Pneumothorax is usually diagnosed when signs of life-threatening tension pneumothorax develop. The case report describes novel data derived from miniature superficial sensors that continuously monitored the amplitude and symmetry of the chest wall tidal displacement (TDi) in a premature infant that suffered from pneumothorax. Off-line analysis of the TDi revealed slowly progressing asymmetric ventilation that could be detected 38 min before the diagnosis was made. The TDi provides novel and valuable information that can assist in early detection and decision making.

We report a case in which a 22q11.2 deletion was diagnosed prenatally in a low-risk pregnancy owing to the finding of transient bilateral pedal edema in the fetus. Microdeletion of chromosome 22q11.2 is the most common deletion syndrome in humans and is associated with a variety of malformations. Particularly common are cardiac defects affecting the outflow tract, found in around 50% of 22q11.2 deletion cases1. Among fetuses with this type of heart defect, 22q11.2 deletion is found in 20% of cases2. Various extracardiac abnormalities are associated with 22q11.2 deletion, as well as significant functional abnormalities, including neurodevelopmental disabilities, immune deficiency and hypocalcemia3. The deletion occurs typically de-novo, but up to 17% of cases are inherited from an affected parent4. The prenatal diagnosis of 22q11.2 deletion has been described since 1997, with fluorescent in-situ hybridization analysis being performed mostly for cases with prenatal detection of a conotruncal heart defect or a family history positive for the deletion1. Many cases with non-cardiac findings possibly go undetected prenatally, as standard cytogenetic testing does not identify this deletion. In the present case, a 29-year-old nulliparous woman attended for routine prenatal ultrasound at 15 weeks' gestation. There were no risk factors for congenital anomalies apart from maternal cleft lip and palate that had been corrected surgically. Transvaginal ultrasound was performed using a Philips IU22 3–10-MHz probe (Bothell, WA, USA). Fetal size was compatible with gestational age. Abnormal sonographic findings in the fetus at 15 weeks included bilateral pedal edema on the dorsal side of the feet (Figure 1 and Videoclip S1), a mildly enlarged, mildly hypokinetic heart with a small pericardial effusion and a persistent left superior vena cava (SVC). The heart structure was otherwise normal. On the follow-up examination at 22 weeks, both the pedal edema and cardiac findings had completely resolved and findings on ultrasound examination were normal except for the persistent left SVC. Amniocentesis was performed and showed normal female karyotype. Further genetic testing, by comparative genomic hybridization analysis, demonstrated a 22q11.2 deletion. The pregnancy was terminated at the request of the parents. In this case, 22q11.2 deletion was diagnosed prenatally based on the observation of transient pedal edema without the presence of a major heart defect. It was an independent finding and unlikely to be related to the mildly hypokinetic heart since other signs of heart failure were absent. Pedal edema in the fetus is an unusual finding. Differential diagnosis includes Turner syndrome, non-lymphatic edema and several hereditary lymphedema syndromes such as lymphedema–distichiasis syndrome, lymphedema and ptosis syndrome, Milroy's primary congenital lymphedema, hereditary lymphedema Type II and congenital recessive type lymphedema5. In our case, resolution of the edema in combination with a normal fetal karyotype excluded these syndromes. Interestingly, the phenomenon of early and transient pedal edema described in the current case resembles the phenomenon of early and transient nuchal edema, a well-established marker for major chromosomal abnormalities, yet the pathogenesis of both is unclear. In conclusion, our finding suggests that 22q11.2 deletion may be included in the differential diagnosis of pedal edema in the fetus. A. Gover*†, A. Rotschild†‡ and M. Bronshtein§ †Carmel Medical Center, Haifa, Israel; ‡The Ruth & Bruce Rappaport Faculty of Medicine, Technion, Haifa, Israel; §Faculty of Social Welfare and Health Science, Haifa University, Haifa, Israel *Correspondence. (e-mail: [email protected]) Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.

Objective: Existing respiratory rate (RR) monitors suffer from inaccuracy. The study assesses the accuracy of a novel modality that monitors lung ventilation with miniature motion sensors. Study Design: RR was measured by three methods: impedance technology, motion sensors and visual count, in babies ( n =9) that breathed spontaneously or with respiratory support and babies ( n =12) that received high-frequency oscillatory ventilation (HFOV). Results: A line close to equality (slope=0.96, r 2 =0.83) was obtained between the motion sensor and the visual count of the RR with narrow 95% limits of agreements (<14.0 b.p.m.). The relationship between the impedance and the visual count showed a lower correlation ( r 2 =0.65) and wider 95% limits of agreements (21.4 b.p.m.). The motion sensor- and the ventilator-determined RRs demonstrated a good agreement during HFOV, whereas the impedance failed to measure the RR during HFOV. Conclusion: Monitoring RR with motion sensors is more accurate compared with the impedance, in infants, in all ventilation modes.

