Vascular dimorphism ensured by regulated proteoglycan dynamics favors rapid umbilical artery closure at birth.

The umbilical artery lumen closes rapidly at birth, preventing neonatal blood loss, whereas the umbilical vein remains patent longer. Here, analysis of umbilical cords from humans and other mammals identified differential arterial-venous proteoglycan dynamics as a determinant of these contrasting vascular responses. The umbilical artery, but not the vein, has an inner layer enriched in the hydrated proteoglycan aggrecan, external to which lie contraction-primed smooth muscle cells (SMC). At birth, SMC contraction drives inner layer buckling and centripetal displacement to occlude the arterial lumen, a mechanism revealed by biomechanical observations and confirmed by computational analyses. This vascular dimorphism arises from spatially regulated proteoglycan expression and breakdown. Mice lacking aggrecan or the metalloprotease ADAMTS1, which degrades proteoglycans, demonstrate their opposing roles in umbilical vascular dimorphism, including effects on SMC differentiation. Umbilical vessel dimorphism is conserved in mammals, suggesting that differential proteoglycan dynamics and inner layer buckling were positively selected during evolution.

Development of an outpatient clinic to provide pertussis vaccinations to maternity patients and family members.

PURPOSE: The implementation of a hospital-based outpatient pertussis prevention program targeting maternity patients and family members is described. SUMMARY: Faced with a rising incidence of pertussis statewide, a large Ohio hospital formed a multidisciplinary team to ensure hospital compliance with current guidelines calling for administration of the tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis (Tdap) vaccine to all maternity patients as well as previously unvaccinated family members and likely neonatal caregivers (i.e., "cocooning"). The team had regularly scheduled meetings to identify and address fiscal, logistic, and practice-related challenges throughout the implementation process. Key challenges included (1) determining the availability of insurance reimbursement for Tdap vaccination services, (2) cultivating support for the vaccination initiative among obstetrics and maternal-fetal medicine specialists, (3) coordinating development and dissemination of educational information to patients and their families at specified points of contact, and (4) establishing an efficient registration process for family members. The outpatient vaccination clinic was located adjacent to the hospital's maternity center in order to provide convenient access. Despite limited clinic hours (three hours daily on weekdays only) and ongoing reimbursement and funding challenges, the program has improved Tdap vaccination rates in the target population and is considered a successful demonstration of the cocooning concept. CONCLUSION: Implementation of an outpatient clinic for neonatal pertussis prevention was well accepted by family members of newborns, and Tdap vaccinations were administered to 329 family members during the first 11 months of clinic operations.

Progesterone inhibits in vitro fetal membrane weakening.

OBJECTIVE: Inflammation/infection and abruption are leading causes of preterm premature rupture of the membranes. Recently, we identified granulocyte-macrophage colony-stimulating factor (GM-CSF) as a critical mediator of both tumor necrosis factor-α- (TNF; modeling inflammation) and thrombin-induced (modeling abruption) weakening of the fetal membranes. We found that (1) TNF and thrombin both induced GM-CSF in the choriodecidua, (2) blockade of GM-CSF action with neutralizing antibodies inhibited both TNF- and thrombin-induced fetal membrane weakening, and (3) GM-CSF alone induced fetal membrane weakening. GM-CSF is thus part of an overlap of the inflammation and abruption-induced fetal membrane weakening pathways. The effects of progesterone analogs on the pathways by which fetal membranes are weakened have not been investigated. We examined the effects of progesterone, medroxyprogesterone acetate (MPA) and 17α-hydroxyprogesterone (HP) on TNF- and thrombin-induced fetal membrane weakening. STUDY DESIGN: Full-thickness fetal membranes from uncomplicated term repeat cesarean deliveries were mounted in Transwell inserts in Minimum Essential Medium alpha and incubated at 37°C in 5% CO2. The choriodecidua side of the fetal membrane fragments were preincubated with progesterone, MPA, HP, or vehicle for 24 hours. Fetal membranes were then exposed to TNF, thrombin, or GM-CSF on the choriodecidua side for an additional 48 hours. The fetal membrane tissues were then strength tested, and medium from the choriodecidua and amnion compartments was assayed for GM-CSF content. RESULTS: TNF and thrombin both weakened fetal membranes and elevated media GM-CSF levels on the choriodecidua side of the fetal membrane. Pretreatment with progesterone, MPA, or HP inhibited both TNF- and thrombin-induced fetal membrane weakening and also inhibited the induced increase in GM-CSF. GM-CSF decreased fetal membrane rupture strength by 68%, which was inhibited by progestogen pretreatment with a potency order: progesterone

