CONGENITAL
MALFORMATIONS
AND
OBSTETRICS
By M. Edward Davis, M.D., and Edith L. Potter, M.D.
Department of Obstetrics and Gynecology, The University of Chicago and the Chicago Lying-in Hospital
ADDRESS: (M.E.D.) 5841 Maryland Avenue, Chicago 37, Illinois.
719
T
HE PROBLEM of malformations in thehuman offspring has become of
increas-ing importance to the obstetrician. The
continued reduction in perinatal mortality
has focused increased attention on every
baby death. The atomic age has brought
with it new knowledge concerning
radi-ation and its possible role in genetic
muta-tions and fetal abnormalities. The present
philosophy of prenatal care is to consider
childbirth a normal, natural physiologic
phenomenon. Preparation for childbirth
in-cludes the education of parents concerning
the reproductive function and all it entails.
Their concern about the possible birth of
an abnormal baby must be combatted by
frank discussions that should be buttressed
by facts, which are often woefully lacking.
This contribution to the Conference on
Teratology will present clinical data
ac-cumulated in a maternity hospital over a
period of years. These data are of more
than casual interest. All of these
mal-formed babies have been autopsied by one
of the authors (E.L.P.) who has had a
special interest in teratology. The maternal
records have been studied and significant
facts catalogued. Some of the recent
pub-lications on this subject will be reviewed
and the problems from the obstetrician’s
point of view will be summarized.
There are generally no major problems
encountered during pregnancy or the
puer-perium that are a direct result of the
pres-ence of a malformed child in the uterus.
Two unusual conditions that may be
ob-served during pregnancy are the amount
of fetal movement perceived by the
expect-ant mother and the amount of amniotic
fluid present in the uterus. With amyotonia
congenita and arthrogryposis, for instance,
no movement may be discernible and with
achrondroplasia, sympodia and other
ab-normalities of bones or joints it may be less
than usual. The amount of amniotic fluid is
notoriously increased in association with
anencephalus; less well-known associations
are with abnormalities of the
gastrointesti-nal and genitourinary tracts. The amniotic
fluid is almost always increased in amount
when the duodenum or upper intestine is
atretic or stenotic and is absent or reduced
to a few milliliters when both kidneys are
absent.
Delivery of the infant may be impossible
in a few instances without operative
inter-ference. Gross hydrocephalus may require
evacuation of fluid before delivery of the
head can be accomplished. Fusion of twins
may require morcellation or delivery by
cesarean section. One variety of
omphalo-cole, in which the placenta makes up one
surface of the sac containing the abdominal
viscera, may be associated with bleeding
because of premature detachment of the
placenta. However, in most varieties of
mal-formations, no disturbances in labor or
de-livery are encountered.
The main problem facing the obstetrician
arises from the need to counsel parents who
have had a malformed child, and to answer
their questions concerning the cause of
such abnormalities and the probability of
repetition in subsequent pregnancies.
Many factors are implicated in the
causa-tion of human malformations, some of
which play a direct role and others
con-tribute indirectly. Laboratory experiments
provide much basic information concerning
the production of anomalies in the offspring
but such procedures cannot be duplicated
in the human. Thus we are forced to study
the clinical records of patients who give
birth to malformed babies in the hope that
this may yield clues to the possible cause
of such anomalies. Rarely, a key
observa-tion by an astute physician provides a
land-mark in our search for information.
The frequency with which malformations
are present in infants at birth is a figure
difficult to determine. In a special study1
Rofib pei’ /000 births
1935 36 37 38 39 40 41 42 43 44 15 46 47 48 49 50 51 52 53 54 55
YEAR3
For infants weighing over 2500 gm
mal-formations were the leading cause of death
given on death certificates, and accounted
for 24% of the deaths; for infants weighin
2500 gm or less malformations ranke
fourth and accounted for only 7%. The
num-ber of malformations in all figures based on
death certificates is probably too low,
be-cause of the low percentage of necropsies,
and the inability to diagnose many internal
anomalies without necropsy.
The incidence of fatal malformations has
remained fairly constant at the Chicago
Lying-in Hospital for the last 20 years. In
Table I it may be noted that the frequency
of perinatal deaths as a result of major
anomalies has varied from 4 to 6 per 1000
births. It is obvious that many infants with
malformations survive to leave the hospital
and are not included in these figures.
Hen-dricks2 reported the incidence of
malforma-tions as 7.4 per 1000 live births in a total of
210,727 live births in Ohio during 1953.
