IJE Advance Access originally published online on January 31, 2008
International Journal of Epidemiology 2008 37(3):486-489; doi:10.1093/ije/dym218
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Cohort Profile: The GECKO Drenthe study, overweight programming during early childhood
1Department of Pediatrics, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
2Department of Epidemiology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
3Well Baby Clinic Foundation Icare, Drenthe, The Netherlands.
4Department of Pediatrics, Martini Hospital, Groningen, The Netherlands.
* Corresponding author. Department of Pediatrics, University Medical Center Groningen, University of Groningen, P.O. Box 30.001, 9700 RB Groningen, The Netherlands. E-mail: c.abee{at}bkk.umcg.nl
Accepted 1 October 2007
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Obesity and overweight can be considered as international problems, since worldwide prevalence is rapidly increasing.1 Not only is this an increasing trend observed in adults, but also children and adolescents are increasingly diagnosed with overweight and obesity.2 The GECKO Drenthe study is a study within the Groningen Expert Center for Kids with Obesity (GECKO) and has been designed to examine in detail environmental and genetic risk factors for childhood obesity.
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The overall aim of GECKO is studying the etiology of overweight and the metabolic syndrome during early childhood. The present study, the GECKO Drenthe, is a population-based birth-cohort study of children born in a 1-year period in Drenthe, one of the northern provinces of The Netherlands. All children will be followed from pregnancy until adulthood. Genetic, biomedical, social, environmental and dietary data for the children and their parents will be collected.
The overall research question concerns the development of body weight and body fat distribution, and how these are determined by mother and child factors. Within this study, important aspects are DNA analysis and metabolic programming.
With close to 3000 children, the study has a power of 95% to detect risk factors for the development of overweight with a relative risk of at least 1.4 (assuming an incidence of 5%, and mean value of the risk factor 20, SD 4).
Moreover, in three regions, each including 
100 children, additional measurements will be performed. In the first region, umbilical cord tissue has already been collected; in the second region, an overweight prevention programme to improve infant motor skills and physical movement will be examined; and in the third region, measurements of body composition and fat distribution will be assessed.
The first sub-study aims to answer the following questions: are there specific gene expressions related to childhood obesity and growth at young age? Do adaptive changes in gene expression play a role?
One midwife practice was asked to collect umbilical cord tissue, which successfully occurred 93 times. This umbilical cord tissue was collected for genomics and proteomics. Evidence suggests that environmental factors in early life not only influence the transcription of genes at that moment, but also later on in life.3–6 There are a huge number of genes within the human genome code for proteins that mediate and/or control nutritional processes.7 Although a large body of information on the number of genes, on chromosomal localization, gene structure and function has been gathered, we are far from understanding the orchestrated way of how they control metabolism. Due to the limited number of umbilical cord tissue samples collected, this sub-study will be a pilot study. The results of this pilot study will be used for future large-scale studies to explore specific research questions on genomics and proteomics.
The second sub-study aims to answer the question: what is the effectiveness of an overweight prevention programme during the first year of life in terms of bringing about changes in anthropometric measures and physical activity scores?
Because the effectiveness of overweight prevention programmes in children and adolescents is questionable and the need for well-designed studies is desirable,8,9 a sample of the children participating in the GECKO Drenthe study will receive an overweight prevention programme early in life. This programme will start in the second week after birth. Few intervention studies that begin at birth have been published.10,11 We believe that an early start for an intervention programme is crucial when it comes to trying to prevent the development of obesity through a positive change in metabolic programming.
Because of this intervention programme, neighbourhoods or villages have been randomized into two groups. All parents of babies born in the intervention group will receive recommendations from a nurse in the Well Baby Clinic, who has been trained by a child physiotherapist. Recommendations will focus on stimulating motor development and increasing physical activity. In an overview of intervention studies in young children a difference of 1.2 units body mass index (BMI) after 1 year has been found.12 To detect this difference two groups of 91 children will be needed (SD 2.5, two-sided alpha 0.05, 1-beta 0.9). To account for a 10% drop-out, 200 children will be included. The data on the group of children within the intervention group will be separated from the data for the total cohort, because this intervention program is likely to interfere with the body composition of the children. As main study parameters the following measurements will be evaluated: anthropometry, motor skills [Albert Infant Motor Scale (AIMS)13 and Bayley Scales of Infant Development Second Edition motor part (BSID-II-NL motor part)]14, as well as physical movements measured by an accelerometer especially made for babies.
