Heel Prick Samples Research Articles

High level of immunoglobulin G targeting mycoplasma or cytomegalovirus in the newborn increases risk of ADHD

Attention-deficit hyperactivity disorder (ADHD) is a neurodevelopmental disorder typically detected in childhood. Although ADHD has been demonstrated to have a strong genetic component, environmental risk factors, such as maternal infections during pregnancy, may also play a role. We therefore measured the immunological response to 5 abundant microorganisms (Toxoplasmosis Gondii, cytomegalovirus (CMV), Herpes Simplex Virus 1, Epstein Barr Virus and mycoplasma pneumoniae) in newborn heel prick samples of 1679 ADHD cases and 2948 matching controls as part of the iPSYCH Danish case-cohort study. We found an association between high anti-CMV (OR 1.30, 95 % CI [1.09,1.55], p = 0.015) and anti-mycoplasma (OR 1.30, 95 % CI [1.07,1.59], p = 0.037) signal and those newborns later being diagnosed with ADHD. The risk estimate remained increased when controlling for ADHD polygenic risk score as well as penicillin prescriptions. We saw a dose–response association with the amount of positive anti-microorganism titers increasing the risk of being diagnosed with ADHD later in life (p = 0.01 for the trend), suggesting that the more activated the immune system is prior to or at birth, the higher the risk is for a later diagnosis with ADHD. If the associations are causal, they emphasize the importance of a healthy life style during pregnancy to reduce the risk of infections when pregnant and the associated risks for the child.

Clotted blood samples in the neonatal intensive care unit: A retrospective, observational study to evaluate interventions to reduce blood sample clotting.

Blood draws for laboratory investigations are essential for patient management in neonatal intensive care units (NICU). When blood samples clot before analysis, they are rejected, which delays treatment decisions and necessitates repeated sampling. To decrease the incidence of rejected blood samples taken for laboratory investigation as a result of clotted sample. This retrospective observational study used routine data on blood draws from preterm infants collected between January 2017 and June 2019 in a 112-cot NICU in Qatar. Quality improvement interventions to reduce the rate of clotted blood samples included: awareness raising and safe sampling workshops with NICU staff, involvement of the neonatal vascular access team, development of a complete blood count (CBC) sample collection pathway, review of sample collection equipment, introducing the Tenderfoot® heel lance, establishment of benchmarks and provision of dedicated blood extraction equipment. First attempt blood draw occurred in 10 706 cases, representing a 96.2% success rate. In 427 (3.8%) cases, the samples were clotted requiring repeat collection. The overall rate of clotted specimens decreased from 4.8% in 2017 and 2018 to 2.4% in 2019, with odds ratios of 1.42 (95% confidence interval [CI] 1.13-1.78, p = .002), 1.46 (95% CI 1.17-1.81, p < .001) and 0.49 (95% CI 0.39-0.63, p < .001), respectively. The majority (87%-95%) of blood samples were by venepuncture using an intravenous (IV) catheter or the NeoSafe™ blood sampling device. Heel prick sampling was the second (2%-9%) most common method. Clotted samples were most frequently associated with needle use, 228 of 427 (53%), and IV cannula, 162 of 427 (38%), with odds ratios of 4.14 (95% CI 3.34-5.13, p < .001) and 3.11 (95% CI 2.51-3.86, p < .001), respectively. Our interventions over 3 years were associated with reduced rates of sample rejection due to clotting, and this led to improved patient experience through fewer repeated samplings. The insights gained from this project can help to improve patient care. Interventions that reduce the rate of blood sample rejection by clinical laboratories can lead to economic savings, timelier diagnostic and treatment decisions, and contribute to an improved quality care experience for all critical care patients, irrespective of age, by reducing the need for repeated phlebotomy and the risk of related complications.

Relationships between feeding and glucose concentrations in healthy term infants during the first five days after birth-the Glucose in Well Babies Study (GLOW).

