Singapore PREconception Study of Long-Term Maternal and Child Outcomes

Study Overview
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Brief Summary
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The study aims to evaluate how preconception and early prenatal environmental factors can potentially influence health outcomes for both mother and child during pregnancy and postnatally.

Detailed Description
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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 8 years of age. Metabolic and mental health of women will also be measured from preconception until 8 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.

Official Title
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Singapore PREconception Study of Long-Term Maternal and Child Outcomes (S-PRESTO)

Conditions
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Metabolic Disease, Neurological and Mental Health Conditions

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Women aged 18-35 years Intention to reside in Singapore for the next 5 years Chinese, Malay, Indian or any combinations of these 3 ethnic groups Planning to conceive within 1 year Able to provide written, informed consent Exclusion Criteria: Have been actively trying to conceive for more than 18 months Currently pregnant Assisted fertility, apart from those taking clomiphene alone in the past 1 month Established pre-existing diabetes (type 1 or type 2) Oral or implanted contraception, or with an IUCD in situ in the past 1 month On systemic steroids in the past 1 month On anticonvulsants in the past 1 month On HIV or Hepatitis B or C medication in the past 1 month Not becoming pregnant after more than 12 months from recruitment Eventual multiple pregnancies Pregnancy complications such as miscarriages, ectopic pregnancy, still birth The partners of the women will also be invited to participate in the study. Upon informed consent, fathers will have blood, urine, hair sampling, buccal swabs, body measurements and cognitive assessment. These will be done along with health and lifestyle questionnaire within one to two study visits. The mothers will consent for their children to have body measurements, cognitive assessment, buccal, hair, stool samples and allergy testing from birth to 8 years of age. Assent will also be taken when the child turns 6.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 35 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Offspring adiposity | Offspring adiposity (total and percentage fat mass) measured by skinfold calipers, air-displacement plethysmography, quantitative magnetic resonance (QMR) and Magnetic resonance imaging (MRI). | Up to 96 months, from birth until 8 years of age | 
| Offspring neurocognitive and behavioural development | Offspring neurocognitive and behavioural development measured by questionnaires, behavioural tasks and brain MRI. | Up to 9 months, from 3-12 months of age | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 |  | Up to 96 months, from birth until 8 years of age | 
| Offspring growth trajectories |  | Up to 96 months, from birth until 8 years of age | 
| Offspring adiposity trajectories (total and percentage fat mass) |  | Up to 96 months, from birth until 8 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 |  | Up to 96 months, from birth until 8 years of age | 
| Offspring epigenetic profile measured through cord, cord blood, and buccal smear samples |  | Up to 96 months, from birth until 8 years of age | 
| Offspring gut microbiome measured through stool samples |  | Up to 96 months, from birth until 8 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 years postpartum | 
| Maternal weight measured by calibrated weighing scale |  | Up to 123 months, between preconception, pregnancy and 8 years postpartum | 
| Changes in maternal weight before, during and after gestation |  | Up to 123 months, between preconception, pregnancy and 8 years postpartum | 
| Maternal body weight status determined by body mass index based on weight (kg) /height (m)2 |  | At preconception visit; 3 months- 8 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 8 years postpartum | 
| Changes in maternal body composition before, during and after gestation |  | Up to 123 months, between preconception, pregnancy and 8 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 |  | Up to 123 months, between preconception, pregnancy and 8 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 |  | Up to 123 months, between preconception, pregnancy and 8 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 |  | Up to 123 months, from preconception to pregnancy and up to 8 years postpartum | 
| Maternal epigenetic profile measured from blood and buccal smear samples |  | Up to 123 months, from preconception to pregnancy and up to 8 years postpartum | 
| Maternal transcription profile measured from blood samples |  | Up to 123 months, from preconception to pregnancy and up to 8 years postpartum | 
| Maternal, paternal and offspring genotyping (blood or buccal samples) |  | Up to 123 months, from preconception to pregnancy and up to 8 years postpartum | 
| Maternal micronutrient status measured from blood samples |  | Up to 123 months, 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 |  | 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 |  | Up to 123 months, between preconception, pregnancy and 8 years postpartum |