Can lactate levels be used as a marker of patent ductus arteriosus in preterm babies?

OBJECTIVE: Serum lactate levels provide information on metabolic capacity at the cellular level. In addition, lactate reflects tissue perfusion and oxygenation status. The aim of this study was to determine the usefulness of high lactate levels as a marker in hemodynamically significant patent ductus arteriosus (hsPDA), which may lead to tissue perfusion defects. METHODS: Preterm infants with gestational age ≤32 weeks and birthweight ≤1500 g were included. Lactate levels were determined at postnatal 48-72 hours before echocardiographic evaluation. Eligible infants were divided into two groups as infants with and without hsPDA. Cut-off values for lactate were taken as lactate >4 mmol/L, identified as a high lactate level. Infants were also divided into two groups according to lactate levels as group I: lactate levels >4 mmol/L and group II: lactate levels ≤4 mmol/L. Haemodynamic PDA and lactate levels were compared. RESULTS: A total of 119 patients with gestational age ≤32 weeks and birthweight ≤1500 g were included in the study. Fifty patients had echocardiographic hsPDA and 69 patients had no PDA. Twelve (24%) of the patients with hsPDA and 22 (31.9%) of the non-hsPDA patients had a lactate level of 4 mmol/L (P = 0.392). There was no correlation between hsPDA presence and lactate levels (P = 0.35). CONCLUSION: High lactate levels are multifactorial and usually indicate impairment of tissue perfusion. There are a number of factors that can lead to impaired tissue perfusion in preterm infants. For the first time in this study, it was shown that lactate levels did not significantly increase in the presence of hemodynamically significant PDA. This may be due to the fact that peripheral tissue perfusion in the presence of hemodynamic PDA does not deteriorate enough to cause an increase in anaerobic metabolism.

Does ibuprofen treatment in patent ductus arteriosus alter oxygen free radicals in premature infants?

Introduction Ibuprofen is used widely to close patent ductus arteriosus in preterm infants. The anti-inflammatory activity of ibuprofen may also be partly due to its ability to scavenge reactive oxygen species and reactive nitrogen species. We evaluated the interaction between oxidative status and the medical treatment of patent ductus arteriosus with two forms of ibuprofen. Materials and methods This study enrolled newborns of gestational age ⩽32 weeks, birth weight ⩽1500 g, and postnatal age 48-96 hours, who received either intravenous or oral ibuprofen to treat patent ductus arteriosus. Venous blood was sampled before ibuprofen treatment from each patient to determine antioxidant and oxidant concentrations. Secondary samples were collected 24 hours after the end of the treatment. Total oxidant status and total antioxidant capacity were measured using Erel's method. RESULTS: This prospective randomised study enrolled 102 preterm infants with patent ductus arteriosus. The patent ductus arteriosus closure rate was significantly higher in the oral ibuprofen group (84.6 versus 62%) after the first course of treatment (p=0.011). No significant difference was found between the pre- and post-treatment total oxidant status and total antioxidant capacity in the groups. Discussion Ibuprofen treatment does not change the total oxidant status or total antioxidant capacity. We believe that the effect of ibuprofen treatment in inducing ischaemia overcomes the scavenging effect of ibuprofen.

Coexistence of Fetal Cardiac Malformation and Maternal Drug-Induced Lupus: Is Lamotrigine Safe?

Lamotrigine (LTG) is a widely used second-generation antiepileptic drug for long-term therapy of epileptic patients. Although LTG monotherapy during pregnancy is assumed to be relatively safe, teratogenic effects related to LTG has been reported previously. The presence of fetal malformations and maternal drug-induced lupus erythematosus concurrently in a pregnant women using LTG have not been reported before. We herein report a term infant with coarctation of aorta and ventricular septal defect, who was born to a mother treated with LTG for epilepsy before conception and throughout pregnancy. The mother was diagnosed with drug-induced lupus erythematosus at the 36th gestational week, and the symptoms resolved after discontinuation of the drug. Fetal cardiac anomalies should be searched in mothers who were exposed to LTG during pregnancy.

Oral paracetamol versus oral ibuprofen in the management of patent ductus arteriosus in preterm infants: a randomized controlled trial.

