Perinatal palliative care: focus on comfort.

Providing comfort while a patient is living with a life-limiting condition or at end of life is the hallmark of palliative care regardless of the patient's age. In perinatal palliative care, the patient is unable to speak for themselves. In this manuscript we will present guidelines garnered from the 15-year experience of the Neonatal Comfort Care Program at Columbia University Irving Medical Center, and how they provide care for families along the perinatal journey. We will describe essential tools and strategies necessary to consider in assessing and providing comfort to infants facing a life-limiting diagnosis in utero, born at the cusp of viability or critically ill where the burden of care may outweigh the benefit.

Parental assessment of comfort in newborns affected by life-limiting conditions treated by a standardized neonatal comfort care program.

OBJECTIVE: To assess the perception of parents concerning the state of comfort maintained in their infants born with life-limiting conditions and treated by a standardized neonatal comfort care program. STUDY DESIGN: Participants were parents (n=35 families) who elected comfort care for their newborns diagnosed with life-limiting conditions. Standardized comfort measures including family/infant bonding, warmth, nutrition/hydration and pain/discomfort management were provided to all infants. Parents consented to receive a questionnaire with quantitative response options and open-ended questions. RESULTS: Forty-two questionnaires (26 from mothers and 16 from fathers) were collected and analyzed. Most parents reported that their child was treated with respect, in a caring, peaceful and non-invasive environment. To the question 'Do you think that overall your baby received comfort' mode response was 'always'. CONCLUSION: Parents of infants with life-limiting conditions perceive that their babies experience comfort as a result of the care provided by the standardized Neonatal Comfort Care Program.

Neonatal outcomes of fetuses diagnosed with life-limiting conditions when individualized comfort measures are proposed.

OBJECTIVE: To describe the neonatal outcomes of a case series of infants who were prenatally diagnosed with potential life-limiting conditions and to whom individualized comfort measures were offered. STUDY DESIGN: This is a retrospective analysis of the postnatal outcomes of a selected population of 49 infants prenatally diagnosed with potential life-limiting conditions whose parents were prenatally referred for counseling to the comfort care team. RESULT: The prenatal diagnosis was confirmed postnatally in 45 infants. The only four survivors had a significant discrepancy between prenatal and postnatal diagnosis. Whether they were treated with individualized comfort measures (n=28) or intensive care (n=17), all the newborns died with similar median age at death (2 days). CONCLUSION: Diagnostic accuracy is the main determinant of outcomes. Provision of intensive care neither prevents the death of infants affected by life-limiting conditions nor prolongs life compared with that of infants treated with individualized comfort measures.

Packed red blood cell transfusion is an independent risk factor for necrotizing enterocolitis in premature infants.

OBJECTIVE: To determine whether a temporal association exists between antecedent packed red blood cell (PRBC) transfusions and necrotizing enterocolitis (NEC) in premature infants. STUDY DESIGN: This case-control study included inborn infants from a single center who developed NEC during a 2-year period. For every NEC infant, two matched controls from the same period were chosen based on gestational age and birth weight. Transfusion-related NEC was defined as antecedent PRBC transfusion within 48 h prior to the onset of any symptoms attributable to NEC. Bivariate analyses were used to compare baseline characteristics of all infants. To determine the raw odds ratio for the presence of exposure (transfusion) versus outcome (NEC), the hospital course (ages 6 to 63 days) of all study infants was divided into 48-h epochs; occurrence of transfusion and NEC was noted within each epoch. Generalized estimating equations were used to estimate the adjusted odds for developing NEC within an epoch with and without antecedent transfusion, controlling chronological age within infant as well as for gestational age, gender, feeding status in prior 48-h epoch and indicators of disease severity. RESULT: There were 3652 48-h epochs and 557 transfusions among 49 NEC infants and 97 controls; 17 infants had transfusion-related NEC, yielding a raw odds ratio of 3.01 (P<0.001). The adjusted odds ratios were 2.97 (P=0.003) for transfusion and 2.76 (P=0.05) for feeding status in the prior 48-h epoch. Infants who were being fed in the 48-h period prior to transfusion were more than eight times more likely to develop NEC than infants who were neither fed nor transfused. CONCLUSION: Antecedent PRBC transfusion appears to be an independent risk factor for developing NEC during the subsequent 48-h period.

Mesenchymal to epithelial conversion in rat metanephros is induced by LIF.

