Newborn Screening by KNUST students,Ghana

Detailed presentation on newborn screening

1. Newborn Screening

2. 01 04 02 05 03 06 Introduction Importance Methods of Newborn Screening Sickle Cell Disease Congenital Adrenal Hyperplasia Galactosemia Outline 07 Congenital Hypothyroidism 08 Conclusio n

3. Introduction 01

4. Introduction Newborn: According to the World Health Organization (WHO), a newborn is a child under 28 days of age. Screening: Screening is the process of evaluating an individual for a particular disease, or risk factor for a disease. Usually involves using a laboratory test to assess a precursor or end product. It leads to early disease detection so that management can be instituted early.

5. Newborn Screening was started in the USA during the 1960s by Dr. Robert Guthrie with phenylketonuria (PKU), which can cause intellectual disabilities if left untreated. History of Newborn Screening

6. Newborn screening in Ghana officially started on 13th February, 1995 with the establishment of the National Newborn Screening Program. One of the commonest childhood diseases screened in Ghana is sickle cell disease which started Kumasi, Ghana, by the Comprehensive Sickle Cell Center at the Children's Hospital of Philadelphia in collaboration with the Ministry of Health and other institutions in Ghana. History of Newborn Screening

7. Newborn screening involves testing newborn babies for certain specific genetic, metabolic and congenital disorders shortly after birth. The importance of newborn screening is to 1. Detect these conditions early, often before symptoms appear, so that intervention and treatment can be made. 2. Early treatment to improve outcomes: 3. Prevention of full blown disease 4. Prevention of complications and Death Importance of Newborn Screening

8. 4. Cost-Effective: identifying diseases early prevents high cost associated with management of full blown disease. 5. Future in utero treatment: This is to alleviate phenotypic features 6. Family Planning: This can help parents make informed decisions about family planning, future pregnancies, and preventive measures for their child's health. Importance of Newborn Screening

9. In Ghana, newborn screening is typically performed within the first few days of a baby's life, ideally before the baby leaves the hospital or health facility. The Ghana Health Service recommends that newborn screening should be conducted within the first 72 hours after birth to ensure timely detection of any potential health conditions. It is important for healthcare providers in Ghana to follow the national guidelines and protocols for newborn screening to ensure that all babies receive the necessary tests and interventions. The screening process usually involves collecting a small blood sample from the baby's heel, which is then sent to a laboratory for testing. When should Newborn Screening be done in Ghana

10. Prevalence: Diseases that are relatively common in the population Severity: Diseases that have serious health consequences eg. phenylketonuria and Congenital hypothyroidism Treatability: Diseases for which effective treatments or interventions are available eg. congenital hypothyroidism 4. Factors considered in the selection of diseases for Newborn Screening

11. 4. Cost-effectiveness: The cost of implementing screening for a particular disease must be weighed against the potential benefits of early detection and treatment. 5. Stakeholder input: Input from healthcare professionals, public health officials, and advocacy groups can help inform decisions about which diseases to include in newborn screening programs. 6. Ethical considerations: Ethical considerations such as the potential impact of screening on families and the rights of parents to make informed decisions about their child's healthcare Factors considered in the selection of diseases for Newborn Screening

12. Methods of neonatal screening Heal prick Cord blood Urine EDTA borate buffer system at pH of 8.4 Developed for cord blood for sickle cell Acid agar electrophoresis Amino acid disorders

13. After screening and confirmation Patient is referred to the appropriate clinic Eg. Congenital Hypothyroidism to Paediatric Endocrine Clinic, Sickle cell to Paediatric Haematology clinic Multidisciplinary care Psychologist Nutritionist/dietician Paediatric specialist in the field Paediatric nurse specialist Pharmacist Patient/family Follow Up and Referral

14. Usually it is treatment is life long Counseling Education which should be continuous To let them understand the nature of the disease Dispel myths Let them understand the nature of treatment Life long Follow Up

15. Replacement therapy for specific enzyme or hormone deficiency Eg. thyroxine hormone replacement therapy in congenital hypothyroidism Omission of specific nutrients in diet Lactose and galactose free diet Symptomatic and specific treatment as in sickle cell Prevention od anaemia Prevention of vaso-oclusive crisis Prevention of infection Follow Up

16. Making sure the keep to appointment Call them if they default Access growth and development Psychological support Follow Up

17. Sickle Cell Disease

18. This is a genetic disorder characterized by abnormal hemoglobin, causing red blood cells to become rigid and sickle-shaped. It refers to a condition in which an individual has 2 abnormal Hb genes, at least one of which is HbS and the resulting features are due to the sickling phenomenon HbS results from a single point mutation in Hb synthesis. There is substitution of valine for glutamic acid at position 6 in the beta-chain giving rise To Hbs . Lysine replaces Glutamic acid at position 6 in HbC . Sickle Cell Disease

