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ABSTRACT: To examine the effect of obesity on maternal and neonatal outcomes in women diagnosed with gestational diabetes mellitus (GDM) and managed with diet only, glyburide, or insulin.
Women with singleton gestations enrolled for outpatient services diagnosed with GDM and without history of pregnancy-related hypertension at enrollment or in a prior pregnancy were identified in a database. Women with GDM controlled by diet only (n = 3918), glyburide (n = 873), or insulin without prior exposure to oral hypoglycemic agents (n = 2229) were included. Pregnancy outcomes were compared for obese versus nonobese women within each treatment group and also compared across treatment groups within the obese and nonobese populations.
Within each treatment group, obesity was associated with higher rates of cesarean delivery, pregnancy-related hypertension, macrosomia, and hyperbilirubinemia (all p < 0.05). Higher rates of pregnancy-related hypertension and hyperbilirubinemia were observed in women receiving glyburide.
Obesity adversely affects pregnancy outcome in women with GDM. Higher rates of pregnancy-related hypertension and hyperbilirubinemia were observed in pregnant women receiving glyburide.
American Journal of Perinatology 05/2012; 29(8):643-8. · 1.32 Impact Factor
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ABSTRACT: Objective: To assess the diagnostic accuracy of vaginal fetal fibronectin (fFN) sampling for predicting preterm birth in asymptomatic women carrying triplet gestations. Methods: An historical cohort of patients carrying triplet gestations between 1998 and 2010 was identified from a single practice by chart review. All patients were screened with fFN testing at 2-3 week intervals from 22 weeks to 32 weeks of gestation. Outcomes evaluated were spontaneous preterm birth prior to 28, 30, and 32 weeks' gestation and delivery within 2 and 3 weeks of testing. Results: There were 56 pregnancies that met criteria for inclusion. For delivery prior to 30 weeks' gestation, the test had a sensitivity of 75%, a specificity of 85.4%, a positive predictive value of 46.2%, a negative predictive value of 95.3%, positive likelihood ratio of 5.13, and a negative likelihood ratio of 0.29 (p < 0.0001). For delivery within 3 weeks of a single fFN assessment, the test had a sensitivity of 53.3%, a specificity of 95.8%, a positive predictive value of 53.3%, a negative predictive value of 95.8%, positive likelihood ratio of 12.7 and negative likelihood ratio of 0.48 (p < 0.0001). Conclusion: Fetal fibronectin testing provides moderate to high prediction of spontaneous preterm birth in triplet gestations.
The journal of maternal-fetal & neonatal medicine: the official journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstetricians 04/2012; 25(10):1921-3. · 1.36 Impact Factor
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Prenatal Diagnosis 12/2011; 31(13):1313. · 2.11 Impact Factor
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ABSTRACT: We examined treatment outcomes in women with severe nausea and vomiting of pregnancy (NVP) receiving outpatient nursing support and either subcutaneous metoclopramide or subcutaneous ondansetron via a microinfusion pump. Among women receiving outpatient nursing services, we identified those diagnosed with severe NVP having a Pregnancy-Unique Quantification of Emesis (PUQE) score of greater than 12 at enrollment and prescribed either metoclopramide (N = 355) or ondansetron (N = 521) by their physician. Maternal characteristics, response to treatment, and start versus stop values were compared between the medication groups. Allocation to group was based on intention-to-treat protocol. Maternal characteristics were similar between the groups. Days to reduction in PUQE score levels were similar (median 2 days, metoclopramide; 3 days, ondansetron; P = 0.206). Alteration from metoclopramide to ondansetron (31.8%) was more frequent than alteration from ondansetron to metoclopramide (4.4%; P < 0.001). Improvement of NVP symptoms and reduced need for hospitalization was noted with both medications. Treatment with either metoclopramide or ondansetron resulted in significant improvement of NVP symptoms with half of women showing a reduction from severe symptoms to moderate or mild symptoms within 3 days of treatment initiation. Alteration in treatment was significantly greater in patients initially prescribed metoclopramide.
American Journal of Perinatology 06/2011; 28(9):715-21. · 1.32 Impact Factor
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ABSTRACT: To examine the impact of maternal obesity on maternal and neonatal outcomes in pregnancies complicated with gestational diabetes mellitus (GDM).
