Fetal and Neonatal Disorders

Visit the link below to download the full version of this book:

https://medipdf.com/product/fetal-and-neonatal-disorders/

Click Download Now

 This treatise is dedicated to
the many research trainees, fellows, associates, and collaborators,
whose devotion to science and concern
for the care of the patient
provided the stimulus for this work.
 List of Contributors

N u m b e r s in p a r e n t h e s e s i n d i c a t e the p a g e o n w h i c h the authors' contributions begin.

ARTHUR J . A M M A N N , D e p a r t m e n t of Pediatrics, University of California,

San Francisco Medical Center, San Francisco, California ( 3 0 5 )
NICHOLAS S. ASSALI, D e p a r t m e n t of Obstetrics and Gynecology, School of
Medicine, T h e Center for the H e a l t h Sciences, University of Cali-
fornia, Los Angeles, California ( 1 , 1 5 3 )
MARY E L L E N AVERY, D e p a r t m e n t of Pediatrics, F a c u l t y of Medicine,
McGill University, Montreal, C a n a d a ( 7 3 )
C. T. BARRETT, D e p a r t m e n t of Pediatrics, School of Medicine, T h e Center
for the H e a l t h Sciences, University of California, Los Angeles,
California ( 1 5 3 )
J . C. D E H A V E N , T h e R a n d Corporation, Santa Monica, California ( 1 5 3 )
SAMUEL KAPLAN, University of Cincinnati, College of Medicine, and
Children's Hospital, Cincinnati, Ohio ( 1 )
SOLOMON A. KAPLAN, D e p a r t m e n t of Pediatrics, School of Medicine, T h e
Center for the H e a l t h Sciences, University of California, Los Angeles,
California ( 1 0 5 )
LAWRENCE M . GARTNER, D e p a r t m e n t of Pediatrics, Albert Einstein Col-
lege of Medicine, of Yeshiva University, T h e Bronx, New York ( 4 5 5 )

xi
xii LIST OF CONTRIBUTORS

M E L V I N HOLLANDER, D e p a r t m e n t of Pediatrics, F o r d h a m Hospital, Miseri-

cordia-Fordham, T h e Bronx, New York (455)

ROBERT C. NEERHOUT, D e p a r t m e n t of Pediatrics, School of Medicine, T h e

Center for the H e a l t h Sciences, University of California, Los Angeles,
California (335)

P H I L L I P STURGEON, D e p a r t m e n t of Pediatrics, School of Medicine, T h e

Center for the H e a l t h Sciences, University of California, Los Angeles,
California (335)

PAOLA S. TIMIRAS, D e p a r t m e n t s of Physiology and Anatomy, University

of California, Berkeley, California (233)

ANTONIA VERNADAKIS, D e p a r t m e n t s of Psychiatry and Pharmacology,

University of Colorado Medical Center, Denver, Colorado (233)
 Preface

This third volume of the treatise on "Pathophysiology of Gestation"

deals with the mechanisms underlying the disorders t h a t affect the fetus
and t h e neonate, particularly those occurring in the early neonatal period.
I n the critical period following birth, the physiological functions of infants
undergo marked transitional changes which serve to a d a p t every system
of the body to the external environment. When these transitional changes
are judged by either fetal or adult standards, they m a y often appear
somewhat pathological. Yet, when analyzed properly in the light of the
knowledge t h a t has been gathered during the last decade regarding fetal
life in utero and the effects of birth, these transitional changes appear
mere physiological adjustment processes to extrauterine life. Therefore,
it is during this period t h a t the t a s k of differentiating between w h a t m a y
be considered a normal physiological process and w h a t m a y represent a
pathological disorder of the neonate often becomes difficult. T h e principal
object of this volume is to ferret these difficulties.
I n the various chapters included in this volume, be it t h a t dealing with
the circulation or water and electrolytes or hematopoiesis, the reader will
first find summarized in a lucid manner the various physiological processes
which assist the fetal organism to adjust to the intrauterine environment.
This is followed by an analysis of the pathophysiological alterations
underlying the disorders t h a t m a y occur during fetal life. T h e normal
physiological changes in each system t h a t occur immediately after clamp-

xiii
xiv PREFACE

ing of the umbilical cord and initiation of breathing are then described
with an eye on pinpointing as to how they differ from both the fetal and
adult standards. Finally, the pathophysiological mechanisms t h a t m a y
t a k e part in generating the various disorders of the neonate are explained
and the general principles of their management are outlined.