There is no statement as to how many of
the infants died. However, many
malforma-tions such as monogolism or cardiac
ab-normalities may not be recognized and
re-ported during the hospital stay of the
new-borns. Furthermore, it is difficult to obtain
a true picture of the frequency of minor
1952, all malformations diagnosed before
the infant left the hospital were tabulated.
In any statement concerning the frequency
of malformations in surviving children two
factors must be taken into account. These
are: (1) the experience of the physician
making the physical examination, the care
exercised in doing it and the completeness
with which observations are recorded, and
(2) the decision of the investigator as to
how much deviation from the average is
re-quired for a condition to be listed as a
mal-formation. Should mongolian spots, nevus
flainmeus, skin tags, inclusion cysts on the
hard palate, hydrocele, undescended testes,
craniotabes, false fontanelles and so on be
included as malformations? In order to
arrive at a figure approximating the 10%
frequency that is being currently bandied
about, many of these and other sirniliar
ab-normalities would have to be included.
In the study at the Chicago Lying-in
Hospital, mongolian spots, nevus flammeus,
palatal inclusion cysts and so on were not
included and, without these, 307 surviving
infants weighing over 2500 gm and 21
un-der 2500 gm were listed as having some
variety of developmental abnormality. If
craniotabes (30), cryptorchidism (45) and
hydrocele (43) were excluded the figure
was reduced to 210. Eight per cent of these
TABLE I
RATIO OF FerAL AND NEONATAL DEATHS FROM MALFORMATIONS TO TOTAL BIRTHS
CHICAGO LYING-IN HOSPITAL
Total Deliveries: 58,847
TABLE II
PERINATAL DEATHS DUE TO CONGENITAL MALFORMATIONS
CHICAGO LYING-IN HOSPITAL
JANUARY 1, 1941 TO JULY 1, 1955
Total Number Fatal Malformations: 240
* One case with no record of maternal age1
CONFERENCE ON TERATOLOGY
Maternal
0,98 (yr) CNS Cardiac GI
GU Skeletal
Multi-pie Major
Ompha-locete Diaph.
Hernia Tumors Pul-monary Totals
UnderQ0 7 2 3 1 1 1 2 - - - 17
20to25 27 6 2 3 2 2 5 2 - - 49
26to30 26 16 10* 11 7 7 - 2 - - 79
SOtoSS 22 7 2 3 5 10 - 4 1 1 65
OverS5 13 7 4 4 2 3 3 1 2 - 39
95 38 21 22 17 23 10 9 3 1 239
were in premature infants (17), a
percent-age approximately the same as for total
births. The total frequency was 42 per 1000
live births. But the majority of these were
minor abnormalities and included such con-ditions as hemangioma and nevus (except
nevus flammeus), extra digits, accessory
auricular appendages and so on which
would interfere in no way with survival or normal development. It is probable that not
more than 10% of all surviving infants listed
as having a malformation, about 4 per 1000
births, suffered a definite handicap. For the same period there were 23 neonatal deaths
and 9 stillbirths from malformations, making
an incidence of 6.4 per 1000 births.
Com-bining these with the surviving, children
believed to be handicapped by a congenital
malformation gives a frequency of about
10 per 1000 total births. Thus about 1% of
all fetuses who pass 20 weeks of
intrauter-ine life suffered from a malformation which was either lethal or seriously interfered
with normal development.
In attempting to assess the importance
of malformations in the total picture of
re-productive failure, one must include preg-nancies which terminate very early, where the frequency of abnormal development is extremely high. Thus, Hertig and Rock3 re-ported abnormalities in 36% of early human conceptuses they removed from the uterus. Streeter4 estimated that the incidence of
de-fective embryos in vertebrates is about 12%.
As it is probable that approximately 20% of
240
all pregnancies terminate before the period
of reportability at about 20 weeks, it is
evident that the frequency of occurrence of abnormal development is many times as
great as the figures for reported fetal and
neonatal deaths would indicate.
The various major anomalies encountered in 240 perinatal deaths in 53,847 consecu-tive deliveries at the Chicago Lying-in
Hospital are listed in Table II.
Malforma-tions of the central nervous system
com-prise almost 40% of the total, cardiac
anom-alies about 16% and gastrointestinal and
genitourinary anomalies about 9% each.
