Risk Factors For Periventricular Leukomalacia Research Articles

Risk Factors for Periventricular Leukomalacia in Preterm Infants: A Systematic Review, Meta-analysis, and GRADE-Based Assessment of Certainty of Evidence

BackgroundWe analyzed the certainty of evidence (CoE) for risk factors of periventricular leukomalacia (PVL) in preterm neonates, a common morbidity of prematurity. MethodsMedline, CENTRAL, Embase, and CINAHL were searched. Cohort and case-control studies and randomised randomized controlled trials were included. Data extraction was performed in duplicate. A random random-effects meta-analysis was utilizedused. CoE was evaluated as per Grading of Recommendations Assessment, Development and Evaluation (GRADE) guidelines. ResultsOne hundred eighty-six studies evaluating 95 risk factors for PVL were included. Of the 2,509,507 neonates assessed, 16,569 were diagnosed with PVL. Intraventricular hemorrhage [adjusted odds ratio: 3.22 (2.52-4.12)] had moderate CoE for its association with PVL. Other factors such as hypocarbia, chorioamnionitis, PPROM >48 hour, multifetal pregnancy reduction, antenatal indomethacin, lack of antenatal steroids, perinatal asphyxia, ventilation, shock/hypotension, patent ductus arteriosus requiring surgical ligation, late-onset circulatory collapse, sepsis, necrotizing enterocolitis, and neonatal surgery showed significant association with PVL after adjustment for confounders (CoE: very low to low). Amongst the risk factors associated with mother placental fetal (MPF) triad, there was paucity of literature related to genetic predisposition and defective placentation. Sensitivity analysis revealed that the strength of association between invasive ventilation and PVL decreased over time (P < 0.01), suggesting progress in ventilation strategies. Limited studies had evaluated diffuse PVL. ConclusionDespite decades of research, our findings indicate that the CoE is low to very low for most of the commonly attributed risk factors of PVL. Future studies should evaluate genetic predisposition and defective placentation in the MPF triad contributing to PVL. Studies evaluating exclusively diffuse PVL are warranted.

Factores Asociados a Hemorragia Intraventricular En Neonatos Atendidos En Un Hospital de Segundo Nivel

Intraventricular hemorrhage (HIV) is a complication in neonates. It originates in the subependymal germinal matrix. This area is irrigated by a network of poorly differentiated vessels without a basement membrane. Also, it is fragile and vulnerable to the hemodynamic instability of cerebral blood flow. It is an important risk factor for periventricular leukomalacia, ventriculomegaly, and hydrocephalus. These neurological pathologies can generate sequelae in the pediatric population such as cerebral palsy (CP). Objective: To identify the factors associated with HIV in neonates treated in the early intervention program of the hospital of specialties of the child and the woman of the Secretary of Health of the State of Querétaro (HENMSESEQ). Material and Methods: Through the review of the clinical files, the factors associated with HIV present in the children attended to in the HENMSESEQ early intervention service were observed in 2015. Cases of HIV were corroborated by means of transfontanel ultrasound, statistical analysis with measures of central tendency, and comparison of the medians of children diagnosed with HIV and without diagnosis. Results: A group of 69 infants attended to in the early intervention program was studied. Out of them, 65.2% (45) were women and 34.3% (24) were men. They had a gestational age of 34.19 ± 4.22 weeks, birth weight of 2116.09 ± 859.36 g, and height of 44.06 ± 6.02 cm. Their stay in the Neonatal Intensive Care Unit (NICU) for the sample was 11.88 ± 16.84 days and they were 8.65 ± 12.20 days with invasive mechanical ventilation. There were 25 cases of HIV diagnosed by transfontanel ultrasound. Out of the 25 cases, 7 (10%) were HIV grade I, 14 (20%) II, 4 (5.7%) III, and no cases of grade IV were diagnosed. Using the Mann-Whitney U test, a difference was found between the groups of neonates diagnosed with HIV and without diagnosis in weeks of gestation, height, weight, APGAR, days of intubation, and days of stay in NICU.

