Metabolic health status and fecundability in a Singapore preconception cohort study

Loy, See Ling; Chan, Daniel Wei Keong; Ku, Chee Wai; Cheung, Yin Bun; Godfrey, Keith M.; Tan, K. L.; Chong, Yap‐Seng; Tan, Kok Hian; Chan, Shiao‐Yng; Chan, Jerry Kok Yen; Yap, Fabian

doi:10.1016/j.ajog.2021.11.1374

Cited by 7 publications

(9 citation statements)

References 36 publications

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“…triacylglycerols, phospholipids and cholesteryl ester) with higher concentrations in non-pregnant subjects that were also positively associated with BMI and glycaemic traits (Additional file 7 : Table S6). These findings are consistent with the previous report on reduced fecundability of women with unhealthy metabolic health status in the same cohort [ 35 ].…”

Section: Discussionsupporting

confidence: 94%

Plasma lipidomic profiling reveals metabolic adaptations to pregnancy and signatures of cardiometabolic risk: a preconception and longitudinal cohort study

Chen

Mir

Bendt

et al. 2023

BMC Med

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Background Adaptations in lipid metabolism are essential to meet the physiological demands of pregnancy and any aberration may result in adverse outcomes for both mother and offspring. However, there is a lack of population-level studies to define the longitudinal changes of maternal circulating lipids from preconception to postpartum in relation to cardiometabolic risk factors. Methods LC-MS/MS-based quantification of 689 lipid species was performed on 1595 plasma samples collected at three time points in a preconception and longitudinal cohort, Singapore PREconception Study of long-Term maternal and child Outcomes (S-PRESTO). We mapped maternal plasma lipidomic profiles at preconception (N = 976), 26–28 weeks’ pregnancy (N = 337) and 3 months postpartum (N = 282) to study longitudinal lipid changes and their associations with cardiometabolic risk factors including pre-pregnancy body mass index, body weight changes and glycaemic traits. Results Around 56% of the lipids increased and 24% decreased in concentration in pregnancy before returning to the preconception concentration at postpartum, whereas around 11% of the lipids went through significant changes in pregnancy and their concentrations did not revert to the preconception concentrations. We observed a significant association of body weight changes with lipid changes across different physiological states, and lower circulating concentrations of phospholipids and sphingomyelins in pregnant mothers with higher pre-pregnancy BMI. Fasting plasma glucose and glycated haemoglobin (HbA1c) concentrations were lower whereas the homeostatic model assessment of insulin resistance (HOMA-IR), 2-h post-load glucose and fasting insulin concentrations were higher in pregnancy as compared to both preconception and postpartum. Association studies of lipidomic profiles with these glycaemic traits revealed their respective lipid signatures at three physiological states. Assessment of glycaemic traits in relation to the circulating lipids at preconception with a large sample size (n = 936) provided an integrated view of the effects of hyperglycaemia on plasma lipidomic profiles. We observed a distinct relationship of lipidomic profiles with different measures, with the highest percentage of significant lipids associated with HOMA-IR (58.9%), followed by fasting insulin concentration (56.9%), 2-h post-load glucose concentration (41.8%), HbA1c (36.7%), impaired glucose tolerance status (31.6%) and fasting glucose concentration (30.8%). Conclusions We describe the longitudinal landscape of maternal circulating lipids from preconception to postpartum, and a comprehensive view of trends and magnitude of pregnancy-induced changes in lipidomic profiles. We identified lipid signatures linked with cardiometabolic risk traits with potential implications both in pregnancy and postpartum life. Our findings provide insights into the metabolic adaptations and potential biomarkers of modifiable risk factors in childbearing women that may help in better assessment of cardiometabolic health, and early intervention at the preconception period. Trial registration ClinicalTrials.gov, NCT03531658.

