Immediate delivery or expectant management in gestational diabetes at term: the GINEXMAL randomised controlled trial.

OBJECTIVE: To evaluate maternal and perinatal outcomes after induction of labour versus expectant management in pregnant women with gestational diabetes at term. DESIGN: Multicentre open-label randomised controlled trial. SETTING: Eight teaching hospitals in Italy, Slovenia, and Israel. SAMPLE: Singleton pregnancy, diagnosed with gestational diabetes by the International Association of Diabetes and Pregnancy Study Groups criteria (IADPSGC), between 38+0 and 39+0 weeks of gestation, without other maternal or fetal conditions. METHODS: Patients were randomly assigned to induction of labour or expectant management and intensive follow-up. Data were analysed by 'intention to treat'. MAIN OUTCOME MEASURES: The primary outcome was incidence of caesarean section. Secondary outcomes were maternal and perinatal mortality and morbidity. RESULTS: A total of 425 women were randomised to the study groups. The incidence of caesarean section was 12.6% in the induction group versus 11.7% in the expectant group. No difference was found between the two groups (relative risk, RR 1.06; 95% confidence interval, 95% CI 0.64-1.77; P = 0.81). The incidence of non-spontaneous delivery, either by caesarean section or by operative vaginal delivery, was 21.0 and 22.3%, respectively (RR 0.94; 95% CI 0.66-1.36; P = 0.76). Neither maternal nor fetal deaths occurred. The few cases of shoulder dystocia were solved without any significant birth trauma. CONCLUSIONS: In women with gestational diabetes, without other maternal or fetal conditions, no difference was detected in birth outcomes regardless of the approach used (i.e. active versus expectant management). Although the study was underpowered, the magnitude of the between-group difference was very small and without clinical relevance. TWEETABLE ABSTRACT: Immediate delivery or expectant management in gestational diabetes at term?

Association of fetal biparietal diameter with mode of delivery and perinatal outcome.

OBJECTIVE: To determine the association between sonographic assessment of fetal biparietal diameter (BPD) and pregnancy outcome. METHODS: This was a retrospective cohort study of pregnancies at 37-42 weeks of gestation which had antepartum sonographic measurement of BPD within 7 days before delivery. Eligibility was limited to singleton pregnancies with neither known structural or chromosomal abnormalities nor prelabor Cesarean delivery (CD). The association of BPD with outcome was analyzed using multivariate logistic regression, receiver-operating characteristics curves and stratification according to BPD quartiles. RESULTS: In total, 3229 women were eligible for analysis, of whom 2483 (76.9%) had a spontaneous vaginal delivery (SVD), 418 (12.9%) underwent operative vaginal delivery (OVD) and 328 (10.2%) underwent CD. The mean BPD in the obstetric intervention groups (OVD and CD) was significantly higher than that in the SVD group (P < 0.001). After adjusting for confounders, increased BPD was an independent risk factor such that higher values of BPD were associated with progressively higher risk of obstetric intervention (adjusted odds ratio, 1.05 for each 1-mm increase in BPD (95% CI, 1.02-1.09)), but no clear cut-off value for obstetric intervention was found. The fourth quartile group (BPD ≥ 97 mm) was associated with a significantly lower SVD rate (P < 0.001) and higher OVD rate (P = 0.04), relative to the first (BPD 88-90 mm) and second (BPD 91-93 mm) quartile groups, with no apparent adverse impact on immediate neonatal outcome. CONCLUSIONS: Increased BPD within the week prior to delivery is an independent risk factor such that higher values of BPD are associated with progressively higher risk of obstetric intervention; however, in our experience, no adverse neonatal outcome resulted from such intervention. Thus, increased BPD should not discourage a trial of vaginal delivery.

Different formulas, different thresholds and different performance-the prediction of macrosomia by ultrasound.

