早产儿暂时性甲状腺功能低下替代治疗临床研究进展

早产儿暂时性甲状腺功能低下(THOP)发生率高,是否给予甲状腺素替代治疗存在分歧.有关THOP的临床研究提示,THOP甲状腺素替代治疗不能降低病死率、呼吸疾病发生率,可降低动脉导管未闭的发生率.胎龄小于28周THOP早产儿给予甲状腺素替代治疗可能改善神经发育预后,胎龄大于28周不能改善神经发育.未来研究应按胎龄确定早产儿甲状腺素正常值;设计良好的根据胎龄分层的临床随机研究,以明确甲状腺素替代治疗对远期神经发育的影响.     

早产儿暂时性低甲状腺素血症

随着新生儿重症监护救治技术的进展,极低出生体质量早产儿存活率明显提高。由于这些早产儿各器官系统结构和生理功能未成熟,新生儿期发病率高,而疾病可进一步影响早产儿的神经发育。甲状腺素在脑发育中具有重要作用,而在早产儿脑发育关键期如发生甲状腺功能紊乱则可对其脑发育产生深远影响。暂时性低甲状腺素血症(THOP)是早产儿最常见的甲状腺功能障碍,与极低出生体质量早产儿不良神经发育结局有关,补充甲状腺素可改善极低出生体质量早产儿发生THOP后的神经发育预后。但目前对早产儿正常神经发育所需的适宜的血清甲状腺素水平尚未明确,因而需要更进一步的随机对照研究为临床提供可靠的证据。     

早产儿暂时性低甲状腺素血症

早产儿暂时性低甲状腺素血症(transient hypothyroxinemia of prematurity,THOP)于20世纪70年代最早提出,最初指孕28～35周早产儿的低甲状腺素血症,当时认为THOP不需要治疗[1].     

早产儿暂时性甲状腺功能减退研究进展

早产儿暂时性甲状腺功能减退表现为出生后的暂时性低甲状腺素血症,其程度与胎龄和出生体重有关.低甲状腺素血症可影响多种器官功能,其中以神经系统发育受影响为主,其治疗目前尚无统一结论.近年研究发现,甲状腺素补充治疗对于胎龄小于27周的早产儿有效,可改善远期神经系统预后.该文对早产儿暂时性甲状腺功能减退的病因、分型、临床表现、治疗方面的研究进展进行综述.     

甲状腺功能异常早产儿干预治疗的随访研究

目的 探讨甲状腺功能异常早产儿给予左旋甲状腺素钠片治疗后对生长发育及甲状腺功能的影响。 方法 选取2013年1月1日至2017年12月31日在云南省第一人民医院产科出生后于该院新生儿科住院,并在该院新生儿随访门诊定期随访生长发育及甲状腺功能情况的早产儿82例为研究对象行回顾性分析。根据甲状腺功能检测结果分为甲状腺功能异常组（观察组,n=31）和甲状腺功能正常组（对照组,n=51）。观察组给予口服左旋甲状腺素钠片,对照组未予干预,比较不同胎龄（28周≤胎龄<32周、32周≤胎龄<34周、34周≤胎龄<37周）两组早产儿定期随访至矫正年龄12月龄时的体格、智力发育情况及甲状腺功能的转归。 结果 不同胎龄两组早产儿随访至矫正年龄12月龄时,体格发育指标（身长、体重、头围）比较差异无统计学意义（P>0.05）。28周≤胎龄<32周和32周≤胎龄<34周早产儿Gesell发育量表各能区评分随访至矫正年龄12月龄时,在观察组和对照组间比较差异无统计学意义（P>0.05）。34周≤胎龄<37周早产儿,观察组的大运动能评分在3月龄和12月龄时低于对照组,精细动作能、语言能、适应性能评分在12月龄时均低于对照组（P<0.05）;个人-社会性能评分在3月龄时低于对照组（P<0.05）,但在12月龄时与对照组比较差异无统计学意义（P>0.05）。甲状腺功能异常早产儿给予左旋甲状腺素钠片治疗,2~4周甲状腺功能均恢复正常,甲状腺功能恢复正常并完全停药的患儿有21例（68%）,其新生儿疾病筛查结果均正常（100%）;未能停药患儿10例（32%）,仅2例筛查结果正常,与甲状腺功能恢复正常并完全停药患儿的新生儿疾病筛查结果比较差异有统计学意义（P<0.05）。 结论 甲状腺功能异常早产儿及早诊断并进行合理规范的治疗,可以在一定程度上减少对生长发育的影响。早产儿甲状腺功能异常多为暂时性,新生儿筛查结果呈阳性的早产儿发展为永久性甲状腺功能异常的可能性大。     

