Prepregnancy adherence to plant-based diet indices and exploratory dietary patterns in relation to fecundability

Background Modest associations have been reported between specific food groups or nutrients and fecundability [measured by time to pregnancy (TTP)]. Examining overall diets provides a more holistic approach towards understanding their associations with fecundability. It is not known whether plant-based diets indices or exploratory dietary patterns are associated with fecundability. Objectives We examine the associations between adherence to 1) plant-based diet indices; and 2) exploratory dietary patterns and fecundability among women planning pregnancy. Methods Data were analyzed from the Singapore Preconception Study of Long-Term Maternal and Child Outcomes (S-PRESTO) study. Prepregnancy diet was assessed using a semi-quantitative FFQ from which the overall, healthful, and unhealthful plant-based diet indices (oPDI, hPDI, and uPDI, respectively) were calculated. Exploratory dietary patterns were derived using factor analysis based on 44 predefined food groups. Participants were categorized into quintiles based on their dietary pattern scores. TTP (expressed in menstrual cycles) was ascertained within a year from the prepregnancy dietary assessment. Discrete-time proportional hazard models, adjusted for confounders, were used to estimate fecundability ratios (FRs) and 95% CIs, with FR > 1 indicating a shorter TTP. Results Among 805 women, 383 pregnancies were confirmed by ultrasound scans. Compared with women in the lowest quintile, those in the highest quintile of the uPDI had reduced fecundability (FR of Q5 compared with Q1, 0.65; 95% CI, 0.46-0.91; P trend, 0.009). Conversely, greater adherence to the hPDI was associated with increased fecundability (1.46; 95% CI, 1.02-2.07; P trend, 0.036). The oPDI was not associated with fecundability. Among the 3 exploratory dietary patterns, only greater adherence to the Fast Food and Sweetened Beverages (FFSB) pattern was associated with reduced fecundability (0.61; 95% CI, 0.40-0.91; P trend, 0.018). Conclusions Greater adherence to the uPDI or the FFSB dietary pattern was associated with reduced fecundability among Asian women. Greater adherence to the hPDI may be beneficial for fecundability, though this requires confirmation by future studies.Peer reviewe

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.publishedVersionPeer reviewe

Maternal starvation primes progeny response to nutritional stress

10.1371/journal.pgen.1009932PLoS Genetics1711e100993

Iron status and risk factors of iron deficiency among pregnant women in Singapore: a cross-sectional study

Abstract Background Iron deficiency is the most prevalent nutrient deficiency and the most common cause of anaemia worldwide. Because of the increased iron requirements during pregnancy, iron deficiency can lead to maternal anaemia and reduced newborn iron stores. We examined the proportion and risk factors of iron deficiency among pregnant women in a developed Asian country. Methods Within a prospective cohort in Singapore, 985 Asian women were assessed for iron status at 26–28 weeks’ gestation, with plasma ferritin and soluble transferrin receptor (sTfR) measurements. Iron status was determined according to plasma ferritin concentrations at ≥30 μg/L (iron sufficiency), 15 to < 30 μg/L (modest iron depletion) and < 15 μg/L (severe iron depletion). Multivariable ordinal logistic regression was used to analyze risk factors for modest and severe iron depletion. Results The median (25-75th percentile) plasma ferritin concentration was 24.2 (19.9–30.6) μg/L. Overall, 660 (67.0%) and 67 (6.8%) women had modest and severe iron depletion, respectively. Higher plasma sTfR was observed in women with severe iron depletion than among those with iron sufficiency (median 17.6 versus 15.5 nmol/L; p < 0.001). Age < 25 years (odds ratio 2.36; 95% confidence interval 1.15–4.84), Malay (2.05; 1.30–3.24) and Indian (1.98; 1.14–3.44) ethnicities (versus Chinese), university qualification (1.64; 1.13–2.38), multiparity (1.73; 1.23–2.44) and lack of iron-containing supplementation (3.37; 1.25–8.53) were associated with increased odds of modest and severe iron depletion. Conclusions Nearly three-quarters of Singaporean women were iron deficient in the early third trimester of pregnancy. These results suggest universal screening and supplementation of at-risk pregnancies may be evaluated as a preventive strategy. Trial registration NCT01174875. Registered 1 July 2010 (retrospectively registered)

Secreted dengue virus NS1 from infection is predominantly dimeric and in complex with high-density lipoprotein