OBJECTIVE: The sonographic prediction of fetal macrosomia affects obstetrical decision regarding the timing and mode of delivery. We aimed to compare the accuracy of various formulas for prediction of macrosomia at different thresholds. STUDY DESIGN: This was a retrospective cohort study of singleton gestations at term, with fetal biometrical measurements taken up to 7 days prior to delivery (2007 to 2014). Sonographic estimated fetal weight was calculated using 20 previously published formulas. Macrosomia prediction was evaluated for every formula utilizing: (1) measures of accuracy (sensitivity, specificity and so on); (2) comparison of the systematic and random errors (SE and RE), and the proportion of estimates within 10% of actual birth weight for macrosomic and non-macrosomic neonates. Performance measurements were evaluated for different macrosomia thresholds: 4000, 4250 and 4500 g. Best performing formula for every threshold was defined as the one with the lowest Euclidean distance (=SQRT(SE2+RE2)). RESULTS: Out of 7977 women who met the inclusion criteria, 754 (9.4%) delivered a neonate weighing ⩾4000 g, 266 (3.3%) delivered a neonate weighing⩾4250 g and 75 (0.9%) delivered a neonate weighing⩾4500 g. Considerable variability was noted between the accuracy parameters of the different formulas, with Woo's formula integrating Abdominal circumference (AC) and femur length (FL) as the most sensitive formula with the highest negative predictive value for all thresholds and Woo's formula using AC, FL and biparietal diameter (BPD) as the most specific for all thresholds. The same formula also demonstrated the best overall accuracy. Regardless of threshold chosen, 80% or more of formulas demonstrated negative systematic error, meaning lower EFW than actual birthweight. As for the Euclidean distance, Hadlock's formula (AC, FL and BPD) ranked the highest for the 4000 and 4250 g thresholds, whereas Shepard's formula (AC and BPD) ranked the highest for the 4500 g threshold. CONCLUSION: Considerable variability exist between formulas for prediction of neonatal macrosomia. Formulas by Hadlock's and Shepard's utilizing AC, BPD±FL were most accurate for macrosomia prediction at 4000, 4250 and 4500 g thresholds, respectively.

Prediction of large for gestational age by various sonographic fetal weight estimation formulas-which should we use?

OBJECTIVE: As sonographic estimation of fetal weight (EFW) carries substantial impact, especially in large-for-gestational-age (LGA) neonates, we aimed to compare the accuracy of various formulas for prediction of LGA neonates. STUDY DESIGN: Retrospective cohort study of singleton gestations at term, with EFW up to 7 days before delivery (2007 to 2014). Small-for-gestational-age neonates were excluded. LGA prediction for various formulas was evaluated by: (i) measures of performance (sensitivity, specificity, etc.); (ii) systematic and random errors (SE and RE) and the proportion of estimates (POEs) exceeding 10% of actual birth weight. Best performing formula was defined as the one with the lowest Euclidean distance [=square root of (SE2+RE2)]. RESULTS: Out of 62 102 deliveries, 7996 met inclusion criteria, of which 1618 neonates were LGA (22%). There was a considerable variation in sensitivity (74.6±16.3%, 23.5% to 99%), specificity (86.3±10.6%, 51.7% to 99.6%), positive predictive value (64.9±12.4%, 35.6% to 93.8%), positive likelihood ratio (LR; 9.3±10.9, 2.1 to 54.2) and negative LR (0.3±0.16, 0.02 to 0.8), a mild variation in the negative predictive value (92.9±3.7%, 82.3% to 99.5%) and a minimal variation in the area under the curve (94.3%, 93.0 to 95.1; mean±s.d., range for all). Absolute SE was higher for the LGA group in 11/20 formulas (55%). The RE and POE were lower in 19/20 (95%) and 14/20 (70%) for the LGA neonates, respectively. CONCLUSION: There is a wide variation in EFW formulas performance for detecting LGA. Hadlock's formula (1985) combining abdominal circumference, femur length and biparietal diameter ranked highest.

The associations between early pregnancy lipid profiles and pregnancy outcomes.

