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Abstract Background The STECLA strain of Anopheles albimanus has been in continuous colony for many years and is the reference strain on which genomic studies for the species are based. Recently, the STECLA strain was demonstrated to be much less susceptible to ivermectin ingested in a blood meal (4-day LC50 of 1468 ng/ml) than all other Anopheles species tested to-date (LC50 values range from 7 to 56 ng/ml). The ability of An. albimanus to survive ingestion of ivermectin at concentrations far beyond that typically found in the blood of ivermectin-treated people or livestock (i.e., 30–70 ng/ml) could invalidate the use of ivermectin as a malaria vector control strategy in areas where An. albimanus is a primary vector. Methods To investigate this, host-seeking An. albimanus were captured in northern Belize and used in membrane feeding bioassays of ivermectin, employing the same methods as described earlier with the STECLA strain. Results Field-collected An. albimanus in Belize were 55 times more susceptible to ingested ivermectin than were the STECLA reference strain. Oral susceptibility to ivermectin in wild An. albimanus from Belize (4-day LC50 of 26 ng/ml) was equivalent to that of other Anopheles species tested. Conclusions Contrary to initial assessments using a highly inbred strain of mosquito, laboratory studies using a field population indicate that ivermectin treatment of livestock could reduce An. albimanus populations in areas of Central America and the Caribbean where malaria transmission may occur. Toxicity screening of ivermectin and other systemic parasiticides for malaria control should examine wild populations of the vector species being targeted.

Introduction. This study investigates gender differences among stroke patients treated in the telestroke network using specific risk factors that contribute to stroke severity. Methods. We examined gender differences in stroke severity among 454 patients hospitalized with acute ischemic stroke (AIS). The logistic regression model was used to predict clinical risk factors associated with stroke severity in men and women AIS patients. Results. In the adjusted analysis, among women patients, increasing age [Odd ratio(OR) = 1.05, 95% CI, 1.017-1.085, P = 0.003], and higher heart rate (OR = 1.031, 95% CI, 1.005-1.058, P=0.021) were associated with worsening neurological functions, while direct admission (OR = 0.191, 95% CI, 0.079‐0.465, P

Abstract Background Most malaria vector control programmes rely on indoor residual spraying of insecticides and insecticide-treated bed nets. This is effective against vector species that feed indoors at night and rest inside the house afterwards. In Central America, malaria vectors have different behaviours and are typically exophagic (i.e., bite outdoors), exophilic (i.e., remain outdoors after feeding), and zoophagic (i.e., as likely to feed on non-humans as humans). Thus, malaria elimination in Central America may require additional tactics. This pilot study investigated whether commercially-available products used to treat livestock for ticks could also be used to kill and/or sterilize zoophagic malaria vectors that feed on treated cattle in Belize. Methods Cattle were treated with either a pour-on formulation of 1% fipronil (3 heifers) or injection of 1% ivemectin (1 heifer). Control heifers (n = 2) were left untreated. Field-collected Anopheles albimanus contained in screen-top cages were strapped onto cattle at 2, 5, 7, and 14 days after treatment. Mosquito mortality was monitored once a day for 4 successive days. Surviving mosquitoes were dissected to assess blood meal digestion and ovarian development. Results A total of 1078 female An. albimanus mosquitoes were fed and monitored for mortality. Both fipronil and ivermectin significantly reduced survivorship of An. albimanus for up to 7 days after treatment. By 14 days, efficacy had declined. The ivermectin treatment completely lost its effectiveness and even though the fipronil-treated heifers were still killing significantly more mosquitoes than the untreated heifers, the amount of mosquito killing had diminished greatly. Both treatments significantly reduced ovary development in mosquitoes fed on treated cattle for the duration of the 2-week trial. Conclusions Treatment of cattle in northern Belize with topical fipronil and injectable ivermectin had significant lethal and sublethal effects on wild An. albimanus females. These results suggest that efforts towards eliminating residual transmission of malaria by zoophagic vectors in Central America may benefit by the judicious, targeted treatment of livestock with mosquitocidal compounds, such as fipronil or ivermectin.

Aedes aegypti and Aedes albopictus vector dengue, chikungunya and Zika viruses. With both species expanding their global distributions at alarming rates, developing effective surveillance equipment is a continuing priority for public health researchers. Sound traps have been shown, in limited testing, to be highly species-specific when emitting a frequency corresponding to a female mosquito wingbeat. Determining male mosquito capture rates in sound traps based on lure frequencies in endemic settings is the next step for informed deployment of these surveillance tools. We field-evaluated Male Aedes Sound Traps (MASTs) set to either 450 Hz, 500 Hz, 550 Hz or 600 Hz for sampling Aedes aegypti and/or Aedes albopictus and compared catch rates to BG-Sentinel traps within Pacific (Madang, Papua New Guinea) and Latin American (Molas, Mexico and Orange Walk Town, Belize) locations. MASTs set to 450-550 Hz consistently caught male Ae. aegypti at rates comparable to BG-Sentinel traps in all locations. A peak in male Ae. albopictus captures in MASTs set at 550 Hz was observed, with the lowest mean abundance recorded in MASTs set to 450 Hz. While significantly higher abundances of male Culex were sampled in MASTs emitting lower relative frequencies in Molas, overall male Culex were captured in significantly lower abundances in the MASTs, relative to BG-Sentinel traps within all locations. Finally, significant differences in rates at which male Aedes and Culex were positively detected in trap-types per weekly collections were broadly consistent with trends in abundance data per trap-type. MASTs at 550 Hz effectively captured both male Ae. aegypti and Ae. albopictus while greatly reducing bycatch, especially male Culex, in locations where dengue transmission has occurred. This high species-specificity of the MAST not only reduces staff-time required to sort samples, but can also be exploited to develop an accurate smart-trap system-both outcomes potentially reducing public health program expenses.

Using a CdTe x Se1−x alloy in CdTe solar cells leads to better performances. Here, Poplawsky et al. show that the photoactive properties of the alloy depend on its chemical composition and structural properties, and derive a phase diagram to further optimize alloy growth for photovoltaic devices.

Ultrasonic spot welding using different welding conditions was applied to join dissimilar metals of galvanized DP590 steel and AZ31B magnesium sheets. In situ high-speed imaging, digital image correlation, and infrared thermography were utilized to quantitatively study the interfacial relative motion, surface indentation, and heat generation across the joint faying interface and the sheet/sonotrode interfaces under the welding condition of moderate welding power and short welding time. For welds made with high power and long welding time, lap shear tensile tests as well as fatigue tests were carried out. Different fracture modes were observed after the lap shear tensile tests and fatigue tests performed under different peak loads. Post-weld cross-sectional analysis with scanning electron microscopy coupled with energy dispersive X-Ray spectroscopy revealed the variation of morphology and chemical composition at the joint interface for welds made with different welding conditions.

Nature Communications 7: Article number: 12537 (2016); Published: 27 July 2016; Updated: 2 September 2016 In Fig. 6 of this article, the division between the zincblende and wurtzite phases is misplaced in the low temperature range. The correct version of Fig. 6 appears below as Fig. 1.

A group of experienced community rehabilitation program staff in New England and Florida provided scenarios describing incidents in their work where the ability to respond appropriately is indicative of or critical to effective job performance. Scenarios were mailed to the group with a request for a narrative description of a recommended solution. The 44 narrative descriptions received were analyzed using qualitative methods to generate a list of 87 competencies in 12 areas. Implications for the design and implementation of community rehabilitation staff training are presented. [ABSTRACT FROM AUTHOR]

