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 p29 weeks gestation enterally received a 14-day course of D-penicillamine, and 34 did not, in an openlabel non-randomized trial. We compared the outcomes of developing 'ROP any stage' and 'ROP requiring surgery' in the recipients vs the nonrecipients. 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 ¼ 0.01 vs nonrecipients) 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.

I. The plan is described of a prospective study of the outcome of 5,964 pregnancies, with special emphasis on the relationship of factors in fetal environment to the incidence of abortions, stillbirths, neonatal mortality and congenital malformations. II. Data are presented on the overall incidence of congenital malformations according to sex, race, weight at delivery, maternal age and order of birth. A. The incidence of congenital malformations among 5,739 products of conception weighing over 500 grams was 7.5%. The rate was 7.0% among infants born alive and surviving the neonatal period, 13.6% among antepartum deaths, 23.3% among intrapartum deaths, 29.6% among neonatal deaths and 70.6% among deaths occurring between the ages of one and 12 months. B. The following relationships in incidence rates among live-born infants surviving the neonatal period were found. 1. The rate among males (8.4%) was half again as high as among females (5.5%). 2. Non-white infants had a higher rate (7.8%) than white infants (6.3%). 3. Infants weighing 2,500 grams or less had a higher proportion with defects (9.7%) than did those weighing over 2,500 grams (6.7%), although this difference occurred entirely among females. 4. Maternal age had no effect on the incidence of congenital malformations. 5. White infants of lower birth order had a lower rate (5.3%) than did those of higher birth orders (8.2%). No difference according to birth order was observed among non-white infants. III. A system of classification of malformations is described and discussed. Incidence rates by organ system groups are presented. A. Less than one-half of the malformations found among live-born infants were suspected or noted at birth. B. Malformations of musculo-skeletal system and skin were more frequent than malformations of other systems. Incidence rates by organ system groups are directly related to problems of diagnosis. C. Of the malformed live-born infants, 14.8% had more than one malformation and in 9.1% more than one system was involved. Of the malformed stillbirths and neonatal deaths, 66.0% had more than one malformation and in 51.1% more than one system was involved.

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The frequency of cardiac murmurs in early infancy has been studied in a large series of unselected infants. In the immediate postnatal examination, a murmur was heard in 1.7 per cent. With repeated examinations, however, at 6 and at 12 months of age, the proportion of infants in whom a cardiac murmur was heard at some time rose to 7.0 per cent of 5,017 full-term singlebirth infants and to 9.9 per cent of 364 premature single-birth infants. Non-white infants had a significantly higher prevalence of murmurs than did white infants at both the 6 and 12 month examinations. Of the 71 full-term infants who had murmurs at the birth examination and were re-examined at both 6 and 12 months, 49 (69 per cent) had no murmurs at either of the later examinations. Of the 150 full-term infants who had murmurs heard for the first time at 6 months and were re-examined at 12 months, 90 (60 per cent) had no murmur at the 12-month examination. Of the total number of 353 murmurs heard in full-term infants, 166 were ultimately interpreted to be functional, and 25 to be organic murmurs. The remaining 162 were inconstantly present, and were probably all functional murmurs. In our experience, a murmur heard at birth carries a 1:12 probability of congenital heart disease; if it is again heard at 6 months, this chance is 1:3; and if the murmur persists to 12 months, the chance is 3:5 that congenital heart disease is present. When a murmur is first heard at 6 months, and persists until 12 months, the probability of congenital heart disease is 1:7; and when a murmur is first heard at 12 months, the probability falls to 1:50. Premature infants were found to be similar to full-term infants in all respects, insofar as their small numbers made comparisons possible. Finally, the relative rarity of cardiac murmurs in the newborn period has been demonstrated once more.