Impact of chorioamnionitis and preeclampsia on neurodevelopmental outcome in preterm infants below 32 weeks gestational age

Aim: Intrauterine conditions may interfere with foetal brain development. We compared the neurodevelopmental outcome between infants <32 weeks gestational age after maternal preeclampsia or chorioamnionitis and controls. Methods: Case‐control study on infants with maternal preeclampsia, chorioamnionitis and controls (each n = 33) matched for gestational age. Neurodevelopment at 2 years was assessed with the Bayley Scales of Infant Development II. Results: A total of 99 infants were included with a median gestational age of 29 weeks (range 25–32). Median mental developmental index (MDI) was 96 in the control, 90 in the chorioamnionitis and 86 in the preeclampsia group. Preeclampsia infants had a lower MDI compared with the control group (univariate p = 0.021, multivariate p = 0.183) and with the chorioamnionitis group (univariate p = 0.242; multivariate p = 0.027). Median psychomotor index was 80.5 in the control, 80 in the preeclampsia and 85 in the chorioamnionitis group and was not different between these three groups (p > 0.05). Chorioamnionitis or preeclampsia exposure was not associated with major neurodevelopmental impairments (cerebral palsy, MDI<70, PDI<70). Conclusion: The results of this preliminary study suggest that preeclampsia and chorioamnionitis play a relatively minor role among risk factors for adverse neurodevelopment outcome. Postnatal factors such as ventilation and bronchopulmonary dysplasia may have a greater impact on neurodevelopmental outcome.     

Clinical measures to preserve cerebral integrity in preterm infants

Impaired psychomotor development, often anteceded by major intraventricular hemorrhage or periventricular leukomalacia, constitutes the most important long-term morbidity of very preterm infants. We reviewed randomized controlled trials aimed at reducing the incidence of brain damage, as detected by ultrasound, or neurodevelopmental impairment during follow-up of preterm infants. Preliminary reports of reduced rates of intraventricular hemorrhage obtained with administration of fresh frozen plasma, ethamsylate, phenobarbitone, or morphine have not been confirmed in subsequent larger trials. Early administration of indomethacin may reduce intraventricular hemorrhage without affecting long-term outcome. Pancuronium, inositol, and vitamin E decreased intraventricular hemorrhage rates but later psychomotor development was not examined. Thyroxin supplementation failed to improve neurodevelopmental outcome while protein enrichment of formula and individualized developmental care appear to be beneficial. The largest reductions in cerebral palsy and neurodevelopmental impairment were achieved by avoidance of postnatal steroids. This finding emphasizes the need to include these late endpoints in any randomized trial involving preterm infants.     

早产儿脑损伤的相关因素分析

目的 分析早产儿脑损伤的影响因素.方法 对2006年1月至2007年10月我院收治的出生时胎龄小于36周的268例早产儿在生后7 d内行头部B超检查.并分析相关临床资料.结果 130例早产儿存在脑损伤,脑损伤的发生率为48.5%,其中脑室出血116例,发生率为43.3%,脑室周围日质软化38例,占14.2%.轻度和重度脑损伤发生率分别为23.5%、13.6%.脑损伤发生与下列因素有关:胎龄小、低出生体质量、窒息、肺透明膜病、呼吸暂停、呼吸衰竭、肺出血、低血糖、感染、低血压、凝血异常、胎膜早破以及宫内感染.结论 脑室出血以及脑室周围白质软化在早产儿中比较常见,其发生与多种因素有关.临床上应避免或治疗引起脑损伤的因素,头部B超可对早产儿脑损伤做出早期诊断.     

Trends in severe brain injury and neurodevelopmental outcome in premature newborn infants: the role of cystic periventricular leukomalacia