OBJECTIVE: To compare the efficacy and safety of oral paracetamol and oral ibuprofen for the pharmacological closure of patent ductus arteriosus (PDA) in preterm infants. STUDY DESIGN: This prospective, randomized, controlled study enrolled 90 preterm infants with gestational age ≤ 30 weeks, birthweight ≤ 1250 g, and postnatal age 48 to 96 hours who had echocardiographically confirmed significant PDA. Each enrolled patient received either oral paracetamol (15 mg/kg every 6 hours for 3 days) or oral ibuprofen (initial dose of 10 mg/kg, followed by 5 mg/kg at 24 and 48 hours). RESULTS: Spontaneous closure rate for the entire study group was 54%. After the first course of treatment, the PDA closed in 31 (77.5%) of the patients assigned to the oral ibuprofen group vs 29 (72.5%) of those enrolled in the oral paracetamol group (P = .6). The reopening rate was higher in the paracetamol group than in the ibuprofen group, but the reopening rates were not statistically different (24.1% [7 of 29] vs 16.1% [5 of 31]; P = .43). The cumulative closure rates after the second course of drugs were high in both groups. Only 2 patient (2.5%) in the paracetamol group and 3 patients (5%) in the ibuprofen group required surgical ligation. CONCLUSION: This randomized, controlled clinical study compared oral paracetamol with ibuprofen in preterm infants and demonstrated that paracetamol may be a medical alternative in the management of PDA.

An unusual cause of refractory persistent pulmonary hypertension of the newborn: anomalous origin of one pulmonary artery.

Persistent pulmonary hypertension of the newborn is a source of considerable mortality and morbidity. Anomalous origin of one pulmonary artery, an uncommon congenital cardiac malformation, is a rare cause of persistent pulmonary hypertension. Here, we report the case of a patient with an anomalous origin of one pulmonary artery from the innominate artery who presented with persistent pulmonary hypertension refractory to treatment.

Serum ibuprofen levels of extremely preterm infants treated prophylactically with oral ibuprofen to prevent patent ductus arteriosus.

AIM: The aim of this study was to explore the effects of early oral ibuprofen administration on the incidence of hemodynamically significant patent ductus arteriosus (hsPDA) and define the association between serum ibuprofen levels and ductal closure. METHOD: Preterm infants with a gestational age of <28 weeks and/or birth weight of <1,000 g were randomized either to the intervention (ibuprofen prophylaxis) or control group. The intervention group received oral ibuprofen 10 mg/kg within 12-24 h after birth followed by 5 mg/kg at 24 and 48 h. Serum ibuprofen levels after the treatment were analyzed in the intervention group, and the incidence of hsPDA and complication rates were compared between two groups. RESULTS: Nineteen infants who received one course (three doses) of prophylactic ibuprofen in the intervention group and 17 infants in the control group who underwent an echocardiographic examination on the fourth day of life were analyzed. hsPDA was observed in five (26 %) infants in the intervention group and ten (58 %) infants in the control group (p = 0.09). In the intervention group two infants experienced gastrointestinal bleeding two infants had spontaneous intestinal perforation, and two infants developed acute kidney failure. Mean serum ibuprofen level was 28.7 ± 16.9 mg/L in the intervention group, and there was no correlation between ibuprofen level obtained on the fourth day and ductal closure. CONCLUSION: Oral ibuprofen prophylaxis reduces the rates of hsPDA even it is not statistically significant. The ductal closure rate did not correlate with serum ibuprofen levels. Due to high prevalence of adverse events observed, our data do not support the use of oral ibuprofen for prophylaxis of hsPDA.

Efficacy and safety of oral versus intravenous ibuprofen in very low birth weight preterm infants with patent ductus arteriosus.

OBJECTIVE: To compare oral ibuprofen with intravenous ibuprofen for closure of patent ductus arteriosus in very low birth weight (VLBW) preterm infants. STUDY DESIGN: In a prospective, randomized study, 102 VLBW preterm infants with patent ductus arteriosus received either intravenous or oral ibuprofen at an initial dose of 10 mg/kg, followed by 5 mg/kg at 24 and 48 hours. The success rate and evaluation of renal tolerance using cystatin-C were the major outcomes. RESULTS: Patent ductus arteriosus closure rate was significantly higher with oral ibuprofen (84.6% versus 62%) after the first course of the treatment (P = .011). The cystatin-C level increased significantly after treatment in the oral group (P = .001), but did not change with intravenous ibuprofen (P = .4). CONCLUSIONS: Oral ibuprofen is more effective than intravenous ibuprofen for ductal closure in VLBW infants. The increase in the cystatin-C level with oral treatment suggests that patients with borderline renal function should be evaluated and followed closely.

A case of maternal phenylketonuria syndrome presenting with unilateral renal agenesis.

