Intrauterine infection with herpes simplex virus, although very rare, has devastating effects on multiple organ systems in the fetus and can lead to in utero fetal demise. The child died within 2 months after recognition. Antiviral drugs, vidarabine and acyclovir are of equal efficacy and toxicity when used in infants with herpes simplex infections. If untreated, these communications expose the pulmonary arterial bed to increased flow and may accelerate the adverse pulmonary vascular remodeling and thus worsen PH.45 Conversely, closing these communications in the presence of PH may result in acute right ventricular (RV) failure with subsequent PH crisis. These cases provide additional evidence that CMV infection may predispose to secondary infection. At 3 months of age, the infant developed HSV encephalitis as manifested by fever, seizures, abnormal CSF indices, abnormal brain MRI, and positive CSF HSV PCR. He reported no history of similar lesions in the past.
Nine (30%) only had cutaneous herpes, four (13%) had CNS herpes, nine (30%) had disseminated disease. Examination of the dorsal and palmar aspects of both hands reveals crops of punched-out and fluid-containing elevated lesions, with some appearing hemorrhagic (Fig. He was initially treated with mechanical ventilation with 100% O2, inhaled nitric oxide (iNO) and subsequently transitioned to Sildenafil. Topical acyclovir may be beneficial in primary infections, and may reduce the duration of symptoms, which usually last 10 to 14 days. Disseminated vesicles have likewise been reported with coxsackievirus infections [2–4], which may ultimately ulcerate or become nodular . The decision was made to obtain a cardiac catheterization at 6 months, which on 21% O2 showed a large PDA with a left-to-right shunt (Qp:Qs of 4.2:1), systemic PA pressures, and PVR of 3 Wood units. New perspectives concerning diagnosis and prevention of neonatal contamination include: identification of asymptomatic primary infections using rapid identification of genital viral antigen during delivery, identification of women with a risk of asymptomatic excretion using specific serology tests for the pregnant woman and her partner, antiviral treatment for men, topical genital treatments, vaccination of women at risk, monoclonal antibodies, new antiviral agents with mechanisms of action independent of viral thymidine kinase.
Definitive studies of Treg depletion and reconstitution including neonatal thymectomy (1, 4), scurfy mice (defective in Foxp3) (5, 6), and humans with foxp3 mutations and autoimmune disease (IPEX syndrome) (7) have demonstrated that Tregs dominantly suppress autoimmune disease from self-reactive T cells. After the procedure, he remained stable on 25% O2 via NC, but 7 days later, he developed acute respiratory deterioration and PH crisis. Echocardiogram showed a small PFO with right-to-left shunt, systemic RV systolic pressures, and poor RV systolic function (FAC of 14%). Despite increasing PH treatment and RV support with iNO, Sildenafil, inotropes, and milrinone, he expired. Baby boy T was born at 26 weeks’ gestation, weighing 780 g. Hospital course was complicated by congenital cutaneous herpes simplex viral infection, prenatally diagnosed supraventricular tachycardia, large secundum ASD, and development of severe BPD. Serial echocardiograms after birth showed a large secundum ASD (range, 8–9 mm) and subsequent evidence of PH (eRVSP > two-thirds systemic at 41 weeks’ corrected age).
The infant had Apgar scores of 5 and 8 at 1 and 5 minutes, respectively. Valacyclovir was decreased to 500 mg twice daily then to 500 mg daily over the next 5 months. His respiratory status improved after ASD closure with weaning off the ventilator to NC, but the echocardiograms continued to show PH, dilated and hypertrophied RV with adequate systolic function (FAC > 35%). One month after ASD closure, he developed acute respiratory failure with worsening PH, RV failure (severe RV dilatation with severe systolic dysfunction FAC of 4%), and cardiac arrest. Work up for bacterial and viral infectious etiology was negative. •Kohl S. His PH and RV function improved gradually over the next 3 weeks.
He was discharged home at 11 months of age with O2, Sildenafil, and diuretic therapy. He continues to be well at 18 months of age without further exacerbations. Although Tregs have been shown to undergo proliferation in peripheral lymph nodes (LN) of neonatal mice in an IL-2-dependent manner (33), the development of naturally occurring Foxp3+ Tregs at this site is less well described. PH in these infants is because of both hypoxia-induced structural changes and increased vasoreactivity.789 Echocardiogram is commonly used to screen for PH, but it correlates poorly with cardiac catheterization especially in estimating the severity.10 Although the structural component could be evaluated during studies at baseline, vasoreactivity to acidemia and hypoxemia could be underestimated. In our first patient, measurements obtained during cardiac catheterization with sedation, mechanical ventilation, and arterial pH of 7.5 and Pco 2 of 40 torr could have underestimated the vasoreactivity component. Infants with BPD are prone to acute exacerbations of their pulmonary disease.1112 These exacerbations may worsen the PH and if severe can result in acute RV failure as happened in our patients. The presence of a left-to-right conduit may act as a pop off for the RV during such episodes and prevent acute RV failure.
But when the pulmonary pressures are subsystemic, patients with left-to-right shunts may benefit from closure of such shunts by preventing pulmonary edema and adverse pulmonary vascular changes from increased pulmonary blood flow.13 Experience with closing such shunts in the presence of PH in infants with BPD is limited. A staged approach by optimizing pulmonary vasodilator therapy before PDA closure and a balloon test occlusion at cardiac catheterization has been suggested.14 del Cerro et al reported their experience with closure of PDAs and ASDs in infants with BPD and PH. The patient’s WBC count and creatinine remained normal during high-dose acyclovir therapy. They reported two sudden deaths, one who had undergone aortopulmonary collaterals closure and another with spontaneous ASD closure.15 Andrews et al reported a case of ASD closure in an infant with PH who required a patch fenestration to be able to come off bypass.5 Atrial septal fenestration was considered in both of our patients, but it was not performed. With current data, we cannot estimate which BPD patients will benefit from closure of left-to-right shunts. However, if PH is well established, there is a potential association between closure of these shunts and RV failure. Because death is possible in the event of a severe PH crisis, caution is advised.