Meconium staining of newborn infants

Meconium staining of newborn infants

MECONIU3~ S T A I N I N G OF N E W B O R N I N F A N T S 1V~URDINA iV[. DESMOND, ~V[.D., JOHN E . LINDLEY, M.D., JACK !VI00RE, M.D., AND CLARENCE A . ...

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MECONIU3~ S T A I N I N G OF N E W B O R N I N F A N T S 1V~URDINA iV[. DESMOND, ~V[.D., JOHN E . LINDLEY, M.D., JACK !VI00RE, M.D., AND CLARENCE A . BROWN, M . D . HOUSTON, TEXAS

ECONIU3/I staining of the amnifluid is one of the classic signs of f e t a l distress in utero. East-

M otie

man I states that fetal distress may

be

suspected w h e n the amniotie fluid presents a yellow-green a p p e a r a n c e and contains meeonium. He writes t h a t the presence of meconium-stained amniotic fluid is not in itself an indication f o r delivery but d e m a n d s close w a t c h i n g of the fetal h e a r t rate. He concludes t h a t this sign is w i t h o u t significance in breech presentation, since it m a y be caused b y mechanical p r e s s u r e on the f e t a l abdomen. Since 1945 Clifford 2 has been int e r e s t e d in the i n f a n t stained with yellow vernix. H e believes t h a t these i n f a n t s h a v e suffered a p r o l o n g e d exposure to m e e o n i u m which has been passed into the amniotie sac. He coneludes t h a t this p h e n o m e n o n folIows f e t a l a n o x i a s e c o n d a r y to p l a c e n t a l dysfunction. I n his experience, the presence of yellow nails and v e r n i x staining has been associated w i t h a h i g h e r n e o n a t a l m o r b i d i t y a n d perin a t a l m o r t a l i t y . This w o r k has been confirmed b y T a y l o r and co-workers ~ in Scotland. Recently, W a l k e r 4 in A b e r d e e n p u b l i s h e d a series of figures in w h i c h he c o r r e l a t e d the p e r cent From the Departments of Pediatrics, Obstetrics, and Pathology, :Baylor University College of Medicine and the Jefferson Davis Hospital. Supported by a grant from the Mead Johnson & Co., Evansville, Ind. 540

s a t u r a t i o n of o x y g e n in the umbilical vein at d e l i v e r y w i t h the regent passage of meconium b y the infant. He f o u n d t h a t a level of o x y g e n saturation of 30 p e r cent or less was assoeiated with the passage of meconium. I-Ie concludes t h a t at this level, " t h e distress l e v e l , " the i n f a n t does not obtain enough o x y g e n t o survive indefinitely in utero. I t is possible t h a t m e c o n i u m m a y be passed in utero by a t w o f o l d m e c h a n i s m following anoxia. V a n Liere 5 r e p o r t s the initial effect of h y p o x i a on the small bowel to be one of hyperperistalsis, soon followed b y ileus. I n the late stages of a n o x i a a r e l a x a t i o n of the s p h i n c t e r ani occurs concomitant w i t h shock a n d flaccidity. 1 I n spite of the potential seriousness of m e c o n i u m - s t a i n e d amniotic fluid at delivery, the recent l i t e r a t u r e cont a i n s f e w references to its incidence. I n 1925 Sehultze 6 f o u n d it occurred in 3 p e r cent of all deliveries. I n a rev i e w of the signs Of f e t a l distress, lV[eCall and F u l s h e r 7 in 1953 r e p o r t e d an incidence of 0.5 p e r cent. Recently W h i t e s f r o m A u s t r a l i a r e p o r t e d an over-all incidence of 5 p e r cent. Since meconium staining of the a m n i o t i e fluid is so f r e q u e n t l y associated w i t h the delivery of vigorous infants, it alone is not u n i v e r s a l l y considered to be an absolute sign of fetal distress. This is emphasized b y the

DESMOND E T A L . :