The third sub-study will answer the question: what is the fat distribution and body composition during the first year of life?
Fat distribution seems to be more important than BMI in terms of the health risk associated with obesity in adults.15–18 To investigate if this is also true in young children, fat distribution by ultrasound and total body fat through wrist-to-ankle Bio-electrical Impedance Analysis (BIA) will be measured at the age of 2 months and then at 7 months. All measurements will be obtained using a strict protocol. In this sub-group of 118 children, we can register the fat distribution and body composition, as well as the changes in these parameters during the first year of life. Knowledge about fat distribution and body composition in infants is limited. These exploratory data will contribute to this knowledge and can serve as the basis for future research in this field.
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All children born from April 2006 to April 2007 and living in Drenthe at the time of birth were allowed to participate in this study. Drenthe is one of the northern provinces of The Netherlands. All pregnant women in this province were invited to participate in the third trimester of their pregnancy. Recruitment took place through obstetricians, midwives and general practitioners, supported by a media campaign. If for any reason a child was not included in the GECKO Drenthe study before birth, a nurse from the Well Baby Clinic invited the parents of the newborn to participate. This study was approved by the Medical Ethics Committee of the University Medical Center Groningen (UMCG).
The Dutch obstetric system is traditionally characterized by extensive primary health services, supported by more specialized care.19 Midwives and general practitioners are responsible for normal deliveries, with obstetricians responsible for those deliveries considered high risk. Prenatal care is given almost 80% of the time by a midwife and 6% by a general practitioner. When a complication during pregnancy or delivery occurs, the woman is referred to an obstetrician. Finally, 40% of pregnant women deliver under the care of a midwife or a general practitioner. Approximately, 30% of all children born in The Netherlands are born at home, most often supervised by a midwife.20
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Data collection began during the last trimester of pregnancy by administering parental questionnaires concerning medical history, social structures, lifestyle, diet and smoking habits. At birth the obstetricians, midwives or general practitioners took an umbilical cord blood sample that was then processed and stored for future analysis. In addition, the placenta weight was measured, and data on pregnancy and delivery were obtained. All neonatal and childhood data will be obtained during regular visits to the Well Baby Clinics. Within the Dutch health care system, the Well Baby Clinics play a central role during the first 4 years of life. More than 95% of all parents will visit these clinics that also provide free immunizations for the baby. During these regular visits to the clinics, questionnaires and anthropometry will be obtained. After the age of 4 years, data will be gathered every other year in collaboration with the school health services.
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During all visits anthropometry of the infants is performed by a strict protocol, including weight, height, head circumference, waist circumference and hip circumference. Questionnaires will be filled out during the visit to the clinic, and in the first 2 years will predominantly be focusing on diet. An overview of the measurements to be taken during the first 2 years of life is given in Table 1.
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Between the ages of two and four, children will be seen an average of once a year at the Well Baby Clinic and thereafter at the school health service. The pattern of measurements will be continued: short questionnaires combined with protocol anthropometric measurements. After 4 years, questionnaires covering both diet and physical activity will be sent to parents and later to the children themselves. Anthropometry will be assessed every other year, in addition to blood sampling in a sample number of participants.
All hospitals (N = 5), midwife practices (N = 18), general practitioners (N = 28) and Well Baby Clinics (N = 61) in the region have agreed to participate in the study. During the recruitment period there was a total of 4778 infants born and of these the parents of 2997 (63%) gave their consent to participate in the study. The number of parents who participated with twins was 25. During the inclusion period no triplets were born in the study region. Of the 2997 participants, a cord blood sample was obtained from 1757 (59%).
