Prenatal diagnosis (or lack thereof) of arthrogryposis multiplex congenita and its impact on the perinatal experience of parents: A retrospective survey

To examine parental experiences during pregnancies affected by Arthrogryposis Multiplex Congenita (AMC) by identifying commonalities, risk factors, and areas for improvement in detection rates, care protocols, and patient experience.


| INTRODUCTION
Arthrogryposis, also referred to as Arthrogryposis Multiplex Congenita (AMC), is defined as joint contractures in two or more body areas that are present at birth.Contractures develop as a result of fetal akinesia during critical weeks of limb development and usually involve the extremities but may also include limitation of full range of movement of the jaw, neck, and spine. 1 AMC is not considered a specific diagnosis but rather an umbrella term referring to a condition that may be present in over 400 different diagnoses with a wide range of outcomes.5][6] Screening for these conditions and others such as cystic fibrosis, Fragile X Syndrome, and Spinal Muscular Atrophy has become a common part of routine prenatal care by ultrasound, non-invasive prenatal testing and genetic testing for carrier status in parents.
Despite the similar incidence of AMC, there is no standard protocol for prenatal screening for AMC or disorders of fetal movement in general.The American College of Obstetrics and Gynecology (ACOG) and The American Institute of Ultrasound in Medicine (AIUM) recommend an initial routine screening ultrasound in the first trimester to evaluate dating and number of fetuses and an anatomy survey at 18-20 weeks wherein the required documentation is merely the presence of the extremities without mention of shape or movement. 7,80][11] Pregnant mothers have reported decreased or abnormal fetal movements in up to 67% of affected pregnancies.Despite this, prenatal diagnosticians have failed to detect AMC prior to birth in 47%-75% of cases. 12,13is retrospective observational cohort survey was developed to collect quantitative data regarding pregnancies affected by arthrogryposis and to qualitatively appreciate parents' experiences during their antenatal, intrapartum, and postpartum care.The results compare antenatally detected cases (ADCs) to postnatally detected cases (PDCs) to search for commonalities and risk factors and to examine the impact of the detection of arthrogryposis (or lack thereof) on the prenatal care experience.This is done with the goals of raising awareness and developing improved protocols and resources.

| METHODS
A survey in the English language was created on an online platform (SurveyMonkey.com) and distributed via social media (Facebook). -61 criteria included age younger than 18 years, not being the biological parent, or cases that did not involve at least two joints or body areas.The method of diagnosis by either medical professional or parental supposition was not specified.The first question provided a description of the survey and obtained consent to participate.Reponses were collected over an 8-month period from March 2020 to October 2020.Quantitative responses were analyzed with the Fisher's exact test with the level of marginal significance set at a p value less than 0.05.Qualitative and freetext responses were reviewed by thematic analysis.The design of the survey did not require a response to each question and thus the denominators varied slightly among questions, though never by more than 2%.

| Respondent characteristics
Of the 379 total respondents, 13 were excluded from not being the parent and two cases were excluded from involving only one joint.An additional 63 started but did not complete all questions, leaving a total of 301 responses for analysis.The demographic characteristics of the respondents are summarized in Table 1.Responses were received from 23 different countries on six continents.The majority of the participants (77%) were 18-34 years old during the subject pregnancy.Nearly 50% of the subject pregnancy children were 5 years old or younger, and the oldest was over 20 years.Respondents identified their race as White or Caucasian (78%), Hispanic/Latino (10%), Asian (3%), Black (2%), or Other (6%).Types of health insurance included a mix of commercial/private (45%), government-funded (32%), military insurance (3%), or none (20%).
The most common type of AMC was Amyoplasia (36%) and 26% of respondents stated no specific type of arthrogryposis had been determined.

