The unexplored role of sedentary time and physical activity in glucose and lipid metabolism-related placental mRNAs in pregnant women who are obese: the DALI lifestyle randomised controlled trial.

OBJECTIVE: We aimed to explore: (i) the association of sedentary time (ST) and physical activity (PA) during pregnancy with the placental expression of genes related to glucose and lipid metabolism in pregnant women who are obese; (ii) maternal metabolic factors mediating changes in these placental transcripts; and (iii) cord blood markers related to the mRNAs mediating neonatal adiposity. DESIGN: Multicentre randomised controlled trial. SETTING: Hospitals in nine European countries. POPULATION: A cohort of 112 pregnant women with placental tissue. METHODS: Both ST and moderate-to-vigorous PA (MVPA) levels were measured objectively using accelerometry at three time periods during pregnancy. MAIN OUTCOME MEASURES: Placental mRNAs (FATP2, FATP3, FABP4, GLUT1 and PPAR-γ) were measured with NanoString technology. Maternal and fetal metabolic markers and neonatal adiposity were assessed. RESULTS: Longer periods of ST, especially in early to middle pregnancy, was associated with lower placental FATP2 and FATP3 expression (P < 0.05), whereas MVPA at baseline was inversely associated with GLUT1 mRNA (P = 0.02). Although placental FATP2 and FATP3 expression were regulated by the insulin-glucose axis (P < 0.05), no maternal metabolic marker mediated the association of ST/MVPA with placental mRNAs (P > 0.05). Additionally, placental FATP2 expression was inversely associated with cord blood triglycerides and free fatty acids (FFAs; P < 0.01). No cord blood marker mediated neonatal adiposity except for cord blood leptin, which mediated the effects of PPAR-γ on neonatal sum of skinfolds (P < 0.05). CONCLUSIONS: In early to middle pregnancy, ST is associated with the expression of placental genes linked to lipid transport. PA is hardly related to transporter mRNAs. Strategies aimed at reducing sedentary behaviour during pregnancy could modulate placental gene expression, which may help to prevent unfavourable fetal and maternal pregnancy outcomes. TWEETABLE ABSTRACT: Reducing sedentary behaviour in pregnancy might modulate placental expression of genes related to lipid metabolism in women who are obese.

Metabolic phenotypes of early gestational diabetes mellitus and their association with adverse pregnancy outcomes.

AIMS: To describe the metabolic phenotypes of early gestational diabetes mellitus and their association with adverse pregnancy outcomes. METHODS: We performed a post hoc analysis using data from the Vitamin D And Lifestyle Intervention for gestational diabetes prevention (DALI) trial conducted across nine European countries (2012-2014). In women with a BMI ≥29 kg/m2 , insulin resistance and secretion were estimated from the oral glucose tolerance test values performed before 20 weeks, using homeostatic model assessment of insulin resistance and Stumvoll first-phase indices, respectively. Women with early gestational diabetes, defined by the International Association of Diabetes and Pregnancy Study Groups criteria, were classified into three groups: GDM-R (above-median insulin resistance alone), GDM-S (below-median insulin secretion alone), and GDM-B (combination of both) and the few remaining women were excluded. RESULTS: Compared with women in the normal glucose tolerance group (n = 651), women in the GDM-R group (n = 143) had higher fasting and post-load glucose values and insulin levels, with a greater risk of having large-for-gestational age babies [adjusted odds ratio 3.30 (95% CI 1.50-7.50)] and caesarean section [adjusted odds ratio 2.30 (95% CI 1.20-4.40)]. Women in the GDM-S (n = 37) and GDM-B (n = 56) groups had comparable pregnancy outcomes with those in the normal glucose tolerance group. CONCLUSIONS: In overweight and obese women with early gestational diabetes, higher degree of insulin resistance alone was more likely to be associated with adverse pregnancy outcomes than lower insulin secretion alone or a combination of both.

Subsequent reproductive outcome among women with peripartum cardiomyopathy: a nationwide study.

