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  • Frey, Sharon, et al. (author)
  • Interference of antibody production to hepatitis B surface antigen in a combination hepatitis A/hepatitis B vaccine
  • 1999
  • In: Journal of Infectious Diseases. - : Oxford University Press (OUP). - 0022-1899 .- 1537-6613. ; 180:6, s. 2018-2022
  • Journal article (peer-reviewed)abstract
    • A randomized trial comparing 3 manufacturing consistency lots of a combination hepatitis A/hepatitis B vaccine to each other and to hepatitis A vaccine and hepatitis B vaccine given separately and concurrently was done to evaluate safety, tolerability, and immunogenicity. Healthy volunteers >/=11 years of age were divided into 4 groups. Each of 3 groups received a separate consistency lot of the combination vaccine, and 1 group received separate but concurrent injections of hepatitis A and hepatitis B vaccines. Injections were given at weeks 0 and 24. The combination vaccine was generally well tolerated. The hepatitis A portion of the combination vaccine produced clinically acceptable high seropositivity rates 4 and 52 weeks after the first injection. The hepatitis B portion of the vaccine did not produce clinically acceptable seropositivity rates 4 weeks after the second injection. Lack of antibody production may be attributed, at least in part, to immunologic interference.
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  • Wannheden, C., et al. (author)
  • Digital Health Technologies Enabling Partnerships in Chronic Care Management : Scoping Review
  • 2022
  • In: Journal of Medical Internet Research. - : JMIR Publications Inc.. - 1438-8871. ; 24:8
  • Journal article (peer-reviewed)abstract
    • Background: An increasing number of patients expect and want to play a greater role in their treatment and care decisions. This emphasizes the need to adopt collaborative health care practices, which implies collaboration among interprofessional health care teams and patients, their families, caregivers, and communities. In recent years, digital health technologies that support self-care and collaboration between the community and health care providers (ie, participatory health technologies) have received increasing attention. However, knowledge regarding the features of such technologies that support effective patient-professional partnerships is still limited. Objective: This study aimed to map and assess published studies on participatory health technologies intended to support partnerships among patients, caregivers, and health care professionals in chronic care, focusing specifically on identifying the main features of these technologies. Methods: A scoping review covering scientific publications in English between January 2008 and December 2020 was performed. We searched PubMed and Web of Science databases. Peer-reviewed qualitative, quantitative, and mixed methods studies that evaluated digital health technologies for patient-professional partnerships in chronic care settings were included. The data were charted and analyzed thematically. The PRISMA-ScR (Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews) checklist was used. Results: This review included 32 studies, reported in 34 papers. The topic of participatory health technologies experienced a slightly increasing trend across publication years, with most papers originating from the United States and Norway. Diabetes and cardiovascular diseases were the most common conditions addressed. Of the 32 studies, 12 (38%) evaluated the influence of participatory health technologies on partnerships, mostly with positive outcomes, although we also identified how partnership relationships and the nature of collaborative work could be challenged when the roles and expectations between users were unclear. Six common features of participatory health technologies were identified: patient-professional communication, self-monitoring, tailored self-care support, self-care education, care planning, and community forums for peer-to-peer interactions. Conclusions: Our findings emphasize the importance of clarifying mutual expectations and carefully considering the implications that the introduction of participatory health technologies may have on the work of patients and health care professionals, both individually and in collaboration. A knowledge gap remains regarding the use of participatory health technologies to effectively support patient-professional partnerships in chronic care management.
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  • Magnus, M. C., et al. (author)
  • Maternal Risk of Cardiovascular Disease After Use of Assisted Reproductive Technologies
  • 2023
  • In: Jama Cardiology. - 2380-6583 .- 2380-6591. ; 8:9, s. 837-845
  • Journal article (peer-reviewed)abstract
    • IMPORTANCE Studies examining the associations of different combinations of intensity-specific aerobic and muscle strengthening activity (MSA) with all-cause and cause-specific mortality are scarce; the few available estimates are disparate.OBJECTIVE To examine the prospective associations of different combinations of moderate aerobic physical activity (MPA), vigorous aerobic physical activity (VPA), and MSA with all-cause, cardiovascular (CVD), and cancer mortality.DESIGN, SETTING, AND PARTICIPANTS This nationwide prospective cohort study used data from the US National Health Interview Survey. A total of 500705 eligible US adults were included in the study and followed up during a median of 10.0 years (5.6 million person-years) from 1997 to 2018. Data were analyzed from September 1 to September 30, 2022. EXPOSURES Self-reported cumulative bouts (75 weekly minutes) of MPA and VPA with recommended MSA guidelines (yes or no) to obtain 48 mutually exclusive exposure categories.MAIN OUTCOMES AND MEASURES All-cause, CVD, and cancer mortality. Participants were linked to the National Death Index through December 31, 2019.RESULTS Overall, 500 705 participants (mean [SD] age, 46.4 [17.3] years; 210 803 [58%] female; 277 504 [77%] White) were included in the study. Compared with the reference group (doing no MPA or VPA and less than recommended MSA), the category associated with the lowest hazard ratio (HR) for all-cause mortality was more than 0 to 75 minutes of MPA combined with more than 150 minutes of VPA and 2 or more MSA sessions per week (HR, 0.50; 95% CI, 0.42-0.59). The optimal combinations for CVD and cancer mortality risk reduction were more than 150 to 225 minutes of MPA, more than 0 to 75 minutes of VPA, and 2 or more MSA sessions per week (HR, 0.30; 95% CI, 0.15-0.57), and more than 300 minutes of MPA, more than 0 to 75 minutes of VPA, and 2 or more MSA sessions per week (HR, 0.44; 95% CI, 0.23-0.82), respectively. Adjusted mortality rates represented an approximately 50% lower mortality rate for all-cause and cancer mortality and an approximately 3-fold lower mortality rate for CVD mortality. CONCLUSIONS AND RELEVANCE This cohort study demonstrated that balanced levels of MPA, VPA, and MSA combined may be associated with optimal reductions of mortality risk. Higher-than-recommended levels of MPA and VPA may further lower the risk of cancer and all-cause mortality, respectively.
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  • Terho, A M, et al. (author)
  • High birth weight and large-for-gestational-age in singletons born after frozen compared to fresh embryo transfer, by gestational week: a Nordic register study from the CoNARTaS group.
