Additional Value of 3-Month Cranial Magnetic Resonance Imaging in Infants with Neonatal Encephalopathy following Perinatal Asphyxia.

OBJECTIVE: To assess the evolution of neonatal brain injury noted on magnetic resonance imaging (MRI), develop a score to assess brain injury on 3-month MRI, and determine the association of 3-month MRI with neurodevelopmental outcome in neonatal encephalopathy (NE) following perinatal asphyxia. METHODS: This was a retrospective, single-center study including 63 infants with perinatal asphyxia and NE (n = 28 cooled) with cranial MRI <2 weeks and 2-4 months after birth. Both scans were assessed using biometrics, a validated injury score for neonatal MRI, and a new score for 3-month MRI, with a white matter (WM), deep gray matter (DGM), and cerebellum subscore. The evolution of brain lesions was assessed, and both scans were related to 18- to 24-month composite outcome. Adverse outcome included cerebral palsy, neurodevelopmental delay, hearing/visual impairment, and epilepsy. RESULTS: Neonatal DGM injury generally evolved into DGM atrophy and focal signal abnormalities, and WM/watershed injury evolved into WM and/or cortical atrophy. Although the neonatal total and DGM scores were associated with composite adverse outcomes, the 3-month DGM score (OR 1.5, 95% CI 1.2-2.0) and WM score (OR 1.1, 95% CI 1.0-1.3) also were associated with composite adverse outcomes (occurring in n = 23). The 3-month multivariable model (including the DGM and WM subscores) had higher positive (0.88 vs 0.83) but lower negative predictive value (0.83 vs 0.84) than neonatal MRI. Inter-rater agreement for the total, WM, and DGM 3-month score was 0.93, 0.86, and 0.59. CONCLUSIONS: In particular, DGM abnormalities on 3-month MRI, preceded by DGM abnormalities on the neonatal MRI, were associated with 18- to 24-month outcome, indicating the utility of 3-month MRI for treatment evaluation in neuroprotective trials. However, the clinical usefulness of 3-month MRI seems limited compared with neonatal MRI.

Placental pathology in full-term infants with hypoxic-ischemic neonatal encephalopathy and association with magnetic resonance imaging pattern of brain injury.

OBJECTIVE: To investigate the relationship between placental pathology and pattern of brain injury in full-term infants with neonatal encephalopathy after a presumed hypoxic-ischemic insult. STUDY DESIGN: The study group comprised full-term infants with neonatal encephalopathy subsequent to presumed hypoxia-ischemia with available placenta for analysis who underwent cerebral magnetic resonance imaging (MRI) within the first 15 days after birth. Macroscopic and microscopic characteristics of the placenta were assessed. The infants were classified according to the predominant pattern of brain injury detected on MRI: no injury, predominant white matter/watershed injury, predominant basal ganglia and thalami (BGT) injury, or white matter/watershed injury with BGT involvement. Maternal and perinatal clinical factors were recorded. RESULTS: Placental tissue was available for analysis in 95 of 171 infants evaluated (56%). Among these 95 infants, 34 had no cerebral abnormalities on MRI, 27 had white matter/watershed injury, 18 had BGT injury, and 16 had white matter/watershed injury with BGT involvement. Chorioamnionitis was a common placental finding in both the infants without injury (59%) and those with white matter/BGT injury (56%). On multinomial logistic regression analysis, white matter/watershed injury with and without BGT involvement was associated with decreased placental maturation. Hypoglycemia was associated with an increased risk of the white matter/BGT injury pattern (OR,5.4; 95% CI, 1.4-21.4). The BGT injury pattern was associated with chronic villitis (OR, 12.7; 95% CI, 2.4-68.7). A placental weight <10th percentile appeared to be protective against brain injury, especially for the BGT pattern (OR, 0.1; 95% CI, 0.01-0.7). CONCLUSION: Placental weight <10th percentile was mainly associated with normal cerebral MRI findings. Decreased placental maturation and hypoglycemia <2.0 mmol/L were associated with increased risk of white matter/watershed injury with or without BGT involvement. Chronic villitis was associated with BGT injury irrespective of white matter injury.

