Safety, efficacy and pharmacokinetics of vedolizumab in patients with simultaneous exposure to an anti-tumour necrosis factor.

BACKGROUND: Data on combination-biologic treatment in (IBD) are still scant. AIM: To explore outcomes of patients co-exposed to anti-TNF and vedolizumab. METHODS: Patients starting vedolizumab having measurable anti-TNF levels after recently stopping adalimumab/infliximab ('VDZ-aTNF' group), were compared with control vedolizumab patients in a retrospective 1:2 matched case-control study. RESULTS: Seventy-five patients were included (25 VDZ-aTNF, 50 VDZ). Adverse events were experienced by 9/25 VDZ-aTNF compared to 13/50 VDZ patients (P = 0.4, follow-up 14 weeks in all). Week 14 clinical remission was attained in 10/25 (40%) of VDZ-aTNF patients versus 23/50 (46%) of VDZ patients (OR = 0.8, 95% CI 0.3-2.1, P = 0.6) and clinical response in 19/25 (76%) versus 39/50 (78%) respectively (OR = 0.9, 95% CI 0.3-2.7, P = 0.8). Corticosteroid-free remission and corticosteroid-free response were experienced by 30% and 54%, respectively, of the entire cohort, and were similar between the two groups. Vedolizumab drug concentrations at week 2, 6 and 14 were similar among VDZ-aTNF and VDZ patients (P > 0.5). Multi-variable analysis showed independent association of some vedolizumab drug-levels time-points with baseline albumin and weight, but not with anti-TNF co-exposure. In a prospective study of a separate cohort of patients starting infliximab (n = 12), the percentage of α4ß7+ memory T cells, slightly but nonsignificantly increased throughout weeks 0, 2 to 14 (26 ± 2.3%, 27.8 ± 2.9%, 29.5 ± 2.6% respectively, P = 0.06). CONCLUSIONS: Vedolizumab/anti-TNF co-exposure did not generate new safety signals during 14-weeks induction, nor did it reduce efficacy or alter vedolizumab pharmacokinetics. These observations may aid the design of future co-biologics trials and also suggest that a deliberate waiting-interval between anti-TNF cessation and subsequent vedolizumab initiation may not be warranted.

Non-fermentative Gram-negative rods bacteremia in children with cancer: a 14-year single-center experience.

PURPOSE: Data on non-fermentative Gram-negative rods (NFGNR) bacteremia in children with malignancies are limited. The aim of this study was to present clinical picture, antimicrobial susceptibility pattern, risk factors for resistance and outcome in NFGNR bacteremia in children with cancer. METHODS: All episodes of NFGNR bacteremia occurring during 2001-2014 in children with cancer in a tertiary-care hospital were retrospectively analyzed. Pseudomonas and Acinetobacter spp. resistant to three or more antibiotic classes and all Stenotrophomonas maltophilia (SM) were defined as multidrug-resistant bacteria (MDR). RESULTS: A total of 80 children (44 males, 0.8-18 years, median 5 years) developed 107 episodes (116 pathogens) of NFGNR bacteremia; Pseudomonas aeruginosa (PA) (51; 43.9%), Acinetobacter baumannii (AB) (21, 18.1%), SM (18, 15.5%); and others (27, 25.2%). The rate of NFGNR bacteremia in children with certain solid tumors (e.g. sarcoma, 12/134 (9.0%)) was comparable to that of hematological malignancies (52/429 (12.2%). Focal infection and septic shock occurred in 16 (14.9%) and four (3.7%) episodes, respectively. Thirty (25.8%) of 116 NFGNR were MDR. The most significant predictors of bacteremia with MDR PA or AB were severe neutropenia (<100 cells/mm3; OR 7.8, p = 0.002), hospital-acquired (OR 16.9, p < 0.0001) and breakthrough (OR 11.2, p < 0.0001) infection. Infection with MDR bacteria was associated with inappropriate empirical therapy. The 30-day mortality was 3/107 (2.8%), all in neutropenic patients with hematological malignancies. CONCLUSIONS: NFGNR bacteremia can present with nonspecific signs or symptoms. MDR NFGNRs are common and compromise treatment options, but mortality is relatively low. Knowledge of local epidemiology, pattern and risk factors for resistance is important to guide empirical therapy.

Acute Bartholin's abscess: microbial spectrum, patient characteristics, clinical manifestation, and surgical outcomes.