NICHOLAS S. ASSALI
 Contents of Other Volumes

Volume I Maternal Disorders

Disorders of Ovulation
Guy E. Abraham, John R. Marshall, and Thomas A. Daane

Disorders of Gamete T r a n s p o r t and I m p l a n t a t i o n

Robert W. Noyes

Disorders of Uterine Functions during Pregnancy, Labor, and Puerpe

Helmuth Vorherr

Disorders of M a t e r n a l Circulatory and Respiratory Adjustments

N. S. Assali and C. R. Brinkman III

Disorders of the Kidney, Fluids, and Electrolytes

Leon C. Chesley

Disorders of the Liver in Pregnancy

Burton Combes and Reuben H. Adams

Disorders of Lactation and the M a m m a r y Gland

M. Reynolds

Author Index—Subject Index

xv
xvi CONTENTS OF OTHER VOLUMES

Volume II Fetal-Placental Disorders

Disorders of Placental Tranfser

Lawrence D. Longo

Disorders of Placental Endocrine Functions

H. H. Simmer

Disorders of Amniotic Fluid

A. W. Liley

Genetic Disorders Affecting Growth and Development

Robert S. Sparkes and Barbara F. Crandall

Environmental Effects on Development—Teratology

James G. Wilson

Author Index—Subject Index

 Ill

Disorders of Circulation

Samuel Kaplan and Nicholas S. Assali

I. I n t r o d u c t i o n 1
II. Fetal Circulation at Term 3
A . D y n a m i c s of F e t a l a n d N e o n a t a l C i r c u l a t i o n 6
B . C o n t r o l of t h e S y s t e m i c a n d P u l m o n a r y V a s c u l a r
Resistances in t h e Fetal and Early Neonatal Period 10
I I I . D i s o r d e r s of F e t a l C i r c u l a t o r y F u n c t i o n s 18
A . A b n o r m a l i t i e s in F e t a l H e a r t R a t e 18
B . Effects of V a s o a c t i v e D r u g s o n t h e F e t u s 23
IV. Isolated Ventricular Septal Defect 25
V . A o r t i c Runoff 28
A . P a t e n t D u c t u s Arteriosus 28
B . Arteriovenous Fistulae 30
V I . Atrial S e p t a l D e f e c t 31
V I I . T r a n s p o s i t i o n of t h e G r e a t Arteries 32
VIII. Ductal Dependence 34
A . H y p o p l a s t i c Left H e a r t S y n d r o m e 35
B. The Coarctation Syndrome 39
C. O b s t r u c t i o n t o R i g h t V e n t r i c u l a r Outflow 43
I X . Valvular Disease 45
A. Pulmonic Stenosis 45
B. Pulmonary Valve Incompetence 47
C. A o r t i c S t e n o s i s 48
D . Tricuspid Valve Disease 48
E. Ebstein's Malformation 49

1
2 SAMUEL KAPLAN AND NICHOLAS S. ASSALI

F . I s o l a t e d F r e e W a l l H y p o p l a s i a of t h e R i g h t V e n t r i c l e
(Uhl's Anomaly) 49
G. C o n g e n i t a l T r i c u s p i d Insufficiency 50
H. Mitral Incompetence 50
X. Pulmonary Venous Hypertension 51
XI. Myocardial Diseases 52
A. Myocarditis 52
B . Endocardial Fibroelastosis 53
C. C a r d i o m y o p a t h y 53
D . Glycogen Storage Disease 54
E. Hyperthyroidism 54
F. Hypothyroidism 54
XII. Arrhythmias 54
A. Supraventricular Tachycardia 55
B. Congenital Complete Heart Block 56
XIII. M e t a b o l i c Effects of C o n g e s t i v e H e a r t F a i l u r e a n d
Hypoxemia 56
A. A c i d - B a s e a n d B l o o d G a s e s 56
B. Hypoglycemia 57
C. H y p o x e m i a 57
XIV. Cardiorespiratory S y m p t o m s w i t h o u t Congenital
Cardiovascular Disease 58
A. Persistent Pulmonary Vascular Obstruction 58
B. Neonatal Polycythemia 59
C. H y p o g l y c e m i a 61
D . T h e C i r c u l a t i o n in B i r t h A s p h y x i a a n d in I n t r a c r a n i a l
Disease 61
E . H e m o l y t i c Disease and t h e Circulation 64
X V . Concluding Remarks 64
References 65

