Possíveis repercussões da reprodução assistida na saúde materno-infantil
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Apr 15, 2025
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Objetivo: Analisar os possíveis impactos da terapia da reprodução assistida (RA) na saúde materna e infantil, tanto a curto quanto a longo prazo. Revisão bibliográfica: Gestações por RA podem apresentar maior tendência a complicações, como pré-eclâmpsia, parto prematuro e tromboembolismo venoso. Nos neonatos, notou-se maior ocorrência de alterações cromossômicas e consequências da prematuridade. Nas crianças, observou-se tendência à hipertensão, obesidade e resistência insulínica, além de maior risco de reações alérgicas, problemas respiratórios, transtorno do espectro autista e atrasos no desenvolvimento psicomotor. Em casos específicos ainda nota-se aumento de leucemia linfoblástica aguda e carcinoma hepático. As mulheres submetidas à RA, principalmente aquelas com histórico de infertilidade, demonstram maior prevalência de câncer de mama, de endométrio e de ovário, embora a relação direta com a técnica seja controversa, devido à influência de fatores subjacentes à subfertilidade. Considerações finais: Apesar dos benefícios, os riscos associados à RA são importantes. As indicações devem ser acompanhadas por abordagens individualizadas e orientações claras aos pacientes, para que estes estejam cientes dos possíveis riscos e desafios à saúde materno-infantil. Ademais, é necessário o incentivo a pesquisas futuras e a realização de estudos de seguimentos longos, considerando vieses de confusão, para garantir uma orientação segura por parte dos profissionais de saúde.
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Como Citar
BorbaV. A. B. de A. e, FernandesY. G., & RosadoL. E. P. (2025). Possíveis repercussões da reprodução assistida na saúde materno-infantil. Revista Eletrônica Acervo Saúde, 25, e19603. https://doi.org/10.25248/reas.e19603.2025
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Revisão Bibliográfica
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Referências
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2. AHMADI H, et al. Long-term effects of ART on the health of the offspring. International Journal of Molecular Sciences, 2023; 24(17): 13564-13564.
3. ALMASI-HASHIANI A, et al. Assisted reproductive technology and the risk of preeclampsia: an updated systematic review and meta-analysis. BMC Pregnancy and Childbirth, 2019; 19(1): 149.
4. ANVISA. 2022. Divulgado relatório sobre fertilização in vitro no país em 2020 e 2021. Disponível em:https ://www.gov.br/anvisa/pt-br/assuntos/noticias-anvisa/2022/divulgado-relatorio-sobre-fertilizacao-in-vitro-no-pais-em-2020-e-2021.
5. ARAÚJO FILHO E, et al. Incidência de malformações congênitas em crianças concebidas através de injeção intracitoplasmática de espermatozoides. Revista Brasileira de Ginecologia e Obstetrícia, 2006; 28(2): 81-90.
6. BALACHANDREN N, et al. Venous thromboembolism associated with medically assisted reproduction (MAR): British fertility society policy and practice guidance for assessment and prevention. Human Fertility, 2024; 27(1).
7. BALLESTA-CASTILLEJOS A, et al. Obstetric and perinatal complications associated with assisted reproductive treatment in Spain. J Assist Reprod Genet, 2019; 36(12): 2435–2445.
8. BANICA AM, et al. Obstetric and perinatal complications associated with assisted reproductive techniques – review. MAEDICA – a Journal of Clinical Medicine, 2021; 16(3): 493–498.
9. BASTOS DG da S, et al. Técnicas de reprodução humana nos casos de infertilidade secundária. Contribuciones a las ciencias sociales, 2024; 17(13): 13227.
10. BERNTSEN S, et al. The health of children conceived by ART: “the chicken or the egg?” Human Reproduction Update, 2019; 25(2): 137-158.
11. BITTAR RE, et al. Repercussões neonatais das gestações múltiplas resultantes de técnicas de reprodução assistida. Revista de Ginecologia e Obstetrícia, 2016; 38(1): 45-50.
12. CARSON C, et al. Asthma in children born after infertility treatment: findings from the UK Millennium Cohort Study. Hum Reprod, 2013; 28: 471–479.
13. FABBRO M, et al. HE4 and CA-125 kinetics to predict outcome in patients with recurrent epithelial ovarian carcinoma: the META4 clinical trial. Front Oncol, 2024; 13: 1308630.
