Placental pathology in perinatal asphyxia: a case-control study.

Introduction: Placentas of term infants with birth asphyxia are reported to have more lesion such as maternal vascular malperfusion (MVM), fetal vascular malperfusion (FVM) and chorioamnionitis with fetal response (FIR) than those of term infants without birth asphyxia. We compared the placental pathology of asphyxiated newborns, including those who developed hypoxic-ischemic encephalopathy (HIE), with non-asphyxiated controls. Methods: We conducted a retrospective case-control study of placentas from neonates with a gestational age ≥ 35 weeks, a birthweight ≥ 1,800 g, and no malformations. Cases were asphyxiated newborns (defined as those with an umbilical artery pH ≤ 7.0 or base excess ≤ -12 mMol, 10-minute Apgar score ≤ 5, or the need for resuscitation lasting >10 min) from a previous cohort, with (n=32) and without (n=173) diagnosis of HIE. Controls were non-asphyxiated newborns from low-risk l (n= 50) or high-risk (n= 68) pregnancies. Placentas were analyzed according to the Amsterdam Placental Workshop Group Consensus Statement 2014. Results: Cases had a higher prevalence of nulliparity, BMI>25, thick meconium, abnormal fetal heart monitoring, and acute intrapartum events than controls (p<0.001). MVM and FVM were more frequent among non-asphyxiated than asphyxiated newborns (p<0.001). There was no significant difference in inflammatory lesions or abnormal umbilical insertion site. Histologic meconium-associated changes (MAC) were observed in asphyxiated newborns only (p= 0.039). Discussion: Our results confirm the role of antepartum and intrapartum risk factors in neonatal asphyxia and HIE. No association between neonatal asphyxia and placental lesions was found, except for in the case of MAC. The association between clinical and placental data is crucial to understanding and possibly preventing perinatal asphyxia in subsequent pregnancies.

Is perinatal asphyxia predictable?

BACKGROUND: The objective of our study was to evaluate the association between perinatal asphyxia and hypoxic-ischemic encephalopathy (HIE) with the presence of ante and intrapartum risk factors and/or abnormal fetal heart rate (FHR) findings, in order to improve maternal and neonatal management. METHODS: We did a prospective observational cohort study from a network of four hospitals (one Hub center with neonatal intensive care unit and three level I Spoke centers) between 2014 and 2016. Neonates of gestational age ≥ 35 weeks, birthweight ≥1800 g, without lethal malformations were included if diagnosed with perinatal asphyxia, defined as pH ≤7.0 or Base Excess (BE) ≤ - 12 mMol/L in Umbical Artery (UA) or within 1 h, 10 min Apgar < 5, or need for resuscitation > 10 min. FHR monitoring was classified in three categories according to the American College of Obstetricians and Gynecologists (ACOG). Pregnancies were divided into four classes: 1) low risk; 2) antepartum risk; 3) intrapartum risk; 4) and both ante and intrapartum risk. In the first six hours of life asphyxiated neonates were evaluated using the Thomson score (TS): if TS ≥ 5 neonates were transferred to Hub for further assessment; if TS ≥ 7 hypothermia was indicated. RESULTS: Perinatal asphyxia occurred in 21.5‰ cases (321/14,896) and HIE in 1.1‰ (16/14,896). The total study population was composed of 281 asphyxiated neonates: 68/5152 (1.3%) born at Hub and 213/9744 (2.2%) at Spokes (p < 0.001, OR 0.59, 95% CI 0.45-0.79). 32/213 (15%) neonates were transferred from Spokes to Hub. Overall, 12/281 were treated with hypothermia. HIE occurred in 16/281 (5.7%) neonates: four grade I, eight grade II and four grade III. Incidence of HIE was not different between Hub and Spokes. Pregnancies resulting in asphyxiated neonates were classified as class 1) 1.1%, 2) 52.3%, 3) 3.2%, and 4) 43.4%. Sentinel events occurred in 23.5% of the cases and FHR was category II or III in 50.5% of the cases. 40.2% cases of asphyxia and 18.8% cases of HIE were not preceded by sentinel events or abnormal FHR. CONCLUSIONS: We identified at least one risk factor associated with all cases of HIE and with most cases of perinatal asphyxia. In absence of risk factors, the probability of developing perinatal asphyxia resulted extremely low. FHR monitoring alone is not a reliable tool for detecting the probability of eventual asphyxia.

Which factors affect the occurrence of severe cerebral lesions in preterm neonates who are born with intrauterine infection?