M E C O N I U M S T A I N I N G OF N E W B O R N

finding that hospital labor and delivery records frequently carry no description of the character of the amniotie fluid. The relationship between meeonium discoloration of the amniotic fluid at birth and difficuIties encountered in the infant born of such a delivery has not been clearly established. I f meeonium is indeed present in amniotic fluid as a result of antenatal hypoxia, it would be of great value to know if an association exists between the presence of such fluid and some of the difficulties encountered during the neonatal period as well as Iater in life, such as cerebral palsy, epilepsy, behavior disorders, and mental deficiency. Since December, 1953, a coordinated study of this problem has been conducted in this institution by the departments of obstetrics, pediatrics, and pathology. Infants born of mothers whose deliveries are complicated by the presence of meeonium-stained amniotic fluid have been observed in the nursery for evidence of neonatal difficulty and for evidence of meeonium staining of the skin and nails. The present report is concerned with the incidence of meeoniumstained amniotlc fluid at delivery, and the characteristic appearance of the infants exposed to such fluid, together with a consideration of the involved pigments. A study of the prenatal and natal factors associated with its prodnetiorL is in progress. SUBJECTS

All patients were seen as inpatients on the obstetrical service of Jefferson Davis City-County ttospital over a thirteen-month period (Dec. 1, 1953, through Jan. 1, 1955, inclusive). Patients here come from the lowest in-

INFANTS

541

come group in the c o m I n u n i t y . Seventy-four per cent are Negro and 26 per cent white (largely LatinAmerican). A large percentage (44 per cent) have had no prenatal care. The average patient stay is fortyeight hours for primiparas and twentyfour hours for multiparas. The color of the amniotic fluid, membranes, cord, and placenta were noted and recorded by the physician attending the delivery. 0nl y deliveries associated with the birth of liveborn infants were considered in this study. After the infants were admitted to the nursery, they were examined by a pediatric resident physician. An attempt was made to note the presence or absence of staining of the infant's body. During the last six months of the study period these infants were placed briefly under a Wood's ultraviolet light as part of the initial physical examination. The delivery immediately subsequent to the one associated with meconiumstained amniotic fluid was utilized as a control delivery. INCIDENCE

Amniotic fluid, described as yellow, green-yellow, or meconium stained, was found to be present at delivery in 407 of 3,865 consecutive deliveries, an incidence of 10.9 per cent. This figure is high compared to those of Schu]tze in 1925 (3 per cent) and McCall and Fulsher in 1953 (0.5 per cent). It is twice that recently reported by White in Australia (5.0 per cent). When the cases of blood incompatibility (nine), high intestinal obstruction (three), and breech delivery (thirteen) are eliminated from the total, the incidence is 9.6 per cent.

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The majority (96.6 per cent) of infants in the meconium-stained amniotie fluid group were of term weight. The percentage of premature deliveries (4.4 per cent) is less than that present in the control series (11.6 per cent). Of the total 408 infants, fourteen (3.4 per cent) died during the neonatal period. Eight of these were term infants. (One infant weighed less than 1,000 grains and was not included in the total.) In t h e control group the neonatal mortality was 1.5 per cent, with one term death. An additional seventy-eight infants experienced some difficulties in the immediate neonatal period, as against twenty-five in the control group. A total of fifty-five (13.4 per cent) infants in the meeomum-stained amniotic fluid series had apnea neonatorum requiring active resuscitation, while this was required in thirteen (3.2 per cent) of the control series. THE

CHARACTER

OF I V I E C O N I U M - S T A I N E D

AfiINIOTIC F L U I D

Normal amniotie fluid is a clear or slightly cloudy solution, slightly alkaline in reaction, with a specific gravity of approximately 1.008. It is hypo~ tonic to maternal serum and is composed of 98 per cent water. The remaining 2 per cent is composed of inorganic salts, urea, creatinine, lanugo hair, vernix, and epithelial cells. The average volume at term is 1,500 c.c. Meconium is a viscid semisolid material composed of 70 to 80 per cent (by d r y weight) mucopolysaccharides, desquamated cells, vernix, lanugo hair, and cholesterol. 1~ I t derives its color from a large amount of bile pigment (biliverdin, bilirubin) excreted b y the fetal biliary tract. It is first found in the gastrointestinal tract of the fetus

