Assisted Reproductive Technology and Birth Defects Among Liveborn Infants in Florida, Massachusetts, and Michigan, 2000-2010 | Congenital Defects | JAMA Pediatrics | JAMA Network
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1.
Sunderam  S, Kissin  DM, Crawford  SB,  et al; Centers for Disease Control and Prevention.  Assisted reproductive technology surveillance—United States, 2012.  MMWR Surveill Summ. 2015;64(6):1-29.PubMedGoogle ScholarCrossref
2.
Centers for Disease Control and Prevention ASfRM, Society for Assisted Reproductive Technology.  2012 Assisted Reproductive Technology National Summary Report. Atlanta, GA: US Dept of Health and Human Services; 2014.
3.
Davies  MJ, Moore  VM, Willson  KJ,  et al.  Reproductive technologies and the risk of birth defects.  N Engl J Med. 2012;366(19):1803-1813.PubMedGoogle ScholarCrossref
4.
Heisey  AS, Bell  EM, Herdt-Losavio  ML, Druschel  C.  Surveillance of congenital malformations in infants conceived through assisted reproductive technology or other fertility treatments.  Birth Defects Res A Clin Mol Teratol. 2015;103(2):119-126.PubMedGoogle ScholarCrossref
5.
Källén  B, Finnström  O, Lindam  A, Nilsson  E, Nygren  KG, Otterblad  PO.  Congenital malformations in infants born after in vitro fertilization in Sweden.  Birth Defects Res A Clin Mol Teratol. 2010;88(3):137-143.PubMedGoogle Scholar
6.
Hansen  M, Kurinczuk  JJ, Milne  E, de Klerk  N, Bower  C.  Assisted reproductive technology and birth defects: a systematic review and meta-analysis.  Hum Reprod Update. 2013;19(4):330-353.PubMedGoogle ScholarCrossref
7.
Wen  J, Jiang  J, Ding  C,  et al.  Birth defects in children conceived by in vitro fertilization and intracytoplasmic sperm injection: a meta-analysis.  Fertil Steril. 2012;97(6):1331-7.PubMedGoogle ScholarCrossref
8.
Pandey  S, Shetty  A, Hamilton  M, Bhattacharya  S, Maheshwari  A.  Obstetric and perinatal outcomes in singleton pregnancies resulting from IVF/ICSI: a systematic review and meta-analysis.  Hum Reprod Update. 2012;18(5):485-503.PubMedGoogle ScholarCrossref
9.
Maheshwari  A, Pandey  S, Shetty  A, Hamilton  M, Bhattacharya  S.  Obstetric and perinatal outcomes in singleton pregnancies resulting from the transfer of frozen thawed versus fresh embryos generated through in vitro fertilization treatment: a systematic review and meta-analysis.  Fertil Steril. 2012;98(2):368-77.e1, 9.PubMedGoogle ScholarCrossref
10.
Pelkonen  S, Hartikainen  AL, Ritvanen  A,  et al.  Major congenital anomalies in children born after frozen embryo transfer: a cohort study 1995-2006.  Hum Reprod. 2014;29(7):1552-1557.PubMedGoogle ScholarCrossref
11.
Pinborg  A, Loft  A, Aaris Henningsen  AK, Rasmussen  S, Andersen  AN.  Infant outcome of 957 singletons born after frozen embryo replacement: the Danish National Cohort Study 1995-2006.  Fertil Steril. 2010;94(4):1320-1327.PubMedGoogle ScholarCrossref
12.
Sazonova  A, Källen  K, Thurin-Kjellberg  A, Wennerholm  UB, Bergh  C.  Obstetric outcome in singletons after in vitro fertilization with cryopreserved/thawed embryos.  Hum Reprod. 2012;27(5):1343-1350.PubMedGoogle ScholarCrossref
13.
Halliday  JL, Ukoumunne  OC, Baker  HW,  et al.  Increased risk of blastogenesis birth defects, arising in the first 4 weeks of pregnancy, after assisted reproductive technologies.  Hum Reprod. 2010;25(1):59-65.PubMedGoogle ScholarCrossref
14.
Ma  S, Rowe  T, Yuen  BH.  Impact of assisted hatching on the outcome of intracytoplasmic sperm injection: a prospective, randomized clinical trial and pregnancy follow-up.  Fertil Steril. 2006;85(4):895-900.PubMedGoogle ScholarCrossref
15.
Jwa  J, Jwa  SC, Kuwahara  A, Yoshida  A, Saito  H.  Risk of major congenital anomalies after assisted hatching: analysis of three-year data from the national assisted reproduction registry in Japan.  Fertil Steril. 2015;104(1):71-78.PubMedGoogle ScholarCrossref
16.
Gupta  S, Fox  NS, Rebarber  A, Saltzman  DH, Klauser  CK, Roman  AS.  Biochemical screening for aneuploidy in patients with donor oocyte pregnancies compared with autologous pregnancies.  J Matern Fetal Neonatal Med. 2014;27(14):1418-1421.PubMedGoogle ScholarCrossref
17.
Källén  B, Finnström  O, Lindam  A, Nilsson  E, Nygren  KG, Olausson  PO.  Blastocyst versus cleavage stage transfer in in vitro fertilization: differences in neonatal outcome?  Fertil Steril. 2010;94(5):1680-1683.PubMedGoogle ScholarCrossref
18.
Wikland  M, Hardarson  T, Hillensjö  T,  et al.  Obstetric outcomes after transfer of vitrified blastocysts.  Hum Reprod. 2010;25(7):1699-1707.PubMedGoogle ScholarCrossref
19.
Mneimneh  AS, Boulet  SL, Sunderam  S,  et al; States Monitoring ART (SMART) Collaborative.  States Monitoring Assisted Reproductive Technology (SMART) Collaborative: data collection, linkage, dissemination, and use.  J Womens Health (Larchmt). 2013;22(7):571-577.PubMedGoogle ScholarCrossref