OBJECTIVES: To determine if the incidence of sonographically detected cystic periventricular leukomalacia (PVL) and periventricular hemorrhagic infarction (PVHI) have changed over the past decade and to determine if a decline in cystic PVL was associated with a change in neurodevelopmental outcome. STUDY DESIGN: Premature newborn infants admitted to our intensive care nursery from 1992 to 2002 were identified in a comprehensive nursery database. Premature newborn infants had routine neurosonography by means of a standardized protocol. Infants weighing < or =1500 g at birth surviving to nursery discharge were enrolled in a nursery follow-up clinic. RESULTS: Adjusting for gestational age, there was a significant decrease in cystic PVL from 1992 to 2002 (P=.003) without a concurrent decrease in PVHI (P=0.5). Cystic PVL and PVHI accounted for only 9 of the 28 cases of cerebral palsy and 12 of 90 cases of abnormal Developmental Scores in infants weighing <1500 g at birth. The decline in cystic PVL was not associated with improved developmental outcome from 1992 to 2002. CONCLUSIONS: The incidence of cystic PVL declined significantly from 1992 to 2002 at our center. Cystic PVL was detected by ultrasound in a minority of infants with abnormal neurodevelopmental outcome, indicating that other forms of cerebral injury account for the majority of abnormal neurodevelopmental outcomes in premature newborn infants.     

组织学绒毛膜羊膜炎与小于34周早产儿脑室周围白质软化的相关性分析

目的探讨组织学绒毛膜羊膜炎(histologic chorioamnionitis,HCA)与<34周早产儿脑室周围白质软化(periventricular leukomalacia,PVL)的相关性。方法选取2018年1月至12月于青岛市妇女儿童医院产科出生、孕母行胎盘病理检查并转入NICU接受治疗、胎龄<34周的早产儿作为研究对象,共计287例。根据孕母胎盘病理检查结果分为HCA阳性组(167例)和HCA阴性组(120例),比较2组患儿的PVL发生率。将研究对象中已诊断为PVL的41例早产儿,根据孕母胎盘病理检查结果及HCA分期标准,分为非HCA组、HCA早期组、HCA中晚期组3组,比较各组PVL严重程度、患儿临床资料、并发症及校正胎龄至6月龄时的随访情况。结果HCA阳性组PVL占19.16%(32/167),HCA阴性组PVL占7.50%(9/120),2组PVL发生率比较差异有统计学意义(P<0.05)。已诊断为PVL的<34周早产儿中,非HCA组21.95%(9/41),HCA早期组31.71%(13/41),HCA中晚期组46.34%(19/41),3组间PVL严重程度、1 min Apgar评分、生后24 h白细胞计数、支气管肺发育不良发生率、住院天数、抗生素应用天数、校正胎龄至6月龄时的智力发育指数(mental development index,MDI)和精神运动发育指数(psychomotor development index,PDI)比较差异均有统计学意义(P均<0.05),且HCA炎症程度与PVL严重程度呈正相关(rs=0.374,P=0.016)。结论HCA与<34周早产儿PVL的发生有相关性,随着HCA炎症程度增加,PVL的发生率、严重程度增加。母亲存在HCA的<34周早产儿随炎症严重程度进展,其生后24 h白细胞计数升高,支气管肺发育不良发生率、抗生素使用率增加,住院时间延长,校正胎龄至6月龄时MDI、PDI分数降低。     

Risk factors for cerebral palsy in preterm infants

OBJECTIVE: To identify crucial factors that precipitate cerebral palsy by controlling confounding factors in logistic regression analyses. DESIGN AND PATIENTS: We retrospectively investigated a cohort of all 922 infants with gestational ages of less than 34 weeks (22-33 weeks), who were admitted to our neonatal intensive care unit between 1990 and 1998. Thirty (3.7%) were diagnosed to have cerebral palsy. We analyzed the prenatal and postnatal clinical variables of the cerebral palsy cases and compared them with 150 randomly selected controls. RESULTS: Risk factors for cerebral palsy identified in univariate analysis were: twin pregnancy, long-term ritodrine tocolysis, respiratory distress syndrome, air leak, surfactant administration, intermittent mandatory ventilation, high frequency oscillation, lowest PaCO2 levels, prolonged hypocarbia during the first 72 h of life, and postnatal steroid therapy. In a conditional multiple logistic model, long-term ritodrine tocolysis, prolonged hypocarbia and postnatal steroid therapy remained associated with an increased risk of cerebral palsy after adjustment for other antenatal and postnatal variables (OR [Odds Ratio] = 8.62, 95% CI [Confidence Interval], 2.18-33.97; OR = 7.81, 95% CI, 1.42-42.92; OR = 21.37, 95% CI, 2.01-227.29, respectively). CONCLUSIONS: Our results suggest that long-term ritodrine tocolysis underlines the development of cerebral palsy. Further assessments of the effect of ritodrine on fetal circulation and nervous system are required. Moreover, possible alternatives to systemic postnatal steroids are needed, and carbon dioxide levels should be more strictly controlled.     

