A Prospective Cohort Study of the Association Between Pregnancy Health and Offspring Developmental & Behavioral Outcomes(Multi-Centered)
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 发起方
- 入组人数
- 3,000
- 试验地点
- 5
- 主要终点
- Homocysteine
研究概览
简要总结
This topic puts forward a hypothesis: genetic and environmental factors such as major depressive disorder during pregnancy, nutritional status of vitamin A, D, E, and folic acid, intestinal microecology, and bisphenol A exposure, may affect the cognitive development level of the offspring through the genetic correlation with attention deficit hyperactivity disorder, developmental delay/intellectual disability, and major depressive disorder, allelic heterogeneity and pleiotropy of ITIH3 mediated by SNP and CACNB2, neurotransmitters like dopamine, and metabolic pathways, thereby increasing the risk of attention deficit hyperactivity disorder and developmental delay/intellectual disability prevalence on offspring.
This topic planning from allelic heterogeneity and pleiotropy of attention deficit hyperactivity disorder and major depressive disorder mediated by SNP, neurotransmitters like dopamine, and metabolic pathways, explores deeply the influences on children's development level and the risk of common neurological disorder caused by genetic and environmental factors during pregnancy, looking for reasonable prevention, early diagnosis of biomarkers and therapeutic targets, in order to provide data support for further improvement and revision of national mother and infant healthcare policy .
详细描述
- Technology Roadmap:①Pregnant Women:Subjects are rolled in the group. ② 21 Weeks of Gestation：Sign informed contents (mother version), test depression scale ( BDI+HAMD ), fill in the basic information questionnaire and collect 3 ml of blood of pregnant women for genetic information extraction. ③Delivery: Sign informed contents(children version), collect 1 ml of umbilical cord blood and 2ml of urine from mother. ④Physical measurements are respectively taken when a child is 3, 6, 12, 24 months old and 3, 6 years old. And the Montreal Children Hospital Feeding Scale will be also respectively completed when a child is 6 and 12 months old. What's more, the investigators plan to carry out developmental screening for the children aged 1, 2, 3 and 6, and if the developmental screening is positive, a diagnostic test then will be carried out. ⑤When children are aged 2, 3 and 6, blood samples are taken from 3 milliliters and urine from 2 milliliters, and nutrients are detected to obtain genetic information. ⑥All biological specimens will be tested for nutrient levels and some other.⑦At last, data analysis is performed on all collected information including physical measurements, feeding behavior questionnaire, all biological specimens and so on.
- Study Protocol： A. Human Subjects Review: Studies must have approval (or be exempt, as appropriate) from a Human Subjects Protection Review Board prior to the enrollment of the first participant to be eligible for registration (Submitted, approved).
B. Register a clinical study: Prior to the launch of the project, pre-registration will be completed at clinicaltrials.gov in the international clinical study register authority.
C. Study cohort: Screening qualified pregnant women volunteered to take part in the study from pregnancy clinics of Chongqing suburban maternity and child health hospital and The Maternal and Child Health Hospital of Hainan Province. 3. Measuring scale: To assess the depression status and degree of the subjects by Hamilton Depression Scale (HAMD) and Beck depression rating scale (BDI); To evaluate the cognitive function of subjects and exclude the patients with mental retardation by Mini-Mental State Examination (MMSE) and Activity of Daily Living Scale（ADL); To screen or identify the cognitive function and level of children in different age groups by Denver development screening scale (DDST) and Gesell Developmental Schedules (Gesell), and combining with the Adaptive Scale of Infant and Children (SM) to assist in the diagnosis of developmental delay/intellectual disability, The Vanderbilt ADHD Diagnostic Rating Scale on diagnosis of ADHD. 4. Data management and statistical analysis plan:
A. All the data is recorded by the professional staff, and checked by a third person to ensure accuracy of data entry; B. All statistical analysis is performed with SAS 9.4. The statistical analysis is completed by the applicant and the professional statisticians in the epidemiology research office of the unit. 5. Recruitment process:
A. To preach related knowledge of major depressive disorder, ADHD, and developmental delay/intellectual disability in the form of obstetrics clinics, network media, and network health management platform,etc; B. Recruitment information is released by platforms such as obstetrics clinics, network health management platforms, etc., to recruit pregnant women; C. The obstetric nurses and professional recruiters (postgraduate students) assist pregnant women to sign informed consents, agree to participate in the study, and promise that the delivery of children would take part in the same sequence of study as well. 6. The required materials of recruitment:
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 年龄范围
- 3 Months 至 72 Months（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Inclusion criteria for pregnant women: Aged 20~49;
- •no cognitive impairment, able to complete the scale test;
- •Hamilton Depression Scale (HAMD questionnaire) is normal (HAMD score <8 points) or mild to moderate positive (HAMD questionnaire score: 8~35 points);
- •Participants are asked for their own written informed content for the study;
排除标准
- •Patients receiving anti-depression therapy during the first 6 months of gestation or during pregnancy;
- •Patients with severe depression with scores of no less than 35 points in the HAMD questionnaire;
- •Patients with other mental disorders;
- •Patients with neurological diseases;
- •Patients with cognitive dysfunction.
