Glutaric aciduria type 1: Diagnosis, clinical features and long-term outcome in a large cohort of 34 Irish patients.

Glutaric aciduria type 1 (GA1) is a rare neurometabolic disorder that can lead to encephalopathic crises and severe dystonic movement disorders. Adherence to strict dietary restriction, in particular a diet low in lysine, carnitine supplementation and emergency treatment in pre-symptomatic patients diagnosed by high-risk screen (HRS) or newborn screen (NBS) leads to a favourable outcome. We present biochemical and clinical characteristics and long-term outcome data of 34 Irish patients with GA1 aged 1-40 years. Sixteen patients were diagnosed clinically, and 17 patients by HRS, prior to introduction of NBS for GA1 in the Republic of Ireland in 2018. One patient was diagnosed by NBS. Clinical diagnosis was at a median of 1 year (range 1 month to 8 years) and by HRS was at a median of 4 days (range 3 days to 11 years). 14/18 (77.8%) diagnosed by HRS or NBS had neither clinical manifestations nor radiological features of GA1, or had radiological features only, compared to 0/16 (0%) diagnosed clinically (p < 0.001). Patients diagnosed clinically who survived to school-age were more likely to have significant cerebral palsy and dystonia (7/11; 63.6% vs. 0/13; 0%, p < 0.001). They were less likely to be in mainstream school versus the HRS group (5/10; 50% vs. 12/13; 92.3%; p = 0.012). Clinical events occurring after 6 years of age were unusual, but included spastic diplegia, thalamic haemorrhage, Chiari malformation, pituitary hormone deficiency and epilepsy. The exact aetiology of these events is unclear.

Implementation and Evaluation of an Electronic Maternal Early Warning Trigger Tool to Reduce Maternal Morbidity.

OBJECTIVE: We compare maternal morbidity and clinical care metrics before and after the electronic implementation of a maternal early warning trigger (MEWT) tool. STUDY DESIGN: This is a study of maternal morbidity and clinical care within three linked hospitals comparing 1 year before and after electronic MEWT implementation. We compare severe maternal morbidity overall as well as within the subcategories of hemorrhage, hypertension, cardiopulmonary, and sepsis in addition to relevant process metrics in each category. We describe the MEWT trigger rate in addition to MEWT sensitivity and specificity for morbidity overall and by morbidity type. RESULTS: The morbidity rate ratio increased from 1.6 per 100 deliveries in the pre-MEWT period to 2.06 per 100 deliveries in the post-MEWT period (incidence rate ratio = 1.28, p = 0.018); however, in cases of septic morbidity, time to appropriate antibiotics decreased (pre-MEWT: 1.87 hours [1.11-2.63] vs. post-MEWT: 0.75 hours [0.31-1.19], p = 0.036) and in cases of hypertensive morbidity, the proportion of cases treated with appropriate antihypertensive medication within 60 minutes improved (pre-MEWT: 62% vs. post-MEWT: 83%, p = 0.040). The MEWT trigger rate was 2.3%, ranging from 0.8% in the less acute centers to 2.9% in our tertiary center. The MEWT sensitivity for morbidity overall was 50%; detection of hemorrhage morbidity was lowest (30%); however, it ranged between 69% for septic morbidity, 74% for cardiopulmonary morbidity, and 82% for cases of hypertensive morbidity. CONCLUSION: Overall, maternal morbidity did not decrease after implementation of the MEWT system; however, important clinical metrics such as time to antibiotics and antihypertensive care improved. We suspect increased morbidity was related to annual variation and unexpected lower morbidity in the pre-MEWT comparison year. Because MEWT sensitivity for hemorrhage was low, and because hemorrhage dominates administrative metrics of morbidity, process metrics around sepsis, hypertension, and cardiopulmonary morbidity are important to track as markers of MEWT efficacy. KEY POINTS: · MEWT was not associated with a decrease in maternal morbidity.. · MEWT was associated with improvements in some clinical care metrics.. · MEWT is more sensitive in detecting septic, hypertensive, and cardiopulmonary morbidities than hemorrhage morbidity..

Society for Maternal-Fetal Medicine Special Statement: Society for Maternal-Fetal Medicine's conflict of interest policy.

