Pregnancy and COVID-19.

There are many unknowns for pregnant women during the coronavirus disease 2019 (COVID-19) pandemic. Clinical experience of pregnancies complicated with infection by other coronaviruses e.g., Severe Acute Respiratory Syndrome (SARS) and Middle Eastern Respiratory Syndrome, has led to pregnant woman being considered potentially vulnerable to severe SARS-CoV-2 infection. Physiological changes during pregnancy have a significant impact on the immune system, respiratory system, cardiovascular function, and coagulation. These may have positive or negative effects on COVID-19 disease progression. The impact of SARS-CoV-2 in pregnancy remains to be determined, and a concerted, global effort is required to determine the effects on implantation, fetal growth and development, labor, and neonatal health. Asymptomatic infection presents a further challenge regarding service provision, prevention, and management. Besides the direct impacts of the disease, a plethora of indirect consequences of the pandemic adversely affect maternal health, including reduced access to reproductive health services, increased mental health strain, and increased socioeconomic deprivation. In this review, we explore the current knowledge of COVID-19 in pregnancy and highlight areas for further research to minimize its impact for women and their children.

Automated Insulin Delivery in Women with Pregnancy Complicated by Type 1 Diabetes.

BACKGROUND: Hybrid closed-loop insulin therapy has shown promise for management of type 1 diabetes during pregnancy; however, its efficacy is unclear. METHODS: In this multicenter, controlled trial, we randomly assigned pregnant women with type 1 diabetes and a glycated hemoglobin level of at least 6.5% at nine sites in the United Kingdom to receive standard insulin therapy or hybrid closed-loop therapy, with both groups using continuous glucose monitoring. The primary outcome was the percentage of time in the pregnancy-specific target glucose range (63 to 140 mg per deciliter [3.5 to 7.8 mmol per liter]) as measured by continuous glucose monitoring from 16 weeks' gestation until delivery. Analyses were performed according to the intention-to-treat principle. Key secondary outcomes were the percentage of time spent in a hyperglycemic state (glucose level >140 mg per deciliter), overnight time in the target range, the glycated hemoglobin level, and safety events. RESULTS: A total of 124 participants with a mean (±SD) age of 31.1±5.3 years and a mean baseline glycated hemoglobin level of 7.7±1.2% underwent randomization. The mean percentage of time that the maternal glucose level was in the target range was 68.2±10.5% in the closed-loop group and 55.6±12.5% in the standard-care group (mean adjusted difference, 10.5 percentage points; 95% confidence interval [CI], 7.0 to 14.0; P<0.001). Results for the secondary outcomes were consistent with those of the primary outcome; participants in the closed-loop group spent less time in a hyperglycemic state than those in the standard-care group (difference, -10.2 percentage points; 95% CI, -13.8 to -6.6); had more overnight time in the target range (difference, 12.3 percentage points; 95% CI, 8.3 to 16.2), and had lower glycated hemoglobin levels (difference, -0.31 percentage points; 95% CI, -0.50 to -0.12). Little time was spent in a hypoglycemic state. No unanticipated safety problems associated with the use of closed-loop therapy during pregnancy occurred (6 instances of severe hypoglycemia, vs. 5 in the standard-care group; 1 instance of diabetic ketoacidosis in each group; and 12 device-related adverse events in the closed-loop group, 7 related to closed-loop therapy). CONCLUSIONS: Hybrid closed-loop therapy significantly improved maternal glycemic control during pregnancy complicated by type 1 diabetes. (Funded by the Efficacy and Mechanism Evaluation Program; AiDAPT ISRCTN Registry number, ISRCTN56898625.).

Plasma steroid concentrations reflect acute disease severity and normalise during recovery in people hospitalised with COVID-19.

