Effect of perinatal asphyxia on thyroid-stimulating hormone and thyroid hormone levels

AIM: To compare serum concentrations of thyroid hormones--T4, T3, free T4 (FT4) and reverse T3 (rT3)--and thyroid-stimulating hormone (TSH) found in the umbilical cord blood of term newborns with and without asphyxia and those found in their arterial blood collected between 18 and 24 h after birth. A further aim of the study was to assess the association between severity of hypoxic-ischemic encephalopathy and altered thyroid hormone and TSH levels, and between mortality and FT4 levels in the arterial blood of newborns between 18 and 24 h of life. METHODS: A case-control study was carried out. The case group comprised 17 term newborns (Apgar score < or = 3 and < or = 5 at the first and fifth minutes; umbilical cord blood pH < or = 7.15) who required bag and mask ventilation for at least one minute immediately after birth. The control group consisted of 17 normal, term newborns (Apgar score > or = 8 and > or = 9 at the first and fifth minutes; umbilical cord blood pH > or = 7.2). Cord blood and arterial blood samples were collected immediately after birth and 18 to 24 h after birth, respectively, and were used in the blood gas analysis and to determine serum concentrations of T4, T3, FT4, rT3 and TSH by radioimmunoassay. All newborns were followed-up until hospital discharge or death. RESULTS: Gestational age, birthweight, sex, size for gestational age, mode of delivery and skin color (white and non-white) were similar for both groups. No differences were found in mean levels of cord blood TSH, T4, T3 and FT4 between the groups. In the samples collected 18 to 24 h after birth, mean levels of TSH, T4, T3 and FT4 were significantly lower in the asphyxiated group than in the control group. Mean concentrations of arterial TSH, T4 and T3 between 18 and 24 h of life were lower than concentrations found in the cord blood analysis in asphyxiated newborns, but not in controls. In addition, asphyxiated newborns with moderate/severe hypoxic-ischemic encephalopathy presented significantly lower mean levels of TSH, T4, T3 and FT4 than those of controls. None of the asphyxiated newborns with FT4 > or = 2.0 ng/dl died; 6 out of the 11 asphyxiated newborns with FT4 < 2.0 ng/dl died. CONCLUSIONS: Serum concentrations of TSH, T4, T3 and FT4 are lower in asphyxiated newborns than in normal newborns between 18 and 24 h of life; this suggests central hypothyroidism secondary to asphyxia. Asphyxiated newborns with moderate/severe hypoxic-ischemic encephalopathy present a greater involvement of the thyroid function and consequently a greater risk of death.     

抗惊厥药物治疗新生儿窒息后缺氧缺血性脑病的Meta分析

目的 总结国内、外抗惊厥药治疗新生儿窒息后缺氧缺血性脑病文献的研究结果,采用Meta分析方法综合评价抗惊厥药治疗新生儿窒息后缺氧缺血性脑病的临床效果,探讨抗惊厥药治疗新生儿窒息后缺氧缺血性脑病的可能性。方法 制定原始文献的纳入标准、排除标准及检索策略,检索PubMed、EMBASE、Ovid、Springer和中国期刊全文数据库等,获得抗惊厥药治疗新生儿窒息后缺氧缺血性脑病的相关文献,使用国际Cochrane中心推荐的方法进行文献质量评价后,采用RevMan 4.22软件对满足纳入标准的抗惊厥药治疗新生儿窒息后缺氧缺血性脑病的RCT研究进行Meta分析。选取死亡率、严重神经系统发育障碍、惊厥发生率、不良反应等作为观察指标,进行定性、定量综合评估。结果 符合纳入标准的5篇RCT研究进入Meta分析,无一项研究有充分的方法学质量和尺度来证明抗惊厥药的使用能有效的降低死亡率或严重神经系统发育障碍。对5项研究的Meta分析显示,围产期窒息后给予巴比妥类药物或常规治疗对死亡率、严重神经系统发育障碍或两者的合并结局均无明显差异。结论 目前,尚不建议对存在围产期窒息的足月儿给予抗惊厥药作为临床常规治疗,远期仍需足够容量的研究来检验抗惊厥药治疗新生儿窒息对降低死亡率或严重神经系统发育障碍率的效用。     

