Long-term neurodevelopmental outcome of neonates born at term with perinatal haemorrhagic stroke: A population-based study.

AIM: To assess the long-term neurodevelopmental outcome of neonates born at term diagnosed with perinatal haemorrhagic stroke (PHS) and investigate the associations among brain territorial involvement, clinical risk factors, and neurodevelopmental outcomes. METHOD: We conducted a population-based study enrolling 55 neonates born at term with PHS confirmed by magnetic resonance imaging born between 2007 and 2017. Long-term neurodevelopmental outcome was assessed using the Bayley Scales of Infant Development, Second Edition, the Brunet-Lézine test, and the Stanford-Binet Intelligence Scales, Fifth Edition. RESULTS: Follow-up was available in 50 (91%) of the infants, at a median age of 60 months (interquartile range 35-88). Forty per cent of the infants developed according to population norms, and developmental disabilities were diagnosed less frequently among neonates with frontal lobe PHS. In a multivariable model, parietal lobe PHS increased the risk for cerebral palsy (odds ratio [OR] 6.7; 95% confidence interval [CI] 1.1-41.4) and cognitive impairment (OR: 23.6; 95% CI: 2.9-194.9), while the involvement of the thalamus and/or basal ganglia was associated with epilepsy (OR: 7.0; 95% CI: 1.3-37.7). Seizures on admission were associated with epilepsy (OR: 10.8; 95% CI: 1.8-64.3). Patients with PHS affecting multiple lobes had poor prognosis. INTERPRETATION: Parietal lobe haemorrhage, the involvement of the thalamus/basal ganglia, PHS affecting multiple lobes, and seizures were independent predictors of chronic neurodevelopmental sequelae, suggesting that the stroke territorial involvement and clinical risk factors influence the outcome of PHS.

Development and validation of an automated assessment tool of echocardiography skills acquired on a neonatal simulator.

INTRODUCTION: Simulators are increasingly used for training in echocardiography. However, there is no objective method to assess the skills acquired. Our objective was to develop and test an automated method to assess echocardiography skills. METHODS: To automate the image quality evaluation, we expanded our previously developed neonatal echocardiography simulator to enable recording of images of the 26 standard cuts and process the image quality. We then compared the automated and visual methods in scoring image quality of the echocardiograms obtained by 22 trainees. RESULTS: Each echocardiographic image representing a slice of a three-dimensional volume possesses 3 axes (X, Y, and Z) that correspond to the roll, pitch, and yaw angles of the transducer, respectively. Therefore, if the placement and orientation of the transducer are correct, the acquired image represents the appropriate cardiac window with the desired orientation in all 3 axes. The automated system gives a score of 0 if the transducer is not in the appropriate cardiac window. A score of 1, 2, or 3 is given if the image falls within the range of one, two, or three angles, respectively. There was no difference in the image quality score between automated and visual assessment methods (46.0 ± 13.0 vs 45.1 ± 14.4, P = .19). The two methods had excellent correlation (r = .95). The bias and precision were 0.9 and 8.8, respectively. CONCLUSIONS: The automated method is comparable to visual method for assessment of image quality. The automated process allows for instantaneous feedback and has the potential to standardize assessment of echocardiography skills of trainees.

Hemodynamic Changes During Rewarming Phase of Whole-Body Hypothermia Therapy in Neonates with Hypoxic-Ischemic Encephalopathy.