We present a case of a female neonate who had a nonimmune hydrops fetalis and severe hemolytic anemia due to a rare combination of glucose-6-phosphate dehydrogenase (G6PD) deficiency and congenital dyserythropoietic anemia. We conclude that in severe cases with persistent anemia one should search after delivery for a second reason other than G6PD deficiency alone.

Context: Term-born children conceived by in vitro fertilisation (IVF) are reportedly taller than naturally conceived (NC) children. High levels of growth promoting hormones and epigenetic imprinting have been suggested as pathogenetic mechanisms. Hypothesis: Tall stature in prematurely born IVF-conceived (IVF-C) children suggests pre- or early implantation imprinting rather than a postnatal effect. Methods: We studied 334 very low birthweight (VLBW: birth weight <1500 g) children born prematurely during 1995–1999 and obtained their anthropometric measures at 6–10 years of age. Perinatal and neonatal data were obtained from the Israeli VLBW database. We compared IVF-C, ovulating agents conceived (OA-C) and naturally conceived (NC) groups of children with respect to their and their parents’ anthropometry and their perinatal/neonatal variables. Results: Childhood height standard deviation scores (SDSs) were greatest in IVF-C (−0.12 (SD 1.25); p<0.022) and insignificantly greater in OA-C (−0.37 (SD 1.02)) as compared to NC (−0.58 (SD 1.36)) children. The IVF-C and NC groups were significantly different regarding 17 parental and perinatal variables; however, multiple regression analysis including these variables showed that, as compared with NC, IVF-C children had significantly older mothers at birth with earlier follow-up during pregnancy and more multi-fetal pregnancies. Conclusions: IVF-C and to a lesser extent OA-C prematurely born children are taller than otherwise NC children. After ruling out postnatal and parental causes, we speculate that pre- or early implantation factors might have contributed to the taller stature of IVF-C children.

A 38-year-old pregnant woman was admitted at 29 weeks of pregnancy to the High Risk Obstetrics Unit at the Carmel Medical Center with a diagnosis of fetal arrhythmia. In her past obstetric history there had been two therapeutic abortions and two spontaneous deliveries of two healthy babies. She had been treated for many years with clonazepam, valproic acid and topiramate in an effort to control her highly resistant epilepsy. During this pregnancy, there were no documented episodes of seizures. Fetal ultrasounds in earlier stages of pregnancy including a complete anatomical scan for fetal anomalies done at 22 weeks of gestation were normal. An amniocentesis performed because of maternal age showed a normal female karyotype. The fetal echocardiography study performed at 29 weeks of gestation documented short events of supraventricular tachycardia (SVT) with a fetal heart rate of up to 260 bpm. SVT events were shown to be sporadic during 24-h hospitalization. Fetal monitoring was performed three times a day for a 1-h period each time, and following that frequent US scans were performed. SVT events lasted from 30 s to 2 min. There were no structural cardiac anomalies and no signs of fetal hydrops. Repeated ultrasound evaluations showed no changes. A decision not to provide fetal treatment was made based on the low frequency of the paroxysmal events and the lack of signs of heart failure in repeated weekly ultrasound studies. A 2690-g baby girl was born spontaneously at 39 weeks of gestation. APGAR score was 9 at both 1 and 5 min respectively. The physical examination was normal except for mild hypotony and sporadic myoclonic jerks. Blood levels of glucose and electrolytes were normal. Initial interpretation concluded that the clonic movements of the baby were related to the withdrawal syndrome of maternal clonazepam therapy. On day two, the jerky movements became more frequent and developed into generalized convulsions, which were difficult to control inspite of treatment with clonazepam (0.05 mg/kg q 12 h); phenobarbital (5 mg/kg maintenance following loading dose) and phenytoin (4 mg/kg following loading dose). A full neurological examination did not reveal focal deficiencies. An EEG showed an abnormal background with continuous persistent bilateral epileptic activity. A cranial ultrasound disclosed extensive hypoechogenic regions in both hemispheres. A brain CT documented extensive bilateral ischaemic areas and gross calcifications of the left basal ganglia (Figure 1). These calcifications were not suggestive of intrauterine toxoplasmosis or cytomegalovirus infections. The nature of these findings indicated that brain damage occurred during pregnancy and not during or after birth. Toxicology evaluation did not support the hypothesis that this extensive brain damage was a result of abnormally high maternal serum levels of clonazepam, valproic acid or topiramate. Neither the mother nor Figure 1—A head CT scan showing extensive bihemispheric areas of infarction. The calcifications present in the brain tissue suggest that the insult occurred earlier during pregnancy