14. FARHUD DD, et al. In-vitro fertilization impact on the risk of breast cancer: A review article. Iran J Public Health, 2021; 50(3): 438–447.
15. FARHUD DD, et al. Strong evidences of the ovarian carcinoma risk in women after IVF treatment: A review article. Iran J Public Health, 2019; 48(12): 2124-2132.
16. FAUQUE P, et al. Do in vitro fertilization, intrauterine insemination or female infertility impact the risk of congenital anomalies in singletons? A longitudinal national French study. Human Reproduction, 2021; 36(3): 808-816.
17. FUJIMOTO A, et al. The outcome of infertility treatment in patients undergoing assisted reproductive technology after conservative therapy for endometrial cancer. Journal of Assisted Reproduction and Genetics, 2014; 31(9): 1189-1194.
18. GARCÍA-PLANELLS J, et al. BRCA, breast cancer and in vitro fertilization: How should we advise our patients? Fertil Steril, 2021; 116(2): 359-360.
19. GRANER VR e BARROS SM O de. Complicações maternas e ocorrências neonatais associadas às gestações múltiplas resultantes de técnicas de reprodução assistida. Revista da Escola de Enfermagem da USP, 2009; 43(1): 103-109.
20. GUI J, et al. In vitro fertilization is associated with the onset and progression of preeclampsia. Placenta, 2020; 89: 50-57.
21. GUO XY, et al. Cardiovascular and metabolic profiles of offspring conceived by assisted reproductive technologies: a systematic review and meta-analysis. Fertil Steril, 2017; 107(3): 622-631-5.
22. HARGREAVE M. Cancer risk among children born after fertility treatment. JAMA Network Open, 2024; 7(5): 249435.
23. HART R e NORMAN RJ. The longer-term health outcomes for children born as a result of IVF treatment. Part II—Mental health and development outcomes. Human Reproduction Update, 2013; 19(3): 244–250.
24. HATTORI H, et al. Association of four imprinting disorders and ART. Clinical Epigenetics, 2019; 11: 21.
25. HVIDTJØRN D, et al. Risk of autism spectrum disorders in children born after assisted conception: a population-based follow-up study. J Epidemiol Community Health, 2011; 65: 497–502.
26. JIANG Y, et al. Infertility and ovarian cancer risk: Evidence from nine prospective cohort studies. International Journal of Cancer, 2020; 147(8): 2121-2130.
27. KÄLLÉN B, et al. Asthma in Swedish children conceived by in vitro fertilisation. Arch Dis Child, 2013; 98(2): 92-96.
28. KATZ D, et al. Beginning IVF treatments after age 30 increases the risk of breast cancer: Results of a case-control study. Breast J, 2008; 14(6): 517-522.
29. KORHONEN P, et al. Calcium supplementation during pregnancy and long-term offspring outcome: A systematic literature review and meta-analysis. Ann N Y Acad Sci, 2022; 1510(1): 36-51.
30. KROENER L, et al. Use of fertility medications and cancer risk: a review and update. Curr Opin Obstet Gynecol, 2017; 29(4): 195-201.
31. LABARTA E, et al. Moderate ovarian stimulation does not increase the incidence of human embryo chromosomal abnormalities in in vitro fertilization cycles. J Clin Endocrinol Metab, 2012; 97(10): 1987-1994.
32. LARCHER L, et al. Ultrasound diagnosis of placental and umbilical cord anomalies in singleton pregnancies resulting from in-vitro fertilization. Placenta, 2023; 131: 58-64.
33. LERNER-GEVA L, et al. Possible risk for cancer among children born following assisted reproductive technology in Israel. Pediatr Blood Cancer, 2017; 64(4).
34. LIBERMAN RF, et al. Assisted Reproductive Technology and Birth Defects: Effects of Subfertility and Multiple Births. Birth Defects Research, 2017; 109(14): 1144-1153.
35. LIU L, et al. Association between assisted reproductive technology and the risk of autism spectrum disorders in the offspring: a meta-analysis. Scientific Reports, 2017; 7: 46207.
36. LUKE B, et al. Factors associated with ovarian hyperstimulation syndrome (OHSS) and its effect on assisted reproductive technology (ART) treatment and outcome. Fertility and Sterility, 2010; 94(4): 1399-1404.
