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Introduction: Children born to mothers with gestational diabetes mellitus (GDM) are at risk of metabolic disturbances such as diabetes mellitus and overweight. However, few have examined the outcome of children whose mothers were at risk of GDM. The aim of the study was to investigate how mothers' risk of developing GDM affects physical health and neurodevelopment of the children at 7 years of age. Material and methods: This is a secondary analysis of a follow‐up study of a multicenter randomized controlled trial including 855 pregnant women, carried out at St. Olavs Hospital, Trondheim University Hospital, and Stavanger University Hospital in Norway from 2007 to 2009. Risk factors for developing GDM included age >40 years, diabetes in near family, previous child with birthweight ≥4500 g and pre‐pregnancy body mass index (BMI) ≥25 kg/m2. Data on GDM risk factors were available for 750 women, who were divided into a risk group if they had one or more risk factors for developing GDM (n = 238) and a no risk (n = 512) group. At 7 years of age, 72 children born to mothers in the risk group and 194 children born to mothers in the no risk group participated. The children's height, weight and physical activity were reported by their parents. Neurodevelopmental outcomes were assessed by using the Five‐to‐Fifteen questionnaire, which includes motor skills, executive functions, perception, memory, language, social skills, and emotional/behavioral problems. Results: Most women had only one risk factor for GDM, and pre‐pregnancy overweight was the most prevalent risk factor. Children of mothers in the risk group had higher birthweight and length. At the 7‐year follow‐up, they had a higher weight and BMI, and the odds ratio of being overweight was 3.0 (95% confidence interval 1.1–8.3). There was no group difference in the children's physical activity and their neurodevelopmental outcomes were similar. Conclusions: We found higher BMI and increased risk of overweight in children born to mothers with one or more risk factors for developing GDM. A focus on preventing pre‐pregnancy overweight should be encouraged. [ABSTRACT FROM AUTHOR]

Women's autonomy and an inclusive society for all individuals are highly valued in Norway. The Norwegian Biotechnology Act changed in 2020 allowing first‐trimester screening and cell‐free DNA for common trisomies to all pregnant women. However, implementing non‐invasive prenatal testing (NIPT) in a public antenatal care program is difficult, because many patients, politicians, and medical professionals do not consider trisomy 21 a severe medical disease. Screening for trisomies at an early gestation might inevitably lead to an increase in pregnancy terminations and making cost–benefit calculations is ethically challenging. Moreover, offering NIPT to all pregnant women is debatable because of the lower prevalence of fetal trisomies in younger women. Therefore, appropriate genetic pre‐test counseling is essential. Furthermore, organizing the service between private institutions and public hospitals poses another debate and challenges both quality and equal access to health services for women across the country. [ABSTRACT FROM AUTHOR]

Objective: Stillbirth is a potentially preventable complication of pregnancy. Identifying women at high risk of stillbirth can guide decisions on the need for closer surveillance and timing of delivery in order to prevent fetal death. Prognostic models have been developed to predict the risk of stillbirth, but none has yet been validated externally. In this study, we externally validated published prediction models for stillbirth using individual participant data (IPD) meta-analysis to assess their predictive performance.Methods: MEDLINE, EMBASE, DH-DATA and AMED databases were searched from inception to December 2020 to identify studies reporting stillbirth prediction models. Studies that developed or updated prediction models for stillbirth for use at any time during pregnancy were included. IPD from cohorts within the International Prediction of Pregnancy Complications (IPPIC) Network were used to validate externally the identified prediction models whose individual variables were available in the IPD. The risk of bias of the models and cohorts was assessed using the Prediction study Risk Of Bias ASsessment Tool (PROBAST). The discriminative performance of the models was evaluated using the C-statistic, and calibration was assessed using calibration plots, calibration slope and calibration-in-the-large. Performance measures were estimated separately in each cohort, as well as summarized across cohorts using random-effects meta-analysis. Clinical utility was assessed using net benefit.Results: Seventeen studies reporting the development of 40 prognostic models for stillbirth were identified. None of the models had been previously validated externally, and the full model equation was reported for only one-fifth (20%, 8/40) of the models. External validation was possible for three of these models, using IPD from 19 cohorts (491 201 pregnant women) within the IPPIC Network database. Based on evaluation of the model development studies, all three models had an overall high risk of bias, according to PROBAST. In the IPD meta-analysis, the models had summary C-statistics ranging from 0.53 to 0.65 and summary calibration slopes ranging from 0.40 to 0.88, with risk predictions that were generally too extreme compared with the observed risks. The models had little to no clinical utility, as assessed by net benefit. However, there remained uncertainty in the performance of some models due to small available sample sizes.Conclusions: The three validated stillbirth prediction models showed generally poor and uncertain predictive performance in new data, with limited evidence to support their clinical application. The findings suggest methodological shortcomings in their development, including overfitting. Further research is needed to further validate these and other models, identify stronger prognostic factors and develop more robust prediction models. © 2021 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology. [ABSTRACT FROM AUTHOR]

