Yvonne W. Wu

Perinatal outcomes in singletons following in vitro fertilization: A meta-analysis

OBJECTIVE: To estimate whether singleton pregnancies following in vitro fertilization (IVF) are at higher risk of perinatal mortality, preterm delivery, small for gestational age, and low or very low birth weight compared with spontaneous conceptions in studies that adjusted for age and parity. DATA SOURCES: We searched MEDLINE, BIOSIS, Doctoral Dissertations On-Line, bibliographies, and conference proceedings for studies from 1978–2002 using the terms “in vitro fertilization,” “female infertility therapy,” and “reproductive techniques” combined with “fetal death,” “mortality,” “fetal growth restriction,” “small for gestational age,” “birth weight,” “premature labor,” “preterm delivery,” “infant,” “obstetric,” “perinatal,” and “neonatal.” METHODS OF STUDY SELECTION: Inclusion criteria were singleton pregnancies following IVF compared with spontaneous conceptions, control for maternal age and parity; 1 of the above outcomes; and risk ratios or data to determine them. Study selection and data abstraction were performed in duplicate after removing identifying information. TABULATION, INTEGRATION, AND RESULTS: Fifteen studies comprising 12,283 IVF and 1.9 million spontaneously conceived singletons were identified. Random-effects meta-analysis was performed. Compared with spontaneous conceptions, IVF singleton pregnancies were associated with significantly higher odds of each of the perinatal outcomes examined: perinatal mortality (odds ratio [OR] 2.2; 95% confidence interval [CI] 1.6, 3.0), preterm delivery (OR 2.0; 95% CI 1.7, 2.2), low birth weight (OR 1.8; 95% CI 1.4, 2.2), very low birth weight (OR 2.7; 95% CI 2.3, 3.1), and small for gestational age (OR 1.6; 95% CI 1.3, 2.0). Statistical heterogeneity was noted only for preterm delivery and low birth weight. Sensitivity analyses revealed no significant changes in results. Early preterm delivery, spontaneous preterm delivery, placenta previa, gestational diabetes, preeclampsia, and neonatal intensive care admission were also significantly more prevalent in the IVF group. CONCLUSION: In vitro fertilization patients should be advised of the increased risk for adverse perinatal outcomes. Obstetricians should not only manage these pregnancies as high risk but also avoid iatrogenic harm caused by elective preterm labor induction or cesarean.

Risk of stroke in children Ethnic and gender disparities

Methods: Using a California-wide hospital discharge database, the authors analyzed all first admissions for stroke in children 1 month through 19 years of age from 1991 through 2000. Incidence rates were estimated as the number of first hospitalizations divided by the person-years at risk; case fatality rates were based on in-hospital deaths. Results: The authors identified 2,278 first admissions for childhood stroke, yielding an annual incidence rate of 2.3 per 100,000 children (1.2 for ischemic stroke, 1.1 for hemorrhagic stroke). Compared with whites, black children were at higher risk of stroke (for ischemic stroke, relative risk [RR] 2.59, 95% CI 2.17 to 3.09, p < 0.0001; subarachnoid hemorrhage [SAH], RR 1.59, CI 1.06 to 2.33, p = 0.02; intracerebral hemorrhage [ICH], RR 1.66, CI 1.23 to 2.13, p = 0.0001). Hispanics, however, had a lower risk of ischemic stroke (RR 0.70, CI 0.60 to 0.82, p < 0.0001) and ICH (RR 0.77, CI 0.64 to 0.93, p = 0.0004), whereas Asians had similar risks as whites. Boys were at higher risk for all stroke types than girls (ischemic stroke, RR 1.25, CI 1.11 to 1.40, p = 0.0002; SAH, RR 1.24, CI 1.00 to 1.53, p = 0.047; ICH, RR 1.34, CI 1.16 to 1.56, p = 0.0001). After eliminating cases with coexisting sickle cell disease, excess stroke risk persisted in blacks; after elimination of trauma, excess stroke risk persisted in boys. Case fatality rates were similar among different ethnic groups. Compared with girls, boys had a higher case fatality rate for ischemic stroke (17 vs 12%; p = 0.002) but not for ICH or SAH. Conclusions: Rates of hospitalization for stroke are higher among black children and boys; sickle cell disease and trauma do not fully account for these findings.

