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The East Flanders Prospective Twin Survey (EFPTS): An Actual Perception

Published online by Cambridge University Press:  29 October 2012

Catherine Derom*
Affiliation:
Centre of Human Genetics, University Hospitals Leuven, & Department of Human Genetics, KU Leuven, Belgium
Evert Thiery
Affiliation:
Department of Neurology, Ghent University Hospital, Ghent University, Ghent, Belgium
Hilde Peeters
Affiliation:
Centre of Human Genetics, University Hospitals Leuven, & Department of Human Genetics, KU Leuven, Belgium
Robert Vlietinck
Affiliation:
Centre of Human Genetics, University Hospitals Leuven, & Department of Human Genetics, KU Leuven, Belgium
Paul Defoort
Affiliation:
Department of Obstetrics and Gynaecology, Ghent University Hospital, Ghent University, Ghent, Belgium
Jean-Pierre Frijns
Affiliation:
Centre of Human Genetics, University Hospitals Leuven, & Department of Human Genetics, KU Leuven, Belgium
*
address for correspondence: Dr Catherine Derom, Kwadenplasstraat 20, B-9070 Destelbergen, Belgium. E-mail: catherine.derom@uzleuven.be

Abstract

The East Flanders Prospective Twin Survey (EFPTS) is a prospective, population-based registry of multiple births in the province of East-Flanders, Belgium. EFPTS has several unique features: it is population-based and prospective, with the possibility of long-term follow-up; the twins (and higher order multiple births) are recruited at birth; basic perinatal data recorded; chorion type and zygosity established; and since 1969 placental biopsies have been taken and frozen at −20 °C for later determination of genetic markers. The EFPTS is the only large register that includes placental data and allows differentiation of three subtypes of monozygotic (MZ) twins based on the time of the initial zygotic division: the dichorionic–diamnionic pairs (early, with splitting before the fourth day after fertilization), the monochorionic–diamnionic pairs (intermediate, splitting between the fourth and the seventh day post-fertilization), and the monochorionic–monoamnionic pairs (late, splitting after the eighth day post-fertilization). Studies can be initiated taking into account primary biases, those originating ‘in utero’. Such studies could throw new light on the controversy over the validity of the classic twin method, the consequences of early embryological events, and the gene–environment interactions as far as periconceptional and intrauterine environment are concerned.

Type
Articles
Copyright
Copyright © The Authors 2012

The East Flanders Prospective Twin Survey (EFPTS) was started in July 1964 at Ghent University, Department of Obstetrics, by Robert Derom and Michel Thiery, a twin himself. At present it is hosted by ‘Twins’, a non-profit association for scientific research in multiple births, and is now partly funded by the department of Human Genetics of the University of Leuven (Belgium), ‘Twins’, and the University of Maastricht (Netherlands).

The main aims of EFPTS are:

  1. 1. the determination of the prevalence of multiple births in a well-defined geographic area and the recording of the obstetrical (duration of pregnancy, pregnancy and birth complications, birth weight, induction of ovulation, placental weight, insertion of the cord) and obstetrico-pediatric outcomes (intrauterine growth, congenital malformations, and perinatal and infant morbidity and mortality)

  2. 2. the investigation of the causes of the multiple pregnancy and the influence of zygosity and moment of zygotic division on the investigated traits on later age such as behavior, learning- and school problems, intelligence, postnatal somatic growth, sexual maturation, blood pressure, stress, (sub)clinical depression, and psychotic symptoms

  3. 3. the determination of the genetic predisposition of the investigated phenotypes and the role of the environment (with special emphasis on the prenatal environment) both individual-specific as well as common environmental influences.

Sample Characteristics

The inclusion criteria are the following: all multiple births in the Province of East Flanders, Belgium (15,800 births per year) from whom at least one of the children, live or stillborn, weighs 500 g or more or, when birth weights are unknown, the gestational age is at least 22 weeks. The specific methodology of this survey includes: the determination of the zygosity of each multiple birth with near certainty to certainty through examination of the placental membranes and vascular anastomoses, blood groups and DNA fingerprints (if necessary), the collection of medical data from gynaecologists and neonatologists, follow-up of the multiples through one of the studies and/or questionnaires.