  • 2021
  • In: Human reproduction (Oxford, England). - : Oxford University Press (OUP). - 1460-2350 .- 0268-1161. ; 36:4, s. 1083-1092
  • Journal article (peer-reviewed)abstract
    • When do the differences in birth weights become apparent between singletons born after frozen embryo transfer (FET) and fresh embryo transfer (fresh ET)?Mean birth weights after FET become significantly higher starting from gestational week (GW) 33 among boys and from GW 34 among girls.In recent years, there has been a steep rise in recorded FET treatments, enabling widespread use of elective single embryo transfer, thus reducing the risks associated with multiple gestations. However, singletons born after FET are heavier and there is a higher risk of large-for-gestational-age (LGA) (birth weight > 90 percentiles) compared to fresh ET. In contrast, risk of small-for-gestational-age (SGA, birth weight < 10 percentiles) is lower in singletons born after FET compared to fresh ET. The reasons, timing and consequences of these differences remain largely unclear. There is limited evidence about whether this difference in growth develops before the last trimester of pregnancy.This retrospective Nordic register-based cohort study compared singletons born after FET (n=17500) to singletons born after fresh ET (n=69510) and natural conception (NC, n=3311588). All live born singletons born between the years 2000 and 2015 in Denmark, Norway and Sweden at gestational age ≥22weeks were included from the population-based Committee of Nordic ART and Safety (CoNARTaS) study population.Children born after FET were compared to those born after fresh ET and NC for mean birth weight and proportion of LGA and SGA for each GW at birth. Chi-square test and tests for relative proportions were used to compare categorical variables and Student's t-test was used to compare continuous variables. Adjusted odds ratios (aORs) for LGA and SGA were calculated using logistic regressions, adjusting for year of birth, maternal age, parity, BMI, chronic hypertension, diabetes, smoking and offspring sex.Mean birth weights were significantly higher after FET compared to fresh ET starting from GW 33 (range from 75g to 228g by week) for boys and starting from GW 34 (range from 90g to 236g by week) for girls. Boys born after FET had a significantly higher proportion of LGA (11.0-15.1%) at birth between GW 36 and 42, compared to those born after fresh ET (7.1-9.4%) (range from P<0.001 to P=0.048 by week). For girls born after FET, the difference was seen between GW 37 and 42 (10.6-13.4%) compared to those born after fresh ET (6.6-8.0%) (range from P<0.001 to P=0.009 by week).The proportion of SGA was significantly lower among boys born after FET (7.6-8.7%) compared to fresh ET (11.9-13.6%) between GW 36 and 42 (range from P<0.001 to P=0.016 by week). For girls born after FET, the difference was seen between GW 38 and 42 (7.0-9.3%) compared to those born after fresh ET (13.0-14.6%) (P<0.001). The proportion of LGA (12.3-15.1%) was significantly higher for boys born after FET between GW 38 and 41 (P<0.001) and for girls born after FET (12.6-13.4%) between GW 37 and 40 (range from P<0.001 to P=0.018 by week), compared to naturally conceived boys (9.7-9.9%) and girls (9.0-10.0%). All singletons born after FET had a higher risk of LGA compared to singletons born after fresh ET (aOR 1.87, 95% CI 1.76-1.98) and singletons born after NC (aOR 1.28, 95% CI 1.22-1.35).There may be residual confounding factors that we were not able to control for, most importantly the causes of preterm birth, which may also influence foetal growth. A further limitation is that we have no knowledge on growth patterns between implantation and GW 22. Finally, the number of children born extremely preterm or post-term was limited even in this large study population.This is, to date, the largest study on birth weights among preterm and term ART singletons with a population-based design and NC control group. The results suggest that the freeze-thaw process is associated with higher birthweights and greater risk of LGA at least in the last trimester of pregnancy. This is an important aspect of the safety profile of ART. More research is needed on the long-term outcome of these children.The CoNARTaS collaboration has received the following funding: the Nordic Trial Alliance: a pilot project jointly funded by the Nordic Council of Ministers and NordForsk [71450], the Central Norway Regional Health Authorities [46045000], the Norwegian Cancer Society [182356-2016], the Nordic Federation of Obstetrics and Gynaecology [NF13041, NF15058, NF16026 and NF17043], the Interreg Öresund-Kattegat-Skagerrak European Regional Development Fund (ReproUnion project) and the Research Council of Norway's Centre of Excellence funding scheme [262700]. None of the authors have any competing interests to declare.ISRCTN11780826.
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  • Wennerholm, U. B., et al. (author)
  • Induction of labour at 41 weeks versus expectant management and induction of labour at 42 weeks (SWEdish Post-term Induction Study, SWEPIS) : multicentre, open label, randomised, superiority trial
  • 2020
  • In: Geburtshilfe und Frauenheilkunde. - : Georg Thieme Verlag KG. - 0016-5751 .- 1438-8804. ; 80:10, s. E76-E76
  • Journal article (other academic/artistic)abstract
    • Objective: To evaluate if induction of labour at 41 weeks improves perinatal and maternal outcomes in women with low risk pregnancies compared with expectant management and induction at 42 weeks.Methods: A multicenter, randomised controlled superiority trial.Women with low risk singleton pregnanies (n = 2760) were randomised to either induction or expectant management group. The primary outcome was a composite perinatal outcome including one or more of stillbirth, neonatal mortality, Apgar score < 7 at five minutes, pH < 7.00 or metabolic acidosis (pH < 7.05 and base deficit >12 mmol/L) in the umbilical artery, hypoxic ischaemic encephalopathy, intracranial haemorrhage, convulsions, meconium aspiration syndrome, mechanical ventilation within 72 hours, obstetric brachial plexus injury. Primary analysis was by intention to treat.Results: The study was stopped early owing to a significantly higher rate of perinatal mortality in the expectant management group (no deaths compared to six deaths, p = 0.03). The primary outcome did not differ: 2.4 % (33/1381) in the induction group and 2.2 % (31/1379) in the expectant management group (RR 1.06, 95 %CI 0.65 to 1.73; p = 0.90). The proportion of caesarean delivery, instrumental vaginal delivery, or any major maternal morbidity did not differ between the groups.Conclusions: There was no significant difference in the primary composite outcome when comparing induction at 41 weeks with expectant management and induction at 42. However, a reduction of the secondary outcome perinatal mortality was observed without increasing adverse maternal outcomes. To offer induction at 41 weeks could be one of few interventions that reduces the rate of stillbirths.
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  • Wennerholm, Ulla-Britt, 1948, et al. (author)
  • Paternal sperm concentration and growth and cognitive development in children born with a gestational age more than 32 weeks after assisted reproductive therapy
  • 2006
  • In: Hum Reprod. ; 21:6, s. 1514-20
  • Journal article (peer-reviewed)abstract
    • BACKGROUND: A possible impact of paternal sperm quality on the outcome in children born after assisted reproductive technologies, especially ICSI, has been discussed. The objective of this study was to assess whether sperm concentration has any influence on growth and cognitive development in children born with a gestational age more than 32 weeks after ICSI or IVF. METHODS: Singleton children born after ICSI (n = 492) or IVF (n = 265) from five European countries were examined at age 5 years. The ICSI group was divided into five subgroups according to paternal sperm origin and sperm concentration: (1) epididymal and testicular sperm group, (2) ejaculated sperm < 1 x 10(6)/ml, (3) ejaculated sperm 1-4.99 x 10(6)/ml, (4) ejaculated sperm 5-19.99 x 10(6)/ml and (5) ejaculated sperm > or = 20 x 10(6)/ml. The IVF group was divided into two subgroups: (1) < 20 x 10(6)/ml and (2) > or = 20 x 10(6)/ml. Growth parameters at birth and age 5 were evaluated. Cognitive development was assessed with the Wechsler Preschool and Primary Scale of Intelligence-Revised. RESULTS: No significant difference was found for gestational age, birth weight and birth weight standard deviation scores (SDS) between the ICSI and IVF sperm groups. No significant difference in height and weight at age 5 or SDS weight or height or BMIs at age 5 was found. There was no significant difference in total intelligence quotient (IQ)--performance or verbal IQ--between the groups. CONCLUSION: We found no indication that growth and cognitive development in ICSI and IVF children differed depending on paternal sperm concentration.
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  • Wiberg-Itzel, E, et al. (author)
  • Determination of pH or lactate in fetal scalp blood in management of intrapartum fetal distress: randomised controlled multicentre trial
  • 2008
  • In: BMJ (International Edition). - : BMJ. - 0959-8146 .- 0959-8138 .- 1756-1833. ; 63:11, s. 687-689
  • Journal article (peer-reviewed)abstract
    • Objective To examine the effectiveness of pH analysis of fetal scalp blood compared with lactate analysis in identifying hypoxia in labour to prevent acidaemia at birth. Design Randomised controlled multicentre trial. Setting Labour wards. Participants Women with a singleton pregnancy, cephalic presentation, gestational age >= 34 weeks, and clinical indication for fetal scalp blood sampling. Interventions Standard pH analysis (n=1496) or lactate analysis (n=1496) with an electrochemical microvolume (5 mu l) test strip device. The cut-off levels for intervention were pH < 7.21 and lactate > 4.8 mmol/l, respectively. Main outcome measure Metabolic acidaemia (pH < 7.05 and base deficit > 12 mmol/l) or pH < 7.00 in cord artery blood. Results Metabolic acidaemia occurred in 3.2% in the lactate group and in 3.6% in the pH group (relative risk 0.91, 95% confidence interval 0.61 to 1.36). pH <7.00 occurred in 1.5% in the lactate group and in 1.8% in the pH group (0.84, 0.47 to 1.50). There was no significant difference in Apgar scores < 7 at 5 minutes (1.15, 0.76 to 1.75) or operative deliveries for fetal distress (1.02, 0.93 to 1.11). Conclusion There were no significant differences in rate of acidaemia at birth after use of lactate analysis or pH analysis of fetal scalp blood samples to determine hypoxia during labour.
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  • Alkmark, Mårten, 1973, et al. (author)
  • Induction of labour at 41 weeks or expectant management until 42 weeks: A systematic review and an individual participant data meta-analysis of randomised trials.
