Expectant management of preeclampsia with severe features diagnosed at less than 24 weeks.

BACKGROUND: The recent American College of Obstetricians and Gynecologists Practice Bulletin offers no guidance on the management of preeclampsia with severe features at <24 weeks of gestation. Historically, immediate delivery was recommended because of poor perinatal outcomes and high maternal morbidity. Recently, advances in neonatal resuscitation have led to increased survival at periviable gestational ages. OBJECTIVE: This study aimed to report perinatal and maternal outcomes after expectant management of preeclampsia with severe features at <24 weeks of gestation. STUDY DESIGN: This was a retrospective case series of preeclampsia with severe features at <24 weeks of gestation at a level 4 center between 2017 and 2023. Individuals requiring delivery within 24 hours of diagnosis were excluded. Perinatal and maternal outcomes were analyzed. Categorical variables from our database were compared with previously published data using chi-square tests. RESULTS: A total of 41 individuals were diagnosed with preeclampsia with severe features at <24 weeks of gestation. After the exclusion of delivery within 24 hours, 30 individuals (73%) were evaluated. The median gestational age at diagnosis was 22 weeks (interquartile range, 22-23). Moreover, 16% of individuals had assisted reproductive technology, 27% of individuals had chronic hypertension, 13% of individuals had pregestational diabetes mellitus, 30% of individuals had previous preeclampsia, and 73% of individuals had a body mass index of >30 kg/m2. The median latency periods at 22 and 23 weeks of gestation were 7 days (interquartile range, 4-23) and 8 days (interquartile range, 4-13). In preeclampsia with severe features, neonatal survival rates were 44% (95% confidence interval, 3%-85%) at 22 weeks of gestation and 29% (95% confidence interval, 1%-56%) at 23 weeks of gestation. There were 2 cases of acute kidney injury (7%) and 2 cases of pericardial or pleural effusions (7%). Overall perinatal survival at <24 weeks of gestation was 30% in our current study vs 7% in previous reports (P=.02). CONCLUSION: For cases of expectant management of preeclampsia with severe features at <24 weeks of gestation, our findings showed an increased perinatal survival rate with decreased maternal morbidity compared with previously published data. This information may be used when counseling on expectant management of preeclampsia with severe features at <24 weeks of gestation.

Implementing a Bundle for Evidence-based Cesarean Delivery May Not Be As Beneficial as Expected: A Multi-center, Pre- and Post- Study.

BACKGROUND: Standardization of procedures improves outcomes. Though systematic reviews have summarized the evidence-based steps (EBS) of cesarean delivery (CD), their bundled implementation has not been investigated. OBJECTIVE: In this pre- and post-implementation trial, we sought to ascertain if bundled EBS of CD, compared to surgeon's preference, improves outcomes. STUDY DESIGN: A StaRI (Standards for Reporting Implementation Studies) compliant, multi-center pre- and post-implementation trial at 4 teaching hospitals was conducted. The pre-implementation period consisted of CD done based on the physicians' preferences for 3 months; educational intervention (e.g., didactics, badge cards, posters, video) occurred at the 4th month. CDs in post-implementation period employed the bundled EBS. A pre-planned 10% randomized audit of both groups assessed adherence and uptake of EBS. The primary outcome was a composite maternal morbidity (CMM), which included estimated blood loss > 1,000 mL, blood transfusion, endometritis, post-partum fever, wound complications, sepsis, thrombosis, ICU admission, hysterectomy, or death. The secondary outcome was a composite neonatal morbidity (CNM) and some of its components were 5-min Apgar score < 7, positive pressure oxygen use, hypoglycemia, or sepsis. A priori Bayesian sample size calculation indicated 700 CD in each group was needed to demonstrate 20% relative reduction (from 15% to 12%) of CMM with 75% certainty. Bayesian logistic regression with neutral priors was used to calculate likelihood of net-improvement in adjusted relative risk (aRR) with 95% credible intervals (CrI). RESULTS: A total of 1,425 consecutive CD (721 in pre- and 704 in post-implementation group) were examined. Audited data indicated that the baseline EBS utilization rate during the pre-implementation period was 79%; after the implementation bundled EBS of CD the audited adherence was 89%-an uptake of 10.0% of the EBS. In four aspects, the maternal characteristics differed significantly in the pre- and post-implementation periods: race/ethnicity, hypertensive disorder, and the relative contribution of the 4 centers to the cohorts and the gestational age at delivery, but the indications for CD and whether its duration was < versus > 60 min did not. The rates of CMM in the pre- and post-implementation groups were 26% and 22%, respectively (aRR, 0.88; 95% CrI, 0.73-1.04), with a 94 % Bayesian probability of a reduction in CMM. The CNM occurred in 37% of the pre- and in 41% of the post-implementation group (aRR, 1.12; 95% CrI 0.98-1.39), with a 95% Bayesian probability of worsening in CNM. When CMM were segregated by preterm (<37 wks) and term (> 37 weeks) CD, the improvement in maternal outcomes persisted; when CNM were segregated by gestational age subgroupsthe potential for worsening neonatal outcomes persisted as well. CONCLUSIONS: Standardization of the evidence-based bundled steps of cesarean delivery resulted in a modest reduction of the composite maternal outcome; however, a paradoxical increase in neonatal composite morbidity was noted. Although individual evidence-based steps may be of value, while awaiting additional intervention trials a formal bundling of such steps is currently not recommended.

