Cohort Profile: The Tongji Maternal and Child Health Cohort (TMCHC)

Abstract

The Tongji Maternal and Child Health Cohort (TMCHC) is a prospective, observational pregnancy and birth cohort study investigating the pre-, peri- and post-natal determinants of mother–child pairs’ health, including nutrition, environmental exposes, lifestyle and genetic factors, through the collection of extensive demographics, anthropometric, nutritional and biological data. A total of 8649 pregnant women aged 17–45 years were recruited prior to 16 weeks of gestation from three hospitals in Wuhan, China from January 2013 to May 2016; 7736 mother–child pairs entered post-partum follow-up. The information of mothers and their partners in pre-gravid were retrospectively collected at enrolment. Detailed information of mothers and offspring at specific trimesters of pregnancy and birth were collected through structured face-to-face interviews and post-partum data of them were obtained when children were aged 1, 3, 6, 12 and 72 months through phone interviews. Any researcher interested in exploring TMCHC data are welcome to contact Prof. Nianhong Yang ([email protected]). The importance of the ‘first 1000 days of life’ is increasingly being recognized and studied, with special attention paid to nutrition and growth. The first 1000 days of life, the time from pregnancy onset to 2 years of age, is a critical window of opportunity for future health and functioning of mother and child.1–3 The Tongji Maternal and Child Health cohort (TMCHC), launched in January 2013 in the city of Wuhan, China, is a prospective observational pregnancy and birth cohort that allows a detailed examination of the first 1000 days of life enabling investigation of early-life factors contributing to mother–child pairs’ health. The study aimed to investigate the pre-, peri- and post-natal determinants of mother–child pairs’ health, including nutrition, environmental exposes, lifestyle and genetic factors, through the collection of extensive demographics, anthropometric, nutritional and biological data. Initial funding was from the National Program on Basic Research Project of China (NO.2013FY114200), with the primary objective to investigate the optimal pregnancy weight gain of Chinese women and to examine the applicability of the Institute of Medicine guidelines by surveying gestational weight gain (GWG) and outcomes of Chinese pregnant women and their offspring. The study was also designed to examine potential determinants of pregnancy outcomes, such as gestational diabetes mellitus (GDM), gestational hypertension, pre-term and so on. Several factors have been evaluated, including nutrition, psychological, behavioural, family and other environmental factors. In addition, we collected data on infant feeding, growth and development as well as data on maternal weight recovery and health post-partum. Available clinical leftover biological samples such as blood and urine were reserved for further analyses. Subsequent funding and collaborations have allowed further studies and continuing follow-up. The Fundamental Research Funds for the Central Universities (HUST2016YXZD040) has supported the assays of urine iodine concentration and trace metals in urine and plasma by inductively coupled plasma–mass spectrometry (ICP–MS). Plasma iron status, oxidative stress, gene and protein expression related to iron metabolism have been measured for their effects on GDM with the support of the National Natural Science Foundation of China (NSFC 81673159), Fundamental Research Funds for the Central Universities (HUST2019kfyXMPY008) and China Postdoctoral Science Foundation (2019M662648). The National Natural Science Foundation of China (NSFC 82073555) supports the assessment of maternal folic acid status during pregnancy and genes related to folic acid metabolism for demonstrating their implications on mother and child health. Three public hospitals across the city of Wuhan, which is located in central China (Figure 1), were carefully selected as sites of participant recruitment. The three hospitals, the Hubei Maternal and Child Health hospital, the Jiangan Maternal and Child Health hospital and the Central Hospital of Wuhan, are located in Wuchang and Hankou districts of Wuhan, and serve ∼35% of all pregnant women in the city and its surrounding rural areas each year. Participants were invited to join the TMCHC study voluntarily at their first routine antenatal visit in the