OBJECTIVE: To delineate the systemic and cerebral hemodynamic response to incremental increases in core temperature during the rewarming phase of therapeutic hypothermia in neonatal hypoxic-ischemic encephalopathy (HIE). STUDY DESIGN: Continuous hemodynamic data, including heart rate (HR), mean arterial blood pressure (MBP), cardiac output by electrical velocimetry (COEV), arterial oxygen saturation, and renal (RrSO2) and cerebral (CrSO2) regional tissue oxygen saturation, were collected from 4 hours before the start of rewarming to 1 hour after the completion of rewarming. Serial echocardiography and transcranial Doppler were performed at 3 hours and 1 hour before the start of rewarming (T-3 and T-1; "baseline") and at 2, 4, and 7 hours after the start of rewarming (T+2, T+4, and T+7; "rewarming") to determine Cardiac output by echocardiography (COecho), stroke volume, fractional shortening, and middle cerebral artery (MCA) flow velocity indices. Repeated-measures analysis of variance was used for statistical analysis. RESULTS: Twenty infants with HIE were enrolled (mean gestational age, 38.8 ± 2 weeks; mean birth weight, 3346 ± 695 g). During rewarming, HR, COecho, and COEV increased from baseline to T+7, and MBP decreased. Despite an increase in fractional shortening, stroke volume remained unchanged. RrSO2 increased, and renal fractional oxygen extraction (FOE) decreased. MCA peak systolic flow velocity increased. There were no changes in CrSO2 or cerebral FOE. CONCLUSIONS: In neonates with HIE, CO significantly increases throughout rewarming. This is due to an increase in HR rather than stroke volume and is associated with an increase in renal blood flow. The lack of change in cerebral tissue oxygen saturation and extraction, in conjunction with an increase in MCA peak systolic velocity, suggests that cerebral flow metabolism coupling remained intact during rewarming.

Changes in mean arterial blood pressure during sildenafil use in neonates with meconium aspiration syndrome or sepsis.

The aim of this study was to evaluate changes in mean blood pressure (MBP) in late preterm and term newborns with meconium aspiration syndrome (MAS) or sepsis who, in addition to inhaled nitric oxide (iNO), received enteral sildenafil for treatment of persistent pulmonary hypertension of the newborn. Data on sildenafil dosing, MBP, and vasopressor/inotrope use were collected for 72 hours after initiation of sildenafil. Groups were compared between "low dose" (<3 mg·kg·d) versus "high dose" (≥ 3 mg·kg·d) and "early" (<7 postnatal days) versus "late" (≥ 7 postnatal days) administration of sildenafil. Seventeen patients were identified. Ten and 7 patients received "low-dose" and "high-dose" sildenafil, respectively, and 8 and 9 patients were started on sildenafil "early" and "late," respectively. At the doses used, sildenafil treatment of infants with MAS and sepsis was not associated with changes in MBP. In addition, vasopressor/inotropic support was weaned in all groups. During the first 72 hours of enteral sildenafil administration in neonates with pulmonary hypertension of the newborn secondary to MAS or sepsis, no significant decrease in MBP or increase in vasopressor/inotrope requirement occurred.

Changes in cardiac function and cerebral blood flow in relation to peri/intraventricular hemorrhage in extremely preterm infants.

OBJECTIVE: To investigate whether changes in cardiac function and cerebral blood flow (CBF) precede the occurrence of peri/intraventricular hemorrhage (P/IVH) in extremely preterm infants. STUDY DESIGN: In this prospective observational study, 22 preterm infants (gestational age 25.9 ± 1.2 weeks; range 23-27 weeks) were monitored between 4 and 76 hours after birth. Cardiac function and changes in CBF and P/IVH were assessed by ultrasound every 12 hours. Changes in CBF were also followed by continuous monitoring of cerebral regional oxygen saturation (rSO2) and by calculating cerebral fractional oxygen extraction. RESULTS: Five patients developed P/IVH (1 patient grade II and 4 patients grade IV). Whereas measures of cardiac function and CBF remained unchanged in neonates without P/IVH, patients with P/IVH tended to have lower left ventricular output and had lower left ventricle stroke volume and cerebral rSO2 and higher cerebral fractional oxygen extraction during the first 12 hours of the study. By 28 hours, these variables were similar in the 2 groups and myocardial performance index was lower and middle cerebral artery mean flow velocity higher in the P/IVH group. P/IVH was detected after these changes occurred. CONCLUSIONS: Cardiac function and CBF remain stable in very preterm neonates who do not develop P/IVH during the first 3 postnatal days. In very preterm neonates developing P/IVH during this period, lower systemic perfusion and CBF followed by an increase in these variables precede the development of P/IVH. Monitoring cardiac function and cerebral rSO2 may identify infants at higher risk for developing P/IVH before the bleeding occurs.

