## Protocol Section
### Identification Module
**NCT ID:** NCT06414655

**Acronym:** ChiTwiMC

**Brief Title:** Multicenter Prospective Cohort Study of Twin Maternal-Child Dyads in China

**Official Title:** Multicenter Prospective Cohort Study of Twin Maternal-Child Dyads in China

#### Organization Study ID Info
**ID:** ChiTwiMC
#### Organization
**Class:** OTHER
**Full Name:** Peking University Third Hospital
### Status Module
#### Completion Date
**Date:** 2026-11-30

**Type:** ESTIMATED

#### Expanded Access Info
#### Last Update Post Date
**Date:** 2024-05-16

**Type:** ACTUAL

**Last Update Submit Date:** 2024-05-09

**Overall Status:** RECRUITING

#### Primary Completion Date
**Date:** 2026-11-30

**Type:** ESTIMATED

#### Start Date
**Date:** 2024-03-01

**Type:** ACTUAL

**Status Verified Date:** 2024-01

#### Study First Post Date
**Date:** 2024-05-16
**Type:** ACTUAL
**Study First Submit Date:** 2024-03-17
**Study First Submit QC Date:** 2024-05-09
### Sponsor Collaborators Module

#### Collaborators

**Class:** OTHER

**Name:** First Affiliated Hospital, Sun Yat-Sen University

**Class:** OTHER

**Name:** Chongqing Medical University

**Class:** OTHER

**Name:** Shengjing Hospital

**Class:** OTHER

**Name:** Peking University

**Class:** OTHER

**Name:** Nankai University

**Class:** OTHER

**Name:** Shanghai First Maternity and Infant Hospital

**Class:** OTHER

**Name:** The First Affiliated Hospital of Anhui Medical University

**Class:** OTHER

**Name:** International Peace Maternity and Child Health Hospital

**Class:** OTHER

**Name:** The Second Hospital of Shandong University

**Class:** OTHER_GOV

**Name:** Shandong Provincial Hospital

#### Lead Sponsor

**Class:** OTHER

**Name:** Peking University Third Hospital

#### Responsible Party

**Type:** SPONSOR

### Oversight Module

**Is FDA Regulated Device:** False

**Is FDA Regulated Drug:** False

### Description Module

**Brief Summary:** Multicenter Prospective Cohort Study of Twin Maternal-Child Dyads in China (ChiTwiMC) is supported by National Key Research and Development Program of China - Reproductive Health and Women's and Children's Health Protection Project. This project is funded by the Ministry of Science and Technology of China under grant number 2023YFC2705900. The ChiTwiMC cohort is led by Professor Wei Yuan from the Department of Gynecology and Obstetrics at Peking University Third Hospital.

**Detailed Description:** The ChiTwiMC Cohort focusing on the serious complications of twin pregnancy, establish a multicenter large prospective mother-child cohort of twin pregnancy covering pregnancy→neonatal period→early childhood, and a multi-variety, multi-stage biobank for the study of adverse outcomes of twin pregnancy. The ChiTwiMC Cohort is planning to recruit 2000 pregnant women aged 18-45 years from 9 large obstetrical center of major University-affiliated Hospitals across China, between December 2023 and May 2026. All women will be enrolled prior to 14 wks of gestation, pregnancy was followed up at 22-28 wks, 30-38 wks of gestation, delivery, postpartum 42 days, 6 months, 12 months. Data including demographics, medical history, reproductive history, clinical diagnosis, treatment information, and pregnancy and birth outcomes will be collected via electronic data capture system. Track the outcome of severe maternal-fetal complications and early neonatal outcomes of twins, and collect biological samples, including peripheral venous blood, hair and cervicovaginal secretions from pregnant women, placenta tissue, amniotic fluid and unbilical cord blood at delivery, meconium and hair from newborns, buccal mucosa from infants and peripheral venous blood from the husband.

