Maternal factors, fetal parameters and the risk of shoulder dystocia

Introduction. Shoulder dystocia is a serious complication of vaginal birth, with an incidence ranging from 0.15% to 2.1% of all births. There are approximately 4 million births per year in the United States and shoulder dystocia will be experienced by approximately 20,000 women each year. Although studies have been reported on shoulder dystocia, few studies have addressed both maternal and fetal risk factors. The purpose of this study was to identify maternal and fetal risk factors for shoulder dystocia while proposing factors that could be used to predict impending shoulder dystocia. ^ Material and methods. Articles were reviewed from Medline Pubmed using the search phrase "Risk factors of shoulder dystocia" and Medline Ovid using the search words "Dystocia", "Shoulder" and "Risk factors". Rigorous selection criteria were used to identify articles to be included in the study. Data collected from identified articles were transferred to STATA 10 software for trend analysis of the incidence of shoulder dystocia and the year of publication and a pair wise correlation was also determined between these two variables. ^ Results. Among a total of 343 studies identified, only 20 met our inclusion criteria and were retained for this review. The incidence of shoulder dystocia ranged from 0.07% to 2% and there was no particular trend or correlation between the incidence of shoulder dystocia and year of publication between 1985 and 2007. Pre-gestational and gestational diabetes, postdatism, obesity, birth weight > 4000g and fundal height at last visit > 40cm were identified as major risk factors in our series of studies. ^ Conclusion. Future strategies to predict shoulder dystocia should focus on pre-gestational and gestational diabetes mellitus, postdatism, obesity, birth weight > 4000g and fundal height at last visit > 40cm. ^

Xenobiotic Metabolism Genes and Clubfoot

Idiopathic or isolated clubfoot is a common orthopedic birth defect that affects approximately 135,000 children worldwide. It is characterized by equinus, varus and adductus deformities of the ankle and foot. Correction of clubfoot involves months of serial manipulations, castings and bracing, with surgical correction needed in forty percent of cases. Multifactorial etiology has been suggested in numerous studies with both environmental and genetic factors playing an etiologic role. Maternal smoking during pregnancy is the only common environmental factor that has consistently been shown to increase the risk for clubfoot. Moreover, a positive family history of clubfoot and maternal smoking increases the risk of clubfoot twenty fold. These findings suggest that genetic variation in smoking metabolism genes may increase susceptibility to clubfoot. Based on this reasoning, we interrogated eight candidate genes, chosen based on their involvement in phase 1 and 2 cigarette smoke metabolism. Twenty-two SNPs and two null alleles in eight genes (CYP1A1, CYP1A2, CYP1B1, CYP2A6, EPHX1, NAT2, GSTM1 and GSTT1) were genotyped in a dataset composed of nonHispanic white and Hispanic multiplex and simplex families. Only one SNP in CYP1A1, rs1048943, had significantly altered transmission in the aggregate and multiplex NHW datasets (p=0.003 and p=0.009). Perturbation of CYP1A1 by rs1048943 polymorphism causes an increase in the amount of harmful, adduct forming metabolic intermediates. A significant gene interaction between EPHX1 and NAT2 was also found (p=0.007). This interaction may affect the metabolism of harmful metabolic intermediates. Additionally, marginal interactions were found for other xenobiotic genes and these interactions may play a contributory role in clubfoot. Importantly, for CYP1A2, significant maternal (p=0.03; RR=1.24; 95% CI: 1.04-1.44) and fetal (p=0.01; RR=1.33; 95% CI: 1.13-1.54) genotypic effects were identified suggesting that both maternal and fetal genotypes impact normal limb development. No association was found for maternal smoking status and tobacco metabolism genes. Together, these results suggest that xenobiotic metabolism genes may play a contributory role in the etiology of clubfoot regardless of maternal smoking status and may impact foot development through perturbation of tobacco metabolic pathways.

Esx1 is an X-chromosome-imprinted regulator of placental formation and fetal growth

Placental formation and genomic imprinting are two important features of embryonic development in placental mammals. Genetic studies have demonstrated that imprinted genes play a prominent role in regulating placental formation. In marsupials, mice and humans, the paternally derived X chromosome is preferentially inactivated in the placental tissues of female embryos. This special form of genomic imprinting may have evolved under the same selective forces as autosomal imprinted genes. This chromosomal imprinting phenomenon predicts the existence of maternally expressed X-linked genes that regulate placental development.^ In this study, an X-linked homeobox gene, designated Esx1 has been isolated. During embryogenesis, Esx1 was expressed in a subset of placental tissues and regulates formation of the chorioallantoic placenta. Esx1 acted as an imprinted gene. Heterozygous female mice that inherit an Esx1-null allele from their father developed normally. However, heterozygous females that inherit the Esx1 mutation from their mother were born 20% smaller than normal and had an identical phenotype to hemizygous mutant males and homozygous mutant females. Surprisingly, although Esx1 mutant embryos were initially comparable in size to wild-type controls at 13.5 days post coitum (E13.5) their placentas were significantly larger (51% heavier than controls). Defects in the morphogenesis of the labyrinthine layer were observed as early as E11.5. Subsequently, vascularization abnormalities developed at the maternal-fetal interface, causing fetal growth retardation. These results identify Esx1 as the first essential X-chromosome-imprinted regulator of placental development that influences fetal growth and may have important implications in understanding human placental insufficiency syndromes such as intrauterine growth retardation (IUGR). ^