Risk of Postpartum Hemorrhage in Hypertensive Disorders of Pregnancy: Stratified by Severity.

OBJECTIVE: We aimed to determine the composite maternal hemorrhagic outcome (CMHO) among individuals with and without hypertensive disorders of pregnancy (HDP), stratified by disease severity. Additionally, we investigated the composite neonatal adverse outcome (CNAO) among individuals with HDP who had postpartum hemorrhage (PPH) versus did not have PPH. STUDY DESIGN: Our retrospective cohort study included all singletons who delivered at a Level IV center over two consecutive years. The primary outcome was the rate of CMHO, defined as blood loss ≥1,000 mL, use of uterotonics, mechanical tamponade, surgical techniques for atony, transfusion, venous thromboembolism, intensive care unit admission, hysterectomy, or maternal death. A subgroup analysis was performed to investigate the primary outcome stratified by (1) chronic hypertension, (2) gestational hypertension and preeclampsia without severe features, and (3) preeclampsia with severe features. A multivariable regression analysis was performed to investigate the association of HDP with and without PPH on a CNAO which included APGAR <7 at 5 minutes, bronchopulmonary dysplasia, intraventricular hemorrhage, necrotizing enterocolitis, seizures, neonatal sepsis, meconium aspiration syndrome, ventilation >6 hours, hypoxic-ischemic encephalopathy, or neonatal death. RESULTS: Of 8,357 singletons, 2,827 (34%) had HDP. Preterm delivery <37 weeks, induction of labor, prolonged oxytocin use, and magnesium sulfate usage were more common in those with versus without HDP (p < 0.001). CMHO was higher among individuals with HDP than those without HDP (26 vs. 19%; adjusted relative risk [aRR] 1.11, 95% CI 1.01-1.22). In the subgroup analysis, only individuals with preeclampsia with severe features were associated with higher CMHO (n = 802; aRR 1.52, 95% CI 1.32-1.75). There was a higher likelihood of CNAO in individuals with both HDP and PPH compared to those with HDP without PPH (aRR 1.49, 95% CI 1.06-2.09). CONCLUSION: CMHO was higher among those with HDP. After stratification, only those with preeclampsia with severe features had an increased risk of CMHO. Among individuals with HDP, those who also had a PPH had worse neonatal outcomes than those without hemorrhage. KEY POINTS: · Individuals with HDP had an 11% higher likelihood of CMHO.. · After stratification, increased CMHO was limited to those with preeclampsia with severe features.. · There was a higher likelihood of CNAO in those with both HDP and PPH compared to HDP without PPH..

Association of adverse outcomes with three-tiered risk assessment tool for obstetrical hemorrhage.

BACKGROUND: Guidelines promote stratification for the risk for postpartum hemorrhage among parturients, although the evidence for the associated differential morbidity among the groups remains inconsistent among published reports. OBJECTIVE: Using the California Maternal Quality Care Collaborative schema modified by the American College of Obstetrics and Gynecology, we compared the composite maternal hemorrhagic outcome and the composite neonatal adverse outcome among singletons who were categorized after delivery by the researchers as low-, medium-, or high-risk for postpartum hemorrhage. We hypothesized that the composite outcomes would be significantly different among the individuals in the different 3-tiered categories. STUDY DESIGN: This was a retrospective cohort study of all singleton parturients with a gestational age of at least 14 weeks who delivered at a single site within 1 year. The composite maternal hemorrhagic outcome included any of the following: estimated blood loss ≥1000 mL, use of uterotonics (excluding prophylactic oxytocin) or Bakri balloon, surgical management of postpartum hemorrhage, blood transfusion, hysterectomy, thromboembolism, admission to the intensive care unit, or maternal death. The composite neonatal adverse outcome included Apgar score <7 at 5 minutes, birth injury, bronchopulmonary dysplasia, intraventricular hemorrhage, neonatal seizure, sepsis, ventilation > 6 hrs., brachial plexus palsy, hypoxic-ischemic encephalopathy, or neonatal death. Multivariable Poisson regression models with robust error variance were used to estimate the adjusted relative risks with 95% confidence intervals. RESULTS: Of the 4544 deliveries in the study period, 4404 (96.7%) met the inclusion criteria, and among them, 1745 (39.6%) were categorized as low, 1376 (31.2%) as medium, and 1283 (29.1%) as high risk. Overall, 941 (21.4%) participants experienced the composite maternal hemorrhagic outcome with 285 (16.4%) of those being in the low-risk group, 319 (23.2%) in the medium-risk group, and 337 (26.3%) in the high-risk group. Among all parturients, 95.7% in the low-, 89.4% in the medium-, and 85.3% in the high-risk group neither had an estimated blood loss or a quantified blood loss ≥1000 mL nor were transfused. After multivariable adjustment and when compared with the low-risk group, there was a significantly higher risk for the composite maternal hemorrhagic outcome in the medium-risk group (adjusted relative risk, 1.23; 95% confidence interval, 1.05-1.43) and in the high-risk group (adjusted relative risk, 1.51; 95% confidence interval, 1.31-1.75). Overall, 366 newborns (8.4%) developed the composite neonatal adverse outcome with 76 (4.2%) in of those being in the low-risk group, 153 (11.3%) in the medium-risk group, and 140 (11.1%) in the high-risk group. After multivariable adjustment and when compared with the low-risk group, there were no significant differences in the composite neonatal adverse outcome in the medium- (adjusted relative risk, 1.27; 95% confidence interval, 0.97-1.68) or the high-risk group (adjusted relative risk, 1.29; 95% confidence interval, 0.98-1.68). CONCLUSION: Although 8 of 10 parturients categorized as high risk neither had blood loss ≥1000 mL nor underwent transfusion, the risk stratification provides information regarding the composite maternal hemorrhagic outcome.

