Safety of deep sedation without intubation during surgical abortion in the independent clinic setting.

OBJECTIVE: To establish the safety of deep sedation without intubation delivered by a certified registered nurse anesthetist (CRNA) in an independent outpatient abortion setting. STUDY DESIGN: We performed a review of clinic Quality and Patient Safety Reports, a daily-maintained report of complications at time of all dilation and curettage (D&C) and dilation and evacuation (D&E) procedures performed at an independently operated, urban, high-volume abortion clinic between March 2013 and August 2017. The clinic provided procedures through 23 weeks 6 days gestation to women at low risk for medical or surgical complications, referring high-risk procedures to a nearby hospital. A CRNA provided anesthesia for all deep sedation procedures. We extracted information on gestational age, risk factors, and clinical course for all patients who experienced any anesthesia-related complication. RESULTS: During the study period, the clinic evaluated 10,297 women for surgical abortion, referring 292 high-risk cases and performing 10,005 procedures (9004 D&C and 1001 D&E), most (9405 [94%]) with deep sedation. We documented six anesthesia-related complications; three (0.03%) in D&C procedures (laryngospasm not requiring intubation [n = 2] and respiratory stridor) and three (0.30%) in D&E procedures (laryngospasm requiring intubation, seizure, and hypotension/bradycardia). Only one patient (0.01%) required intubation. CONCLUSIONS: Anesthesia-related complications in the setting of deep sedation without intubation during surgical abortion were exceedingly rare, supporting the safety of this form of anesthesia for low-risk patients in an independent community clinic setting. IMPLICATIONS: Independent community clinics, where the majority of abortion procedures are performed within the U.S., can provide safe anesthesia care using deep sedation provided by CRNA professionals. This care delivery model, which includes triaging patient eligibility, reassuringly provides anesthesia as safely as other greater resourced care delivery settings.

Demographic, Clinical, and Counseling Factors Associated with the Selection of Pregnancy Termination Method in the Second Trimester for Fetal and Pregnancy Anomalies.

OBJECTIVE: Despite women's preference for induction of labor (IOL) or dilation and evacuation (D&E) for pregnancy termination in the setting of second trimester fetal or pregnancy abnormality, many women are not given a choice between delivery methods. We investigated patient and clinical related factors associated with selecting IOL or D&E. METHODS: This retrospective cohort experienced pregnancy termination at 17-24 weeks of gestation for fetal anomaly, intrauterine fetal demise, or premature previable rupture. We compared the demographic, reproductive, social, and clinical experience variables between women who select IOL and D&E, adjusting for confounders through logistic regression. RESULTS: One hundred eleven women (21.6%) selected IOL and 403 (78.4%) selected D&E. Greater proportions of women of color (p < .01), lower education (p < .01), lower employment (p < .01), and lower status jobs (p < .01) selected IOL. Women selected D&E more often for chromosomal anomaly (p < .01). In adjusted analyses, women with intrauterine fetal demise (odds ratio [OR], 9.8; 95% confidence interval [CI], 2.8-34.7), premature previable rupture (OR, 110; 95% CI, 23.0-526.8), prior substance use disorder (OR, 35.5; 95% CI-2.7, 473.7), or counseling from obstetrics (OR, 3.3; 95% CI-1.3, 8.4), pediatrics (OR, 3.3; 95% CI-1.3, 8.6), or social services (OR, 12.6; 95% CI, 4.2-37.3) had higher odds of selecting IOL. CONCLUSIONS: Patient characteristics, medical factors, and type of counseling are associated with the selection between D&E and IOL for anomalous pregnancies. Institutional, regional, and state policies should permit women both delivery methods to preserve autonomous decision-making at the time of pregnancy termination.

Global hypermethylation in fetal cortex of Down syndrome due to DNMT3L overexpression.

Down syndrome (DS) is caused by a triplication of chromosome 21 (HSA21). Increased oxidative stress, decreased neurogenesis and synaptic dysfunction from HSA21 gene overexpression are thought to cause mental retardation, dementia and seizure in this disorder. Recent epigenetic studies have raised the possibility that DNA methylation has significant effects on DS neurodevelopment. Here, we performed methylome profiling in normal and DS fetal cortices and observed a significant hypermethylation in ∼4% of probes in the DS samples compared with age-matched normals. The probes with differential methylation were distributed across all chromosomes, with no enrichment on HSA21. Functional annotation and pathway analyses showed that genes in the ubiquitination pathway were significantly altered, including: BRCA1, TSPYL5 and PEX10 HSA21 located DNMT3L was overexpressed in DS neuroprogenitors, and this overexpression increased the promoter methylation of TSPYL5 potentially through DNMT3B, and decreased its mRNA expression. DNMT3L overexpression also increased mRNA levels for TP53 and APP, effectors of TSPYL5 Furthermore, DNMT3L overexpression increased APP and PSD95 expression in differentiating neurons, whereas DNMT3LshRNA could partially rescue the APP and PSD95 up-regulation in DS cells. These results provide some of the first mechanistic insights into causes for epigenetic changes in DS, leading to modification of genes relevant for the DS neural endophenotype.

