中国七大城市早产儿脑损伤发生率的多中心调查报告(英文)

目的中华医学会儿科学分会新生儿学组组织国内7个城市的10家三级甲等医院进行了早产儿脑损伤多中心协作研究。该文报告其中早产儿脑损伤发生率的调查结果。方法 2005年1月至2006年8月期间,各参加单位对所有胎龄<37周的早产儿在生后3 d内常规进行初次床边头颅B超检查,以后每隔3～7 d复查1次,直至出院。结果 9单位总脑室内出血(IVH)发生率和重度IVH发生率分别为10.8%(406/3 768)和2.4%(92/3 768),其中I级IVH 22.6%(92/406),Ⅱ级54.7%(222/406),Ⅲ级17.2%(70/406),Ⅳ级5.4%(22/406);10医院中总脑室周围白质软化(PVL)发生率和囊性PVL发生率分别为2.3%(112/4 933)和0.3%(16/4 933),其中Ⅰ级PVL 85.7%(96/112),Ⅱ级12.5%(14/112),Ⅲ级1.8%(2/112)。发生重度IVH的可能高危因素为阴道分娩(OR=1.874,95%CI=1.172～2.997,P<0.01)、围产期窒息(OR=1.598,95%CI=1.077～2.372,P<0.05)、机械呼吸(OR=3.98...     

胎盘组织炎症对早产儿脑室内出血发病风险的影响

目的 评价早产儿胎盘组织炎症反应程度及其病程进展对早产儿脑室内出血发病风险的影响.方法 收集2008年3月至2009年9月三所医院分娩的493例早产儿临床资料,对其胎盘组织绒毛膜羊膜炎症反应进行分级分期,利用头颅B超、CT和MRI等影像学手段对脑室内出血诊断并分级.结果 产妇绒毛膜羊膜炎患病率为30.0%(148/493),早产儿脑室内出血患病率为20.9%(103/493).在校正了早产儿胎龄、性别、体重、胎膜早破以及分娩方式等因素后,胎盘Ⅱ级和Ⅲ级炎症,以及胎盘Ⅱ期和Ⅲ期炎症分别是早产儿脑室内出血的独立危险因素,其比值比分别为1.33(95%CI:1.02～1.87),2.01(95%CI:1.54～2.73),1.33(95%CI:1.02～1.87)和2.01(95%CI:1.54～2.73).结论 早产儿胎盘绒毛膜羊膜炎组织病理不同分期、分级与早产儿脑室内出血患病风险密切相关.     

血液制品的钠供应与极早产儿的严重脑室内出血有关

目的该研究旨在调查极早产儿的钠供应量、液体量及钠失衡与严重脑室内出血(IVH)之间的关系。方法数据来源于瑞典极早产儿研究(EXPRESS)队列,包含2004至2007年间出生的所有22~26周极早产儿,并进行巢式病例对照研究。将严重IVH(3级或脑室周围出血性梗死)患儿作为病例组,选择出生日期与病例组患儿最为接近且医院、性别、胎龄和出生体重相匹配的未患IVH早产儿作为对照组(n=70病例-对照配对)。     

连续腰穿治疗早产儿重度脑室内出血疗效观察

早产儿因其特殊的解剖结构,易发生颅内出血,以脑室内出血(intraventricular hemorrhage,IVH)最多见,发生率达65%以上[1],IVH的并发症主要为脑积水,近年来连续腰穿(LP)是治疗IVH较为肯定的方法.自1999年以来,我院新生儿中心对重度脑室内出血早产儿采用LP治疗方法,现将疗效总结如下.     