37. OCUMED A, et al. Infertilidade e os riscos associados às técnicas de reprodução assistida. Revista Brasileira de Reprodução Assistida, 2005; 9(3): 113-118.
38. OLAUSSON N, et al. Changes in the plasma microvesicle proteome during the ovarian hyperstimulation phase of assisted reproductive technology. Scientific Reports, 2020; 10(1): 13645.
39. ORGÉAS CC, et al. Breast cancer incidence after hormonal infertility treatment in Sweden: a cohort study. American Journal of Obstetrics and Gynecology, 2009; 200(1): 72-172-7.
40. PAPPO I, et al. The possible association between IVF and breast cancer incidence. Ann Surg Oncol, 2008; 15(4): 1048-1055.
41. PEIPERT BJ, et al. Impact of in vitro fertilization state mandates for third party insurance coverage in the United States: a review and critical assessment. Reprod Biol Endocrinol, 2022; 20(1): 111.
42. REIGSTAD, M. M., et al. Risk of breast cancer following fertility treatment—a registry based cohort study of parous women in Norway. Int J Cancer, 2015; 136(5): 1140-1148.
43. RIOS P, et al. Medically Assisted Reproduction and Risk of Cancer Among Offspring. JAMA Netw Open, 2024; 7(5): 249429.
44. RIZZUTO I, et al. Risk of ovarian cancer in women treated with ovarian stimulating drugs for infertility. Cochrane Database Syst Rev, 2019; 6(6): 8215.
45. ROVA K, et al. Venous thromboembolism in relation to in vitro fertilization: an approach to determining the incidence and increase in risk in successful cycles. Fertil Steril, 2012; 97(1): 95-100.
46. SANDVEI MS, et al. Risk of ovarian cancer in women who give birth after assisted reproductive technology (ART)—a registry-based Nordic cohort study with follow-up from first pregnancy. British Journal of Cancer, 2023; 128(5): 825-832.
47. SARGISIAN N, et al. Congenital heart defects in children born after assisted reproductive technology: a CoNARTaS study. European Heart Journal, 2024; 45(45): 4840-4858.
48. SCHERRER U, et al. Systemic and pulmonary vascular dysfunction in children conceived by assisted reproductive technologies. Circulation, 2012; 125: 1890–1896.
49. SENNSTRÖM M, et al. Thromboembolism and in vitro fertilization - a systematic review. Acta Obstetricia et Gynecologica Scandinavica, 2017; 96(9): 1045-1052.
50. SIRISTATIDIS C, et al. Controlled ovarian hyperstimulation for IVF: impact on ovarian, endometrial and cervical cancer—a systematic review and meta-analysis. Human Reproduction Update, 2013; 19(2): 105-123.
51. SKALKIDOU A, et al. Risk of endometrial cancer in women treated with ovary-stimulating drugs for subfertility. Cochrane Database of Systematic Reviews, 2017; 3: CD010931.
52. SPECTOR LG, et al. Association of in vitro fertilization with childhood cancer in the United States. JAMA Pediatrics, 2019; 173(6): 190392.
53. SPECTOR LG, et al. Genetic and nongenetic risk factors for childhood cancer. Pediatric Clinics of North America, 2015; 62(1): 11-25.
54. STEWART LM, et al. In vitro fertilization is associated with an increased risk of borderline ovarian tumours. Gynecologic Oncology, 2013; 129(2): 372-376.
55. SUNDH KJ, et al. Cancer in children and young adults born after assisted reproductive technology: a Nordic cohort study from the Committee of Nordic ART and Safety (CoNARTaS). Human Reproduction, 2014; 29: 2050–2057.
56. VALENZUELA-ALCARAZ B, et al. Assisted reproductive technologies are associated with cardiovascular remodeling in utero that persists postnatally. Circulation, 2013; 128: 1442–1450.
57. VAN DEN BELT-DUSEBOUT AW, et al. Ovarian stimulation for in vitro fertilization and long-term risk of breast cancer. JAMA, 2016; 316(3): 300.
58. VELEZ MP, et al. Infertility and risk of autism spectrum disorder in children. JAMA Network Open, 2023; 6(11): 2343954.
59. WENG SS, et al. Assisted reproductive technology and risk of childhood cancers. JAMA Network Open, 2022; 5(8): 2230157.
