Environmental Exposure, Genetics Predisposition, Metabolic Disease, Neurological and Mental Health Conditions, Psychology, Social, Skin Condition, Socioeconomic Factors
Conditions
Keywords
Cohort Study, Birth Cohort, Longitudinal Study, Pregnancy, Growth, Developmental Origins of Health and Disease, DOHaD, Epidemiology, Maternal Health, Infant Health, Child Health, Health Outcomes, Postnatal Exposure, Perinatal Exposure, Environmental Factors, Nutrition, Genetics
Brief summary
We aim to test the following primary hypothesis that nutrition, lifestyle, and maternal emotional health prior to pregnancy and/or during the first trimester alter the expression of metabolic or neurodevelopmental endophenotypes with accompanying effects on the epigenome/transcriptome of the offspring.
Detailed description
It is now evident that prenatal stage represents a window of susceptibility for early life exposure that can have an effect on developing fetus, with potential long-lasting consequences for offspring growth and development. Emerging research suggest that the environmental modulation of tissue development and function may even occur both before and soon after conception but as yet, limited study has been conducted to investigate the relationship of preconception and early prenatal life conditions, including nutrition, lifestyle and environmental factors, with maternal and offspring health. This prospective preconception cohort study recruited 1054 women who plan to get pregnant. The investigators will assess the women metabolically, nutritionally and epigenetically, then monitor them from their first missed menses with nutritional surveys and assays and repeated bio-sampling to birth followed by assessment in the women of lactation and lactational nutrition. Biochemical and molecular analyses will be done on the cord and placenta at birth and in buccal smears at frequent postnatal intervals. The women's partners will also be recruited on consent. Phenotypic measures of body composition and core neurodevelopmental measures will be followed in the offspring from birth until 10 years of age. Metabolic and mental health of women will also be measured from preconception until 10 years postpartum. At delivery phase, there are 373 mother-child pairs with 80% of fathers enrolled in the study as well. This study allows understanding of the potential triggers during early life environment, including nutritional and lifestyle factors, emotional wellbeing, socio-economic status, microbiome, pollutants, metabolomics and epigenetics, which can independently or collectively influence metabolic and neural phenotypes in the offspring and mother. This will help to establish what future directions may hold in terms of possible preventive strategies that may lead to decreased prevalence of metabolic diseases and mental/ neurological disorders.
Interventions
None listed
Sponsors
KK Women's and Children's Hospital
National University Health System, Singapore
Institute for Human Development and Potential (IHDP), Singapore
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Healthy volunteers
Yes
Inclusion criteria
of Mother Participants: 1. Women aged 18-35 years 2. Intention to reside in Singapore for the next 5 years 3. Chinese, Malay, Indian or any combinations of these 3 ethnic groups 4. Planning to conceive within 1 year 5. Able to provide written, informed consent
Exclusion criteria
of Mother Participants: 1. Have been actively trying to conceive for more than 18 months 2. Currently pregnant 3. Assisted fertility, apart from those taking clomiphene alone in the past 1 month 4. Established pre-existing diabetes (type 1 or type 2) 5. Oral or implanted contraception, or with an IUCD in situ in the past 1 month 6. On systemic steroids in the past 1 month 7. On anticonvulsants in the past 1 month 8. On HIV or Hepatitis B or C medication in the past 1 month 9. Not becoming pregnant after more than 12 months from recruitment 10. Eventual multiple pregnancies 11. Pregnancy complications such as miscarriages, ectopic pregnancy, still birth The partners of the women will also be invited to participate in the study. Babies born from these mothers will be followed up until the child is 9 years of age.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Offspring adiposity | From birth until 10 years of age | Offspring adiposity (total and percentage fat mass) measured by skinfold calipers, air-displacement plethysmography, quantitative magnetic resonance (QMR), Bioelectrical Impedance Analysis (BIA), and Magnetic resonance imaging (MRI). |
| Offspring neurocognitive and behavioural development | From 3-12 months up till 10 years of age | Offspring neurocognitive and behavioural development measured by questionnaires, behavioural tasks and brain MRI. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Duration of gestation | Up to 42 weeks, between estimated date of conception based on ultrasound scan and date of delivery | — |
| Fetal growth measured by ultrasound scan | Up to 30 weeks, between 6-36 weeks of gestation | — |
| Offspring body weight measured by calibrated weighing scale | From birth until 10 years of age | — |