Inductive signals cause conversion of mesenchyme into epithelia during the formation of many organs. Yet a century of study has not revealed the inducing molecules. Using a standard model of induction, we found that ureteric bud cells secrete factors that convert kidney mesenchyme to epithelia that, remarkably, then form nephrons. Purification and sequencing of one such factor identified it as leukemia inhibitory factor (LIF). LIF acted on epithelial precursors that we identified by the expression of Pax2 and Wnt4. Other IL-6 type cytokines acted like LIF, and deletion of their shared receptor reduced nephron development. In situ, the ureteric bud expressed LIF, and metanephric mesenchyme expressed its receptors. The data suggest that IL-6 cytokines are candidate regulators of mesenchymal to epithelial conversion during kidney development.

Partial liquid ventilation (PLV) and lung injury: is PLV able to modify pulmonary vascular resistance?

INTRODUCTION: Partial liquid ventilation (PLV) with perfluorocarbons can be advantageous in treating lung injury. We studied this phenomenon in isolated piglet lungs devoid of systemic detractors by studying the changes in pulmonary vascular resistance (PVR) after lung injury with and without PLV. The following questions were asked. (1) Does PLV alone affect PVR in the uninjured lung? (2) Does PLV prevent the increase in PVR associated with oleic acid-induced lung injury? (3) Does PLV modify the increase in PVR associated with oleic acid lung injury? (4) Are the prophylactic and therapeutic effects of PLV on the increased PVR associated with oleic acid-induced lung injury different? METHODS: Neonatal piglet (3 to 4 kg) lungs were prepared without pulmonary ischemia, hypoxia, or reperfusion injury for in situ study. Before pulmonary vascular isolation (eg, aortic and ductus arteriosus ligation) the pulmonary artery (PA) and left atrium (LA) were cannulated and attached to a blood-primed perfusion circuit (flow; 80 mL/kg/min). Pressure-limited volume-cycled ventilation (FiO2, 0.21; TV, 15 mL/kg; PIP, 25 cm H2O) was accomplished via occlusive tracheostomy. Blood gas parameters were monitored continuously and maintained within normal range (SpaO2, 75%; pH, 7.35 to 7.45; pCO2, 35 to 45 torr). Pulmonary artery pressure (Ppa), left atrial pressure (PLa) and pulmonary blood flow (Qpa) were recorded and PVR calculated (PVR = Ppa - Pla/Qpa). After achieving a stable baseline with gas ventilation only, the animal preparations were assigned to one of the following four groups. In group 1 (n = 7) PLV was given alone, using endotracheally administered perfluorodecalin (15 mL/kg). In group 2 (Prophylactic, n = 7) PLV was given prophylactically 60 minutes before lung injury induced by injecting oleic acid (OA) at 0.08 mL/kg into the pulmonary artery. In group 3 (Therapeutic, n = 8) PLV was given 60 minutes after OA-induced lung injury. PPA, PLA, and QPA were measured and PVR was calculated. In group 4 (n = 7) OA was given alone. Significance of differences between groups was obtained by repeated measures analysis of variance (ANOVA). Results were expressed as mean +/- SEM (mm Hg/L/Kg). RESULTS: Group I showed baseline PVR of the normoxic gas ventilated animals was 127 +/- 19 mm Hg/L/kg. PVR 180 minutes after PLV administration was 160 +/- 15 mm Hg/L/kg (P = ns v baseline). In group 2 after OA infusion, PVR increased from 109 +/- 13 to 281 +/- 26 mm Hg/L/kg (P < .01 v baseline), and 60 minutes later, PVR decreased to 193 +/- 22 mm Hg/L/kg (P < .05 v OA). In group 3 PVR on gas ventilation, before lung injury, was 137 +/- 28 mm Hg/L/kg. Sixty minutes after OA infusion, PVR increased to 314 +/- 23 mm Hg/L/kg (P < .01 v baseline). After 60 additional minutes of PLV, PVR decreased to 201 +/- 31 mm Hg/L/kg, (P < .05 v maximum). In group 4 baseline PVR was 96 +/- 16 mm Hg/L/kg. After 120 minutes of OA injection, PVR increased to 414 +/- 20 mm Hg/L/kg (P < .01 v baseline). Endpoint analysis of PVR at the conclusion of the recording interval showed no difference between group 2 and group 3 (P = not significant [ns]). CONCLUSIONS: (1) PLV does not significantly after PVR in the uninjured lung when given for 2 hours; (2) prophylactic administration of PLV prevents the sustained increase in PVR known to be induced by OA injury; (3) PLV abates OA-induced elevation in PVR when given therapeutically after injury; and (4) Prophylactic and therapeutic PLV have similar effects on PVR in the OA-injured lung.

Iodine, thyroid function, and very low birth weight infants.

