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AbstractBoth zygosity and chorionicity provide important information in twin research. The East Flanders Prospective Twin Survey (EFPTS) determines zygosity and chorionicity at birth and therefore provides a gold standard for the testing of diagnostic parameters that can be used to determine chorionicity. The aim of the present study was to investigate whether birthweight discordancy can be used as an indicator of chorionicity. The study sample consisted of 4,060 live-born twin pairs from the EFPTS. We studied MZ twins, using univariate and multivariate logistic regression analyses to calculate odds ratios (OR) and 95% confidence intervals (CI) of being MC in relation to discordancy level. Diagnostic parameters, including sensitivity and specificity, were calculated. A two-fold cross-validation was carried out and a bootstrap distribution with 10,000 samples was created to estimate the standard deviations. For discordancy levels of below 10%, 10–15%, 15–20%, 20–25% and above 25%, the ORs (95% CI) were 1.16 (0.91–1.47), 1.38 (1.05–1.80), 2.13 (1.51–3.01), 2.73 (1.73–4.29) and 2.81 (2.81–4.35) respectively. There were no gender differences. Sensitivity was 42.2% (SD 5.6%), specificity was 72.8% (SD 6.3%), positive predictive value was 72.8% (1.5%) and the negative predictive value was 39.2% (0.7%). In conclusion, although a higher discordancy level resulted in higher ORs of being an MC twin, birthweight discordancy level can only be used to some weak extent as a proxy for chorionicity, highlighting the need to assess and record chorionicity data in obstetrical units.

AbstractThe East Flanders Prospective Twin Survey (EFPTS) is a registry of multiple births in the province of East Flanders, Belgium. Since its start in 1964, over 10,000 twin-pairs have been registered. 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 are recorded; chorion type and zygosity are established; since 1969, placental biopsies have been taken and frozen at –20°C for future research. Since its origin, the EFPTS has included placental data and allows differentiation of three subtypes of monozygotic twins based on the time of the initial zygotic division: the dichorionic–diamniotic pairs (early, with splitting before the fourth day after fertilization), the monochorionic–diamniotic pairs (intermediate, splitting between the fourth- and the seventh-day postfertilization) and the monochorionic–monoamniotic pairs (late, splitting after the eighth day postfertilization). Studies can be initiated taking into account primary biases, those originating 'in utero'. Such studies could throw new light on the consequences of early embryological events and the gene–environment interactions as far as periconceptional and intrauterine environment are concerned.

AbstractThe purpose of this study is to present curves of estimated placental growth in twins and to evaluate the relative contribution of gestational age, zygosity, chorionicity, fusion of the placentas, sex of the individual and of the twin pair, site of the umbilical cord insertion, birth order, maternal age, and parity. Perinatal data and placental data were obtained from 6315 live-born twin pairs from the East Flanders Prospective Twin Survey. Of 4318 twin pairs, with no missing values, the placental weights of different gestational ages were analyzed using a nonlinear multivariate Gaussian regression. Two groups were distinguished: (1) twins with two separate placentas, and (2) twins with only one placental mass (one placenta in case of monochorionic twins or two fused placentas in case of dichorionic placentas). Overall, placental weight was influenced by gestational age, fusion of the placentas, and parity. In the case of one placental mass, monozygotic dichorionic twins had the lowest weights. If two separate placentas were present, birth order played a role in favor of the first-born twin. For parity and zygosity, the differences were most pronounced between 27 and 29 weeks, whereas the difference for birth order was most pronounced between 33 and 37 weeks. In conclusion, basic physiological characteristics, routinely examined at birth, influence placental weight. Taking these covariates into account allows a better evaluation of the placental weight given a gestational age, as an indicator of growth.