Trajectory of inflammatory and microglial activation markers in the postnatal rabbit brain following intrauterine endotoxin exposure

BackgroundMaternal infection is a risk factor for periventricular leukomalacia and cerebral palsy (CP) in neonates. We have previously demonstrated hypomyelination and motor deficits in newborn rabbits, as seen in patients with cerebral palsy, following maternal intrauterine endotoxin administration. This was associated with increased microglial activation, primarily involving the periventricular region (PVR). In this study we hypothesized that maternal intrauterine inflammation leads to a pro-inflammatory environment in the PVR that is associated with microglial activation in the first 2 postnatal weeks. MethodsTimed pregnant New Zealand white rabbits underwent laparotomy on gestational day 28 (G28). They were randomly divided to receive lipopolysaccharide (LPS; 20μg/kg in 1mL saline) (Endotoxin group) or saline (1mL) (control saline, CS group), administrated along the wall of the uterus. The PVR from the CS and Endotoxin kits were harvested at G29 (1day post-injury), postnatal day1 (PND1, 3day post-injury) and PND5 (7days post-injury) for real-time PCR, ELISA and immunohistochemistry. Kits from CS and Endotoxin groups underwent longitudinal MicroPET imaging, with [11C]PK11195, a tracer for microglial activation. ResultsWe found that intrauterine endotoxin exposure resulted in pro-inflammatory microglial activation in the PVR of rabbits in the first postnatal week. This was evidenced by increased TSPO (translocator protein) expression co-localized with microglia/macrophages in the PVR, and changes in the microglial morphology (ameboid soma and retracted processes). In addition, CD11b level significantly increased with a concomitant decline in the CD45 level in the PVR at G29 and PND1. There was a significant elevation of pro-inflammatory cytokines and iNOS, and decreased anti-inflammatory markers in the Endotoxin kits at G29, PND1 and PND5. Increased [11C]PK11195 binding to the TSPO measured in vivo by PET imaging in the brain of Endotoxin kits was present up to PND14–17. ConclusionsOur results indicate that a robust pro-inflammatory microglial phenotype/brain milieu commenced within 24h after LPS exposure and persisted through PND5 and in vivo TSPO binding was found at PND14–17. This suggests that there may be a window of opportunity to treat after birth. Therapies aimed at inducing an anti-inflammatory phenotype in microglia might promote recovery in maternal inflammation induced neonatal brain injury.

Risk factors of periventricular leukomalacia in singleton infants born from 23rd to 26th weeks of gestation – Retrospective study

IntroductionPeriventricular leukomalacia (PVL) is one of the most common hypoxic-ischemic pathologies among preterm newborns. The bracket most vulnerable to PVL are newborns born before 34 weeks’ gestation, especially those with very low and extremely low birth weights. In a population of very low birth weight newborns, the frequency of periventricular white matter injury (PWMI) including PVL is 5–15%. The aim of our study was to verify the potential risk factors of the occurrence of PVL among infants born between 23 and 26 weeks’ gestation. MethodsThe retrospective study included a group of 115 unrelated infants born between 23 and 26 week's gestation, hospitalized in the Neonatal Intensive Care in the Department of Neonatology, Poznan University of Medical Sciences in 2010–2014, born in the clinic or transported to it after birth in the hospital of lower references. The diagnosis of PVL was based on transcranial ultrasound. ResultsPVL was diagnosed in 17 (14.8%), including 5 (29.4%) infants born from 23 to 24 weeks’ gestation and 12 (70.6%) born from 25 to 26 weeks gestation. Higher incidence of PVL was found among infants born outside tertiary hospital (OR 7.933 (2.206–35.19); p=0.0005) and newborns diagnosed with III and IV intraventricular hemorrhage (IVH) (OR 3.273 (1.042–10.28); p=0.036). ConclusionsDelivery in the third-level hospital as well as IVH prevention significantly reduces the risk of PVL. Well-developed prenatal care, fetus transport in utero and delivery in the third-level hospital seem to be crucial in the prevention of this pathology.