19. Sickle Cell Disease primarily affects people of African, Mediterranean, Middle Eastern, and Indian descent. The trait is estimated to be as high as 20-25% in Ghana  (up to 30% in Nigeria). The prevalence of SCD is 2% of all newborns (National Screening Programme figures-Kumasi). Frequency of AS 20% in southern Ghana and 10% in Northern Ghana. Frequency of AC 20% Northern Ghana and 10% Southern Ghana. > 90% of SCD cases are either SS or SC;  SS is about 67% in the Paediatric and Adolescent population 6.5% of all pediatric admissions in KATH Epidemiology

20. Methodology: Babies are screened at birth or at well-baby visits within days or a few weeks after birth. Mothers are asked to come for results within 4 weeks and failing that, an extensive tracking system is used to deliver results to the homes of families with babies with possible-SCD (P-SCD). Tracking relies solely on information obtained from mothers at the time of screening. The goal is to enrol P-SCD babies into the sickle cell clinic by eight weeks of age. Pregnant women, parents with children and the general public are regularly educated about the screening program. Children with Sickle Cell Disease receive comprehensive care through the Sickle Cell Clinic at Komfo Anokye Teaching Hospital. Protocol For Sickle Cell Disease Screening

21. Screening typically involves a blood test to detect abnormal hemoglobin. Methods include: High-performance liquid chromatography (HPLC) Isoelectric focusing (IEF) Cellulose Acetate Electrophoresis M olecular genetic testing (e.g. Polymerase C hain R eaction). Screening Methods and Diagnosis

22. Isoelectric focusing (IEF) The IEF-based gel electrophoresis distinctively separates haemoglobin variants into bands including HbF , HbA , HbS , HbA2 and HbC . These bands are compared with reference standards. It is the most popular newborn screening method and it is the one commonly used in Kumasi. Requires more expensive equipment and expertise than those for Hb electrophoresis. Able to separate HbF from the other common HbS used for newborn screening. Screening Methods and Diagnosis

23. Complications include: Sickle cell Dactylitis Increased susceptibility to infections Acute splenic sequestration Strokes Acute osteomyelitis Vasocclusive pain episodes Schooling problems (absenteeism) Complications

24. Screening of newborns for sickle cell disease (SCD) allows early initiation of prophylactic therapy, parental education, and comprehensive management, which results in reduced mortality. Positive results trigger early intervention and treatment to prevent complications. Treatment may include medications (e.g., hydroxyurea), blood transfusions, pain management, and antibiotics for infection prevention. These strategies – penicillin prophylaxis, immunization, and hydroxycarbamide – are available in Ghana. Management and Treatment

25. Congenital Adrenal Hyperplasia

26. Congenital adrenal hyperplasia (CAH) is an autosomal recessive disease emerging from a single mutation of genes for enzymes that are responsible for the production of glucocorticoids, mineralocorticoids, or sex steroids from cholesterol, by the adrenal glands. In the most common form of CAH, there is deficiency of the 21-hydroxylase enzyme resulting in inadequate amount of cortisol and aldosterone. This version is called CAH due to 21-hydroxylase deficiency. Congenital Adrenal Hyperplasia

27. The classic form, also known as the severe form, occurs in 1:15,000 births worldwide, while the non-classic or mild form occurs in approximately 1:1,000 births worldwide. In Ghana the incidence of Disorders of Sexual Development is 28/10000 ( Ameyaw E, Asafo-Agyei SB, Hughes IA, et al. Arch Dis Child 2019;104:636–638 Cx ) Epidemiology

28. Signs of classic salt-wasting CAH may include: Male-like genitals in girls Poor feeding Sleeping longer or more often (lethargy) Vomiting Weight loss or failure to gain weight normally Gets upset easily (irritability) Shock Rapid heart rate Signs of the classic simple-virilizing form of CAH can include: Early onset of body hair Male-like genitals in girls Small testicles in boys Large penis in boys Signs of Classic CAH

29. Newborn screening for Congenital Adrenal Hyperplasia (CAH) detects babies affected by deficiency in the adrenal enzyme 21-hydroxylase which is the most common cause of Congenital Adrenal Hyperplasia. Untreated CAH within the first week of life can cause progressive salt wasting crises during the first week of life result in in significant morbidity and mortality. Newborn screening for congenital adrenal hyperplasia is ideal when the newborn is screened between 48-72 hours after birth. Protocol for screening Congenital Adrenal Hyperplasia (CAH)

