Fetal liver iron overload: the role of MR imaging.

OBJECTIVE: To assess the potential role of MR imaging in the diagnosis of fetal liver iron overload. METHODS: We reviewed seven cases of abnormal liver signal in fetuses referred to MR imaging in a context of suspected congenital infection (n = 2), digestive tract anomalies (n = 3) and hydrops fetalis (n = 2). The average GA of the fetuses was 31 weeks. The antenatal diagnoses were compared with histological data (n = 6) and postnatal work-up (n = 1). RESULTS: Magnetic resonance imaging demonstrated unexpected abnormal fetal liver signal suggestive of iron overload in all cases. The iron overload was confirmed on postnatal biopsy (n = 2) and fetopathology (n = 4). The final diagnosis was hepatic hemosiderosis (haemolytic anaemia (n = 2) and syndromal anomalies (n = 2)) and congenital haemochromatosis (n = 3). In all cases, the liver appeared normal on US. CONCLUSIONS: Magnetic resonance is the only imaging technique able to demonstrate liver iron overload in utero. Yet, the study outlines the fundamental role of MR imaging in cases of congenital haemochromatosis. The antenatal diagnosis of such a condition may prompt ante-(in the case of recurrence) or neonatal treatment, which might improve the prognosis.

Neurodevelopmental outcome at 2 years in children born preterm treated by amnioreduction or fetoscopic laser surgery for twin-to-twin transfusion syndrome: comparison with dichorionic twins.

OBJECTIVE: We sought to assess long-term neurodevelopment of children born prematurely treated for twin-to-twin transfusion syndrome and dichorionic (DC) twins. STUDY DESIGN: In all, 21 and 88 children treated with amnioreduction (AR) and fetoscopic laser surgery (FLS), respectively, and 222 DC twins matched for gestational age at delivery were assessed with Ages and Stages Questionnaire and standardized examination at 2 years of age. RESULTS: Normal development was noted in 81% in the AR group, 88.6% in the FLS group, and 93.1% in the DC twins. Minor and major neurologic impairment was found in 9.5% and 9.5% following AR, in 6.8% and 4.6% of FLS children, and in 3.4% and 3.4% in DC twins, respectively. Ages and Stages Questionnaire assessment was similar in FLS and DC children but scores were lower (P = .01) and domains were more often abnormal (60% vs 27%; P = .005) following AR. CONCLUSION: Neurodevelopmental outcome is similar in twin-to-twin transfusion syndrome survivors treated by FLS and in DC control subjects; but survivors treated with AR have an increased risk of neurodevelopmental delay at 2 years of age.

A multicenter, randomized, placebo-controlled trial of prophylactic recombinant granulocyte-colony stimulating factor in preterm neonates with neutropenia.

OBJECTIVE: To test the hypothesis that prophylactic treatment of neutropenic premature neonates with recombinant granulocyte-colony stimulating factor (rG-CSF) would reduce the incidence of nosocomial infections (NIs). STUDY DESIGN: A total of 25 neonatal intensive care units participated in this multicenter, randomized, double-blind, placebo-controlled trial. Premature infants of gestational age (GA)

Neonatal outcome in preterm monochorionic twins with twin-to-twin transfusion syndrome after intrauterine treatment with amnioreduction or fetoscopic laser surgery: comparison with dichorionic twins.

OBJECTIVE: The purpose of this study was to compare neonatal outcome in preterm neonates after twin-to-twin transfusion syndrome (TTTS) that was treated by amnioreduction or fetoscopic laser surgery (FLS) and in dichorionic neonates who were matched for gestational age at birth. STUDY DESIGN: Neonatal outcome was assessed in 137 TTTS preterm neonates who were treated primarily with either amnioreduction (n = 36) or FLS (n = 101) and compared with dichorionic twins (n = 242) who were delivered at our center at 24-34 weeks of gestation. RESULTS: Adverse neonatal outcome (death or severe cerebral lesions) was more frequent in the amnioreduction group than in the FLS and dichorionic groups. Overall neonatal outcome was comparable in FLS and dichorionic infants. However, neonatal morbidity was higher in FLS neonates at <30 weeks of gestation that was related mainly to failed laser therapy. CONCLUSION: In preterm TTTS cases, neonatal morbidity decreases independently with gestational age and after successful FLS. Neonatal morbidity that was specific of TTTS was higher in the amnioreduction group and in cases with failed laser therapy.