苯巴比妥预防早产儿脑室内出血的多中心调查报告

目的 作为早产儿脑室内出血（IVH）的预防药物,苯巴比妥一直以来颇存争议,褒贬参半,近年来已不再被推荐在早产儿中预防应用。为了客观评估苯巴比妥对早产儿IVH的预防效果,在中华医学会儿科分会新生儿学组的发起下,国内十余家大型医院于2005年1月始进行了为期近两年的早产儿脑损伤多中心协作研究。方法 2005年1月至2006年8月期间,3家单位对所有胎龄≤34周的早产儿和2家单位对所有胎龄〈37周早产儿在生后6 h内给予苯巴比妥负荷量20 mg/kg,24 h后再予维持量5 mg/（kg&#183;d）共5 d。对所有早产儿在生后7 d内常规进行初次床边头颅B超检查,以后每隔3-7 d复查一次,直至出院。结果 5家单位接受苯巴比妥预防的早产儿共1 574例作为预防组,5家单位中主要因疏忽而漏予苯巴比妥的早产儿以及另4家单位未接受苯巴比妥预防的所有早产儿共1 433例为对照组。两组在胎龄、出生体重、性别、Apgar评分以及分娩方式之间的差异均无统计学意义。预防组IVH和重度IVH发生率分别为9.8%（154/1574例）和2.0%（32/1574例）;对照组IVH和重度IVH发生率分别为14.1%（202/1433例）和3.6%（52/1433例）。两组在IVH和重度IVH发生率之间的差异均有统计学意义（χ^2=13.364,P=0.000;χ^2=7.034,P=0.008）。预防组由重度IVH向轻度IVH的转变率明显高于对照组（62.5% vs 1.9%,连续性校正χ^2=21.201,P=0.000）。对两组高危因素分析显示,应用苯巴比妥可明显改善因机械呼吸而容易导致的IVH加重现象。结论 调查数据基本可反映我国主要大城市中苯巴比妥预防早产儿IVH的实际疗效。结果显示,苯巴比妥对早产儿IVH具有良好的预防作用,尤其可以肯定其在稳定病情、减轻IVH严重程度的效果,可为新生儿学组制定我国相应的早产儿脑损伤防治方案提供参考。根据这项多中心调查结果,可以推荐对早产儿在生后早期常规应用苯巴比妥预防IVH。     

早产儿脑室内出血的相关因素

目的探讨早产儿脑室内出血(IVH)发病相关因素及临床特点。方法调查172例早产儿胎龄、体质量、出生情况,通过床旁颅脑彩超确诊早产儿IVH,记录IVH临床表现、彩超结果,并与同期入院无IVH早产儿进行比较。结果1.胎龄与IVH发生有关(χ2=6.40P=0.011);2.出生体质量与IVH发生有关(χ2=26.49P=0);3.早产儿IVH多于生后72h内出现临床症状,生后5d内确诊,且多数早产儿IVH程度较轻,无明显临床症状;4.重度窒息早产儿较轻度窒息早产儿IVH发生率高、程度重。结论胎龄、出生体质量及窒息程度与早产儿IVH的发生呈线性关系;多数早产儿IVH无明显临床表现;床旁颅脑超声是诊断早产儿IVH可靠、敏感和简便的手段。     

早产儿脑损伤的患病率和危险因素

目的 探讨早产儿脑损伤的患病率和危险因素,为预防或降低早产儿脑损伤提供依据.方法 对2005年1月-2006年12月美国圣路易斯华盛顿大学儿童医院NICU收治的胎龄小于37周的早产儿的临床资料进行回顾性分析,按胎龄分组,计算脑损伤的患病率,采用多因素Logistic回归模型确立危险因素.结果 本组早产儿总的脑室内出血(IVH)和脑室周围白质软化(PVL)的患病率分别为17.7%和4.9%,而存活病例的患病率分别为14.4%和4.5%.按胎龄分组,IVH和PVL的患病率分别为:23~<25周龄组48.1% 和14.8%、25~<28周龄组35.2%和11.2%、28~<33周龄组13.8%和3.1%、33~<37周龄组2.8%和1.7%.坏死性小肠结肠炎、PDA、机械通气(MV)是IVH的独立危险因素,而胎龄、5 min Apgar评分为保护因素(负相关);IVH、MV、母亲产前或产时感染是PVL的危险因素,而出生体质量和女性为保护因素.同时IVH是导致早产儿死亡的危险因素.结论 胎龄越小,脑损伤的患病率越高;围生期感染、窒息缺氧以及影响脑血流的因素如PDA和MV等与早产儿脑损伤的发生密切相关.     