OF P E D I A T R I C S

after the fourth or fifth month of gestation. The color is usually described as dark green-brown to black2 However, during the course of this study it was noted that, although meeonium is usually dark, it may be lighter in color, with a mustard yellow or a tan appearance. On exposure to light and air the color becomes darker, tending toward a uniform green-black. Meconium-stained amniotic fluids range from a green to tan to orange-yellow, according to the color of the p a r e n t meconium. On four occasions the infant at delivery was found to be passing yellow meeonium which was associated with a similar coloration of the amniotie fluid. Some abnormal fluids were, as noted by Clifford, extremely scant and viscid. The early fluid passed on r u p t u r e of the membranes often appeared less viscid than that which followed the delivery of the fetus. I t was noted that the white linen draping the patient t e n d e d to assume a yellow stain regardless of w h e t h e r the amniotic fluid was green or yellow in color. THE DURATION OF EXPOSURE TO MECONIUfC[-STAINEDAMNIOTIC FLUID REQUIRED FOR STAINING OF THE I~ZFANT If, as it has been postulated b y Clifford and Walker, the passage of meeonium-stained amniotic fluid is an indication of fetal hypoxia, it then becomes of interest to find how long a time is required for the various parts of the fetus and placenta to show visible staining. This would permit a rough estimation of the length of time before delivery when the oxygen saturation of the fetus becomes low enough to cause the fetus to pass meconium while in utero.

DESMOND

ET

AL. :

1VIECONIUM

STAINING

N o r m a l n e w b o r n i n f a n t s less t h a n 24 hours of age and b o r n of deliveries in which the amniotie fluid was n o t e d to be clear were utilized as experimental subjects. The feet were immersed in r u b b e r gloves containing meeonium solutions or a b n o r m a l amniotie fluids. A f t e r exposure for various periods, t h e feet were washed u n d e r r u n n i n g water, the moisture rem o v e d w i t h a b s o r b e n t paper, and the nails checked for yellow staining u n d e r n a t u r a l light. The resuIts are shown in Table I. A m i n i m u m of f o u r to six hours is r e q u i r e d for staining u n d e r these conditions. I t m a y t h e n

OF

NEWBORN

INFANTS

543

ing was n o t e d at twelve hours in one instance, a n d at f o u r t e e n hours in another. These pet'iods c o r r e s p o n d w i t h those seen in vivo. I n two eases m e m b r a n e s were artificially r u p t u r e d to induce labor. In both, the fetal head was b a l l o t t e d above the inlet to p e r m i t free escape of fluid. A t the time of amniotomy, the amniotic fluids were clear. I n one instance the i n f a n t was delivered f o u r a n d one-half hours a f t e r amniotomy. Staining of the nails was p r e s e n t but not of the vernix and cord. I n the second instance, the i n f a n t was delivered f o u r t e e n hours

T A B L E ~. D U R A T I O N 01~ E X P O S U R E OF ~NFANTS' N A I L S TO IVIECONIUM OE IV~ECONIUI~-STAINED fl~MNIOTIC FLUIDS N E C E S S A R Y F 0 R STAINING TO B E C O M E VISIBLE IN N A T U R A L A N D ULTKAVIOLET LIGIIT

Normal meeonium in saline Pooled m e e o n i u m stained amniotic fluids

CONCENTI~ATION

NUMBER OF CASES

1% 5%

4 4

10%

3

Undiluted

6

be concluded t h a t if the nails of the i n f a n t show slight yellow staining the time of meeonium p a s s a g e was at least f o u r to six hours p r i o r to delivery. I t is difficult to d e t e r m i n e this more precisely f o r a n y one infant, since there are several v a r i a b l e s involved (i.e., the a m o u n t of bile p i g m e n t present in meeonimn, the a m o u n t of meconium passed, and the a m o u n t of amniotie fluid p r e s e n t ) . N o r m a l v e r n i x was placed into m e c o n i u m - s t a i n e d amniotie fluid and i n c u b a t e d at b o d y t e m p e r a t u r e . At intervals the v e r n i x was r e m o v e d b y filtration and w a s h e d with distilled water, The first definite yellow stain-

T I M E REQUIRED FOR MINIMAL YELLOW S T A I N I N G OF N A I L S

11~-2 hr. 1-2 hr. 4:5 min.-1 hr. 4:-6 hr.

