Relationship About Pregnancy Health and Offspring Developmental &Behavioral Outcomes
Relationship About Pregnancy Health and Offspring Developmental &Behavioral Outcomes
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 .
1. 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.

 2. 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:

 Manufacture recruiting advertisements of major depressive disorder, ADHD, developmental
 delay/intellectual disability related knowledge and disease hazards, the importance of
 early diagnosis, recruitment information of pregnant women and their children enrolled
 in the study (for example: network media recruitment advertisement, WeChat H5
 recruitment advertisement, network health management platform recruitment advertisement,
 etc.).

 7. Benefit Assessment： A. The pregnant women volunteered to participate in the study are
 able to enjoy regular check-ups (once every three months, including height, weight,
 blood pressure, mood questionnaires, etc.); B. Eligible children volunteer to
 participate in the study, all can enjoy free physical examination (height, weight) at
 the age of 1, 2, 3, and 6, moreover according to age to enjoy free screening or
 diagnostic test related to cognitive development level and attention deficit
 hyperactivity disorder test; C. The parents of all the children involved can receive the
 knowledge of parenting through WeChat or network health management platform, and be
 provided with free parenting seminars regularly; D. High-risk pregnant women and
 children are given priority access to the superior hospital for diagnosis and treatment;
 E. All subjects are eligible for the the nutrient level test of preferential price, 16S
 test (intestinal flora detection) of the preferential price , free related genetic test;
 F. Study may solve some urgent problems in the prevention and treatment of developmental
 disabilities such as ADHD, developmental delay/intellectual disability, and contribute
 to promoting maternal and child health, improving the quality of the population, and
 promoting the sustained and healthy development of the national economy.

 8. Risk Assessment ( illustrate the possible risk rate and take measures to ensure that
 risk is minimized in a possible range):

 A. Possible risk: the probability of subjects losing to follow-up (loss ratio of 5 to
 10% due to various reasons); B. Measurements: The professional staff would regularly
 contact with the mother or the child by phone or Wechat. And after the birth of a child,
 childbearing knowledge or childcare lectures are regularly provided for the parents.

 9. Special crowd protection:

 A.In the course of the study, obstetricians, psychologists, and childcare doctors are all
 involved in providing health care for pregnant women, mothers and children.

 B. At the same time, please protect the subjects' privacy and not to give out the information
 of the subjects. All subjects' personal information is treated with confidentiality and this
 study data is only used in the study design scope to ensure that the subjects' privacy is not
 invaded.
Inclusion Criteria:

 1. Inclusion criteria for pregnant women: Aged 20~49;

 2. no cognitive impairment, able to complete the scale test;

 3. Hamilton Depression Scale (HAMD questionnaire) is normal (HAMD score <8 points) or
 mild to moderate positive (HAMD questionnaire score: 8~35 points);

 4. Participants are asked for their own written informed content for the study;

 Exclusion Criteria:

 1. Patients receiving anti-depression therapy during the first 6 months of gestation or
 during pregnancy;

 2. Patients with severe depression with scores of no less than 35 points in the HAMD
 questionnaire;

 3. Patients with other mental disorders;

 4. Patients with neurological diseases;

 5. Patients with cognitive dysfunction.