Mode of Delivery and Long-Term Health-Related Quality-of-Life Outcomes: A Prospective Population-Based Study.

BACKGROUND: Relatively little is known about the effects of mode of delivery on long-term health-related quality-of-life outcomes. Furthermore, no previous study has expressed these outcomes in preference-based (utility) metrics. METHODS: The study population comprised 2,161 mothers recruited from a prospective population-based study in the East Midlands of England encompassing live births and stillbirths between 32+0 and 36+6 weeks' gestation and a sample of term-born controls. Perinatal data were extracted from the mothers' maternity records. Health-related quality-of-life outcomes were assessed at 12 months postpartum, using the EuroQol Five Dimensions (EQ-5D) measure with responses to the EQ-5D descriptive system converted into health utility scores. Descriptive statistics and multivariable analyses were used to estimate the relationship between the mode of delivery and health-related quality-of-life outcomes. RESULTS: The overall health-related quality-of-life profile of the women in the study cohort mirrored that of the English adult population as revealed by national health surveys. A significantly higher proportion of women delivering by cesarean delivery reported some, moderate, severe, or extreme pain or discomfort at 12 months postpartum than women undergoing spontaneous vaginal delivery. Multivariable analyses, using the Ordinary Least Squares estimator revealed that, after controlling for maternal sociodemographic characteristics, cesarean delivery without maternal or fetal compromise was associated with a significant EQ-5D utility decrement in comparison to spontaneous vaginal delivery among all women (-0.026; p = 0.038) and among mothers of term-born infants (-0.062; p < 0.001). Among mothers of term-born infants, this result was replicated in models that controlled for all maternal and infant characteristics (utility decrement of -0.061; p < 0.001). The results were confirmed by sensitivity analyses that varied the categorization of the main exposure variable (mode of delivery) and the econometric strategy. CONCLUSIONS: Among mothers of term-born infants, cesarean delivery without maternal or fetal compromise is associated with poorer long-term health-related quality of life in comparison to spontaneous vaginal delivery. Further longitudinal studies are needed to understand the magnitude, trajectory, and underpinning mechanisms of health-related quality-of-life outcomes following different modes of delivery.

The cytoplasmic 60 kDa progesterone receptor isoform predominates in the human amniochorion and placenta at term.

BACKGROUND: The mechanism that initiates human parturition has been proposed to be 'functional progesterone withdrawal' whereby the 116 kDa B-isoform of the progesterone receptor (PR-B) switches in favour of the 94 kDa A-isoform (PR-A) in reproductive tissues. Recently, other PR isoforms, PR-S, PR-C and PR-M generated from the same gene have been identified and partially characterised. METHODS AND RESULTS: Using immunohistochemical, western blotting and RT-PCR techniques, evidence is provided that indicates the major PR isoform present in human term fetal membranes (amnion and chorion) and syncytiotrophoblast of the placenta is neither of the classical nuclear PR-B or PR-A isoforms but is the N-terminally truncated 60 kDa PR-C isoform. Evidence is also provided that this 60 kDa isoform resides in the cytoplasm of the expressing cell types. Data are also presented to show that PR-B, PR-A and PR-S isoforms are essentially absent from the amnion and chorion, whereas PR isoforms A, B, C and S are all present in the decidua, with PR-A being the major isoform. The syncytiotrophoblast of the placenta contains the cytoplasmic 60 kDa isoform, but not isoforms PR-A, PR-B or PR-S. CONCLUSION: The major PR isoform in the amnion, chorion and placenta is a 60 kDa protein that could be PR-C, suggesting that the cytoplasmic isoform has a specific role in extra-embryonic tissues and may be involved in the regulation of human parturition.

The progesterone receptor in human term amniochorion and placenta is isoform C.