three hospitals if they met the following criteria: (i) ≤16 weeks of gestation; (2) intended to have their subsequent antenatal examinations performed in one of the three hospitals; (3) intended to deliver in one of the three hospitals. A unique five-digit identification number was then assigned to each participant. The number corresponded to the pregnancy, not to the woman. A woman could join twice where she would be given two identification numbers for her separate pregnancies. A study logo on the cover of antenatal records was used to distinguish pregnant women who had joined the TMCHC study and to ensure specific data collection by trained investigators. Location of the Tongji Maternal and Child Health Cohort The recruitment process started from January 2013 to May 2016. Figure 2 shows the numbers recruited in the cohort and participant flows over time. A total of 13 165 eligible women were invited to participate the study and 8649 (65.7%) agreed; these individuals were subsequently examined and interviewed. Of the 8649 participants, 691 withdrew from the study due to geographical moves, citing a loss of interest and time with the study, or unknown reasons. Of the remaining 7958 participants who were followed up at delivery, 219 experienced a miscarriage, 3 were stillbirths and a final sample size of 7736 mother–child pairs went to the next stage of follow-up. At post-partum 1, 3, 6, 12, 24 and 72 months, the mother–child pairs have been followed up by phone interviews. By the age of 24 months, 6699 of 7736 (86.6%) mother–child pairs with live births had been followed up at least once and 4412 (57%) remained. The reasons for loss to follow-up included: unable to contact by telephone (n = 2562), withdrew consent (n = 756) or due to infant deaths (n = 6); 72-month post-partum follow-up is ongoing. Progress of the Tongji Maternal and Child Health Cohort According to the recommendation by the Working Group on Obesity in China,4 67.9% of participants were categorized as of normal weight, 19.9% as underweight, 10.1% as overweight and 2.1% as obese based on their self-reported pre-weight and height measured at enrolment. Table 1 shows the comparison of baseline characteristics of the participants between those who were followed up at delivery (n = 7958) and those lost to follow-up (n = 691). Women lost to follow-up were younger, less educated, with lower-income and more likely to be multiparous. Supplementary Table S1 (available as Supplementary data at IJE online) shows the remaining mother–baby pairs at 72 months compared with those lost to follow-up. Distribution of socio-demographic characteristics in the Tongji Maternal and Child Health Cohort Data are presented as n (%) or mean ± SD; CNY, Chinese Yuan; 1 CNY ≈ 0.16 US dollars; P-values for differences in socio-demographic characteristics between participants with and without delivery outcomes were obtained by independent sample t-test for continuous variables and χ2 test for categorical variables. The study protocol included detailed follow-up interviews across pre-, peri- and post-natal periods, with a wide range of data collection (Tables 2 and 3). The information on mothers and their partners in pre-gravid was retrospectively collected at enrolment. Study schedule of the Tongji Maternal and Child Health Cohort during pregnancy and at delivery NO2, nitrogen dioxide; PM2.5, particulate matter with an aerodynamic diameter of ≤2.5 μm; PM1.0, particulate matter with an aerodynamic diameter of ≤1.0 μm. Study schedule of the Tongji Maternal and Child Health Cohort from post-natal 1 week to 72 months w, week; mo, month. The follow-up procedure was consistent across the three hospitals, where interview rooms were set up. At the time of routine prenatal care, all participants were requested to visit the interview room and be examined by trained investigators. They were asked to complete questionnaires specific to their weeks of gestation, and their body weights and blood pressures were measured and recorded. During pregnancy, venous blood samples were obtained at ∼16 and 24–28 weeks of gestation, and the day before delivery, when blood tests for Oscar, 75-g oral glucose tolerance test and other clinical-biochemistry tests were performed. The collection of urine samples was conducted at ∼16, 24–28 and 36–40 weeks of gestation, respectively. Using the study logo pasted onto the cover of the prenatal care records, on-site trained investigators could easily