I. Introduction

A striking increase has occurred during the last decade in our knowl-
edge of the fetal circulation and the changes t h a t occur at birth. T h e
development of new investigative techniques has permitted early detec-
tion of fetal cardiac a r r h y t h m i a s and has shed light on the various
factors t h a t control the pulmonary and systemic circulation in the fetal
and neonatal periods. Among the various circulatory aspects t h a t have
been clarified are such important functions as the cardiac output and
its relative distribution, the control of the systemic and pulmonary
vasomotor tones particularly with respect to the role played by the
 1. DISORDERS OF CffiCULATION 3

respiratory gases and the placenta, the dynamics of ductus arteriosus

circulation and the mechanisms of its closure, etc.
T h e availability of this wealth of information regarding the behavior
of the fetal and neonatal cardiovascular system in the normal condition
has provided a good background for understanding the pathophysiology
of m a n y of the perinatal circulatory disorders.
Perinatal heart diseases encompass a wide variety of altered hemo-
dynamic states, some of which m a y begin long before birth and m a y
exert their influences in utero. In others, these abnormal states m a y
only become manifest during the transitional and dynamically changing
situation in the immediate neonatal period when the circulation a d a p t s
to extrauterine life. At this time, d r a m a t i c changes occur because gas
exchange is transferred from the placenta to the infant's lung.
This review begins with a brief survey of the various factors t h a t
control the systemic and pulmonary circulation before and after birth.
T h e survey will then be used to pinpoint the various hemodynamic a b -
normalities t h a t underlie the various cardiovascular disorders t h a t affect
the fetus and the neonate.

II. Fetal Circulation at Term

Information concerning the fetal circulation near t e r m has been

derived primarily from lambs and probably can be applied to man.
Angiographic studies by B a r c l a y et al. (22) and later by Lind and
Wegelius (107) demonstrated the p a t t e r n of venous return to the fetal
heart, the intracardiac blood flow, and the course of the blood ejected
from the heart. Q u a n t i t a t i v e studies of flows, pressures and resistances
have been made by m a n y investigators (9, 11, 15-17, 49, 155, 156).
T h e pertinent information regarding the anatomical characteristics
of the fetal circulation is illustrated in Fig. 1 ; the p a t h w a y s followed
by the blood in the fetal and early neonatal periods are schematically
represented in the diagrams of Figs. 2 and 3 . T h e morphology of the
fetal circulation m a y be summarized as follows: Umbilical venous blood
which returns from the placenta, flows a t an average of about 1 7 5 m l / k g
-1
m i n and at a pressure of about 1 2 m m H g (9). This blood is relatively
well oxygenated with a saturation of almost 8 5 % and a P02 of about
3 0 m m Hg. About one-half of the umbilical venous blood bypasses the
hepatic circulation and flows through the ductus venosus to the inferior
vena cava (Fig. 1 ) . Although this oxygenated blood becomes mixed with
other blood returning from the caudal p a r t of the body through the
4 SAMUEL KAPLAN AND NICHOLAS S. ASSALI

F I G 1. A n a t o m y of the circulatory s y s t e m in the fetal l a m b .

inferior vena cava, it is still relatively more oxygenated t h a n the other

blood columns entering the right heart. T h e blood from the inferior
vena cava passes to the left atrium after traversing the foramen ovale;
it then flows into the left ventricle and is ejected into the ascending
aorta. T h u s the coronary, cerebral and upper extremity arteries are
perfused with blood having a higher P02 t h a n t h a t perfusing other p a r t s
of the body except the liver. On the other hand, the superior caval
blood which is considerably less oxygenated t h a n the inferior vena cava
 1. DISORDERS OF CIRCULATION 5