The purpose of this investigation was to evaluate the patient characteristics, clinical manifestations, microbiology, and modes of treatment of a large cohort of women with acute Bartholin's abscess, from a single medical center. A retrospective study was undertaken of all women diagnosed with acute Bartholin's gland abscess who were admitted to the gynecology department in a university-affiliated tertiary hospital in central Israel from January 2004 to December 2013. A total of 267 women were included in the study. The mean age at diagnosis was 33.5 ± 12.1 years and the mean hospitalization period was 1.4 ± 0.9 days. Pain presented in 152 (56.9 %), swelling in 81 (30.3 %), and fever in 34 (12.7 %). Leukocytosis was detected in 149 (55.8 %). The three main treatment modalities were: antibiotics (75.7 %), abscess drainage (19.1 %), and marsupialization (80.9 %). Bacterial infections were detected in 154 (57.7 %) cultures, Escherichia coli presented in 59 (22.1 %), and Streptococcus species in 27 (10.1 %). The clinical and patient characteristics were similar between women with bacterial and sterile Bartholin's abscesses, though leukocytosis was more prevalent among women with bacterial infections. E. coli was the single most frequent pathogen in cultures of acute Bartholin's abscess. Respiratory tract-associated organisms were also common. This study indicates the polymicrobial spectrum of acute Bartholin's abscess.

Robotic blue-dye sentinel lymph node detection for endometrial cancer - Factors predicting successful mapping.

OBJECTIVE: Sentinel lymph node (SLN) mapping has emerged as a viable option for the treatment of patients with endometrial cancer. We report our initial experience with SLN mapping algorithm, and examine the factors predicting successful SLN mapping. METHODS: We analyzed all data recorded in our institute on robotic blue-dye SLN detection mapping from the time it was first introduced to our department in January 2012-December 2014. Data included patient demographics, SLN allocation, operating room times, and pathology results. RESULTS: During the study period, 74 patients had robotic assisted surgery for endometrial cancer with attempted SLN mapping. SLN was found overall in 46 patients (62.1%). At first, SLN was detected in only 50% of cases, but after performing 30 cases, detection rates rose to 84.6% (OR = 3.34, CI 1.28-8.71; p = 0.003). Univariate analysis showed a higher detection rate with methylene blue than patent blue dye, 74.3% vs. 52.3% (OR = 2.744, 95% CI 1.026-7.344; p = 0.042). In multivariate analysis, high body mass index (BMI) was associated with failed mapping (OR = 0.899; 95% CI 0.808-1.00), as was the presence of lymph-vascular space invasion (LVSI) (OR = 0.126; 95% CI 0.24-0.658) and few cases per surgeon (OR = 1.083, 95% CI 1.032-1.118). Factors related to uterine pathology itself, including tumor histology, grade, method of diagnosis, the presence of an endometrial polyp, and lower uterine segment involvement were not found to be associated with successful mapping. CONCLUSIONS: Surgeon experience, BMI and LVSI may affect the success rate of SLN mapping for endometrial cancer. These factors should be investigated further in future studies.

Risk factors for recurrence after Le Fort colpocleisis for severe pelvic organ prolapse in elderly women.

INTRODUCTION: We investigated parameters associated with recurrence after partial (Le Fort) colpocleisis surgery for severe pelvic organ prolapse (POP) in elderly women. METHODS: A retrospective cohort study included all women who underwent partial colpocleisis in a single tertiary center from February 2007 through July 2013 for stage 3 or 4 triple compartment prolapse. Inclusion criteria were age over 60, sexually inactive, medical comorbidities, increased risk for comprehensive reconstructive pelvic surgery, and refusal or failure to use a pessary as a conservative non-surgical treatment. Exclusion criteria were post-menopausal bleeding, pelvic malignancy, and the desire to preserve coital function. RESULTS: The study group included 47 women of mean age 77.3 ± 8.2 (range 61-91 years). All had medical comorbidities. Fourteen patients (29.8%) had undergone previous hysterectomy. All patients underwent partial colpocleisis and perineorrhaphy. Seven women (14.9%) underwent mid-urethral sling for urinary incontinence. Mean follow-up was 14.8 ± 10.3 months (range, 2-37 months) and mean hospitalization, 3.5 ± 1.5 days (range, 2-9 days). There were no intraoperative complications. Postoperative complications comprised lower urinary tract infection (n = 2). Objective cure (according to vaginal examination) was 80.9% (38/47), and subjective (according to symptoms), 91.5% (43/47). No patient regretted the loss of sexual function. The main reasons for prolapse recurrence were statistically significant longer post-operative vaginal length and wider genital hiatus. CONCLUSIONS: Objective and subjective cure rates of Le Fort colpocleisis for the treatment of severe POP were high with low morbidity. Parameters associated with prolapse recurrence were longer postoperative vaginal length and wider genital hiatus.