A vital mission of the Society for Maternal-Fetal Medicine is to provide independent, objective, scientifically based information and recommendations for providers, patients, and payors of high-risk pregnancy care. To ensure that these recommendations are free from bias, special interest, or the perception of either, a publicly transparent process for disclosing relevant financial and nonfinancial interests (disclosures of interest) and management of potential conflicts of interest are essential. Educational and research presentations also require proper disclosure to allow attendees to properly assess information presented at the Society for Maternal-Fetal Medicine events. The Society for Maternal-Fetal Medicine established a task force to review the current Society for Maternal-Fetal Medicine policies and procedures as they pertain to disclosure of interest and conflict of interest. To establish current best practices in disclosure of interest and conflict of interest definitions, reporting, and conflict of interest mitigation, members of the task force reviewed external literature, including policies of other medical organizations. The Society for Maternal-Fetal Medicine is committed to a continuous process of improvement in the approach to these issues and will revise this policy as indicated.

Ibuprofen and Postpartum Blood Pressure in Women With Hypertensive Disorders of Pregnancy: A Randomized Controlled Trial.

OBJECTIVE: To evaluate the effect of ibuprofen on blood pressure in women with a diagnosis of hypertensive disorders of pregnancy and mild hypertension during the immediate postpartum period. METHODS: In this double-blind controlled trial, we randomly assigned women with a diagnosis of hypertensive disorders of pregnancy and mild hypertension to receive a postpartum analgesic regimen with either ibuprofen or acetaminophen. The primary outcome was average mean arterial pressure during the postpartum hospital stay. Prespecified secondary outcomes included use of breakthrough opioid pain medications, length of hospital stay, and postpartum diuresis, defined as urine output of at least 200 mL/hour for 4 hours. A sample size of 56 participants was needed to detect a difference of 6 mm Hg in average mean arterial pressure between the study groups. RESULTS: From January 17, 2017, to February 24, 2018, 61 participants were randomized and completed the trial, 31 participants in the ibuprofen group and 30 in the control group. Baseline characteristics were similar between groups. Postpartum average arterial pressure did not differ between study groups (93±8 mm Hg for those in the ibuprofen group vs 93±7 mm Hg in the control group, P=.93). Breakthrough opioid medications were requested by 24% of the participants in the ibuprofen group compared with 30% in the control group (P=.62). The ibuprofen group did not have a longer length of stay (48 hours vs 43 hours in the control group) or decreased rate of postpartum diuresis (61% in ibuprofen group vs 77% in the control group, P=.2). CONCLUSION: In women with hypertensive disorders of pregnancy and mild hypertension, ibuprofen did not increase postpartum blood pressure compared with women not receiving nonsteroidal antiinflammatory drugs. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov NCT03011567.

A Validation Study of Maternal Early Warning Systems: A Retrospective Cohort Study.

OBJECTIVE: We compare validation characteristics of four early warning systems for maternal morbidity. STUDY DESIGN: We used a retrospective cohort of severe maternal morbidity cases between January 2016 and December 2016 compared with a cohort of controls. We determined if the modified early obstetric warning score (MEOWS), maternal early recognition criteria (MERC), modified early warning system (MEWS), or maternal early warning trigger (MEWT) would have alerted. We developed criteria to determine which of these alerts was considered clinically "relevant." RESULTS: We reviewed 79 morbidity cases and 123 controls. MEOWS and MERC were more sensitive than MEWS or MEWT (67.1 and 67.1% vs. 19% and 40.5%, p < 0.001); however, MEWT and MEWS were more specific (88.6% MEWT and 93.5% MEWS vs. 51.2% MEOWS and 60.2% MERC, p < 0.001). In the control population, 70% of MEWT alerts still appeared "relevant" to the clinical scenario in contrast to the MEOWS (32%) or MERC systems (31%). CONCLUSION: There are limited comparative data regarding how early warning systems perform in an American population for maternal morbidity. None of the systems performs with high sensitivity and specificity. High-volume, high-acuity units may decide that the lower sensitivity of the MEWT is relatively acceptable when considering the high false trigger rate of the other more sensitive systems. In addition, triggers in the MEWT system were more likely to be clinically relevant even in cases that did not have severe morbidity.

Comparison of staples vs subcuticular suture in class III obese women undergoing cesarean: a randomized controlled trial.