OBJECTIVE: Endocrine systems are disrupted in acute illness, and symptoms reported following coronavirus disease 2019 (COVID-19) are similar to those found with clinical hormone deficiencies. We hypothesised that people with severe acute COVID-19 and with post-COVID symptoms have glucocorticoid and sex hormone deficiencies. DESIGN/PATIENTS: Samples were obtained for analysis from two UK multicentre cohorts during hospitalisation with COVID-19 (International Severe Acute Respiratory Infection Consortium/World Health Organisation [WHO] Clinical Characterization Protocol for Severe Emerging Infections in the UK study), and at follow-up 5 months after hospitalisation (Post-hospitalisation COVID-19 study). MEASUREMENTS: Plasma steroids were quantified by liquid chromatography-mass spectrometry. Steroid concentrations were compared against disease severity (WHO ordinal scale) and validated symptom scores. Data are presented as geometric mean (SD). RESULTS: In the acute cohort (n = 239, 66.5% male), plasma cortisol concentration increased with disease severity (cortisol 753.3 [1.6] vs. 429.2 [1.7] nmol/L in fatal vs. least severe, p < .001). In males, testosterone concentrations decreased with severity (testosterone 1.2 [2.2] vs. 6.9 [1.9] nmol/L in fatal vs. least severe, p < .001). In the follow-up cohort (n = 198, 62.1% male, 68.9% ongoing symptoms, 165 [121-192] days postdischarge), plasma cortisol concentrations (275.6 [1.5] nmol/L) did not differ with in-hospital severity, perception of recovery, or patient-reported symptoms. Male testosterone concentrations (12.6 [1.5] nmol/L) were not related to in-hospital severity, perception of recovery or symptom scores. CONCLUSIONS: Circulating glucocorticoids in patients hospitalised with COVID-19 reflect acute illness, with a marked rise in cortisol and fall in male testosterone. These findings are not observed 5 months from discharge. The lack of association between hormone concentrations and common post-COVID symptoms suggests steroid insufficiency does not play a causal role in this condition.

Impact of COVID-19 on gestational diabetes pregnancy outcomes in the UK: A multicentre retrospective cohort study.

OBJECTIVE: To determine the impact of implementing emergency care pathway(s) for screening, diagnosing and managing women with gestational diabetes (GDM) during COVID-19. DESIGN: Retrospective multicentre cohort. SETTING: Nine National Health Service (NHS) Hospital Trusts/Health boards in England and Scotland. POPULATION: 4915 women with GDM pre-pandemic (1 April 2018 to 31 March 2020), and 3467 women with GDM during the pandemic (1 May 2020 to 31 March 2021). METHODS: We examined clinical outcomes for women with GDM prior to and during the pandemic following changes in screening methods, diagnostic testing, glucose thresholds and introduction of virtual care for monitoring of antenatal glycaemia. MAIN OUTCOME MEASURES: Intervention at birth, perinatal mortality, large-for-gestational-age infants and neonatal unit admission. RESULTS: The new diagnostic criteria more often identified GDM women who were multiparous, had higher body mass index (BMI) and greater deprivation, and less frequently had previous GDM (all p < 0.05). During COVID, these women had no differences in the key outcome measures. Of the women, 3% were identified with pre-existing diabetes at antenatal booking. Where OGTT continued during COVID, but virtual care was introduced, outcomes were also similar pre- and during the pandemic. CONCLUSIONS: Using HbA1c and fasting glucose identified a higher risk GDM population during the pandemic but this had minimal impact on pregnancy outcomes. The high prevalence of undiagnosed pre-existing diabetes suggests that women with GDM risk factors should be offered HbA1c screening in early pregnancy.

Healthcare professionals' views about how pregnant women can benefit from using a closed-loop system: Qualitative study.

BACKGROUND: Interest is growing in how closed-loop systems can support attainment of within-target glucose levels amongst pregnant women with type 1 diabetes. We explored healthcare professionals' views about how, and why, pregnant women benefitted from using the CamAPS FX system during the AiDAPT trial. METHODS: We interviewed 19 healthcare professionals who supported women using closed-loop during the trial. Our analysis focused on identifying descriptive and analytical themes relevant to clinical practice. RESULTS: Healthcare professionals highlighted clinical and quality-of-life benefits to using closed-loop in pregnancy; albeit, they attributed some of these to the continuous glucose monitoring component. They emphasised that the closed-loop was not a panacea and that, to gain maximum benefit, an effective collaboration between themselves, the woman and the closed-loop was needed. Optimal performance of the technology, as they further noted, also required women to interact with the system sufficiently, but not excessively; a requirement that they felt some women had found challenging. Even where healthcare professionals felt that this balance was not achieved, they suggested that women had still benefitted from using the system. Healthcare professionals reported difficulties predicting how specific women would engage with the technology. In light of their trial experiences, healthcare professionals favoured an inclusive approach to closed-loop rollout in routine clinical care. CONCLUSIONS: Healthcare professionals recommended that closed-loop systems be offered to all pregnant women with type 1 diabetes in the future. Presenting closed-loop systems to pregnant women and healthcare teams as one pillar of a three-party collaboration may help promote optimal use.

