Obstetric antecedents of intraventricular hemorrhage and periventricular leukomalacia in the low-birth-weight neonate

doi:10.1016/S0002-9378(97)70485-X

American Journal of Obstetrics and Gynecology

Volume 176, Issue 2, February 1997, Pages 275-281

https://doi.org/10.1016/S0002-9378(97)70485-X Get rights and content

Abstract

OBJECTIVE: Neonatal intraventricular hemorrhage and periventricular leukomalacia have a strong correlation with eventual neurologic deficit. Our objective was to correlate obstetric factors with the development of these lesions.

STUDY DESIGN: Seven hundred forty-five consecutive inborn neonates with birth weights from 500 to 1750 gm were divided into three clinical groups: premature rupture of membranes, refractory preterm labor with intact membranes, and delivery initiated by the physician for maternal or fetal indications. Neonatal neurosonography was performed on days 3 and 7 of life and results were described as normal or abnormal. Abnormal scans included intraventricular hemorrhage seen within 3 days and echodense or echolucent periventricular leukomalacia seen within 7 days of life. Major abnormalities included intraventricular hemorrhage grades 3 and 4, intraventricular hemorrhage with periventricular leukomalacia, and echolucent periventricular leukomalacia. Abnormal scans were correlated with groups of origin and clinical and histologic chorioamnionitis.

RESULTS: Abnormal scans occurred in 33% of cases of premature rupture of membranes and in 38.9% of cases of preterm labor compared with 17.7% of physician-initiated cases (p < 0.000001). Major lesions occurred in 17.6% of cases of premature rupture of membranes, 21.4% of cases of preterm labor, and 1.1% of physician-initiated cases (p < 0.0000001). Clinical chorioamnionitis occurred in 19.7% of cases of premature rupture of membranes, 11.9% of cases of preterm labor, and 1.1% of physician-initiated cases (p < 0.001) and was associated with a significant increase in the incidence (p ≤ 0.005) and severity (p ≤ 0.007) of these lesions. Histologic chorioamnionitis occurred in 59.9% of cases of premature rupture of membranes, 43.2% of cases of preterm labor, and 8% of physician-initiated cases and did not correlate significantly with the incidence or severity of abnormal scans. These findings were independent of gestational age.

CONCLUSIONS: The incidence and severity of intraventricular hemorrhage and periventricular leukomalacia were significantly increased in premature rupture of membranes and preterm labor compared with the physician-initiated cases. Clinical chorioamnionitis increased the incidence and severity of these lesions.(Am J Obstet Gynecol 1997;176:275-81.)

Section snippets

Methods

The study was conducted at a tertiary care facility with a yearly delivery rate of 1200 to 1300 and a LBW rate (<2501 gm) of 20% to 24%. The high LBW rate is the result of maternal transports, with predominant indications for maternal transfer being premature rupture of membranes, preterm labor, and maternal disorders requiring preterm delivery. The study includes all inborn neonates with birth weights of 500 to 1750 gm born from January 1990 through June 1995. Three groups of origin—premature

Results

Seven hundred eighty-five consecutive neonates with birth weights of 500 and 1750 gm born between January 1990 through June 1995 were studied. Exclusions included 36 who died on day 1 and 4 who were transferred to other institutions before 7 days of life and therefore did not have neurologic imaging according to protocol requirements. In the final study group of 745 neonates, there were 279 in the premature rupture of membranes group, 285 in the preterm labor group, and 181 in the

Comment

The LBW neonate has an inherent gestational age–dependent vulnerability for long-term neurologic deficit. In the absence of genetic, infectious, and metabolic causes, these deficits are primarily due to major intraventricular hemorrhage and echolucent periventricular leukomalacia. Grades 3 and 4 intraventricular hemorrhage have been shown in several studies to result in a significantly higher rate of motor problems compared with gestational age– and birth weight–matched controls. Echolucent

