PROGRAM EFFECTS ON DECREASING MORBIDITY AND MORTALITY

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PROGRAM

EFFECTS

ON DECREASING

MORBIDITY

AND MORTALITY

Newborn

Screening

in New York City

Ranjeet

Grover,

MD

From the New York City Department of Health, New York

In the absence of a cure for sickle cell disease,

the successful management of this disorder involves

prevention and early intervention of complications

associated with the disease. Sickle cell screening at

birth can minimize the impact of the disease in the

infants and their families for the following reasons:

(1) Early diagnosis could ensure early placement of

the affected infants into a comprehensive care

sys-tem for appropriate health care. (2) In the

compre-hensive care system, parents could be educated

about early signs and symptoms of life-threatening

complications such as acute splenic sequestration

crisis, increased susceptibility to overwhelming in-fections, and the need to contact physicians for

prompt medical intervention. (3) Early diagnosis

can provide the option for possible prophylaxis

against pneumococcal infection, a leading cause of

mortality among these patients. (4) Screening of

newborns for sickle cell could also provide the

fam-ilies with genetic information of potential value to

assist them in making informed decisions about

future reproduction.

Statewide screening of newborns for sickle cell

anemia was implemented in New York by law in

1975. Early experience with the newborn screening

program in New York City was dismal mainly

be-cause of the lack of a follow-up program. Of the 111,421 initial filter paper blood specimens tested in one year from New York City, 370 were identified as presumptively positive for sickle cell disease and a capillary blood specimen was requested for repeat testing to confirm the filter paper diagnosis. How-ever, only 195 (53%) of the repeat specimens

re-quested were received in the laboratory for testing,

and sickle cell disease was diagnosed in 47 infants.

In 1978, with the funds available from the

Ge-netic Disease Act, a newborn screening follow-up

program was set up at the New York City Health

Department to provide the following services: (1)

case retrieval of presumptively positive specimens

for repeat testing to confirm the filter paper

diag-nosis; (2) referral ofpatients with diagnosed disease

for ongoing medical care; and (3) communication

systems to provide testing and counseling to the families of trait newborns.

As a result, in the following year, 144 of the 152

infants with presumptively positive results were

retested, and sickle cell disease was diagnosed in 141 newborns, and all were referred for medical care. Since then, our experience with follow-up of infants with presumptively positive results has

im-TABLE 1. Mortality Among Children With Sickle Cell

Disease Identified (January 1980 Through December

1984) _______

No. of

Infants

Newborns with sickle cell dis- 759

ease referred for follow-up care

Data received from follow-up fa- 708 cilities by the end of 1985

Deaths reported 10*

Sepsis 6

Acute sickle cell crisis 1

Cerebral vascular accident 1

Pneumonia 1

Congenital heart disease 1

and heart failure

* Eight infants died in New York City and two died out

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proved, and lately more than 99% have been

re-tested.

In New York state, filter paper specimens

col-lected for phenylketonuria screening are used for initial screening for sickle cell. The laboratory

pro-cedures used are electrophoresis by cellulose acetate

and citrate agar. Our experience has demonstrated

that these techniques are reliable and reproducible

for diagnosis of sickle cell disease.’ Of the 759 newborns referred during the 5-year period for

fol-low-up, diagnosis of sickle cell disease was

con-firmed in 738 patients by the follow-up clinics.

Twenty-one infants did not go to the referred

din-ids and did not return for follow-up. Of the 738

retested in the follow-up clinics, diagnosis in 32 patients was reclassified from one form of sickle

cell disease to another, but none of the infants with

the disease was found to have sickle cell trait.

With regard to accuracy of trait diagnosis, trait

hemoglobin diagnosis on filter paper specimens is

considered final, and no repeat testing is requested;

hence, misdiagnosis in this category could not be

excluded. However, studies were performed in the

families of about 30% of newborns during the

pre-vious 5-year period, and no infant with the trait

was found to have sickle cell disease.