OBJECTIVE: To evaluate the association between early pregnancy lipid profiles and pregnancy outcomes. STUDY DESIGN: Retrospective 6 months analysis of 5218 singleton pregnant women. Each participant's demographic and medical data were collected by questionnaires and medical records. Total cholesterol (TC), triglycerides (TG), high-density lipid cholesterol (HDL-C) and low-density lipid cholesterol (LDL-C) levels were divided into quartiles, and the women were categorized as having low (<25th percentile), referent (25 to <75th percentile) or high (>75th percentile) TC, TG, HDL-C and LDL-C values. Differences between groups were tested using t-test and Pearson's χ2-test. Binary logistic regression and multivariate analysis was conducted to evaluate the associations between lipid values and the risk of pregnancy outcomes. RESULTS: (1) Women who subsequently developed adverse pregnancy outcomes had higher levels of TC, TG, LDL-C and lower levels of HDL-C during early pregnancy (<14 gestational weeks). (2) A trend toward an increasing incidence of adverse pregnancy outcomes was noted with increasing levels of TC, TG and LDL-C, and decreasing level of HDL-C. (3) The more numbers of TC, TG and LDL-C above 75th percentile and HDL-C inferior to 25th percentile women had, the higher their risk of developing adverse pregnancy outcomes. (4) Low TG level was a protective factor for gestational diabetes mellitus (GDM) (<1.44 mmol l-1, odds ratio (OR)=0.706, 95% confidence interval (CI), 0.586 to 0.852) and large for gestational age infants (LGA) (<1.44 mmol l-1, OR=0.769, 95% CI, 0.631 to 0.936), and low LDL-C (<1.89 mmol l-1) level was protective factor for preterm birth. High TG (>1.40 mmol l-1, OR=1.327, 95% CI, 1.130 to 1.558), TC (>4.29 mmol l-1, OR=1.250, 95% CI, 1.062 to 1.471), and LDL-C (>2.62 mmol l-1, OR=1.25, 95% CI, 1.069 to 1.480) levels and a low HDL-C (<1.89 mmol l-1, OR=1.190, 95% CI, 1.007 to 1.405) level were associated with increased risk of GDM. A high TG (>1.40 mmol l-1, OR=1.550, 95% CI, 1.025 to 2.343) level was related to high risk of pre-eclampsia (PE), while a high LDL-C (>2.62 mmol l-1, OR=1.400, 95% CI, 1.100 to 1.781) level was risk factor for macrosomia. (5) After adjusting for confounders, early pregnancy TC was an independent risk factor for GDM (ajusted odds ratio [aOR]=1.184, 95% CI, 1.085 to 1.291), TG level was independently associated with the prevalence of GDM (aOR=1.253, 95% CI, 1.141 to 1.375) and PE (aOR=1.245, 95% CI, 1.023 to 1.516), and LDL-C level was significantly associated with risk of GDM (aOR=1.162, 95% CI, 1.052 to 1.283) and preterm birth (aOR=1.264, 95% CI, 1.065, 1.501). CONCLUSIONS: Early pregnancy high levels of TC, TG, LDL-C and low level of HDL-C may be predictive biomarkers for adverse pregnancy outcomes, while early pregnancy low TC, TG, LDL-C levels and high HDL-C levels could have some protective roles.

Relationship of maternal birth weight on maternal and neonatal outcomes: a multicenter study in Beijing.

OBJECTIVE: Birth weight is an important indicator for childhood and adulthood diseases. Published studies lack information on the relative contribution of women's own birth weight to the course of her pregnancy, not only for maternal but especially to neonatal outcome. The aim of the study was to evaluate the relationship of maternal birth weight on maternal and perinatal complications during pregnancy. STUDY DESIGN: Medical and obstetrical data were collected from 5479 women at 15 hospitals in Beijing, by a systemic cluster sampling survey conducted from 20 June 2013 to 30 November 2013. These women were categorized into five groups, according to their own birth weight: low birth weight (⩽2500 g, n=275), sub-optimal birth weight (2500 to 2999 g, n=1079), optimal birth weight (3000 to 3499 g, n=2590; 3500 to 3999 g, n=1085) and high birth weight (⩾4000 g, n=450). The occurrence of maternal and neonatal complications was recorded and compared among the groups. Statistical analysis was performed by SPSS 20.0 and values of P<0.05 were considered to be statistically significant. RESULTS: Low maternal birth weight was associated with higher rates of gestational diabetes mellitus (χ2=21.268, P=0.006) and hypertensive disorders (χ2=10.844, P=0.028). The latter association was strongest in women with a pre-pregnancy body mass index above 25 kg m-2. Low maternal birth weight was also associated with an apparently higher incidence of preterm labor (χ2=18.27, P=0.001) and hypertriglyceridemia (χ2=2.739, P=0.027) in pregnancy. An association between women with low birth weight and a significantly higher rate of small for gestational age infants (χ2=93.507, P<0.001) and low birth weight (χ2=36.256, P<0.001) was detected. High maternal birth weight was associated with an increased risk of pre-pregnancy overweight and obesity (P<0.001), as well as for large for gestational age infants (χ2=93.507, P<0.001) and macrosomia (χ2=72.594, P<0.001). CONCLUSIONS: In our study, high or low maternal birth weight was strongly associated with maternal and perinatal adverse pregnancy outcomes. This suggests that by controlling the birth weight of female infants among the normal range, adverse outcomes may be decreased in the future and for the following generations.

