Bryan T. Oshiro

Decreasing Elective Deliveries Before 39 Weeks of Gestation in an Integrated Health Care System

OBJECTIVE: The American College of Obstetricians and Gynecologists has recommended that elective deliveries not be performed before 39 weeks of gestation, to minimize prematurity-related neonatal complications. Because a worrisome number of elective deliveries were occurring before 39 weeks of gestation in our system, we developed and implemented a program to decrease the number of these early term elective deliveries. Secondary objectives were to monitor relevant clinical outcomes. METHODS: The electronic medical records of an integrated health care system involving nine labor and delivery units in Utah were queried to establish the incidence of patients admitted for elective induction of labor or planned elective cesarean delivery. These facilities have open staff models with obstetricians, family practitioners, and certified nurse midwives. Guidelines were developed and implemented to discourage early term elective deliveries. The prevalence of early term elective deliveries was tracked and reported back regularly to the obstetric leadership and obstetric departments at each facility. RESULTS: The baseline prevalence of early term elective deliveries was 28% of all elective deliveries before the initiation of the program. Within 6 months of initiating the program, the incidence of near-term elective deliveries decreased to less than 10% and after 6 years continues to be less than 3%. A reduced length of stay in labor and delivery occurred with the introduction of the program, and there were no adverse effects on secondary clinical outcomes. CONCLUSION: With institutional commitment, it is possible to substantially reduce and sustain a decline in the incidence of elective deliveries before 39 weeks of gestation. LEVEL OF EVIDENCE: III

Endotoxin, interleukin-1β, interleukin-6, or tumor necrosis factor-α do not acutely stimulate isolated murine myometrial contractile activity

Objectives: Endotoxin, interleukin-1 β, interleukin-6, and tumor necrosis factor-α have been implicated in the pathogenesis of preterm labor, but their acute effect on myometrial contractile activity is unknown. The objective of this study was to determine their effect on isolated pregnant murine myometrial contractile activity. Study Design: Isometric contractions were measured in myometrium isolated from pregnancy day 18 Swiss-Webster mice. Frequency, duration, amplitude, and integrated area were compared before and after the addition of endotoxin (10 3 and 10 4 ng/ml) ( n = 6), interleukin-1β (10 and 10 ng/ml) ( n = 6), interleukin-6 (1 and 10 ng/ml) ( n = 6), and tumor necrosis factor-α (1 and 10 ng/ml) ( n = 6). Results were analyzed with the Wilcoxon rank-sum test. Results: The addition of endotoxin, interleukin-1β, interleukin-6, or tumor necrosis factor-α did not result in a change in the contractile activity of isolated pregnant murine myometrium compared with control. Conclusion: Endotoxin, interleukin-1 β, interleukin-6, and tumor necrosis factor-α do not acutely increase isolated murine myometrial contractile activity.

Remodeling of the Cervix and Parturition in Mice Lacking the Progesterone Receptor B Isoform

Withdrawal of progestational support for pregnancy is part of the final common pathways for parturition, but the role of nuclear progesterone receptor (PGR) isoforms in this process is not known. To determine if the PGR-B isoform participates in cervical remodeling at term, cervices were obtained from mice lacking PGR-B (PGR-BKO) and from wild-type (WT) controls before or after birth. PGR-BKO mice gave birth to viable pups at the same time as WT controls during the early morning of Day 19 postbreeding. Morphological analyses indicated that by the day before birth, cervices from PGR-BKO and WT mice had increased in size, with fewer cell nuclei/area as well as diminished collagen content and structure, as evidenced by optical density of picrosirius red-stained sections, compared to cervices from nonpregnant mice. Moreover, increased numbers of resident macrophages, but not neutrophils, were found in the prepartum cervix of PGR-BKO compared to nonpregnant mice, parallel to findings in WT mice. These results suggest that PGR-B does not contribute to the growth or degradation of the extracellular matrix or proinflammatory processes associated with recruitment of macrophages in the cervix leading up to birth. Rather, other receptors may contribute to the progesterone-dependent mechanism that promotes remodeling of the cervix during pregnancy and in the proinflammatory process associated with ripening before parturition. A progesterone-mediated receptor mechanism that does not involve the progesterone receptor-B isoform maintains pregnancy and regulates cervical remodeling and parturition.

Characterization of an animal model of pregnancy-induced vitamin D deficiency due to metabolic gene dysregulation

Vitamin D deficiency has been associated with pregnancy complications such as preeclampsia, gestational diabetes, and recurrent miscarriage. Therefore, we hypothesized differences in vitamin D status between healthy [Sprague-Dawley (SD) and Lewis (LW)] and complicated [Brown Norway (BN)] rat pregnancies. In SD, LW, and BN rats, we analyzed the maternal plasma levels of the vitamin D metabolites 25-OH-D and 1,25-(OH)2-D at prepregnancy, pregnancy, and postpartum. Analysis of the active metabolite 1,25-(OH)2-D showed a twofold increase in pregnant SD and LW rats but a nearly 10-fold decrease in pregnant BN rats compared with nonpregnant controls. BN rats had a pregnancy-dependent upregulation of CYP24a1 expression, a key enzyme that inactivates vitamin D metabolites. In contrast, the maternal renal expression of CYP24a1 in SD and LW rats remained constant throughout pregnancy. Analysis of the vitamin D receptor (VDR) indicated that LW and SD but not BN rats experience a pregnancy-induced 10-fold decrease in maternal renal VDR protein levels. Further analysis of bisulfite-converted and genomic DNA indicated that the observed differences in maternal renal regulation of CYP24a1 during pregnancy and lactation are not due to differences in CYP24a1 promoter methylation or single-nucleotide polymorphisms. Finally, supplementation with 1,25-(OH)2-D significantly improved the reproductive phenotype of BN rats by increasing litter size and maternal-fetal weight outcomes. We conclude that BN rats represent a novel animal model of pregnancy-specific vitamin D deficiency that is linked to pregnancy complications. Vitamin D deficiency in BN rats correlates with maternal renal CYP24a1 upregulation followed by CYP27b1 upregulation.