30. Aim To prevent neonatal salt crisis and mortality especially amongst boys within the first week of life. To avoid incorrect gender designation on newborn girls with highly virilized genitals and resulting sequelae To detect simple virilizing forms in order to avoid hyper androgenization Protocol for screening Congenital Adrenal Hyperplasia (CAH)

31. Detection of CAH This is based on the measurements of 17 hydroxyprogesterone levels in capillary blood samples obtained from the heel of the patient and impregnated in a blotting paper at 48hrs of life. For babies with birth weight less than 1500g , a further sample is collected at 2 weeks and for those less than 1000g a further sample is collected at 4 weeks Positive test will indicate high levels of 17 hydroxyprogesterone. Note that each laboratory has its own established cut off points based on the baby's sex, birthweight and gestational age. Protocol for screening Congenital Adrenal Hyperplasia (CAH)

32. False negatives can occur when physiological factors such as illness and delayed adrenal enzyme expression in the newborn cause elevated blood levels of 17 hydroxyprogesterone as well as pre-terms and boys. False positives can occur when samples are taken before 48hrs of life, also in preterms due to adrenal enztme immaturity. Protocol for screening Congenital Adrenal Hyperplasia (CAH)

33. Newborns with CAH are referred to a paediatrician endocrinologist who will determine whether a clinical referral or a repeat specimen will be required. However, newborns with CAH require long term glucocorticoid preplacement therapy The aim of treatment with medications is to reduce excess androgen production and replace deficient hormones. Glucocorticoid treatment mitigates rapid postnatal growth and progressive virilization in both males and females. Management and follow up

34. Galactosemia

35. Galactosemia basically means galactose in the blood. This is as a result of deficiency of enzymes which will break down galactose in the body. This causes the accumulation of galactose, a type of sugar found in milk and dairy products , in the blood. This high level of galactose can end up being toxic to the body. This condition can pose a huge risk to babies as the breastmilk and formulas they constantly feed on is made up of galactose. This is why early detection is very necessary to reduce the amount of complications associated with this condition. Galactosemia

36. Vomiting Diarrhoea Severe weight loss Lethargy Loss of appetite Jaundice These symptoms begin to appear a few days after birth when the baby starts feeding Clinical Presentation of Galactosemia

37. Galactos e mia is generally considered to be a rare condition, with estimates suggesting that it affects 1 in 30,000 to 60,000 live births. The epidemiology of galactosemia in Ghana is not well documented and there is limited data on the prevalence of this condition in the country. However it is seen in Ghana and other low income countries, there may be challenges in terms of access to diagnostic testing and specialised care for such disorders. Epidemiology

38. Galactosemia is not part of the routine screenings done for babies here in Ghana. Screening for galactosemia involves blood testing. A capillary blood sample is taken from the heel of the baby about 72 hours after birth and sent to the lab for analysis to measure the levels of galactose and GALT enzyme. Increased galactose levels and decreased GALT ( Galactose-1 - phosphate uridylyltransferase ) activity suggest that the baby has galactosemia. Protocol for screening Galactosemia

39. Normal range for galactose in the newborn is a total gal a ctose less than 10mg/dl. If the baby has galactose levels higher than this you now test for level of GALT enzyme in the blood .  GALT enzyme The normal range for GALT enzyme activity is between 18.5 to 28.5 units per gram of h a emoglobin . Results below this level are suggestive of galactosemia. Interpretation of Results

40. Babies who test positive for galactosemia undergo further diagnostic testing, typically genetic testing to identify the exact gene which has undergone mutation resulting in galactosemia. The three genes here are the GALT (galactose-1-phosphate uridylyltransferase ) gene, GALK1 (galactokinase) gene and GALE (UDP-galactose-4-epimerase) gene. Follow up testing

41. 1. Change in diet: Babies with galactosemia must be taken of milk based formula and given soy based formula to prevent symptoms associated with galactosemia. Also, since they are not going to take in milk through out their lives, patients with galactosemia tend to have low levels of calcium and so must be given calcium supplements daily. This can be given alongside vitamin D. 2. Rehabilitation: Even with adequate treatment some children with galactosemia end up with learning disabilities and speech delays. So as part of their treatment plan they should be sent for speech therapy . For children with learning disabilities , they will benefit fro m , individual education plans best suited to help them at their own pace . Follow up T reatment

42. Congenital Hypothyroidism

43. This is the deficiency of thyroid hormone present at birth. A newborn with congenital hypothroidism is not able to produce the normal amout of thyroid hormones. It is the most preventable cause of intelluctual disability and delay in treament can lead to irreversible neurological deficits. The thyroid hormone is very essential in the development of a newborn because it plays a role in growth, energy metabolism and neurodevelopment. The thyroid hormones play a role mainly in neuronal differentiation, synapsis development and myelination thus regulating central nervous development. Congenital Hypothyroidism

