Kruti Acharya

A Pilot Study to Explore Knowledge, Attitudes, and Beliefs about Sickle Cell Trait and Disease

INTRODUCTION In the United States, newborn screening programs universally identify newborns with sickle cell disease (SCD) and heterozygote carriers (sickle cell trait [SCT]). Although there is a consensus to disclose SCT to parents, there are limited empirical data about whether and how this information is transmitted to the carrier children. METHODS In-person questionnaires were administered to parents with SCT and parents of a child with either SCD or SCT to examine the knowledge, attitudes, beliefs, and disclosure patterns about SCT of parents. RESULTS Fifty-three adults were interviewed, half (27) of whom had a child with SCD. There was significant misunderstanding about sickle cell inheritance (mean score, 68%), but parents who have a child with SCD have better knowledge compared to those without a child with SCD (78% vs 58%, p = .002). Respondents perceive minimal stigma associated with SCT. Unless there is an affected proband, individuals with SCT rarely receive counseling or education outside of the family. CONCLUSIONS There is significant misinformation about what it means to be a carrier and its health and reproductive implications. Formal professional counseling is rare, especially for those families without an affected proband. Strategies to increase the utilization of counseling and improve genetic literacy are necessary.

Maternal knowledge and attitudes about newborn screening for sickle cell disease and cystic fibrosis

Illinois introduced mandatory newborn screening (NBS) for sickle cell disease (SCD) in 1989 and for cystic fibrosis (CF) in 2008. We examined maternal understanding of NBS for SCD and CF, and their knowledge of the genetics, symptoms, and treatments of both conditions. Our methods consisted of conducting interviews of inpatient post‐partum women (>18 years and English speaking). Our results showed that of the 388 eligible participants, 34 self‐identified as sickle cell carriers, 1 with SCD and 1 as a CF carrier. Almost 3/4 were African American (282/387). Although all but 5 women had prenatal care, only 35% (133/378) recalled their prenatal care provider mentioning NBS, and only 56% (217/388) of participants recalled nursery staff mentioning NBS. There was more self‐reported familiarity with SCD (3.32/5) than CF (1.97/5, P < 0.001). Over 2/3 (260/388) of participants could not answer CF knowledge questions because they had never heard of CF. Among those who had heard of the conditions, mean knowledge scores were 66% for SCD (n = 372) and 63% for CF (n = 128). Bivariate analysis identified education, age, race, marital status, and insurance status as statistically significant. After linear regression education remained significant for both conditions. We conclude that in a sample of predominantly African American post‐partum women, we found poor understanding of NBS, greater familiarity with SCD, and significant knowledge gaps for both SCD and CF. There are many missed educational opportunities for educating parents about NBS and specific conditions included in NBS panels in both the obstetric clinics and the nursery.

Fragile X screening: Attitudes of genetic health professionals

Although genetic health professionals (GHP) are major stakeholders in developing and implementing fragile X (FrX) testing and screening guidelines, their attitudes about FrX testing and population screening are virtually absent in the literature. A survey was conducted of physician geneticists (geneticists) and genetic counselors (GC). The survey addressed GHPs attitudes towards (1) prenatal FrX carrier screening; (2) pre‐ and full mutation screening of male and female newborns; (3) the single best time for FrX screening over the lifespan; and (4) their willingness to test a normally developing child with a positive family history. Surveys were completed by 30% (273/894) of eligible GHP. Attitudes of geneticists and GC were mostly indistinguishable. The single most favored screening approaches were (1) preconception screening targeted at women with a positive family history (43%); and (2) universal preconception screening (29%). While only 6% and 11% declared universal prenatal and universal newborn screening (NBS) as the ideal time respectively, 73% and 60% respectively would support such programs. GHP would design a NBS program to test male and female infants and to identify both pre‐ and full mutations. Over half would agree to order FrX testing on some normally developing children with a positive family history. In expanding FrX testing and screening to low risk individuals, GHP prefer preconception screening as the single best time. The majority also support prenatal screening and NBS. If NBS were to be introduced, GHP prefer screening to identify boys and girls with both pre‐ and full mutations.

Policy considerations in designing a fragile X population screening program.