抗惊厥药治疗足月新生儿围生期窒息临床疗效的Meta分析

目的 总结国内、外抗惊厥药治疗新生儿围生期窒息文献的研究结果,采用Meta分析方法综合评价抗惊厥药治疗新生儿围生期窒息临床疗效,探讨抗惊厥药治疗新生儿围生期窒息的可能性.方法 制定原始文献的纳入标准、排除标准及检索策略,检索PubMed、EMBASE、Ovid、Springer和中国期刊全文数据库等,获得抗惊厥药治疗新生儿围生期窒息的相关文献,使用国际Cochrane中心推荐的方法进行文献质量评价,以病死率、严重神经系统发育障碍发生率、新生儿期惊厥发生率和不良反应发生率等作为观察指标,进行定性和定量综合评估.采用RevMan 4.22软件进行Meta分析.结果 依据纳入和排除标准,共纳入5篇RCT文献,其中文献质量评价1篇为B级,4篇为C级.治疗组4篇文献予苯巴比妥治疗,1篇文献予硫喷妥钠治疗;对照组均予常规治疗.Meta分析结果显示:抗惊厥药治疗组与对照组比较,病死率差异无统计学意义(RR＝1.13,95%CI:0.59～2.17);严重神经系统发育障碍发生率差异无统计学意义(RR=0.61,95%CI:0.30～1.22);死亡和严重神经系统发育障碍合并发生率差异无统计学意义(RR=0.65,95%CI:0.30～1.41);新生儿期惊厥发生率差异无统计学意义(RR=0.76,95%CI:0.45～1.31).结论 目前,不建议对存在围生期窒息的足月新生儿给予抗惊厥药作为临床常规治疗.远期疗效仍需多中心和大样本RCT研究来检验抗惊厥药治疗新生儿围生期窒息对降低病死率或严重神经系统发育障碍发生率的效用.     

Effect of phototherapy on thyroid stimulatory hormone and free thyroxine levels

Objective : To study the effect of phototherapy for neonatal hyperbilirubinaemia on thyroid function as neonatal thyroid screening is sometimes performed during exposure to phototherapy. Methodology : Infants with non-haemolytic hyperbilirubinaemia were sequentially allocated to fibre-optic phototherapy, conventional daylight phototherapy, or a combination of both. Bilirubin concentration was monitored 12 hourly by capillary blood sampling; venous blood was sampled for thyroid stimulating hormone (TSH) and free thyroxine (fT₄) determinations, at start of exposure, at 24 h, end of exposure and 1 day later. Comparable unexposed infants served as controls. Results : All 123 study infants and 25 controls remained well during the study. Bilirubin levels declined during phototherapy, being most rapid in the combination group. The TSH and fT₄ values at start of exposure were 3.86 ± 0.41 mU/L (mean ± SEM) and 33.20 ± 1.16 pmol/L, respectively, in the fibre-optic group, 3.62 ± 0.38 mU/L and 37.22 ± 1.76 pmol/L in the daylight group, and 4.40 ± 0.48 mU/L and 29.91 ± 1.13 pmol/L in the combined group, compared with 5.77 ± 0.40 mU/L and 34.46 ± 1.68 pmol/L in the control group. The TSH and fT₄ values declined with increasing age in the phototherapy and control groups with end of exposure values of 2.90 ± 0.28mU/L and 27.71 ± 0.71 pmol/L, 2.77 ± 0.31 mU/L and 33.52 ± 1.22pmol/L, and 3.44 ± 0.30 mU/L and 27.54 ± 0.88 pmol/L, respectively, compared with 4.21 ± 0.61 mU/L and 27.19 ± 2.33 pmol/L (at 72 h) in the control group. The pattern of TSH and fT₄ decline in the exposed and control groups was similar, being related to increasing age. Conclusions : The validity of neonatal thyroid screening is not affected by fibre-optic or conventional phototherapy or by both combined.     