HEAD AND
UPPER TRUNK

AORTA

£3
HEAD AND
UPPER TRUNK
PA*

LUNGS AORTA

SVC
il
I VC
\+UV
UA
H PLACENTA 1
LUNGS

ABDOMINAL ABDOMINAL
VISCERA AND VISCERA AND
LOWER TRUNK LOWER TRUNK

FIGS. 2 and 3 . D i a g r a m s of the circulation in t h e normal fetus and in the

transitional period s o o n after birth.
FIG. 2 (left). I n the fetus a large fraction of the umbilical v e n o u s b l o o d enters
the d u c t u s v e n o s u s ( D V ) a n d b y p a s s e s the liver. T h i s r e l a t i v e l y well o x y g e n a t e d
b l o o d flows across t h e f o r a m e n o v a l e t o the left heart, which preferentially perfuses
the h e a d a n d upper trunk. Superior v e n a caval b l o o d ( S V C ) is e j e c t e d b y t h e
right heart i n t o t h e p u l m o n a r y artery ( P A ) and d u c t u s arteriosus. T h i s flows
t o the p l a c e n t a as well as t o the a b d o m i n a l viscera a n d lower trunk. Interrupted
lines indicate a l o w p u l m o n a r y b l o o d flow a n d t h a t flow from ascending aorta
across the aortic i s t h m u s is also diminished.
FIG. 3 (right). I n the transitional n e o n a t a l period, placental flow is obliterated
and p u l m o n a r y b l o o d flow is greatly increased. P o t e n t i a l bidirectional s h u n t i n g
m a y occur across t h e d u c t u s arteriosus or right to left s h u n t i n g across the foramen
o v a l e . D V = d u c t u s v e n o s u s ; I V C = inferior v e n a c a v a ; S V C = superior v e n a c a v a ;
R A = right a t r i u m ; L A = left a t r i u m ; R V = right v e n t r i c l e ; L V = left v e n t r i c l e ;
P A = p u l m o n a r y artery; D A = d u c t u s arteriosus.

blood traverses the tricuspid valve and flows primarily to the right
ventricle and pulmonary artery (Figs. 2 and 3 ) . Only a negligible portion
of the superior caval blood crosses the foramen ovale to the left atrium.
About 6 5 % of the blood ejected by the right ventricle into the main
pulmonary artery bypasses the lungs and is shunted across the ductus
6 SAMUEL KAPLAN AND NICHOLAS S. ASSALI

TABLE I
a
Data on Blood Flows in the Fetal and Neonatal Conditions, and in the Adult at Rest

Site Fetal Neonatal Adult

P u l m o n a r y a r t e r y (right v e n t r i c u l a r o u t p u t ) 148 150 70

6
A s c e n d i n g a o r t a (left v e n t r i c u l a r o u t p u t ) 110 140 70
D u c t u s arteriosus 108 0
T o t a l cardiac o u t p u t ( a s c e n d i n g a o r t a +
d u c t u s flow) 220 130 70
Foramen ovale 60 0 0
U m b i l i c a l v e i n flow 170
C
TSR d 28 50
TPR 150 19

° F i g u r e s are t h e a v e r a g e of v a r i o u s series a n d are e x p r e s s e d in milliliters per k i l o -

g r a m , per m i n u t e .
6
A s c e n d i n g aortic flow d o e s n o t i n c l u d e c o r o n a r y flow.
c
T S R = t o t a l s y s t e m i c resistance.
d
T R P = t o t a l p u l m o n a r y resistance.

arteriosus into the descending a o r t a ; the remaining portion goes to the

lung (9, 17, 49). Hence, the blood in the descending aorta has a P 0 2
of about 19-22 m m H g . T h e combined blood flow of the ductus arteriosus
and the left ventricular output constitute the total amount of blood
distributed by the fetal heart to organs and tissues, and has been termed
the fetal effective cardiac output (9) ; it amounts to about 220 m l / k g
-1
min (Table I ) . Approximately 6 5 % of this total output returns to
the placenta via the umbilical arteries; the remaining 3 5 % is distributed
to the various organs and regions of the fetal body (9, 49).