早产儿重度脑室周围-脑室内出血临床高危因素分析

目的 探讨早产儿重度脑室周围-脑室内出血的高危因素.方法 选择2008 -2009年我院新生儿重症监护病房重度脑室周围-脑室内出血的早产儿为观察组,同期轻度脑室周围-脑室内出血早产儿为对照组,对引起早产儿脑室周围-脑室内出血可能的15项临床因素进行统计学分析.结果 观察组32例,死亡6例,放弃治疗12例;对照组93例,死亡1例,放弃治疗2例.单因素分析显示,胎龄、出生体重、前置胎盘、产时窒息、宫内窘迫、低氧血症、高碳酸血症、机械通气、吸入高浓度氧等与早产儿重度脑室周围-脑室内出血有关(P均＜0.05).多因素Logistic回归分析显示,胎龄(OR=3.545)、出生体重(OR=3.453)、产时窒息(OR=3.232)、机械通气(OR =3.643)和吸入高浓度氧(OR=3.449)为早产儿重度脑室周围-脑室内出血的高危因素(P均＜0.05).结论 早产儿脑室周围-脑室内出血的高危因素较多,而且预后差,早期预防早产儿重度脑室周围-脑室内出血并采取积极干预措施具有重要意义.     

应用苯巴比妥预防早产儿脑室内出血九年疗效评估

目的　该文进行九年总结及评价苯巴比妥的实际预防早产儿脑室内出血 (IVH)疗效。方法　回顾 1994年至 2 0 0 3年期间入住新生儿病房、曾经头颅B超检查的早产儿有效病例 331例 ,其中 113例应用苯巴比妥作为预防组 ,接受苯巴比妥负荷量 2 0mg/kg ,分两次间隔 12h静脉给予 ,负荷量 12h后再静脉给予维持量每日5mg/kg ,共 4～ 5d。预防组所有患儿接受苯巴比妥的平均时龄为生后 14 .0h(1～ 72h) ,其中本院患儿为 12 .0h(1～ 72h) ,外院为 17.5h(1～ 4 8h)。 2 18例未用苯巴比妥的患儿作为对照组。结果　对照组中IVH程度更为严重 ,其重度IVH的发生率占出血患儿的 2 1.2 % ,较预防组的重度IVH发生率高出近 15个百分点 ,两组在重度IVH发生率之间的差异呈非常显著性意义 (P <0 .0 1)。预防组中IVH由轻度向重度的转变率为 4 .5 % ,由重度向轻度的转变率为 10 0 %。对照组中IVH由轻度向重度的转变率为 2 3.3% ,由重度向轻度的转变率为 6 .3% ,两组在IVH轻重程度转变之间的差异呈非常显著性意义 (χ2 =13.77,P <0 .0 1和 χ2 =2 5 .78,P <0 .0 1)。结论　对早产儿在生后早期应用苯巴比妥预防IVH具有一定的效果 ,尤其可稳定病情 ,显著减轻脑室内出血的严重度。但需指出的是 ,药物预防并不是减少脑室内出血发生的唯一手     

