What is Genetic Newborn Screening Test and who is it for?

What is Newborn Screening?

A newborn screening (NBS) test looks for various developmental, genetic, and metabolic disorders in the newborn. This allows steps to be taken before symptoms develop. Most of these illnesses are extremely rare, but can be treated if caught early. Early testing for these conditions allows physicians and parents to take timely measures to manage, treat, or intervene in disease progression, allowing the baby to lead a healthy, normal life. All babies must be screened at birth, irrespective of whether they look healthy or not, since there can be conditions that may not manifest in ways that make the child look unhealthy. For example, Phenylketonuria (PKU) testing screens the infant’s system for the ability to process phenylalanine – a compound present in several protein-rich foods and some sweeteners. If the infant is phenylketonuriac (a baby who has the condition), he would be unable to metabolise phenylalanine, whose levels in the blood and tissues increase, resulting in brain damage. However, if diagnosed early, the baby can be put on a special diet early on, and ill effects of the disease can thus be prevented. Another great example would be that of hypothyroidism. Babies affected by hypothyroidism are unable to produce sufficient quantities of the thyroid hormone. If these babies are treated with thyroid hormone supplements from the start, they can avoid the delayed growth and brain damage which would inevitably happen, if the hypothyroidism goes unchecked and untreated. Here too, early diagnosis is imperative to ensure that the child leads a long and healthy life.

While close to 80% conditions most commonly affecting the baby at birth can be managed easily (such as PKU and hypothyroidism), there are a few conditions which, sadly, cannot be treated with the same ease. However, knowing about those conditions early on is equally important and helpful. For example, if a baby has sickle cell anemia, there isn’t much that can be done at this point to cure disease from the root. Medical intervention is important. However, babies affected by sickle cell disease are at a high risk for developing harmful infections. A daily dose of penicillin (for example) may be recommended by the pediatrician to prevent these infections. Even though the antibiotic will not change the fact that the child has sickle cell anemia, it will ensure that the risk of “opportunistic” infections is reduced drastically.

“Knowledge is power”, and early intervention can save a lot of time, money and in some cases, your life! However, in order to intervene early, one needs to be tested early, and that’s where a genetic newborn screen comes into play. One thing we all must remember is that the laws of genetics apply to us all, whether or not we chose to learn about them.


The Goal of NBS: Early detection of children at increased risk for selected metabolic or genetic diseases so that medical treatment can be promptly initiated to avert metabolic crises and prevent irreversible neurological and developmental problems.


Since their introduction in the 1960s, newborn screening services have been offered to every parent soon as their child is born. Conducted at 24-48 hours post birth, the blood sample collected from the baby via a simple heel prick is subjected to a battery of biochemical tests to screen for a select number of inherited conditions, as per the guidelines established by the American College of Medical Genetics (ACMG).

A little background: NBSAnalytes image

Infant wellness management  is a key focus area in public healthcare. By ensuring that the national childbirth programme and
neonatal care is top notch, the overall burden of disease on our society can be reduced, over time.

Dr. Robert Guthrie is widely acknowledged as one of the pioneers in the NBS sector. He designed and performed the first biochemical assay for PKU in newborns. The spread of awareness and subsequent implementation of screening in hospital wards saw significant progress in the 1960s. Some of the major milestones in NBS are:

  • Initially focussed on mental retardation, NBS programmes now target multiple genetic conditions which cause critically severe
    outcomes such as cardiac, auditory (hearing), muscular and immune function.
  • The timeline of events in global NBS has only seen improvement – from a broadened scope (in terms of conditions detected and timely reporting) to the accuracy of testing (in terms of specificity).  Thanks to the advent of DNA analysis for molecular confirmation, NBS can now save lives better and faster with added precision.
  • The Newborn Screening Quality Assurance Program (NSQAP) was established in 1978, by the Centers for Disease Control and Prevention (CDC), USA for ensuring that all newborn screening tests are performed by adhering to quality standards and guidelines. The NSQAP also works continuously towards enhancing the scope, efficiency and availability of NBS.

Current scenario (India)

Indian newborns (along with China, Pakistan, Bangladesh and Indonesia) make up 50% of the global newborn population. Screening them for disease has become imperative for global health organizations. Given that there is social value attached to blood marriages (consanguinity), India is host to many prevalent, inherited syndromes. According to recent reports, 6-10% of the consanguineous marriages in India result in genetic transmission of disease.

One in 25 Indians is a carrier for beta-thalassemia. A major proportion of the thalassemia cases reported in newborns is due to unidentified carriers (parents) and zero access to counseling/testing options. Cystic fibrosis, sickle-cell anaemia and haemophilia A are other common genetic diseases that are diagnosed in Indian newborns. All these conditions are single-gene disorders that can be detected (and managed) by timely screening and counseling.

Apart from metropolitan cities, the rest of the country still needs a vast improvement in terms of awareness, resources and access. Government-funded NBS programmes are yet to become a reality.


Current methods of NBS – merits and demerits?

In traditional NBS, laboratory methods such as High Performance Liquid Chromatography (HPLC), Tandem Mass Spectrometry, Liquid Chromatography–Mass Spectrometry (LC-MS) and Immunoassays are used to measure biomarkers; e.g., the amino acid phenylalanine is measured during the PKU test and the level of 17α- hydroxyprogesterone (17-OHP) is measured to detect congenital adrenal hyperplasia (CAH). These techniques have replaced older, indirect methods such as microbiological culture and identification (used by Guthrie).

