Clinical analysis of 33 cases with neonatal cerebral infarction

Objective: To investigate the etiology, clinical manifestations, diagnosis, treatment and prognosis of neonatal cerebral infarction (NCI) to further improve the understanding of the disease. Methods: Clinical data and follow-up results of 33 cases of NCI in neonatal intensive care unit of a first-class hospital from September 2009 to September 2019 were retrospectively analyzed. Results: All 33 patients were diagnosed with NCI by MRI. Among them, 31 cases (93.94%) were full-term infants, 25 cases (75.76%) were mother’s first birth, and 18 (54.55%) cases were males. Pregnancy complications were reported in 18 cases (54.55%), and 19 cases (57.58%) had perinatal hypoxia history. Seizures were the most common first symptom and clinical manifestation in the course of disease (81.8%). There were 27 cases (81.82%) of patent foramen ovale (PFO) among NCI cohort. Ischemic cerebral infarction occurred in 32 cases (96.97%). The middle cerebral artery and its branches were more frequently involved, mainly on the left side. The acute stage of NCI was managed by symptomatic support treatment, and the recovery stage involved mainly rehabilitation treatment. Among the 33 cases, five cases were lost to follow-up, two patients died, 26 patients survived without complications, one case had cerebral palsy, one case had language retardation, and six cases had dyskinesia. Poor prognosis was associated with the involvement of deep gray matter nuclei or multiple lobes, and intrapartum complications. Vaginal mode of delivery and longer hospital stay were associated with better prognosis. Conclusions: Complications leading to placental circulation disorder during pregnancy and perinatal hypoxia are common high-risk factors of NCI. The seizure is the most common clinical manifestation. There is a possible correlation between PFO and NCI. Involvement of deep gray matter or multiple lobes and intrapartum complications may indicate poor prognosis, while vaginal delivery and prolonged hospitalizations are associated with better prognosis of NCI. doi: https://doi.org/10.12669/pjms.37.7.4720 How to cite this:Yang N, He X, Yin C, Zhao L. Clinical analysis of 33 cases with neonatal cerebral infarction. Pak J Med Sci. 2021;37(7):---------. doi: https://doi.org/10.12669/pjms.37.7.4720 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

MO1012ACUTE KIDNEY INJURY IN PREMATURE INFANTS EXPOSED TO PERINATAL HYPOXIA

Background and Aims Features of nephrogenesis and functional state of the kidneys of premature infants makes them extremely vulnerable to the damaging effects of hypoxia. The imperfection of traditional methods of diagnosis and non-specific clinical manifestations of ischemic nephropathy in premature infants requires the study of new informative diagnostic tests that would indicate the development of a pathological process in the renal tissue. The aim is to early diagnose acute kidney injury in preterm infants exposed to perinatal hypoxia, based on the study of renal blood flow and laboratory markers - cystatin C in serum, lipocalin and interleukin-18 in urine. Method We examined premature infants exposed to perinatal hypoxia and had signs of injury of kidney depending on gestational age: 65 infants with gestational age <32 weeks and 50 infants with gestational age > 32 weeks. The group of comparison included 25 premature newborns who were born without hypoxia and without signs of kidney injury. Blood and urine samples were obtained at 2-4 days of life. Ultrasound examination of the kidneys was performed at 3-5 days of life. Results The level of CysC in the serum of infants with gestational age <32 and> 32 weeks significantly exceeded this level in infants of the group of comparison (in infants with gestational age <32 weeks -2.50 [2.14; 3.26] ng/ml, in infants with gestational age> 32 weeks - 1.89 (1.49; 2.45] ng/ml), p <0.01. The value of NGAL in the urine of infants with gestational age <32 weeks - Me 96.03 [38,6; 131.23] ng/ml UCr and of infants with gestational age > 32 weeks - Me 75.10 [31,24; 126.6] ng/ml UCr against Me 25.9 [8.24; 44.64] ng/mg UCr in infants of the group of comparison (p <0.01). IL-18 in the urine of infants with gestational age <32 weeks and > 32 weeks was significantly higher than that in infants of the group of comparison (Me 27.98 [25.49; 29.51] pg/mg UCr, Me 22.0 [19.6; 25.63] pg/mg UCr, and 17.41 [13.96; 18.78] pg/mg UCr, respectively, p <0.01). According to the results of duplex scanning, the maximum systolic flow rate in the trunk of the renal artery (Vmax) in infants with gestational age <32 weeks (35.62 ± 3.2 cm/s) was lower than in infants of the group of comparison (p <0.05). Decreased IR less than 0.6 in 19 (29.3 ± 5.6%) infants with gestational age <32 weeks and in 12 (24.0 ± 6.4%) infants with gestational age > 32 weeks indicates vasodilation and, possibly arteriovenous shunting. The pulsation index in infants with gestational age <32 weeks and > 32 weeks (0.88 ± 0.1 and 0.98 ± 0.1) was significantly lower than in the group of comparison (p <0.05). Conclusion Early (2-4 days of life) and significant (p<0.01) increase in serum cystatin C, interleukin-18 and lipocalin associated with neutrophil gelatinase in the urine indicate endogenous renal dysfunction, damage to the proximal renal tubules in premature infants who were exposed to perinatal hypoxia. Significant decrease in the maximum systolic flow rate in the trunk of the renal artery and pulsation index (p<0.05) in premature infants who underwent perinatal hypoxia indicate a significant impact of circulatory disorders on the formation of hypoxic nephropathy.