COL4A1 Mutations Associated with a Characteristic Pattern of Intracranial Calcification

Intracranial calcification (ICC) is a relatively common radiological finding in children undergoing investigation for neurological disorders. Many causes are recognised, and ICC is often regarded as a non-specific sign.From an ongoing study of ICC, we identified 5 patients with characteristic radiological features, in whom a mutation in the COL4A1 gene was found.All patients had CT and MR imaging. MR images demonstrated features of periventricular leukomalacia with irregular dilatation of the lateral ventricles with or without porencephaly, loss of hemispheric white matter volume, and high signal on T2 and FLAIR sequences within periventricular and deep white matter. Calcification was apparent on MR in 4 patients. CT scans demonstrated spot and linear calcification in the subependymal region and around areas of porencephaly. Calcification was also visible in the deep cerebral white matter and basal ganglia. 1 patient showed calcification in the central pons.ICC occurs in COL4A1-related disease. The radiological features are distinct from other conditions demonstrating recognisable patterns of ICC, such as congenital cytomegalovirus infection and Aicardi-Goutiéres syndrome. In the absence of a known risk factor for periventricular leukomalacia, the presence of these radio-logical findings should suggest the possibility of COL4A1-related disease.

The Role of Hypocarbia in the Development of Cystic Periventricular Leukomalacia

Abstract: Cystic periventricular leukomalacia (PVL) is one of the most severe and frequent cause of cerebral palsy in children surviving preterm birth. The pathogenesis of PVL yet is not completely understood. The majority of the theories consider the necrotic foci to be hypoxic-ischemic lesions, resulting from impaired perfusion at the vascular border zones between ventriculopedal and ventriculofugal arteries, as the latter are poorly developed in preterm infants. Besides periventricular vascular anatomic factors and pressure-passive cerebral circulation the intrinsic vulnerability of cerebral white matter (a particular vulnerability of rapidly differentiating oligodendroglial cells) of preterm infants plays an important role. An alternative view focuses on the role of intrauterine infection and the fetal inflammatory response syndrome. Hypocarbia has been identified as an independent risk factor for PVL in many studies. As far as the pathogenesis of PVL is complex and likely multifactorial, the influence of hypocarbia on subsequent white matter damage is most striking in postnatal acquired and late onset cystic PVL. This review analyses clinical trials demonstrating an association between hypocarbia and PVL. Physiological studies on cerebrovascular autoregulation and animal studies presented in this review try to elucidate the underlying mechanisms.

Late-onset circulatory dysfunction of premature infants and late-onset periventricular leukomalacia

The sudden appearance of hypotension and oliguria without obvious cause following stable circulation and respiration in preterm infants is frequent in Japan. Such episodes are referred to as late-onset circulatory dysfunction of premature infants (LCD). Volume expanders and inotropic agents are often ineffective against this condition, whereas i.v. steroids are significantly effective. A major problem is that cystic periventricular leukomalacia (PVL) often develops a few weeks after an episode. The aim of the present study was to clarify the risk factors, including LCD, related to cystic PVL. A case-control study was performed for preterm infants who were delivered at <33 weeks of gestation and admitted to seven neonatal intensive care units in Japan. Cystic PVL infants were stratified into early-onset PVL diagnosed within 28 days of age and late-onset PVL diagnosed after more than 28 days of age. The reported and new risk factors for PVL, for each group of PVL infants, and for all PVL infants, were compared with controls. Thirty-two infants were diagnosed with cystic PVL (17 early-onset and 15 late-onset). All PVL infants significantly differed from controls on Apgar score, number of abortions and pregnancies, intraventricular hemorrhage, and LCD. LCD was diagnosed in 28.1% of both PVL groups compared with 6.3% of controls (P = 0.02). Multivariate analysis demonstrated significant association between late-onset PVL and LCD. LCD was significantly associated with cystic PVL, especially late-onset PVL. Elucidating the cause of LCD might reduce the incidence of PVL and improve the neurological prognosis of preterm infants.