不同时机应用枸橼酸咖啡因对早产儿结局及神经发育影响的比较研究

目的探讨不同时机应用枸橼酸咖啡因对早产儿结局及神经发育的影响。方法选取2018年1月至6月于我院新生儿重症监护室住院治疗的胎龄小于32周、体重小于1500 g的早产儿共113例为研究对象,按开始使用枸橼酸咖啡因的日龄分为早期治疗组(日龄≤1 d,53例)和晚期治疗组(1 d<日龄≤10 d,60例),回顾性收集并比较两组患儿围生期的基本情况、治疗过程、临床结局,并针对神经发育情况随访至12月龄。结果早期治疗组患儿支气管肺发育不良、动脉导管未闭及脑室内出血/脑室周围白质软化的发生率低于晚期治疗组,差异均有统计学意义(均P<0.05)。早期治疗组纠正胎龄40周时新生儿神经行为测定评分高于晚期治疗组,差异有统计学意义(P<0.05)。早期治疗组纠正胎龄3月龄时智力发育指数高于晚期治疗组,纠正胎龄至12月龄时智力发育指数及运动发育指数均高于晚期治疗组,差异均有统计学意义(均P<0.05)。结论早期应用枸橼酸咖啡因可改善早产儿结局,改善神经系统预后。     

脂肪干细胞生物活性分泌物防治早产儿脑白质损伤的安全性及早期疗效北大核心CSCD

目的探索脂肪干细胞生物活性分泌物（ASCBS）鞘内注射防治早产儿脑白质损伤（WMI）的安全性和疗效。方法按统一标准在多个医疗中心分3个胎龄组募集63例WMI早产儿,A组：胎龄24～28^＋6周,21例;B组：胎龄29～32^＋6周,20例;C组：胎龄33～36^＋6周,22例。各胎龄组以抛硬币的方法随机分为治疗组及对照组,治疗组连续3 d每天1次腰椎穿刺并鞘内注射ASCBS。于矫正胎龄足月进行新生儿行为神经测定（NBNA）,于矫正月龄6个月通过贝利婴幼儿发展量表（BSID）、Peabody运动发育量表第2版（PDMS-2）进行神经发育评估,比较2组间早产儿存活率、NBNA评分、智力发育指数（MDI）、精神运动发育指数（PDI）及PDMS-2发育商。结果63例中包括治疗组31例,对照组32例,所有病例中只有治疗组1例失访。治疗组未发现治疗相关不良反应,所有胎龄组中治疗组及对照组存活率及早产并发症发生率比较差异均无统计学意义（均P〉0.05）。治疗A组的纠正6月龄的粗大运动发育商及总运动发育商高于对照A组,差异均有统计学意义（粗大运动发育商：治疗A组98.330±6.282、对照A组90.330±3.777,P＝0.040;总运动发育商：治疗A组97.330±4.803、对照A组91.000±4.472,P＝0.023）,其余结果未发现组间差异。结论ASCBS治疗早产儿WMI具有较好安全性,并能促进24～28周出生胎龄早产儿的运动发育。     

单胎濒死儿发生的围生期危险因素分析（英文翻译）

目的 研究早产儿校正18~24月龄时的体格生长和神经发育水平。 方法 利用早产儿出院后随访系统,前瞻性收集2018年4月—2021年12月在暨南大学附属深圳市宝安区妇幼保健院定期随访的484例早产儿校正18~24月龄的体格生长数据和神经发育评估数据。219例足月儿作为对照。采用儿童神经心理行为检查量表2016版评估神经发育水平。根据胎龄分组（超早产儿组、极早产儿组、中期早产儿组、晚期早产儿组和足月儿组）,比较各组体格生长和神经发育水平。 结果 除中期早产儿组年龄别身长Z值高于足月儿组（P=0.038）,其余各早产儿组的体格生长指标与足月儿组比较差异均无统计学意义（均P>0.05）。各早产儿组总发育商（developmental quotient,DQ）均低于足月儿组（均P<0.05）;除社会行为能区外,超、极早产儿组其他各能区DQ均低于足月儿组（均P<0.05）;胎龄<32周早产儿全面发育迟缓发生率（16.7%）显著高于足月儿组（6.4%）（P=0.012）,全面发育迟缓发生率有随着胎龄减小而升高的趋势（P=0.026）。 结论 早产儿校正18~24月龄时体格生长可完成追赶,但神经发育水平落后于足月儿,应特别重视胎龄<32周早产儿的神经发育监测及早期干预。     