OBJECTIVE: To describe the subsequent reproductive outcome for a Danish nationwide cohort of women with peripartum cardiomyopathy (PPCM). DESIGN: Nationwide historic cohort study. SETTING: Secondary and tertiary centres across Denmark. SAMPLE: Women with PPCM. METHODS: Sixty-one women with PPCM during 2005-2014 were identified in a nationwide, registry-based study and the diagnosis was validated through audit of patient records. A new search for subsequent reproductive outcome in this cohort from 2005-2016 was conducted in the Danish National Birth Registry and the Danish National Patient Registry. Detailed clinical data were obtained from patient records. MAIN OUTCOME MEASURES: Sterilisations and subsequent reproductive outcomes after PPCM, including all pregnancies, miscarriages, terminations and deliveries. RESULTS: Of 61 women with PPCM, 13 (21%) had a total of 16 subsequent pregnancies resulting in one miscarriage, seven early terminations, one ectopic pregnancy and seven liveborn children. There were no maternal deaths or significant cardiac events during pregnancy, but one woman, who gave birth to a liveborn child, had a relapse of PPCM 7 weeks postpartum. None of the six women who had a first trimester termination, experienced relapse of PPCM. Of the 13 women with a subsequent pregnancy, 62% had prior to this been advised against a new pregnancy due to the risk of recurrent PPCM. A total of four women (6.6%) were sterilised. CONCLUSION: Peripartum cardiomyopathy affects women's reproduction with few subsequent pregnancies resulting in a liveborn child. The finding of a 1/7 relapse among women with recovered LVEF is in accordance with most previous studies. TWEETABLE ABSTRACT: Outcome in pregnancies after peripartum cardiomyopathy: results from the first nationwide study.

Mental health in early pregnancy is associated with pregnancy outcome in women with pregestational diabetes.

AIM: To explore the role of early pregnancy health-related quality of life, anxiety, depression and locus of control for pregnancy outcome in women with pregestational diabetes. METHODS: This was a cohort study of 148 pregnant women with pregestational diabetes (118 with Type 1 diabetes and 30 with Type 2 diabetes), who completed three internationally validated questionnaires: the 36-item Short-Form Health Survey, the Hospital Anxiety and Depression Scale and the Multidimensional Health Locus of Control survey at 8 weeks. Selected pregnancy outcomes were preterm delivery (< 37 weeks) and large for gestational age infants (birth weight > 90(th) percentile). Differences between groups in the questionnaires were analysed using an unpaired t-test. RESULTS: Women with preterm deliveries (n = 28) had lower (i.e. worse) mean (sd) quality-of-life scores for the two 36-item Short-Form Health Survey scales, Role-Emotional [58.3 (38.1) vs. 82.9 (31.3); P = 0.0005] and Mental Health [67.7 (20.4) vs. 75.2 (15.8), P = 0.04], and a lower score for the 36-item Short-Form Health Survey scale Mental Component Summary (42.8 (13.1) vs. 48.8 (9.7), P = 0.03) in early pregnancy, compared with women with term deliveries. Depression symptoms (Hospital Anxiety and Depression Scale depression score ≥ 8) were more frequent in women with preterm vs. term deliveries (seven (25%) vs. six women (5%); P = 0.003), while levels of anxiety and locus of control were similar in these two groups. No difference in early pregnancy scores for health-related quality of life, anxiety, depression and locus of control were seen in women delivering large or appropriate for gestational age infants. CONCLUSIONS: Poor mental quality of life and the presence of depressive symptoms in early pregnancy were associated with preterm delivery in women with pregestational diabetes.

Fetal growth in relation to gestational weight gain in women with type 2 diabetes: an observational study.

AIMS: To evaluate fetal growth in relation to gestational weight gain in women with Type 2 diabetes. METHODS: A retrospective cohort study of 142 consecutive pregnancies in 28 women of normal weight, 39 overweight women and 75 obese women with Type 2 diabetes (pre-pregnancy BMI < 25, 25-29.9, ≥ 30 kg/m2, respectively). Gestational weight gain was categorized as excessive (exceeding the US Institute of Medicine recommendations) or as non-excessive (within or below the Institute of Medicine recommendations). RESULTS: Excessive and non-excessive gestational weight gain were seen in 61 (43%) and 81 women (57%) with a median (range) gestational weight gain of 14.3 (9-32) vs. 7.0 (-5-16) kg (P < 0.001), respectively. Infants of women with excessive gestational weight gain were characterized by higher birth weight (3712 vs. 3258 g; P = 0.001), birth weight z-score (1.14 vs. -0.01, P = 0.001) and prevalence of large-for-gestational-age infants (48 vs. 20%; P < 0.001). In normal weight, overweight and obese women with non-excessive gestational weight gain, the median weight gain in the first half of pregnancy was 371, 114 and 81 g/week, and in the second half of pregnancy 483, 427 and 439 g/week, respectively. In multiple linear regression analysis, gestational weight gain was associated with a higher infant birth weight z-score independent of pre-pregnancy BMI, smoking, HbA1c and insulin dose at last visit, ethnicity and parity [ß=0.1 (95% CI 0.06-0.14), P < 0.001]. CONCLUSIONS: Infant birth weight was almost 0.5 kg higher in women with Type 2 diabetes and excessive gestational weight gain than in women with Type 2 diabetes and non-excessive weight gain.

