Neonatal Screening Program of Congenital Hypothyroidism: How Can We (Still) Improve?

doi:10.21203/rs.3.rs-689419/v1

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Neonatal Screening Program of Congenital Hypothyroidism: How Can We (Still) Improve?

https://doi.org/10.21203/rs.3.rs-689419/v1

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Background: Congenital hypothyroidism (CH) has severe and irreversible neurological consequences for the child if treatment is not readily initiated, which justifies fast diagnosis. Screening of CH is a universal procedure well established in Portugal. It is based on measuring the pituitary thyroid stimulating hormone. The physiology of maturation of the pituitary-thyroid axis is incomplete at delivery in preterm and very-low birth weight babies (VLBW), which raises concerns with respect to the standard timing of CH diagnosis.

The Portuguese Neonatal Screening Program recommends testing preterm/VLBW babies at three time points. The purpose of this study was to assess compliance of these guidelines.

Methods: Questionnaires were sent to neonatal care units (NCU) and to general practitioner community health units in two time periods.

Results: All NCU have written guidelines and the great majority follows the recommendations. Few NCU still postpone the first collection for newborns with protein intake restrictions, some retest new-borns in special circumstances, and a great number still use iodine disinfectants.

Conclusions: This study shows that performing the metabolic screening is a well standardized procedure that can still be improved: not delaying the first collection, retesting sick and medicated babies, and avoiding iodine disinfectants.

Health Economics & Outcomes Research

Congenital hypothyroidism

iodine

neonatal screening

thyroid

thyroid-stimulating hormone

thyroxine

very-low birth weight

The National Neonatal Screening Program started in Portugal in 1979 with the screening of phenylketonuria. In 1980, the screening of (permanent) congenital hypothyroidism (CH) was added and later expanded to other 24 conditions. This screening program is a case study of success; in a couple of years a voluntary procedure became a universal attitude: since 1996 the coverage rate is close to 100% and the time between collecting samples and starting treatment in cases of CH decreased from 30 days in 1996 to the actual 10 days (annual reports from National Institute of Health Dr Ricardo Jorge). The incidence of CH has been described as increasing worldwide [1–6] due to, among other causes, environmental changes, and survival of preterm babies [4–6, 7–9]. Part of this increase is also attributable to the lowering of cut-off values. In Portugal, the accumulated incidence was 1:4300 in 1983 and 1:2842 in 2020 (latest available data from annual reports) (corresponding to a total of 1388 babies diagnosed since screening started).

CH is the most common cause of neonatal thyroid disorder. It causes neurodevelopmental disability and mental retardation if not treated immediately. CH can be classified as permanent (if requiring lifelong treatment) or transient [defined as increased serum thyroid-stimulating hormone (TSH) levels during neonatal period with normal thyroid function without the need of prolonged treatment]. Transient CH may be secondary to iodine deficiency or excess and to maternal and neonatal conditions [3, 5, 7].

CH results in decreased thyroid hormone synthesis due a morphological abnormality or dysfunction of the thyroid. During gestation, until the 20th week, the foetus is completely dependent of maternal thyroid hormone supply. This relies on proper placenta function and depends on the thyroid status of the mother and sufficient iodine intake. Foetal hypothalamic-pituitary-thyroid axis matures slowly throughout gestation, with the foetal thyroid starting to produce relevant amounts of hormones by mid-gestation. Therefore, maternal contribution of thyroid hormones continues throughout gestation and until delivery whenever there is foetal insufficient production, as is the case in CH. Thyroid hormones are necessary for normal cellular homeostasis, being crucial for brain development. Thyroxine (T4) is the main hormone synthesized and secreted by the thyroid gland; triiodothyronine (T3) is the biologically active hormone, locally produced in the tissues by the action of deiodinase enzymes. A decrease in circulating free hormone levels triggers the hypothalamic-pituitary-thyroid axis, leading to the stimulation of the thyroid gland by the pituitary-released TSH [10, 11].

At birth, with cord clamping and approximately by 30 minutes of life, there is a spur in TSH with a subsequent increase of T4 by day two. This hormonal raise is impaired or delayed in preterm babies (particularly under 30 weeks of gestation) and in very-low birth weighted (VLBW) babies, in situations of iodine deficiency, iodine overload (due to disinfectants) and other situations rather frequent in the neonatal period (e.g. use of specific medication, maternal non-thyroidal disease) [10–13].