Clinical data show several factors which
may be related to the development of anomalies. Age of the mother is one of
these. In Table III it will be noted that
although 4.34% of these deliveries occurred
TABLE fli
MATERNAL AGE AND MALFORMATION AMONG INFANTS
CHICAGO LYING-IN HOSPITAL
JANUARY 1, 1941 TO JULY 1, 1966
Maternal
Age (yr)
%
of TotalDeliveries
%
of Total Malformation.Under 20 4.34 7.08
20to25 26.08 20.42
25to30 33.88 33.33
SOtoSS 22.98 22.92
Over 35 12.72 16.25
1000 births in mothers under 15 years of
age as compared to 8.6 in mothers 15 to 19
years old and 7.1 from 20 to 25 years of age,
when it was the lowest. Reproduction
im-mediately after puberty results in an
in-creased possibility of anomalies.
The end of the reproductive period is
also more likely to result in malformations
than are the middle years of life. Thus in
our data, 12.72% of all births occurred in
women over 35 years old but women who
gave birth to malformed babies made up
16.25% of the group of women giving birth
to malformed children. Hendricks2 found
an incidence of 11.3 malformations per 1000
births in mothers 40 to 44 years old and of
26 in mothers over 44 years old. The lowest
frequency in that series was between 25
and 29 years of age when the incidence was
6.4.
Although these data, covering perinatal
mortality in our hospital and the Ohio study
of live births, emphasize the importance of
age as a factor in the causation of
mal-formations, they do not present its true
sig-nificance. Some malformations are not
recognized at birth, are not recorded, and
do not appear in the figures presented by
maternity hospitals or in vital statistics.
Mongolism is a classic example. Although
it is often possible to make a diagnosis of
this anomaly in the early days after birth,
this condition escapes detection in some
newborns and some pediatricians postpone
a positive diagnosis until the baby is
sev-eral months old. The incidence of
mon-golism has been shown to rise rapidly with
increasing age after 35 years and, according
to Book and Reed,5 it occurs 40 times more
often in mothers over 45 years old than in
the decade between 20 and 30 years.
East-man6 noted that one-third of all babies with
mongolism are born to mothers over 40
years old although these mothers comprise
from 2 to 4% of all pregnant women. The
baby with mongolism is a very serious
social and medical problem, and Benda7
estimated that there are more than 600,000
living mongols. Most obstetricians are
in-dined to discourage pregnancy in women
over 40 years of age for many reasons but
tions of the child. Penrose8 recently
re-ported data from England and Wales in
which he implicated both parents and
noted an increased age as well as an
in-creased difference in age between the
father and mother in’ the causation of
achondroplasia. He feels that “older germ
cells possessed by older parents might be
likely to show deterioration in the form of
genetic changes.” Mongolism is in a special
category related primarily to maternal age
and thought not to be a result of gene
muta-tion.
The malformation rate is higher among
males than females even though some
mal-formations occur predominately in females.
In 49 babies with anencephalus delivered
at the Chicago Lying-in Hospital, 40 were
female. On the other hand, among more
than 40 fetuses and infants with complete
renal agenesis who came to necropsy, part
of whom were born in other Chicago hos-pitals, only 4 were female. In Hendricks’
study2 of live births the malformation rate
for males was 7.8 per 1000 births in
con-trast to 6.7 for females. Expressed as a
ratio between the sexes this difference is
even more striking; among total births in
Ohio the ratio was 105.6 males to 100
fe-males; in the group with malformations it
was 123.8 males to 100 females.
Multiple births increase the hazard of
malformed offspring. Hendricks2 reported a
rate of 9.2 per 1000 live births in twins in
contrast to the over-all rate of 7.2. He states that the rate of twinning rises progressively
to age 40. The incidence of malformations
also increases with age, and the rise
parallels the increasing incidence of twins
with age, although the frequency of
mal-formations is about twice as great as that
of twins. Thus, the presence of twins and
the likelthood of malformations increase
progressively with advancing years.
Hen-dricks suggests there is “a possible
com-pounding of teratologies in the older
ma-ternal group-the unfortunate teratology of
congenital malformation compounded on
the benign teratology of ‘littering’-in this
instance, twinning.”
mal-formations. It is true that a good many
mal-formed babies are born prematurely and
weigh less than 2500 gm. But in all
likeli-hood prematurity is only incidental to the
malformation and in our series
malforma-tions were not of appreciably greater
fre-quency among premature infants.