AbstractThe assessment of fetal growth is an essential component of good antenatal care, especially for twins. The aims of this study are to develop twin-specific intrauterine 'growth' charts, based on cross-sectional birthweight data, for monochorionic and dichorionic twins according to sex and parity, and to detect twins at risk for neonatal death by comparing the use of twin-specific and singleton charts. The study sample consisted of 76,471 singletons and 8454 twins (4227 pairs) born in East Flanders (Belgium). Birthweights were analyzed using a nonlinear Gaussian regression. After 33 weeks of gestation, the birthweights of twins started to deviate from singletons (difference of 900 grams at 42 weeks). Birthweights of dichorionic twins continued to increase, whereas those of monochorionic twins decreased after week 40 (difference of more than 300 g at 42 weeks). After 31 weeks of gestation, neonatal mortality increased as centile decreased, and was especially high if birthweight was below the twin-specific third centile: .032 (below) versus .007 (above). Using singleton centiles, this was less obvious. In conclusion, twin-specific growth charts, taking chorionicity into account, are more accurate to detect twins at risk for neonatal death. Therefore the presented charts, based on cross-sectional birthweight data, enable an improved assessment of twin growth.

AbstractInsulin resistance and obesity are underlying causes of type 2 diabetes and therefore much interest is focused on the potential genes involved. A series of anthropometric and metabolic characteristic were measured in 240 MZ and 112 DZ twin pairs recruited from the East Flanders Prospective Twin Survey. Microsatellite markers located close to ABCC8, ADIPOQ, GCK, IGF1, IGFBP1, INSR, LEP, LEPR, PPARγ and the RETN gene were genotyped. Univariate single point variance components linkage analyses were performed using two methods: (1) the standard method, only comprising the phenotypic and genotypic data of the DZ twin pairs and (2) the extended method, also incorporating the phenotypic data of the MZ twin pairs. Suggestive linkages (LOD > 1) were observed between the ABCC8 marker and waist-to-hip ratio and HDL-cholesterol levels. Both markers flanking ADIPOQ showed suggestive linkage with triglycerides levels, the upstream marker also with body mass and HDL-cholesterol levels. The IGFBP1 marker showed suggestive linkage with fat mass, fasting insulin and leptin levels and the LEP marker showed suggestive linkage with birth weight. This study suggests that DNA variants in ABCC8, ADIPOQ, IGFBP1 and LEP gene region may predispose to type 2 diabetes. In addition, the two methods used to perform linkage analyses yielded similar results. This was however not the case for birth weight where chorionicity seems to be an important confounder.

A growing number of children born are conceived through in vitro fertilisation (IVF), which has been linked to an increased risk of adverse perinatal outcomes, as well as altered growth profiles and cardiometabolic differences in the resultant individuals. Some of these outcomes have also been shown to be influenced by the use of different IVF culture media and this effect is hypothesised to be mediated epigenetically, e.g. through the methylome. As such, we profiled the umbilical cord blood methylome of IVF neonates that underwent preimplantation embryo development in two different IVF culture media (G5 or HTF), using the Infinium Human Methylation EPIC BeadChip. We found no significant methylation differences between the two groups in terms of: (i) systematic differences at CpG sites or regions, (ii) imprinted sites/genes or birth weight-associated sites, (iii) stochastic differences presenting as DNA methylation outliers or differentially variable sites, and (iv) epigenetic gestational age acceleration. ; We thank the IVF couples who have agreed for their children to participate in this study. We thank all the employees of the IVF clinics and obstetrics departments involved in recruiting participants and collecting samples for this study. We thank E. Pishva for his consultation regarding data analysis and for the critical reading of the manuscript. This study was funded by March of Dimes (6-FY13-153). It was further supported by the stichting fertility foundation, EVA (Erfelijkheid Voortplanting & Aanleg) speciality programme (grant no. KP111513) of Maastricht University Medical Centre (MUMC+), and the Horizon 2020 innovation (ERIN) (grant no. EU952516) of the European Commission. We thank the FLEHS Supervisory Board for the provision of data. The FLEHS studies are commissioned, financed, and steered by the Flemish Government (Department of Economy, Science and Innovations, Agency for Care and Health and Department of Environment). The FLEHS dataset has been generated by the Flemish Center of Expertise on ...