Objective: Despite the well-recognized association between pre-existing diabetes mellitus and stillbirth or perinatal mortality, there remain knowledge gaps about the strength of association across different populations. The primary objective of this systematic review and meta-analysis was to quantify the association between pre-existing diabetes and stillbirth or perinatal mortality, and secondarily, to identify risk factors predictive of stillbirth or perinatal mortality among those with pre-existing diabetes., Data Sources: MEDLINE, EMBASE, Cochrane Database of Systematic Reviews, and Cochrane Central Register of Controlled Trials from inception to April 2022., Methods of Study Selection: Cohort studies and randomized controlled trials in English or French that examined the association between pre-existing diabetes and stillbirth or perinatal mortality (as defined by the original authors) or identified risk factors for stillbirth and perinatal mortality in individuals with pre-existing diabetes were included. Data extraction was performed independently and in duplicate with the use of prespecified inclusion and exclusion criteria. Assessment for heterogeneity and risk of bias was performed. Meta-analyses were completed with a random-effects model., Tabulation, Integration, and Results: From 7,777 citations, 91 studies met the inclusion criteria. Pre-existing diabetes was associated with higher odds of stillbirth (37 studies; pooled odds ratio [OR] 3.74, 95% CI, 3.17-4.41, I2 =82.5%) and perinatal mortality (14 studies; pooled OR 3.22, 95% CI, 2.54-4.07, I2 =82.7%). Individuals with type 1 diabetes had lower odds of stillbirth (pooled OR 0.81, 95% CI, 0.68-0.95, I2 =0%) and perinatal mortality (pooled OR 0.73, 95% CI, 0.61-0.87, I2 =0%) compared with those with type 2 diabetes. Prenatal care and prepregnancy diabetes care were significantly associated with lower odds of stillbirth (OR 0.26, 95% CI, 0.11-0.62, I2 =87.0%) and perinatal mortality (OR 0.41, 95% CI, 0.29-0.59, I2 =0%)., Conclusion: Pre-existing diabetes confers a more than threefold increased odds of both stillbirth and perinatal mortality. Maternal type 2 diabetes was associated with a higher risk of stillbirth and perinatal mortality compared with maternal type 1 diabetes., Systematic Review Registration: PROSPERO, CRD42022303112., Competing Interests: Financial Disclosure Lois E. Donovan reports in-kind donations and reduced costs for study supplies for investigator-initiated trials from Medtronic, Dexcom, Tandem Diabetes Care, and Inter-analytics. Patricia Lemieux reports receiving honorary from Dexcom for their advisory board. Jennifer M. Yamamoto has received in-kind donations for study supplies from Abbott. The other authors did not report any potential conflicts of interest., (Copyright © 2024 by the American College of Obstetricians and Gynecologists. Published by Wolters Kluwer Health, Inc. All rights reserved.)

Aims/hypothesis: This study aimed to describe the relationship between breastfeeding episodes and maternal glucose levels, and to assess whether this differs with closed-loop vs open-loop (sensor-augmented pump) insulin therapy., Methods: Infant-feeding diaries were collected at 6 weeks, 12 weeks and 24 weeks postpartum in a trial of postpartum closed-loop use in 18 women with type 1 diabetes. Continuous glucose monitoring (CGM) data were used to identify maternal glucose patterns within the 3 h of breastfeeding episodes. Generalised mixed models adjusted for breastfeeding episodes in the same woman, repeat breastfeeding episodes, carbohydrate intake, infant age at time of feeding and early pregnancy HbA 1c . This was a secondary analysis of data collected during a randomised trial (ClinicalTrials.gov registration no. NCT04420728)., Results: CGM glucose remained above 3.9 mmol/l in the 3 h post-breastfeeding for 93% (397/427) of breastfeeding episodes. There was an overall decrease in glucose at nighttime within 3 h of breastfeeding (1.1 mmol l -1 h -1 decrease on average; p=0.009). A decrease in nighttime glucose was observed with open-loop therapy (1.2 ± 0.5 mmol/l) but was blunted with closed-loop therapy (0.4 ± 0.3 mmol/l; p<0.01, open-loop vs closed-loop)., Conclusions/interpretation: There is a small decrease in glucose after nighttime breastfeeding that usually does not result in maternal hypoglycaemia; this appears to be blunted with the use of closed-loop therapy., (© 2024. The Author(s).)

Objectives: Closed-loop insulin delivery has the potential to offer women with type 1 diabetes a break from intense diabetes self-care efforts postpartum. Our aim in this study was to explore the views and opinions of hybrid closed-loop users and their partners in the first 24 weeks postpartum., Methods: This qualitative study was embedded in a controlled study of women with type 1 diabetes randomized to closed-loop insulin delivery (MiniMed™ 670G or 770G) or sensor-augmented pump use for 1 to 11 weeks 6 days postpartum, with all on closed-loop delivery from 12 to 24 weeks postpartum. Semistructured interviews were conducted with 16 study participants and their partners at 12 and 24 weeks postpartum. Thematic analyses were used to examine participants' and partners' experiences., Results: Participants' positive perceptions of closed-loop use related to reduced hypoglycemia, in contrast to previous experiences with nonautomated insulin delivery. These perceptions were balanced against frustrations with the system, allowing blood glucose levels to be higher than desired. Closed-loop use did not influence infant feeding choice, but infant feeding and care impacted participants' diabetes management. Partners expressed uncertainty about the closed loop taking away control from participants who were highly skilled with diabetes self-management., Conclusions: Participants reported that closed-loop insulin delivery resulted in less time spent in hypoglycemia when compared with the previously used nonautomated delivery. Yet, participants desired a greater understanding of the workings of the closed-loop algorithm. Our study provides potential users with realistic expectations about the experience with the MiniMed 670G or 770G closed-loop system in the postpartum period., (Copyright © 2024 Canadian Diabetes Association. Published by Elsevier Inc. All rights reserved.)

Objective: This study aimed to evaluate the efficacy of closed-loop insulin delivery postpartum., Research Design and Methods: In this open-label, randomized controlled trial, postpartum individuals with type 1 diabetes were randomized to hybrid closed-loop insulin delivery with the MiniMed 670G/770G system in automode or sensor-augmented pump therapy in the first 12-weeks postpartum followed by a continuation phase with closed-loop insulin delivery for all until 24 weeks postpartum., Results: Eighteen participants (mean ± SD age 32 ± 3.5 years, diabetes duration 22 ± 7.3 years, and early pregnancy HbA1c 52 ± 6.8 mmol/mol [6.9 ± 0.9%]) completed 24 weeks of postpartum follow-up. In the randomized phase, percent time in range 70-180 mg/dL (3.9-10 mmol/L) did not differ between groups (79.2 ± 8.7% vs. 78.2 ± 6.0%; P = 0.41). Participants randomized to closed-loop insulin delivery spent less time <70 mg/dL (3.9 mmol/L) and <54 mg/dL (3.0 mmol/L) (1.7 ± 0.8% vs. 5.5 ± 3.3% [P < 0.001] and 0.3 ± 0.2% vs. 1.1 ± 0.9% [P = 0.008]). Time >180 mg/dL (10 mmol/L) was not different between groups (18.7 ± 8.8% vs. 15.9 ± 7.7%; P = 0.21). In the continuation phase, those initially randomized to sensor-augmented pump therapy had less time <70 mg/dL after initiation of closed-loop insulin delivery (5.5 ± 3.3% vs. 3.3 ± 2.2%; P = 0.039). The closed-loop group maintained similar glycemic metrics in both study phases. There were no episodes of diabetic ketoacidosis or severe hypoglycemia in the randomized or continuation phase in either group., Conclusions: Women randomized to closed-loop insulin delivery postpartum had less hypoglycemia than those randomized to sensor-augmented pump therapy. There were no safety concerns. These findings are reassuring for use of closed-loop insulin delivery postpartum because of its potential to reduce hypoglycemia., (© 2023 by the American Diabetes Association.)