The objective of this study was to investigate possible differences in uterine artery pulsatility index (UtAPI) between pregnant women with PCOS and healthy controls and to explore possible effects of metformin on UtAPI. Material and Methods. The study was conducted in a tertiary center. Forty-eight pregnant women diagnosed with PCOS before pregnancy and 124 healthy pregnant women were included. Women with PCOS were randomly assigned to metformin 2000 mg daily or a placebo. UtAPI was measured five times during 1st and 2nd trimesters of pregnancy in women with PCOS and four times in healthy controls. Results. There was no difference in UtAPI between PCOS women and healthy controls at any point in time (p=0.34–0.77). In women with PCOS, randomly assigned to metformin 2000 mg or placebo, UtAPI was unaffected by metformin two hours after intake of the first dose of study medication (p=0.34). All PCOS women, regardless of randomization, had higher UtAPI two hours after intake of study medication and a meal compared to before a meal (p=0.02). Conclusions. In the first and second trimesters of pregnancy, there was no difference in UtAPI between women with PCOS and healthy controls. Metformin had no immediate effect on the UtAPI. Interestingly, blood flow decreased after a meal, suggesting that time since last meal should be taken into consideration when interpreting the results of UtAPI measurements in pregnancy. This trial is registered with ClinicalTrials.gov (NCT00466622) Metformin in Pregnant PCOS women (PregMet) (NCT00159536). [ABSTRACT FROM AUTHOR]

To ensure optimal calcium accrual in the fetal skeleton, a substantial rise occurs in 1,25-dihydroxyvitamin D (1,25(OH)2D), but is dependent on sufficient 25-hydroxyvitamin (25(OH)D). Large longitudinal studies addressing free 25(OH)D and 1,25(OH)2D during pregnancy are scarce. We aimed to assess levels of and relationship between 25(OH)D, 1,25(OH)2D, vitamin D-binding protein (DBP), parathyroid hormone (PTH), and free 25(OH)D during pregnancy; determinants of vitamin D status; and association between vitamin D indices or PTH and pregnancy outcomes (gestational diabetes mellitus and birthweight). Altogether 855 pregnant Norwegian Caucasian women from Trondheim and Stavanger (latitude 63°N and 58°N) were recruited; 94 were lost to follow-up. The study was originally a randomized controlled trial (2007–2009) with gestational diabetes as primary outcome. Data were collected in second and third trimester. In third trimester, 246 (34%) had vitamin D insufficiency and 52 (7%) deficiency (25(OH)D <50 and <30nmol/L, respectively). During wintertime in third trimester, 61 (47%) from Trondheim and 23 (51%) from Stavanger exhibited vitamin D insufficiency. PTH was elevated in 27 (3.7%). Estimate of change between trimesters was (95% CI): 25(OH)D -1.8 (-2.8 to -0.7) nmol/L, DBP 0.62 (0.57 to 0.66) μmol/L, calculated free 25(OH)D -1.7 (-2.0 to -1.4) pmol/L, PTH 0.81 (0.72 to 0.90) pmol/L, 1,25(OH)2D (sub-analysis) 31.4 (CI 24.7 to 38.2) pmol/L. A decrease in 1,25(OH)2D occurred in 45% of those with vitamin D deficiency, and they also exhibited lower levels than women with adequate vitamin D status. No association of vitamin D indices and PTH with pregnancy outcomes was observed. Women in Trondheim displayed lower 25(OH)D levels, despite minor latitudinal differences. Less than one-fifth adhered to the authorities’ vitamin D recommendations. These findings demonstrate that hypovitaminosis D is prevalent among pregnant women living in northern latitudes, especially during the dark season, and there is an unmet need to ensure adequate vitamin D intake. [ABSTRACT FROM AUTHOR]