  • 2020
  • In: PLoS medicine. - : Public Library of Science (PLoS). - 1549-1676 .- 1549-1277. ; 17:12
  • Journal article (peer-reviewed)abstract
    • The risk of perinatal death and severe neonatal morbidity increases gradually after 41 weeks of pregnancy. Several randomised controlled trials (RCTs) have assessed if induction of labour (IOL) in uncomplicated pregnancies at 41 weeks will improve perinatal outcomes. We performed an individual participant data meta-analysis (IPD-MA) on this subject.We searched PubMed, Excerpta Medica dataBASE (Embase), The Cochrane Library, Cumulative Index of Nursing and Allied Health Literature (CINAHL), and PsycINFO on February 21, 2020 for RCTs comparing IOL at 41 weeks with expectant management until 42 weeks in women with uncomplicated pregnancies. Individual participant data (IPD) were sought from eligible RCTs. Primary outcome was a composite of severe adverse perinatal outcomes: mortality and severe neonatal morbidity. Additional outcomes included neonatal admission, mode of delivery, perineal lacerations, and postpartum haemorrhage. Prespecified subgroup analyses were conducted for parity (nulliparous/multiparous), maternal age (<35/≥35 years), and body mass index (BMI) (<30/≥30). Aggregate data meta-analysis (MA) was performed to include data from RCTs for which IPD was not available. From 89 full-text articles, we identified three eligible RCTs (n = 5,161), and two contributed with IPD (n = 4,561). Baseline characteristics were similar between the groups regarding age, parity, BMI, and higher level of education. IOL resulted overall in a decrease of severe adverse perinatal outcome (0.4% [10/2,281] versus 1.0% [23/2,280]; relative risk [RR] 0.43 [95% confidence interval [CI] 0.21 to 0.91], p-value 0.027, risk difference [RD] -57/10,000 [95% CI -106/10,000 to -8/10,000], I2 0%). The number needed to treat (NNT) was 175 (95% CI 94 to 1,267). Perinatal deaths occurred in one (<0.1%) versus eight (0.4%) pregnancies (Peto odds ratio [OR] 0.21 [95% CI 0.06 to 0.78], p-value 0.019, RD -31/10,000, [95% CI -56/10,000 to -5/10,000], I2 0%, NNT 326, [95% CI 177 to 2,014]) and admission to a neonatal care unit ≥4 days occurred in 1.1% (24/2,280) versus 1.9% (46/2,273), (RR 0.52 [95% CI 0.32 to 0.85], p-value 0.009, RD -97/10,000 [95% CI -169/10,000 to -26/10,000], I2 0%, NNT 103 [95% CI 59 to 385]). There was no difference in the rate of cesarean delivery (10.5% versus 10.7%; RR 0.98, [95% CI 0.83 to 1.16], p-value 0.81) nor in other important perinatal, delivery, and maternal outcomes. MA on aggregate data showed similar results. Prespecified subgroup analyses for the primary outcome showed a significant difference in the treatment effect (p = 0.01 for interaction) for parity, but not for maternal age or BMI. The risk of severe adverse perinatal outcome was decreased for nulliparous women in the IOL group (0.3% [4/1,219] versus 1.6% [20/1,264]; RR 0.20 [95% CI 0.07 to 0.60], p-value 0.004, RD -127/10,000, [95% CI -204/10,000 to -50/10,000], I2 0%, NNT 79 [95% CI 49 to 201]) but not for multiparous women (0.6% [6/1,219] versus 0.3% [3/1,264]; RR 1.59 [95% CI 0.15 to 17.30], p-value 0.35, RD 27/10,000, [95% CI -29/10,000 to 84/10,000], I2 55%). A limitation of this IPD-MA was the risk of overestimation of the effect on perinatal mortality due to early stopping of the largest included trial for safety reasons after the advice of the Data and Safety Monitoring Board. Furthermore, only two RCTs were eligible for the IPD-MA; thus, the possibility to assess severe adverse neonatal outcomes with few events was limited.In this study, we found that, overall, IOL at 41 weeks improved perinatal outcome compared with expectant management until 42 weeks without increasing the cesarean delivery rate. This benefit is shown only in nulliparous women, whereas for multiparous women, the incidence of mortality and morbidity was too low to demonstrate any effect. The magnitude of risk reduction of perinatal mortality remains uncertain. Women with pregnancies approaching 41 weeks should be informed on the risk differences according to parity so that they are able to make an informed choice for IOL at 41 weeks or expectant management until 42 weeks. Study Registration: PROSPERO CRD42020163174.
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  • Bonduelle, M, et al. (author)
  • A multi-centre cohort study of the physical health of 5-year-old children conceived after intracytoplasmic sperm injection, in vitro fertilization and natural conception
  • 2005
  • In: Hum Reprod. ; 20:2, s. 413-9
  • Journal article (peer-reviewed)abstract
    • BACKGROUND: Over a million children have been born from assisted conception worldwide. Newer techniques being introduced appear less and less 'natural', such as intracytoplasmic sperm injection (ICSI), but there is little information on these children beyond the neonatal period. METHODS: 540 ICSI conceived 5-year-old children from five European countries were comprehensively assessed, along with 538 matched naturally conceived children and 437 children conceived with standard IVF. RESULTS: Of the 540 ICSI children examined, 63 (4.2%) had experienced a major congenital malformation. Compared with naturally conceived children, the odds of a major malformation were 2.77 (95% CI 1.41-5.46) for ICSI children and 1.80 (95% CI 0.85-3.81) for IVF children; these estimates were little affected by adjustment for socio-demographic factors. The higher rate observed in the ICSI group was due partially to an excess of malformations in the (boys') urogenital system. In addition, ICSI and IVF children were more likely than naturally conceived children to have had a significant childhood illness, to have had a surgical operation, to require medical therapy and to be admitted to hospital. A detailed physical examination revealed no further substantial differences between the groups, however. CONCLUSIONS: Singleton ICSI and IVF 5-year-olds are more likely to need health care resources than naturally conceived children. Assessment of singleton ICSI and IVF children at 5 years of age was generally reassuring, however, we found that ICSI children presented with more major congenital malformations and both ICSI and IVF children were more likely to need health care resources than naturally conceived children. Ongoing monitoring of these children is therefore required.
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  • Bonduelle, M., et al. (author)
  • Medical follow-up study of 5-year-old ICSI children
  • 2004
  • In: Reprod Biomed Online. ; 9:1, s. 91-101
  • Journal article (peer-reviewed)abstract
    • Children born after intracytoplasmic sperm injection (ICSI) are still a matter of concern. The purposes of the present study were to investigate the physical outcome in 5-year-old children born after ICSI and compare them with children born after spontaneous conception. Three hundred singleton children from Belgium, Sweden and the USA, born after ICSI, were matched by maternal age, child age and gender. In one centre, matching was also performed for maternal education. The main end-point was growth. Secondary end-points were general health, e.g. common diseases, chronic illnesses, surgical interventions and physical/neurological examinations. Standard deviation scores assessed growth. Growth assessed as stature at follow-up was similar in the two groups, despite a higher rate of preterm birth and low birth weight in the ICSI children. Common diseases and chronic illnesses occurred at similar rates in both groups. More ICSI children underwent surgical interventions and required other therapy e. g. physiotherapy and dietary therapy. Physical/neurological examinations revealed few abnormalities in either group. In conclusion, infertility treatment by ICSI does not adversely affect growth during childhood. The children's general health seems satisfactory.
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  • Cobo, Teresa, et al. (author)
  • Intra-amniotic inflammation predicts microbial invasion of the amniotic cavity but not spontaneous preterm delivery in preterm prelabor membrane rupture.
  • 2012
  • In: Acta obstetricia et gynecologica Scandinavica. - : Wiley. - 1600-0412 .- 0001-6349.