Antenatal detection of arthrogryposis afforded an opportunity
for additional testing and services (Table 3).Amniocentesis was offered to 82% of ADCs.Referrals to maternal fetal medicine (62%) and genetic counseling (65%) were also common.The option for termination of pregnancy was discussed by 84% of ADC respondents.

| Obstetric and maternal conditions
Maternal health conditions among pregnancies affected by AMC were similar to background rates seen in unaffected pregnancies (Table 4).Bleeding or spotting in the first and/or second trimester was reported by 21% of all respondents, while 17% reported hyperemesis gravidarum and 12% experienced a viral illness or fever.
Forty-six percent of respondents were primigravidas.Breech presentation at delivery was 40% and 10% reported an abnormally shaped uterus.

| Delivery methods and outcomes
The majority of all deliveries were performed by generalist OB/GYN physicians (61%), with ADCs being more likely than PDCs to be delivered by a high-risk specialist (p = <0.01).Overall, 62% of deliveries occurred by cesarean section (46% primary, 16% repeat).
There was an increased likelihood (p = 0.01) of a primary cesarean delivery among ADCs compared with PDCs.ADCs reported a change in the type (33%), the timing (28%) and location (51%) of their delivery due to detection of arthrogryposis, being less likely to deliver and by 27% of those born at or beyond 37 weeks (40% of ADCs, 20% of PDCs, p = 0.025).

| Provider support and educational resources
The 112 parents who learned of their child's arthrogryposis antenatally (ADCs) described the information they received about arthrogryposis with variable responses.Examples of the wide spectrum of reported adjectives included accurate (28%), compassionate (27%), scary (61%), confusing (39%), depressing (37%), and inconsistent (34%).The utility of the information received was considered somewhat helpful by 34% and not at all helpful by 31% (Table 6).On a sliding scale of 0-100, ADCs averaged a rating of 39/100 when asked whether their prenatal care improved their understanding of arthrogryposis prior to delivery and an average rating of 38/100 when asked how prepared they felt for the delivery and care of their child with AMC.ADCs rated the knowledge level about arthrogryposis of their various providers with average scores for specialists including orthopedics, genetics, neurology (65/ 100), therapists including physical/occupational, speech, nutrition (42/100), pediatricians (29/100), and pregnancy providers (19/100).
Eighty-four percent of ADCs had discussions with their providers regarding the option for pregnancy termination (abortion) with a mix of favorable and unfavorable impressions of the encounter (Table 6).Presumably, none of the parents in this survey chose to terminate since a requisite for participation was to be the parent of a child born with AMC.
Both ADCs and PDCs were asked whether signs of arthrogryposis that could have led to an earlier detection were observed but not appreciated antenatally.Responses included perceived decreased fetal movement (43%), abnormal limb shape or movement on ultrasound (40%), baby always in the same position on ultrasound (37%), abnormal fluid level (17%) and no unusual findings noted (18%).Overall, 33% of respondents felt their concerns were not adequately addressed by their providers (17% of ADCs, 43% of PDCs).

| Qualitative responses regarding parental experience
Respondents were asked a series of free-response questions (Appendix A), giving them a chance to reflect on their overall experiences with their providers during and after their AMC pregnancy.
Common themes arose in the observations and recommendations from parents: � Evaluation of limb shape and movement should be a standard part of a routine ultrasound during pregnancy.
� Providers often dismissed a mother's perception of decreased fetal movement, especially when it was her first pregnancy.

� Providers seemed inadequately knowledgeable about arthrogryposis and gave inaccurate diagnoses and prognoses
� Providers should admit when they do not have answers and be willing to refer to specialists.
� Providers commonly presented "worst case scenarios" while failing to provide a sense of hope or a positive outlook.� Providers should be more cognizant of parents' emotional health and provide better resources for education, social support, and coordination of care during and after birth.
� Some providers were perceived to impose personal beliefs or to pressure parents during discussions about pregnancy termination.
Appendix B provides representative direct quotes from respondents.

