Polymorphisms in the promoter region of the interleukin-10 (IL-10) gene in women with cervical insufficiency.

OBJECTIVE: Our objective was to determine whether polymorphisms in the promoter region of the interleukin-10 gene are more common in women with cervical insufficiency compared with controls. STUDY DESIGN: We conducted a case-control study. Histories and blood were obtained from 121 cases and 157 controls. DNA was extracted and purified by using Puregene kits. Samples were analyzed for the interleukin-10 -1082 G/A polymorphism and interleukin-10.G microsatellite in the interleukin-10 gene promoter region. RESULTS: The -1082 G/A polymorphism in the promoter region of the interleukin-10 gene occurred with similar frequency in cases and controls. The interleukin-10.G microsatellite contained 10 alleles (G6-G16). The G13 allele was present more frequently in cases (24.1%) compared with controls (14.6%) (P = .05). CONCLUSION: Interleukin-10 is known to down-regulate inflammation. The G13 allele in the interleukin-10.G microsatellite occurred more frequently in women with cervical insufficiency compared with controls, suggesting that alterations in inflammatory processes may play a role in cervical insufficiency.

Thromboprophylaxis and pregnancy outcomes in asymptomatic women with inherited thrombophilias.

OBJECTIVE: Our objective was to evaluate the effect of thromboprophylaxis on pregnancy outcomes in asymptomatic women with inherited thrombophilias. STUDY DESIGN: This was a retrospective cohort study of asymptomatic pregnant women with inherited thrombophilias. Medical records were reviewed for pregnancy events, diagnosis of thrombophilias, and management in subsequent pregnancies. Outcomes in women who were and were not treated with thromboprophylaxis were compared using Fisher's exact test and logistic regression. RESULTS: Fifty-three women had 75 pregnancies subsequent to their diagnosis of thrombophilia. Women treated with heparin had similar rates of live births (86% vs 82%; P = .8, Fisher's exact test) as those not treated. The odds ratio of live birth in all pregnancies for women treated with heparin was compared with untreated women and was 1.9 (95% confidence interval, 0.5-6.3). CONCLUSION: Pregnancy outcomes are often good in asymptomatic women with thrombophilias in the absence of treatment. Treatment of these women during pregnancy should be considered investigational.

Genetics of pregnancy loss.

Pregnancy loss is a common problem in reproductive-aged women. Although most cases of pregnancy loss are sporadic, some couples experience recurrent pregnancy loss, a challenging clinical dilemma. A variety of possible etiologies have been described for both sporadic and recurrent pregnancy loss. This review focuses on the genetic abnormalities that may contribute to this clinical problem and delineates strategies for genetic evaluation and clinical management in subsequent pregnancies.

Collagen 1Alpha1 and transforming growth factor-beta polymorphisms in women with cervical insufficiency.

OBJECTIVE: To estimate whether polymorphisms in the collagen 1Alpha1 gene (COL1Alpha1) and the transforming growth factor-beta gene (TGF-beta;1) are more common in women with cervical insufficiency than in those without the condition. METHODS: Medical, obstetric, and family histories and blood were obtained from women with (n=121) and those without (n=165) cervical insufficiency. DNA was extracted and purified by using commercial DNA isolation kits. Samples were analyzed for variants in two genes, the COL1A1 intron 1SP1 and TGF-beta Arg-25-Pro polymorphism, by using an allele-specific polymerase chain reaction assay. RESULTS: Thirty-four of 125 (27.2%) women with cervical insufficiency had at least one first-degree female relative affected. The frequency of the homozygous TT genotype in the COL1A1 gene was increased in women with a history of cervical insufficiency compared with controls (10.8% compared with 3.1%, P=.04). The TGF-beta polymorphisms (ArgPro and ProPro) also were increased in cases (38.3% compared with 14.6%, P<.001). CONCLUSION: Over one fourth of women with cervical insufficiency have a family history of cervical insufficiency, and the COL1A1 intron 1SP1 and TGF-beta Arg-25-Pro polymorphisms are associated with the condition. These observations suggest that, in part, cervical insufficiency is mediated by genetic factors. LEVEL OF EVIDENCE: II.

Genetics of the cervix in relation to preterm birth.

Preterm birth is the most significant problem encountered in obstetrics in the developed world. Genetic factors are thought to play a role in a proportion of preterm births, and candidate genes have been studied in several areas relevant to parturition. Abnormal cervical function, a clinical spectrum, including cervical insufficiency (CI), is a contributing factor to the overall problem of preterm birth. There are many risk factors and etiologies for CI. However, it is becoming clear that, at least in part, a genetic predisposition to CI plays a role in the condition. Specifically, genes related to connective tissue metabolism and inflammation have been shown to be associated with CI.

