Dorte Hvidtjørn
Aarhus University
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JAMA Pediatrics | 2009
Dorte Hvidtjørn; Laura A. Schieve; Diana E. Schendel; Bo Jacobsson; Claus Sværke; Poul Thorsen
OBJECTIVE To assess the existing evidence of associations between assisted conception and cerebral palsy (CP), autism spectrum disorders (ASD), and developmental delay. DATA SOURCES Forty-one studies identified in a systematical PubMed and Excerpta Medica Database (EMBASE) search for articles published from January 1, 1996, to April 1, 2008. STUDY SELECTION Studies written in English comparing children born after assisted conception with children born after natural conception assessing CP, ASD, and developmental delay, based on original data with a follow-up of 1 year or more. Main Exposures In vitro fertilization (IVF) with or without intracytoplasmic sperm injection or ovulation induction with or without subsequent intrauterine insemination. MAIN OUTCOME MEASURES Cerebral palsy, ASD, and developmental delay. RESULTS Nine CP studies showed that children born after IVF had an increased risk of CP associated with preterm delivery. In our meta-analysis including 19 462 children exposed to IVF, we estimated a crude odds ratio of 2.18 (95% confidence interval, 1.71-2.77). Eight ASD studies and 30 studies on developmental delay showed inconsistent results. No studies assessed the risk of CP, ASD, or developmental delay in children born after ovulation induction exclusively. CONCLUSIONS Methodological problems were revealed in the identified studies, and the gaps in our knowledge about the long-term outcomes of children born after assisted conception are considerable, including a lack of information on the long-term consequences of ovulation induction. Possible associations with ASD and developmental delay need assessment in larger studies. Studies on assisted conception and CP from countries outside of Scandinavia are needed, including detailed information on time to pregnancy, underlying cause of infertility, and type of IVF treatment.
Pediatrics | 2006
Dorte Hvidtjørn; Jakob Grove; Diana E. Schendel; Michael Væth; Erik Ernst; Lene Nielsen; Poul Thorsen
OBJECTIVE. Our aim was to assess the incidence of cerebral palsy among children conceived with in vitro fertilization and children conceived without in vitro fertilization. METHODS. A population-based, cohort study, including all live-born singletons and twins born in Denmark between January 1, 1995, and December 31, 2000, was performed. Children conceived with in vitro fertilization (9255 children) were identified through the In Vitro Fertilization Register; children conceived without in vitro fertilization (394713) were identified through the Danish Medical Birth Register. Cerebral palsy diagnoses were obtained from the National Register of Hospital Discharges. The main outcome measure was the incidence of cerebral palsy in the in vitro fertilization and non-in vitro fertilization groups. RESULTS. Children born after in vitro fertilization had an increased risk of cerebral palsy; these results were largely unchanged after adjustment for maternal age, gender, parity, small-for-gestational age status, and educational level. The independent effect of in vitro fertilization vanished after additional adjustment for multiplicity or preterm delivery. When both multiplicity and preterm delivery were included in the multivariate models, preterm delivery remained associated strongly with the risk of cerebral palsy. CONCLUSIONS. The large proportions of preterm deliveries with in vitro fertilization, primarily for twins but also for singletons, pose an increased risk of cerebral palsy.
Journal of Epidemiology and Community Health | 2011
Dorte Hvidtjørn; Jakob Grove; Diana E. Schendel; Laura A. Schieve; Claus Sværke; Erik Ernst; Poul Thorsen
Objectives To assess the risk of autism spectrum disorders (ASD) in children born after assisted conception compared with children born after natural conception. Design Population-based follow-up study. Setting All children born alive in Denmark 1995–2003. Participants 588 967 children born in Denmark from January 1995 to December 2003. Assisted conception was defined as in vitro fertilisation (IVF) with or without intracytoplasmic sperm injection and ovulation induction (OI) with or without subsequent insemination. Children exposed to IVF or OI were identified in the IVF Register and in the Danish Drug Prescription Register. Main outcome measures A diagnosis of ASD in the Danish Psychiatric Central Register. Results 33 139 (5.6%) of all children born in Denmark in 1995–2003 resulted from assisted conception, 225 of whom (0.68%) had a diagnosis of ASD. Of the 555 828 children born in this period after natural conception, 3394 (0.61%) had a diagnosis of ASD. The follow-up time was 4–13 years (median 9 years). In crude analyses, children born after assisted conception had an increased risk of a diagnosis of ASD: crude hazard rate ratio (HRR) 1.25 (95% CI 1.09 to 1.43). In analyses adjusting for maternal age, educational level, parity, smoking, birth weight and multiplicity, the risk disappeared: adjusted HRR 1.13. (95% CI 0.97 to 1.31). However, subgroup analyses that suggest possible associations in women who received follicle stimulating hormone indicate the need for further study. Discussion This population-based follow-up study found no risk of ASD in children born after assisted conception.