Electrochemical determination of low levels of uranyl by a vibrating gold microelectrode.

In this work we report the sensitive electroanalytical detection of uranium(VI) in aqueous solutions. Uranium commonly exists in aqueous solutions in the form of its oxo ion, uranyl (U(VI)O2(2+)). The detection of uranyl has been accomplished by us through its deposition upon reduction by two electrons to the insoluble UO2 using a bare disk gold macroelectrode and anodic stripping voltammetry (ASV). This gave an unsatisfactory detection limit of ca. 1 × 10(-5) M uranyl. Moreover, the evolution of hydrogen bubbles blocked the electrode surface as a result of water reduction at negative deposition potential (-0.7 V vs Ag/AgCl). The application of a 25 µm diameter Au microwire electrode on which UO2 precipitated at negative potential (-1.2 V) improved substantially the detection limit. Further improvement was accomplished by vibrating the microwire working electrode, which increased the amounts of UO2 deposition due to decreasing the diffusion layer. The effect of the vibrating amplitude and frequency on the electroanalytical response was studied and optimized. Eventually, a detection limit of ca. 1 × 10(-9) M uranyl was achieved using a 5 min deposition time, -1.2 V deposition potential, and vibrating the electrode at frequency of 250 Hz and amplitude of 6 V.

Enhanced spontaneous backscattering in Brillouin dynamic gratings.

Spontaneous Brillouin backscattering, which accompanies the operation of Brillouin dynamic gratings (BDGs) setups, is investigated both theoretically and experimentally. It is shown that this noisy emission, which cannot be separated from the signal of interest, contains not only the probe spontaneous Brillouin backscattering but also a significant contribution from the spontaneous/stimulated acoustic field, originating from the high-frequency writing pump. In the absence of the low-frequency writing pump and for a strong enough high-frequency writing pump, the observed Stokes noise can exhibit an average backscattered power much higher than that from the probe alone.

Disrupted abdominal laparotomy wounds in gynaecologic oncology patients: benefits of active surgical re-closure.

OBJECTIVE: To assess the outcome of active management of disrupted wounds through surgical approximation and re-closure. METHOD: A prospective, non-comparative study, on all consecutive patients with disrupted laparotomy wounds treated at a tertiary medical centre, from November 2009 to December 2011. Data on patient demographics, diagnosis, type of abdominal incision, initial closure technique, infections and results of secondary re-closure were collected from the medical files. All patients underwent bedside closure with an en bloc mass suture mattress technique, performed by two attending gynaecologic oncologists. RESULTS: Of 197 patients who underwent abdominal laparotomy during the study period, 31 (16%) had a disrupted wound. Following surgical re-closure, 26 wounds (84%) were completely healed or needed only minor additional care by follow up on day 10. Five wounds (16%) failed primary management and required re-suturing; all subsequently healed. There were no long-term complications. CONCLUSION: Active surgical re-closure of disrupted abdominal laparotomy wounds is safe and effective in patients after treatment surgically for Müllerian malignancies.

Emergency service in an ambulatory outpatient women's health centre.

In order to optimise the service for patients who require an emergency service, and to meet patient needs, we conducted a study in Shillo ambulatory outpatient women's health centre, affiliated to Rabin Medical Center and Tel Aviv University. The study population consisted of 512 women, aged 25 - 55 years, attending the centre for emergency consultation and urgent obstetrics and gynaecological day care. Before the doctor's visit and at the end of the session, the women were asked to complete a 20-item questionnaire survey. The most common complaints were related to pregnancy complications (29%). Significant improvement in their problems was reported by almost 70% of these women; 20% thought that the information they received was inadequate or unsatisfactory. Less than 10% were referred to the hospital for further care such as surgery. Most of the women (96%) reported that they would continue to use these emergency services in the future if needed. There was a statistically significant difference between the doctors' opinion and the nurse regarding the urgency and severity of the patients' problems. The nurses graded them lower than did the doctors. There was also a statistically significant difference between patients' opinion and the nurses and the doctors regarding the urgency and severity of the patients' problems. The patients graded the problems as more urgent and more severe than the nurses or doctors. We concluded that an ambulatory emergency service is an essential part of an ideal ambulatory womens' health centre but it requires substantial progress to meet the patients' needs.