The World Health Organization recommends breastfeeding be commenced as soon as possible after birth. Amongst other benefits, early feeding is expected to support the metabolic transition after birth, but effects on blood glucose concentrations are controversial. We sought to describe the changes in interstitial glucose concentrations after feedings over the first five postnatal days. In healthy singleton term infants, all feeds were recorded using a smart phone app. Glucose concentrations were measured by blinded interstitial monitoring, calibrated by heel-prick capillary samples 2-4 times/d. Feeding sessions were included if a start and end time were recorded, and if the interval between the start of successive feeds was >90 min. The area under the glucose concentration curve (AUC) was calculated by trapezoidal addition from baseline (median of the 3 measurements before the beginning of the session). The maximum deviation (MD) was the greatest change in glucose concentration (positive or negative) from baseline to the next feeding session or 180 min, whichever came first. Data were analyzed using Stata V17 and are presented as mean (95% CI) in mmol/L. Data were available for 62 infants and 1,770 feedings. The glucose response to breastfeeding was not different from zero on day 1 [day 1 AUC 0.05 (-0.00, 0.10), MD 0.06 (-0.05, 0.16)], but increased thereafter (day 3 (AUC 0.23 (0.18, 0.28), MD 0.41 (0.32, 0.50), day 5 AUC 0.11 (0.06, 0.16), MD 0.28 (0.18, 0.37), p < 0.001 for age effect). Glucose response increased with increased duration of breastfeeding (<30 min AUC 0.06 (0.02,0.09), MD 0.12 (0.04,0.19), >30 min AUC 0.20 (0.16, 0.23) MD 0.37 (0.30, 0.44), p < 0.001 for duration effect) and this was observed even in the first 2 days (<30 min AUC-0.02 (-0.06, 0.03), MD -0.06 (-0.15, 0.03), >30 min AUC 0.12 (0.08, 0.16), MD 0.19 (0.11, 0.27), overall p < 0.001 for age x duration interaction). In feeding sessions that were not breastfeeding, the glucose response was greater after formula than after expressed human milk [AUC 0.29 (0.15, 0.29), MD 0.48 (-0.12, 0.61)], and greater after feed volumes >20 ml than <10 ml [20-30 ml AUC 0.19 (0.01, 0.27), MD 0.23 (-0.01, 0.46)]. The glucose response to feeding in the days after birth increases with postnatal age and duration of the feeding episode. Breastfeeding for <30 min has little effect on glucose concentrations in the first two days.

Real world external validation of metabolic gestational age assessment in Kenya.

Using data from Ontario Canada, we previously developed machine learning-based algorithms incorporating newborn screening metabolites to estimate gestational age (GA). The objective of this study was to evaluate the use of these algorithms in a population of infants born in Siaya county, Kenya. Cord and heel prick samples were collected from newborns in Kenya and metabolic analysis was carried out by Newborn Screening Ontario in Ottawa, Canada. Postnatal GA estimation models were developed with data from Ontario with multivariable linear regression using ELASTIC NET regularization. Model performance was evaluated by applying the models to the data collected from Kenya and comparing model-derived estimates of GA to reference estimates from early pregnancy ultrasound. Heel prick samples were collected from 1,039 newborns from Kenya. Of these, 8.9% were born preterm and 8.5% were small for GA. Cord blood samples were also collected from 1,012 newborns. In data from heel prick samples, our best-performing model estimated GA within 9.5 days overall of reference GA [mean absolute error (MAE) 1.35 (95% CI 1.27, 1.43)]. In preterm infants and those small for GA, MAE was 2.62 (2.28, 2.99) and 1.81 (1.57, 2.07) weeks, respectively. In data from cord blood, model accuracy slightly decreased overall (MAE 1.44 (95% CI 1.36, 1.53)). Accuracy was not impacted by maternal HIV status and improved when the dating ultrasound occurred between 9 and 13 weeks of gestation, in both heel prick and cord blood data (overall MAE 1.04 (95% CI 0.87, 1.22) and 1.08 (95% CI 0.90, 1.27), respectively). The accuracy of metabolic model based GA estimates in the Kenya cohort was lower compared to our previously published validation studies, however inconsistency in the timing of reference dating ultrasounds appears to have been a contributing factor to diminished model performance.

Screening of hypothyroidism disorder in newborns by heel prick level of thyroid-stimulating hormones.

