1. |
- Haahr, Thor, et al.
(författare)
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Vaginal dysbiosis in pregnancy associates with risk of emergency caesarean section: a prospective cohort study
- 2022
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Ingår i: Clinical Microbiology and Infection. - Oxford, United Kingdom : Elsevier. - 1198-743X .- 1469-0691. ; 28:4, s. 588-595
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: To investigate changes in vaginal microbiota during pregnancy, and the association between vaginal dysbiosis and reproductive outcomes.Methods: A total of 730 (week 24) and 666 (week 36) vaginal samples from 738 unselected pregnant women were studied by microscopy (Nugent score) and characterized by 16S rRNA gene sequencing. A novel continuous vaginal dysbiosis score was developed based on these methods using a supervised partial least squares model.Results: Among women with bacterial vaginosis in week 24 (n = 53), 47% (n = 25) also had bacterial vaginosis in week 36. In contrast, among women without bacterial vaginosis in week 24, only 3% (n = 18) developed bacterial vaginosis in week 36. Vaginal samples dominated by Lactobacillus crispatus (OR 0.35, 95% CI 0.20–0.60) and Lactobacillus iners (OR 0.40, 95% CI 0.23–0.68) in week 24 were significantly more stable by week 36 when compared with other vaginal community state types. Vaginal dysbiosis score at week 24 was associated with a significant increased risk of emergency, but not elective, caesarean section (OR 1.37, 955 CI 1.15–1.64, p < 0.001), suggesting a 37% increased risk per standard deviation increase in vaginal dysbiosis score.Conclusions: Changes in vaginal microbiota from week 24 to week 36 of pregnancy correlated with bacterial vaginosis status and vaginal community state type. A novel vaginal dysbiosis score was associated with a significantly increased risk of emergency, but not elective, caesarean section. This was not found for bacterial vaginosis or any vaginal community state type and could point to the importance of investigating vaginal dysbiosis as a nuanced continuum instead of crude clusters.
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2. |
- Vogelezang, Suzanne, et al.
(författare)
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Novel loci for childhood body mass index and shared heritability with adult cardiometabolic traits.
- 2020
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Ingår i: PLoS genetics. - : Public Library of Science (PLoS). - 1553-7404. ; 16:10
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Tidskriftsartikel (refereegranskat)abstract
- The genetic background of childhood body mass index (BMI), and the extent to which the well-known associations of childhood BMI with adult diseases are explained by shared genetic factors, are largely unknown. We performed a genome-wide association study meta-analysis of BMI in 61,111 children aged between 2 and 10 years. Twenty-five independent loci reached genome-wide significance in the combined discovery and replication analyses. Two of these, located near NEDD4L and SLC45A3, have not previously been reported in relation to either childhood or adult BMI. Positive genetic correlations of childhood BMI with birth weight and adult BMI, waist-to-hip ratio, diastolic blood pressure and type 2 diabetes were detected (Rg ranging from 0.11 to 0.76, P-values <0.002). A negative genetic correlation of childhood BMI with age at menarche was observed. Our results suggest that the biological processes underlying childhood BMI largely, but not completely, overlap with those underlying adult BMI. The well-known observational associations of BMI in childhood with cardio-metabolic diseases in adulthood may reflect partial genetic overlap, but in light of previous evidence, it is also likely that they are explained through phenotypic continuity of BMI from childhood into adulthood.
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3. |
- Abel, Marianne Hope, et al.
(författare)
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Insufficient maternal iodine intake is associated with subfecundity, reduced foetal growth, and adverse pregnancy outcomes in the Norwegian Mother, Father and Child Cohort Study.
- 2020
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Ingår i: BMC medicine. - : Springer Science and Business Media LLC. - 1741-7015. ; 18:1
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Tidskriftsartikel (refereegranskat)abstract
- Severe iodine deficiency impacts fertility and reproductive outcomes. The potential effects of mild-to-moderate iodine deficiency are not well known. The aim of this study was to examine whether iodine intake was associated with subfecundity (i.e. >12months trying to get pregnant), foetal growth, and adverse pregnancy outcomes in a mild-to-moderately iodine-deficient population.We used the Norwegian Mother, Father and Child Cohort Study (MoBa) and included 78,318 pregnancies with data on iodine intake and pregnancy outcomes. Iodine intake was calculated using an extensive food frequency questionnaire in mid-pregnancy. In addition, urinary iodine concentration was available in a subsample of 2795 pregnancies. Associations were modelled continuously by multivariable regression controlling for a range of confounding factors.The median iodine intake from food was 121μg/day and the median urinary iodine was 69μg/L, confirming mild-to-moderate iodine deficiency. In non-users of iodine supplements (n=49,187), low iodine intake (<100-150μg/day) was associated with increased risk of preeclampsia (aOR=1.14 (95% CI 1.08, 1.22) at 75 vs. 100μg/day, p overall <0.001), preterm delivery before gestational week 37 (aOR=1.10 (1.04, 1.16) at 75 vs. 100μg/day, p overall=0.003), and reduced foetal growth (-0.08 SD (-0.10, -0.06) difference in birth weight z-score at 75 vs. 150μg/day, p overall <0.001), but not with early preterm delivery or intrauterine death. In planned pregnancies (n=56,416), having an iodine intake lower than ~100μg/day was associated with increased prevalence of subfecundity (aOR=1.05 (1.01, 1.09) at 75μg/day vs. 100μg/day, p overall=0.005). Long-term iodine supplement use (initiated before pregnancy) was associated with increased foetal growth (+0.05 SD (0.03, 0.07) on birth weight z-score, p<0.001) and reduced risk of preeclampsia (aOR 0.85 (0.74, 0.98), p=0.022), but not with the other adverse pregnancy outcomes. Urinary iodine concentration was not associated with any of the dichotomous outcomes, but positively associated with foetal growth (n=2795, p overall=0.017).This study shows that a low iodine intake was associated with restricted foetal growth and a higher prevalence of preeclampsia in these mild-to-moderately iodine-deficient women. Results also indicated increased risk of subfecundity and preterm delivery. Initiating iodine supplement use in pregnancy may be too late.
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4. |
- Aberšek, Nina, et al.
(författare)
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Calprotectin levels in amniotic fluid in relation to intra-amniotic inflammation and infection in women with preterm labor with intact membranes: A retrospective cohort study
- 2022
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Ingår i: European Journal of Obstetrics & Gynecology and Reproductive Biology. - : Elsevier BV. - 1872-7654 .- 0301-2115. ; 272, s. 24-29
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To evaluate the concentrations of calprotectin in amniotic fluid with respect to intra-amniotic inflammation and infection and to assess the presence or absence of bacteria in the amnio-chorionic niche with respect to presence or absence of intra-amniotic inflammation. Study design: Seventy-nine women with singleton pregnancies and preterm labor with intact membranes (PTL) were included in the study. Amniotic fluid was collected at the time of admission by amniocentesis and calprotectin levels were analyzed from frozen/thawed samples using ELISA. Interleukin (IL)-6 concentration was measured by point-of-care test. Samples from amniotic fluid and the amnio-chorionic niche (space between amniotic and chorionic membranes) were microbiologically analyzed. Microbial invasion of the amniotic cavity (MIAC) was diagnosed based on a positive PCR result for Ureaplasma species, Mycoplasma hominis, 16S rRNA or positive culture. Intra-amniotic inflammation (IAI) was defined as amniotic fluid point-of-care IL-6 concentration ≥ 745 pg/mL. The cohort of included women was divided into 4 subgroups based on the presence or absence of IAI/MIAC; i) intra-amniotic infection, ii) sterile IAI, iii) intra-amniotic colonization and iv) neither MIAC nor IAI. Results: Women with intra-amniotic infection had a significantly higher intra-amniotic calprotectin concentration (median; 101.6 µg/mL) compared with women with sterile IAI (median; 9.2 µg/mL), women with intra-amniotic colonization (median; 2.6 µg/mL) and women with neither MIAC nor IAI (median 4.6 µg/mL) (p = 0.001). Moreover, significantly higher amniotic fluid calprotectin concentration was seen in women who delivered within 7 days (p = 0.003). A significant negative correlation was found between amniotic fluid calprotectin and gestational age at delivery (rho = 0.32, p = 0.003). Relatively more bacteria in the amnio-chorionic niche were found in the sterile IAI group compared with the other groups. Conclusions: Calprotectin concentrations in amniotic fluid were significantly higher in the intra-amniotic infection group compared with the other groups. Moreover, the bacterial presence in the amnio-chorionic niche was higher in IAI group.
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5. |
- Aberšek, Nina, et al.
(författare)
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Characterizing of intra-amniotic inflammatory changes associated with chronic inflammation in the placenta marked by elevated amniotic fluid interferon gamma-induced protein 10 (IP-10) in pregnancies complicated by preterm prelabor rupture of membranes.
- 2024
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Ingår i: European Journal of Obstetrics and Gynecology and Reproductive Biology: X. - 2590-1613 .- 1872-7654. ; 296, s. 292-298
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Tidskriftsartikel (refereegranskat)abstract
- This study aimed to determine the occurrence of intra-amniotic inflammatory changes associated with chronic inflammation in the placenta, marked by elevated levels of interferon gamma-induced protein 10 (IP-10) (≥2200pg/mL) in the amniotic fluid of women with preterm prelabor rupture of membranes (PPROM). Specifically, the study investigated whether these intra-amniotic inflammatory changes were more common in women with microbial invasion of amniotic cavity (MIAC) and intra-amniotic inflammation (IAI), as indicated by increased amniotic fluid interleukin (IL)-6 concentration (≥3000pg/mL).A cohort of 114 women with singleton pregnancies complicated by PPROM between 24+0 and 36+6 weeks of gestation were included. Amniotic fluid samples were obtained via amniocentesis upon admission. MIAC diagnosis involved aerobic and anaerobic cultures, as well as polymerase chain reaction (PCR) analysis of the amniotic fluid. Immunoassay tests and enzyme-linked immunosorbent assay (ELISA) were used to determine IL-6 and IP-10 concentrations, respectively.Among the participants, 19.3% and 15.8% had MIAC and IAI, respectively. The occurrence of intra-amniotic inflammatory changes associated with chronic inflammation in the placenta was similar between women with and without MIAC (25% vs. 40.9%, p=0.136, adjusted p=0.213). The rate of intra-amniotic inflammatory changes associated with chronic inflammation in the placenta was significantly higher in women with IAI compared to those without, after adjusting for gestational age at sampling (55.6% vs. 22.9%, p=0.005, adjusted p=0.011).This study revealed comparable rates of intra-amniotic inflammatory changes associated with chronic inflammation in the placenta in women with and without MIAC, but a higher prevalence of intra-amniotic inflammatory changes associated with chronic inflammation in the placenta in women with IAI. These findings suggest involvement of chronic inflammation even in women with PPROM with acute intra-amniotic inflammation.