Rupture très prématurée des membranes: physiopathologie des conséquences neurologiques

The premature rupture of membranes (PROM) is responsible for 30 % of the premature births because of a high risk of associated chorioamnionitis. PROM and the perinatal infection are recognized as 2 of the main risk factors of periventricular leukomalacia and white matter disease in very preterm neonates. Inflammation associated with PROM is likely to induce neuronal or glial cell death at a developmental stage of great vulnerability for the developing brain. Several mechanisms (release of cytokines, accumulation of free radicals, excitotoxicity, apoptosis...) account for this deleterious effect. The decision to actively extract a fetus subjected to a fetal inflammatory response syndrome should take account of the risks of a proved intrauterine infection for both the mother and the fetus and the risks for the neonate related to a very preterm birth per se. A reasonable attitude seems not to maintain a fetus in an undoubtful septic context in utero if a preterm birth in the very short term appears unevitable. Practically, no consensus gives a recommendation between aggressive or conservative management in case of PROM within 30 and 34 weeks'gestation. Expectant management seems to be indicated before 28 weeks'gestation and intentional delivery could be recommended beyond 34 weeks'gestation due to increased maternal risks compared to relatively low incidence of the complications of prematurity at this term.

Cumulative Index of Exposure to Hypocarbia and Hyperoxia as Risk Factors for Periventricular Leukomalacia in Low Birth Weight Infants

Hypocarbia and hyperoxia are risk factors for periventricular leukomalacia in low birth weight infants. The association of a cumulative index of exposure to hypocarbia and hyperoxia and periventricular leukomalacia has not been evaluated. Our goal was to examine the relationship between cumulative index of exposure to hypocarbia and hyperoxia and periventricular leukomalacia during the first 7 days of life in low birth weight infants. Blood gas results were recorded in 6-hour intervals among low birth weight infants in a prospective data registry. Cumulative index of exposure to hypocarbia was calculated as the difference between arterial carbon dioxide level and 35 mmHg multiplied by the time interval in hours for each 6-hour block in a 24-hour day for the first 7 days of life. Cumulative index of exposure to hyperoxia was calculated in the same manner for arterial oxygen level >80 mm Hg. The relationship between exposure to hypocarbia, hyperoxia, and periventricular leukomalacia was examined in 778 infants with blood gas and cranial sonography data. Twenty-one infants had periventricular leukomalacia. Hypocarbia occurred in 489 infants and hyperoxia in 502 infants. Infants with periventricular leukomalacia were more likely to have a lower gestational age and to require delivery room resuscitation than those without periventricular leukomalacia. More infants in the highest quartile of exposure to hypocarbia had periventricular leukomalacia compared to those with no hypocarbia. Risk of periventricular leukomalacia was increased in infants with the highest quartile of exposure to hypocarbia after adjusting for maternal and neonatal variables, none to be associated with periventricular leukomalacia. Cumulative index exposure to hyperoxia was not related to periventricular leukomalacia. Cumulative exposure to hypocarbia and not hyperoxia was independently related to risk of periventricular leukomalacia in low birth weight infants.

