Therapeutic Drug Monitoring Is a Feasible Tool to Personalize Drug Administration in Neonates Using New Techniques: An Overview on the Pharmacokinetics and Pharmacodynamics in Neonatal Age.

Therapeutic drug monitoring (TDM) should be adopted in all neonatal intensive care units (NICUs), where the most preterm and fragile babies are hospitalized and treated with many drugs, considering that organs and metabolic pathways undergo deep and progressive maturation processes after birth. Different developmental changes are involved in interindividual variability in response to drugs. A crucial point of TDM is the choice of the bioanalytical method and of the sample to use. TDM in neonates is primarily used for antibiotics, antifungals, and antiepileptic drugs in clinical practice. TDM appears to be particularly promising in specific populations: neonates who undergo therapeutic hypothermia or extracorporeal life support, preterm infants, infants who need a tailored dose of anticancer drugs. This review provides an overview of the latest advances in this field, showing options for a personalized therapy in newborns and infants.

Rates of Fentanyl Positivity in Neonatal Urine Following Maternal Analgesia During Labor and Delivery.

BACKGROUND: Fentanyl is commonly given as an analgesic during labor and delivery. The extent of transplacental drug transfer and fetal exposure is not well studied. We analyzed the relationship between neonatal urine fentanyl results and various peripartum factors. METHODS: A total of 96 neonates with urine toxicology screening between January 2017 and September 2018 were included in the study. Medical record review was used to obtain maternal, neonatal, and anesthesia parameters. A subset of 9 specimens were further tested for levels of fentanyl and norfentanyl by liquid chromatography-tandem mass spectrometry. RESULTS: In 29% (n = 24) of cases associated with fentanyl-containing labor analgesia, neonatal toxicology screens were positive for the presence of fentanyl. Positive test results strongly correlated with the cumulative dose and duration of labor analgesia (P < 0.001). The odds of positive neonatal fentanyl screen results increased 4-fold for every 5 hours of maternal exposure to labor analgesia. Importantly, however, neonatal outcomes for infants with positive and negative urine fentanyl screens were the same. CONCLUSIONS: Our study establishes that maternal fentanyl analgesia is strongly associated with positive neonatal urine fentanyl screens and suggests that more judicious use of these laboratory tests may be warranted.

Longitudinal metabolic and gut bacterial profiling of pregnant women with previous bariatric surgery.

OBJECTIVE: Due to the global increase in obesity rates and success of bariatric surgery in weight reduction, an increasing number of women now present pregnant with a previous bariatric procedure. This study investigates the extent of bariatric-associated metabolic and gut microbial alterations during pregnancy and their impact on fetal development. DESIGN: A parallel metabonomic (molecular phenotyping based on proton nuclear magnetic resonance spectroscopy) and gut bacterial (16S ribosomal RNA gene amplicon sequencing) profiling approach was used to determine maternal longitudinal phenotypes associated with malabsorptive/mixed (n=25) or restrictive (n=16) procedures, compared with women with similar early pregnancy body mass index but without bariatric surgery (n=70). Metabolic profiles of offspring at birth were also analysed. RESULTS: Previous malabsorptive, but not restrictive, procedures induced significant changes in maternal metabolic pathways involving branched-chain and aromatic amino acids with decreased circulation of leucine, isoleucine and isobutyrate, increased excretion of microbial-associated metabolites of protein putrefaction (phenylacetlyglutamine, p-cresol sulfate, indoxyl sulfate and p-hydroxyphenylacetate), and a shift in the gut microbiota. The urinary concentration of phenylacetylglutamine was significantly elevated in malabsorptive patients relative to controls (p=0.001) and was also elevated in urine of neonates born from these mothers (p=0.021). Furthermore, the maternal metabolic changes induced by malabsorptive surgery were associated with reduced maternal insulin resistance and fetal/birth weight. CONCLUSION: Metabolism is altered in pregnant women with a previous malabsorptive bariatric surgery. These alterations may be beneficial for maternal outcomes, but the effect of elevated levels of phenolic and indolic compounds on fetal and infant health should be investigated further.