The Role of Cerclage in Subsequent Pregnancy following Previable Prelabor Rupture of Membranes.

OBJECTIVE: This study aimed to ascertain the outcomes associated with a cervical cerclage among individuals with a history of previable prelabor rupture of membranes (PROM). STUDY DESIGN: This study was a retrospective cohort study conducted at a single tertiary center between 2011 and 2021. We included individuals with a history of previable (before 24 weeks) PROM and the subsequent viable pregnancy. Women with multifetal gestation, preterm birth (PTB) or cerclage in previous gestation, or abdominal cerclage after trachelectomy were excluded. Primary outcome was PTB rate (delivery <37 weeks). Recurrence of preterm PROM and adverse composite maternal and neonatal outcomes (CMO and CNO) were evaluated as secondary outcomes. CMO included any of the following: suspected chorioamnionitis, endometritis, red blood cell transfusion, uterine rupture, unplanned hysterectomy, or death. CNO included any of the following: previable PTB (<24 weeks of gestation), bronchopulmonary dysplasia, grade 3 or 4 intraventricular hemorrhage, necrotizing enterocolitis, mechanical ventilation, seizures, hypoxic ischemic encephalopathy, or death. RESULTS: During the study period, 118 individuals had a history of previable PROM and a documented subsequent pregnancy, out of which 74 (62.7%) met inclusion criteria. Nineteen (25.7%) of eligible individuals underwent a cerclage for prior previable PROM and were compared with controls (n = 55, 74.3%). Women who underwent a cerclage had higher rates of PTB < 37 weeks (63.2 vs. 10.9%, p < 0.001; odds ratio [OR]: 14.00, 95% confidence interval [CI]: 3.97-49.35) and < 34 weeks (21.1 vs. 3.6%, p = 0.03; OR: 7.07, 95% CI: 1.18-42.39) compared with those without cerclage. Furthermore, recurrent preterm PROM and previable PTB rates were higher among patients who underwent cerclage. The survival curve further indicated that individuals with cerclage delivered earlier. CMO and CNO rates were similar in those with and without cerclage. CONCLUSION: Cerclage placement in individuals with prior previable PROM was associated with higher rates of recurrent preterm PROM and PTB. KEY POINTS: · The management of individuals in a subsequent pregnancy following previable PROM is a conundrum.. · Cerclage following previable PROM is associated with higher rates of recurrent preterm PROM and PTB.. · Composite maternal and neonatal outcome rates were similar in those with and without cerclage..

Factors associated with exclusive formula feeding among individuals with low-risk pregnancies in the United States.

BACKGROUND: Better understanding of the factors associated with formula feeding during the hospital stay can help in identifying potential lactation problems and promote early intervention. Our aim was to ascertain factors associated with exclusive formula feeding in newborns of low-risk pregnancies. METHODS: A population-based, retrospective study using the United States vital statistics datasets (2014-2018) evaluating low-risk pregnancies with a nonanomalous singleton delivery from 37 to 41 weeks. People with hypertensive disorders, or diabetes, were excluded. Primary outcome was newborn feeding (breast vs exclusive formula feeding) during hospital stay. Adjusted relative risks (aRRs) with 95% confidence intervals (CI) were calculated. RESULTS: Of the 19 623 195 live births during the study period, 11 605 242 (59.1%) met inclusion criteria and among them, 1 929 526 (16.6%) were formula fed. Factors associated with formula feeding included: age < 20 years (aRR 1.31 [95% CI 1.31-1.32]), non-Hispanic Black (1.42, 1.41-1.42), high school education (1.69, 1.69-1.70) or less than high school education (1.94, 1.93, 1.95), Medicaid insurance (1.52, 1.51, 1.52), body mass index (BMI) < 18.5 (1.10, 1.09-1.10), BMI 25-29.9 (1.09, 1.09-1.09), BMI 30-34.9 (1.19, 1.19-1.20), BMI 35-39.9 (1.31, 1.30-1.31), BMI ≥ 40 (1.43, 1.42-1.44), multiparity (1.29, 1.29-1.30), lack of prenatal care (1.49, 1.48-1.50), smoking (1.75, 1.74-1.75), and gestational age (ranged from 37 weeks [1.44, 1.43-1.45] to 40 weeks [1.11, 1.11-1.12]). CONCLUSIONS: Using a large cohort of low-risk pregnancies, we identified several modifiable factors associated with newborn feeding (eg, prepregnancy BMI, access to prenatal care, and smoking cessation). Improving the breast feeding initiation rate should be a priority in our current practice to ensure equitable care for all neonates.

