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

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ClinicalTrials.gov Identifier: NCT03725878
Recruitment Status : Recruiting
First Posted : October 31, 2018
Last Update Posted : July 2, 2019
Sponsor:
Collaborators:
Minhang Maternal and Children Health Hospital
Songjiang Maternal and Children Health Hospital
Information provided by (Responsible Party):
Guoying huang, Children's Hospital of Fudan University

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.

Condition or disease Intervention/treatment Phase
Birth Defects Procedure: Standard tertiary interventions of birth defects Procedure: Additional preconception health care Procedure: Additional health care procedures during and after pregnancy Not Applicable

Detailed Description:

According to World health Organization (WHO), approximately 3.2 million children are born with birth defect(s) worldwide and the incidence of birth defects in China is 5.6%. Birth defects are the main cause of fetal death, infant mortality and morbidity, and long-term disability. Congenital heart defects, oral clefts, hydrocephalus, neural tube defects and mental retardation are most common birth defects in China. Though the etiology of birth defects is still unknow, many studies indicated that maternal key nutrition factors, especially maternal folic acid status, during periconception played an important role in organogenesis, reducing the incidence of neural tube defects, congenital heart diseases and some other birth defects.

Our project is a single-blind, cluster randomized controlled trial that aim at evaluating whether hospital-based tertiary intervention approaches reduce the incidence of birth defects (compound primary outcomes, including neural tube defects, congenital heart defects, cleft lips and palates, hydrocephalus, alimentary tract malformations or urological deformities) that identified at middle of gestation via ultrasound or clinical observation at birth. Every couple attending premarital check or preconception physical examination from Minhang and Songjiang district in Shanghai will be recruited. Recruited couples are to draw blood samples and invite to complete questionnaires that collecting informations on diet supplementation. Comprehensive interventions before conception are based on serum folate, red blood cell folate, homocysteine, vitamin B12 and fasting glycemic and lipids profiles. Single nucleotide polymorphisms related to folate and homocysteine matalism pathway will be genotyped in participants with sufficient intake of folic acid but unknown deficiency of the nutrients. Venous blood of pregnant women and questionnaires about the supplementation of key nutrients at the first antenatal visit are also obtained. NT examination, Down's screening, and ultrasound examination results are collected during the second trimester (15-24 gestational week), then routine prenatal genetic counseling, assessment, and diagnosis are provided according to the local policy to those pregnant women with positive screen results indicating high risk of fatal birth defects. Newborns with above mentioned birth defects are provided green channel to clinical specialty team for further diagnosis, surgical correction and rehabilitation guidance. Clinical follow up will be conducted till 6-month old for the prognosis of treatment. The current project will provide evidence on the necessity and effectiveness of preconception intervention focusing on sufficient folate nutrition levels in prevention of birth defects.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 2200 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: cluster rondomization with average cluster size =100 pregnancies.
Masking: Single (Participant)
Masking Description: This is a single-blind randomized controlled trial, participants are blinded from their preconceptional folate nutrition status.
Primary Purpose: Prevention
Official Title: Effectiveness of Comprehensive Tertiary Interventions on Incidence and Clinical Outcomes of Birth Defects : a Cluster Randomisation Intervention Trial
Actual Study Start Date : October 31, 2018
Estimated Primary Completion Date : June 30, 2021
Estimated Study Completion Date : December 31, 2021

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Folic Acid
Drug Information available for: Folic acid

Arm Intervention/treatment
Experimental: Interventional
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
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.
Other Name: Routine preconception and pregnant health cares

Procedure: Additional preconception health care
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.
Other Name: Individualized guide for folic acid supplementary

Procedure: Additional health care procedures during and after pregnancy
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.
Other Name: Green channels for antenatal care and postnatal care

Active Comparator: Control
Standard tertiary interventions of birth defects; Additional health care procedures during and after pregnancy.
Procedure: Standard tertiary interventions of birth defects
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.
Other Name: Routine preconception and pregnant health cares

Procedure: Additional health care procedures during and after pregnancy
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.
Other Name: Green channels for antenatal care and postnatal care




Primary Outcome Measures :
  1. Incidence of total fetal birth defects found during the second trimester, still birth, and neontal birth defects identified after delivery [ Time Frame: From the confirmation of pregnant to 28 days after birth ]

    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. )



Secondary Outcome Measures :
  1. Incidence rate of total abortion because of the affected congenital defects [ Time Frame: From the confirmation of pregnant to the 28th gestational week ]
    Reasons of abortion are recorded

  2. Incidence of death or severe organ dysfunctions [ Time Frame: From birth to 6 months after delivery ( can be expanding to the end of the 7th month) ]
    Severe organ dysfunctions were defined based on specialty clinical examinaitons

  3. Extra medical cost that relates to affecting any birth defects during pregnancy and after birth [ Time Frame: From confirmation of pregnancy to one year old after birth ]
    Additional medical cost that exceeds normal pregnancies and children within one year old



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Ages Eligible for Study:   18 Years to 45 Years   (Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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

Exclusion Criteria:

-


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03725878


Contacts
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Contact: Wei L Yan, Ph.D 86 21 64931215 ext 86 21 64931215 yanwl@fudan.edu.cn
Contact: Ying G Huang, MD, Ph.D 86-21-64931928 ext 86-21-64931913 gyhuang@shmu.edu.cn

Locations
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China, Shanghai
Children Hospital of Fudan University Recruiting
Shanghai, Shanghai, China, 201102
Contact: Guoying Huang    (21)64931928    gyhuang@shmu.edu.cn   
Sponsors and Collaborators
Children's Hospital of Fudan University
Minhang Maternal and Children Health Hospital
Songjiang Maternal and Children Health Hospital
Investigators
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Study Chair: Ying G Huang, MD, Ph.D Children's Hospital of Fudan University
  Study Documents (Full-Text)

Documents provided by Guoying huang, Children's Hospital of Fudan University:
Statistical Analysis Plan  [PDF] January 2, 2019


Publications:
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Responsible Party: Guoying huang, Professor, Children's Hospital of Fudan University
ClinicalTrials.gov Identifier: NCT03725878     History of Changes
Other Study ID Numbers: 2016YFC1000500(6)
First Posted: October 31, 2018    Key Record Dates
Last Update Posted: July 2, 2019
Last Verified: December 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Guoying huang, Children's Hospital of Fudan University:
Birth Defects
periconception
randomized controlled trial
folate
Additional relevant MeSH terms:
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Congenital Abnormalities
Folic Acid
Hematinics
Vitamin B Complex
Vitamins
Micronutrients
Nutrients
Growth Substances
Physiological Effects of Drugs