Richard E. Scammon

The prenatal growth and natal involution of the human suprarenal gland.

Two organs of the human body undergo a remarkable reduction in size following birth, these are the uterus and the suprarenal glands. The neonatal loss in mass of the suprarenals seems to have been first noted by Scheel. 1 It is due in great part, if not entirely, to a degeneration of the inner and middle layers of the cortex. This process was first described by Starkel and Wegrzynowski 2 and, shortly after, independently by Thomas, 3 Kern, 4 and Armour and Elliott. 5 It has been pointed out that the neonatal loss in size of the uterus is preceded by a period of marked growth of this viscus in the latter part of fetal life, and that this neonatal involution reduces the organ to essentially the dimensions which would have obtained had the early fetal growth rate remained unchanged. Since the suprarenals undergo a neonatal involution which is concomitant with that of the uterus, it seems desirable to determine whether they also show a period of increased growth in the latter part of prenatal life. The present study is based on observations on the weights of 1087 pairs of suprarenal glands; 425 of fetuses, 338 of newborn infants, stillborn or dying within 2 days after birth, and 324 of children over 2 days and under 1 year of age. The course of growth of these structures is shown in the accompanying figure in which the suprarenal weight is plotted against the total body weight (as indicated on the base line scale) and the computed prenatal age and observed postnatal age, as indicated on the upper boundary line of the graph. The observations on fetal material indicate that the growth of the suprarenals before birth is proportional to the growth in body-weight for the relation between these weights is approximately rectilinear throughout the fetal period.

A study of the ossification centers of the wrist, knee and ankle at birth, with particular reference to the physical development and maturity of the newborn

Abstract 1.1. The inferior femoral epiphysis, judging from all available data, is present in about 1 case in 20 in the eighth fetal month, in 1 case in 3 in the ninth month, in 6 cases in 7 in the tenth month, and in about 19 cases in 20 at birth (full-term infants). If not present at birth, the center appears before the close of the first postnatal month. In our own series the center was present in 98 per cent of all newborn children. 2.2. The superior tibial epiphysis, judging from all available material, is almost never present before the ninth fetal month. It is found in 1 case in 17 in the ninth month, about 2 cases in 5 in the tenth month and in about seven-eights of all full-term newborn children. It was present in 81 per cent of the cases in our series. 3.3. The cuboid, according to all available data, first appears at about the beginning of the ninth fetal month. It is present, on the average, in about 1 case in 25 in the ninth month, in about 1 case in 4 in the tenth month, and in about 3 cases in 5 in full-term newborn children. In our own series the center was present in a much smaller per cent of all cases than is reported by other investigators (38 per cent). 4.4. Two carpal ossification centers, those of the os capitatum (os magnum) and of the os hamatum (unciform), may be present in the newborn. In our series the os capitatum was present in 15 per cent and the os hamatum in 9 per cent of all cases. 5.5. There is a close relation between total body-length and frequency of ossification of the several centers discussed in this paper. A similar, but less close, correlation exists between frequency of ossification and the body-weight. 6.6. In our material the correlation of body-weight, total body-length and frequency of ossification with menstrual age was quite close for the middle members of the series ranging in menstrual age from 270 to 300 days. But the outlying cases (having a menstrual age of less than 270 or more than 300 days) show little relation between these measures of bodily development and age as determined from the menstrual history. 7.7. Our evidence points to the conclusion that ossification proceeds slightly more rapidly in females than in males during intrauterine life even though the weight and dimensions of the females are less than those of the males. 8.8. Our observations show no direct evidence of any relation between parity and the rate of ossification in intrauterine life. 9.9. Variations in the number of ossification centers present for individual bones were limited to the os capitatum and os cuboideum. The latter is formed from an extremely variable number of centers. When anomalies in the number of centers are present they are often asymmetrical. 10.10. Variations in the order of appearance of centers were decidedly unusual in our material, being confined to premature ossification of the os cuboideum (2 cases) and of the premature ossification os capitatum (2 cases). 11.11. The usual order of appearance of the centers under consideration is as follows: (a) Inferior femoral epiphysis; (b) Superior tibial epiphysis; (c) Cuboid; (d) Os capitatum; (e) Os hamatum.