Chronic perinatal hypoxia delays cardiac maturation in a mouse model for cyanotic congenital heart disease

We utilized a new mouse model of chronic perinatal hypoxia to simulate the hypoxic myocardial conditions present in cyanotic congenital heart disease. Hypoxia caused numerous abnormalities in cardiomyocyte gene expression, the electrophysiologic substrate of the heart, and contractile function. Taken together, alterations observed in the neonatal period suggest delayed cardiac development immediately following hypoxia.

Perinatal hypoxia and the risk of severe Molar-Incisor Hypomineralisation (MIH): a retrospective analysis of the pH value of umbilical arterial blood after birth

Purpose Molar-Incisor Hypomineralisation (MIH) remains a widespread developmental disorder of the teeth with a still largely unknown etiology. Perinatal events were blamed in previous studies for the development of MIH. The aim of the present study was to evaluate the influence of perinatal hypoxia—determined by the pH value of the umbilical cord blood—and to investigate its correlation with severe MIH retrospectively. In addition, cesarean section was recorded as differentiation variable. Methods A total number of 138 children (mean age 8.0 years ± 1.7), who were treated for severe MIH in a dental office in Berlin between the years 2008 and 2019, were included in the study. The control group was comprised of patients with the same date of birth (44 children, mean age 7.7 years ± 1.7). Information on the pH value of the arterial blood from the umbilical cord taken immediately after birth, whose recording is mandatory in Germany, was received from the parents by letter survey requesting the entries from the German Child Health Booklet. Results In the group of the male children born without cesarean section, the pH value of the control group was significantly lower (7.19 ± 0.09) than the pH value of the MIH group (7.27 ± 0.07, p = 0.0008). In female children born with or without cesarean section as well as in male children born by cesarean section there were no significant differences between the MIH and control group. Conclusions No significant association between MIH and the pH value of the umbilical cord blood or birth by cesarean section could be found in the examined patient population.

Perinatal events associated with birth asphyxia and hypoxic-ischemic encephalopathy in a middle-income country: A multicenter, observational study.