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6. |
- Adam, Sumaiya, et al.
(författare)
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Pregnancy as an opportunity to prevent type 2 diabetes mellitus: FIGO Best Practice Advice.
- 2023
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Ingår i: International journal of gynaecology and obstetrics: the official organ of the International Federation of Gynaecology and Obstetrics. - 1879-3479. ; 160:Suppl 1, s. 56-67
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Forskningsöversikt (refereegranskat)abstract
- Gestational diabetes (GDM) impacts approximately 17 million pregnancies worldwide. Women with a history of GDM have an 8-10-fold higher risk of developing type 2 diabetes and a 2-fold higher risk of developing cardiovascular disease (CVD) compared with women without prior GDM. Although it is possible to prevent and/or delay progression of GDM to type 2 diabetes, this is not widely undertaken. Considering the increasing global rates of type 2 diabetes and CVD in women, it is essential to utilize pregnancy as an opportunity to identify women at risk and initiate preventive intervention. This article reviews existing clinical guidelines for postpartum identification and management of women with previous GDM and identifies key recommendations for the prevention and/or delayed progression to type 2 diabetes for global clinical practice.
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7. |
- Adam, Sumaiya, et al.
(författare)
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Pregnancy as an opportunity to prevent type 2 diabetes mellitus: FIGO Best Practice Advice.
- 2023
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Ingår i: International journal of gynaecology and obstetrics: the official organ of the International Federation of Gynaecology and Obstetrics. - : Wiley. - 1879-3479 .- 0020-7292. ; 160:Suppl 1, s. 56-67
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Forskningsöversikt (refereegranskat)abstract
- Gestational diabetes (GDM) impacts approximately 17million pregnancies worldwide. Women with a history of GDM have an 8-10-fold higher risk of developing type 2 diabetes and a 2-fold higher risk of developing cardiovascular disease (CVD) compared with women without prior GDM. Although it is possible to prevent and/or delay progression of GDM to type 2 diabetes, this is not widely undertaken. Considering the increasing global rates of type 2 diabetes and CVD in women, it is essential to utilize pregnancy as an opportunity to identify women at risk and initiate preventive intervention. This article reviews existing clinical guidelines for postpartum identification and management of women with previous GDM and identifies key recommendations for the prevention and/or delayed progression to type 2 diabetes for global clinical practice.
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8. |
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9. |
- Allvin, Kerstin, 1970, et al.
(författare)
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Altered umbilical sex steroids in preterm infants born small for gestational age.
- 2020
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Ingår i: Journal of Maternal-Fetal & Neonatal Medicine. - : Informa UK Limited. - 1476-7058 .- 1476-4954. ; 33:24, s. 4164-4170
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Tidskriftsartikel (refereegranskat)abstract
- Boys born small for gestational age (SGA) are at increased risk of testicular dysgenesis syndrome, and girls born SGA face the risk of polycystic ovary syndrome later in life. Our aim was to study whether neonates born SGA have an altered profile of steroid hormones at birth.A total of 168 singletons (99 boys, 69 girls) born at 32.0-36.9 gestational weeks were recruited to a population-based, university hospital, single-center study. Of these, 31 infants (17 boys, 14 girls) were born SGA. The concentrations of dehydroepiandrosterone sulfate (DHEAS), androstenedione, testosterone, dihydrotestosterone, estrone, estradiol, cortisone, and cortisol were analyzed in umbilical cord serum with mass spectrometry.Girls born SGA had higher levels of androstenedione than girls born appropriate for gestational age (AGA) (4.0 versus 2.6nmol/L, p = 0.002). Boys born SGA had lower levels of estrone than boys born AGA (33822 versus 62471pmol/L, p = 0.038). Infants born SGA had lower levels of cortisone than infants born AGA, both in girls (340 versus 579nmol/L, p = 0.010) and in boys (308 versus 521nmol/L, p = 0.045). Furthermore, boys born SGA had a higher cortisol/cortisone ratio than boys born AGA (0.41 versus 0.25, p = 0.028). Gestational age correlated with DHEAS (boys r = 0.48, p = 0.000, girls r = 0.35, p = 0.013), and cortisol (boys r = 0.48, p = 0.000, girls r = 0.29, p = 0.039).In moderate-to-late preterm infants born SGA we observed a different steroid hormone profile in cord serum. Girls born SGA show increased levels of androstenedione and boys born SGA show decreased levels of estrone in cord serum, which could be related to placental aromatase deficiency in intrauterine growth restriction.
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10. |
- Amaral, Eliana, et al.
(författare)
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Vaccination during pregnancy: A golden opportunity to embrace.
- 2023
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Ingår i: International journal of gynaecology and obstetrics: the official organ of the International Federation of Gynaecology and Obstetrics. - 1879-3479. ; 163:2, s. 476-83
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Forskningsöversikt (refereegranskat)abstract
- Immunization strategies are part of routine pregnancy care to prevent infectious diseases in the mother, the fetus, and the newborn. Maternal immunization recommendations followed the recognition of the consequences of infectious diseases in pregnancy, including vertical transmission and perinatal consequences. The recent COVID-19 pandemic highlighted the issue of vaccination among pregnant individuals. Recommendations vary globally; however, Tdap, influenza, and, recently, COVID-19 vaccines are routinely recommended during pregnancy. There are several new maternal immunization products in the pipeline, including those directed against malaria, cytomegalovirus, Group B Streptococcus, herpes simplex virus, and respiratory syncytial virus. Important challenges must be addressed in all countries to guarantee that pregnant individuals and their babies receive the best care possible, including uptake of recommended immunizations by their entire target population groups. These challenges include disseminating appropriate data for vaccine recommendations and many others, such as ensuring stakeholder endorsement, achieving in-country distribution and administration, adequate vaccine supply, and a well-organized healthcare system, ideally offering the immunization free of charge. More recently, the hesitancy of pregnant women to receive immunizations highlights the relevance of cultural aspects and other contextual factors affecting vaccine uptake among pregnant individuals.
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11. |
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12. |
- Ankarcrona, Victoria, et al.
(författare)
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Obstetric anal sphincter injury after episiotomy in vacuum extraction: an epidemiological study using an emulated randomized trial approach
- 2021
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Ingår i: BJOG : an international journal of obstetrics and gynaecology. - : Wiley. - 1471-0528 .- 1470-0328. ; 128:10, s. 1663-1671
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Tidskriftsartikel (refereegranskat)abstract
- To emulate a randomized controlled trial investigating if lateral or mediolateral episiotomy compared to no episiotomy reduces the prevalence of obstetric anal sphincter injury (OASIS) in nulliparous women delivered with vacuum extraction.A population-based observational study.Sweden.63 654 nulliparous women delivered with vacuum extraction derived from the Swedish Medical Birth Register 2000-2011, with a live singleton baby without known malformations in cephalic presentation in gestational week ≥34+0, and subject to lateral or mediolateral episiotomy or no episiotomy.The effect of episiotomy was calculated using a causal doubly robust estimation method based on propensity scores. Results are presented as the average treatment effect and numbers needed to treat (NNT).OASIS (third- and fourth-degree perineal injury) in nulliparous women delivered with vacuum extraction.Episiotomy was associated with a reduction in OASIS from 15.5% to 11.8%, average treatment effect -3.66% (95% CI -4.31 to -3.01) and NNT 27. Third-degree perineal injuries were reduced from 14.0% to 10.9% (-3.08, 95% CI -3.71 to -2.42) with NNT 32. Fourth-degree perineal injuries were reduced from 1.6% to 1.0 % (-0.58%, 95% CI -0.79 to -0.37) with NNT 172.Lateral or mediolateral episiotomy reduced the prevalence of OASIS in nulliparous women delivered with vacuum extraction, compared to women with no episiotomy.
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13. |
- Anumba, Dilly, et al.
(författare)
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FIGO good practice recommendations on optimizing models of care for the prevention and mitigation of preterm birth.
- 2024
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Ingår i: International journal of gynaecology and obstetrics: the official organ of the International Federation of Gynaecology and Obstetrics. - 1879-3479.
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Tidskriftsartikel (refereegranskat)abstract
- The global challenge of preterm birth persists with little or no progress being made to reduce its prevalence or mitigate its consequences, especially in low-resource settings where health systems are less well developed. Improved delivery of respectful person-centered care employing effective care models delivered by skilled healthcare professionals is essential for addressing these needs. These FIGO good practice recommendations provide an overview of the evidence regarding the effectiveness of the various care models for preventing and managing preterm birth across global contexts. We also highlight that continuity of care within existing, context-appropriate care models (such as midwifery-led care and group care), in primary as well as secondary care, is pivotal to delivering high quality care across the pregnancy continuum-prior to conception, through pregnancy and birth, and preparation for a subsequent pregnancy-to improve care to prevent and manage preterm birth.
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14. |
- Ayres-de-Campos, Diogo, et al.