BACKGROUND: Obesity is a risk factor for infectious morbidity and wound complications after cesarean delivery. There are currently insufficient data to determine optimal skin closure technique for cesarean delivery, specifically for those women with class III obesity, defined as a body mass index ≥40 kg/m2. OBJECTIVE: We sought to compare stainless steel staples vs subcuticular suture for skin closure for cesarean delivery in class III obese women with body mass index ≥40 kg/m2. STUDY DESIGN: We conducted a randomized controlled trial at 2 teaching hospitals from 2015 through 2016 in which women with body mass index ≥40 kg/m2 undergoing cesarean delivery were randomly assigned to stainless steel staples or subcuticular suture skin closure. The primary outcome was composite wound complication defined as superficial or deep separation and infection occurring up to 6 weeks following delivery. Secondary outcomes included operative time, and patient pain and satisfaction scores. RESULTS: A total of 242 women were enrolled. In all, 119 in the staples group and 119 in the subcuticular suture group were analyzed. Maternal demographics and characteristics were similar in both groups. The composite wound complication frequency was 19.3% in the staples group and 17.6% in the subcuticular suture group (P = .74) with an overall wound complication incidence of 18.5% in the entire study cohort. There were also no differences in the frequencies of infection, or in superficial or deep wound separation between the 2 study groups. In a univariate analysis of predictors of wound complications, only current tobacco use was a significant predictor of wound complications (relative risk, 4.97; 95% confidence interval, 1.37-18.03; P = .02). Fewer women with staple closure would choose the same method with a future delivery (P = .01), however, self-reported pain and concern about wound healing were equal between the 2 groups. CONCLUSION: In class III obese women undergoing cesarean delivery, there was no difference in composite wound outcome up to 6 weeks postpartum between those who had staples and those who had subcuticular suture skin closure.

Measuring severe maternal morbidity: validation of potential measures.

BACKGROUND: Both maternal mortality rate and severe maternal morbidity rate have risen significantly in the United Sates. Recently, the Centers for Disease Control and Prevention introduced International Classification of Diseases, 9th revision, criteria for defining severe maternal morbidity with the use of administrative data sources; however, those criteria have not been validated with the use of chart reviews. OBJECTIVE: The primary aim of the current study was to validate the Centers for Disease Control and Prevention International Classification of Diseases, 9th revision, criteria for the identification of severe maternal morbidity. This analysis initially required the development of a reproducible set of clinical conditions that were judged to be consistent with severe maternal morbidity to be used as the clinical gold standard for validation. Alternative criteria for severe maternal morbidity were also examined. STUDY DESIGN: The 67,468 deliveries that occurred during a 12-month period from 16 participating California hospitals were screened initially for severe maternal morbidity with the presence of any of 4 criteria: (1) Centers for Disease Control and Prevention International Classification of Diseases, 9th revision, diagnosis and procedure codes; (2) prolonged postpartum length of stay (>3 standard deviations beyond the mean length of stay for the California population); (3) any maternal intensive care unit admissions (with the use of hospital billing sources); and (4) the administration of any blood product (with the use of transfusion service data). Complete medical records for all screen-positive cases were examined to determine whether they satisfied the criteria for the clinical gold standard (determined by 4 rounds of a modified Delphi technique). Descriptive and statistical analyses that included area under the receiver operating characteristic curve and C-statistic were performed. RESULTS: The Centers for Disease Control and Prevention International Classification of Diseases, 9th revision, criteria had a reasonably high sensitivity of 0.77 and a positive predictive value of 0.44 with a C-statistic of 0.87. The most important source of false-positive cases were mothers whose only criterion was 1-2 units of blood products. The Centers for Disease Control and Prevention International Classification of Diseases, 9th revision, criteria screen rate ranged from 0.51-2.45% among hospitals. True positive severe maternal morbidity ranged from 0.05-1.13%. When hospitals were grouped by their neonatal intensive care unit level of care, severe maternal morbidity rates were statistically lower at facilities with lower level neonatal intensive care units (P < .0001). CONCLUSION: The Centers for Disease Control and Prevention International Classification of Diseases, 9th revision, criteria can serve as a reasonable administrative metric for measuring severe maternal morbidity at population levels. Caution should be used with the use of these criteria for individual hospitals, because case-mix effects appear to be strong.

Increased 3-gram cefazolin dosing for cesarean delivery prophylaxis in obese women.

