Defective development and reproductive wastage in the United States

Defective development and reproductive wastage in the United States GABRIEL STICKLE. M.A. New Yurko New York

REP R 0 IJ IT C T I V E wastage is defined herein as including all the pmducts of conceptioll which fail to de\'t'lop into viahle infants surviving- a period of at least one year beyond delivery. At Succl'ssi\'e points in time on'r some -1-0 weeks of gestation and a subsequent 52 weeks of postnatal develop'llent, tiwrl'fon', any gin'n cohort of conceptions consist~ of varying- proportions of live embryos and fetuses, embryos and fetuses which han' died, live infants, and infants who haw died. As shown in Fig. I, the status of every member of the cohort changes either once or twice during this interval, usually from a Ii\'(' fetus to a live infant, but sometimes from a live fetus to a dead fetus or from a live fetus to a live infant to a dead infant. As indicated by the inflections of the curves, the heaviest volume of transitions tend to occur soon after conception and toward the end of pregnancy. Only involuntary terminations of pregnancy have been considered as elements of fetal attrition in this analysis. Data on induced abortions are not regarded as sufficiently reliable for inclusion. A description of the methods employed to estimate the weekly survival rate within a cohort of conceptions may be found in the Appendix.

million an' ahorted spontaneously, arc mis_ calTied. or an' born dead. The remaining 4 million art' horn ali\('. hut about 100,000 of these hahit·s fail to sun'in' infancy. Conseqtll'ntly. ilion- lin's an' lost during pregnancy and infancy tlran during the entire subseqlll'nt span of lift'. Puttinl!; this another way, t1H' risk of dving- during- the pt'riod from cOlICt'ption to agt' one is ten times as great as tire risk of (kinl!; during an equal interval of tillle at age fill and twice as great as at agt' 80. As shown in Fig. 1 and Table I, an estimated 112 per thousand conceptions are aborted spontaneously during the first 3 wl'eks of pregnancy. These losses continue to accrm', at a deceieratl'd pace. to 185 through 7 weeks, 210 through II weeks, and 269 by the end of the nineteenth week of gestation, Refore 20 wl'eks of gestation, only a few viable infants arc born. By the end of 27 weeks, howl'\'l'r, -I- of every 1,000 conceptions ha\'e resulted in live births, but practically all of these premature infants die within one week of delin-ry. After 35 w{'eks of gestation, the live birth rate has risen to about 27 per 1,000 conceptions; after 39 weeks, to 170; and after -1-0 w{'eks, to 6H per 1,000. By this tillie, howevcr, miscarriages and stillbirths han> swelled the fetal loss ratio to 29-1 and deaths of premature infants have risen to about 8, for a total loss of 302, leaving a balance of 69B living products of gestation out of thl' original cohort of 1,000. Live births dUI"ing- w{'eks -1-1 to ·H are estimated at 61 pt'r 1,000, bringing the total ratio of live births to 705 per 1,000 conceptions. Additional infant deaths and stillbirths beyond term inflate the total loss ratio by the

Pattern of survival

Based on the level of live births in 196-1 (the latest year for which complete national data are published), it may be estimated that 5.7 million conceptions occur in the United States each year. Of this total, nearly 1.7 From the National Foundation.

442

Reproductive wastage

Volum .. IIXl NlImbc)" :\

w I i _. I. (

III11UI.'\1\ 0

11,,11 ''''11 ,.f P"'

Inc Con Il.Ilh \

h\ 11111111 ..

end of 44 weeks to 308 per 1,000 conceptions, leaving a balance of 692 surviving infants. Attrition beyond 44 weeks proceeds at a greatly reduced rate, leaving 690 survivors at 53 weeks and 688 at 92 weeks following conception. Thus, an estimated 312 of every 1,000 conceptions terminate either in a fetal death (295) or in an infant death (17). About 38 per cent of the fetal deaths take place during the first 3 weeks of pregnancy; another 43 per cent occur in weeks 4 to 11; and 10 per cent occur during weeks 12 to 19. The remaining 9 per cent of the fetal deaths take place after 19 weeks of gestation, nearly 6 per cent beyond the twenty-seventh week. In absolute terms, based On a 1964 live birth denomi-

I ..

443

pIlon

r .. 0"

It ..1.,1' I'll

11100

, .. no

"linn.

nator, the annual fetal death estimate is distributed as shown in Table II. Table III presents estimates of the number of fetal and infant deaths in each time interval covered by this analysis.

Causes of fetal loss National data on causes of fetal death are not routinely published in the United States primarily because a large proportion of fetal death certificates in this country either fail to designate cause or carry a poorly defined cause. Relatively few definitive studies have been made of the causes of early fetal loss. Nevertheless, Carrl has shown that about 24 per cent of spontaneous abortions before 20 weeks of gestation are associated with a major

444

F.·b,uary I. 1968

Stickle

Am. J. Ob,!. & Gynee.

Table I. Estimated survival rate per 1,000 products of gestation, by weeks elapsed since conception, l'nited States, 196~ -H;~-e-ks-~-LiI~----Cu";;--C~mu~1 Cumu~

followin!! conuption

o

3 7 1\

15 19 27

:H 35

39 40 42

44

48

53

57 61 66 92

productJ of Kl'S. tation

1,000 1l1l8 1115 760 7:\9 7:\1

71H 714 712 706 698 693 692 691 690 690 689 6119 6HIl

latil'e fetal death,

lative live birth,

\

latit't' infant death,

112 185

:NO

261 269 271l 2111 2H2 2117 294 295 295 295 295 295 295 29.') 295

*

4 10

27 170 644

696 705 705 70S 705 70S 705 705

•

4 5 6 7 Il

1'2 t:l H

15 15 16 16 17

*1.,'.. than 0.5.