| DISCUSSION
This survey sheds light on many obstetric considerations for pregnancies affected by arthrogryposis.The objective data characterize common clinical findings in maternal, fetal, and neonatal evaluations, while the subjective responses describe parents' experiences.
Collectively, the data highlight the need for improved awareness of arthrogryposis among providers and improved protocols to aide in its detection and guide obstetric care.
Our survey has some limitations.While previous studies have demonstrated the utility of online surveys including costeffectiveness, ease of distribution to and recruitment of specific target populations, and immediate collection of responses in an electronic fashion, 14 it is recognized that an exact number of potential participants reached and subsequent response rates are unable to be calculated.Due to the online nature of recruitment, While it may be expected that fetuses with limited movement are more likely than unaffected fetuses to remain in a breech presentation or require a cesarean delivery as seen in our data, it is notable that a cesarean delivery did not appear to be protective against broken bones as might be intuitively expected.It should also be reassuring to providers that even though the structural and functional abnormalities may appear antenatally to be profound, the majority of children were relatively stable after delivery and went home within a week after birth.It was not able to be determined whether more severe conditions correlated with a higher rate of antenatal detection.When the need for mechanical ventilation was used as a surrogate for non-orthopedic severity among full term deliveries, there was no difference between ADCs and PDCs, while the need for a feeding tube reached statistical significance.Other studies have shown that certain signs such as hydrops, nuchal edema, scoliosis, and absent stomach filling may provide early prognostic value with regard to unfavorable outcomes. 15is study demonstrates a low rate of detection of arthrogryposis in affected pregnancies (37%), which is consistent with previously reported rates of 25%-53%. 12,13Even among pregnancies within the past 5 years, with the most current technology and standards of care, the detection rate was only 46%.Protocols to standardize ultrasound assessment of limb shape and fetal movement during the first trimester nuchal translucency scan and the fetal anatomy scan at 18-22 weeks have been proposed. 13,16,17Unfortunately, such recommendations have yet to be included in the standards from professional societies such as ACOG and AIUM.It has been shown that 15 min is sufficient time to perform an assessment of fetal movement. 11In our survey, clubfoot deformity was present in 83% and clenched hand in 51%.Breech presentation was 10 times more common than the general population (40% vs. 4%). 18 propose the following enhancements to routine prenatal Our survey also highlights the need for better awareness, education, and understanding of arthrogryposis among providers of obstetric care.Clinicians with such training could be better equipped to offer more thorough and accurate diagnoses and prognoses to expectant parents as well as to provide the empathy and compassion that parents deserve.Recent publications have proposed detailed algorithms and care pathways for clinicians to follow after AMC has been detected, including suggested referrals, imaging studies, invasive testing for genetic studies, plans for delivery and counseling for future pregnancies. 19,20Our survey supports the need for and utility of such guidelines, as ADCs were able to prepare for delivery and early infancy, while PDCs were left with little confidence in their obstetric providers as they hurried to understand their child's condition and seek appropriate care.The emotional stress placed on families should not be taken lightly, as demonstrated by the many unfavorable parental experiences displayed in this survey.
There is a clear need for more educational materials and resources for parents.The vast majority of parents reported utilizing social media and Internet search engines to find information about arthrogryposis.Unfortunately, when one enters the term "arthrogryposis" into any popular search engine, the first results displayed are quite dismal and outdated.There are valuable online resources in the form of support groups on social media, websites, and national registries to which informed providers can point expecting parents.The large response rate to our survey reflects the wide acceptance of the use of Internet and social media platforms to find information and connect socially with people from all over the world with similar circumstances.

| CONCLUSION
Although the incidence of arthrogryposis is similar to that of other congenital conditions, the awareness among obstetric providers and protocols for prenatal screening trail significantly behind.Continued efforts to collect quantitative data on these pregnancies could allow for a broader understanding and generalizable obstetric recommendations.More inclusive screening protocols could potentially lead to improved detection rates, which could in turn afford more expecting parents the opportunity to educate themselves, make accurately informed decisions, and prepare for the delivery and care of their affected child.Improved education among providers of obstetric care could allow for better recognition of arthrogryposis and its impact on the care of the pregnancy and encourage utilization of published recommendations to provide such care in a more empathetic and compassionate manner.