Decreased immune response to hepatitis B eight years after routine vaccination in Israel.

BACKGROUND AND AIM: Although immunization of infants against hepatitis B virus (HBV) is the most effective way to prevent infection, duration of the afforded protection is unknown. Titers of anti-HBV antibodies decline with time, especially during the first few years after vaccination. Anti-HBV antibody levels were measured in the serum of vaccinated children in order to determine the duration of the response afforded by the primary course of HBV vaccine. METHODS: The immunity derived from the HBV vaccine was assessed by measuring antibody levels in 122 healthy children who were vaccinated in a routine vaccination program in Israel. RESULTS: Ninety-four children (77.1%) had detectable antibodies levels (HBsAb titer > or = 10 mIU/ml): 59 (48.4%) of the children had high antibodies levels (HBsAb titer > 100 mIU/ml). Twenty-eight children (22.9%) had undetectable antibodies levels (HBsAb titer < 10 mIU/ml). When the children were divided into three groups according to the time elapsed since vaccination, it was found that the antibody levels declined with time (p < 0.009). Most of the children with undetectable antibody levels belonged to the 5 to 8-y post-vaccination group (36.1% vs 20% and 14.6% for the 2.5 to 5-y and 1 to 2.5-y groups, respectively, p < 0.01). The mean HBsAb declined in relation to the length of time post-vaccination (226.9 +/- 248.2 mIU/ml for 1-2.5 y post-vaccination, 199.0 +/- 235.7 mIU/ml for 2.5-5 y and 90.4 +/- 138.5 for 5-8 y, p < 0.05). No correlation was found between HBsAb titers and gestational age, birthweight and parental origin, although females generated higher mean antibody levels than males (207.3 +/- 217 mIU/ml vs 141.9 +/- 218.9 mIU/ml, p < 0.05). CONCLUSION: Our data demonstrate a steady decline in anti-HBV titers over time after routine vaccination against HBV in Israel. The most significant decline occurred 5-8 y post-vaccination.

Strict glycemic control in diabetic pregnancy-implications for second-trimester screening for Down syndrome.

OBJECTIVES: Studies in the early 1990s showed that the normal levels of the biochemical markers used to screen for Down syndrome in the second trimester of pregnancy differ between healthy women and women with insulin-dependent diabetes mellitus (IDDM). Thereafter, most laboratories adopted correcting factors to adjust for these differences. However, the current validity of these factors in light of the recent improvements in glycemic control in diabetic pregnancy has not been investigated. METHODS: The sample consisted of 35 pregnant women with strictly controlled IDDM and 40 healthy controls matched for age and gestational week. All women had singleton pregnancies and were followed till delivery. RESULTS: Comparison of the triple test results between the two groups after adjustment with the traditional corrective factors yielded no significant differences in serum levels of any of the markers (unconjugated estriol, human chorionic gonadotrophin, alpha-fetoprotein). CONCLUSIONS: These results suggest that the recent improvement in glycemic control of pregnant women with IDDM changes the metabolic milieu that might cause the biochemical differences with healthy pregnant patients.

Cervical length evaluation by transvaginal sonography in nongravid women with a history of preterm delivery.

OBJECTIVE: To evaluate cervical length in the nongravid period in women with a past history of preterm delivery. METHODS: The study population comprised 54 women who had delivered spontaneously before 34 weeks of gestation. Etiology of preterm delivery was suspected to be related to cervical incompetence, defined as a painless and progressive dilatation of the cervix in the absence of other causes. Patients with pre-eclampsia, intrauterine growth restriction, uterine anomalies, fetal anomalies, multiple gestation and similar complications were excluded. Shortening of the cervix was recorded during pregnancy in all study patients. One hundred and four women matched for age, parity and body mass index who had given birth at term served as the control group. Cervical length was evaluated in all women at least 12 weeks after delivery by transvaginal sonography in the mid-sagittal plane. RESULTS: The mean gestational age at delivery was 30.8 +/- 1.2 weeks in the study group and 38.8 +/- 2.1 weeks in the control group (P = 0.03). The mean cervical length in the two groups was 36 +/- 6 and 38 +/- 4 mm, respectively. This difference was not statistically significant (P = 0.9). CONCLUSIONS: In nongravid women with unexplained preterm delivery there is no difference in cervical length compared to patients who deliver at term. Shortening of the cervix is most probably a reversible phenomenon that occurs during pregnancy and represents a failure of the competence mechanism to adapt to pregnancy.