Background: Thyroid hormones are vital for fetal development and regulation of neuropsychological function. Therefore an adequate amount of thyroid hormone levels are necessary for brain development cognitive function. Newborn screening for congenital hypothyroidism is a great achievement in preventive medicine. Screening for hypothyroidism disorder using heel prick samples is considered essential for preventing intellectual dysfunction and delayed growth. The objective of the present study was to determine the frequency of hypothyroidism disorder in newborns.&#x0D; Methodology: A cross-sectional study was conducted at Abbasi Shaheed Hospital, Gynae &amp; Obstetrics Department, Karachi, Pakistan. Blood samples were obtained from 257 neonates between 3rd &amp; 5th day after birth by the heel prick method. Babies of Mothers having thyroid diseases were excluded from the study. Serum Thyroid-stimulating hormones (TSH) were tested using the enzyme-linked immunosorbent assay method. Newborn serum TSH &gt; 20 miu/L was considered abnormal.&#x0D; Results: The overall mean age of neonates was 3.47 ± 0.57 days. Out of the total 257 neonates screened, female babies had higher TSH levels and congenital hypothyroidism was found in 4(1.55%) cases. The observed mean TSH level was 4.09 ± 0.24 mIU/L. &#x0D; Conclusion: In conclusion, the observed frequency of neonatal hypothyroidism in this single-center study prompts the need for early screening and diagnosis. The screening should be included in the post-natal period to prevent sequels associated with hypothyroidism for timely diagnosis and treatment of newborns.

Neonatal heel prick screening TSH concentration in the Netherlands as indicator of iodine status

BackgroundNeonatal Thyroid Stimulating Hormone (nTSH) is proposed as indicator of iodine deficiency in a population. Population’s iodine sufficiency is indicated by a proportion of the newborns less than 3% having nTSH above 5 mIU/L. The aim of this study was to explore the Dutch neonatal heel prick screening TSH data to assess iodine status in the Netherlands and identify determinants and potential confounders of this assessment.MethodsAll newborns born in the Netherlands between 2007 and 2015 with a heel prick collection at day 3-7 were included (n = 1,435,600), except preterm neonates and baby’s with a low birth weight. Total T4 was measured for all children, nTSH was measured in the ~ 20% children with lowest total T4.ResultsThe proportion with nTSH > 5mIU/L fluctuated between 0.6-1.3% in 2007-2015. nTSH was significantly associated with laboratory performing the nTSH assay and age of heel prick sampling. The overall increasing trend in proportion nTSH >1mIU/L was confounded by the laboratories with different and changed assays.ConclusionsThe low proportion neonates with high nTSH suggests a sufficient iodine status in the Netherlands. Whether the increased proportion nTSH>1mIU/L over the years is an early indicator of deterioration of the iodine status remains unclear, due to differences and changes in analytical assays. nTSH might be a valuable and inexpensive way to get crude insight in the (trend in) iodine status, but more research is needed on the validity and potential conditions.

Development of a novel approach for the second-tier estimation of homocysteine in dried blood spot using tandem mass spectrometry

Tandem mass spectrometry (TMS) -based screening for homocystinuria in the routine newborn screening (NBS) primarily relies on the elevated levels of methionine (Met) in the dried blood spot (DBS) of affected neonates. However, due to the lack of required specificity of Met as a marker for homocystinuria, an additional re-sampling and follow-up analytical testing for a definitive diagnosis, emphasis us to develop second-tier testing for a more specific marker, that is homocysteine (HCY) in the same residual blood spot without any new sample. Objective: The objective of the study was to develop a novel approach for the second-tier estimation of total HCY in residual blood spot using TMS. Materials and Methods: Retrospective analysis of DBS from all neonates with deranged levels of Met and Met to phenylalanine in primary NBS was included in the study. The study duration was for a period of 24 months (November 2015-October 2017). Heel prick samples were collected within 24–72 h of birth and after the first feed. Further, the samples with abnormal Met was analyzed for total HCY by isotopic dilution approach using multiple reaction monitoring modes for mass transition m/z 136?90 for HCY, m/z 140?94 for d4-homocysteine, and m/z 269.2?134.4 for d8-HCY. Results: The newly developed methodology demonstrated a sensitive method for the quantification of total HCY over a linear range of 2 ?mol/L–100 ?mol/L. Assay validation parameters such as intraday and interday assay precision, accuracy, and recovery were also within an acceptable range. Conclusion: In the present study, an in-house tandem mass spectrometric-based assay for the quantification of total HCY was developed which can be employed as an important strategy for the differential diagnosis of homocystinuria in neonates.