  • Journal article (peer-reviewed)abstract
    • Objective. To predict microbial invasion of the amniotic cavity (MIAC) and spontaneous preterm delivery within seven days using a panel of selected proteins from amniotic fluid in a Swedish population of preterm prelabor membrane rupture (PPROM). Design. Prospective cohort study. Setting. Evaluation of intra-amniotic inflammation in preterm premature rupture of membranes. Population. Sixty-six pregnant women with preterm prelabor membrane rupture at 22(+0-) 33(+6) weeks' gestational age. Methods. Twenty-seven amniotic fluid proteins were assayed by a multiple immunoassay. Main outcome measures. The intra-amniotic inflammatory response was evaluated according to the presence of MIAC and the risk of spontaneous preterm delivery within seven days. A prediction model was constructed using logistic regression. Results. The overall rates of MIAC and spontaneous preterm delivery within seven days were 20% and 50%, respectively. There was a higher inflammatory response in women with MIAC than without. Earlier gestational age at delivery and lower birthweight were observed in the presence of microbial invasion of the amniotic cavity. Amniotic fluid Interleukin (IL)-6 and IL-10 were the best predictors of MIAC in terms of sensitivity (69%), specificity (81%), positive predictive value (47%), negative predictive value (91%) and positive likelihood ratio of 3.6. There were no differences in intra-amniotic inflammatory response according to the risk of spontaneous preterm delivery within seven days. Conclusion. Amniotic fluid IL-6 and IL-10 are the best inflammatory biomarkers to predict MIAC in women with PPROM. Intra-amniotic inflammation does not predict the occurrence of spontaneous preterm delivery within seven days of PPROM.
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  • Fadl, Helena, 1965-, et al. (author)
  • Changing diagnostic criteria for gestational diabetes in Sweden-a stepped wedge national cluster randomised controlled trial-the CDC4G study protocol
  • 2019
  • In: Bmc Pregnancy and Childbirth. - : Springer Science and Business Media LLC. - 1471-2393. ; 19:1
  • Journal article (peer-reviewed)abstract
    • Background The optimal criteria to diagnose gestational diabetes mellitus (GDM) remain contested. The Swedish National Board of Health introduced the 2013 WHO criteria in 2015 as a recommendation for initiation of treatment for hyperglycaemia during pregnancy. With variation in GDM screening and diagnostic practice across the country, it was agreed that the shift to new guidelines should be in a scientific and structured way. The aim of the Changing Diagnostic Criteria for Gestational Diabetes (CDC4G) in Sweden () is to evaluate the clinical and health economic impacts of changing diagnostic criteria for GDM in Sweden and to create a prospective cohort to compare the many long-term outcomes in mother and baby under the old and new diagnostic approaches. Methods This is a stepped wedge cluster randomised controlled trial, comparing pregnancy outcomes before and after the switch in GDM criteria across 11 centres in a randomised manner. The trial includes all pregnant women screened for GDM across the participating centres during January-December 2018, approximately two thirds of all pregnancies in Sweden in a year. Women with pre-existing diabetes will be excluded. Data will be collected through the national Swedish Pregnancy register and for follow up studies other health registers will be included. Discussion The stepped wedge RCT was chosen to be the best study design for evaluating the shift from old to new diagnostic criteria of GDM in Sweden. The national quality registers provide data on the whole pregnant population and gives a possibility for follow up studies of both mother and child. The health economic analysis from the study will give a solid evidence base for future changes in order to improve immediate pregnancy, as well as long term, outcomes for mother and child.
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  • Hagman, A., et al. (author)
  • Obstetric Outcomes in Women With Turner Karyotype EDITORIAL COMMENT
  • 2012
  • In: Obstetrical and Gynecological Survey. - 0029-7828. ; 67:4, s. 228-229
  • Journal article (other academic/artistic)abstract
    • There is concern over the high risk of cardiovascular complications, hypertensive disorders, and other adverse obstetric outcomes among pregnant women with Turner syndrome (TS). A diagnosis of TS is made in some women late in life or not at all. Spontaneous pregnancies are rare in women with TS and are associated with a high rate of complications, especially miscarriage. The use of assisted reproductive techniques is an option for these women; pregnancy and implantation rates after oocyte donation in women with TS seem to be comparable with those without TS who need this treatment. Few data are available on obstetric outcome in pregnant women with TS. The aim of this retrospective population-based cohort study was to compare maternal and neonatal outcomes among singleton pregnancies of women with and without TS. Data on births occurring between 1973 and 2007 from the Swedish Genetic Turner Register and the Swedish Medical Birth Register were cross-linked. Obstetric outcome in infants born to women with TS was compared with a reference group of 56,000 women from the general population. Mean gestational age and birth weight were adjusted for maternal age. Outcome in TS women with twins was described separately. A total of 115 women with TS gave birth to 208 children (202 singletons and 3 sets of twins) during the study period. The TS diagnosis was unknown in 52% of the women before the first delivery. Women in the TS group were older at the first delivery than women in the reference group; median age was 30 years and 26 years, respectively (P < 0.0001). There was a trend toward more women with TS having preeclampsia during their first pregnancy (6.3 vs. 3.0%; P = 0.07). One woman suffered from an aortic dissection during her second spontaneous pregnancy. Compared with the reference group, the median gestational age was shorter in children in the TS group (-6.4 days, P = 0.0067), and median birth weight was lower (-208 g, P = 0.001); however, no significant difference was found in median standard deviation scores for weight and length at birth. The rate of cesarean delivery was higher in the TS group than in the reference group (35.6% vs. 11.8%, respectively, P < 0.0001). There was no significant difference in birth defects between groups. These findings show that women with a TS karyotype have mostly favorable obstetric outcomes. Singletons of women with TS have a shorter gestational age but a similar size at birth. The data also show no difference in birth defects between women with and without TS.
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  • Henningsen, A. A., et al. (author)
  • Imprinting disorders in children born after ART: a Nordic study from the CoNARTaS group
  • 2020
  • In: Human Reproduction. - : Oxford University Press (OUP). - 0268-1161 .- 1460-2350. ; 35:5, s. 1178-1184
  • Journal article (peer-reviewed)abstract
    • STUDY QUESTION: Is the risk of imprinting disorders increased in children conceived after ART? SUMMARY ANSWER: We found an adjusted odds ratio (AOR) of 2.84 [95% CI: 1.34-6.01] for Beckwith-Wiedemann syndrome in ART children, while the risk of Prader-Willi syndrome, Silver-Russell syndrome or Angelman syndrome was not increased in children conceived after ART. WHAT IS KNOWN ALREADY: Earlier studies, most of them small, have suggested an association between ART and imprinting disorders. STUDY DESIGN, SIZE, DURATION: This was a binational register-based cohort study. All children conceived by ART in Denmark (n = 45 393, born between 1994 and 2014) and in Finland (n = 29 244, born between 1990 and 2014) were identified. The full background populations born during the same time periods in the two countries were included as controls. Odds ratios of imprinting disorders in ART children compared with naturally conceived (NC) children were calculated. The median follow-up time was 8 years and 9 months for ART children and 11 years and 9 months for NC children. PARTICIPANTS/MATERIALS, SETTING, METHODS: From the national health registries in Denmark and Finland, we identified all children diagnosed with Prader-Willi syndrome (n = 143), Silver-Russell syndrome (n = 69), Beckwith-Wiedemann syndrome (n = 105) and Angelman syndrome (n = 72) born between 1994/1990 and 2014, respectively. MAIN RESULTS AND THE ROLE OF CHANCE: We identified a total of 388 children diagnosed with imprinting disorders; 16 of these were conceived after ART. The overall AOR for the four imprinting disorders in ART children compared with NC children was 1.35 [95% CI: 0.80-2.29], but since eight ART children were diagnosed with Beckwith-Wiedemann syndrome, the AOR for this specific imprinting disorder was 2.84 [95% CI: 1.34-6.01]. The absolute risk of Beckwith-Wiedemann syndrome in children conceived after ART was still low: 10.7 out of 100 000 newborns. The risks of Prader-Willi syndrome, Silver-Russell syndrome and Angelman syndrome were not increased in children conceived after ART. LIMITATIONS, REASONS FOR CAUTION: Imprinting disorders are rare events and our results are based on few ART children with imprinting disorders. The aetiology is complex and only partly clarified, and the clinical diagnoses are challenged by a broad phenotypic spectrum. WIDER IMPLICATIONS OF THE FINDINGS: In the existing studies, results on the risk of imprinting disorders in children conceived after ART are ambiguous. This study adds that the risk of imprinting disorders in ART children is very small and perhaps restricted to Beckwith-Wiedemann syndrome.
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28.
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29.
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31.