Women with singleton pregnancies and GDM enrolled in an outpatient GDM education, surveillance and management program were identified. Maternal and neonatal pregnancy outcomes were compared for obese (pre-pregnancy BMI ≥ 30 kg/m(2)) and non-obese (pre-pregnancy BMI < 30 kg/m(2)) women and for women across five increasing pre-pregnancy BMI categories.
A total of 3798 patients were identified. Maternal obesity was significantly associated with the need for oral hypoglycemic agents or insulin, development of pregnancy-related hypertension, interventional delivery, and cesarean delivery. Adverse neonatal outcomes were also significantly increased including stillbirth, macrosomia, shoulder dystocia, need for NICU admission, hypoglycemia, and jaundice. When looking across five increasing BMI categories, increasing BMI was significantly associated with the same adverse maternal and neonatal outcomes.
In women with GDM, increasing maternal BMI is significantly associated with worse maternal and neonatal outcomes.
The journal of maternal-fetal & neonatal medicine: the official journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstetricians 03/2011; 24(5):723-7. · 1.36 Impact Factor
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ABSTRACT: The objective of this study is to evaluate neonatal and maternal outcomes of multiple gestations undergoing delayed-interval delivery at a single institution. A 10-year retrospective review of medical records of patients followed by a Maternal-Fetal Medicine practice in a university-based setting was performed. Patients met criteria for inclusion if a single fetus was delivered spontaneously between 16 and 28 weeks of gestation and a planned attempt was made to prolong the gestation for the remaining fetus(es). Nineteen pregnancies met criteria for inclusion. The median gestational age at delivery of the first fetus was 20 (2)/(7) weeks and the last fetus was 25 (1)/(7) weeks. The median latency was 16 days (range 0 to 152 days). Three patients (15.8%) delivered within 24 hours. There was a 15.8% survival rate for the firstborn fetus and a 53.8% survival rate for all retained fetuses (p = 0.01). There was a 31.6% incidence of serious maternal morbidity related to the procedure. One patient required a postpartum hysterectomy due to massive hemorrhage and uterine atony. Delayed-interval delivery is associated with a higher neonatal survival rate when retained fetuses are compared with firstborn fetuses. However, the procedure is associated with a significant risk of serious maternal morbidity.
American Journal of Perinatology 02/2011; 28(2):91-6. · 1.32 Impact Factor
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ABSTRACT: Abstract Background Metastatic colon cancer is one of the leading causes of cancer-related death worldwide, with disease progression and metastatic spread being closely associated with angiogenesis. We investigated whether an antiangiogenic gene transfer approach using the Sleeping Beauty (SB) transposon system could be used to inhibit growth of colorectal tumors metastatic to the liver. Results Liver CT26 tumor-bearing mice were hydrodynamically injected with different doses of a plasmid containing a transposon encoding an angiostatin-endostatin fusion gene (Statin AE) along with varying amounts of SB transposase-encoding plasmid. Animals that were injected with a low dose (10 μg) of Statin AE transposon plasmid showed a significant decrease in tumor formation only when co-injected with SB transposase-encoding plasmid, while for animals injected with a higher dose (25 μg) of Statin AE transposon, co-injection of SB transposase-encoding plasmid did not significantly affect tumor load. For animals injected with 10 μg Statin AE transposon plasmid, the number of tumor nodules was inversely proportional to the amount of co-injected SB plasmid. Suppression of metastases was further evident in histological analyses, in which untreated animals showed higher levels of tumor cell proliferation and tumor vascularization than animals treated with low dose transposon plasmid. Conclusion These results demonstrate that hepatic colorectal metastases can be reduced using antiangiogenic transposons, and provide evidence for the importance of the transposition process in mediating suppression of these tumors.
Molecular Cancer. 01/2011;
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ABSTRACT: Salmonella enterica serovar Typhimurium preferentially colonizes tumors in vivo and has proven to be an effective biologic vector. The attenuated S. enterica Typhimurium strain chi4550 was engineered to express truncated human interleukin-2 and renamed SalpIL2. Previously, we observed that a single oral administration of SalpIL2 reduced tumor number and volume, while significantly increasing local and systemic natural killer (NK) cell populations in an experimental metastasis model. Here we report that in nontumor-bearing mice, a single oral dose of SalpIL2 resulted in increased splenic cytotoxic T and NK cell populations that returned to control levels by 4 weeks post oral administration. Though SalpIL2 was detected in mouse tissues for up to 10 weeks, no prolonged alterations in peripheral blood serum chemistry or complete blood cell counts were observed. Similarly, comparative histopathological analysis of tissues revealed no significant increase in pyogranulomas in SalpIL2-treated animals with respect to saline controls. In Rag-1 knockout mice, which have severely impaired B and T cell function, SalpIL2 reduced growth of hepatic metastases. Furthermore, SalpIL2 altered expression of several proinflammatory cytokines and chemokines in the serum of mice with pulmonary osteosarcoma metastases. These data further suggest that SalpIL2 is avirulent and induces a cell-mediated antitumor response.