Background and aims: Matrix metalloproteinase 9 (MMP9) is an enzyme that may affect degradation of several extracellular matrix (ECM) components in the pelvic ligaments during pregnancy. Previous studies indicate that genetic variations in the gene encoding MMP9 may affect the enzymatic activity. One such genetic variant is a single nucleotide polymorphism (SNP), rs17576 A>G. In this study we investigated whether the MMP9 SNP rs17576 A>G may be associated with increased lumbopelvic pain in 838 pregnant woman. The study was registered with ClinicalTrials.gov (NCT 00476567) on May 21, 2007. Methods: Lumbopelvic pain-intensity was measured by visual analog scale (VAS) at two time points during pregnancy, T1 (18-22 weeks), T2 (32-36 weeks) and 3 months after delivery. Blood samples were collected at each point and SNP genotyping was carried out using predesigned TaqMan SNP genotyping assays. Results: The results showed a significant association between the number of G alleles and pain-intensity in the evening at T2. The pain among G/G carriers was higher than among A/G carriers, which in turn was higher than among the A/A carriers. The most pronounced association between the G allele and pain-intensity was observed in primiparae. Conclusions: We conclude that the MMP9 rs17576 A>G polymorphism is associated with increased lumbopelvic pain-intensity during pregnancy. The present data support the hypothesis that lumbopelvic pain during pregnancy may be related to a relaxin -- MMP9 -- tissue remodeling mechanism. Implications: The present findings may be important for future mechanistic studies on how MMP9 rs17576 A>G may affect changes in the ECM components in pelvic ligaments and lumbopelvic pain-intensity during pregnancy. [ABSTRACT FROM AUTHOR]

Background: Maternal obesity associates with complications during pregnancy and childbirth. Our aim was to investigate if exercise during pregnancy in overweight/obese women could influence birth weight or other neonatal and maternal outcomes at delivery. Material and methods: This is a secondary analysis of a randomised controlled trial of exercise training in pregnancy for women with body mass index (BMI) ≥ 28 kg/m2. Ninety-one women (31.3 ± 4.3 years, BMI 34.5 ± 4.2 kg/m2) were allocated 1:1 to supervised exercise during pregnancy or to standard care. The exercise group was offered three weekly training sessions consisting of 35 minutes of moderate intensity walking/running followed by 25 minutes of strength training. Data from 74 women (exercise 38, control 36) were analysed at delivery. Results: Birth weight was 3719 ± 695 g in the exercise group and 3912 ± 413 g in the control group (CI -460.96, 74.89, p = 0.16). Birth weight > 4000 g was 35% in the exercise group and 52% in the control group (p = 0.16). Mean gestational age at delivery was 39.1 weeks in the exercise group and 39.5 weeks in the control group (CI -1.33, 0.43, p = 0.31). No significant between-group differences were found in neonatal body size, skinfold thickness, placental weight ratio, or Apgar score. The prevalence of caesarean section was 24% in the exercise group and 17% in the control group (CI 0.20, 2.05, p = 0.57). Mean length of hospital stay was 4.8 days in the exercise group and 4.5 days in the control group (CI -0.45, 1.00, p = 0.45). Conclusions: Offering supervised exercise during pregnancy for overweight and obese women did not influence birth weight or other neonatal and maternal outcomes at delivery. However our trial was limited by low sample size and poor adherence to the exercise protocol, and further research is needed. Trial registration: ClinicalTrials.gov [ABSTRACT FROM AUTHOR]