Long-term follow-up review of patients who underwent laminectomy for lumbar stenosis: a prospective study.

OBJECT: Decompressive laminectomy for stenosis is the most common operation performed in the lumbar spine in older patients. This prospective study was designed to evaluate long-term results in patients with symptomatic lumbar stenosis. METHODS: Between January 1984 and January 1995, 170 patients underwent surgery for lumbar stenosis (86 patients), lumbar stenosis and herniated disc (61 patients), or lateral recess stenosis (23 patients). The male/female ratio for each group was 43:43, 39:22, and 14:9, respectively. The average age for all groups was 61.4 years. For patients with lumbar stenosis, the success rate was 88.1 % at 6 weeks and 86.7% at 6 months. For patients with lumbar stenosis and herniated disc, the success rate was 80% at 6 weeks and 77.6% at 6 months, with no statistically significant difference between the two groups. For patients with lateral recess stenosis, the success rate was 58.7% at 6 weeks and 63.6% at 6 months; however, the sample was not large enough to be statistically significant. One year after surgery a questionnaire was sent to all patients; 163 (95.9%) responded. The success rate in patients with stenosis had declined to 69.6%, which was significant (p = 0.012); the rate for patients with stenosis and herniated disc was 77.2%; and that for lateral recess stenosis was 65.2%. Another follow-up questionnaire was sent to patients 1 to 11 years after surgery (average 5.1 years); 146 patients (85.9%) responded, 10 (5.9%) were deceased, and 14 (8.2%) were lost to follow-up review. At 1 to 11 years the success rate was 70.8% for patients with stenosis, 66.6% for those with stenosis and herniated disc, and 63.6% for those with lateral recess stenosis. Eleven patients who underwent reoperation were included in the group of patients whose surgeries proved unsuccessful, regardless of their ultimate outcome. There was no statistically significant difference in outcome between 1 year and 1 to 11 years with respect to stenosis, stenosis with herniated disc, and lateral recess stenosis. CONCLUSIONS: In conclusion, long-term improvement after laminectomy was maintained in two-thirds of these patients.

Elevation of internal auditory canal pressure by vestibular schwannomas.

OBJECTIVE: The exact mechanism of hearing loss, the most common presenting symptom in patients with vestibular schwannomas, remains unclear. To test whether increased pressure in the internal auditory canal from tumor growth is responsible for this clinical finding, the intracanalicular pressure in patients harboring these tumors was measured. STUDY DESIGN: Prospective study. SETTING: Tertiary referral hospital. PATIENTS: Fifteen consecutive patients undergoing a retrosigmoid approach for resection of vestibular schwannomas were included in the study. INTERVENTION: The intracanalicular pressure in every patient was measured by introducing a pressure microsensor into the internal auditory canal. The pressure readings, which were performed before tumor resection, were then correlated with tumor size and respective preoperative hearing status. RESULTS: Placement of the pressure monitor into the internal auditory canal revealed a biphasic waveform in every patient. Whereas the mean intracanalicular pressure was 20 mm Hg, there was significant variability among patients (range, 1-45 mm Hg). The intracanalicular pressure directly correlated with the amount of tumor in the internal auditory canal (r > 0.63, p < 0.012) but not with the total tumor size (r 0.075). Furthermore, eight patients with class A preoperative hearing (American Academy of Otolaryngology-Head and Neck Surgery classification) had lower intracanalicular pressures than did five patients with class B hearing (16 +/- 5 vs. 28 +/- 4). Although this observation suggested an inverse correlation between the intracanalicular pressure and hearing function, the difference between the two groups was not statistically significant (p = 0.14). CONCLUSION: Pressure on the cochlear nerve as a result of tumor growth in the internal auditory canal may be responsible for hearing loss in patients with vestibular schwannomas. Modification of surgical techniques to address the elevated intracanalicular pressure may be beneficial in improving hearing preservation in these patients.