Brain temperature in neonates with hypoxic-ischemic encephalopathy during therapeutic hypothermia.

OBJECTIVE: To noninvasively determine brain temperature of neonates with hypoxic-ischemic encephalopathy (HIE) during and after therapeutic hypothermia. STUDY DESIGN: Using a phantom, we derived a calibration curve to calculate brain temperature based on chemical shift differences in magnetic resonance spectroscopy. We enrolled infants admitted for therapeutic hypothermia and assigned them to a moderate HIE (M-HIE) or severe HIE (S-HIE) group based on Sarnat staging. Rectal (core) temperature and magnetic resonance spectroscopy data used to derive regional brain temperatures (basal ganglia, thalamus, and cortical gray matter) were acquired concomitantly during and after therapeutic hypothermia. We compared brain and rectal temperature in the M-HIE and S-HIE groups during and after therapeutic hypothermia using 2-tailed t-tests. RESULTS: Eighteen patients (14 with M-HIE and 4 with S-HIE) were enrolled. As expected, both brain and rectal temperatures were lower during therapeutic hypothermia than after therapeutic hypothermia. Brain temperature in patients with S-HIE was higher than in those with M-HIE both during (35.1 ± 1.3°C vs 33.7 ± 1.2°C; P < .01) and after therapeutic hypothermia (38.1 ± 1.5°C vs 36.8 ± 1.3°C; P < .01). The brain-rectal temperature gradient was also greater in the S-HIE group both during and after therapeutic hypothermia. CONCLUSION: For this analysis of a small number of patients, brain temperature and brain-rectal temperature gradient were higher in neonates with S-HIE than in those with M-HIE during and after therapeutic hypothermia. Further studies are needed to determine whether further decreasing brain temperature in neonates with S-HIE is safe and effective in improving outcome.

Predictors of 2-year cognitive performance after laser surgery for twin-twin transfusion syndrome.

OBJECTIVE: The purpose of this study was to determine risk factors for poor cognitive performance among children who are treated with in utero selective laser photocoagulation of communicating vessels for twin-twin transfusion syndrome. STUDY DESIGN: This was a prospectively enrolled cohort study. Cognitive performance at age 2 years (±6 weeks) was assessed with the Battelle Developmental Inventory 2nd Edition (BDI-2). Multilevel regression models evaluated risk factors for poor cognitive performance at shared (pregnancy) and individual (child) levels. In addition to development, blindness, deafness, and cerebral palsy were assessed based on physical examination. A priori power analysis determined that a sample of ≥100 children was required for adequate statistical power (0.80). RESULTS: One hundred children (57 families) were evaluated. Total BDI-2 score was within normal range (mean, 101.3 ± [SD]12.2); 1 child had a BDI-2 score of <70. Individual child-level risk factors for lower BDI-2 included male sex (ß = -0.37; P < .01), lower head circumference (ß = 0.28; P < .01), and higher diastolic blood pressure (ß = -0.29; P < .01). At the pregnancy level, lower maternal education (ß = 0.60; P < .001), higher Quintero stage (ß = -0.36; P < .01), and lower gestational age at birth (ß = 0.30; P < .01) were associated with worse cognitive outcomes. Donor/recipient status, gestational age at surgery, fetal growth restriction, and co-twin fetal death were not risk factors. The rate of neurodevelopmental impairment (blindness, deafness, cerebral palsy, and/or a BDI-2 score <70) was 4%. CONCLUSION: Overall cognitive performance quotients were in the normal range, with risk factors for poor outcomes seen at the pregnancy and child levels. Clinical and socioeconomic characteristics can identify at-risk children who need additional interventions.