### Conditions Module

**Conditions:**

- Twin Pregnancy, Antepartum Condition or Complication

- Twin to Twin Transfusion as Antepartum Condition

- Pre-Term

- Pre-Eclampsia

- Twin Monochorionic Diamniotic Placenta

- Twin Dichorionic Diamniotic Placenta

- High Risk Pregnancy

- Twin Placenta

### Design Module

#### Bio Spec

**Description:** Collecting peripheral venous blood from husband, hair during the first trimester, peripheral venous blood and cervicovaginal secretions during the first trimester, second trimester, late pregnancy before labor, placental tissue, amionic fluid and umbilical cord blood during delivery, hair, meconium of newborns, and buccal mucosa from infants.

**Retention:** NONE_RETAINED

#### Design Info

**Observational Model:** COHORT

**Time Perspective:** PROSPECTIVE

#### Enrollment Info

**Count:** 2000

**Type:** ESTIMATED

**Study Type:** OBSERVATIONAL

### Outcomes Module

#### Primary Outcomes

**Description:** Preterm delivery is defined as delivery between 28 and 37 gestational weeks.

**Measure:** Rate of preterm delivery

**Time Frame:** From inclusion to delivery

**Description:** Preeclampsia is defined as the condition occurring in pregnant women after 20 weeks of gestation, characterized by systolic blood pressure ≥140 mmHg and/or diastolic blood pressure ≥90 mmHg, accompanied by any of the following: a urinary protein quantification ≥0.3 g/24 h, or a urine protein/creatinine ratio ≥0.3, or random urine protein ≥ (+) (as a method of examination when protein quantification is not feasible). In the absence of proteinuria, the condition may still be diagnosed if there is involvement of any organ or system, including but not limited to critical organs such as the heart, lungs, liver, kidneys, or abnormalities in the hematological, digestive, or neurological systems, as well as complications affecting the placenta-fetus.

**Measure:** Rate of preeclampsia

**Time Frame:** From inclusion to delivery

**Description:** TTTS is diagnosed in monochorionic diamniotic twin pregnancies when there is a discordance in amniotic fluid volumes, with one fetus exhibiting polyhydramnios and the other oligohydramnios. Specifically, before 20 weeks of gestation, the condition is diagnosed if one fetus (the recipient) has a deepest vertical pocket (DVP) of amniotic fluid ≥8cm, while the other fetus (the donor) has a DVP ≤2cm; after 20 weeks of gestation, the diagnosis is made if one fetus (the recipient) has a DVP ≥10cm, while the other fetus (the donor) has a DVP ≤2cm.

**Measure:** Rate of twin-to-twin transfusion syndrome (TTTS)

**Time Frame:** From inclusion to delivery

**Description:** sFGR is diagnosed in monochorionic diamniotic twin pregnancies when one fetus has an estimated fetal weight below the 10th percentile for its gestational age, and there is a discrepancy of ≥25% in the estimated fetal weights between the two fetuses.

**Measure:** Rate of selective fetal growth restriction (sFGR)

**Time Frame:** From inclusion to delivery

**Description:** Fetal brain injury is an abnormality in the structural and functional integrity of the cerebrum, cerebellum, or brainstem during the gestational period, caused by various factors such as hypoxic-ischemic events, infections, hemorrhage, congenital malformations, and genetic metabolic disorders.

**Measure:** Rate of fetal brain injury

**Time Frame:** From inclusion to delivery

**Description:** Brain injury refers to damage to the central nervous system resulting from various risk factors during pregnancy, childbirth, and the neonatal period. Clinically, it manifests as central motor disorders, cognitive impairments, language disorders, visual and auditory impairments, as well as difficulties in social interaction and psychological and behavioral disorders. It needs pregnant history or birth history, (such as one of twin intrauterine fetal death, Intrauterine distress), manifestation, and ultrasound, CT, MRI, electroencephalogram to make a definite diagnosis.

**Measure:** Rate of neonatal brain injury

**Time Frame:** From inclusion to delivery

**Description:** Early childhood developmental delay of the offspring refers to a significant lag or delay in achieving age-appropriate developmental milestones across one or more domains, including cognitive, language, motor, social-emotional, and adaptive skills, during the early years of life (typically from birth to 5 years of age) in comparison to established norms or peers. The assessment of early childhood developmental delay is conducted using standardized scales such as Ages Stages Questionnaires (Third Edition), Gesell Developmental Schedules, and Bayley Scales of Infant and Toddler Development. The actual measurement process will be depending on the routine pediatric settings and resources available at each participating institution.