Similarly, Hardy-Weinberg statistics applied to black newborns identified with hemoglobinopathies

during the 1-year period showed that the computed

incidence of disease was comparable to the observed

frequency considering the lack of precisely defined population and mating between the members of

different ethnic groups with different hemoglobin

gene frequency.2

On the other hand, of the 168 infants identified as having FAST and F Hb variants at birth, 20 were found to have trait hemoglobinopathies when

retested by Hb electrophoresis and isoelectric

fo-cusing at 1 year of age.3

Of the 759 infants referred for medical care

dur-ing the 5-year follow-up period, data were available

for 708 patients. There were 51 children reported

to have been lost for follow-up for more than 6

months. Ten of the 708 patients were reported to have died during the 5-year period. Eight died in New York City and two died out of the United States. Age at the time of death was in the range of 15 months to 3’/2 years.

Precise data concerning mortality among chil-dren with sickle cell disease before the institution of the New York City follow-up program are not available. However, the following significant

obser-vations were made concerning the eight known

deaths that occurred during the early years of the

state program (January 1976 to May 1978): (1) Only

three of the eight families were aware of the sickle

cell disease diagnosis in their infants at the time of

death. (2) Only one of the five infants identified by

filter paper testing was retested to confirm the presumptively positive diagnosis. (3) Two deaths

were classified as sudden infant death syndrome

because of a lack of precise diagnosis.

Similarly, experience of the western upstate New

York group4 revealed that two of the 14 patients

with sickle cell anemia had died during infancy,

and only one family was aware of the sickle cell

disease diagnosis at the time of death.

Screening is primarily done to identify the

new-borns with sickle cell disease, but the test proce-dures used to identify the newborns with disease

identify the traits as well. However, the issue of

trait finding, a by-product of sickle cell disease

screening, is seldom addressed. Even though

new-born screening is not the optimal method of finding

couples at risk, the birth of an AS newborn to a

black couple in the United States increases their

probability of subsequently having a child with

sickle cell disease from one in 576 to one in 48, and

the odds increase to one in four if both parents have sickle cell trait.5

CONCLUSION

Our experience demonstrates that the diagnosis

of sickle cell disease at birth along with early

inter-vention can reduce mortality among identified

pa-tients. However, accurate screening of newborns in

the absence of a comprehensive follow-up program

is of limited value.

Our experience with trait follow-up indicates that

couples at risk should be sought both by testing the

parents of trait newborns and by testing the

moth-ers in the prenatal period.

Our recommendations are that programs for

sic-kle cell screening of newborns should be structured

on the basis of clearly defined goals and should

ensure the following services: a newborn screening

laboratory under strict quality control with back-up facilities for special test procedures and

inter-pretation of test results; an efficient and effective

mechanism for recall of infants with presumptively

positive results and referral of patients with the

sickle cell disease diagnosis; treatment centers with

a high standard of medical care to provide

compre-hensive care to patients with sickle cell disease and

their families; skilled genetic counseling for the

families of newborns with sickle cell disease and

trait, including the information available concern-ing prenatal diagnosis for couples at risk; broad-based and ongoing education for professionals,

par-aprofessionals, and the public at large to enhance

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evaluate the effectiveness and success of the pro- screening program for newborns in New York City

(1979-1980). Am J Pediatr Hematol Oncol 1983;73:249-252

gram in achieving the goals set forth. 3. Grover R, Sehmi AK: Outcome of screening diagnosis of variant hemoglobins detected at birth, abstracted. APS/

SPR, No. 755, 1986, p 281a

4. Warren NS, Carter TP, Humbert JR, et a!: Experience of

REFERENCES western upstate New York group with newborn screening

for hemoglobinopathies. J Pediatr 1982;100:373-377

1. Scriver CR: Genetic screening: Implications for preventive 5. Grover R, Newman 5, Wethers D, et a!: Newborn screening medicine. Am J Pediatr Hematol Oncol 1983;73:243-245 for hemoglobinopathies: The benefit beyond the target. Am

2. Grover R, Shahidi 5, Fisher B, et al: Current sickle cell J Pediatr Hematol Oncol 1986;76:1191-1192,1236-1237

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1989;83;819

Pediatrics

Ranjeet Grover

Newborn Screening in New York City