Can birthweight discordancy within monozygotic twin pairs be used as an indicator of chorionicity?

Both 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.

Twin-specific intrauterine 'growth' charts based on cross-sectional birthweight data.

The 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.

Twin birth weight standards.

OBJECTIVE: The aim of this study was to present customized twin-specific birth weight standards. The relative contribution of gestational age, maternal factors, twin factors and placental factors to the birth weight was evaluated in a multivariate approach. SUBJECTS AND METHODS: Perinatal data were obtained from 10,177 live-born twins from the East Flanders Prospective Twin Survey. Of 8,454 twins (4,227 pairs), of whom all data were available, the birth weights at different gestational ages were analyzed using a non-linear multivariate gaussian regression. RESULTS: All considered covariates influenced birth weight of twins significantly, with the exception of sex of the co-twin and mode of conception and delivery. At 37 weeks of gestation, a difference of >1 kg existed between favourable and adverse prenatal environment. Up to 40 weeks, sex, site of the umbilical cord, parity, and birth order had a greater influence on birth weight than zygosity, chorionicity and fusion of the placentas. From 34 weeks on, the birth weight of the second-born twin deviated and after 40 weeks, birth weight of monozygotic monochorionic twins dropped, while the other twins continued to grow. CONCLUSION: Customized twin-specific birth weight standards, which take these covariates into account, offer the opportunity for a better assessment of the influence of birth weight of the twin on neonatal health in future research. Already the Developmental Origins of Health and Disease hypothesis showed that these prenatal conditions might also be important for the follow-up of the twin.

Curves of placental weights of live-born twins.

The 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.

High frequency of iatrogenic monozygotic twins with administration of clomiphene citrate and a change in chorionicity.

The data of the population-based, prospective survey of multiple births in East Flanders, Belgium, show that a greater proportion of monozygotic twins is observed with clomiphene citrate as sole treatment compared with other ovulatory drugs. Among iatrogenic monozygotic twins, the ratio of monochorionic versus dichorionic pairs is higher compared with spontaneous twins.

The East Flanders Prospective Twin Survey (EFPTS).

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 ascertained at birth; basic perinatal data recorded; chorion type and zygosity established; and since 1969 placental biopsies have been taken and frozen at -20 degrees C for later determination of genetic markers. The EFPTS is the only large register that includes placental data and allows differentiation of 3 subtypes of monozygotic (MZ) twins based on the time of the initial zygotic division: the dichorionic-diamnionic pairs (early, before the 4th day after fertilization), the monochorionic-diamnionic pairs (intermediate, between the 4th and the 7th day post fertilization), and the monochorionic-monoamnionic pairs (late, after the 8-day post fertilization). This added a new dimension to didymology (the science of twins; didymos is the Greek word for twin): the timing of MZ twinning. 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 (before and just after implantation of the embryo), the origin of congenital malformations, the sex proportion of multiples, the gene-environment interactions as far as intrauterine environment is concerned, to name but a few.

Preterm birth in twins after subfertility treatment: population based cohort study.

OBJECTIVES: To assess gestational length and prevalence of preterm birth among medically and naturally conceived twins; to establish the role of zygosity and chorionicity in assessing gestational length in twins born after subfertility treatment. DESIGN: Population based cohort study. SETTING: Collaborative network of 19 maternity facilities in East Flanders, Belgium (East Flanders prospective twin survey). PARTICIPANTS: 4368 twin pairs born between 1976 and 2002, including 2915 spontaneous twin pairs, 710 twin pairs born after ovarian stimulation, and 743 twin pairs born after in vitro fertilisation or intracytoplasmic sperm injection. MAIN OUTCOME MEASURES: Gestational length and prevalence of preterm birth. RESULTS: Compared with naturally conceived twins, twins resulting from subfertility treatment had on average a slightly decreased gestational age at birth (mean difference 4.0 days, 95% confidence interval 2.7 to 5.2), corresponding to an odds ratio of 1.6 (1.4 to 1.8) for preterm birth, albeit confined to mild preterm birth (34-36 weeks). The adjusted odds ratios of preterm birth after subfertility treatment were 1.3 (1.1 to 1.5) when controlled for birth year, maternal age, and parity and 1.6 (1.3 to 1.8) with additional control for fetal sex, caesarean section, zygosity, and chorionicity. Although an increased risk of preterm birth was therefore seen among twins resulting from subfertility treatment, the risk was largely caused by a first birth effect among subfertile couples; conversely, the risk of prematurity was substantially levelled off by the protective effect of dizygotic twinning. CONCLUSIONS: Twins resulting from subfertility treatment have an increased risk of preterm birth, but the risk is limited to mild preterm birth, primarily by virtue of dizygotic twinning.