Periventricular leukomalacia is common after neonatal cardiac surgery

Objectives Periventricular leukomalacia is necrosis of the cerebral white matter adjacent to the lateral ventricles and results from injury to immature oligodendroglia. In infants without congenital heart disease, periventricular leukomalacia is associated with an increased incidence of developmental delay and attention deficit/hyperactivity disorder. The incidence of periventricular leukomalacia and the risk factors for development of periventricular leukomalacia after infant cardiac surgery are not known. Methods Magnetic resonance imaging of the brain was performed 6 to 14 days after cardiac surgery utilizing cardiopulmonary bypass with or without deep hypothermic circulatory arrest in 105 neonates and infants ≤ 6 months of age. Results Median age at surgery was 6 days (range 1-178), with 82 neonates (age ≤ 30 days). Periventricular leukomalacia was found in 44 of the neonates (54%) compared with 1 of 23 infants (4%). Forward logistic regression using age at surgery as a continuous variable identified a model containing longer total support time (cardiopulmonary bypass plus deep hypothermic circulatory arrest), lower systolic blood pressure at cardiac intensive care unit admission postoperatively, lower minimum diastolic blood pressure, and P o 2 in the first 48 hours after surgery. When age at surgery was considered as a dichotomous variable (neonate versus infant), younger age at surgery replaced systolic blood pressure, P o 2, and total support time in the model. Lower minimum diastolic blood pressure was a significant risk factor in both models. Conclusions Periventricular leukomalacia was found in >50% of neonates after cardiac surgery but rarely in older infants. Hypoxemia and hypotension in the early postoperative period, particularly diastolic hypotension, may be important risk factors for periventricular leukomalacia.

Periventricular leukomalacia following neonatal and infant cardiac surgery

The dramatic reduction in surgical mortality following repair of congenital heart defects has been accompanied by increasing recognition of adverse neurodevelopmental sequelae in some children. Neurodevelopmental abnormalities following neonatal and infant cardiac surgery include mild cognitive impairment, expressive speech and language abnormalities, impaired attention and executive function, impaired visual and spatial motor skills, as well as learning disabilities. These defects result in a significant need for early intervention, as well as rehabilitative and special education services. Central nervous system injury following repair of congenital heart defects results from a complex interaction of patient specific and environmental factors. Recent studies suggest that cerebral white matter injury characterized by periventricular leukomalacia (PVL) is common in infants with congenital heart disease particularly following cardiac surgery. Studies at our institution show that this occurs in greater than 50% of neonates following cardiac surgery, but is rare in older infants. Prolonged exposure to cardiopulmonary bypass (with or without deep hypothermic circulatory arrest) is a risk factor for PVL, possibly secondary to the systemic inflammatory response to cardiopulmonary bypass. Hypotension and hypoxemia in the early postoperative period, especially diastolic hypotension, significantly increase the risk of PVL. Future studies are needed to determine significance of PVL as a marker for long-term developmental dysfunction.

Significance of clinical risk factors of cystic periventricular leukomalacia in infants with different birthweights

Fifteen appropriate-for-date premature low-birthweight infants with cystic periventricular leukomalacia (PVL) were studied. The infants were stratified into three birthweight groups: less than 1000 g, 1000 g and greater but less than 1500 g, and 1500 g or greater. Reported and new risk factors for PVL were compared with control patients for all patients and each birthweight group. Hypocarbia was significantly related to cystic PVL, especially in infants with birthweight 1000 g or greater (p < 0.03). Sensitivity to hypocarbia might be decreased in infants with birthweight less than 1000 g due to therapy or prematurity. In the group with birthweight less than 1000 g, the proportion of cystic PVL infants on continuous intra-arterial blood-pressure monitoring tended to be lower than the controls, with an almost significant difference (p= 0.05). The duration of tocolysis was significantly longer in the cystic PVL infants than in the controls when the birthweight was greater than 1500 g (p < 0.04). For some risk factors, a significant difference or a tendency of difference was demonstrated only after stratifying the birthweight. For others, the difference became insignificant after stratification. Assessing risk factors after stratifying by birthweight or degree of prematurity is therefore useful. Conclusion: The results suggest that hypocarbia should be avoided to prevent cystic PVL, especially in infants with birthweight of 1000 g or greater, continuous intra-arterial blood-pressure monitoring may be important in infants with birthweight less than 1000 g, and fetal status should be monitored carefully when the duration of tocolysis is prolonged, especially in infants with birthweight of 1500 g or more.