Simple empirical formulae for expressing the lineal growth of the human fetus

In the quantitative study of the growth of the human body there is often need for simple and accurate formulæ for expressing the relation between body-length and prenatal age. Empirical formulæ for lineal growth in the fetal period (3 lunar months to birth) have been published by Hassee 1 , Henry and Bastien 2 , and Scammorn 3 . No one of these is entirely satisfactory, for the first gives results which are not in accord with modern findings regarding prenatal lineal growth, the second is highly complicated, and the third is primarily for use in estimating the length from the age, whereas one usually desires to determine the age from the length. Practicable formulæ of this kind should fulfill the following conditions: (a) They should express age in terms of body-length for the entire fetal period (3 months to birth). (b) They should give a close fit to reliable data on the subject. (c) They should be in simple form, which will permit their application with ordinary arithmetic without the use of tables of special functions and the like. With these conditions in mind the following formulæ have been developed on the basis of the data of Mall 4 . When Malls observations are placed in graphic form they approximate a parabola having the general form: T = a + bL + cL2, where T is the age in fetal or lunar months (calculated from the first day of the last menstruation), L is the total or crown-heel length in cm., and a, b and c are constants. The specific formula for expressing this relations is: This may be simplified to: For estimating the crown-heel length from the age, the formula may be transformed into : These formulæ may also be modified for further use. According to Mall, the cohabitation age averages 10 clays less than the menstrual age which is estimated from the first day of the last menstruation, and the individual deviations from this average are quite small. Therefore, the formula for menstrual age may be modified to to express the cohabitation age.

Empirical formulae for the postnatal growth of the human brain and its major divisions

Although several graphs have been published illustrating the post-natal growth of the human brain, as well as a few of the growth of the major divisions of the structure, apparently no attempt has been made to analyze these curves and to develop formulæ for the expression of the relation between brain weight and age between birth and maturity. We have made a series of calculations of this type and have computed empirical formulæ for the growth of the encephalon as a whole, the cerebrum, the cerebellum, and the pons, medulla and mid brain, from birth to 20 years. These formulæ have been determined from the weighted average of male and female brain weights. While it will no doubt be possible to develop slight varients of these formulæ for the weight of the entire brain and of the cerebrum for males and females separately, our data indicate that it is hardly practicable to establish separate curves for the sexes, on the basis of the material now available, for the weight of the cerebellum and the brain stem. Likewise no attempt has been made to correct graphically or mathematically for the effect of disease on the weight of the brain although all records of cases involving any brain pathology were rigidly excluded. The curves and formulæ, therefore, represent the growth of the organ in a hospital rather than in the general population. When plotted against age and tested graphically all the curves of the postnatal growth of the brain approach hyperbolae and may be expressed approximately by the general formulae: In these formulae, Y is the weight of the brain or brain-part, X is the age in years and a, b and c are empirically determined constants.

The Regional Growth in Surface Area of the Human Body in Prenatal Life

The surface areas of the chief regions of the body were determined for 12 fetuses ranging from 3.27 to 47.22 cm. in total or crown heel length and from 1.26 to 2463.0 gm. in weight. The details of the material and method employed are described in a preceding paper. The regions delimitated were head, neck and trunk (including the perineal region and the penis and scrotum in the males), the upper extremities (both sides), and the lower extremities (both sides including gluteal regions). From geometrical considerations, that were found to be applicable to measurements of the surface area of the body as a whole, it was thought that an adequate expression for representing the relation of the surface area of a part to body length might be: Sp = aLb, or, log Sp = log a + log L·b where Sp is the area of the part in question, L is the total or crown heel length of the body and b is an exponent approaching 2. Graphic tests on double logarithmic paper indicated that this surmise was justified. When fitted by the method of averages the following expressions were obtained: Sh =0.1767L1,997 (1) St = 0.1191L2,207 (2) Su = 0.0244L2,449 (3) S1 = 0.0216L2,632 (4) where Sh is the area of the head St is the area of the trunk, Su is the area of the upper extremities and S1 is the area of the lower extremities. The mean absolute deviation of the observed from the calculated values by formula (1) is 12.2 sq. cm. and the mean relative deviation is 9.9%. Omitting the first observation, (on a specimen 3.27 cm. in length) the mean relative deviation is 8.4%. The mean deviation (taken without regard to sign) of the observed from the calculated values given by formula (2) is 21.0 sq. cm. and the mean relative deviation is 13.2%, or omitting the first observation, 12.8%. The mean absolute deviation (taken without regard to sign) of the observed from calculated values by formula (3) is 12.1 sq. cm. and the mean relative deviation is 12.2%, or omitting the first observation, 11.0%.