Episodes of hypocarbia and early-onset sepsis are risk factors for cystic periventricular leukomalacia in the preterm infant

Background

Septic episodes in preterm infants recently have been reported to be associated with periventricular leukomalacia (PVL). The role of hypocarbia as an independent risk factor for PVL in clinical studies raises many questions without conclusive answers.

Aims

To evaluate risk factors for cystic PVL focussing on the influence of hypocarbia.

Study design

Retrospective single centre case-control study.

Subjects

Preterm infants 24 to 35 weeks of gestational age and matched (1:2 for gender, birth year, gestational age and birth weight) controls.

Outcome measures

Multivariate analysis of perinatal factors being associated with cystic PVL diagnosed by serial ultrasound examinations.

Results

Univariate analysis of risk factors revealed lower 5 and 10 min Apgar scores, and higher rates of neonatal seizures, early-onset sepsis, neonatal steroids, respiratory distress syndrome with surfactant replacement therapy, and episodes of hypocarbia significantly being associated with PVL. Multivariate analysis using a logistic regression model revealed early-onset sepsis and hypocarbia being significantly associated with PVL (p = .022 and .024, respectively). Lowest PaCO₂ values did not differ as did not the duration of hypocarbia, but the onset of hypocarbia was significantly later in PVL cases compared to controls (mean 26 vs. 15 h, p = .033). Neurodevelopmental follow-up at a median time of 46 months was poor showing 88% of the cases having an adverse neurological outcome.

Conclusion

We found early-onset sepsis and episodes of hypocarbia within the first days of life being independently associated with PVL.     

Antenatal steroids may reduce adverse neurological outcome following chorioamnionitis: neurodevelopmental outcome and chorioamnionitis in premature infants

OBJECTIVE: To examine the effect of antenatal steroid exposure and in utero inflammation on the development of severe intraventricular haemorrhage, periventricular leukomalacia and long-term neurological outcome in infants less than 30 completed weeks gestation. METHOD: Infants less than 30 completed weeks gestation from January 1996 to July 2001 were identified from a prospectively managed database. Placental pathology was reviewed for the presence or absence of chorioamnionitis and funisitis. Infants were divided into three groups depending on the degree of exposure to fetal inflammation (no inflammation, chorioamnionitis only and chorioamnionitis and funisitis). Data relating to gestational age, birthweight, sex, antenatal steroid exposure, surfactant treatment, days of positive pressure ventilation and days of oxygen requirement were collected. Cerebral ultrasound studies were examined for evidence of intraventricular or intraparenchymal echodensity and periventricular leukomalacia. Long-term neurological outcome was assessed by neurological examination for cerebral palsy and by Griffiths Mental Developmental Assessment for general developmental quotient. RESULTS: Two hundred and twenty infants were identified. The mean gestational age was 27.7 weeks and the mean birthweight 1092 g. Seventy-two per cent of mothers had received a complete course of antenatal steroids. The risk of Grade III intraventricular haemorrhage or intraparenchymal echodensity was associated with exposure to in utero inflammation if a complete course of antenatal steroids had not been received (P = 0.002). This association did not exist if a complete course of antenatal steroids was given (P = 0.62). Fourteen infants had cerebral palsy (7%). The presence of cerebral palsy was also associated with in utero inflammation in the absence of complete antenatal steroid cover (P = 0.03) and not in the presence of complete cover (P = 0.59). The mean general developmental quotient on Griffiths Mental Developmental Assessment at 12 months or 3 years was not affected by exposure to in utero inflammation regardless of antenatal steroid exposure. CONCLUSION: Risk of intraventricular haemorrhage or intraparenchymal echodensity and cerebral palsy was associated with in utero inflammation in the absence of a complete course of antenatal steroids. A complete course of antenatal steroids appeared to extinguish any association between in utero inflammation and adverse neurological outcome.     