**Measure:** Rate of early childhood developmental delay of the offspring

**Time Frame:** Within 1 year after delivery

**Description:** Each child is measured twice. If the difference is less than 0.1 cm, the average of the two measurements is taken. If the difference is greater than 0.1 cm, the measurement is repeated.

**Measure:** Children's height

**Time Frame:** Within 1 year after delivery

**Description:** Each newborn is measured twice. If the difference is less than 0.01 kg, the average of the two measurements is taken. If the difference is greater than 0.01 kg, the measurement is repeated.

**Measure:** Children's weight

**Time Frame:** Within 1 year after delivery

#### Secondary Outcomes

**Description:** Women's physiological and psychological changes during pregnancy will affect sleep, and the occurrence of bad sleep during pregnancy is more common. It is generally assessed by a sleep questionnaire.

**Measure:** Rate of sleep disorders

**Time Frame:** From inclusion to delivery

**Description:** Maternal mental health is as important as physical health, and good maternal mental health helps to promote the physical and mental health of the baby, as well as their own physical condition and natural childbirth. The condition of pregnant women is generally assessed by psychiatric departments.

**Measure:** Rate of mental and phycological disorders

**Time Frame:** From inclusion to delivery

**Description:** The death of one fetus for twin pregnancy，the occurrence in the second and third trimesters of pregnancy has substantial adverse effects on surviving infants.

**Measure:** Rate of single intrauterine fetal demise

**Time Frame:** From inclusion to delivery

**Description:** Take two consecutive measurements on the same arm, the systolic blood pressure more than 140 mmHg and (or) the diastolic blood pressure more than 90 mmHg. High blood pressure may lead to severe complications such as preclampsia and clampsia.

**Measure:** Rate of gestational hypertension

**Time Frame:** From inclusion to delivery

**Description:** Diagnosed with gestational diabetes through an oral glucose tolerance test (OGTT). The blood glucose threshold of fasting, 1 h and 2 h after taking oral glucose was 5.1, 10.0, 8.5 mmolL, respectively, and the blood glucose level reached or exceeded the above criteria at any time point was diagnosed as GDM. GDM is clearly associated with adverse pregnancy outcomes such as fetal macrosomia, cesarean section delivery, preterm birth, and preeclampsia

**Measure:** Rate of gestational diabetes mellitus

**Time Frame:** From inclusion to delivery

**Description:** Deaths during pregnancy or less than 42 days after termination of pregnancy.

**Measure:** Number of maternal death

**Time Frame:** From inclusion to delivery

**Description:** After 28 gestational weeks, the fetus dies before or during delivery

**Measure:** Rate of stillbirth

**Time Frame:** From inclusion to delivery

**Description:** Each newborn is measured twice. If the difference is less than 0.01 kg, the average of the two measurements is taken. If the difference is greater than 0.01 kg, the measurement is repeated.

**Measure:** Birth weight

**Time Frame:** At delivery

**Description:** Each newborn is measured twice. If the difference is less than 0.1 cm, the average of the two measurements is taken. If the difference is greater than 0.1 cm, the measurement is repeated.

**Measure:** Birth length

**Time Frame:** At delivery

### Eligibility Module

**Eligibility Criteria:** Inclusion Criteria:

* Twin pregnancies
* Female aged between 18-45 years
* Gestational age is less than 14 weeks
* Planning to receive prenatal healthcare and delivery service at the study hospital
* Signing informed concent and willing to participate

Exclusion Criteria:

* Women with mental disorders or serious maternal illness that is not eligible to participate
* Inability to provide informed consent
* Pregnant women not registered in our hospital

**Healthy Volunteers:** True

**Maximum Age:** 45 Years

**Minimum Age:** 18 Years

**Sampling Method:** PROBABILITY_SAMPLE

**Sex:** FEMALE

**Standard Ages:**

- ADULT

**Study Population:** The ChiTwiMC is a prospective cohort that will enroll 2000 pregnant women aged 18-45 years and over from 9 large obstetrical centers of University-Affiliated Hospitals (Peking University Third Hospital; First Affiliated Hospital, Sun Yat-Sen University; Chongqing Medical University; Shengjing Hospital; Shanghai First Maternity and Infant Hospital; The First Affiliated Hospital of Anhui Medical University; International Peace Maternity and Child Health Hospital; The Second Hospital of Shandong University; Shandong Provincial Hospital). These hospitals located at 7 supercities (Beijing, Shanghai, Guangzhou, Shenyang, Jinan, Chongqing, and Hefei) of China. Pregnant women who are planning to receive prenatal healthcare and delivery in those hospitals are potential candidates for the study.

