Alfredo García-Alix

Multiple organ involvement in perinatal asphyxia

OBJECTIVES (1) To evaluate the frequency and spectrum of severity of multisystem dysfunction after perinatal asphyxia and (2) to analyze the relationship between the clinical and biochemical markers of perinatal asphyxia and multiorgan involvement. STUDY DESIGN Seventy-two consecutive term newborn infants with perinatal asphyxia were studied prospectively. Systematic neurologic, renal, pulmonary, cardiac, and gastrointestinal evaluations were performed. Involvement of each organ was classified as moderate or severe. RESULTS Involvement of one or more organs occurred in 82% of the infants; the central nervous system (CNS) was most frequently involved (72%). Severe CNS injury (7 infants) always occurred with involvement of other organs, although moderate CNS involvement was isolated in 14 infants. Renal involvement occurred in 42%, pulmonary in 26%, cardiac in 29%, and gastrointestinal in 29% of the infants; 15% neonates had renal failure and 19% had respiratory failure. The Apgar scores at 1 and 5 minutes were the only perinatal factors related to the number of organs involved and the severity of involvement; the Apgar score at 5 minutes had the stronger independent association. No relationship or organ dysfunction was found with the umbilical cord arterial blood pH, meconium-stained amniotic fluid, umbilical cord abnormalities, presentation, or type of delivery. CONCLUSIONS Our findings indicate that the Apgar score at 5 minutes, in infants who have other criteria for asphyxia, is the perinatal marker that may best identify infants at risk of organ dysfunction.

The phenotypic spectrum of congenital Zika syndrome

In October 2015, Zika virus (ZIKV) outbreak the Brazilian Ministry of Health (MoH). In response, the Brazilian Society of Medical Genetics established a task force (SBGM‐ZETF) to study the phenotype of infants born with microcephaly due to ZIKV congenital infection and delineate the phenotypic spectrum of this newly recognized teratogen. This study was based on the clinical evaluation and neuroimaging of 83 infants born during the period from July, 2015 to March, 2016 and registered by the SBGM‐ZETF. All 83 infants had significant findings on neuroimaging consistent with ZIKV congenital infection and 12 had confirmed ZIKV IgM in CSF. A recognizable phenotype of microcephaly, anomalies of the shape of skull and redundancy of the scalp consistent with the Fetal Brain Disruption Sequence (FBDS) was present in 70% of infants, but was most often subtle. In addition, features consistent with fetal immobility, ranging from dimples (30.1%), distal hand/finger contractures (20.5%), and feet malpositions (15.7%), to generalized arthrogryposis (9.6%), were present in these infants. Some cases had milder microcephaly or even a normal head circumference (HC), and other less distinctive findings. The detailed observation of the dysmorphic and neurologic features in these infants provides insight into the mechanisms and timings of the brain disruption and the sequence of developmental anomalies that may occur after prenatal infection by the ZIKV.

Ultrasonographic findings in thalamus and basal ganglia in term asphyxiated infants

Three severely asphyxiated term neonates demonstrated bilateral hyperechogenicity in the thalamus and basal ganglia. During evolution, areas of attenuated echogenicity appeared in these structures at the same time as periventricular cysts were evident in 2 patients with coexistent periventricular leukomalacia. All 3 patients developed ventricular dilatation; in the 2 patients with periventricular leukomalacia, the ventricular border was irregular in the outer (dorsal) margin, and interhemispheric fissures were widened as a manifestation of cerebral atrophy. Furthermore, the thalamic inner (ventral) margins of the lateral ventricles were irregular in all 3 patients. This previously unrecognized finding points to a particular form of cerebral atrophy localized in the gangliothalamic region that contributes to the development of ventriculomegaly. The reported sonographic sequence implies profound damage in the thalamus and basal ganglia in asphyxiated infants which undoubtedly has contributed to the poor outcomes of our patients.

Natural history of ventricular dilatation in preterm infants: prognostic significance

Cerebral ultrasounds were prospectively performed in 100 infants weighing 1,500 gm or less in order to evaluate the prognostic significance of ventricular dilatations and their associated findings. There was no difference in the incidence of ventricular dilatation (24%) between patients with or without periventricular hemorrhage (PVH). Although patients with PVH developed ventricular dilatation significantly earlier than infants without PVH, no differences were observed in severity, location, head circumference growth, or intracranial pressure between the groups. Ventricular dilatation was statistically related to PVH grade III and PVH with parenchymal involvement; grades moderate-to-severe of periventricular echogenicity; and cystic periventricular leukomalacia (PVL). Ventricular dilatation persisted longer than 6 weeks in 61% of infants and had irregular margins in 62%. The latter were significantly related to cystic PVL. Seventy-seven of 100 infants examined were followed until 20 months corrected age. Ventricular dilatation mainly when persistent and with irregular margins was associated with handicaps. We conclude that ventricular dilatation is frequent in very low-birth weight infants. Furthermore, its occurrence may be independent of PVH. Persistent ventricular dilatation with irregular margins, even in its mild forms, suggests a parenchymal lesion and guarded prognosis.