绒毛膜羊膜炎对早产儿脑损伤的影响

目的：探讨绒毛膜羊膜炎与早产儿脑损伤的相关性。方法：选取2008年6月至2011年6月出生的早产儿（28~34周）共88例。根据是否存在绒毛膜羊膜炎,分为病例组(41例)和对照组（47例）。所有的病例生后定期行头颅B超检查,生后3~7 d行颅脑弥散加权成像（DWI）检查,且于纠正胎龄 40 周时行颅脑MRI 检查,比较两组脑室周围白质软化（PVL）和脑室周围-脑室内出血（PVH-IVH）的发生情况。结果：病例组PVL的发生率为32%,对照组PVL的发生率为6%,两组比较差异有统计学意义（P<0.05）。而两组PVH-IVH的发生率分别为27%和23%,差异无统计学意义（P＞0.05）。结论：绒毛膜羊膜炎与早产儿脑损伤有一定的关系,可使早产儿PVL的发生率增加,而对PVH-IVH的影响不大。     

NICU出院早产儿1岁时神经发育预后及干预依从性对其的影响

目的：了解NICU抢救存活早产儿在1岁时的神经发育状况及其影响因素,重点讨论干预依从性对其预后的影响。方法：患儿出院后予以早期干预指导和随访,1岁时进行智能发育测试（CDCC）评估,了解神经发育概况。按照智力发育指数（MDI）和精神运动发育指数（PDI）将患儿分为神经行为发育异常组（MDI或PDI任何一项＜70）、临界组（MDI或PDI任何一项为70~85之间）和正常组（MDI或PDI均＞85）。列举可能对神经行为发育产生影响的社会家庭因素和临床相关因素,利用单因素方差分析和卡方检验的方法进行筛选,对于可能的高危因素进行logistic回归分析,了解各因素相对危险度。根据家长对患儿进行干预的具体情况将其分为依从性良好（每周进行家庭干预≥4 d,每天干预时间合计超过30 min,并在1年内能够随访≥5次）和依从性差二组,进一步分析干预依从性对其神经发育预后的影响。结果：210例患儿CDCC评分正常、临界和异常者分别为123例（58.6％）、61例（29.0％）和26例（12.4％）,共有精神发育落后儿18例（8.6％）和脑瘫儿9例（4.3％）。干预依从性良好者（111例）的MDI及PDI得分,分别为97.15±17.38,94.23±18.55均明显高于干预依从性差者的89.87±18.92,87.20±19.12;干预依从性好组脑瘫的发生率（3/111,2.7％）也低于干预依从性差者（5/99,6.1％）。另外,父母亲文化水平、多胎、颅内出血、呼吸暂停等也是影响早产儿神经发育预后的危险因素。结论：早产儿是神经发育伤残的髙危人群,尤其是NICU抢救成活的危重新生儿。早期干预可以改善高危早产儿的神经发育预后。［中国当代儿科杂志,2007,9（3）：193-197］     

Gender differences in neurodevelopmental outcomes among extremely preterm, extremely-low-birthweight infants

AIM: To determine whether gender-specific responses to perinatal and neonatal events and exposures explain the male disadvantage in early childhood outcomes. METHODS: Infants were in the National Institute of Child Health and Human Development (NICHD) Neonatal Research Network, born 1/1/1997-12/31/2000, <28 wk, with neurodevelopmental follow-up at 18-22 mo corrected age. We evaluated and compared univariate and multivariate associations of risk factors with neurodevelopmental outcomes for girls and boys. Neurodevelopmental impairment (NDI) was one or more of the following: moderate--severe cerebral palsy (CP), Bayley Mental (MDI) or Psychomotor (PDI) Development Indices <70, deafness or blindness. RESULTS: Boys (n=1216) were more likely than girls (n=1337) to have adverse outcomes (moderate--severe CP: 10.7% vs 7.3%; MDI < 70: 41.9% vs 27.1%; NDI: 48.1% vs 34.1%). Major risk factors were also more common in boys. Independent multivariate associations of risk factors with outcome differed by gender, but not consistently in favor of girls. In multivariate models including both girls and boys, male gender remained an independent risk factor for MDI < 70 (2.0, 95% CI 1.6-2.5) and NDI (1.8, 95% CI 1.5-2.2). CONCLUSION: Perinatal, neonatal and early childhood factors confer similar incremental risk or protection to boys and girls, but boys appear to have inherently greater baseline risk. Unmeasured biological variables likely contribute to the preterm male neurodevelopmental outcome disadvantage.     