An examination of the relationship between maternal and neighborhood-level characteristics and intrauterine growth retardation in Harris County, Texas, 1999--2001

The persistence of low birth weight and intrauterine growth retardation (IUGR) in the United States has puzzled researchers for decades. Much of the work that has been conducted on adverse birth outcomes has focused on low birth weight in general and not on IUGR. Studies that have examined IUGR specifically thus far have focused primarily on individual-level maternal risk factors. These risk factors have only been able to explain a small portion of the variance in IUGR. Therefore, recent work has begun to focus on community-level risk factors in addition to the individual-level maternal characteristics. This study uses Social Ecology to examine the relationship of individual and community-level risk factors and IUGR. Logistic regression was used to establish an individual-level model based on 155, 856 births recorded in Harris County, TX during 1999-2001. IUGR was characterized using a fetal growth ratio method with race/ethnic and sex specific mean birth weights calculated from national vital records. The spatial distributions of 114,460 birth records spatially located within the City of Houston were examined using choropleth, probability and density maps. Census tracts with higher than expected rates of IUGR and high levels of neighborhood disadvantage were highlighted. Neighborhood disadvantage was constructed using socioeconomic variables from the 2000 U.S. Census. Factor analysis was used to create a unified single measure. Lastly, a random coefficients model was used to examine the relationship between varying levels of community disadvantage, given the set of individual-level risk factors for 152,997 birth records spatially located within Harris County, TX. Neighborhood disadvantage was measured using three different indices adapted from previous work. The findings show that pregnancy-induced hypertension, previous preterm infant, tobacco use and insufficient weight gain have the highest association with IUGR. Neighborhood disadvantage only slightly further increases the risk of IUGR (OR 1.12 to 1.23). Although community level disadvantage only helped to explain a small proportion of the variance of IUGR, it did have a significant impact. This finding suggests that community level risk factors should be included in future work with IUGR and that more work needs to be conducted. ^

AMERICAN TRYPANOSOMIASIS (CHAGAS') DISEASE - A STUDY OF FETO-MATERNAL MORBIDITY AND MORTALITY

The possibility of a relationship between American Trypanosomiasis (Chagas') disease and pregnancy outcome was analyzed measuring feto-maternal morbidity and mortality in a sample of 604 pregnant women and their offspring seen at the Hospital Universitario de Maternidad y Neonatologia in Cordoba, Argentina during 1979.^ A cross-sectional, "case-comparison" investigation was employed to determine the degree of risk between having a reactive chagasic serologic test and a negative pregnancy outcome as determined by abortion, stillbirth, and infant death prior to one week of age. Patients were selected using a dichotomous, 0-1 scale with either the presence or the absence of a reactive Machado-Guerreiro complement fixation serologic blood test result.^ The data obtained were analyzed using appropriate statistical techniques for measuring the comparisons between the case and control groups under various demographic and socioeconomic variables such as, age, marital status, educational attainment, and residence. Similarly, additional biological variables of birth order, maternal and fetal complications, and prematurity were examined.^ From the analysis of the data obtained in this investigation, no definite conclusions can be reached regarding the risk of having an unsuccessful pregnancy outcome in the presence of a reactive serologic finding because the study design was a cross-sectional one and the number of events were too few for an adequate analysis. Notwithstanding these limitations, the results obtained, after statistical adjustments were employed, demonstrated that women with a reactive test result were older, were of a higher parity, and were less educated. Marital status and residence were not significant variables. The risk of pregnancy wastage, however, was almost twice as frequent in the reactive group as in the non-reactive group of women. Statistically significant differences in maternal morbidity involved two complications, polyhydramnios and varicosities of the lower extremities and vulva; while in the newborn, infection was higher in infants whose mothers exhibited a reactive serologic test result.^ In summary, what this research study has shown is the need for engaging in a larger, longitudinal study for an in-depth exploration of feto-maternal morbidity and mortality--an investigation that would corraborate or refute the findings of this study.^