Feizal Waffarn

Delayed repair of congenital diaphragmatic hernia with early high-frequency oscillatory ventilation during preoprative stabilization

PURPOSE The authors reviewed their experience in the management of CDH after the introduction of early high-frequency oscillatory ventilation (HFOV) during the preoperative stabilization period and delayed CDH repair. METHODS This is a retrospective analysis of 24 consecutive infants with CDH treated at University of California, Irvine Medical Center (UCIMC) during a 36-month period from January 1993 to December 1996. RESULTS Two patients were excluded from the study: one fetus with a prenatal diagnosis was referred for fetal surgery; one infant received CDH repair at another institution 2 weeks before transfer to UCIMC. Eight (36%) infants were inborn, and nine (41%) had a prenatal diagnosis of CDH. Median gestational age was 40 weeks (range, 29 to 42 weeks). Median birth weight was 3,019 g (range, 1,205 to 4,337 g). The defect was left sided in 18 infants (86%). Twenty-one infants were intubated within 5 hours of life, 15 had an AaDO2 greater than 610, 11 had an oxygenation index greater than 40, and 11 had a pH of less than 7.2. The median ratio of pulmonary artery pressure to systemic blood pressure was 0.93 (range, 0.51 to 1.15) in 12 infants. Eighteen infants were placed on HFOV within a median of 1 hour of life. Nitric oxide was given to six infants and surfactant to eight. Four infants were referred for extracorporeal membrane oxygenation (ECMO). Repair of CDH was performed on infants at a median age of 33.5 hours (range, 5.5 to 322). Six (30%) received a prosthetic patch. Overall 18 of 22 infants survived (81%); three survivors received ECMO. Two infants of the survivor group had congenital heart anomalies: one ventricular septal defect (VSD) and one double-outlet right ventricle with a VSD. Of the four nonsurvivors, one had lethal cardiac anomalies and bilateral CDH, two had severe bilateral pulmonary hypoplasia (one received ECMO), and one infant was a 29-week premature baby who did not qualify for ECMO. CONCLUSION We report a survival rate of 81% (18 of 22) with the management of CDH by delayed surgical repair, early postnatal HFOV, and selective referral for ECMO.

Fetal Programming of Body Composition, Obesity, and Metabolic Function: The Role of Intrauterine Stress and Stress Biology

Epidemiological, clinical, physiological, cellular, and molecular evidence suggests that the origins of obesity and metabolic dysfunction can be traced back to intrauterine life and supports an important role for maternal nutrition prior to and during gestation in fetal programming. The elucidation of underlying mechanisms is an area of interest and intense investigation. In this perspectives paper we propose that in addition to maternal nutrition-related processes it may be important to concurrently consider the potential role of intrauterine stress and stress biology. We frame our arguments in the larger context of an evolutionary-developmental perspective that supports roles for both nutrition and stress as key environmental conditions driving natural selection and developmental plasticity. We suggest that intrauterine stress exposure may interact with the nutritional milieu, and that stress biology may represent an underlying mechanism mediating the effects of diverse intrauterine perturbations, including but not limited to maternal nutritional insults (undernutrition and overnutrition), on brain and peripheral targets of programming of body composition, energy balance homeostasis, and metabolic function. We discuss putative maternal-placental-fetal endocrine and immune/inflammatory candidate mechanisms that may underlie the long-term effects of intrauterine stress. We conclude with a commentary of the implications for future research and clinical practice.

Effects of Antenatal Corticosteroids on the Hypothalamic-Pituitary-Adrenocortical Axis of the Fetus and Newborn: Experimental Findings and Clinical Considerations

The hypothalamic-pituitary-adrenocortical (HPA) axis is a major neuroendocrine pathway that modulates the stress response. The glucocorticoid, cortisol, is the principal end product of the HPA axis in humans and plays a fundamental role in maintaining homeostasis and in fetal maturation and development. Antenatal administration of synthetic glucocorticoids (GCs) accelerates fetal lung maturation and has significantly decreased neonatal mortality and morbidity in infants born before 34 weeks of gestation. Exposure to excess levels of endogenous GCs and exogenous GCs (betamethasone and dexamethasone) has been shown to alter the normal development trajectory. The development and regulation of the fetal HPA axis is discussed and the experimental animal evidence presented suggests long-term adverse consequences of altered HPA function. The clinical data in infants exposed to GCs also suggest altered HPA axis function over the short term. The longer-term consequences of antenatal GC exposure on HPA axis function and subtler neurodevelopmental outcomes including adaptation to stress, cognition, behavior, and the cardiovascular and immune responses are poorly understood. Emerging clinical strategies and interventions may help in the selection of mothers at risk for preterm delivery who would benefit from existing or future formulations of antenatal GCs with a reduction in the associated risk to the fetus and newborn. Detailed longitudinal long-term follow-up of those infants exposed to synthetic GCs are needed.