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Section: Discussionsupporting

confidence: 94%

Plasma lipidomic profiling reveals metabolic adaptations to pregnancy and signatures of cardiometabolic risk: a preconception and longitudinal cohort study

Chen

Mir

Bendt

et al. 2023

BMC Med

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“…The pre-ovulatory follicular fluid from obese women has been shown to have increased levels of glucose, lactate and insulin [ 10 ]. Such changes in metabolic status have been linked to a reduced fertility [ 31 ] and poor embryo outcome [ 32 ]. Furthermore, elevated levels of leptin associated with obesity can inhibit LH-stimulated estradiol production in granulosa cells, as well as inhibit the insulin-induced ovarian steroidogenesis, thus impeding follicle development [ 33 , 34 ].…”

Section: Parental Diet and Obesitymentioning

confidence: 99%

Parental Programming of Offspring Health: The Intricate Interplay between Diet, Environment, Reproduction and Development

et al. 2022

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As adults, our health can be influenced by a range of lifestyle and environmental factors, increasing the risk for developing a series of non-communicable diseases such as type 2 diabetes, heart disease and obesity. Over the past few decades, our understanding of how our adult health can be shaped by events occurring before birth has developed into a well-supported concept, the Developmental Origins of Health and Disease (DOHaD). Supported by epidemiological data and experimental studies, specific mechanisms have been defined linking environmental perturbations, disrupted fetal and neonatal development and adult ill-health. Originally, such studies focused on the significance of poor maternal health during pregnancy. However, the role of the father in directing the development and well-being of his offspring has come into recent focus. Whereas these studies identify the individual role of each parent in shaping the long-term health of their offspring, few studies have explored the combined influences of both parents on offspring well-being. Such understanding is necessary as parental influences on offspring development extend beyond the direct genetic contributions from the sperm and oocyte. This article reviews our current understanding of the parental contribution to offspring health, exploring some of the mechanisms linking parental well-being with gamete quality, embryo development and offspring health.

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“…34 This was highlighted by a recent study that showed that metabolic health status, rather than BMI, played a greater role in fecundability. 35 Therefore, interpregnancy BMI loss may not truly reflect the metabolic health status of those in our study, which may possibly confound the positive effects of weight loss in overweight and obese women. Furthermore, changes in body composition and fat distribution between pregnancies in these women who were overweight or obese may impact on subsequent pregnancy outcomes.…”

Section: Discussionmentioning

confidence: 87%

Distribution and association of interpregnancy weight change with subsequent pregnancy outcomes: a cohort study using electronic medical records

Cheng

et al. 2022

Preprint

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Objective To examine the change in maternal body mass index (BMI) between the first two deliveries and outcomes in the second delivery. Design Cohort study using electronic medical records. Setting and population 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. Methods Analysis was limited to women with BMI available for both pregnancies, which was standardised/adjusted to 12 weeks gestation. The difference between gestational-age-adjusted BMI in both pregnancies was calculated as the change in interpregnancy BMI. The risk ratios (RR) of pregnancy outcomes were estimated using modified Poisson regression models with confounder adjustment. Main outcome measures Low birthweight (<2.5 kg), high birthweight (≥4 kg), small-for-gestational-age, large-for-gestational-age, preterm delivery, gestational diabetes, elective and emergency caesarean deliveries. Results 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 a higher risk of low birthweight delivery (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. Conclusion Our study demonstrated the importance of returning to pre-pregnancy weight and maintaining a stable interpregnancy BMI, to achieve better pregnancy outcomes.

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Metabolic health status and fecundability in a Singapore preconception cohort study

Cited by 7 publications

References 36 publications

Plasma lipidomic profiling reveals metabolic adaptations to pregnancy and signatures of cardiometabolic risk: a preconception and longitudinal cohort study

Plasma lipidomic profiling reveals metabolic adaptations to pregnancy and signatures of cardiometabolic risk: a preconception and longitudinal cohort study

Parental Programming of Offspring Health: The Intricate Interplay between Diet, Environment, Reproduction and Development

Distribution and association of interpregnancy weight change with subsequent pregnancy outcomes: a cohort study using electronic medical records

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