Effectiveness of Comprehensive Tertiary Interventions on Incidence and Clinical Outcomes of Birth Defects

NCT03725878 | Completed DMC

• 1 other identifier: 2016YFC1000500(6)
• Study Type: interventional
• Target: 4,808
• Locations: 1 country
• Sites: 1

Brief Summary

This project is a single blind cluster randomized controlled trial with a purpose of assessing the effectiveness of a comprehensive tertiary interventions (before pregnancy, during pregnancy and after delivery) on the incidence and the clinical outcomes of birth defects in a preparing-for-pregancy population in Shanghai. The preconception intervention is focused on identifying individuals whose red blood cell folate level is below recommended level for preventing neural tube defects (400ng/ml) or with elevated homocysteine level (over th 80th percentiles, 6.8 µmol/L) , and modifying their folate deficiency status to normal before pregnancy.

Conditions

Birth Defects

Keywords

Birth Defects; periconception; randomized controlled trial; folate

Outcome Measures

Primary Outcomes (1)

• Incidence of total fetal birth defects found during the second trimester, still birth, and neontal birth defects identified after delivery

  This is a composite outcome: the total number of fetus defects detected by Down's syndrome screenings, NT examinations and Ultrasound image examinations during the second trimester, stillbirth, and the number of birth defects after delivery diagnosed by clinical team. (Defects are classified in consistent with our birth defect monitoring policy, which have 24 types of defects: Anencephalus; Spina bifida; Encephalocele; Congenital Hydrocephalus; Cleft Palate; Cleft Lip; Cleft Lip with Cleft Palate; Microtia (including Anotia); Deformity of external ear(s) (except Microtia and Anotia); Esophageal atresia or stenosis; Anorectal atresia (including Congenital Anorectal Malformations); Hypospadia; Ectopocystis; Pes Equinovarus; Polydactylism; Syndactylia; Limb shortening; Congenital Diaphragmatic Hernia; Pcromphalus; Celoschisis; Conjoined Twins; Trisomy 21 syndrome; Congenital heart disease; Others. )

  From the confirmation of pregnant to 28 days after birth

Secondary Outcomes (5)

• Incidence rate of total abortion because of the affected congenital defects

  From the confirmation of pregnant to the 28th gestational week

• Incidence of death or severe organ dysfunctions

  From birth to 6 months after delivery ( can be expanding to the end of the 7th month)

• Extra medical cost that relates to affecting any birth defects during pregnancy and after birth

  From confirmation of pregnancy to one year old after birth

• incidence of congenital heart defect

  from conception to one year old

• Total pregnancy loss

  from conception to 28 gestational weeks

Study Arms (2)

Interventional

EXPERIMENTAL

Standard tertiary interventions of birth defects; Additional preconception health care; Additional health care procedures during and after pregnancy.

Procedure: Standard tertiary interventions of birth defects; Procedure: Additional preconception health care; Procedure: Additional health care procedures during and after pregnancy

Control

ACTIVE COMPARATOR

Standard tertiary interventions of birth defects; Additional health care procedures during and after pregnancy.

Procedure: Standard tertiary interventions of birth defects; Procedure: Additional health care procedures during and after pregnancy

Interventions

Standard tertiary interventions of birth defects PROCEDURE

Couples eligible for reproductive policy are entitled to routine health cares including general health cares (health education, medical history inquiry, physical examinations, consulting guidance and pregnancy outcome follow-up) and medical examinations (laboratory examinations, virus screenings and image examinations). But nutrients status are not included in these examinations, such as folate, vitamin B12, and macroelements, et al. Regular antenatal cares are required, such as deformity screening by ultrasound. Routine neonatal screenings are conducted to diagnose infant with birth defect timely.

Also known as: Routine preconception and pregnant health cares

Control; Interventional

Additional preconception health care PROCEDURE

Various studies have revealed that folate is essential in early embryo development, whereas folate level evaluation in periconception women is not included in routine health cares. Therefore, we evaluate subject's folate level by serum and red blood cell folate examination. By combination of folate supplement obtained by questionnaire,folate level evaluated by examinations and folate metabolism ability evaluated by genotyping key enzymes in folate metabolism, an individualized folic acid supplementary guide is given to subjects. Red blood cell folate concentration \>400 ng/ml before pregnancy is recommended.