Glucose concentrations within target, appropriate gestational weight gain, adequate lifestyle, and, if necessary, antihypertensive treatment and low-dose aspirin reduces the risk of pre-eclampsia, preterm delivery, and other adverse pregnancy and neonatal outcomes in pregnancies complicated by type 1 diabetes. Despite the increasing use of diabetes technology (ie, continuous glucose monitoring and insulin pumps), the target of more than 70% time in range in pregnancy (TIRp 3·5-7·8 mmol/L) is often reached only in the final weeks of pregnancy, which is too late for beneficial effects on pregnancy outcomes. Hybrid closed-loop (HCL) insulin delivery systems are emerging as promising treatment options in pregnancy. In this Review, we discuss the latest evidence on pre-pregnancy care, management of diabetes-related complications, lifestyle recommendations, gestational weight gain, antihypertensive treatment, aspirin prophylaxis, and the use of novel technologies for achieving and maintaining glycaemic targets during pregnancy in women with type 1 diabetes. In addition, the importance of effective clinical and psychosocial support for pregnant women with type 1 diabetes is also highlighted. We also discuss the contemporary studies examining HCL systems in type 1 diabetes during pregnancies., Competing Interests: Declaration of interests KBen reports research funding and receipt of study devices from Medtronic for the investigator-initiated CRISTAL study, receipt of study devices from Dexcom, received consulting fees from AstraZeneca and Eli Lilly, and served on the speaker bureau for Novo Nordisk, AstraZeneca, and Mundipharma. SP reports grants from Dexcom and National Institute of Health (NIH), research support from Medtronic, and payment from diaTribe for an online article and participation on a DSMB from Sansum Diabetes Research Institute. LED reports grants from Diabetes Canada, Calgary Health Trust and Alberta Diabetes Institute, and in-kind, reduced cost, and loan of study devices from Medtronic, Dexcom, and Tandem Diabetes Care. CJL reports grants from the Helmsley Foundation, NIH (1R01DK120358–0), Tandem, Dexcom, Insulet, and Abbott Diabetes. CM reports consulting fees from Novo Nordisk, Sanofi, Merck Sharp and Dohme, Eli Lilly, AstraZeneca, Boehringer Ingelheim, Roche, Medtronic, ActoBio Therapeutics, Pfizer, Insulet, and Zealand Pharma, and serves or has served on the speaker bureau for Novo Nordisk, Sanofi, Eli Lilly, Boehringer Ingelheim, AstraZeneca, and Novartis. DSF reports grants from the Canadian Institute for Health Research; in-kind, reduced cost, and loan of study devices from Tandem Diabetes Care and Dexcom; has served on an advisory board for Novo Nordisk; and received honoraria from Sanofi and Novo Nordisk. RP reports multiple grants from ZonMw and Leading the Change (Netherlands governmental health-care research funds). SES has made webinars and a podcast on time in range and diabetes in pregnancy in cooperation with Abbott Diabetes, Medtronic, Eli Lilly, and Sanofi, and has served in advisory boards from Novo Nordisk and Eli Lilly. EB has received research funding from the Juvenile Diabetes Research Foundation and Dexcom and receipt of study devices from Dexcom. YCK reports grants from the Helmsley Foundation and NIH (1R01DK120358–0), product support from Dexcom, and is serving as site Principal Investigator on grants from Medtronic Diabetes, Tandem Diabetes, and Dexcom. ERM received research grants from Novo Nordisk for a randomised controlled trial investigating the use of faster aspart in comparison with aspart in pregnant women with pre-existing diabetes, a study evaluating the effect of insulin pump treatment in an international prospective cohort, and for the EXPECT study on the effect of insulin Degludec in comparison with insulin detemir in pregnant women with type 1 diabetes. In addition, ERM received funding from Novo Nordisk for lectures on diabetes in pregnancy and for attending the European Association for the Study of Diabetes Annual Meeting 2022. TB has received honoraria for participation on advisory boards for Novo Nordisk, Sanofi, Eli Lilly, Medtronic, Provention Bio, and Indigo Diabetes, and as a speaker for Astra Zeneca, Eli Lilly, Novo Nordisk, Medtronic, Abbott, Dexcom, Sanofi, and Roche. TB's institution, University Medical Centre Ljubljana, has received research grant support and travel expenses from Abbott, Medtronic, Novo Nordisk, Sanofi, Sandoz, Novartis, the EU, and the NIH–National Institute of Diabetes and Digestive and Kidney Diseases., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background: Most commercially available automated insulin delivery (AID) systems are not approved for pregnancy use. Information regarding use of the Tandem t:slim X2 insulin pump with Control-IQ™ technology in pregnancy is lacking., Aims: This case series aimed to explore glycaemic and qualitative experiences of four early adopters of Control-IQ technology in pregnancy., Methods: Participants used Control-IQ technology in pregnancy and postpartum and consented to analysis of glycaemic data and semi-structured interviews., Results: Case 1 began Control-IQ technology at 10 weeks gestation. Her pregnancy glucose time-in-range (3.5-7.8 mmol/L [63-140 mg/dL]) increased from 58.7% to 73.3% by third trimester. Cases 2-4 began using Control-IQ technology 0-2 months preconception. Pregnancy time-in-range glucose increased from 73.4% to 78.7%, 78% to 83.6%, and 46.5% to 71.9% between first and third trimesters, respectively. A mid-pregnancy decline in time-in-range glucose was observed in two of the four participants related to suboptimal pump setting adjustments and delays in sensor and infusion set replacement. No diabetic ketoacidosis or severe hypoglycaemia occurred. All participants reported reduced diabetes management burden and improved sleep with Control-IQ technology use., Conclusions: Early adopters of Control-IQ technology safely used this system off-label in pregnancy and reported reduced diabetes management burden and improved sleep. The largest glycaemic improvements were observed among those with the lowest pregnancy time-in-range glucose at the beginning of pregnancy. Participants with low pregnancy glucose time-in-range increased their time-in-range with Control-IQ technology use and participants with high pregnancy glucose time-in-range maintained and increased their time-in-range with less diabetes management burden., (© 2023 The Authors. Diabetic Medicine published by John Wiley & Sons Ltd on behalf of Diabetes UK.)

Background: No standardised questionnaires have been specifically developed to assess the considerable demands of managing type 1 diabetes (T1D) during pregnancy., Aims: This study aimed to explore what domains of measurement are important to quality of life during pregnancy with TID and to assess if standardised questionnaires, used by previous researchers, adequately capture patients' reported experience of TID in pregnancy., Methods: A qualitative inquiry was conducted using semi-structured focus groups with Canadian women who have experienced T1D in pregnancy. Participants were asked open-ended questions about experiences managing T1D during pregnancy and whether options on standardised tools captured their pregnancy experiences. Audio from focus groups was transcribed verbatim. Two researchers independently analysed the transcripts using inductive thematic analysis. Salient ideas, experiences and key words were coded iteratively and grouped into broader themes and subsequently reviewed by five participants., Results: The sample included nine participants. Emergent themes included changes in day-to-day routines to manage T1D in pregnancy, fear of hyperglycaemia during pregnancy and of hypoglycaemia postpartum. Participants felt that existing options on standardised questionnaires did not adequately quantify diabetes interference in work, family time, planned activities and sleep, and did not address hyperglycaemia fear., Conclusions: Existing standardised questionnaires do not adequately capture patient-reported outcomes of greatest importance for those living with T1D in pregnancy. Future research assessing the impact of therapies on quality-of-life measures in TID pregnancies should quantify their influence on day-to-day activities, adjust measures of sleep quality and capture fear of hyperglycaemia in pregnancy and hypoglycaemia postpartum., (© 2023 The Authors. Diabetic Medicine published by John Wiley & Sons Ltd on behalf of Diabetes UK.)

Background: There is limited information regarding the association between missed appointments and neonatal outcomes for diabetes in pregnancy., Study Methods: This retrospective live birth cohort included pregnant women with Type 1 or 2 diabetes who attended specialized clinics from 2008 to 2020. The association between at least one missed antenatal diabetes appointments and outcomes were assessed using logistic regression and reported as adjusted odds ratios (aOR) (95% confidence interval). Mediation analyses were conducted to examine if above target HbA1c mediated these relationships., Results: The cohort included 407 and 902 women with Type 1 and 2 diabetes, respectively, of whom 25.1% and 34.5% missed at least one appointment. Women with Type 1 diabetes who missed an appointment were more likely to have a caesarean section (aOR 1.95 [1.15, 3.31]) and their babies more likely to be admitted to the neonatal intensive care unit (aOR 2.25 [1.35, 3.75]). Women with Type 2 diabetes who missed an appointment were more likely to have a large-for-gestational-age infant (aOR 1.61 [1.13, 2.28]), and an extreme large-for-gestational-age infant (aOR 1.69 [1.02, 2.81]) compared with women who did not miss appointments. Above target HbA1c mediated the relationship between missed appointments and caesarean delivery in Type 1 diabetes and large-for-gestational age and extreme large-for-gestational age in Type 2 diabetes., Conclusion: In individuals with Type 1 and 2 diabetes, there are differences in neonatal outcomes between those who missed an appointment compared to those who did not. It remains unclear if missed diabetes appointments are causative or a marker of other health behaviours or risk factors leading to neonatal morbidity., (© 2022 Diabetes UK.)