Limitations of traditional NBS:

  • Newborns typically do not display symptoms for metabolic disease until a few weeks into their lives. Traditional NBS would report the disease based on clinical developments, and can fail to pick up the presence of abnormality. Genetic testing serves as an ideal support for final diagnosis.
  • Cannot serve as a stand-alone screening test since there could be false positives.
  • NICU- and preterm-baby samples are difficult to process, as it would require greater optimization due to low levels of available analyte.
  • No mutation/root cause analysis


The limitations of Traditional NBS using NICU and Preterm births as an example:

Preterm birth:

Babies born alive before 37 weeks of pregnancy is completed are defined to have preterm birth. According to WHO report updated in 2015, the key facts are:

  • It is estimated that around 15 million children are born preterm each year.
  • Preterm birth complications are the leading cause of death among children under the age of 5 – amounting to almost 1 million deaths globally, in 2013 alone!
  • Three-quarters of them could be saved with current, cost-effective, and timely interventions.
  • Across a list of 184 countries, the rate of preterm birth ranges from 5% to 18% of babies born.

The 6 countries with the greatest number of preterm births:

  • India: 35,19,100
  • China: 1,172,300
  • Nigeria: 7,73,600
  • Pakistan: 7,48,100
  • Indonesia: 6,75,700
  • The United States of America: 5,17,400

BabyMap Supplemental Newborn Screening is intended to provide a holistic approach for newborn health care by coupling both genetic and biochemical tests and thus providing insights into the underlying genetic conditions.


Challenges with conventional newborn screening in the NICU:

A preterm newborn requires special treatment following birth as the child’s body is acclimating to new surroundings earlier than anticipated. Several factors as listed below put premature newborns at risk for false newborn screening results.  

  • Delayed Development: Premature babies have early entrance into the world, and so may have altered metabolic system and produce false results.
  • Treatment Types: Preterm infants receive altered nutrition through alternate treatments and medications and this could cause false readings to the conventional NBS.

Newborn screening regulations for preterm or ill infants include multiple conventional NBS tests spaced at different intervals – such as screening on admission to the NICU, again after 48-72 hours, and once again at 28 days of age or upon discharge. Since the metabolic analyte varies depending on the health condition of the baby, the test is done thrice for more accurate results. The time sensitivity of these conditions makes diagnosis and treatment pivotal for neonatal care. BabyMap, being a genetic test whose results do not vary with the health condition of the baby, it is the perfect answer!


Benefits of Genetic Testing in the NICU:

As the conventional NBS is done metabolically, different levels in the blood are tested for abnormalities.  There are several factors that can alter these levels in the blood and lead to false readings. Following abnormal metabolic screening, additional genetic testing is often required to confirm a diagnosis. BabyMap screens the child’s DNA for genetic abnormalities that cause a disorder. DNA is an individual’s “blueprint” and is unlikely to alter due to health status, medications, or other preterm influences. With the use of Next Generation sequencing, newborns will receive the most comprehensive screening results. BabyMap offers most reliable results to fragile newborns in the NICU.


BabyMap offers genetic screening to 171 detectable metabolic conditions. The targeted conditions were chosen due to available treatment options that often when detected early and managed well leads to a healthy child. Early detection is key for successful treatment and management. BabyMap provides fast results to help confirm diagnosis, rule out life threatening diseases, and possibly save a life.
BabyMap and a conventional Newborn Screening is essential for all patients within the NICU.


Why BabyMap is the ultimate test for NBS:


  • Super-fast results  – We can “deliver” in less than 96 hours!
  • Root cause confirmation – Genetic report of the presence/absence of mutations is a physician’s advantage for targeted treatment.
  • Excellent coverage – Five to six percent of mental retardation cases in Indian children is due to metabolic disease (galactosemia, urea cycle disorder, etc). Apart from these conditions, BabyMap also tests for all metabolic diseases, as per ACMG recommendations.
  • State-of-the-art technology: Next Generation Sequencing allows simultaneous detection of multiple gene defects, via a single laboratory workflow. This also facilitates a significant reduction in cost compared against conventional genotyping.
  • Higher “aversion” rate – By testing the baby’s DNA within a short window of opportunity (before symptoms appear), it has been proved that a greater number of infant deaths can be prevented.  Nearly 80% of the conditions are completely manageable through nutritional intervention.
  • Reflex testing available for abnormal screening results (from traditional NBS)


 Importance of NBS

DNA-based Newborn Screening examines genes for metabolic disease and other inherited conditions. Genes that are known to cause genetic conditions are analyzed. This adds a layer of accuracy and comprehensiveness to traditional biochemical NBS, and, is a powerful tool in picking up newborns for whom early diagnosis and intervention will ensure healthy and normal development.

BabyMap Newborn Screening brings advanced genetic technology to Newborn Screening. Here are a few reasons why BabyMap is the perfect choice for parents who want to be proactive and give their children the very best start in life:

  • DNA Based: BabyMap tests DNA – the “blueprint” that codes for health or disease- for changes that could indicate a serious but preventable genetic condition  
  • Quick Results: Since DNA is typically unchanged (compared against fluctuations in levels of biochemicals) BabyMap can be performed immediately after birth. There is no need to wait for 48 hours before the baby’s metabolism kicks in.  
  • Coverage: BabyMap Newborn Screening tests over 106 genes that are clinically linked to 171 genetic conditions  
  • Confirmatory Testing: Since BabyMap is DNA based, it does not require extensive follow-up testing or additional confirmatory testing. It is a genetic test that can be used for screening as well confirmation.