Impact of urine osmolality/urine sodium on the timing of diuretic phase and non-invasive ventilation support: Differences from late preterm to term neonates.

BACKGROUND: Extracellular fluid retained in the lungs lead to respiratory distress in both late preterm (LP) and term neonates. The relationship between urine parameters toward the diuresis and the duration of ventilation postnatally is unknown. To find the correlation between the diuretic phase with urine parameters in the first 4 days after birth and the duration of non-invasive ventilation (NIV). METHODS: Serial measurements of urine osmolality (Uosm), urine sodium (UNa), and urine output (U/O) in neonates were collected at 5 time periods (T1:0-12 postnatal hours, T2:12-24 postnatal hours, T3:24-48 postnatal hours, T4:48-72 postnatal hours, T5:72-96 postnatal hours) were recorded. The correlations were analyzed in late preterm and term neonates. RESULTS: Ninety-seven neonates were included. Negative correlation between Uosm and U/O were observed. LP neonates (n=26) and term neonates (n=71) had differences with Uosm at T2, UNa at T4, T5, and U/O at T2, T3. Factors of U/O < 1 ml/kg/hr at T1 (odds ratio (OR) = 20.0; 95% confidence interval (CI) 1.796-222.776; p = 0.015) or Uosm > 273 mOsm/L at T1 (OR = 9.0; 95% CI 1.031-78.574; p = 0.047) in LP neonates and UNa > 26.5 mEq/L at T5 (OR = 23.625; 95% CI 2.683-79.276; p < 0.01) in term neonates were associated with prolonged NIV use (> 120 hours). CONCLUSION: We speculate the significant correlation between Uosm/UNa and the diuretic phase. The LP neonates acquire earlier diuretic phase than the term neonates. The Uosm/UNa in the first few postnatal days had the correlation with the duration of NIV support.

Associations of early life urinary triclosan concentrations with maternal, neonatal, and child thyroid hormone levels.

BACKGROUND: Triclosan, an antimicrobial agent used in some consumer products, reduces endogenous thyroid hormone concentrations in rodents. Despite ubiquitous triclosan exposure and the importance of thyroid hormones for normal fetal development, few human studies have examined the impact of triclosan exposure on maternal, neonatal, or child thyroid hormones. METHODS: In the HOME Study, a prospective cohort from Cincinnati, OH, we measured urinary triclosan concentrations up to three times in pregnant women between 16weeks and delivery, and up to three times in children between age 1-3years. We quantified serum concentrations of thyroid stimulating hormone and total and free thyroxine and triiodothyronine in mothers at 16-weeks gestation (n=202), neonates at delivery (n=274), and children at age 3years (n=153). We estimated covariate-adjusted differences in thyroid hormones with a 10-fold increase in triclosan using linear regression and multiple informants models. RESULTS: Triclosan was not associated with thyroid hormones during pregnancy. We observed a few associations of triclosan concentrations with thyroid hormone concentrations in neonates at delivery and children at age 3years. Higher gestational triclosan, particularly around the time of delivery, was associated with lower cord serum total thyroxine (ß: 0.3µg/dL; 95% CI: -0.6, -0.0). Childhood triclosan, particularly at age 1year, was positively associated with total thyroxine at age 3years (ß: 0.7µg/dL; 95% CI: 0.3, 1.2). CONCLUSION: Our findings suggest that triclosan exposure may influence some features of neonatal and early child thyroid function. Given the large number of comparisons we made, these findings should be replicated in other cohorts.

Urinary iodine concentrations in mothers and their term newborns in country with sufficient iodine supply.