Early assessment of visual function in full term newborns

BACKGROUND: The assessment of visual function is part of all the neonatal neurological examination but it is often limited to the evaluation of ocular movements and the ability to fix and follow a target. AIM OF THE STUDY: To develop a simple battery of test items assessing different aspects of visual function that could be used as early as 48 h after birth. STUDY DESIGN AND SUBJECTS:: The final battery, which has been used in 50 full term low risk neonates, includes 9 items assessing ocular motility, both spontaneous and with focus on a visual target, fixation and tracking (horizontal, vertical and in an arc), the ability to discriminate stripes of different spatial frequency, and attention at distance. RESULTS: The battery proved easy to perform and did not require long training. The testing did not require a specific setting and was easy to use even for infants in incubators. The equipment is small and cleanable. CONCLUSION: Our paper suggests that a simple battery, which can be performed in 5/10 min, can be easily applied and provides useful information on various aspects of early neonatal visual function.     

甲状腺激素对大鼠瘦素水平的影响(英文)

目的：下丘脑-垂体-甲状腺轴可能影响瘦素的分泌和代谢。该研究探讨甲状腺功能减低和甲状腺功能亢进时甲状腺激素对血清瘦素水平和脂肪瘦素mRNA水平的影响。方法：应用他巴唑和优甲乐人工造成大鼠甲状腺功能减低和甲状腺功能亢进状态,分别于用药10天、停药10天检测用药组、停药组和正常对照大鼠血清瘦素、T3、T4、TSH浓度、体重和脂肪瘦素的mRNA水平。结果：甲减用药组、甲亢用药组和正常对照组大鼠血清瘦素与体重均有相关性(P<0.05),相关系数分别0.84、0.83、0.94。去除体重因素,甲亢用药组、停药组血清瘦素和脂肪瘦素mRNA水平和正常对照组相比无明显差别(P>0.05),而甲减用药组血清瘦素(0.68±0.07 ng/ml)和脂肪瘦素mRNA水平(0.39±0.02)显著低于停药组(1.98±0.09 ng/ml)(0.87±0.05)和正常对照组(2.14±0.46 ng/ml)(0.95±0.03)(P<0.05)。结论：甲状腺素可能对血清瘦素的稳定分泌起一定的作用。［中国当代儿科杂志,2004, 6(5): 369-372］     

Cerebral blood flow velocity in term newborns following intrapartum fetal asphyxia

Twenty-six term newborns with intrapartum fetal asphyxia, determined biochemically (umbilical artery base deficit < 12mmol/1), were compared with 59 normal newborns to determine the effect of intrapartum fetal asphyxia on newborn blood pressure and cerebral blood flow velocity following delivery. Cerebral blood flow velocity observations with concurrent measures of blood pressure and heart rate were obtained during the 24 h after delivery and after 24 h. After delivery, diastolic blood pressure in the newborns of the asphyxia group was significantly greater than that of the newborns of the normal group and this difference persisted after 24 h. Cerebral blood flow velocity in the newborns of the asphyxia group was of the same order as that of the newborns of the normal group during the 24 h after delivery. However, there was a significant increase in both peak systolic and end-diastolic blood flow velocity after 24 h. The duration of metabolic acidosis may be a factor in the occurrence of this delayed cerebral blood flow velocity response. Observations of cerebral blood flow velocity should be continued for more than 24 h following delivery to determine the effect of intrapartum fetal asphyxia.     

