2018-19 TOW #13: Newborn screening

Newborn screening has helped revolutionize our ability to detect metabolic and hematologic diseases in infants. While the vast majority of screens are normal, when we catch those rare diseases before any symptoms start, we are reminded just how remarkable this process is (as per my experience in clinic last week). Two of our program graduates contributed to the materials for this topic, Drs Dave Higgins and Beth Tarini MD MPH, a national expert.

Materials to review:

Key points in newborn screening:

  1. When did it start and how is it done? The first sensitive, inexpensive, and easily performed newborn screening test was developed by Dr. Robert Guthrie in 1962. Prior to Guthrie’s assay for hyperphenyalaninemia, infants with suspected phenylketonuria (PKU) were diagnosed at 6-8 weeks of age. Within 10 years the testing was used nationwide. Now many diseases can be detected with tandem mass spectrometry technique (we screen for about 30 on our state screening). Key criteria for screening is which diseases have accurate, safe, effective testing and follow-up treatment available.
  2. What are the most common diseases detected? Congenital hypothyroidism, hemoglobinopathies, congenital adrenal hyperplasia, CF, and galactosemia. In WA each year 174,000 specimens from about 86,000 newborns are tested. Approximately 170 – 200 infants have one of the conditions. A one-time fee ($69.00 in 2014) for each baby screened funds this testing.
  3. What’s the reliability of screening tests? Sensitivity is approaching 99% for most disorders. However, false-positives remain a big problem, particularly for endocrinopathies: one study found as many as 50 false-positives for 1 true-positive. Studies have shown that up to 20% of families maintain some concern about the health of their child after false-positive screening results, so reviewing this information with families is key.
  4. Why a 2nd screening? A 2nd screening between 7-14 days of life is recommended (though not required in our state), primarily to detect congenital hypothyroidism. About 15% of hypothyroidism cases are missed on the first screen.
  5. What to do when a test is positive? Key information we should review with parents includes basic description of the disease process in question, that there are false positives, especially for some diseases, and next steps in evaluation and treatment (e.g., repeat testing on same sample, speaking to a specialist early in the evaluation process). Refer to the WA state newborn screening website for more guidance.

TOW #18: Lead screening

We are continuing our advocacy-related theme topics over the next few weeks during the REACH Pathway month. There has been tremendous advocacy done by pediatricians to help prevent and address lead toxicity. Most recently this has included the inspiring work by pediatrician Dr. Mona Hanna-Attisha in Flint MI who was one of the first people to raise awareness about dangerous lead levels in the water supply 2 years ago. We are fortunate to have two prominent environmental health pediatricians, Drs. Catherine Karr and Sheela Sathyanarayana, in the general pediatrics team here at UW who do research and advocacy to keep children safe from toxins. They both contributed to this teaching topic.

Materials for this week:

Take-home points for lead screening

  1. What is a safe blood lead level (BLL)? Based on strong research evidence, no measurable BLL is considered safe. Neurotoxicity associated with lower BLLs has been established by overwhelmingly consistent evidence from meta-analysis, so primary prevention of lead exposure is paramount. All detectable BLLs are reportable in WA State and the health department follows up with all BLLs > 5 mcg/dL.
  2. Why screen for lead? While lead is toxic to multiple body systems, the developing brain is particularly vulnerable. Most lead toxicity in the US is sub-clinical, only found on blood testing. Even low levels (<10mcg/dL) may be associated with behavioral problems (such as attention, aggression) and learning difficulties. Children aged 9-24 months are highest risk due to normal exploratory behavior – crawling, teething, putting non food objects in the mouth. Absorption across the gut is greater in children than adults.
  3. What are the sources of elevated lead levels? Ingestion of lead-containing dust or soil is the highest source, usually from old paint in homes built before 1950, but up through 1978, and homes from these eras being remodeled. As we have learned from Flint MI, lead is also in water sources, from contaminated water and old pipes. There are also newer sources of lead in imported products including candies, food, spices, make-up, and ceramics.
  4. Who should receive blood lead testing? In WA state, the 2016 guidelines identify children with these risk factors: 1) Lives in or regularly visits any house built before 1950 or built before 1978 with recent or ongoing renovations or remodeling, 2) From a low income family (<130% of the poverty level). (Federal law mandates screening for all children covered by Medicaid), 3) Known to have a sibling or frequent playmate with an elevated blood lead level, 4) Is a recent immigrant, refugee, foreign adoptee, or child in foster care, 5) Has a parent or principal caregiver who works professionally or recreationally with lead, 6) Uses traditional, folk, or ethnic remedies or cosmetics. Unfortunately, screening questionnaires have not reliably identified kids, as one of our residents found for a topic review at Harborview, so when in doubt, screen.
  5. What do you do with an elevated level? The PEHSU provides a summary of key next steps based on BLL results on their website. Next steps will include evaluation for anemia/nutrition since this may impact lead absorption, as well as determining the need for imaging or medical management.