OBJECTIVE: The main aim of the study was to evaluate maternal and newborn urinary iodine concentrations according to the usage of iodine supplementation during pregnancy. METHODS: Thirty-seven women with singleton uncomplicated pregnancies and their newborns were included in this study. Maternal urine samples were obtained at the time of delivery and on the third day after delivery. Newborn urine samples were obtained on the third day after delivery. Urinary iodine concentrations were determined by the alkaline ashing of urine specimens followed by the Sandell-Kolthoff reaction using brucine as a colorimetric marker. RESULT: The overall rate of the usage of iodine supplementation during pregnancy was 54% (20/37). Women who used the iodine supplementation during the pregnancy did not have different urinary iodine concentrations neither at the time of delivery (p = 0.23), nor on the third day after delivery (p = 0.65) in comparison to women without extra iodine supplementation. Newborns from pregnancies with regular iodine supplementation had higher urine iodine concentrations on the third day after delivery (p = 0.02). When women were split into several subgroups based on the daily dosage of iodine supplementation (200, 150, and 50 µg daily and without iodine supplementation), no differences were found in maternal urine iodine concentrations at the time of delivery (p = 0.51) and on the third day after delivery (p = 0.63). Different levels were found in newborn urine iodine concentrations among the subgroups of newborns from pregnancies with different daily doses of iodine supplementation and from pregnancies without iodine supplementation during pregnancy (p = 0.05). CONCLUSIONS: Iodine supplementation during pregnancy affects newborn urine concentrations but not maternal urine concentrations.

Health term-born girls had higher levels of urine neutrophil gelatinase-associated lipocalin than boys during the first postnatal days.

UNLABELLED: Neutrophil gelatinase-associated lipocalin (NGAL) is one of the most extensively examined biological markers for early prediction of acute kidney injury, but there is a lack of data on normal NGAL values in healthy term-born infants. This encouraged us to established serum and urine levels using samples collected from 38 girls and 50 boys, born at a median age of 39 weeks, during the first 48 hours after birth. CONCLUSION: Our findings showed that urine NGAL, but not serum levels, were significantly higher in girls than in boys.

Longitudinal patterns of urine biomarkers in infants across gestational ages.

BACKGROUND: Urinary biomarkers may be indicators of acute kidney injury (AKI), although little is known of their developmental characteristics in healthy neonates across a full range of gestational age (GA). The purpose of this study was to examine patterns of urinary biomarkers across GA groups from birth to 3 months of age. METHODS: Fifty-two infants ranging from 24 to 41 weeks' GA had urine assayed from birth through 3 months of age for 7 biomarkers including albumin (ALB), beta-2-microglobulin (B2M), cystatin-C (CysC), epidermal growth factor (EGF), neutrophil-gelatinase-associated lipocalin (NGAL), osteopontin (OPN), and uromodulin (UMOD). RESULTS: Of the seven urinary biomarkers, EGF and UMOD increased while others decreased with advancing GA. By 3 months of age, EGF and UMOD had increased in preterm infants to levels similar to those of term infants. UMOD/ml and EGF/ml appeared to be predominantly developmental biomarkers distinguishing estimated glomerular filtration rate (GFR) <30 ml/min/1.73 m(2) with receiver operator characteristic area under the curve (ROC-AUC) of 0.82; p = 0.002. When factored by urine creatinine CysC/cr + ALB/cr were the most significant functional markers with AUC = 0.79; p = 0.004; sensitivity 96 %; specificity 58 %. CONCLUSIONS: Among healthy neonates, urinary biomarkers vary with GA. These data support the use of urinary biomarkers in the assessment of normal kidney development in the absence of injury.

Neurological outcomes in symptomatic congenital cytomegalovirus-infected infants after introduction of newborn urine screening and antiviral treatment.