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The fetus can deploy a local or systemic inflammatory response when exposed to microorganisms or, alternatively, to non-infection-related stimuli (e.g., danger signals or alarmins). The term “Fetal Inflammatory Response Syndrome” (FIRS) was coined to describe a condition characterized by evidence of a systemic inflammatory response, frequently a result of the activation of the innate limb of the immune response. FIRS can be diagnosed by an increased concentration of umbilical cord plasma or serum acute phase reactants such as C-reactive protein or cytokines (e.g., interleukin-6). Pathologic evidence of a systemic fetal inflammatory response indicates the presence of funisitis or chorionic vasculitis. FIRS was first described in patients at risk for intraamniotic infection who presented preterm labor with intact membranes or preterm prelabor rupture of the membranes. However, FIRS can also be observed in patients with sterile intra-amniotic inflammation, alloimmunization (e.g., Rh disease), and active autoimmune disorders. Neonates born with FIRS have a higher rate of complications, such as early-onset neonatal sepsis, intraventricular hemorrhage, periventricular leukomalacia, and death, than those born without FIRS. Survivors are at risk for long-term sequelae that may include bronchopulmonary dysplasia, neurodevelopmental disorders, such as cerebral palsy, retinopathy of prematurity, and sensorineuronal hearing loss. Experimental FIRS can be induced by intra-amniotic administration of bacteria, microbial products (such as endotoxin), or inflammatory cytokines (such as interleukin-1), and animal models have provided important insights about the mechanisms responsible for multiple organ involvement and dysfunction. A systemic fetal inflammatory response is thought to be adaptive, but, on occasion, may become dysregulated whereby a fetal cytokine storm ensues and can lead to multiple organ dysfunction and even fetal death if delivery does not occur (“rescued by birth”). Thus, the onset of preterm labor in this context can be considered to have survival value. The evidence so far suggests that FIRS may compound the effects of immaturity and neonatal inflammation, thus increasing the risk of neonatal complications and long-term morbidity. Modulation of a dysregulated fetal inflammatory response by the administration of antimicrobial agents, anti-inflammatory agents, or cell-based therapy holds promise to reduce infant morbidity and mortality.
Maternal chorioamnionitis & long term neurological morbidity in the offspring
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Citation Excerpt :
Studies have shown that preterm infants born to mothers with chorioamnionitis are at risk for adverse neurodevelopmental outcome.5,23,24 Several authors have observed an increased risk of severe intraventricular hemorrhage (IVH) and/or periventricular leukomalacia (PVL)25–30 in preterm infants exposed to chorioamnionitis. A large meta-analysis showed that clinical chorioamnionitis was significantly associated with the development of cystic periventricular leukomalacia and cerebral palsy (CP), but histological chorioamnionitis was only associated with development of periventricular leukomalacia in preterm infants.31
Chorioamnionitis is a common and potentially devastating complication of pregnancy associated with maternal and perinatal adverse outcomes.
To evaluate a possible association between maternal chorioamnionitis and long-term pediatric neurological morbidity.
A population-based retrospective cohort analysis was performed comparing the risk of long-term neurological morbidity. Pediatric neurological morbidity evaluated included hospitalizations with neurological morbidity. Kaplan–Meier survival curves were constructed to compare the cumulative neurological morbidity and a Cox regression model was used to control for confounders.
238 622 newborns were included. Of them, 0.5% were born to mothers with chorioamnionitis. 3.1% offspring were hospitalized with a neurological condition. Total neurological morbidity was not significantly more common in the chorioamnionitis group (3.8% vs. 3.1% respectively, OR 1.23, 95% CI 0.9–1.6, p = 0.147). However, a significant and independent association was noted between maternal chorioamnionitis and cerebral palsy. (0.5% vs. 0.1%, OR 5.77, 95% CI 2.5–13.0, p = 0.001). In a Cox proportional hazards model, controlling for preterm delivery, birthweight, maternal factors and mode of delivery the association between chorioamnionitis and cerebral palsy remained significant (adjusted HR = 2.78, 95% CI 1.20–6.43, P = 0.016).
Maternal chorioamnionitis is associated with cerebral palsy in the offspring, independently of other birth circumstances such as preterm delivery and birthweight.
Cerebral Palsy and Intellectual Disability in the Children of Women With Chronic Kidney Disease
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This study examined the risk of adverse maternal and neonatal outcomes, especially cerebral palsy and intellectual disability, in pregnant women with and without chronic kidney disease and their children.