早产儿甲状腺功能障碍的研究进展

下丘脑-垂体-甲状腺轴在胎龄30~35周逐渐发育成熟。随着早产儿救治水平的提高,存活早产儿的胎龄逐渐降低,低龄早产儿甲状腺轴发育不成熟,同时早产儿更容易发生各系统并发症,如缺血缺氧、严重感染等,加重对甲状腺的影响。临床上发现越来越多的早产儿合并先天性甲状腺功能减低症、暂时性低甲状腺素血症、高促甲状腺激素血症、延迟促甲状...     

晚期早产儿和早期足月儿1岁时神经心理发育水平的随访研究

目的 探讨晚期早产儿和早期足月儿1岁时的神经心理发育水平。方法 选择矫正年龄为1岁的1 257名儿童为研究对象。根据其出生时胎龄分为4组：早期早产儿（胎龄28~33⁺⁶周）、晚期早产儿（胎龄34~36⁺⁶周）、早期足月儿（胎龄37~38⁺⁶周）及完全足月儿（胎龄39~41⁺⁶周）。采用Gesell发展量表评估其神经心理发育水平,比较各组儿童在1岁时神经心理发育状况。结果 4组儿童1岁时5大能区（适应性、大运动、精细动作、语言、个人社交）发育商的差异均有统计学意义（P < 0.05）,且均表现为完全足月儿 > 早期足月儿 > 晚期早产儿 > 早期早产儿的趋势（P < 0.05）;各能区发育迟缓率也均表现为完全足月儿最低,早期早产儿最高（P < 0.05）。与完全足月儿相比,早期足月儿适应能力发育落后的风险增加（OR=1.796,P < 0.05）;晚期早产儿适应能力和精细动作发育落后的风险较高,OR值分别为2.651、2.679（P < 0.05）;早期早产儿适应能力、精细动作和个人社交能力发育落后的风险较高,OR值分别为4.069、3.710、3.515（P < 0.05）。结论 儿童1岁时神经心理发育落后的风险随出生胎龄的增加而降低,呈现剂量反应效应。早期足月儿和晚期早产儿仍然存在不同程度的发育落后,应重视早期足月儿和晚期早产儿的保健随访。     

TSH, FT4 and T3T evaluation in normal and preterm hospitalized newborns]

Thyroid hormones are essential for foetus and newborn development. Preterm newborns present low levels for thyroid hormones. These low levels are related with disorder in psychomotor and neurological development. In the literature, several studies concerning newborns treated with thyroid hormone have been realized in different conditions; however, there is no consensus about preterm newborn supplementation benefit. OBJECTIVE: The aim of the study was to defined hormonal values used for normal and preterm newborns. MATERIAL AND METHODS: We reported TSH, T3T and T4L levels for 195 normal or preterm newborns, eutrophic or small for gestational age (SGA). RESULTS: A positive correlation was found between hormonal level and gestational age. This work allowed us to define a threshold for preterm newborn according to their gestational age. CONCLUSION: Owing to lack of consensus, those values are useful for clinical and biological follow-up of thyroid function for newborns at risk (SGA and preterm before 32 weeks) during the first year of life. Finally, it would be interesting to study systematic supplementation of thyroid hormone for those infants in a prospective study.     

The nonimpact of gestational age on neurodevelopmental outcome for ventilated survivors born at 23-28 weeks of gestation

Aim: It has long been known that survival of preterm infants strongly depends upon birth weight and gestational age. This study addresses a different question – whether the gestational maturity improves neurodevelopmental outcomes for ventilated infants born at 23–28 weeks who survive to neonatal intensive care unit (NICU) discharge. Methods: We performed a prospective cohort study of 199 ventilated infants born between 23 and 28 weeks of gestation. Neurodevelopmental impairment was determined using the Bayley Scales of Infant Development‐II at 24 months. Results: As expected, when considered as a ratio of all births, both survival and survival without neurodevelopmental impairment were strongly dependent on gestational age. However, the percentage of surviving infants who displayed neurodevelopmental impairment did not vary with gestational age for any level of neurodevelopmental impairment (MDI or PDI <50, <60, <70). Moreover, as a higher percentage of ventilated infants survived to NICU discharge at higher gestational ages, but the percentage of neurodevelopmental impairment in NICU survivors was unaffected by gestational age, the percentage of all ventilated births who survived with neurodevelopmental impairment rose – not fell – with increasing gestation age. Conclusion: For physicians, parents and policy‐makers whose primary concern is the presence of neurodevelopmental impairment in infants who survive the NICU, reliance on gestational age appears to be misplaced.     