### Contacts Locations Module

#### Central Contacts

**Contact 1:**

**Email:** weiyuanbysy@163.com

**Name:** Yuan Wei, PhD, MD

**Phone:** 01082267852

**Role:** CONTACT

**Contact 2:**

**Email:** wtc17@pku.edu.cn

**Name:** Tianchen Wu, PhD

**Role:** CONTACT

#### Locations

**Location 1:**

**City:** Hefei

**Contacts:**

***Contact 1:***

- **Email:** dr_yinzongzhi@qq.com

- **Name:** Zongzhi Yin

- **Role:** CONTACT

**Country:** China

**Facility:** The First Affiliated Hospital of Anhui Medical University

**State:** Anhui

**Status:** RECRUITING

**Zip:** 230001

**Location 2:**

**City:** Peking

**Contacts:**

***Contact 1:***

- **Email:** weiyuanbysy@163.com

- **Name:** Yuan Wei, PhD, MD

- **Role:** CONTACT

***Contact 2:***

- **Email:** wtc17@pku.edu.cn

- **Name:** Tianchen Wu, PhD

- **Role:** CONTACT

**Country:** China

**Facility:** Peking University Third Hospital

**State:** Beijing

**Status:** RECRUITING

**Zip:** 100191

**Location 3:**

**City:** Peking

**Contacts:**

***Contact 1:***

- **Email:** xlwang@bjmu.edu.cn

- **Name:** Xiaoli Wang

- **Role:** CONTACT

**Country:** China

**Facility:** Peking University

**State:** Beijing

**Status:** RECRUITING

**Zip:** 10091

**Location 4:**

**City:** Chongqing

**Contacts:**

***Contact 1:***

- **Email:** dingyb@cqmu.edu.cn

- **Name:** Yubin Ding

- **Role:** CONTACT

**Country:** China

**Facility:** Chongqing Medical University

**State:** Chongqing

**Status:** RECRUITING

**Zip:** 400010

**Location 5:**

**City:** Guangzhou

**Contacts:**

***Contact 1:***

- **Email:** luoyanm@mail.sysu.edu.cn

- **Name:** Yanmin Luo

- **Role:** CONTACT

**Country:** China

**Facility:** First Affiliated Hospital, Sun Yat-Sen University

**State:** Guangdong

**Status:** RECRUITING

**Zip:** 510000

**Location 6:**

**City:** Shenyang

**Contacts:**

***Contact 1:***

- **Email:** Weij@sj-hospital.org

- **Name:** Jun Wei

- **Role:** CONTACT

**Country:** China

**Facility:** Shengjing Hospital

**State:** Liaoning

**Status:** RECRUITING

**Zip:** 110000

**Location 7:**

**City:** Jinan

**Contacts:**

***Contact 1:***

- **Email:** adokemeng@163.com

- **Name:** Jinlai Meng

- **Role:** CONTACT

**Country:** China

**Facility:** Shandong Provincial Hospital

**State:** Shandong

**Status:** RECRUITING

**Zip:** 250021

**Location 8:**

**City:** Jinan

**Contacts:**

***Contact 1:***

- **Email:** hongfz@sdu.edu.cn

- **Name:** Fanzhen Hong

- **Role:** CONTACT

**Country:** China

**Facility:** The Second Hospital of Shandong University

**State:** Shandong

**Status:** RECRUITING

**Zip:** 250033

**Location 9:**

**City:** Shanghai

**Contacts:**

***Contact 1:***

- **Email:** wyanlin@163.com

- **Name:** Yanlin Wang

- **Role:** CONTACT

**Country:** China

**Facility:** International Peace Maternity and Child Health Hospital

**State:** Shanghai

**Status:** RECRUITING

**Zip:** 200030

**Location 10:**

**City:** Shanghai

**Contacts:**

***Contact 1:***

- **Email:** zougangshcn@sina.com

- **Name:** Gang Zou

- **Role:** CONTACT

**Country:** China

**Facility:** Shanghai First Maternity and Infant Hospital

**State:** Shanghai

**Status:** RECRUITING

**Zip:** 201204

**Location 11:**

**City:** Tianjin

**Contacts:**

***Contact 1:***

- **Email:** lshuai@nankai.edu.cn