Risk of Recurrent Childhood Arterial Ischemic Stroke in a Population-Based Cohort: The Importance of Cerebrovascular Imaging

OBJECTIVE. Few data exist regarding rates and predictors of recurrence after childhood arterial ischemic stroke. We sought to establish such rates within a large, multiethnic population and determine whether clinical vascular imaging predicts recurrence. PATIENTS AND METHODS. In a population-based cohort study, we collected data on all documented cases of arterial ischemic stroke among 2.3 million children (<20 years old) enrolled in a northern Californian managed care plan from January 1993 to December 2004. Perinatal strokes were those that occurred by 28 days of life. Data on cerebrovascular imaging (conventional or magnetic resonance angiography), including presence of vascular abnormalities, were abstracted from official radiology reports. We used Kaplan-Meier survival-analysis techniques to determine rates and predictors of recurrent stroke. RESULTS. Among 181 incident childhood stroke cases (84 perinatal; 97 later childhood), there were 16 recurrent strokes (1 after a perinatal stroke) at a median of 2.7 months. The 5-year cumulative recurrence rates were 1.2% after perinatal stroke and 19% after later childhood stroke. Of the 97 children with later childhood strokes, 52 received cerebrovascular imaging, predominantly magnetic resonance angiography (n = 36) and conventional angiography (n = 26). Although there were no recurrences among children with normal vascular imaging, children with a vascular abnormality had a 5-year cumulative recurrence rate of 66%. CONCLUSIONS. Strokes recur in one fifth of cases of later childhood arterial ischemic stroke but are rare after perinatal stroke. Among the later childhood cases, cerebrovascular imaging identifies those at highest risk for recurrence.

Incidence and mortality of generalized convulsive status epilepticus in California

BackgroundFew population-based studies of status epilepticus have been performed in the United States. ObjectiveTo determine the incidence, case fatality, and demographics of generalized convulsive status epilepticus (GCSE) in the state of California. MethodsUsing a state-wide hospital discharge database, the authors identified all hospitalizations from 1991 through 1998 with a discharge diagnosis of convulsive status epilepticus. They identified the first admission for each individual to estimate the incidence of GCSE. In-hospital case fatality rates were calculated, and multivariate analysis was performed to determine predictors of death during hospitalization. Secondary diagnoses were analyzed by retrieving all discharge diagnoses accompanying the diagnosis of GCSE. ResultsThe incidence rate of GCSE was 6.2/100,000 population and fell by 42% between the years 1991 and 1998 from 8.5 to 4.9/100,000. The rate of GCSE was highest among children under the age of 5 (7.5/100,000) and among the elderly (22.3/100,000). Blacks also demonstrated a relatively high incidence of GCSE (13.4/100,000). The case fatality for incident admissions was 10.7%, with increasing age being the only significant predictor in multivariate analysis. Case fatality was highest in patients who also carried a diagnosis of anoxia, CNS infection, or stroke. ConclusionsThe incidence of GCSE requiring hospitalization has fallen over the last decade and is lower than that reported in previous studies. The case fatality is also lower than that reported previously. Further studies are needed to determine the cause of this decline in incidence and mortality of GCSE.

Predictors of outcome in perinatal arterial stroke: A population-based study

Some infants with perinatal arterial ischemic stroke (PAS) experience development of cerebral palsy (CP), epilepsy, and cognitive impairment, whereas others have a normal outcome. Previous prognostic studies rarely have included all diagnosed cases of PAS within a population. Among 199,176 infants born within Kaiser Permanente from 1997 to 2002, we electronically identified head imaging reports and physician diagnoses suggesting stroke. The diagnosis of PAS was confirmed by review of brain imaging and medical records. Presentation of PAS was considered delayed if symptoms were only noted after 28 days. Outcomes were determined by chart review. Of 40 infants with PAS, 36 were observed over 12 months. Abnormal outcomes included CP (58%), epilepsy (39%), language delay (25%), and behavioral abnormalities (22%). A delayed presentation was associated with increased risk for CP (relative risk [RR], 2.2; 95% confidence interval [CI], 1.2–4.2). Radiological predictors of CP included large stroke size (RR, 2.0; 95% CI, 1.2–3.2) and injury to Brocas area (RR, 2.5; 95% CI, 1.3–5.0), internal capsule (RR, 2.2; 95% CI, 1.1–4.4), Wernickes area (RR, 2.0; 95% CI, 1.1–3.8), or basal ganglia (RR, 1.9; 95% CI, 1.1–3.3). Among infants with PAS, specific radiological findings and a lack of symptoms in the newborn period are associated with increased risk for CP. Ann Neurol 2005