Maternal phenylketonuria (mPKU) during pregnancy leads to the risk of spontaneous abortion or a teratogenic syndrome depending on the level of maternal phenylalaninemia. Mental retardation, microcephaly, congenital cardiopathy and intrauterine growth retardation are frequently seen in patients who intake an unrestricted diet before conception. The clinical picture shows variation in classic PKU. Severe neurological symptoms are not seen in all untreated cases of PKU syndromes. For this reason, mPKU can be seen in undiagnosed mothers. We hereby present a case who underwent investigations due to the presence of microcephaly and congenital cardiopathy. The diagnosis of PKU syndrome of the mother was determined following assessment of the baby. Furthermore, the unilateral renal agenesis that was detected in our case is the first case reported in the literature in which mPKU accompanies renal agenesis.

Fetal and neonatal cardiac rhabdomyomas: clinical presentation, outcome and association with tuberous sclerosis complex.

Rhabdomyoma is the most common pediatric heart tumor. Cardiac rhabdomyomas (CRs) have a natural history of spontaneous regression and are closely associated with tuberous sclerosis complex (TSC). We aimed to evaluate the clinical presentation and outcome of CRs and their association with TSC. Patients with CRs diagnosed in last six years were retrospectively analyzed. A total of 25 tumors were identified in seven patients by echocardiography. Three patients were diagnosed prenatally by fetal echocardiography, three patients in the neonatal period and one patient in early infancy. The median followup period was two years (range: 5 months-6 years). Five patients (71%) had multiple tumors. Three patients had arrhythmias and two patients required surgery. Only 36% (9/25) of the tumors regressed. TSC was diagnosed in four patients during the follow-up. CRs may have different presentations and clinical course. Surgery is only necessary when hemodynamically significant obstruction is present. As CRs are associated with long-term development of TSC and other diagnostic features are not yet typically apparent in the prenatal and neonatal periods, careful evaluation and follow-up are essential to exclude TSC.

The birth prevalence of selected major congenital anomalies: Six-year's experience in a tertiary care maternity hospital.

AIM: To evaluate the birth prevalence of specifically selected major congenital anomalies and to determine the correlated neonatal and maternal characteristics. MATERIAL AND METHODS: Data were collected retrospectively from hospital-based records of infants who were born at 22 completed weeks of gestation with a birth weight of more than 500 g in Zekai Tahir Burak Gynecology Training and Research Hospital between 2013 and 2018. Abortions, stillbirths, and terminated pregnancies due to fetal anomalies were excluded. Average annual prevalences were calculated for each selected major congenital anomaly. RESULTS: The total prevalence of congenital anomalies was 9.97 per 1000 in 102 379 live birth cohorts. The prevalence of severe congenital heart anomalies (SI-SII) was found as 21.1 per 10 000 live births. Down syndrome and meningomyelocele were the second and third most common anomalies, after congenital heart defects (13.87 and 9.97 per 10 000 live births, respectively). The prevalence of anomalies requiring specific surgery was found as 4.3 per 1000 live births. Congenital heart disease was present in 31.7% of patients who had Down syndrome. Atrioventricular septal defect accounted for 53.3% of congenital heart anomalies detected in Down syndrome. The prevalence of Down syndrome in babies of mothers aged 35 years and older was found as 46.67 per 10 000, which was significantly higher than in the group aged under 35 years (8.24 per 10 000). On the other hand, the prevalence of gastroschisis in babies of mothers aged 19 years and under was found as 5.81 per 10 000, which was higher than in the group aged 20 years and over (0.84 per 10 000). CONCLUSION: The actual magnitude of the number of births affected by congenital anomalies in Turkey is unknown. In our study, congenital heart diseases, Down syndrome, and meningomyelocele were found to be the most common congenital anomalies, respectively.

Aortic Arch Thrombosis Associated with Fetal Cytomegalovirus Viremia.

Cytomegalovirus(CMV) associated thrombosis has been reported sporadically in the medical literature; however, its antenatal scenario has not been documented. We herein present the antenatal, Doppler's ultrasound and magnetic resonance angiographic features of thrombosis in the aortic arch showing extension toward the medial lumen of the brachiocephalic trunk with critical occlusion of the left common carotid artery and left subclavian artery in a term fetus to raise obstetricians'/ neonatologists'/pediatric cardiologists' awareness for the association between CMV viremia and intrauterine thrombosis that caused cerebral injury, neurodevelopmental impairment, and permanent sequela.

Drug resistant fetal arrhythmia in obstetric cholestasis.

Obstetric cholestasis (OC) is a pregnancy specific liver disease characterized by increased levels of bile acid (BA) and pruritus. Raised maternal BA levels could be associated with intrauterine death, fetal distress, and preterm labor and also alter the rate and rhythm of cardiomyocyte contraction and may cause fetal arrhythmic events. We report a case of drug resistant fetal supraventricular tachycardia and concomitant OC. Conclusion. If there are maternal OC and concomitant fetal arrhythmia, possibility of the resistance to antiarrhythmic treatment should be kept in mind.