BACKGROUND: Newborn screening for urinary cytomegalovirus (CMV) and early introduction of antiviral treatment are expected to improve neurological outcomes in symptomatic congenital CMV-infected infants. This cohort study prospectively evaluated neurological outcomes in symptomatic congenital CMV-infected infants following the introduction of hospital-based newborn urinary CMV screening and antiviral treatment. SUBJECTS/METHODS: Following institutional review board approval and written informed consent from their parents, newborns were prospectively screened from 2009 to 2014 for urinary CMV-DNA by PCR within 1 week after birth at Kobe University Hospital and affiliated hospitals. CMV-positive newborns were further examined at Kobe University Hospital, and those diagnosed as symptomatic were treated with valganciclovir for 6 weeks plus immunoglobulin. Clinical neurological outcomes were evaluated at age ⩾12 months and categorized by the presence and severity of neurologic sequelae. RESULTS: Urine samples of 6348 newborns were screened, with 32 (0.50%) positive for CMV. Of these, 16 were diagnosed with symptomatic infection and 12 received antiviral treatment. Four infants developed severe impairment (33%), three developed mild impairment (25%), and five developed normally (42%). CONCLUSIONS: This is the first Japanese report of neurological assessments in infants with symptomatic congenital CMV infection who received early diagnosis and antiviral treatment. Urinary screening, resulting in early diagnosis and treatment, may yield better neurological outcomes in symptomatic congenital CMV-infected infants.

Metabolomics application in maternal-fetal medicine.

Metabolomics in maternal-fetal medicine is still an "embryonic" science. However, there is already an increasing interest in metabolome of normal and complicated pregnancies, and neonatal outcomes. Tissues used for metabolomics interrogations of pregnant women, fetuses and newborns are amniotic fluid, blood, plasma, cord blood, placenta, urine, and vaginal secretions. All published papers highlight the strong correlation between biomarkers found in these tissues and fetal malformations, preterm delivery, premature rupture of membranes, gestational diabetes mellitus, preeclampsia, neonatal asphyxia, and hypoxic-ischemic encephalopathy. The aim of this review is to summarize and comment on original data available in relevant published works in order to emphasize the clinical potential of metabolomics in obstetrics in the immediate future.

Arginine-guanidinoacetate-creatine pathway in preterm newborns: creatine biosynthesis in newborns.

The phosphocreatine/creatine system is fundamental for the proper development of the embryonic brain. Being born prematurely might alter the creatine biosynthesis pathway, in turn affecting creatine supply to the developing brain. We enrolled 53 preterm and very preterm infants and 55 full-term newborns. The levels of urinary guanidinoacetate, creatine, creatinine and amino acids were measured in the preterm and very preterm groups, 48 h and 9 days after birth and at discharge, and 48 h after birth in the full-term group. Guanidinoacetate concentrations of both preterm and very preterm newborns were significantly higher at discharge than the values for the full-term group at 48 h, while very preterm infants showed urinary creatine values significantly lower than those measured in the full-term group. Our results suggest an impairment of the creatine biosynthesis pathway in preterm and very preterm newborns, which could lead to creatine depletion affecting the neurological outcome in prematurely born infants.

Transient postnatal secretion of androgen hormones is associated with acne and sebaceous gland hypertrophy in early infancy.

CONTEXT: Sebaceous gland hypertrophy (SGH) and acne-like skin eruptions are frequent during the first months of life, yet the etiology and prevalence of these conditions in infants are not clear. OBJECTIVE: The objective of the study was to evaluate the association of postnatal androgens with SGH and acne in infants. DESIGN: This was a longitudinal, monthly follow-up from 1 wk (D7) to 6 months of age (M1-M6). PATIENTS: Patients included 54 full-term (FT; 26 boys) and 48 preterm (PT; gestational age at birth 27.7-36.6 wk, 22 boys) infants. MAIN OUTCOME MEASURES: The occurrence of SGH (present/absent) and acne (5-10, 10-50, and >50 papules) was registered and compared with urinary levels of dehydroepiandrosterone and its sulphate and testosterone measured by liquid chromatography-tandem mass spectrometry. RESULTS: SGH was observed in 89% of FT and 96% of PT infants (P = 0.28). Acne (more than five papules) was observed in 91% of FT infants and in 75% of PT infants (P = 0.06). Both SGH and acne were associated with developmental rather than calendar age: SGH was limited to postmenstrual age less than 46 wk and acne was not observed less than 37 wk of postmenstrual age. Urinary androgen levels showed severalfold differences in magnitude between sexes and between the FT and PT groups. After grouping according to sex and maturity, the occurrence of SGH and the severity of acne were associated with higher urinary dehydroepiandrosterone sulphate and testosterone levels in each group. CONCLUSIONS: SGH and acne are common during the first months of life and associated with endogenous, physiologically elevated levels of androgens originating from the adrenals and gonads. These data suggest a novel role for postnatal androgen secretion in infancy.