T I M E REQUIRED FOR LOSS OF NORMAL NAIL COLOR UNDER UV L I G H T

1 hr. 4:5 min.-1 hr. 30 min.-1 hr. 2-4: hr.

a f t e r amniotomy. This i n f a n t showed yellow staining of the v e r n i x as well as of the cord a n d the nails. The conditions u n d e r which these infants were b o r n are not strictly c o m p a r a b l e to the usual conditions, since the time of i n t r a u t e r i n e m e e o n i u m passage was not k n o w n a n d since, w h e n meeonium was passed, it was p r e s e n t e d to the f e t a l surface in high concentration, considerable amniotie fluid h a v i n g been passed w i t h the ataniotomy. The umbilical cord a n d superficial skin tend to assume the color of the amniotic fluid a n d a p p e a r yellow, green, or bronze in tint. V e r n i x and nails, howeve% a p p e a r u n i f o r m l y y e b

544

THE

JOURNAL

OF

since desquamation may be seen in the presence of clear amniotic fluid and after apparently normal deliveries. However, in those patients desquamation is usually less extensive.

low, regardless of the color of the amniotic fluid. In intensely stained infants, the tongue, and posterior pharynx may be coated with mecoIlium. The placenta tends to assume the color of the amniotic fluid. The pigment is deposited on the fetal surface and washes off readily under running water. The skin of the infant so involved may be normal, or may show various degrees of desquamation. This is cir-

1.2t.f", i

PEDIATRICS

THE

PIGMENTS

INVOLVED IN

STAINING

OF THE

MECONIUM

INFANT

The absorption spectra of normal amniotic fluid, diluted meconium solution, and meconium-stained amniotic fluids were performed with the Beck-

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Amniotic Fluid ultracentrifugation

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WAVE LENGTH m.~ Fig.

L--Absorption

spectra

of n o r m a l

a m n i o t f c fluid, m e c o n i u m - s t a i n e d meeonium.

cinate or moth-eaten in type. The desquamation progresses proximally from the palmar aspect of the distal phalanx toward the palm, and outward from the metacarpal phalangeal joint. On the body it may be seen extending outward from the axilla and groin. On occasion the desquamarion may be so severe as to approach that of the macerated stillborn fetus. This process cannot be due entirely to the presence of meconium,

amniotic

fluid,

and

man speetrophotometer (Fig. ]). These fluids show a peak in the region of 410 m~. This represents the " S o r e t band," an absorption peak typical of compounds containing a porphyrirL nucleus. This peak remains after ultracentrifugation at 27,000 r.p.m, for one hour, a speed calculated to throw down the mucopolysaecharides present in the solution. Normal amniotic fluid, meconium, and meconium-stained amniotic fluid

DESMO~'qD E T A L . :

~VIECONIUM S T A I N I N G OF N E W B O R N

545

Chloroform Extracts Of:

032

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009 ~. 0.08 007 0.06 "~ to

INFANTS

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WAVE LENGTH m~u F i g . 2.--Absorption s p e c t r & of c h l o r o f o r m e x t r a c t s of m e c o n i u m , n o r m a l m e e o n i u m - s t a i n e d a r n n t o t i c fluid.

&mniotic fluid

0.15 o Yellow Vernix

/o-q

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0.13 0.12

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To Meconium-Stoined Fluid For 48 Hours 9 NormolVernix

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and yellow vernix.

and

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THE

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were e x t r a c t e d with chloroform and passed t h r o u g h the spectrophotometer (Fig: 2). These extracts show a uniform peak at 460 mt~--a peak typical of commercial bilirubin. These extracts gave a positive reaction with the diazo and F o u c h e t ' s reagents, reactions typical of bilirubin. Alcoholic extracts of meeonium and meeoniumstained fluids gave a similar peak at 460 mt~. Chloroform extracts were made of normal vcrnix, yellow vernix (from an i n f a n t b o r n of a delivery in which meconium-stained fluid was present), and n o r m a l vernix incubated for forty-eight hours with meconimnstained fluid (Fig. 3). The l a t t e r two extracts also showed a typical bilirubin peak at 460 mt~. Biliverdin is a known constituent of meconium and meeonium-stained amniotic fluid. A t t e m p t s to demonstrate the presence of biliverdin in yellow v e r n i x were unsuccessful in this laboratory. It thus appears that vernix easeosa, suspended in a meeonium solution which contains a mixture of pigments, selectively tends to absorb more of the yellow pigment. This may be due in p a r t to the relative insolubility of the green pigment, biverdin. It has been shown t h a t bilirubin has the p r o p e r t y of p e n e t r a t i n g the surface monolayers of cholesterol, a normal constituent of vernix caseosa. In addition, bilirubin possesses the capacity for binding to protein2 3 This p r o p e r t y of bilirubin m a y possibly be the e x p l a n a t i o n for the yellow color of skin and nails seen a f t e r the inf a n t ' s b o d y has been suspended in meeonium-stained fluid.