A first look at women's perspectives on noninvasive prenatal testing to detect sex chromosome aneuploidies and microdeletion syndromes.

OBJECTIVE: The aim of this study is to explore women's opinions about the use of noninvasive prenatal testing (NIPT) to assess the risk of sex chromosome aneuploidies and microdeletion syndromes. METHODS: Focus groups were conducted with women who were currently pregnant or had recently delivered. Qualitative analysis using interpretive description was used to generate study findings. RESULTS: Thirty-one women (mean age 32.4 years) participated in the focus groups. Participants were unfamiliar with sex chromosome aneuploidies but expressed support for the use of NIPT to detect these conditions. Participants were uncertain about the utility and actionability of receiving information about microdeletion syndromes with variable or unknown phenotypic expression. Participants voiced their desire to be informed of all conditions assessed by NIPT prior to testing. They considered clinicians to be the key provider of such information, although stated that patients have a responsibility to be knowledgeable prior to testing in order to support informed decision making. CONCLUSIONS: The use of NIPT to identify sex chromosome aneuploidies and microdeletion syndromes will introduce new challenges for clinicians to ensure pregnant women have the information and resources to make informed choices about NIPT when used for these conditions.

It's More Than a Blood Test: Patients' Perspectives on Noninvasive Prenatal Testing.

Noninvasive prenatal testing (NIPT) offers pregnant women a new risk assessment tool for fetal aneuploidy that is superior to conventional screening tests. We conducted focus groups with women who were currently pregnant or had recently delivered in the past year to characterize their perspectives about NIPT and to explore factors they would consider during decision making about its use. Women identified accuracy, early timing, testing ease, and determination of fetal sex as advantages of NIPT over other screens, and the noninvasive method of NIPT as an advantage over diagnostic tests. False positive and false negative results, anxiety, cost and insurance coverage were seen as disadvantages of NIPT. Women who do not want fetal aneuploidy information most likely will not undergo NIPT, despite its advantages over other screening tests. However, given its advantages, the decision to have NIPT is straightforward for women who want genetic information about the fetus. Women emphasized the need to make autonomous, private, and informed choices about NIPT, as they would with any prenatal genetic testing option. These perspectives may guide clinicians to conduct effective and clinically relevant counseling with pregnant women who consider utilizing this new genetic technology.

First-trimester and second-trimester screening at a community hospital: experience from the first year of implementation.

OBJECTIVE: To review the first-year experience implementing a new early screening during pregnancy program for aneuploidy in a community hospital and compare this program with the screening program immediately preceding its implementation. METHODS: The electronic medical records of all pregnant patients referred from May 17, 2005, through December 31, 2006, for genetic counseling were reviewed for maternal characteristics, indication for referral, a priori and adjusted risk of aneuploidy, and patient choice for screening or testing. The new early screening program (nuchal translucency group) consisted of additional educational materials, nuchal translucency, serum biochemical analytes, quad screening, and invasive testing when indicated. This cohort was compared with the patients who received traditional genetic screening or testing (pre-nuchal translucency) immediately preceding the nuchal translucency program. RESULTS: A total of 101 patients were included in the pre-nuchal translucency group compared with 359 patients in the nuchal translucency group. The most common reason for referral was advanced maternal age; there were no differences in the maternal characteristics between the two groups. Forty-six percent of patients in the early screening program underwent an invasive procedure compared with 76% in the pre-nuchal translucency group (odds ratio 0.26, 95% confidence interval 0.15-0.42; P<.001). CONCLUSION: Early screening programs in a single community hospital are feasible and appear to result in a significant reduction in the number of invasive procedures with excellent patient satisfaction and acceptance.