早产儿暂时性低甲状腺素血症与脑损伤及神经行为学相关性研究

目的 通过对早产儿甲状腺素水平测定及脑、神经行为发育测评,分析甲状腺素水平与脑损伤、神经行为学的相关性.方法 选取2009年11月至2010年4月,上海交通大学附属上海市儿童医院新生儿科收治的早产儿52例,生后6 h内留取血清样本,放射免疫法测定T3、T4、TSH值.所有患儿出生后3 d行头颅B超检查,每周复查1次,出院前行头颅MRI检查.根据头颅MRI结果将患儿分为3组:无脑损伤组(33例)、脑室内出血组(10例)、脑白质损伤组(9例).所有患儿于纠正胎龄40±2周时行新生儿20项行为神经测定.结果 3组患儿TSH均正常,排除先天性甲状腺功能减低症;共8例早产儿甲状腺功能正常,占15.4%(8/52);另44例早产儿甲状腺功能均低下,占84.6%(44/52).无脑损伤组T3、T4水平高于脑室内出血组及脑白质损伤组,并以脑白质损伤组T3、T4水平最为低下,3组间比较差异有统计学意义(P＜0.05).无脑损伤组患儿行为能力、被动肌张力、主动肌张力及总分4项得分显著高于有脑损伤的两组患儿,且脑室内出血组患儿得分又高于脑白质损伤组患儿,3组间比较差异有统计学意义(P＜0.05).结论 早产儿脑损伤越严重,甲状腺素水平越低.有脑损伤的早产儿神经行为学评分较无脑损伤的早产儿低.     

Adverse neurodevelopmental outcome in preterm infants: risk factor profiles for different gestational ages

Aim: Assessment of risk predictors for adverse neurodevelopmental outcome at 1 year of age in preterm infants with a gestational age <30 weeks (Group I) and 30–32 weeks (Group II).
Methods: Between January 2003 and December 2006, we prospectively enrolled 310 live-born infants between 23 and 32 weeks of gestation. The association between candidate risk factors and delayed motor or mental development (Bayley Scales of infant development II; psychomotor or mental developmental index <85) was analysed by means of logistic regression analysis.
Results: Two hundred and fifty infants were eligible for follow-up, and 205 (82.0%) completed the follow-up visit. Intracerebral haemorrhage, small for gestational age and late-onset sepsis were associated with an increased risk for delayed development in Group I (p < 0.05, each). Premature rupture of membranes was a risk condition relevant to Group II. Antenatal steroids were associated with a decreased risk of neurodevelopmental delay in both groups.
Conclusion: This study identified distinct risk factors for adverse outcome in preterm infants of lower (<30 weeks) and higher (30–32 weeks) gestational age. In the lower gestational age group, neonatal risk predictors are most important. Antenatal steroids appear to decrease the risk for adverse outcome in both age groups.     

Compared outcomes of very preterm infants born in 2000 and 2005

AIM: To compare neonatal and 2-year outcomes in very premature infants born 5 years apart. METHODS: Prospective observational study of infants born before 33 weeks' gestation in 2000 or 2005 admitted to a neonatal intensive care unit in France. We collected perinatal data and evaluated motor, cognitive, neurosensory and behavioural outcomes at 2 years of age. Results: We included 170 infants in 2000 and 173 in 2005. The significant differences in neonatal outcomes were decreases in postnatal corticosteroid use and in percentage of infants with head circumference below the 3rd percentile on days 7 (25% vs. 13%) and 30 (30% vs. 17%). At 2 years of age, rates of follow-up were 87% in 2000 and 94% in 2005. The cerebral palsy rate was 6% in both cohorts. The overall rate of motor disabilities diminished from 30% (41/137) to 18% (26/142), and the rate of mild motor disabilities decreased from 24% to 12%. Rates of cognitive, behavioural and neurosensorial impairments were similar. Conclusion: Between 2000 and 2005, motor impairments at 2 years of age diminished in very preterm children (but not cerebral palsy rates). We observed a reduced use of postnatal corticosteroids and a decreased percentage of neonates with head circumference below the third percentile.     