| Offspring pubertal assessment | From 7 until 10 years of age | Pubertal assessment by Tanner staging |
| Offspring growth trajectories | From birth until 10 years of age | — |
| Offspring adiposity trajectories (total and percentage fat mass) | From birth until 10 years of age | — |
| Offspring anogenital distance measured by Vernier calipers | Up to 12 months, from birth until 12 months of age | — |
| Offspring allergic wellbeing measured by skin examination and skin prick test | Up to 60 months, from 1 week until 5 years of age | — |
| Offspring skin microbiome collected by sterile tape strips | Up to 60 months, from 1 week until 5 years of age | — |
| Offspring metabolomics, lipidomics and pollutant profile measured through biospecimens such as cord, cord blood, heel prick blood, and hair samples | From birth until 24 months of age | — |
| Offspring epigenetic profile measured through cord, cord blood, and buccal smear samples | From birth until 6 years of age | — |
| Offspring gut microbiome measured through stool samples | From birth until 10 years of age | — |
| Maternal glucose tolerance status measured by Oral Glucose Tolerance Test (OGTT) | At preconception, 27-28 weeks of gestation, 3 months and 2, 3, 4, 6, 8, 10 years postpartum | — |
| Maternal weight measured by calibrated weighing scale | Between preconception, pregnancy and 10 years postpartum | — |
| Changes in maternal weight before, during and after gestation | Between preconception, pregnancy and 10 years postpartum | — |
| Maternal body weight status determined by body mass index based on weight (kg) /height (m)2 | At preconception visit; 3 months-10 years postpartum | — |
| Maternal body composition measured by skinfold calipers, air-displacement plethysmography, bioelectrical impedance analysis and dual-energy X-ray absorptiometry (DXA) | Up to 123 months, between preconception, pregnancy (only using skinfold caliper) and 10 years postpartum | — |
| Changes in maternal body composition before, during and after gestation | Up to 123 months, between preconception, pregnancy and 10 years postpartum | — |
| Maternal cardiovascular health (subsample) measured through clinical examination | At preconception, 27-28 weeks of gestation, 6 months postpartum | — |
| Maternal blood pressure measured by semi-automatic blood pressure device | Between preconception, pregnancy and 10 years postpartum | — |
| Maternal allergic wellbeing measured by questionnaires and skin prick test | Up to 40 months, between preconception, pregnancy and 18 months postpartum | — |
| Maternal skin microbiome collected by sterile tape strips | 34-36 weeks of gestation and 18 months postpartum | — |
| Maternal mental health/emotional wellbeing measured by questionnaires and behavioural tasks | Between preconception, pregnancy and 10 years postpartum | — |
| Mode of delivery | Delivery | — |
| Pregnancy complications obtained from questionnaires and clinical documents | Up to 41 weeks, between early pregnancy and delivery | — |
| Time to pregnancy | Up to 12 months, between the date of last menstrual period obtained from the first preconception visit and before conception (if pregnant) or the most recent follow up (if not pregnant) | — |
| Pregnancy and live birth rates based on ultrasound scan | Between early pregnancy and delivery | — |
| Maternal metabolomics, lipidomics and pollutant profile measured from biospecimens such as blood, urine, hair | From preconception to pregnancy and up to 10 years postpartum | — |
| Maternal epigenetic profile measured from blood and buccal smear samples | From preconception to pregnancy and up to 10 years postpartum | — |
| Maternal transcription profile measured from blood samples | From preconception to pregnancy and up to 10 years postpartum | — |
| Maternal, paternal and offspring genotyping (blood or buccal samples) | From preconception to pregnancy and up to 10 years postpartum | — |
| Maternal micronutrient status measured from blood samples | From preconception to pregnancy and up to 10 years postpartum | — |
| Maternal microbiota composition profile measured from stool and epithelial (breast, vaginal and rectal) swab samples | Up to 24 months, preconception, to pregnancy, pre-delivery and 6 weeks postpartum | — |
| Breast milk macronutrient profile | Up to 6 months, from 1 week to 6 months postpartum | — |
| Breast milk micronutrient profile | Up to 6 months, from 1 week to 6 months postpartum | — |
| Breast milk metabolomic profile | Up to 6 months, from 1 week to 6 months postpartum | — |
| Breast milk epigenetic profile | Up to 6 months, from 1 week to 6 months postpartum | — |
| Maternal and infant transcriptomics (including of breast milk) | Up to 28 months, between preconception, pregnancy and 6 months postpartum | — |
| Influence of parental and offspring genotypes, body compositions, lifestyle and diet on the above primary and secondary outcomes | Between preconception, pregnancy and 10 years postpartum | — |
Countries
Singapore
Contacts
PRINCIPAL_INVESTIGATORJerry Kok Yen Chan
KK Women's and Children's Hospital
Outcome results
None listed