استفاده از تکنولوژی کمک کننده به تولید مثل، ناباروری، و بروز اختلالات طیف اوتیسم گزارش شده توسط والدین
|کد مقاله||سال انتشار||مقاله انگلیسی||ترجمه فارسی||تعداد کلمات|
|31571||2015||19 صفحه PDF||سفارش دهید||محاسبه نشده|
Publisher : Elsevier - Science Direct (الزویر - ساینس دایرکت)
Journal : Research in Autism Spectrum Disorders, Volume 9, January 2015, Pages 77–95
In this study, we explored the relationship between the rise in the incidence of autism spectrum disorder (ASD), the rise in the use of assisted reproductive technology (ART), and the role of infertility. We compared the incidence of ASD in children conceived with and without the use of ART. We also considered the incidence of ASD in children whose parents reported issues of infertility. Ninety families completed a confidential questionnaire and reported use of ART, ASD diagnoses of their children, infertility, parent age at time of conception, socioeconomic status, and other variables. We obtained information for a total of 163 children. Findings indicate that there is not a significant difference in the incidence of ASD diagnoses among participants who used ART compared to those that did not. Additionally, infertility was not found to be associated with increased rates of ASD diagnoses. Limitations include small sample sizes and reliance on parent report. Implications are discussed.
Current estimates by the Center for Disease Control (CDC) indicate that one in 68 children are diagnosed with autism spectrum disorder (ASD). This is a significant increase from the published figures from 2000 that reported one in 150 children was diagnosed with ASD. Recently there has been a proliferation of studies that seek to determine the cause(s) of the disorder. Many have found genetic mutations associated with ASD (e.g., Giza et al., 2010 and Miles, 2011) and others suggest high heritability of the disorder (Hallmayer et al., 2011). Other risk factors implicated in the manifestation of ASD include parental age, socioeconomic status, infertility (e.g., Davies et al., 2012, Leslie, 2004 and Shimada et al., 2012) and shortened gestation (Leavy et al., 2013 and Schieve et al., 2014). At present, a single cause has not been identified. Researchers studying ASD epidemiology overwhelmingly agree that there is likely not a single cause but rather a combination of factors that cause the disorder, and the combination is likely related to gene-environment interactions. However, research that considers combinations of variables across populations is limited, and findings vary widely among studies. In addition to the increase in the incidence of ASD, the incidence of live births as a result of the use of assisted reproduction technology (ART) is also on the rise. Based on the 1992 Fertility Clinic Success Rate and Certification Act, the CDC (2012) defines ART as any fertility measure taken that manipulates both the egg and the sperm. Typical ART procedures include removal of eggs from the ovaries, collection of sperm, laboratory combination, and either reinsertion or donation to another carrier. These include in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI). By this definition, procedures that manipulate the sperm only (e.g., intrauterine insemination) or medications taken to stimulate egg production (without the intention of egg retrieval) do not qualify as ART. ART procedures that do fall under this definition have the potential to affect the genetic structure of the genome, fertilized eggs and embryo (Lu et al., 2013 and Shimada et al., 2012) and some studies have found that their use, particularly ICSI, may result in chromosomal abnormalities (Bonduelle et al., 2002). Known risk factors of ART use include preterm labor, low birth weight, multiple births, birth defects, and adverse psychological outcomes (Beydoun et al., 2010 and Klemetti et al., 2006). The use of ART has recently been introduced as a possible associated risk factor of ASD. Of note is that ART use appears to have a higher rate of use among certain populations that may already have an elevated risk of having a child diagnosed with ASD, such as those with increased maternal and paternal age at the time of conception (Sandin et al., 2012 and Shimada et al., 2012) those with mental health issues (Klemetti, Raitanen, Sihvo, Saarni, & Koponen, 2010), and fertility problems (Davies et al., 2012, Grether et al., 2013, Lyall et al., 2012 and Zhu et al., 2006). Despite these risks, there has been a steady and significant increase in the number of clinics that provide ART services and the number of infants born as a result of ART use. In 2012, the CDC reported that the use of ART has doubled in the past decade and estimated that over 1% of all children born in the US were conceived through ART. According to CDC's ART Fertility Clinic Success Rates Reports, 64,681 cycles were performed in 1996 (14,501 live births; 20,840 infants). That number increased to 134,260 cycles in 2005 (38,910 live births; 52,041 infants). In 2011, 163,038 ART cycles were performed, resulting in almost 48,000 live births (61,610 infants). 1.1. Risks of ART use The incidence of birth defects in children conceived via certain types of ART (ART+) is higher than that noted in the rest of the population (e.g., CDC, 2009 and Davies et al., 2012). Compared to children conceived without the use of ART (ART−), the CDC (2011) reports a higher risk of pre-term delivery and of low and very low birth weight (c.f. Zachor & Itzchak, 2011) and an increased probability of multiple-fetus pregnancy associated with various types of ART use (Lu et al., 2013). Even singleton infants conceived via ART are reported to be at a higher risk for adverse perinatal outcomes, compared to infants conceived without the use of ART (Davies et al., 2012 and Knoester et al., 2008). Additionally, the women who used any type of assisted conception in Davies et al.’s (2012) study had a higher rate of incidence of stillbirth, delivery by cesarean section and delivery at less than 37 weeks. Mothers who conceived using ART were less likely to have a male singleton and their children had lower birth weights than children of mothers who did not conceive using ART. These risks seem to increase with particular causes of infertility (Davies et al., 2012), and increased maternal (Sandin et al., 2012) and paternal age (e.g., Parner et al., 2011, Shimada et al., 2012 and Smith et al., 2014). The National ART Surveillance System (NASS), the only CDC-approved ART monitoring system, reports patient demographics, obstetrical and medical