60. WILLIAMS CL, et al. Risks of ovarian, breast, and corpus uteri cancer in women treated with assisted reproductive technology in Great Britain, 1991-2010: data linkage study including 2.2 million person years of observation. BMJ, 2018; 362: 2644.
61. YEUNG EH, et al. Infertility treatment and children’s longitudinal growth between birth and 3 years of age. Human Reproduction, 2016; 31: 1621–1628.
62. YU L, et al. Ovulation induction drug and ovarian cancer: an updated systematic review and meta-analysis. Journal of Ovarian Research, 2023; 16(1): 24.
63. YUSUF BEEBEEJAUN, et al. Risk of breast cancer in women treated with ovarian stimulation drugs for infertility: a systematic review and meta-analysis. Fertility and Sterility, 2021; 116(1): 198-207.
64. ZHU JL, et al. Infertility, infertility treatment and psychomotor development: the Danish National Birth Cohort. Paediatric and Perinatal Epidemiology, 2009; 23: 98–106.
2. AHMADI H, et al. Long-term effects of ART on the health of the offspring. International Journal of Molecular Sciences, 2023; 24(17): 13564-13564.
3. ALMASI-HASHIANI A, et al. Assisted reproductive technology and the risk of preeclampsia: an updated systematic review and meta-analysis. BMC Pregnancy and Childbirth, 2019; 19(1): 149.
4. ANVISA. 2022. Divulgado relatório sobre fertilização in vitro no país em 2020 e 2021. Disponível em:https ://www.gov.br/anvisa/pt-br/assuntos/noticias-anvisa/2022/divulgado-relatorio-sobre-fertilizacao-in-vitro-no-pais-em-2020-e-2021.
5. ARAÚJO FILHO E, et al. Incidência de malformações congênitas em crianças concebidas através de injeção intracitoplasmática de espermatozoides. Revista Brasileira de Ginecologia e Obstetrícia, 2006; 28(2): 81-90.
6. BALACHANDREN N, et al. Venous thromboembolism associated with medically assisted reproduction (MAR): British fertility society policy and practice guidance for assessment and prevention. Human Fertility, 2024; 27(1).
7. BALLESTA-CASTILLEJOS A, et al. Obstetric and perinatal complications associated with assisted reproductive treatment in Spain. J Assist Reprod Genet, 2019; 36(12): 2435–2445.
8. BANICA AM, et al. Obstetric and perinatal complications associated with assisted reproductive techniques – review. MAEDICA – a Journal of Clinical Medicine, 2021; 16(3): 493–498.
9. BASTOS DG da S, et al. Técnicas de reprodução humana nos casos de infertilidade secundária. Contribuciones a las ciencias sociales, 2024; 17(13): 13227.
10. BERNTSEN S, et al. The health of children conceived by ART: “the chicken or the egg?” Human Reproduction Update, 2019; 25(2): 137-158.
11. BITTAR RE, et al. Repercussões neonatais das gestações múltiplas resultantes de técnicas de reprodução assistida. Revista de Ginecologia e Obstetrícia, 2016; 38(1): 45-50.
12. CARSON C, et al. Asthma in children born after infertility treatment: findings from the UK Millennium Cohort Study. Hum Reprod, 2013; 28: 471–479.
13. FABBRO M, et al. HE4 and CA-125 kinetics to predict outcome in patients with recurrent epithelial ovarian carcinoma: the META4 clinical trial. Front Oncol, 2024; 13: 1308630.
14. FARHUD DD, et al. In-vitro fertilization impact on the risk of breast cancer: A review article. Iran J Public Health, 2021; 50(3): 438–447.
15. FARHUD DD, et al. Strong evidences of the ovarian carcinoma risk in women after IVF treatment: A review article. Iran J Public Health, 2019; 48(12): 2124-2132.
16. FAUQUE P, et al. Do in vitro fertilization, intrauterine insemination or female infertility impact the risk of congenital anomalies in singletons? A longitudinal national French study. Human Reproduction, 2021; 36(3): 808-816.
17. FUJIMOTO A, et al. The outcome of infertility treatment in patients undergoing assisted reproductive technology after conservative therapy for endometrial cancer. Journal of Assisted Reproduction and Genetics, 2014; 31(9): 1189-1194.
18. GARCÍA-PLANELLS J, et al. BRCA, breast cancer and in vitro fertilization: How should we advise our patients? Fertil Steril, 2021; 116(2): 359-360.
