Children with genetic conditions in the United States: Prevalence estimates from the 2016-2017 National Survey of Children's Health.

PURPOSE: Estimating the overall prevalence of genetic conditions among children in the United States and the burden of these conditions on children and their families has been challenging. The redesigned National Survey of Children's Health provides an opportunity to examine the prevalence and burden. METHODS: We used the combined 2016-2017 National Survey of Children's Health to estimate the prevalence of genetic conditions among children aged 0 to 17 years (N = 71,522). Bivariate analyses were used to assess differences in sociodemographic characteristics, health-related characteristics, and health care utilization between children with and without genetic conditions. RESULTS: In 2016-2017, the prevalence of children aged 0 to 17 years with a reported genetic condition was approximately 0.039, roughly equating to 2.8 million children. A greater percentage of children with genetic conditions had a physical (50.9% vs 24.8%), mental (27.9% vs 5.8%), or behavioral/developmental/intellectual condition (55.6% vs 14.4%) than children without a genetic condition. Furthermore, they used more care and had more unmet health needs (7.6% vs 2.9%). CONCLUSION: This study provides an estimate of the overall prevalence of children living with genetic conditions in the United States based on a nationally representative sample. It also highlights the physical, mental, and behavioral health needs among children with genetic conditions and their unmet health care needs.

Newborn screening timeliness quality improvement initiative: Impact of national recommendations and data repository.

BACKGROUND: Newborn screening (NBS) aims to achieve early identification and treatment of affected infants prior to onset of symptoms. The timely completion of each step (i.e., specimen collection, transport, testing, result reporting), is critical for early diagnosis. Goals developed by the Secretary of Health and Human Services' Advisory Committee on Heritable Disorders in Newborns and Children (ACHDNC) for NBS timeliness were adopted (time-critical results reported by five days of life, and non-time-critical results reported by day seven), and implemented into a multi-year quality improvement initiative (NewSTEPS 360) aimed to decrease the time to result reporting and intervention. METHODS: The NBS system from specimen collection through reporting of results was assessed (bloodspot specimen collection, specimen shipping, sample testing, and result reporting). Annual data from 25 participating NBS programs were analyzed; the medians (and interquartile range, IQR) of state-specific percent of specimens that met the goal are presented. RESULTS: The percent of specimens collected before 48 hours of life increased from 95% (88-97%) in 2016 to 97% (IQR 92-98%) in 2018 for the 25 states, with 20 (80%) of programs collecting more than 90% of the specimens within 48 hours of birth. Approximately 41% (IQR 29-57%) of specimens were transported within one day of collection. Time-critical result reporting in the first five days of life improved from 49% (IQR 26-74%) in 2016 to 64% (42%-71%) in 2018, and for non-time critical results from 64% (IQR 58%-78%) in 2016 to 81% (IQR 68-91%) in 2018. Laboratories open seven days a week in 2018 reported 95% of time-critical results within five days, compared to those open six days (62%), and five days (45%). CONCLUSION: NBS programs that participated in NewSTEPs 360 made great strides in improving timeliness; however, ongoing quality improvement efforts are needed in order to ensure all infants receive a timely diagnosis.

Case Definitions for Conditions Identified by Newborn Screening Public Health Surveillance.

Newborn screening (NBS) identifies infants with rare conditions to prevent death or the onset of irreversible morbidities. Conditions on the Health and Human Services Secretary's Recommended Uniform Screening Panel have been adopted by most state NBS programs, providing a consistent approach for identification of affected newborns across the United States. Screen-positive newborns are identified and referred for confirmatory diagnosis and follow-up. The designation of a clinically significant phenotype precursor to a clinical diagnosis may vary between clinical specialists, resulting in diagnostic variation. Determination of disease burden and birth prevalence of the screened conditions by public health tracking is made challenging by these variations. This report describes the development of a core group of new case definitions, along with implications, plans for their use, and links to the definitions that were developed by panels of clinical experts. These definitions have been developed through an iterative process and are piloted in NBS programs. Consensus public health surveillance case definitions for newborn screened disorders will allow for consistent categorization and tracking of short- and long-term follow-up of identified newborns at the local, regional, and national levels.

Interactions of atropine with heterologously expressed and native alpha 3 subunit-containing nicotinic acetylcholine receptors.

(1) Atropine, a classical muscarinic antagonist, has been reported previously to inhibit neuronal nicotinic acetylcholine receptors (nAChRs). In the present study, the action of atropine has been examined on alpha3beta4 receptors expressed heterologously in Xenopus oocytes and native nAChRs in medial habenula neurons. (2) At concentrations of atropine often used to inhibit muscarinic receptors (1 micro M), responses induced by near-maximal nicotine concentrations (100 micro M) at negative holding potentials (-65 mV) are inhibited (14-30%) in a reversible manner in both alpha4 and alpha3 subunit-containing heteromeric nAChRs. Half-maximal effective concentrations (IC(50) values) for atropine inhibition are similar for the four classes of heteromeric receptors studied (4-13 micro M). (3) For alpha3beta4 nAChRs in oocytes, inhibition by atropine (10 micro M) is not overcome at higher concentrations of agonist, and is increased with membrane hyperpolarization. These results are consistent with non-competitive antagonism--possibly ion channel block. (4) At low concentrations of both nicotine (10 micro M) and atropine (<10 micro M), potentiation ( approximately 25%) of alpha3beta4 nAChR responses in oocytes is observed. The relative balance between potentiation and inhibition is dependent upon membrane potential. (5) In rat medial habenula (MHb) neurons, atropine (0.3-3.0 micro M) inhibited nicotine-induced responses in both a concentration and membrane potential-dependent manner (at -40 mV, IC(50)=4 micro M), similar to the effects on alpha3beta4-nAChRs in oocytes. However, unlike heterologously expressed receptors, potentiation was barely detectable at depolarized membrane potentials using low concentrations of nicotine (3-10 micro M). Conversely, the weak agonist, choline (1-3 mM) was observed to augment responses of MHb nAChRs.