Heparin and low-molecular-weight heparin (enoxaparin) significantly ameliorate experimental colitis in rats.

BACKGROUND AND AIMS: The anticoagulants, unfractionated heparin and low-molecular-weight heparin, demonstrated anti-inflammatory effects in animal models and in humans. Because of its dual effects, high-dose heparin was proposed as a therapeutic modality for ulcerative colitis. We investigated whether a low dose of low-molecular-weight heparin-enoxaparin (Clexane, Rhône-Poulenc Rorer, France)-ameliorates the inflammatory response in two models of experimental colitis. METHODS: Colitis was induced in rats by intrarectal administration of dinitrobenzene sulphonic acid. Enoxaparin (40, 80 and 200 microg/kg) or unfractionated heparin (100, 200 and 400 U/kg) were administered subcutaneously immediately after the induction of damage. Enoxaparin, 80 microg/kg, was also administered after induction of colitis by intrarectal administration of iodoacetamide. Rats were sacrificed 1, 3 or 7 days after induction of injury. Colonic damage was assessed macroscopically and histologically. Mucosal prostaglandin E2 generation, myeloperoxidase and nitric oxide synthase activities and tumour necrosis factor-alpha levels in blood were determined. RESULTS: Enoxaparin and heparin significantly ameliorated the severity of dinitrobenzene sulphonic acid- and iodoacetamide-induced colitis as demonstrated by a decrease in mucosal lesion area, colonic weight and mucosal myeloperoxidase and nitric oxide synthase activities. The dose-response curve had a bell-shaped configuration: enoxaparin, 80 microg/kg, and unfractionated heparin, 200 U/kg, were the optimal doses. CONCLUSIONS: Low-dose enoxaparin and unfractionated heparin ameliorate the severity of experimental colitis. This effect is related to their anti-inflammatory rather than anticoagulant properties.

Pregnancy outcome in women with primary renal disease.

BACKGROUND: The preconception and intraconception parameters that are relevant to outcome in women with underlying renal disease remain controversial. OBJECTIVES: To analyze the types and frequencies of short- and long-term (2 years after delivery) maternal and neonatal complications in 38 patients with primary renal disease (46 pregnancies), most of them with mild renal insufficiency. METHODS: Logistic regression models were formulated to predict successful outcome. RESULTS: Successful pregnancy outcome (live, healthy infant without severe handicap 2 years after delivery) was observed in 98% of the patients with primary renal disease. Factors found to be significantly predictive of successful outcome were absence of pre-existing hypertension, in addition to low preconception serum uric acid level. CONCLUSIONS: Most women with primary renal disease who receive proper prenatal care have a successful pregnancy outcome. Worse pregnancy outcome was observed in women with moderate or severe renal failure. Fitted logistic models may provide useful guidelines for counseling women with preexisting renal disease about their prospects for a successful pregnancy in terms of immediate and long-term maternal and neonatal outcome.

Evaluation of low serum vitamin B(12) in the non-anaemic pregnant patient.

Low serum vitamin B(12) concentrations in pregnancy may not indicate true megaloblastic anaemia. In the present study we compared biochemical indices of vitamin B(12) deficiency (serum homocysteine and urine methylmalonic acid) in non-anaemic pregnant women with and without low serum vitamin B(12) concentrations. The groups were matched for age, parity and gestational age. No differences were found, and all values were within normal range. These results suggest that the measurement of low serum B(12) concentrations in pregnant women should be followed by analysis at the biochemical level before vitamin B(12) injections are started.

Twinning project: Israel and Georgia--the birth of a diabetes-in-pregnancy centre in Georgia.