Non-invasive imaging of functional pancreatic islet beta-cell mass in people with type 1 diabetes mellitus.

AIMS: To investigate whether manganese-enhanced magnetic resonance imaging can assess functional pancreatic beta-cell mass in people with type 1 diabetes mellitus. METHODS: In a prospective case-control study, 20 people with type 1 diabetes mellitus (10 with low (≥50 pmol/L) and 10 with very low (<50 pmol/L) C-peptide concentrations) and 15 healthy volunteers underwent manganese-enhanced magnetic resonance imaging of the pancreas following an oral glucose load. Scan-rescan reproducibility was performed in 10 participants. RESULTS: Mean pancreatic manganese uptake was 31 ± 6 mL/100 g of tissue/min in healthy volunteers (median 32 [interquartile range 23-36] years, 6 women), falling to 23 ± 4 and 13 ± 5 mL/100 g of tissue/min (p ≤ 0.002 for both) in people with type1 diabetes mellitus (52 [44-61] years, 6 women) and low or very low plasma C-peptide concentrations respectively. Pancreatic manganese uptake correlated strongly with plasma C-peptide concentrations in people with type1 diabetes mellitus (r = 0.73, p < 0.001) but not in healthy volunteers (r = -0.054, p = 0.880). There were no statistically significant correlations between manganese uptake and age, body-mass index, or glycated haemoglobin. There was strong intra-observer (mean difference: 0.31 (limits of agreement -1.42 to 2.05) mL/100 g of tissue/min; intra-class correlation, ICC = 0.99), inter-observer (-1.23 (-5.74 to 3.27) mL/100 g of tissue/min; ICC = 0.85) and scan-rescan (-0.72 (-2.9 to 1.6) mL/100 g of tissue/min; ICC = 0.96) agreement for pancreatic manganese uptake. CONCLUSIONS: Manganese-enhanced magnetic resonance imaging provides a potential reproducible non-invasive measure of functional beta-cell mass in people with type 1 diabetes mellitus. This holds major promise for investigating type 1 diabetes, monitoring disease progression and assessing novel immunomodulatory interventions.

Positive maternal mental health during pregnancy and mental and behavioral disorders in children: A prospective pregnancy cohort study.

BACKGROUND: The role of positive maternal mental health during pregnancy in child mental health remains largely unknown. We investigated whether positive maternal mental health during pregnancy is associated with lower hazards of mental and behavioral disorders in children and mitigates the adverse effects of negative maternal mental health. METHODS: Among 3,378 mother-child dyads of the Prediction and Prevention of Preeclampsia and Intrauterine Growth Restriction study, mothers reported their positive mental health biweekly throughout pregnancy with the Positive and Negative Affect Schedule, the Spielberger State Anxiety Inventory Curiosity scale, and a visual analogue scale for social support, and negative mental health with the Center for Epidemiologic Studies Depression Scale. We extracted data on their mental and behavioral disorder diagnoses from a nationwide medical register. This register provided data on their children's mental and behavioral disorder diagnoses as well, from birth until 8.4-12.8 (Median = 10.2, Interquartile Range 9.7-10.8) years of age. RESULTS: A positive maternal mental health composite score during pregnancy was associated with a lower hazard of any mental and behavioral disorder among all children [Hazard Ratio (HR) = 0.79, 95% Confidence Interval (CI) 0.71 - 0.87] and among children of mothers experiencing clinically relevant depressive symptoms during pregnancy [HR = 0.80, 95%CI 0.64 - 1.00] and/or mental and behavioral disorders before or during pregnancy [HR = 0.69, 95%CI 0.55-0.86]. These associations were independent of covariates. CONCLUSIONS: Children whose mothers had more positive mental health during pregnancy were less likely to develop mental and behavioral disorders. Protective effects were seen also among children of mothers facing mental health adversities before or during pregnancy.

