产妇高血压增加婴儿卒中风险

明尼阿波利斯——一项大型回顾性分析提示，如果产妇患有高血压和产时发热，那么其所生育的婴儿将面临较高的缺血性卒中风险。而妊娠期糖尿病这一产妇高血压和新生儿低血糖的危险因素，却并不增加婴儿卒中的风险。

每10万名新生儿中约有2~4人会在出生后28天内发生缺血性卒中，其中大约60%在出生后立即发生，通常伴有新生儿惊厥，而其余40%的卒中婴儿会在儿童期因神经或认知发育异常而就诊时获得诊断。南加州大学家庭与预防医学系的Joshua Mann博士及其同事对2000~2007年间出生并参加南加州医疗补助计划的226,117名儿童(包括199,934名足月儿)进行了回顾性分析。

Joshua Mann博士

在这些儿童中，43人在出生后30天内被诊断为缺血性卒中，118人在出生后30~364天内获得诊断，二者中分别有37人和96人被确诊为缺血性卒中(定义为至少有1个缺血性卒中ICD-9编码，或者单次诊断为缺血性卒中且有1种提示卒中的神经认知异常)。

与非卒中婴儿相比，出生后30 天内和365天内发生缺血性卒中者的母亲均更常患有高血压(分别为14% vs. 32.5%，P=0.0004；14% vs. 28%；P＜0.0001)。产时发热在出生后365天内发生卒中者的母亲中明显更多见(4.9% vs. 1.2%；P＜0.0001)，但在出生后30 天内发生卒中者的母亲中则不存在这一现象。不论是出生后30天还是365天内发生卒中的婴儿，其母亲的糖尿病患病率均未明显增高。

校正多种人口统计学及其他混淆因素的逻辑回归分析显示，高血压产妇所生的婴儿在30天内发生任何卒中(定义为≥1次诊断提示缺血性卒中)或确诊为缺血性卒中的风险均增加1倍以上，OR值分别为2.31和2.75，P值分别为0.0071和0.0021)。产时发热则使任何卒中和确诊为缺血性卒中的风险分别增加2倍(OR，3.36；P=0.048)和3倍(OR，4.02；P=0.025)。母亲糖尿病并不显著增加任何卒中(OR，0.35；P=0.08)或确诊卒中(OR，0.40；P=0.13)的风险。

研究者还发现了一些与出生后365天内卒中风险增加相关的协变因素，包括产伤(OR，5.99)、产时窒息(OR，11.42)、镰状细胞病(OR，3.58)、镰状细胞特质(OR，2.45)、先天性感染(OR，5.39)、新生儿感染(OR，6.06)、脑膜炎(OR，6.05)、脑炎(OR，3.99)以及儿童血栓形成倾向(OR，157.99)。母亲高血压与上述因素之间存在协同作用。

研究者还介绍，近期一项纳入44例卒中患儿的研究显示，卒中发生时间对结局有影响：在1~6岁期间发生卒中的儿童，其神经精神结局优于在1岁以前或6岁以后发生卒中的儿童(Child Neuropsychol. 2011 Dec. 6 [doi:10.1080/09297049.2011.639756])。

Joshua Mann博士总结称：“尚需开展进一步研究，以确定这些关联的潜在机制，以及对高危婴儿的有效预防措施。”

这项研究的资金来源于卫生资源服务管理部门的母儿健康拨款。Mann博士及其同事报告称无利益冲突。

爱思唯尔  版权所有

By: PATRICE WENDLING, Ob.Gyn. News Digital Network

MINNEAPOLIS – Maternal hypertension and intrapartum fever increase the risk for ischemic stroke in infants, a large retrospective analysis suggests.

Gestational diabetes, a known risk factor for maternal hypertension and neonatal hypoglycemia, does not increase stroke risk.

"Additional research is needed to determine the mechanism underlying these associations and to develop effective preventive methods for high-risk infants," Dr. Joshua R. Mann reported at the meeting.
 
Approximately 2-4 children per 10,000 births experience ischemic stroke in the first 28 days of life. Roughly 60% of infants present immediately, typically with neonatal seizures. In the remaining 40%, stroke is recognized later in childhood during evaluation for abnormal neurologic or cognitive development.

There were 43 cases of ischemic stroke before 30 days of life and 118 additional cases diagnosed from day 30 through 364 days in the retrospective analysis of 226,117 children (199,934 full-term births) born from 2000 through 2007 and enrolled in the South Carolina Medicaid program.

Of these, 37 cases and 96 cases, respectively, had confirmed ischemic strokes, defined as more than one ICD-9 code for ischemic stroke or a single diagnosis of ischemic stroke plus a neurocognitive condition that could be indicative of stroke.

Compared with infants without stroke, maternal hypertension was significantly more common for infants with ischemic stroke before 30 days (32.5% vs. 14%; P value = .0004) and before 365 days (28% vs. 14%; P less than .0001), reported Dr. Mann of family and preventive medicine at the University of South Carolina, Columbia.

Fever at delivery was significantly more common in mothers of infants with stroke prior to 365 days (4.9% vs. 1.2%; P less than .0001), but not in those with stroke before 30 days (4.6% vs. 1.2%; P = .09).

Maternal diabetes was not significant at either time point.

In a logistic regression analysis that adjusted for a broad range of demographic and other confounding risk factors, infants born to mothers with hypertension had more than twice the risk of any stroke, defined as one or more diagnoses indicating ischemic stroke, before 30 days (odds ratio 2.31; P = .0071), or a confirmed ischemic stroke (OR 2.75; P = .0021), he said.

Maternal fever at delivery more than tripled the risk of any ischemic stroke (OR 3.36; P = .048) and quadrupled the risk of confirmed ischemic stroke (OR 4.02; P = .025), he reported in a poster presentation.

Maternal diabetes did not significantly increase the odds of any stroke (OR 0.35; P = .08) or confirmed stroke (OR 0.40; P = .13).

Although it was not the primary goal of the study, the investigators also found multiple child characteristics to be associated with increased odds of any stroke prior to 365 days. The significant covariates were birth trauma (OR 5.99), birth asphyxia (OR 11.42), sickle cell disease (OR 3.58), sickle cell trait (OR 2.45), congenital infection (OR 5.39), neonatal infection (OR 6.06), meningitis (OR 6.05), encephalitis (OR 3.99) and child thrombophilia, which had a staggering odds ratio of 157.99.

There was also evidence of synergy between maternal hypertension and the presence of at least one other risk factor for stroke diagnosed before 365 days.

A recent study among 44 children indicated that the timing of the stroke has a bearing on outcomes. Children who had a stroke between 1 and 6 years had better neuropsychological outcomes than did children who had a stroke before age 1 or after age 6 (Child Neuropsychol. 2011 Dec. 6 [doi:10.1080/09297049.2011.639756]).

The full paper is in press with the journal Developmental Medicine and Child Neurology, Dr. Mann noted.

Funding for the study was provided by a Health Resources Services Administration Maternal Child Health grant. Dr. Mann and his coauthors reported having no disclosures.