Effect of chorioamnionitis on neurodevelopmental outcome in preterm infants

OBJECTIVE: To assess the association of neurodevelopmental outcome with the placental diagnosis of chorioamnionitis in very low-birth-weight infants. METHODS: One hundred seventy-seven surviving very low-birth-weight infants, 22 to 29 weeks' gestational age, born after varying severity of chorioamnionitis, were evaluated at a mean +/- SD age of 19 +/- 6 months' corrected age with Bayley Scales of Infant Development II and neurologic examination. Select maternal and infant variables were abstracted from the medical records. Neonatal morbidities, Mental Developmental Index (MDI) score, Psychomotor Developmental Index (PDI) score, probability of normal MDI and PDI scores (>84), and cerebral palsy between the chorioamnionitis and the control groups were assessed, controlling for gestational age, sex, and the maternal use of steroids and antibiotics. RESULTS: The chorioamnionitis group of 102 infants was compared with 75 control infants (mean +/- SD birth weight, 947 +/- 236 g and 966 +/- 219 g, respectively; mean +/- SD gestational age, 26.1 +/- 2.8 weeks and 27.1 +/- 1.5 weeks, respectively). Infants with chorioamnionitis, compared with controls, had a significantly higher incidence of intraventricular hemorrhage (30% vs 13%) and retinopathy of prematurity (68% vs 42%). Cerebral palsy was diagnosed in 8.6% of the infants with chorioamnionitis and 6.6% of the controls. The MDI and PDI scores were similar between the chorioamnionitis and control groups (mean +/- SD MDI score, 96 +/- 16 vs 97 +/- 18 and mean +/- SD PDI score, 94 +/- 19 vs 92 +/- 19, respectively). CONCLUSIONS: In very low-birth-weight infants we found a higher incidence of intraventricular hemorrhage and retinopathy of prematurity but similar MDI and PDI scores and risk of cerebral palsy associated with chorioamnionitis.     

住院早产儿脑室内出血10年回顾性调查及影响因素分析

目的　调查住院早产儿脑室内出血 (IVH)发生率及其影响因素。方法　对 1993～ 2 0 0 2年 10年间入住新生儿病房、曾经头颅B超检查的所有住院早产儿进行分析 ,应用SIGMAB超诊断仪对早产儿进行床边头颅B超检查。结果　 392例早产儿的平均胎龄为 (34 0± 2 1)周 ,平均出生体重为 (2 13± 0 5 3)kg。平均头颅B超初次检查时间为生后 (5 3± 6 3)d ,其中本院出生患儿为 (4 0± 2 0 )d ,外院出生患儿为 (7 0± 8 0 )d ,两者有非常显著性意义。总的IVH发生率为 5 6 6 % (2 2 2 / 392 ) ,重度IVH发生率为 16 3% (6 4 / 392 )。早产儿的胎龄愈小 ,出生体重愈低 ,其IVH发生率愈高 ,出血程度也趋严重。围产期窒息、家中自娩、机械通气、产妇为外来民工等因素与早产儿IVH及其出血程度密切相关。结论　鉴于早产儿IVH的高发生率及约一半IVH早产儿无明显临床症状 ,建议对所有早产儿在生后早期应常规进行床边头颅B超检查     

Hyperbilirubinemia, hypocarbia and periventricular leukomalacia in preterm infants: relationship to cerebral palsy

This study comprised 103 preterm infants with a gestational age less than 33 weeks who were born in Tampere University Hospital and who were followed up to two years of age. Sixty-four perinatal variables were compared to ultrasound findings in the neonatal period and neurologic handicap at the age of two years. Duration of hypocarbia (PCO2 < or = 30 mmHg) during the first 72 h and hyperbilirubinemia (the mean level of serum total bilirubin) at three days of age were independently and significantly related to periventricular leukomalacia, but not directly to cerebral palsy. The only perinatal variables related independently and significantly to cerebral palsy at two years of age were periventricular leukomalacia and ventriculomegaly. According to these results, periventricular leukomalacia was the main predictor of cerebral palsy in preterm infants. In addition to hypocarbia, hyperbilirubinemia may also be involved in the pathogenesis of extensive (severe cystic) periventricular leukomalacia.