OBJECTIVE: The purpose of this study was to evaluate which factors affect the occurrence of neonatal ultrasonographic evidence of severe cerebral lesions in the presence of intrauterine infection. STUDY DESIGN: From a cohort of 567 singleton neonates who were born between 24.0 and 31.6 weeks of gestation, we identified the 180 infants with histologic and/or clinical evidence of intrauterine infection. We excluded stillbirths and congenital anomalies. Obstetric and neonatal variables were related to evidence of severe neonatal ultrasonographic cerebral lesions with the use of logistic regression analysis. RESULTS: Severe cerebral lesions were identified in 10% of infants (18/180). After we controlled for variables that were clinically relevant, logistic regression analysis demonstrated that ultrasound evidence of severe neonatal cerebral lesions was associated independently with antenatal administration of corticosteroids (adjusted odds ratio, 0.3; 95% CI, 0.11-0.88; P = .03) and occurrence of placental abruption (adjusted odds ratio, 5.4; 95% CI, 1.4-20.7; P = .02). CONCLUSION: Antenatal administration of corticosteroids in the presence of intrauterine infection has a protective effect on the risk of ultrasonographic evidence of severe neonatal cerebral lesions.

Predictors of umbilical artery acidosis in preterm delivery.

OBJECTIVE: The purpose of this study was to investigate the significance of preterm acidosis and its risk factors. STUDY DESIGN: From a cohort of 786 consecutive singleton neonates who were born after spontaneous or iatrogenic preterm delivery at 24.0-33.6 weeks of gestation from January 1993 to December 2005 with an evaluation of umbilical artery pH at delivery, we extracted demographic, obstetric, neonatal, and placental histologic variables and related them to umbilical artery evidence of fetal acidemia, which was defined as pH <7.10. Excluded were stillbirths and neonates with major congenital anomalies. Fetal distress was defined as nonreassuring fetal hearth rate tracing or biophysical profile or appearance of thick meconium at delivery. Statistical analysis included 1-way analysis of variance and logistic regression with a probability value of <.05 considered significant. RESULTS: Neonates with umbilical cord evidence of acidosis (n = 34) were born more frequently after abruption (P < .001), fetal distress (P < .001), and by cesarean delivery (P < .04) and were born less frequently after a complete course of corticosteroids (P = .03) and labor (P = .05) than nonacidotic babies (n = 752). Acute inflammatory lesions at placental histologic evaluation were less frequent (P = .049), and placental vascular lesions were more common in acidotic than in nonacidotic preterm neonates (P = .039). Logistic regression analysis demonstrated that cord acidosis was associated independently with the occurrence of abruptio placentae (odds ratio, 7.3; 95% CI, 2.9, 18.8), fetal distress (odds ratio, 12.0; 95% CI, 4.9, 18.3), and vascular placental lesions (odds ratio, 2.8; 95% CI, 1.2, 6.8) CONCLUSION: In preterm infants, umbilical artery acidosis is significantly more common in the presence of placental abruption, fetal distress, and histologic evidence of placental vascular disease.

A pharmacological study on pegylated asparaginase used in front-line treatment of children with acute lymphoblastic leukemia.

BACKGROUND AND OBJECTIVES: Pegylated-asparaginase (PEG-ASP) has been traditionally used as a second-line preparation in children with acute lymphoblastic leukemia (ALL) presenting with clinical allergy to native asparaginase (ASP) products. The main goal of the present study was to investigate the pharmacological effects of the administration of PEG-ASP given as a first-line product in children with ALL. DESIGN AND METHODS: PEG-ASP serum enzymatic activity and serum and cerebrospinal fluid (CSF) levels of asparagine were investigated in 20 children with newly diagnosed ALL enrolled in the ongoing AIEOP ALL 2000 protocol and treated with PEG-ASP as a first-line ASP preparation. During induction the drug was administered at the dosage of 1,000 U/m2 i.v. on days 12 and 27. During reinduction the drug was administered only once at the same dosage. RESULTS: Among the 20 patients treated in induction serum PEG-ASP activity equalled or exceeded 100 U/L in 18/18, 11/11 and 15/18 of the samples available on days 22, 25 and 27, respectively, and in 16/16, 12/15 and 5/8 samples available on days 36, 39 and 45, respectively. In the 15 patients treated during reinduction serum PEG-ASP activity > or =100 U/L was observed in 14/15, 11/14, 6/10, and 0/12 samples available on days 11, 15, 18 and 23, respectively, after the administration of the drug. Serum asparagine levels were below the detection limit (< or =0.2 microM) in all patients/samples and at all time points evaluated during induction; during reinduction only one patient had detectable asparagine levels from day 11. CSF asparagine levels were below the detection limit of the method only in a few patients during both induction and reinduction. INTERPRETATION AND CONCLUSIONS: PEG-ASP given as a first-line ASP product in the context of an intensive chemotherapy protocol for pediatric ALL allowed adequate plasma enzymatic activity and asparagine depletion during both exposures to the drug. However, CSF asparagine depletion was inadequate.