A. Dynamics of Fetal and Neonatal Circulation

A number of studies have shown t h a t the salient hemodynamic differ-

ences between the fetal and the adult circulation are as follows {9,
15-17, 27, 37, 38, 49, 155) :
1. I n the fetus, the pulmonary vascular resistance is considerably
higher t h a n the systemic vascular resistance. N e t pulmonary blood flow,
estimated from the algebraic difference between main pulmonary artery
and ductus flows, is very reduced. Immediately after lung expansion
and umbilical cord clamping, pulmonary vascular resistance falls precipi-
tously, while systemic vascular resistance rises. N e t pulmonary flow in-
creases five- to sixfold because all of the right ventricular output supple-
mented by whatever blood is still flowing through the p a t e n t ductus
 1. DISORDERS OF CmCULATION 7

now goes to the lung. T a b l e I compares fetal, neonatal, and adult values
for the various blood flows and for the pulmonary and systemic vascular
resistances.
2. Because of the higher pulmonary vascular resistance, mean pres-
sures in the pulmonary artery and right ventricle are higher t h a n those
in the aorta and left ventricle (Table I ; Fig. 4 ) . This pressure gradient
during intrauterine life drives the blood flow in the ductus arteriosus
from right to left. Also, probably because of the elevated pulmonary
vascular pressure and resistance, the right ventricle of the fetus is more
prominent in terms of work and thickness t h a n the left ventricle.
Immediately after lung expansion and cord clamping, pulmonary
artery and right ventricular pressures fall progressively while aortic and
left ventricular pressures rise promptly (Table I ; Fig. 4 ) . Because of
the reversal in the pressure gradient, ductus arteriosus blood flow changes
direction and becomes left to right. Also, because of the reduction in
pulmonary vascular resistance, the right ventricle begins to lose its
dominance and its walls become progressively thinner. I n contrast, the
left ventricle begins to gain functional dominance and slowly becomes
thicker and thicker.
3. T h e effective cardiac output of the fetus (estimated from the alge-
braic sum of left ventricular output and ductus flow) is three times
as high as t h a t of the adult per kilogram of body weight (Table I ) .
This high output is brought about by the presence of the ductus arteri-
osus which diverts about 6 5 % of the right ventricular output toward
the systemic circulation.
After lung expansion and cord clamping effective cardiac output falls
for two reasons {9, 15-17). T h e first reason is related to the change
in ductus flow direction which becomes from left to right. This change
diverts some blood from the aorta toward the pulmonary vascular bed.
When the ductus eventually closes, the two ventricles begin working
in series and the output of one becomes equal to t h a t of the other.
T h e second factor responsible for the decrease in the effective cardiac
output is the rise in the systemic vascular resistance subsequent to the
elimination of the low resistance system of the placental circulation.
I t is clear from the description of these hemodynamic characteristics
t h a t the ductus arteriosus circulation influences a great deal the magni-
tude of the blood flow destined to the systemic circulation including
the placenta and t h a t going to the lungs in both the fetal and in the
early neonatal periods. T h e factors t h a t control the blood flow through
the ductus arteriosus are somewhat complex (9, 17, 120). T h e y include:
(1) the pressure gradient between the p u l m o n a r y and systemic circuits;
(2) the magnitude of the right ventricular o u t p u t ; (3) the degree of
 8

4
1

-i
ck
LEFT VIENTRIC
PRESSURE

1 1 1

r-tf)cm
11

ce
AORTIC PRESS

Κ Α cm
1 1
mm Hg

ο m o mo<oq m ο
1

<

—J
I*
Lü

2£l
c
C L E
ig ε
fei*
S uj
FIG. 4. Pattern of pressure changes in the four heart chambers and in the pulmonary and systemic circulation before and after
SAMUEL KAPLAN AND NICHOLAS S. ASSALI

lung expansion and cord clamping. After lung ventilation, right ventricular and pulmonary artery pressures fall precipitously.
Left ventricular and aortic pressures initially fall because of the change in the direction of ductus bloodflow;these pressures
increase thereafter particularly after cord clamping. The increase in systemic pressure after elimination of the placenta occurred
despite high blood oxygenation. Both atrial pressures increase, but the increment in the left is greater than that in the right
(From N. S. Assali, ed., "Biology of Gestation," Vol. II. Academic Press, New York, 1968.)