Effect of perinatal asphyxia on thyroid hormones

OBJECTIVE: To verify the effect of perinatal asphyxia on thyroid hormone levels in term newborn infants. METHODS: We carried out a case-control study with 17 term and asphyxiated (A) and 17 term and control (N) newborn infants at the Hospital de Clínicas de Porto Alegre. Patients were paired according to color of skin, sex, type of delivery, gestational age, and weight at birth. We collected umbilical cord plasma T4, T3, free T4, reverse T3, and TSH after 18 to 24 hours of life and from asphyxiated and control newborn infants. RESULTS: There were no differences in thyroid hormones of cord blood, with the exception of reverse T3, which was higher in A than in controls [median (25th-75th percentile): A= 2(1.4-2); N= 1.41 (1.13-1.92); P=0.037)]. Thyroid hormone levels were lower in A than in controls on samples collected within 18-24 hours after birth, except for reverse T3, which was similar in both groups [average -/+ SD: T4 A= 9.79 -/+ 2.59; N=14.68 -/+ 3.05; P<0.001; median T3 A= 40.83 (37.4-80.4); N= 164 (56.96-222.5); P=0.003; average -/+ SD: free T4 A=1.85 -/+ 0.92; N= 2.8 -/+ 0.74; P=0.004; median: reverse T3 A=1.54 (1.16-1.91); N=1.31(0.87-2); P=0.507; TSH A=9.1 (6.34-12.95); N=14.5(12.9-17.85); P=0.008]. CONCLUSIONS: Our data suggest that lower T4, free T4, and T3 levels are secondary to lower TSH levels in asphyxiated newborns; also, peripheral metabolism of T4 in asphyxiated infants can be altered due to low T3 and normal reverse T3 levels.     

Clinical aspects of induced hypothermia in full term neonates with perinatal asphyxia

Moderate hypothermia is a novel neuroprotective therapy for full term neonates with severe perinatal asphyxia. Although the therapy appears to be safe, admission to a level III neonatal intensive care unit of these patients is justified. Potential complications include hypotension, tube obstruction due to sticky secretions, severe bradycardia, and thrombocytopenia. Furthermore, doses of commonly used drugs such as sedatives, anticonvulsants and antibiotics should be adjusted during hypothermia and on rewarming, and should be monitored carefully. Further studies aiming at optimizing onset, duration, and depth of hypothermia in neonates are necessary. Combination of hypothermia with drugs may further improve neuroprotection in asphyxiated full term neonates.     

Cardiac enzyme levels in myocardial dysfunction in newborns with perinatal asphyxia

Objective  To study the usefulness of cardiac enzymes in evaluating myocardial damage in perinatal asphyxia. Methods  Thirty term babies with perinatal asphyxia and without any congenital malformations were selected as cases. They were compared with thirty healthy term babies without asphyxia. Myocardial dysfunction was evaluated using clinical, electrocardiography, echocardiography and cardiac enzymes i.e, troponin-T and CK-MB levels. Results  Among the 30 cases 23 had evidence of myocardial involvement while one baby in the control group had ECG evidence compatible with cardiac involvement. Cardiac enzymes were significantly increased in babies with perinatal asphyxia. The mean level of C-troponin-T among cases and controls were 0.22±0.28 and 0.003±0.018 while CK-MB levels were 121±77.4 IU/L and 28.8 ± 20.2 IU/L respectively. C-troponin-T had higher sensitivity and specificity compared to CK-MB levels. Moreover, C troponin-T levels correlated well with severity and outcome in babies with perinatal asphyxia. Conclusion  C-Tropopnin assay is useful in evaluating the severity of myocardial damage and outcome in perinatal asphyxia.     

Late rise of thyroid stimulating hormone in ill newborns

OBJECTIVES: To determine the frequency and characteristics of late rise of thyroid stimulating hormone (LRT) among ill newborns. INFANTS AND METHODS: Data were retrospectively analyzed from infants in intensive care settings with abnormal thyroid tests over 13 months. Thyroid tests were performed by filter paper if neonatal intensive care >4 weeks or serum if clinically indicated. LRT was defined as thyroid stimulating hormone (TSH) >10 microIU/ml after normal TSH on initial newborn screen. RESULTS: LRT was identified in 13 infants. Of 736 admissions to the neonatal intensive care unit (NICU), 10 (1.4%) had LRT. Excluding 3/10 with diagnosis at <1 week of age the frequency is 0.95%. Three additional cases occurred in other ICUs. TSH elevation resolved in 6/13 (group A, TSH 10.6-20.6 microIU/ml) and persisted in 7/13 necessitating treatment (group B, TSH 10.5-1326 microIU/ml). 7/13 had birth weights <1500 g. 11/13 had gestational ages <37 weeks. LRT was associated with surgery, sepsis workup, dopamine, and gastrointestinal disorders. CONCLUSIONS: LRT was not infrequent in ill newborns. Most were premature and half were not very low birth weight. We recommend monitoring of thyroid function by serum specimen in ill newborns with prolonged ICU care regardless of birth weight.     