Associations between parental type 2 diabetes risk and offspring birthweight and placental weight: a survival analysis using the Walker cohort.

AIMS/HYPOTHESIS: Low birthweight (BW) is associated with the development of type 2 diabetes. Genome-wide analyses have identified a strong genetic component to this association, with many BW-associated loci also involved in glucose metabolism. We hypothesised that offspring BW and placental weight (PW) are correlated with parental type 2 diabetes risk, reflecting the inheritance of diabetes risk alleles that also influence fetal growth. METHODS: The Walker cohort, a collection of birth records from Dundee, Scotland, from the 1950s and the 1960s was used to test this hypothesis by linking BW and PW measurements to parental health outcomes. Using data from SCI-Diabetes and the national death registry, we obtained health records for over 20,000 Walker parents. We performed Fine-Gray survival analyses of parental type 2 diabetes risk with competing risk of death, and Cox regression analyses of risk of death, independently in the maternal and paternal datasets, modelled by offspring BW and PW. RESULTS: We found significant associations between increased paternal type 2 diabetes risk and reduced offspring BW (subdistribution hazard ratio [SHR] 0.92 [95% CI 0.87, 0.98]) and PW (SHR 0.87 [95% CI 0.81, 0.94]). The association of maternal type 2 diabetes risk with offspring BW or PW was not significant. Lower offspring BW was also associated with increased risk of death in both mothers (HR 0.91 [95% CI 0.89, 0.94]) and fathers (HR 0.95 [95% CI 0.92, 0.98]), and higher offspring PW was associated with increased maternal mortality risk (HR 1.08 [95% CI 1.04, 1.13]) when adjusted for BW. CONCLUSIONS/INTERPRETATION: We identified associations between offspring BW and reduced paternal type 2 diabetes risk, most likely resulting from the independent effects of common type 2 diabetes susceptibility alleles on fetal growth, as described by the fetal insulin hypothesis. Moreover, we identified novel associations between offspring PW and reduced paternal type 2 diabetes risk, a relationship that might also be caused by the inheritance of diabetes predisposition variants. We found differing associations between offspring BW and PW and parental risk of death. These results provide novel epidemiological support for the use of offspring BW and PW as predictors for future risk of type 2 diabetes and death in mothers and fathers.

AiDAPT: automated insulin delivery amongst pregnant women with type 1 diabetes: a multicentre randomized controlled trial - study protocol.

BACKGROUND: Pregnant women with type 1 diabetes strive for tight glucose targets (3.5-7.8 mmol/L) to minimise the risks of obstetric and neonatal complications. Despite using diabetes technologies including continuous glucose monitoring (CGM), insulin pumps and contemporary insulin analogues, most women struggle to achieve and maintain the recommended pregnancy glucose targets. This study aims to evaluate whether the use of automated closed-loop insulin delivery improves antenatal glucose levels in pregnant women with type 1 diabetes. METHODS/DESIGN: A multicentre, open label, randomized, controlled trial of pregnant women with type 1 diabetes and a HbA1c of ≥48 mmol/mol (6.5%) at pregnancy confirmation and ≤ 86 mmol/mol (10%) at randomization. Participants who provide written informed consent before 13 weeks 6 days gestation will be entered into a run-in phase to collect 96 h (24 h overnight) of CGM glucose values. Eligible participants will be randomized on a 1:1 basis to CGM (Dexcom G6) with usual insulin delivery (control) or closed-loop (intervention). The closed-loop system includes a model predictive control algorithm (CamAPS FX application), hosted on an android smartphone that communicates wirelessly with the insulin pump (Dana Diabecare RS) and CGM transmitter. Research visits and device training will be provided virtually or face-to-face in conjunction with 4-weekly antenatal clinic visits where possible. Randomization will stratify for clinic site. One hundred twenty-four participants will be recruited. This takes into account 10% attrition and 10% who experience miscarriage or pregnancy loss. Analyses will be performed according to intention to treat. The primary analysis will evaluate the change in the time spent in the target glucose range (3.5-7.8 mmol/l) between the intervention and control group from 16 weeks gestation until delivery. Secondary outcomes include overnight time in target, time above target (> 7.8 mmol/l), standard CGM metrics, HbA1c and psychosocial functioning and health economic measures. Safety outcomes include the number and severity of ketoacidosis, severe hypoglycaemia and adverse device events. DISCUSSION: This will be the largest randomized controlled trial to evaluate the impact of closed-loop insulin delivery during type 1 diabetes pregnancy. TRIAL REGISTRATION: ISRCTN 56898625 Registration Date: 10 April, 2018.