OF PEDIATRICS THE LAMP

USE IN

OF

THE

THE

WOOD'S

ULTRAVIOLET

RECOGNITION

OF

MECO -

24IUM S T A I N I N G

At the midpoint of the s t u d y it was n o t e d that infants exposed to meconium-stained a m n i o t i c fluids showed some degree of dull orangered fluorescence when placed u n d e r a W o o d ' s lamp.* This fluorescence usually parallels the degree of visible staining but is more easily recognized, p a r t i c u l a r l y when infants b o r n a f t e r n o r m a l delivery are utilized as control subjects. The degree of fluorescence begins to fade within six to twelve hours a f t e r birth and is usually not present a f t e r t w e n t y - f o u r hours except in extreme cases (Plate II). The type of W o o d ' s light used was of the long-wave type (360 minute Hanovia type ]0103"). I t is necessary that the infant's eyes be protected from the ultraviolet lamp during exposure. Under ultraviolet light the normal nail border and the umbilical cord appear bluish white and the intact skin purple. Desquamating skin appears white. Infants exposed to meconiumstained amniotic fluids for long periods show a dull orange-red fluorescence at the free nail border, periungal tissues, and over desquamating or m a c e r a t e d skin. Yellow v e r n i x may or m a y not show this phenomenon. W h e n the nails of normal infants are exposed to meeonium or to meeonium-stained amniotic fluids, the progression of color development, as seen u n d e r the W o o d ' s lamp, appears to be as follows: (1) the loss of the normal blue-white color of the nail, (2)" the appearance of a dull tan color * H a n o v i a C h e m i c a l a n d M f g . Co., N e w a r k , New Jersey.

DESMOND ET AL.: MECONIUI~[ STAINING OF lkIEWBORN INFANTS

J . PEDIAT. ~0u

P l a t e I.

P l a t e II. Plate I.--Meconium staining of the newborn infant. Plate II.--A drawing of the appearance of meconium

s t a i n i n g u n d e r t h e ~Vood's l i g h t .

]95(;

DESMOND E T AL. :

MECONIUM

S T A I N I N G OF N E W B O R N I N F A N T S

of nail and periungal tissues, and (3) the appearance of the characteristic orange-red fluorescence. The first stage usually appears before visible yellow staining m a y be seen in natural light. Three h u n d r e d fifty consecutive infants were placed u n d e r the W o o d ' s lamp. Six infants, in whose records the amniotie fluids were described as clear, showed some degree of change u n d e r the W o o d ' s lamp. A f t e r having been checked with the obstetrician, the records were found to be in error in three cases. In the remaining three, the obstetrician did not recall the color of the amniotie fluid. Thus, the association of orange fluorescence with meeonium staining of the amniotie fluid is a close one and it m a y be assumed t h a t if this color is present u n d e r the W o o d ' s lamp meeonium or bile pigments were probably present in the amniotie fluid. The color given by meeonium must, however, be distinguished from that given by large dosage of the group B vitamins or the tetracycline antibiotics. It was n o t e d t h a t the nails, skin, and cord of some infants showed a striking greenish yellow fluorescence. This was of g r e a t e r intensity than that shown b y meconium staining'. In each instance the mother had been t r e a t e d with intravenous vitamin B or one of the tetracycline antibioties within t w e n t y - f o u r hours prior to delivery. Two mothers were given 1 c.c. of intravenous vitamin B complex (Betalake) in 5 per cent glucose infusion. At delivery eight and twelve hours later, respectively, the amniotie fluid was noted to be clear. Under the Woo'd's light, these fluids showed an intense yellow-g r e e n fluorescence.