Acetazolamide for the management of chronic metabolic alkalosis in neonates and infants.

In this study, we evaluated the efficacy and safety of acetazolamide in the management of chronic metabolic alkalosis in neonates and infants with chronic respiratory insufficiency. A retrospective chart review of 90 patients treated with acetazolamide between 2006 and 2007 admitted to the neonatal intensive care unit was performed. Blood gases and electrolytes obtained at baseline and by 24 hours after acetazolamide administration were compared. Compared with baseline and after 24 hours of acetazolamide, mean measured serum bicarbonate (29.5±3.7 vs. 26.9±3.8 mEq/L, P<0.001) and base excess (10.0±3.4 vs. 4.8±4.0 mEq/L, P<0.001) were significantly lower. No significant differences in other electrolytes, blood urea nitrogen, and urine output were noted, except for an increased serum chloride and creatinine. Uncompensated respiratory acidosis developed in 4 (3.1%) treatment courses. Acetazolamide may be effective in decreasing serum bicarbonate in carefully selected patients. Its use and safety as an adjunctive therapy for chronic metabolic alkalosis in neonates and infants with chronic respiratory insufficiency needs further study.

Effect of carbon dioxide on cerebral blood flow velocity in preterm infants during postnatal transition.

AIM: High arterial carbon dioxide (PaCO2 ) and cerebral reperfusion are associated with peri/intraventricular haemorrhage. Our aim was to study the relationship between PaCO2 and cerebral blood flow (CBF) in preterm infants during postnatal transition. METHODS: We prospectively studied ≤30 weeks' gestation haemodynamically stable preterm infants during the first three postnatal days (n = 21; gestational age 25.8 ± 1.4 weeks). We measured middle cerebral artery mean flow velocity (MCA-MV) as a surrogate for CBF at the time of blood gas analysis. RESULTS: We obtained 78 PaCO2 -MCA-MV data pairs. The expected positive linear relationship between PaCO2 and MCA-MV was absent on the first postnatal day, equivocal on the second and present on the third. Using piecewise bilinear regression models, we identified PaCO2 breakpoints at 52.7 and 51.0 mmHg for postnatal days two and three, respectively. CONCLUSION: In haemodynamically stable preterm neonates, the expected positive linear relationship between PaCO2 and CBF may be absent on postnatal day one. On postnatal day three, and possibly day two, a PaCO2 threshold exists for this relationship, above which CBF becomes reactive to PaCO2 . We speculate that the enhanced CBF response to PaCO2 above the threshold contributes to the reperfusion injury and partly explains the association between hypercapnia and peri/intraventricular haemorrhage.

Maintenance of whole-body therapeutic hypothermia during patient transport and magnetic resonance imaging.

Therapeutic hypothermia has become standard treatment for neonatal hypoxic-ischemic encephalopathy (HIE), with brain MRI commonly performed after the child has been rewarmed. However, early imaging during hypothermia might provide information important in designing clinical trials that refine and personalize therapeutic hypothermia. We tested a protocol to ensure safety and maintenance of hypothermia during in-hospital transport and MRI. MRI during therapeutic hypothermia was performed in 13 newborns on the 2nd-3rd postnatal days. Mean one-way transport time was 20.0 ± 3.3 min. Mean rectal temperatures (°C) leaving the unit, upon arrival at the MR suite, during MRI scan and upon return to the unit were 33.5 ± 0.3 °C, 33.3 ± 0.3 °C, 33.1 ± 0.4 °C and 33.4 ± 0.3 °C, respectively. Using our protocol therapeutic hypothermia was safely and effectively continued during in-hospital transport and MRI without adverse effects.

pH effects on cardiac function and systemic vascular resistance in preterm infants.