Enhanced recovery after scheduled cesarean delivery: a prospective pre-post intervention study.

OBJECTIVE: To assess whether an early recovery after surgery (ERAS) pathway after scheduled cesarean delivery was associated with a reduction in postoperative length of stay compared with standard perioperative care. METHODS: This was a prospective pre- and post-intervention study. Women were included if they were between 18 and 45 years of age and delivered a singleton, term, non-anomalous fetus via scheduled cesarean delivery by a provider within an academic practice. The ERAS pathway consisted of 23 evidence-based components regarding preoperative, intraoperative, and postoperative care. The primary outcome was the rate of postoperative length of stay of 3 or more days. Secondary outcomes included total postoperative narcotic use, postoperative complications, 30-day hospital readmission rates, and quality of recovery questionnaire scores. RESULTS: A total of 116 women were included. There were no significant differences in patient characteristics between the pre- and post-implementation groups in the post-implementation group, surgery time was longer (78.3 ± 27.8 vs 59.1 ± 19.2 min, p < .001) and blood loss volume was higher (910.3 ± 405.1 vs 729.1 ± 202.0, p = .003), compared to pre-implementation group. An ERAS pathway was not associated in a significant reduction in postoperative length of stay of 3 or more days (70.7% vs 75.9%, p = .529). It was also not significantly associated with a difference in postoperative narcotic use, maximum pain score, transfusion, postoperative complications or hospital readmission rates. CONCLUSION: An early recovery after surgery pathway after scheduled cesarean delivery was not associated with a reduction in postoperative length of stay or narcotic use, though the recovery scores were better after implementation.

Eclampsia in the 21st century.

The reported incidence of eclampsia is 1.6 to 10 per 10,000 deliveries in developed countries, whereas it is 50 to 151 per 10,000 deliveries in developing countries. In addition, low-resource countries have substantially higher rates of maternal and perinatal mortalities and morbidities. This disparity in incidence and pregnancy outcomes may be related to universal access to prenatal care, early detection of preeclampsia, timely delivery, and availability of healthcare resources in developed countries compared to developing countries. Because of its infrequency in developed countries, many obstetrical providers and maternity units have minimal to no experience in the acute management of eclampsia and its complications. Therefore, clear protocols for prevention of eclampsia in those with severe preeclampsia and acute treatment of eclamptic seizures at all levels of healthcare are required for better maternal and neonatal outcomes. Eclamptic seizure will occur in 2% of women with preeclampsia with severe features who are not receiving magnesium sulfate and in <0.6% in those receiving magnesium sulfate. The pathogenesis of an eclamptic seizure is not well understood; however, the blood-brain barrier disruption with the passage of fluid, ions, and plasma protein into the brain parenchyma remains the leading theory. New data suggest that blood-brain barrier permeability may increase by circulating factors found in preeclamptic women plasma, such as vascular endothelial growth factor and placental growth factor. The management of an eclamptic seizure will include supportive care to prevent serious maternal injury, magnesium sulfate for prevention of recurrent seizures, and promoting delivery. Although routine imagining following an eclamptic seizure is not recommended, the classic finding is referred to as the posterior reversible encephalopathy syndrome. Most patients with posterior reversible encephalopathy syndrome will show complete resolution of the imaging finding within 1 to 2 weeks, but routine imaging follow-up is unnecessary unless there are findings of intracranial hemorrhage, infraction, or ongoing neurologic deficit. Eclampsia is associated with increased risk of maternal mortality and morbidity, such as placental abruption, disseminated intravascular coagulation, pulmonary edema, aspiration pneumonia, cardiopulmonary arrest, and acute renal failure. Furthermore, a history of eclamptic seizures may be related to long-term cardiovascular risk and cognitive difficulties related to memory and concentration years after the index pregnancy. Finally, limited data suggest that placental growth factor levels in women with preeclampsia are superior to clinical markers in prediction of adverse pregnancy outcomes. This data may be extrapolated to the prediction of eclampsia in future studies. This summary of available evidence provides data and expert opinion on possible pathogenesis of eclampsia, imaging findings, differential diagnosis, and stepwise approach regarding the management of eclampsia before delivery and after delivery as well as current recommendations for the prevention of eclamptic seizures in women with preeclampsia.

Low Transverse versus Midline Abdominal Skin Incisions for in utero Spina Bifida Repair.