Hemorrhagic shock and encephalopathy syndrome – the markers for an early HSES diagnosis

Background

Infants born at extreme prematurity are at high risk of developmental disability. A major risk factor for disability is having a low level of thyroid hormone described as hypothyroxinaemia, which is recognised to be a frequent phenomenon in these infants. Derangements of critical thyroid function during the sensitive window in prematurity when early development occurs, may have a range of long term effects for brain development. Further research in preterm infants using neuroimaging techniques will increase our understanding of the specificity of the effects of hypothyroxinaemia on the developing foetal brain. This is an explanatory double blinded randomised controlled trial which is aimed to assess the effect of thyroid hormone supplementation on brain size, key brain structures, extent of myelination, white matter integrity and vessel morphology, somatic growth and the hypothalamic-pituitary-adrenal axis.

Methods

The study is a multi-centred double blinded randomised controlled trial of thyroid hormone supplementation in babies born below 28 weeks' gestation. All infants will receive either levothyroxine or placebo until 32 weeks corrected gestational age. The primary outcomes will be width of the sub-arachnoid space measured using cranial ultrasound and head circumference at 36 weeks corrected gestational age. The secondary outcomes will be thyroid hormone concentrations, the hypothalamic pituitary axis status and auxological data between birth and expected date of delivery; thyroid gland volume, brain size, volumes of key brain structures, extent of myelination and brain vessel morphology at expected date of delivery and markers of morbidity which include duration of mechanical ventilation and/or oxygen requirement and chronic lung disease. Trial registration Current Controlled Trials ISRCTN89493983     

Thyroid function and dysfunction in premature infants

During the past four decades major advances in the management of premature infants have led to progressive reduction in mortality. During this period mortality in very low birth weight infants (VLBW, <1500 grams and <30 weeks gestation age) has decreased, and more than 50% of infants less than 24 weeks gestation age now survive, increasing the population of VLBW infants in intensive care nursery environments. Thyroid function in these infants is characterized by decreased TSH and T4 responses to parturition, low serum total T4 and TSH levels and variable free T4 concentrations during the first 2-4 postnatal weeks of life. These features reflect a state of transient hypothalamic-pituitary or central hypothyroidism. There is a high prevalence of morbidity in these infants, as well, often associated with further reductions in serum total T4, T3, TBG and TSH concentrations and variable levels of free T4 and reverse T3, resembling the non-thyroidal illness (NTI) syndrome in adults. The etiologic roles of thyroid system immaturity and NTI in the transient hypothyroxinemia of prematurity (THOP) and the impact of THOP on the subsequent neurological deficits in VLBW infants remains unclear. Several thyroxine supplementation trials have been conducted with inconclusive results. Further studies are planned or in progress.     

惠州地区不同胎龄早产儿甲状腺功能检测及影响因素分析

目的 探讨不同胎龄早产儿甲状腺功能特点及其影响因素。方法 选择本院新生儿科2012年1~12月收治的早产儿为研究对象。按胎龄分为28~31周组、32~34周组及35~36周组,选取同期本院产科出生的健康足月新生儿30名为对照组。分别在生后第1天和第14天检测新生儿静脉血血清游离三碘甲状腺原氨酸（FT3）、游离甲状腺激素（FT4）以及促甲状腺激素（TSH）,并分析其影响因素。结果 各组新生儿生后14天血清FT3、FT4、TSH水平均显著低于生后第1天（P〈0.05）。35~36周组和对照组生后第1、14天血清FT3、FT4水平均高于28~31周组和32~34周组,32~34周组高于28~31周组（P〈0.05）。TSH水平生后第1天35~36周组和对照组高于28~31周组和32~34周组,生后第14天28~31周组和32~34周组高于35~36周组和对照组（P〈0.05）。早产儿生后第1天影响甲状腺功能的因素为胎龄、出生体重及窒息、缺氧缺血性脑病、呼吸窘迫征综合征、休克等严重疾病;生后第14天影响因素为胎龄和出生体重。结论 早产儿下丘脑-垂体-甲状腺轴发育不成熟,生后14天检测甲状腺功能具有重要临床意义。     