Biologics: Targets & Therapy 01/2010; 4:61-73.
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ABSTRACT: To investigate outcomes of twin gestations with advanced maternal age (AMA).
Historical cohort of twin gestations cared for by a maternal-fetal medicine faculty practice. Outcomes of patients with AMA (70) and non-AMA (75) were compared. AMA was defined as age > or =35. Analysis including mode of delivery, gestational age at delivery and overall complications was performed. Significance was determined using the chi-square test or the Student's t-test.
The Cesarean rate for AMA was significantly greater compared to non-AMA (80.0% vs. 54.7%; p = 0.001). The main reason for the increased rate was uterine dysfunction. The mean gestational age at delivery for AMA was significantly greater than for non-AMA (36.7 weeks vs. 35.4 weeks; p = 0.02). There were no differences in rates of other adverse outcomes including gestational hypertension, pre-eclampsia, gestational diabetes, suspected fetal growth restriction, preterm birth, low birth weight or low birth weight percentiles. This remained true when we compared the 32 women ages > or =40 years to 118 women ages <40 years.
Among twin pregnancies, AMA women are not at an increased risk of adverse pregnancy outcomes, aside from an increased rate of cesarean delivery.
The journal of maternal-fetal & neonatal medicine: the official journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstetricians 06/2009; 22(7):593-6. · 1.36 Impact Factor
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ABSTRACT: Idiopathic chronic childhood constipation (ICCC) includes children who are severely constipated and who are resistant to behavioral or medical treatments. These children are distinguished from those with Hirschsprung's disease (HSCR) by the presence of enteric ganglia in rectal biopsy specimens. We investigated potential autonomic dysfunction by examining nerves in rectal mucosa.
Immunostaining, confocal microscopy, and nerve analysis were performed on formalin-fixed and on Zamboni-fixed rectal biopsy specimens from children who were severely constipated. A computer-assisted neuron tracing technique was used to determine mucosal nerve density in Zamboni-fixed biopsy sections.
Nerves in Zamboni-fixed biopsy specimens were better stained than in formalin-fixed biopsy specimens. Regardless of fixation method, a deficiency of mucosal nerves was observed in ICCC when compared to children who are not constipated. Analysis of autotraced mucosal nerves confirmed the deficiency in ICCC biopsy specimens. Mucosal nerves were also severely deficient in patients with HSCR, even in transitional segments that contained ganglia.
Most patients with ICCC had decreased innervation of the rectal mucosa. Because mucosal nerves are critical for the peristaltic reflex, water secretion, and absorption, their deficiency can be related to patient constipation. Mucosal nerve density provides a pathologic basis for diagnosis of dysfunction in children who do not have HSCR but are chronically constipated. The study validates the neuron tracing method for objective evaluation of mucosal innervation.
Journal of Pediatric Surgery 05/2009; 44(4):773-82. · 1.45 Impact Factor
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ABSTRACT: We investigated whether abnormal concentrations of first-trimester free-beta subunit human chorionic gonadotropin (fsshCG) and pregnancy-associated plasma protein A (PAPP-A) are associated with preterm delivery in twin gestations. This was a hospital-based, retrospective study of 70 twin gestations between 11 (1)/ (7) and 13 (6)/ (7) weeks' gestation undergoing first-trimester screening. Free betahCG and PAPP-A multiples of the median were determined by our laboratory standards. Odds ratios (ORs) were estimated that compared the prevalence of very preterm (< 32 weeks), preterm (> or = 32 and < 37 weeks), and term birth (> or = 37 weeks) between the lower and higher percentile groups for each analyte. FsshCG levels < or = 25th percentile were associated with very preterm birth < 32 weeks' gestation (OR 5.10; 95% confidence interval [CI]: 1.19 to 21.95), but not with preterm birth > or = 32 and < 37 weeks' gestation (OR 0.50; 95% CI: 0.16 to 1.61). PAPP-A was not associated with very preterm (OR 2.95; 95% CI: 0.69 to 12.60) or preterm birth (OR 0.71; 95% CI: 0.23 to 2.21). Low first-trimester fsshCG was a strong predictor for very preterm birth in twin gestations. Low first-trimester PAPP-A was associated with a trend in increased risk of very preterm birth.