Real-time continuous glucose monitoring as a tool to prevent severe hypoglycaemia in selected pregnant women with Type 1 diabetes - an observational study.

AIMS: Among women with Type 1 diabetes who have had severe hypoglycaemia the year before pregnancy, 70% also experience this complication in pregnancy, and particularly in the first half of pregnancy. We evaluated whether routine use of real-time continuous glucose monitoring from early pregnancy onwards could prevent severe hypoglycaemia in these women. METHODS: All 136 consecutive pregnant women with Type 1 diabetes referred to our centre were asked about severe hypoglycaemic events in the year before pregnancy and early in pregnancy at their first antenatal visit. Women with a relevant recent history were informed about their additional high risk of severe hypoglycaemia, their treatment was focused on restricted insulin doses during the first 16 gestational weeks, and they were offered real-time continuous glucose monitoring on top of self-monitored plasma glucose measurements. RESULTS: Among 28 women with a recent history of severe hypoglycaemia, 12 (43%) used real-time continuous glucose monitoring from a median (range) of 10 (7-13) gestational weeks for 10 (1-32) weeks. Among these 12 women, eight had experienced a total of 34 (range 1-11) severe hypoglycaemic events in the year before pregnancy and nine had experienced 23 (range 1-10) events early in pregnancy. After initiation of real-time continuous glucose monitoring, two (17%) women experienced one event each. The incidence rates of severe hypoglycaemia were 2.8,17.5 and 0.3 events/patient-year. Among the 16 women in the high risk group not using real-time continuous glucose monitoring, the corresponding figures were 1.6, 5.0 and 0.1 events/patient-year. CONCLUSIONS: Further evaluation is required to determine whether continuous real-time continuous glucose monitoring from early pregnancy onwards in highly selected women may reduce the risk of severe hypoglycaemia. Other elements of focused intervention probably also contribute to the risk reduction.

Reconstruction of occluded pelvis markers during marker-based motion capture with industrial exoskeletons.

Industrial back support exoskeletons are a promising solution to alleviate lumbar musculoskeletal strain. Due to the complexity of spinal loading, evaluation of EMG data alone has been considered insufficient to assess their support effects, and complementary kinematic and dynamic data are required. However, the acquisition of marker-based kinematics is challenging with exoskeletons, as anatomical reference points, particularly on the pelvis, are occluded by exoskeleton structures. The aim of this study was therefore to develop and validate a method to reliably reconstruct the occluded pelvic markers. The movement data of six subjects, for whom pelvic markers could be placed while wearing an exoskeleton, were used to test the reconstructions and compare them to anatomical landmarks during lifting, holding and walking. Two separate approaches were used for the reconstruction. One used a reference coordinate system based on only exoskeleton markers (EXO), as has been suggested in the literature, while our proposed method adds a technical marker in the lumbar region (LUMB) to compensate for any shifting between exoskeleton and pelvis. Reconstruction with EXO yielded on average an absolute linear deviation of 54 mm ± 16 mm (mean ± 1SD) compared to anatomical markers. The additional marker in LUMB reduced mean deviations to 14 mm ± 7 mm (mean ± 1SD). Both methods were compared to reference values from the literature for expected variances due to marker placement and soft tissue artifacts. For LUMB 99% of reconstructions were within the defined threshold of 24 mm ±9 mm while for EXO 91% were outside.

Genetic architecture of oral glucose-stimulated insulin release provides biological insights into type 2 diabetes aetiology.