The prenatal growth and natal involution of the human uterus.

The human uterus undergoes a marked reduction in length and weight in the first few weeks following birth. This was first described by Lyubetski, 1 and later, independently, by Bayer 2 and by Conte. 3 This reduction takes place through hypoplasia and hypotrophy of the uterine muscle, together with a disappearance of the marked natal hyperemia of the organ. It is supposed to be caused by the withdrawal at birth of a hormone produced by the placenta, the ovary or the tissues of both of these structures, (Aschner, 4 Herrmann, 5 Fellner, 6 , 7 Frank, 8 , 9 and others.) Little is known of the fetal growth of the uterus which precedes this natal reduction. The present study is based upon a total of 207 observations on the length of the uterus, 89 of fetal uteri, 62 of uteri of infants stillborn or dying within 48 hours after birth, and 56 uteri of children over 2 days and under 1 year of age. A graphic analysis of this material is shown in the accompanying figure, in which the mean uterus length for 5 cm. intervals of total or crown-heel body-length, is plotted against the total body-length (as indicated on the base-line scale), and the computed age, (as indicated on the upper scale of the graph). Starting with an average length of about 2.5 mm. in the 5 to 10 cm. interval of crown-heel length, the viscus grows at a slow and fairly constant absolute rate, with respect to the total body-length, until approximately 7 lunar months (about 35 cm. crown-heel length). At this stage the average length of the uterus is approximately 17 mm.

The Prenatal Growth of the Human Thymus.

The weight of the human thymus in the fetal period is characterized by great variability. Therefore a large number of observations are necessary to demonstrate even the approximate course of prenatal growth of this organ. The ponderal growth of the thymus, with respect to body-weight, has been studied in a series of 1043 weighings of the organ from human fetuses under 4000 grams in total (dead) body weight. In no instances were observations made on fetuses living over 48 hours. As shown in Figure 1, the relation appears to be rectilinear. It may be approximated by the empirical formula: where “TW” is the weight of the thymus in grams and “BW” is the (dead) weight of the total body in grams. This formula was computed from the means of thymus-weight and of body-weight for the ten 400 gram intervals of body-weight from 0 to 4000 grams (weighting by the square root of the number of observations in each interval). The calculated values show a mean, weighted, absolute deviation of 0.248 grams from the observed averages. The mean, weighted, relative deviation is 6.03 per cent. This relative deviation lies mainly in the two lower weight-intervals, the mean, weighted, relative deviation for the upper eight intervals being 3.31 per cent. The relation of thymus-weight to body-length is shown in Fig. 2. As in the preceding series, in no instances were observations made on fetuses living over 48 hours. Two approximate, empirical expressions have been developed for this relationship, the first by using the mean thynius-weights and body-lengths for the 5 centimeter intervals of body-llength from 5 to 60 centimeters (based upon 1216 observations), and the second by using the means of thymus-weight and body-length for the 5 centimeter intervals from 5 to 55 centimeters (based upon 1152 observations).