Morphine does not provide adequate analgesia for acute procedural pain among preterm neonates.

BACKGROUND: Morphine alleviates prolonged pain, reduces behavioral and hormonal stress responses induced by surgery among term neonates, and improves ventilator synchrony and sedation among ventilated preterm neonates, but its analgesic effects on the acute pain caused by invasive procedures remain unclear. OBJECTIVE: To investigate the analgesic efficacy of intravenously administered morphine on heel stick-induced acute pain among preterm neonates. DESIGN: This study was nested within a prospective, randomized, double-blind, multicenter, placebo-controlled trial (the NEOPAIN Trial). SETTING: A tertiary-care NICU in a teaching hospital. PARTICIPANTS: Forty-two preterm neonates undergoing ventilation. INTERVENTIONS: Neonates were randomized to either the morphine (loading dose of 100 microg/kg, followed by infusions of 10-30 microg/kg per hour according to gestation, N = 21) or placebo (5% dextrose infusions, N = 21) group. Pain responses to 3 heel sticks were evaluated, ie, before the loading dose (T1), 2 to 3 hours after the loading dose (T2), and 20 to 28 hours after the loading dose (T3). MAIN OUTCOMES MEASURES: Pain was assessed with the Douleur Aiguë Nouveau-né (DAN) scale (behavioral pain scale) and the Premature Infant Pain Profile (PIPP) (multidimensional pain scale); plasma morphine levels were measured at T3. RESULTS: Infants in the placebo and morphine groups had similar gestational ages (mean +/- SD: 27.2 +/- 1.7 vs 27.3 +/- 1.8 weeks) and birth weights (972 +/- 270 vs 947 +/- 269 g). Mean +/- SD DAN pain scores at T1, T2, and T3 were 4.8 +/- 4.0, 4.6 +/- 2.9, and 4.7 +/- 3.6, respectively, for the placebo group and 4.5 +/- 3.8, 4.4 +/- 3.7, and 3.1 +/- 3.4 for the morphine group. The within-group factor (pain at T1, T2, and T3) was not statistically different over time. The between-group analysis (infants receiving placebo versus those receiving morphine) showed no significant differences. Mean +/- SD PIPP pain scores at T1, T2, and T3 were 11.5 +/- 4.8, 11.1 +/- 3.7, and 9.1 +/- 4.0, respectively, for the placebo group and 10.0 +/- 3.6, 8.8 +/- 4.9, and 7.8 +/- 3.6 for the morphine group. The within-group factor was statistically different over time. The between-group analysis showed no significant differences. Mean +/- SD plasma morphine levels at T3 were 0.44 +/- 1.79 ng/mL and 63.36 +/- 33.35 ng/mL for the placebo and morphine groups, respectively. There was no correlation between plasma morphine levels and pain scores at T3 (DAN, R = -0.05; PIPP, R = -0.02). CONCLUSIONS: Despite its routine use in the NICU, morphine given as a loading dose followed by continuous intravenous infusions does not appear to provide adequate analgesia for the acute pain caused by invasive procedures among ventilated preterm neonates.

Endoscopic laser surgery versus serial amnioreduction for severe twin-to-twin transfusion syndrome.

