| 1. |
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| 2. |
- Henningsen, A. A., et al.
(författare)
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Imprinting disorders in children born after ART: a Nordic study from the CoNARTaS group
- 2020
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Ingår i: Human Reproduction. - : Oxford University Press (OUP). - 0268-1161 .- 1460-2350. ; 35:5, s. 1178-1184
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Tidskriftsartikel (refereegranskat)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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| 3. |
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| 4. |
- Henningsen, A. K. A., et al.
(författare)
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Risk of congenital malformations in live-born singletons conceived after intracytoplasmic sperm injection: a Nordic study from the CoNARTaS group
- 2023
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Ingår i: Fertility and Sterility. - 0015-0282 .- 1556-5653. ; 120:5, s. 1033-1041
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Tidskriftsartikel (refereegranskat)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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| 5. |
- Magnus, M. C., et al.
(författare)
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Maternal Risk of Cardiovascular Disease After Use of Assisted Reproductive Technologies
- 2023
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Ingår i: Jama Cardiology. - 2380-6583 .- 2380-6591. ; 8:9, s. 837-845
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Tidskriftsartikel (refereegranskat)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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| 6. |
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| 7. |
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| 8. |
- Petersen, S. H., et al.
(författare)
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Time trends in placenta-mediated pregnancy complications after assisted reproductive technology in the Nordic countries
- 2020
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Ingår i: American Journal of Obstetrics and Gynecology. - : Elsevier BV. - 0002-9378 .- 1097-6868. ; 223:2
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Tidskriftsartikel (refereegranskat)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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| 9. |
- Pulakka, A, et al.
(författare)
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Preterm birth and asthma and COPD in adulthood: a nationwide register study from two Nordic countries
- 2023
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Ingår i: The European respiratory journal. - : European Respiratory Society (ERS). - 1399-3003 .- 0903-1936. ; 61:6
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Tidskriftsartikel (refereegranskat)abstract
- Preterm birth affects lungs in several ways but only few studies have follow-up until adulthood. We investigated the association of the entire spectrum of gestational ages with specialist care episodes for obstructive airway disease (asthma and chronic obstructive pulmonary disease, COPD) at age 18–50 years. We used nationwide register data on 706 717 people born 1987–1998 in Finland (4.8% preterm) and 1 669 528 born 1967–1999 in Norway (5.0% preterm). Care episodes of asthma and COPD were obtained from specialised healthcare registers, available in Finland 2005–2016 and in Norway 2008–2017. We used logistic regression to estimate odds ratios (OR) for having a care episode with either disease outcome. Odds of any obstructive airway disease in adulthood were 2–3-fold for those born <28 or 28–31 completed weeks, compared with those born full-term (39–41 completed weeks), persisting after adjustments. For individuals born at 32–33, 34–36 or 37–38 weeks, the odds were 1.1- to 1.5-fold. Associations were similar in the Finnish and the Norwegian data and among people aged 18–29 and 30–50 years. For COPD at age 30–50 years, the OR was 7.44 (95% CI 3.49–15.85) for those born <28 weeks, 3.18 (2.23–4.54) for those born 28–31 weeks, and 2.32 (1.72–3.12) for those born 32–33 weeks. Bronchopulmonary dysplasia in infancy increased the odds further for those born <28 and 32–31 weeks. Preterm birth is a risk factor for asthma and COPD in adulthood. The high odds of COPD calls for diagnostic vigilance when adults born very preterm present with respiratory symptoms.
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| 10. |
- Pulakka, A, et al.