Objective: In the MiTy (Metformin in Women With Type 2 Diabetes in Pregnancy) randomized trial of metformin versus placebo added to insulin, we found numerous benefits with metformin but identified an increased proportion of infants who were small for gestational age (SGA). We aimed to determine the predictors of SGA in order to individualize care., Research Design and Methods: Using logistic regression, we assessed baseline maternal characteristics as predictors of SGA. We compared maternal/neonatal outcomes in SGA metformin and placebo groups using the t, χ2, or Fisher exact test, as appropriate., Results: Among the 502 mothers, 460 infants were eligible for this study. There were 30 infants with SGA in the metformin group (12.9%) and 15 in the placebo group (6.6%) (P = 0.026). Among SGA infants, those in the metformin group were delivered significantly later than those in the placebo group (37.2 vs. 35.3 weeks; P = 0.038). In adjusted analyses, presence of a comorbidity (chronic hypertension and/or nephropathy) (odds ratio [OR] 3.05; 95% CI 1.58-5.81) and metformin use (OR 2.26; 95% CI 1.19-4.74) were predictive of SGA. The absolute risk of SGA was much higher in women receiving metformin with comorbidity compared with women receiving metformin without comorbidity (25.0% vs. 9.8%)., Conclusions: In this study, we observed a high percentage of SGA births among women with type 2 diabetes and chronic hypertension and/or nephropathy who were treated with metformin. Therefore, with the aim of reducing SGA, it is reasonable to be cautious in our use of metformin in those with type 2 diabetes and chronic hypertension or nephropathy in pregnancy., (© 2022 by the American Diabetes Association.)

Background and Objectives: To understand patterns of care and circumstances surrounding end of life in patients with intracranial gliomas., Methods: We retrospectively analyzed end-of-life circumstances in patients with intracranial high-grade gliomas at Columbia University Irving Medical Center who died from January 2014 to February 2019, including cause of death, location of death, and implementation of comfort measures and resuscitative efforts., Results: There were 152 patients (95 men, 57 women; median age at death 61.5 years, range 24-87 years) who died from January 2014 to February 2019 with adequate data surrounding end-of-life circumstances. Clinical tumor progression (n = 117, 77.0%) was the most common cause of death, with all patients transitioned to comfort measures. Other causes included, but were not limited to, infection (19, 12.5%); intratumoral hemorrhage (5, 3.3%); seizures (8, 5.3%); cerebral edema (4, 2.6%); pulmonary embolism (4, 2.6%); autonomic failure (2, 1.3%); and hemorrhagic shock (2, 1.3%). Multiple mortal events were identified in 10 (8.5%). Seventy-three patients (48.0%) died at home with hospice. Other locations were inpatient hospice (40, 26.3%); acute care hospital (34, 22.4%), including 27 (17.8%) with and 7 (4.6%) without comfort measures; skilled nursing facility (4, 3.3%), including 3 (2.0%) with and 1 (0.7%) without comfort measures; or religious facility (1, 0.7%) with comfort measures. Acute cardiac or pulmonary resuscitation was performed in 20 patients (13.2%)., Discussion: Clinical tumor progression was the most common (77.0%) cause of death, followed by infection (12.5%). Hospice or comfort measures were ultimately implemented in 94.7% of patients, although resuscitation was performed in 13.2%. Improved understanding of circumstances surrounding death, frequency of use of hospice services, and frequency of resuscitative efforts in patients with gliomas may allow physicians to more accurately discuss end-of-life expectations with patients and caregivers, facilitating informed care planning., (Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.)

Aims/hypothesis: Controversy exists over whether gestational diabetes increases the risk of stillbirth. The aim of this review was to examine the association between gestational diabetes and stillbirth., Methods: We performed searches of the published literature to May 2021. Study selection and data extraction were performed in duplicate by independent reviewers. Meta-analyses of summary measures were conducted using random-effect models for cohort and case-control studies separately. The study protocol was registered in PROSPERO (registration ID CRD42020166939)., Results: From 9981 citations, 419 were identified for full-text review and 73 met inclusion criteria (n = 70,292,090). There was no significant association between gestational diabetes and stillbirth in cohort studies (pooled OR 1.04 [95% CI 0.90, 1.21]; I 2 86.1%) or in case-control studies (pooled OR 1.57 [95% CI 0.83, 2.98]; I 2 94.8%). Gestational diabetes was associated with lower odds of stillbirth among cohort studies presenting with an adjusted OR (pooled OR 0.78 [95% CI 0.68, 0.88]; I 2 42.7%). Stratified analyses by stillbirth ≥28 weeks' gestation, studies published prior to 2013 and studies identified as low quality demonstrated a significantly higher odds of stillbirth in meta-regression (p = 0.016, 0.023 and 0.005, respectively). Egger's test for all included cohort studies (p = 0.018) suggests publication bias for the main meta-analysis., Conclusions/interpretation: Given the substantial heterogeneity across studies, there are insufficient data to define the relationship between stillbirth and gestational diabetes adequately. In the main analyes, gestational diabetes was not associated with an increased risk of stillbirth. However, heterogeneity across studies means this finding should be interpreted cautiously., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Maternal weight gain during pregnancy is required for fetal development; however, excess gestational weight gain is associated with increased maternal and neonatal morbidity. We aimed to determine the proportion of Canadian women who gained excess weight during pregnancy and to identify risk factors for excess gestational weight gain., Methods: Self-reported data on maternal weight gain were collected from the 2015/16 and 2017/18 cycles of the Canadian Community Health Survey (CCHS), a cross-sectional population-based survey. We included females aged 15 to 54 years with data on height, prepregnancy weight and gestational weight gain. We defined excess gestational weight gain in terms of preconception body mass index (BMI) according to the 2009 guideline of the US Institute of Medicine. We used logistic regression to evaluate potential risk factors for excess gestational weight gain., Results: Of 1 335 615 Canadian women (weighted from approximately 9300 survey respondents), 422 043 (32%) gained excess weight during pregnancy. Women with obesity had 33% lower odds of gaining excess weight relative to women with overweight (odds ratio 0.67, 95% confidence interval 0.48-0.94). Risk factors for excess gestational weight gain were lower education level, white or Indigenous identity, smoking, mood disorder, anxiety disorder and Canadian citizenship., Interpretation: One-third of Canadian women in this survey had excess gestational weight gain during pregnancy, and women with obesity had lower odds of gaining excess weight during pregnancy relative to women with overweight. Strategies are needed to reduce the proportion of Canadian women who gain excess weight during pregnancy, regardless of preconception BMI., Competing Interests: Competing interests: None declared., (© 2021 CMA Joule Inc. or its licensors.)

Aims: (1) To determine the likelihood of full breastfeeding at 3 months postpartum in women with and without diabetes in pregnancy (DiP); (2) to explore the associations between diabetes management practices and infant feeding practices in those who had DiP and (3) to examine women's experiences of feeding their infants after having DiP., Methods: The quantitative study used data from Alberta Pregnancy Outcomes and Nutrition (APrON) cohort study. Participants who had DiP (n = 62) were matched 1:3 to participants without DiP for pre-pregnancy BMI, parity, mode of delivery and pre-term birth. Infant feeding questionnaires, prospective breastfeeding diaries and medical chart data were analysed to determine likelihood of fully breastfeeding at 3 months postpartum. For the qualitative study, interviews were conducted with postpartum women who had DiP to explore the experiences of infant feeding. Interviews were thematically analysed, and the results were compared between women who were categorized as 'full breast feeders' or 'mixed feeders'., Results: The odds of fully breastfeeding were 50% lower in women with DiP than women without DiP (OR: 0.50, 95% CI 0.25-0.99, p = 0.04). Qualitative interviews identified that although all women showed resilience in the face of infant feeding challenges, those who were fully breastfeeding reported seeking out external infant feeding supports, for example, classes or Doula's. Mixed Feeders perceived there was a lack of infant feeding information and support given to them prior to giving birth., Conclusion: Women with DiP may require additional prenatal and postnatal infant feeding support to be better prepared to overcome feeding challenges they may face., (© 2021 Diabetes UK.)