The genetics of ß-cell function (BCF) offer valuable insights into the aetiology of type 2 diabetes (T2D)1,2. Previous studies have expanded the catalogue of BCF genetic associations through candidate gene studies3-7, large-scale genome-wide association studies (GWAS) of fasting BCF8,9 or functional islet studies on T2D risk variants10-14. Nonetheless, GWAS focused on BCF traits derived from oral glucose tolerance test (OGTT) data have been limited in sample size15,16 and have often overlooked the potential for related traits to capture distinct genetic features of insulin-producing ß-cells17,18. We reasoned that investigating the genetic basis of multiple BCF estimates could provide a broader understanding of ß-cell physiology. Here, we aggregate GWAS data of eight OGTT-based BCF traits from ~26,000 individuals of European descent, identifying 55 independent genetic associations at 44 loci. By examining the effects of BCF genetic signals on related phenotypes, we uncover diverse disease mechanisms whereby genetic regulation of BCF may influence T2D risk. Integrating BCF-GWAS data with pancreatic islet transcriptomic and epigenomic datasets reveals 92 candidate effector genes. Gene silencing in ß-cell models highlights ACSL1 and FAM46C as key regulators of insulin secretion. Overall, our findings yield insights into the biology of insulin release and the molecular processes linking BCF to T2D risk, shedding light on the heterogeneity of T2D pathophysiology.

Real-time continuous glucose monitoring during labour and delivery in women with Type 1 diabetes - observations from a randomized controlled trial.

AIMS: To explore whether real-time continuous glucose monitoring during labour and delivery supplementary to hourly self-monitored plasma glucose in women with Type 1 diabetes reduces the prevalence of neonatal hypoglycaemia. METHODS: Women with Type 1 diabetes participating in a randomized controlled trial on the effect of real-time continuous glucose monitoring in pregnancy were included in this study. Twenty-seven of 60 (45%) women in the intervention arm used real-time continuous glucose monitoring during labour and delivery, supplementary to hourly self-monitored plasma glucose. Real-time continuous glucose monitoring glucose data covering the last 8 h prior to delivery were retrospectively evaluated, and maternal hypo- and hyperglycaemia were defined as glucose values ≤ 3.9 mmol/l and > 7.0 mmol/l, respectively. Women in the control arm (n = 59) solely used self-monitored plasma glucose. Neonatal hypoglycaemia was defined as a 2-h plasma glucose < 2.5 mmol/l. RESULTS: In infants of women using real-time continuous glucose monitoring during labour and delivery, 10 (37%) developed neonatal hypoglycaemia vs. 27 (46%) infants in the control arm (P = 0.45). Among 10 infants with and 17 infants without neonatal hypoglycaemia within the real-time continuous glucose monitoring arm, median maternal self-monitored plasma glucose was 6.2 (range 4.2-7.8) vs. 5.6 (3.3-8.5) mmol/l (P = 0.26) during labour and delivery, with maternal hyperglycaemia present in 17 (0-94) vs. 4 (0-46)% of the time (P = 0.02), and birthweight was 4040 (3102-4322) vs. 3500 (1829-4320) g (P = 0.04). Maternal hypoglycaemia up to delivery was relatively rare. CONCLUSIONS: The prevalence of neonatal hypoglycaemia was comparable between infants of women using real-time continuous glucose monitoring supplementary to self-monitored plasma glucose during labour and delivery and infants of women solely using self-monitored plasma glucose.

Hypoglycaemia during pregnancy in women with Type 1 diabetes.

AIMS: To explore incidence, risk factors, possible pathophysiological factors and clinical management of hypoglycaemia during pregnancy in women with Type 1 diabetes. METHODS: Literature review. RESULTS: In women with Type 1 diabetes, severe hypoglycaemia occurs three to five times more frequently in early pregnancy than in the period prior to pregnancy, whereas in the third trimester the incidence of severe hypoglycaemia is lower than in the year preceding pregnancy. The frequency distribution of severe hypoglycaemia is much skewed, as 10% of the pregnant women account for 60% of all recorded events. Risk factors for severe hypoglycaemia during pregnancy include a history with severe hypoglycaemia in the year preceding pregnancy, impaired hypoglycaemia awareness, long duration of diabetes, low HbA(1c) in early pregnancy, fluctuating plasma glucose values (≤ 3.9 mmol/l or ≥ 10.0 mmol/l) and excessive use of supplementary insulin injections between meals. Pregnancy-induced nausea and vomiting seem not to be contributing factors. CONCLUSIONS: Striving for near-normoglycaemia with focus on reduction of plasma glucose fluctuations during pregnancy should have high priority among clinicians with the persistent aim of improving pregnancy outcome among women with Type 1 diabetes. Pre-conception counselling, carbohydrate counting, use of insulin analogues, continuous subcutaneous insulin infusion (insulin pump) therapy and real-time continuous glucose monitoring with alarms for low glucose values might be relevant tools to obtain near-normoglycaemia without episodes of severe hypoglycaemia.