Early identification of brain injury in infants with hypoxic ischemic encephalopathy at high risk for severe impairments: accuracy of MRI performed in the first days of life

BackgroundDespite therapeutic hypothermia 30-70% of newborns with moderate or severe hypoxic ischemic encephalopathy will die or survive with significant long-term impairments. Magnetic resonance imaging (MRI) in the first days of life is being used for early identification of these infants and end of life decisions are relying more and more on it. The purpose of this study was to evaluate how MRI performed around day 4 of life correlates with the ones obtained in the second week of life in infants with hypoxic-ischemic encephalopathy (HIE) treated with hypothermia.MethodsProspective observational cohort study between April 2009 and July 2011. Consecutive newborns with HIE evaluated for therapeutic hypothermia were included. Two sequential MR studies were performed: an •early’ study around the 4th day of life and a •late’ study during the second week of life. MRI were assessed and scored by two neuroradiologists who were blinded to the clinical condition of the infants.ResultsForty-eight MRI scans were obtained in the 40 newborns. Fifteen infants underwent two sequential MR scans. The localization, extension and severity of hypoxic-ischemic injury in early and late scans were highly correlated. Hypoxic-ischemic injury scores from conventional sequences (T1/T2) in the early MRI correlated with the scores of the late MRI (Spearman ρ = 0.940; p < .001) as did the scores between diffusion-weighted images in early scans and conventional images in late MR studies (Spearman ρ = 0.866; p < .001). There were no significant differences in MR images between the two sequential scans.ConclusionsMRI in the first days of life may be a useful prognostic tool for clinicians and can help parents and neonatologist in medical decisions, as it highly depicts hypoxic-ischemic brain injury seen in scans performed around the second week of life.

Neonatal hypoxic‐ischaemic encephalopathy: most deaths followed end‐of‐life decisions within three days of birth

To investigate the circumstances surrounding end‐of life decisions (EoL) of infants with hypoxic‐ischaemic encephalopathy (HIE) and examine changes over a 10‐year period.

Neonatal neurological morbidity associated with uterine rupture.

Abstract Aims: To compare neonatal neurological morbidity associated with uterine rupture with morbidity associated with a non-reassuring fetal status. Methods: We conducted a retrospective cohort analysis. Twenty-one cases of term infants delivered after a symptomatic uterine rupture were analyzed and compared with a randomly selected group of 63 infants born after a non-reassuring fetal heart rate pattern. Results: Prevalence of uterine rupture was 0.058%. Maternal factors and infant general data were similar in both groups. Infants delivered after a uterine rupture had lower Apgar scores at 1 and 5 min, lower umbilical blood pH, and required more advanced resuscitation than infants delivered after a non-reassuring fetal status. Prevalence of hypoxic-ischemic encephalopathy in the uterine rupture group was 33%, compared with 5% in the other group (P<0.01, relative risk 3.7). Four infants in the uterine rupture group (19%) had moderate or severe encephalopathy; all of them had also multisystem dysfunction and an adverse outcome. No infant in the non-reassuring fetal status group showed moderate or severe encephalopathy. Conclusions: Uterine rupture is a considerable sentinel event that involves a high rate of early and late neurological morbidity in the newborn infant.

Retained central venous lines in the newborn: report of one case and systematic review of the literature.

The use of percutaneously inserted central catheters (PICCs) is an established practice in most NICUs. With the widespread use of these catheters, an increasing number of PICC complications has been reported in neonates. We present one case of a PICC retained and tethered in the vein in a very low birth weight infant, as well as a systematic review of PICC retention cases. Ten previous cases of PICC retention in neonates were found. Among those cases, the most common associated factors were coagulase-negative staphylococcus catheter colonization/bacteremia and long duration of catheterization. Occlusion was not a useful sign for predicting catheter retention. Once retention was established, heparin or urokinase instillations were ineffective. Although surgical exploration was sometimes required, firm, continuous traction applied to the catheter over several hours or intermittent, moderately strong pulling maneuvers were successful in 44.4 percent of the cases in which they were performed. Traction did not show major side effects. Our case provides additional support for use of traction as the initial approach in the management of this rare complication.

Congenital syphilis: β2-microglobulin in cerebrospinal fluid and diagnosis of neurosyphilis in an affected newborn

Abstract Meningoencephalitis in neonatal congenital syphilis (CS) is a difficult diagnosis because of the limitation of standard cerebrospinal fluid (CSF) tests. This limitation means that new markers in CSF tests are needed to establish whether meningitis is present in presumptive cases of CS. β2-Microglobulin (β2-m) is raised in CSF recovered from neonates with central nervous system (CNS) infections, but it does not correlate with cellular count or proteins in the CSF. We present a preterm newborn with symptomatic CS. First-day CSF showed 50 cells/mm3, protein of 220 mg/dL and a β2-m concentration of 16.9 mg/dL (normal <2.25 mg/dL). Serial determinations of β2-m showed a marked reduction (76%) after 10 days of appropriate treatment. At 30 days of life, β2-m was already within the normal range (1.8 mg/dL). Cerebral ultrasonography showed ventricular dilatation, moderate periventricular echogenicity, subependimal hemorrhages, and linear hyperechoic areas in the thalamus and basal ganglia. We suggest that β2-microglobulin is very useful in the diagnosis of CNS involvement and in monitoring the response to treatment. In addition, infants with CS may exhibit CNS imaging findings similar to those observed in other intrauterine CNS infections.

Treatment with bisphosphonates in severe hypercalcemia due to subcutaneous fat necrosis in an infant with hypoxic-ischemic encephalopathy

Subcutaneous fat necrosis (SCFN) is a rare entity that occurs generally in term or post-term newborns exposed to perinatal stressing factors. These cutaneous lesions appear during the first weeks of life and their potential complications, such as hypercalcemia, determine the prognosis. We present a full-term newborn with SCFN lesions that appeared at the age of 12 days and who, 1 week later, developed moderate hypercalcemia. In our patient, the standard treatment was not enough to normalize calcemia and, in order to prevent secondary effects, etidronate therapy was initiated and it successfully normalized calcium levels. When SCFN is diagnosed, it is important to detect early hypercalcemia and treat it aggressively. This case provides further evidence of etidronate as an alternative and effective treatment for moderate–severe hypercalcemia.