BACKGROUND:Obesity is associated with an increased risk of adverse pregnancy outcomes. Lifestyle-intervention studies have not shown improved outcomes. Metformin improves insulin sensitivity and in pregnant patients with gestational diabetes it leads to less weight gain than occurs in those who do not take metformin.METHODS:In this double-blind, placebo-controlled trial, we randomly assigned pregnant women without diabetes who had a body-mass index (BMI; the weight in kilograms divided by the square of the height in meters) of more than 35 to receive metformin, at a dose of 3.0 g per day, or placebo (225 women in each group) from 12 to 18 weeks of gestation until delivery. The BMI was calculated at the time of study entry (12 to 18 weeks of gestation). The primary outcome was a reduction in the median neonatal birth-weight z score by 0.3 SD (equivalent to a 50% reduction, from 20% to 10%, in the incidence of large-for-gestational-age neonates). Secondary outcomes included maternal gestational weight gain and the incidence of gestational diabetes and of preeclampsia, as well as the incidence of adverse neonatal outcomes. Randomization was performed with the use of computer-generated random numbers. The analysis was performed according to the intention-to-treat principle.RESULTS:A total of 50 women withdrew consent during the trial, which left 202 women in the metformin group and 198 in the placebo group. There was no significant between-group difference in the median neonatal birth-weight z score (0.05 in the metformin group [interquartile range, -0.71 to 0.92] and 0.17 in the placebo group [interquartile range, -0.62 to 0.89], P=0.66). The median maternal gestational weight gain was lower in the metformin group than in the placebo group (4.6 kg [interquartile range, 1.3 to 7.2] vs. 6.3 kg [interquartile range, 2.9 to 9.2], P<0.001), as was the incidence of preeclampsia (3.0% vs. 11.3%; odds ratio, 0.24; 95% confidence interval, 0.10 to 0.61; P=0.001). The incidence of side effects was higher in the metformin group than in the placebo group. There were no significant between-group differences in the incidence of gestational diabetes, large-for-gestational-age neonates, or adverse neonatal outcomes.CONCLUSIONS:Among women without diabetes who had a BMI of more than 35, the antenatal administration of metformin reduced maternal weight gain but not neonatal birth weight. (Funded by the Fetal Medicine Foundation; ClinicalTrials.gov number, NCT01273584; EudraCT number, 2008-005892-83.).

OBJECTIVE:To investigate whether first-trimester biochemical markers of placentation, including pregnancy-associated plasma protein-A (PAPP-A) and placental growth factor (PLGF), are altered in women that subsequently develop gestational diabetes mellitus (GDM) and to examine their potential value in improving the performance of screening for GDM by maternal characteristics and medical history. METHODS:The study population of 31,225 singleton pregnancies, including 787 cases that developed GDM, was drawn from women undergoing routine prospective screening for pregnancy complications at 11-13 weeks' gestation. Maternal serum PAPP-A and PLGF were measured and the levels were expressed as multiples of the median (MoM) after adjustment for maternal characteristics and medical history. The performance of screening for GDM by maternal factors and MoM values of PAPP-A and PLGF was evaluated by receiver operating characteristic (ROC) curves. RESULTS:In the GDM group, compared to the unaffected group, the median PAPP-A was reduced (0.949, 95% CI 0.913-0.987 MoM) (p=0.0009) and median PLGF was increased (1.053, 95% CI 1.023-1.083 MoM) (p=0.004). The performance of screening for GDM by maternal factors was not improved by the addition of PAPP-A and/or PLGF. CONCLUSIONS:First trimester maternal serum PAPP-A and PLGF are not useful in screening for GDM.

Objectives: To develop and validate a prediction model for gestational diabetes mellitus (GDM) at 11-13 weeks' gestation based on maternal characteristics and history and to compare its performance with the method recommended by the National Institute of Health and Care Excellence (NICE) and five other published prediction models. Methods: A predictive logistic regression model for GDM was developed from 1,827 cases (2.4%) who developed GDM and 73,334 unaffected controls. A 5-fold cross-validation study was performed to validate this model and to compare its performance with those of the NICE guidelines and the previously published models. Results: In the logistic regression model, maternal age, weight, height, racial origin, family history of diabetes, use of ovulation drugs, birth weight, and previous history of GDM were found to be significant predictors of GDM. In screening for GDM in the 5-fold cross-validation study, detection rates (DRs) were higher (p < 0.0001) for the proposed model (DR = 83.2%) than for the NICE guidelines (DR = 77.5%) for a false positive rate of approximately 40% (determined by NICE). The area under the receiver operating characteristic curve of the new model was higher (p < 0.0001) than that of the previous five models (0.823 vs. 0.688-786). Conclusions: Early effective screening for GDM can be achieved based on maternal characteristics and history.

This is a case of chronic cavitating pulmonary aspergillosis complicated by bacterial infection in a 71-year-old gentleman.He had a history of chronic obstructive pulmonary disease (COPD; severe, Forced expiratory volume in 1 s=0.94) and was treated with Seretide and Tiotropium.Prior to this illness he had a good functional status.He presented with a 1-month history of progressive shortness of breath.Chest radiograph showed a large welldemarcated cavity in the left upper zone (figure 1).Further investigation by CT showed a large 10×10 cm cavitating lesion in the left upper lobe (figure 2).Bronchoscopy and bronchoalveolar lavage were performed and Aspergillus fumigans cultured.He had a positive Aspergillus precipitans with a titre of 1 in 16.Cultures for acid fast bacilli were negative (figure 3).He was successfully treated with a combination of antifungals and antibiotics.The treatment included 13 days of Fungizone 50 mg daily with Piperacillin/Tazobactam