Reproductive and metabolic adaptation to multistressor training in women.

Hypothalamic-pituitary-gonadal (HPG) axis suppression in exercising women can be caused by low energy availability (EA), but the impact of a real-world, multistressor training environment on reproductive and metabolic function is unknown. This study aimed to characterize reproductive and metabolic adaptation in women undertaking basic military training. A prospective cohort study in women undertaking 11-month initial military training (n = 47) was carried out. Dynamic low-dose 1-h gonadotrophin-releasing hormone (GnRH) tests were completed after 0 and 7 mo of training. Urine progesterone was sampled weekly throughout. Body composition (dual X-ray absorptiometry), fasting insulin resistance (homeostatic modeling assessment 2, HOMA2), leptin, sex steroids, anti-Müllerian hormone (AMH), and inhibin B were measured after 0, 7, and 11 mo with an additional assessment of body composition at 3 mo. Luteinizing hormone (LH) and follicle-stimulating hormone (FSH) responses were suppressed after 7 mo (both P < 0.001). Among noncontraceptive users (n = 20), 65% had regular (23-35 days) cycles preenrollment, falling to 24% by 7 mo of training. Of women in whom urine progesterone was measured (n = 24), 87% of cycles showed no evidence of ovulation. There was little change in AMH, LH, and estradiol, although inhibin B and FSH increased (P < 0.05). Fat mass fluctuated during training but at month 11 was unchanged from baseline. Fat-free mass did not change. Visceral adiposity, HOMA2, and leptin increased (all P < 0.001). HPG axis suppression with anovulation occurred in response to training without evidence of low EA. Increased insulin resistance may have contributed to the observed pituitary and ovarian dysfunction. Our findings are likely to represent an adaptive response of reproductive function to the multistressor nature of military training.NEW & NOTEWORTHY We characterized reproductive endocrine adaptation to prolonged arduous multistressor training in women. We identified marked suppression of hypothalamic-pituitary-gonadal (HPG) axis function during training but found no evidence of low energy availability despite high energy requirements. Our findings suggest a complex interplay of psychological and environmental stressors with suppression of the HPG axis via activation of the hypothalamic-pituitary adrenal (HPA) axis. The neuroendocrine impact of nonexercise stressors on the HPG axis during arduous training should be considered.

Impact of routine clinic measurement of serum C-peptide in people with a clinician-diagnosis of type 1 diabetes.

AIMS/HYPOTHESIS: The aim of this study was to determine the impact of the routine use of serum C-peptide in an out-patient clinic setting on individuals with a clinician-diagnosis of type 1 diabetes. METHODS: In this single-centre study, individuals with type 1 diabetes of at least 3 years duration were offered random serum C-peptide testing at routine clinic review. A C-peptide ≥200 pmol/L prompted further evaluation of the individual using a diagnostic algorithm that included measurement of islet cell antibodies and genetic testing. Where appropriate, a trial of anti-diabetic co-therapies was considered. RESULTS: Serum C-peptide testing was performed in 859 individuals (90% of the eligible cohort), of whom 114 (13.2%) had C-peptide ≥200 pmol/L. The cause of diabetes was reclassified in 58 individuals (6.8% of the tested cohort). The majority of reclassifications were to type 2 diabetes (44 individuals; 5.1%), with a smaller proportion of monogenic diabetes (14 individuals; 1.6%). Overall, 13 individuals (1.5%) successfully discontinued insulin, while a further 16 individuals (1.9%) had improved glycaemic control following the addition of co-therapies. The estimated total cost of the testing programme was £23,262 (~€26,053), that is, £27 (~€30) per individual tested. In current terms, the cost of prior insulin therapy in the individuals with monogenic diabetes who successfully stopped insulin was approximately £57,000 (~€64,000). CONCLUSIONS/INTERPRETATION: Serum C-peptide testing can easily be incorporated into an out-patient clinic setting and could be a cost-effective intervention. C-peptide testing should be strongly considered in individuals with a clinician-diagnosis of type 1 diabetes of at least 3 years duration.