(författare)
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Preterm birth and asthma and COPD in adulthood: a nationwide register study from two Nordic countries
- 2023
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Ingår i: The European respiratory journal. - : European Respiratory Society (ERS). - 1399-3003 .- 0903-1936. ; 61:6
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Tidskriftsartikel (refereegranskat)abstract
- Preterm birth affects lungs in several ways but only few studies have follow-up until adulthood. We investigated the association of the entire spectrum of gestational ages with specialist care episodes for obstructive airway disease (asthma and chronic obstructive pulmonary disease, COPD) at age 18–50 years. We used nationwide register data on 706 717 people born 1987–1998 in Finland (4.8% preterm) and 1 669 528 born 1967–1999 in Norway (5.0% preterm). Care episodes of asthma and COPD were obtained from specialised healthcare registers, available in Finland 2005–2016 and in Norway 2008–2017. We used logistic regression to estimate odds ratios (OR) for having a care episode with either disease outcome. Odds of any obstructive airway disease in adulthood were 2–3-fold for those born <28 or 28–31 completed weeks, compared with those born full-term (39–41 completed weeks), persisting after adjustments. For individuals born at 32–33, 34–36 or 37–38 weeks, the odds were 1.1- to 1.5-fold. Associations were similar in the Finnish and the Norwegian data and among people aged 18–29 and 30–50 years. For COPD at age 30–50 years, the OR was 7.44 (95% CI 3.49–15.85) for those born <28 weeks, 3.18 (2.23–4.54) for those born 28–31 weeks, and 2.32 (1.72–3.12) for those born 32–33 weeks. Bronchopulmonary dysplasia in infancy increased the odds further for those born <28 and 32–31 weeks. Preterm birth is a risk factor for asthma and COPD in adulthood. The high odds of COPD calls for diagnostic vigilance when adults born very preterm present with respiratory symptoms.
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| 11. |
- Quist-Paulsen, P., et al.
(författare)
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T-cell acute lymphoblastic leukemia in patients 1-45 years treated with the pediatric NOPHO ALL2008 protocol
- 2020
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Ingår i: Leukemia. - : Springer Science and Business Media LLC. - 0887-6924 .- 1476-5551. ; 34:2, s. 347-357
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Tidskriftsartikel (refereegranskat)abstract
- The NOPHO ALL2008 is a population-based study using an unmodified pediatric protocol in patients 1-45 years of age with acute lymphoblastic leukemia. Patients with T-ALL were given a traditional pediatric scheme if fast responding (minimal residual disease (MRD) < 0.1% day 29), or intensive block-based chemotherapy if slow responding (MRD > 0.1% day 29). Both treatment arms included pediatric doses of high-dose methotrexate and asparaginase. If MRD >= 5% on day 29 or >= 0.1% after consolidation, patients were assigned to allogeneic hematopoietic stem cell transplantation. The 5-year overall survival of the 278 T-ALL patients was 0.75 (95% CI 0.69-0.81), being 0.82 (0.74-0.88) for patients 1.0-9.9 years, 0.76 (0.66-0.86) for those 10.0-17.9 years, and 0.65 (0.55-0.75) for the older patients. The risk of death in first remission was significantly higher in adults (12%) compared with the 1-9 years group (4%). The MRD responses in the three age groups were similar, and only a nonsignificant increase in relapse risk was found in adults. In conclusion, an unmodified pediatric protocol in patients 1-45 years is effective in all age groups. The traditional pediatric treatment schedule was safe for all patients, but the intensive block therapy led to a high toxic death rate in adults.
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| 12. |
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| 13. |
- Terho, A M, et al.
(författare)
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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
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Ingår i: Human reproduction (Oxford, England). - : Oxford University Press (OUP). - 1460-2350 .- 0268-1161. ; 36:4, s. 1083-1092
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Tidskriftsartikel (refereegranskat)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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| 14. |
- Westvik-Johari, K., et al.