Candida spp. isoladas da urina de recém-nascidos de uma Unidade deTerapia Intensiva Neonatal / Candida spp. isolated from the urine of a newborns Neonatal Intensive Care Unit

Espécies de Candida são responsáveis por cerca de 80% das infecções fúngicas no ambiente hospitalar. O objetivo do trabalho foi detectar a presença de espécies de Candida na urina de recém-nascidos [RNs] internados em Hospital Universitário. Foram coletadas cinquenta urinas de RNs e realizado exame direto com hidróxido de potássio a 20% e cultura em ágar de Sabouraud dextrosado. A identificação foi realizada através do sistema automatizado MicroScan®. Dos RNs analisados, 21 (42%) apresentaram positividade para candidíase. As espécies isoladas foram C. albicans, 8 (38,1%), C. tropicalis, 5 (23,8%), C. famata, 4 (19%), C. stellatoidea, 2 (9,5%), C. zeylanoides e C. catenulata, 1 (4,8%). Ao exame direto, houve positividade em 95% das amostras e em 100% das cultura. A mortalidade associada à candidíase foi de 9,5% em pacientes com baixo peso e idade gestacional inferior a 34 semanas. É indispensável a realização de estudos que contribuam para a valorização dosquadros de colonização por leveduras e que visem diminuir as taxas de infecção...

Is newborn melatonin production influenced by magnetic fields produced by incubators?

BACKGROUND: During permanence in most incubators, newborns are very close to the electric engine, which represents a source of electromagnetic fields (EMF). Previous studies demonstrated a decrease in melatonin production in adults and animals exposed to EMF. AIMS: To assess melatonin production in a group of newborns exposed to EMF, and to evaluate whether removing the babies from the source of MF can affect melatonin production. STUDY DESIGN AND SUBJECTS: We have recruited 28 babies (study group), who had spent at least 48 h in incubator where we had previously assessed the presence of significant EMF. We have measured their mean 6-hydroxy-melatonin-sulfate (6OHMS) urine excretion at the end of their permanence in the incubators, and compared it with their mean 6OHMS excretion after having been put in cribs, where EMF are below the detectable limit (<0.1mG). We have also measured urine 6OHMS twice, with an interval of 48h, in a control group of 27 babies who were not exposed to EMF during both samples. RESULTS: Mean 6OHMS/cr values were respectively 5.34±4.6 and 7.68±5.1ng/mg (p=0.026) when babies were exposed to EMF in incubators, and after having been put in the crib. In the control group, mean 6OHMS/cr values in the first and in the second sample were respectively 5.91±5.41 vs 6.17±3.94ng/mg (p=0.679). CONCLUSIONS: The transitory increase in melatonin production soon after removing newborns from incubators demonstrates a possible influence of EMF on melatonin production in newborns. Further studies are needed to confirm these data.

Inositol phosphoglycan P-type in infants of preeclamptic mothers.

BACKGROUND: Inositol phosphoglycan P-type (P-IPG) has consistently found to be elevated during active preeclampsia, although the biosynthetic source has to be identified yet. This multicenter prospective cross-sectional case-control study evaluated the fetus/newborn as the source of P-IPG. METHODS: A urine specimen was collected longitudinally for three consecutive days after delivery from 90 newborns and their mothers, and ordered according to clinical diagnosis of preeclampsia, gestational hypertension, or healthy pregnancy. RESULTS: The urinary excretion of P-IPG on day 0 was higher in the mothers in all groups (p < 0.05) with higher levels in preeclamptic women (p < 0.01) in the mothers compared to their newborns in the preeclamptic group (p<0.01). The difference persisted at least two days post partum. CONCLUSION: Findings of this study confirm the specificity of the increase in urinary excretion of P-IPG in preeclamptic mothers at day of birth compared to healthy pregnancy and GH, but does not extend to their newborns.

