Volumetric changes in brain MRI of infants with hypoxic-ischemic encephalopathy and abnormal neurodevelopment who underwent therapeutic hypothermia.

BACKGROUND: Hypoxic-ischemic encephalopathy (HIE) is a severe neonatal complication that can result in 40-60 % of long-term morbidity. Magnetic Resonance Imaging (MRI) is a noninvasive method which is usually performed before discharge to visually assess acquired cerebral lesions associated with HIE and severity of lesions possibly providing a guide for detecting adverse outcomes. This study aims to evaluate the impact of HIE on brain volume changes observed in MRI scans performed at a mean 10 days of life, which can serve as a prognostic indicator for abnormal neurodevelopmental (ND) outcomes at 18-24 months among HIE infants. METHODS: We retrospectively identified a cohort of HIE patients between June 2013 and March 2017. The inclusion criteria for therapeutic hypothermia (TH) were a gestational age ≥35 weeks, a birth weight ≥1800 g, and the presence of ≥ moderate HIE. Brain MRI was performed at a mean 10 days of life and brain volumes (total brain volume, cerebral volume, cerebellar volume, brain stem volume, and ventricle volume) were measured for quantitative assessment. At 18-24 months, the infants returned for follow-up evaluations, during which their cognitive, language, and motor skills were assessed using the Bayley Scales of Infant and Toddler Development III. RESULTS: The study recruited a total of 240 infants between 2013 and 2017 for volumetric brain MRI evaluation. Among these, 83 were normal control infants, 107 were TH-treated HIE infants and 37 were HIE infants who did not receive TH due to contraindications. Clinical evaluation was further proceeded. We compared the brain volumes between the normal control infants (n = 83) with normal ND but TH-treated HIE infants (n = 76), abnormal ND TH-treated HIE infants (n = 31), and the severe HIE MRI group with no TH (n = 37). The abnormal ND TH-treated HIE infants demonstrated a significant decrease in brainstem volume and an increase in ventricle size (p < 0.001) (Table 4). Lastly, the severe brain MRI group who did not receive TH showed significantly smaller brain stem (p = 0.006), cerebellar (p = 0.006) and cerebrum volumes (p = 0.027), accompanied by larger ventricular size (p = 0.013) compared to the normal control group (Table 5). CONCLUSION: In addition to assessing the location of brain injuries in MRI scans, the reduction in brain stem volume coupled with an increase in ventricular volume in HIE infants may serve as a biomarker indicating severe HIE and adverse long-term ND outcomes among HIE infants who either received therapeutic hypothermia (TH) treatment or not.

Impact of increased paternal age on neonatal outcomes in very-low-birth-weight infants.

OBJECTIVE: Despite the trend of increasing paternal age, its impact on neonatal outcomes, particularly in preterm infants, has not been thoroughly investigated. We aimed to evaluate the perinatal characteristics and neonatal outcomes associated with paternal age. METHODS: Electronic medical records of very low-birthweight infants admitted to our unit from July 2013 to March 2022 were reviewed. Infants grouped according to paternal age (<35 years, 35-39 years, and ≥40 years) were analyzed for differences in perinatal findings and neonatal outcomes. RESULTS: A total of 637 infants were included (194, 294, and 149 in the <35, 35-39, and ≥40 years groups, respectively). The increase in paternal age paralleled the increase in maternal age. The Z-score of head circumference at birth was significantly different between the groups, showing the lowest median value in the ≥40 years group. Small-for-gestational age (Odds ratio 71.074, p < .001, 95% confidence interval 19.337 - 261.236) and male sex (Odds ratio 3.309, p < .034, 95% confidence interval 1.089 - 8.425), but not paternal or maternal age groups were significant factors associated with head circumference Z-scores less than -2 standard deviation based on the multivariable logistic regression analysis. Infants affected by chromosomal or genetic anomaly were more frequently identified (3.4 vs 0.0 vs 0.5%) in the ≥40 years group than in the other two groups. When infants with anomalies or critical illnesses were excluded, overall neonatal outcomes did not statistically differ according to paternal age. CONCLUSION: Although increased paternal age ≥40 years may be associated with relatively smaller head circumferences, the impact on fetal head growth does not imply a definite risk for microcephaly. Nonetheless, based on the possible negative impact on chromosomal/genetic anomaly, increased paternal age warrants attention, even though neonatal outcomes concerning prematurity were not significantly affected. A large-scale longitudinal study is needed to further elucidate the impact of advanced paternal age in preterm infants and provide guidelines for appropriate antenatal counseling and surveillance.