AIMS: To determine the effectiveness of a joint Israeli-Georgian twinning project aimed at introducing modern methods of perinatal care to Georgian women with pregestational diabetes mellitus. METHODS: A Diabetes-in-Pregnancy Centre was established in Georgia (in the former USSR). Thirty-two women with Type 1 diabetes mellitus participated in the first stage of the study (January 1997-June 1998). All were maintained under strict metabolic surveillance starting at least three months prior to conception and were given organized instruction in methods of self-monitoring of glucose levels, insulin dose adjustment, dietary management and close fetal surveillance throughout pregnancy. A second stage of the project was started in January 1998 and aimed at the diagnosis of gestational diabetes mellitus (GDM). RESULTS: Of the 32 women, 20 had had a total of 44 prior pregnancies without proper perinatal care (1990-96); only five (11.3%) ended in the birth of a healthy infant. On entry to the study, all 32 patients had unsatisfactory metabolic indices. HbA1c levels decreased significantly from the preconception period (P<0.001) and were maintained at the lower level throughout pregnancy; insulin doses decreased significantly until the third trimester (P<0.01) and then increased (P<0.001). Since January 1997, 21 women have become pregnant. Eighteen have given birth, 12 (67%) by Caesarean section and six (33%) by vaginal delivery. Gestational age at birth was 36-39 weeks, and birth weight ranged from 2300 to 4100 g. The only neonatal complications were mild respiratory distress syndrome and hypoglycaemia. There were no significant maternal complications in the 236 women screened, eight were diagnosed as having GDM and 12 impaired glucose tolerance. They were actively managed to a successful outcome. CONCLUSIONS: The establishment of the Diabetes-in-Pregnancy Centre in the Republic of Georgia has significantly reduced the prior high pre-programme perinatal morbidity and mortality as well as the incidence of maternal complications in pre-GDM as well as in GDM.

Prolonged elimination half-life of phenol after dermal exposure.

BACKGROUND: Phenol is a general protoplastic poison which has been in use in medicine and industry for decades. It is readily absorbed through the skin causing both local and systemic toxicity. CASE REPORT: A 47-year-old male had 90% phenol spilled over his left foot and shoe (3% of body surface area). After a 4 1/2-hour exposure, manifestations included confusion, vertigo, faintness, hypotension, ventricular premature beats, atrial fibrillation, dark-green urine, and tense swelling, blue-black discoloration, hypalgesia, and hypoesthesia of the affected area. Treatment consisted of irrigation with copious amounts of water, incisions, and supportive measures. RESULTS: Peak serum phenol was 21.6 micrograms/mL, considered in the fatal range. Peak urine phenol plus urine-conjugated phenol was 13,416 mg/g creatinine, indicating a major absorption. Elimination half-life was 13.86 hours, considerably longer than previously reported. CONCLUSIONS: Prolonged skin contact with concentrated phenol in an occlusive environment may result in a major absorption and a long elimination half-life even if the area involved is small. Prolonged elimination may be explained by extensive tissue distribution or by "slow-release reservoir" properties of the skin. Such exposure may be associated with severe systemic and local toxicities. Immediate removal from exposure and aggressive decontamination of the skin are essential to reduce these risks.

Antepartum management protocol. Timing and mode of delivery in gestational diabetes.

We sought to determine whether strict glycemic control during diabetic pregnancy combined with elective early induction of labor reduces the rate of cesarean delivery and fetal birth trauma. We used a population-based longitudinal design covering three periods corresponding to changes in the management protocol for diabetic pregnancy at our center: 1) 1980-1989: no set level of maternal glycemia, elective cesarean section when estimated fetal weight was 4,500 g or more, and no elective early induction; 2) 1990-1992: desired mean maternal glycemia < or = 5.8 mmol/l, elective cesarean section when estimated fetal weight was 4,000 g or more, and elective early induction at 40 weeks for large-for-gestational-age fetuses; 3) 1993-1995: desired mean maternal glycemia < or = 5.3 mmol/l, elective cesarean section when estimated fetal weight was 4,000 g or more, and elective early induction at 38 weeks for large-for-gestational-age fetuses. Outcome of diabetic pregnancies was compared for the three periods, relative to that of the normal population. There was a gradual, constant, and significant decline in the incidence of macrosomia (17.9, 14.9, and 8.8%, respectively; P < 0.05) and large-for-gestational-age fetuses (23.6, 21.0, and 11.7%; P < 0.05) coupled with a gradual, nonsignificant decrease in cesarean deliveries (20.6, 18.4, and 16.2%) and in cases of shoulder dystocia (1.5, 1.2, and 0.6%), to rates close to those of the normal population. Our data show that maintaining strict control of maternal diabetes and adhering to an active management protocol for early elective delivery based on the estimated fetal weight have a significant effect on reducing the rate of macrosomia, thereby affecting the incidence of both traumatic births and cesarean deliveries.