Severe dengue infections are characterized by endothelial dysfunction shown to be associated with the secreted nonstructural protein 1 (sNS1), making it an attractive vaccine antigen and biotherapeutic target. To uncover the biologically relevant structure of sNS1, we obtained infection-derived sNS1 (isNS1) from dengue virus (DENV)-infected Vero cells through immunoaffinity purification instead of recombinant sNS1 (rsNS1) overexpressed in insect or mammalian cell lines. We found that isNS1 appeared as an approximately 250 kDa complex of NS1 and ApoA1 and further determined the cryoEM structures of isNS1 and its complex with a monoclonal antibody/Fab. Indeed, we found that the major species of isNS1 is a complex of the NS1 dimer partially embedded in a high-density lipoprotein (HDL) particle. Crosslinking mass spectrometry studies confirmed that the isNS1 interacts with the major HDL component ApoA1 through interactions that map to the NS1 wing and hydrophobic domains. Furthermore, our studies demonstrated that the sNS1 in sera from DENV-infected mice and a human patient form a similar complex as isNS1. Our results report the molecular architecture of a biological form of sNS1, which may have implications for the molecular pathogenesis of dengue

Iron status and risk factors of iron deficiency among pregnant women in Singapore: A cross-sectional study

Background Iron deficiency is the most prevalent nutrient deficiency and the most common cause of anaemia worldwide. Because of the increased iron requirements during pregnancy, iron deficiency can lead to maternal anaemia and reduced newborn iron stores. We examined the proportion and risk factors of iron deficiency among pregnant women in a developed Asian country. Methods Within a prospective cohort in Singapore, 985 Asian women were assessed for iron status at 26–28 weeks’ gestation, with plasma ferritin and soluble transferrin receptor (sTfR) measurements. Iron status was determined according to plasma ferritin concentrations at ≥30 μg/L (iron sufficiency), 15 to &lt; 30 μg/L (modest iron depletion) and &lt; 15 μg/L (severe iron depletion). Multivariable ordinal logistic regression was used to analyze risk factors for modest and severe iron depletion. Results The median (25-75th percentile) plasma ferritin concentration was 24.2 (19.9–30.6) μg/L. Overall, 660 (67.0%) and 67 (6.8%) women had modest and severe iron depletion, respectively. Higher plasma sTfR was observed in women with severe iron depletion than among those with iron sufficiency (median 17.6 versus 15.5 nmol/L; p &lt; 0.001). Age &lt; 25 years (odds ratio 2.36; 95% confidence interval 1.15–4.84), Malay (2.05; 1.30–3.24) and Indian (1.98; 1.14–3.44) ethnicities (versus Chinese), university qualification (1.64; 1.13–2.38), multiparity (1.73; 1.23–2.44) and lack of iron-containing supplementation (3.37; 1.25–8.53) were associated with increased odds of modest and severe iron depletion. Conclusions Nearly three-quarters of Singaporean women were iron deficient in the early third trimester of pregnancy. These results suggest universal screening and supplementation of at-risk pregnancies may be evaluated as a preventive strategy

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

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

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

Maternal Height, Gestational Diabetes Mellitus and Pregnancy Complications.

AIMS: To explore the glucose-overload hypothesis of artefactual gestational diabetes (GDM) diagnosis in shorter women during oral glucose tolerance testing (OGTT), by investigating associations between height and maternal glycemia; and GDM and pregnancy complications in height-groups. METHODS: Women from GUSTO (n=1100, 2009-2010) and NUH (n=4068, 2017-2018) cohorts underwent a two and three time-point mid-gestation 75g 2-hour OGTT, respectively. GDM-related complications (hypertensive disorders of pregnancy, preterm delivery, emergency cesarean section, neonatal intensive care unit admission, macrosomia, birthweight) were compared within shorter and taller groups, dichotomized by ethnic-specific median height. RESULTS: Using WHO-1999 criteria, 18.8% (GUSTO) to 22.9% (NUH) of women were diagnosed with GDM-1999; and by WHO-2013 criteria, 21.9% (NUH) had GDM-2013. Each 5-cm height increment was inversely associated with GDM-1999 (adjusted odds ratio [aOR, 95%CI]=0.81 [0.76-0.87], 2h-glycemia (adjusted β [95%CI]=-0.171mmol/L [-0.208,-0.135]) and 1h-glycemia (aβ=-0.160mmol/L [-0.207,-0.112]). The inverse association between height and 2h-glycemia was most marked in “Other” ethnicities (Eurasians/Caucasians/mixed/other Asians) and Indians, followed by Chinese, then Malays. Compared with non-GDM, GDM-1999 was associated with preterm delivery (aOR=1.76 [1.19-2.61]) and higher birthweight (aβ=57.16g [20.95,93.38]) only among taller but not shorter women. CONCLUSIONS: Only taller women had an increased odds of GDM-related pregnancy complications. An artefactual GDM diagnosis due to glucose-overload among shorter women is plausible