The success of the pilot study by Saul et al.[1] reaffirms the feasibility of Fragile X (FrX) syndrome detection in newborn males.[2–6] One unique aspect of this study is its reporting of the consent rate. Three hundred eighty five of 1844 (21%) postpartum women refused to have their newborn males screened, although reasons were not ascertained.[1] Twenty-one percent is a high rate of refusal compared to the <3% refusal rate in Massachusetts and 10% refusal in California when tandem mass spectrometry (MS/MS) was first introduced as pilot programs.[7,8] It is also high compared to the <8% refusal rate in Wales for screening newborn males for Duchenne Muscular Dystrophy (DMD).[9] FrX screening is more similar to that of DMD screening because of the focus on male infants for a condition in which early treatment has not been shown to prevent long-term morbidity or mortality. One possible explanation for the lower consent rate is that the decision was made to require mothers to sign a consent form approved by an institutional review board (IRB). In Massachusetts, the New England Newborn screening program provided in-service training at all birth units in more than 55 Massachusetts hospitals, offered many statewide educational programs, and redesigned lab slips to distinguish those who consented from those who did not.[7] The consent was verbal, not written, and was obtained by clinical staff. In California, when MS/MS was offered as a pilot study, the biggest obstacle was getting hospitals to offer the screening to infants. It was found that only 48% of infants were offered screening.[8] When offered, 90% of the mothers consented and 10% declined.[8] Again, consent was verbal and obtained by clinical staff. In Wales, parents were given an information sheet in the hospital but consent was not obtained until the midwife home visit at day of life 6 or 7.[9] Again the consent was verbal not written and was obtained by clinical staff.[9] Thus the study by Saul et al. may have had a lower consent rate because of the requirement for written consent and the participation of research personnel to obtain the consent. Traditionally, newborn screening (NBS) in the United States has been mandatory. This policy has been justified on the grounds of promoting equity through universal access.[10] Although studies show that parents are more concerned about being informed about NBS programs than about whether or not they have provided explicit consent,[11,12] the American Academy of Pediatrics and the Institute of Medicine have both questioned why NBS is exceptional. [13,14] There are many pediatric opportunities that are beneficial and yet require parental permission (e.g., immunizations). Nevertheless, as NBS expands beyond the traditional criteria for public health screening,[15] the role of consent will attain greater significance. Putting consent issues aside, the pilot study raises a fundamental question about the goals of a screening program. The study by Saul et al..1] and most other studies use polymerase chain reaction (PCR)-based technologies.[2–6] A standard PCR protocol for amplifying the fragile X mental retardation-1 gene (FMR1) trimucleotide repeat lets the researchers distinguish between those with 200 repeats), and those who are in the gray area (having between 45 and 55 repeats).[16] In females, a single band on PCR testing represents either 1) a normal female with two normal FMR1 genes of similar repeat number that make them relatively indistinguishable; 2) a chromosomal abnormality (e.g., Turner syndrome or Androgen Insensitivity syndrome); or 3) a large mutation that poorly expands by PCR. An estimated one-fourth of all female samples initially screened by PCR would have a single band.[16] Southern blot testing would then be required to distinguish those with and without an abnormal FMR1 gene. Because southern blot testing is quite labor intensive, females were traditionally excluded from PCR-based FrX population screening protocols.[16] However, in 2007, Strom et al. reported on a high-throughput technique using capillary Southern analysis (CSA) for FrX detection in both males and females that minimizes the number of samples that need southern blot confirmatory testing.[16] Although Strom et al. proposed their methodology for prenatal population screening, they acknowledged its potential use in NBS.[16] The development of the CSA technique described by Strom et al. 16] forces us to ask why research continues to focus on FrX NBS methodologies geared only to male infants? The benefits of a NBS program according to Saul et al. would be both to detect young boys who could benefit from early developmental services, and to give parents reproductive information.[1] Consider the first claim regarding developmental services. If one believes that early developmental services are beneficial, then one must ask how one can justify excluding female infants? One answer is that only half of females with full mutations will have some degree of cognitive and behavioral disability and their symptoms will often be less severe than the symptoms of their male counterparts.[16] But for those girls who are delayed, early developmental services would be helpful. A fear is that some girls will be inappropriately classified as having developmental delays. This may lead to unnecessary participation in early developmental services, but there are no data to suggest that such participation would be harmful. Inappropriate labeling by itself however can be quite harmful by causing stigma, discrimination, and lower achievement due to self-fulfilling prophecies.[17,18] Thus, from a developmental perspective it is ambiguous at best whether screening infant girls for FrX syndrome is more beneficial than harmful. The second claim of a screening program, however, is to provide reproductive information to parents. To achieve this goal, the diagnosis of pre-mutation and full mutation girls and boys would be more useful than restricting the diagnoses to affected and carrier males. However, pediatricians and policy makers become uncomfortable when the goal of NBS is described as providing reproductive information for parents.[10,13,14] If the goal is to educate parents about their reproductive risks, then it would be preferable to screen the women or couple pre-conception and not to use children as the canaries in the coal mine.[16] This would allow women to decide prenatally (preferably pre-conception) what risks they are willing to take and how they want to manage a high-risk pregnancy before an affected child is born. While the method proposed by Saul et al. could not be applied to the prenatal period, the method by Strom et al. could. There is precedence for routine prenatal screening for mental retardation and developmental disabilities. Until the mid-1980s, the American College of Obstetrics and Gynecology (ACOG) recommended prenatal screening for Down syndrome only for high risk women (e.g., advanced maternal age), but with the discovery that maternal serum alpha fetoprotein is decreased in women whose pregnancies are complicated by Down syndrome, routine prenatal screening of all women became the norm.[19] In fact, California requires that physicians document those who refuse.[20] ACOG’s current recommendations for prenatal screening for FrX is limited to those with a family history of mental retardation or FrX. syndrome.[21] An accurate automated high throughput FrX screening program could lead ACOG to reconsider this recommendation and to propose routine prenatal FrX screening. The major disadvantage of implementing prenatal screening for FrX rather than newborn screening is the greater disparity in access to prenatal genetic testing than to neonatal screening.[22] If diagnosis early in childhood offers significant benefits, unequal prenatal access could justify screening all newborns rather than infants identified as high risk prenatally. Supporters of NBS assert that early diagnosis is essential to procure early developmental services.[23] However, any child with developmental delays is eligible for early developmental services, and with routine developmental screening assessments, developmental delays are clinically identifiable in the first years of life.[24] Referral to early developmental services can be made even before a specific diagnosis is made. A genetic evaluation of all children with developmental disabilities is medically indicated for prognostic purposes and should be offered,[25] although uptake may not be universal because of the reproductive implications that the diagnosis may hold. Population screening for FrX is on the horizon. The study by Saul et al. focused on NBS because of the technology used. However, the decision whether to provide prenatal and/or neonatal screening should be based on well-articulated and transparent goals. That is, values rather than technology should guide policy decisions. The lack of cure for FrX syndrome and the association of pre-mutation carrier status with reproductive risk and other adult-onset conditions means that all screening program must be accompanied by a robust informed consent process. To the extent that the study by Saul et al. is at all representative, we should anticipate that a large number of women and/or parents will refuse.