TOW #12: Iron deficiency anemia

One of the major nutritional deficiencies worldwide is iron deficiency (ID) and iron deficiency anemia (IDA), so it’s an important area of pediatric nutrition for us to review and understand.

Materials for this week:

Take-home points:

  1. Epidemiology: Since the 1970s we have made significant progress identifying and screening for iron deficiency, but it remains the most common nutrient deficiency worldwide. In the US it is estimated that about 8% of infants and toddlers have iron deficiency. Some believe this may be underestimated (see Magge et al).
  2. What are the effects of iron deficiency? Iron deficiency is associated with poorer cognitive and social-emotional outcomes and has  persistent effects, but treatment can improve outcomes. Unfortunately, most of that data is from developing countries; in a systematic review for the USPSTF, data were lacking in developed countries, and no RCTs were available for routine screening to prevent IDA.
  3. Who should we screen? Iron deficiency screening is recommended by the AAP for all children between 9-12 months: labs recommended vary. At a minimum Hct/Hgb identifies anemia and adding Zinc Protoporphyrin to Heme ratio (ZPPH) (an inexpensive and widely available test) can help identify iron deficiency that precedes anemia (but note ZPPH is also elevated from lead and anemia of chronic disease).
  4. What are important risk factors for iron deficiency? Risk factors include prematurity, cow milk consumption before 1 year of age, drinking more than 24 oz/day of cow’s milk per day after 1 year, low income status, and restricted diets for any reason.
  5. What is the recommended treatment? Treat iron deficient children with 3-6 mg/kg of elemental iron daily until sufficient and then 2-3 months after to ensure adequate iron stores. Typically we repeat blood tests 1-3 months after starting therapy (some test at 1 month, others wait until further in) to ensure response and compliance and/or do additional work-up if not improving.

TOW #34: Iron deficiency anemia

Next week’s topic is on iron deficiency anemia (IDA). Always an important topic in gen peds, as IDA is the most significant nutrient deficiency worldwide and also in the US.

Materials:

Take home points on IDA:

  1. Epidemiology: Since the 1970s we have made significant progress identifying and screening for iron deficiency, but it remains the most common nutrient deficiency worldwide. Almost 10% of toddlers have been diagnosed with iron deficiency in a national U.S. sample, and many believe this may be underestimated.
  2. Significance: Iron deficiency is associated with poorer cognitive and social-emotional outcomes and has  persistent effects, but treatment can improve outcomes.
  3. Risk factors: include prematurity, cow milk consumption before 1 year of age, drinking more than 24 oz/day of cow’s milk per day after 1 year, low income status, menstruating adolescents, elite athletes, and restricted diets for any reason.
  4. Screening: Iron deficiency screening is recommended for all children between 9-12 months and again among adolescent females within a year of menstruation. Labs recommended vary. At a minimum Hct/Hgb identifies anemia and adding ZPPH (inexpensive and widely available) can help identify iron deficiency that precedes anemia (but note ZPPH is also elevated from lead and anemia of chronic disease). The Mentzer index, equal to the MCV divided by the RBC count, can help to pinpoint iron deficiency. An index >13.5 is suggestive of iron deficiency, <11.5 is suggestive of thalassemia minor. (Remember, the bone marrow cannot produce RBCs normally in IDA, so the RBC count is lower and the ratio is higher.)
  5. Treatment: treat iron deficient children with 3-6 mg/kg of elemental iron daily until sufficient and then 2-3 months after to ensure adequate iron stores. Typically we repeat measures 1 month after starting therapy to ensure a response and ensure compliance and/or do additional work-up if not improving.