Cerebral Palsy in a Term Population: Risk Factors and Neuroimaging Findings

OBJECTIVE. The purpose of this work was to study risk factors and neuroimaging characteristics of cerebral palsy in term and near-term infants. PATIENTS AND METHODS. Among a cohort of 334339 infants ≥36 weeks’ gestation born at Kaiser Permanente Medical Care Program in northern California in 1991–2003, we identified infants with cerebral palsy and obtained clinical data from electronic and medical charts. Risk factors for cerebral palsy among infants with different brain abnormalities were compared using polytomous logistic regression. RESULTS. Of 377 infants with cerebral palsy (prevalence: 1.1 per 1000), 273 (72%) received a head computed tomography or MRI. Abnormalities included focal arterial infarction (22%), brain malformation (14%), and periventricular white matter abnormalities (12%). Independent risk factors for cerebral palsy were maternal age >35, black race, and intrauterine growth restriction. Intrauterine growth restriction was more strongly associated with periventricular white matter injury than with other neuroimaging findings. Nighttime delivery was associated with cerebral palsy accompanied by generalized brain atrophy but not with cerebral palsy accompanied by other brain lesions. CONCLUSIONS. Cerebral palsy is a heterogeneous syndrome with focal arterial infarction and brain malformation representing the most common neuroimaging abnormalities in term and near-term infants. Risk factors for cerebral palsy differ depending on the type of underlying brain abnormality.

Ventriculoperitoneal shunt complications in California: 1990 to 2000.

BACKGROUNDRisk factors for ventriculoperitoneal (VP) shunt complications have not been assessed with population cohort data since the advent of modern surgical techniques. We examined demographic factors and VP shunt complications in a population-based retrospective cohort study of all nonfederal California hospital admissions between 1990 and 2000. METHODSWe identified all admissions in a statewide administrative hospital discharge database that indicated a VP shunt insertion. Repeat hospital admissions within California generating a discharge diagnosis of surgical shunt complication, defined as a shunt replacement, revision, removal, or exploration, represented the primary outcome of interest. We performed Kaplan-Meier survival analyses and Cox proportional hazards modeling to analyze sex, age, ethnicity, socioeconomic status based on payer status, and type of hydrocephalus in relation to the risk of shunt complications. RESULTSThe annual population incidence of VP shunt placement was 5.5 per 100,000. Among 14,455 individuals with 65,040 person-years of follow-up, the cumulative complication rate at 5 years was 32%. Children demonstrated a higher rate of shunt complications than did adults at 5 years (48 versus 27%, P < 0.0001). The following demographic factors were independently associated with increased risk of shunt complications: male sex (hazard ratio [HR], 1.1; 95% confidence interval [CI], 1.03–1.2), low socioeconomic status (HR, 1.2; 95% CI, 1.1–1.3), and age younger than 19 years (HR, 1.6; 95% CI, 1.4–1.7). Compared with communicating hydrocephalus, obstructive hydrocephalus was also associated with increased risk of shunt complications (HR, 1.7; 95% CI, 1.5–1.9). CONCLUSIONVP shunt complications are common, especially in children. Further study is needed to explain the associations between demographic factors and elevated shunt complication rates.

