Bjørn Bay

Fertility treatment and risk of childhood and adolescent mental disorders: register based cohort study

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.

Prenatal alcohol exposure - a systematic review of the effects on child motor function.

Objective. To systematically review the available evidence on the effects of prenatal alcohol exposure on motor function in humans. Design. Systematic review. Population. Pregnant women and their offspring. Methods. The search strategy included Medline, Embase, The Cochrane Library and Scopus. The authors read titles and abstracts, and the articles that met the predefined criteria for inclusion were obtained and the full text read. The articles were assessed for quality using the Newcastle–Ottawa Quality Assessment Scale. Main outcome measures. Motor function measured on standardized or validated tests. Results. The search resulted in 311 titles and abstracts, of which 39 were found relevant for inclusion. The findings of this review suggest a negative effect when the maternal consumption exceeded a certain level. Of all studies reporting a maternal intake of more than four drinks/day, only one study showed no effect on motor function, and of all studies reporting intake levels of less than 10 drinks/week, only one study showed deficit on the childrens motor function. Conclusions. While it appears consistent that high daily alcohol intake is associated with deficits in gross and fine motor function, and low weekly intake is not associated with such deficits, the issue of binge drinking is unsettled.

Assisted reproduction and child neurodevelopmental outcomes: a systematic review

OBJECTIVE To systematically review the existing literature on neurodevelopmental outcomes in children born after medically assisted reproduction compared with those of children born after spontaneous conception. DESIGN Systematic review. SETTING Not applicable. PATIENT(S) Children born after medically assisted reproduction vs. reference groups of spontaneously conceived children. INTERVENTION(S) Data were reviewed from worldwide published articles, without restrictions as to publication year or language. A total of 80 studies included between 31 and 2,446,044 children. MAIN OUTCOME MEASURE(S) Child neurodevelopmental outcomes categorized as cognitive, behavioral, emotional or psychomotor development, or diagnoses of mental disorders. RESULT(S) For infants, studies on psychomotor development showed no deficits, but few investigated cognitive or behavioral development. Studies on toddlers generally reported normal cognitive, behavioral, socio-emotional, and psychomotor development. For children in middle childhood, development seems comparable in children born after assisted reproduction and controls, although fewer studies have been conducted with follow-up to this age. Very few studies have assessed neurodevelopmental outcomes among teens, and the results are inconclusive. Studies investigating the risk of diagnoses of mental disorders are generally large, with long follow-up, but the results are inconsistent. CONCLUSION(S) It may tentatively be concluded that the neurodevelopment of children born after fertility treatment is overall comparable to that in children born after spontaneous conception.

Danish sperm donors across three decades: motivations and attitudes

OBJECTIVE To study the motivation and attitudes toward donor anonymity, economic compensation, and insemination of lesbian and single women among Danish sperm donors in 2012 compared with the two preceding decades. DESIGN Anonymous survey. SETTING Danish sperm bank. PATIENT(S) Sperm donors active in 2012 (n = 97), 2002 (n = 62), and 1992 (n = 41). INTERVENTION(S) All donors who donated sperm in the study period were asked to participate. The results were compared with those of previous surveys from the same sperm bank. MAIN OUTCOME MEASURE(S) Motivation and attitudes toward donor anonymity, economic compensation, and insemination of lesbian and single women. RESULT(S) In 2012, the most frequently stated factor was altruism, motivating 90% of the sperm donors, which was not significantly different from the previous surveys. If economic compensations were removed, only 14% would continue to donate. The proportion of anonymous donors who would stop their donations if anonymity was abolished was 51%, 56%, and 67% in 1992, 2002, and 2012, respectively. A significantly increasing proportion of donors felt positive about donation to lesbian couples. CONCLUSION(S) The motivation for sperm donation is multifaceted and primarily based on economic compensation and altruism. Most Danish donors would stop their donations if economic compensation or anonymity were abolished.

Fertility treatment and child intelligence, attention, and executive functions in 5‐year‐old singletons: a cohort study

To assess the association of fertility treatment and subfertility with offspring intelligence, attention, and executive functions in 5‐year‐old singletons.

The association of pre‐pregnancy alcohol drinking with child neuropsychological functioning

To examine the effects of pre‐pregnancy alcohol drinking on child neuropsychological functioning.

Obstetric and neonatal outcomes of pregnancies conceived after preimplantation genetic diagnosis: cohort study and meta-analysis

Preimplantation genetic diagnosis (PGD) may pose risks to pregnancy outcome owing to the invasiveness of the biopsy procedure. This study compares outcome of singleton and twin clinical pregnancies conceived after fresh embryo transfers of PGD (n = 89) and matched intracytoplasmic sperm injection (ICSI) pregnancies (n = 166). The study was carried out in a single university affiliated centre. Because of the paucity of available data, a literature-based meta-analysis of studies comparing neonatal outcome of PGD and ICSI pregnancies was also conducted. In the retrospective cohort study, obstetric and neonatal outcome were available in 67 PGD and 118 ICSI pregnancies. Perinatal outcomes were comparable between PGD and ICSI pregnancies. Meta-analysis revealed similar outcomes, except for higher rate of low birth weight (<2500 g) neonates in ICSI twin pregnancies (RR 0.86, 95% CI 0.74 to 1.0). Mean birth weight, gestational age at birth, pre-term deliveries (<37 weeks) and malformations were all comparable. In this cohort study and subsequent meta-analysis, no association was found between PGD conceived pregnancies and risks of adverse neonatal or obstetrical outcomes compared with ICSI pregnancies. Hence, blastomere biopsy for PGD does not seem to increase the risk for adverse perinatal outcome compared with ICSI pregnancies.