Background: Risk factors for neonatal encephalopathy differ across high- and low-income countries. Evidence of demographic characteristics and factors associated with perinatal hypoxia of infants who are at-risk for HIE in Southeast Asia is needed. Our primary objective was to investigate the intrapartum characteristics of infants ≥32 weeks’ gestational age (GA) born with low Apgar scores. Secondary objectives were to determine perinatal hypoxic events, and the characteristics and outcomes of infants ≥35 weeks GA with hypoxic-ischemic encephalopathy (HIE). Methods: A multicenter, retrospective, study was conducted. Individual charts were reviewed of infants with 5-minute Apgar scores ≤5 who were admitted to 4 tertiary centers in Thailand over 5 years. Events associated with perinatal hypoxia and outcomes were extracted. Variables were compared using chi-square, Fisher-exact test, two-independent sample t tests, ANOVA and Mann-Whitney. Data were analyzed using SPSS Statistics version 18.0. A p-value <0.05 was considered statistically significant.Results: Among 120235 infants, 454 had 5-mintue Apgar scores ≤5 (average: 3.8 per 1000 live births). The estimated frequency of HIE in ≥32 weeks’ GA infants was 1.5 per 1000 livebirths. Ninety-seven percent of the mothers’ received antenatal care. After exclusions, 316 infants and 314 mothers comprised the final sample. Common intrapartum complications were abnormal fetal heart rate (38.5%) and meconium-stained amniotic fluid (19.1%). Infants ≥35 weeks GA had mean ± standard deviation (SD) birthweight of 3003.4 ± 590.5 g; 10% were small-for-GA. Among ≥35 weeks GA infants with HIE, 42% had metabolic acidosis, 53% experienced sentinel, hypoxic perinatal events and advanced resuscitation was instituted in 92%. The severity of encephalopathy was reported in 99% of subjects. Eighty-five infants (62.5%) met all eligibility criteria for therapeutic hypothermia (TH) and 48 (56.5% of eligible infants) received treatment. The overall mortality rate was 29.4%.Conclusion: Maternal and intrapartum characteristics of infants at-risk for perinatal asphyxia in Thailand were comparable to reports from high-income countries. To improve recruitment for TH in middle-income, South-East Asian countries, strategies to raise HIE awareness among practitioners and more simplified TH eligible criteria are warranted to encourage timely transfer to referral centers for treatment.

Isolated necrosis of central tegmental tracts due to neonatal hypoxic-ischemic encephalopathy: MRI findings

Perinatal hypoxia is an old entity that still prevails today and may lead to neurological sequelae that can go unnoticed until a certain age, generating many costs for public health. In this case report, we demonstrate on magnetic resonance imaging an unusual pattern of perinatal hypoxia in a preterm 5-month-old infant, involving the central tegmental tracts and briefly discuss its possible pathophysiology.

Hypoxia-induced inhibition of mTORC1 activity in the developing lung: a possible mechanism for the developmental programming of pulmonary hypertension

Perinatal hypoxia induces permanent structural and functional changes in the lung and its pulmonary circulation that are associated with the development of pulmonary hypertension (PH) in later life. The mechanistic target of the rapamycin (mTOR) pathway is vital for fetal lung development and implicated in hypoxia-associated PH, yet its involvement in the developmental programming of PH remains unclear. Pregnant C57/BL6 dams were placed in hyperbaric (760 mmHg) or hypobaric chambers during gestation (505 mmHg, day 15 through postnatal day 4) or adulthood (420 mmHg, postnatal day 21 through 8wks). Pulmonary hemodynamics and right ventricular systolic pressure (RVSP) were measured at 8wks. mTOR pathway proteins were assessed in fetal (day 18.5) and adult lung (8wks). Perinatal hypoxia induced PH during adulthood, even in the absence of a sustained secondary hypoxic exposure, as indicated by reduced pulmonary artery acceleration time (PAAT) and peak flow velocity through the pulmonary valve, as well as greater RVSP, RV wall thickness and RV/LV weight. Such effects were independent of increased blood viscosity. In fetal lung homogenates, hypoxia reduced the expression of critical downstream mTOR targets, most prominently total and phosphorylated 4EBP1, as well as vascular endothelial growth factor, a central regulator of angiogenesis in the fetal lung. In contrast, adult offspring of hypoxic dams tended to have elevated p4EBP1 compared to controls. Our data suggest that inhibition of mTORC1 activity in the fetal lung as a result of gestational hypoxia may interrupt pulmonary vascular development and thereby contribute to the developmental programming of PH.