Newborn Screening using Dried Blood Spot for Seven Metabolic Disorders- A Retrospective Study from a Tertiary Care Hospital in Southern India

Introduction: Newborn Screening (NBS) is an important public health measure in many developed countries. In developing countries like India, the benefits of NBS have been acknowledged and that screening is slowly gaining attention. Aim: To estimate the proportion for seven conditions screened in a tertiary care hospital in Southern India namely Congenital Hypothyroidism (CH), Congenital Adrenal Hyperplasia (CAH), Glucose-6-Phosphate Dehydrogenase (G6PD) deficiency, Biotinidase Deficiency (BD), Galactosemia, Phenylketonuria (PKU) and Cystic Fibrosis (CF). Materials and Methods: The present descriptive study was conducted at a tertiary care teaching hospital in Southern India during a three year period between January 2018 to December 2020. A retrospective analysis of the results of NBS by dried blood spots was done. There were 3152 live births during this period out of which 1649 babies were screened (52% coverage). Heel prick samples after 48 hour of life and prior to discharge were analysed by quantitative assessment. Neonates having positive screening results were recalled by telephonic call for confirmatory tests. Results: The CH, BD and G6PD deficiency were the most common disorders with a proportion of 1:824, 1:1649 and 1:1649, respectively. Galactosemia, CF and PKU were not found in study population. Conclusion: These results need to be corroborated with larger studies from the same geographical area.

Drive-through transcutaneous bilirubin screening for neonatal jaundice: A safe and efficient system during the COVID-19 pandemic.

The coronavirus disease 2019 (COVID-19) cases was on an increasing trend, including in Malaysia. The Malaysian Ministry of Health had implemented a range of measures, such as the use of masks and social distancing, to reduce the risk of transmission. Traditionally, newborns are evaluated for neonatal jaundice using visual assessment, a capillary heel prick and serum bilirubin (SB) sampling in primary health-care clinics. This approach requires the physical presence of both parents and their newborns in the primary health-care clinics, causing crowding and increasing the risk of COVID-19 infections. To alleviate crowding, we implemented the transcutaneous bilirubin drive-through (DT) service, which is an established, non-invasive, painless and rapid method to determine the bilirubin levels. Throughout the screening, both parents and baby will be confined to their car. A total of 1842 babies were screened in our DT setting from April to July 2020. Of the total babies, 298 (16.1%) required venesection for SB measurement and 85 required admission for phototherapy. None with severe jaundice were missed since the implementation of this service. The average test duration per neonate was less than 5 min, while conventional venous bilirubin laboratory testing required an average of 1.5 h per neonate. The cost of the SB laboratory test and consumables was approximately USD 5 per test, with an estimated cost savings of USD 7720. DT screening may be introduced in health-care settings to reduce crowding and eliminate the need of painful blood sampling in newborns.

Newborn Screening for Five Conditions in a Tertiary Care Government Hospital in Bengaluru, South India-Three Years Experience.

Newborn screening is the need of the hour in a developing country like India as there is paucity of data from studies conducted in government hospitals with large sample size. The purpose of the study is to estimate incidence rate and recall rates for five conditions screened in the neonatal period namely congenital hypothyroidism, congenital adrenal hyperplasia, glucose-6-phosphate dehydrogenase (G6PD) deficiency, galactosemia and phenyl ketonuria (PKU). The study was conducted at VaniVilas Hospital attached to Bangalore Medical College and Research Institute. A retrospective analysis of the results of newborn screening programme during a 3-year period between January 2016 and December 2018 was done. There were 47623 livebirths during this period out of which 41027 babies were screened (coverage-86% of total livebirths). Heelprick samples after 48 h of life and prior to discharge were analysed by quantitative assessment. Neonates having positive screening results were recalled by telephonic call for repeat screening and confirmatory tests. G6PD deficiency was the most common disorder with an incidence of 1:414, followed by congenital hypothyroidism and Congenital Adrenal Hyperplasia with an incidence of 1:2735 and 1:4102, respectively. Galactosemia and PKU were found to be rare in our population. The overall average recall rate was 0.6% which meant that 24 normal newborns were recalled for testing for one confirmed case. The recall rate was relatively higher for galactosemia and G6PD deficiency which was at 0.25% each compared to the other conditions where it was below 0.05%. The results of the study emphasize the need for universal newborn screening especially in all government hospitals with large birth cohorts.