20.
Zhang  Y, Cohen  B, Macaluso  M, Zhang  Z, Durant  T, Nannini  A.  Probabilistic linkage of assisted reproductive technology information with vital records, Massachusetts 1997-2000.  Matern Child Health J. 2012;16(8):1703-1708.PubMedGoogle ScholarCrossref
21.
Canfield  MA, Honein  MA, Yuskiv  N,  et al.  National estimates and race/ethnic-specific variation of selected birth defects in the United States, 1999-2001.  Birth Defects Res A Clin Mol Teratol. 2006;76(11):747-756.PubMedGoogle ScholarCrossref
22.
Parker  SE, Mai  CT, Canfield  MA,  et al; National Birth Defects Prevention Network.  Updated National Birth Prevalence estimates for selected birth defects in the United States, 2004-2006.  Birth Defects Res A Clin Mol Teratol. 2010;88(12):1008-1016.PubMedGoogle ScholarCrossref
23.
Morris  JK, Wald  NJ, Mutton  DE, Alberman  E.  Comparison of models of maternal age-specific risk for Down syndrome live births.  Prenat Diagn. 2003;23(3):252-258.PubMedGoogle ScholarCrossref
24.
Kissin  DM, Kawwass  JF, Monsour  M, Boulet  SL, Session  DR, Jamieson  DJ; National ART Surveillance System Group.  Assisted hatching: trends and pregnancy outcomes, United States, 2000-2010.  Fertil Steril. 2014;102(3):795-801.PubMedGoogle ScholarCrossref
25.
Waller  DK, Shaw  GM, Rasmussen  SA,  et al; National Birth Defects Prevention Study.  Prepregnancy obesity as a risk factor for structural birth defects.  Arch Pediatr Adolesc Med. 2007;161(8):745-750.PubMedGoogle ScholarCrossref
26.
Palomba  S, de Wilde  MA, Falbo  A, Koster  MP, La Sala  GB, Fauser  BC.  Pregnancy complications in women with polycystic ovary syndrome.  Hum Reprod Update. 2015;21(5):575-592.PubMedGoogle ScholarCrossref
27.
Centers for Disease Control and Prevention.  Update on overall prevalence of major birth defects–Atlanta, Georgia, 1978-2005.  MMWR Morb Mortal Wkly Rep. 2008;57(1):1-5.PubMedGoogle Scholar
28.
Hansen  M, Kurinczuk  JJ, de Klerk  N, Burton  P, Bower  C.  Assisted reproductive technology and major birth defects in Western Australia.  Obstet Gynecol. 2012;120(4):852-863.PubMedGoogle ScholarCrossref
29.
Olson  CK, Keppler-Noreuil  KM, Romitti  PA,  et al.  In vitro fertilization is associated with an increase in major birth defects.  Fertil Steril. 2005;84(5):1308-1315.PubMedGoogle ScholarCrossref
30.
Reefhuis  J, Honein  MA, Schieve  LA, Correa  A, Hobbs  CA, Rasmussen  SA; National Birth Defects Prevention Study.  Assisted reproductive technology and major structural birth defects in the United States.  Hum Reprod. 2009;24(2):360-366.PubMedGoogle ScholarCrossref
31.
Zhu  JL, Basso  O, Obel  C, Bille  C, Olsen  J.  Infertility, infertility treatment, and congenital malformations: Danish national birth cohort.  BMJ. 2006;333(7570):679.PubMedGoogle ScholarCrossref
32.
Zwink  N, Jenetzky  E, Schmiedeke  E,  et al; CURE-Net Consortium.  Assisted reproductive techniques and the risk of anorectal malformations: a German case-control study.  Orphanet J Rare Dis. 2012;7:65.PubMedGoogle ScholarCrossref
33.
Tararbit  K, Houyel  L, Bonnet  D,  et al.  Risk of congenital heart defects associated with assisted reproductive technologies: a population-based evaluation.  Eur Heart J. 2011;32(4):500-508.PubMedGoogle ScholarCrossref
34.
Ginsburg  ES, Baker  VL, Racowsky  C, Wantman  E, Goldfarb  J, Stern  JE.  Use of preimplantation genetic diagnosis and preimplantation genetic screening in the United States: a Society for Assisted Reproductive Technology Writing Group paper.  Fertil Steril. 2011;96(4):865-868.PubMedGoogle ScholarCrossref
35.
Natoli  JL, Ackerman  DL, McDermott  S, Edwards  JG.  Prenatal diagnosis of Down syndrome: a systematic review of termination rates (1995-2011).  Prenat Diagn. 2012;32(2):142-153.PubMedGoogle ScholarCrossref
36.
Fedder  J, Loft  A, Parner  ET, Rasmussen  S, Pinborg  A.  Neonatal outcome and congenital malformations in children born after ICSI with testicular or epididymal sperm: a controlled national cohort study.  Hum Reprod. 2013;28(1):230-240.PubMedGoogle ScholarCrossref
37.
Massaro  PA, MacLellan  DL, Anderson  PA, Romao  RL.  Does intracytoplasmic sperm injection pose an increased risk of genitourinary congenital malformations in offspring compared to in vitro fertilization? A systematic review and meta-analysis.  J Urol. 2015;193(5)(suppl):1837-1842.PubMedGoogle ScholarCrossref
38.
Pinborg  A, Lidegaard  O, Freiesleben  Nl, Andersen  AN.  Vanishing twins: a predictor of small-for-gestational age in IVF singletons.  Hum Reprod. 2007;22(10):2707-2714.PubMedGoogle ScholarCrossref
39.
Cragan  JD, Khoury  MJ.  Effect of prenatal diagnosis on epidemiologic studies of birth defects.  Epidemiology. 2000;11(6):695-699.PubMedGoogle ScholarCrossref
Original Investigation
June 6, 2016

