Joseph Pardo

Is immunosuppression therapy in renal allograft recipients teratogenic? A single‐center experience

The aim of the study was to determine whether immunosuppressive agents used in renal allograft recipients are teratogenic or otherwise associated with pregnancy outcome. The study population consisted of 38 renal allograft recipients treated with combinations of prednisone, azathioprine, cyclosporin A, and tacrolimus attending our Hypertension in Pregnancy Clinic. The 48 live offspring of 73 pregnancies in this group were evaluated for major congenital malformations and mild errors of morphogenesis. Findings were compared with those in 48 offspring of 41 women with primary renal disease not treated with immunosuppressive drugs. Pregnancy outcome parameters were also compared between the study and control groups in the perinatal period and on a long‐term basis (2–7 years after birth). Two major anomalies (4.2%), subcoronal hypospadias and rudimentary thumb, and 10 mild errors of morphogenesis (20.8%) were detected in the study group. These rates did not differ significantly from those in the control group (4.2% and 16.6%, respectively). Pregnancy outcome was worse in the renal transplant patients than in the women with primary renal disease in terms of prematurity (60% vs. 21%, Pu2009=u20090.001), growth restriction (52% vs. 17%, Pu2009=u20090.001), and hospitalization in a neonatal intensive care unit (35% vs. 6%, Pu2009=u20090.01). In conclusion, the similar prevalence of major anomalies and mild errors of morphogenesis in offspring of the renal transplant patients and the women with primary renal disease suggests that immunosuppressive therapy is not a teratogenic factor. It may, however, be associated with worse pregnancy outcome.

The missing forgotten intrauterine contraceptive device

Failure to locate the strings of an intrauterine contraceptive device may mean that the device is within the uterine cavity, was expelled or, worst of all, has perforated the uterine wall. We describe a 36-year-old woman complaining of infertility in whom two missing devices were found within the pelvis after having perforated the uterus. This report demonstrates the need to investigate every case of a missing intrauterine contraceptive device. An algorithm for the proper management of such cases is suggested.

Hearing outcome of infants with congenital cytomegalovirus and hearing impairment

Background Congenital cytomegalovirus (cCMV) is the most common non-genetic cause of childhood sensorineural hearing loss. Antiviral treatment has been shown to prevent hearing deterioration in these infants. However, studies focused on infants with hearing impairment at birth and on the specific degree of impairment and further improvement or deterioration are lacking. Objective To investigate the relationship between hearing status at birth and any change in hearing status at the end of a prolonged follow-up period, after receiving 12u2005months of antiviral treatment in children born with hearing impairment due to congenital cCMV. Methods Clinical, laboratory, radiological and audiological data of all infants with cCMV infection followed in our centre between 2005 and 2013 were reviewed. Treatment with antiviral medication for hearing impairment found during the neonatal period was12u2005months of gan/valganciclovir. Hearing studies were performed only on infants who had been followed up for more than 1u2005year after treatment. Results Hearing impairment at birth was found in 54 (36.2%) of the 149 infants diagnosed with symptomatic cCMV, and found in 77 affected ears; unilateral in 31 (57.4%) and bilateral in 23 (42.6%). After 1u2005year of antiviral treatment and a long-term follow-up of the 77 affected ears at baseline, 50 (64.9%) had improved, 22 (28.6%) remained unchanged and 5 (6.5%) had deteriorated. Most improved ears (38/50=76%) returned to normal hearing. Improvement was most likely to occur in infants born with mild or moderate hearing loss and less in those with severe impairment. Conclusions We found that infants born with cCMV and hearing impairment, receiving 12u2005months of antiviral treatment, showed significant improvement in hearing status. The probability of hearing improvement seems inversely related to the severity of the impairment at birth.

The effect of time of day on outcome of unscheduled cesarean deliveries

Objective.u2003To assess the association between time of day and characteristics and complications rate of cesarean sections. Methods.u2003We conducted a retrospective cohort study of all women who underwent an unscheduled (non-elective) cesarean section (CS) between 1997 and 2007 in a single tertiary medical center. Maternal and neonatal outcome and duration of CS were analyzed according to the work shift. Multivariable logistic regression analysis was used to determine whether shift number is an independent risk factor for maternal or neonatal adverse outcome. Results.u2003There were overall 9944 unscheduled CS during the study period, of them 2995 (30.1%) were operated on the morning shift, 4618 (46.4%) on the evening shift, and 2331 (23.5%) on the night shift. The characteristics of the women in each of the shifts were overall similar. Women who underwent CS during night shift had a higher rate of endometritis and wound infection, postpartum hemorrhage requiring hemotransfusion, and prolonged postoperative hospitalization. The rate of adverse neonatal outcome was similar in the three working shifts. After adjustment for potential confounders by multivariable logistic regression analysis, maternal morbidity was significantly higher for women operated on night shift. The risk of neonatal morbidity was unrelated to the working shift. Overall duration of CS, time required for induction of anesthesia, and net operation time were all significantly higher during the night shift compared with the morning and evening shift. Conclusion.u2003CSs performed during night shift are associated with longer operative time and an increased risk for maternal, but not neonatal, morbidity.

Cobalamin (vitamin B12) metabolism during pregnancy.

Approximately 20% of women show a physiologic drop in serum vitamin B12 level during pregnancy. Establishment of the latter requires direct measurement of metabolites related to the vitamin-B12-dependent pathways. Although the fetal compartment contains the products of fetal and maternal metabolism and provides a window into fetal metabolism the dynamics and physiology of the transplacental transport of these metabolites has been hardly studied. We sought to assess the relationship between the maternal and fetal compartments with regard to the metabolism of folate cobalamin and homocysteine (Hcy) and their correlation to hematological indices. (excerpt)

Lenticulostriated vasculopathy is a high-risk marker for hearing loss in congenital cytomegalovirus infections

This study investigated the relationship between lenticulostriated vasculopathy (LSV) and hearing loss in 141 infants with congenital cytomegalovirus (cCMV) infection.

