miscarriage compared to those with stable pregnancies (depressive: 33.1% vs. 17.0%, p = 0.008; anxiety: 48.8% vs. 23.7%, p < 0.0001). Amongst their partners, there was a non-significant trend towards a similar finding (depressive: 10.3% vs. 7.2%, p = 0.439; anxiety: 23.5% vs. 18.9%, p = 0.478). Threatened miscarriage remained significantly associated with major depressive symptomatology after adjusting for potential confounders among women (OR 2.70; 95% CI 1.55, 4.71; p < 0.0001) but not among their partners (OR 1.47; 95% CI 0.56, 3.87; p = 0.430). LIMITATIONS: This study is limited by its cross-sectional design and relatively small sample size for male partners. CONCLUSION: Antenatal depressive and anxiety symptomatology affects one in four women in their first trimester, with even higher prevalence among women facing threatened miscarriage. Targeted depression and anxiety screening that includes women facing threatened miscarriages may facilitate early and efficient detection and management of mental health problems among pregnant women.

Development of a new patient-derived xenograft humanised mouse model to study human-specific tumour microenvironment and immunotherapy.

OBJECTIVE: As the current therapeutic strategies for human hepatocellular carcinoma (HCC) have been proven to have limited effectiveness, immunotherapy becomes a compelling way to tackle the disease. We aim to provide humanised mouse (humice) models for the understanding of the interaction between human cancer and immune system, particularly for human-specific drug testing. DESIGN: Patient-derived xenograft tumours are established with type I human leucocyte antigen matched human immune system in NOD-scid Il2rg-/- (NSG) mice. The longitudinal changes of the tumour and immune responses as well as the efficacy of immune checkpoint inhibitors are investigated. RESULTS: Similar to the clinical outcomes, the human immune system in our model is educated by the tumour and exhibits exhaustion phenotypes such as a significant declination of leucocyte numbers, upregulation of exhaustion markers and decreased the production of human proinflammatory cytokines. Notably, cytotoxic immune cells decreased more rapidly compared with other cell types. Tumour infiltrated T cells have much higher expression of exhaustion markers and lower cytokine production compared with peripheral T cells. In addition, tumour-associated macrophages and myeloid-derived suppressor cells are found to be highly enriched in the tumour microenvironment. Interestingly, the tumour also changes gene expression profiles in response to immune responses by upregulating immune checkpoint ligands. Most importantly, in contrast to the NSG model, our model demonstrates both therapeutic and side effects of immune checkpoint inhibitors pembrolizumab and ipilimumab. CONCLUSIONS: Our work provides a model for immune-oncology study and a useful parallel-to-human platform for anti-HCC drug testing, especially immunotherapy.