American Journal of Perinatology 04/2009; 26(7):491-4. · 1.32 Impact Factor
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ABSTRACT: Complications from previously published techniques for laparoscopic gastrostomy tube placement include skin pressure necrosis and extraluminal migration. We developed a modified technique utilizing subcutaneous stay-sutures in order to minimize such complications. This study aimed to identify, quantify, and characterize complications of the modified procedure.
Charts were reviewed of all pediatric patients undergoing laparoscopic gastrostomy tube placement over 79 months. Complications requiring reoperation, readmission, or outpatient treatment were identified and classified as major or minor.
Laparoscopic gastrostomy tubes were placed via modified procedure in 82 patients. Two (2.44%) high-risk patients with significant comorbidities were readmitted for wound infections, two (2.44%) received outpatient antibiotics for cellulitis, and three (3.66%) developed stitch abscesses which resolved with local care. None of the patients had initial intraperitoneal placement, intraperitoneal location upon tube replacement, extraluminal migration, tube-related pressure necrosis, or procedure-related death.
Subcutaneous placement of absorbable stay-sutures for laparoscopic gastrostomy tubes offers significant benefits. We eliminated complications associated with presence of external sutures, as well as those associated with early suture removal. This modified technique avoids additional visits for suture removal, avoids pressure necrosis from external stay-sutures, and provides improved adherence of stomach to abdominal wall, thereby preventing extraluminal migration and intraperitoneal tube replacement.
Pediatric Surgery International 03/2009; 25(4):349-53. · 1.25 Impact Factor
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ABSTRACT: We evaluated outcomes following tocolysis discontinuation in singleton pregnancies between 33.0 and 36.9 weeks' gestation. We performed a retrospective analysis of singleton pregnancies prescribed continuous subcutaneous terbutaline tocolysis. Patients without indicated preterm delivery discontinuing treatment between 33.0 and 36.9 weeks were evaluated ( N = 4253). Data were grouped by week at treatment discontinuation. Outcomes were compared for each week. Approximately 55% (2316/4253) delivered preterm (< 37 weeks). After treatment discontinuation, 58.1% (2472/4253) of patients delivered within 7 days and 41.2% (1752/4253) within 3 days. Median number of days from discontinuation to delivery was 5 (range, 0 to 65). Incidence of low birth weight (< or = 2500 g), neonatal intensive care unit admissions, days in nursery, and estimated charges decreased with each additional week of tocolysis (all P < 0.05, adjusted for multiple comparisons). Tocolysis discontinuation prior to term is associated with late-preterm birth, adverse neonatal outcomes, and increased estimated health care costs.
American Journal of Perinatology 01/2009; 26(5):351-5. · 1.32 Impact Factor
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ABSTRACT: Patients with multiple gestations, low-lying placentas, velamentous cord insertions, and history of assisted conception should be evaluated carefully for a vasa previa. Serial surveillance for signs of preterm labor and elective cesarean delivery at 34 to 35 weeks after corticosteroids for fetal lung maturity is a reasonable management strategy for vasa previa in multiple gestations.
American Journal of Perinatology 11/2008; 25(9):587-9. · 1.32 Impact Factor
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ABSTRACT: The purpose of this study was to evaluate the Down syndrome detection rate at a 5% screen positive rate in first-trimester screening for twins.
This was a retrospective study from August 2005 to July 2007 of twins who underwent first-trimester screening with nuchal translucency, nasal bone, pregnancy-associated plasma protein-A, and free beta-hCG. Risks were calculated on the basis of the Fetal Medicine Foundation twin algorithm. The model simulated distributions of unaffected and affected cases at 12 weeks of gestation.
Two thousand ninety-four twin pregnancies (4188 fetuses) met the inclusion criteria. The addition of nasal bone to nuchal translucency, pregnancy-associated plasma protein-A, and free beta-hCG increased the Down syndrome detection rate from 79-89% at a 5% screen-positive rate.