Determinants of birthweight and intrauterine growth in liveborn twins.

We explored the relationship of umbilical cord insertion and fusion of placentas with birthweight in monozygotic monochorionic (MZ MC), monozygotic dichorionic (MZ DC), and dizygotic (DZ) twins. In addition, we evaluated some of the possible factors responsible for the restricted intrauterine growth of twins compared with singletons. The birthweight of 4529 liveborn twin pairs of the East Flanders Prospective Twin Survey was prospectively recorded, placentas were examined, and site of umbilical cord insertion was determined after delivery. Birthweight of 76 490 liveborn singletons was obtained from the Study Centre for Perinatal Epidemiology (SPE). Infants with a peripheral cord insertion weighed 150 g less (P < 0.001) than infants with a central cord insertion. DZ infants had a significantly (P < 0.001) higher incidence of central cord insertion than MZ DC and MZ MC infants. MZ DC infants with fused placentas and a peripheral cord insertion weighed on average 300 g less (P < 0.01) than infants with separate placentas and a central cord insertion. In DZ infants, fusion of the placentas did not affect birthweight. Twins gain less weight per week of gestation than singletons from 32 weeks onwards (twins: 128 g, 156 g, 75 g and singletons: 118 g, 251 g, 149 g, weeks 27-31,32-36, 37-42 respectively). From week 32 onwards, parity, birth rank, cord insertion and number of placentas also influenced birthweight of twins. We conclude that the difference between the birthweights of DZ, MZ DC, and MZ MC infants may originate from the least favourable antenatal situation, namely fused placentas with a peripheral cord insertion, which occurs most frequently in MZ twins. Gestation is the main determinant of birthweight. Other placental and maternal factors have a modest but significant influence on prenatal growth.

Gender mix: does it modify birthweight--outcome association?

Gender mix, especially the supposed hormone transfer in utero of the male fetus to his female co-twin, is a highly debated controversial subject. It occurs in animals (free-martin syndrome in the cow) but its existence in man has not been convincingly demonstrated. Two aspects of gender mix effects in man, birthweight and cognitive development, were studied in the Belgian East Flanders Prospective Twin Survey, a large population-based registry of multiple maternities, characterised by accurate data on pregnancy, placental structure and zygosity. The birthweight of the female member of the pair is not influenced by the male co-twin but, unexpectedly, the female twin enhances to a slight degree the birthweight of her male co-twin by prolonging the gestation for a few days. Also unexpectedly, in an opposite direction, the cognitive development, as measured by the IQ (WISC-R) of the female twin rises as compared with controls if her birthweight exceeds that of her male co-twin.

Retrospective determination of chorion type in twins using a simple questionnaire.

This study investigates the validity of retrospective determination of chorion type by asking the question to the mother about the number of placentas. In the "East Flanders Prospective Twin Survey" (EFPTS), accurate information on the placentation and zygosity of the multiples was collected prospectively. The mothers of 231 monozygotic (95 dichorionic and 136 monochorionic) twins and 255 dizygotic twins were asked to fill in a simple questionnaire regarding 1). the zygosity and 2). the number of placentas of their twins. The accuracy of the response to the question on "the number of placentas" was 60% for monozygotic twins and 37% for dizygotic twins. The accuracy of the response to the question on the zygosity of the twins was 93% for monozygotic and 95% for dizygotic twins. If the questionnaire was used for the determination of chorion type, a total of 31 monozygotic twins (13%) should have been assigned as dichorionic on the fact that there were two separate placentas. Of these, 10 (32%) are monochorionic and 12 (39%) were falsely reported as having two placentas. We conclude from these findings that this simple questionnaire method is unreliable for the retrospective determination of the chorion type.

The East Flanders Prospective Twin Survey (EFPTS).

The East Flanders Prospective Twin Survey (EFPTS) is a registry of multiple births in the province of East-Flanders, Belgium. It 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 ascertained at birth; basic perinatal data are recorded; chorion type and zygosity are established; and since 1969 placental biopsies have been taken and frozen at -20 degrees 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, before the fourth day after fertilisation), the monochorionic-diamnionic pairs (intermediate, between the fourth and the seventh day post fertilisation), and the monochorionic-monoamnionic pairs (late, after the eight day post fertilisation). This added a new dimension to didymology (the science of twins; delta iota delta upsilon mu omicron zeta = twins): the timing of twinning. Studies can be initiated on primary biases, those originating "in utero". Such studies may throw new light on the controversy over the validity of the classic twin method, the consequences of early embryological events (before and just after implantation of the embryo), the origin of congenital malformations, the sex proportion of multiples, the gene-environment interactions as far as intrauterine environment is concerned, to name but a few.