OBJECTIVE: The purpose of this study was to determine tissue concentrations of cefazolin after the administration of a 3-g prophylactic dose for cesarean delivery in obese women (body mass index [BMI] >30 kg/m(2)) and to compare these data with data for historic control subjects who received 2-g doses. Acceptable coverage was defined as the ability to reach the minimal inhibitory concentration (MIC) of 8 µg/mL for cefazolin. STUDY DESIGN: We conducted a 2-phase investigation. The current phase is a prospective cohort study of the effects of obesity on tissue concentrations after prophylactic 3-g cefazolin doses at the time of cesarean delivery. Concentration data after 3-g were compared with data for historic control subjects who had received 2-g. Three grams of parenteral cefazolin was given 30-60 minutes before skin incision. Adipose samples were collected at both skin incision and closure. Cefazolin concentrations were determined with the use of a validated high-performance liquid chromatography assay. RESULTS: Twenty-eight obese women were enrolled in the current study; 29 women were enrolled in the historic cohort. BMI had a proportionally inverse relationship on antibiotic concentrations. An increase of the cefazolin dose dampened this effect and improved the probability of reaching the recommended MIC of ≥8 µg/mL. Subjects with a BMI of 30-40 kg/m(2) had a median concentration of 6.5 µg/g (interquartile range [IQR], 4.18-7.18) after receiving 2-g vs 22.4 µg/g (IQR, 20.29-34.36) after receiving 3-g. Women with a BMI of >40 kg/m(2) had a median concentration of 4.7 µg/g (IQR, 3.11-4.97) and 9.6 µg/g (IQR, 7.62-15.82) after receiving 2- and 3-g, respectively. With 2 g of cefazolin, only 20% of the cohort with a BMI of 30-40 kg/m(2) and none of the cohort with a BMI of >40 kg/m(2) reached an MIC of ≥8 µg/mL. With 3-g, all women with a BMI of 30-40 kg/m(2) reached target MIC values; 71% of the women with a BMI of >40 kg/m(2) attained this cutoff. CONCLUSION: Higher adipose concentrations of cefazolin were observed after the administration of an increased prophylactic dose. This concentration-based pharmacology study supports the use of 3 g of cefazolin at the time of cesarean delivery in obese women. Normal and overweight women (BMI <30 kg/m(2)) reach adequate cefazolin concentrations with the standard 2-g dosing.

Murine typhus in a pregnant woman.

BACKGROUND: Murine typhus is a flea-borne disease caused by Rickettsia typhi. Although uncommon in most of the United States, it is endemic in Southern California. Most cases are unrecognized given its nonspecific viral symptoms and rare complications. CASE: A pregnant patient presented with complaints of fever and chills. Physical examination was benign. Laboratory abnormalities included elevated transaminases, proteinuria, and thrombocytopenia. The patient gave a history of exposure to cats and opossums in an area endemic for murine typhus. After empiric treatment with azithromycin, her clinical symptoms and laboratory abnormalities promptly improved. Serologies confirmed acute infection with R. typhi. CONCLUSION: Although the signs and symptoms of murine typhus can mimic other pregnancy-related complications, a high index of suspicion in endemic areas can lead to the correct diagnosis and prompt treatment.

A retrospective review of ampicillin-sulbactam and amoxicillin + clavulanate vs cefazolin/cephalexin and erythromycin in the setting of preterm premature rupture of membranes: maternal and neonatal outcomes.

OBJECTIVE: The purpose of this study was to compare the efficacy and outcomes of 2 different antibiotic regimens that are used to prolong latency in preterm premature rupture of membranes. The primary objective was to determine whether the use of ampicillin-sulbactam/amoxicillin + clavulanate was associated with an increased risk of necrotizing enterocolitis. STUDY DESIGN: A retrospective review of pregnancies that were complicated by preterm premature rupture of membranes from 1999-2006 at 2 institutions was performed. Outcomes were compared between subjects who received parenteral ampicillin-sulbactam followed by oral amoxicillin + clavulanate (protocol A) and subjects who received parenteral cefazolin and erythromycin followed by oral cephalexin and erythromycin (protocol B). RESULTS: There were 147 women who were evaluated; 88 women received protocol A, and 59 women received protocol B. There were no differences in latency period, gestational age at delivery, or route of delivery. The incidence of necrotizing enterocolitis was 8.0% and 10.2% for protocol A and protocol B, respectively (P = .64). CONCLUSION: Ampicillin-sulbactam/amoxicillin + clavulanate was not associated with an increase in neonatal necrotizing enterocolitis. Erythromycin in combination with cefazolin and cephalexin is an effective latency antibiotic regimen.

Bladder prolapse through a patent urachus: fetal and neonatal features.