(författare)
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European Association of Perinatal Medicine (EAPM), European Board and College of Obstetricians and Gynaecologists (EBCOG), European Midwives Association (EMA). Joint position statement : Substandard and disrespectful care in labour - because words matter
- 2024
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Ingår i: European Journal of Obstetrics, Gynecology, and Reproductive Biology. - : Elsevier. - 0301-2115 .- 1872-7654. ; 296, s. 205-207
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Tidskriftsartikel (refereegranskat)abstract
- Substandard or disrespectful care during labour should be of serious concern for healthcare professionals, as it can affect one of the most important events in a woman's life. Substandard care refers to the use of interventions that are not considered best -practice, to the inadequate execution of interventions, to situations where bestpractice interventions are withheld from patients, or there is lack of adequate informed consent. Disrespectful care refers to forms of verbal and non-verbal communication that affect patients' dignity, individuality, privacy, intimacy, or personal beliefs. There are many possible underlying causes for substandard and disrespectful care in labour, including difficulties in modifying behaviours, judgmental or paternalistic attitudes, personal interests and individualism, and a human tendency to make less arduous, less difficult, or less stressful clinical decisions. The term "obstetric violence" is used in some parts of the world to describe various forms of substandard and disrespectful care in labour, but suggests that it is mainly carried out by obstetricians and is a serious form of aggression, carried out with the intent to cause harm. We believe that this term should not be used, as it does not help to identify the underlying problem, its causes, or its correction. In addition, it is generally seen by obstetricians and other healthcare professionals as an unjust and offensive term, generating a defensive and less collaborative mindset. We reach out to all individuals and institutions sharing the common goal of improving women's experience during labour, to work together to address the underlying causes of substandard and disrespectful care, and to develop common strategies to deal with this problem, based on mutual comprehension, trust and respect
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15. |
- Ayres-de-Campos, Diogo, et al.
(författare)
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EUROPEAN ASSOCIATION OF PERINATAL MEDICINE (EAPM) EUROPEAN MIDWIVES ASSOCIATION (EMA) Joint position statement: Caesarean delivery rates at a country level should be in the 15-20 % range
- 2024
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Ingår i: European Journal of Obstetrics and Gynecology and Reproductive Biology: X. - 2590-1613. ; 294, s. 76-78
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Tidskriftsartikel (refereegranskat)abstract
- While cesarean deliveries performed for health indications can save lives, unnecessary cesareans cause unjustifiable health risks for the mother, newborn, and for future pregnancies. Previous recommendations for cesarean delivery rates at a country level in the 10-15% range are currently unrealistic, and the proposed concept that striving to achieve specific rates is not important has resulted in a confusing message reaching healthcare professionals and the public. It is important to have a clear understanding of when cesarean delivery rates are deviating from internationally acceptable ranges, to trigger the implementation of healthcare policies needed to correct this problem. Based on currently existing scientific evidence, we recommend that cesarean delivery rates at a country level should be in the 15-20% range. This advice is based on the demonstration of decreased maternal and neonatal mortalities when national cesarean delivery rates rise to circa 15%, but values exceeding 20% are not associated with further benefits. It is also based on real-world experiences from northern European countries, where cesarean delivery rates in the 15-20% range are associated with some of the best maternal and perinatal quality indicators in the world. With the increase in cesarean delivery rates projected for the coming years, experience in provision of intrapartum care may come under threat in many hospitals, and recovering from this situation is likely to be a major challenge. Professional and scientific societies, together with healthcare authorities and governments need to prioritize actions to reverse the upward trend in cesarean delivery rates observed in many countries, and to strive to achieve values as close as possible to the recommended range.
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16. |
- Barman, Malin, 1983, et al.
(författare)
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Maternal dietary selenium intake is associated with increased gestational length and decreased risk of preterm delivery
- 2020
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Ingår i: British Journal of Nutrition. - 0007-1145 .- 1475-2662. ; 123:2, s. 209-219
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Tidskriftsartikel (refereegranskat)abstract
- The first positive genome-wide association study on gestational length and preterm delivery showed associations with a gene involved in the selenium metabolism. In this study we examine the associations between maternal intake of selenium and selenium status with gestational length and preterm delivery in 72,025 women with singleton live births from the population based, prospective Norwegian Mother, Father and Child Cohort Study (MoBa). A self-reported, semi-quantitativ food-frequency questionnaire answered in pregnancy week 22 was used to estimate selenium intake during the first half of pregnancy. Associations were analysed with adjusted linear and cox regressions. Selenium status was assessed in whole blood collected in gestational week 17 (n=2,637). Median dietary selenium intake was 53 (IQR: 44-62) μg/day, supplements provided additionally 50 (30-75) μg/day for supplement-users (n=23,409). Maternal dietary selenium intake was significantly associated with prolonged gestational length (β per SD=0.25, 95% CI=0.07-0.43) and decreased risk for preterm delivery (n=3,618, HR per SD=0.92, 95% CI=0.87-0.98). Neither selenium intake from supplements nor maternal blood selenium status was associated with gestational length or preterm delivery. Hence, this study showed that maternal dietary selenium intake, but not intake of selenium containing supplements, during the first half of pregnancy was significantly associated with decreased risk for preterm delivery. Further investigations, preferably in the form of a large RCT, are needed to elucidate the impact of selenium on pregnancy duration.
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17. |
- Beaumont, Robin N, et al.
(författare)
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Genome-wide association study of placental weight identifies distinct and shared genetic influences between placental and fetal growth.
- 2023
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Ingår i: Nature genetics. - 1546-1718 .- 1061-4036. ; 55:11, s. 1807-19
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Tidskriftsartikel (refereegranskat)abstract
- A well-functioning placenta is essential for fetal and maternal health throughout pregnancy. Using placental weight as a proxy for placental growth, we report genome-wide association analyses in the fetal (n=65,405), maternal (n=61,228) and paternal (n=52,392) genomes, yielding 40 independent association signals. Twenty-six signals are classified as fetal, four maternal and three fetal and maternal. A maternal parent-of-origin effect is seen near KCNQ1. Genetic correlation and colocalization analyses reveal overlap with birth weight genetics, but 12 loci are classified as predominantly or only affecting placental weight, with connections to placental development and morphology, and transport of antibodies and amino acids. Mendelian randomization analyses indicate that fetal genetically mediated higher placental weight is causally associated with preeclampsia risk and shorter gestational duration. Moreover, these analyses support the role of fetal insulin in regulating placental weight, providing a key link between fetal and placental growth.
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18. |
- Benedetto, Chiara, et al.
(författare)
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FIGO Preconception Checklist: Preconception care for mother and baby.
- 2024
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Ingår i: BJOG: An International Journal of Obstetrics and Gynaecology. - 1470-0328 .- 1471-0528. ; 165:1, s. 1-8
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Tidskriftsartikel (refereegranskat)abstract
- The preconception period is a unique and opportunistic time in a woman's life when she is motivated to adopt healthy behaviors that will benefit her and her child, making this time period a critical "window of opportunity" to improve short- and long-term health. Improving preconception health can ultimately improve both fetal and maternal outcomes. Promoting health before conception has several beneficial effects, including an increase in seeking antenatal care and a reduction in neonatal mortality. Preconception health is a broad concept that encompasses the management of chronic diseases, including optimal nutrition, adequate consumption of folic acid, control of body weight, adoption of healthy lifestyles, and receipt of appropriate vaccinations. Use of the FIGO Preconception Checklist, which includes the key elements of optimal preconception care, will empower women and their healthcare providers to better prepare women and their families for pregnancy.
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19. |
- Berglundh, Sofia, et al.
(författare)
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Maternal caffeine intake during pregnancy and child neurodevelopment up to eight years of age-Results from the Norwegian Mother, Father and Child Cohort Study.
- 2021
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Ingår i: European journal of nutrition. - : Springer Science and Business Media LLC. - 1436-6215 .- 1436-6207. ; 60:2, s. 791-805
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Tidskriftsartikel (refereegranskat)abstract
- Current knowledge of the effect of prenatal caffeine exposure on the child's neurodevelopment is contradictory. The current study aimed to study whether caffeine intake during pregnancy was associated with impaired child neurodevelopment up to 8years of age.A total of 64,189 full term pregnancies from the Norwegian Mother, Father and Child Cohort Study were included. A validated food-frequency questionnaire administered at gestational week 22 was used to obtain information on maternal caffeine intake from different sources. To assess child neurodevelopment (behaviour, temperament, motor development, language difficulties) validated scales were used to identify difficulties within each domain at 6, 18, 36months as well as 5 and 8years of age. Adjusted logistic regression models and mixed linear models were used to evaluate neurodevelopmental problems associated with maternal caffeine intake.Prenatal caffeine exposure was not associated with a persistently increased risk for behaviour, temperament, motor or language problems in children born at full-term. Results were consistent throughout all follow-ups and for different sources of caffeine intake. There was a minor trend towards an association between consumption of caffeinated soft drinks and high activity level, but this association was not driven by caffeine.Low to moderate caffeine consumption during pregnancy was not associated with any persistent adverse effects concerning the child's neurodevelopment up to 8years of age. However, a few previous studies indicate an association between high caffeine consumption and negative neurodevelopment outcomes.
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20. |
- Bergman, Lina, 1982, et al.
(författare)
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Study for Improving Maternal Pregnancy And Child ouTcomes (IMPACT): a study protocol for a Swedish prospective multicentre cohort study
- 2020
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Ingår i: BMJ Open. - : BMJ. - 2044-6055 .- 2044-6055. ; 10:9, s. e033851-e033851
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Tidskriftsartikel (refereegranskat)abstract
- Introduction First-trimester pregnancy risk evaluation facilitates individualised antenatal care, as well as application of preventive strategies for pre-eclampsia or birth of a small for gestational age infant. A range of early intervention strategies in pregnancies identified as high risk at the end of the first trimester has been shown to decrease the risk of preterm pre-eclampsia (<37 gestational weeks). The aim of this project is to create the Improving Maternal Pregnancy And Child ouTcomes (IMPACT) database; a nationwide database with individual patient data, including predictors recorded at the end of the first trimester and later pregnancy outcomes, to identify women at high risk of pre-eclampsia. A second aim is to link the IMPACT database to a biobank with first-trimester blood samples. Methods and analysis This is a Swedish prospective multicentre cohort study. Women are included between the 11th and 14th weeks of pregnancy. At inclusion, pre-identified predictors are retrieved by interviews and medical examinations. Blood samples are collected and stored in a biobank. Additional predictors and pregnancy outcomes are retrieved from the Swedish Pregnancy Register. Inclusion in the study began in November 2018 with a targeted sample size of 45 000 pregnancies by end of 2021. Creation of a new risk prediction model will then be developed, validated and implemented. The database and biobank will enable future research on prediction of various pregnancy-related complications. Ethics and dissemination Confidentiality aspects such as data encryption and storage comply with the General Data Protection Regulation and with ethical committee requirements. This study has been granted national ethical approval by the Swedish Ethical Review Authority (Uppsala 2018-231) and national biobank approval at Uppsala Biobank (18237 2 2018 231). Results from the current as well as future studies using information from the IMPACT database will be published in peer-reviewed journals.