British Journal of Obstetrics and Gynaecology | 2008
Lene Nielsen; Diana E. Schendel; Jakob Grove; Dorte Hvidtjørn; Bo Jacobsson; Trine Landau Josiassen; Mogens Vestergaard; Peter Uldall; Poul Thorsen
Objective To investigate the association of asphyxia‐related conditions (reducing blood flow or blood oxygen levels in the fetus) with spastic cerebral palsy (CP) considering different gestational age groups and the timing of risk.
Human Reproduction | 2010
Dorte Hvidtjørn; Jakob Grove; Diana E. Schendel; Claus Sværke; Laura A. Schieve; Peter Uldall; Erik Ernst; Bo Jacobsson; Poul Thorsen
BACKGROUND This paper assesses the risk of cerebral palsy (CP) in children born after assisted conception compared with children born after natural conception (NC). METHODS This population based follow-up study included all 588,967 children born in Denmark from 1995 to 2003. Assisted conception was defined as IVF, with or without ICSI, and ovulation induction (OI), with or without subsequent insemination. RESULTS There were 33 139 (5.6%) children born in Denmark from 1995 to 2003 as a result of assisted conception and through to June 2009, 1146 (0.19%) children received a CP diagnosis. Children born after assisted conception had an increased risk of a CP diagnosis, crude hazard rate ratio (HRR) 1.90 (95% CI: 1.57-2.31) compared with NC children. Divided into IVF and OI children compared with NC children, the risk was HRR 2.34 (95% CI: 1.81-3.01) and HRR 1.55 (95% CI: 1.17-2.06), respectively. When we included the intermediate factors multiplicity and gestational age in multivariate models, the risk of CP in assisted conception disappeared. In general, children with CP born after assisted conception had similar CP subtypes and co-morbidities as children with CP born after NC. CONCLUSION The risk of CP is increased after both IVF and OI. The increased risk of CP in children born after assisted conception, and in particular IVF, is strongly associated with the high proportion of multiplicity and preterm delivery in these pregnancies. A more widespread use of single embryo transfer warrants consideration to enhance the long-term health of children born after IVF.
Paediatric and Perinatal Epidemiology | 2009
Jin Liang Zhu; Olga Basso; Carsten Obel; Dorte Hvidtjørn; Jørn Olsen
Babies born of infertile couples, regardless of treatment, have a higher risk of preterm birth and low birthweight, conditions associated with delayed development. We examined developmental milestones in singletons as a function of parental infertility [time to pregnancy (TTP) > 12 months] and infertility treatment. From the Danish National Birth Cohort (1997-2003), we identified 37 897 singletons born of fertile couples (TTP < or = 12 months), 4351 born of infertile couples conceiving naturally (TTP > 12 months), and 3309 born after infertility treatment. When the children were about 18 months old, mothers reported 12 developmental milestones by responding to structured questions. We defined a failure to achieve the assessed milestone or the minimal numbers of milestones in a summary (motor, or cognitive/language skills) as delay. Naturally conceived children born of infertile couples had a pattern of psychomotor development similar to that of children born of fertile couples, but increasing TTP correlated with a modest delay. When the analysis was restricted to infertile couples (treated and untreated), children born after treatment showed a slight delay in cognitive/language development (odds ratio 1.24, [95% confidence interval 1.01, 1.53]) for not meeting at least three out of six cognitive/language milestones); children born after intracytoplasmic sperm injection (ICSI) had the highest estimated relative risk of delay for most milestones, especially motor milestones. These results suggest that a long TTP may be associated with a modest developmental delay. Infertility treatment, especially ICSI, may be associated with a slight delay for some of these early milestones.