Body composition and its components in preterm and term newborns: A cross-sectional, multimodal investigation

A prospective, cross‐sectional, observational study in preterm and term infants was performed to compare multimodal measurements of body composition, namely, limb ultrasound, bone quantitative ultrasound, and dual X‐ray absorptiometry (DXA). One hundred and two preterm and term infants appropriate for gestational age were enrolled from the newborn nursery and neonatal intensive care unit. Infants were included when they were medically stable, in an open crib, on full enteral feeds and within 1 week of anticipated discharge. Correlations among the various measurements of body composition were performed using standard techniques. A comparison between preterm infant (born at 28–32 weeks) reaching term to term‐born infants was performed. Limb ultrasound estimates of cross‐sectional areas of lean and fat tissue in a region of tissue (i.e., the leg) were remarkably correlated with regional and whole‐body estimates of fat‐free mass and fat obtained from DXA suggesting the potential usefulness of muscle ultrasound as an investigative tool for studying aspects of body composition in this fragile population. There was a weak but significant correlation between quantitative ultrasound measurements of bone strength and DXA‐derived bone mineral density (BMD). Preterm infants reaching term had significantly lower body weight, length, head circumference, muscle and fat cross‐sectional area, bone speed of sound, whole‐body and regional lean body mass, fat mass, and BMD compared to term‐born infants. Current postnatal care and nutritional support in preterm infants is still unable to match the in‐utero environment for optimal growth and bone development. The use of relatively simple bedside, noninvasive body composition measurements may assist in understanding how changes in different components of body composition early in life affect later growth and development. Am. J. Hum. Biol. 2010.

Pulmonary toxicity associated with nitric oxide in term infants with severe respiratory failure.

We prospectively analyzed airway specimens from 24 newborn infants. Inhaled nitric oxide (< or = 20 ppm for 1 to 4 days to 12 infants) did not affect the concentrations of the lipid peroxidation product, the surface activity, or the cytokines (interleukin-1, granulocyte-macrophage colony-stimulating factor, interleukin-1 receptor antagonist). Nitrotyrosine was detected after 10 days of life in the two infants requiring prolonged ventilation, suggesting toxicity of endogenous nitric oxide.

Obstetric characteristics and fetal heart rate patterns of infants who convulse during the newborn period

Seizure activity in the immediate neonatal period has been shown to correlate with long-term neurological handicap. The perinatal course of 34 term and 32 preterm infants who developed seizure activity in the neonatal period was compared to that of 66 matched control infants without neonatal seizure activity. The incidence of antenatal complications and abnormal fetal heart rate patterns and the percentages of abnormal labor, operative delivery, and low Apgar scores were significantly greater in the study infants than in the control infants. Earlier onset of seizure activity was seen in term versus preterm infants and term infants with abnormal versus normal fetal heart rate patterns. Management decisions regarding intervention or nonintervention based on fetal heart rate patterns were deemed appropriate in 31 of 34 term infants, yet short- and long-term neurological sequelae were significant.

Granulocyte-Macrophage Colony-Stimulating Factor in Amniotic Fluid and in Airway Specimens of Newborn Infants

Granulocyte-macrophage colony-stimulating factor (GM-CSF), a cytokine that promotes white cell maturation, participates in the metabolism of pulmonary surfactant. Little is known on the production of GM-CSF during pregnancy or the neonatal period. We studied how the concentrations of GM-CSF in amniotic fluid (AF) or in tracheal aspirates (TA) of newborn infants are influenced by length of gestation, postnatal age, as well as conditions affecting the mother or the fetus. One hundred and forty-three AF samples from 143 pregnant patients (gestational age range, 28-42 wk) and 202 TA samples from 82 neonates(gestational age, 24-42.5 wk, postnatal age 0.2 d to 4 wk) were analyzed for GM-CSF using ELISA. In patients with intact membranes, AF GM-CSF increased as a function of gestational age; the concentrations were below 7.5 ng/L(detection limit of the assay) (n = 5), 18.6 ± 2.3 ng/L(n = 56), and 56.7 ± 7.9 ng/L (n = 58) at gestational ages between 28 and 32 wk, between 32 and 37 wk, and in term patients, respectively (linear regression: r = 0.404, p = 0.001). Among patients at less than 33 wk of gestation, those with intact membranes had a median AF GM-CSF concentration under the detection limit(n = 7), whereas in those with preterm premature rupture of membranes, the concentration was 50.1 ± 22.2 ng/L (n = 16)(p = 0.002). Among term patients, those in labor had higher AF GM-CSF than those without signs of labor. TA GM-CSF at less than 12 h of age correlated with gestational age (r = 0.654, p = 0.0002,n = 28); thereafter, TA GM-CSF increased, and gestation dependence disappeared. We conclude that GM-CSF in AF and in fetal lung liquid is developmentally regulated and GM-CSF production increases in inflammatory conditions during pregnancy.