胎盘组织炎症对早产儿脑室内出血发病风险的影响

目的评价早产儿胎盘组织炎症反应程度及其病程进展对早产儿脑室内出血发病风险的影响。方法收集2008年3月至2009年9月三所医院分娩的493例早产儿临床资料,对其胎盘组织绒毛膜羊膜炎症反应进行分级分期,利用头颅B超、CT和MRI等影像学手段对脑室内出血诊断并分级。结果产妇绒毛膜羊膜炎患病率为30.0%(148/493),早产儿脑室内出血患病率为20.9%(103/493)。在校正了早产儿胎龄、性别、体重、胎膜早破以及分娩方式等因素后,胎盘Ⅱ级和Ⅲ级炎症,以及胎盘Ⅱ期和Ⅲ期炎症分别是早产儿脑室内出血的独立危险因素,其比值比分别为1.33(95%CI:1.02～1.87),2.01(95%CI:1.54～2.73),1.33(95%CI:1.02～1.87)和2.01(95%CI:1.54～2.73)。结论早产儿胎盘绒毛膜羊膜炎组织病理不同分期、分级与早产儿脑室内出血患病风险密切相关。     

Incidence of brain injuries in premature infants with gestational age ≤34 weeks in ten urban hospitals in China

Background

There is a large number (1.5 million per year) of premature births in China. It is necessary to obtain the authentic incidences of intraventricular hemorrhage (IVH) and periventricular leukomalacia (PVL), the common brain injuries, in Chinese premature infants. The present multicenter study aimed to investigate the incidence of brain injuries in premature infants in ten urban hospitals in China.

Methods

The research proposal was designed by the Subspecialty Group of Neonatology of Pediatric Society of the Chinese Medical Association. Ten large-scale urban hospitals voluntarily joined the multicenter investigation. All premature infants with a gestational age ≤34 weeks in the ten hospitals were subjected to routine cranial ultrasound within three days after birth, and then to repeated ultrasound every 3–7 days till their discharge from the hospital from January 2005 to August 2006. A uniform data collection sheet was designed to record cases of brain injuries.

Results

The incidences of overall IVH and severe IVH were 19.7% (305/1551) and 4.6% (72/1551), respectively with 18.4% (56/305) for grade 1, 58.0% (177/305) for grade 2, 17.7% (54/305) for grade 3 and 5.9% (18/305) for grade 4 in nine hospitals. The incidences of overall PVL and cystic PVL were 5.0% (89/1792) and 0.8% (14/1792) respectively, with 84.3% (75/89) for grade 1, 13.5% (12/89) for grade 2, and 2.2% (2/89) for grade 3 in the ten hospitals. The statistically significant risk factors that might aggravate the severity of IVH were vaginal delivery (OR=1.883, 95% CI: 1.099–3.228, P=0.020) and mechanical ventilation (OR=4.150, 95% CI: 2.384–7.223, P=0.000). The risk factors that might result in the development of cystic PVL was vaginal delivery (OR=21.094, 95% CI: 2.650–167.895, P=0.000).

Conclusions

The investigative report can basically reflect the incidence of brain injuries in premature infants in major big cities of China. Since more than 60% of the Chinese population live in the rural areas of China, it is expected to undertake a further multicenter investigation covering the rural areas in the future.     

我国早产儿脑室周围白质软化发生率的多中心调查报告

目的：在中华医学会儿科分会新生儿学组的发起下，国内十余家大型医院于2005年1月始进行了为期近两年的《早产儿脑损伤》多中心协作研究。该文报告我国10家三级甲等医院近两年对早产儿脑室周围白质软化（PVL）发生率的调查结果。方法：2005年1月至2006年8月期间，各参加单位对所有胎龄<37周的早产儿在生后7 d内常规进行初次床边头颅B超检查，以后每隔3～7 d复查一次，直至出院。结果：10单位共出生或收住早产儿4 933例，总PVL发生率为2.3％（112/4 933），囊性PVL发生率为0.3％（16/4 933）。分别为I级PVL 85.7％（96/112），II级PVL 12.5%（14/112），III级PVL 1.8％（2/112），无IV级PVL。4家妇婴医院的早产儿PVL总发生率非常显著低于6家综合性或儿童专科医院（1.4% vs. 2.8％）（χ2＝10.284，P<0.01）。与发生囊性PVL相关的可能高危因素为阴道分娩和机械呼吸。结论：该调查数据基本可以反映我国主要大城市早产儿PVL发生率的情况。提高对PVL尤其是非囊性脑室周围白质损伤的超声识别率，是今后临床要大力加强的重点     