OBJECTIVE: The 2 types of maternal skin incisions for in utero spina bifida repair are low transverse (LT) incision perceived to be cosmetic benefit and midline longitudinal (ML) incision, typically associated with a reduction in surgical time and lower blood loss. Our objective was to compare short- and long-term outcomes associated with these 2 types of skin incisions following in utero spina bifida repair. METHODS: Prospective observational cohort of 72 patients undergoing fetal spina bifida repair at a single institution between September 2011 and August 2018. The decision for the type of incision was at the discretion of the surgeons. The primary outcome was total operative time. Secondary outcomes included an analog scale of wound pain score on postoperative day 3, duration of postoperative stay, and postoperative wound complications within the first 4 weeks. The Patient Scar Assessment Questionnaire, a validated questionnaire, was obtained for all patients (≥6 months from delivery) using 4 categories (appearance, consciousness, satisfaction with appearance and with symptoms), with higher scores reflecting a poorer perception of the scar. RESULTS: There were 43 women (59.7%) in the LT group and 29 (40.3%) in the ML group. In all patients, the same incision was used during cesarean delivery. The total operative time was higher in the LT group by 33 min (p < 0.001), primarily due to abdominal wall incision time (open and closure). No significant differences were found between the groups in pain score, length of postoperative stay, or the rate of wound complications. Fifty-three patients (73.6%) responded to the questionnaire, 36/43 from the LT group and 17/29 from the ML group. There was no difference in the scores of appearance, consciousness, and satisfaction with appearance and symptoms between the groups. CONCLUSION: ML incisions shorten operative times without altering long-term incision-related satisfaction when compared to LT incisions.

Preeclampsia: The Need for a Biological Definition and Diagnosis.

The centuries-old approach to the prevention of eclampsia and its associated maternal morbidity and mortality is based on the recognition of the presence of premonitory signs and symptoms such as hypertension and proteinuria. The spectrum of preceding signs and symptoms came to be known as preeclampsia, which is debatably considered to be an early stage on a clinical continuum possibly leading to eclampsia. The premonitory signs and symptoms were then construed as diagnostic criteria for the poorly understood syndrome of preeclampsia, and this led to a perpetual debate that remains subject to wide disagreement and periodic updates. In this commentary, we will draw attention to the fact that the criteria for preeclampsia should be viewed from the prism of a screening test rather than as diagnostic of a condition in itself. Focusing research on developing better diagnostic and screening methods for what is clinically important, namely maternal and perinatal morbidity and mortality from hypertensive disorders of pregnancy, a long overdue upgrade from what was possible centuries ago, will ultimately lead to better management approaches to what really matters.

Factors Associated with Formula Feeding among Late Preterm Neonates.

OBJECTIVE: Late preterm births (delivery at 34-36 weeks) account for nearly three quarters of the preterm births and among them there is a knowledge gap about an important aspect of infant care: breast versus formula feeding. The aim of this study was to assess factors associated with formula feeding in late preterm neonates. STUDY DESIGN: Secondary analysis of a multicenter randomized trial of antenatal corticosteroids for women at risk for late preterm birth. All women with a singleton pregnancy who delivered at 340/7 to 366/7 weeks were included. Women with no information on neonatal feeding or known fetal anomalies were excluded. The outcome evaluated was the type of neonatal feeding during hospital stay. Maternal and neonatal characteristics were compared among women who initiated breast versus formula feeding. Adjusted relative risks (aRRs) for formula feeding with 95% confidence intervals (CIs) were calculated. RESULTS: Of the 2,831 women in the parent trial, 2,329 (82%) women met inclusion criteria and among them, 696 (30%) were formula feeding. After multivariable regression, the following characteristics were associated with an increased risk of formula feeding: maternal age < 20 years (aRR: 1.47, 95% CI: 1.20-1.80) or ≥35 years (aRR: 1.19, 95% CI: 1.02-1.40), never married status (aRR: 1.39, 95% CI: 1.20-1.60), government-assisted insurance (aRR: 1.41, 95% CI: 1.16-1.70), chronic hypertension (aRR: 1.19, 95% CI: 1.01-1.40), smoking (aRR: 1.51, 95% CI: 1.31-1.74), cesarean delivery (aRR: 1.16, 95% CI: 1.03-1.32), and admission to neonatal intensive care unit (aRR: 1.31, 95% CI: 1.16-1.48). Hispanic ethnicity (aRR: 0.78, 95% CI: 0.64-0.94), education >12 years (aRR: 0.81, 95% CI 0.69-0.96), and nulliparity (aRR 0.71, 95% CI: 0.62-0.82) were associated with a reduced risk for formula feeding. CONCLUSION: In this geographically diverse cohort of high-risk deliveries, 3 out 10 late preterm newborns were formula fed. Smoking cessation was a modifiable risk factor that may diminish the rate of formula feeding among late preterm births. KEY POINTS: · Three of ten late preterm do not benefit from breastfeeding.. · Demographic characteristics are associated with type of feeding.. · Smoking cessation may improve the rate of breastfeeding..

Perioperative Glucocorticoid Therapy for Patients with Adrenal Insufficiency: Dosing Based on Pharmacokinetic Data.

