Parent Perspective on Childhood Development after Assisted Reproductive Technology: A National Survey.

Assisted reproductive technology (ART) is an increasingly common mechanism for conception, but parents' perspectives of newborn development after ART have not been extensively studied.[ 1 ] The potential impact of ART on childhood developmental milestones is complicated by the correlation between ART and risk of prematurity and low birth weight, both of which are associated with developmental delay.[ 2 3 4 ] Many studies have focused on the clinical question of whether the outcomes for children born from ART are impacted by maternal fertility factors and their disease state or the technology of assisted reproduction itself. Studies to date have conflicting evidence on the impact ART has on newborn development when compared to naturally conceived children.[ 5 6 7 8 ] This begs the question: how do we counsel our patients and how have they been interpreting their own child's development after conception via ART? This study aims to investigate the parent perspective on childhood developmental milestones after the use of ART compared to spontaneous conception. Our results demonstrate that parents of both groups report similar developmental milestones at most ages.

Using a digital survey, data were collected on parent perspectives of newborn development after ART and spontaneous conception. Invitation to participate was sent via E-mail to users of the mobile parenting application ( Ovia Parenting ). Surveys were collected from August 30, 2018, to September 12, 2018. Those who participated were offered to be entered into a random drawing to win one of the four 100-dollar gift cards to encourage participation. All surveys were collected and analyzed in a de-identifiable fashion. The questionnaire was developed using the CDC guidelines for developmental milestones and modified for a sixth-grade reading level[ 9 ] [ Appendix 1 ]. After a sample of 1881 respondents answered the survey, data collection was discontinued. Inclusion criteria consisted of women identifying as at least 18 years of age, who have given birth to a living child, and willing to complete the survey. Exclusion criteria included incomplete surveys and women who had not given birth to a living child. This study was IRB approved (at Rush University Medical Center, Chicago, IL). All analyses were conducted using SPSS software (IBM Corporation, Chicago, IL, USA). Findings were compared between spontaneously conceived newborns and those conceived with ART. Analysis was performed with Chi-square cross-tabulations and ANOVA. Raw data demonstrating the total number of milestones met were also collected. We further stratified participants into three groups: (1) those who did not meet any milestones or met only one, (2) those who met a moderate number of milestones (two if there were only three milestones listed or three if four milestones were listed), and (3) those who met all milestones for a given age (maximum of four). At pediatric visits, questionnaires are used to assess these milestones from a parent perspective and missing a single milestone is used as a warning sign that further evaluation is necessary.[ 10 ] Therefore, we further categorized our findings by grouping comparisons into those who met all milestones for an age group compared to those who were perceived to have met less than all milestones listed. Recognizing that prematurity is associated with delayed milestone attainment, a subgroup analysis was performed where prematurely delivered children were excluded, analyzing only births at or after 37 weeks gestation by parent report. Analysis regarding all milestones met was stopped at 24 months because the number of subjects ranged from 0 to 3 in the ART group; otherwise, questionnaire data are reported up to 60 months.

The survey was electronically sent to 112,663 users of the mobile application. Of those users, 12% (13,600) opened the E-mail, and 24% (3321) of those clicked the survey link. A total of 2739 users initiated the survey and 69% (1881) of those fully completed the survey [ Figure 1 ]. Among the complete respondents, 87.7% (1652) conceived spontaneously and 12.2% (229) conceived using assisted reproductive technologies. Electronic survey responses The majority of respondents delivered vaginally at or after 37 weeks; however, preterm delivery was more common in the ART group [ Table 1 ]. This difference was statistically significant as a greater proportion of the ART group had delivered prematurely, 11.3% versus 7.2% in the ART and spontaneous conception groups, respectively. However, patients in the subgroup analysis did not differ significantly in other demographic factors and the groups were comparable as was true in the original analysis. The newborns in both ART and spontaneous groups were within a normal percentile for growth by their first pediatric appointment, had no parent identified birth defect, went home with their mother, and did not require a NICU admission or surgery. Differences existed within maternal demographics, with the ART group being more likely to have a bachelor's degree, annual household income over 150,000 USD, and report partnership status as married. While the majority delivered vaginally, cesarean delivery was significantly more likely to occur in the ART group (38.0%) versus the spontaneous group (30.6%). Advanced maternal age was also more common in the ART group compared to spontaneous conception, 36.7% versus 16.2% ( P < 0.05) [ Table 1 ]. Demographics IUI=Intrauterine insemination, IVF= In vitro fertilization, DOR=Diminished ovarian reserve, PCOS=Polycystic ovarian syndrome, VBAC=Vaginal birth after cesarean, ART=Assisted reproductive technologies The ART group included individuals who used a variety of methods for conception, including infertility medication (91; 39.7%), intrauterine insemination (89; 38.9%), andin vitro fertilization (78; 34.1%). A total of 12.2% (28) of ART respondents reported more than one method. Within this group, 59.4% (136) of respondents reported a formal diagnosis of infertility and 164 (71.6%) tried to conceive for over a year. Participants self-reported their etiology for infertility; the most common reason was “unknown” (46; 20.1%), followed by polycystic ovarian syndrome (34; 14.85%) and diminished ovarian reserve (15; 14.8%). Other less common etiologies included male factor, tubal disease, and endometriosis. Parents overall, including those having had preterm deliveries, reported their children reaching similar developmental milestones at most ages [ Table 2 and Figure 2 ]. A significant difference existed at 12 months, with those who had used ART being more likely to report that their child met all milestones compared to those who had spontaneously conceived ( P < 0.05). Although this was found at 12 months, the difference did not persist to later ages for developmental milestones. Parent perspective on number of centers for disease control milestones met by their child * P <0.05. ART=Assisted reproductive technologies Percentage of children perceived by parents to meet all milestones The subgroup analysis included only infants delivered full term, 37 weeks or greater. The demographics of the patients in the subgroup analysis was similar, including significantly more patients of advanced maternal age in the ART group versus the spontaneous group, other than there being no significant difference in the method of delivery. This subanalysis excluded 7.2% (119) of the spontaneous conception group and 11.3% (26) of the original ART group [ Table 1 ]. A significant difference favoring more milestones met by those who conceived by ART was noted at 4 months, 9 months, and 12 months of age ( P < 0.05) [ Table 3 and Figure 3 ]. Differences did not persist past 12 months. Parent perspective on number of centers for disease control milestones met by their child excluding preterm deliveries * P <0.05. ART=Assisted reproductive technologies Subanalysis of parent perspective after term deliveries