结局指标
主要结局
Homocysteine
时间窗: delivery
Homocysteine is measured for the mothers at first visit during 21 weeks of gestation and delivery. It is measured by HPLC and tandem mass spectrometry. The concentration of homocysteine less than 11.4umol/L is normal for men and less than 10.4 umol/L for women.
Bisphenol A
时间窗: 72 months
The concentration of bisphenol A is measured for mother at delivery and for children aged 2 and 6. The investigators measured the concentration of urine in order to compare the differences of children between high dose of BPA with low dose of BPA. However, as far as we know, the normal range of bisphenol A has not been reported at home and abroad. We also want to explore the relationship between bisphenol A and neuropsychiatric development.
Changes in Denver Developmental Screening Test results within 72 months of age
时间窗: 72 months
The DDST is taking at the age of 12 months,24 months,36months and 72months respectively ,consists of 104 items, spread 4 domains, such as gross motor, fine motor, language and personal-social skill. A normal score means no delay in any domain and no more than one caution; an abnormal score means two or more domains with two or more delays or one domain with two or more delays and another domains with one delay; a suspect score means one or more domains with one delay and more than one cautions or one domain with two or more delays; a score of untestable means enough refused items that the score would be suspect if they had been delays.
Changes in Vitamin D
时间窗: 72 months
Vitamin D is measured for the mothers at first visit during 21 weeks of gestation and delivery, for the children is 24 months, 36 months and 72 months respectively. It is measured by HPLC and tandem mass spectrometry. the measurement of the concentration of 25-OH-D3 as that of vitamin D. It is below 30 nmol/L considered as Vitamin D deficiency, 30-50 nmol/L considered as Vitamin D insufficiency, over 50 nmol/L considered as Vitamin D sufficiency.
Changes in Vitamin E
时间窗: 72 months
Vitamin E is measured for the mothers at first visit during 21 weeks of gestation and delivery, for the children is 24 months, 36 months and 72 months respectively. It is measured by HPLC and tandem mass spectrometry. It is normal range with the concentration of 11.6-46.4 umol/L.
Changes in Gesell Developmental Schedules test results within 72 months of age
时间窗: 72 months
The GDS is taking at the age of 12 months,24 months, 36 months and 72 months respectively , evaluate a child's cognitive, language, motor and social-emotional responses in five strands: adaptation, gross motor, fine motor, language and personal-social skill, then schedule operates off what is known as an individual's developmental quotient (DQ). Diagnostic criteria: the score of DQ≥86: normal, 76-85: marginal , 55-75: mild mental retardation, 40-54: moderate mental retardation, 25-39: severe mental retardation, and ≤25 : extremely severe mental retardation.
The Vanderbilt Attention Deficit Hyperactivity Disorder Diagnostic Rating Scale
时间窗: 72 months
The Vanderbilt ADHD Diagnostic Rating Scale (VADRS) is for children at the age of 72 months. Scores of 2 or 3 on a single Symptom question reflect often-occurring behaviors. Scores of 4 or 5 on Performance questions reflect problems in performance. To meet the diagnosis of ADHD, one must have at least 6 positive responses to either the inattentive 9 or hyperactive 9 core symptoms, or both.
Changes in vitamin A
时间窗: 72 months
Vitamin A is measured for the mothers at first visit during 21 weeks of gestation and delivery, for the children is 24 months, 36 months and 72 months respectively. It is measured by HPLC and tandem mass spectrometry. And it is considered as Vitamin A deficiency when the concentration is below 0.70 umol/L, 0.70-1.05 umol/L is considered as marginal vitamin A deficiency, 1.05-2.56 umol/L is considered as normal range, and over 2.56 umol/L is considered as Vitamin A excess.
the Adaptive Scale of Infant and Children
时间窗: 72 months
This scale is assessed for the children at the age of 72 months. Extremely low (≤5), severely low (6 points), moderately low (8 points), marginal (9 points), normal (10 points), more than normal (11 points), excellent (12 points), very good (13 points).
次要结局
- Hamilton Depression Scale(21 weeks of pregnancy)
- Folate(24 months)
- Change of weight for height Z-score(WHZ)(72 months)
- Activity of Daily Living Scale(21 weeks of pregnancy)
- Beck depression rating scale(21 weeks of pregnancy)
- Mini-Mental State Examination(21 weeks of pregnancy)
- Changes in the Montreal Children Hospital Feeding Scale within 12 months of age(12 months)
- Change of the weight for Age Z-score(WAZ)(72 months)
- Change of the height for age Z-score(HAZ)(72 months)
- Ferritin(24 months)
研究者
Chen Li
Vice Director, Professor
Children's Hospital of Chongqing Medical University