Patient satisfaction and barriers to initiating real-time continuous glucose monitoring in early pregnancy in women with diabetes.

AIM: To evaluate self-reported satisfaction and barriers to initiating real-time continuous glucose monitoring in early pregnancy among women with pregestational diabetes. METHODS: Fifty-four women with Type 1 diabetes and 14 women with Type 2 diabetes were offered continuous glucose monitoring for 6 days at median 9 (range 6-14) gestational weeks and were asked to answer a semi-structured questionnaire on patient satisfaction. RESULTS: Median HbA1c was 49 (range 34-86) mmol/mol) [6.6 (5.3-10.0) %] and duration of diabetes was 12 (0.5-37) years. Continuous glucose monitoring was used for 6 (0.5-7) days, with 43 (65%) women using continuous glucose monitoring for at least 5 days. The women experienced 2.7 (0-12) alarms per 24 h, of which approximately one third was technical alarms and one third disturbed their sleep. Sixteen women (24%) reported discomfort with continuous glucose monitoring during daytime and twelve (18%) during sleep. Many women reported improved diabetes understanding (52%) and would recommend continuous glucose monitoring to others (83%). Twenty-four patients (36%) had continuous glucose monitoring removed earlier than planned ( before the intended 6 days of initial monitoring). Ten women (15%) did not wish to use continuous glucose monitoring again in pregnancy. Main causes behind early removal of continuous glucose monitoring were self-reported skin irritation, technical problems and continuous glucose monitoring inaccuracy. No differences were found in continuous glucose monitoring use, inconvenience or compliance with respect to diabetes type. CONCLUSIONS: The majority of pregnant women with diabetes found real-time continuous glucose monitoring useful and the intervention was equally tolerated regardless of diabetes type. Nevertheless, continuous glucose monitoring was frequently removed earlier than planned, primarily because of skin irritation, technical problems and inaccuracy.

Gestational diabetes mellitus in Europe: prevalence, current screening practice and barriers to screening. A review.

BACKGROUND: Gestational diabetes mellitus is a potentially serious condition that affects many pregnancies and its prevalence is increasing. Evidence suggests early detection and treatment improves outcomes, but this is hampered by continued disagreement and inconsistency regarding many aspects of its diagnosis. METHODS: The Vitamin D and Lifestyle Intervention for Gestational Diabetes Mellitus Prevention (DALI) research programme aims to promote pan-European standards in the detection and diagnosis of gestational diabetes and to develop effective preventive interventions. To provide an overview of the context within which the programme will be conducted and its findings interpreted, systematic searching and narrative synthesis have been used to identify and review the best available European evidence relating to the prevalence of gestational diabetes, current screening practices and barriers to screening. RESULTS: Prevalence is most often reported as 2-6% of pregnancies. Prevalence may be lower towards the Northern Atlantic seaboard of Europe and higher in the Southern Mediterranean seaboard. Screening practice and policy is inconsistent across Europe, hampered by lack of consensus on testing methods, diagnostic glycaemic thresholds and the value of routine screening. Poor clinician awareness of gestational diabetes, its diagnosis and local clinical guidelines further undermine detection of gestational diabetes. CONCLUSIONS: Europe-wide agreement on screening approaches and diagnostic standards for gestational diabetes could lead to better detection and treatment, improved outcomes for women and children and a strengthened evidence base. There is an urgent need for well-designed research that can inform decisions on best practice in gestational diabetes mellitus screening and diagnosis.

A high concentration of prorenin in early pregnancy is associated with development of pre-eclampsia in women with type 1 diabetes.

