BACKGROUND. Newborn screening programs now identify children with >30 biochemical genetic disorders. False-positive identifications may increase as disorders are added to screening panels. Concerns arise regarding the potential impact on parental stress, family relationships, and perceptions of the child's health.
METHODS. Parents of 173 infants with false-positive screening results for a biochemical genetic disorder in the expanded newborn screening panel were compared with parents of 67 children with normal screening results. Parents completed an interview that elicited information about demographic features, child and parental health, and understanding of newborn screening. Parents also completed the parenting stress index.
RESULTS. Parents in the false-positive group attained higher total scores on the PSI than did parents in the normal-screened group, scoring higher on the parent-child dysfunction subscale and the difficult child subscale. Only approximately one third of parents in the false-positive group reported knowing the correct reason for repeat screening. Mothers who reported knowing the correct reason for their child's repeat screening test experienced less total stress than did mothers who were misinformed, were not informed, or did not remember.
CONCLUSIONS. False-positive screening results may affect parental stress and the parent-child relationship. Improved communication with parents regarding the need for repeat screening tests may reduce the negative impact of false-positive results.
- newborn screening
- parental stress
- vulnerable child
- nocebo phenomenon
- parent-child relationship
Recent expansion of newborn screening for biochemical genetic disorders has led not only to an increase in positive identifications but also to a dramatic increase in false-positive test results. A false-positive result is an initial out-of-range screening result that does not indicate a metabolic disorder with additional evaluation of the child. Generally these results are not laboratory mistakes but rather are transient findings or indications of variant or carrier status. When needed, typically repeat specimens in expanded newborn screening are requested after an infant's discharge from the nursery.1 Expanded newborn screening with tandem mass spectrometry for >20 disorders has a 0.33% false-positive rate and an overall incidence of ∼1 case per 2400 infants.2 Therefore, of the >4 million infants born in the United States each year, ∼13000 are likely to receive a false-positive result, with at least 550 from New England alone.3 Apart from a “PKU anxiety syndrome” described in 1968 in relation to false-positive screening for phenylketonuria (PKU), little is known about the subsequent impact on parental stress, family relationships, and perceptions of the child's health.
This report describes parental responses to false-positive newborn screening results among a cohort of children born after February 1, 1999, when expanded newborn screening began in Massachusetts. This cohort represents a subset of children enrolled in an expanded newborn screening study for metabolic disorders that includes children identified with biochemical genetic disorders through expanded newborn screening, as well as parents in the false-positive cohort.4
Enrollment and Study Procedures
Mothers and fathers of infants who had a false-positive screening result for 1 of the 20 biochemical genetic disorders added to the newborn screening panel were invited to participate when a referral was made for additional confirmatory testing. Participants were enrolled by a private screening laboratory in Pennsylvania, which contributed 82% of the cases, and by metabolic centers in Massachusetts when follow-up testing was performed there. To be categorized a false-positive result for this study, the initial screening result must have been an abnormal reading, an indication of a specific metabolic disorder, or inconclusive. Parents of children with such results were sent a letter explaining the study ≥6 months after the diagnosis of a metabolic disorder had been ruled out. Parents who did not “opt out” by returning a response card indicating a preference not to be contacted were called to participate in a telephone interview. Both the initial letter and the telephone call contained the elements of an informed consent form, including descriptions of the study, confidentiality measures, potential risks, and benefits. Although both parents were invited, it was acceptable if only 1 parent participated. On occasion, when the second parent wanted to participate but was unable to complete the telephone interview, questionnaires were returned by mail.
The comparison group for the false-positive cohort consisted of parents of 6- to 12-month-old children with normal screening results, selected sequentially from the Commonwealth of Massachusetts Department of Public Health Birth Registry of Vital Records and Statistics. Birth registry data include only children born to married couples and contain the date of birth, birth weight, parents' names, birth hospital, and hometown. All recruitment occurred between February 1, 1999, and February 28, 2004. All parent participants were interviewed once. Additional follow-up interviews were not included in the study design.
Exclusions included parents of children who had died and parents of newborns whose birth weight was <2500 g. The latter exclusion avoided recruitment of parents of premature newborns, who frequently experience transient initial newborn screening abnormalities.5 Human studies approval for the study was obtained annually from the institutional review board of Children's Hospital Boston. By design, the number of false-positive participants exceeded the number of participants in the comparison group. Statistical methods that did not require balanced sample sizes were selected.
Data Collection Instruments
Parents first completed a structured interview, which consisted of questions related to child and parental health, understanding of the newborn screening process, and background information. Parents provided short answers or ratings on a 5-point Likert scale. The same interview was given to both groups of parents, and parents in the false-positive group were asked additional questions about the repeat screen.