Clinical Implications for Children Born With Congenital Cytomegalovirus Infection Following a Negative Amniocentesis.

BACKGROUNDnRecently, congenital cytomegalovirus (cCMV) infection was reported irrespective of a negative amniotic fluid prenatal analysis for cytomegalovirus (CMV). The question of whether this phenomenon represents low sensitivity of the test or late development of fetal infection (after amniocentesis) was discussed, but not answered. However, if late transmission is the rule, then infants born with cCMV after negative amniocentesis would be expected to carry better prognosis than those who tested positive.nnnMETHODSnData of all infants with cCMV infection, followed in 2 pediatric centers from 2006 to 2015, were reviewed. Infant outcome after birth of symptomatic vs asymptomatic disease was compared with infants born after a negative amniocentesis (study group) and those with a positive amniocentesis (control group).nnnRESULTSnAmniocentesis was performed in 301 pregnancies of our cohort of infants with cCMV and was negative for CMV in 47 (15.6%). There were fewer symptomatic cCMV neonates in the study group than in the control group (4.3% vs 25%; P < .001). Hearing impairment at birth was also less frequent in the study group (2.2% vs 17.4%; P = .012). None of the children in the study group had neurologic sequelae at long-term follow up, compared with 13 (14.1%) in the control group (P < .001).nnnCONCLUSIONSnAlthough negative amniocentesis does not exclude cCMV, infants with cCMV born after a negative amniocentesis seldom present with mild clinical symptoms or cerebral ultrasound features at birth. These children also have a very good long-term outcome. Our findings support the theory of a late development of fetal infection, after the time of the amniocentesis.

Treatment of Late-Onset Hearing Loss in Infants With Congenital Cytomegalovirus Infection

Objective. To evaluate the effect of antiviral treatment on late-onset hearing loss in infants with congenital cytomegalovirus infection. Design. The database of all infants who had normal hearing at birth, and treated for late-onset hearing loss was collected. The primary study endpoint was the need for a cochlear implant at the last follow-up visit. Results. Twenty-one infants met the inclusion criteria. Brain stem–evoked response audiometry testing revealed hearing loss in 35 of 42 ears (83%). Mean age at diagnosis of hearing loss was 7.4 ± 3.7 months and onset of antiviral therapy 10.3 ± 7.8 months. None of the ears showed further deterioration as referred to pretreatment values. Hearing thresholds improved in 29 ears (69%). None of the patients needed a cochlear implant. Conclusions. In children with late-onset hearing loss due to cytomegalovirus infection, antiviral treatment appears to prevent further deterioration and produce improvement. Controlled studies are needed to verify this observation.

Management of Bacteriuria in Veterans Affairs Hospitals

BackgroundnBacteriuria contributes to antibiotic overuse through treatment of asymptomatic bacteriuria (ASB) and long durations of therapy for symptomatic urinary tract infections (UTIs), yet large-scale evaluations of bacteriuria management among inpatients are lacking.nnnMethodsnInpatients with bacteriuria were classified as asymptomatic or symptomatic based on established criteria applied to data collected by manual chart review. We examined frequency of treatment of ASB, factors associated with treatment of ASB, durations of therapy, and frequency of complications including Clostridium difficile infection, readmission, and all-cause mortality within 28 days of discharge.nnnResultsnAmong 2225 episodes of bacteriuria, 64% were classified as ASB. After excluding patients with non-UTI indications for antibiotics, 72% of patients with ASB received antibiotics. When evaluating only patients not meeting SIRS criteria, 68% of patients with ASB received antibiotics. The mean (±SD) days of antibiotic therapy for ASB, cystitis, CA-UTI and pyelonephritis were 10.0 (4.5), 11.4 (4.7), 12.0 (6.1), and 13.6 (5.3), respectively. In sum, 14% of patients with ASB were treated for greater than 14 days, and fluoroquinolones were the most commonly used empiric antibiotic for ASB [245/691 (35%)]. Complications were rare but more common among patients with ASB treated with antibiotics.nnnConclusionsnThe majority of bacteriuria among inpatient veterans is due to ASB with high rates of treatment of ASB and prolonged durations of therapy for ASB and symptomatic UTIs.

Congenital cytomegalovirus infection following antenatal negative diagnostic amniotic fluid analysis – A single center experience

Objective:To determine the perinatal outcome of confirmed congenital cytomegalovirus (CMV) infection despite a negative prenatal amniotic-fluid analysis. Methods: A retrospective cohort study of all neonates diagnosed with congenital CMV infection from January 2006 to December 2011 despite negative results on polymerase chain reaction and shell’s vial assays of amniotic fluid. Data were collected on all neonates by physical examination, blood work-up (complete blood count, bilirubin, liver enzymes), fundoscopy, brainstem evoked response (BSER), and brain ultrasound, at birth and during follow-up in the neonatal period. Results: The study group included 10 patients with primary congenital CMV infection during pregnancy. Follow-up time ranged from 1 to 62 months (median, 17 months). Four patients had consistently normal findings throughout follow-up, and three developed mild hepatosplenomegaly (1–32 months). In the remaining four offspring, brain ultrasound preformed after birth revealed lenticular striated vasculopathy (LSV) and in three of them the BSER test showed decreased hearing ability. Treatment with ganciclovir/valganciclovir was administered at age of 2 weeks, 2, 18, and 32 months. The BSER normalized after 9 and 12 months of treatment in two patients for whom follow-up data were available. Conclusion: Negative findings on amniotic-fluid tests for CMV do not rule out neonatal infection with clinical morbidity.