Purpose of Review: To review the current evidence for the use of metformin in pregnancy for women with type 2 diabetes., Recent Findings: A large, multicenter, double-blind randomized controlled trial found that women with type 2 diabetes in pregnancy treated with metformin as an adjunct to insulin therapy had less gestational weight gain, insulin requirements, caesarian sections, macrosomia, and neonatal adiposity, but more neonates were small for gestational age (SGA) compared with insulin alone. It is unclear if the higher number of SGA infants are a direct result of metformin exposure or mediated through other effects such as less gestational weight gain and improved glycemic control. Additional follow-up studies of offspring exposed to metformin in utero are required. Metformin may be a useful adjunctive treatment for women with type 2 diabetes in pregnancy to help meet glycemic targets if there are no concerns for or indications of SGA., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Women with hypothyroidism before pregnancy often require an increase in their levothyroxine dosage to maintain a euthyroid state during pregnancy. The objectives of this study were to investigate: (i) the frequency and distribution of thyrotropin (TSH) testing and levothyroxine dosage adjustment by gestational age, (ii) the magnitude of levothyroxine increase by the underlying etiology of hypothyroidism, and (iii) the relationship of overtreatment or undertreatment during pregnancy with adverse pregnancy outcomes among women using thyroid replacement before pregnancy. Methods: A retrospective cohort study of pregnancies in women on thyroid replacement before pregnancy in Alberta, Canada, was performed. Women using thyroid replacement anytime during the two years before pregnancy who delivered between October 2014 and September 2017 were included. Delivery records, physician billing, and laboratory and pharmacy administrative data were linked. Outcomes included characteristics of TSH testing, levothyroxine dosing, and pregnancy outcomes. The frequency and gestational timing of TSH testing and levothyroxine adjustments were calculated. Multiple logistic regression was used to test whether pregnancies with TSH <0.10 mIU/L (overtreatment) or TSH ≥10.00 mIU/L (undertreatment) compared with control pregnancies (TSH 0.10-4.00 mIU/L) were associated with adverse pregnancy and neonatal outcomes. Results: Of the 10,680 deliveries, 8774 (82.2%) underwent TSH testing at least once during pregnancy, at a median gestational age of six weeks. An adjustment of levothyroxine dosage was made for 4321 (43.7%) during pregnancy. TSH in pregnancy below 0.10 mIU/L increased the odds of preterm delivery when compared with control pregnancies (adjusted odds ratio, 2.14 [95% confidence interval 1.51-2.78]). TSH ≥10.00 mIU/L during pregnancy was not associated with any adverse pregnancy or neonatal outcomes in the multivariable analysis. Conclusions: Although most women on thyroid replacement before conception had TSH measured at some point during pregnancy, it is concerning that 17.8% did not. Levothyroxine overtreatment in pregnancy was associated with preterm delivery. These findings suggest that clinicians should be careful to avoid overtreatment with levothyroxine in pregnancy.

Objective: To evaluate the effect of levothyroxine therapy on pregnancy outcomes compared with placebo or no treatment in women without overt hypothyroidism with presence of thyroid peroxidase antibodies (TPOAb) and/or thyroglobulin antibodies (TgAb)., Design: Systematic review and meta-analysis of randomised controlled trials STUDY ELIGIBILITY CRITERIA: Prespecified criteria for inclusion were: randomised trials of levothyroxine versus control (placebo or no treatment) among women with positive TPOAb or TgAb who were pregnant or considering conception., Data Sources: Ovid MEDLINE, EMBASE, CINAHL, Cochrane Database of Systematic Reviews and Cochrane Central Register of Controlled Trials were searched from 1980 to 5 November 2020., Outcome Measures: Prespecified data elements were extracted and where appropriate, meta-analyses were conducted. Main outcomes include pregnancy achieved, miscarriage, preterm delivery and live birth., Risk of Bias Assessment: Cochrane Risk of Bias Tool for Quality Assessment of Randomised Controlled Trials., Results: From 3023 citations, 79 citations were identified for full-text review. Of these, six trials (total of 2263 women) were included for qualitative and quantitative analyses. Risk of bias was deemed low for only one trial. There was no significant difference in the relative risk (RR) of pregnancy achieved (RR 1.03; 95% CI 0.93 to 1.13), miscarriage (RR 0.93; 95% CI 0.76 to 1.14), preterm delivery (RR 0.66; 95% CI 0.39 to 1.10) or live births (RR 1.01; 95% CI 0.89 to 1.16) in thyroid autoimmune women treated with levothyroxine compared with controls. Sensitivity analyses of preterm birth identified study quality and timing of levothyroxine initiation as sources of heterogeneity., Conclusions: Among pregnant women or women planning conception, with thyroid autoimmunity, there is a lack of evidence of benefit for levothyroxine use (moderate to high Grading of Recommendations, Assessment, Development and Evaluations). Recommendations to use levothyroxine in this setting need to be reconsidered., Prospero Registration Number: CRD42019130459., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Although metformin is increasingly being used in women with type 2 diabetes during pregnancy, little data exist on the benefits and harms of metformin use on pregnancy outcomes in these women. We aimed to investigate the effects of the addition of metformin to a standard regimen of insulin on neonatal morbidity and mortality in pregnant women with type 2 diabetes., Methods: In this prospective, multicentre, international, randomised, parallel, double-masked, placebo-controlled trial, women with type 2 diabetes during pregnancy were randomly assigned from 25 centres in Canada and four in Australia to receive either metformin 1000 mg twice daily or placebo, added to insulin. Randomisation was done via a web-based computerised randomisation service and stratified by centre and pre-pregnancy BMI (<30 kg/m 2 or ≥30 kg/m 2 ) in a ratio of 1:1 using random block sizes of 4 and 6. Women were eligible if they had type 2 diabetes, were on insulin, had a singleton viable pregnancy, and were between 6 and 22 weeks plus 6 days' gestation. Participants were asked to check their fasting blood glucose level before the first meal of the day, before the last meal of the day, and 2 h after each meal. Insulin doses were adjusted aiming for identical glucose targets (fasting glucose <5·3 mmol/L [95 mg/dL], 2-h postprandial glucose <6·7 mmol/L [120 mg/dL]). Study visits were done monthly and patients were seen every 1-4 weeks as was needed for standard clinical care. At study visits blood pressure and bodyweight were measured; patients were asked about tolerance to their pills, any hospitalisations, insulin doses, and severe hypoglycaemia events; and glucometer readings were downloaded to the central coordinating centre. Participants, caregivers, and outcome assessors were masked to the intervention. The primary outcome was a composite of fetal and neonatal outcomes, for which we calculated the relative risk and 95% CI between groups, stratifying by site and BMI using a log-binomial regression model with an intention-to-treat analysis. Secondary outcomes included several relevant maternal and neonatal outcomes. The trial was registered with ClinicalTrials.gov, NCT01353391., Findings: Between May 25, 2011, and Oct 11, 2018, we randomly assigned 502 women, 253 (50%) to metformin and 249 (50%) to placebo. Complete data were available for 233 (92%) participants in the metformin group and 240 (96%) in the placebo group for the primary outcome. We found no significant difference in the primary composite neonatal outcome between the two groups (40% vs 40%; p=0·86; relative risk [RR] 1·02 [0·83 to 1·26]). Compared with women in the placebo group, metformin-treated women achieved better glycaemic control (HbA 1c at 34 weeks' gestation 41·0 mmol/mol [SD 8·5] vs 43·2 mmol/mol [-10]; 5·90% vs 6·10%; p=0·015; mean glucose 6·05 [0·93] vs 6·27 [0·90]; difference -0·2 [-0·4 to 0·0]), required less insulin (1·1 units per kg per day vs 1·5 units per kg per day; difference -0·4 [95% CI -0·5 to -0·2]; p<0·0001), gained less weight (7·2 kg vs 9·0 kg; difference -1·8 [-2·7 to -0·9]; p<0·0001) and had fewer caesarean births (125 [53%] of 234 in the metformin group vs 148 [63%] of 236 in the placebo group; relative risk [RR] 0·85 [95% CI 0·73 to 0·99]; p=0·031). We found no significant difference between the groups in hypertensive disorders (55 [23%] in the metformin group vs 56 [23%] in the placebo group; p=0·93; RR 0·99 [0·72 to 1·35]). Compared with those in the placebo group, metformin-exposed infants weighed less (mean birthweight 3156 g [SD 742] vs 3375 g [742]; difference -218 [-353 to -82]; p=0·002), fewer were above the 97th centile for birthweight (20 [9%] in the metformin group vs 34 [15%] in the placebo group; RR 0·58 [0·34 to 0·97]; p=0·041), fewer weighed 4000 g or more at birth (28 [12%] in the metformin group vs 44 [19%] in the placebo group; RR 0·65 [0·43 to 0·99]; p=0·046), and metformin-exposed infants had reduced adiposity measures (mean sum of skinfolds 16·0 mm [SD 5·0] vs 17·4 [6·2] mm; difference -1·41 [-2·6 to -0·2]; p=0·024; mean neonatal fat mass 13·2 [SD 6·2] vs 14·6 [5·0]; p=0·017). 30 (13%) infants in the metformin group and 15 (7%) in the placebo group were small for gestational age (RR 1·96 [1·10 to 3·64]; p=0·026). We found no significant difference in the cord c-peptide between groups (673 pmol/L [435] in the metformin group vs 758 pmol/L [595] in the placebo group; p=0·10; ratio of means 0·88 [0·72 to 1·02]). The most common adverse event reported was gastrointestinal (38 events in the metformin group and 38 events in the placebo group)., Interpretation: We found several maternal glycaemic and neonatal adiposity benefits in the metformin group. Along with reduced maternal weight gain and insulin dosage and improved glycaemic control, the lower adiposity and infant size measurements resulted in fewer large infants but a higher proportion of small-for-gestational-age infants. Understanding the implications of these effects on infants will be important to properly advise patients who are contemplating the use of metformin during pregnancy., Funding: Canadian Institutes of Health Research, Lunenfeld-Tanenbaum Research Institute, University of Toronto., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Background: Screening in pregnancy for subclinical hypothyroidism, often defined as thyroid-stimulating hormone (TSH) greater than 2.5 mIU/L or greater than 4.0 mIU/L, is controversial. We determined the frequency and distribution of TSH testing by gestational age, as well as TSH values associated with treatment during pregnancy and the frequency of postpartum continuation of thyroid hormone therapy., Methods: We performed a retrospective cohort study of pregnancies in Alberta, Canada. We included women without thyroid disease who delivered between October 2014 and September 2017. We used delivery records, physician billings, and pharmacy and laboratory administrative data. Our key outcomes were characteristics of TSH testing and the initiation and continuation of thyroid hormone therapy. We calculated the proportion of pregnancies with thyroid testing and the frequency of each specific thyroid test., Results: Of the 188 490 pregnancies included, 111 522 (59.2%) had at least 1 TSH measurement. The most common time for testing was at gestational week 5 to 6. Thyroid hormone therapy was initiated at a median gestational age of 7 (interquartile range 5-12) weeks. Among women with first TSH measurements of 4.01 to 9.99 mIU/L who were not immediately treated, the repeat TSH measurement was 4.00 mIU/L or below in 67.9% of pregnancies. Thyroid hormone was continued post partum for 44.6% of the women who started therapy during their pregnancy., Interpretation: The findings of our study suggest that current practice patterns may contribute to overdiagnosis of hypothyroidism and overtreatment during pregnancy and post partum., Competing Interests: Competing interests: None declared., (© 2020 Joule Inc. or its licensors.)