OBJECTIVE: To investigate the effect of pH on cardiac function and systemic vascular resistance (SVR) in preterm infants. STUDY DESIGN: In this prospective observational study, we evaluated hemodynamically stable, ≤ 30 weeks' gestation preterm infants during the first 2 postnatal weeks. Cardiac function was assessed by echocardiography at the time of arterial blood draw for clinically indicated blood gas analysis. Data were separately analyzed for the transitional (days 1-3) and post-transitional (days 4-14) periods. RESULTS: We evaluated 147 pairs of arterial blood gases and echocardiograms in 29 preterm neonates (gestational age = 26.2 ± 1.5 weeks). Arterial pH ranged from 7.02-7.46. There was no linear relationship between pH and shortening fraction or stress-velocity index in transitional or post-transitional periods. We found a weak negative linear relationship between pH and left ventricular output and a positive linear relationship between pH and SVR only during the post-transitional period. These relationships were maintained after adjustment for the degree of base deficit. Arterial CO2 had effects similar to pH on myocardial function. CONCLUSIONS: Unlike adults, myocardial contractility remains relatively unaffected by acidosis even at pH values close to 7.00 in hemodynamically stable preterm neonates during the first 2 postnatal weeks. However, as in adults, worsening acidosis in preterm neonates after the immediate transitional period is associated with a decrease in SVR along with an increase in left ventricular output. Thus, although myocardial contractility remains unaffected in preterm neonates during the first 2 postnatal weeks, the vascular response to acidosis undergoes a relatively rapid postnatal maturational process.

Prevention of Chronic Morbidities in Extremely Premature Newborns with LISA-nCPAP Respiratory Therapy and Adjuvant Perinatal Strategies.

Less invasive surfactant administration techniques, together with nasal continuous airway pressure (LISA-nCPAP) ventilation, an emerging noninvasive ventilation (NIV) technique in neonatology, are gaining more significance, even in extremely premature newborns (ELBW), under 27 weeks of gestational age. In this review, studies on LISA-nCPAP are compiled with an emphasis on short- and long-term morbidities associated with prematurity. Several perinatal preventative and therapeutic investigations are also discussed in order to start integrated therapies as numerous organ-saving techniques in addition to lung-protective ventilations. Two thirds of immature newborns can start their lives on NIV, and one third of them never need mechanical ventilation. With adjuvant intervention, these ratios are expected to be increased, resulting in better outcomes. Optimized cardiopulmonary transition, especially physiologic cord clamping, could have an additively beneficial effect on patient outcomes gained from NIV. Organ development and angiogenesis are strictly linked not only in the immature lung and retina, but also possibly in the kidney, and optimized interventions using angiogenic growth factors could lead to better morbidity-free survival. Corticosteroids, caffeine, insulin, thyroid hormones, antioxidants, N-acetylcysteine, and, moreover, the immunomodulatory components of mother's milk are also discussed as adjuvant treatments, since immature newborns deserve more complex neonatal interventions.

Perinatal stroke: management guideline / Perinatalis stroke: Vizsgálati irányelv

A perinatalis stroke egy heterogen neurologiai szindroma, mely agyi erserules kovetkezteben alakul ki, es hosszu tavon altalaban kronikus neurologiai kimenetellel jar. Az akut stroke-ok koze a perinatalis arterias ischaemias stroke, a sinusthrombosis es a perinatalis verzeses stroke tartozik. A kes??bb, altalaban 4-8 honapos kor kozott motoros aszimmetriat okozo korkepeket feltetelezetten perinatalis eredet?? stroke-nak nevezzuk. A magneses rezonancias perinatalis stroke-ot. Az ujabb adatok szerint a perinatalis stroke incidenciaja 1 korul van 1100 elveszuletesb??l (1/1100). Bar a stroke-os ujszulottek 40%-a kes??bb tunetmentesen fejl??dik, a tobbiek hosszu tavu neurologiai kimenetele koros, es a karosodas spektrumahoz cerebralparesis, epilepszia, kognitiv karosodas, magatartaszavar, beszedzavar es/vagy valamilyen erzekszervi karosodas tartozik. Az utobbi id??ben tobb tanulmany vizsgalta a rizikotenyez??k, az MR-kepek es a kimenetel osszefuggeset. A jelen osszefoglalo kozlemenyben a perinatalis stroke perinatalis stroke vizsgalatanak meneter??l es terapiajarol iranyelvet keszitettunk.