(författare)
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The challenges of selective fertility and carryover effects in within-sibship analyses: the effect of assisted reproductive technology on perinatal mortality as an example
- 2023
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Ingår i: International Journal of Epidemiology. - : Oxford University Press (OUP). - 0300-5771 .- 1464-3685. ; 52:2, s. 403-413
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Tidskriftsartikel (refereegranskat)abstract
- Background Within-sibship analyses show lower perinatal mortality after assisted reproductive technology (ART) compared with natural conception (NC), a finding that appears biologically unlikely. We investigated whether this may be attributed to bias from selective fertility and carryover effects. Methods Using data from national registries in Denmark (1994-2014), Finland (1990-2014) and Norway and Sweden (1988-2015), we studied 5 722 826 singleton pregnancies, including 119 900 ART-conceived and 37 590 exposure-discordant sibships. Perinatal mortality at the population level and within sibships was compared using multilevel logistic regression with random and fixed intercepts, respectively. We estimated selective fertility as the proportion of primiparous women with and without perinatal loss who had a second delivery, and carryover effects through bidirectional and crosswise associations. Results Population analysis showed higher perinatal mortality among ART conception compared with NC (odds ratio 1.21, 95% CI 1.13 to 1.30), whereas within-sibship analysis showed the opposite (OR 0.36, 95% CI 0.31 to 0.43). Primiparous women with perinatal loss were more likely to give birth again (selective fertility) and to use ART in this subsequent pregnancy (carryover effects), resulting in strong selection of double-discordant sibships with death of the naturally conceived and survival of the ART-conceived sibling. After controlling for conception method and outcome in the first pregnancy, ART was not consistently associated with perinatal mortality in the second pregnancy. Conclusions Whereas population estimates may be biased by residual confounding, within-sibship estimates were biased by selective fertility and carryover effects. It remains unclear whether ART conception contributes to perinatal mortality.
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| 15. |
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| 16. |
- Henningsen, A. K. A., et al.
(författare)
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Trends over time in congenital malformations in live-born children conceived after assisted reproductive technology
- 2018
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Ingår i: Acta Obstetricia Et Gynecologica Scandinavica. - : Wiley. - 0001-6349 .- 1600-0412. ; 97:7, s. 816-823
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Tidskriftsartikel (refereegranskat)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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| 19. |
- Klemetti, R., et al.
(författare)
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Puberty disorders among ART-conceived singletons: a Nordic register study from the CoNARTaS group
- 2022
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Ingår i: Human Reproduction. - : Oxford University Press (OUP). - 0268-1161 .- 1460-2350. ; 37:10, s. 2402-2411
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Tidskriftsartikel (refereegranskat)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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| 20. |
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| 21. |
- Norrman, Emma, et al.
(författare)
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Type 1 diabetes in children born after assisted reproductive technology: a register-based national cohort study
- 2020
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Ingår i: Human Reproduction. - : Oxford University Press (OUP). - 0268-1161 .- 1460-2350. ; 35:1, s. 221-231
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Tidskriftsartikel (refereegranskat)abstract
- References STUDY QUESTION Do children born after assisted reproductive technology (ART) have an increased risk of developing type 1 diabetes? SUMMARY ANSWER Children born after ART were found to have an increased risk of type 1 diabetes in the unadjusted analysis, while after adjustment this association was only significant in children born after frozen embryo transfer. WHAT IS KNOWN ALREADY? Some studies raise concerns as to whether fertility treatments may influence long-term morbidity in children born after ART. Elevated blood pressure and altered glucose metabolism have been found after ART in a few studies. STUDY DESIGN, SIZE, DURATION A register-based national cohort study that included all children born in Sweden between 1985 and 2015-in total, 3138540 children-was carried out. PARTICIPANTS/MATERIAL, SETTING, METHODS The study was population-based and all live-born singleton children born after ART (n=47938) or spontaneous conception (SC) (n=3090602) were included. The ART cohort comprised 36727 children born after fresh embryo transfer and 11211 children born after frozen embryo transfer. Several national registries were used together with data from Statistics Sweden. MAIN RESULTS AND THE ROLE OF CHANCE In total, 202 children born after ART and 17916 children born after SC developed type 1 diabetes, corresponding to 43.4 and 35.5 per 100000 person-years at risk (hazard ratio [HR] 1.23; 95% confidence interval [CI], 1.07 to 1.42). Mean follow-up was 9.7 (SD 6.4) years for ART children and 16.3 (SD 9.2) years for SC children. After adjustment for calendar year of birth, HR for type 1 diabetes was 1.13; 95% CI, 0.98-1.30. After further adjustment for sex, maternal age, country of birth, educational level, smoking and parental diabetes, HR was 1.07; 95% CI, 0.93-1.23. In subgroup analyses, an association was found between frozen embryo transfer and type 1 diabetes (adjusted HR 1.52; 95% CI, 1.08-2.14 and 1.41; 95% CI, 1.05-1.89 for frozen versus fresh and frozen versus SC, respectively). When comparing intracytoplasmic sperm injection to in vitro fertilization, no difference was found (adjusted HR 1.08; 95% CI, 0.77-1.51). LIMITATIONS, REASONS FOR CAUTION Limitations were the missing data and residual confounding caused by unknown confounders. Furthermore, the control group consisted of all children not conceived by ART and not non-ART children from subfertile mothers. The study was also performed in only singletons and not in the total ART population. WIDER IMPLICATIONS OF THE FINDINGS Type 1 diabetes is a serious disease, affecting human life in several ways, including risk of serious complications, reduced life span and a life-long treatment. Our results are generally reassuring, showing no increase in diabetes in ART children compared to children born after SC after adjustment for relevant confounders. The observation of an association between children born after frozen embryo transfer and type 1 diabetes, although based on subgroup analyses with a limited number of children and modest in size, is however a reason for concern.