  • Henningsen, A. K. A., et al. (author)
  • Risk of congenital malformations in live-born singletons conceived after intracytoplasmic sperm injection: a Nordic study from the CoNARTaS group
  • 2023
  • In: Fertility and Sterility. - 0015-0282 .- 1556-5653. ; 120:5, s. 1033-1041
  • Journal article (peer-reviewed)abstract
    • Objective: To investigate whether the risk of major congenital malformations is higher in live-born singletons conceived with intracytoplasmic sperm injection (ICSI) compared with in vitro fertilization (IVF)?Design: Nordic register-based cohort study.Setting: Cross-linked data from Medical Birth Registers and National ART and Patient Registers in Denmark, Norway and Sweden. Data were included from the year the first child conceived using ICSI was born: Sweden, 1992; Denmark, 1994; and Norway, 1996. Data were included until 2014 for Denmark and 2015 for Norway and Sweden. Patient(s): All live-born singletons conceived using fresh ICSI (n = 32,484); fresh IVF (n = 47,178); without medical assistance (n = 4,804,844); and cryo-ICSI (n = 7,200) during the study period. Intervention(s): Different in vitro conception methods, and cryopreservation of embryos.Main Outcome Measure(s): Risk of major congenital malformations on the basis of International Classification of Diseases codes. The European Concerted Action on Congenital Anomalies and Twins was used to differentiate between major and minor malformations. Result(s): Among singletons conceived using fresh ICSI, 6.0% had a major malformation, compared with 5.3% of children conceived using fresh IVF; 4.2% of children conceived without medical assistance; and 4.9% of children conceived using cryoICSI; adjusted odds ratio (AOR) 1.07 (95% confidence interval [CI] 1.01-1.14) in ICSI vs. IVF; and AOR 1.28 (95% CI, 1.23- 1.35) in ICSI vs. no medical assistance; and AOR 1.11 (95% CI, 0.99-1.26) in ICSI fresh vs. cryo-ICSI. When malformations were grouped by different organ systems, children conceived using ICSI had a higher risk of respiratory and chromosomal malformations compared with children conceived using IVF, but there were very few cases in each group. When categorizing children conceived using ICSI according to treatment indication (male factor infertility only vs. other indications), we found a higher risk of hypospadias when ICSI was performed because of male factor infertility only (AOR 1.85 [95% CI 1.03-332]). The indications for ICSI changed over time, as male factor infertility did not remain the primary indication for ICSI throughout the study period.Conclusion(s): In this large cohort study, we found the risk of major malformations in live-born singletons to be slightly higher after fresh ICSI compared with fresh IVF. These findings should be considered when choosing the assisted reproductive technology method for couples without male factor infertility. (Fertil Sterile 2023;120:1033-41. (c) 2023 by American Society for Reproductive Medicine.) El resumen esta disponible en Espanol al final del articulo.
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32.
  • Henningsen, A. K. A., et al. (author)
  • Trends over time in congenital malformations in live-born children conceived after assisted reproductive technology
  • 2018
  • In: Acta Obstetricia Et Gynecologica Scandinavica. - : Wiley. - 0001-6349 .- 1600-0412. ; 97:7, s. 816-823
  • Journal article (peer-reviewed)abstract
    • Children born after assisted reproductive technology, particularly singletons, have been shown to have an increased risk of congenital malformations compared with children born after spontaneous conception. We wished to study whether there has been a change in the past 20 years in the risk of major congenital malformations in children conceived after assisted reproductive technology compared with children spontaneously conceived. Material and methodsPopulation-based cohort study including 90 201 assisted reproductive technology children and 482 552 children spontaneously conceived, born in Denmark, Finland, Norway and Sweden. Both singletons and twins born after in vitro fertilization, intracytoplasmatic sperm injection and frozen embryo transfer were included. Data on children were taken from when the national Nordic assisted reproductive technology registries were established until 2007. Multiple logistic regression analyses were used to estimate the risks and adjusted odds ratios for congenital malformations in four time periods: 1988-1992, 1993-1997, 1998-2002 and 2003-2007. Only major malformations were included. ResultsThe absolute risk for singletons of being born with a major malformation was 3.4% among assisted reproductive technology children vs. 2.9% among children spontaneously conceived during the study period. The relative risk of being born with a major congenital malformation between all assisted reproductive technology children and children spontaneously conceived remained similar through all four time periods (p = 0.39). However, we found that over time the number of children diagnosed with a major malformation increased in both groups across all four time periods. ConclusionWhen comparing children conceived after assisted reproductive technology and spontaneously conceived, the relative risk of being born with a major congenital malformation did not change during the study period.
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34.
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35.
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36.
  • Johanzon, M., et al. (author)
  • Extreme preterm birth: onset of delivery and its effect on infant survival and morbidity
  • 2008
  • In: Obstetrics & Gynecology. - 0029-7844. ; 111:1, s. 42-50
  • Journal article (peer-reviewed)abstract
    • OBJECTIVE: To investigate whether correlations could be found between the onset of preterm delivery and infant outcome, that is, survival and major morbidity. METHODS: The study was a retrospective, hospital-based cohort study. All women with a live fetus on admission, giving birth at 22(+0) to 27(+6) weeks of gestation between 1998 and 2003 were included. The deliveries were subdivided into those that began with either preterm labor, preterm premature rupture of membranes (PROM), or iatrogenic preterm delivery. These groups were compared for survival and survival without major morbidity (intraventricular hemorrhage grade 3-4, periventricular leukomalacia, retinopathy of prematurity grade 3-4, bronchopulmonary dysplasia, or necrotizing enterocolitis) at discharge. RESULTS: The cause of the preterm birth was preterm labor in 154 of 288 (53%), preterm PROM 83 of 288 (29%), and iatrogenic preterm delivery 51 of 288 (18%). There were 83% liveborn children, and 67% survived until discharge. Survival was lower for preterm PROM (54%) than for preterm labor (75%) and iatrogenic preterm delivery (67%). Multivariable analyses showed that survival was positively associated with gestational age and antenatal steroid treatment. Negative associations concerning survival were found for preterm PROM and being small for gestational age. Survival without major morbidity did not differ significantly between the groups and was positively associated with gestational age and negatively associated with being small for gestational age. CONCLUSION: Infant survival was significantly lower when the onset of preterm delivery was preterm PROM as compared with preterm labor and iatrogenic delivery. For surviving infants there was no significant difference in major morbidity between the groups. LEVEL OF EVIDENCE: III.
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37.
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38.
  • Klemetti, R., et al. (author)
  • Puberty disorders among ART-conceived singletons: a Nordic register study from the CoNARTaS group
  • 2022
  • In: Human Reproduction. - : Oxford University Press (OUP). - 0268-1161 .- 1460-2350. ; 37:10, s. 2402-2411
  • Journal article (peer-reviewed)abstract
    • STUDY QUESTION Do ART-conceived children have an increased risk for puberty disorders? SUMMARY ANSWER Both ART-conceived boys and girls had a higher risk of puberty disorders; early puberty was more common among girls and late puberty among boys. WHAT IS KNOWN ALREADY Some physiological differences in growth and metabolism have been reported for ART-conceived children compared to non-ART-conceived children. Knowledge on pubertal development and disorders in ART-conceived children is limited. STUDY DESIGN, SIZE, DURATION A register-based cohort study was carried out including data from 1985 to 2015. The Committee of Nordic Assisted Reproductive Technology and Safety (CoNARTaS) study population consists of all live and stillborn children, as well as their mothers, registered in the Medical Birth Registers during the study period in Denmark, Sweden, Finland and Norway. PARTICIPANTS/MATERIALS, SETTING, METHODS A total of 122 321 ART-conceived singletons and 6 576 410 non-ART singletons born in Denmark (1994-2014), Finland (1990-2014), Norway (2002-2015) and Sweden (1985-2015) were included. Puberty disorders were defined using International Classification of Diseases and Related Health Problems (ICD)-9/ICD-10 codes and classified in the following groups: late puberty (6268/E30.0), early puberty (2591 and 2958/E30.1 and E30.8) and unspecified disorders (V212 and V579/E30.9 and Z00.3 as well as Z51.80 for Finland). The results in Cox regression were adjusted for maternal age, parity, smoking, gestational diabetes, chronic hypertension, hypertensive disorders during pregnancy and country, and further for either gestational age, birthweight, small for gestational age or large for gestational age. MAIN RESULTS AND THE ROLE OF CHANCE There were 37 869 children with diagnoses related to puberty disorders, and 603 of them were born after ART. ART-conceived children had higher risks for early (adjusted hazard ratio (aHR) 1.45, 95% CI: 1.29-1.64) and late puberty (aHR 1.47, 95% CI: 1.21-1.77). Girls had more diagnoses related to early puberty (aHR 1.46, 95% CI: 1.29-1.66) and boys with late puberty (aHR 1.55, 95% CI: 1.24-1.95). LIMITATIONS, REASONS FOR CAUTION Using reported puberty disorders with ICD codes in health care registers might vary, which may affect the numbers of cases found in the registers. Register data may give an underestimation both among ART and non-ART-conceived children, especially among non-ART children, who may not be as carefully followed as ART-conceived children. Adjustment for causes and duration of infertility, mothers' own puberty characteristics and BMI, as well as children's BMI, was not possible because data were not available or data were missing for the early years. It was also not possible to compare ART to non-ART siblings or to study the pubertal disorders by cause of subfertility owing to a small number of discordant sibling pairs and a large proportion of missing data on cause of subfertility. WIDER IMPLICATIONS OF THE FINDINGS This large, register-based study suggests that ART-conceived children have a higher risk for puberty disorders. However, the mechanisms of infertility and pubertal onset are complex, and ART is a rapidly advancing field with various treatment options. Studying the pubertal disorders of ART-conceived offspring is a continuing challenge. STUDY FUNDING/COMPETING INTEREST(S) This work was supported by the Nordic Trial Alliance: a pilot project jointly funded by the Nordic Council of Ministers and NordForsk (71450), the Central Norway Regional Health Authorities (46045000), the Nordic Federation of Obstetrics and Gynaecology (NF13041, NF15058, NF16026 and NF17043), the Interreg oresund-Kattegat-Skagerrak European Regional Development Fund (ReproUnion project), the Research Council of Norway's Centre of Excellence funding scheme (262700), the Swedish state under the agreement between the Swedish government and the county councils, the ALF-agreement (ALFGBG-70940) and FLUX Consortium 'Family Formation in Flux-Causes, Consequences and Possible Futures', funded by the Strategic Research Council, Academy of Finland (DEMOGRAPHY 345130). The funders had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript. The authors have no conflicts of interest to disclose.