This national survey's principal finding suggests that parents' perspective of childhood milestone achievement among those who conceived using ART and those who conceived spontaneously do not significantly differ from one another. When a significant difference was noted in milestones between the two groups, it favored those who conceived by ART, but this difference did not persist over time. Strengths of this study include the national offering of the digital survey and the large sample size. This research contributes a unique perspective to the literature, the perspective of the parent, rather than a health-care professional. This is a retrospective study asking respondents to recall their child's developmental milestones, creating the opportunity for recall bias. In addition, the data are all self-reported and not corroborated against the perspective of a medical professional. The number of respondents who conceived by spontaneous conception outnumbers the respondents using ART. In 2015, 1.7% of the infants born in the US were conceived with ART.[ 11 ] Our ART population represented 13.9% of respondents. The higher overall ART population could be owed to a higher probability of those patients downloading the app and participating in surveys. Those infants delivered prematurely were excluded as they decreased the number of respondents with children over the age of 24 months to a degree that conclusions and/or comparisons could not be made. As described in Table 2 and Figure 2 , differences between parent perspectives of children born after ART compared to spontaneous conception became the same with increasing age of the child. A difference existed at the 12-month mark, where the ART group described their children as having met more milestones. This difference did not persist at the subsequent milestone marks. Similarly, in the full-term subanalysis, parents who conceived using ART assigned more milestone achievements to their child compared to those who spontaneously conceived. Again, these differences did not persist through consecutive time periods. This study, analyzing the parent perspective rather than the perspective of a medical provider, is unique. Parents have been identified as highly accurate in screening for developmental delay in children.[ 12 13 ] As a result, this study suggests a similar developmental trajectory when comparing spontaneously conceived children to ART conceived children, based on parental assessment. The differences that were significant were found in the ART group; however, this finding did not persist over time. This could be that there were fewer children in the older age groups or that the difference was not medically relevant. The process of conceiving through ART can be demanding and stressful, this may also impact the parent's perception of their newborn. Based on these results, children born after ART are more likely to have their parents report that they are meeting all milestones than children born from spontaneous conception. The reason for this is not investigated in our study. Previous investigators have found similar findings, suggesting that ART does not negatively impact childhood cognitive/behavioral development. Even when differences were noted, they seemed to equate over time. For example, one study of children ages 8-10 years old found a significant difference favoring ART conceived children's balancing skills. However, this difference in skill level resolved by age 10.[ 14 ] A 2018 review by Morin and Seli highlights that researchers to date have had similar findings, which suggest that there are not cognitive developmental differences between children conceived through ART versus spontaneous conception.[ 15 ] Further investigation and long-term follow-up is required to corroborate these findings. In conclusion, parents who conceived spontaneously and those who used ART reported similar developmental milestones reached at most ages for their children. These findings can be used to provide improved counseling to prospective parents undergoing ART. Future steps should compare a medical perspective of childhood development after ART to the parent perspective to confirm these suggested findings. Fertility Centers of Illinois. There are no conflicts of interest.