Parents next completed the parenting stress index (PSI), short form.6 This is a 36-item questionnaire that provides a total stress score and 3 subscale scores, namely, parental distress, parent-child dysfunctional interaction, and difficult child. The normal range for total stress scores is 55 to 85, with scores of >85 considered to be in the clinical range in which treatment may be necessary.6 The PSI also provides a defensive responding index, which is an internal index of validity based on the parent's responses. Scores of ≤10 for this index indicate that the validity of the total stress and subscale scores is questionable. The α reliability coefficients are .91 for the total stress score and .80 to .87 for the scaled scores.6 The short-form PSI has a correlation of .95 with the full-length PSI.6
Parents completed the interview separately. Copies of the PSI and a short form of the interview, which included questions related to child health, were mailed to second parents unable to complete a telephone interview.
Content analysis of the interview by 2 independent raters was used to derive 3 categories based on parents' suggestions for making the newborn screening process a more positive experience.7 Categories included adequacy of information about newborn screening and test results, reactions regarding newborn screening, and the length of time to receive confirmation of the false-positive result. The percentage of agreement between 2 independent raters was 95% for a total of 132 comments.
The Hollingshead scale was used to derive socioeconomic status.8 The scale incorporates level of education and occupational status (each coded from 1 to 7) to predict overall socioeconomic status (coded from 1 to 5).8 Low scores indicate higher educational levels, occupational status, and social position.
For parental responses regarding characteristics of the child and family, information from the mother's interview was analyzed unless it was unavailable, in which case information from the father's interview was used. For the parent-specific indices, results were calculated separately for mothers and fathers.
The characteristics of children, parents, and families in the false-positive group were compared with those in the normal-screened group by using the Wilcoxon rank sum test for continuous and scale variables and Fisher's exact test for dichotomous variables. The number of hospitalizations occurring before 6 months of age was compared for the 2 groups by using Poisson regression.
For the PSI, subjects who failed the defensive responding index (scores of ≤10) were dropped from the analyses. To illuminate the unadjusted comparisons of PSI scores for the false-positive and normal-screened groups, linear regression analysis was used to estimate differences in PSI scores between the 2 groups, with adjustment for demographic characteristics in which the groups differed. Adjusted P values for these differences were estimated with the Van Elteren test, which is a stratified extension of the Wilcoxon rank sum test. All P values were 2-sided, and values of <.05 were considered significant.
The sample included parents of 173 children with false-positive results and 67 children with normal newborn screening results. A total of 233 mothers (167 false- positive and 66 normal-screened) and 123 fathers (86 false-positive and 37 normal-screened) were interviewed. For 116 infants (80 false-positive and 36 normal-screened), both parents responded. The number of enrolled families divided by the number of families contacted determined the participation rates, which were 81% for the false-positive group and 55% for the normal-screened group. Two hundred eighty-one families of children with false-positive results could not be recruited within 6 months after confirmation of the false-positive result, because of a backlog of cases and inadequate staffing when the study started or incorrect follow-up information. Two hundred six normal-screened families could not be contacted because of a lack of correct mailing addresses or telephone numbers.
As noted in Table 1, the false-positive group was similar to the comparison group in terms of gender, birth order, ethnicity, primary language spoken in the home, and percentage of families with other children with medical problems. The source for normal-screened children contained only married parents, whereas some children in the false-positive group came from single-parent families (P < .001). In the false-positive group, children were older at the time of evaluation (mean: 13.3 months; SD: 3.7 months), compared with the normal-screened group (mean: 6.4; SD: 0.9 months; P < .001). The false-positive group was of lower socioeconomic status (mean: 3.0; SD: 1.1), compared with the normal-screened group (mean: 2.3; SD: 0.9; P < .001).
Health Outcomes and Parental Stress
Although parents in the 2 groups reported similar degrees of worry about their child's health, mothers in the false-positive group reported more worry about their child's future (mean: 2.4; SD: 1.4), compared with mothers in the normal-screened group (mean: 1.9; SD: 1.0; P = .04). In the false-positive group, mothers rated themselves as less healthy (mean: 4.0; SD: 0.9), compared with mothers in the normal-screened group (mean: 4.4; SD: 0.7; P = .002). Fifteen percent of mothers in the false-positive group reported that their child required extra parental care, compared with 3% of mothers in the normal-screened group (P = .01). Fathers in the false-positive group did not differ from fathers in the normal-screened group in reporting worry about their child's future, personal health, and their child's extra care requirements.
As shown in Table 2, mothers in the false-positive group reported higher overall stress on the PSI than did mothers in the normal-screened group. Seventeen mothers in the false-positive group (11%) but no mothers in the normal-screened group scored in the clinical range (P = .008). The differences between groups were more pronounced on the total score, difficult child, and parent-child dysfunctional interaction subscales (P < .001) than on the parental distress subscale (P = .08). Fathers in the false-positive group also registered higher overall stress on the PSI than did fathers in the normal-screened group (Table 2), especially on the total score (P = .02), difficult child (P = .05), and parent-child dysfunctional interaction subscales (P = .004).
