Long QT Syndrome Screening in Newborns

Long QT syndrome (LQTS) is a genetic disorder characterized by a prolonged QT interval on
the ECG and occurrence of syncope, ventricular arrhythmias, and sudden death. LQTS is a
major cause of sudden death in infants, children, and young adults. Treatment by β-blockers
and/or placement of an implantable cardioverter defibrillator (ICD) are effective in
preventing sudden death, if the diagnosis of LQTS is made early.

The efficacy of ECG screening of newborns for LQTS has been demonstrated in Italy.
Furthermore, within the national healthcare system in Italy, universal ECG screening in
newborns (<30 days old) is cost-effective. The U.S. debate for universal LQTS screening
started in the mid-2000's. In a 2007survey completed by North American pediatric
cardiologists, 27% favored optional ECG screening of newborns, whereas 11% supported
mandatory screening (363 responses, 35% response rate). There may be stronger support for
universal screening, now that more data are available.

Obtaining a good standard 12-lead EKG on a neonate in the clinic is difficult and time
consuming. If an ECG device for newborn screening were readily available, reliable, easy to
use, and cost-effective, then universal screening of all 4 million newborns in the U.S. each
year would identify 2,000 infants with LQTS who are at risk for sudden death, assuming the
prevalence is the same as in Italy. Perhaps more than 300 deaths per year from SIDS could be
prevented, as well as many more sudden deaths in children, adolescents, and young adults.

During Phase I of this project, a new device was developed to meet this clinical need
(called QTScreen). In Phase II, the aim is to test the capacity of QTScreen for LQTS
screening in newborns and the feasibility of home screening by parents in an ethnically
diverse population of Northern and Southern California. The results of this clinical trial
may validate the device as a screening tool for LQTS, and also provide important scientific
data for supporting newborn screening for LQTS in the U.S.

The 4 main objectives are:

1. To validate the capacity of QTScreen for LQTS screening in newborns. This will be a
clinical trial on 4,000 newborns, conducted at the Los Angeles Biomedical Research
Institute (LABioMed).

2. To determine the extent to which parents are able to use QTScreen on their babies at
home.

3. To survey end-user experience and opinions. The target users of QTScreen are parents.
Participating parents will be asked to complete a survey, to obtain data for further
development of the device.

4. To estimate the LQTS prevalence in California. To date, the only population-based
estimate of LQTS prevalence is 1 in 2,000 in Italy. In a recent study in Japan, 4,285
1-month-old infants had ECG screening. The LQTS prevalence was not reported, because
only 10% of subjects with QTc values >450 msec had gene testing. There has been no
population-based study of LQTS in the US. In a study of 707 children with hearing loss
in California, 2 subjects had potassium voltage-gated channel KQT-like subfamily member
1 (KCNQ1 potassium channel) mutations, truncation or splicing. This trial will provide
data on the LQTS prevalence in California.

Study Sites:

Study procedures will be conducted at subjects' homes. Subjects will be recruited from LA
BioMed at Harbor-UCLA Medical Center, Providence Little Company of Mary Medical
Center-Torrance, Santa Clara Valley Medical Center, and St. Francis Medical Center. Approval
from each of the recruitment sites will be obtained prior to commencing recruitment.

Consent:

Consent will be sought from one parent only. Parents will be given the opportunity to
thoroughly read the consent form and to ask questions.

Risk/Benefit:

ECG is a routine test performed on infants, children and adults every day in the hospital
for many years with no problems or adverse events. The QTScreen system used in this study is
a simplified way of performing an ECG test on infants. Some subjects may undergo genetic
testing as part of this research and there are some risks associated with genetic testing,
such as emotional and confidentiality.

There is a very small risk of infection or rash related to the procedure involved in ECG
testing. The subject may feel some discomfort from the sticky patches placed on and removed
from his/her chest. Discomfort will be minimized by using an adhesive remover wipe which is
commercially available and used by hospitals. Although infection is very unlikely to occur,
rules and procedures of the nursery and clinic will be followed. This includes cleaning the
ECG equipment and sanitizing it using a disinfecting wipe before and after each use to
prevent infection.

The effects of drawing blood are usually pain, bleeding and/or a bruise where the needle is
inserted. Occasionally the area around the vein may swell. Serious complications such as a
blood clot or infection may occur but these are rare. Some people feel faint when having
blood drawn. Necessary precautions, such as gloves and proper sterilization, will be taken
to minimize pain and infection. A small amount of local anesthetic cream may be placed on
the child's forearm.

Appropriate precautions will be used to minimize the risks associated with this project and
feel that in general the risks associated with this project are low.

The information gained from this study will help to find ways to possibly simplify the ECG
test. This research study may also lead to a better understanding of LQTS which can provide
important insight for future treatments and research. Therefore the general feeling is that
the benefits of this project outweigh the risks.

Inclusion Criteria:

1. Born at ≥36 weeks of gestation.

2. Birth weight 2.5-4.5 kg

Exclusion Criteria:

1. Babies that have been born with a heart disease.

2. Babies who have a skin condition, allergies, or chest deformities making ECG on the
chest difficult or impossible.