Most middle-high income countries have nationwide CH-screening programmes (measuring TSH and/or T4 in a blood spot obtained from heel prick and drawn in filter paper-Guthrie card) for early identification and treatment of this condition. Given the normal TSH surge at delivery, the screening is commonly performed at days 3–6 [14]. As for preterm (< 30 weeks + 6 days at delivery) and VLBW babies (birth weight < 1500 g), the present Portuguese neonatal metabolic screening consensus (like that of many other international societies/countries) advise three blood collections: the first between day 3–6, the second at two weeks after birth and the third by the fourth week of life [14–19].

The Portuguese Neonatal Screening Program uses the primary TSH test strategy to screen for CH; measurement of total T4 (TT4) is used as second-tier test to confirm diagnosis. The cut-off values for recall changed throughout the years. Since 2006, TSH levels on the range 10–20 mU/L imply measurement of TT4; whenever TT4 < 6,5 mcg/dL, a new sample is requested. In the case of preterm/VLBW babies, by default, TSH and TT4 are measured in a second sample since 2009 and in a third sample since 2014.

Many situations in the neonatal period, besides prematurity and VLBW, may affect thyroid function, thus interfering with the diagnosis of CH. Given that any impairment of thyroid status (either isolated hypothyroxinemia or hypothyroidism) may cause neurodevelopmental disorders, screening should be repeated, and children must be carefully followed up until normalization of thyroid function or evolution to permanent HC [20–24].

In the present study we assessed the national practice of the Neonatal Screening Program, inquiring neonatal care units (NCU) (public national level II and III) and local (county) general practitioner community health units (GPU).

Deliveries in Portugal occur in hospitals where new-borns stay for, at least, 48 h. After discharge mothers are advised to go to GPUs for initiating follow-up and to perform the sample collection. Newborns staying in hospitals beyond 48 h have their screening performed in those institutions. In both cases blood samples are collected to Guthrie cards and sent by mail to the National Institute of Health where the metabolic screening is performed.

To ascertain the policy of neonatal screening practices a questionnaire was sent to 31 [from a total of 34 (91%)] NCUs and to 26 local (for geographical convenience; all units from the municipality Guimarães) GPUs. The questionnaires were sent to both doctors and nurses (to avoid self-reporting bias and to assess intra team communication). For the NCUs the questionnaires were sent in 2011 and in 2020; to the GPUs solely in 2020.

The responses retrieved from the questionnaires were considered per unit (when both nurses and doctors replied the responses were compiled and assessed for consistency). Data was analysed using simple descriptive statistical analysis.

Neonatal units’ questionnaire

Thirteen NCUs (42% response rate) shared their policy; responses from doctors and nurses were obtained from 6 NCUs. All NCUs have written guidelines for the neonatal screening; inconsistency of the replies (different responses to circumstances of retest: using specific drugs, critically ill babies and before blood transfusions) was however observed in 3 NCUs. Table 1 summarizes the findings.

The timing of sample collection was mostly between 48 and 144 h (day 2–6) of life. In 85% of the NCUs, postponing beyond 48 h was related to situations of no enteral feeding and low protein intake. In such cases, screening was performed after 2–3 days of enteral/parenteral feeding with some minimum protein intake.

Different practices were observed for recalls. Three (23%) NCUs repeated the screening in case of medication use (dopamine, caffeine and corticosteroids), with varied moments of retesting (15–30 days after the end of medication); retesting ill patients was reported in 4 NCUs (31%). A second screening was performed in babies with Down syndrome in 15% of the units. Neonatal screening is obtained previously to blood transfusions or exchange transfusion in 31% of the respondents.

With respect of preterm less than 30 weeks/VLBW, all NCUs repeated the screening within the recommended timing.

Use of iodinated disinfectants were reported in 39% of the NCUs; one reported no information with that respect.

Whenever hospital discharge occurred on weekends, neonatal screening was performed before discharge in most NCUs (85%).

When collecting the sample, nurses explained the procedure to parents and offered an informative flyer in all cases.

Guthrie cards were sent by regular post, on weekdays; the details of the procedure was unknown to the clinical staff.

Of notice, screening procedures improved from 2011 to 2020: more NCUs have written guidelines, the time of collecting samples was reduced and retesting of preterm/VLBW babies increased. However, iodinated disinfectants are still used and postponing the sample collection due to absence of protein intake is still a practice.