6家医院147例脑损伤早产儿的多中心随访报告

目的：在中华医学会儿科学分会新生儿学组的发起下,国内十余家三级甲等医院于2005年1月始进行了为期20月的《早产儿脑损伤》多中心协作研究。该文报告其中6家医院对脑损伤早产儿临床随访的调查结果。方法：2005年1月至2006年8月期间,6家医院对在新生儿早期诊断为脑室内出血（IVH）和脑室周围白质软化（PVL）的早产儿出院后进行定期随访,综合体格、神经系统、智力测试及头颅B超随访结果,将早产儿列为正常、边缘水平及发育不良。结果：6单位147例脑损伤早产儿中,IVH 141例,PVL 36例,其中30例合并IVH＋PVL。总评价结果呈正常为51.4％,呈边缘水平或发育不良分别为38.4％和10.7％。头围、身长、体重均落后者占13.4％;脑瘫发生频率在I级PVL为 7.1％,II级PVL为28.6％,III级PVL为100％;智力测试显示12.7％呈现发育迟缓;头颅B超结果显示30％呈现脑损伤后遗改变。结论：该多中心调查数据可基本反映我国主要大城市脑损伤早产儿短期预后状况,约10％脑损伤早产儿呈现体格、运动及智能发育不良预后。期待各单位继续对更多脑损伤早产儿进行长期跟踪随访,尤其宜关注围学龄期及青春期可能发生的行为问题。［中国当代儿科杂志,2009,11（3）：166-172］     

Intraventricular hemorrhage in extremely small premature infants

The incidence, timing, severity, and outcome of intraventricular hemorrhage (IVH) were studied in extremely small premature infants with birth weights (BWs) between 500 and 700 g; 366 infants with BWs between 701 and 1500 g, admitted during the same period, served as a comparison group. Intraventricular hemorrhage occurred in 34 (62%) of 55 infants with BWs less than 700 g vs 91 (25%) of the 366 comparison infants. In the group with BWs less than 700 g, IVH occurred in the first 18 hours, from 19 to 72 hours, and after 72 hours of life in 62%, 20%, and 18% of the infants, respectively. In the comparison group, the occurrence for these periods was 13%, 82%, and 5%, respectively. The severity of IVH in infants with BWs less than 700 g was grade III (with or without intraparenchymal hemorrhage) in 97% of the lesions, but in the comparison group such severe IVH accounted for only 32% of the lesions. Intraventricular hemorrhage was a common contributor to death in the infants with BWs less than 700 g. Thus, in 24 infants who died before 72 hours of life, 21 infants (88%) had severe IVH. In addition, intracranial hemorrhage (four infants with IVH and two infants with intracerebellar hemorrhage) occurred late (days 8 to 25) and contributed to death in six of the infants with BWs less than 700 g. These data indicate that in comparison with larger premature infants, infants with BWs less than 700 g exhibit a higher incidence of IVH, which is more severe, occurs earlier, and is associated more often with a fatal outcome. In addition, late and lethal intracranial hemorrhage is also more likely to occur in these smaller infants.     

Increased serum levels of interleukin 6 are associated with severe intraventricular haemorrhage in extremely premature infants