Association of maternal serum concentration of hydroxylated polychlorinated biphenyls with maternal and neonatal thyroid hormones: The Hokkaido birth cohort study

BackgroundEvidence on the toxicity of hydroxylated metabolites of polychlorinated biphenyls (OH-PCBs) for thyroid hormones (TH) is limited, and the underlying mechanism remains unknown. ObjectivesWe aimed to investigate the effects of environmental prenatal exposure to OH-PCBs and maternal and neonatal TH levels, taking the maternal-fetal TH transfer into account. MethodsIn this prospective birth cohort (the “Hokkaido study”) we included 222 mother-neonate pairs. We measured five OH-PCB isomers in maternal serum samples either during pregnancy or within 5 days of delivery. Thyroid stimulating hormone (TSH) and free thyroxine (FT4) levels were obtained from maternal blood samples at an early gestational stage (median; 11.1 weeks) and from heel prick samples of neonates between 4 and 7 days after birth. Multiple linear regression analysis and structural equation modeling (SEM) were performed to investigate the associations between maternal OH-PCB and maternal and neonatal TH levels. ResultsMedian concentration of ∑OH-PCBs was 25.37 pg/g wet weight. The predominant isomer was 4-OH-CB187, followed by 4-OH-CB146+3-OH-CB153. In the fully adjusted linear regression analysis, maternal ∑OH-PCBs was positively associated with maternal FT4, and 4-OH-CB187 was positively associated with both maternal and neonatal FT4 levels. Maternal OH-PCBs showed no significant association with TSH among mothers and neonates. Path analysis indicated the indirect pathway from 4-OH-CB187 exposure to increased neonatal FT4, via maternal THs and neonatal TSH. ConclusionsThese findings suggest that maternal exposure to OH-PCBs during pregnancy may increase both maternal and neonatal FT4 levels. Neonatal FT4 is presumed to be increased by prenatal 4-OH-CB187 indirectly, and this process may be mediated by maternal THs and neonatal TSH.

Postnatal Gestational Age Estimation Using Newborn Metabolic Profiles: A Validation Study in Matlab, Bangladesh

Background: Accurate preterm birth data are necessary for population health surveillance and to guide preterm birth initiatives. Gestational age is not routinely or accurately documented in many low-resource nations, however. Metabolic testing of newborn dried blood spots has been used to develop algorithms that yield accurate preterm birth estimates in North America. This study sought to validate published gestational age estimation models in infants born in Bangladesh. Methods: This was a prospective cohort study nested within the Preterm and Stillbirth Study, Matlab. The gestational age of all infants was confirmed by first trimester ultrasound. Cord blood and heel-prick blood spots were collected and analyzed at a provincial newborn screening facility in Ottawa, Canada. The performance of previously-published gestational age algorithms developed from heel-prick data to derive gestational age and preterm birth estimates was evaluated. Findings: 1036 cord blood and 487 heel-prick samples were collected from 1069 unique newborns. When applied to heel-prick metabolic profiles, published algorithms correctly estimated gestational age to within 1.07 weeks and accurately estimated gestational age to within 2 weeks for 94.3% of infants. Model performance was modestly reduced when applied to cord blood samples and accurately estimated gestational age to within 2 weeks for 90.3% of infants. Areas under the curve for distinguishing preterm births from term births were 0.945 (95%CI 0.890-0.999) for heel-prick samples and 0.894 (95%CI 0.853-0.935) for cord blood data. Interpretation: Metabolic gestational age dating provides accurate population-level estimates of gestational age and preterm birth burden. Models are effective on data obtained from both heel prick and cord blood, with the latter as a potentially more feasible option for deriving preterm birth estimates in low resource settings. Funding: This study was supported by the Bill & Melinda Gates Foundation [OPP1141535]. Declaration of Interest: The authors report no conflicts of interest Ethical Approval: Mothers provided informed consent for their infants to be included in the PreSSMat birth cohort and to have clinical data, cord blood and newborn heel prick samples collected and analysed. The present study was approved by the Research Review and Ethical Review Committees of the International Centre for Diarrhoeal Disease Research, Bangladesh (PR-16039). Approvals were also obtained from the Research Ethics Boards of the Ottawa Health Science Network (20160219-01H), and the Children’s Hospital of Eastern Ontario (16/20E).

Comparison the Effectiveness of Breastfeeding, Oral 25% Dextrose, Kangaroo-Mother Care Method, and EMLA Cream on Pain Score Level Following Heal Pick Sampling in Newborns: a randomized clinical trial.