Renal and mesenteric tissue oxygenation in preterm infants treated with oral ibuprofen.

BACKGROUND: Hemodynamically significant patent ductus arteriosus (PDA) is a common problem in preterm infants which often causes significant morbidities. Although PDA induces alterations in various tissue perfusion, there is scarce information about the effect of oral ibuprofen on hemodynamics of regional tissues. OBJECTIVE: To investigate, using near-infrared spectroscopy, the effect of oral ibuprofen on renal and mesenteric tissue oxygenation and oxygen extraction in preterm infants with a diagnosis of hemodynamically significant PDA. PATIENTS AND METHODS: Fifteen infants (gestational age <32 weeks) with the diagnosis of hemodynamically significant PDA treated with oral ibuprofen were monitored for near-infrared spectroscopy - determined renal and mesenteric oxygenation. The infants with PDA were matched for gestational age, postnatal age with infants without PDA, who served as control subjects. RESULTS: In infants with PDA, mean arterial blood pressure was significantly lower compared with the control infants [39.3 (range:36-54) versus 51 (range:43-66) mmHg, respectively; p < 0.001)]. There were no significant differences in regional oxygen saturation and fractional oxygen extraction of renal and mesenteric tissues in PDA and control infants (p > 0.05). And ibuprofen treatment did not negatively influence renal and mesenteric oxygenation and extraction in infants with PDA (p > 0.05). CONCLUSION: Renal and mesenteric tissue oxygenation and oxygen extraction were preserved in preterm infants with a diagnosis of hemodynamically significant PDA treated with oral ibuprofen.

Echogenic focus in the fetal left ventricular cavity: is it a false tendon?

OBJECTIVE: To draw attention to the left ventricular false tendon which can be misinterpreted as echogenic focus in the fetus. METHODS: The study group consisted of 9 fetuses out of the 161 who had been misdiagnosed for left ventricular false tendon as echogenic focus by obstetricians. Fetal echocardiography and 2-D color Doppler echocardiography were performed in the pre-postnatal period. The standard fetal echocardiographic views (4,5 chamber views, long axis view of the left ventricle, short axis view of the ventricles and great arteries, three vessels and trachea view, long axis views of the duct and aortic arch) were obtained for each case. RESULTS: Of the 161 fetuses with echogenic focus in the left ventricle which underwent fetal echocardiography, 9 (5.6%) were diagnosed with false tendons present in the left ventricular cavity with no other cardiovascular anomaly. Six out of 9 patients underwent amniocentesis as follows: for age of over 35 years (two patients), abnormal double-triple screening tests plus echogenic focus (two patients) and soft ultrasonographic markers including echogenic focus (two patients). These fetuses revealed no cardiovascular and other systemic pathology or dysmorphism except for false tendons in the left ventricular cavity. CONCLUSION: False tendon should be taken into account as differential diagnosis of left ventricular echogenic focus in the fetus. Misinterpretation of false tendon as echogenic focus may cause unnecessary fetal invasive approach and maternal anxiety, especially when it arises with a background of borderline fetal findings and knowledge.

A different first-choice drug in the medical management of patent ductus arteriosus: oral paracetamol.

BACKGROUND AND OBJECTIVES: Patent ductus arteriosus (PDA) is a significant cause of morbidity and mortality in preterm infants. This case series was conducted to investigate the usefulness of paracetamol as a first choice for the treatment of PDA in preterm infants. SUBJECTS AND METHODS: Preterm infants were prospectively enrolled. Treatment with oral paracetamol was started at a dose of 15 mg/kg every 6 h for 3 d, with echocardiographic evaluation performed at the end of the treatment and 2 d after the treatment. Serum paracetamol levels were also evaluated for 24 h after the first dose to ensure the absorption and reaching the therapeutic level. RESULTS: A total of six preterm infants were prospectively enrolled. Five infants with PDA were successfully treated with oral paracetamol. Only one patient did not respond to paracetamol treatment whereas another one received a second cure due to reopening of the ductus. CONCLUSION: Paracetamol may be a useful treatment option for the primer treatment of PDA in preterm infants. If paracetamol is shown to be effective in a large series, because of low risk of side effects, low cost and preparation is available in enteral form, it may be an advantageous alternative at PDA treatment.

Intravenous paracetamol treatment in the management of patent ductus arteriosus in extremely low birth weight infants.