Growth of Human Nervous System. I. Growth of Cerebral Surface

The interest in the extent and variability of the cortex of the human brain has led to a number of estimates of the surface area of the cerebrum (generally in the adult) by a variety of ingenious methods. 1 - 7 We have attempted to extend these studies by an experimental investigation of this area through a portion of the developmental period (from the fourth fetal or lunar month of prenatal life to 2 postnatal years) and in maturity. Our technique is described in detail in a forthcoming paper. 8 Briefly stated, the method consists of sectioning formalin fixed brains enclosed in a matrix with a mechanical device into slices 2 to 3.5 mm. in thickness. The area is then determined by measuring the outline of each section with a chartometer and multiplying the reading by the thickness of the section. The surface of the cerebrum is approximated by the sum of the values so obtained. Attempts to improve this technique by computing the sections as segments of cones and taking the means of their anterior and posterior outlines did not increase the accuracy of our determinations. Twenty cerebri were so studied. Figure 1 shows 10 of these drawn to scale (left lateral views) to illustrate the changes in size and form and in the configuration of the sulci in the series. In measuring these structures figures were obtained for both “total” and “free” surface. “Total” surface indicates the entire cerebral surface including that portion buried in all of the cerebral fissures regardless of their depth. “Free” surface is a term used for the visible or external surface of the cerebrum only. In determining this value the chartometer was passed around the periphery of each section but only dipped into the lips of the sulci to the shallow point where their sides meet.

Growth of Human Nervous System. II. Indices of Relation of Cerebral Volume to Surface in Developmental Period

The estimation of the area of the human cerebrum has become a matter of considerable interest since the mass of the cerebral cortex is closely related to the surface area of the brain. This subject has been investigated by a quantitative study of 20 brains ranging in age from the fourth (lunar) month of prenatal life to the close of the fifth decade and in volume from about 5 cc. to over 1000 cc. The method of measuring surface area is described in other papers 1 , 2 and the volume was determined by the displacement method. Various indices of the relation of cerebral volume to surface are shown in Table I and in Fig. 1. In both the table and the figure the observations are arranged in order of cerebral volume. Column (b) of the table and panel (A) of Fig. 1 show the index of “total” surface area divided by cerebral volume (surface in sq. cm., volume in cc.). The index drops slowly at first, until the cerebrum has a volume of nearly 100 cc. (in the eighth lunar month), and shows practically no regular trend of change thereafter. A better index is the “total” surface of the cerebrum divided by the two-thirds power of the cerebral volume, for this measure considers the factor of dimensionality. The index thus determined [Table I, column (d), Fig. 1, panel (B)] shows no prominent change until the cerebrum attains a volume of nearly 100 cc. (in the eighth fetal or lunar month) and rises abruptly to a new plateau at a period (just before birth) when there is relatively little increase in volume, and thereafter shows little significant change. There could hardly be a better demonstration of the great relative increase in cerebral surface area by fissuration in later fetal life.

Growth of Long-bones of Human Fetus as Illustrated by the Tibia.

The growth in length of the human tibia in the latter part of prenatal life has been studied quantitatively from observations, made chiefly by Corrado 1 and by Tamassia, 2 on a series of 152 fetuses. The data include the total body-length, the total length of the tibia, the length of the tibial diaphysis, and the combined lengths of the superior and inferior (cartilagenous) tibial epiphyses. Regression formulae have been computed for certain relationships between these values and are given, with other data, in Table I. Fig. 1 shows the distributions of these observations and their regressive lines. These formulae indicate that, in the period under consideration, the growth in length of the tibia and the lineal growth of its various parts are directly proportional to the growth in total or crown-heel length. The empirical formulae for the total length of the tibia and for the length of the tibial diaphysis, with respect to total body-length, are characterized by negative second constants, as are the various empirical formulae which have been developed for the external dimensions of the lower extremities (Calkins and Scammon 3 ). The empirical formulae for the epiphyses, on the other hand, show positive second constants. Therefore, while the lengths of the tibia as a whole and of its diaphysis are becoming relatively, as well as absolutely, greater, the epiphyses are becoming relatively shorter, although absolutely longer. Fig. 2 shows the calculated growth in length of the tibia and its several parts in the last trimester of prenatal life. The relation of the lengths of these structures to age, in fetal or lunar months, has been computed by the use of the empirical formula of Scammon and Calkins 4 for the relation between time and total body-length in the fetal period.