Karen J. Gibbins

Maternal and fetal morbidity associated with uterine rupture of the unscarred uterus

OBJECTIVE We sought to report obstetric and neonatal characteristics and outcomes following primary uterine rupture in a large contemporary obstetric cohort and to compare outcomes between those with primary uterine rupture vs those with uterine rupture of a scarred uterus. STUDY DESIGN This was a retrospective case-control study. Cases were defined as women with uterine rupture of an unscarred uterus. Controls were women with uterine rupture of a scarred uterus. Demographics, labor characteristics, and obstetric, maternal, and neonatal outcomes were compared. Primary rupture case outcomes were also compared by mode of delivery. RESULTS There were 126 controls and 20 primary uterine rupture cases. Primary uterine rupture cases had more previous live births than controls (3.6 vs 1.9; P < .001). Cases were more likely to have received oxytocin augmentation (80% vs 37%; P < .001). Vaginal delivery was more common among cases (45% vs 9%; P < .001). Composite maternal morbidity was higher among primary uterine rupture mothers (65% vs 20%; P < .001). Cases had a higher mean estimated blood loss (2644 vs 981 mL; P < .001) and higher rate of blood transfusion (68% vs 17%; P < .001). Women with primary uterine rupture were more likely to undergo hysterectomy (35% vs 2.4%; P < .001). Rates of major composite adverse neonatal neurologic outcomes including intraventricular hemorrhage, periventricular leukomalacia, seizures, and death were higher in cases (40% vs 12%; P = .001). Primary uterine rupture cases delivering vaginally were more likely to ultimately undergo hysterectomy than those delivering by cesarean (63% vs 9%; P = .017). CONCLUSION Although rare, primary uterine rupture is particularly morbid. Clinicians must remain vigilant, particularly in the setting of heavy vaginal bleeding and severe pain.

Surgical treatments for vulvar and vaginal dysplasia: a randomized controlled trial.

OBJECTIVE: To compare pain, adverse effects and recurrence of dysplasia in patients with vaginal intraepithelial neoplasia or vulvar intraepithelial neoplasia prospectively treated by carbon dioxide laser or ultrasonic surgical aspiration. METHODS: Patients were randomly assigned to receive treatment by laser or ultrasonic surgical aspiration from 2000–2005. Preoperative biopsy was done to confirm presence of dysplasia. Patients completed a visual analog scale regarding pain and were evaluated at 2–4 weeks to assess scarring, wound healing, and adverse effects. Patients returned every 3 months for 1 year for pelvic examination and cytology to assess recurrence. Follow-up colposcopy and biopsy were used at the discretion of the treating physician. Student t test, &khgr;2, analysis of variance and multiple logistic regression were used for analysis. RESULTS: One hundred ten patients were randomly assigned. Ninety-six (87.3%) patients completed 1 year follow-up. Mean age of patients was 48.5 years. Mean visual analog scale score was significantly lower in patients treated by ultrasonic surgical aspiration (20.7 compared with 35.1; P=.032). For patients with vulvar lesions, there was less scarring with ultrasonic surgical aspiration (P<.01). Recurrence overall was 25% and was similar for ultrasonic surgical aspiration compared with laser (relative risk 0.96, 95% confidence interval 0.64–1.50, number needed to treat 95.6). Recurrence was associated with younger age (P<.01). CONCLUSION: Patients treated with ultrasonic surgical aspiration for vulvar and vaginal dysplasia reported less postoperative pain. Vulvar scarring was more common in patients treated by the laser. There was no difference in recurrence of dysplasia during a 1-year follow-up period between the two surgical modalities. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, www.clinicaltrials.gov, NCT00394758 LEVEL OF EVIDENCE: I

Evaluation of the clinical use of magnesium sulfate for cerebral palsy prevention.

