Unequal placental sharing and birth weight discordance in monochorionic diamniotic twins
Department of Obstetrics, Gynecology, and Reproductive Sciences, University of California, San Francisco, CA, USA. American journal of obstetrics and gynecology
(Impact Factor: 4.7).
08/2006; 195(1):178-83. DOI: 10.1016/j.ajog.2006.01.015
The purpose of this study was to define the association between unequal placental sharing and birth weight discordance in monochorionic/diamniotic twin pregnancies.
The study comprised a prospective cohort of monochorionic/diamniotic twin pregnancies who were delivered in Kaiser Permanente-Northern California, 1997-2003. Dye injection studies of fresh postpartum placentas were performed. Placental sharing, cord insertion combinations, vascular anastomoses, gestational age, and birth weights were recorded. Statistical comparisons of birth weight and gestational age were made with the Student t test. Rates of birth weight discordance were compared with the chi-square test. Multivariate logistic regression models analyzed the relationship between variables of interest.
Mean birth weights for larger and smaller twins were 2400 g and 2109 g, respectively. Twenty-two percent of the monochorionic/diamniotic twin pairs had birth weight discordance > or = 20%, and 8% of these pairs had twin-twin transfusion syndrome. Monochorionic/diamniotic twin pairs with unequal placental sharing had a 9.8 times greater likelihood of birth weight discordance (95% CI, 5.4-17.9) as compared with those pairs with equal placental sharing.
Unequal placental sharing is a significant risk factor for birth weight discordance in monochorionic/diamniotic twins. Antenatal diagnosis of unequal placental sharing would enable improved counseling in the setting of monochorionic/diamniotic twins.
Available from: Mario Giuffrè
- "The causes of twin growth discordance are often unknown. The most important is considered to be monochorionicity, mainly because of unequal sharing, or of velamentous cord insertions in the IUGR twin . Other possible causes are “intrauterine crowding” and the presence of malformations [21-23]. "
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Twins, compared to singletons, have an increased risk of perinatal mortality and morbidity, due mainly to a higher prevalence of preterm birth and low birthweight. Intrauterine growth restriction (IUGR) is also common and can affect one or both fetuses. In some cases, however, one twin is much smaller than the other (growth discordance). Usually, high birthweight discordance is associated with increased perinatal morbidity. The aim of this study is to describe the epidemiological features of a population of twins at birth, with particular reference to the interpretation and clinical effects of birthweight discordance.
We evaluated retrospectively the clinical features of 70 infants born from twin pregnancies and assessed birthweight discordance in 31 pregnancies where both twins were followed at our institution. Discordance was treated both as a continuous and a categorical variable, using a cutoff of 18%. Possible relationships between birthweight discordance and other variables, such as maternal age, gestational age, birthweight percentile, number of SGA newborns in the pair, Hematocrit (Ht) discordance and neonatal anemia, prevalence of malformations, neonatal morbidity and death, were analyzed.
In our cohort birthweight percentile decreased slightly with increasing gestational age. Birthweight discordance, on the contrary, increased slightly with the increase of gestational age.A high discordance is associated to the presence of one SGA twin, with the other AGA or LGA. In our population, all 6 pregnancies in which discordance exceeded 18% belonged to this category (one SGA twin).Ht discordance at birth is associated to the presence of neonatal anemia in a twin, but it is not significantly related to weight discordance.Finally, in our case history, weight discordance is not associated in any way with the prevalence of malformations, morbidity and mortality.
Birthweight discordance is an important indicator of complications that act asymmetrically on the two fetuses, affecting intrauterine growth in one of them, and usually determining the birth of a SGA infant.Our case history shows a significant statistical association between pair discordance and IUGR in one of the twins, but we could not demonstrate any relationship between discordance and the prevalence of malformations, morbidity and mortality.