identify the participants of the study once the mother was admitted to the research hospitals for delivery. Cord blood and placental samples were collected at birth when possible. Information regarding both the delivery and newborn were recorded by midwives and collected immediately post-partum. The bodyweight of the mother was measured within 24 h post-partum and information on onset of lactation and the feeding behaviour were collected by trained investigators at the hospital bedside. In some rare cases in which the participants delivered in places other than the three hospitals, they were approached by phone to conduct questionnaires and to collect information on themselves and their newborn upon and after delivery. Mother–child pairs were prospectively followed up at 1, 3, 6, 12, 24 and 72 months after childbirth. Bodyweight and length of the infants were measured by nurses in community clinics where mothers brought their infants for routine healthcare. The information on children and their parents was collected by either home interview or telephone. TMCHC has a collection of extensive demographic, anthropometric, nutritional and biological data for each participant starting from enrolment. Tables 2 and 3 display the detailed information collected at each follow-up. Both 24-h dietary recall and a validated semi-quantitative food frequency questionnaire (FFQ)5 were used to assess the dietary exposure of the participants in early, mid- and late pregnancy. Maternal physical activity and sleep were assessed using a questionnaire that referenced the questions of the International Physical Activity Questionnaire6 and Pittsburgh Sleep Quality Index,7 respectively. The Edinburgh Postnatal Depression Scale8 was used to assess maternal depressive symptoms pre-natally at 35–40 weeks of gestation and post-natally at 1 week post-partum. The LATCH tool which evaluated five different characteristics (“Latch, Audible swallowing, Type of nipple, Comfort, Help”) of breastfeeding assessment tool9,10 was used for targeting early breastfeeding support at Day 1 post-partum. The maternal anthropometry, biomakers, air pollutants, whole-genome sequencing and development of offspring that have been measured or are being measured are also listed in the tables. Our studies mainly focused on the pre-, peri- and post-natal determinants of mother–child pairs’ health, including nutrition, environmental exposures, lifestyle and genetic factors. Considering the different dietary habits among populations from different regional, ethnic and cultural backgrounds, we designed a FFQ based on the dietary habits of Chinese pregnant women. Our data demonstrated that the FFQ was reliable and valid to assess the dietary intake of the study participants.5Table 4 summarizes the key findings until now. The analyses on the interaction of nutrition, environmental exposures and lifestyle factors with genetic factors on the outcomes of mothers and their children are ongoing. Summary of the key findings of the Tongji Maternal and Child Health Cohort GWG, gestational weight gain; GDM, gestational diabetes mellitus; TTP, transthyretin; TP, total protein; Alb, albumin; GGT, gamma-glutamyl transferase; ALP, alkaline phosphatase; TMAO, trimethylamine-N-oxide; Sb, antimony; Ni, nickel; PM2.5, particulate matter with an aerodynamic diameter of ≤2.5 μm; NO2, nitrogen dioxide; RTI, respiratory tract infection. Our cohort study indicated that the optimal GWG for Chinese underweight, normal weight and overweight pregnant women were 12.0–17.0, 9.0–14.0 and 7.0–11.0 kg, respectively.11 Important determinants related to the risk of GDM included: GWG prior to glucose screening,12 maternal dietary nutrients and phytochemical intakes (vitamin C,13 lycopene14 and total polyphenols15), dietary patterns,16–18 dietary supplementation (iron19 and folic acid20 supplement), environmental particulate matter with an aerodynamic diameter of ≤2.5 μm (PM2.5) exposure,21 metals exposure [antimony (Sb)22 and nickel (Ni)23] and sleep quality.24 In addition, we also found that several serum indexes including serum ferritin,25 trimethylamine-N-oxide (TMAO),26 transthyretin (TTP),27 gamma-glutamyl transferase (GGT),28 alkaline phosphatase (ALP)29 and direct bilirubin30 levels during early–middle pregnancy were associated with the risk of GDM. Several factors were observed to be associated with fetal growth, including dietary patterns, biomarkers, environmental pollutants and sleep