Background: Gestational diabetes mellitus (GDM) increases the risk for preeclampsia and macrosomia. GDM is conventionally diagnosed by an oral glucose tolerance test (OGTT). Hemoglobin A1c (HbA1c) is a marker for the average glucose level the last 2-3 months. We aimed to study if HbA1c alone or in combination with patient characteristics can be used to screen for GDM and reduce the number of OGTTs, and whether it could predict preeclampsia or birth weight. Methods: 855 women from a previous study on the effect of exercise on GDM prevalence were eligible, whereof 677 were included. GDM was diagnosed by WHO 1999 criteria (GDM-WHO) and modified IADPSG criteria (GDM-IADPSG), at pregnancy weeks 18-22 and 32-36. HbA1c analyzed at pregnancy weeks 18-22 and 32-36, variables from patient history and clinical examination were considered for logistic regression models. The diagnostic accuracy was assessed by ROC curve analysis. Results: Accumulated GDM prevalence was 6.7% by WHO and 7.2% by modified IADPSG criteria. Nearly a third could potentially have avoided an OGTT by using HbA1c to exclude GDM-IADPSG with a sensitivity of 88% at week 18-22 and 97% at week 32-36. Further, 16% could have avoided an OGTT with a sensitivity of 96% using HbA1c at week 18-22 to exclude GDM-IADPSG throughout pregnancy. HbA1c was not accurate at diagnosing GDM-IADPSG, and it was inaccurate at screening for GDM-WHO at any time point. Adding other predictors did not increase the number of potentially avoidable OGTTs significantly. HbA1c was not significantly associated with preeclampsia or birth weight. Conclusions: HbA1c could potentially reduce the number of OGTTs. [ABSTRACT FROM AUTHOR]

Women with obesity have increased risk for hyperglycemia during pregnancy, with negative health consequences for mother and child. We aimed to investigate adherence to nutritional recommendations in early pregnancy and to examine associations between early pregnancy dietary intake and late pregnancy glycemia among women with obesity. We included 120 women with pre-pregnancy body mass index (BMI) ≥30 kg/m2 who participated in one of two randomized controlled trials. The participants completed a food frequency questionnaire in early pregnancy (gestational weeks 12–22). Fasting and 120 min glucose tolerance after ingestion of 75 g glucose were assessed in late pregnancy (gestational weeks 32–37). About 90% of the participants reported early pregnancy diary intake within the recommendations. Average intakes of vitamin D, iron, and folate were below recommended levels. High intakes of dairy products and protein in early pregnancy were associated with lower fasting glucose in late pregnancy, whereas high intake of bread was associated with lower 120 min glucose. There were no clear associations between single dietary variables and gestational diabetes mellitus (GDM) diagnosis in late pregnancy. In conclusion, some early pregnancy dietary variables were associated with late pregnancy glycemia. Potential causality of these findings should be investigated in future studies. [ABSTRACT FROM AUTHOR]

Background: The objective of this study was to examine the association of maternal and paternal height with pregnancy length, and with the risk of pre- and post-term birth. In addition we aimed to study whether cardiovascular risk factors could explain possible associations. Methods: Parents who participated in the Nord-Trøndelag Health Study (HUNT 2; 1995-1997) were linked to offspring data from the Medical Birth Registry of Norway (1997-2005). The main analyses included 3497 women who had delivered 5010 children, and 2005 men who had fathered 2798 pregnancies. All births took place after parental participation in HUNT 2. Linear regression was used to estimate crude and adjusted differences in pregnancy length according to parental heights. Logistic regression was used to estimate crude and adjusted associations of parental heights with the risk of pre- and post-term births. Results: We found a gradual increase in pregnancy length by increasing maternal height, and the association was essentially unchanged after adjustment for maternal cardiovascular risk factors, parental age, offspring sex, parity, and socioeconomic measures. When estimated date of delivery was based on ultrasound, the difference between mothers in the lower height quintile (<163 cm cm) and mothers in the upper height quintile (≥ 173 cm) was 4.3 days, and when estimated date of delivery was based on last menstrual period (LMP), the difference was 2.8 days. Shorter women (< 163 cm) had lower risk of post-term births, and when estimated date of delivery was based on ultrasound they also had higher risk of pre-term births. Paternal height was not associated with pregnancy length, or with the risks of pre- and post-term births. Conclusions: Women with shorter stature had shorter pregnancy length and lower risk of post-term births than taller women, and when EDD was based on ultrasound, they also had higher risk of preterm births. The effect of maternal height was generally stronger when pregnancy length was based on second trimester ultrasound compared to last menstrual period. The association of maternal height with pregnancy length could not be explained by cardiovascular risk factors. Paternal height was neither associated with pregnancy length nor with the risk of pre- and post-term birth. [ABSTRACT FROM AUTHOR]