Differences in marital status and socioeconomic status between the 2 groups were not responsible for the observed differences in PSI scores. Comparison of PSI scores between the false-positive and normal-screened groups with adjustment for marital status was not possible because there were no unmarried families in the normal-screened group. Only mothers' parent-child dysfunctional interaction scores varied significantly according to family marital status in the false-positive group. Table 3 shows that adjusting for family socioeconomic status did not change any of the conclusions from Table 2 for mothers. For fathers, the differences in total scores and subscales between the false-positive group and the normal-screened group with adjustment for family socioeconomic status were similar to the unadjusted differences, although the adjusted differences were no longer statistically significant.
Parental Responses to the Informing Process
As shown in Table 4, only 35% of mothers and 31% of fathers knew the correct reason for their child needing a repeat screen. Mothers in the false-positive group who knew the correct reason for the repeat screen reported lower stress levels on the PSI, including the total score (P = .005) and difficult child (P = .03), and parent-child dysfunctional interaction (P = .003) subscales (Table 5). Fathers who knew a correct reason for the repeat screen did not exhibit lower stress levels on the PSI. Whether the parents received the result, did not receive the result, or were unsure if they had received the result was not related to parental stress (P > .12 for mothers and P ≥ .35 for fathers on the total score and all subscales with the Kruskal-Wallis test).
Parents in the false-positive group shared their thoughts about what could have made the screening process a more positive experience. Sixty-one percent of parents expressed a need for more information about newborn screening and the test result, 13% described ambivalent reactions regarding newborn screening, and 26% voiced concerns about the length of time to receive confirmation of the false-positive result. According to parental report, the median age of the child at the time of the repeat screen was 14 days (range: 2–135 days). Fifty-three of 154 parents reported that their child was >2 weeks of age at the time of the repeat screen. The median time from the repeat screen to learning the result was 7 days (range: 1–330 days). Twenty-nine of 90 parents reported a time of >2 weeks. In addition, 50% of parents surveyed indicated that they were never told or did not recall being told the result of the repeat screen. It is possible that some of these parents were told but did not recall receiving the information. Twenty-two percent of these parents reported being told to expect “no news is good news,” and 24% needed to ask their pediatrician specifically for the results of the repeat screen.
Results from this study indicate that a false-positive result from an expanded newborn screening test may affect parents' perceptions of their child's health, parental stress, and the parent-child relationship. The majority of parents revealed a lack of understanding regarding expanded newborn screening, as well as a need for more information. As evidence of their unfamiliarity with newborn screening, many parents described the newborn screening test as a procedure (ie, “the heel prick”), rather than as a process to identify potentially affected children.
The PKU anxiety syndrome that was described as a typical reaction to a false- positive PKU test is characterized by acute or chronic anxiety, expressed by parents as uncertainties about the test results and worry regarding their child's health.9–11 Among parents of infants with false-positive hypothyroidism results, sleep disturbances, maternal crying, shock, and infant feeding problems were reported.10–12 According to Essex et al,13 contact with maternal stress during infancy may increase the susceptibility of the infant's hypothalamic-pituitary-adrenal system to later stress exposure.
Increased parental stress and altered parent-child relationships were also documented in studies screening for cystic fibrosis, hearing problems, diabetes mellitus, and metabolic disorders.14–17 Those studies suggested that parents were more overprotective and more focused on physical symptoms of their child when a false-positive result occurred. This might explain a trend toward an increase in child hospitalizations during the first 6 months of life among false-positive children in our study (mean: 0.17 hospitalization vs 0.08 hospitalization; P = .09). Another recent study identified insecure attachment relationships among infants with false-positive cystic fibrosis results from newborn screening, even when evaluated 12 to 18 months after the child's birth.18 Stress resulting from a false-positive newborn screen might alter parental ability or readiness to heed infant signals and needs, which might affect the quality of the parent-child relationship.10,11 This might account for lower maternal health scores and for the high level of parent-child dysfunctional interaction noted in our study. In addition, high scores on the parent-child dysfunctional interaction subscale suggest that the parent-child bond either is threatened or has never been established adequately.7
Parents also may experience a false-positive screening result as a significant threat to the child's well-being.11,19 Earlier studies on the impact of acute illnesses among children identified the “vulnerable child syndrome.”20 Other studies applied the vulnerable child syndrome to include (1) a condition or even a “nondisease” (eg, false-positive result) in a child, (2) parents who misinterpret that condition or its sequelae, and (3) parents who exhibit sustained unjustifiable anxiety about the child's vulnerability to future events.21 Parents whose child received a false-positive test result continued to fear that their child might be developmentally delayed, even after subsequent negative test results.21 Similarly, in our study, mothers who did not know the reason for the repeat screen reported higher stress levels on the PSI than did mothers who knew the correct reason for the repeat screen.