Effect of perinatal factors on cord blood thyroid stimulating hormone levels

OBJECTIVE: To study the influence of perinatal factors on cord blood (CB) TSH levels. INFANTS AND METHODS: In a prospective cross-sectional study, CB TSH levels were measured in 1,590 live-born infants using IRMA. The effect of various perinatal factors on the CB TSH levels was analyzed statistically. RESULTS: The mean TSH level in the study group was 10.6 +/- 6.7 microU/ml (range 0.01-66.4 microU/ml). A significant fall in CB TSH levels was noted with increasing gestational age. A similar decline was noted in TSH levels with increase in birth weight. No significant difference in TSH levels was noted between males and females, or AGA and SGA (n = 296) infants. Infants with birth asphyxia (Apgar score < 4 at 5 min) had significantly higher CB TSH levels (mean 31 microU/ml, n = 18) as compared to those without (mean 10.4 microU/ml) (p < 0.01). The highest TSH levels were noted in neonates delivered by forceps extraction (mean 29.4 microU/ml, n = 17) and lowest levels in infants born by elective Caesarian section (mean 8.7 microU/ml, n = 149). CONCLUSION: CB TSH levels fall with increase in gestational age while birth asphyxia and difficult deliveries tend to elevate them.     

Effect of clofibrate in jaundiced term newborns

Objective: Clofibrate is a glucuronosyl transferase inducer that has been proposed to increase the elimination of bilirubin in neonates with hyperbilirubinemia. The aim of this study was to characterize the therapeutic effect of clofibrate in neonates born at full term and present with non-hemolytic jaundice.Methods: A clinical controlled study was performed in two groups of healthy full term neonates. Thirty neonates were treated with a single oral dose of clofibrate (100 mg/kg) plus phototherapy (clofibrate-treated group) while another 30 neonates (control group) received only phototherapy.Result: The mean plasma total bilirubin levels of 12^th, 24^th and 48^th hours were significantly lower in the clofibrate-treated group as compared with the control group (P<0.0001, P<0.0001 and P=0.004, respectively). Treatment with clofibrate also resulted in a shorter duration of jaundice and a decreased use of phototherapy (P<0.0001). No side effects were observed.Conclusion: Although other pharmacological agents such as metalloporphyrins and Sn-mesoporphyrin also seem to be effective in decreasing bilirubin production, these products are not available for routine use and cannot be used because the safety of these drugs has to be confirmed prior to their widespread use. Therefore, clofibrate is now the only available pharmacological treatment of neonatal jaundice.     

围生期窒息对新生儿糖代谢影响

目的　研究围生期窒息对新生儿血糖及其调节激素的影响。方法　对 4 0例窒息儿生后 72h进行连续血糖监测 ,同时测定血清皮质醇 (CT)、胰岛素 (INS)、胰高血糖素 (GC)和生长激素 (GH)水平。结果　轻度窒息对新生儿糖代谢无影响 ;重度窒息生后 6h血糖最高 ,36h最低 (P <0 .0 1)。 4种激素水平明显增高 (P <0 .0 1) ,多元线性回归分析发现重度窒息 6～ 12h血糖与CT和GC水平呈显著正相关 (P <0 .0 1)。结论　应激反应对新生儿重度窒息后高血糖发生起重要作用 ,监测血糖对重度窒息患儿非常重要 ,治疗时不宜应用糖皮质激素和胰岛素。     

Serum levels of lysozyme in term and preterm newborns.

Serum lysozyme levels were studied in term babies at the time of delivery and again between 7th and 30th postnatal days, and in preterm babies on the 1st, 3rd, and 5th postnatal days. Levels in term babies at delivery (mean 2.28 mug/ml) were similar to those found in adults, but they fell between the 7th and 30th postnatal days. In premature babies lysozyme levels on the first day of live (mean (0.82 mug/ml) were lower than in term babies. They tended to rise during the first 5 days, by which time they had reached levels found in term babies between the 7th and 30th days. The low lysozyme levels in preterm and in term babies after the first few days of life may contribute to the poor ability of the newborn baby to localize infection and to kill bacteria extracellularly.     