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The number of babies born in the Drenthe province from April 2006 to April 2007 was 4778. The main reasons for not participating in this study were anxiety that participation would take too much time or parents not being interested in any kind of research. Of the 2997 children included, 52% were of male gender, 5% were born prematurely, the mean gestational age was 39.8 weeks (SD 1.7) and the mean birth weight was 3564 g (SD 546). These gender rates were similar to Dutch data figures generally. The rate of preterm births (between 24 and 37 weeks) was lower than the recent national survey (5 versus 6.2%).21 This small discrepancy was probably caused by the fact that the parents of preterm infants did not feel like participating in a study because of the anxiety that accompanied the birth of their baby.
The figures were similar for boys and girls, although boys were slightly (not significantly) heavier at birth: 3623 g (SD 553) versus 3505 g (SD 533). No significant gender differences were found between the neonates condition after delivery. One minute after birth, the Apgar score of 23.6% of the children was below 9 and of 3.0% below 7. After 5 min, this score increased to 4.5% below 9 and 0.6% below 7.
Some clinical characteristics of the parents and the pregnancy are given in Table 2.
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The strength of this study lies in the unselected study population. Moreover, the province Drenthe has a relative stable population for many generations. All obstetricians, midwives, general practitioners and Well Baby Clinics in Drenthe are participating in this study. The implementation of the GECKO Drenthe in the regular healthcare programme makes it appealing to participate. In view of these two advantageous factors, a low dropout rate is expected. Preliminary data show that in the first year of data collection, which is an intense period for participants, the drop-out was 4.5%. In addition, this study is a prospective study that overcomes any problems due to information bias.
The emphasis on ‘metabolic programming’ in the GECKO Drenthe is a strength compared with other prospective birth cohort studies. Programming is an epigenetic phenomenon by which nutrition and hormonal, physical, psychological, as well as other stressful events acting in a critical period of life such as gestation and lactation, modify certain physiological functions in a prolonged way.4 Recently, the importance of programming has become obvious,3–5,22 and the need for cohort studies starting in pregnancy has been clearly shown. We satisfied this need by designing this prospective birth cohort study with the emphasis placed on metabolic programming. Compared with other studies, more detailed obstetric, environmental and anthropometric data will be collected to improve our knowledge of metabolic programming.
Moreover, this study has been specifically designed to answer research questions focused on childhood obesity. Compared with other cohort studies, more detailed measures will be collected such as body composition and fat distribution of the infants, umbilical cord tissue, data with regard to the obstetric data, as well as physical-activity measurements.
One potential limitation of our study is selection bias. As expected, ethnic minorities were less willing to cooperate. More specifically, people from ethnic minorities are represented in 9.1% of the population of Drenthe, while only in 6.0% of our study population. However, regarding overweight and education levels in parents no selection bias existed. Therefore, we feel that the overall selection bias is negligible. We have access to data from the register where all newborns are registered, so it will be possible to correct for potential selection bias in specific analyses. Since we are looking for risk factors in the development of obesity, the follow-up for this cohort is more important than its representativeness. Another potential limitation is that data will be collected by different people. Various Well Baby Clinics are cooperating that can result in inter-observer problems. To reduce this inter-observer variation, protocols have been set up to describe anthropometric measurements in detail, and training sessions have been given to all staff.
In conclusion, GECKO Drenthe is a large birth-cohort study focusing on the development of overweight. This will provide answers to questions concerning metabolic programming early in life, which greatly determines the current worldwide epidemic of obesity. Answering these questions will make a more focused and tailored preventive programme for obesity possible.
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All data will be stored confidentially and anonymously. Personal data will be handled according to the Dutch Personal Data Protection Act. The data are not freely available in the public domain, but specific proposals for collaboration are welcomed. For more information or remarks regarding the study please contact one of the principle investigators (email: p.j.j.sauer{at}bkk.umcg.nl).
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GECKO is supported and funded by an unrestricted grant from Hutchison Whampoa Ltd, University of Groningen and Well Baby Clinic Foundation Icare.
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