Available from: Dora Baczyk
- "This difference is mainly attributed to the twin –twin-transfusion syndrome (TTTS) and severe discordant intrauterine growth (Duncan et al., 1997; Lopriore et al., 2009). Both of these complications are conventionally explained by the characteristic gross anatomical differences and angio-architecture of each side of the MC twin placenta (Fick et al., 2006), while TTTS is classically explained by an imbalance in blood flow between the twins through surface arteriovenous placental vascular anastomoses (De Paepe et al., 2010; Baschat et al., 2011; Lopriore et al., 2011). Current opinion favors a central role for abnormalities in inter-twin vascular connections in discordant growth and TTTS in MC twins, especially since these diseases often overlap; however, more fundamental factors must operate to mediate differences in fetal growth for the following reasons: first, the difference in placental share in discordant MC twins does not always reflect the difference in growth between the twins (Kusanovic et al., 2008). "
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ABSTRACT: Severely-growth discordant monochorionic (MC) twins offer a unique opportunity to study fetal and placental growth based on a similar genetic background and maternal host environment where the healthy twin serves as an ideal control. Differences in development of monochorionic twins may therefore be due to differential epigenetic regulation of genes involved in placental development and function. Growth-discordant twins are known for abnormal angio-architecture in the placenta of the smaller twin. Since the reasons for this phenotype are mostly unknown this study was aimed to investigate expression and regulation of genes known to be involved in angiogenesis.We studied 10 severely growth-discordant monochorionic twin placentas (birth weight difference≥20%) without twin-twin-transfusion syndrome (TTTS) and 5 growth-concordant monochorionic twin placentas. Growth discordant twin placentas were phenotyped by histology. Placental mRNA expression of 88 angiogenesis related genes were measured by PCR array. Enzyme-linked immuno-sorbent assay (ELISA) and immuno-histochemistry were used to confirm PCR results. EpiTYPTER for DNA methylation was used to determine if methylation ratios were responsible for differential gene expression.The PCR array analysis showed significant mRNA up-regulation in the placental share of the smaller twin for several genes. These included Leptin (24.6 fold, p=0.017), Flt1 (fms-like tyrosine kinase 1, 2.4 fold, p=0.016) and Eng (Endoglin, 1.86 fold, p= 0.078). None of the other 84 angiogenesis related genes showed significant differences. ELISA confirmed significantly increased Leptin protein expression (49.22 vs. 11.03 pg/mL, p=0.049) in the smaller twin of the discordant growth cohort. Leptin expression in smaller twins' placentas was associated with elevated DNA methylation of the Leptin promotor region suggesting the inhibition of binding of a transcriptional activator / inhibitor in that region. We attempted to overcome the limitation of sample size by careful patient selection. We minimized any bias in placental sampling by random sampling from two different sites and by avoiding sampling from areas with grossly visible abnormalities using a standardized sampling protocol.In conclusion, the smaller twin's placenta is characterized by differentially-increased gene expressions for Flt1 and Eng mRNA that may be causally-associated with the villous pathology driven by abnormal feto-placental angiogenesis. The substantial up-regulation of Leptin mRNA may be epigenetically conferred and relevant to the post-natal risk of metabolic syndrome in IUGR offspring with placental pathology. Growth discordant MC twins offer unique insights into the epigenetic basis of perinatal programming.
Available from: Anne Örtqvist
- "One group of children at risk for IUGR is twins and especially monochoriotic twins. Several studies have found that an unequal distribution of the placenta is a major reason for differences in birth weight and selective IUGR in monochoriotic twin pregnancies 43,86,87. This inequality could possibly be an effect of intertwin artery-to-artery anastomoses 88 (Fig. 1C). "
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ABSTRACT: Early genetic and environmental factors have been discussed as potential causes for the high prevalence of asthma and allergic disease in the western world, and knowledge on fetal growth and its consequence on future health and disease development is emerging.
This review article is an attempt to summarize research on fetal growth and risk of asthma and allergic disease. Current knowledge and novel findings will be reviewed and open research questions identified, to give basic scientists, immunologists and clinicians an overview of an emerging research field.
PubMed-search on pre-defined terms and cross-references.
Several studies have shown a correlation between low birth weight and/or gestational age and asthma and high birth weight and/or gestational age and atopy. The exact mechanism is not yet clear but both environmental and genetic factors seem to contribute to fetal growth. Some of these factors are confounders that can be adjusted for, and twin studies have been very helpful in this context. Suggested mechanisms behind fetal growth are often linked to the feto-maternal circulation, including the development of placenta and umbilical cord. However, the causal link between fetal growth restriction and subsequent asthma and allergic disease remains unexplained. New research regarding the catch-up growth following growth restriction has posited an alternative theory that diseases later on in life result from rapid catch-up growth rather than intrauterine growth restriction per se. Several studies have found a correlation between a rapid weight gain after birth and development of asthma or wheezing in childhood.
Asthma and allergic disease are multifactorial. Several mechanisms seem to influence their development. Additional studies are needed before we fully understand the causal links between fetal growth and development of asthma and allergic diseases.
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