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| 24. |
- Opdahl, S., et al.
(författare)
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Risk of hypertensive disorders in pregnancies following assisted reproductive technology: a cohort study from the CoNARTaS group
- 2015
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Ingår i: Human Reproduction. - : Oxford University Press (OUP). - 0268-1161 .- 1460-2350. ; 30:7, s. 1724-1731
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Tidskriftsartikel (refereegranskat)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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| 26. |
- Rönö, K., et al.
(författare)
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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
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Ingår i: Fertility and Sterility. - : Elsevier BV. - 0015-0282 .- 1556-5653. ; 117:5, s. 1026-1037
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Tidskriftsartikel (refereegranskat)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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| 30. |
- Spangmose, A. L., et al.
(författare)
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Obstetric and perinatal risks in 4601 singletons and 884 twins conceived after fresh blastocyst transfers: a Nordic study from the CoNARTaS group
- 2020
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Ingår i: Human Reproduction. - 0268-1161 .- 1460-2350. ; 35:4, s. 805-815
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Tidskriftsartikel (refereegranskat)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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| 32. |
- Wennberg, Anna Lena, 1968, et al.
(författare)
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Effect of maternal age on maternal and neonatal outcomes after assisted reproductive technology
- 2016
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Ingår i: Fertility and Sterility. - : Elsevier BV. - 0015-0282. ; 106:5, s. 1142-1149
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To compare the effect of maternal age on assisted reproductive technology (ART) and spontaneous conception (SC) pregnancies regarding maternal and neonatal complications. Design: Nordic retrospective population-based cohort study. Data from national ART registries were cross-linked with national medical birth registries. Patient(s): A total of 300,085 singleton deliveries: 39,919 after ART and 260,166 after SC. Main Outcome Measure(s): Hypertensive disorders in pregnancy (HDP), placenta previa, cesarean delivery, preterm birth (PTB; <37 weeks), low birth weight (LBW; <2,500 g), small for gestational age (SGA), and perinatal mortality (>= 28 weeks). Adjusted odds ratios (AORs) were calculated. Associations between maternal age and outcomes were analyzed. Result(s): The risk of placenta previa (AOR 4.11-6.05), cesarean delivery (AOR 1.18-1.50), PTB (AOR 1.23-2.19), and LBW (AOR 1.44-2.35) was significantly higher in ART than in SC pregnancies for most maternal ages. In both ART and SC pregnancies, the risk of HDP, placenta previa, cesarean delivery, PTB, LBW, and SGA changed significantly with age. The AORs for adverse neonatal outcomes at advanced maternal age (>35 years) showed a greater increase in SC than in ART. The change in risk with age did not differ between ART and SC for maternal outcomes at advanced maternal age. Conclusion(s): Having singleton conceptions after ART results in higher maternal and neonatal outcome risks overall, but the impact of age seems to be more pronounced in couples conceiving spontaneously. (C) 2016 by American Society for Reproductive Medicine.
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