Diagnosis and treatment of an anuric premature infant with severe respiratory compromise and a normal renal ultrasound (US), is a difficult task that requires a multidisciplinary approach. A 29‐week gestation premature male infant, born after 5 weeks of worsening oligohydramnios, was ventilated for respiratory distress and remained anuric. Intensive clinical investigations and pediatric nephrology consultation that predicted very poor prognosis were followed by progressive renal failure, electrolyte imbalance, respiratory failure, ventricular arrhythmia, and finally cardiac arrest and death on day 5. In view of the predicted poor outcome, and after discussion with the parents, a decision was made not to start peritoneal dialysis (PD), and to offer only palliative therapy, with comfort care alone. Pre and postnatal diagnosis lead, in this case, to an ethical challenge that focuses on the question of futility. Copyright © 2006 John Wiley & Sons, Ltd.

Splanchnic ischemia/reperfusion (I/R) induces a systemic inflammatory response with acute lung injury. Impaired production of endothelial nitric oxide (NO) plays a key role in this process. We evaluated the effects of early treatment with inhaled NO (iNO) on lung microcirculatory inflammatory changes during splanchnic I/R. I/R was induced in rats by occlusion of the superior mesenteric artery (SMA; 40 min) and reperfusion (90 min). Four groups were studied: Control, anesthesia only; Sham, all surgical procedures without I/R, ventilated with air; Air, SMA I/R, ventilation with air; and NO, SMA I/R, ventilation with NO (20 ppm) starting 10 min before reperfusion. Intravital video microscopy was used to monitor pulmonary macromolecular flux and capillary flow velocity (CFV). Leukocyte infiltration was determined by morphometry. SMA I/R decreased mean arterial blood pressure, capillary CFV (P < 0.01), and shear rate (P < 0.01), and increased pulmonary macromolecular leak by 138% +/- 8% (P < 0.001). iNO markedly attenuated the increase in macromolecular leak (P < 0.01), blunted the decrease in capillary CFV (P < 0.05) and shear rate (P < 0.05), and prevented the increase in leukocyte infiltration of the lungs after SMA I/R (P < 0.05). The direct, real-time, in vivo data suggest that early institution of low-dose iNO therapy effectively ameliorates the acute remote pulmonary inflammatory response after splanchnic I/R.

A premature female infant weighing 753 g was born by emergency caesarean delivery due to maternal chorioamnionitis at 26 weeks' gestation. She received ventilatory support and surfactant. On day 6, after respiratory deterioration, she had a significant episode of oxygen desaturation and bradycardia. Transillumination of the chest revealed a right pneumothorax. Insertion of a chest drain improved the clinical condition, but radiography revealed a residual pneumothorax. Large amount of continuous air draining through the chest-tube raised the suspicion of a broncho-pleural fistula. Despite re-insertion of additional drains, the following days were marked by recurrent, protracted pneumothoraces of the right lung. Review of the radiographs revealed a thin catheter at the level of the carina towards the right costophrenic angle (Figure). It was presumed to be part of the closed tracheal suction system used in our unit. The infant underwent rigid bronchoscopy and the foreign body was extracted with the use of a small semi-rigid grasper. A 5.5-cm length catheter (the distal part of the closed suction system) was removed from the right bronchus. In the subsequent days, the thoracic drains were withdrawn and the patient was weaned off ventilation two weeks later. It is unclear how the suction catheter was separated. Two possible explanations were considered. The suction catheter may not have been withdrawn completely after suctioning and part of the suction tube was inadvertently separated while shortening the endotracheal tube. Or, there was a defect in the suction catheter itself. In either case, additional suctioning may have lodged the tube into the lung. Examining the catheter under high magnification did not help to elucidate how the separation occurred. Although suctioning is a crucial and frequent procedure for the intensive care staff, there continues to be a need for improving suctioning methods.