We report a term male neonate who was born with a large, red, tubular, mucosa-lined umbilical mass containing a patent lumen. Prenatal ultrasonographic screening at 20 to 28 weeks of gestation revealed a large cyst at the umbilicus, communicating with the urinary bladder. The cyst resolved at 32 weeks, and a small solid mass was newly seen on the fetal abdominal wall, inferior to the umbilical cord insertion. At operation, the mass was discovered to be the prolapsed, open, everted dome of the urinary bladder. The dome was resected, and the bladder was repaired in 2 layers after identification of the ureteral orifices. Bladder prolapse through a patent urachus can be predicted by prenatal ultrasound and has a distinct neonatal appearance.

Interpretation of traumatic lumbar punctures: who can go home?

OBJECTIVE: To determine whether a ratio of observed to predicted (O:P) cerebrospinal fluid (CSF) white blood cells (WBCs) after a traumatic lumbar puncture (LP) can be used to predict which patients do not have meningitis and can safely be discharged from the hospital. METHODS: A retrospective medical record review was performed on 2 cohorts of previously healthy children who had received an LP at Children's Memorial Hospital in Chicago, IL. All children were older than 1 month and had a red blood cell (RBC) count in the CSF >500/mm(3). Cohort 1 consisted of children who were examined in 1990 through 1999 and had CSF cultures positive for a bacterial pathogen. Cohort 2 consisted of children who were tested during January through December 1999 and had a CSF culture negative for any bacterial pathogen. Exclusion criteria included patients who received antibiotics within 72 hours before evaluation, patients with a previous neurosurgical procedure or CNS bleed, and patients whose complete blood count was not done within 6 hours of LP. The predicted CSF WBC count was calculated using the formula CSF WBC (predicted) = CSF RBC x (blood WBC/blood RBC). The O:P ratio was obtained by dividing the observed CSF WBC by the predicted CSF WBC. The simple ratio of WBCs to RBCs was also calculated. Sensitivity, specificity, positive predictive value, and negative predictive value were calculated to predict the absence of disease. Receiver operator characteristic curves were generated for the O:P ratio and the WBC:RBC ratio. Continuous variables were analyzed with Mann-Whitney U test. RESULTS: Among the 57 patients who fit all of the study criteria, 12 (21%) had positive CSF cultures for bacterial pathogens. The patients with meningitis were significantly older (median: 7.8 months; range: 1-106 months) than the patients without meningitis (median: 1.3 months; range: 1-139 months). The O:P ratio was significantly lower in the patients without meningitis (median: 0.064; range: 0.000054-1.09) as compared with patients with meningitis (median: 1.26; range: 0.045-4.72). The WBC:RBC ratio was significantly lower in the patients without meningitis (median: 0.001; range: 0-4.46) as compared with patients with meningitis (median: 1.98; range: 0.04-24.45). The specificity and positive predictive value of an O:P ratio

Professional interpreters and bilingual physicians in a pediatric emergency department: effect on resource utilization.

OBJECTIVE: To determine the impact of interpreters and bilingual physicians on emergency department (ED) resource utilization. DESIGN: Cohorts defined by language concordance and interpreter use were prospectively studied preceding and following the availability of dedicated, professional medical interpreters. SETTING: Pediatric ED in Chicago, Ill. PARTICIPANTS: We examined 4146 visits of children (aged 2 months to 10 years) with a presenting temperature of 38.5 degrees C or higher or a complaint of vomiting or diarrhea; 550 families did not speak English. In 170 cases, the treating physician was bilingual. In 239, a professional interpreter was used. In the remaining 141, a professional medical interpreter was unavailable. MAIN OUTCOME MEASURES: Incidence and costs of diagnostic testing, admission rate, use of intravenous hydration, and length of ED visit. RESULTS: Regression models incorporated clinical and demographic factors. Compared with the English-speaking cohort, non-English-speaking cases with bilingual physicians had similar rates of resource utilization. Cases with an interpreter showed no difference in test costs, were least likely to be tested (odds ratio [OR], 0.73; 95% confidence interval [CI], 0.56-0.97), more likely to be admitted (OR, 1.7; 95% CI, 1.1-2.8), and no more likely to receive intravenous fluids, but had longer lengths of visit (+16 minutes; 95% CI, 6.2-26 minutes). The barrier cohort without a professional interpreter had a higher incidence (OR, 1.5; 95% CI, 1.04-2.2) and cost (+$5.78; 95% CI, $0.24-$11.21) for testing and was most likely to be admitted (OR, 2.6; 95% CI, 1.4-4.5) and to receive intravenous hydration (OR, 2.2; 95% CI, 1.2-4.3), but showed no difference in length of visit. CONCLUSION: Decision making was most cautious and expensive when non-English-speaking cases were treated in the absence of a bilingual physician or professional interpreter.