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21. |
- Bianchi, Ana, et al.
(författare)
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FIGO good practice recommendations on delayed umbilical cord clamping.
- 2021
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Ingår i: International journal of gynaecology and obstetrics: the official organ of the International Federation of Gynaecology and Obstetrics. - : Wiley. - 1879-3479. ; 155:1, s. 34-36
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Forskningsöversikt (refereegranskat)abstract
- Delayed cord clamping in the first minute in preterm infants born before 34weeks of gestation improves neonatal hematologic measures and may reduce mortality without increasing any other morbidity. In term-born babies, it also seems to improve both the short- and long-term outcomes and shows favorable scores in fine motor and social domains. However, there is insufficient evidence to show what duration of delay is best. The current evidence supports not clamping the cord before 30seconds for preterm births. Future trials could compare different lengths of delay. Until then, a period of 30seconds to 3minutes seems justified for term-born babies.
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22. |
- Burckova, Hana, et al.
(författare)
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Intra-amniotic inflammatory complications in preterm prelabor rupture of membranes and long-term neurodevelopmental outcomes of infants: a systematic review.
- 2021
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Ingår i: The journal of maternal-fetal & neonatal medicine : the official journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstetricians. - : Informa UK Limited. - 1476-4954. ; 35:25, s. 5993-8
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Tidskriftsartikel (refereegranskat)abstract
- To perform a systematic review of the literature available on the association between the presence of microbial invasion of the amniotic cavity (MIAC) and/or intra-amniotic inflammation and long-term neurodevelopmental outcomes of infants from pregnancies complicated by preterm prelabor rupture of membranes (PPROM).A literature search, from their earliest entries to May 2020, was performed by employing three electronic databases (Web of Science, PubMed, and Scopus). The selection criteria were as follows: (1) singleton pregnancies with PPROM; (2) available information regarding MIAC and/or intra-amniotic inflammation; (3) long-term (at least one year of the corrected age) neurodevelopmental outcomes of respective infants.The initial search identified 10,953 articles, of which 8 were selected for full-text reading; however, none were included in the review owing to the following reasons: (i) spontaneous preterm labor with intact membranes and/or indicated (iatrogenic) preterm delivery were included in the studies without providing separate data for PPROM (n=5); (ii) long-term, at least one year of the corrected age, neurodevelopmental outcomes of infants were not assessed (n=1); (iii) the presence of both the abovementioned reasons (n=1); (iv) amniotic fluid was not assessed, and a long-term neurodevelopmental outcome was not evaluated (n=1).The literature search provides evidence of a knowledge gap in the association between the presence of MIAC and/or intra-amniotic inflammation and long-term neurodevelopmental outcomes in infants with PPROM.
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23. |
- Chalupska, Martina, et al.
(författare)
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Intra-Amniotic Infection and Sterile Intra-Amniotic Inflammation in Cervical Insufficiency with Prolapsed Fetal Membranes: Clinical Implications.
- 2021
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Ingår i: Fetal diagnosis and therapy. - : S. Karger AG. - 1421-9964 .- 1015-3837. ; 48:1, s. 58-69
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was to identify the rates of 2 phenotypes of intra-amniotic inflammation: intra-amniotic infection (with microbial invasion of the amniotic cavity [MIAC]) and sterile intra-amniotic inflammation (without MIAC), and their outcomes, among women with cervical insufficiency with prolapsed fetal membranes.This is a retrospective study of women admitted to the Department of Obstetrics and Gynecology, University Hospital Hradec Kralove between January 2014 and May 2020. Transabdominal amniocentesis to evaluate intra-amniotic inflammation (amniotic fluid interleukin-6) and MIAC (culturing and molecular biology methods) was performed as part of standard clinical management.In total, 37 women with cervical insufficiency and prolapsed fetal membranes were included; 11% (4/37) and 43% (16/37) of them had intra-amniotic infection and sterile intra-amniotic inflammation, respectively. In women with intra-amniotic infection and sterile intra-amniotic inflammation, we noted shorter intervals between admission and delivery (both p < 0.0001), and lower gestational age at delivery (p < 0.0001 and p = 0.004) and percentiles of birth/abortion weight (p = 0.03 and p = 0.009, respectively) than in those without intra-amniotic inflammation.Both phenotypes of intra-amniotic inflammation, with sterile intra-amniotic inflammation being more frequent, are associated with worse outcomes in pregnancies with cervical insufficiency with prolapsed fetal membranes.
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24. |
- Chen, Jing, et al.
(författare)
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Dissecting maternal and fetal genetic effects underlying the associations between maternal phenotypes, birth outcomes, and adult phenotypes: A mendelian-randomization and haplotype-based genetic score analysis in 10,734 mother-infant pairs.
- 2020
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Ingår i: PLoS medicine. - : Public Library of Science (PLoS). - 1549-1676. ; 17:8
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Tidskriftsartikel (refereegranskat)abstract
- Many maternal traits are associated with a neonate's gestational duration, birth weight, and birth length. These birth outcomes are subsequently associated with late-onset health conditions. The causal mechanisms and the relative contributions of maternal and fetal genetic effects behind these observed associations are unresolved.Based on 10,734 mother-infant duos of European ancestry from the UK, Northern Europe, Australia, and North America, we constructed haplotype genetic scores using single-nucleotide polymorphisms (SNPs) known to be associated with adult height, body mass index (BMI), blood pressure (BP), fasting plasma glucose (FPG), and type 2 diabetes (T2D). Using these scores as genetic instruments, we estimated the maternal and fetal genetic effects underlying the observed associations between maternal phenotypes and pregnancy outcomes. We also used infant-specific birth weight genetic scores as instrument and examined the effects of fetal growth on pregnancy outcomes, maternal BP, and glucose levels during pregnancy. The maternal nontransmitted haplotype score for height was significantly associated with gestational duration (p = 2.2 × 10-4). Both maternal and paternal transmitted height haplotype scores were highly significantly associated with birth weight and length (p < 1 × 10-17). The maternal transmitted BMI scores were associated with birth weight with a significant maternal effect (p = 1.6 × 10-4). Both maternal and paternal transmitted BP scores were negatively associated with birth weight with a significant fetal effect (p = 9.4 × 10-3), whereas BP alleles were significantly associated with gestational duration and preterm birth through maternal effects (p = 3.3 × 10-2 and p = 4.5 × 10-3, respectively). The nontransmitted haplotype score for FPG was strongly associated with birth weight (p = 4.7 × 10-6); however, the glucose-increasing alleles in the fetus were associated with reduced birth weight through a fetal effect (p = 2.2 × 10-3). The haplotype scores for T2D were associated with birth weight in a similar way but with a weaker maternal effect (p = 6.4 × 10-3) and a stronger fetal effect (p = 1.3 × 10-5). The paternal transmitted birth weight score was significantly associated with reduced gestational duration (p = 1.8 × 10-4) and increased maternal systolic BP during pregnancy (p = 2.2 × 10-2). The major limitations of the study include missing and heterogenous phenotype data in some data sets and different instrumental strength of genetic scores for different phenotypic traits.We found that both maternal height and fetal growth are important factors in shaping the duration of gestation: genetically elevated maternal height is associated with longer gestational duration, whereas alleles that increase fetal growth are associated with shorter gestational duration. Fetal growth is influenced by both maternal and fetal effects and can reciprocally influence maternal phenotypes: taller maternal stature, higher maternal BMI, and higher maternal blood glucose are associated with larger birth size through maternal effects; in the fetus, the height- and metabolic-risk-increasing alleles are associated with increased and decreased birth size, respectively; alleles raising birth weight in the fetus are associated with shorter gestational duration and higher maternal BP. These maternal and fetal genetic effects may explain the observed associations between the studied maternal phenotypes and birth outcomes, as well as the life-course associations between these birth outcomes and adult phenotypes.
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25. |
- Cobo, Teresa, et al.
(författare)
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A Rapid Amniotic Fluid Interleukin-6 Assessment for the Identification of Intra-Amniotic Inflammation in Women with Preterm Labor and Intact Membranes.
- 2021
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Ingår i: Fetal diagnosis and therapy. - : S. Karger AG. - 1421-9964 .- 1015-3837. ; 48:5, s. 327-332
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Tidskriftsartikel (refereegranskat)abstract
- A multivariable predictive model has recently been developed with good accuracy to predict spontaneous preterm delivery within 7 days in women with preterm labor (PTL) and intact membranes. However, this model measures amniotic fluid (AF) interleukin (IL)-6 concentrations using the ELISA method, thereby limiting clinical implementation. The main objectives of this study were to validate the automated immunoassay as a quantitative method to measure AF IL-6 in women with PTL and to evaluate the diagnostic performance of AF IL-6 alone and as part of a multivariable predictive model to predict spontaneous delivery in 7 days with this automated method.This is a retrospective observational study in women with PTL below 34 weeks who underwent amniocentesis to rule out microbial invasion of the amniotic cavity. Women with clinical signs of chorioamnionitis, cervical length measurement at admission >5th centile, maternal age <18 years, and no consent to perform amniocentesis for this indication were excluded. The local Institutional Review Boards approved the study (HCB/2019/0940). Analysis of AF IL-6 Concentrations: AF IL-6 concentrations were measured using an automated Cobas e602 electrochemiluminescence immunoanalyzer and Human IL-6 Quantikine ELISA kit.Of the entire study group (n = 100), 38 women spontaneously delivered within 7 days after admission. Both laboratory methods showed good agreement (intraclass correlation coefficient: 0.937 (95% confidence interval [CI] 0.908-0.957); p < 0.001). Diagnostic performance of AF IL-6 to predict spontaneous delivery within 7 days when it was included in the multivariable predictive model showed an area under the receiver operating characteristic curve of 0.894 (95% CI 0.799-0.955), sensitivity of 97%, specificity of 74%, positive predictive value of 73%, negative predictive value of 97%, positive likelihood ratio (LR) of 3.7, and negative LR of 0.045.While both analytical methods were comparable for measuring AF IL-6 concentrations in women with PTL, the Cobas immunoanalyzer provided rapid diagnosis of intra-amniotic inflammation within minutes. The predictive model showed a good diagnostic performance to target women at high risk of spontaneous delivery within 7 days.