Table 1

Response of the neonatal care units to the inquiries in 2011 and 2020
Inquiry	2011	2020
Number of NCUs	14	13
Written guidelines	86%	100%
Blood collection beyond day 6	36%	8%
Postponing screen by absence of protein intake	43%	85%
Sample collection before blood/exchange transfusion	21%	31%
Retesting preterm/VLBW babies	79%	100%
Retesting ill babies using specific medication	36%	38%
Retesting Down syndrome babies	7%	15%
Use of iodinated disinfectants use	36%	38%

GPU questionnaire

Eleven local GPUs responded to the questionnaires (48% response rate).

Table 2 summarizes the findings.

Only 1 GPU retested preterm babies 2 weeks after the first collection. In the case of VLBW babies 27% of the GPU repeated the screening (2 weeks after the first collection and when the baby reached 2500g). Only 1 GPU retested babies with Down syndrome (4 weeks after the first collection).

All GPUs performed the sample collections solely on weekdays, Guthrie cards were sent by institutional mail and in all cases an informative flyer was delivered.

Table 2

Response of the community health units to the inquiry in 2020
Inquiry	2020
Number of replies	11
Written guidelines	82%
Blood collection beyond day 6	0%
Postponing screen by absence of protein intake	Information not available
Sample collection before blood/exchange transfusion	Information not available
Retesting preterm babies	9%
Retesting VLBW babies	27%
Retesting ill babies using specific medication	Information not available
Retesting Down syndrome babies	9%
Use of iodinated disinfectants	0%

The present study shows that the recommended timing for screening, ideally between days 3–6 after delivery, is not complied by all health care units. This supports the need for action, particularly the establishment of clearer written guidelines and standard procedures.

In some units the CH screening is postponed in children fed with no protein intake. This represents no reason for delay since the absence of protein intake does not compromise the assessment. Of notice, this procedure was already observed in 2011 and no improvement has occurred, which highlights the need to reinforce information on best practice guidelines.

Early CH diagnosis and treatment may optimize children’s psychomotor development and prevent neurological disability. Diverse approaches to the screening are used worldwide: TSH determination, T4 measurement or a combined strategy of primary TSH with TT4 as a second-tier test (the ideal screening approach, though the most expensive) [7]. Portugal adopted the latter.

Particular groups of neonates are described to have increased risk of CH; these include preterm and VLBW babies, in which a second and a third sample collection are recommended by several Paediatric Endocrinology Societies [14–19]. The reason for these additional measurements relies on the expected lag in the postnatal TSH rise (absence or delay of TSH surge) and on potential hypothyroxinemia, due to hypothalamic-pituitary-thyroid axis immaturity. Both are strongly influenced by the gestational age: the lower the gestational age, the lower and delayed the TSH, TT4 and FT4 peaks [18, 20, 21–27]. Several studies have reported that screening solely based on an increase of TSH levels likely results in a failure to detect CH in most preterm/VLBW babies. As such, repetition of the diagnosis and inclusion of T4 measurement likely justifies the higher rate of diagnosis CH and/or a CH with delayed TSH rise in this population [1, 2, 4, 6, 28, 29]. The guidelines for additional screening in preterm/VLBW babies are presently in place in all NCU and GPU, which represents an improvement of the situation from 2011 (when retesting was below 80%). The standard screening time is between day 3 and 6, the first recall blood sample two weeks after birth (day 14–15) and the second recall at the fourth week. It is of relevance to refer that in extreme preterm babies, the third sample should not be collected prior to 30 weeks (desirably at 32 weeks), which deserves particular attention in revised guidelines.

The environment of NCUs is very adverse to thyroid function, even for full term babies. Babies seriously ill, using dopamine, caffeine and corticosteroids are likely to present impaired thyroid function [15, 28, 30]. Dopamine inhibits TSH and T4 secretion [28, 31–33]; caffeine may increase the expression of the gene encoding for TSH [30]; corticosteroids may lead to reduction of T3 and TSH levels and elevation of reverse T3 [33, 34]; many other drugs may affect thyroid function (e.g. aminophylline, heparin, amiodarone). In nonthyroidal illness (also called sick euthyroid syndrome) babies are described to have low serum T3 levels, normal to low TT4, elevated reverse T3 and normal TSH [34, 35]. Therefore, babies on medication should repeat the screening [24, 37, 38], a procedure not widely accomplished for Portuguese babies, as observed here.