BMJ | 2013
Bjørn Bay; Erik Lykke Mortensen; Dorte Hvidtjørn; Ulrik Schiøler Kesmodel
Objective To assess the mental health of children born after fertility treatment by comparing their risk of mental disorders with that of spontaneously conceived children. Design Prospective register based cohort study. Setting Nationwide register based information from Danish National Health Registers cross linked by a unique personal identification number assigned to all citizens in Denmark. Participants All children born in Denmark in 1995-2003 with follow-up in 2012 when the children were aged 8-17; 33 139 children were conceived after fertility treatment and 555 828 children were born after spontaneous conception. Main outcome measures Absolute risks and hazard ratios for overall and specific mental disorders estimated with adjustment for potential confounding variables. Estimated association between the risk of mental disorders and subtypes of procedures, hormone treatments, gamete types, and cause of infertility. Results The risk of mental disorders in children born after in vitro fertilisation or intracytoplasmic sperm injection was low, and was no higher than in spontaneously conceived children, except for a borderline significant increased risk of tic disorders (hazard ratio 1.40, 95% confidence interval 1.01 to 1.95; absolute risk 0.3%). In contrast, children born after ovulation induction with or without insemination had low but significantly increased risks of any mental disorder (1.20, 1.11 to 1.31; absolute risk 4.1%), autism spectrum disorders (1.20, 1.05 to 1.37; 1.5%), hyperkinetic disorders (1.23, 1.08 to 1.40; 1.7%), conduct, emotional, or social disorder (1.21, 1.02 to 1.45; 0.8%), and tic disorders (1.51, 1.16 to 1.96; 0.4%). There was no risk systematically related to any specific type of hormone drug treatment. Conclusions There was a small increase in the incidence of mental disorders in children born after ovulation induction/intrauterine insemination. Children born after in vitro fertilisation/intracytoplasmic sperm injection were found to have overall risk comparable with children conceived spontaneously.
Human Reproduction | 2010
Jin Liang Zhu; Dorte Hvidtjørn; Olga Basso; Carsten Obel; Poul Thorsen; Peter Uldall; Jørn Olsen
BACKGROUND Children born after in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) have been reported to have a higher risk of cerebral palsy (CP), perhaps due to the higher frequency of preterm birth, multiple births or vanishing embryo in the pregnancies. However, it has been suggested that the underlying infertility may be part of the pathway. In this study, we examined whether untreated subfecundity (measured by time to pregnancy) or infertility treatment was associated with an increased risk of CP in the offspring. METHODS Using the Danish National Birth Cohort (1997-2003), we compared children born after 0-2 months of waiting time to pregnancy (n = 35 848) with those born after a time to pregnancy of 3-5 months (n = 15 361), 6-12 months (n = 11 528) and >12 months (n = 7387), as well as those born after IVF/ICSI (n = 3617), ovulation induction with or without intrauterine insemination (n = 3000), and unplanned pregnancies (n = 13 462). CP cases were identified through the Danish CP Register. RESULTS In total, 165 (0.18%) children were diagnosed with CP in the entire cohort. We found no significant association between time to pregnancy and the risk of CP in children conceived spontaneously. Children born after IVF/ICSI had an increased risk of CP, even after adjustment for preterm birth and multiplicity (hazard ratio 2.30, 95% confidence interval 1.12-4.73). CONCLUSIONS Subfecundity per se did not appear to be associated with the risk of CP in children, whereas being born after IVF/ICSI conferred an increased risk.
Human Reproduction | 2009
Dorte Hvidtjørn; Jakob Grove; Diana E. Schendel; Laura A. Schieve; Erik Ernst; Jørn Olsen; Poul Thorsen
BACKGROUND An increasing number of children are born after assisted conception and in surveillance programmes information on mode of conception is often achieved via maternal self-report. We assessed the validity of self-reported assisted conception in The Danish National Birth Cohort (DNBC), a prospective pregnancy cohort. Here, the term assisted conception refers to IVF, ICSI, ovulation induction and insemination. METHODS We compared self-reported assisted conception in the DNBC to corresponding data from Danish national registers; the IVF Register and Danish Drug Prescription Register, providing method of conception in the entire population. In the DNBC, 101,042 women accepted the invitation in early pregnancy from 1996 to 2002. Our final study population comprised 88,151 DNBC women aged 20 years and older who participated in the first DNBC interview with a pregnancy resulting in a live born child. RESULTS In the DNBC, assisted conception was reported with a sensitivity of 83% and positive predictive value of 88%. Misclassification was largely explained by ambiguous phrasing of the DNBC interview question and interview skip patterns. Women with false negative reporting were more often multipara (P < 0.001) and older (P = 0.027 for IVF/ICSI and P = 0.002 for ovulation induction). The risk ratio (RR) for being born preterm in IVF/ICSI children was lower for children identified via the DNBC, RR 3.61 (95% confidence interval (CI) 3.31-3.94), than the IVF Register, RR 4.36 (95% CI 4.02-4.74). CONCLUSIONS There was a high positive predictive value of self-reported assisted conception in the DNBC, but the structure of the DNBC interview represented a problem and misclassification could introduce bias.
British Journal of Obstetrics and Gynaecology | 2016
Dorte Hvidtjørn; Chun Sen Wu; Diana E. Schendel; E. Thorlund Parner; T Brink Henriksen
To assess whether mothers who lost a child from stillbirth or in the first week of life have an increased overall mortality and cause‐specific mortality.