Neurodevelopmental outcome of infants with birth asphyxia treated with magnesium sulfate

BACKGROUND: A neuroprotective effect of MgSO(4) has been shown in some animal models of perinatal hypoxic-ischemic brain damage. The aim of the present paper was to determine whether postnatal MgSO(4) infusion (250 mg/kg per day i.v. for 3 days, in combination with dopamine) is safe in infants with severe birth asphyxia, and also observe effects on neurodevelopmental outcome at 18 months. METHODS: Inclusion criteria were clinical history consistent with perinatal asphyxia; gestational age at least 37 weeks; 5 min Apgar score < or =6; failure to initiate spontaneous respiration within 10 min after birth; and symptoms of encephalopathy. On each day MgSO(4) was infused over 1 h in combination with dopamine (5 microg/kg per min). Changes in vital signs, clinical course of encephalopathy, laboratory variables, and adverse events were monitored. Infants were followed for 18 months. RESULTS: Thirty infants were studied. Mean birthweight was 2878 g; mean gestational age, 39.6 weeks, and median 5 min Apgar score, 3. All required endotracheal intubation for resuscitation. Median age at MgSO(4) initiation was 5 h. All infants had moderate or severe hypoxic-ischemic encephalopathy. Mean serum Mg(2+) concentration remained at least 1.3 mmol/L. MgSO(4) caused no change in physiological variables including mean arterial pressure. Two infants died as neonates, while six of 28 survivors had severe neurodevelopmental disability at 18 months; the remaining 22 had no neurodevelopmental disability. CONCLUSION: Postnatal infusion of MgSO(4) with dopamine caused no change in physiological variables. Deaths and severe sequelae were less frequent than in reported cases with the same grade of hypoxic-ischemic encephalopathy severity, and this treatment may improve neurodevelopmental outcome in infants with severe birth asphyxia.     

Diagnosis of thyroid function in premature infants in intensive care

In 87 premature infants of an neonatal intensive care unit (gestational age 28-37 weeks) serum-T4, -fT4 and TSH were investigated on day 10, 20 and 30 and at term respectively, in addition to the usual TSH-screening (capillary specimen) on day 5. In 47 neonates (54%) T4 and fT4 were found to be low, including all infants under 30 weeks of gestational age and all ventilated infants. Screening TSH was not elevated but in some cases with iodine contamination. 12 of 13 infants in whom TRH-stimulation was performed showed significant response of TSH. We conclude that compromised thyroid function, common in prematures and infants under intensive care, is similar to the euthyroid sick syndrome in adults and does not require therapy. Replacement of thyroid hormone is only indicated in neonates with increased TSH.     

Developmental changes in catecholamine requirement, volume load and corticosteroid supplementation in premature infants born at 22 to 28 weeks of gestation

Background

Due to circulatory instability, premature infants require volume loads, catecholamines and steroid supplementation to improve mortality and neurodevelopmental outcome. However, a complete quantitative analysis concerning the relationship between supplementation and gestational age, especially in infants born at 22 to 24 weeks of gestation, is lacking.

Aim

To investigate whether less mature infants need higher doses of catecholamine, volume loads and steroid, and whether those who require higher doses have poorer outcome. Study design: A retrospective, observational study was performed at a tertiary center in a university setting. Among the consecutive 221 premature infants born at 22 to 28 weeks of gestation, we selected 108 infants who had no apparent pathological conditions other than prematurity. Catecholamines, volume loads and steroid, given to attain sufficient blood pressure and urinary output, were quantitatively analyzed during the first 24 hours. Outcome measures: Quantity of catecholamines, volume expanders and steroid supplementation as a function of gestational age and childhood outcome at 2 years.

Results

Catecholamines and volume loads were increased in a step-wise manner with decreasing gestational age. Intact survival rate was significantly lower in infants born before 25 weeks of gestation compared with the more mature infants. Among infants born at 22 to 24 weeks' gestation, catecholamine and volume load increased significantly in poor outcome infants compared with good outcome infants.

Conclusions

From a developmental viewpoint, progressively larger doses of catecholamine, volume expanders and corticosteroid are required to stabilize circulatory adaptation to neonatal life in infants between 22 to 28 weeks of gestation.