history, parental infertility diagnosis, clinical parameters of the ART procedure, and information on resultant pregnancies. NASS, however, does not report on long-term outcomes or health status of children born as a result of ART use. Long-term developmental and psychological outcomes of children conceived via ART have been of interest to researchers since ART's early use. Of the first cohort to be conceived through ART, many later reported various psychological health problems (Beydoun et al., 2010). Studies of older children and adolescents conceived via ART also reported various psychological health problems, disorders of behavioral and emotional development (Klemetti et al., 2006), and externalizing and more withdrawn and depressed behaviors (cf. Knoester et al., 2008 and Wagenaar et al., 2008), and cognitive delays (Ponjaert-Kristoffersen et al., 2005 and Sandin et al., 2013). However, no differences of mental and psychomotor abilities were found in comparing 2 year-olds who were conceived using ICSI and without the use of ART (Nekkebroeck, Bonduelle, Desmyttere, Van den Broeck, & Ponjaert-Kristoffersen, 2008). These conflicting results indicate the need for longer follow-up for children conceived using ART. Several studies have examined the prevalence of ASD in children conceived via ART. The preliminary evidence suggests that the prevalence of ASD is higher in children conceived via ART than those who were conceived without assistance (see Knoester, Helmerhorst, van der Westerlaken, Walther, & Veen, 2007). Shimada et al. (2012) conducted a chart review of people in Japan diagnosed with ASD, attention deficit hyperactivity disorder (ADHD), and Tourette's syndrome. Results indicated that ART use among parents of children with ASD was 1.8 times higher than that of the general population. However, no significant difference in rate of ART use was found for parents of children with ADHD and Tourette's compared to the general population. ART use among parents of children with ASD in Israel has also been reported to be significantly higher than that of the general populations (Zachor & Itzchak, 2011). 1.2. Pilot study In order to examine whether there is an increased risk of having a child diagnosed with ASD or other communication disorder (CD) with use of ART, the authors conducted a pilot study. Parents of children conceived using ART (ART+, n = 13) and without the use of ART (ART−, n = 66) (total n = 79) were asked to complete a confidential questionnaire ( Appendix A), available online or as a paper copy, which contained questions about the method of conception, medications taken, and/or surgical procedures implemented, parental age at time of conception, parents’ education level, socio-economic status, pre-, peri-, and post-natal history, and attainment of developmental milestones. ART was defined as all medically assistive measures taken to increase the chances of conception involving one or more of the following: the sperm, the egg, fertility-related pharmaceutical use. The responses of parents of who used ART were compared with those who did not. Findings indicated that the proportion of parents who had children diagnosed with ASD and/or CD was not significantly higher in children conceived via ART (n = 7/13, 53.85%) compared to those conceived without assistance (n = 38/66, 57.58%) (proportion ART+/ASD+/CD+ = 0.9352 × ART− (p = 0.8094, ns); the sample odds ratio is 0.8596 (p = 0.8041, ns). Although findings indicated that the ART+ and ART− groups were not significantly different for incidence of ASD/CD, it should be noted our sample was small and comprised predominantly of parents of children with ASD. This made it difficult to compare groups with such a skewed sample. Information regarding the attainment of developmental milestones was not considered due to high number of responses of “Do not remember.” Information on issues of infertility was not obtained. Additionally, certain issues became apparent with the survey design. Parents were asked to complete one survey for each child. However, this process was very time consuming, particularly filling in parent background information, which was identical across surveys. Parents of more than one child reported completing only one survey for their child with a diagnosis, and not completing additional survey(s) for their typically developing child(ren). This made it impossible to examine ART use across births within a family. To address the issues of the pilot survey, the questionnaire was revised for the current study. 1.3. Aims of current study The purpose of the current study was to examine the incidence of ASD in children conceived using ART compared with the incidence of ASD among children conceived without assistance. Rates of infertility were considered. We hypothesized that the use of ART will increase the risk of having a child diagnosed with ASD. We also anticipated that those who have a history of infertility will have an increased risk of having a child diagnosed with ASD compared to those who do not. Understanding the risk factors of autism spectrum disorders is pertinent for early detection and diagnosis.
نتیجه گیری انگلیسی
The current study provides support for ART use in the general population without increased risk of ASD diagnoses. Additionally, our findings do not demonstrate a significant increase in rates of ASD diagnoses in children of parents who report issues of infertility compared to parents who do not have reported issues. Due to our limited sample size, research should continue to monitor outcomes of children conceived using ART and children of parents with issues of infertility. Additional factors such as maternal and paternal age should be considered. Early feeding difficulties should be explored to determine or rule out an early warning sign of ASD or CD. The information obtained through our study, combined with other epidemiological data, could help to identify and rule out risk factors of a child being diagnosed with ASD and other communication disorders. Our data demonstrate the difficulty in making associations of assumed epidemiological environmental factors with later diagnoses of ASD and CD. Like other studies that consider these associations, our findings are limited to the population surveyed with limited generalizability. Additionally, parent reported use of ART and diagnoses may not be accurate due to failure to disclose or undiagnosed disorders at the time of participation. Ideally, these associations will continue to be explored through parent report, chart review, and assessment.