19. GRANER VR e BARROS SM O de. Complicações maternas e ocorrências neonatais associadas às gestações múltiplas resultantes de técnicas de reprodução assistida. Revista da Escola de Enfermagem da USP, 2009; 43(1): 103-109.
20. GUI J, et al. In vitro fertilization is associated with the onset and progression of preeclampsia. Placenta, 2020; 89: 50-57.
21. GUO XY, et al. Cardiovascular and metabolic profiles of offspring conceived by assisted reproductive technologies: a systematic review and meta-analysis. Fertil Steril, 2017; 107(3): 622-631-5.
22. HARGREAVE M. Cancer risk among children born after fertility treatment. JAMA Network Open, 2024; 7(5): 249435.
23. HART R e NORMAN RJ. The longer-term health outcomes for children born as a result of IVF treatment. Part II—Mental health and development outcomes. Human Reproduction Update, 2013; 19(3): 244–250.
24. HATTORI H, et al. Association of four imprinting disorders and ART. Clinical Epigenetics, 2019; 11: 21.
25. HVIDTJØRN D, et al. Risk of autism spectrum disorders in children born after assisted conception: a population-based follow-up study. J Epidemiol Community Health, 2011; 65: 497–502.
26. JIANG Y, et al. Infertility and ovarian cancer risk: Evidence from nine prospective cohort studies. International Journal of Cancer, 2020; 147(8): 2121-2130.
27. KÄLLÉN B, et al. Asthma in Swedish children conceived by in vitro fertilisation. Arch Dis Child, 2013; 98(2): 92-96.
28. KATZ D, et al. Beginning IVF treatments after age 30 increases the risk of breast cancer: Results of a case-control study. Breast J, 2008; 14(6): 517-522.
29. KORHONEN P, et al. Calcium supplementation during pregnancy and long-term offspring outcome: A systematic literature review and meta-analysis. Ann N Y Acad Sci, 2022; 1510(1): 36-51.
30. KROENER L, et al. Use of fertility medications and cancer risk: a review and update. Curr Opin Obstet Gynecol, 2017; 29(4): 195-201.
31. LABARTA E, et al. Moderate ovarian stimulation does not increase the incidence of human embryo chromosomal abnormalities in in vitro fertilization cycles. J Clin Endocrinol Metab, 2012; 97(10): 1987-1994.
32. LARCHER L, et al. Ultrasound diagnosis of placental and umbilical cord anomalies in singleton pregnancies resulting from in-vitro fertilization. Placenta, 2023; 131: 58-64.
33. LERNER-GEVA L, et al. Possible risk for cancer among children born following assisted reproductive technology in Israel. Pediatr Blood Cancer, 2017; 64(4).
34. LIBERMAN RF, et al. Assisted Reproductive Technology and Birth Defects: Effects of Subfertility and Multiple Births. Birth Defects Research, 2017; 109(14): 1144-1153.
35. LIU L, et al. Association between assisted reproductive technology and the risk of autism spectrum disorders in the offspring: a meta-analysis. Scientific Reports, 2017; 7: 46207.
36. LUKE B, et al. Factors associated with ovarian hyperstimulation syndrome (OHSS) and its effect on assisted reproductive technology (ART) treatment and outcome. Fertility and Sterility, 2010; 94(4): 1399-1404.
37. OCUMED A, et al. Infertilidade e os riscos associados às técnicas de reprodução assistida. Revista Brasileira de Reprodução Assistida, 2005; 9(3): 113-118.
38. OLAUSSON N, et al. Changes in the plasma microvesicle proteome during the ovarian hyperstimulation phase of assisted reproductive technology. Scientific Reports, 2020; 10(1): 13645.
39. ORGÉAS CC, et al. Breast cancer incidence after hormonal infertility treatment in Sweden: a cohort study. American Journal of Obstetrics and Gynecology, 2009; 200(1): 72-172-7.
40. PAPPO I, et al. The possible association between IVF and breast cancer incidence. Ann Surg Oncol, 2008; 15(4): 1048-1055.
41. PEIPERT BJ, et al. Impact of in vitro fertilization state mandates for third party insurance coverage in the United States: a review and critical assessment. Reprod Biol Endocrinol, 2022; 20(1): 111.