Peripartum and neonatal outcomes of small‐for‐gestational‐age infants with gastroschisis

Neonates with gastroschisis are often small for gestational age (SGA) based on population nomograms. Our objective was to evaluate the effect of SGA on perinatal and neonatal outcomes in cases of gastroschisis.

Quality Improvement Opportunities to Prevent Preterm Births

Quality improvement initiatives have been successfully employed in many areas of medicine, but few have been implemented in preventing prematurity (or preterm birth), which continues to be one of the most common complications in obstetrics, and the leading cause of perinatal morbidity and mortality in the United States. Due to the complex nature of the causes of prematurity, developing and instituting a quality improvement program to prevent prematurity can be challenging. However, using proven quality improvement principles and techniques, along with institutional will and commitment, are invaluable in rapidly implementing evidence-based initiatives for the prevention of preterm births.

Effect of antepartum meconium staining on perinatal and neonatal outcomes among pregnancies with gastroschisis

Abstract Objective: To investigate the association between meconium staining and perinatal and neonatal outcomes in pregnancies with gastroschisis. Methods: Retrospective analysis of infants with prenatally diagnosed gastroschisis born in two academic medical centers between 2008 and 2013. Neonatal outcomes of deliveries with and without meconium staining were compared. Primary outcome was defined as any of the following: neonatal sepsis, prolonged mechanical ventilation, bowel atresia or death. Secondary outcomes were preterm delivery, preterm-premature rupture of membranes (PPROM) and prolonged hospital length of stay. Results: One hundred and eight infants with gastroschisis were included of which 56 (52%) had meconium staining at delivery. Infants with meconium staining had a lower gestational age at delivery (36.3 (±1.4) versus 37.0 (±1.2) weeks, p = 0.007), and a higher rate of PPROM (25% versus 8%, p = 0.03) than infants without meconium. Meconium staining was not significantly associated with the primary composite outcome or with any of its components. After adjustments, meconium staining remained significantly associated with preterm delivery at <36 weeks [odds ratio OR = 4.0, 95% confidence intervals (CI): 1.5–11.4] and PPROM (OR = 3.8, 95%CI: 1.2–14.5). Conclusions: Among infants with gastroschisis, meconium staining was associated with prematurity and PPROM. No significant increase in other adverse neonatal outcomes was seen among infants with meconium staining, suggesting a limited prognostic value of this finding.

Pregnancy outcome in Swiss-Webster mice infected with Chlamydia trachomatis.

Objective: The objective of this study was to observe pregnancy outcomes in mice infected transvaginally with Chlamydia trachomatis. Methods: Pregnant mice were inoculated transvaginally with either C. trachomatis (CT) or sterile calf serum (CON) on pregnancy day 4. Pregnancy outcomes as well as genital tract histology and culture were compared. Statistical analysis was performed using Fishers exact test and Students t-test. Results: Twenty-four of 26 CT mice had positive uterine cultures for C. trachomatis. Inflammation occurred in 9 (34.6%) (P = 0.002, 95% confidence interval = 1.7–3.5) and intrauterine fetal demise occurred in 5 (19.2%) (P = 0.05, 95% confidence interval = 1.6–2.9) of CT mice. No mice in the CON group (0/24) had positive uterine cultures, developed inflammation, or experienced intrauterine fetal demise. Conclusions: Lower genital tract chlamydial infection is associated with intrauterine fetal demise in Swiss-Webster mice.

Utility of third trimester sonographic measurements for predicting SGA in cases of fetal gastroschisis

Objective:To assess the accuracy of different sonographic estimated fetal weight (EFW) cutoffs, and combinations of EFW and biometric measurements for predicting small for gestational age (SGA) in fetal gastroschisis.Study Design:Gastroschisis cases from two centers were included. The sensitivity, specificity, positive and negative predictive values (PPV and NPV) were calculated for different EFW cutoffs, as well as EFW and biometric measurement combinations.Results:Seventy gastroschisis cases were analyzed. An EFW<10% had 94% sensitivity, 43% specificity, 33% PPV and 96% NPV for SGA at delivery. Using an EFW cutoff of <5% improved the specificity to 63% and PPV to 41%, but decreased the sensitivity to 88%. Combining an abdominal circumference (AC) or femur length (FL) z-score less than −2 with the total EFW improved the specificity and PPV but decreased the sensitivity.Conclusion:A combination of a small AC or FL along with EFW increases the specificity and PPV, but decreases the sensitivity of predicting SGA.

Mumps, Measles, Rubella, and Roseola

Mumps is a contagious disease primarily of children and young adults. It is characterized by painful swelling of the parotid glands, but may involve several organs including the salivary glands, pancreas, meninges, and gonads.