Influence of fetal gender on the concentration of interleukin-1 receptor antagonist in amniotic fluid and in newborn urine

ABSTRACT: IL-1 receptor antagonist (IL-1ra) is a cytokine that blocks the effects of IL-1 by binding to IL-1 receptors without inducing signal transduction. Amniotic fluid contains high concentrations of IL-1ra. The purpose of this study was 1) to analyze whether factors related to the mother or the fetus influence amniotic fluid IL-1ra concentration, and 2) to study whether the fetus is a source of IL-1ra. Two hundred two specimens of amniotic fluid, as well as 21 urine samples from newborn infants, were analyzed. Women carrying a female fetus had a higher concentration of amniotic fluid IL-1ra than those carrying a male fetus (female 136.4 ± 6.1 μg/L, n = 83; male 74.7 ± 3.7 μg/L, n = 119; p < 0.0001, unpaired two-sided t test). Length of gestation, presence or absence of labor signs, or elevated IL-1β in amniotic fluid did not affect the concentration of IL-1ra in amniotic fluid. Urine of infants taken during the first 48 h of life contained a high concentration of IL-1ra (91.1 ± 17.5 μg/L). The urinary IL-1ra concentration was higher in female newborns than in male newborns (females 124.0 ± 25.2 μg/L, n = 11; males 54.9 ± 19.1 μg/L, n = 10; p = 0.04). We conclude that 1) the concentration of IL-1ra in amniotic fluid and newborn urine is dependent on the gender of the fetus and of the newborn and 2) fetal urine is a major source of amniotic fluid IL-1ra. The higher IL-1ra in female-bearing gestations may contribute to the better resistance of female fetuses against preterm birth and perinatal infections.

New endotracheal tube adaptor reducing cardiopulmonary effects of suctioning.

The continuous recordings of arterial oxygen saturation (SaO2) and beat-to-beat heart rate before, during, and after tracheobronchial suctioning were studied in eight preterm infants with severe RDS receiving mechanical ventilation. Two suctioning procedures were alternatively performed in each infant; In procedure A, disconnection of the ventilator and preoxygenation preceded suctioning; in procedure B, a special suction adaptor was used without ventilatory interruption or preoxygenation; 128 suctionings were performed with each procedure and the changes in heart rate (HR) and SaO2 during suctioning were compared. Although in both procedures, HR and SaO2 decreased during suctioning, the degree of bradycardia and arterial blood oxygen desaturation were significantly smaller in magnitude and shorter in duration during procedure B. These data indicate advantages of the suction adaptor in minimizing bradycardia and hypoxia from airway suction.

A pulsed Doppler echocardiographic study of the postnatal changes in pulmonary artery and ascending aortic flow in normal term newborn infants

Postnatal circulatory adaptations were studied with Doppler echocardiographic measures of flow velocity in the main pulmonary artery (PA) and ascending aorta (Ao) in 45 normal full-term neonates at 5 hours and at 27 hours after birth. PA flow velocity integral (FVI) was measured as the area under the systolic flow velocity curve and reflected total systemic flow in the presence of a left-to-right shunt through the ductus arteriosus. This index increased from 5 and 27 hours age, while Ao FVI, reflecting total pulmonary flow, remained unchanged. Evidence of a left-to-right ductal shunt demonstrated as diastolic retrograde flow in the main PA was detected in 42 neonates at 5 hours and in only four subjects after 27 hours of age, indicating a patent ductus arteriosus at 5 hours of age and its subsequent closure. In the PA, acceleration time (AT) increased while pre-ejection period to ejection time ratio (PEP/ET) decreased from 5 to 27 hours of age, reflecting the physiologic fall in PA pressure. In the Ao, FVI, AT, and PEP/ET remained unchanged, suggesting little change in left ventricular function.