Other groups of neonates are at risk of CH, but guidelines are far from consensual: in our sample 31% NCUs retested babies with Down syndrome and 15% of them retested babies before a blood or exchange transfusion. These two clinical situations are not included in the current Portuguese guidelines. Other risk categories of neonates include twins (especially same-sex twins) and preterm babies older than 30 weeks (especially if small for gestational age), clinical conditions that may require repetition of the metabolic screening [15, 22]; this deserves to be analysed in terms of the cost-benefit if to be universally applied.

One special word with respect to iodine. Preterm babies are very prone to thyroid dysfunction due to excessive iodine [7, 39–41]. If a very immature thyroid is exposed to a great amount of iodine, it will stop functioning (Wolff-Chaikoff effect) to avoid overproduction of thyroid hormones. This arrest may lead to transitory hypothyroidism that may persist until maturation of the gland (36–40 weeks), especially in iodine deficient populations as it is the case of Portugal [42]. In fact, due to the increased permeability of the skin and decreased renal clearance, a single use of iodinated disinfectants in maternal caesarean, vaginal douching, neonatal skin disinfection or iodinated contrast media may lead to hypothyroidism [18, 43]. The most popular iodinated disinfectant used in caesareans has 10⁵ mcg of iodine/mL. Since new-borns need around 150–180 mcg/day of iodine, a single use may lead to neonatal iodine overload, even in full term babies. For this reason, there is a strong recommendation to exclude iodine-based disinfectants from maternal, obstetrics and neonatal wards, which unfortunately is still not done in many of the units in our study.

A final note on the timing between sample collection and assessment. While collection is mostly done within the recommended timing, the results of the test may be compromisingly delayed due to administrative procedures of Guthrie cards mailing. The reasons for this delay reside on mailing just on working days (and most likely not on all working days), use of ordinary rather than express mail or even requesting that mailing is done by the parents. Guidelines to optimize the time between collection and assessment outcome are needed.

This study has limitations. Questionnaires were sent to 91% of the public national NCUs and to all CPUs of a single geographic region (Guimarães), with a response rate under 50% (42% in case of NCUs and 48% for GPUs). It also did not include private NCUs. As such it may not be generalizable to the whole country. Selection and reporting bias cannot be excluded; those who responded may be the best performers. Still, the information obtained alerts for the need to improve communication and to revise and update current guidelines with respect to new-born screening.

The present study suggests that procedures with respect to CH have improved since 2011. More importantly, it revealed that current guidelines and practices need to be ameliorated, namely: not delaying the neonatal screening in babies not being fed or with no protein intake, collecting samples between day 3 and 6 after delivery, decreasing the time between collection and assessment, enforce the need for three testing times for preterm and VLBW babies, enforce the need of recall for babies (term or preterm) hospitalized in NCUs, and prohibiting the use of iodine-based disinfectants in maternal, obstetrics and neonatal wards.

We expect, with this study, to contribute to new guidelines on CH to be implemented by the national screening program.

CH: congenital hypothyroidism; GPU: local (county) general practitioner community health unit; NCU: neonatal care unit; T3: triiodothyroinie, T4: thyroxine; TT4: total T4; TSH: thyroid-stimulating hormone; VLBW: very-low birth weight babies

Ethics approval and consent to participate

The study was approved by the ethics committee and the clinical academic center of Hospital Senhora de Oliveira (#72/2019).

Consent for publication

Not applicable.

Availability of data and materials

The data are available from the corresponding author and can be shared upon reasonable requests.

Competing interests

The authors have no competing interests.

Funding

This research did not receive specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

Authors' contributions

Maria José Costeira: conceptualization, methodology, analysis, investigation, writing original draft.

Andreia Martins: methodology, data curation.

Raquel Reis: data curation.

Laura Vilarinho: investigation, writing original draft.

Joana Palha: validation, analysis, investigation, writing original draft.

All authors reviewed the manuscript.