Introduction: Women with diabetes, and their infants, have an increased risk of adverse events due to excess fetal growth. Earlier delivery, when fetuses are smaller, may reduce these risks. This study aimed to evaluate the week-specific risks of maternal and neonatal morbidity/mortality to assist with obstetrical decision making., Material and Methods: In this population-based cohort study, women with type 1 diabetes (n = 5889), type 2 diabetes (n = 9422) and gestational diabetes (n = 138 917) and a comparison group without diabetes (n = 2 553 243) who delivered a singleton infant at ≥36 completed weeks of gestation between 2004 and 2014 were identified from the Canadian Institute of Health Information Discharge Abstract Database. Multivariate logistic regression was used to determine the week-specific rates of severe maternal and neonatal morbidity/mortality among women delivered iatrogenically vs those undergoing expectant management., Results: For all women, the absolute risk of severe maternal morbidity/mortality was low, typically impacting less than 1% of women, and there was no significant difference in gestational age-specific severe maternal morbidity/mortality between iatrogenic delivery and expectant management among women with any form of diabetes. Among women with gestational diabetes, iatrogenic delivery was associated with an increased risk of neonatal morbidity/mortality compared with expectant management at 36 and 37 weeks' gestation (76.7 and 27.8 excess cases per 1000 deliveries, respectively) and a lower risk of neonatal morbidity/mortality at 38, 39 and 40 weeks' gestation (7.9, 27.3 and 15.9 fewer cases per 1000 deliveries, respectively). Increased risks of severe neonatal morbidity following iatrogenic delivery compared with expectant management were also observed for women with type 1 diabetes at 36 (98.3 excess cases per 1000 deliveries) and 37 weeks' gestation (44.5 excess cases per 1000 deliveries) and for women with type 2 diabetes at 36 weeks' gestation (77.9 excess cases per 1000 deliveries) weeks., Conclusions: The clinical decision regarding timing of delivery is complex and contingent on maternal-fetal wellbeing, including adequate glycemic control. This study suggests that delivery at 38, 39 or 40 weeks' gestation may optimize neonatal outcomes among women with diabetes., (© 2019 The Authors. Acta Obstetricia et Gynecologica Scandinavica published by John Wiley & Sons Ltd on behalf of Nordic Federation of Societies of Obstetrics and Gynecology (NFOG).)

Aims: To determine if in-target intrapartum glucose control is associated with neonatal hypoglycaemia in women with type 1, type 2 or gestational diabetes., Methods: This was a retrospective cohort study of pregnant women with diabetes and their neonates. The primary exposure was in-target glucose control, defined as all capillary glucose values within the range 3.5-6.5 mmol/l during the intrapartum period. The primary outcome, neonatal hypoglycaemia, was defined as treatment with intravenous dextrose therapy. Multiple logistic regression was used to examine the association between maternal intrapartum glycaemic control and neonatal hypoglycaemia, adjusting for covariates., Results: Intrapartum glucose testing was available for 157 (86.3%), 267 (76.3%) and 3256 (52.4%) women with type 1, type 2 and gestational diabetes, respectively. In the univariate analysis, in-target glycaemic control was significantly associated with neonatal hypoglycaemia in women with gestational diabetes, but not in women with type 1 or 2 diabetes. However, after adjustment for important neonatal factors (large for gestational age, preterm delivery and infant sex), intrapartum in-target glycaemic control was not significantly associated with neonatal hypoglycaemia in women regardless of diabetes type [adjusted odds ratios 0.4 (95% CI 0.1, 1.4), 0.7 (95% CI 0.3, 1.3) and 0.7 (95% CI 0.5, 1.0) for women with type 1, type 2 and gestational diabetes, respectively]., Conclusions: There was no significant association between in-target glycaemic control and neonatal hypoglycaemia after adjustment for neonatal factors. Given the high risk of maternal hypoglycaemia and the resources required, future trials should consider whether more relaxed intrapartum glycaemic targets may be safer and yield similar neonatal outcomes., (© 2019 The Authors. Diabetic Medicine published by John Wiley & Sons Ltd on behalf of Diabetes UK.)

Aims/hypothesis: We performed a systematic review and meta-analysis to determine whether exposure to maternal pre-existing diabetes in pregnancy is associated with neurocognitive or behavioural outcomes in offspring., Methods: We searched MEDLINE, EMBASE, PsychINFO, the Cochrane Database of Systematic Reviews and Scopus for studies that examined any neurocognitive or behavioural outcomes in offspring of mothers with pre-existing diabetes in pregnancy in accordance with a published protocol (PROSPERO CRD42018109038). Title and abstract review, full-text review and data extraction were performed independently and in duplicate. Risk of bias was assessed using the Newcastle-Ottawa scale. Meta-analyses of summary measures were performed using random-effects models., Results: Nineteen articles including at least 18,681 exposed and 2,856,688 control participants were identified for inclusion. Exposure to maternal pre-existing diabetes in pregnancy was associated with a lower pooled intelligence quotient in the offspring (pooled weighted mean difference -3.07 [95% CI -4.59, -1.55]; I 2  = 0%) and an increased risk of autism spectrum disorders (effect estimate 1.98 [95% CI 1.46, 2.68]; I 2  = 0%). There was also an increased risk of attention deficit/hyperactivity disorder (pooled HR 1.36 [95% CI 1.19, 1.55]; I 2  = 0%), though this was based on only two studies. Although most studies were found to be high quality in terms of participant selection, in many studies, comparability of cohorts and adequacy of follow-up were sources of bias., Conclusions/interpretation: There is evidence to suggest that in utero exposure to maternal pre-existing diabetes is associated with some adverse neurocognitive and behavioural outcomes. It remains unclear what the role of perinatal factors is and the degree to which other environmental factors contribute to these findings.