Contact with the families of the multiples is maintained by a biannual newsletter and a TWIN hotline for the public and the parents of twins with psychological, educational, medical, or practical problems, and the organization of evening meetings where the parents of multiples just meet with each other and exchange experiences. These services to families with multiple births are a joint venture of EFPTS and the Association for Scientific Research in Multiple Births (Twins) and are mainly based on the work of volunteers.

Between 1964 and 2011, 8,588 twin pairs and 238 triplets were registered and investigated (see Table 1). The EFPTS sample is representative of the total twin population of East Flanders, with more than 95% registered multiple births since the 1990s (Loos et al., Reference Loos, Derom, Vlietinck and Derom1998). Presently, more than 3,000 twin pairs have been enrolled in more than 10 major studies, and some 2,000 DNA extractions have been performed. In some of these studies, the parents and sibs of the twins were also examined.

TABLE 1 The Number of Twin Pairs in the EFPTS Born Between 1964 and 2011 by Zygosity, Chorion Type, and Sex

A Summary of Major Findings

Some of the most important results are reported to illustrate the scope of our studies.

FIGURE 1 Yearly numbers of spontaneous and iatrogenic twin maternities: EFPTS 1985–2011.

Discussion

Criticism has been addressed to the classical twin studies with regard to the assumption of equal intrauterine environments of MZ twins. The most important examples of potentially unequal intrauterine environments are undoubtedly chorionicity, zygosity, and the origin of the pregnancy, spontaneous or ART. Other factors, however, must also be considered: gestational age, birth sequence, birth weight, the mode of delivery, and presentation of both twins.

With a sizeable group of more than 900 DC-MZ, 1,800 MC-MZ, and 2,450 ART twin pairs the EFPTS can perform classic twin studies with no biases, that is, studies that are based on the crucial assumption that MZ and DZ twins, spontaneous and ART twins, have a similar intrauterine environment. Previous results have indicated that this could not be the case (Delbaere et al., Reference Delbaere, Goetgeluk, Derom, Bacquer, Sutter and Temmerman2007; Loos et al., Reference Loos, Beunen, Fagard, Derom, Vlietinck and Phillips2001d; Verstraelen et al., Reference Verstraelen, Goetgeluk, Derom, Vansteelandt, Derom, Goetghebeur and Temmerman2005). Comparison of DC-MZ, MC-MZ, and DZ twins will allow to evaluate the degree of gene–environment interactions as the prenatal environment is concerned. In contrast to all DC-MZ and DZ twins, MC-MZ twins share their chorion, most of them share their blood supply and, therefore, their immune system during intrauterine life. This could have long-term effects on phenotypes in later life (Martin et al., Reference Martin, Boomsma and Machin1997; Phillips, Reference Phillips1993).

There is now growing evidence that ART can induce epigenetic variation that might be transmitted to the next generation and that subfertility itself is a risk factor for imprinting diseases (van Montfoort et al., Reference van Montfoort, Hanssen, De Sutter, Viville, Geraedts and de Boer2012). With more than 2,450 twins and 200 triplets being born after various techniques of ART, whether born after fertility treatment without further intervention (ovulation induction only) or after IVF/ICSI or related techniques, EFPTS is the ideal resource for the long-term follow-up study of these multiples on a population-based manner.

As retrospective analysis of the placentation is still impossible to carry out and multiples born after ovulation induction only are hard to detect retrospectively, the effect of chorion type, origin of the pregnancy, and the epigenetic phenomena on phenotypes in later life will remain one of the primary goal of the research with EFPTS.

Acknowledgments

Research projects were aided by grants coming mainly from the Fund for Scientific Research — Flanders, the Praeventiefonds (The Netherlands), the Dutch Foundation for Scientific Research, the Bertarelli Foundation, and the Marguerite-Marie Delacroix Foundation.

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Figure 0

TABLE 1 The Number of Twin Pairs in the EFPTS Born Between 1964 and 2011 by Zygosity, Chorion Type, and Sex

Figure 1

FIGURE 1 Yearly numbers of spontaneous and iatrogenic twin maternities: EFPTS 1985–2011.

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