5~7

The infants' nails and cords showed a similar color. When tetracycline (500 rag. Achromycin) was given I.V. to two normal mothers twelve and t w e n t y - f o u r hours prior to delivery, the fluid showed a slight yellow coloration u n d e r n a t u r a l light and m a r k e d green-yellow fluoreseenee u n d e r the W o o d ' s lamp. The i n f a n t s ' nails and cords showed a marked greenish yellow fluorescence. This is easily diff e r e n t i a t e d f r o m the dull orange seen after meconium staining. The pigment or pigments responsible for the nail and skin fluorescence are not known. The probability is, however, that the color is due to p o r p h y r i n compounds which a' r e known constituents of meeonium. 1~ In addition, it has been shown that p o r p h y r i n compounds, at physiologic pH, m a y be expected to couple readily to basic proteins. 11 C o p r o p o r p h y r i n has been identified in the plasma of the fetus and newborn infant and in meconium. Needham ~4 states t h a t a physiologic porphyria is present during fetal life and can be ascribed to the vigorous hematopoiesis characteristic of this period. The m a j o r i t y of investigators ~5 t o d a y agree that p o r p h y r i n f o r m a t i o n n o r m a l l y occurs during hemoglobin synthesis and that the p o r p h y r i n s f o u n d in feces represent intermediates or by-products of hemoglobin synthesis. It is believed that excessive quantities of Type I eoprop o r p h y r i n result f r o m an increase in rate of hemoglobin synthesis whereas accumulation and excretion of Type I I I t e n d to occur a f t e r interference with the synthesis of heine2 5 Meeonium and meconium-stained amniotic fluid usually show no fluorescence u n d e r the W o o d ' s lamp.

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However, two specimens of meconium did show a dull red-orange fluorescence directly. Qualitative tests for porphyrin were strongly positive in these instances. One of the infants had severe hemolytic disease (Rh) and one had polyeythemia with a hemoglobin level of twenty-four grams at birth. Subsequently, specimens of meeonium, meeonium-stained amniotic fluids, normal amniotic fluids, and vernix were extracted quantitatively for porphyrin content and separated by means of paper chromatography according" to the method of Rappaport and associates *~ (Table II). The only porphyrin compounds identified TABLE I I .

OF PEDIATRICS

per cent. When corrected for blood incompatibility, high intestinal obstruction, and breech delivery, the incidence was 9.6 per cent. 2. Meeonium staining of the amniotie fluid is associated primarily with the delivery of infants of term weight (96.4 per cent). 3. The neonatal mortality rate was 3.4 per cent and the neonatal morbidity rate 22.8 per cent, as compared with a neonatal mortality rate of 1.5 per cent and a morbidity rate of 6.1 per cent in the control group. 4. The time required for minimal nail staining to appear after exposure of the infants' nails to meeoniumstained amniotie fluid is four to six

T t t E CONCENTRATION OF COPROPORPI~YRIN ]: AND ~[I~ IN ~V~ECONIUMt 2~MNIOTIC FLUID, AND VERNIX NUIVfBER SA1V[PLES

Meconium Meconium-stained amniotic fluid Normal amniotic fluids Yellow vernix Normal vernix

5

COPOPOI~PtIYRIN I (#G/ML. OR GRA1V[) AVERAGE [ RANGE 89 23-141

5 3 3 2

in meeonium and meconium-stained amniotic fluids were eoproporphyrin I and III. These, however, were found in amounts greater than those previously reported in the literature. lr Coproporphyrin I and I I I may not be the only fluorescent pigments present in these fluids, however, since in some specimens fluorescence was present up to but not following esterifleation with methanol hydrochloride. CONCLUSIONS

1. The incidence of meconium staining of the amniotic fluid in a series of 3,967 consecutive deliveries in a charity hospital was found to be 10.9

2.7

t.4-3.7 Traces Traces None

..