Baseline values of candidate urine acute kidney injury biomarkers vary by gestational age in premature infants.

Acute kidney injury (AKI) is common in premature infants and is associated with poor outcomes. Novel biomarkers can detect AKI promptly. Because premature infants are born with underdeveloped kidneys, baseline biomarker values may differ. We describe baseline values of urinary neutrophil gelatinase-associated lipocalin (NGAL), IL-18, kidney injury molecule-1 (KIM-1), osteopontin (OPN), beta-2 microglobulin (B2mG), and Cystatin-C (Cys-C). Next, we test the hypothesis that these biomarkers are inversely related to GA. Candidate markers were compared according to GA categories in 123 infants. Mixed linear regression models were performed to determine the independent association between demographics/interventions and baseline biomarker values. We found that urine NGAL, KIM-1, Cys-C, and B2mG decreased with increasing GA. With correction for urine creatinine (cr), these markers and OPN/cr decreased with increasing GA. IL-18 (with or without correction for urine creatinine) did not differ across GA categories. Controlling for other potential clinical and demographic confounders with regression analysis shows that NGAL/cr, OPN/cr, and B2mG/cr are independently associated with GA. We conclude that urine values of candidate AKI biomarkers are higher in the most premature infants. These findings should be considered when designing and analyzing biomarker studies in newborn with AKI.

Urinary neutrophil gelatinase-associated lipocalin at birth predicts early renal function in very low birth weight infants.

Preterm infants are exposed to conditions that can impair renal function. We evaluated the ability of serum and urinary neutrophil gelatinase-associated lipocalin (sNGAL and uNGAL) to predict renal function in the first weeks of life. From September 2008 to July 2009, infants weighing ≤1500 g at birth with no major congenital anomalies or sepsis were eligible. We measured sNGAL and uNGAL levels at birth. To evaluate renal function, we determined changes in serum creatinine (sCreat) and estimated GFR (eGFR) from birth to d 21. Forty neonates (mean GA, 27 ± 2 wk) completed the study. Renal function improved in 32 of 40 (80%) infants (normal renal function, NRF group) (sCreat, from 0.97 ± 0.2 to 0.53 ± 0.13 mg/dL; eGFR, from 15.3 ± 4.1 to 28.6 ± 7.9 mL/min), whereas renal function worsened in 8 of 40 (20%) infants (impaired renal function, IRF group) (sCreat, from 0.71 ± 0.27 to 0.98 ± 0.43 mg/dL; eGFR from 23 ± 14.7 to 16.4 ± 9.1 mL/min). The uNGAL/urinary creatinine (uCreat) ratio at birth was higher in the IRF group (31.05 ng/mg) than the NRF group (6.0 ng/mg), and uNGAL was significantly higher in IRF group, detecting IRF with a cutoff of 100 ng/mL. uNGAL levels at birth may have a predictive role in very LBW (VLBW) infants.

Manejo intrahospitalario: infección urinaria en el recién nacido / Management nosocomial urinary tract infection in the newborn

La decisión de hospitalizar o no un niño con Infección Urinaria (IU) no debe sustentarse de forma exclusiva en el diagnóstico de pielonefritis aguda, ya que estudios recientes han mostrado que en los pacientes con buen estado general y, sin antecedentes de uropatía importante, el tratamiento ambulatorio con antibióticos por vía oral es eficaz y seguro. Por ello, la decisión de ingreso se debe basar fundamentalmente en la valoración de la situación clínica del paciente y el riesgo estimado de complicaciones generales. En esta revisión se evalúa la eficacia y seguridad de los antibióticos que se utilizan para tratar pielonefritis aguda en niños que requieren ser hospitalizados, se especifican los agentes antibióticos óptimos, así como la vía de administración y la duración del tratamiento adecuadas para este grupo de pacientes. Asimismo, se revisan los aspectos particulares de la IU en el neonato, debido a las características especiales del sistema inmune en este grupo de edad.