AIMS/HYPOTHESIS: The aim of this study was to investigate whether components of the renin-angiotensin system and semicarbazide-sensitive amine oxidase (SSAO) are associated with the development of pre-eclampsia in women with type 1 diabetes. METHODS: This was an observational study of 107 consecutive pregnant women with type 1 diabetes (median duration 16 years [range 1-36 years], HbA(1c) 6.6% [range 4.9-10.5%]) in early pregnancy. At 8, 14, 21, 27 and 33 weeks and once within 5 days postpartum, blood was sampled for measurements of prorenin, renin, angiotensinogen, ACE and SSAO. HbA(1c), blood pressure and urinary albumin excretion were recorded. Pre-eclampsia was defined as blood pressure >140/90 mmHg and proteinuria ≥300 mg/24 h after 20 weeks. RESULTS: Pre-eclampsia developed in nine women (8%) with longer diabetes duration (median 20 [range 10-32] vs 16 [range 1-36] years, p = 0.04), higher SSAO concentrations (592 [range 372-914] vs 522 [range 264-872] mU/l, p = 0.04) and a tendency towards higher prorenin levels (136 [range 50-296] vs 101 [range 21-316] ng angiotensin I ml(-1) h(-1), p = 0.06) at 8 weeks compared with women without pre-eclampsia. Levels of renin, angiotensinogen and ACE did not differ in the two groups. Throughout pregnancy, prorenin and SSAO levels were 30% (p = 0.004) and 16% (p = 0.04) higher, respectively, in women developing pre-eclampsia. Using multivariate logistic regression analysis, prorenin concentration at 8 weeks was associated with pre-eclampsia (OR 4.4 [95% CI 1.5-13.0], p = 0.007), i.e. an increase of prorenin of 100 ng angiotensin I ml(-1) h(-1) implies a 4.4 times higher risk of subsequent pre-eclampsia. CONCLUSIONS/INTERPRETATION: In type 1 diabetic women with pre-eclampsia, a higher concentration of prorenin in early pregnancy and higher levels of prorenin and SSAO throughout pregnancy were seen.

Cognitive function in adult offspring of women with Type 1 diabetes.

AIMS: Maternal diabetes may affect offspring cognitive function. The objective of the study was to evaluate cognitive function and potential predictors hereof in adult offspring of women with Type 1 diabetes. METHODS: We conducted a follow-up study of adult offspring of women with Type 1 diabetes (n = 158) and a reference group from the background population (n = 118). The main outcome measure was offspring cognitive function measured by global cognitive score, derived from Raven's Progressive Matrices and three verbal subtests from the Weschler Adult Intelligence Scale. RESULTS: Offspring of women with Type 1 diabetes obtained lower global cognitive scores (94.8 vs. 100.0, P = 0.004) than offspring from the background population. When adjusted for confounders, the groups no longer differed significantly (difference 0.4, 95% CI -3.3 to 4.). Positive predictors of cognitive function in offspring of women with diabetes were family social class, parental educational level, maternal diabetes duration, male gender and offspring age, whereas parity ≥ 1 and gestational age < 34 weeks were negative predictors. We found no association with maternal glycaemia during pregnancy or with neonatal hypoglycaemia. CONCLUSIONS: Impaired cognitive function in adult offspring of women with Type 1 diabetes compared with the background population apparently reflects differences with respect to well-known confounders. However, harmful effects of maternal hyperglycaemia may be mediated through delivery at < 34 weeks.

[Reconstructive surgery of cranio-orbital injuries].

The aim of study was to optimize evaluation and surgery of cranioorbital injuries in different periods after trauma. Material and methods. We analyzed 374 patients with cranioorbital injuries treated in Burdenko Neurosurgery Institute in different periods after trauma from January 1998 till April 2010. 288 (77%) underwent skull and facial skeleton reconstructive surgery within 24 hours - 7 years after trauma. Clinical and CT examination data were used for preoperative planning and assessment of surgery results. Stereolithographic models (STLM) were applied for preoperative planning in 89 cases. The follow-up period ranged from 4 months up to 10 years. Results. In 254 (88%) of 288 patients reconstruction of anterior skull base, upper and/or midface with restoration of different parts of orbit was performed. Anterior skull base CSF leaks repair, calvarial vault reconstruction, maxillar and mandibular osteosynthesis were done in 34 (12%) cases. 242 (84%) of 288 patients underwent one reconstructive operation, while 46 (16%)--two and more (totally 105 operations). The patients with extended frontoorbital and midface fractures commonly needed more than one operation--in 27 (62.8%) cases. Different plastic materials were used for reconstruction in 233 (80.9%) patients, of those in 147 (51%) cases split calvarial bone grafts were preferred. Good functional and cosmetic results were achieved in 261 (90.6%) of 288 patients while acceptable were observed in 27 (9.4%). Conclusion. Active single-stage surgical management for repair of combined cranioorbital injury in acute period with primary reconstruction optimizes functional and cosmetic outcomes and prevents the problems of delayed or secondary reconstruction. Severe extended anterior skull base, upper and midface injuries when intracranial surgery is needed produced the most challenging difficulties for adequate reconstruction. Randomized trial is required to define the extent and optimal timing of reconstructive surgery in patients with severe traumatic brain injury and craniofacial injury in acute period of trauma.