duration. Our data showed that a maternal dietary pattern enriched in beans and vegetables is beneficial for effectively controlling GWG and increasing birthweight.31 Maternal iodine insufficiency and excess coexisted during early pregnancy and they both adversely affected fetal growth.32 There was a reverse U-shaped association between maternal serum albumin (Alb) and fetal growth.33 Our study also demonstrated that maternal nitrogen dioxide (NO2) exposure34 during pregnancy and sleeping duration35 in early pregnancy was associated with fetal growth. It is well known that breastfeeding is of great benefit to mother–child pairs’ health. Our study also demonstrated the beneficial effect of breastfeeding on the normal growth and development of infants.36 In addition, delayed lactogenesis37 might have an adverse effect on the maintenance of breastfeeding. In the first 6 months of life, routine vitamin D supplementation to infants was associated with a decreased risk of respiratory tract infection (RTI), irrespective of infant feeding,38 and those exposed to environmental tobacco smoke during both pregnancy and infancy had an increased the risk of upper RTI.39 During the complementary feeding period, introducing more diverse food groups had a protective effect against allergic diseases in the second year of life.40 A list of TMCHC publications is available at our website (http://faculty.hust.edu.cn/yangnianhong/zh_CN/lwcg/1913214/list/index.htm). The major strength of TMCHC is the combination of large sample size and detailed information of pre-, peri- and post-natal parental and offspring characteristics. Extensive data collected on mothers and offspring along with available specimens enable research opportunities in areas related to the pre-, peri- and post-natal determinants for mother–child pairs’ health, including nutritional, environmental, lifestyle and genetic factors. This study has some limitations. First, this cohort is almost exclusively Han Chinese, which reduces confounding but also limits generalizability to other ethnic groups. Second, the information of mothers and their offspring after delivery was obtained by phone and the measurement of the infant body weight and length were conducted in different community clinics, which may result in variations in data collection. The TMCHC co-investigators welcome formal proposals and will consider these at their monthly meetings. Anonymized data are available to proposers through collaborative agreements. To learn more about the TMCHC cohort, please contact Prof. Nianhong Yang ([email protected]). The study was in accordance with the ethical standards laid down in the Declaration of Helsinki and was approved by the ethics review committee of Tongji Medical College of Huazhong University of Science and Technology. Each participant was informed of the study protocol by trained investigators, and informed consent was obtained for the usage of her information and biological samples. See ‘Can I get hold of the data?’ above. Supplementary data are available at IJE online. C.Z., R.C., X.Z., Y.Z., C.L., L.H., Q.L., S.X., X.C., T.X., W.W., Q.G., H.Z., Y.W., M.H., J.W., W.C., X.L., W.W., L.L., H.W., D.G., N.L., D.L., T.T., J.G., W.H., W.Z., D.X., L.G., H.Z., J.L. and S.Y.: contributed to the collection of data and biological specimens. G.Z., X.W., X.Z., M.W., S.Y., X.C., T.T., M.T., W.Z., D.X., H.Z., J.L. and S.Y.: contributed to the assays of biological specimens. C.Z., S.W., M.X., G.S., G.X., Z.N., J.W., L.H., Z.J., X.Y. and H.Y.: contributed to the supervision of data collection. C.Z.: drafted the manuscript. N.Y.: is responsible for leading the cohort, has full access to all the data and takes responsibility for the integrity of the data and the accuracy of the data analysis. All authors read and approved the final manuscript. This work was funded by the National Program on Basic Research Project of China (NO.2013FY114200), the Fundamental Research Funds for the Central Universities (HUST2016YXZD040, HUST2019kfyXMPY008) and the National Natural Science Foundation of China (NSFC 81673159, 82073555) for N.Y. and the China Postdoctoral Science Foundation (2019M662648) for C.Z. The authors are indebted to all the cohort members and their families, the practices that allowed us to access their databases and the staff at the primary care sciences research centre who helped administer the project. None declared.

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