Prenatal testing for intellectual disability: misperceptions and reality with lessons from Down syndrome.

Down syndrome is the most common cause of intellectual disability. In the United States, it is recommended that prenatal testing for Down syndrome be offered to all women. Because of this policy and consequent public perception, having Down syndrome has become a disadvantage in the prenatal period. However, in the postnatal period, there may be some advantage in having Down syndrome. To help parents make informed decisions about screening and testing, it is crucial to reconcile divergent prenatal and postnatal perspectives. Advancements in genetic technologies will also impact the informed consent process and need to be considered.

Developmental and behavioral pediatricians' attitudes toward screening for fragile X.

Developmental and behavioral pediatricians (DBP) diagnose and care for children with fragile X syndrome. Their attitudes toward FMR1 newborn screening (NBS) and FMR1 carrier testing in childhood could highlight potential pitfalls with FMR1 NBS. We conducted a cross-sectional survey with an adjusted response rate of 61%. Among DBP, 74% supported universal FMR1 NBS, preferring to identify both full mutations and premutations. DBP also support FMR1 testing of asymptomatic siblings. Although DBP support testing for premutations at various points in the lifespan, DBP are not familiar with the array of fragile X-associated disorders (FXAD). Targeted educational interventions are needed to ensure that all health care providers have the knowledge and competence to consent and to counsel families on FXAD.

Disparities in adversity among children with autism spectrum disorder: a population-based study.

People with autism spectrum disorders (ASDs) experience disparities in health. An important but overlooked risk factor for health disparities in the ASD population is adverse childhood experiences (ACEs). The purpose of this study was to identify the prevalence of ACEs among families of children with and without ASD, using a population‐based sample.

Victimization and restricted participation among young people with disabilities in the US child welfare system

The aim of this study was to assess the role of disability and victimization in young peoples participation in developmentally salient activities by analyzing a nationally representative group of young people from the child welfare system (CWS).

A Pilot Study to Evaluate Awareness of and Attitudes About Prenatal and Neonatal Genetic Testing in Postpartum African American Women

OBJECTIVE A pilot study to determine whether prenatal and neonatal sickle cell tests conform to the guidelines established by the American Congress of Obstetricians and Gynecologists and the American Academy of Pediatrics. METHODS The project was initially structured as a pair of in-person interviews of postpartum women at the University of Chicago, the first collecting medical information and the second surveying the ethical, social, and legal implications (ELSI) of sickle cell trait (SCT). Due to inadequate enrollment, we elected to focus only on the second survey. Descriptive statistics and bivariate analyses were performed. RESULTS A convenience sample was established from 205 women who had completed surveys of whom 12 (6%) received no prenatal care. Of the 60 women who completed both surveys, 15 (25%) were unsure of their hemoglobinopathy status. Of the 50 results we could verify, 2 women (4%) incorrectly recalled their hemoglobinopathy status. Of the 193 women who received prenatal care and completed the ELSI survey, 47 knew their hemoglobinopathy status from a previous pregnancy and 1 had sickle cell disease. Of the remaining 145 women, 53 (37%) recalled hemoglobinopathy testing during this pregnancy and 44 (30%) were unsure. Only 56 (39%) recalled being told they could refuse testing. Of the 115 women whose infants had newborn screening done prior to the interview, only 51 (44%) recalled discussions with a pediatric provider. CONCLUSION Despite professional guidelines that stress the importance of education, counseling, and consent for prenatal and neonatal testing, postpartum women do not recall these conversations.

Medical Therapy for Inappropriate Sexual Behaviors in a Teen With Autism Spectrum Disorder.

Teens with autism spectrum disorder often exhibit sexual behaviors in public that are disturbing to parents, teachers, and peers. Some have proposed that such behaviors can be curtailed with hormonal suppression. There is information on the Internet suggesting that such medications work, and some reports in the peer-reviewed medical literature support these claims. Such medications can have serious side effects. In this paper, we present a case in which parents requested such treatment of their teenage son with autism spectrum disorder.