D-Penicillamine administration and the incidence of retinopathy of prematurity.

OBJECTIVE: We compared the development of retinopathy of prematurity (ROP) among 49 preterm neonates:; 15 who were treated during the first 2 weeks of life with D-penicillamine and 34 who were not. METHODS: During a 15-month period beginning 1 March, 2005, 15 preterm neonates <1000 g birth weight or < or =29 weeks gestation enterally received a 14-day course of D-penicillamine, and 34 did not, in an open-label non-randomized trial. We compared the outcomes of developing 'ROP any stage' and 'ROP requiring surgery' in the recipients vs the non-recipients. Potential toxicities of the D-penicillamine were examined by comparing specific laboratory tests, growth velocities, transfusion requirements, discharge hemoglobin concentrations and supplemental O(2) at discharge. RESULTS: The 34 non-treated and the 15 D-penicillamine treated patients were of similar gestational age (26.5+/-1.8 vs 26.6+/-2.2 weeks, mean+/-s.d.) and birth weight (887+/-222 vs 849+/-187 g). Four of the 34 non-recipients died. Eighteen of the 30 survivors (60%) developed ROP and seven of the 30 (23%) had ROP surgery. One of the 15 D-penicillamine recipients died. Three of the 14 survivors (21%) developed ROP (P=0.01 vs non-recipients) and all three had ROP laser surgery. No increase in elevated creatinine, direct or indirect bilirubin, thrombocytopenia or neutropenia was apparent in those treated with D-penicillamine. The D-penicillamine recipients did not receive more transfusions and did not have lower hemoglobin concentrations at discharge. They did not have lower velocities of weight gain at 14, 28 and 56 days, and were not discharged on supplemental O(2) at a rate exceeding that of the non-recipients. CONCLUSIONS: In this non-randomized, single-centered comparison analysis, a 14-day course of D-penicillamine resulted in no apparent short-term toxicity. The treatment was associated with elimination of Stage I and Stage II ROP, decreasing the overall odds of developing ROP from 60 to 21%. However, this approach did not reduce the odds of ROP surgery. Perhaps higher doses of D-penicillamine or longer treatment periods or other prophylactic approaches will be required to reduce ROP surgery among the most immature neonates.

A pilot trial testing the feasibility of administering D-penicillamine to extremely low birth weight neonates.

OBJECTIVE: We enterally administered a 14-day course of 3-mercapto-D-valine (D-penicillamine) to five extremely low birth weight (ELBW) neonates, as a step toward assessing this therapy as a means of reducing the incidence or severity of retinopathy of prematurity (ROP). METHODS: The study drug (100 mg/ml) was given by nasogastric tube at a dose of 100 mg/k every 8 h for three days, and then 50 mg/k once per day for 11 additional days. Logbooks were maintained by the bedside nurses to record signs of possible immediate intolerance. Laboratory tests assessed hepatic, renal, and hematologic toxicity. ROP was scored according to the ICROP guidelines. Comparisons were with a cohort of 139 consecutive recent neonates of the same birth weight and gestational age range. RESULTS: Five neonates were enrolled in the study, and all received the full course of study drug as planned. Signs of immediate intolerance of the study drug were not observed in any. The study patients did not have a higher incidence, than that of the cohort group, in creatinine elevation, thrombocytopenia, neutropenia, hyperbilirubinemia, or abnormal liver function test. Four of the five had no ROP and one developed transient stage 1, compared with a 54% occurrence of ROP in the cohort. CONCLUSIONS: It is feasible to enterally administer a 14-day course of 3-mercapto-D-valine to ELBW neonates and the suspension appears to be well tolerated. These results suggest that phase II safety and preliminary efficacy trials can be undertaken.

Histologic features of placentas and abortion specimens from women with antiphospholipid and antiphospholipid-like syndromes.

OBJECTIVE: Antiphospholipid syndrome is characterized by recurrent pregnancy loss, thrombosis, and antiphospholipid antibodies. However, some women with clinical features of antiphospholipid syndrome test negative for antiphospholipid antibodies ("antiphospholipid-like syndrome"). Women with antiphospholipid and antiphospholipid-like syndromes have serum immunoglobulin G that harms murine pregnancy, suggesting that the mechanisms of fetal death may be similar in both groups. The objective of our study was to determine whether patients with antiphospholipid and antiphospholipid-like syndromes share pathophysiology by comparing the histology of gestational tissues from these groups. METHODS: Placenta and abortion specimens were obtained from 44 pregnancies in 26 women with antiphospholipid syndrome and 37 pregnancies in 21 women with antiphospholipid-like syndrome. Of these, 16 pregnancies with antiphospholipid syndrome and 8 with antiphospholipid-like syndrome were treated with a variety of medications intended to improve pregnancy outcome. Placentas from 31 elective pregnancy terminations and 40 pregnancies complicated by idiopathic preterm delivery served as an additional control group. Twenty histologic parameters were systematically assessed by a single investigator who was blinded to the clinical status of the specimens. Histopathologic findings were compared among groups using multivariate logistic regression analysis. RESULTS: Antiphospholipid syndrome pregnancies included 15 spontaneous abortions, 13 fetal deaths, and 16 live births. Pregnancies in the antiphospholipid-like syndrome group resulted in 5 spontaneous abortions, 30 fetal deaths, and one live birth. Gestational tissues from antiphospholipid and antiphospholipid-like syndrome pregnancies were similar for every histologic feature tested. Decidua from women with both antiphospholipid and antiphospholipid-like syndromes had more necrosis, acute and chronic inflammation, and vascular thrombus compared to controls. Placental tissue from antiphospholipid and antiphospholipid-like syndrome pregnancies showed more infarction, intravascular fibrin deposition, syncytial knot formation, and fibrosis than controls. Histologic features were variable within groups. There were no histologic differences in tissues from live births and pregnancy losses, or in treated and untreated pregnancies. CONCLUSIONS: Placental histopathology is similar in antiphospholipid and antiphospholipid-like syndrome pregnancies, suggesting that these disorders may share pathophysiology. Histologic findings in women with APS are non-specific and may not differentiate between women with APS and APS-like syndromes.