Background. Prevention of lumbopelvic pain in pregnancy has been sparsely studied. One aim of this study was to assess if a 12-week training program during pregnancy can prevent and/or treat lumbopelvic pain. A randomized controlled trial was conducted at Trondheim University Hospital and three outpatient physiotherapy clinics. Three hundred and one healthy nulliparous women were included at 20 weeks of pregnancy and randomly allocated to a training group (148) or a control group (153). Methods. The outcome measures were self-reported symptoms of lumbopelvic pain (once per week or more), sick leave, and functional status. Pain drawing was used to document the painful area of the body. The intervention included daily pelvic floor muscle training at home, and weekly group training over 12 weeks including aerobic exercises, pelvic floor muscle and additional exercises, and information related to pregnancy. Results. At 36 weeks of gestation women in the training group were significantly less likely to report lumbopelvic pain: 65/148 (44%) versus 86/153 (56%) (p=0.03). Three months after delivery the difference was 39/148 (26%) in the training group versus 56/153 (37%) in the control group (p=0.06). There was no difference in sick leave during pregnancy, but women in the training group had significantly (p=0.01) higher scores on functional status. Conclusions. A 12-week specially designed training program during pregnancy was effective in preventing lumbopelvic pain in pregnancy. [ABSTRACT FROM AUTHOR]

In women with polycystic ovary syndrome, C-reactive protein levels and D-dimer, antithrombin III, activated protein Cesistance, and activated partial thromboplastin time were unaffected by metformin treatment throughout pregnancy. Protein C levels increased slightly in the metformin group compared with the placebo group. [Copyright &y& Elsevier]

Background: There is sparse documentation on pregnancy outcomes in women with axial spondyloarthritis (axSpA) and psoriatic arthritis (PsA). Data on disease activity are often lacking, preventing the direct investigation of the effect of inflammation on pregnancy outcomes. A caesarean section (CS) implies a higher risk for complications than vaginal delivery. It delays mobilisation after birth necessary to counteract inflammatory pain and stiffness., Objective: To explore a possible association of inflammatory active disease and CS rates in women with axSpA and PsA., Methods: Data from the Medical Birth Registry of Norway (MBRN) were linked with data from RevNatus, a Norwegian nationwide observational register recruiting women with inflammatory rheumatic diseases. Singleton births in women with axSpA (n=312) and PsA (n=121) included in RevNatus 2010-2019 were cases. Singleton births, excluding mothers with rheumatic inflammatory diseases, registered in MBRN during the same period time (n=575 798) served as population controls., Results: CS occurred more frequently in both axSpA (22.4%) and PsA (30.6%) groups compared with population controls (15.6%), with even higher frequencies in inflammatory active axSpA (23.7%) and PsA (33.3%) groups. Compared with population controls, women with axSpA had higher risk for elective CS (risk difference 4.4%, 95% CI 1.5% to 8.2%) but not emergency CS. Women with PsA had higher risk for emergency CS (risk difference 10.6%, 95% CI 4.4% to 18.7%) but not elective CS., Conclusion: Women with axSpA had higher risk for elective and women with PsA for emergency CS. Active disease amplified this risk., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Women with obesity have increased risk for hyperglycemia during pregnancy, with negative health consequences for mother and child. We aimed to investigate adherence to nutritional recommendations in early pregnancy and to examine associations between early pregnancy dietary intake and late pregnancy glycemia among women with obesity. We included 120 women with pre-pregnancy body mass index (BMI) ≥30 kg/m 2 who participated in one of two randomized controlled trials. The participants completed a food frequency questionnaire in early pregnancy (gestational weeks 12-22). Fasting and 120 min glucose tolerance after ingestion of 75 g glucose were assessed in late pregnancy (gestational weeks 32-37). About 90% of the participants reported early pregnancy diary intake within the recommendations. Average intakes of vitamin D, iron, and folate were below recommended levels. High intakes of dairy products and protein in early pregnancy were associated with lower fasting glucose in late pregnancy, whereas high intake of bread was associated with lower 120 min glucose. There were no clear associations between single dietary variables and gestational diabetes mellitus (GDM) diagnosis in late pregnancy. In conclusion, some early pregnancy dietary variables were associated with late pregnancy glycemia. Potential causality of these findings should be investigated in future studies.