OBJECTIVE: Clinical trials support the efficacy and safety of magnesium sulfate for cerebral palsy prevention. We evaluated the implementation of a clinical protocol for the use of magnesium for cerebral palsy prevention in our large womens hospital, focusing on uptake, indications, and safety. METHODS: We performed a review of selected gravidas with threatened or planned delivery before 32 weeks of gestation from October 2007 to February 2011. The primary study outcome was the change in the rate of predelivery administration of magnesium sulfate over this time period. RESULTS: Three hundred seventy-three patients were included. In 2007, before guideline implementation, 20% of eligible gravidas (95% confidence interval [CI] 9.1–35.6%) received magnesium before delivery compared with 93.9% (95% CI 79.8–99.3%) in the final 2 months of the study period (P<.001). Dosing did not vary significantly over the 4 study years: the median number of treatments was one, the total predelivery median dose ranged from 15 to 48 g, and the median duration of therapy ranged from 3 to 12 hours. After 3 years, magnesium administration was almost universal among patients diagnosed with preeclampsia, preterm labor, or preterm premature rupture of membranes (95.4%), whereas patients delivered preterm for fetal growth restriction were significantly less likely to receive predelivery magnesium (44%, P<.001). No maternal or perinatal magnesium-attributable morbidity was noted. Among patients eligible for the protocol who received magnesium, 84.2% delivered before 32 weeks of gestation. CONCLUSION: It is feasible to implement a magnesium sulfate cerebral palsy prevention protocol into clinical practice. LEVEL OF EVIDENCE: III

Magnesium Sulfate: Past, Present, and Future

First used anecdotally for the control of eclamptic seizures in the early 1900s, magnesium sulfate remains 1 of the most commonly used medications in obstetric practice today. Over the past 95 years, there have been countless research studies investigating the efficacy of magnesium sulfate for the management of eclampsia, preeclampsia, preterm labor, and most recently for prevention of cerebral palsy. The majority of this evidence undeniably supports the use of magnesium sulfate as the drug of choice for the prevention and treatment of eclampsia when evidence of severe disease is present. On the other hand, studies have not shown magnesium sulfate to be comparably more effective than other tocolytics for treating preterm labor, nor is there agreement on whether the evidence supports its use as a neuroprotective agent for prevention of cerebral palsy. The exact mechanism of action of magnesium sulfate remains largely hypothetical, and parenteral use has the potential to cause significant morbidity in high doses. This article reviews magnesium sulfates remarkable history in obstetric practice and includes a summary of the evidence related to each of the controversies. An initial review of the physiology of magnesium sulfate is essential to understanding pharmacodynamic actions, dosing guidelines, and safety requirements.

Diagnostic Tests for Evaluation of Stillbirth: Results From the Stillbirth Collaborative Research Network