The decision to hospitalize a child with urinary tract infection should not rely exclusively on the diagnosis of acute pyelonephritis, for recent studies have demonstrated that ambulatory treatment with oral antibiotics is safe and efficient in patients with good general status and no history of urological abnormalities. For this reason, the decision to admit the patient should be based on the assessment of clinical conditions and the estimated risk of general complications. This review evaluates the efficiency and safety of antibiotics employed in children with acute pyelonephritis who require hospitalization, specifies the appropriate antibiotics, as well as the route and length of the treatment. Particular aspects of urinary tract infection in the newborn due to the special characteristics of the immune system at this age are also reviewed.

Neonatal thyroid status in an area of iodine sufficiency.

BACKGROUND: Iodine deficiency constitutes a public health problem in many countries worldwide. Fetal neurodevelopment is affected by maternal iodine intake. The aim of present study was to assess urinary iodine excretion (UIE) in the 3 trimesters of pregnancy and evaluate its association with newborn thyroid function in Tehran, an area of iodine sufficiency. METHODS: Based on median urinary iodine in 3 trimesters, 138 pregnant women were divided into 2 groups with UIE<150 (group I) and UIE ≥ 150 µg/l (group II). Cord blood samples of their newborns were evaluated for serum concentrations of TSH, T3, T4, free T4 (FT4), and thyroglobolin. Quartiles of UIE were also determined. Correlations between mothers' UIE and newborns' thyroid function in both groups were investigated. RESULTS: Fifty-two pregnant women (38%) had median UIE<150 µg/l and 86 had (62%) UIE ≥ 150 µg/l. Median UIE in groups I and II in the 1st, 2nd, and 3rd trimesters were 125 and 212 µg/l, 97 and 213 µg/l, 93 and 227 µg/l, respectively. No significant difference was seen in thyroid function of newborns in the 2 groups. Mean concentrations of T4, T3, FT4, and TSH of newborn did not show significant difference in median UIE of mothers in various quartiles. CONCLUSION: This study shows that newborns, irrespective of mothers' UIE, in an area with a sustained iodine supplementation program, may not be at risk of alterations in thyroid functions.

Urinary excretion of vitamin K metabolites in term and preterm infants: relationship to vitamin K status and prophylaxis.

Little is known about the metabolic turnover and excretion of vitamin K in healthy newborn infants and the metabolic consequences of prophylactic regimens designed to protect against vitamin K deficiency bleeding (VKDB). We measured the excretion of two urinary metabolites (≤ 24 h) of vitamin K (5C- and 7C-aglycones) in term infants before (n = 11) and after (n = 5) a 1000 µg i.m. dose of vitamin K1 (K1) and in preterm infants after 200 µg i.m. (n = 4), 500 µg i.m. (n = 4), or 200 µg i.v. (n = 5). In preterm infants, we also measured serum K1, vitamin K1 2,3-epoxide, and PIVKA-II at 5 d postpartum. Before prophylaxis, the rate of 5C- and 7C-aglycone excretion was 25 times lower than adults, reflecting low vitamin K stores at birth. After prophylaxis, the excretion rate correlated to K1 dose (r = 0.6) but was two orders of magnitude lower than that in adults, probably reflecting the immaturity of neonatal catabolism. All term and 10 of 13 preterm infants mainly excreted 5C-aglycone. We present evidence that increased excretion of the 7C-aglycone was associated with metabolic overload because of the exposure to high-tissue K1 concentrations. Measurement of the 5C- and 7C-aglycones may facilitate longitudinal studies of vitamin K status in neonates and aid the development of improved prophylactic regimens.