BackgroundToday, it is considered that infants can feel pain, and it can have several adverse effects on their development. Although different interventions, such as skin-to-skin contact (kangaroo mother care method), glucose solutions, breastfeeding, and local anesthetic agents, have been evaluated to reduce infants’ pain, there is no clinical trial available to identify the best method.ObjectiveThe aim of this study was to compare the efficacy of four methods of relieving infants’ pain, i.e., breastfeeding, oral 25% dextrose, kangaroo mother care method (KMCM), and EMLA cream based on a pain score level following heal-prick sampling in term newborns.MethodsIn this double-blind, controlled, randomized clinical trial, full term, and healthy infants in Shahid Motahhari Hospital, Marvdasht, Shiraz Province, Iran were studied. Infants were randomly allocated to four groups of interventions, i.e., A: breast milk feeding (n=42), B: oral 25% dextrose (n=40), C: KMCM (n=38), and D: KMCM ointment (n=40). All interventions were applied 15 minutes before heel-prick sampling. To evaluate the pain level in infants, the Neonatal Infant Pain Scale (NIPS) questionnaire was used. The data were analyzed with SPSS version 16 by ANOVA and the chi-squared tests.ResultsOne hundred and sixty-one infants (93 males, 68 females) with an age range of 3 to 5 days were studied. There was no significant difference between the groups in terms of gender (p=0.113), weight (p=0.059), and baseline pain score level (p=0.904). The breastfeeding method showed the lowest pain score in comparison to the other interventions (A=5.52±2.22, B=6.45±1.88, C=6.84±1.96, D=7.37±1.95; p=0.001) after the heel-prick sampling.ConclusionIt seems that, among the four methods of interventions in this study, the most effective method of lowering perceived pain in infants undergoing painful procedures was proven to be breastfeeding.Trial RegistrationThis study is registered in the Iranian Registry of Clinical Trials with the registration number of IRCT20151201253256N1.FundingThis research was supported financially by the Research Council of the International Campus of Shiraz University of Medical Sciences.

Normative Data for Thyroid Stimulating Hormone for Screening of Congenital Hypothyroidism.

To generate normative data for thyroid stimulating hormone (TSH) levels in heel prick samples collected from newborns from 24h to 7 d of age. Five regional laboratories were designated as the testing laboratories. Dried blood spots (DBS) from babies (> or = 34 wk of gestation) were collected by heel prick at least after 24h and within seven days after birth. TSH estimation was done using time resolved fluoroimmunoassay. Values above 20mIU/L were labelled as presumptive positive. Hour interval specific normative data was categorized at 6h intervals. Another category placed was division into 24-72h category, 73-96h and 99-168h. Percentile charts were calculated across these specified intervals. Samples analysed were 104,006 collected cumulatively from the 5 centers. Of the total samples analysed for TSH, 92.8% had values less than 5 mIU/l. When TSH values were interpreted with respect to time, a steady decrease with time was observed. Of the babies' samples, 48,839 were collected between 24 and 48h, 23,983 between 49 to 72h and 30,883 were collected after 72h. The mean TSH concentration demonstrated a steady decline from 24h to 168h. It is apparent that 10 mIU/l is the 97.5th percentile value even when corrected for gender, birth weight and age at sampling. Thus 10 mIU/l seems to be the right cutoff beyond which a second sample should be sought. This is the largest series reported with a broader population mix with representations of both urban (including slums) as well as a rural population. As this study excluded preterm babies, the utility of cut offs generated is not applicable to this subset and also to critically sick neonates. However, this study gives a true representation of the normative values for majority of the newborns born at term with weight appropriate for the gestation.

Higher prevalence of permanent congenital hypothyroidism in the Southwest of Iran mostly caused by dyshormonogenesis: a five-year follow-up study.