Author’s details

¹Neonatal Intensive Care Unit- Hospital Senhora da Oliveira- Guimarães, Rua dos Cutileiros, Creixomil. 4835-044 Guimarães, Portugal. [email protected]; [email protected];

[email protected]

²Newborn Screening, Metabolism & Genetics Unit, National Institute of Health Dr Ricardo Jorge, Rua Alexandre Herculano 321, 4000-053 Porto, Portugal. [email protected]

³Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Braga, Portugal. Campus Gualtar, 4710-057 Braga, Portugal. [email protected]

⁴ICVS/3B’s, PT Government Associate Laboratory, Braga/Guimarães, Portugal.

⁵Clinical Academic Center, Braga, Portugal. Hospital de Braga, Lugar de Sete Fontes, S. Victor, 4710-243 Braga, Portugal

Corbetta C, Weber G, Cortinovis F, Calebiro D, Passoni A, Vigone MC, et al. L. A 7-year experience with low blood TSH cutoff levels for neonatal screening reveals an unsuspected frequency of congenital hypothyroidism (CH). Clin Endocrinol. 2009;71(5):739–45. https://doi.org/10.1111/j.1365-2265.2009.03568.x
Woo HC, Lizarda A, Tucker R, Mitchell ML, Vohr B, Oh W, et al. Congenital Hypothyroidism with a Delayed Thyroid-Stimulating Hormone Elevation in Very Premature Infants: Incidence and Growth and Developmental Outcomes. J Pediatr. 2011;158(4):538–42. https://doi.org/10.1016/j.jpeds.2010.10.018.
Nagasaki K, Minamitani K, Anzo M, Adachi M, Ishii T, Onigata K, et al. Guidelines for Mass Screening of Congenital Hypothyroidism (2014 revision). Mass Screening Committee, Japanese Society for Pediatric Endocrinology, Japanese Society for Mass Screening. Clin Pediatr Endocrinol. 2015;24 (3):107–33. https://doi.org/10.1297/cpe.24.107
Hashemipour M, Hovsepian S, Ansari A, Keikha M, Khalighinejad P, Niknam N. Screening of congenital hypothyroidism in preterm, low birth weight and very low birth weight neonates: A systematic review. Pediatr Neonatol. 2018;59(1):3–14. http://dx.doi.org/10.1016/j.pedneo.2017.04.006.
McGrath N, Hawkes CP, McDonnell CM, Cody D, O’Connell SM, Mayne PD, et al. Incidence of Congenital Hypothyroidism Over 37 Years in Ireland. Pediatrics. 2018;142:e20181199. https://doi.org/10.1542/peds.2018-1199.
Kaluarachchi DC, Allen DB, Eickhoff JC, Dawe SJ, Baker MW. Increased Congenital Hypothyroidism Detection in Preterm Infants with Serial Newborn Screening. J Pediatr. 2019;207:220–5. http://dx.doi.org/10.1016/j.jpeds.2018.11.044.
Ahmad N, Irfan A, Al Saedi SA. Congenital hypothyroidism: Screening, diagnosis, management, and outcome. J Clin Neonatol. 2017;6:64–70.
Hinton CF, Harris KB, Borgfeld L, Drummond-Borg M, Eaton R, Lorey F, et al. Trends in incidence rates of congenital hypothyroidism related to select demographic factors: data from the United States, California, Massachusetts, New York, and Texas. Pediatrics. 2010;125 Suppl 2: S37-47. http://dx.doi.org/10.1542/peds.2009-1975D.
Mitchell M, Hsu H-W. Unresolved Issues in the Wake of Newborn Screening for Congenital Hypothyroidism. J Pediatr. 2016;173:228–30. http://dx.doi.org/10.1016/j.jpeds.2016.03.
Thorpe-Beeston JG, Nicolaides KH, McGregor AM. Fetal thyroid function. Thyroid. 1992;2(3):207–17. http://dx.doi.org/10.1089/thy.1992.2.207.
Sack J. Thyroid function in pregnancy-maternal-fetal relationship in health and disease. Pediatr Endocrinol Rev. 2003;1 Suppl 2:170–6; discussion 176.
Polak M. Human fetal thyroid function. Endocr Dev. 2014;26:17–25. http://dx.doi.org/10.1159/000363152.
Chapman AK, Farmer ZJ, Mastrandrea LD, Matlock KA. Neonatal Thyroid Function and Disorders. Clin Obstet Gynecol. 2019;62(2):373–87. http://dx.doi.org/10.1097/GRF.0000000000000434.