Also known as: Individualized guide for folic acid supplementary

Interventional

Additional health care procedures during and after pregnancy PROCEDURE

Fetus with birth defect will be referred to a tertiary hospital to receive genetic assessments and prenatal diagnosis to reduce unnecessary abortions. A 6-months follow up will be conducted to follow children's birth outcomes. It also helps clinical team to give early diagnosis and treatment for children with birth defect to reduce disability and improve life quality of defect children.

Also known as: Green channels for antenatal care and postnatal care

Control; Interventional

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Females and their husbands attend pre-pregnancy physical examinations from Minhang distrit and Songjiang distrit in Shanghai.
• Couples who have planned to be pregnant within a year
• Women are between 18 and 45 years old

Sponsors & Collaborators

• Children's Hospital of Fudan University: lead
• Minhang Maternal and Children Health Hospital: collaborator
• Songjiang Maternal and Children Health Hospital: collaborator

Study Sites (1)

Children Hospital of Fudan University

Shanghai, Shanghai Municipality, 201102, China

Location

Related Publications (4)

• Liu S, Joseph KS, Luo W, Leon JA, Lisonkova S, Van den Hof M, Evans J, Lim K, Little J, Sauve R, Kramer MS; Canadian Perinatal Surveillance System (Public Health Agency of Canada). Effect of Folic Acid Food Fortification in Canada on Congenital Heart Disease Subtypes. Circulation. 2016 Aug 30;134(9):647-55. doi: 10.1161/CIRCULATIONAHA.116.022126.

  PMID: 27572879 BACKGROUND

• Czeizel AE, Dudas I, Vereczkey A, Banhidy F. Folate deficiency and folic acid supplementation: the prevention of neural-tube defects and congenital heart defects. Nutrients. 2013 Nov 21;5(11):4760-75. doi: 10.3390/nu5114760.

  PMID: 24284617 BACKGROUND

• Ebadifar A, KhorramKhorshid HR, Kamali K, Salehi Zeinabadi M, Khoshbakht T, Ameli N. Maternal Supplementary Folate Intake, Methylenetetrahydrofolate Reductase (MTHFR) C677T and A1298C Polymorphisms and the Risk of Orofacial Cleft in Iranian Children. Avicenna J Med Biotechnol. 2015 Apr-Jun;7(2):80-4.

  PMID: 26140186 BACKGROUND

• Li M, Zhang Y, Chen X, Wang D, Ji M, Jiang Y, Dou Y, Ma X, Sheng W, Yan W, Huang G. Effectiveness of community-based folate-oriented tertiary interventions on incidence of fetus and birth defects: a protocol for a single-blind cluster randomized controlled trial. BMC Pregnancy Childbirth. 2020 Aug 20;20(1):475. doi: 10.1186/s12884-020-03154-w.

  PMID: 32819312 DERIVED

MeSH Terms

Conditions

Congenital Abnormalities

Interventions

Prenatal Care; Postnatal Care

Condition Hierarchy (Ancestors)

Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Intervention Hierarchy (Ancestors)

Patient Care; Therapeutics; Maternal Health Services; Community Health Services; Health Services; Health Care Facilities Workforce and Services; Perinatal Care

Study Officials

• Ying G Huang, MD, Ph.D

  Children's Hospital of Fudan University

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Masking Details: This is a single-blind randomized controlled trial, participants are blinded from their preconceptional folate nutrition status.
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Model Details: cluster rondomization with average cluster size =100 pregnancies.

Study Record Dates

• First Submitted: October 24, 2018
• First Posted: October 31, 2018
• Study Start: October 31, 2018
• Primary Completion: October 8, 2023
• Study Completion: September 10, 2024
• Last Updated: February 20, 2025

Record last verified: 2025-02

Locations

CN (1)