In total, 156 pregnancies involving 139 women with chronic kidney disease who were treated at our center between 2001 and 2010 were identified. We also selected 3067 women without chronic kidney disease who delivered their infants without suffering any medical complications during the same period as control groups. Long-term neonatal prognosis was assessed based on the frequencies of cerebral palsy and/or intellectual disability.
The pregnant women had the following types of chronic kidney disease: immunoglobulin A nephropathy (n = 54), glomerulonephritis (n = 17), chronic renal failure (n = 16), nephrotic syndrome (n = 12), nephritis (n = 11), diabetic nephropathy (n = 10), congenital malformations and deformations (n = 10), purpura nephritis (n = 7), and others (n = 19). Of the children who were born to mothers with chronic kidney disease, one developed cerebral palsy, and another developed cerebral palsy with intellectual disability. Seven of the children who were born to mothers without chronic kidney disease developed cerebral palsy. The posterior probability of these conditions was 0.01900 and 0.002610 in the children born to mothers with and without chronic kidney disease, respectively. A primiparous mother (odds ratio [OR]: 4.07, 95% confidence interval [CI]): 2.78 to 5.95), preeclampsia (OR: 6.44, 95% CI: 3.92 to 10.59), grade 1 to 4 intraventricular hemorrhaging (OR: 7.71, 95% CI: 2.05 to 28.92), and an Apgar score of less than 7 at five minutes (OR: 0.51, 95% CI: 0.27 to 0.96) were found to influence the risk of cerebral palsy and/or intellectual disability in children born to women with chronic kidney disease.
We found that the incidence of cerebral palsy and/or intellectual disability is 7.2-fold higher in children born to women with chronic kidney disease than in those born to women without chronic kidney disease.
Leading causes of preterm delivery as risk factors for intraventricular hemorrhage in very preterm infants: results of the EPIPAGE 2 cohort study
2017, American Journal of Obstetrics and Gynecology
Intraventricular hemorrhage is a major risk factor for neurodevelopmental disabilities in preterm infants. However, few studies have investigated how pregnancy complications responsible for preterm delivery are related to intraventricular hemorrhage.
We sought to investigate the association between the main causes of preterm delivery and intraventricular hemorrhage in very preterm infants born in France during 2011 between 22-31 weeks of gestation.
The study included 3495 preterm infants from the national EPIPAGE 2 cohort study who were admitted to neonatal intensive care units and had at least 1 cranial ultrasound assessment. The primary outcome was grade I-IV intraventricular hemorrhage according to the Papile classification. Multinomial logistic regression models were used to study the relationship between risk of intraventricular hemorrhage and the leading causes of preterm delivery: vascular placental diseases, isolated intrauterine growth retardation, placental abruption, preterm labor, and premature rupture of membranes, with or without associated maternal inflammatory syndrome.
The overall frequency of grade IV, III, II, and I intraventricular hemorrhage was 3.8% (95% confidence interval, 3.2–4.5), 3.3% (95% confidence interval, 2.7–3.9), 12.1% (95% confidence interval, 11.0–13.3), and 17.0% (95% confidence interval, 15.7–18.4), respectively. After adjustment for gestational age, antenatal magnesium sulfate therapy, level of care in the maternity unit, antenatal corticosteroids, and chest compressions, infants born after placental abruption had a higher risk of grade IV and III intraventricular hemorrhage compared to those born under placental vascular disease conditions, with adjusted odds ratios of 4.3 (95% confidence interval, 1.1–17.0) and 4.4 (95% confidence interval, 1.1–17.6), respectively. Similarly, preterm labor with concurrent inflammatory syndrome was associated with an increased risk of grade IV intraventricular hemorrhage (adjusted odds ratio, 3.4; 95% confidence interval, 1.1–10.2]). Premature rupture of membranes did not significantly increase the risk.
Relationships between the causes of preterm birth and intraventricular hemorrhage were limited to specific and rare cases involving acute hypoxia-ischemia and/or inflammation. While the emergent nature of placental abruption would challenge any attempts to optimize management, the prenatal care offered during preterm labor could be improved.
Fetal and Maternal Responses to Intraamniotic Infection
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^☆: From the Departments of Obstetrics and Gynecology, Radiology, Neonatology, Pathology, and Basic Sciences, New York Medical College, Westchester County Medical Center.

^☆☆: Reprint requests: Uma Verma, MD, Westchester County Medical Center, Department of Obstetrics and Gynecology, Macy East, 2nd Floor, Valhalla, NY 10595.

^★: 6/1/78133

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Obstetric antecedents of intraventricular hemorrhage and periventricular leukomalacia in the low-birth-weight neonate☆,☆☆,★

Abstract

Section snippets

Methods

Results

Comment

Lancet

J Pediatr

Brain Dev

J Neurol Sci

Am J Obstet Gynecol

Am J Obstet Gynecol

Am J Obstet Gynecol

Cerebral palsy

N Engl J Med

Antecedents of cerebral palsy: multivariate analysis of risk

N Engl J Med

The frequency of cerebral palsy: a review of populations studies in industrialized nations since 1950: the epidemiology of cerebral palsies

Modern epidemiology

Applied logistic regression