The incidence of congenital hypothyroidism (CH) varies globally. This 5-year study aimed to determine the prevalence of permanent CH in the southwest of Iran. Between January 2007 and December 2009, all newborns in Ahvaz, the biggest city in the southwest of Iran, were screened for CH using a heel-prick sample for thyrotropin (TSH) levels. Subjects with TSH ≥ 5 mU/L were evaluated for T4-TSH. Infants with T4 < 6.5 µg/dL, TSH > 10 mU/L, and normal T4 but persistent (> 60 days) high TSH were considered to have CH. After the third birthday, treatment was discontinued, and T4-TSH was reevaluated; subjects with TSH ≥ 10 mU/L were investigated using thyroid Tc99 scintigraphy (TS). Based on TS, they were classified as normal, dysgenetic, or athyretic (agenesis). Screening was performed for 86,567 neonates, and 194 were confirmed to have CH (100 males; F/M = 0.94; overall incidence 1:446). After the third birthday, reevaluation was performed in all (except 18 that were not accessible). From 176 patients, 81 (46%) were diagnosed with permanent CH, and 95 were discharged as transient. Considering the same percentage in the lost cases, the prevalence of permanent CH was found to be 1:970. TS performed for 53 of the permanent subjects found agenesis/dysgenesis in 25 (F:M = 15:10) and a normal result in 28 (F:M = 11:17), indicating dyshormonogenesis as the cause in more than 50% of subjects. The incidence of CH in this area was found to be higher than that in other countries but less than the incidence rate reported in central Iran. The large number of transient cases of CH suggests environmental or maternal causes for the incidence rather than a genetic basis.

The Impact of Iodine Status on the Recall Rate of the Screening Program for Congenital Hypothyroidism: Findings from Two National Studies in Iran.

Back ground: Iodine deficiency is one of the important factors in increasing the recall rate in congenital hypothyroidism (CH) screening programs. The present study assessed whether the iodine status of the general population may predict the recall rate or vice versa. Methods: In the current national study, among 1,382,229 live births delivered between March 2010 and March 2011, 1,288,237 neonates were screened for detecting CH by TSH (thyroid stimulating hormone) measurement via heel prick sampling. Simultaneously, a total of 11,280 school-aged children, aged 7–8 years, were selected using random multi-cluster sampling for measurement of urinary iodine. Results: A negative correlation was found between median urinary iodine (MUI) and the recall rate (r = −0.33, p = 0.03). No correlation was found between MUIC (median urinary iodine concentration) and the incidence rate of CH. Linear regression analysis showed a 0.1% increase in the recall rate for a one unit decrease in MUIC (β = −0.11, 95% CI: −0.2, −0.1, p = 0.03). MUIC, at a cut-off point of 144.7 µg/L, was predictive for a recall rate < 3% (p = 0.05). Conclusion: Frequencies of TSH ≥ 5 mU/L may be a more sensitive indicator for iodine status during pregnancy rather than in the general population. As higher recall rates reflect inadequate iodine nutrition, sufficient iodine supplementation is needed to reduce the recall rate in such communities.

Thyroid homeostasis in mother\u2013child pairs in relation to maternal iodine status: the MISA study

Background/Objectives:Iodine deficiency during pregnancy may influence maternal and foetal thyroid function with the risk of causing neurocognitive and psychomotor deficits in the offspring. The objective of this study was to assess iodine status in pregnant women from Northern Norway and to investigate the influence of iodine status on maternal and infant thyroid function.Subjects/Methods:Women from the Northern Norway Mother-and-Child contaminant Cohort Study (MISA) donated a blood and urine sample at three visits during their pregnancy and postpartum period (in second trimester, 3 days and 6 weeks after delivery. N=197). Women were assigned to iodine status groups according to urine iodine concentrations (UICs) in second trimester and mixed effects linear models were used to investigate potential associations between iodine status and repeated measurements of thyroid-stimulating hormone (TSH), thyroid hormones (THs), TH-binding proteins and thyroid peroxidase antibodies. Associations between maternal iodine status and TSH in heel prick samples from the infants were investigated with linear regression.Results:Median UIC in second trimester was 84 μg/l (range 18–522) and 80% had UIC below recommended level (<150 μg/l). Iodine-deficient women had higher concentrations of T3, FT3 and FT4 (estimated differences (confidence intervals) of 0.10 nmol/l (0.01, 0.17), 0.16 pmol/l (0.05, 0.26) and 0.45 pmol/l (0.10, 0.78), respectively) compared with iodine-sufficient women. The concentrations varied within normal reference ranges, but the majority of women with subclinical hypothyroidism were iodine deficient. Maternal iodine status did not influence infant TSH concentrations.Conclusions:This study indicate iodine deficiency among pregnant women in Norway. Iodine status during pregnancy influences maternal thyroid homeostasis and is therefore a risk factor for foetal and infant development.

Persistent organic pollutants and thyroid function in mother-child pairs. A multipollutant assessment.

