Clinical trial NCT03531658: Singapore PREconception Study of Long-Term Maternal and Child Outcomes
Official title: Singapore PREconception Study of Long-Term Maternal and Child Outcomes (S-PRESTO)
Study type: OBSERVATIONAL
Overall status: ACTIVE_NOT_RECRUITING
Conditions: Metabolic Disease
Neurological and Mental Health Conditions
Genetics Predisposition
Skin Condition
Environmental Exposure
Socioeconomic Factors
Psychology, Social
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
Lead sponsor: KK Women's and Children's Hospital
Sponsor class: OTHER_GOV
Collaborators: name: National University Health System, Singapore
name: Institute for Human Development and Potential (IHDP), Singapore
First posted: 2018-05-22
Enrollment: 1054
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Healthy women aged between 18 and 35 who are actively planning to conceive within a 1-year time frame upon recruitment, and later along with their children born from the indexed pregnancy.

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 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.

Eligibility criteria: 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.

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