Maternal depression and inflammation during pregnancy.

BACKGROUND: Maternal depression during pregnancy increases the risk for adverse developmental outcomes in children. However, the underpinning biological mechanisms remain unknown. We tested whether depression was associated with levels of and change in the inflammatory state during pregnancy, if early pregnancy overweight/obesity or diabetes/hypertensive pregnancy disorders accounted for/mediated these effects, and if depression added to the inflammation that typically accompanies these conditions. METHODS: We analyzed plasma high-sensitivity C-reactive protein (hsCRP) and glycoprotein acetyls at three consecutive stages during pregnancy, derived history of depression diagnoses before pregnancy from Care Register for Healthcare (HILMO) (N = 375) and self-reports (N = 347) and depressive symptoms during pregnancy using the Center for Epidemiological Studies Depression Scale completed concurrently to blood samplings (N = 295). Data on early pregnancy body mass index (BMI) and diabetes/hypertensive pregnancy disorders came from medical records. RESULTS: Higher overall hsCRP levels, but not change, during pregnancy were predicted by history of depression diagnosis before pregnancy [HILMO: mean difference (MD) = 0.69 standard deviation (s.d.) units; 95% confidence interval (CI) 0.26-1.11, self-report: MD = 0.56 s.d.; 95% CI 0.17-0.94] and higher depressive symptoms during pregnancy (0.06 s.d. per s.d. increase; 95% CI 0.00-0.13). History of depression diagnosis before pregnancy also predicted higher overall glycoprotein acetyls (HILMO: MD = 0.52 s.d.; 95% CI 0.12-0.93). These associations were not explained by diabetes/hypertensive disorders, but were accounted for and mediated by early pregnancy BMI. Furthermore, in obese women, overall hsCRP levels increased as depressive symptoms during pregnancy increased (p = 0.006 for interaction). CONCLUSIONS: Depression is associated with a proinflammatory state during pregnancy. These associations are mediated by early pregnancy BMI, and depressive symptoms during pregnancy aggravate the inflammation related to obesity.

Associations of antenatal glucocorticoid exposure with mental health in children.

BACKGROUND: Synthetic glucocorticoids, to enhance fetal maturation, are a standard treatment when preterm birth before 34 gestational weeks is imminent. While morbidity- and mortality-related benefits may outweigh potential neurodevelopmental harms in children born preterm (<37 gestational weeks), this may not hold true when pregnancy continues to term (⩾37 gestational weeks). We studied the association of antenatal betamethasone exposure on child mental health in preterm and term children. METHODS: We included 4708 women and their children, born 2006-2010, from the Prediction and Prevention of Pre-eclampsia and Intrauterine Growth Restriction Study with information on both antenatal betamethasone treatment and child mental and behavioral disorders from the Finnish Hospital Discharge Register from the child's birth to 31 December 2016. Additional follow-up data on mother-reported psychiatric problems and developmental milestones were available for 2640 children at 3.5 (s.d. = 0.07) years-of-age. RESULTS: Of the children, 187 were born preterm (61 betamethasone-exposed) and 4521 at term (56 betamethasone-exposed). The prevalence of any mental and behavioral, psychological development, emotional and behavioral, and comorbid disorders was higher in the betamethasone-exposed, compared to non-exposed children [odds ratio 2.76 (95% confidence interval 1.76-4.32), 3.61 (2.19-5.95), 3.29 (1.86-5.82), and 6.04 (3.25-11.27), respectively]. Levels of psychiatric problems and prevalence of failure to meet the age-appropriate development in personal-social skills were also higher in mother-reports of betamethasone-exposed children. These associations did not vary significantly between preterm and term children. CONCLUSIONS: Antenatal betamethasone exposure may be associated with mental health problems in children born preterm and in those who end up being born at term.