BACKGROUND: Perioperative glucocorticoid therapy for patients with adrenal insufficiency (AI) is currently based on anecdotal reports, without supporting pharmacokinetic data. METHODS: We determined the half-life, clearance, and volume of distribution of 2 consecutive intravenously (IV)-administered doses of hydrocortisone (15 or 25 mg every 6 hours) to 22 dexamethasone-suppressed healthy individuals and used the data to develop a novel protocol to treat 68 patients with AI who required surgical procedures. Patients received 20 mg of hydrocortisone orally 2 to 4 hours before intubation and were started on 25 mg of IV hydrocortisone every 6 hours for 24 hours and 15 mg every 6 hours during the second day. Nadir cortisol concentrations were repeatedly measured during that period. RESULTS: In healthy individuals, cortisol half-life was longer when the higher hydrocortisone dose was administered (2.02 ± 0.15 vs 1.81 ± 0.11 hours; P < 0.01), and in patients with AI, the half-life was longer than in healthy individuals given the same hydrocortisone dose. In both populations, the cortisol half-life increased further with the second hormone injection. Prolongation of cortisol half-life was due to decreased hydrocortisone clearance and an increase in its volume of distribution. Nadir cortisol levels determined throughout the 48 postoperative hours were within the range of values and often exceeded those observed perioperatively in patients without adrenal dysfunction. CONCLUSIONS: Cortisol pharmacokinetics are altered in the postoperative period and indicate that lower doses of hydrocortisone can be safely administered to patients with AI undergoing major surgery. The findings of this investigation call into question the current practice of administering excessive glucocorticoid supplementation during stress.

Increased androgen secretion in patients with prolactinomas: the impact of altered HPA function.

BACKGROUND AND OBJECTIVES: Earlier studies suggested that hyperprolactinemia was associated with elevated serum DHEA-S levels. The importance of DHEA-S measurements in the diagnosis of adrenal insufficiency prompted us to assess adrenal androgen levels in hyperprolactinemic subjects with normal or impaired function. METHODS: Prospective study including 122 medically treated and 26 surgically patients with prolactinomas. Serum PRL, DHEA and DHEA-S levels were measured before and repeatedly after cabergoline therapy and also in the perioperative period of surgically treated patients. RESULTS: Serum PRL levels decreased (P < 0.001) in all 101 medically treated patients with normal HPA function from 728.3 ± 1507 reaching 29.1 ± 39 and 14.9 ± 24.4 µg/L at 3 and 12 months, respectively. Concurrently serum DHEA-S levels decreased (P < 0.001) from 245.9 ± 196 to 216.2 ± 203.3 and to 169.7 ± 121.1 µg/dl at 3 and 12 months, respectively. These effects were reversed in 19 patients who discontinued treatment and were re-demonstrated after therapy resumption. Among the 22 surgically treated patients with normal HPA, peri-operative PRL levels decreased rapidly (P < 0.001) with a parallel decline in serum DHEA-S levels (P = 0.03). Strong correlations were noted between PRL and DHEA-S decrements observed with medical or surgical therapy. Medically (n = 21) and surgically (n = 4) patients with impaired HPA function had very low DHEA-S values that were unchanged despite marked reductions in PRL secretion. CONCLUSION: Hyperprolactinemia is associated with a reproducible and reversible increase in serum DHEA-S that was observed in medically- and surgically-treated patients with normal HPA function. Thus, a normal age- and gender-adjusted serum DHEA-S level continues to imply normal HPA function even among hyperprolactinemic subjects.

Intratumoral Rathke's Cleft Cyst Remnants Within Craniopharyngioma, Pituitary Adenoma, Suprasellar Dermoid, and Epidermoid Cysts: A Ubiquitous Signature of Ectodermal Lineage or a Transitional Entity?

BACKGROUND: The authors present cystic epithelial masses in the suprasellar region which on histopathology revealed 4 mixed tumors having simple cuboidal epithelium of Rathke's Cleft Cyst (RCC) elements trapped within pituitary adenoma, epidermoid cyst, dermoid cyst, and papillary craniopharyngioma respectively. OBJECTIVE: To highlight the developmental theory of ectodermal continuum in the realm of suprasellar epithelial cystic lesions and examines the cardinal aspects that distinguish RCC from its confounder, ciliary craniopharyngioma. METHODS: The authors performed a medical chart review on 4 patients who had coexisting RCC with craniopharyngioma, pituitary adenoma, suprasellar dermoid, and epidermoid cysts. RESULTS: This series of unique suprasellar lesions elucidate the spectrum of cases from Rathke's cyst to other suprasellar epithelial cysts including a recently identified clinical entity called ciliary craniopharyngioma, which authors feel is a misnomer. The authors also report the first case of ruptured dermoid cyst admixed with elements of Rathke's cyst elements and xanthogranuloma in neurosurgical literature. CONCLUSION: We propose that the new entity of ciliary craniopharyngioma could be just another variant of RCC elements nested within a typical papillary or adamantinomatous lesion. Further study is warranted to understand the implications of natural history with tumors containing RCC elements.

Alterations in hypothalamic-pituitary-adrenal function immediately after resection of adrenal adenomas in patients with Cushing's syndrome and others with incidentalomas and subclinical hypercortisolism.