BACKGROUND: Treatment options for the closure of a hemodynamically significant patent ductus arteriosus (hsPDA) include medical therapy such as ibuprofen and indomethacin and surgical ligation. OBJECTIVE: To evaluate the efficacy of intravenous paracetamol in preterm infants with hsPDA whose feeding was contraindicated or had feeding intolerance. METHODS: Preterm infants with hsPDA were started on intravenous paracetamol treatment with parental consent. Paracetamol was administered at a dose of 60 mg/kg/day, in four divided doses, for a period of 3 days. In the absence of closure of hsPDA, treatment was extended up to 6 days, after which echocardiographic examination was performed. RESULTS: A total of 10 preterm infants were included in the study with a median gestational age of 27(4/7) weeks (minimum-maximum: 24-29) and a median birth weight of 775 g (590-990). The first dose of intravenous paracetamol was given after a median of 6 days (2-15). On echocardiographic examination, median internal ductal diameter was 2 mm (1.5-3), with a median left atrium-to-aortic root ratio of 1.95 (1.6-2.2). Intravenous paracetamol resulted in successful closure of hsPDA in all patients. CONCLUSIONS: This study is the first case series in the literature which used intravenous paracetamol treatment for hsPDA. We believe that intravenous paracetamol could be used as an alternative drug for infants. Further prospective randomized-controlled trials are needed to evaluate the efficacy of intravenous paracetamol for the closure of hsPDA.

Effects of red cell transfusion on cardiac output and perfusion index in preterm infants.

OBJECTIVE/AIM: The present investigation was designed to study the effect of blood transfusion on cardiac output and perfusion index. The aim was to demonstrate a relationship between hematocrit, lactate, cardiac output and perfusion index in anemic preterm infants and to investigate significant changes in these parameters induced by RBC transfusion. METHODS: Anemic infants who were under 35 weeks of gestational age (GA) and were in a stable clinical condition without respiratory or cardiac problems, signs of sepsis, or renal disease at the time of investigation were enrolled in the study. Enrolled infants received 15 ml/kg pure red blood cells over 4 h. Hematocrit and lactate levels were studied before and after transfusion. Cardiac output was measured by an ultrasound device (USCOM 1A) and perfusion index was monitored by pulse oximeter (MasimoRad7). RESULTS: Cardiac output decreased by 9% (p < 0.05), due to decrease in heart rate by 10% (p < 0.05) and stroke volume significantly by 5% (p < 0.05) both in left and right sided cardiac measurements. Perfusion index significantly increased and lactate levels significantly decreased after transfusion (p < 0.05). Htc was inversely correlated with lactate levels, HR, CI and CO (r = -0.33, p = 0.01; r = -0.53, p = 0; r = -0.37, p = 0.004, r = -0.28, p = 0.03). PI was not significantly correlated with Htc levels before and after transfusion (r = 0.07, p = 0.7 and r = 0.007, p =0.97). CONCLUSION: Our data support that heart rate, CO and CI and lactate levels increased as a response to anemia in preterm infants and RBC transfusion improved perfusion index suggesting better tissue oxygenation.

Oral versus intravenous ibuprofen for patent ductus arteriosus closure: a randomised controlled trial in extremely low birthweight infants.

OBJECTIVE: To compare the efficacy and safety of oral versus intravenous ibuprofen for the pharmacological closure of patent ductus arteriosus (PDA) in less mature preterm infants. DESIGN: Prospective, randomised controlled study. SETTING: Tertiary neonatal intensive care unit. PATIENTS AND INTERVENTIONS: The study enrolled 80 preterm infants with gestational age ≤28 weeks, birth weight <1000 g, postnatal age 48 to 96 h, and had echocardiographically confirmed significant PDA. Seventy extremely low birthweight (ELBW) preterm infants received either intravenous or oral ibuprofen randomly as an initial dose of 10 mg/kg, followed by 5 mg/kg at 24 and 48 h. MAIN OUTCOME MEASURES: The success rate and the safety of the drugs in ELBW preterm infants were the major outcomes. RESULTS: PDA closure rate was significantly higher with oral ibuprofen (83.3% vs 61.7%) after the first course of the treatment (p=0.04). Although the primary closure rate was marginally higher in the oral ibuprofen group, the need for a second course of ibuprofen during the whole hospitalisation was similar between groups: 11 of 36 in oral versus 15 of 34 in intravenous groups (p=0.24) because of a higher reopening rate in the oral group. In addition to no increase in side effects with oral ibuprofen use, the need for postnatal steroid use for chronic lung disease was significantly lower in oral ibuprofen group (p=0.001). CONCLUSIONS: Oral ibuprofen is as effective as intravenous ibuprofen for PDA closure even in ELBW infants.