42. REIGSTAD, M. M., et al. Risk of breast cancer following fertility treatment—a registry based cohort study of parous women in Norway. Int J Cancer, 2015; 136(5): 1140-1148.
43. RIOS P, et al. Medically Assisted Reproduction and Risk of Cancer Among Offspring. JAMA Netw Open, 2024; 7(5): 249429.
44. RIZZUTO I, et al. Risk of ovarian cancer in women treated with ovarian stimulating drugs for infertility. Cochrane Database Syst Rev, 2019; 6(6): 8215.
45. ROVA K, et al. Venous thromboembolism in relation to in vitro fertilization: an approach to determining the incidence and increase in risk in successful cycles. Fertil Steril, 2012; 97(1): 95-100.
46. SANDVEI MS, et al. Risk of ovarian cancer in women who give birth after assisted reproductive technology (ART)—a registry-based Nordic cohort study with follow-up from first pregnancy. British Journal of Cancer, 2023; 128(5): 825-832.
47. SARGISIAN N, et al. Congenital heart defects in children born after assisted reproductive technology: a CoNARTaS study. European Heart Journal, 2024; 45(45): 4840-4858.
48. SCHERRER U, et al. Systemic and pulmonary vascular dysfunction in children conceived by assisted reproductive technologies. Circulation, 2012; 125: 1890–1896.
49. SENNSTRÖM M, et al. Thromboembolism and in vitro fertilization - a systematic review. Acta Obstetricia et Gynecologica Scandinavica, 2017; 96(9): 1045-1052.
50. SIRISTATIDIS C, et al. Controlled ovarian hyperstimulation for IVF: impact on ovarian, endometrial and cervical cancer—a systematic review and meta-analysis. Human Reproduction Update, 2013; 19(2): 105-123.
51. SKALKIDOU A, et al. Risk of endometrial cancer in women treated with ovary-stimulating drugs for subfertility. Cochrane Database of Systematic Reviews, 2017; 3: CD010931.
52. SPECTOR LG, et al. Association of in vitro fertilization with childhood cancer in the United States. JAMA Pediatrics, 2019; 173(6): 190392.
53. SPECTOR LG, et al. Genetic and nongenetic risk factors for childhood cancer. Pediatric Clinics of North America, 2015; 62(1): 11-25.
54. STEWART LM, et al. In vitro fertilization is associated with an increased risk of borderline ovarian tumours. Gynecologic Oncology, 2013; 129(2): 372-376.
55. SUNDH KJ, et al. Cancer in children and young adults born after assisted reproductive technology: a Nordic cohort study from the Committee of Nordic ART and Safety (CoNARTaS). Human Reproduction, 2014; 29: 2050–2057.
56. VALENZUELA-ALCARAZ B, et al. Assisted reproductive technologies are associated with cardiovascular remodeling in utero that persists postnatally. Circulation, 2013; 128: 1442–1450.
57. VAN DEN BELT-DUSEBOUT AW, et al. Ovarian stimulation for in vitro fertilization and long-term risk of breast cancer. JAMA, 2016; 316(3): 300.
58. VELEZ MP, et al. Infertility and risk of autism spectrum disorder in children. JAMA Network Open, 2023; 6(11): 2343954.
59. WENG SS, et al. Assisted reproductive technology and risk of childhood cancers. JAMA Network Open, 2022; 5(8): 2230157.
60. WILLIAMS CL, et al. Risks of ovarian, breast, and corpus uteri cancer in women treated with assisted reproductive technology in Great Britain, 1991-2010: data linkage study including 2.2 million person years of observation. BMJ, 2018; 362: 2644.
61. YEUNG EH, et al. Infertility treatment and children’s longitudinal growth between birth and 3 years of age. Human Reproduction, 2016; 31: 1621–1628.
62. YU L, et al. Ovulation induction drug and ovarian cancer: an updated systematic review and meta-analysis. Journal of Ovarian Research, 2023; 16(1): 24.
63. YUSUF BEEBEEJAUN, et al. Risk of breast cancer in women treated with ovarian stimulation drugs for infertility: a systematic review and meta-analysis. Fertility and Sterility, 2021; 116(1): 198-207.
64. ZHU JL, et al. Infertility, infertility treatment and psychomotor development: the Danish National Birth Cohort. Paediatric and Perinatal Epidemiology, 2009; 23: 98–106.