OBJECTIVE To estimate the usefulness of each diagnostic test in the work-up for potential causes of stillbirth. METHODS A secondary analysis of 512 stillbirths enrolled in the Stillbirth Collaborative Research Network from 2006 to 2008 was performed. The Stillbirth Collaborative Research Network was a multisite, geographically, racially, and ethnically diverse, population-based study of stillbirth in the United States. Participants underwent standardized evaluations that included maternal interview, medical record abstraction, biospecimen collection, fetal autopsy, and placental pathology. Also, most participants had a clinical work-up that included karyotype, toxicology screen, syphilis serology, antibody screen, fetal-maternal hemorrhage testing, and testing for antiphospholipid antibodies as well as testing performed on biospecimens for research purposes. Previously, each participant had been assigned probable and possible causes of death using the Initial Causes of Fetal Death classification system. In this analysis, tests were considered useful if a positive result established (or helped to establish) this cause of death or a negative result excluded a cause of death that was suspected based on the clinical history or other results. RESULTS The usefulness of each test was as follows: placental pathology 64.6% (95% confidence interval [CI] 57.9-72.0), fetal autopsy 42.4% (95% CI 36.9-48.4), genetic testing 11.9% (95% CI 9.1-15.3), testing for antiphospholipid antibodies 11.1% (95% CI 8.4-14.4), fetal-maternal hemorrhage 6.4% (95% CI 4.4-9.1), glucose screen 1.6% (95% CI 0.7-3.1), parvovirus 0.4% (95% CI 0.0-1.4), and syphilis 0.2% (95% CI 0.0-1.1). The utility of the tests varied by clinical presentation, suggesting a customized approach for each patient. CONCLUSION The most useful tests were placental pathology and fetal autopsy followed by genetic testing and testing for antiphospholipid antibodies.OBJECTIVE To estimate the usefulness of each diagnostic test in the work-up for potential causes of stillbirth. METHODS A secondary analysis of 512 stillbirths enrolled in the Stillbirth Collaborative Research Network from 2006 to 2008 was performed. The Stillbirth Collaborative Research Network was a multisite, geographically, racially, and ethnically diverse, population-based study of stillbirth in the United States. Participants underwent standardized evaluations that included maternal interview, medical record abstraction, biospecimen collection, fetal autopsy, and placental pathology. Also, most participants had a clinical work-up that included karyotype, toxicology screen, syphilis serology, antibody screen, fetal-maternal hemorrhage testing, and testing for antiphospholipid antibodies as well as testing performed on biospecimens for research purposes. Previously, each participant had been assigned probable and possible causes of death using the Initial Causes of Fetal Death classification system. In this analysis, tests were considered useful if a positive result established (or helped to establish) this cause of death or a negative result excluded a cause of death that was suspected based on the clinical history or other results. RESULTS The usefulness of each test was as follows: placental pathology 64.6% (95% confidence interval [CI] 57.9-72.0), fetal autopsy 42.4% (95% CI 36.9-48.4), genetic testing 11.9% (95% CI 9.1-15.3), testing for antiphospholipid antibodies 11.1% (95% CI 8.4-14.4), fetal-maternal hemorrhage 6.4% (95% CI 4.4-9.1), glucose screen 1.6% (95% CI 0.7-3.1), parvovirus 0.4% (95% CI 0.0-1.4), and syphilis 0.2% (95% CI 0.0-1.1). The utility of the tests varied by clinical presentation, suggesting a customized approach for each patient. CONCLUSION The most useful tests were placental pathology and fetal autopsy followed by genetic testing and testing for antiphospholipid antibodies.

Magnesium sulfate for cerebral palsy prevention.

Magnesium sulfate (MgSO4) has been shown to prevent cerebral palsy among children born to women at high risk of early preterm delivery. Three large, randomized placebo-controlled trials and a subsequent Cochrane Review suggest this intervention can decrease rates of cerebral palsy by 32% with a number needed to treat of 63 to prevent one case. Not only is MgSO4 familiar to obstetricians, it also has an excellent safety profile. Simple protocols exist to help guide clinicians in using MgSO4 for this indication. Evaluation of actual clinical practice shows that this use is both feasible and can be accomplished parsimoniously.

Pregnancy complications in spontaneous and assisted conceptions of women with infertility and subfertility factors. A comprehensive review

In the literature, there is growing evidence that assisted reproductive techniques increase the risk of pregnancy complications in subfertile couples. Moreover, many concomitant preconception risk factors for subfertility are frequently present in the same subject and increase the risk of pregnancy complications. This review aimed to summarize in a systematic fashion the best current evidence regarding the effects of preconception maternal factors on maternal and neonatal outcomes. A literature search up to March 2016 was performed in IBSS, SocINDEX, Institute for Scientific Information, PubMed, Web of Science and Google Scholar. An evidence-based hierarchy was used to determine which articles to include and analyse. Available data show that the risk of pregnancy complications in spontaneous and assisted conceptions is likely multifactorial, and the magnitude of this risk is probably very different according specific subgroups of patients. Notwithstanding the only moderate level and quality of the available evidence, available data suggest that the presence and the treatment of specific preconception cofactors of subfertility should be always taken into account both in clinical practice and for scientific purposes.