BACKGROUND: Monochorionic twin pregnancies complicated by severe twin-to-twin transfusion syndrome at midgestation can be treated by either serial amnioreduction (removal of large volumes of amniotic fluid) or selective fetoscopic laser coagulation of the communicating vessels on the chorionic plate. We conducted a randomized trial to compare the efficacy and safety of these two treatments. METHODS: Pregnant women with severe twin-to-twin transfusion syndrome before 26 weeks of gestation were randomly assigned to laser therapy or amnioreduction. We assessed perinatal survival of at least one twin (a prespecified primary outcome), survival of at least one twin at six months of age, and survival without neurologic complications at six months of age on the basis of the number of pregnancies or the number of fetuses or infants, as appropriate. RESULTS: The study was concluded early, after 72 women had been assigned to the laser group and 70 to the amnioreduction group, because a planned interim analysis demonstrated a significant benefit in the laser group. As compared with the amnioreduction group, the laser group had a higher likelihood of the survival of at least one twin to 28 days of age (76 percent vs. 56 percent; relative risk of the death of both fetuses, 0.63; 95 percent confidence interval, 0.25 to 0.93; P=0.009) and 6 months of age (P=0.002). Infants in the laser group also had a lower incidence of cystic periventricular leukomalacia (6 percent vs. 14 percent, P=0.02) and were more likely to be free of neurologic complications at six months of age (52 percent vs. 31 percent, P=0.003). CONCLUSIONS: Endoscopic laser coagulation of anastomoses is a more effective first-line treatment than serial amnioreduction for severe twin-to-twin transfusion syndrome diagnosed before 26 weeks of gestation.

Crossover trial of analgesic efficacy of glucose and pacifier in very preterm neonates during subcutaneous injections.

OBJECTIVE: Very preterm newborns undergo multiple invasive procedures. Nonpharmacological interventions are valuable alternatives for pain relief during minor procedures in neonates. Oral sucrose analgesia has been widely studied in term and preterm neonates during painful procedures. The analgesic effect of oral glucose in very preterm infants has not yet been reported. The objectives of this study were to assess the analgesic effect of orally administered glucose and to determine the synergetic analgesic effect of glucose and pacifiers during subcutaneous injections in very preterm neonates using a validated behavioral acute pain rating scale. DESIGN: Two crossover trials. SETTING: One neonatal intensive care unit in a community-based general hospital. METHODS: A prospective study was conducted in 40 very preterm neonates. Each infant received 2 treatments in a crossover manner during 2 consecutive subcutaneous injections of erythropoietin. The first trial (25 infants) was intended to compare oral 30% glucose (0.3 mL) versus placebo (0.3 mL of sterile water); the second trial (15 infants) compared oral 30% glucose (0.3 mL) versus oral 30% glucose (0.3 mL) followed by sucking a pacifier. The primary outcome measure was the evaluation of pain induced by a subcutaneous injection of erythropoietin, using Douleur Aiguë Nouveau-né scale (0 no pain, 10 maximum pain). RESULTS: Twenty-four infants completed the study in the first trial and 15 in the second one. Mean (95% confidence interval [CI]) gestational age, birth weight, postnatal age, and weight at inclusion for neonates in the first and second trial were, respectively, 28.1 (95% CI: 27.3-29.0) and 29.1 (95% CI: 27.8-30.4) weeks, 1036 (95% CI: 944-1128) and 995 (95% CI: 848-1141) g, 26.4 (95% CI: 22.4-30.3) and 26 (95% CI: 22.0-29.9) days, and 1234 (95% CI: 1120-1348) and 1209 (95% CI: 1059-1359) g. In the first trial, median (interquartile) pain scores for placebo and 30% glucose, respectively, were 7 (2.5-9.75) and 4.5 (1-6). In the second trial, median (interquartile) pain scores for 30% glucose and for 30% glucose plus pacifier, respectively, were 4 (2-7) and 4 (1-6). CONCLUSIONS: A small dose of 0.3 mL of 30% oral glucose has an analgesic effect in very preterm neonates during subcutaneous injections. This effect is clinically evident because it can be detected by a behavioral pain rating scale. The synergetic analgesic effect of glucose plus sucking a pacifier is less obvious in very preterm neonates as opposed to what other studies have showed in full-term infants.