Background: Disruption of thyroid homeostasis has been indicated in human studies targeting effects of persistent organic pollutants (POPs). Influence on the maternal thyroid system by POPs is of special interest during pregnancy, as such effects could impair infant thyroid homeostasis. Objectives: We investigated the association between POPs and thyroid stimulating hormone (TSH) and thyroid hormones (THs) in mother and child pairs from the Northern Norway Mother-and-Child Contaminant Cohort Study (MISA). Methods: Nineteen POPs and ten thyroid parameters were analysed in serum from 391 pregnant women in their second trimester. In addition, TSH concentrations in heel prick samples from the infants were analysed by the Norwegian Newborn Screening program. Association studies with a multipollutant approach were performed using multivariate analyses; partial least squares (PLS) regression, hierarchical clustering and principle component analysis (PCA). Results: Several POPs were significantly associated to maternal TSH and THs: i) PFOS was positively associated with TSH; ii) PCBs, HCB and nonachlors were inversely associated to T3, T4 and FT4; and, iii) PFDA and PFUnDA were inversely associated to T3 and FT3. After mutual adjustments for the other contaminants, only PFDA and PFUnDA remained significantly associated to T3 and FT3, respectively. Infants born by mothers within the highest TSH quartile had 10% higher mean concentrations of TSH compared to children born by mothers in the lowest TSH quartile. Conclusion: The present results suggest that background exposures to POPs can alter maternal thyroid homeostasis. This research contributes to the understanding of multipollutant exposures using multivariate statistical approaches and highlights the complexity of investigating environmental concentrations and mixtures in regards to maternal and infant thyroid function.

Persistent Organic Pollutants and the Association with Maternal and Infant Thyroid Homeostasis: A Multipollutant Assessment.

Background:Disruption of thyroid homeostasis has been indicated in human studies targeting effects of persistent organic pollutants (POPs). Influence on the maternal thyroid system by POPs is of special interest during pregnancy because such effects could impair infant thyroid homeostasis.Objectives:We investigated the association between POPs and thyroid-stimulating hormone (TSH) and thyroid hormones (THs) in mother and child pairs from the Northern Norway Mother-and-Child Contaminant Cohort Study (MISA).Methods:Nineteen POPs and 10 thyroid parameters were analyzed in serum from 391 pregnant women in their second trimester. In addition, TSH concentrations in heel-prick samples from the infants were analyzed by the Norwegian Newborn Screening program. Association studies with a multipollutant approach were performed using multivariate analyses; partial least squares (PLS) regression, hierarchical clustering, and principal component analysis (PCA).Results:Several POPs were significantly associated with TSH and THs: a) PFOS was positively associated with TSH; b) PCBs, HCB, and nonachlors were inversely associated with T3, T4, and FT4; and, c) PFDA and PFUnDA were inversely associated with T3 and FT3. After mutual adjustments for the other contaminants, only PFDA and PFUnDA remained significantly associated with T3 and FT3, respectively. Infants born to mothers within the highest TSH quartile had 10% higher mean concentrations of TSH compared with children born to mothers in the lowest TSH quartile.Conclusion:The present results suggest that background exposures to POPs can alter maternal thyroid homeostasis. This research contributes to the understanding of multipollutant exposures using multivariate statistical approaches and highlights the complexity of investigating environmental concentrations and mixtures in regard to maternal and infant thyroid function.Citation:Berg V, Nøst TH, Pettersen RD, Hansen S, Veyhe AS, Jorde R, Odland JØ, Sandanger TM. 2017. Persistent organic pollutants and the association with maternal and infant thyroid homeostasis: a multipollutant assessment. Environ Health Perspect 125:127–133; http://dx.doi.org/10.1289/EHP152

Determination of a steroid profile in heel prick blood using LC-MS/MS.

The aim of this study was to improve the sensitivity of the congenital adrenal hyperplasia (CAH) neonatal screening by including second-tier steroid profiling on a DBS using LC-MS. We developed a method to measure the steroid profile in DBS and established gestational age-specific reference ranges of cortisol, cortisone, 11-deoxycortisol, 21-deoxycortisol, 17-hydroxyprogesterone, testosterone, Δ4-androstenedione, corticosterone and 11-deoxycorticosterone using 450 heel prick samples of neonates, participating in the Dutch Screening Program. Analyzing 92 cards with a positive CAH screening showed that only 21-deoxycortisol was 100% specific for diagnosed CAH patients. Steroid precursors can be measured in DBS and we suggest to implement the method as a second tier testing for CAH in The Netherlands.