44. The overall incidence ranges from 1 in 3,000 to 1 in 4,000 live births with variation among different ethnicity. It is more common in females as compared to males in a ratio of 1.5 to 2:1 and common in multiple births, older mothers and preterm infants. Epidemiology

45. Most newborns have no or few clinical features at birth due to the transfer of partial thyroxine hormone transfer. Early signs may appear within the first week of life in severe cases. The early signs include; hypotonia, large anterior and posterior fontanelle, feeding difficulties, prolonged jaundice, poor or hoarse cry, constipation, lethargy. Late manifestations occur after 6 weeks of life and they include depressed nasal bridge, puffy eyelids, large tongue, hyporeflexia, hypotension, anaemia, umbilical hernia etc Newborns with CH can also develop respiratory distress due to myxedema of the airway and this characterized by noisy breathing, nasal stuffiness and intermittent perioral cyanosis. Clinical features of newborns with Congenital Hypothyroidism

46. Clinical features of newborns with Congenital Hypothyroidism

47. The priority of newborn screening is early detection of primary CH. Newborns with CH are usually asymptomatic at birth. NBS is obtained via a heel prick on dried whole blood spot samples on filter paper cards. The most specific test for detecting primary CH is TSH measurement but T4 measurement is more sensitive as it includes rare hypothalamic hypothroidism. Multiple factors can affect NBS results as thyroid physiology in neonates is dynamic. Also interpretation of the results requires knowledge about the age at specimen collection, prematurity status and clinical state of the newborn. Newborn screening of Congenital Hypothyroidism

48. Newborn screening is usually performed between 2 and 4 days of life. There are 3 screening methods; Initial TSH measurements with backup T4 measurements Initial T4 measurements with backup TSH measurements Simultaneous T4 and TSH measurements. This is the ideal screening method. Newborn screening of Congenital Hypothyroidism

49. Low free T4 and high TSH confirms diagnosis of primary CH Normal free T4 and high TSH confirms compensated or subclinical hypothyroidism Low free T4 and low or normal TSH can suggest the possibility of central CH but this is usually accompained by other pituitary hormone deficiencies such as growth hormone deficiency. Intepretation of thyroid function tests.

50. Primary CH may be masked due to suppression of TSH secretion caused by hypothalamic- pituitary immaturity, or effects of serious neonatal illness. Delayed TSH elevation is usually seen in preterms, very ill neonates and low birth weight babies. The second screening is done at 2 weeks of age or at discharge from the hospital. For preterms TSH is measured on days 3-5 after 1 week, at 2 weeks and at 4 weeks. The screening can also be repeated in newborns exposed iodine. TSH cut off level of 10mU/L or greater is considered positive for primary CH. When to repeat screening

51. Thyroid imaging studies Thyroid ultrasound Thyroid radio nuclear uptake scan Thyroid antibodies Serum thyroglobulin Urine iodine concentration Additional laboratory evaluation

52. Measurement of TSH Screening is performed by measurement of the levels of TSH at 48h post birth . A capillary blood sample is obtained from the newborn by heel puncture and collected on standard filter paper . Confirmation of congenital hypothyroidism V enous blood tests for TSH and free thyroxine [fT4] . Thyroglobulin levels are measured to assess for the presence of the thyroid gland. A ntithyroid antibodies and iodine levels are measured to assess for transient hypothyroidism . Imaging tests, such as thyroid ultrasound and scintigraphy, are very useful in determining the aetiology of CHT. Protocol for neonatal screening for congenital hypothyroidism

53. Reporting test results This is a key step in the diagnosis and treatment of CHT. The purpose is to help parents understand the benefits of early diagnosis in the prevention of brain damage, teach them how to correctly administer drug and importance of follow up. Protocol for neonatal screening for congenital hypothyroidism

54. A detailed personal and family history is taken on each visit and fT4 levels are measured to ensure thyroid hormone levels are within normal range. C linical follow-up for congenital hypothyroidism

55. Treatment should start the day the diagnosis is made, and its initiation should not be delayed pending performance of additional diagnostic tests . Treatment of congenital hypothyroidism

56. At age 3 years, patients without a definitive diagnosis may undergo re-evaluation. Definitive diagnosis of congenital hypothyroidism

57. Health Resources and Services Administration. https://newbornscreening.hrsa.gov/conditions/congenital-adrenal-hyperplasia NORD. https://rarediseases.org/rare-diseases/congenital-adrenal-hyperplasia/ National Library of Medicine, UpToDate. References