Dose-dependent hemodynamic and metabolic effects of vasoactive medications in normotensive, anesthetized neonatal piglets.

The developmentally regulated hemodynamic effects of vasoactive medications have not been well characterized. We used traditional and near-infrared spectroscopy monitoring technologies and investigated the changes in heart rate, blood pressure, common carotid artery (CCA) blood flow (BF), cerebral, renal, intestinal, and muscle regional tissue O2 saturation, and acid-base and electrolyte status in response to escalating doses of vasoactive medications in normotensive anesthetized neonatal piglets. We used regional tissue O2 saturation and CCA BF as surrogates of organ and systemic BF, respectively, and controlled minute ventilation and oxygenation. Low to medium doses of dopamine, epinephrine, dobutamine, and norepinephrine increased blood pressure and systemic and regional BF in a drug-specific manner, whereas milrinone exerted minimal effects. At higher doses, dopamine, epinephrine, and norepinephrine but not dobutamine decreased systemic, renal, intestinal, and muscle BF, while cerebral BF remained unchanged. Epinephrine induced significant increases in muscle BF and serum glucose and lactate concentrations. The findings reveal novel drug- and dose-specific differences in the hemodynamic response to escalating doses of vasoactive medications in the neonatal cardiovascular system and provide information for future clinical studies investigating the use of vasoactive medications for the treatment of neonatal cardiovascular compromise.

New NANN Practice Guideline: the management of hypotension in the very-low-birth-weight infant.

The Management of Hypotension in the Very-Low-Birth-Weight Infant: Guideline for Practice, developed by Lyn Vargo, PhD, RN, NNP-BC, and Istvan Seri, MD, PhD, in 2011 under the auspices of the National Association of Neonatal Nurse Practitioners, focuses on the challenging topic of clinical management of systemic hypotension in the very low-birth-weight (VLBW) infant during the first 3 days of postnatal life. The recommendations and rationale in the excerpt below from the complete online publication are based on the best evidence available through both neonatal research and consultation of experts on the subject. They suggest a conservative, evidence-based treatment approach for the management of hypotension in the VLBW infant during the first 3 days of postnatal life that is logical, safe, and physiologically sound. The insufficient fund of knowledge on transitional cardiovascular physiology in general and pathophysiology in particular makes establishment of strict guidelines on the treatment of hypotension in VLBW neonates impossible. What becomes clear when presenting the evidence is how much more we need to know. Readers are strongly encouraged to refer to the complete text of the guideline, which has been endorsed by the American Academy of Pediatrics, for further understanding of this complex topic. The guideline is available free of charge at www.nann.org (click on Guidelines in the Education section).

The role of brain territorial involvement and infection/inflammation in the long-term outcome of neonates with arterial ischemic stroke: A population-based cohort study.