In addition, the delivery of the false-positive result may create a “nocebo phenomenon.”22 Although not widely known, this heuristic may explain the reactions of parents to a false-positive newborn screening result. The nocebo phenomenon occurs when “expectations of sickness” and the emotional responses to such expectations cause illness or distress.22 Nocebos can be triggered through unfavorable messages from the health care system or from the patient's psychological and social environment.23 In newborn screening, the delivery of a false-positive screening result may engender stress among parents by creating expectations of illness for an otherwise healthy child. This may also account for the increased worries about their child's future among parents in the false-positive group.
This study has some limitations because of potential sample differences. The disparity in the children's ages between the false-positive and normal-screened groups could have biased results. However, the instrument used to measure parental stress, the PSI, is considered age independent for small increments of age. Test-retest reliability coefficients were reported to remain stable after a 1-year interval.24
Although the false-positive group was recruited primarily from Pennsylvania and the normal-screened group from Massachusetts, these groups did not differ in characteristics of birth order, ethnicity, and employment status. The differences in socioeconomic and marital status were considered as possible confounders but were determined not to account for the observed differences in PSI scores.
This study suggests that false-positive results may lead to increased parental stress. This is especially true for parents who have not received adequate information about newborn screening. Therefore, the negative effects of false-positive newborn screening results might be mitigated through improved parental education. The timing of parental education about expanded screening and the speed with which a metabolic disorder can be ruled out also may be important. Specific communication plans for informing parents, fact sheets, and better distribution of newborn screening information materials during the prenatal and postnatal periods might be initiatives to consider to alleviate parental stress regarding false-positive results.
We thank Leslie Kalish, ScD, for statistical advice and Kevin Antshel, PhD, and Michelle Noble, PhD, for assistance with the qualitative measures used in this study. We also thank all of those who contributed to this study over the years by interviewing or recruiting subjects, especially Laura Finkelson, PsyD, Deborah Lobbregt, and Jennifer Timque. In addition, we are grateful to Edwin Naylor, PhD, and Philip Vaughan, MD, of Pediatrix. Lastly, we thank the families who participated in this study.
- Accepted November 17, 2005.
- Address correspondence to Elizabeth A. Gurian, BS, Department of Medicine, Children's Hospital Boston, 1 Autumn St, Room 526, Boston, MA 02115. E-mail:
The authors have indicated they have no financial relationships relevant to this article to disclose.
- ↵Sorensen JR, Levy H, Mangione TW, et al. Parental response to repeat testing of infants with “false-positive” results in a newborn screening program. Pediatrics.1984;73 :183– 187
- ↵Schulze A, Lindner M, Kohlmüller D, et al. Expanded newborn screening for inborn errors of metabolism by electrospray ionization-tandem mass spectrometry: results, outcome, and implications. Pediatrics.2003;111 :1399– 1406
- ↵Tymstra T. False positive results in screening tests: experiences of parents of children screened for congenital hypothyroidism. Fam Pract.1986;3 :92– 96
- ↵Abidin RR. Parenting Stress Index (PSI). 3rd ed. Odessa, FL: Psychological Assessment Resources; 1995
- ↵Strauss A, Corbin J. Basics of Qualitative Research: Techniques and Procedures for Developing Grounded Theory. 2nd ed. Newbury Park, CA: Sage Publications; 1998
- ↵Hollingshead AB. Hollingshead two factor index of social position. In: Miller DC, ed. Handbook of Research Design and Social Measurement. 5th ed. Newbury Park, CA: Sage Publications; 1991: 351–359
- ↵Bodegård G, Fyrö K, Larsson A. Psychological reactions in 102 families with a newborn who has a falsely positive screening test for congenital hypothyroidism. Acta Paediatr Scand Suppl.1983;304 :2– 21
- Clemens CJ, Davis SA, Bailey AR. The false-positive in universal hearing screening. Pediatrics.2000;106 (1). Available at: www.pediatrics.org/cgi/content/full/106/1/e7
- ↵Green M. Vulnerable child syndrome and its variants. Pediatr Rev.1986;8 :75– 80
- ↵Leslie LK, Boyce WT. Consultation with the specialist: the vulnerable child. Pediatr Rev.1996;17 :323– 326
- ↵Abidin RR. Parenting Stress Index: Professional Manual. 3rd ed. Odessa, FL: Psychological Assessment Resources; 1995
- Copyright © 2006 by the American Academy of Pediatrics