BACKGROUND: Patients with cortisol secreting adrenal adenomas present with Cushing's syndrome (CS), while 5-15% of subjects with adrenal incidentalomas have subclinical hypercortisolism (SH) as they have biochemical abnormalities suggesting autonomous cortisol secretion without associated clinical features of CS. GOALS: Examine HPA function immediately after resection of either of these adenomas and utilize the data to decide on initiating glucocorticoid replacement. METHODS: ACTH, cortisol, and DHEA-S levels were measured frequently for 8 h after adrenalectomy in 14 patients with CS and 19 others with incidentalomas + SH. Glucocorticoids were withheld before/during surgery and administered 6-8 h postoperatively to those who had cortisol levels of <3 ug/dL (83 nmol/L). RESULTS: Preoperatively, incidentalomas + SH patients had larger tumors, higher ACTH, and DHEA-S but lower dexamethasone-suppressed serum cortisol levels than those with CS. Postoperatively, ACTH levels increased in both groups: (90.1 ± 31.6; 24.1 ± 14.4 ng/L, respectively; P < 0.001). Postoperative ACTH levels correlated negatively with preoperative Dexamethasone-suppressed cortisol concentrations in both groups. Patients with CS had steeper decline in cortisol concentrations than those with incidentalomas + SH. All patients with CS had hypocortisolemia requiring glucocorticoid therapy for several months, while only 5/19 with incidentalomas + SH had cortisol levels <3 ug/dL;(83 nmol/L) 6-8 h after adrenalectomy and received hydrocortisone replacement therapy for ≤4 weeks. CONCLUSIONS: Surgical stress stimulates HPA function even in patients with hypercortisolemia. Patients with incidentalomas + SH have incomplete HPA suppression that allows more robust response to surgical stress than that observed in patients with CS. HPA assessment immediately after surgical resection of adrenal incidentalomas identified those requiring glucocorticoid replacement before discharge.

Loss of placental growth factor ameliorates maternal hypertension and preeclampsia in mice.

Preeclampsia remains a clinical challenge due to its poorly understood pathogenesis. A prevailing notion is that increased placental production of soluble fms-like tyrosine kinase-1 (sFlt-1) causes the maternal syndrome by inhibiting proangiogenic placental growth factor (PlGF) and VEGF. However, the significance of PlGF suppression in preeclampsia is uncertain. To test whether preeclampsia results from the imbalance of angiogenic factors reflected by an abnormal sFlt-1/PlGF ratio, we studied PlGF KO (Pgf-/-) mice and noted that the mice did not develop signs or sequelae of preeclampsia despite a marked elevation in circulating sFLT-1. Notably, PlGF KO mice had morphologically distinct placentas, showing an accumulation of junctional zone glycogen. We next considered the role of placental PlGF in an established model of preeclampsia (pregnant catechol-O-methyltransferase-deficient [COMT-deficient] mice) by generating mice with deletions in both the Pgf and Comt genes. Deletion of placental PlGF in the context of COMT loss resulted in a reduction in maternal blood pressure and increased placental glycogen, indicating that loss of PlGF might be protective against the development of preeclampsia. These results identify a role for PlGF in placental development and support a complex model for the pathogenesis of preeclampsia beyond an angiogenic factor imbalance.

The Relationship of Assisted Reproductive Technology on Perinatal Outcomes in Triplet Gestations.

OBJECTIVE: To assess whether assisted reproductive technology (ART) is associated with increased risk of adverse perinatal outcomes in triplet gestations compared with spontaneous conception. STUDY DESIGN: Secondary analysis of a multicenter randomized trial for the prevention of preterm birth in multiple gestations. Triplets delivered at ≥ 24 weeks were studied. The primary outcome was the rate of composite neonatal morbidity (CNM) that included one or more of the following: bronchopulmonary dysplasia, respiratory distress syndrome, necrotizing enterocolitis, culture proven sepsis, pneumonia, retinopathy of prematurity, intraventricular hemorrhage, periventricular leukomalacia, or perinatal death. RESULTS: There were 381 triplets (127 women) of which 89 patients conceived via ART and 38 patients spontaneously. Women with ART were more likely to be older, Caucasian, married, nulliparous, have higher level of education, and develop pre-eclampsia. Spontaneously conceived triplets were more likely to delivery at an earlier gestation (31.2 ± 3.5 vs 32.8 ± 2.7 weeks) (p = 0.009) with a lower birth weight (p < 0.001). After adjusting for confounders, no differences were noted in culture proven sepsis, perinatal death, CNM, respiratory distress syndrome, or Apgar score < 7 at 5 minutes. All remaining perinatal outcomes were similar. CONCLUSION: Triplets conceived by ART had similar perinatal outcomes compared with spontaneously conceived triplets.

Caesarean Delivery Surgical Site Infection: What are Expected Rates and Potentially Modifiable Risk Factors?