Effect of hyperbilirubinemia on intestinal permeability in healthy term newborns

We investigated the effect of serum bilirubin (SB) on intestinal permeability (IP) of healthy, term, birth weight appropriate for gestational age neonates before phototherapy. IP was measured by the dual probe (lactulose/mannitol) sugar absorption test (SAT) performed on the third day of life in 12 healthy jaundiced newborns (total bilirubin 249 +/- 39.75 micromol/L) and compared to that of 12 non-jaundiced newborns (total bilirubin 83.79 + 37.62 micromol/L) matched for sex, gestational age, birth weight and Apgar score. Jaundiced newborns have a significantly higher La/Ma ratio than non-jaundiced (0.31 +/- 0.28 vs. 0.053 +/- 0.043; p < 0.0004). A significant correlation was found between serum bilirubin level and La/Ma ratio (r = 0.56 p < 0.006). CONCLUSION: Our study demonstrates a direct effect of UCB on gut epithelial barrier of at-term newborns in whom UCB appears to be responsible for an alteration of IP that theoretically may lead to a passage of macromolecules through the intestinal epithelium increasing the risk of sensitization.     

Serum pro-hepcidin levels in term and preterm newborns with sepsis

Background:  An iron regulatory peptide hormone, hepcidin, is also part of the innate immune system and is strongly induced during infections and inflammation. The aim of the present study was to determine serum levels of the 60 aa pro-hormone form of hepcidin (pro-hepcidin) in full-term and preterm newborns with sepsis and to determine the possible relationships between pro-hepcidin levels and serum iron and complete blood count parameters.
Methods:  Fifteen preterm newborns with sepsis, 17 healthy preterm, six full-term newborns with sepsis and 16 healthy full-term newborns were included the study. Blood samples were collected from patients with sepsis at the time of clinical diagnosis. Each blood sample was analyzed for complete blood count, serum iron and ferritin concentrations, iron-binding capacity, and pro-hepcidin level.
Results:  The mean serum pro-hepcidin level (mean ± SD) in preterm neonates with sepsis and in healthy preterm newborns was 565.4 ± 519.5 ng/mL and 279.8 ± 227.6 ng/mL, respectively ( P <  0.05). The mean serum pro-hepcidin level in full-term newborns with sepsis and in healthy full-term neonates was 981.4 ± 415.4 ng/mL and 482 ± 371.9 ng/mL, respectively ( P <  0.05). Although the mean serum ferritin levels in the two groups with sepsis were higher when compared with the healthy groups, the difference was not statistically significant in full-term newborns. No statistically significant correlations were found between serum pro-hepcidin levels and any other parameters in each group.
Conclusions:  Serum pro-hepcidin levels were higher in newborns with sepsis (either premature or full-term) than they were in healthy newborns at the time of clinical diagnosis.     

新生儿高胆红素血症与胃动素胃泌素水平的相关性研究(英文)

目的：新生儿高胆红素血症患儿常出现胃肠道症状。该研究目的是探讨高胆红素血症 (高胆 )对新生儿胃肠激素水平的影响及其可能的发生机制。方法：应用放射免疫分析法 (RIA)对 5 0例高胆患儿空腹状态下血中胃动素、胃泌素浓度进行测定 ,并以 30例正常新生儿作为对照。结果：高胆组患儿血浆胃动素浓度 (6 5 9±37ng/L)明显高于对照组 (4 86± 2 8ng/L) ,差异有显著性意义 (P <0 .0 1) ,且与血清胆红素水平呈正相关 ;血清胃泌素浓度 (12 8± 9ng/L)与对照组 (132± 11ng/L)比较差异无显著性 (P >0 .0 5 )。结论：高胆红素血症新生儿的某些胃肠道症状可能与胃动素分泌异常有关。