OLIG2 over-expression impairs proliferation of human Down syndrome neural progenitors.

Mental retardation and early Alzheimer's disease (AD) have generally been attributed to progressive neuronal loss in the developing and mature Down syndrome (DS) brain. However, reduced neuronal production during development could also contribute to the smaller brain size and simplified gyral patterning seen in this disorder. Here, we show impairments in proliferation within the ventricular zone (VZ) of early DS fetal cortex and in cultured early passage DS human neural progenitors (HNPs). We find that the reduced proliferative rates correspond temporally with increased expression of the chromosome 21 (HSA21) associated, oligodendrocyte transcription factor OLIG2 at 14-18 weeks gestational age (GA) (period of neurogenesis). Moreover, the DS HNPs adopt more oligodendrocyte-specific features including increased oligodendrocyte marker expression, as well as a reduction in KCNA3 potassium channel expression and function. We further show that OLIG2 inhibition or over-expression regulates potassium channel expression levels and that activation or inhibition of these channels influences the rate of progenitor proliferation. Finally, neural progenitors from Olig2 over-expressing transgenic mice exhibit these same impairments in proliferation and potassium channel expression. These findings suggest that OLIG2 over-expression inhibits neural progenitor proliferation through changes in potassium channel activity, thereby contributing to the reduced neuronal numbers and brain size in DS.

S100B and APP promote a gliocentric shift and impaired neurogenesis in Down syndrome neural progenitors.

Down syndrome (DS) is a developmental disorder associated with mental retardation (MR) and early onset Alzheimer's disease (AD). These CNS phenotypes are attributed to ongoing neuronal degeneration due to constitutive overexpression of chromosome 21 (HSA21) genes. We have previously shown that HSA21 associated S100B contributes to oxidative stress and apoptosis in DS human neural progenitors (HNPs). Here we show that DS HNPs isolated from fetal frontal cortex demonstrate not only disturbances in redox states within the mitochondria and increased levels of progenitor cell death but also transition to more gliocentric progenitor phenotypes with a consequent reduction in neuronogenesis. HSA21 associated S100B and amyloid precursor protein (APP) levels are simultaneously increased within DS HNPs, their secretions are synergistically enhanced in a paracrine fashion, and overexpressions of these proteins disrupt mitochondrial membrane potentials and redox states. HNPs show greater susceptibility to these proteins as compared to neurons, leading to cell death. Ongoing inflammation through APP and S100B overexpression further promotes a gliocentric HNPs phenotype. Thus, the loss in neuronal numbers seen in DS is not merely due to increased HNPs cell death and neurodegeneration, but also a fundamental gliocentric shift in the progenitor pool that impairs neuronal production.

Generation of neural stem cells from discarded human fetal cortical tissue.

Neural stem cells (NSCs) reside along the ventricular zone neuroepithelium during the development of the cortical plate. These early progenitors ultimately give rise to intermediate progenitors and later, the various neuronal and glial cell subtypes that form the cerebral cortex. The capacity to generate and expand human NSCs (so called neurospheres) from discarded normal fetal tissue provides a means with which to directly study the functional aspects of normal human NSC development. This approach can also be directed toward the generation of NSCs from known neurological disorders, thereby affording the opportunity to identify disease processes that alter progenitor proliferation, migration and differentiation. We have focused on identifying pathological mechanisms in human Down syndrome NSCs that might contribute to the accelerated Alzheimer's disease phenotype. Neither in vivo nor in vitro mouse models can replicate the identical repertoire of genes located on human chromosome 21. Here we use a simple and reliable method to isolate Down syndrome NSCs from aborted human fetal cortices and grow them in culture. The methodology provides specific aspects of harvesting the tissue, dissection with limited anatomical landmarks, cell sorting, plating and passaging of human NSCs. We also provide some basic protocols for inducing differentiation of human NSCs into more selective cell subtypes.

Uterine evacuation for second-trimester fetal death and maternal morbidity.