Non-invasive risk scores do not reliably identify future cirrhosis or hepatocellular carcinoma in Type 2 diabetes: The Edinburgh type 2 diabetes study.

BACKGROUND: The incidence of cirrhosis and hepatocellular carcinoma (HCC) is increased in Type 2 diabetes, primarily secondary to non-alcoholic fatty liver disease (NAFLD). European guidelines recommend screening for NAFLD in Type 2 diabetes. American guidelines, while not advocating a screening protocol, suggest using non-invasive markers of fibrosis for risk-stratification and guiding onward referral. AIMS: To test the ability of individual fibrosis scores and the European screening algorithm to predict 11-year incident cirrhosis/HCC in an asymptomatic community cohort of older people with Type 2 diabetes. METHODS: The Edinburgh Type 2 Diabetes Study investigated men and women with Type 2 diabetes (n = 1066, aged 60-75 at baseline). Liver markers were measured at baseline and year 1; steatosis and fibrosis markers were calculated according to independently published calculations. During 11 years of follow-up, cases of cirrhosis and HCC were identified. RESULTS: Forty-three out of 1059 participants with no baseline cirrhosis/HCC developed incident disease. All scores were significantly associated with incident liver disease by odds ratio (P < .05). The ability of the risk-stratification tools to accurately identify those who developed incident cirrhosis/HCC was poor with low-positive predictive values (5-46%) and high false-negative and -positive rates (up to 60% and 77%) respectively. When fibrosis risk scores were used in conjunction with the European algorithm, they performed modestly better than when applied in isolation. CONCLUSIONS: In a cohort with a moderately low incidence of cirrhosis/HCC, existing risk scores did not reliably identify participants at high risk. Better prediction models for cirrhosis/HCC in people with Type 2 diabetes are required.

Short- and long-term outcomes of gestational diabetes and its treatment on fetal development.

Globally the prevalence of gestational diabetes mellitus (GDM) is rising mainly due to the increase in maternal obesity. A number of different methods to screen for and diagnose GDM have been described although consensus on the preferred methods does not yet exist. GDM has significant short- and long-term health risks for the mother, developing fetus and the children born to mothers with GDM. Short-term risks for the fetus include macrosomia (excessive birthweight), shoulder dystocia, birth trauma, and hypoglycaemia in the immediate postpartum period. Long-term risks for offspring born to mothers with GDM include increased rates of childhood and adulthood obesity and an increased cardiometabolic risk. A number of pharmacological treatments for GDM have been identified, these include insulin and oral glucose-lowering drugs metformin and glibenclamide. Whilst these oral glucose-lowering drugs show similar short-term childhood outcomes to insulin there is increasing evidence that these drugs may have adverse long-term outcomes on children and adults exposed to the drugs in utero. Future research on treatments for GDM should include long-term follow- up of children exposed to glucose lowering medication in utero to determine the long-term cardiometabolic risk in the offspring born to mothers with GDM.

Psychological Distress among Syrian Refugee Women and a Control Group in an Urban Settlement in Beirut- a Pilot Study.

The Syrian conflict has created approximately five million refugees. Of these, more than one million have settled in Lebanon. This project aimed to determine the prevalence of psychological distress (PD) amongst Syrian refugee mothers compared to a control group of local mothers living in the same informal urban settlement in Beirut. A convenient sample was selected from a primary care center. The General Health Questionnaire-12 items (GHQ-12) was administered to determine PD amongst women who were pregnant within 2 years of the study. Data was analyzed using SPSS. Sixty women were enrolled; 35 were Syrian refugees. All women had PD. The mean GHQ-12 scores were 7.5 and 7.2 for the control and Syrian refugee mothers, respectively. When asked about stressors, 91.7% of the women stated poverty. Syrian refugee women had similar PD as women who were not displaced and did not experience direct war related hostilities.

Consequences of being overweight or obese during pregnancy on diabetes in the offspring: a record linkage study in Aberdeen, Scotland.