- **Name:** Ling Shuai

- **Role:** CONTACT

**Country:** China

**Facility:** Nankai University

**State:** Tianjin

**Status:** RECRUITING

**Zip:** 300071

#### Overall Officials

**Official 1:**

**Affiliation:** Obstetrics and Gynecology Department of Peking University Third Hospital

**Name:** Yuan Wei, PhD, MD

**Role:** STUDY_CHAIR

### IPD Sharing Statement Module

**Description:** We have decided that the program will be confidential and not open to other researchers

**IPD Sharing:** NO

## Derived Section

### Condition Browse Module - Ancestors

- ID: D000010335

- Term: Pathologic Processes

- ID: D000046110

- Term: Hypertension, Pregnancy-Induced

- ID: D000011248

- Term: Pregnancy Complications

- ID: D000005261

- Term: Female Urogenital Diseases and Pregnancy Complications

- ID: D000091642

- Term: Urogenital Diseases

- ID: D000000751

- Term: Anemia, Neonatal

- ID: D000000740

- Term: Anemia

- ID: D000006402

- Term: Hematologic Diseases

- ID: D000007232

- Term: Infant, Newborn, Diseases

### Condition Browse Module - Browse Branches

- Abbrev: BXS

- Name: Urinary Tract, Sexual Organs, and Pregnancy Conditions

- Abbrev: All

- Name: All Conditions

- Abbrev: BC15

- Name: Blood and Lymph Conditions

- Abbrev: BC16

- Name: Diseases and Abnormalities at or Before Birth

- Abbrev: BC14

- Name: Heart and Blood Diseases

- Abbrev: Rare

- Name: Rare Diseases

### Condition Browse Module - Browse Leaves

- ID: M7633

- Name: Eclampsia

- Relevance: HIGH

- As Found: Eclampsia

- ID: M14106

- Name: Pre-Eclampsia

- Relevance: HIGH

- As Found: Pre-Eclampsia

- ID: M25869

- Name: Premature Birth

- Relevance: LOW

- As Found: Unknown

- ID: M8460

- Name: Fetofetal Transfusion

- Relevance: HIGH

- As Found: Twin to Twin Transfusion

- ID: M10024

- Name: Hypertension

- Relevance: LOW

- As Found: Unknown

- ID: M25635

- Name: Hypertension, Pregnancy-Induced

- Relevance: LOW

- As Found: Unknown

- ID: M14127

- Name: Pregnancy Complications

- Relevance: LOW

- As Found: Unknown

- ID: M2875

- Name: Urogenital Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M27093

- Name: Female Urogenital Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M8399

- Name: Female Urogenital Diseases and Pregnancy Complications

- Relevance: LOW

- As Found: Unknown

- ID: M4070

- Name: Anemia

- Relevance: LOW

- As Found: Unknown

- ID: M4081

- Name: Anemia, Neonatal

- Relevance: LOW

- As Found: Unknown

- ID: M9490

- Name: Hematologic Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M10276

- Name: Infant, Newborn, Diseases

- Relevance: LOW

- As Found: Unknown

- ID: T2019

- Name: Eclampsia

- Relevance: HIGH

- As Found: Eclampsia

- ID: T5768

- Name: Twin to Twin Transfusion Syndrome

- Relevance: HIGH

- As Found: Twin to Twin Transfusion

### Condition Browse Module - Meshes

- ID: D000004461

- Term: Eclampsia

- ID: D000011225

- Term: Pre-Eclampsia

- ID: D000005330

- Term: Fetofetal Transfusion

- ID: D000004194

- Term: Disease

### Misc Info Module

- Version Holder: 2024-05-31