OBJECTIVE: To estimate maternal morbidity associated with uterine evacuation for second-trimester fetal demise compared with that associated with induced second-trimester abortion. METHODS: This retrospective cohort study compared the maternal outcomes of two cohorts: 1) women diagnosed with fetal demise between 14 and 24 weeks who subsequently underwent dilation and evacuation or induction of labor; and 2) women undergoing induced abortion between 14 and 24 weeks by either dilation and evacuation or induction of labor. The primary outcome was major maternal morbidity. Assuming morbidity rates of 11% for fetal demise and 1% for induced second-trimester abortion, 94 patients were needed per group to detect significant difference in maternal morbidity (80% power, 5% alpha). RESULTS: We identified 121 women with fetal demise and 121 women who underwent induced abortion for inclusion. There were no maternal deaths. In crude and adjusted analyses, treatment for fetal demise was not associated with increased maternal morbidity (25 of 121) compared with induced abortion (27 of 121) (adjusted odds ratio [OR], 1.15; 95% confidence interval [CI], 0.57-2.32). There were more blood transfusions in the fetal demise group (N=7) compared with the induced-abortion group (N=1) (P=.07). Induction of labor was more morbid than dilation and evacuation after adjusting for confounders (OR 5.36; 95% CI 2.46-11.69), primarily as a result of increased odds of infection requiring intravenous antibiotics. Gestational age of 20 weeks or greater was significantly associated with maternal morbidity (OR 2.59; 95% CI 1.39-4.84). CONCLUSION: In the second trimester, uterine evacuation for fetal demise was not significantly associated with maternal morbidity compared with induced abortion. Induction of labor was more morbid than dilation and evacuation as a result of an increased risk of presumed infection. LEVEL OF EVIDENCE: II.

Uterine artery embolization to treat hemorrhage following second-trimester abortion by dilatation and surgical evacuation.

BACKGROUND: This study was conducted to review cases of second-trimester postabortal hemorrhage (PAH) occurring at a private women's health facility that were treated with uterine artery embolization (UAE). METHODS: A retrospective review was conducted on all second-trimester terminations performed at a private women's health facility between 1999 and 2006. Cases of PAH treated with UAE were reviewed in detail, reviewing progress, operative and discharge notes along with anesthesia records. RESULTS: Fifteen cases of PAH were identified among 3936 second-trimester terminations that were performed. Seven cases were identified in which UAE was used to treat PAH. Etiologies leading to hemorrhage varied in the seven cases as did the presence of coexisting factors such as infection and anatomic lesions. All cases were successfully treated by UAE, requiring no additional surgical intervention. CONCLUSION: Given the success of embolization, we offer this as an alternative to exploratory surgery and hysterectomy and as a first-line approach in cases of PAH after conservative management strategies have failed.

Changes in abortion provider practices in response to the Partial-Birth Abortion Ban Act of 2003.

BACKGROUND: The April 2007 Supreme Court Gonzalez v. Gonzalez v. Carhart decision upheld the Partial-Birth Abortion Ban Act of 2003. We conducted a pilot study that measured the impact of the ban in one state with a diverse pool of second-trimester abortion providers. STUDY DESIGN: A survey was administered via telephone to key informants at each facility in Massachusetts where second-trimester abortions are performed in order to assess clinical and administrative changes following the Supreme Court decision. RESULTS: Five hospital-based practices introduced injections to induce fetal demise prior to dilation and evacuation for later second-trimester abortions. One site stopped providing dilation and evacuation abortions in the absence of fetal or maternal indications, and another significantly decreased its volume of procedures. Training opportunities were decreased, and costs at three facilities increased. CONCLUSIONS: The Partial-Birth Abortion Ban Act of 2003 resulted in a range of practice changes in Massachusetts, particularly in hospitals. These changes reflect adherence to legal and policy mandates and not the availability of new scientific evidence. Further study to assess the impact of the ban in states with fewer providers is warranted.

Emergency contraception knowledge after a community education campaign.

BACKGROUND: This study evaluates the effectiveness of a community education campaign in the Boston community of Jamaica Plain conducted by the Massachusetts Emergency Contraception (EC) Network aimed at improving public knowledge of EC. STUDY DESIGN: Pre- and postintervention surveys of reproductive-age women were conducted to evaluate the effectiveness of the community education campaign. Knowledge of EC was compared before and after the intervention using surveys of community-based samples of women. RESULTS: One hundred eighty-eight and 290 women participated in the preintervention and postintervention surveys, respectively. Following the intervention, women were significantly more likely to have heard of EC (91% vs. 82%, p=.007), know the mechanism of action of EC (49% vs. 39%, p=.04), have discussed EC with a health care provider (38% vs. 25%, p=.003) and have received an advance prescription for EC (22% vs. 12%, p=.004), as well as were more likely to use EC in the future if needed (79% vs. 63%, p=.0002). CONCLUSION: This grassroots-based community education campaign on EC was effective in improving EC knowledge in this Boston community.