title: Effects of in vitro fertilization and maternal characteristics on perinatal outcomes: a population-based study using siblings.
abstract: OBJECTIVE
  To study birthweight in consecutively born sibling singletons conceived with and without in vitro fertilization (IVF) to disentangle the effects of maternal characteristics from those of the IVF treatment itself.
  
  
  METHODS
  Population-based study.
  
  
  METHODS
  Not applicable.
  
  
  METHODS
  Firstborn and secondborn children from a 9-year birth cohort (1999-2007) comprising of 272,551 women who conceived two siblings.
  
  
  METHODS
  No intervention; children were conceived naturally or through IVF.
  
  
  METHODS
  Birthweight.
  
  
  RESULTS
  The study included 545,102 children born by natural conception (NC) or IVF with the data set obtained from the population-based Netherlands Perinatal Registry (PRN) containing information on pregnancies, deliveries, and neonatal outcomes. We used two approaches: [1] the intersibling approach and [2] the sibling-ship approach. In the first approach we included children born to four groups of mothers who conceived in the following order (numbers indicate birth order): NC1-NC2 (reference, n = 254,721), IVF1-NC2 (n = 1342), NC1-IVF2 (n = 471), and IVF1-IVF2 (n = 687). Several comparisons were made to interpret the effects of IVF and maternal characteristics separately. In the second approach, perinatal outcomes of IVF children (n = 1,813) were compared with those of their NC siblings (n = 1,813). The intersibling analyses suggested an association between maternal characteristics and a lower birthweight, with estimates of the maternal effect ranging from -7 g (95% CI, -40; 26) to -101 g (95% CI, -170; -32). Neither the intersibling analyses nor the sibling-ship analyses indicated an additional adverse effect of IVF treatment itself.
  
  
  CONCLUSIONS
  Maternal characteristics of subfertile women are associated with a lower birthweight. In vitro fertilization treatment itself does not additionally contribute to a lower birthweight in the offspring.
authors.affiliation: Department of Paediatrics, Division Developmental Neurology (CA85), University Medical Center Groningen, University of Groningen, Groningen, the Netherlands. Electronic address: jorienseggers@gmail.com.
authors.forename: Jorien
authors.initials: J
authors.lastname: Seggers
authors.affiliation: Department of Obstetrics and Gynaecology, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands; Department of Obstetrics and Gynaecology, Center for Reproductive Medicine, University of Amsterdam, Amsterdam, the Netherlands; Department of Obstetrics and Gynaecology, Medical Center Alkmaar, Alkmaar, the Netherlands.
authors.forename: Martina
authors.initials: M
authors.lastname: Pontesilli
authors.affiliation: Department of Medical Informatics, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands.
authors.forename: Anita C J
authors.initials: ACJ
authors.lastname: Ravelli
authors.affiliation: Department of Obstetrics and Gynaecology, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands.
authors.forename: Rebecca C
authors.initials: RC
authors.lastname: Painter
authors.affiliation: Department of Paediatrics, Division Developmental Neurology (CA85), University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.
authors.forename: Mijna
authors.initials: M
authors.lastname: Hadders-Algra
authors.affiliation: Department of Obstetrics and Gynaecology, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands.
authors.forename: Maas Jan
authors.initials: MJ
authors.lastname: Heineman
authors.affiliation: Department of Obstetrics and Gynaecology, Center for Reproductive Medicine, University of Amsterdam, Amsterdam, the Netherlands.
authors.forename: Sjoerd
authors.initials: S
authors.lastname: Repping
authors.affiliation: Department of Obstetrics and Gynaecology, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands; School of Pediatrics and Reproductive Health, University of Adelaide, Adelaide, South Australia, Australia.
authors.forename: Ben Willem J
authors.initials: BWJ
authors.lastname: Mol
authors.affiliation: Department of Obstetrics and Gynaecology, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands; Department of Clinical Epidemiology, Biostatistics, and Bioinformatics, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands.
authors.forename: Tessa J
authors.initials: TJ
authors.lastname: Roseboom
authors.affiliation: Department of Obstetrics and Gynaecology, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands; Department of Medical Informatics, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands.
authors.forename: Sabine
authors.initials: S
authors.lastname: Ensing
mesh_terms: D001724:Birth Weight / Q000235:genetics; D005260:Female; D005298:Fertility; D005307:Fertilization in Vitro / Q000009:adverse effects; D006801:Humans; D007230:Infant, Low Birth Weight; D007231:Infant, Newborn; D007246:Infertility / Q000175:diagnosis / Q000453:epidemiology / Q000503:physiopathology / Q000628:therapy*; D050498:Live Birth; D009426:Netherlands / Q000453:epidemiology; D011247:Pregnancy; D011248:Pregnancy Complications / Q000175:diagnosis / Q000453:epidemiology* / Q000235:genetics; D012042:Registries; D012307:Risk Factors; D035781:Siblings; D020554:Sperm Injections, Intracytoplasmic; D013997:Time Factors; D016896:Treatment Outcome
keywords: Assisted reproductive technology; in vitro fertilization; perinatal outcomes; siblings; subfertility