Management of group B Streptococcus in pregnant women with penicillin allergy.

OBJECTIVE: To determine whether group B Streptococcus (GBS)-colonized pregnant women who report a history of penicillin allergy can safely undergo diagnostic evaluation to rule out or confirm the potential for an IgE-mediated (allergic) reaction to penicillin. STUDY DESIGN: Over 18 months, all pregnant women with GBS-positive vaginal/rectal cultures and a history of penicillin allergy were referred to the Department of Allergy and Immunology for a history and possible skin testing. Patients who had experienced anaphylaxis were advised to continue avoiding penicillin and were not skin tested. Women without such a history underwent immediate hypersensitivity (percutaneous and intradermal) testing using 2 penicillin reagents with controls. If skin testing was negative, intrapartum antimicrobial prophylaxis with intravenous penicillin was administered. RESULTS: Of 28 patients with both GBS colonization and "penicillin allergy," 25 (89%) had negative skin testing to penicillin and received intrapartum penicillin for GBS prophylaxis without adverse reactions. Skin testing was positive in 2 patients, and intrapartum penicillin was not administered. Penicillin skin testing was not performed on 1 patient due to a history of anaphylaxis from penicillin. CONCLUSION: These results indicate that most pregnant women reporting penicillin allergy undergo negative skin tests and are able to safely receive intrapartum penicillin GBS prophylaxis.

Vaginal delivery after ileal pouch-anal anastomosis: a word of caution.

PURPOSE: This study was designed to evaluate the impact of childbirth on anal sphincter integrity and function, functional outcome, and quality of life in females with restorative proctocolectomy and ileal pouch-anal anastomosis. METHODS: The patients who had at least one live birth after ileal pouch-anal anastomosis were asked to return for a comprehensive assessment. They were asked to complete the following questionnaires: the Short Form-36, Cleveland Global Quality of Life scale, American Society of Colorectal Surgeons fecal incontinence severity index, and time trade-off method. Additionally, anal sphincter integrity (endosonography) and manometric pressures were measured by a medical physician blinded to the delivery technique. Anal sphincter physiology also was evaluated with electromyography and pudendal nerve function by nerve terminal motor latency technique. RESULTS: Of 110 eligible females who had at least one live birth after ileal pouch-anal anastomosis, 57 participated in the study by returning for clinical evaluation to the clinic and 25 others by returning the quality of life and functional outcome questionnaires. Patients were classified into two groups: patients who had only cesarean section delivery after ileal pouch-anal anastomosis (n = 62) and patients who had at least one vaginal delivery after ileal pouch-anal anastomosis (n = 20). The mean follow-up from the date of the most recent delivery was 4.9 years. The vaginal delivery group had significantly higher incidence of an anterior sphincter defect by anal endosonography (50 percent) vs. cesarean section delivery group (13 percent; P = 0.012). The mean squeeze anal pressure was significantly higher in the patients who had only cesarean section delivery (150 mmHg) after restorative proctocolectomy than patients who had at least one vaginal delivery (120 mmHg) after restorative proctocolectomy (P = 0.049). Quality of life evaluated by time trade-off method also was significantly better in the cesarean section delivery group (1) vs. vaginal delivery group (0.9; P < 0.001). CONCLUSIONS: The risk of the sphincter injury and quality of life measured by time trade-off method are significantly worse after vaginal delivery compared with cesarean section in patients with ileal pouch-anal anastomosis. In the short-term, this does not seem to substantially influence pouch function or quality of life; however, the long-term effects remain unknown, thus obstetric concern may not be the only factor dictating the type of delivery in this group of patients. A planned cesarean section may eliminate these potential and factual concerns in ileal pouch-anal anastomosis patients.