Anom-alies often interfere with proper nutrition
and growth. The weight of the baby may
be reduced by the absence or dwarfing of
major parts of the body. Some mothers who
carry grossly malformed fetuses develop an
excessive accumulation of amniotic fluid
which distends the uterine cavity and may
initiate labor prematurely. Lastly the
ob-stetrician may induce labor in the presence
of polyhydramnios.
The role played by heredity in the
pro-duction of human malformations is difficult
to determine. In some nonfatal
malforma-tions such as abnormalities of the digits,
certain types of harelip, cleft palate, club
feet, and so on, heredity is often
responsi-ble. In some of the more severe
disturb-ances such as achondroplasia,
osteopsathy-rosis and so on the condition may be
in-herited or may occur as a gene mutation,
to then be inherited through subsequent
generations. The type of lethal factor
recog-nized in over 80 conditions in birds,
ro-dents, cattle and other animals, in which a
gene when heterozygous produces only a
mild variation from the normal pattern, but
when homozygous produces a
malforma-tion incompatible with survival, has never
been proven to exist in man. The part
played by heredity is made particularly
hard to assess since the application of
vari-ous types of noxious agents can be shown
experimentally to produce malformations
identical with those which may be induced
by defective genes.
Women vary in their ability to bear
chil-dren and some women have very poor
re-productive histories. In a large maternity
service it is not uncommon to find
indivi-duals who have no living children, or
per-haps one child following a number of
un-successful pregnancies. Women bearing a
malformed child often have such histories.
Thus, infertility, abortion, stillbirth,
neo-natal deaths and malformations may be
in-terrelated. Women who are investigated or
treated for sterility, following which they
conceive, will abort in 20 to 25% of all cases.
The woman with an unsatisfactory
repro-ductive history is likely to still be trying
to obtain a child as she approaches those
critical years at the end of her reproductive
lifetime when the incidence of abnormal
babies is unusually high. Whether the
mal-formed baby is the result of environmental
factors, abnormal hormonal support,
nutri-tional inadequacies, systemic disease or
poor genes, or whether all of these factors
play interrelated roles, is a question that can
rarely be answered in an individual case.
Basic studies of the physiology of human
reproduction may provide some of the
an-swers.
SUMMARY
The existence of a malformation in a
fetus is not often associated with
abnormali-ties of pregnancy or labor. The chief
con-cern of the obstetrician is in counseling the
parents concerning future childbearing.
Malformations were reported by the
Na-tional Office of Vital Statistics as
responsi-ble for 4.4 neonatal deaths per 1000 live
births during the first 3 months of 1950.
They accounted for 24% of the deaths of
infants weighing over 2500 gm; 7% of the
deaths of infants weighing under 2500 gm;
that were born in the U.S. during this
in-terval.
In a study of 5000 consecutive births at
the Chicago Lying-in Hospital in 1951 and
1952, 210 surviving infants were found to
have certain conditions considered to be
malformations. It was thought that not more
than 10% of these infants, or 4.2 per 1000
births, would be handicapped by the
mal-formations. Coupling this with the deaths
and stillbirths occurring during the same
period gives a total of 10.6 per 1000 births.
Thus about 1% of reported births are infants
with lethal or handicapping malformations
which can be diagnosed at or soon after
birth.
Lethal malformations involved the
cen-tral nervous system more often than any
other part of the body, with anencephaly
the most common single anomaly. Cardiac
malformations were second, with those of
the gastrointestinal and genitourinary tracts
about equal in third and fourth places.
Malformations occur more commonly in
non-REFERENCES
1. Relation of weight at birth to cause of death
and age at death in neonatal period:
United States early 1950. National Office
of Vital Statistics, 36:No. 6, Feb. 23,
1956.
2. Hendricks, C. H.: Congenital
malforma-tions: Analysis of the 1953 Ohio records.
Obst. & Gynec., 6:592, 1955.
3. Hertig, A. T., and Rock,
J.:
Series ofpoten-tissues and their relation to intrauterine amputation. Carnegie Institution of
Wash-ington, 1930, Pub. No. 414.
5. BOOk,
J.
A., and Reed, S. C.: Empiric riskfigures in mongolism. J.A.M.A., 143:730, 1950.
6. Eastman, N.
J.,
ed.: Williams’ Obstetrics,10th Ed. New York, Appleton, 1950.
7. Bends, C. E.: Prenatal maternal factors in
mongolism. J.A.M.A., 139:979, 1949.
8. Penrose, L. S.: Parental age and mutation.