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26. |
- Cobo, Teresa, et al.
(författare)
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Risk factors for spontaneous preterm delivery.
- 2020
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Ingår i: International journal of gynaecology and obstetrics: the official organ of the International Federation of Gynaecology and Obstetrics. - : Wiley. - 1879-3479. ; 150:1, s. 17-23
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Tidskriftsartikel (refereegranskat)abstract
- There is a substantial variation in rates of preterm delivery between different parts of the world. The understanding of these variations, as well as the biological mechanisms behind spontaneous preterm delivery, is limited. Although the benefit of antenatal interventions has been shown to be limited, using well-known risk factors for spontaneous preterm delivery to select the correct pregnant women for targeted interventions is important from both a medical and caregiving perspective.To provide an introduction to a substantial research area dealing with risk factors of spontaneous preterm delivery.Risk factors in this review were classified as demographical, obstetrical, and gynecological and those related to the current pregnancy according to high-quality evidence of recent literature.An introduction to a substantial research area in maternal and fetal medicine was provided that might help clinicians to better understand the risk factors related to preterm delivery and select the correct pregnant women for targeted interventions.
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27. |
- Dar, Pe'er, et al.
(författare)
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Cell-free DNA screening for prenatal detection of 22q11.2 deletion syndrome.
- 2022
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Ingår i: American journal of obstetrics and gynecology. - : Elsevier BV. - 1097-6868 .- 0002-9378. ; 227:1
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Tidskriftsartikel (refereegranskat)abstract
- Prenatal screening has historically focused primarily on detection of fetal aneuploidies. Cell-free DNA (cfDNA) now enables noninvasive screening for subchromosomal copy number variants, including 22q11.2 deletion syndrome (22q11.2DS or DiGeorge syndrome), which is the most common microdeletion and a leading cause of congenital heart defects and neurodevelopmental delay. Although smaller studies have demonstrated the feasibility of screening for 22q11.2DS, large cohort studies with postnatal confirmatory testing to assess test performance have not been reported.To assess the performance of SNP-based cfDNA prenatal screening for detection of 22q11.2DS.Patients who had SNP-based cfDNA prenatal screening for 22q11.2DS were prospectively enrolled at 21 centers in 6 countries. Prenatal or newborn DNA samples were requested in all cases for genetic confirmation with chromosomal microarray. The primary outcome was sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of cfDNA for detection of all deletions, including the classical deletion and nested deletions that are ≥500kb, in the 22q11.2 low copy repeat A-D region. Secondary outcomes included the prevalence of 22q11.2DS and performance of an updated cfDNA algorithm that was evaluated blinded to pregnancy outcome.Of 20,887 women enrolled, genetic outcome was available in 18,289 (87.6%). Twelve 22q11.2DS cases were confirmed in the cohort, including five (41.7%) nested deletions, yielding a prevalence of 1:1524. In the total cohort, cfDNA reported 17,976 (98.3%) as low risk for 22q11.2DS and 38 (0.2%) as high-risk; 275 (1.5%) were non-reportable. Overall, 9 of 12 cases of 22q11.2 were detected, yielding a sensitivity of 75.0% (95% CI: 42.8, 94.5); specificity of 99.84% (95% CI: 99.77, 99.89); PPV of 23.7% (95% CI: 11.44, 40.24) and NPV of 99.98% (95% CI: 99.95, 100). None of the cases with a non-reportable result was diagnosed with 22q11.2DS. The updated algorithm detected 10/12 cases (83.3%; 95% CI: 51.6-97.9) with a lower false positive rate (0.05% vs. 0.16%, p<0.001) and a PPV of 52.6% (10/19; 95% CI 28.9-75.6).Noninvasive cfDNA prenatal screening for 22q11.2DS can detect most affected cases, including smaller nested deletions, with a low false positive rate.
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28. |
- Dar, Pe'er, et al.
(författare)
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Cell-free DNA screening for trisomies 21, 18 and 13 in pregnancies at low and high risk for aneuploidy with genetic confirmation
- 2022
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Ingår i: American journal of obstetrics and gynecology. - : Elsevier BV. - 1097-6868 .- 0002-9378. ; 227:2
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Tidskriftsartikel (refereegranskat)abstract
- Cell-free DNA (cfDNA) non-invasive prenatal screening for trisomy (T) 21, 18, and 13 has been rapidly adopted into clinical practice. However, prior studies are limited by lack of follow up genetic testing to confirm outcomes and accurately assess test performance, particularly in women at low-risk for aneuploidy.To compare the performance of cfDNA screening for T21, T18 and T13 between women at low and high-risk for aneuploidy in a large, prospective cohort with genetic confirmation of results.A multicenter prospective observational study at 21 centers in 6 countries. Women who had SNP-based cfDNA screening for T21, T18 and T13 were enrolled. Genetic confirmation was obtained from prenatal or newborn DNA samples. Test performance and test failure (no-call) rates were assessed for the cohort and women with low and high prior risk for aneuploidy were compared. An updated cfDNA algorithm, blinded to pregnancy outcome, was also assessed.20,194 were enrolled at median gestational age of 12.6 weeks (IQR:11.6, 13.9). Genetic outcomes were confirmed in 17,851 (88.4%): 13,043 (73.1%) low-risk and 4,808 (26.9%) high-risk for aneuploidy. Overall, 133 trisomies were diagnosed (100 T21; 18 T18; 15 T13). cfDNA screen positive rate was lower in low- vs. high-risk (0.27% vs. 2.2%, p<0.0001). Sensitivity and specificity were similar between groups. The positive predictive value (PPV) for the low and high-risk groups was 85.7% vs. 97.5%, p=0.058 for T21; 50.0% vs. 81.3%, p=0.283 for T18; and 62.5% vs. 83.3, p=0.58 for T13, respectively. Overall, 602 (3.4%) patients had no-call result after the first draw and 287 (1.61%) after including cases with a second draw. Trisomy rate was higher in the 287 with no-call results than patients with a result on a first draw (2.8% vs. 0.7%, p=0.001). The updated algorithm showed similar sensitivity and specificity to the study algorhitm with a lower no-call rate.In women at low-risk for aneuploidy, SNP-based cfDNA has high sensitivity and specificity, PPV of 85.7% for T21 and 74.3% for the three common trisomies. Patients who receive a no-call result are at increased risk of aneuploidy and require additional investigation.
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29. |
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30. |
- Daskalakis, George, et al.
(författare)
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European guidelines on perinatal care: corticosteroids for women at risk of preterm birth.
- 2023
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Ingår i: The journal of maternal-fetal & neonatal medicine : the official journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstetricians. - : Informa UK Limited. - 1476-4954 .- 1476-7058. ; 36:1
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Tidskriftsartikel (refereegranskat)abstract
- of recommendationsCorticosteroids should be administered to women at a gestational age between 24+0 and 33+6weeks, when preterm birth is anticipated in the next seven days, as these have been consistently shown to reduce neonatal mortality and morbidity. (Strong-quality evidence; strong recommendation). In selected cases, extension of this period up to 34+6weeks may be considered (Expert opinion). Optimal benefits are found in infants delivered within 7days of corticosteroid administration. Even a single-dose administration should be given to women with imminent preterm birth, as this is likely to improve neurodevelopmental outcome (Moderate-quality evidence; conditional recommendation).Either betamethasone (12mg administered intramuscularly twice, 24-hours apart) or dexamethasone (6mg administered intramuscularly in four doses, 12-hours apart, or 12mg administered intramuscularly twice, 24-hours apart), may be used (Moderate-quality evidence; Strong recommendation). Administration of two "all" doses is named a "course of corticosteroids".Administration between 22+0 and 23+6weeks should be considered when preterm birth is anticipated in the next seven days and active newborn life-support is indicated, taking into account parental wishes. Clear survival benefit has been observed in these cases, but the impact on short-term neurological and respiratory function, as well as long-term neurodevelopmental outcome is still unclear (Low/moderate-quality evidence; Weak recommendation).Administration between 34+0 and 34+6weeks should only be offered to a few selected cases (Expert opinion). Administration between 35+0 and 36+6weeks should be restricted to prospective randomized trials. Current evidence suggests that although corticosteroids reduce the incidence of transient tachypnea of the newborn, they do not affect the incidence of respiratory distress syndrome, and they increase neonatal hypoglycemia. Long-term safety data are lacking (Moderate quality evidence; Conditional recommendation).Administration in pregnancies beyond 37+0weeks is not indicated, even for scheduled cesarean delivery, as current evidence does not suggest benefit and the long-term effects remain unknown (Low-quality evidence; Conditional recommendation).Administration should be given in twin pregnancies, with the same indication and doses as for singletons. However, existing evidence suggests that it should be reserved for pregnancies at high-risk of delivering within a 7-day interval (Low-quality evidence; Conditional recommendation). Maternal diabetes mellitus is not a contraindication to the use of antenatal corticosteroids (Moderate quality evidence; Strong recommendation).A single repeat course of corticosteroids can be considered in pregnancies at less than 34+0weeks gestation, if the previous course was completed more than seven days earlier, and there is a renewed risk of imminent delivery (Low-quality evidence; Conditional recommendation).
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31. |
- Denault, William R P, et al.
(författare)
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A fast wavelet-based functional association analysis replicates several susceptibility loci for birth weight in a Norwegian population.
