Fighting for Normalcy
Newborn screening ups the chances of correcting metabolic disorders
Since 1996 the Newborn Screening Program (NSP) has screened more than 266,000 newborns ensuring early treatment and improvement in the lives of 3,253 babies with endocrine and metabolic disorders. Compared with other developing nations like Indonesia and Vietnam, the Philippines posts a higher screening rate of 2.8 percent (based on 1.5 million births in 1998). Exactly 266 government and private hospitals (including a few lying-in clinics) nationwide take part in the program.
The NSP started as a pilot study by a team of pediatricians and obstetricians known as the Newborn Screening Study Group under the National Institutes of Health (NIH). Headed by doctors Carmencita Padilla and Carmelita Domingo it lasted from June 1996 to December 2000, collaborating with the Royal Alexandra Hospital for Children in Australia.
"We started without funding and we were doing the pilot study for free," recalled Dr. Sylvia Estrada, head of the newborn screening laboratory at the NIH. "Our office then was at the Philippine General Hospital's Pediatric Research Laboratories, and the running of samples was done free by the New South Wales Australian Laboratory, with which we were affiliated. We invited many hospitals to participate but only 24 responded."
The doctors initially funded the project themselves until donations slowly came in. Said Estrada: "We set up a program, Sponsor a Child/Sponsor a Newborn, and sought help from other doctors/individuals. By far one of the most consistent corporate sponsors is Wyeth Philippines. They've been there [since] our organizational meetings; [they] printed our flyers and educational materials, even though they had no specific gains because they are not marketing the special metabolic formulas for children afflicted by these conditions."
The pilot study initially screened for CH, CAH, galactosemia (Gal), phenylketonuria (PKU), and homocysteinuria. After the pilot study showed the prevalence of the various conditions, the NSP was included in the CHILD 2025 program of the Department of Health in March 1999. Homocysteinuria however, was removed from the NSP because no case was picked up during the pilot study.
Screening Process
Blood from a heel prick is blotted on special filter paper. Adequate blood samples must be obtained and air-dried for satisfactory results. The sample should ideally be obtained two days after birth to prevent false positive and false negative results. The samples are sent for laboratory analysis, which takes four to seven days from receipt of the sample at the NBS laboratory.
Much of the difficulty lies in tracking the patients screened, relaying the results to the family, and advising parents of confirmatory testing if initial screening is positive.
In preparation for the nationwide implementation of NBS, the NSP and DoH are working on a manual of operations to guide and facilitate the screening process. They plan to have one central reference laboratory under which several newborn screening centers will be established nationwide. These centers will facilitate specimen collection, perform the screening tests, releasing the results and recalling the patients.
The screening program has so far shown G6PD to have the highest prevalence rate of one in 61 newborn Filipinos. But Estrada said this figure is not accurate because of the poor recall rate of 44 percent, mainly because the serum confirmatory test is expensive (PhP700), not to mention there is only one laboratory in the country doing the confirmatory testing. "So we have no way of telling whether the rest of the 56 percent who haven't been confirmed are really positive," said Estrada.
G6PD is also the most common enzymatic deficiency worldwide, according to Estrada. It is prevalent among Greeks, Italians, Sephardic Jews, southern Chinese (Cantonese), Thais, and people of African descent. The trait is X-linked and manifests as red blood cell destruction within 48 to 96 hours after ingestion of or exposure to an oxidizing substance like sulfonamides, antimalarials, naphthaquinolones, and fava beans. The resulting hemolysis causes jaundice, hemolytic anemia, and kernicterus.
Estrada noted that the Philippine variant of G6PD is not as fatal as those seen in other countries. "The 'Union' variant, that originated from somebody who came from La Union, is the most common in the Philippines," she said. It is potentially dangerous especially to those who don't know they have G6PD and get inadvertently exposed to naphthalene balls and oxidizing substances. They could get a very bad hemolytic crisis.
CH is the second most common condition with a prevalence of one in 3,100, a little higher than the worldwide incidence of one in 3,500. CH results from lack of thyroid hormones to regulate metabolism and growth of the brain and tissues. Mental and growth retardation occurs if thyroid hormones are not administered by the fourth week of life.
CAH runs third with a prevalence of one in 5,700 vis-à-vis the worldwide rate of one in 12,000. Because it is more life-threatening compared with other inborn metabolic diseases, it has a higher recall rate for confirmatory testing.
PKU is less prevalent (one in 66,600 compared with one in 25,000 in the US). "In the Philippines we have not detected a case of classical PKU. Our four cases of hyperalaninemias (HPA) can tolerate higher protein loads compared to patients with classical PKU. HPA patients only get speech delays but not the seizures and severe mental retardation associated with classical PKU," said Estrada.
Galactosemia has the lowest prevalence (one in 87,300 versus the worldwide prevalence of one in 40,000). Galactosemia and phenylketonuria are autosomal recessive metabolic diseases. In galactosemia, intake of galactose-containing milk and dairy products builds up galactose, which is not metabolized by the body. Too much galactose results in cataracts, liver, and brain damage. Phenylketonuria occurs when the amino acid phenylalanine cannot be converted to tyrosine. Buildup of phenylalanine leads to mental retardation, developmental and growth delays, and hypopigmentation.
Plans are afoot to expand the NSP beginning with a pilot study on the prevalence of maple syrup urine disease (MSUD). "Anecdotally, we have picked up more than 40 cases in the last ten years in PGH alone. That is fairly high," Estrada said. MSUD is a fatal metabolic disorder where the amino acids leucine, isoleucine, and valine accumulate causing neurologic problems.
In developed countries use of the tandem mass spectrometer (MS-MS) allows screening for as many as 20 metabolic and endocrine disorders from a simple blood test. But the machine is expensive (it costs PhP16 million), and so are the reagents used for testing. And Estrada warned that the technology is a "double-edged sword." Many of the diseases that can be screened may actually be of no clinical significance while others have no available treatment, she said.
Newborn screening for the five conditions in the Philippines costs PhP550. A cheaper package of PhP310 tests for CH and CAH, which are given priority because of the mental retardation and developmental delay associated with CH and the life-threatening symptoms and sexual mistyping associated with CAH.
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