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39.
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42.
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43.
  • Opdahl, S., et al. (author)
  • Risk of hypertensive disorders in pregnancies following assisted reproductive technology: a cohort study from the CoNARTaS group
  • 2015
  • In: Human Reproduction. - : Oxford University Press (OUP). - 0268-1161 .- 1460-2350. ; 30:7, s. 1724-1731
  • Journal article (peer-reviewed)abstract
    • STUDY QUESTION: Is the risk of hypertensive disorders in pregnancies conceived following specific assisted reproductive technology (ART) procedures different from the risk in spontaneously conceived (SC) pregnancies? SUMMARY ANSWER: ART pregnancies had a higher risk of hypertensive disorders, in particular following cryopreservation, with the highest risk seen in twin pregnancies following frozen-thawed cycles. WHAT IS KNOWN ALREADY: The risk of hypertensive disorders is higher in ART pregnancies than in SC pregnancies. The increased risk maybe partly explained by multiple pregnancies and underlying infertility, but a contribution from specific ART procedures has not been excluded. STUDY DESIGN, SIZE, DURATION: Population-based cohort study, including sibling design with nationwide data from health registers in Sweden, Denmark and Norway. PARTICIPANTS/MATERIALS, SETTING, METHODS: All registered ART pregnancies and a sample of SC pregnancies with gestational age >= 22 weeks from 1988 to 2007 were included. ART singleton pregnancies (n = 47 088) were compared with SC singleton pregnancies (n = 268 599), matched on parity and birth year. ART twin pregnancies (n = 10 918) were compared with SC twin pregnancies (46 674). We used logistic regression to estimate adjusted odds ratios and risk differences for hypertensive disorders in pregnancies following IVF, ICSI and fresh or frozen-thawed cycles. We also compared freshand frozen-thawed cycles within mothers who had conceived following both procedures using conditional logistic regression (sibling analysis). MAIN RESULTS AND THE ROLE OF CHANCE: Hypertensive disorders were reported in 5.9% of ART singleton and 12.6% of ART twin pregnancies. Comparing singleton pregnancies, the risk of hypertensive disorders was higher after all ART procedures. The highest risk in singleton pregnancies was seen after frozen-thawed cycles [risk 7.0%, risk difference 1.8%, 95% confidence interval (CI) 1.2-2.8]. Comparing twin pregnancies, the risk was higher after frozen-thawed cycles (risk 19.6%, risk difference 5.1%, 95% CI 3.0-7.1), but not after fresh cycles. In siblings, the risk was higher after frozen-thawed cycles compared with fresh cycles within the same mother (odds ratio 2.63, 95% CI 1.73-3.99). There were no clear differences in risk for IVF and ICSI. LIMITATIONS, REASONS FOR CAUTION: The number of ART siblings in the study was limited. Residual confounding cannot be excluded. In addition, we did not have information on all SC pregnancies in each woman's history, and could therefore not compare risk in ART versus SC pregnancies in the same mother. WIDER IMPLICATIONS OF THE FINDINGS: Pregnancies following frozen-thawed cycles have a higher risk of hypertensive disorders, also when compared with fresh cycle pregnancies by the same mother. The safety aspects in frozen-thawed cycles merit further attention. STUDY FUNDING/COMPETING INTEREST(S): Funding was received from the European Society for Human Reproduction and Embryology, the University of Copenhagen, the Danish Agency for Science, Technology and Innovation, the Nordic Federation of Societies of Obstetrics and Gynecology and the Liaison Committee between the Central Norway Regional Health Authority and the Norwegian University of Science and Technology. None of the authors has any competing interests to declare.
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44.
  • Petersen, S. H., et al. (author)
  • Time trends in placenta-mediated pregnancy complications after assisted reproductive technology in the Nordic countries
  • 2020
  • In: American Journal of Obstetrics and Gynecology. - : Elsevier BV. - 0002-9378 .- 1097-6868. ; 223:2
  • Journal article (peer-reviewed)abstract
    • Background: The use of assisted reproductive technology is increasing worldwide and conception after assisted reproduction currently comprises 3%–6% of birth cohorts in the Nordic countries. The risk of placenta-mediated pregnancy complications is greater after assisted reproductive technology compared with spontaneously conceived pregnancies. Whether the excess risk of placenta-mediated pregnancy complications in pregnancies following assisted reproduction has changed over time, is unknown. Objectives: To investigate whether time trends in risk of pregnancy complications (hypertensive disorders in pregnancy, placental abruption and placenta previa) differ for pregnancies after assisted reproductive technology compared with spontaneously conceived pregnancies during 3 decades of assisted reproduction treatment in the Nordic countries. Study Design: In a population-based cohort study, with data from national health registries in Denmark (1994–2014), Finland (1990–2014), Norway (1988–2015) and Sweden (1988–2015), we included 6,830,578 pregnancies resulting in delivery. Among these, 146,998 (2.2%) were pregnancies after assisted reproduction (125,708 singleton pregnancies, 20,668 twin pregnancies and 622 of higher order plurality) and 6,683,132 (97.8%) pregnancies were conceived spontaneously (6,595,185 singleton pregnancies, 87,106 twin pregnancies and 1,289 of higher order plurality). We used logistic regression with post-estimation to estimate absolute risks and risk differences for each complication. We repeated analyses for singleton and twin pregnancies, separately. In subsamples with available information, we also adjusted for maternal body mass index, smoking during pregnancy, previous cesarean delivery, culture duration, and cryopreservation. Results: The risk of each placental complication was consistently greater in pregnancies following assisted reproductive technology compared with spontaneously conceived pregnancies across the study period, except for hypertensive disorders in twin pregnancies, where risks were similar. Risk of hypertensive disorders increased over time in twin pregnancies for both conception methods, but more strongly for pregnancies following assisted reproductive technology (risk difference, 1.73 percentage points per 5 years; 95% confidence interval, 1.35–2.11) than for spontaneously conceived twins (risk difference, 0.75 percentage points; 95% confidence interval, 0.61–0.89). No clear time trends were found for hypertensive disorders in singleton pregnancies. Risk of placental abruption decreased over time in all groups. Risk differences were –0.16 percentage points (95% confidence interval, –0.19 to –0.12) and –0.06 percentage points (95% confidence interval, –0.06 to –0.05) for pregnancies after assisted reproduction and spontaneously conceived pregnancies, respectively, for singletons and multiple pregnancies combined. Over time, the risk of placenta previa increased in pregnancies after assisted reproduction among both singletons (risk difference, 0.21 percentage points; 95% confidence interval, 0.14–0.27) and twins (risk difference, 0.30 percentage points; 95% confidence interval, 0.16–0.43), but remained stable in spontaneously conceived pregnancies. When adjusting for culture duration, the temporal increase in placenta previa became weaker in all groups of assisted reproductive technology pregnancies, whereas adjustment for cryopreservation moderately attenuated trends in assisted reproductive technology twin pregnancies. Conclusions: The risk of placenta-mediated pregnancy complications following assisted reproductive technology remains higher compared to spontaneously conceived pregnancies, despite declining rates of multiple pregnancies. For hypertensive disorders in pregnancy and placental abruption, pregnancies after assisted reproduction follow the same time trends as the background population, whereas for placenta previa, risk has increased over time in pregnancies after assisted reproductive technology. © 2020 Elsevier Inc.