- 2021
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Ingår i: BMC genomics. - : Springer Science and Business Media LLC. - 1471-2164. ; 22:1
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Tidskriftsartikel (refereegranskat)abstract
- Birth weight (BW) is one of the most widely studied anthropometric traits in humans because of its role in various adult-onset diseases. The number of loci associated with BW has increased dramatically since the advent of whole-genome screening approaches such as genome-wide association studies (GWASes) and meta-analyses of GWASes (GWAMAs). To further contribute to elucidating the genetic architecture of BW, we analyzed a genotyped Norwegian dataset with information on child's BW (N=9,063) using a slightly modified version of a wavelet-based method by Shim and Stephens (2015) called WaveQTL.WaveQTL uses wavelet regression for regional testing and offers a more flexible functional modeling framework compared to conventional GWAS methods. To further improve WaveQTL, we added a novel feature termed "zooming strategy" to enhance the detection of associations in typically small regions. The modified WaveQTL replicated five out of the 133 loci previously identified by the largest GWAMA of BW to date by Warrington et al. (2019), even though our sample size was 26 times smaller than that study and 18 times smaller than the second largest GWAMA of BW by Horikoshi et al. (2016). In addition, the modified WaveQTL performed better in regions of high LD between SNPs.This study is the first adaptation of the original WaveQTL method to the analysis of genome-wide genotypic data. Our results highlight the utility of the modified WaveQTL as a complementary tool for identifying loci that might escape detection by conventional genome-wide screening methods due to power issues. An attractive application of the modified WaveQTL would be to select traits from various public GWAS repositories to investigate whether they might benefit from a second analysis.
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32. |
- Denault, William R P, et al.
(författare)
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Wavelet Screening: a novel approach to analyzing GWAS data.
- 2021
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Ingår i: BMC bioinformatics. - : Springer Science and Business Media LLC. - 1471-2105. ; 22:1
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Tidskriftsartikel (refereegranskat)abstract
- Traditional methods for single-variant genome-wide association study (GWAS) incur a substantial multiple-testing burden because of the need to test for associations with a vast number of single-nucleotide polymorphisms (SNPs) simultaneously. Further, by ignoring more complex joint effects of nearby SNPs within a given region, these methods fail to consider the genomic context of an association with the outcome.To address these shortcomings, we present a more powerful method for GWAS, coined 'Wavelet Screening' (WS), that greatly reduces the number of tests to be performed. This is achieved through the use of a sliding-window approach based on wavelets to sequentially screen the entire genome for associations. Wavelets are oscillatory functions that are useful for analyzing the local frequency and time behavior of signals. The signals can then be divided into different scale components and analyzed separately. In the current setting, we consider a sequence of SNPs as a genetic signal, and for each screened region, we transform the genetic signal into the wavelet space. The null and alternative hypotheses are modeled using the posterior distribution of the wavelet coefficients. WS is enhanced by using additional information from the regression coefficients and by taking advantage of the pyramidal structure of wavelets. When faced with more complex genetic signals than single-SNP associations, we show via simulations that WS provides a substantial gain in power compared to both the traditional GWAS modeling and another popular regional association test called SNP-set (Sequence) Kernel Association Test (SKAT). To demonstrate feasibility, we applied WS to a large Norwegian cohort (N=8006) with genotypes and information available on gestational duration.WS is a powerful and versatile approach to analyzing whole-genome data and lends itself easily to investigating variousomics data types. Given its broader focus on the genomic context of an association, WS may provide additional insight into trait etiology by revealing genes and loci that might have been missed by previous efforts.
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33. |
- Edsjö, Anders, et al.
(författare)
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Building a precision medicine infrastructure at a national level : The Swedish experience
- 2023
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Ingår i: Cambridge Prisms: Precision Medicine. - : Cambridge University Press. - 2752-6143. ; 1
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Forskningsöversikt (refereegranskat)abstract
- Precision medicine has the potential to transform healthcare by moving from one-size-fits-all to personalised treatment and care. This transition has been greatly facilitated through new high-throughput sequencing technologies that can provide the unique molecular profile of each individual patient, along with the rapid development of targeted therapies directed to the Achilles heels of each disease. To implement precision medicine approaches in healthcare, many countries have adopted national strategies and initiated genomic/precision medicine initiatives to provide equal access to all citizens. In other countries, such as Sweden, this has proven more difficult due to regionally organised healthcare. Using a bottom-up approach, key stakeholders from academia, healthcare, industry and patient organisations joined forces and formed Genomic Medicine Sweden (GMS), a national infrastructure for the implementation of precision medicine across the country. To achieve this, Genomic Medicine Centres have been established to provide regionally distributed genomic services, and a national informatics infrastructure has been built to allow secure data handling and sharing. GMS has a broad scope focusing on rare diseases, cancer, pharmacogenomics, infectious diseases and complex diseases, while also providing expertise in informatics, ethical and legal issues, health economy, industry collaboration and education. In this review, we summarise our experience in building a national infrastructure for precision medicine. We also provide key examples how precision medicine already has been successfully implemented within our focus areas. Finally, we bring up challenges and opportunities associated with precision medicine implementation, the importance of international collaboration, as well as the future perspective in the field of precision medicine.
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34. |
- Englund-Ögge, Linda, et al.
(författare)
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Maternal characteristics and pregnancy outcomes in the NICE birth cohort: an assessment of self-selection bias
- 2022
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Ingår i: Journal of Maternal-Fetal and Neonatal Medicine. - : Informa UK Limited. - 1476-7058 .- 1476-4954. ; 35:25, s. 9014-9022
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Tidskriftsartikel (refereegranskat)abstract
- Background: Prospective birth cohorts are essential for identifying associations between exposures and outcomes. However, voluntary participation introduces a potential bias due to self selection since the persons that chose to participate may differ in background characteristics and behaviors. Objectives: To investigate potential bias due to self-selection in the Nutritional impact onImmunological maturation duringChildhood in relation to theEnvironment (NICE) birth cohort in northern Sweden. Methods: Women in the NICE birth cohort (N = 621) were compared to nonparticipating pregnant women in Norrbotten County in northern Sweden who were eligible for participation (N = 4976) regarding maternal characteristics and lifestyle. Maternal characteristics and pregnancy outcomes were compared between the groups and associations between exposures (smoking, folic acid, BMI, parity, education) and pregnancy outcomes (birth weight and gestational age) were analyzed by linear regression analyses, examining any interaction with the group. Results: NICE participants were more highly educated, older and more likely to cohabit than the non-participants. They more often took folic acid and multivitamin supplements and less often smoked during early pregnancy. Pregnancy outcomes (mode of delivery, gestational age at delivery, birth weight and APGAR score) did, however, not differ significantly between participants and non-participants. Smoking, BMI, education and parity affected gestational age and birth weight, but the associations were of similar magnitude in participants and non-participants, with no significant effect on the group. Conclusion: Self-selection to the NICE study was evident in some factors related to lifestyle and socioeconomic characteristics but did not appear to skew pregnancy outcomes or alter well-known effects of certain lifestyle parameters on pregnancy outcomes.
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35. |
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36. |
- Flatley, Christopher, et al.
(författare)
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Placental weight centiles adjusted for age, parity and fetal sex
- 2022
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Ingår i: Placenta. - : Elsevier BV. - 1532-3102 .- 0143-4004. ; 117, s. 87-94
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Tidskriftsartikel (refereegranskat)abstract
- The weight of the placenta can be indicative of efficacy in nutrient and oxygen supply. Furthermore, it has been suggested that a measure of the placenta's ability to adequately supply nutrients to the fetus can be found in the relationship between birth weight and placental weight expressed as a ratio. Our aim was to develop age adjusted placenta weight and birth weight to placenta weight ratio reference curves that are stratified by maternal parity and fetal sex.We included singleton, non-anomalous births with a gestational age inclusive of 28+0 weeks to 42+6 weeks. Excluded were pregnancies of multiplicity, fetuses with congenital abnormalities, stillbirths and pregnancies that had placental complications (ie placenta previa or abruption). Generalised additive model for location, shape and scale (GAMLSS) was used to fit reference curves.We stratified 97,882 pregnancies by maternal nulliparity status and fetal sex. Extensive assessment model goodness-of-fit showed appropriate modeling and accurate fit to the four parameters of distribution. Our results show accurate model fit of the reference curves to the data. We demonstrated that the influence that parity has on the placenta weight is far greater than that exerted by fetal sex, and that the difference is dependent on gestational age.This is the largest presentation of age and parity adjusted placenta weight and feto-placental weight ratio reference ranges to date. The difference observed between nulliparous and multiparous pregnancies could be explained by biological memory and the remnants of maternal endo-myometrial vascularity after the first pregnancy.
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37. |
- Franks, P. W., et al.
(författare)
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Technological readiness and implementation of genomic-driven precision medicine for complex diseases
- 2021
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Ingår i: Journal of Internal Medicine. - : Wiley. - 0954-6820 .- 1365-2796. ; 290:3, s. 602-620
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Forskningsöversikt (refereegranskat)abstract
- The fields of human genetics and genomics have generated considerable knowledge about the mechanistic basis of many diseases. Genomic approaches to diagnosis, prognostication, prevention and treatment - genomic-driven precision medicine (GDPM) - may help optimize medical practice. Here, we provide a comprehensive review of GDPM of complex diseases across major medical specialties. We focus on technological readiness: how rapidly a test can be implemented into health care. Although these areas of medicine are diverse, key similarities exist across almost all areas. Many medical areas have, within their standards of care, at least one GDPM test for a genetic variant of strong effect that aids the identification/diagnosis of a more homogeneous subset within a larger disease group or identifies a subset with different therapeutic requirements. However, for almost all complex diseases, the majority of patients do not carry established single-gene mutations with large effects. Thus, research is underway that seeks to determine the polygenic basis of many complex diseases. Nevertheless, most complex diseases are caused by the interplay of genetic, behavioural and environmental risk factors, which will likely necessitate models for prediction and diagnosis that incorporate genetic and non-genetic data.
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38. |
- Frier, Emily M, et al.
(författare)
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Consortium for the Study of Pregnancy Treatments (Co-OPT): An international birth cohort to study the effects of antenatal corticosteroids.