BACKGROUND: Neonatal arterial ischemic stroke (NAIS) carries the risk of significant long-term neurodevelopmental burden on survivors. AIMS: To assess the long-term neurodevelopmental outcome of term neonates diagnosed with NAIS and investigate the associations among brain territorial involvement on MRI, clinical risk factors and neurodevelopmental outcomes. STUDY DESIGN: Population-based cohort study. SUBJECTS: Seventy-nine term neonates with NAIS confirmed by MRI born between 2007 and 2017. OUTCOME MEASURES: Long-term neurodevelopmental outcome assessed using the Bayley Scales of Infant Development-II, the Brunet-Lézine test and the Binet Intelligence scales-V. RESULTS: Follow-up was available in 70 (89%) of the subjects enrolled, at a median age of 60 months [IQR: 35-84]. Normal neurodevelopmental outcome was found in 43% of the patients. In a multivariable model, infants with main MCA stroke had an increased risk for overall adverse outcome (OR: 9.1, 95% CI: 1.7-48.0) and a particularly high risk for cerebral palsy (OR: 55.9, 95% CI: 7.8-399.2). The involvement of the corticospinal tract without extensive stroke also increased the risk for cerebral palsy/fine motor impairment (OR: 13.5, 95% CI: 2.4-76.3). Multiple strokes were associated with epilepsy (OR: 9.5, 95% CI: 1.0-88.9) and behavioral problems (OR: 4.4, 95% CI: 1.1-17.5) and inflammation/infection was associated with cerebral palsy (OR: 9.8, 95% CI: 1.4-66.9), cognitive impairment (OR: 9.2, 95% CI: 1.8-47.8) and epilepsy (OR: 10.3, 95% CI: 1.6-67.9). CONCLUSIONS: Main MCA stroke, involvement of the corticospinal tract, multiple strokes and inflammation/infection were independent predictors of adverse outcome, suggesting that the interplay of stroke territorial involvement and clinical risk factors influence the outcome of NAIS.

Impact of syringe size on the performance of infusion pumps at low flow rates.

OBJECTIVE: To evaluate the impact of syringe size on start-up delay and the time to reach 50% and 90% of target flow rates, using two commercially available syringe infusion pumps at infusion rates of < or =1 mL/hr. DESIGN: Two syringes (Terumo) of different size (10-mL and 50-mL), using two syringe infusion pumps (Pump A, Terumo Terufusion Infusion Pump TE-331; and Pump B, Braun Perfusor Compact S) were studied. Effective fluid delivery was measured at 0.4 mL/hr, 0.8 mL/hr, and 1.0 mL/hr for the initial 60 mins, using the gravimetric method. Instant flow was calculated as volume difference for every 1-min interval per minute. Start-up delay was defined as time in minutes of 0 flow from the start of infusion. Syringe placement, bubble removal, infusion line priming, and positioning were standardized for all measurements, using new syringes and infusion lines. Each experiment was repeated six times. Statistical analysis was performed, using a nonparametric test (Mann-Whitney U test). SETTING: None. PATIENTS: None. INTERVENTIONS: None. RESULTS: Using the 50-mL syringe, the start-up delay was consistently higher and the time to reach 50% and 90% of target flow were significantly longer, independent of which syringe infusion pump was used. At every flow rate studied, the pumps did not reach the target flow rate before 60 mins with the 50-mL syringe. With the 10-mL syringe, target flow rate was achieved before 20 mins for both pumps. CONCLUSIONS: Our findings demonstrate a clinically relevant impact of syringe size on syringe infusion pump performance at low flow rates. The time to reach 50% and 90% of target flow are significantly longer, using the 50-mL syringe compared with the 10-mL syringe, and the time to reach 50% of target flow is independent of the longer start-up delay. Based on our findings, we speculate that smaller syringe sizes and higher infusion rates are preferable for continuous drug infusions, particularly when prompt establishment of the drug effect is critical.

Intrauterine exposure to mycophenolate mofetil and multiple congenital anomalies in a newborn: possible teratogenic effect.

There is very little data linking the use of immunomodulating agents following solid organ transplantation in pregnant women with specific congenital anomalies in the offspring. Here we report on a late preterm infant with multiple, nonsyndromic, congenital anomalies including microtia/anotia, cleft lip and palate, micrognathia, ocular hypertelorism, microphthalmia and cataracts, complex congenital heart disease, rib anomalies, and intestinal malrotation. The similarity of the complex anomalies in our case to other reported cases suggests that the abnormalities are likely due to mycophenolate mofetil alone or in combination with other immunosuppressive medications taken by the mother during pregnancy.