Analysis of hip joint loading during walking with different shoe types using instrumented total hip prostheses.

Hip joint loads need careful consideration during postoperative physiotherapy after joint replacement. One factor influencing joint loads is the choice of footwear, but it remains unclear which footwear is favorable. The objective of the present study was to investigate the influence of footwear on hip joint loads in vivo. Instrumented hip endoprostheses were used for in vivo load measurements. The parameters resultant contact force (Fres), bending moment (Mbend) and torsional moment (Mtors) were evaluated during treadmill walking at 4 km/h with different shoe types. In general, footwear tended to increase hip joint loading, with the barefoot shoe having the least influence. Fres and Mbend were significantly increased during heel strike for all shoe types in comparison to barefoot walking, with everyday shoe (34.6%; p = 0.028 and 47%; p = 0.028, respectively) and men's shoe (33.2%; p = 0.043 and 41.1%; p = 0.043, respectively) resulting in the highest changes. Mtors at AbsMax was increased by all shoes except for the barefoot shoe, with the highest changes for men's shoe (+ 17.6%, p = 0.043) and the shoe with stiffened sole (+ 17.5%, p = 0.08). Shoes, especially those with stiff soles or elaborate cuishing and guiding elements, increase hip joint loads during walking. The influence on peak loads is higher for Mtors than for Fres and Mbend. For patients in which a reduction of hip joints loads is desired, e.g. during physiotherapy after recent surgery or to alleviate symptoms of osteoarthritis, low profile shoes with a flexible sole may be preferred over shoes with a stiff sole or elaborate cushioning elements.

Progression of diabetic retinopathy during pregnancy in women with type 2 diabetes.

AIMS/HYPOTHESIS: We studied the progression of diabetic retinopathy during pregnancy in women with type 2 diabetes. METHODS: Fundus photography was performed at median 10 (range 6-21) and 28 (27-37) gestational weeks in 80 of 110 (73%) consecutively referred pregnant women with type 2 diabetes. Diabetic retinopathy was classified in five stages. Progression was defined as at least one stage of deterioration of diabetic retinopathy and/or development of macular oedema on at least one eye between the two examinations. Macular oedema was defined as retinal thickening and/or hard exudates within a diameter of 1,500 microm in the macula area. RESULTS: Diabetic retinopathy, mainly mild, was present in 11 (14%) women in early pregnancy. Median duration of diabetes was 3 years (range 0-16 years). At baseline, HbA(1c) was 6.4% (1.0) (mean [SD]), systolic BP 121 (13) and diastolic BP 72 (9) mmHg. Prior to pregnancy, 22 (28%) women had been on insulin treatment. During pregnancy 74 women (93%) were treated with insulin and 11 (14%) with antihypertensive medication. Progression of diabetic retinopathy was observed in 11 (14%) women. Progression was mainly mild, but one woman with poor glycaemic control and uncontrolled hypertension progressed from mild retinopathy to sight-threatening retinopathy with proliferations, clinically significant macular oedema and impaired vision in both eyes. Progression of diabetic retinopathy was associated with a longer duration of diabetes (p = 0.03) and insulin treatment before pregnancy (p = 0.004). CONCLUSIONS/INTERPRETATION: Despite a low risk of progression of retinopathy in pregnant women with type 2 diabetes, sight-threatening deterioration did occur.

Pregnancy-induced sight-threatening diabetic retinopathy in women with Type 1 diabetes.