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45.
  • Ponjaert-Kristoffersen, I, et al. (author)
  • International collaborative study of intracytoplasmic sperm injection-conceived, in vitro fertilization-conceived, and naturally conceived 5-year-old child outcomes: cognitive and motor assessments
  • 2005
  • In: Pediatrics. ; 115:3
  • Journal article (peer-reviewed)abstract
    • OBJECTIVE: To date, very few studies have been conducted on the neurodevelopmental well-being of children conceived through intracytoplasmic sperm injection (ICSI). The limitations of these studies often include a lack of comparison with a demographically matched, naturally conceived (NC) group and the investigation of only very young children, with relatively small samples sizes. One study showed that there were no differences in IQ scores among ICSI-conceived, in vitro fertilization (IVF)-conceived, and NC children at 5 years of age. Unfortunately, psychomotor development was not assessed in that study. Because findings regarding these children's cognitive and motor development are inconclusive, the aim of this study was to shed more light on the cognitive and motor development of 5-year-old ICSI-conceived children. METHODS: A total of 511 ICSI-conceived children were compared with 424 IVF-conceived children and 488 NC controls. Children were recruited in 5 European countries, ie, Belgium, Denmark, Greece, Sweden, and the United Kingdom. Participation rates ranged from 45% to 96% in the ICSI and IVF groups and from 34% to 78% in the NC group. Cognitive and motor development was assessed with the Wechsler Preschool and Primary Scale of Intelligence-Revised (WPPSI-R) and McCarthy Scales of Children's Abilities (MSCA) Motor Scale, respectively. The WPPSI-R consists of 2 major scales, ie, Verbal and Performance, each including 6 subtests. The 6 Performance Scale subtests are object assembly, geometric design, block design, mazes, picture completion, and animal pegs. The 6 Verbal Scale subtests are information, comprehension, arithmetic, vocabulary, similarities, and sentences. Scores on the Performance and Verbal Scale subtests are summed to yield the performance IQ (PIQ) and verbal IQ (VIQ), respectively. Scores on both the Performance Scale and the Verbal Scale yield the full-scale IQ (FSIQ). IQ scales have a mean score of 100 and a SD of 15. Each subtest has a mean score of 10 and a SD of 3. The MSCA consists of 6 scales, ie, Verbal, Perceptual-Performance, Quantitative, General Cognitive, Memory, and Motor Scale. In this study, only the Motor Scale was administered. This scale assesses the child's coordination during performance of a variety of gross- and fine-motor tasks. Leg coordination, arm coordination, and imitative action tests provide measures of gross-motor ability. Draw-a-design and draw-a-child assess fine-motor coordination, as revealed by the levels of hand coordination and finger dexterity. The mean score for this test is 50, with a SD of . RESULTS: No differences were identified among ICSI, IVF, and NC children with respect to VIQ, PIQ, or FSIQ scores of the WPPSI-R. Furthermore, there were no differences between groups regarding the discrepancy between VIQ and PIQ scores. These results were not influenced by gender, country, or maternal educational level. However, in the subgroup of firstborn children with mothers who gave birth at an older age (33-45 years), NC children obtained significantly better VIQ and FSIQ scores than did children conceived through assisted reproductive technologies. These differences in VIQ and FSIQ scores between ICSI/IVF and NC children were relative, because NC children scored <1 IQ point higher than ICSI/IVF children. Therefore, these scores show no clinical relevance. For Verbal Scale subtests, variables such as age of the mother at the time of the birth, educational level of the mother, and gender and nationality of the child interacted with mode of conception, resulting in clinically irrelevant differences between scores for the ICSI/IVF and NC groups on the arithmetic, vocabulary, and comprehension subtests. For Performance Scale subtests, these same demographic factors interacted with mode of conception for the block design, object assembly, and animal pegs subtests, again resulting in clinically irrelevant differences among groups. In the 3 groups (ICSI, IVF, and NC), we observed equal numbers of children scoring below 1 SD from the mean on the WPPSI-R and the MSCA. CONCLUSIONS: This study includes a substantial number of children from several European countries. Apart from a few interaction effects between mode of conception and demographic variables, no differences were found when ICSI, IVF, and NC scores on the WPPSI-R and MSCA Motor Scale were compared. Nevertheless, the aforementioned interaction effects could indicate that demographic variables such as maternal age at the time of the birth and maternal educational level play different roles in the cognitive development of IVF and ICSI children, compared with NC children. Additional research is needed to explore and verify this finding. Previous studies revealed that ICSI children, in comparison with NC children, more frequently obtained scores below 1 SD from the mean on 3 subtests of the Performance Scale (object assembly, block design, and mazes) or showed a trend of 5.2% of ICSI children, compared with 2.5% of IVF children and 0.9% of NC children, obtaining a score below 1 SD from the mean, but those findings were not confirmed in this study. Here no differences were found among the 3 groups in the numbers of children scoring below 1 SD from the mean on the VIQ, PIQ, and FSIQ tests and the Verbal and Performance Scale subtests. Motor development results were somewhat more conclusive. There were no differences between the scores of ICSI, IVF, and NC children on the MCSA Motor Scale. No interaction effects were found between mode of conception and demographic variables, indicating that these results are not influenced by gender, nationality, maternal educational level, or maternal age at the time of the birth. Furthermore, equal proportions of children in all 3 groups scored below 1 SD from the mean. The results of this study are reassuring for parents who conceived through ICSI (or IVF). The findings indicate that the motor and cognitive development of their offspring is very similar to that of NC children. However, demographic factors such as maternal educational level and maternal age at the time of the birth might play different roles in the cognitive development of ICSI and IVF children, compared with NC children.
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46.
  • Ponjaert-Kristoffersen, I, et al. (author)
  • International collaborative study of intracytoplasmic sperm injection-conceived, in vitro fertilization-conceived, and naturally conceived 5-year-old child outcomes: cognitive and motor assessments
  • 2005
  • In: Pediatrics. - : American Academy of Pediatrics (AAP). - 1098-4275 .- 0031-4005. ; 115:3
  • Journal article (peer-reviewed)abstract
    • Objective. To date, very few studies have been conducted on the neurodevelopmental well-being of children conceived through intracytoplasmic sperm injection (ICSI). The limitations of these studies often include a lack of comparison with a demographically matched, naturally conceived (NC) group and the investigation of only very young children, with relatively small samples sizes. One study showed that there were no differences in IQ scores among ICSI-conceived, in vitro fertilization (IVF)-conceived, and NC children at 5 years of age. Unfortunately, psychomotor development was not assessed in that study. Because findings regarding these children's cognitive and motor development are inconclusive, the aim of this study was to shed more light on the cognitive and motor development of 5-year-old ICSI-conceived children.
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47.
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48.