Diffusion-weighted imaging changes in cerebral watershed distribution following neonatal encephalopathy are not invariably associated with an adverse outcome.

AIM: Patterns of injury in term-born infants with neonatal encephalopathy following hypoxia-ischaemia are seen earlier and are more conspicuous on diffusion-weighted magnetic resonance imaging (DW-MRI) than on conventional imaging. Although the prognostic value of DW-MRI in infants with basal ganglia and thalamic damage has been established, data in infants in whom there is extensive injury in a watershed distribution are limited. The aim of this study was to assess cognitive and functional motor outcome in a cohort of infants with changes in a predominantly watershed distribution injury on neonatal cerebral MRI, including DWI. METHOD: DW-MRI findings in infants with neonatal encephalopathy following hypoxia-ischaemia were evaluated retrospectively. Twenty-two infants in whom DWI changes exhibited a predominantly watershed distribution were enrolled in the study (10 males, 12 females; mean birthweight 3337 g, 2830-3900 g; mean gestational age 40.5 wks, 37.9-42.1 wks). Follow-up MRI data at the age of 3 months (n=15) and over the age of 18 months (n=7) were analysed. In survivors, neurodevelopmental outcome was assessed with the Griffiths Mental Development Scales at the age of at least 18 months. Amplitude-integrated electroencephalography was used to score background patterns and the occurrence of epileptiform activity. RESULTS: DW-MRI revealed abnormalities that were bilateral in all infants and symmetrical in 10. The posterior regions were more severely affected in five infants and the anterior regions in three. Watershed injury occurred in isolation in 10 out of 22 infants and was associated with involvement of the basal ganglia and thalami in the other 12, of whom seven died. Cystic evolution, seen on MRI at age 3 months, occurred in three of the 15 surviving infants. Neurodevelopmental assessment of the surviving infants was performed at a median age of 35 months (range 18-48 mo). Of the five survivors with basal ganglia and thalamic involvement, two developed cerebral palsy, one had a developmental quotient of less than 85, and two had a normal outcome. Of the 10 infants with isolated watershed injury, nine had an early normal motor and cognitive outcome. In all infants with a favourable outcome, background recovery was seen on amplitude integrated EEG within 48 hours after birth. CONCLUSION: Extensive DWI changes in a watershed distribution in term-born neonates are not invariably associated with adverse sequelae, even in the presence of cystic evolution. Associated lesions of the basal ganglia and thalami are a better predictor of adverse sequelae than the extent and severity of the watershed abnormalities seen on DW-MRI.

Role of thrombophilic factors in full-term infants with neonatal encephalopathy.

BACKGROUND: Neonatal encephalopathy (NE) is a serious condition, primarily seen following hypoxia-ischemia (HI). Two different patterns of brain injury can be recognized on magnetic resonance imaging (MRI): white matter/watershed (WM/WS) or basal ganglia/thalamus (BGT) injury. Whether these patterns of injury can be attributed to different associated risk factors still needs to be established. METHODS: In 118 infants with clinical signs of NE following perinatal HI, thrombophilic factors, such as factor V Leiden and prothrombin gene mutation, C677T and A1298C polymorphisms in the methylenetetrahydrofolate reductase (MTHFR) gene, and plasma levels of homocysteine and lipoprotein(a), were prospectively investigated. Antenatal and perinatal variables were studied. RESULTS: WM/WS injury was seen in 45 infants, BGT injury in 40, and normal neuroimaging in 33. Antenatal factors did not differ across these groups. The BGT pattern was associated with lower Apgar scores, whereas the WM/WS pattern was associated with hypoglycemia (<2.0 mmol/l), CT or TT 677 polymorphism in the MTHFR gene, and plasma homocysteine levels in the upper quartile. CONCLUSION: In infants with NE following perinatal HI, the WM/WS pattern of injury was associated with hypoglycemia, the MTHFR 677CT or TT genotype, and higher levels of plasma homocysteine. BGT injury showed an association with signs suggestive of acute HI.

