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.
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 9 years of age. Metabolic and mental health of women will also be measured from preconception until 9 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.
Study Type
OBSERVATIONAL
Enrollment
1,054
KK Women's and Children's Hospital
Singapore, Singapore
Offspring adiposity
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).
Time frame: From birth until 9 years of age
Offspring neurocognitive and behavioural development
Offspring neurocognitive and behavioural development measured by questionnaires, behavioural tasks and brain MRI.
Time frame: From 3-12 months up till 9 years of age
Duration of gestation
Time frame: Up to 42 weeks, between estimated date of conception based on ultrasound scan and date of delivery
Fetal growth measured by ultrasound scan
Time frame: Up to 30 weeks, between 6-36 weeks of gestation
Offspring body weight measured by calibrated weighing scale
Time frame: From birth until 9 years of age
Offspring pubertal assessment
Pubertal assessment by Tanner staging
Time frame: From 7 until 9 years of age
Offspring growth trajectories
Time frame: From birth until 9 years of age
Offspring adiposity trajectories (total and percentage fat mass)
Time frame: From birth until 9 years of age
Offspring anogenital distance measured by Vernier calipers
Time frame: Up to 12 months, from birth until 12 months of age
Offspring allergic wellbeing measured by skin examination and skin prick test
Time frame: Up to 60 months, from 1 week until 5 years of age
Offspring skin microbiome collected by sterile tape strips
Time frame: 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
Time frame: From birth until 9 years of age
Offspring epigenetic profile measured through cord, cord blood, and buccal smear samples
Time frame: From birth until 9 years of age
Offspring gut microbiome measured through stool samples
Time frame: From birth until 9 years of age
Maternal glucose tolerance status measured by Oral Glucose Tolerance Test (OGTT)
Time frame: At preconception, 27-28 weeks of gestation, 3 months and 2, 3, 4, 6, 8 years postpartum
Maternal weight measured by calibrated weighing scale
Time frame: Between preconception, pregnancy and 9 years postpartum
Changes in maternal weight before, during and after gestation
Time frame: Between preconception, pregnancy and 9 years postpartum
Maternal body weight status determined by body mass index based on weight (kg) /height (m)2
Time frame: At preconception visit; 3 months-9 years postpartum
Maternal body composition measured by skinfold calipers, air-displacement plethysmography, bioelectrical impedance analysis and dual-energy X-ray absorptiometry (DXA)
Time frame: Up to 123 months, between preconception, pregnancy (only using skinfold caliper) and 8 years postpartum
Changes in maternal body composition before, during and after gestation
Time frame: Up to 123 months, between preconception, pregnancy and 8 years postpartum
Maternal cardiovascular health (subsample) measured through clinical examination
Time frame: At preconception, 27-28 weeks of gestation, 6 months postpartum
Maternal blood pressure measured by semi-automatic blood pressure device
Time frame: Between preconception, pregnancy and 9 years postpartum
Maternal allergic wellbeing measured by questionnaires and skin prick test
Time frame: Up to 40 months, between preconception, pregnancy and 18 months postpartum
Maternal skin microbiome collected by sterile tape strips
Time frame: 34-36 weeks of gestation and 18 months postpartum
Maternal mental health/emotional wellbeing measured by questionnaires and behavioural tasks
Time frame: Between preconception, pregnancy and 9 years postpartum
Mode of delivery
Time frame: Delivery
Pregnancy complications obtained from questionnaires and clinical documents
Time frame: Up to 41 weeks, between early pregnancy and delivery
Time to pregnancy
Time frame: 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
Time frame: Between early pregnancy and delivery
Maternal metabolomics, lipidomics and pollutant profile measured from biospecimens such as blood, urine, hair
Time frame: From preconception to pregnancy and up to 8 years postpartum
Maternal epigenetic profile measured from blood and buccal smear samples
Time frame: From preconception to pregnancy and up to 8 years postpartum
Maternal transcription profile measured from blood samples
Time frame: From preconception to pregnancy and up to 8 years postpartum
Maternal, paternal and offspring genotyping (blood or buccal samples)
Time frame: From preconception to pregnancy and up to 8 years postpartum
Maternal micronutrient status measured from blood samples
Time frame: From preconception to pregnancy and up to 8 years postpartum
Maternal microbiota composition profile measured from stool and epithelial (breast, vaginal and rectal) swab samples
Time frame: Up to 24 months, preconception, to pregnancy, pre-delivery and 6 weeks postpartum
Breast milk macronutrient profile
Time frame: Up to 6 months, from 1 week to 6 months postpartum
Breast milk micronutrient profile
Time frame: Up to 6 months, from 1 week to 6 months postpartum
Breast milk metabolomic profile
Time frame: Up to 6 months, from 1 week to 6 months postpartum
Breast milk epigenetic profile
Time frame: Up to 6 months, from 1 week to 6 months postpartum
Maternal and infant transcriptomics (including of breast milk)
Time frame: 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
Time frame: Between preconception, pregnancy and 9 years postpartum
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