Significance of clinical risk factors of cystic periventricular leukomalacia in infants with different birthweights

Fifteen appropriate-for-date premature low-birthweight infants with cystic periventricular leukomalacia (PVL) were studied. The infants were stratified into three birthweight groups: less than 1000 g, 1000 g and greater but less than 1500 g, and 1500 g or greater. Reported and new risk factors for PVL were compared with control patients for all patients and each birthweight group. Hypocarbia was significantly related to cystic PVL, especially in infants with birthweight 1000 g or greater (p < 0.03). Sensitivity to hypocarbia might be decreased in infants with birthweight less than 1000 g due to therapy or prematurity. In the group with birthweight less than 1000 g, the proportion of cystic PVL infants on continuous intra-arterial blood-pressure monitoring tended to be lower than the controls, with an almost significant difference (p = 0.05). The duration of tocolysis was significantly longer in the cystic PVL infants than in the controls when the birthweight was greater than 1500 g (p < 0.04). For some risk factors, a significant difference or a tendency of difference was demonstrated only after stratifying the birthweight. For others, the difference became insignificant after stratification. Assessing risk factors after stratifying by birthweight or degree of prematurity is therefore useful. The results suggest that hypocarbia should be avoided to prevent cystic PVL, especially in infants with birthweight of 1000 g or greater, continuous intra-arterial blood-pressure monitoring may be important in infants with birthweight less than 1000 g, and fetal status should be monitored carefully when the duration of tocolysis is prolonged, especially in infants with birthweight of 1500 g or more.

Are Neonatal Brain Lesions due to Intrauterine Infection Related to Mode of Delivery?

Studies of antenatal and intrapartum factors involved in the development of cerebral palsy have identified intrauterine infection and chorioamnionitis as high risk situations for white matter damage, especially periventricular leukomalacia. To characterise adverse or protective perinatal factors further, we undertook a multiple regression analysis of selected perinatal events in a population of 110 inborn premature neonates with documented chorioamnionitis. In the total population of 110 infants delivered at between 25 and 32 weeks, 101 (92%) survived the first week of life and two were subsequently excluded. Of the 99 remaining infants, 20 (20%) developed periventricular leukomalacia including 16 (80%) cystic lesions. Forty-five (45%) babies were born by lower segment caesarean section, and for 37 of these, this was carried out before labour. Fetal presentation at delivery was breech in 14 (26%) of those born vaginally and 23 (52%) of those born by lower segment caesarean section (OR 3 [95% CI 1.3-7]). Among predetermined perinatal risk factors for periventricular leukomalacia, logistic regression analysis showed that delivery by caesarean section was associated with a dramatic decrease in the incidence of periventricular leukomalacia (OR 0.15 [95% CI 0.04-0.57]). These preliminary results warrant confirmation and preferably a prospective study before considering caesarean section as a protective perinatal factor of periventricular leukomalacia.

Obstetric risk factors for periventricular leukomalacia among preterm infants.

To evaluate the obstetric antecedents of cystic periventricular leukomalacia and transient echodense periventricular lesions among preterm infants. A cohort study of preterm singleton infants born between 25 and 33 weeks gestation. Pavia, Italy. Three hundred and forty-nine infants admitted to a Division of Neonatal Intensive Care who were screened for periventricular leukomalacia. The obstetric factors in infants with either cystic periventricular leukomalacia or transient echodense periventricular lesions were compared to those in infants with negative cranial ultrasonographic findings. Stepwise multiple logistic regression analysis was used to evaluate the association between risk factors and outcomes adjusting for confounders. The prevalence of cystic periventricular leukomalacia and transient echodense lesions was 5.7% (20/349) and 14% (49/349), respectively. The main risk factors for cystic leukomalacia were first trimester haemorrhage (OR 4.49; 95% CI 1.63-12.39), maternal urinary tract infection on admission (OR 5.71; 95% CI 1.91-17.07), and neonatal acidosis (pH < 7.2) at birth (OR 5.97; 95% CI 1.93-18.52). Meconium-stained amniotic fluid (OR 3.95; 95% CI 1.42-10.98) and long term (> 72 hours) ritodrine tocolysis (OR 2.54; 95% CI 1.28-5.05) were associated with an increased risk of echodense lesions. The likelihood of overall leukomalacia (cystic plus echodense periventricular lesions) was increased among cases with meconium-stained amniotic fluid (OR 4.06; 95% CI 1.65-10.0), long-term ritodrine tocolysis (OR 2.56; 95% CI 1.38-4.72), maternal infection (OR 1.73; 95% CI 1.0-3.0), and acidosis at birth (OR 1.98; 95% CI 1.0-3.98). This study confirms that maternal infection, acidosis at birth, and meconium-stained amniotic fluid increase the risk of periventricular leukomalacia in preterm infants. Long-term ritodrine use seems to increase the risk for transient echodense lesions.

