Clinical trial NCT02737644: Peri-conception Key Nutritional Factors and Congenital Heart Disease
Official title: Peri-conception Key Nutritional Factors and Primary Prevention of Congenital Heart Disease(CHD)
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Congenital Heart Disease
Keywords: Congenital Heart Disease
Key Nutritional Factors
conception
pregnant
Lead sponsor: Children's Hospital of Fudan University
Sponsor class: OTHER
First posted: 2016-04-14
Enrollment: 37000
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: All couples attending pre-pregnancy physical examination from 11 districts in Shanghai from March 2016, or pregnant women present at first antenatal care \< 14 week of gestation

Brief summary: The study is a nested case-control study and the purpose is to describe the status of key nutrients(eg.folic acid and vitamins) supplementation among pregnant women in Shanghai, to find out the association between the level of serum key nutrients during peri-conceptional period and the incidence of congenital heart defects (CHD) in newborn, and to provide better preconception care.

Detailed description: Congenital heart defects (CHD) are among the most common major congenital anomalies with an incidence of about 8-12/1,000 live births worldwide. The mechanism of CHD is still unclear. Many studies indicated that the level of key nutrients (eg.folic acid and vitamins) during peri-conceptional period might affect the incidence of CHD, but the evidence is limited. The study aimed to explore the association between serum key nutrients during peri-conceptional period and the incidence of CHD in newborn. All couples attending pre-pregnancy physical examination from 11 districts (Minhang District, Huangpu District, Xuhui District, Changning District, Jingan District, Putuo District, Yangpu District, Jiading District, Pudong District，Songjiang District, Qingpu District) in Shanghai from March 2016, are recruited and their blood samples and questionnaires about the supplementation of key nutrients are collected. During the gestation, venous blood of pregnant women at all of three trimesters is taken. Besides, questionnaires about the supplementation of key nutrients at the first antenatal visit are also obtained. The level of serum folic acid, vitamin A and vitamin B12 at preconception and during gestation are measured. Finally, investigators identifies those whose newborns developed CHD during follow-up as the cases. Then, investigators selects four controls for each case from the rest of the cohort by matching on constitutional determinants of CHD such as age and sex. Participants are identified by national identification number during the follow up. The level of serum key nutrients is compared in cases and controls. Univariate and multivariate association analyses will be performed to identify risk factors to CHD by using multivariate logistic regression model.

Eligibility criteria: Inclusion Criteria:

* attend pre-pregnancy physical examination from 11 districts in Shanghai, OR pregnant women present at first antenatal care \< 14 week of gestation
* plan to deliver in Shanghai

Exclusion Criteria:

* none

Primary outcomes:
measure: preconceptional maternal serum folate level
timeFrame: usually 6 months before pregnancy
Secondary outcomes:
measure: early conceptional maternal serum folate deficiency
timeFrame: first antenatal visit (usually 12th-16th gestational week)
measure: The status of serum Vitamin D level
timeFrame: periconception period ( defined as around 6 months before and the first 3 months of gestation
measure: Pre-conceptional maternal diet folic acid supplement intake
timeFrame: preconception examination (usually 0-6 months before pregnancy)
measure: Peri-conceptional maternal plasma homocysteine level
timeFrame: peri-conception examination ( defined as about 6 months before and 3 months after conception
measure: neonatal congenital heart disease(CHD) status
timeFrame: Congenital heart disease screening during 6-72 hours after delivery
measure: Peri-conceptional paternal serum folate level
timeFrame: usually between 0-6 months before and 3 months after conception)
Other outcomes:
Locations:
city: Shanghai
country: China
facility: Children Hospital of Fudan University
state: Shanghai
Study officials:
affiliation: Children's Hospital of Fudan University
name: Ying G Huang, PHD
role: STUDY_CHAIR
References:
citation: Reller MD, Strickland MJ, Riehle-Colarusso T, Mahle WT, Correa A. Prevalence of congenital heart defects in metropolitan Atlanta, 1998-2005. J Pediatr. 2008 Dec;153(6):807-13. doi: 10.1016/j.jpeds.2008.05.059. Epub 2008 Jul 26.
citation: Ionescu-Ittu R, Marelli AJ, Mackie AS, Pilote L. Prevalence of severe congenital heart disease after folic acid fortification of grain products: time trend analysis in Quebec, Canada. BMJ. 2009 May 12;338:b1673. doi: 10.1136/bmj.b1673.
citation: Peyvandi S, Rychik J, Zhang X, Shea JA, Goldmuntz E. Preconceptual Folic Acid Use and Recurrence Risk Counseling for Congenital Heart Disease. Congenit Heart Dis. 2015 May-Jun;10(3):219-25. doi: 10.1111/chd.12206. Epub 2014 Jul 24.
citation: Chen H, Zhang Y, Wang D, Chen X, Li M, Huang X, Jiang Y, Dou Y, Wang Y, Ma X, Sheng W, Jia B, Yan W, Huang G; SPCC (Shanghai Preconception Cohort) Group. Periconception Red Blood Cell Folate and Offspring Congenital Heart Disease : Nested Case-Control and Mendelian Randomization Studies. Ann Intern Med. 2022 Sep;175(9):1212-1220. doi: 10.7326/M22-0741. Epub 2022 Aug 23.
citation: Wang D, Zhang Y, Jiang Y, Ye Y, Ji M, Dou Y, Chen X, Li M, Ma X, Sheng W, Huang G, Yan W; SPCC group. Shanghai Preconception Cohort (SPCC) for the association of periconceptional parental key nutritional factors with health outcomes of children with congenital heart disease: a cohort profile. BMJ Open. 2019 Nov 24;9(11):e031076. doi: 10.1136/bmjopen-2019-031076.