Association between coffee or caffeine consumption and fecundity and fertility: a systematic review and dose–response meta-analysis

Objective The aim was to investigate whether coffee or caffeine consumption is associated with reproductive endpoints among women with natural fertility (ie, time to pregnancy [TTP] and spontaneous abortion [SAB]) and among women in fertility treatment (ie, clinical pregnancy rate or live birth rate). Design This study was a systematic review and dose–response meta-analysis including data from case–control and cohort studies. Methods An extensive literature search was conducted in MEDLINE and Embase, with no time and language restrictions. Also, reference lists were searched manually. Two independent reviewers assessed the manuscript quality using the Newcastle–Ottawa Scale (NOS). A two-stage dose–response meta-analysis was applied to assess a potential association between coffee/caffeine consumption and the outcomes: TTP, SAB, clinical pregnancy, and live birth. Heterogeneity between studies was assessed using Cochrane Q-test and I2 statistics. Publication bias was assessed using Egger’s regression test. Results The pooled results showed that coffee/caffeine consumption is associated with a significantly increased risk of SAB for 300 mg caffeine/day (relative risk [RR]: 1.37, 95% confidence interval [95% CI]: 1.19; 1.57) and for 600 mg caffeine/day (RR: 2.32, 95% CI: 1.62; 3.31). No association was found between coffee/caffeine consumption and outcomes of fertility treatment (based on two studies). No clear association was found between exposure to coffee/caffeine and natural fertility as measured by fecundability odds ratio (based on three studies) or waiting TTP (based on two studies). Conclusion Results from this meta-analysis support the growing evidence of an association between coffee/caffeine intake and the risk of SAB. However, viewing the reproductive capacity in a broader perspective, there seems to be little, if any, association between coffee/caffeine consumption and fecundity. In general, results from this study are supportive of a precautionary principle advised by health organizations such as European Food Safety Authority (EFSA) and World Health Organization (WHO), although the advised limit of a maximum of two to three cups of coffee/200–300 mg caffeine per day may be too high.

Fertility Treatment and Childhood Epilepsy - a Nationwide Cohort Study.

Background: Fertility treatment includes hormonal stimulation of the woman and in vitro manipulation of gametes and embryos that may influence prenatal brain development. We aimed to investigate the association between fertility treatment and childhood epilepsy, including specific types of treatment and indications, as well as subtypes of epilepsy. Methods: In this nationwide birth cohort study, we included all pregnancies in Denmark resulting in live-born singletons, 1995–2003. Children conceived by fertility treatment and children developing epilepsy (until 2013) were identified from Danish national registers. Results: A total of 565,116 pregnancies were included; 8,071 children (1.4%) developed epilepsy. Children conceived after ovulation induction or intrauterine insemination had a slightly higher risk of childhood epilepsy (hazard ratio [HR]: 1.15; 95% confidence interval [CI]: 1.00, 1.31). The association was more pronounced for the subtypes idiopathic generalized and focal epilepsy. Regarding the specific hormonal treatments, only clomiphene citrate was associated with an increased risk of childhood epilepsy, also in a sibling analysis (HR: 2.07; 95% CI: 1.05, 4.08). In vitro fertilization or intracytoplasmic sperm injection was not associated with an overall increased risk of childhood epilepsy but with idiopathic generalized epilepsy (HR: 1.43; 95% CI: 0.99, 2.05). No clear associations were seen regarding other treatment types or indications. Conclusions: Children conceived by ovulation induction or intrauterine insemination with clomiphene citrate may be at slightly increased risk of childhood epilepsy. Furthermore, children conceived by in vitro fertilization or intracytoplasmic sperm injection may be at slightly increased risk of idiopathic generalized epilepsy.

PS-354 Assisted Reproduction And Somatic Morbidity In Childhood – A Systematic Review

Background Worldwide, more than five million babies have been born as a result of assisted reproduction technology. Safety aspects are therefore crucial to consider. Aim By review of the literature to assess if children conceived by assisted reproduction technology are at increased risk of somatic morbidity after the newborn period compared with spontaneously conceived children. Methods Medline/Pubmed, Embase and The Cochrane Library were searched on May 20, 2013. Studies on assisted reproduction technology and post-neonatal somatic diseases were included in the systematic review. Furthermore, health care contacts, chronic illnesses, surgery, medication and mortality were considered. Cohort and case-control studies were included. To assess the risk of bias in the individual studies, quality of all studies were evaluated independently by two of the authors, using the Newcastle-Ottawa Scale. The PRISMA statement for systematic reviews was followed. Results Thirty-eight studies, out of 819 identified studies, were included. Results indicate that children conceived by assisted reproduction technology are at increased risk of leukaemia and retinoblastoma, asthma and obstructive bronchitis, genitourinary diseases, and epilepsy or convulsions when compared with spontaneously conceived children. Furthermore, it appears that children conceived by assisted reproduction technology are hospitalised longer per admission, compared with spontaneously conceived children. Conclusion Children conceived by assisted reproduction technology may be at increased risk of various somatic diseases in childhood compared with spontaneously conceived children.