COPROFORPHYRIN III (#G/ML. OR GRAM ) AVERAGE [ RANGE 101 26-192 2.2

0.9-3.6 Traces Traces None

hours. A longer period, twelve to fourteen hours, is required for staining of the vernix easeosa. 5. Infants exposed to meeonium or meconium-stained amniotic fluid show a dull orange-red fluorescence under the Wood's ultraviolet lamp. This procedure may be of help in the recognition of these infants. The color produced may be due to the presence in meeonium of coproporphyrin I and III which has penetrated nails and skin. This color must be differentiated from the glowing yellow-green fluorescence found on the infant's nails, cord, and skin after the mother has undergone recent therapy with

DESMOND ET AL. : 1V[ECONIU1V[ STAINING OF NEWBORN INFANTS vitamin B complex or the tetracycline group of antibiotics. 6. T h e p i g m e n t s t a i n i n g t h e n a i l s and vernix may be bilirubin. We wish to thank the nurses, residents, and interns who cooperated in this study and made it possible. The authors express appreciation to Dr. J. Gust, Dr. D. Rappaport, and Mrs. Catherine Calvert for the use of their facilities and for assistance with the porphyrin determinations. REFERENCES 1. Eastman, N. J.: Obstetrics, ed. 10, New York, 1950, Appleton-Century-Crofts, pp. 985-990. 2. Clifford, S. It.: Clinical Significance of Yellow Staining of the Yernix Caseosa, Skin, Nails, and Umbilical Cord, Am. J. Dis. Child. 69: 327, 1945. 3. Taylor, W. C., /[ames, J. A., and Henderson, ft. L.: The Significance of YeI]ow Vernix in the Newborn, Arch. Dis. Childhood 29: 442, 1952. 4. Walker, J.: Foetal Anoxia, J. Obst. & Gynaec. Brit. Emp. 61: 162, 1954. 5. Van Liere, E. 5.: Anoxia; Its Effect on the Body, Chicago, 1942, The University of Chicago Press, pp. 159-189. 6. Schultze, M.: The Significance of the Passage of Meconium During Labor, Am. /L Obst. & Gynec. 10: 83, 1925.

549

7. McCall, J. O., and Fulsher, i% W.: A Study of F e t a l Distress: Its Interpretation and Significance, Am. J. Obst. & Gynec. 65: 1006, 1953. 8. Wbite~ V. T.: The Significance and Management of Meconium in the Liquor Amnii During Labor, M. J. Australia 1: 641, 1955. 9. Smith, C. A.: The Physlo]ogy of the Newborn Infant, ed. 2, Springfield, Ii1., Charles C Thomas, Publisher, p. 193. 10. Rapoport, S., and Buchanan, D. J.: The Composition of Meconlum; The Isolation of Blood Group Specific Polysaccharldes, Science 112: 150, 1950. 11. Cantarow, A , and Schepartz, B.: Biochemistry, Philadelphia, 1954, W. B. Saunders Company, pp. 107-124. 12. Lemberg, 1%, and Legge, J. W.: tIematin Compounds and Bile Pigments, New York~ 1949, Interseience Publishers, Inc. 13. Stenhagen, E., and Rid]eal, E. V.: The Interactions Between Porphyrlns and Lipoid and Protein Monolayers, Biochem. ft. 33: 1591, 1939. 14. Needham, J.: Biochemistry and !Vforphogenesis, London, 1942, Cambridge University Press, p. 644. 15. Lemberg, R., and Legge, 5. W.: ibld, p. 593. 16. Rappaport, D. A., Calvert, C. R., Loeffier, R. K., and Gast, 3. I-I.: The Chromatographic Separation and Determination of Porphyrin Methyl Esters, Analytic Chem. 27: 820, 1955. 17. Lemberg, R., and Legge, J. W.: ibld, p. 588.

Sudden Deaths in I n f a n c y

Oct. 31, 1740. A daughter of Thomas Dibble J r aged about 2 months--just about an hour before it was left in bed as we]l to appearance as ever but lying still when they went to look at it found it dead--since, I was told it was well in the evening and when the mother got up, she laid it on her arms thinking it was asleep & about an hour after found it dead & stiff probably died in the night. March 7, 1741. A Son of Jonathan Conkling aged about 6 weeks died in the night by her mother---not knowing when it died. DEATI~I EEC0gDS Of Easthampton, New York.