Array comparative genomic hybridization for genetic evaluation of fetal loss between 10 and 20 weeks of gestation.

OBJECTIVE: To estimate genomic copy number changes in fetal loss between 10 and 20 weeks of gestation using array comparative genomic hybridization. METHODS: This was a prospective series of 35 women who experienced pregnancy loss between 10-20 weeks of gestation with either normal karyotype (n=9) or no conventional cytogenetic testing (n=26). DNA was isolated from fetal tissue and parental blood. Array comparative genomic hybridization was performed on DNA from fetal tissue using a whole genome BAC array chip. Copy number changes in fetal tissue were then compared against databases of benign copy number changes. Parental DNA was analyzed using the same BAC array in cases that contained suspected pathogenic copy number changes. In cases where de novo copy number changes were detected in fetal DNA, further characterization was performed using a 244K oligonucleotide microarray. RESULTS: DNA was successfully isolated in 30 of 35 (86%) of cases. Array comparative genomic hybridization was performed in all of these. De novo copy number changes were detected in six (20%) cases using the Spectral chip and confirmed in four (13%) cases using the Agilent chip. These ranged in size from 93-289 Kb and mapped on 5p, 13q and Xq22. In the cases with de novo copy number changes, the higher-density Agilent array detected additional changes (20-1,310 Kb). CONCLUSION: Array comparative genomic hybridization detected de novo copy number changes in 13% of cases where routine cytogenetic testing was normal or not performed. These involved large regions of DNA and may provide novel explanations for some cases of otherwise unexplained pregnancy loss. LEVEL OF EVIDENCE: III.

Toward automated analysis of biofilm architecture: bias caused by extraneous confocal laser scanning microscopy images.

An increasing number of studies utilize confocal laser scanning microscopy (CLSM) for in situ visualization of biofilms and rely on the use of image analysis programs to extract quantitative descriptors of architecture. Recently, designed programs have begun incorporating procedures to automatically determine threshold values for three-dimensional CLSM image stacks. We have found that the automated threshold calculation is biased when a stack contains images lacking pixels of biological significance. Consequently, we have created the novel program Auto PHLIP-ML to resolve this bias by iteratively excluding extraneous images based on their area coverage of biomass. A procedure was developed to identify the optimal percent area coverage value used for extraneous image removal (PACVEIR). The optimal PACVEIR was defined to occur when the standard deviation of mean thickness, determined from replicate image stacks, was at a maximum, because it more accurately reflected inherent structural variation. Ten monoculture biofilms of either Ralstonia eutropha JMP228n::gfp or Acinetobacter sp. strain BD413 were tested to verify the routine. All biofilms exhibited an optimal PACVEIR between 0 and 1%. Prior to the exclusion of extraneous images, JMP228n::gfp appeared to develop more homogeneous biofilms than BD413. However, after the removal of extraneous images, JMP228n::gfp biofilms were found to form more heterogeneous biofilms. Similarly, JMP228n::gfp biofilms grown on glass surfaces vis-à-vis polyethylene membranes produced significantly different architectures after extraneous images had been removed but not when such images were included in threshold calculations. This study shows that the failure to remove extraneous images skewed a seemingly objective analysis of biofilm architecture and significantly altered statistically derived conclusions.

Preconception counseling for women with thrombophilia.

Inherited thrombophilias are a heterogeneous group of coagulation disorders that predispose individuals to thromboembolic events. This group of conditions is the major risk factor for thromboembolism during pregnancy and the puerperium. In addition, thrombophilias have been associated with several adverse obstetric events, including pregnancy loss, preeclampsia, placental abruption, and intrauterine growth restriction. An increased risk for these obstetric complications has prompted many authorities to recommend screening and treating pregnant women for thrombophilias. Optimal obstetric management, however, is controversial as thrombophilias are common and many affected individuals are asymptomatic. Indeed, pregnancy outcome in most women with thrombophilias is normal. The most commonly identified inherited thrombophilias are the factor V Leiden and prothrombin G20210A gene mutations. More rare thrombophilias include protein C and S deficiencies, antithrombin III deficiency. Although relatively common, the association between hyperhomocysteinemia and associated mutations (such as the C677 T methylenetetrahydro-folate reductase) and obstetric complications is controversial.

Plasmapheresis for the treatment of intrahepatic cholestasis of pregnancy refractory to medical treatment.

Pruritus associated with intrahepatic cholestasis of pregnancy (ICP) is usually mild but some cases are refractory to medical treatment. We report a case of intractable ICP that was successfully treated with plasmapheresis. Plasmapheresis should be considered for ICP that is refractory to traditional therapies.