Multifetal Pregnancy Reduction: A Possible Risk Factor for Periventricular Leukomalacia in Premature Newborns

Objective: To investigate the possible role of multifetal pregnancy reduction as a risk factor for the development of periventricular leukomalacia, which has been associated with prematurity and twin pregnancies. Design: A case-control study. Setting: In Vitro Fertilization Unit and Intensive Care Nursery of the Tel Aviv Sourasky Medical Center, Tel Aviv, Israel. Patient(s): A total of 1,401 consecutive preterm infants who were born between January 1, 1994, and December 31, 1995. Intervention(s): Cranial ultrasonographic evaluation of each infant within 3 days of birth. Main Outcome Measure(s): Premature infants who developed periventricular leukomalacia (cases) were compared with premature infants who did not develop this disorder (controls) when multifetal pregnancy reduction was considered. Result(s): Fourteen premature infants developed periventricular leukomalacia. Of these, 28.6% (4 infants) were exposed to multifetal pregnancy reduction, compared with 1.9% of the controls, giving an odds ratio (OR) of 20.9 (95% confidence interval [CI] 5.5–79.4). Adjustment of this OR for IVF treatment (OR, 18.6; 95% CI, 1.8–140.3), twinning (OR, 6.3; 95% CI, 1.3–30.3), and for both IVF treatment and twinning simultaneously (OR, 8.5; 95% CI, 1.7–42.2) did not explain all the observed associations between periventricular leukomalacia and multifetal pregnancy reduction. Conclusion(s): Our data suggest that multifetal pregnancy reduction may be an additional risk factor for periventricular leukomalacia among premature infants, regardless of twinning.

Risk Factors for Cystic Periventricular Leukomalacia in Very-Low-Birth-Weight Infants † 1232

Cystic periventricular leukomalacia (PVL) occurs most commonly in very-low-birth-weight (VLBW, <1500 gm) infants and is associated with poor developmental outcome. Ischemia has been implicated in the pathogenesis of PVL and recently intrapartum magnesium sulfate (MAG) treatment has been suggested to be neuroprotective; however, clinically relevant risk factors and preventive measures for PVL in VLBW infants remain unclear. We performed a retrospective, matched case-control study of the predictors of PVL in all infants <1500 gm BW from 6/90 to 12/95, during which early and late sonographic screening was routine. We studied anteparum, intrapartum, and postnatal factors, concentrating on vascular, respiratory, and infectious factors, and on intrapartum MAG exposure. We identified 1417 VLBW infants and 54 cases of cystic PVL (inc. 3.8%) and matched 54 controls with normal sonograms (latest at least 30 days) for ±150 gm BW and date of birth. Controls and cases were similar in mean BW (978±234 vs 945±250gm) and gestational age (28±2 wks). PVL cases were more likely to be outborn (37% vs 19%), to have a rapid(≤3 hrs) period from rupture of membranes (ROM) to birth (62% vs 41%), to have a patent ductus arteriousus (60% vs 37%), and to have a higher max PaCO2 in the first 72 hrs (55±16 vs 48±16) and were less likely to have pre-eclampsia (4%vs 15%) (all P≤0.05). The proportions of any intrapartum MAG, tocolytic MAG, steroid use, chorioamnionitis, SGA, RDS, and indomethacin use were similar. When controlled for indomethacin use, MAG use, PaCO2, and delivery location, a logistic regression model determined that predictors for PVL were as in Table. We conclude that PDA and rapid labor course are risk factors for PVL and that pre-eclampsia is more important than MAG use in reducing brain injury.