Purpose of Review: To review the latest evidence for dietary interventions for treatment of gestational diabetes (GDM)., Recent Findings: High-quality systematic reviews demonstrate no major advantages between the low-carbohydrate or calorie-restricted diets. However, the low glycemic index (GI) diet, characterized by intake of high-quality, complex carbohydrates, demonstrated lower insulin use and reduced risk of macrosomia in multiple reviews. Recent evidence suggests the Mediterranean diet is safe in pregnancy, though trials are needed to determine its efficacy over conventional dietary advice. Currently, there are insufficient data to support the safety of the ketogenic diet for the treatment of GDM. The low GI diet may improve maternal and neonatal outcomes in GDM. The liberalized carbohydrate intake is less restrictive, culturally adaptable, and may improve long-term maternal adherence. Further research is needed to establish the optimal, most sustainable, and most acceptable medical nutrition therapy for management of women with GDM.

Aims: To examine the relationship between maternal glycaemic control and risk of neonatal hypoglycaemia using conventional and continuous glucose monitoring metrics in the Continuous Glucose Monitoring in Type 1 Diabetes Pregnancy Trial (CONCEPTT) participants., Methods: A secondary analysis of CONCEPTT involving 225 pregnant women and their liveborn infants. Antenatal glycaemia was assessed at 12, 24 and 34 weeks gestation. Intrapartum glycaemia was assessed by continuous glucose monitoring measures 24 hours prior to delivery. The primary outcome was neonatal hypoglycaemia defined as glucose concentration < 2.6 mmol/l and requiring intravenous dextrose., Results: Neonatal hypoglycaemia occurred in 57/225 (25.3%) infants, 21 (15%) term and 36 (40%) preterm neonates. During the second and third trimesters, mothers of infants with neonatal hypoglycaemia had higher HbA 1c [48 ± 7 (6.6 ± 0.6) vs. 45 ± 7 (6.2 ± 0.6); P = 0.0009 and 50 ± 7 (6.7 ± 0.6) vs. 46 ± 7 (6.3 ± 0.6); P = 0.0001] and lower continuous glucose monitoring time-in-range (46% vs. 53%; P = 0.004 and 60% vs. 66%; P = 0.03). Neonates with hypoglycaemia had higher cord blood C-peptide concentrations [1416 (834, 2757) vs. 662 (417, 1086) pmol/l; P < 0.00001], birthweight > 97.7th centile (63% vs. 34%; P < 0.0001) and skinfold thickness (P ≤ 0.02). Intrapartum continuous glucose monitoring was available for 33 participants, with no differences between mothers of neonates with and without hypoglycaemia., Conclusions: Modest increments in continuous glucose monitoring time-in-target (5-7% increase) during the second and third trimesters are associated with reduced risk for neonatal hypoglycaemia. While more intrapartum continuous glucose monitoring data are needed, the higher birthweight and skinfold measures associated with neonatal hypoglycaemia suggest that risk is related to fetal hyperinsulinemia preceding the immediate intrapartum period., (© 2019 Diabetes UK.)

Background: Population-, assay-, and trimester-specific reference intervals for thyroid function tests are necessary to assess thyroid status accurately and manage thyroid disease throughout pregnancy. This study's objective was to verify if the manufacturer's recommended trimester-specific reference intervals for thyroid tests and the American Thyroid Association's recommended total thyroxine (TT4) pregnancy reference intervals were verifiable and appropriate for use in the authors' multicultural population., Methods: Blood samples were obtained from the following sources: stored frozen surplus blood from women undergoing routine aneuploidy screening (first- and second-trimester samples, n = 274), women participating in an observational cohort study (second- and third-trimester samples, n = 135), and blood collected from women presenting for assessment to the labor and delivery ward (third-trimester samples, n = 35). Exclusions included thyroid medication or disease and positive thyroid peroxidase antibodies (anti-TPO). Samples were analyzed for thyrotropin (TSH), free T4 (fT4), free triiodothyronine (fT3), TT4, and anti-TPO using the Roche Cobas 8000 Modular e602 electrochemiluminescence immunoassay., Results: Nine percent of the aneuploidy screening samples were excluded prior to thyroid testing due to maternal use of thyroid medication. Six percent of analyzed samples were excluded: 5.9% with positive anti-TPO and one with a TSH >10 mIU/L. The manufacturer's recommended trimester-specific reference intervals for TSH were not verified by described standardized methods. Therefore, 95th percentile reference intervals were determined using a minimum number of samples. Reference intervals for TSH and fT4 were as follows: 9-12 weeks, 0.18-2.99 mIU/L and 11-19.2 pmol/L; second trimester, 0.11-3.98 mIU/L and 10.5-18.2 pmol/L; and third trimester, 0.48-4.71 mIU/L and 9.0-16.1 pmol/L, respectively. The TT4 reference interval after 19 weeks' gestation was 77-186 nmol/L., Conclusions: This study provides a simple approach to verify or establish trimester-specific thyroid function reference intervals in local populations. The TT4 reference interval was lower than the interval proposed by the American Thyroid Association, suggesting the need for further study of TT4 in pregnancy and reliance on locally established fT4 reference intervals after 19 weeks, especially when there are no equivalent reference intervals for TT4.

Aims/hypothesis: This study aimed to examine the association of maternal diabetes, being large for gestational age (LGA) and breast-feeding with being overweight or obese in pre-school-aged children., Methods: Data on height and weight at the time of their pre-school (age 4-6 years) immunisation visit between January 2009 and August 2017, as well as breast-feeding status in the first 5 months of life, for 81,226 children born between January 2005 and August 2013 were linked with maternal hospitalisation and outpatient records and birth registry data. Children were grouped into six categories based on maternal diabetes status during pregnancy (no diabetes, gestational diabetes or pre-existing diabetes) and birthweight (appropriate for gestational age [AGA] or LGA). WHO criteria were used to identify children who were overweight or obese., Results: There were 69,506 children in the no diabetes/AGA group (control), 5926 in the no diabetes/LGA group, 4563 in the gestational diabetes/AGA group, 573 in the gestational diabetes/LGA group, 480 in the pre-existing diabetes/AGA group and 178 in the pre-existing diabetes/LGA group. The rate of being overweight/obese at pre-school age ranged from 20.5% in the control group to 42.9% in the gestational diabetes/LGA group. The adjusted attributable risk per cent for LGA alone (39.4%) was significantly higher than that for maternal gestational diabetes (16.0%) or pre-existing diabetes alone (15.1%); the risk for the combinations of gestational diabetes/LGA and pre-existing diabetes/LGA were 50.1% and 39.1%, respectively. Further stratification of the pre-existing diabetes groups found the prevalence of being overweight/obese was 21.2% in the type 1/AGA group, 31.4% in the type 1/LGA group (similar to those in the no diabetes groups), 26.7% in the type 2/AGA group and 42.5% in the type 2/LGA group. Breast-feeding was associated with a lower likelihood of being overweight/obese in childhood in all groups except gestational diabetes/LGA and pre-existing diabetes/LGA (both type 1 and type 2)., Conclusion/interpretation: LGA is a stronger marker for risk of being overweight/obese in early childhood, compared with maternal diabetes during pregnancy. Rates of being overweight/obese in childhood were highest in LGA children born to mothers with gestational diabetes or pre-existing type 2 diabetes. Breast-feeding was associated with a lower risk of being overweight/obese in childhood in the majority of children; however, this association was not maintained in LGA children of mothers with diabetes.

Aims: To assess the association between vascular complications of diabetes and the risk of congenital malformations in pregnant women with Type 1 diabetes., Methods: We conducted an observational retrospective cohort study in women with Type 1 diabetes who received care consecutively from three tertiary care diabetes-in-pregnancy clinics in Calgary, Alberta, Canada. Multivariable logistic regression was used to assess the association between vascular complications (retinopathy, nephropathy and pre-existing hypertension) and congenital malformations in offspring of women with Type 1 diabetes., Results: Of 232 women with Type 1 diabetes, 49 (21%) had at least one vascular complication and there were 52 babies with congenital malformations. Maternal age (31.8 ± 5.0 vs. 29.4 ± 4.7 years, P < 0.01), diabetes duration (20.9 ± 6.7 vs. 11.2 ± 7.4 years, P < 0.01) and pre-eclampsia rate (12.5% vs. 1.3%, P < 0.01) were higher in mothers with vascular complications than in those without. Multivariable analyses showed that vascular complications were not associated with an increased risk of congenital malformations (odds ratio 1.16, 95% confidence interval 0.46 to 2.88)., Conclusions: Vascular complications are common, occurring in one-fifth of pregnant women with Type 1 diabetes, and in this study do not appear to be associated with an increased risk of congenital malformations in children., (© 2018 Diabetes UK.)

