Coproporphyrin Excretion in Amniotic Fluid and Urine from Premature Infants: A Possible Maturation Defect

Abstract

ExtractCoproporphyrin analysis was performed on urine from 17 male and 7 female premature infants (birth wt 1.5-4.5 kg, average 1.7 kg). Six specimens of amniotic fluid obtained before elective abortion induced by saline solution infusion were also examined. Normal adult control subjects excreted 24.6y0 5.6y0 of total coproporphyrin as coproporphyrin I. Twenty-three premature infants excreted 59.4y0 A 17.3%as coproporphyrin I, significantly higher amounts than control subjects (P < 0.001).Coproporphyrin I excretion in six specimens of amniotic fluid was 84.9y0 '0 fo.470, significantly higher than in urine from adults and premature infants ( P < 0.001). SpeculationThese results raise the possibility of a similar hepatic excretory defect in porphyrin metabolism in the developing fetus and in the Dubin-Johnson syndrome. I n the fbrmer, the defect is developmental; in the latter, it is lifelong and is present in obligate heterozygotes. Uroporphyrinogen I11 cosynthetase normally catalyzes conversion of porphobilinogen to isomer I11 rather than isomer I porphyrins.Developmental deficiency of this enzyme may be responsible for the observed pattern of coproporphyrin isomers seen in the fetus and neonate.

Developmental changes in urinary coproporphyrin ratio in premature infants

“…For 17 male and seven female premature infants with birth weights of 1.7 kg, it was approximately 0.51 . Furthermore, urine samples were collected on different days after birth in newborns with a corrected gestational age of 30–65 weeks and the UCP (I/ [I + III]) was demonstrated to be negatively correlated with the corrected gestational age .…”

“…The UCP (I/ [I + III]) in full‐term healthy male newborns was reported to be almost 80% on day 1 after birth and decreased gradually to the level equivalent to that of infants and adults by day 10 . Furthermore, the UCP (I/ [I + III]) was reported to be approximately 59.4% in premature infants, and the corrected gestational age was demonstrated to be negatively correlated with UCP (I/ [I + III]) in infants with a corrected gestational age of 30–65 weeks . To improve our understanding, we examined the developmental changes in UCP (I/ [I + III]) in premature infants born before 32 weeks of gestation.…”

Bilirubin Metabolism and its Disorders

“…Biliary excretion of conjugated bilirubin, glutathione-conjugated BSP, iopanoic acid, and ICG is decreased, whereas taurocholate transport is normal. 399,400 The secretion of the organic cation procaine amide ethobromide is unaffected 400 and, interestingly, the secretion of unconjugated BSP is unimpaired. 401 These sheep have a mild hyperbilirubinemia, with 60% of the bilirubin being conjugated.…”

“…397,398 Although neonates normally have elevated urinary content of coproporphyrin I as compared to adults, levels are not as high as seen in Dubin-Johnson syndrome. 399 In obligate heterozygotes (e.g., unaffected parents or children of subjects with Dubin-Johnson syndrome), total urinary coproporphyrin excretion was reduced by 40% of normal. 397,399 The mechanism of the abnormal urinary porphyrin excretion and its relationship to the organic anion transport defect are not known.…”

“…399 In obligate heterozygotes (e.g., unaffected parents or children of subjects with Dubin-Johnson syndrome), total urinary coproporphyrin excretion was reduced by 40% of normal. 397,399 The mechanism of the abnormal urinary porphyrin excretion and its relationship to the organic anion transport defect are not known. When the history and physical examination are consistent, the urinary coproporphyrin excretion pattern is diagnostic of Dubin-Johnson syndrome.…”