First Report of Pythium myriotylum on Lemna gibba in Israel.

Much interest has focused on duckweed as an alternative food source. Commercial production of Lemna gibba was initiated in Israel in 1991. During the summers of 1994 and 1995, Lemna gibba was grown commercially in covered ponds. In these two seasons, the plants were found to be infected by Pythium myriotylum, which has previously been reported as a pathogen of duckweed (1). In the ponds where the plants were held at high density, small, wilted, white patches of plants were recognized in early June. By the end of the month over 70% of the plants were infected and died. Microscopic examination of infected plants showed the presence of fungal appressoria and mycelial growth. Fungi were isolated from the plants onto potato dextrose agar (PDA). Ten isolates grown on PDA for 7 days were used to inoculate healthy plants. After 12 days, symptoms developed on plants at 28 or 32°C. Symptoms were similar to those observed on pond-grown plants. Plants maintained at 17 or 22°C did not become infected. The results from the pond and laboratory work showed that high plant density and temperature above 24°C were necessary for infection, and infection takes place by hyphal elements that spread in the water. This is the first report of Pythium myriotylum on Lemna gibba in Israel. Reference: (1) E. Rejmankova et al. Veröff. Geobot. Inst. Eidg. Tech. Hochsch. Stift. Rübel, Zür. 87:178, 1986.

Safety and efficacy of donor lymphocyte infusions following mismatched stem cell transplantation.

The use of a mismatched allograft necessitates T cell depletion for prevention of uncontrolled graft-versus-host disease (GVHD), thus impairing a graft-versus-leukemia effect. Data on donor lymphocyte infusion (DLI) after mismatched stem cell transplantation are lacking. Our experience with 28 patients (treated with 59 mismatched DLIs; range, 1-7) is described. The procedure was prophylactic in 6 patients (9 DLIs) and therapeutic in 22 (50 DLIs). DLI dose ranged from 10(2) to 1.5 x 10(9) T cells/kg. In the 6 patients receiving prophylactic DLI, complete remission was maintained in 5; however, 2 died from GVHD. Clinical response to therapeutic DLI was seen in 6 of 22 (27.3%) patients; a greater tumor burden produced a lower response. GVHD appeared in 13 of 28 patients. Surprisingly, a greater HLA mismatch was associated with a lower risk of GVHD, with 3 of 19 DLIs in 3/6 matching and 16 of 29 DLIs in 5/6 matching with similar follow-up. Nevertheless, no correlation between efficacy and HLA mismatching was noted. Death was frequent and usually related to the basic disease rather than to DLI complications. We conclude that mismatched DLI is feasible and may be effective, especially if given soon after transplantation. Future developments using cell therapy with selective or targeted anticancer activity are warranted, with special attention to prophylactic treatment of T cell depleted mismatched allografts recipients.

Lymphocyte-induced angiogenesis factor is produced by L3T4+ murine T lymphocytes, and its production declines with age.

Lymphocyte-induced angiogenesis factor (LIA) is a product of T lymphocytes which has been shown to stimulate new vessel formation. Because immune senescence most profoundly affects T lymphocyte functions, we suspected that LIA production would decline with age. An assay for angiogenesis stimulated by allogeneic reaction was performed by injecting spleen cells from young or old donor mice into the skin of irradiated allogeneic recipient mice. The spleen cells from young mice induced a significantly greater number of vessels than did cells from older mice. In additional experiments, spleen cells from young and old animals were treated with a monoclonal antibody GK 1.5) directed at the L3T4 antigen on murine T helper lymphocytes. Such treatment significantly reduced the new vessel formation induced by young lymphocytes but had no effect on that induced by lymphocytes from old animals. Studies employing indirect immunofluorescence demonstrated that the proportion of L3T4+ cells in the mononuclear fraction of splenocytes was nearly identical in both young and old mice. From these investigations we can conclude that (1) L3T4+ lymphocytes are responsible for LIA production, and (2) production, like that of other T lymphokines, declines with age.