Singapore PREconception Study of Long-Term Maternal and Child Outcomes

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

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Metabolic Disease; Neurological and Mental Health Conditions

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 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.

• Study Type: Observational
• Enrollment (Actual): 1054

Contacts and Locations

Study Locations

• Singapore
  • Singapore, Singapore
    • KK Women's and Children's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 35 years (Adult)
• Accepts Healthy Volunteers: Yes

• 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.

Description

Inclusion Criteria:

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:

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. 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.

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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

Secondary Outcome Measures

Outcome Measure	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 anogenital distance measured by Vernier calipers	Up to 12 months, from birth until 12 months of age
Maternal cardiovascular health (subsample) measured through clinical examination	At preconception, 27-28 weeks of gestation, 6 months 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
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 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
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 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 blood pressure measured by semi-automatic blood pressure device	Up to 123 months, between preconception, pregnancy and 8 years postpartum
Maternal mental health/emotional wellbeing measured by questionnaires and behavioural tasks	Up to 123 months, between preconception, pregnancy and 8 years postpartum
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
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

Other Outcome Measures

Outcome Measure	Time Frame
Offspring health obtained from questionnaires and clinical documents	Up to 96 months, from birth until 8 years of age
Maternal health obtained from questionnaires and clinical documents	Up to 123 months, between preconception, pregnancy and 8 years postpartum

Collaborators and Investigators

• Sponsor: KK Women's and Children's Hospital
• Collaborators: Singapore Institute for Clinical Sciences; National University Health System, Singapore
• Investigators: Principal Investigator: Jerry Kok Yen Chan, KK Women's and Children's Hospital

Publications and helpful links

General Publications

• Li LJ, Du R, Loy SL, Chong YS, Chan JKY, Wong TY, Eriksson JG, Huang Z, Zhang C. Retinal microvasculature and risk of spontaneous abortion in multiethnic Southeast Asian women. Fertil Steril. 2022 Oct;118(4):748-757. doi: 10.1016/j.fertnstert.2022.06.033. Epub 2022 Aug 16.
• Lim SX, Loy SL, Colega MT, Lai JS, Godfrey KM, Lee YS, Tan KH, Yap F, Shek LP, Chong YS, Eriksson JG, Chan JKY, Chan SY, Chong MF. Prepregnancy adherence to plant-based diet indices and exploratory dietary patterns in relation to fecundability. Am J Clin Nutr. 2022 Feb 9;115(2):559-569. doi: 10.1093/ajcn/nqab344.
• Huang L, Loy SL, Chen WQ, Eriksson JG, Chong YS, Huang Z, Chan JKY, Wong TY, Kramer M, Zhang C, Li LJ. Retinal microvasculature and time to pregnancy in a multi-ethnic pre-conception cohort in Singapore. Hum Reprod. 2021 Oct 18;36(11):2935-2947. doi: 10.1093/humrep/deab197.
• Lim SX, Colega MT, M Ayob MN, Robinson SM, Godfrey KM, Bernard JY, Lee YS, Tan KH, Yap F, Shek LP, Chong YS, Eriksson JG, Chan JK, Chan SY, Chong MF. Identification and reproducibility of dietary patterns assessed with a FFQ among women planning pregnancy. Public Health Nutr. 2021 Jun;24(9):2437-2446. doi: 10.1017/S1368980021001178. Epub 2021 Mar 22.
• Loy SL, Ku CW, Lai AEQ, Choo XH, Ho AHM, Cheung YB, Godfrey KM, Chong YS, Gluckman PD, Shek LP, Tan KH, Yap FKP, Chan SY, Chan JKY. Plasma glycemic measures and fecundability in a Singapore preconception cohort study. Fertil Steril. 2021 Jan;115(1):138-147. doi: 10.1016/j.fertnstert.2020.07.014. Epub 2020 Oct 15.

Study record dates

Study Major Dates

• Study Start (Actual): February 27, 2015
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2026

Study Registration Dates

• First Submitted: August 27, 2017
• First Submitted That Met QC Criteria: May 8, 2018
• First Posted (Actual): May 22, 2018

Study Record Updates

• Last Update Posted (Actual): October 12, 2023
• Last Update Submitted That Met QC Criteria: October 10, 2023
• Last Verified: January 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Metabolic Diseases
• Other Study ID Numbers: 2014/692/D

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No