Splanchnic ischemia-reperfusion (I/R) causes tissue hypoxia that triggers local and systemic microcirculatory inflammatory responses. We evaluated the effects of hyperoxia in I/R induced by 40-min superior mesenteric artery (SMA) occlusion and 120-min reperfusion in four groups of rats: 1) control (anesthesia only), 2) sham operated (all surgical procedures without vascular occlusion; air ventilation), 3) SMA I/R and air, 4) SMA I/R and 100% oxygen ventilation started 10 min before reperfusion. Leukocyte rolling and adhesion in mesenteric microvessels, pulmonary microvascular blood flow velocity (BFV), and macromolecular (FITC-albumin) flux into lungs were monitored by intravital videomicroscopy. We also determined pulmonary leukocyte infiltration. SMA I/R caused marked decreases in mean arterial blood pressure (MABP) and blood flow to the splanchnic and hindquarters vascular beds and pulmonary BFV and shear rates, followed by extensive increase in leukocyte rolling and adhesion and plugging of >50% of the mesenteric microvasculature. SMA I/R also caused marked increase in pulmonary sequestration of leukocytes and macromolecular leak with concomitant decrease in circulating leukocytes. Inhalation of 100% oxygen maintained MABP at significantly higher values ( P < 0.001) but did not change regional blood flows. Oxygen therapy attenuated the increase in mesenteric leukocyte rolling and adherence ( P < 0.0001) and maintained microvascular patency at values not significantly different from sham-operated animals. Hyperoxia also attenuated the decrease in pulmonary capillary BFV and shear rates, reduced leukocyte infiltration in the lungs ( P < 0.001), and prevented the increase in pulmonary macromolecular leak ( P < 0.001), maintaining it at values not different from sham-operated animals. The data suggest that beneficial effects of normobaric hyperoxia in splanchnic I/R are mediated by attenuation of both local and remote inflammatory microvascular responses.

To the Editor. High-frequency oscillatory ventilation (HFOV) has become a very common mode of ventilation in many centers. In some of them it is used as a rescue mode of ventilation and in others as the primary mode of ventilation of newborn infants requiring mechanical ventilatory support. …

AIM:To examine the relation between grade III-IV periventricular/intraventricular haemorrhage (PVH/IVH) and antenatal exposure to tocolytic treatment in very low birthweight (VLBW) premature infants.STUDY DESIGN:The study population consisted of 2794 infants from the Israel National VLBW Infant Database, of gestational age 24-32 weeks, who had a cranial ultrasound examination during the first 28 days of life. Infants of mothers with pregnancy induced hypertension or those exposed to more than one tocolytic drug were excluded. Of the 2794 infants, 2013 (72%) had not been exposed to tocolysis and 781 (28%) had been exposed to a single tocolytic agent. To evaluate the effect of tocolysis and confounding variables on grade III-IV PVH/IVH, the chi(2) test, univariate analysis, and a logistic regression model were used.RESULTS:Of the 781 infants (28%) exposed to tocolysis, 341 (12.2%) were exposed to magnesium sulphate, 263 (9.4%) to ritodrine, and 177 (6.3%) to indomethacin. The overall incidence of grade III-IV PVH/IVH was 13.4%. In the multivariate logistic regression analysis, the following factors were related significantly and independently to grade III-IV PVH/IVH: no prenatal steroid treatment, low gestational age, one minute Apgar score 0-3, respiratory distress syndrome, patent ductus arteriosus, mechanical ventilation, and pneumothorax. Infants exposed to ritodrine tocolysis (but not to the other tocolytic drugs) were at significantly lower risk of grade III-IV PVH/IVH after adjustment for other variables (odds ratio = 0.3; 95% confidence interval 0.2 to 0.6).CONCLUSION:This study suggests that antenatal exposure of VLBW infants to ritodrine tocolysis, in contrast with tocolysis induced by magnesium sulphate or indomethacin, was associated with a lower incidence of grade III-IV PVH/IVH.

To the Editor. Midazolam, a relatively new sedative and muscle relaxant that belongs to the benzodiazepine family, has lately started to be part of the arsenal of drugs used in the neonatal intensive care units.There are a few reports and studies related to the benefits and safety of its use in premature infants. Few side effects were reported as a 12% to 43% decrease in the midcerebral blood flow velocity after a transient drop in the systemic blood pressure, after administration to ventilated infants.1–3 Involuntary epileptiform movements were observed as well after intravenous bolus injection of 0.2 mg/kg midazolam.4Three premature infants in our unit suffered from accentuated myoclonic jerks, resembling clonic seizures, within 5 minutes after they received a slow bolus administration of 0.1 mg/kg of midazolam for sedation. The babies were born at 24, 25, and 26 weeks' gestation, with an average weight of 671 ± 170 g. The drug was administrated to the first infant on day 28, to the second infant on day 32, and to the third infant on day 2. It was the first time this medication was administrated to each of the infants. Changes in oxygen saturation, respiratory rate, heart rate, skin color, or blood pressure were not observed. The abnormal movements resolved within 5 to 10 minutes after they started. Three other infants who received midazolam during the same period did not suffer from any evident side effects.The actual mechanism of this effect is unclear. It could be related to the hemodynamic changes described in the cerebral blood flow, cortical inhibition, or changes induced in neurotransmitters or specific receptors stimulatory/inhibitory activity.Although in the mentioned references midazolam is considered as relatively safe for use in the VLBW premature infant, more information about the pharmacology of this drug and effects on the developing brain are needed to consider its safe use in those infants.