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Risk factors include extrinsic (uterine/placental) factors and intrinsic (fetal neuromuscular and genetic) factors � Guidelines for prenatal care following prenatal detection have been proposed but are not yet routinely recommended What does this study add? � Our data reproduce previous detection rates and risk factors and identify additional factors � Evaluation of fetal movement is an underappreciated tool in the detection of AMC � Antenatal detection impacts the mode, timing, and location of delivery � Parental experiences have not previously been reported and are important considerations for utilization of published care guidelines Facebook groups supporting families and people with arthrogryposis were identified via the Facebook search function, including Arthrogryposis Moms, AMC Families, AMC Support Inc, ARTHROGRYPOSIS, The Arthrogryposis Group (UK), AMC, AMC (unser kleiner sonnenschein) and Take Time for AMC.Posts to these groups included a brief explanation of the survey, a hyperlink with which to participate, and an encouragement to share the survey with other AMC friends and family who may not be members of the targeted Facebook groups.Reminder posts were made at regular intervals throughout the enrollment period.It was assumed that people may be members of more than one support group and posts included a comment that any individual should respond only once.The anonymous survey included 57 quantitative and qualitative questions about respondents' experiences during the antepartum, intrapartum, and postpartum stages (Appendix A).If arthrogryposis was not detected until birth, the program used skip logic to automatically move the respondent past questions regarding their detection-specific care during pregnancy to questions regarding only the intrapartum and postnatal phases of the pregnancy.The survey was submitted to our institution's Human Research Review Board and deemed exempt as no personal identifying information was collected.Biological parents of children with a diagnosis of arthrogryposis were eligible to participate in this survey if they were at least LEMIN ET AL.
our results were subject to selection bias as participation required access to the Internet, fluency in the English language, and selfidentified membership within a group designated for the specific purpose of arthrogryposis support.Parents who chose to terminate their affected pregnancy or those whose child is no longer living are less likely to be active in such groups and would therefore be likely underrepresented, thus skewing our data to include fewer ADCs and fewer severe cases.Survey responses were also subject to recall bias.Many parents recall pregnancies from fewer than 5 years ago, but some were over 20 years in the past, during which time technology and standards of care have changed.The survey relied on respondents to remember the content of medical information given to them by their providers and the accuracy of this information, including the specific type of ultrasound examination performed or content evaluated therein, could not be independently verified.With its robust number of responses, this survey highlights several obstetric considerations.Previously reported risk factors for AMC, such as uterine overcrowding by structural anomalies and multiple gestation, as well as insults affecting placental perfusion during critical weeks of gestation, such as bleeding or viral infection, were again appreciated in our results.1 Maternal perception of fetal movement, though often clinically underacknowledged, was a commonality worthy of prompting a more thorough investigation into limb shape and movement when reported.The survey did not delineate the gestational weeks over which this fetal movement was noted, whether it was consistently or intermittently observed.Overall, ADCs more commonly endorsed decreased or absent fetal movement than PDCs, though this retrospective observation may be subject to hindsight bias as the outcome was known at the time of the survey.It is unclear whether the report of decreased movement prompted a more thorough evaluation of the limbs (thus leading to the diagnosis), or whether the knowledge of the diagnosis heightened a mother's awareness of the decreased movement.Future studies with more delineation of maternal perception of fetal movement and the resulting follow-up studies would provide important clinical insight into this diagnostic tool.

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All first and second trimester exams should include evaluation of fetal movement � All anatomy surveys should evaluate the shape and movement of each limb � Further investigation with targeted evaluation of the extremities is warranted with the following findings: � Clubfoot deformity or clenched hands 620 Persistently decreased or absent fetal movement, whether by maternal perception or sonographic appearance � Persistence of fetus in the same position over serial exams, especially breech presentation or position of the knees and/or elbows Maternal bleeding or viral illness in the first and early second trimesters ADCs were most commonly diagnosed in the second trimester.In the third trimester, available space within the uterus and amniotic fluid becomes limited, making individual limb shape and movement more difficult to evaluate.Additionally, third trimester growth scans are not routinely performed in otherwise uncomplicated pregnancies.If a case of AMC is detected in the third trimester, attempts should be made to characterize the nature of joint contractures and to evaluate growth and amniotic fluid volume.
Physical findings during ultrasound and at birth.Maternal conditions during pregnancy.Characteristics of delivery.
T A B L E 2home within the first week of life (52% of ADCs, 62% of PDCs), whereas 16% were discharged more than 30 days after birth (22% of ADCs, 13% of PDCs) and 1% died prior to discharge (2% of ADCs, 0% of PDCs) (Table5).Mechanical ventilation was required by 19% of all neonates (19% of ADCs, 19% of PDCs) and 13% of those born at or beyond 37 weeks (12% of ADCs, 12% of PDCs).Use of a feeding tubeT A B L E 4 Information from providers to ADCs about arthrogryposis.
T A B L E 6LEMIN ET AL.