American Academy of Pediatrics, Rose SR; Section on Endocrinology and Committee on Genetics, American Thyroid Association, Brown RS; Public Health Committee, Lawson Wilkins Pediatric Endocrine Society, Foley T, Kaplowitz PB, Kaye CI, Sundararajan S, Varma SK. Update of newborn screening and therapy for congenital hypothyroidism. Pediatrics. 2006;117(6):2290–303. http://dx.doi.org/10.1542/peds.2006-0915.
van Trotsenburg P, Stoupa A, Léger J, Rohrer T, Peters C, Fugazzola L, et al. Congenital Hypothyroidism: A 2020–2021 Consensus Guidelines Update-An ENDO-European Reference Network Initiative Endorsed by the European Society for Pediatric Endocrinology and the European Society for Endocrinology. Thyroid. 2021;31(3):387–419. http://dx.doi.org/10.1089/thy.2020.0333.
Kaluarachchi DC, Allen DB, Eickhoff JC, Dawe SJ, Baker MW. Thyroid-Stimulating Hormone Reference Ranges for Preterm Infants. Pediatrics. 2019;144(2):e20190290. http://dx.doi.org/10.1542/peds.2019-0290.
Jacob H, Peters C. Screening, diagnosis and management of congenital hypothyroidism: European Society for Paediatric Endocrinology Consensus Guideline. Arch Dis Child Educ Pract Ed. 2015;100(5):260–3. http://dx.doi.org/10.1136/archdischild-2014-307738.
McCormick Q, Pitts L, Hughes Z. Follow-up of infants with congenital hypothyroidism and low total thyroxine/thyroid stimulating hormone on newborn screen. Ann Pediatr Endocrinol Metab. 2019;24(4):237–42. http://dx.doi.org/10.6065/apem.2019.24.4.237.
Bijarnia S, Wilcken B, Wiley VC. Newborn screening for congenital hypothyroidism in very-low-birth-weight babies: the need for a second test. J Inherit Metab Dis. 2011;34(3):827–33. http://dx.doi.org/10.1007/s10545-011-9286-8.
Williams FLR, Hume R. Perinatal Factors Affecting Thyroid Hormone Status in Extreme Preterm Infants. Semin Perinatol. 2008;32(6):398–402. http://dx.doi.org/10.1053/j.semperi.2008.09.004
Silva SAB, Chagas AJ, Goulart EMA, Silva GAB, Marçal LV, Gomes MNA, et al. Screening for Congenital Hypothyroidism in Extreme Premature and/or Very Low Birth Weight Newborns: The Importance of a Specific Protocol. J Pediatr Endocrinol Metab. 2010;23(1–2):45–52. http://dx.doi.org/10.1515/jpem.2010.23.1-2.45.
Liu C, Wang K, Guo J, Chen J, Chen M, Xie Z, et al. Small for gestational age is a risk factor for thyroid dysfunction in preterm newborns. BMC Pediatr. 2020;20(1):179. http://dx.doi.org/10.1186/s12887-020-02089-7
Bhatia V. Hypothyroxinemia in Preterm Neonates: Not Always Hypothyroidism. Indian J Pediatr. 2019;86(8):671–2. https://doi.org/10.1007/s12098-019-03015-1.
Slaughter JL, Meinzen-Derr J, Rose SR, Leslie ND, Chandrasekar R, Linard SM, et al. The Effects of Gestational Age and Birth Weight on False-Positive Newborn-Screening Rates. Pediatrics. 2010;126(5):910–6. http://dx.doi.org/10.1542/peds.2010-0943
Chung HR. Screening and management of thyroid dysfunction in preterm infants. Ann Pediatr Endocrinol Metab. 2019;24(1):15–21. https://doi.org/10.6065/apem.2019.24.1.15.
Yoon SA, Chang YS, Ahn SY, In Sung S, Park WS. Initial and delayed thyroid-stimulating hormone elevation in extremely low-birth-weight infants. BMC Pediatr. 2019;19(1):347. https://doi.org/10.1186/s12887-019-1730-1
Kim H-R, Jung YH, Choi CW, Chung HR, Kang, M-J, Kim BI. Thyroid dysfunction in preterm infants born before 32 gestational weeks. BMC Pediatr. 2019;19(1):391. https://doi.org/10.1186/s12887-019-1792-0.