In twins, first-trimester screening with nasal bone is valuable. The improved Down syndrome detection rate can help these high-risk patients with the decision-making process of whether to pursue invasive testing with its associated pregnancy loss risk.
American journal of obstetrics and gynecology 10/2008; 199(3):283.e1-3. · 3.28 Impact Factor
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ABSTRACT: The purpose of this study was to describe the successful management of a recurrent cervical pregnancy with local injection and to review similarly treated cases to determine adverse outcomes.
A case of a recurrent cervical pregnancy treated with transvaginal local injection was reported. A MEDLINE English language search identified 90 cases of cervical pregnancy treated with local therapy. This literature was analyzed with regard to the various demographic and outcome variables described.
Successful use of the transvaginal local approach is described. A review of cases identified a mean maternal age of 33.6 years with a mean gestational age at diagnosis of 7.5 weeks. Bleeding was the most common presenting sign (79%). The mean beta-human chorionic gonadotropin level at the time of diagnosis was 27,798 IU with an average time to resolution of 7.5 weeks. The most common risk factor was a history of curettage (69%), followed by previous cesarean delivery (35%). An additional dose of methotrexate was needed in 6% of cases. Bleeding requiring alternate procedures was present in 5% of cases. There were no complications in 81% of cases. The need for transfusion and development of infection were seen in 3% of cases each. There was 1 case (1.1%) requiring hysterectomy, and no maternal deaths were reported.
Conservative management of cervical pregnancy using local injection has been reported to have a low complication rate and a high efficacy for cure.
Journal of ultrasound in medicine: official journal of the American Institute of Ultrasound in Medicine 08/2007; 26(7):959-65. · 1.25 Impact Factor
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ABSTRACT: Diagnostic peritoneal lavage (DPL) is a technique designed to sample the peritoneal cavity for evidence of catastrophic pathology, while incurring minimum risk. The authors describe two unstable pediatric patients, one with acute lymphoblastic leukemia and shock and one with Fanconi anemia on high-frequency oscillation after stem cell transplantation, both presumed to have intra-abdominal perforation. DPL was uneventfully performed at the bedside in both patients. The authors suggest DPL be considered as an alternative to laparotomy in critically ill pediatric oncology and stem cell transplantation patients.
Journal of Pediatric Hematology/Oncology 01/2005; 26(12):824-6. · 1.16 Impact Factor
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ABSTRACT: The purpose of this study was to assess the validity of vaginal fetal fibronectin as a screening test for spontaneous preterm birth in patients with cervical cerclage.
A historic cohort of 117 patients who underwent cervical cerclage placement between 1996 and 2002 were identified. All patients were followed up in a maternal-fetal medicine faculty practice in a university setting. Serial fetal fibronectin samples of vaginal secretions were collected every 2 to 3 weeks, starting at 22 weeks of gestation and continuing until 32 weeks or delivery, whichever came first.
There were 81 singleton, 23 twin, 12 triplet, and 1 quadruplet pregnancies. There were 61 ultrasound-indicated, 47 prophylactic, and 9 emergency cerclages that were placed. Most cerclages were of the modified Shirodkar type (95%) with a median gestational age at cerclage placement of 16.6 weeks. Overall, 33.3% of gestations were delivered spontaneously before 37 weeks of gestation; 17.1% of gestations were delivered spontaneously before 34 weeks. For deliveries within 2 weeks and 3 weeks of a single fetal fibronectin assessment, the test had a sensitivity of 50% and 48.3%, a specificity of 90% and 91.1%, a positive predictive value of 16.3% and 28.6%, and a negative predictive value of 97.9% and 96%, respectively. Subgroup analysis by number of fetuses (singleton, twin, and higher order multiple gestations) revealed similar values. For delivery before 34 weeks of gestation, fetal fibronectin had a sensitivity of 50%, a specificity of 78.4%, a positive predictive value of 33.3%, and a negative predictive value of 88%.
This study is the first to evaluate the use of vaginal fetal fibronectin assessments to screen for preterm birth in patients who had undergone cervical cerclage procedures. We conclude that this test has similar validity to predict spontaneous preterm delivery in these high-risk pregnancies, as in previously published cohorts.
American Journal of Obstetrics and Gynecology 12/2003; 189(5):1368-73. · 3.47 Impact Factor
