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A 28-week gestation male was born 4 days ago to a G3P3 mother who had an emergency C-section due to placenta previa. He is being ventilated with high pressures for respiratory distress syndrome. On physical examination his breath sounds are symmetric and he has a grade III/VI systolic heart murmur. An echocardiogram is obtained to evaluate the murmur and a patent ductus arteriosus is identified. The medical student that you are working with asks what treatment option for the patent ductus arteriosus will improve neurodevelopmental outcomes in childhood for this baby. Your best response is:
B. Surgical ligation
C. Prostaglandin E1
E. No treatment options will improve neurodevelopmental outcomes
The ductus arteriosus serves an important role in fetal life by connecting the pulmonary artery and descending aorta, serving to direct ventricular output away from the fetal lungs and towards the placenta. While the ductus arteriosus may remain patent for the first several days of life, rising arterial PO2 causes constriction of the muscle in the wall of the ductus, leading to closure. After 48 hours, most PDAs in term babies will be closed and in uncomplicated preterm babies (typically greater than 27 weeks) with minimal respiratory problems, the ductus arteriosus closes in the same time frame.However, in approximately one-third of babies born before 30 weeks the ductus arteriosus fails to close. Signs of a patent ductus arteriosus (PDA) are a long systolic murmur at the upper sternal edge, bounding peripheral pulses, increased pulse pressure, and increased precordial cardiac impulses, although not all PDAs will have physical signs. A PDA can lead to left-to-right shunting and have multiple consequences, including pulmonary edema, chronic lung disease/bronchopulmonary dysplasia, heart failure, intraventricular hemorrhage, necrotizing enterocolitis and death. Indomethacin is a nonspecific prostaglandin synthetase inhibitor that has classically been used in neonatology to close PDAs because it is successful 75-90% of the time. Risks of indomethacin use include oliguria, gastrointestinal bleeding and perforation, hyponatremia, and transient reductions in blood flow to organs. Current research, however, does not show any improvement in long-term neurodevelopmental outcomes and many of the risks of a PDA can be accounted for by the immature gestation. B: A ductal left-to-right shunt will create an increase in pulmonary blood flow and, in the setting of preterm respiratory distress, can lead to pulmonary edema and decreased lung compliance, which in turn can prolong the duration of artificial respiration that is needed, increase the oxygen need. For these reasons, surgical ligation of a PDA is often used when a symptomatic PDA has failed to close with medical treatment. Unfortunately, neonates that undergo PDA ligation have higher rates of pneumothorax and retinopathy of prematurity and studies have not shown that ligation after failed medical treatment protects babies from adverse outcomes. C: Prostaglandin E1 is used to maintain ductal patency in patients with a cyanotic congenital heart defect. In ductal-dependent congenital heart defects, a patent ductus is necessary to provide adequate systemic blood flow, pulmonary blood flow, and to enhance intercirculatory mixing. Adverse effects of prostaglandin E1 include apnea, hypotension, hyperthermia, and electrolyte abnormalities. D: Recently trials comparing indomethacin with another prostaglandin synthetase inhibitor, ibuprofen, have shown similar efficacy of PDA closure with less negative effects on organ blood flow and reduced incidence of transient renal side effects. However, neither indomethacin nor ibuprofen use are associated with improved neurodevelopmental outcomes when used in treating a PDA. E: Timing of PDA treatment, when performed, occurs at one of three points: prophylactic treatment, targeted presymptomatic treatment, or when the ductus arteriosus becomes clinically symptomatic. Although many symptomatic PDAs are treated, there is no evidence of any benefits in terms of outcome, including chronic lung disease and mortality. Studies looking at prophylactic treatment of a PDA utilizing indomethacin to high-risk neonates within the first 24 hours have shown reduced incidence of PDA ligation, grade 3 or 4 intraventricular hemorrhage, and periventricular leukomalacia. Despite this, neurodevelopmental outcomes at 2 years of age are not improved, thus there is no long-term advantage despite the short-term advantages.
Hamrick S, Hansmann H. Patent ductus arteriosus in the preterm infant. Pediatrics. 2010;125(5):1020-30. Rolland A, et al. Natural evolution of patent ductus arteriosus in the extremely preterm infant. Arch Dis Child. 2015;100(1):F55-58. Chorne N, et al. Patent ductus arteriosus and its treatment as risk factors for neonatal and neurodevelopmental morbidity. Pediatrics. 2007;119(6):1165-74. Polin R, et al. Workbook in Practical Neonatology. 4th Ed. Philadelphia: Saunders Elsevier. 2007.
Which of the following is incorrect regarding the diagnosis of intellectual disability?
A. Developmental history is key in diagnosis
B. Neuropsychological testing can be helpful in identifying psychopathology if the patient’s cognitive profile does not match up well with his or her environmental situation
C. Thorough medical and neurological evaluation is important in the diagnosis of intellectual disability and before being given a diagnosis of psychiatric or behavioral disorder
D. There are correctable causes of cognitive impairment and behavioral disturbance
A. Developmental history, school performance and social adaptations are key to diagnosing intellectual disability. B. Neuropsychological testing helps in confirming diagnosis; testing has scales that quantify patient’s strengths and deficits. C. There are multiple causes of intellectual disability that can be identified via laboratory analysis- including metabolic causes, toxin exposure and chromosomal abnormalities, however there is no single lab test for intellectual disability. Many patients with developmental delay do not have any known laboratory abnormalities. D. Correctable causes of cognitive and behavioral disturbance include- vision and hearing impairment, seizure disorders, recent head injury.
Theodore A. Stern, MD, Jerrold F. Rosenbaum, MD, Maurizio Fava, MD, Joseph Biederman, MD and Scott Rauch, MD (2008). Massachusetts General Hospital Comprehensive Clinical Psychiatry. Mosby.
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