BACKGROUND: Intraventricular haemorrhage (IVH) and periventricular leucomalacia (PVL) in premature infants presumably have many causes. It has been proposed that inflammatory processes in the fetomaternal unit play an important role in the pathogenesis of these lesions. OBJECTIVE: To study the correlation of postpartum serum interleukin 6 (IL6) concentration as a marker of inflammation and neonatal cerebral morbidity in preterm infants < 28 weeks of gestational age. METHODS: A total of 88 infants were grouped according to maximum serum IL6 levels within 12 hours post partum: group A (n = 50), < or = 100 pg/ml; group B (n = 38), > 100 pg/ml. Ultrasound studies and clinical assessment were performed routinely. RESULTS: IVH was noted significantly more often in group B (24/38; 63%) than in group A (19/50; 38%) (p = 0.02). In a multiple logistic regression model, raised serum IL6 independently predicted development of severe IVH (odds ratio 8.4; 95% confidence interval 2.85 to 24.9; p = 0.0001). CONCLUSIONS: Raised serum IL6 may serve as a marker for severe IVH in infants < 28 weeks of gestational age. Although cerebral morbidity in premature infants is determined by different variables, the identification of systemic inflammation can help to define the need for anti-inflammatory strategies to prevent cerebral morbidity.     

Effect of maternal tocolysis on the incidence of severe periventricular/intraventricular haemorrhage in very low birthweight infants.

AIM: To examine the relation between grade III-IV periventricular/intraventricular haemorrhage (PVH/IVH) and antenatal exposure to tocolytic treatment in very low birthweight (VLBW) premature infants. STUDY DESIGN: The study population consisted of 2794 infants from the Israel National VLBW Infant Database, of gestational age 24-32 weeks, who had a cranial ultrasound examination during the first 28 days of life. Infants of mothers with pregnancy induced hypertension or those exposed to more than one tocolytic drug were excluded. Of the 2794 infants, 2013 (72%) had not been exposed to tocolysis and 781 (28%) had been exposed to a single tocolytic agent. To evaluate the effect of tocolysis and confounding variables on grade III-IV PVH/IVH, the chi(2) test, univariate analysis, and a logistic regression model were used. RESULTS: Of the 781 infants (28%) exposed to tocolysis, 341 (12.2%) were exposed to magnesium sulphate, 263 (9.4%) to ritodrine, and 177 (6.3%) to indomethacin. The overall incidence of grade III-IV PVH/IVH was 13.4%. In the multivariate logistic regression analysis, the following factors were related significantly and independently to grade III-IV PVH/IVH: no prenatal steroid treatment, low gestational age, one minute Apgar score 0-3, respiratory distress syndrome, patent ductus arteriosus, mechanical ventilation, and pneumothorax. Infants exposed to ritodrine tocolysis (but not to the other tocolytic drugs) were at significantly lower risk of grade III-IV PVH/IVH after adjustment for other variables (odds ratio = 0.3; 95% confidence interval 0.2 to 0.6). CONCLUSION: This study suggests that antenatal exposure of VLBW infants to ritodrine tocolysis, in contrast with tocolysis induced by magnesium sulphate or indomethacin, was associated with a lower incidence of grade III-IV PVH/IVH.     

Reduction of cerebral hemorrhage and respiratory distress syndrome in premature infants by avoiding perinatal asphyxia

Intra- and periventricular haemorrhage (IVH/PVH) and, under certain conditions, the respiratory distress syndrome (RDS) seem to be typical sequelae of perinatal asphyxia in preterm born infants. Therefore, an association of IVH/PVH and RDS can be expected. We have retrospectively analyzed the data of 118 premature infants born between 1982 and 1986, weighing between 750 and 1499 g. 11 of these had experienced a severe IVH/PVH and a severe RDS at the same time, whereas 75 infants did not develop either of those. (2 of the 118 showed a severe IVH/PVH without evidence of severe RDS whereas 29 developed severe RDS without signs of serious IVH/PVH. 1 could not be evaluated due to missing data). This association of severe intracerebral haemorrhage and severe respiratory distress syndrome was statistically significant (p less than 0.005). The number of severe IVH/PVH has decreased during 1984-1986 in comparison to 1982/83 (4/76 vs. 9/42; p less than 0.05); the incidence of severe RDS has slightly declined. Comparing the perinatal conditions we found that the infants of the years 1984-1986 were more rarely delivered after an interval exceeding 24 h after premature rupture of the membranes (p less than 0.05), were more often delivered by caesarean section (p less than 0.005), and were nearly always primarily cared for by an experienced paediatrician (p less than 0.01). There were no significant differences between these two groups as far as dexamethasone-prophylaxis, mean birth weight, percentage of small-for-gestational-age infants and mean Apgar scores were concerned.(ABSTRACT TRUNCATED AT 250 WORDS)     