Perinatal Stroke in Children With Motor Impairment: A Population-Based Study

Objective. Risk factors for perinatal arterial stroke (PAS) are poorly understood. Most previous studies lack an appropriate control group and include only infants with symptoms in the newborn period. We set out to determine prenatal and perinatal risk factors for PAS. Methods. In a population-based, case-control study nested within the cohort of 231 582 singleton infants who were born at ≥36 weeks’ gestation in Northern California Kaiser hospitals from 1991 to 1998, we searched electronically for children with motor impairment and reviewed their medical records to identify diagnoses of PAS. Control subjects were randomly selected from the study population. A medical record abstractor reviewed delivery records without knowledge of case status. Results. The prevalence of PAS with motor impairment was 17/100 000 live births. Of 38 cases, 26 (68%) presented after 3 months of age with hemiparesis or seizures. All 12 newborns with acute stroke symptoms had seizures. A delayed presentation was more common in children with moderate to severe motor impairment than among infants with only mild motor abnormalities (24 of 31 vs 2 of 7). Prepartum risk factors significantly associated with PAS in multivariate analysis were preeclampsia (odds ratio [OR]: 3.6; 95% confidence interval [CI]: 1.1–11.4) and intrauterine growth restriction (OR: 5.3; 95% CI: 1.5–18.6). Newborns with PAS were also at higher risk of delivery complications, such as emergency cesarean section (OR: 6.8; 95% CI: 2.7–16.6), 5-minute Apgar <7 (OR: 23.6; 95% CI: 4.1–237), and resuscitation at birth (OR: 4.5; 95% CI: 1.6–12.3). Conclusions. Preeclampsia and intrauterine growth restriction (IUGR) may be independent risk factors for perinatal stroke resulting in motor impairment. Large multicenter studies that include all children with perinatal stroke are needed to determine further the risk factors and outcome of perinatal stroke.

Imaging Data Reveal a Higher Pediatric Stroke Incidence Than Prior US Estimates

Background and Purpose— Prior annualized estimates of pediatric ischemic stroke incidence have ranged from 0.54 to 1.2 per 100 000 US children but relied purely on diagnostic code searches to identify cases. We sought to obtain a new estimate using both diagnostic code searches and searches of radiology reports and to assess the relative value of these 2 strategies. Methods— Using the population of 2.3 million children (<20 years old) enrolled in a Northern Californian managed care plan (1993 to 2003), we performed electronic searches of (1) inpatient and outpatient diagnoses for International Classification of Diseases, 9th Revision codes suggestive of stroke and cerebral palsy; and (2) radiology reports for key words suggestive of infarction. Cases were confirmed through chart review. We calculated sensitivities and positive predictive values for the 2 search strategies. Results— We identified 1307 potential cases from the International Classification of Diseases, 9th Revision code search and 510 from the radiology search. A total of 205 ischemic stroke cases were confirmed, yielding an ischemic stroke incidence of 2.4 per 100 000 person-years. The radiology search had a higher sensitivity (83%) than the International Classification of Diseases, 9th Revision code search (39%), although both had low positive predictive values. For perinatal stroke, the sensitivity of the stroke International Classification of Diseases, 9th Revision codes alone was 12% versus 57% for stroke and cerebral palsy codes combined; the radiology search was again the most sensitive (87%). Conclusions— Our incidence estimate doubles that of prior US reports, a difference at least partially explained by our use of radiology searches for case identification. Studies relying purely on International Classification of Diseases, 9th Revision code searches may underestimate childhood ischemic stroke rates, particularly for neonates.

Chiari Type I Malformation in a Pediatric Population

The natural history of Chiari I malformation in children remains unclear. A population-based retrospective cohort study was therefore conducted. Radiology reports from all head and spine magnetic resonance imaging scans (n = 5248) performed among 741,815 children under age 20 within Kaiser Northern California, 1997-1998, were searched for Chiari I. Medical records and imaging studies were reviewed to determine clinical and radiographic predictors of significant neurologic symptoms, defined as moderate to severe headache, neck pain, vertigo, or ataxia. The 51 patients identified with Chiari I represented 1% of the children who had head or spine magnetic resonance imaging scans performed during the study period. Headache (55%) and neck pain (12%) were the most common symptoms. Syringomyelia was present in 6 patients (12%) at initial diagnosis; no new syrinxes developed during follow-up. Older age at time of diagnosis was associated with increased risk of headache (odds ratio OR = 1.3, 95% confidence interval CI = 1.1-1.5) and significant neurologic symptoms (OR = 1.2, 95% CI = 1.04-1.4). Chiari I, an underrecognized cause of headaches in children, is also frequently discovered incidentally in children without symptoms. Larger and longer-term studies are needed to determine the prognosis and optimal treatment of pediatric Chiari I.