  • Rönö, K., et al. (author)
  • The neurodevelopmental morbidity of children born after assisted reproductive technology: a Nordic register study from the Committee of Nordic Assisted Reproductive Technology and Safety group
  • 2022
  • In: Fertility and Sterility. - : Elsevier BV. - 0015-0282 .- 1556-5653. ; 117:5, s. 1026-1037
  • Journal article (peer-reviewed)abstract
    • Objective: To assess the risk of neurodevelopmental disorders in singletons born after the use of assisted reproductive technology (ART) compared with singletons born without the use of ART. Design: Nordic register-based study. Setting: Cross-linked data from Medical Birth Registers and National ART and Patient Registers; liveborn singletons in 1995–2014 in Denmark and Finland, 2005–2015 in Norway, and 1995–2015 in Sweden with follow-up to 2014 (Denmark and Finland) or 2015 (Norway and Sweden). Patients: A total of 5,076,444 singletons: 116,909 (2.3%) born with and 4,959,535 (97.7%) born without the use of ART (non-ART). Interventions: In vitro fertilization, intracytoplasmic sperm injection, and fresh and frozen embryo transfer. Main Outcome Measures: The primary outcomes (International Statistical Classification of Diseases and Related Health Problems, Tenth Revision, codes) were learning and motor functioning disorders (F80–F83), autism spectrum disorder (F84), attention-deficit/hyperactivity disorder and conduct disorders (F90–F92), and tic disorders (F95). Crude hazard ratios (HRs) and adjusted hazard ratios (aHRs) with 95% confidence intervals were calculated. Results: Singletons in the ART cohort had a higher adjusted risk of learning and motor functioning disorders (HR, 1.01 [0.96–1.07]; aHR, 1.17 [1.11–1.24]) and a tendency toward a higher risk of autism spectrum disorder (HR, 1.12 [1.04–1.21]; aHR, 1.07 [0.98–1.16]) and attention-deficit/hyperactivity disorder and conduct disorders (HR, 0.82 [0.77–0.86]; aHR, 1.17 [0.99–1.12]) but not of tic disorders (HR, 1.21 [1.06–1.38]; aHR, 1.17 [0.96–1.27]). No differences in risk were found between children born after in vitro fertilization and intracytoplasmic sperm injection or after fresh and frozen embryo transfer. Conclusions: Our findings of only small differences in neurodevelopment between ART and non-ART singletons are reassuring and in line with previous studies. © 2022 American Society for Reproductive Medicine
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49.
  • Spangmose, A. L., et al. (author)
  • Obstetric and perinatal risks in 4601 singletons and 884 twins conceived after fresh blastocyst transfers: a Nordic study from the CoNARTaS group
  • 2020
  • In: Human Reproduction. - 0268-1161 .- 1460-2350. ; 35:4, s. 805-815
  • Journal article (peer-reviewed)abstract
    • STUDY QUESTION: Are obstetric and perinatal outcomes in pregnancies after fresh blastocyst transfer (BT) comparable with those born after fresh cleavage stage transfer (CT) and spontaneous conception (SC)? SUMMARY ANSWER: Fresh BT is associated with a higher risk of placental and perinatal complications. WHAT IS KNOWN ALREADY: BT optimizes the selection of top-quality embryos and increases pregnancy and live birth rates per transfer compared to CT. However, concerns have been raised as extended culture duration may increase obstetric complications and impair perinatal outcomes. Previous studies have shown a higher risk of preterm birth (PTB) among infants born after BT compared with CT. Pregnancies after BT are also prone to a higher risk of same-sex twins after single embryo transfer (SET). STUDY DESIGN, SIZE, DURATION: A retrospective register-based cohort study used data from Denmark, Norway and Sweden including three cohorts: 56557 singletons and 16315 twins born after fresh IVF/ICSI cycles and 2808323 SC singletons in Denmark (birth years 1997-2014), Norway (2010-2015) and Sweden (2002-2015). Of the fresh IVF/ICSI singletons, 4601 were born after BT and 51956 after CT. The twin cohort consisted of 884 fresh IVF/ICSI children born after BT and 15431 fresh IVF/ICSI children born after CT. PARTICIPANTS/MATERIALS, SETTING, METHODS: Data were obtained from a large Nordic cohort of children born after ART and SC initiated by the Committee of Nordic ART and Safety (CoNARTaS). The CoNARTaS cohort was established by cross-linking National ART-, Medical Birth-, and National Patients Registers using the unique personal identification number, allocated to every citizen in the Nordic countries. Obstetric and perinatal outcomes after BT, CT and SC were compared using logistic regression analysis. For perinatal outcomes, we calculated gestational age based on the date of oocyte pick-up (OPU) and in sensitivity analyses on data from Denmark and Norway, we also calculated gestational age based on the second-trimester ultrasonography (US) scan. Risk of pregnancies with same-sex twins after SET was used as a proxy for risk of monozygotic twins. Adjustments were made for child's sex, birth year, parity (0 or >1), maternal age, body mass index, smoking, educational level, fertilization method (IVF/ICSI), the number of aspirated oocytes, SET and country. Information on educational level and the number of aspirated oocytes was not available for Norway. Children born after frozen embryo transfer were not included. The birth cohorts were restricted according to the year in which BT was introduced in the different countries. MAIN RESULTS AND THE ROLE OF CHANCE: A higher risk of placenta previa was found in singleton pregnancies after BT compared with CT (adjusted odds ratio [aOR] 2.11 [95% CI 1.76; 2.52]). Singletons born after BT had a higher risk of PTB (aOR 1.14 [95% CI 1.01; 1.29]) compared with CT singletons, when estimated based on OPU. Furthermore, an altered male/female ratio (aOR 1.13 [95% CI 1.06; 1.21]) with more males following BT compared with CT was seen. Risk of same-sex twins after SET was higher after single BT compared with single CT (aOR 1.94 [95% CI 1.42; 2.60]). LIMITATIONS, REASONS FOR CAUTION: Residual confounding cannot be excluded, in particular related to duration and cause of infertility that we could not adjust for due to lack of reliable data. WIDER IMPLICATIONS OF THE FINDINGS: Extended embryo culture to the blastocyst stage has the potential to compromise obstetric and perinatal outcomes in fresh cycles. These results are important since an increasing number of IVF/ICSI treatments are performed as BT. STUDY FUNDING/COMPETING INTEREST(S): NORDFORSK (project no: 71450). The Research Fund of Rigshospitalet, Copenhagen University Hospital. ReproUnion Collaborative study, co-financed by the European Union, Interreg V ÖKS. Grants from Swedish state under the agreement between the Swedish government and the county councils, the ALF-agreement (LUA/ALF 70940), Hjalmar Svensson Research Foundatio . The Research Council of Norway through its Centres of Excellence funding scheme, project number 262700. None of the authors has any conflicts of interests to declare regarding this study. TRIAL REGISTRATION NUMBER: ISRCTN11780826. © The Author(s) 2020. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.
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50.
  • Storgaard, M., et al. (author)
  • Obstetric and neonatal complications in pregnancies conceived after oocyte donation: a systematic review and meta-analysis
  • 2017
  • In: Bjog-an International Journal of Obstetrics and Gynaecology. - : Wiley. - 1470-0328. ; 124:4, s. 561-572
  • Research review (peer-reviewed)abstract
    • Background Approximately 50 000 oocyte donation OD) treatment cycles are now performed annually in Europe and the US. Objectives To ascertain whether the risk of adverse obstetric and perinatal/neonatal outcomes is higher in pregnancies conceived by OD than in pregnancies conceived by conventional in-vitro fertilisation IVF)/intracytoplasmic sperm injection ICSI) or spontaneously. Search Strategy A systematic search was performed in the PubMed, Cochrane and Embase databases from 1982-2016. Primary outcomes were hypertensive disorders of pregnancy, preeclampsia PE), gestational diabetes mellitus, postpartum haemorrhage, caesarean section, preterm birth, low birthweight and small for gestational age. Selection criteria Inclusion criteria were original studies including at least five OD pregnancies with a control group of pregnancies conceived by conventional IVF/ICSI or spontaneous conception, and case series with > 500 cases reporting one or more of the selected complications. Studies not adjusting for plurality were excluded. Data collection and analysis Thirty-five studies met the inclusion criteria. A random-effects model was used for the meta-analyses. Main results For OD pregnancies versus conventional IVF/ ICSI pregnancies the risk of PE was adjusted odds ratio (AOR) 2.11 (95% CI, 1.42-3.15) in singleton and AOR 3.31 (95% CI, 1.616.80) in multiple pregnancies. The risks of preterm birth and low birthweight in singletons were AOR 1.75 (95% CI, 1.39-2.20) and 1.53 (95% CI, 1.16-2.01), respectively. Conclusions OD conceptions are associated with adverse obstetric and neonatal outcomes. To avoid the additional increase in risk from multiplicity, single-embryo transfer should be the choice of option in OD cycles.
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