Apoptosis and White Matter Injury in Preterm Infants

White matter injury in premature infants with or without intraventricular hemorrhage (IVH) remains an important cause of neonatal mortality and neurologic morbidity. The contribution of apoptosis to the cellular death in white matter injury in the preterm infant is unclear. The objective of this study was to determine whether apoptosis contributes to the cellular death in premature infants with cranial ultrasound (US) evidence of IVH and asymmetric periventricular echogenicity (PVE). Brain tissue incorporating frontoparietal white matter was obtained from 21 infants: 6 infants with severe IVH and asymmetric PVE (grade 1V IVH) on US (group 1); 9 infants with minimal IVH or normal US who died within 21 days (group II); and 6 infants with minimal IVH or normal US who died later (group III). The presence of DNA fragmentation, typical of apoptosis, was determined using a terminal deoxytransferase-mediated dUTD nick-end labeling (TUNEL) assay. The TUNEL index for group I infants was significantly greater, i.e., 2.75 ± 1.94% versus 0.84 ± 0.70% for group II and 0.42 ± 0.22 for group III infants (P = 0.004). Most cells showing reactivity had morphologic characteristics consistent with astrocytes and oligodendroglia. The number of white matter cells showing morphologic changes consistent with apoptosis, such as nuclear blebs and karyorrhexis, was also quantitated and was significantly more numerous in group I than in group II infants, i.e., 0.51 ± 0.64% versus 0.02 ± 0.05% (P = 0.0005), and group III infants, i.e., 0.10 ± 0.18% (P = 0.03). These findings implicate apoptosis as a contributing mechanism for the cellular death in infants with IVH and asymmetric PVE. Strategies aimed at preventing the white matter injury will need to incorporate methods of inhibiting the ongoing process of apoptosis. Received March 14, 2001; accepted October 25, 2001.     

Increased risk of intraventricular hemorrhage in preterm infants with thrombophilia

The multifactorial etiology of cerebral intraventricular hemorrhage (IVH) may involve coagulation disturbances and venous infarction. We tested whether coagulation abnormalities associated with adult venous thrombosis would constitute a risk factor for IVH in newborn infants. In 22 infants (gestational age 24.3--39.9 wk, median 28.0 wk) with neonatal IVH grade II to IV, the frequencies of congenital resistance to activated protein C due to a point mutation in the factor V gene (Gln506-FV) and a polymorphism in the prothrombin gene (G20210A-FII) were assessed and compared with those observed in 29 premature newborn infants without IVH and in 302 (Gln506-FV) or 526 (G20210A-FII) healthy adults. In infants with IVH, four (18%) heterozygous carriers of Gln506-FV and one (5%) heterozygous carrier of G20210A-FII were found. One infant without IVH was heterozygous for Gln506-FV (3%). When compared with the frequency of Gln506-FV in the general population, the odds ratio for being a carrier of Gln506-FV for patients with IVH was 5.9 (95% confidence interval 1.7--20.3, p = 0.013) and for patients without IVH 0.9 (95% confidence interval 0.1--7.6, p > 0.99). The absolute risk of IVH in a newborn infant with heterozygous Gln506-FV and born before 30 wk of gestation was estimated at 80%, whereas the corresponding risk for all infants born before 30 wk was 14%. Gln506-FV was more common in newborn infants with IVH than in the general population, whereas there was no difference in the frequencies of Gln506-FV in infants without IVH and in the general population. Thus, Gln506-FV may be a risk factor of IVH. The risk of IVH in a premature infant with Gln506-FV or other established thrombophilic coagulation abnormality may be considerable.