Assisted Reproductive Technology and Birth Defects Among Liveborn Infants in Florida, Massachusetts, and Michigan, 2000-2010

Author Affiliations
  • 1National Center for Chronic Disease Prevention and Health Promotion, Centers for Disease Control and Prevention, Atlanta, Georgia
  • 2University of South Florida, Tampa
  • 3National Center on Birth Defects and Developmental Disabilities, Centers for Disease Control and Prevention, Atlanta, Georgia
  • 4Massachusetts Department of Public Health, Boston
  • 5Michigan Department of Health and Human Services, Lansing
  • 6Florida Department of Health, Tallahassee
JAMA Pediatr. 2016;170(6):e154934. doi:10.1001/jamapediatrics.2015.4934
Abstract

Importance  Use of assisted reproductive technology (ART) has been associated with increased risks for birth defects. Variations in birth defect risks according to type of ART procedure have been noted, but findings are inconsistent.

Objectives  To examine the prevalence of birth defects among liveborn infants conceived with and without ART and to evaluate risks associated with certain ART procedures among ART-conceived infants.

Design, Setting, and Participants  Used linked ART surveillance, birth certificates, and birth defects registry data for 3 states (Florida, Massachusetts, and Michigan). Methods for ascertaining birth defect cases varied by state. Resident live births during 2000 to 2010 were included, and the analysis was conducted between Feburary 2015 and August 2015.

Exposures  Use of ART among all live births and use of certain ART procedures among ART births.

Main Outcome and Measures  Prevalence of selected chromosomal and nonchromosomal birth defects that are usually diagnosed at or immediately after birth.

Results  Of the 4 618 076 liveborn infants between 2000 and 2010, 64 861 (1.4%) were conceived using ART. Overall, the prevalence of 1 or more of the selected nonchromosomal defects was 58.59 per 10 000 for ART infants (n = 389) vs 47.50 per 10 000 for non-ART infants (n = 22 036). The association remained significant after adjusting for maternal characteristics and year of birth (adjusted risk ratio [aRR], 1.28; 95% CI, 1.15-1.42). Similar differences were observed for singleton ART births vs their non-ART counterparts (63.69 per 10 000 [n = 218] vs 47.17 per 10 000 [n = 21 251]; aRR, 1.38; 95% CI, 1.21-1.59). Among multiple births, the prevalence of rectal and large intestinal atresia/stenosis was higher for ART births compared with non-ART births (aRR, 2.39; 95% CI, 1.38-4.12). Among ART births conceived after fresh embryo transfer, infants born to mothers with ovulation disorders had a higher prevalence of nonchromosomal birth defects (aRR, 1.53; 95% CI, 1.13-2.06) than those born to mothers without the diagnosis, and use of assisted hatching was associated with birth defects among singleton births (aRR, 1.55; 95% CI, 1.10-2.19). Multiplicity-adjusted P values for these associations were greater than .05.

Conclusions and Relevance  Infants conceived after ART had a higher prevalence of certain birth defects. Assisted hatching and diagnosis of ovulation disorder were marginally associated with increased risks for nonchromosomal birth defects; however, these associations may be caused by other underlying factors.

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