There is currently no universally accepted standard of care treatment for low-grade gliomas, a molecularly heterogeneous group of tumors with similarly heterogeneous clinical outcomes. Risk stratification by clinical and molecular features is useful to help determine which patients benefit the most from adjuvant treatment. The addition of combination chemotherapy with procarbazine, lomustine, and vincristine confers survival advantage, as likely does temozolomide, but radiochemotherapy may not be appropriate for all patients owing to its toxicity profile. We review the approach to treatment in patients with low-grade gliomas with an emphasis on the clinical trials focusing on adjuvant chemotherapy in this population., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Objective: To compare glycemic control, quality of life, and pregnancy outcomes of women using insulin pumps and multiple daily injection therapy (MDI) during the Continuous Glucose Monitoring in Women With Type 1 Diabetes in Pregnancy Trial (CONCEPTT)., Research Design and Methods: This was a prespecified analysis of CONCEPTT involving 248 pregnant women from 31 centers. Randomization was stratified for pump versus MDI and HbA 1c . The primary outcome was change in HbA 1c from randomization to 34 weeks' gestation. Key secondary outcomes were continuous glucose monitoring (CGM) measures, maternal-infant health, and patient-reported outcomes., Results: At baseline, pump users were more often in stable relationships ( P = 0.003), more likely to take preconception vitamins ( P = 0.03), and less likely to smoke ( P = 0.02). Pump and MDI users had comparable first-trimester glycemia: HbA 1c 6.84 ± 0.71 vs. 6.95 ± 0.58% (51 ± 7.8 vs. 52 ± 6.3 mmol/mol) ( P = 0.31) and CGM time in target (51 ± 14 vs. 50 ± 13%) ( P = 0.40). At 34 weeks, MDI users had a greater decrease in HbA 1c (-0.55 ± 0.59 vs. -0.32 ± 0.65%, P = 0.001). At 24 and 34 weeks, MDI users were more likely to achieve target HbA 1c ( P = 0.009 and P = 0.001, respectively). Pump users had more hypertensive disorders ( P = 0.011), mainly driven by increased gestational hypertension (14.4 vs. 5.2%; P = 0.025), and more neonatal hypoglycemia (31.8 vs. 19.1%, P = 0.05) and neonatal intensive care unit (NICU) admissions >24 h (44.5 vs. 29.6%; P = 0.02). Pump users had a larger reduction in hypoglycemia-related anxiety ( P = 0.05) but greater decline in health/well-being ( P = 0.02)., Conclusions: In CONCEPTT, MDI users were more likely to have better glycemic outcomes and less likely to have gestational hypertension, neonatal hypoglycemia, and NICU admissions than pump users. These data suggest that implementation of insulin pump therapy is potentially suboptimal during pregnancy., (© 2018 by the American Diabetes Association.)

Background: Gestational diabetes mellitus (GDM) can be diagnosed in pregnant women by increased fasting plasma glucose alone, which eliminates the need for performing a 75 g oral glucose tolerance test (OGTT). If whole blood glucose meters are used to triage fasting samples in order to decide whether to give the glucose drink, a cutpoint with appropriate sensitivity and specificity for elevated fasting plasma glucose is needed., Methods: The number of GDM diagnoses by increased fasting plasma glucose alone was determined from specimens collected and tested at core laboratories in urban hospitals, rural health centers, and from specimens collected at patient phlebotomy service centers (PSCs) for plasma testing at a central laboratory. The number of glucose drinks avoided was counted after implementing the diagnostic cutoff of ≥95 mg/dL (5.3 mmol/L) at urban hospitals and rural health centers, which have on-site plasma testing, and after selecting a PSC meter fasting venous whole blood glucose cutpoint after calculating sensitivity and specificity for plasma glucose ≥95 mg/dL (5.3 mmol/L) using logistic regression., Results: Among 4850 OGTTs, there were 1315 GDM diagnoses annually, of which 409 were from increased fasting plasma glucose. Ninety-one percent of OGTTs were performed at PSCs. If a fasting plasma glucose cutpoint of ≥95 mg/dL (5.3 mmol/L) was implemented at urban hospitals and rural health centers and a meter fasting venous whole blood glucose cutpoint of ≥108 mg/dL (6.0 mmol/L) (25% sensitivity, 99.9% specificity) was implemented at PSCs, the drink would be appropriately avoided by 145 patients/year, and inappropriately avoided by 3 patients/year. After implementing these cutpoints, the drink was appropriately avoided in 91 patients during a 36-week period, with none inappropriately avoiding it., Conclusion: Modifying fasting glucose cutpoints reduced unnecessary diagnostic OGTTs in pregnant women., (© 2018 American Association for Clinical Chemistry.)

We present the case of a 23-year-old woman with a long-standing history of recurrent left-sided pleural effusion unrelated to her menstrual cycle. At her last presentation, non-contrast-enhanced chest CT showed a pleural effusion and a lower left hemithorax mass, both large enough to cause complete collapse of the lower lobe and partial collapse of the upper lobe. Thoracoscopic surgery revealed a multilobulated mass originating from the dome of the diaphragm with pleural deposits. Histopathology diagnosed this as a calcifying fibrous tumour of the pleura, a rare benign tumour with excellent prognosis when completely excised., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2018. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: To determine in women with subclinical hypothyroidism diagnosed in pregnancy whether levothyroxine treatment compared with control, impacts important obstetrical or childhood outcomes (specifically IQ) in randomised controlled trials., Design: Systematic review and meta-analysis., Study Eligibility Criteria: Randomised trials which met all the following were included: (1) reported original data of women with subclinical hypothyroidism diagnosed in pregnancy (by any prespecified study definition); (2) randomised to either levothyroxine or control (placebo or no treatment); (3) reported obstetrical outcomes and/or childhood neurodevelopmental outcomes and (4) published from 1980 to January 2018 in either English or French language., Data Sources: Medline, EMBASE, CINAHL, Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials and ClinicalTrials.gov., Outcome Measures: Obstetrical, neonatal and childhood outcomes including: miscarriage, gestational hypertension, pre-eclampsia, preterm delivery, mode of delivery, neonatal intensive care unit admission, birth weight, gestational age at delivery, childhood IQ and neurodevelopmental scores. Risk of bias assessment Cochrane Risk of Bias Tool (Modified) for Quality Assessment of Randomised Controlled Trials RESULTS: Three trials of low to unclear risk of bias with 1837 participants were included. Two studies were meta-analysed for maternal and neonatal outcomes and two studies for childhood IQ. No statistically significant differences were found for any clinical outcomes with levothyroxine therapy compared with control., Limitations: Only three trials were identified for inclusion., Conclusions: This review, based on three randomised trials in women with subclinical hypothyroidism diagnosed in pregnancy, found no evidence of benefit of levothyroxine therapy on obstetrical, neonatal, childhood IQ or neurodevelopmental outcomes. Current trial evidence does not support the treatment of subclinical hypothyroidism diagnosed in pregnancy., Prospero Registration Number: CRD4201707980., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2018. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose of Review: Pituitary tumors account for approximately 17% of all intracranial neoplasms, with the majority being pituitary adenomas. Often, these are found incidentally during a workup for headache; however, the relationship between symptom and pathology remains unclear. The purpose of this article is to review the most recent literature on the epidemiology, pathophysiology, and management of headaches in patients with pituitary tumors., Recent Findings: The current literature is limited, with few prospective trials focusing on this question. With the exception of pituitary apoplexy, the relationship between headaches and pituitary masses remains unclear. Intervention does not always improve headache and can lead to development of new headache syndromes. Further research is needed to better elucidate the relationship between pituitary tumors and headaches. Headache alone is rarely an indication for surgical management of a pituitary adenoma.