Are neonatal brain lesions due to intrauterine infection related to mode of delivery?

Studies of antenatal and intrapartum factors involved in the development of cerebral palsy have identified intrauterine infection and chorioamnionitis as high risk situations for white matter damage, especially periventricular leukomalacia. To characterise adverse or protective perinatal factors further, we undertook a multiple regression analysis of selected perinatal events in a population of 110 inborn premature neonates with documented chorioamnionitis. In the total population of 110 infants delivered at between 25 and 32 weeks, 101 (92%) survived the first week of life and two were subsequently excluded. Of the 99 remaining infants, 20 (20%) developed periventricular leukomalacia including 16 (80%) cystic lesions. Forty-five (45%) babies were born by lower segment caesarean section, and for 37 of these, this was carried out before labour. Fetal presentation at delivery was breech in 14 (26%) of those born vaginally and 23 (52%) of those born by lower segment caesarean section (OR 3 [95% CI 1.3-7]). Among predetermined perinatal risk factors for periventricular leukomalacia, logistic regression analysis showed that delivery by caesarean section was associated with a dramatic decrease in the incidence of periventricular leukomalacia (OR 0.15 [95% CI 0.04-0.57]). These preliminary results warrant confirmation and preferably a prospective study before considering caesarean section as a protective perinatal factor of periventricular leukomalacia.

O-129 Multifetal pregnancy reduction—a possible risk factor for periventricular leukomalacia in premature newborns

O-129 Multifetal pregnancy reduction—a possible risk factor for periventricular leukomalacia in premature newborns

Interleukin-6 concentrations in umbilical cord plasma are elevated in neonates with white matter lesions associated with periventricular leukomalacia

OBJECTIVE: Periventricular leukomalacia, a common brain white matter lesion in preterm neonates, is a major risk factor for cerebral palsy. Recently, cytokines (i.e., tumor necrosis factor and interleukin-lJ~) have been implicated as mediators for the development of periventricular leukomalacia. The purpose of this study was to examine the relationship between umbilical cord plasma levels of tumor necrosis factor-cq interleukin-l[3, interleukin-6, and interleukin-1 receptor antagonist and the occurrence of periventricular leukomalacia in preterm neonates. STUDY DESIGN: Umbilical cord blood was collected from 172 consecutive preterm births (25 to 36 weeks). Periventricular leukomalacia-associated lesions were diagnosed by brain ultrasonography within the first 3 days of life. Tumor necrosis factor-cq interleukin-ll3, interleukin-6, and interleukin-1 receptor antagonist were measured by sensitive and specific enzyme-linked immunoassay methods. Umbilical cord arterial pH was measured at birth. Statistical analysis was performed with multiple logistic regression and receiver operating characteristic curve analysis. RESULTS: Periventricular leukomalacia-associated lesions were present in 14.5% (25/172) of infants. Plasma concentrations of interleukin-6 but not of tumor necrosis factor-cq interleukin-l[3, and interleukin-1 receptor antagonist were significantly higher in neonates with periventricular leukomalacia-associated lesions than in those without these lesions (median 718, range 400 pg/ml had a sensitivity of 72% (18/25) and a specificity of 74% (108/147) in the identification of periventricular leukomalacia-associated lesions. Multivariate analysis showed that umbilical cord interleukin-6 was an independent risk factor for periventricular leukomalacia (odds ratio 6.2, p < 0.002) after correction for known confounding variables (i.e., gestational age at birth, umbilical artery pH, chorioamnionitis). CONCLUSIONS: Interleukin-6 concentrations in umbilical cord plasma are elevated in neonates with periventricular ieukomalacia-associated lesions. Our data support the hypothesis that periventricular leukomalacia may be the result of cytokine-mediated brain injury. (AM J OBSTET GYNECOL 1996;174:1433-40.)