- 2023
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Ingår i: PloS one. - : Public Library of Science (PLoS). - 1932-6203. ; 18:3
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Tidskriftsartikel (refereegranskat)abstract
- Antenatal corticosteroids (ACS) are widely prescribed to improve outcomes following preterm birth. Significant knowledge gaps surround their safety, long-term effects, optimal timing and dosage. Almost half of women given ACS give birth outside the "therapeutic window" and have not delivered over 7 days later. Overtreatment with ACS is a concern, as evidence accumulates of risks of unnecessary ACS exposure.The Consortium for the Study of Pregnancy Treatments (Co-OPT) was established to address research questions surrounding safety of medications in pregnancy. We created an international birth cohort containing information on ACS exposure and pregnancy and neonatal outcomes by combining data from four national/provincial birth registers and one hospital database, and follow-up through linked population-level data from death registers and electronic health records.The Co-OPT ACS cohort contains 2.28 million pregnancies and babies, born in Finland, Iceland, Israel, Canada and Scotland, between 1990 and 2019. Births from 22 to 45 weeks' gestation were included; 92.9% were at term (≥ 37 completed weeks). 3.6% of babies were exposed to ACS (67.0% and 77.9% of singleton and multiple births before 34 weeks, respectively). Rates of ACS exposure increased across the study period. Of all ACS-exposed babies, 26.8% were born at term. Longitudinal childhood data were available for 1.64 million live births. Follow-up includes diagnoses of a range of physical and mental disorders from the Finnish Hospital Register, diagnoses of mental, behavioural, and neurodevelopmental disorders from the Icelandic Patient Registers, and preschool reviews from the Scottish Child Health Surveillance Programme. The Co-OPT ACS cohort is the largest international birth cohort to date with data on ACS exposure and maternal, perinatal and childhood outcomes. Its large scale will enable assessment of important rare outcomes such as perinatal mortality, and comprehensive evaluation of the short- and long-term safety and efficacy of ACS.
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39. |
- Frøen, J Frederik, et al.
(författare)
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FIGO good practice recommendations on the importance of registry data for monitoring rates and health systems performance in prevention and management of preterm birth.
- 2021
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Ingår i: International journal of gynaecology and obstetrics: the official organ of the International Federation of Gynaecology and Obstetrics. - : Wiley. - 1879-3479. ; 155:1, s. 5-7
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Forskningsöversikt (refereegranskat)abstract
- FIGO calls for strengthening of health information systems for reproductive, maternal, newborn, and child health services, co-designed with users, to ensure the timely accessibility of actionable high-quality data for all stakeholders engaged in preventing and managing preterm birth consequences. FIGO calls for strengthening of investments and capacity for implementing digital registries and the continuity of reproductive, maternal, newborn, and child health services in line with WHO recommendations, and strengthening of the science of implementation and use of registries-from local quality improvement to big data exploration.
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40. |
- Gadsbøll, Kasper, et al.
(författare)
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Current use of noninvasive prenatal testing in Europe, Australia and the USA: A graphical presentation.
- 2020
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Ingår i: Acta obstetricia et gynecologica Scandinavica. - : Wiley. - 1600-0412 .- 0001-6349. ; 99:6, s. 722-730
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Tidskriftsartikel (refereegranskat)abstract
- Noninvasive prenatal testing (NIPT), using cell-free fetal DNA, has increasingly been adopted as a screening tool for fetal aneuploidies. Several studies have discussed benefits and limitations of NIPT compared to both ultrasound and invasive procedures, but in spite of some shortcomings NIPT has become extensively used within the last five years. This study aims to describe the current use of NIPT in Europe, Australia and the USA.We conducted a survey to describe the current use of NIPT. Colleagues filled in a simple email-based questionnaire on NIPT in their own country, providing information on: 1) Access to NIPT, 2) NIPT's chromosomal coverage, 3) financial coverage of NIPT for the patient and 4) the proportion of women using NIPT in pregnancy. Some data are best clinical estimates, due to a lack of national data.In Europe, 14 countries have adopted NIPT into a national policy/program. Two countries (Belgium and the Netherlands) offer NIPT for all pregnant women, whereas most other European countries have implemented NIPT as an offer for higher risk women after first trimester screening. In Australia, either Combined First Trimester Screening (cFTS) or NIPT are used as primary prenatal screening tests. In the USA, there are no national consensus policies on the use of NIPT, however, NIPT is widely implemented. In most European countries offering NIPT, the proportion of women using NIPT is well below 25%. In the Netherlands, Austria, Italy, Spain and most Australian and American States, 25-50% of women have NIPT performed and only in Belgium it is above 75%. In most countries NIPT reports on trisomy 13, 18 and 21, and often also on sex chromosome aneuploidies. Only in Belgium, the Netherlands, Lithuania, Greece, Cyprus and Italy is NIPT offered predominantly as a genome-wide test (including some microdeletions or a whole genome coverage).NIPT has been widely adopted throughout Europe, Australia and the USA, but only some countries/states have a national policy on the use of NIPT. The variation in NIPT utilization is considerable.
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41. |
- Gawel, Danuta, et al.
(författare)
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Clinical translation of genomic medicine : Stor potential när genomikdata kan implementeras i klinisk rutin.
- 2021
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Ingår i: Läkartidningen. - 1652-7518. ; 118
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Tidskriftsartikel (refereegranskat)abstract
- Recent technical developments and early clinical examples support that precision medicine has potential to provide novel diagnostic and therapeutic solutions for patients with complex diseases, who are not responding to existing therapies. Those solutions will require integration of genomic data with routine clinical, imaging, sensor, biobank and registry data. Moreover, user-friendly tools for informed decision support for both patients and clinicians will be needed. While this will entail huge technical, ethical, societal and regulatory challenges, it may contribute to transforming and improving health care towards becoming predictive, preventive, personalised and participatory (4P-medicine).
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42. |
- Gawel, Danuta, 1988-, et al.
(författare)
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Stor potential när genomikdatakan implementeras i klinisk rutin : [Clinical translation of genomic medicine]
- 2021
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Ingår i: Läkartidningen. - : Sveriges Läkarförbund. - 0023-7205 .- 1652-7518. ; 118
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Forskningsöversikt (refereegranskat)abstract
- Recent technical developments and early clinical examples support that precision medicine has potential to provide novel diagnostic and therapeutic solutions for patients with complex diseases, who are not responding to existing therapies. Those solutions will require integration of genomic data with routine clinical, imaging, sensor, biobank and registry data. Moreover, user-friendly tools for informed decision support for both patients and clinicians will be needed. While this will entail huge technical, ethical, societal and regulatory challenges, it may contribute to transforming and improving health care towards becoming predictive, preventive, personalised and participatory (4P-medicine).
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43. |
- Golubinskaya, Veronika, 1974, et al.
(författare)
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Expression of S100A Alarmins in Cord Blood Monocytes Is Highly Associated With Chorioamnionitis and Fetal Inflammation in Preterm Infants
- 2020
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Ingår i: Frontiers in Immunology. - : Frontiers Media SA. - 1664-3224. ; 11
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Tidskriftsartikel (refereegranskat)abstract
- Background: Preterm infants exposed to chorioamnionitis and with a fetal inflammatory response are at risk for neonatal morbidity and adverse outcome. Alarmins S100A8, S100A9, and S100A12 are expressed by myeloid cells and have been associated with inflammatory activation and monocyte modulation. Aim: To study S100A alarmin expression in cord blood monocytes from term healthy and preterm infants and relate results to clinical findings, inflammatory biomarkers and alarmin protein levels, as well as pathways identified by differentially regulated monocyte genes. Methods: Cord blood CD14+ monocytes were isolated from healthy term (n = 10) and preterm infants (<30 weeks gestational age, n = 33) by MACS technology. Monocyte RNA was sequenced and gene expression was analyzed by Principal Component Analysis and hierarchical clustering. Pathways were identified by Ingenuity Pathway Analysis. Inflammatory proteins were measured by Multiplex ELISA, and plasma S100A proteins by mass spectrometry. Histological chorioamnionitis (HCA) and fetal inflammatory response syndrome (FIRS) were diagnosed by placenta histological examination. Results: S100A8, S100A9, and S100A12 gene expression was significantly increased and with a wider range in preterm vs. term infants. High S100A8 and S100A9 gene expression (n = 17) within the preterm group was strongly associated with spontaneous onset of delivery, HCA, FIRS and elevated inflammatory proteins in cord blood, while low expression (n = 16) was associated with impaired fetal growth and physician-initiated delivery. S100A8 and S100A9 protein levels were significantly lower in preterm vs. term infants, but within the preterm group high S100A gene expression, spontaneous onset of labor, HCA and FIRS were associated with elevated protein levels. One thousand nine hundred genes were differentially expressed in preterm infants with high vs. low S100A alarmin expression. Analysis of 124 genes differentially expressed in S100A high as well as FIRS and HCA groups identified 18 common pathways and S100A alarmins represented major hubs in network analyses. Conclusion: High expression of S100A alarmins in cord blood monocytes identifies a distinct clinical risk group of preterm infants exposed to chorioamnionitis and with a fetal inflammatory response. Gene and pathway analyses suggest that high S100A alarmin expression also affects monocyte function. The connection with monocyte phenotype and inflammation-stimulated S100A expression in other cell types (e.g., neutrophils) warrants further investigation.
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44. |
- Gravett, Michael G, et al.
(författare)
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Assessment of current biomarkers and interventions to identify and treat women at risk of preterm birth.
- 2024
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Ingår i: Frontiers in medicine. - 2296-858X. ; 11
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Forskningsöversikt (refereegranskat)abstract
- Preterm birth remains an important global problem, and an important contributor to under-5 mortality. Reducing spontaneous preterm birth rates at the global level will require the early identification of patients at risk of preterm delivery in order to allow the initiation of appropriate prophylactic management strategies. Ideally these strategies target the underlying pathophysiologic causes of preterm labor. Prevention, however, becomes problematic as the causes of preterm birth are multifactorial and vary by gestational age, ethnicity, and social context. Unfortunately, current screening and diagnostic tests are non-specific, with only moderate clinical risk prediction, relying on the detection of downstream markers of the common end-stage pathway rather than identifying upstream pathway-specific pathophysiology that would help the provider initiate targeted interventions. As a result, the available management options (including cervical cerclage and vaginal progesterone) are used empirically with, at best, ambiguous results in clinical trials. Furthermore, the available screening tests have only modest clinical risk prediction, and fail to identify most patients who will have a preterm birth. Clearly defining preterm birth phenotypes and the biologic pathways leading to preterm birth is key to providing targeted, biomolecular pathway-specific interventions, ideally initiated in early pregnancy Pathway specific biomarker discovery, together with management strategies based on early, mid-, and-late trimester specific markers is integral to this process, which must be addressed in a systematic way through rigorously planned biomarker trials.