OBJECTIVE: This study sought to determine baseline Caesarean delivery (CD) surgical site infection (SSI) rates in various patient subgroups and to identify potentially modifiable and non-modifiable risk factors for SSI. METHODS: This is a secondary analysis of a multicentre CD registry. Women who underwent CD were divided into SSI versus no SSI. SSI was defined as an infection that occurred in the part of the body where the surgery took place, within 30 days of surgery. Clinical characteristics and potential risk factors were compared between groups. RESULTS: Of 57 182 women, 3696 (6.5%) had SSI. SSI rates were higher in primary versus repeat CD (9.7% vs. 4.2%; P <0.001), and in CD after labour vs. no labour (9.5% vs. 3.8%; P <0.001). After adjustment for confounding factors, low transverse CD (adjusted OR [aOR] 0.7 [0.6-0.9]), CD performed between 7 pm and 7 am (aOR 0.9 [0.83-0.98]), primary CD (aOR 0.5 [0.5-0.6]), and intrapartum antibiotics (aOR 0.3 [0.1-0.4]) were associated with a decreased in the rate of SSI. Black race (aOR 1.9 [1.7-2.1]), tobacco use (aOR 1.4 [1.2-1.6]), increasing American Society of Anesthesiologists category (aOR 1.3 [1.1-1.6]), vertical skin incision (aOR 1.2 [1.1-1.3], emergency CD (aOR 1.3 [1.1-1.5]), and postpartum transfusion (aOR 2.7 [2.1-3.6]) were associated with an increase in the rate of SSI. CONCLUSION: This study estimates the CD SSI rates in different subgroups and serves as a baseline for future trials designed to develop preventive guidelines and protocols.

The Value of Perioperative Levels of ACTH, DHEA, and DHEA-S and Tumor Size in Predicting Recurrence of Cushing Disease.

Context and Objectives: Despite the development of hypocortisolemia after corticotroph surgical adenomectomy, 15% to 20% patients have recurrence of Cushing disease (CD). In this study, we investigated the effect of tumor size and the value of perioperative assessment of corticotropin (ACTH) and adrenal steroid levels in predicting recurrence. Design: Perioperatively, no glucocorticoids were administered until the serum cortisol was ≤3 µg/dL. Blood samples were obtained before and repeatedly after adenomectomy in 79 patients with CD. Of these, 66 had a nadir serum cortisol of ≤3.0 µg/dL and clinical and biochemical remissions. During a median follow-up of 131 months, 11 of 66 had disease recurrence (REC), whereas 55 of 66 did not (NO-REC). Results: Preoperative hormone levels in the REC and NO-REC groups were similar. After adenomectomy, a brief and similar increase in ACTH, cortisol, and dehydroepiandrosterone (DHEA) levels was observed in both groups followed by gradual decline in those levels. Although REC and NO-REC patients had similar cortisol levels (3.4 ± 1.7 µg/dL vs 2.9 ± 2.2 µg/dL) at the 36th postoperative hour, their respective ACTH (33 ± 7.1 ng/L vs 12.1 ± 5.4 ng/L; P < 0.0001), DHEA (3.8 ± 1.7 ng/mL vs 1.2 ± 1.1 ng/mL; P = 0.005), and dehydroepiandrosterone sulphate (DHEA-S) (143.9 ± 45.2 µg/dL vs 48.9 ± 38.2 µg/dL; P < 0.0001) were higher. At nadir hypocortisolemia, perioperative ACTH levels were >20 in all REC patients and <20 ng/L in the NO-REC group. Patients with REC had larger tumors than those with NO-REC. Conclusion: Recurrent CD is characterized by persistent perioperative ACTH secretion after adenomectomy. Higher perioperative levels of ACTH, DHEA, and DHEA-S are highly predictive of future disease recurrence, particularly in those with profound hypocortisolemia.

Clopidogrel-Induced Insulin Autoimmune Syndrome: A Newly Recognized Cause of Hypoglycemia in a Patient Without Diabetes.

Insulin autoimmune syndrome (IAS), defined as hyperinsulinemic hypoglycemia with high titers of anti-insulin antibodies, is frequently reported in Japanese patients but rarely observed in whites. We report in this study on a 79-year-old white male without diabetes who developed IAS following exposure to clopidogrel, a drug not previously known to cause hypoglycemia. The patient presented with recurrent symptomatic hypoglycemia. During one episode, serum glucose was 45 mg/dL, whereas insulin and C-peptide levels were 40,000 mIU/mL and 40 ng/mL, respectively. Additional studies revealed no intake of insulin or its secretagogues, whereas anti-insulin antibody titer was high (59.3 nmol/L). Although total insulin levels were consistently high, free insulin concentrations (polyethylene glycol precipitation) were appropriate for ambient glycemia. The patient was found to have HLA-DRB1*0404, a feature often reported in Japanese patients with IAS. Three weeks prior to symptom onset, he was started on clopidogrel, a drug that does not have a sulfhydryl group, but its active metabolite does. Clopidogrel was switched to a nonsulfhydryl antiplatelet agent, and glucocorticoid therapy was initiated. Shortly thereafter, the frequency of hypoglycemic episodes decreased, and glucocorticoids were tapered over the ensuing 3 months. No hypoglycemic episodes were noted during 6 months of observation after discontinuing glucocorticoids, whereas the total insulin and anti-insulin antibody levels normalized. The data indicate that IAS should be considered in the differential diagnosis of hyperinsulinemic hypoglycemia in seemingly well individuals, even when no drugs known to cause IAS were used. Clinical suspicion of IAS can avoid expensive imaging and unnecessary surgery in affected patients.