Impact of preterm premature rupture of membranes and oligohydramnios on in-hospital outcomes of very-low-birthweight infants.

OBJECTIVE: To analyze neonatal outcomes in very-low-birthweight (VLBW) infants depending on the presence of preterm premature rupture of membranes (PPROM), oligohydramnios, or both. METHODS: The electronic medical records of VLBW infants admitted during the study period, January 2013 to September 2018, were reviewed. Neonatal outcomes (primary outcome: neonatal death; secondary outcome: neonatal morbidity) were compared depending on whether the infant was affected by PPROM or oligohydramnios. Logistic regression analysis was performed to assess the association of PPROM and oligohydramnios with neonatal outcomes. RESULTS: Three hundred and nineteen VLBW infants were included: (1) 141 infants in the PPROM group vs. 178 infants in the non-PPROM group, and (2) 54 infants in the oligohydramnios group vs. 265 infants in the non-oligohydramnios group. The infants affected by PPROM were at significantly younger gestational ages at birth with lower 5-min Apgar scores than those not affected by PPROM. Histologic chorioamnionitis was significantly more frequent in the PPROM group than in the non-PPROM group. The proportions of small-for-gestational-age infants and infants affected by multiple births were significantly higher in the non-PPROM group. The median (interquartile range) PPROM latency and onset were 50.5 (9.0 - 103.0) h and 26.6 (24.1 - 28.5) weeks, respectively. Based on the logistic regression analysis assessing the association of PPROM and oligohydramnios with the significant neonatal outcome, oligohydramnios was significantly associated with neonatal death (odds ratio [OR] = 2.831, 95% confidence interval [CI] 1.447 - 5.539), air leak syndrome (OR = 2.692, 95% CI 1.224 - 5.921), and persistent pulmonary hypertension (PPH) (OR = 2.380, 95% CI 1.244 - 4.555). PPROM per se was not associated with any neonatal outcome. However, early onset PPROM and prolonged PPROM latency were associated with neonatal morbidity and mortality. When PPROM was accompanied by oligohydramnios, it was associated with increased odds for PPH (OR = 2.840, 95% CI 1.335 - 6.044), retinopathy of prematurity (OR = 3.308, 95% CI 1.325 - 8.259), and neonatal death (OR = 2.282, 95% CI 1.021 - 5.103). CONCLUSION: PPROM and oligohydramnios affect neonatal outcomes differently. Oligohydramnios, but not PPROM, is a significant risk factor for adverse neonatal outcomes, which is presumably related to pulmonary hypoplasia. Prenatal inflammation appears to complicate neonatal outcomes in infants affected by early PPROM and prolonged PPROM latency.

The prognosis of refractory hypotension and severe intraventricular hemorrhage in very low birth weight infants.

BACKGROUND: The increased survival rate among very low birth weight infants has resulted in a higher risk for developing neuro-complications such as intraventricular hemorrhage (IVH), periventricular leukomalacia (PVL), and adverse neurodevelopmental outcomes. PURPOSE: We examined refractory hypotension experienced within a week of life in association with severe IVH (grades 3-4) among very low birth weight infants (VLBWIs). METHOD: Between Jan 2014 and Dec 2017, the clinical data of 191 VLBWIs were retrospectively chart reviewed. Of a total of 191 VLBWIs, 71.2% (136/191) had IVH, and 28.7% (55/191) had severe IVH. RESULTS: The VLBWI with severe IVH group (grade 3-4) presented with a significantly lower gestational age along with higher use of postnatal hydrocortisone for refractory hypotension within a week of life. Resuscitation at delivery, pulmonary hemorrhage, neonatal seizure, and PVL were significantly more frequent in the severe IVH group (P < .05). Higher mortality occurred in the VLBWI with severe IVH group (P < .001). The multivariable logistic regression analysis consistently showed that refractory hypotension within a week of life and neonatal seizures were significantly associated with severe IVH. Those in the severe IVH and refractory hypotension groups had significantly lower composite cognitive, language, motor scores in Bayley Scales of Infant and Toddler Development III scores at corrected 18-24 months. CONCLUSION: Refractory hypotension within a week of life and seizures were consistently associated with severe IVH and developmental delay at corrected 18-24 months. VLBWI who experienced refractory hypotension within a week of life may indicate a more vulnerable clinical setting with a higher risk for developmental delay.

Compositional Differences of Meconium Microbiomes of Preterm and Term Infants, and Infants That Developed Necrotizing Enterocolitis or Feeding Intolerance.