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45. |
- Grobman, William A, et al.
(författare)
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FIGO good practice recommendations on the use of pessary for reducing the frequency and improving outcomes of preterm birth.
- 2021
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Ingår i: International journal of gynaecology and obstetrics: the official organ of the International Federation of Gynaecology and Obstetrics. - : Wiley. - 1879-3479. ; 155:1, s. 23-25
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Forskningsöversikt (refereegranskat)abstract
- A pessary is a device made of synthetic material that is placed in the vagina and has been used for prevention of preterm birth. It has been suggested that a potential mechanism of the pessary is alteration of the cervico-uterine angle to a more posterior position, which reduces cervical compression in women with a singleton pregnancy and a short cervical length. Pessaries should not be used in routine clinical care to reduce the frequency of preterm birth or to improve outcomes (e.g. neonatal outcomes) related to preterm birth. In women with a twin pregnancy-regardless of cervical length-pessaries should not be used in routine clinical care to reduce the frequency of preterm birth or to improve outcomes (e.g. neonatal outcomes) related to preterm birth. Presently there is no sufficient evidence suggesting that pessaries should be used as a standard treatment to prevent preterm birth; their use should be reserved for study populations.
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46. |
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47. |
- Gustin, Klara, et al.
(författare)
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Assessment of Joint Impact of Iodine, Selenium, and Zinc Status on Women's Third-Trimester Plasma Thyroid Hormone Concentrations
- 2022
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Ingår i: Journal of Nutrition. - : Elsevier BV. - 1541-6100 .- 0022-3166. ; 152:7, s. 1737 -1746
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Tidskriftsartikel (refereegranskat)abstract
- Background Iodine is essential for synthesizing thyroid hormones, but other micronutrients are also required for optimal thyroid function. However, there is a lack of data on combined micronutrient status in relation to thyroid hormones in pregnancy. Objectives We aimed to assess the joint associations of iodine, selenium, and zinc status with plasma concentrations of thyroid hormones and thyroid-stimulating hormone (TSH) in pregnancy. Methods We included 531 pregnant women (aged 22-40 y) participating in a Swedish birth cohort who provided blood and spot urine samples in gestational weeks 27-33 (mean: 29). Associations of urinary iodine concentration (UIC), plasma selenium concentration, and plasma zinc concentration (measured by inductively coupled plasma mass spectrometry) with plasma hormone concentrations [total and free thyroxine (tT4, fT4), total and free triiodothyronine (tT3, fT3), and TSH] were explored with Bayesian kernel machine regression (BKMR; n = 516; outliers excluded) and multivariable-adjusted linear regression (n = 531; splined for nonlinear associations). Results Median (IQR) micronutrient concentrations were 112 mu g/L (80-156 mu g/L) for UIC, 67 mu g/L (58-76 mu g/L) for plasma selenium, and 973 mu g/L (842-1127 mu g/L) for plasma zinc; the former 2 median values were below recommended concentrations (150 mu g/L and 70 mu g/L, respectively). Mean +/- SD TSH concentration was 1.7 +/- 0.87 mIU/L, with 98% < 4 mIU/L. BKMR showed a positive trend of joint micronutrient concentrations in relation to TSH. Plasma zinc was most influential for all hormones but tT3, for which plasma selenium was most influential. In adjusted linear regression models, zinc was positively associated with tT4, tT3, and TSH, and <1200 mu g/L also with fT4 and fT3. Selenium was inversely associated with fT3, and Conclusions Pregnant women's plasma TSH concentrations in the early third trimester increased with increasing joint status of iodine, selenium, and zinc. Zinc and selenium were more influential than iodine for the hormone concentrations. Multiple micronutrients need consideration in future studies of thyroid hormone status.
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48. |
- Gustin, Klara, et al.
(författare)
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Low-level maternal exposure to cadmium, lead, and mercury and birth outcomes in a Swedish prospective birth-cohort
- 2020
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Ingår i: Environmental Pollution. - : Elsevier BV. - 0269-7491 .- 1873-6424. ; 265
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Tidskriftsartikel (refereegranskat)abstract
- Observational studies have indicated that low-to-moderate exposure to cadmium (Cd), lead (Pb), and mercury (Hg) adversely affects birth anthropometry, but results are inconclusive. The aim of this study was to elucidate potential impact on birth anthropometry of exposure to Cd, Pb, and Hg in pregnant women, and to identify the main dietary sources. In the NICE (Nutritional impact on Immunological maturation during Childhood in relation to the Environment) birth-cohort in northern Sweden, blood and urine were collected from pregnant women in early third trimester. Cd, Pb and Hg were measured in erythrocytes (n = 584), and Cd also in urine (n = 581), by inductively coupled plasma mass spectrometry. Dietary data were collected through a semi-quantitative food frequency questionnaire administered in mid-third trimester. Birth anthropometry data were extracted from hospital records. In multivariable-adjusted spline regression models, a doubling of maternal erythrocyte Cd (median: 0.29 μg/kg) above the spline knot of 0.50 μg/kg was associated with reduced birth weight (B: −191 g; 95% CI: −315, −68) and length (−0.67 cm; −1.2, −0.14). The association with birth weight remained when the analysis was restricted to never-smokers. Likewise, a doubling of erythrocyte Hg (median 1.5 μg/kg, mainly MeHg) above 1.0 μg/kg, was associated with decreased birth weight (−59 g; −115, −3.0), and length (−0.29 cm; −0.54, −0.047). Maternal Pb (median 11 μg/kg) was unrelated to birth weight and length. Erythrocyte Cd was primarily associated with intake of plant derived foods, Pb with game meat, tea and coffee, and Hg with fish. The results indicated that low-level maternal Cd and Hg exposure were associated with poorer birth anthropometry. Further prospective studies in low-level exposed populations are warranted.
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49. |
- Gustin, Klara, et al.
(författare)
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Mediation by Thyroid Hormone in the Relationships Between Gestational Exposure to Methylmercury and Birth Size
- 2024
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Ingår i: Exposure and Health. - : Springer. - 2451-9685 .- 2451-9766. ; 16:2, s. 357-368
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Tidskriftsartikel (refereegranskat)abstract
- Our previous studies have linked gestational methylmercury exposure, originating from seafood, to changes in maternal thyroid hormones and infant birth size in a Swedish birth cohort. Herein we aimed to determine associations between maternal thyroid hormones and infant birth size and elucidate if maternal hormones could mediate the relationship between methylmercury and lower birth size. In 515 women, without known thyroid disease, we assessed metal exposure by erythrocyte mercury concentrations (mainly methylmercury, reflecting exposure over the past months) in early third trimester measured with inductively coupled plasma-mass spectrometry. Plasma concentrations of total and free thyroxine (tT4 and fT4) and triiodothyronine (tT3 and fT3), and thyroid-stimulating hormone (TSH) were measured at an accredited clinical laboratory. In multivariable-adjusted linear regression models, maternal tT3 (per 1 nmol/L increase) was positively associated with birth weight (B: 125 g; 95% CI 36, 214) and length (B: 0.59 cm; 95% CI 0.21, 0.97). Maternal fT4 was inversely associated with birth weight (B: − 33 g; 95% CI − 57, − 9.5), driven by obese women (n = 76). Causal mediation analyses suggested that a doubling of erythrocyte mercury (> 1 µg/kg; n = 374) was associated with a mean tT3-mediated decrease in birth weight of 11 g (95% CI − 25, − 1.6) and in birth length of 0.1 cm (95% CI − 0.12, − 0.01), both equivalent to about 12% of the total effect. To conclude, tT3 was positively associated with infant birth size. Reduced tT3 levels appeared to mediate a minor part of the inverse association between methylmercury exposure and birth size.
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50. |
- Gustin, Klara, et al.
(författare)
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Thyroid hormones in relation to toxic metal exposure in pregnancy, and potential interactions with iodine and selenium
- 2021
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Ingår i: Environment International. - : Elsevier BV. - 0160-4120 .- 1873-6750. ; 157
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Tidskriftsartikel (refereegranskat)abstract
- Background: Several endocrine-disrupting metals may affect thyroid function, but the few available studies of exposure during pregnancy and thyroid hormones are inconclusive. Objective: To explore if environmental exposure to cadmium (Cd), lead (Pb), and methylmercury (MeHg) impacts thyroid function in pregnancy, and interacts with iodine and selenium status. Methods: Women in a Swedish birth cohort provided blood and urine samples in early third trimester. Concentrations of erythrocyte Cd, Pb, and Hg (n = 544), urinary Cd and iodine (n = 542) and plasma selenium (n = 548) were measured using inductively coupled plasma-mass spectrometry. Free and total thyroxine (fT4, tT4) and triiodothyronine (fT3, tT3), and thyroid stimulating hormone (TSH), were measured in plasma (n = 548) with electrochemiluminescence immunoassays. Metal-hormone associations were assessed in regression models, and metal mixture effects and metal-nutrient interactions were explored in Bayesian kernel machine regression (BKMR). Results: In multivariable-adjusted regression models, a doubling of urinary Cd was associated with a mean increase in tT4 of 2.7 nmol/L (95% CI: 0.78, 4.6), and in fT3 and tT3 of 0.06 pmol/L (0.02, 0.10) and 0.09 nmol/L (0.05, 0.13), respectively. A doubling of urinary Cd was associated with a −0.002 (−0.003, −0.001) and −0.03 (−0.05, −0.02) decrease in the fT4:tT4 and fT3:tT3 ratio, respectively. A doubling of erythrocyte Hg (>1 µg/kg) was associated with a decrease in fT3 and tT3 by −0.11 pmol/L (−0.16, −0.05) and −0.11 nmol/L (−0.16, −0.06), respectively, and a −0.013 (−0.02, −0.01) decrease in the fT3:fT4 ratio. BKMR did not indicate any mixture effect of toxic metals or interactions between metals and iodine or selenium in relation to the hormones. Conclusion: Our findings suggest that exposure to Cd and Hg, at levels globally prevalent through the diet, may affect thyroid function during pregnancy, independently of iodine and selenium levels. Further studies on potential implications for maternal and child health are warranted.
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