Pathway analysis of genetic factors associated with spontaneous preterm birth and pre-labor preterm rupture of membranes.

BACKGROUND: Pre-term birth (PTB) remains the leading cause of infant mortality and morbidity. Its etiology is multifactorial, with a strong genetic component. Genetic predisposition for the two subtypes, spontaneous PTB with intact membranes (sPTB) and preterm prelabor rapture of membranes (PPROM), and differences between them, have not yet been systematically summarised. METHODS AND FINDINGS: Our literature search identified 15 association studies conducted in 3,600 women on 2175 SNPs in 274 genes. We used Ingenuity software to impute gene pathways and networks related to sPTB and PPROM. Detailed insight in the defined functional ontologies clearly separated integrated datasets for sPTB and PPROM. Our analysis of upstream regulators of genes suggests that glucocorticoid receptor (NR3C1), peroxisome proliferator activated receptor γ (PPARG) and interferon regulating factor 3 (IRF3) may be sPTB specific. PPROM-specific genes may be regulated by estrogen receptor2 (ESR2) and signal transducer and activator of transcription (STAT1). The inflammatory transcription factor NFκB is linked to both sPTB and PPROM, however, their inflammatory response is distinctly different. CONCLUSIONS: Based on our analyses, we propose an autoimmune/hormonal regulation axis for sPTB, whilst pathways implicated in the etiology of PPROM include hematologic/coagulation function disorder, collagen metabolism, matrix degradation and local inflammation. Our hypothesis generating study has identified new candidate genes in the pathogenesis of PPROM and sPTB, which should be validated in large cohorts.

Multiple ectopic leiomyomas of the abdominal rectus muscles after gasless laparoscopic uterine myomectomy.

PURPOSE: To describe and analyze the first case of multiple ectopic leiomyomas of the abdominal rectus muscles in a patient who had undergone gasless laparoscopic uterine myomectomy (GLM) 10 years before. METHODS: A 41-year-old woman, who had undergone GLM 10 years before, having presented multiple palpable masses of the abdominal wall, underwent minilaparotomic excision of six abdominal masses. RESULTS: Six round well-circumscribed masses of the abdominal rectus muscles, measuring, respectively, 3.8 × 1.7, 2.9 × 0.9, 0.8 × 0.5, 0.7 × 0.3, 10 × 0.8 and 0.5 × 0.4 cm, were excised. The major lesion was situated close to the right trocar site of the previous GLM, the other smaller tumors were located in the umbilical area and left abdominal region. On histopathologic examination, the abdominal lumps were categorized as leiomyoma. CONCLUSIONS: Ectopic leiomyomatosis is an uncommon complication after GLM, and does not justify follow-up in all asymptomatic cases. However, the gynecologists should bear this unusual condition in mind, and inform the patients that leiomyoma fragments can grow in ectopic sites.

Histomorphometric characteristics of first trimester chorionic villi in pregnancies with low serum pregnancy-associated plasma protein-A levels: relationship with placental three-dimensional power doppler ultrasonographic vascularization.

OBJECTIVE: To evaluate histomorphometric vascular characteristics from samples obtained by chorionic villus sampling (CVS) in pregnancies with low serum pregnancy-associated plasma protein-A (PAPP-A) levels and to relate these findings to three-dimensional (3D) placental volume and power Doppler vascularization. METHODS: Immediately before CVS, placental 3D-power Doppler ultrasonography was performed at 11 + 0 to 13 + 6 weeks in 12 pregnancies with PAPP-A concentrations <0.3 multiples of median (MoM) as well as in 11 control women. Using a standardized setting placental volume, vascularization index (VI), flow index (FI), and vascularization flow index (VFI) were measured. Histomorphometric parameters of villi were blindly evaluated with a video-computerized-image-analysis system. RESULTS: Pregnancies with low PAPP-A showed a significantly reduced number of capillary vessels per villus cross-section (p = 0.005) and a smaller capillary diameter (p = 0.041). Placental vascular indices were significantly related to the number of fetal capillary vessels per villus (VI: r = 0.51, p = 0.03; FI: r = 0.48, p = 0.04; VFI: r = 0.56, p = 0.01). CONCLUSIONS: Differences in placental vascularization are present in first trimester in pregnancies with low PAPP-A and they are associated to altered 3D placental Doppler indices.

First-trimester placental volume and vascularization measured by 3-dimensional power Doppler sonography in pregnancies with low serum pregnancy-associated plasma protein a levels.

OBJECTIVE: The purpose of this study was to investigate the first-trimester placental volume and 3-dimensional (3D) power Doppler vascularization of pregnancies with low serum pregnancy-associated plasma protein A (PAPP-A) levels and to relate these findings to pregnancy outcomes. METHODS: Three-dimensional power Doppler sonography of the placenta was performed at gestational ages of 11 weeks to 13 weeks 6 days in 84 pregnancies with PAPP-A concentrations of less than 0.4 multiple of the median (MoM). With a standardized setting, the placental volume and vascularization index (VI), flow index (FI), and vascularization-flow index (VFI) were calculated and related to pregnancy outcomes. RESULTS: Pregnancy outcomes were as follows: 57 pregnancies with birth weights at or above the 10th percentile (group A), 16 pregnancies with birth weights below the 10th percentile and normal Doppler findings in the umbilical artery throughout gestation (group B), and 11 pregnancies with birth weights below the 10th percentile and abnormal umbilical Doppler findings later in gestation (group C). No differences were found in PAPP-A levels among groups. Placental volume values were significantly lower than reference limits, but no differences were found between groups. In groups A and B, there were no significant differences in 3D Doppler indices. However, these indices were significantly lower in group C (VI mean difference, -1.904; P < .001; FI mean difference, -1.939; P < .001; VFI mean difference, -1.944; P < .001). Placental vascular indices were significantly related to the severity of intrauterine growth restriction (IUGR; VI, r = 0.438; P < .001; FI, r = 0.482; P < .001; VFI, r = 0.497; P < .001) but not to the PAPP-A MoM and placental volume values. CONCLUSIONS: Low serum maternal PAPP-A levels are associated with altered 3D placental Doppler indices, and these changes are related to subsequent development of IUGR and adverse pregnancy outcomes.