The mechanism that initiates human parturition has been proposed to be functional progesterone withdrawal whereby the 116-kDa B isoform of the progesterone receptor (PR-B) switches in favor of the 94-kDa A isoform (PR-A) in reproductive tissues. Recently other PR isoforms, PR-S, PR-C, and PR-M generated from the same gene have been identified and partially characterized. Using immunohistochemical, Western blotting, and RT-PCR techniques, evidence is provided that the major PR isoform present in human term fetal membranes (amnion and chorion) and syncytiotrophoblast of the placenta is neither of the classical nuclear PR-B or PR-A isoforms but is the N terminally truncated 60-kDa PR-C isoform. Evidence is also provided that the PR-C isoform resides in the cytoplasm of the expressing cell types. Data are also presented to show that PR-B, PR-A, and PR-S isoforms are essentially absent from the amnion and chorion, whereas PR isoforms A, B, C, and S are all present in the decidua, with PR-A being the major isoform. The syncytiotrophoblast of the placenta contains the cytoplasmic PR-C isoform but not PR-A, PR-B, or PR-S. The major PR isoform in the amnion, chorion, and placenta is PR-C, suggesting that the cytoplasmic PR-C isoform has a specific role in extraembryonic tissues and may be involved in the regulation of human parturition.

Relationship between antenatal inflammation and antenatal infection identified by detection of microbial genes by polymerase chain reaction.

Although antenatal infection is thought to play an important role in the pathogenesis of preterm labor and neonatal diseases, the exact mechanisms are largely unknown. We sought to clarify the relationship between antenatal infection and intrauterine and neonatal inflammation. Samples were obtained from 41 preterm infants of <33 wk gestation delivered to 36 mothers and analyzed for the presence of 16s ribosomal RNA (16s rRNA) genes using PCR and for the proinflammatory cytokines IL-6 and IL-8. In 16 (44%) mother-baby pairings, at least one sample was found to be positive for the presence of 16s rRNA genes. All but one of the positive samples were from mothers presenting with preterm prelabor rupture of membranes (pPROM) or in spontaneous idiopathic preterm labor. A strong association was found between the presence of 16s rRNA genes and chorioamnionitis and with funisitis. A marked increase in IL-6 and IL-8 was noted in all tissues positive for 16s rRNA genes, including placenta, fetal membranes, cord blood serum, and, where samples were available, in bronchoalveolar lavage fluid (BAL) and in amniotic fluid. Interestingly, gastric fluid was always positive for 16s rRNA genes if any other intrauterine or BAL sample was positive, suggesting that this sample may provide an alternative to amniotic fluid to identify antenatal infection. In conclusion, we have found that microbial genes are particularly prevalent in pPROM and spontaneous preterm labor groups and that their presence is strongly associated with a marked intrauterine inflammatory response.

Mapping of zones of altered morphology and chorionic connective tissue cellular phenotype in human fetal membranes (amniochorion and decidua) overlying the lower uterine pole and cervix before labor at term.

OBJECTIVE: The purpose of this study was to determine the location, frequency, and extent of altered fetal membrane morphology before term labor and its relation to myofibroblast activation in their connective tissue layers. STUDY DESIGN: Fetal membranes that were obtained from 10 women who underwent prelabor cesarean delivery at 38 to 39 weeks of gestation underwent biopsy examination with respect to the internal os of the cervix. The thickness of their constituent layers was measured, and the numbers of alpha-smooth muscle actin immunoreactive cells (ie, marker of myofibroblast activation) within the reticular layer were counted. RESULTS: A region that measured 119+/-21cm(2), that exhibited altered morphology of the fetal membranes from the lower uterine pole, and that was characterized by increased connective tissue thickness and decreased thickness of the cellular layers was demonstrated in all patients. In 8 of 10 patients, this region was centered on the location of the Babcock tissue forceps. Within this region was an area of fetal membranes that exhibited alpha-smooth muscle actin immunoreactivity in the cells of the reticular layer and whose number correlated with parameters of altered morphology. CONCLUSION: All patients before labor at term possess an area of fetal membranes that are located in the lower uterine pole that exhibit altered morphology that is associated with myofibroblastic activation in the chorionic connective tissue.