Ultrasound safety is of particular importance in fetal and neonatal scanning. Fetal tissues are vulnerable and often still developing, the scanning depth may be low, and potential biological effects have been insufficiently investigated. On the other hand, the clinical benefit may be considerable. The perinatal period is probably less vulnerable than the first and second trimesters of pregnancy, and ultrasound is often a safer alternative to other diagnostic imaging modalities. Here we present step-by-step procedures for obtaining clinically relevant images while maintaining ultrasound safety. We briefly discuss the current status of the field of ultrasound safety, with special attention to the safety of novel modalities, safety considerations when ultrasound is employed for research and education, and ultrasound of particularly vulnerable tissues, such as the neonatal lung. This CME is prepared by ECMUS, the safety committee of EFSUMB, with contributions from OB/GYN clinicians with a special interest in ultrasound safety., Competing Interests: Declaration of financial interestsReceipt of research funding: no; receipt of payment/financial advantage for providing services as a lecturer: no; paid consultant/internal trainer/salaried employee: no; patent/business interest/shares (author/partner, spouse, children) in company: no; patent/business interest/shares (author/partner, spouse, children) in sponsor of this CME article or in company whose interests are affected by the CME article: no.Declaration of non-financial interestsThe authors declare that there is no conflict of interest., (Thieme. All rights reserved.)

Background: Gestational diabetes mellitus (GDM) increases the risk for preeclampsia and macrosomia. GDM is conventionally diagnosed by an oral glucose tolerance test (OGTT). Hemoglobin A1c (HbA1c) is a marker for the average glucose level the last 2-3 months. We aimed to study if HbA1c alone or in combination with patient characteristics can be used to screen for GDM and reduce the number of OGTTs, and whether it could predict preeclampsia or birth weight., Methods: 855 women from a previous study on the effect of exercise on GDM prevalence were eligible, whereof 677 were included. GDM was diagnosed by WHO 1999 criteria (GDM-WHO) and modified IADPSG criteria (GDM-IADPSG), at pregnancy weeks 18-22 and 32-36. HbA1c analyzed at pregnancy weeks 18-22 and 32-36, variables from patient history and clinical examination were considered for logistic regression models. The diagnostic accuracy was assessed by ROC curve analysis., Results: Accumulated GDM prevalence was 6.7 % by WHO and 7.2 % by modified IADPSG criteria. Nearly a third could potentially have avoided an OGTT by using HbA1c to exclude GDM-IADPSG with a sensitivity of 88 % at week 18-22 and 97 % at week 32-36. Further, 16 % could have avoided an OGTT with a sensitivity of 96 % using HbA1c at week 18-22 to exclude GDM-IADPSG throughout pregnancy. HbA1c was not accurate at diagnosing GDM-IADPSG, and it was inaccurate at screening for GDM-WHO at any time point. Adding other predictors did not increase the number of potentially avoidable OGTTs significantly. HbA1c was not significantly associated with preeclampsia or birth weight., Conclusions: HbA1c could potentially reduce the number of OGTTs.