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Congenital Hypothyroid Screening among Low Birth Weight Infants, Michigan, 2005-2007

Congenital Hypothyroid Screening among Low Birth Weight Infants, Michigan, 2005-2007. Steven J. Korzeniewski, MA, MSc, Maternal & Child Health Epidemiology Section Manager Violanda Grigorescu, MD, MSPH, William I. Young, Ph.D.

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Congenital Hypothyroid Screening among Low Birth Weight Infants, Michigan, 2005-2007

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  1. Congenital Hypothyroid Screening among Low Birth Weight Infants, Michigan, 2005-2007 Steven J. Korzeniewski, MA, MSc, Maternal & Child Health Epidemiology Section Manager Violanda Grigorescu, MD, MSPH, William I. Young, Ph.D. Bureau of Epidemiology, Division of Genomics, Perinatal Health and Chronic Disease Epidemiology

  2. Outline Brief overview of thyroid function and rationale for NICU protocol NICU screening algorithm Pre-Post NICU algorithm CH detection by birth weight Concerns & discussion of newly detected cases (implications of three-year follow-up) Conclusion/Public Health implications

  3. Hypothalamic-pituitary-thyroid axis T4 is stimulated by secretion of TSH by the pituitary. Low T4 (negative feedback) causes hypothalamus to secrete thyrotropin releasing hormone (TRH) which stimulates release of TSH thereby stimulating the thyroid gland to increase secretion of T4. When the thyroid does not respond to TSH stimulation (primary CH), due to dysgenesis or dyshormonogenesis, the result is low T4 and high TSH. Hypothalamus TRH + T3, T4 - Pituitary Gland T3, T4 - TSH + Thyroid (-) inhibition (+) stimulation

  4. CH Detection in Premature Infants Maturity of the endocrine system influences initial dried blood spot TSH values. Some premature infants with CH have late rising TSH and are therefore not detectable by an initial screen at 24-36hrs of life NICU/LBW screening protocol implemented (2007) to account for unreliable screens in premature newborns

  5. NICU/LBW Screening Algorithm

  6. Number of Infants Screened by Birth Weight, Michigan, 2007

  7. NICU Protocol Evaluation Conclusions NICU protocol inclusion criteria currently does not consider gestational age. GA is thought to be a better indicator of maturity than BW; however, concerns about data quality have led the latter to be used. Adding very preterm and below (GA < 32 wks) infants would add 215 infants based on 2007 data. We are evaluating the impact of: increasing the birthweight inclusion criterion to ~2300g, adding very preterm and below (GA < 32 wks) infants, and eliminating 2nd screens for infants born weighing less than ~1,000g-1,500g. Clinical Laboratory Standards Institute (CLSI) has a subcommittee working on a proposed standard for NBS of SCBU/NICU infants

  8. Who are we detecting? Is the 10 fold increase in risk of CH among infants < 1800g compared to those >= 1800g real? Standard of care is to follow-up CH cases until at least age three years (AAP Guidelines) Diagnostic verification recommended (permanent vs. transient CH) Thyroid function trial Rate and outcome of diagnostic verification unknown

  9. CH Three Year Follow-up of ‘Borderline’ Cases ‘Borderline’ was initially considered as having pre-treatment serum TSH values below the 15Th percentile. We recently expanded our criteria to include cases below the 25th percentile and now plan to follow all cases to age 3 years. Survey developed and pilot tested in collaboration with PEAC endocrinologists Medical management data maintained by NBS Follow-up program used to locate cases’ physicians. LTFU mitigated by use of MCIR and phone based survey

  10. Demographics of Michigan CH Cases Detected by NBS Classified by Pre-Treatment Serum TSH/FT4 Values, 9/2003-9/2007

  11. Preliminary Findings of the CHThree year follow-up study Preliminary findings indicate: 47% (9/19) of cases with completed diagnostic re-evaluation to date appear not to have permanent CH. A surprising number of patients (families) have stopped treatment of their own accord (7/23 with completed follow-up); this phenomenon requires further study. One case (family) described miscommunication with health care provider and lack of follow-up as impetus to treatment cessation. While all patients who stopped treatment on their own are thought to be transient CH (confirmation of transient CH is pending TSH value receipt- two patients have provided such confirmation to date), only 2/12 cases evaluated by an endocrinologist/hcp are considered transient. This finding may have implications for the method of diagnostic re-evaluation. Some cases were confirmed based on increasing treatment dosage at approximately 6 months of age; should this preclude three year thyroid challenge? Questions remain about process and outcome of three year CH re-evaluation.

  12. Overall Conclusions Newborn screening at 24-36hrs of life does not detect children with CH having late rising TSH NICU screening protocols increase CH detection significantly It is possible that some moderately LBW children having CH and late rising TSH remain undetected. NICU algorithm inclusion criteria require further evaluation Gestational age should likely be considered It is possible that many borderline cases, which likely includes children with CH detected by the 2nd or 3rd screen, are transient Such cases are more likely to be male, LBW, NICU births, and/or racial minorities Three year follow-up is of critical importance to differentiate transient from permanent CH, particularly in states conducting routine second screens or having NICU/LBW protocols.

  13. Acknowledgements Bill Young, Manger, Newborn Screening Follow-up Program Violanda Grigorescu, Director, Division of Genomics, Perinatal Health & Chronic Disease Epidemiology Newborn Screening Follow-up Staff Pediatric Endocrine Advisory Committee

  14. Thank You KorzeniewskiS@Michigan.gov http://www.michigan.gov/mchepi

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