Placenta previa and maternal hemorrhagic morbidity

Abstract Objective: Placenta previa is associated with maternal hemorrhage, but most literature focuses on morbidity in the setting of placenta accreta. We aim to characterize maternal morbidity associated with previa and to define risk factors for hemorrhage. Methods: This is a secondary cohort analysis of the NICHD Maternal–Fetal Medicine Units Network Cesarean Section Registry. This analysis included all women undergoing primary Cesarean delivery without placenta accreta. About 496 women with previa were compared with 24,201 women without previa. Primary outcome was composite maternal hemorrhagic morbidity. Non-hemorrhagic morbidities and risk factors for hemorrhage were also evaluated. Results: Maternal hemorrhagic morbidity was more common in women with previa (19 versus 7%, aRR 2.6, 95% CI 1.9–3.5). Atony requiring uterotonics (aRR 3.1, 95% CI 2.0–4.9), red blood cell transfusion (aRR 3.8, 95% CI 2.5–5.7), and hysterectomy (aRR 5.1, 95% CI 1.5–17.3) were also more common with previa. For women with previa, factors associated with maternal hemorrhage were pre-delivery anemia, thrombocytopenia, diabetes, magnesium use, and general anesthesia. Conclusion: Placenta previa is an independent risk factor for maternal hemorrhagic morbidity. Some risk factors are modifiable, but many are intrinsic to the clinical scenario.

Stillbirth, hypertensive disorders of pregnancy, and placental pathology

INTRODUCTION Stillbirth, preeclampsia, and gestational hypertension (PE/GH) have similar clinical risk factors and redundant placental pathology. We aim to discern if stillbirth with PE/GH has a particular phenotype by comparing stillbirths with and without PE/GH. METHODS Secondary analysis of the Stillbirth Collaborative Research Network, a population-based cohort study of all stillbirths and a sample of live births from 2006 to 2008 in five catchment areas. We compared placental pathology between stillbirths and with and without PE/GH, stratified by term or preterm. We also compared placental pathology between stillbirths and live births with PE/GH. RESULTS 79/518 stillbirths and 140/1200 live births had PE/GH. Amongst preterm stillbirths, there was higher feto-placental ratio in PE/GH pregnancies (OR 1.24 [1.11, 1.37] per unit increase), and there were more parenchymal infarctions (OR 5.77 [3.18, 10.47]). Among PE/GH pregnancies, stillbirths had increased maternal and fetal vascular lesions, including retroplacental hematoma, parenchymal infarction, fibrin deposition, fetal vascular thrombi, and avascular villi. DISCUSSION Stillbirth pregnancies are overwhelmingly associated with placental lesions. Parenchymal infarctions are more common in PE/GH preterm stillbirths, but there is significant overlap in lesions found in stillbirths and PE/GH.

Pre-eclampsia as a manifestation of antiphospholipid syndrome: assessing the current status.

The presence of antiphospholipid antibodies is considered a risk factor for pre-eclampsia. Two meta-analyses and a number of case-control and cohort studies have found associations between pre-eclampsia and lupus anticoagulant, anticardiolipin, and/or anti-β2 glycoprotein I. However, existing literature is inconsistent, with varying severity of pre-eclampsia phenotype examined, differing aPL titer cutoffs used to define positive status, and an overwhelming lack of repeat confirmatory aPL testing. This calls into question the link between aPLs and pre-eclampsia, or at least makes it less well defined. There is evidence for a mechanistic pathway between aPLs and adverse pregnancy outcomes (APOs) including pre-eclampsia via the complement pathway. Complement appears to be overactive in pregnancies affected by APOs. A mouse model has show that the fetal wastage caused by treatment with human aPLs can be salvaged by either creating genetic knockouts along the complement, TNF-alpha, and tissue factor pathways or be treating mice with monoclonal antibodies blocking key complement factors. Thus, this is worth further investigation to clarify the likely association of aPLs and pre-eclampsia in humans, as well is to further evaluate the interaction with complement in human pregnancies.