OBJECTIVE: Research was undertaken to test two hypotheses. First, during the early neonatal period, thyroid function of very low birth weight (VLBW) infants is suppressed by exposure to iodine-containing antiseptic solutions and/or iodized contrast media. Second, this suppression is more pronounced in small for gestational age (SGA) infants. METHODS: Urinary iodine concentration and thyroid function measurements were obtained prospectively from 44 VLBW infants with gestational ages at birth of 30 +/- 2.3 weeks and weights of 1223 +/- 231 g. Eleven of these infants were SGA. The infants were grouped according to iodine exposure: 18 infants had no increased exposure and served as control infants; 9 infants were exposed to an iodine-containing antiseptic (povidone iodine); 12 infants were exposed to an iodized contrast medium (iopamidol); and 5 infants were exposed to both agents. Urinary iodine and serum free triiodothyronine, free thyroxine, and thyrotropin were measured on days 1, 7, 14, 21, and 28 of life. RESULTS: During the period of maximum exposure (days 1 to 7), the concentration of iodine in the urine of study infants was 2 to 4 orders of magnitude greater than that in the urine of control infants (123 +/- 141 micrograms/L). During the subsequent 3 weeks, levels of urinary iodine in study infants returned to levels that were not significantly different from controls. On day 7 of life, iodine-exposed infants had a significantly higher mean thyrotropin level than control infants, whereas on day 28, free triiodothyronine and thyroxine levels were lower. Of the 26 iodine-exposed infants, 6 had transient hyperthyrotropinemia and 2 had transient hypothyroidism. When exposed to iodine, SGA infants had more labile thyroid function than normally grown iodine-exposed or control infants. These SGA infants had significantly lower levels of thyroid hormones in umbilical cord blood, increased production of thyroid hormones on day 14 of life, and lower levels again at 1 month. CONCLUSION: In VLBW infants, the use of iodine-containing antiseptic solutions and iodized contrast media results in massive uptake of iodine that is associated with alterations in thyroid function. It is reasonable to suggest that, whenever possible, iodized products should be avoided in VLBW infants, because their routine use results in exposure to excessive loads of iodine, which can be associated with hyperthyrotropinemia and hypothyroidism.

Clinical significance of fetal intracranial hemorrhage.

OBJECTIVE: We reviewed our experience with six consecutive cases of fetal intracranial hemorrhage and the cases published in the English literature in an attempt to devise an original prognostic scoring system for antenatal intracranial hemorrhage. STUDY DESIGN: The series included the cases of fetal intracranial hemorrhage detected at our institution between 1992 and 1994 by transabdominal ultrasonography. In addition, we performed an English literature search (Medline computer search, National Library of Medicine) of all reported cases of a prenatal diagnosis of intracranial hemorrhage. The prenatal ultrasonographic findings were correlated with the clinical outcome, which was divided into (1) normal outcome or mild neurologic sequelae and (2) poor outcome (severe neurologic impairment and fetal or neonatal death). RESULTS: Six cases of intracranial hemorrhage were detected in a population of 6641 pregnancies (0.9/1000) at our institution. Parenchymal involvement was present in three cases. Review of the English literature revealed 35 additional cases with prenatal ultrasonographic findings and postnatal follow-up. The total cases (n = 41) were divided into three groups: (1) isolated intraventricular hemorrhage (n = 20), (2) parenchymal hemorrhage (n = 13), and (3) subdural or subarachnoid hemorrhage (n = 8). Overall, poor outcome was present in 68% of cases, including 45% (9/20) of intraventricular hemorrhage, 92% (12/13) of parenchymal hemorrhage, and 88% (7/8) of subdural or subarachnoid hemorrhage. The heterogeneity of the intraventricular hemorrhage group in both severity of antenatal findings and outcome prompted us to devise a prognostic scoring system based on prenatal ultrasonographic lesions, grouping cohorts with similar outcomes. Outcome was favorable in 100% (5/5) of grade 1 intraventricular hemorrhage cases, in 50% (6/12) of grade 2 cases, and in 0% (0/3) of grade 3 cases. CONCLUSIONS: Fetal intracranial hemorrhage can be classified on the basis of the anatomic location of the intracranial bleeding. The prognosis is poor in nearly 90% of parenchymal and subdural hemorrhages, whereas it is better in the subgroup with intraventricular hemorrhage. The prognostic scoring system we propose for intraventricular hemorrhage may assist the physician in providing patients with prognostic information.

Ureteropelvic junction obstruction in utero and ex utero.

Seventy cases of ureteropelvic junction obstruction, bilateral or unilateral, were followed prospectively throughout gestation and postnatally for an average of 2.3 years. Cases of ureteropelvic junction obstruction with a renal pelvis dilated less than 1 cm uniformly did well; those with a pyelectasis more than 2 cm, both bilateral and unilateral, had a favorable outcome in approximately three-quarters. Surprisingly, pelvis dilatation between 1-2 cm had a better outcome if bilateral than if unilateral.