The primary aim of this study was to investigate the compositional differences of the first passed meconium microbiome in preterm and term infants, and the secondary aim was to compare the meconium microbiomes of preterm and term infants that later developed necrotizing enterocolitis (NEC)/Feeding intolerance (FI) compared to those that did not develop NEC/FI. During the study period, a total of 108 preterm and term newborns' first passed meconium occurring within 72 hours of birth were collected and microbiome analyzed. Meconium microbiomes showed a disruption in the percentages of the core microbiome constituents in both the phylum and genus levels in infants born < 30 weeks of gestational age (GA) compared to those born ≥ 30 weeks of GA. In the phylum level, Bacteroidetes and Firmicutes, and in the genus level, Prevotella and Bacteroides, were predominant, with Prevotella accounting for 20−30% of the relative abundance. As GA increased, a significant increase in the relative abundance of Bacteroidetes (P for trend < 0.001) and decrease in Proteobacteria (P for trend = 0.049) was observed in the phylum level. In the genus level, as GA increased, Prevotella (P for trend < 0.001) and Bacteroides (P for trend = 0.002) increased significantly, whereas Enterococcus (P for trend = 0.020) decreased. Compared to the control group, the meconium of infants that later developed NEC/FI had significantly lower alpha diversities but similar beta-diversities. Furthermore, the NEC/FI group showed a significantly lower abundance of Bacteroidetes (P < 0.001), and higher abundance of Firmicutes (P = 0.034). To conclude, differences were observed in the composition of the first passed meconium in preterm and term infants that later develop NEC/FI compared to those that did not.

Plasma B-type natriuretic peptide cannot predict treatment response to ibuprofen in preterm infants with patent ductus arteriosus.

Plasma B-type natriuretic peptide (BNP) is a useful marker for diagnosis of hemodynamically significant PDA (hsPDA) and serial BNP measurement is also valuable for monitoring treatment response. This retrospective study was performed to evaluate whether plasma BNP level can predict treatment response to ibuprofen in preterm infants born at <30 weeks of gestation with hsPDA. Plasma BNP was measured before (baseline) and 12 to 24 h after (post-treatment) completion of the first (IBU1) and second (IBU2) course of ibuprofen. We compared the BNP levels of responders (closed or insignificant PDA) with those of non-responders (hsPDA requiring further pharmacologic or surgical closure) to each course of ibuprofen. The treatment response rates for IBU1 (n = 92) and IBU2 (n = 19) were 74% and 26%, respectively. In IBU1, non-responders had lower gestational age and birth weight than responders (both, P = 0.004), while in IBU2, non-responders had lower birth weight (P = 0.014) and platelet counts (P = 0.005) than responders; however, baseline BNP levels did not differ significantly between responders and non-responders in either IBU1 (median 1,434 vs. 1,750 pg/mL) or IBU2 (415 vs. 596 pg/mL). Post-treatment BNP was a useful marker for monitoring treatment efficacy of IBU1 and IBU2 for hsPDA with a cut-off value of 331 pg/mL (P < 0.001) and 423 pg/mL(P < 0.010), respectively. We did not identify a cut-off baseline BNP level that could predict treatment response to ibuprofen in preterm infants with hsPDA.

Moyamoya syndrome in a patient with Noonan-like syndrome with loose anagen hair.

BACKGROUND: Noonan-like syndrome with loose anagen hair is one of the RASopathies characterized by Noonan syndrome-like features with unique ectodermal abnormalities. This syndrome is caused by mutations in the SHOC2 gene. We encountered a patient with moyamoya syndrome associated with Noonan-like syndrome with loose anagen hair presenting with transient ischemic attacks. PATIENT DESCRIPTION: A 6-year-old girl was diagnosed with Noonan-like syndrome with loose anagen hair because of profound short stature and ectodermal anomalies such as sparse and easily pluckable hair. A heterozygous mutation of c.4A>G (p.S2G) in the SHOC2 gene was identified, and recombinant human growth hormone therapy was initiated at 8 years of age. At age 10, she manifested recurrent left hemiplegia. Moreover, cerebrovascular imaging revealed occlusion or narrowing of both internal carotid arteries and both middle cerebral arteries with distal moyamoya-like vessels. She is treated with aspirin and calcium channel blocker. CONCLUSIONS: We describe the first case of Noonan-like syndrome with loose anagen hair associated with moyamoya syndrome, although it has been reported to be associated with a few cases of other RASopathies, including Noonan, cardiofaciocutaneous, and Costello syndromes. This report emphasizes the associations between cerebrovascular anomalies and Noonan-like syndrome with loose anagen hair.