Chaudhari M, Slaughter JL. Thyroid Function in the Neonatal Intensive Care Unit. Clin Perinatol. 2018;45(1):19–30. https://doi.org/10.1016/j.clp.2017.10.005
Vigone MC, Caiulo S, Di Frenna M, Ghirardello S, Corbetta C, Mosca F, et al. Evolution of thyroid function in preterm infants detected by screening for congenital hypothyroidism. J Pediatr. 2014;164(6):1296–302. https://doi.org/10.1016/j.jpeds.2013.12.048..
Lee JH, Kim SW, Jeon GW, Sin JB. Thyroid dysfunction in very low birth weight preterm infants. Korean J Pediatr. 2015;58(6):224–9. http://dx.doi.org/10.3345/kjp.2015.58.6.224
Filippi L, Cecchi A, Tronchin M, Dani C, Pezzati M, Seminara S, et al. Dopamine infusion and hypothyroxinaemia in very low birth weight preterm infants. Eur J Pediatr. 2004;163(1):7–13. http://dx.doi.org/10.1007/s00431-003-1359-8..
Filippi L, Pezzati M, Poggi, C, Rossi S, Cecchi A, Santoro C. Dopamine versus dobutamine in very low birthweight infants: endocrine effects. Arch Dis Child Fetal Neonatal Ed. 2007; 92(5):F367-71. http://dx.doi.org/10.1136/adc.2006.098566.
Arai H, Goto R, Matsuda T, Takahashi T. Relationship between free T4 levels and postnatal steroid therapy in preterm infants. Pediatr Int. 2009;51(6):800–3. http://dx.doi.org/10.1111/j.1442-200x.2009.02852.x
Silva MHBN, Araujo MCK, Diniz EMA, Ceccon MEJR, Carvalho WB. Nonthyroidal illnesses syndrome in full-term newborns with sepsis. Arch Endocrinol Metab. 2015;59(6):528–34. http://dx.doi.org/10.1590/2359-3997000000111.
Hemmati F, Pishva N. Evaluation of thyroid status of infants in the intensive care setting. Singapore Med J. 2009;50(9):875–8.
Zung A, Palmon RB, Golan GA, Troitzky M, Eventov-Friedman S, Marom R, et al. Risk Factors for the Development of Delayed TSH Elevation in Neonatal Intensive Care Unit Newborns. J Clin Endocrinol Metab. 2017;102(8):3050–5. http://dx.doi.org/10.1210/jc.2017-00701
Fisher DA. Thyroid function and dysfunction in premature infants. Pediatr Endocrinol Rev. 2007;4(4):317–28.
Larson C, Hermos R, Delaney A, Daley D, Mitchell M. Risk factors associated with delayed thyrotropin elevations in congenital hypothyroidism. J Pediatr. 2003;143(5):587–91. http://dx.doi.org/ 10.1067/S0022 3476(03)00332–9.
Ares S, Quero J, de Escobar GM. Iodine balance, iatrogenic excess, and thyroid dysfunction in premature newborns. Semin Perinatol. 2008;32(6):407–12. http://dx.doi.org/10.1053/j.semperi.2008.09.006.
Ares S, Quero J, Durán S, Presas MJ, Herruzo R, Morreale de Escobar G. Iodine content of infant formulas and iodine intake of premature babies: high risk of iodine deficiency. Arch Dis Child Fetal Neonatal Ed. 1994;71(3):F184-91. http://dx.doi.org/10.1136/fn.71.3.f184.
Ares S, Escobar-Morreale HF, Quero J, Durán S, Presas MJ, Herruzo R, et al. Neonatal hypothyroxinemia: effects of iodine intake and premature birth. J Clin Endocrinol Metab. 1997;82(6):1704–12. http://dx.doi.org/10.1210/jcem.82.6.4019.
Costeira MJ, Oliveira P, Ares S, de Escobar GM, Palha JA. Iodine status of pregnant women and their progeny in the Minho Region of Portugal. Thyroid. 2009;19(2):157–63. http://dx.doi.org/10.1089/thy.2008.0249.
Pinsker JE, McBayne K, Eduards M, Jensen K, Crudo DC, Bauer AJ. Transient Hypothyroidism in Premature Infants After Short-term Topical Iodine Exposure: An Avoidable Risk? Pediatr Neonatol. 2013;54(2):128–31. http://dx.doi.org/10.1016/j.pedneo.2012.10.005

No competing interests reported.

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Neonatal Screening Program of Congenital Hypothyroidism: How Can We (Still) Improve?

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