Risk factors for perinatal arterial ischaemic stroke in full-term infants: a case-control study.

OBJECTIVE: The incidence of perinatal arterial ischaemic stroke (PAIS) is about 1 in 2300 live births. Evidence about the aetiology is still lacking. The aim of this study was to identify maternal, perinatal and neonatal risk factors for symptomatic PAIS in full-term infants. METHODS: Each full-term infant with PAIS was matched to three healthy controls for gestational age, date of birth and hospital of birth. Antenatal and perinatal risk factors were studied using univariate and multivariate conditional logistic regression analysis. RESULTS: Fifty-two infants were diagnosed with PAIS. Significant risk factors in the univariate analysis (p<0.05) were nulliparity (64% vs 47%), maternal fever (>38°C) during delivery (10% vs 1%), fetal heart rate decelerations (63% vs 16%), meconium-stained amniotic fluid (44% vs 17%), emergency caesarean section (35 vs 2%), Apgar score (1 min) ≤3 (29% vs 1%), Apgar score (5 min) <7 (25% vs 1%), umbilical artery pH <7.10 (56% vs 10%), hypoglycaemia <2.0 mmol/l (29% vs 3%) and early-onset sepsis/meningitis (14% vs 2%). In the multivariate analysis, maternal fever (OR 10.2; 95% CI 1.3 to 78.5), Apgar score (5 min) <7 (OR 18.1; 95% CI 3.4 to 96.8), hypoglycaemia <2.0 mmol/l (OR 13.0; 95% CI 3.2 to 52.6) and early-onset sepsis/meningitis (OR 5.8; 95% CI 1.1 to 31.9) were significantly associated with PAIS. CONCLUSIONS: Maternal fever during delivery and early-onset sepsis/meningitis were found to be involved with PAIS as was previously noted. Apgar score (5 min) <7 and hypoglycaemia were found to be important risk factors in term PAIS.

Atypical timing and presentation of periventricular haemorrhagic infarction in preterm infants: the role of thrombophilia.

AIM: Periventricular haemorrhagic infarction (PVHI) is a complication of preterm birth associated with cardiorespiratory instability. To date, the role of thrombophilia as a possible additional risk factor in infants with atypical timing and presentation of PVHI has not been investigated. METHOD: This was a retrospective cohort study of preterm infants who developed PVHI with an atypical timing and presentation either of antenatal onset or late in the postnatal course in the absence of a preceding sudden deterioration of their clinical condition. In infants with atypical PVHI mutation analysis of the factor V Leiden (G1691A), prothrombin (G20210A) gene, and C677T and A1298C polymorphisms in the MTHFR gene was performed, and plasma lipoprotein(a) and homocysteine levels were measured. RESULTS: Sixty-two preterm infants who presented with a PVHI were studied. Seventeen had an atypical presentation (seven males, 10 females; median birthweight 1170g [range 580-1990g]; median gestational age 30.6wks [range 28.7-33.7wks]). The typical PVHI group comprised 28 males and 17 females (median birthweight 1200g [range 670-2210g]; median gestational age 29.6wks [range 25.3-33.6wks]). Among the 17 infants with atypical presentation, the factor V Leiden mutation was found in seven infants (41%) as well as in the mothers of six of these seven infants; in one infant this was concomitant with a prothrombin gene mutation. A polymorphism in the MTHFR gene was also present in these infants. In two infants with an atypical presentation who were tested for this, a mutation in the COL4A1 gene was found (reported previously). All but two of the infants with an atypical presentation developed spastic unilateral cerebral palsy. INTERPRETATION: An atypical presentation of PVHI in preterm infants tends to occur more often in the presence of thrombophilia. Testing of thrombophilia, especially factor V Leiden and prothrombin gene mutation, is recommended in these infants.