AIMS: To determine the progression of diabetic retinopathy in pregnant women with diabetes offered tight glycaemic and blood pressure control. METHODS: A prospective study of 102 (87%) out of 117 consecutive pregnant women with Type 1 diabetes for median 16 years (range 1-36) and HbA(1c) 6.7% (4.9-10.8) in early pregnancy. Fundus photography was performed at 8 and 27 weeks. Retinopathy was classified in five stages. Diabetic macular oedema was classified as present in a mild form or as clinically significant macular oedema (CSMO). Progression was defined as at least one stage of deterioration of retinopathy and/or development of macular oedema in at least one eye. Sight-threatening progression was defined as loss of visual acuity>or=0.2 on Snellen's chart or laser treatment performed during pregnancy due to proliferative retinopathy or CSMO. RESULTS: Diabetic retinopathy was present at inclusion in at least one eye in 64 (63%) women and proliferative retinopathy and macular oedema were present in nine and 16 women, respectively. Progression of retinopathy occurred in 28 (27%) women. Sight-threatening progression occurred in six women; in three, visual acuity deteriorated and four required laser treatment. Sight-threatening progression was associated with presence of macular oedema (P=0.007), impaired visual acuity (P=0.03) and higher blood pressure (P=0.016) in early pregnancy, but not with HbA1c, decline in HbA1c, or prevalence of severe hypoglycaemia. CONCLUSIONS: Loss of visual acuity and the need for laser treatment during diabetic pregnancy remain clinical problems associated with presence of macular oedema, visual impairment and higher blood pressure in early pregnancy.

Preterm delivery and risk of subsequent cardiovascular morbidity and type-II diabetes in the mother.

OBJECTIVE: Preterm delivery has been shown to be associated with subsequent maternal cardiovascular morbidity. However, the impact of the severity and recurrence of preterm delivery on the risk of specific cardiovascular events and the metabolic syndrome in the mother, have not been investigated. DESIGN: National registry-based retrospective cohort study. SETTING: Women delivering in Denmark from 1978 to 2007. POPULATION: Women with a first singleton delivery (n = 782 287), and with a first and second singleton delivery (n = 536 419). METHODS: Cox proportional hazard models, with the gestational age stratified into four groups as primary exposure. We made adjustments for maternal age, year of delivery, hypertensive pregnancy disorders, fetal growth deviation, placental abruption and stillbirth. MAIN OUTCOME MEASURES: Subsequent maternal hypertension, ischaemic heart diseases, thromboembolism and type-II diabetes. RESULTS: After a first delivery at 32-36 completed weeks of gestation, the adjusted risk of subsequent type-II diabetes increased 1.89-fold (1.69-2.10) and the risk of thromboembolism increased 1.42-fold (1.24-1.62). Women having a preterm delivery in the first pregnancy and a term delivery in the second had a 1.58-fold (1.34-1.86) increased risk of type-II diabetes and a 1.18-fold (0.96-1.44) increased risk of thromboembolism. Women having two preterm deliveries had a 2.30-fold (1.71-3.10) increased risk of type-II diabetes and a 1.80-fold (1.29-2.50) increased risk of thromboembolism. CONCLUSIONS: Preterm delivery is independent of other pregnancy complications associated with subsequent maternal overt type-II diabetes and thromboembolism. The recurrence of preterm delivery will augment these risks.

Sports and leisure-time physical activity in pregnancy and birth weight: a population-based study.

We examined the association between sports and other leisure-time physical activities during pregnancy and birth weight of babies born after 37 completed weeks of gestation. All Danish-speaking pregnant women attending routine antenatal care at the Department of Obstetrics, Aarhus University Hospital, Denmark, from August 1989 to September 1991 were invited to participate in the study. A total of 4458 healthy women who delivered after 37 completed gestational weeks participated in this study. The associations between sports (0, 1-2, 3+ h/week) or leisure-time physical activity (sedentary, light, and moderate to heavy) and birth weight were examined by linear and logistic regression and adjusted for potential confounding factors such as smoking, parity, schooling, pre-pregnancy body mass index and gestational age. The results showed that pregnant women who practiced sports or were moderate to heavy leisure-time physical active during the early second or the early third trimester gave birth to infants with a similar birth weight as inactive women. The proportion of newborns with a low (<2500 g) or a high birth weight (>/=4500 g) was also unchanged. In conclusion, in this large population-based study, we found no association between sports and leisure-time physical activity and low-birth weight, high-birth weight, or average-birth weight.