AIMS/HYPOTHESIS: Maternal obesity in pregnancy is associated with cardiovascular disease and mortality rate in the offspring. We aimed to determine whether maternal obesity is also associated with increased incidence of type 2 and type 1 diabetes in the offspring, independently of maternal diabetes as a candidate mechanistic pathway. METHODS: Birth records of 118,201 children from 1950 to 2011 in the Aberdeen Maternity and Neonatal Databank were linked to Scottish Care Information-Diabetes, the national register for diagnosed diabetes in Scotland, to identify incident and prevalent type 1 and type 2 diabetes up to 1 January 2012. Maternal BMI was calculated from height and weight measured at the first antenatal visit. The effect of maternal obesity on offspring outcomes was tested using time-to-event analysis with Cox proportional hazards regression to compare outcomes in offspring of mothers in underweight, overweight or obese categories of BMI, compared with offspring of women with normal BMI. RESULTS: Offspring of obese (BMI ≥30 kg/m2) and overweight (BMI 25-29.9 kg/m2) mothers had an increased hazard of type 2 diabetes compared with mothers with normal BMI, after adjustment for gestation when weight was measured, maternal history of diabetes before pregnancy, maternal history of hypertension, age at delivery, parity, socioeconomic status, and sex of the offspring: HR 3.48 (95% CI 2.33, 5.06) and HR 1.39 (1.06, 1.83), respectively. CONCLUSIONS/INTERPRETATION: Maternal obesity is associated with increased incidence of type 2 diabetes in the offspring. Evidence-based strategies that reduce obesity among women of reproductive age and that might reduce the incidence of diabetes in their offspring are urgently required.

Fetal programming of neuropsychiatric disorders by maternal pregnancy depression: a systematic mini review.

BACKGROUND: Maternal depression complicates a large proportion of pregnancies. Current evidence shows numerous harmful effects on the offspring. Reviews, which include depression, concluded that stress has harmful effects on the offspring's outcomes neuro-cognitive development, temperament traits, and mental disorders. OBJECTIVE: This mini review of recent studies, sought to narrow the scope of exposure and identify studies specifically assessing prenatal depression and offspring neuropsychiatric outcomes. STUDY ELIGIBILITY CRITERIA: The review included longitudinal, cohort, cross-sectional, clinical, quasi-experimental, epidemiological, or intervention study designs published in English from 2014 to 2018. PARTICIPANTS: Study populations included mother-child dyads, mother-father-child triads, mother-alternative caregiver-child triads, and family studies utilizing sibling comparisons. METHODS: We searched PubMED and Web of Science. Study inclusion and data extraction were based on standardized templates. The quality of evidence was assessed using the Newcastle-Ottawa Scale (NOS). RESULTS: Thirteen studies examining neuropsychiatric outcomes were included. We judged the evidence to be moderate to high quality. CONCLUSIONS: Our review supports that maternal prenatal depression is associated with neuropsychiatric adversities in children. IMPLICATIONS: Future investigations should unravel the biological underpinnings and target timely interventions as early in pregnancy as possible to prevent offspring neuropsychiatric harms.

Intergenerational Transmission of Birth Weight Across 3 Generations.

While previous studies have shown intergenerational transmission of birth weight from mother to child, whether the continuity persists across 3 generations has rarely been assessed. We used the Aberdeen Maternity and Neonatal Databank (United Kingdom) to examine the intergenerational correlations of birth weight, birth weight adjusted for gestational age and sex, and small- and large-for-gestational-age births across 3 generations among 1,457 grandmother-mother-child triads. All participants were born between 1950 and 2015. The intergenerational transmission was examined with linear regression analyses. We found that grandmaternal birth weight was associated with grandchild birth weight, independently of prenatal and sociodemographic covariates and maternal birth weight (B = 0.12 standard deviation units, 95% confidence interval: 0.07, 0.18). Similar intergenerational continuity was found for birth weight adjusted for sex and gestational age as well as for small-for-gestational-age births. In conclusion, birth weight and fetal growth showed intergenerational continuity across 3 generations. This supports the hypothesis that the developmental origins of birth weight and hence later health and disease are already present in earlier generations.