Table II. Estimated number of fetal deaths by weeks elapsed following conception W uks following conception

0-3 4-11 12-19 20-27 28-35 36+

Total

I EJtimated fetal deaths 640,000 731,000 166,000 51,000 23,000 74,000 1,685,000

error in chromosome division, Waxman and a~sociates'2 figures are even higher: between 40 and 50 per cent of successful cultures. Somewhat more information is available for the latter part of pregnancy. In a study of Marden and associates,3 7 of 22 stillbirths had one or more major anomalies; McDonald'i found that 24 of 63 stillbirths in her study had gross malformations or Rh isoimmunization; and Bierman and associates' reported that 8 of the 23 stillbirths in their study had congenital defects. Table IV shows percentage distributions of reported fetal deaths by cause for four coun-

tries. Th('s(' are the ollly countries in a recent report of the World Ht'alth Organization 6 for which catlsl' of death was specificd for at least 75 per ct'll t of tht' ft'tal dt'a tlls. When tilt' ill-defined and unspt'cified causes are dimin
Postnatal losses Infant deaths probably accotlnt for less than 6 pCI' cent of the total \'IllUllle of reproductive wastage in the L'nitcd States. Never_ theless, both professional and lay attention has tended to focus upon this component, presumably because of the widely held convictiOll that products of gestation born alive possess greater intrinsic value, morally and socially, than the unborn. Another considera_ tion undoubtedly has been the belief that opportunities for insuring survival and for reducing disability arc greater among the liveborn infants who are thought to be more "accessible" to care than the embryo or fetus. In evaluating this attitude, it may be useful to consider the extent to which the transition from fetal life to postnatal life alters the risks to which the product of gestation is subject. Table V shows the major causes of infant deaths in the United States. As in the prenatal period, congenital defects continue to constitute a leading cause of death, followed by immaturity and then by postnatal asphyxia and atelectasis. These three sets of causes are interdependent since the duration of pregnancy determines not only the maturity status of the fetus, but his respiratory "readiness" and, consequently, his susceptibility to asphyxia or

Volu,"., 11K) Number :J

Reproductive wastage

445

Table III. Estimated number of fetal and infant deaths among 5,712,750 conceptions annually in the United States, by weeks elapsed following conception* Weeks following conception

No. of fetlll deaths

0- 3 4-7 8-11 12-15 16-19 20-2 7 28-:11 32-35

Full-term

Total fetal and infant deaths

Total

21,912 2,414 1,711 1,554 6,::19:1 5, 106 ::I.1l27 2,791 2,135 1,743 1,400 1,167 1,050 881 828

258 21,226 6,196 7,566 7,269 1,797 22,107 2,515 1,770 1,591 6 ,4 75 5 ,150 3.844 2,801 2,143 1,749 1,400 1,167 1,050 881 828

639,829 417 ,03 1 314,201 119,967 45,960 72,641 23 ,33 4 13,279 35,833 41,786 27,602 2,714 1,7 85 1,595 6,475 5 ,150 3,844 2,801 2,143 1,749 1,400 1,167 1,050 881 828

54,912

99,783

1,785,045

6 :~ 9 ,1l29

417,031 314,201 119,967 45,702 51,415 17,138 5,713 28,5M 39.989 5,495 199 15 4

36- :~9

40 41 42 4:1 44 45-48 49-53 54-57 58-61 62-66 67-70 71-7475-79 80-83 84-87 118-92 Total

No . of infant deaths Prnllature

1,685,262

·Pres~ntalion of t"~timatt's to the

258 21,2:16 6.196 7.566 7,269 1,797 195 101 59 37 82 44 17 10 8 6

44,1171

last digit insu res that the vt'l-tical and horil.ontal sums agree exactly with the totals shown

but should nut be interprctrd to imply acruracy to that rxtcnt.

Table IV. Percentage distribution of reported fetal deaths in four countries, by cause ( 1961-1963) * CauJt Placental and cord anomalies Congcnital malformation of fetus Erythroblastosis Toxemia of prcgnancy Other diseases of preg nancy Difficulties in labor Birth injury Othcr specified causcs IlI-dl'fincd and unspecifil'd causes Total

Canada

The Netherlands

England and Wales

New Zealand

:17.1 13 .5 7.2 6.5 1.5 6.2 1.0 4.9 22 . 1

25.9 10.7 4.3 15. 1 .8 B.8 1.0 9.2 24.2

27.7 18.8 4.5 13.8 3.4 7.6 2.5 4 .3 17.4

33.7 14.0 5.9 10. 1 7.2 4.7 1.5 5 .7 17.2

100.0

100.0

100.0

100.0

-F'rom the World Health Organization. Epidemiul""ical and Vital Statistics Report, 19:6, 1966.

atelectasis. Moreover, as Shapiro and others~ have shown, the incidence of significant anomalies in the premature is at least twice as high as in the full-term infant. As indicated in Table V, prematurity is a contributory factor in nearly three fourths of the infant deaths attributed to asphyxia and

atelectasis and is associated with most of the so-called ill-defined lethal conditions as well as a majority of fatal injuries during the birth process. Altogether, prematurity is di. rectly or indirectly involved in 45 per cent of all the deaths under one year of age.

446

Stickle

.\fIt.

Tahle V. Infant deaths by caLIse, l'nited States i l9fil ', - --

-

-

-

-

-

-_.

--- - -

Total

So.

Cau(~

J.

F,·luuary I. t 968 ()h~1.

& GYIlt'C.

- - - - - - -- - -- - - - - - -

7r 0/ total

r'(

.\' o.

5.6

IfU6·1

IB .7

1,0:17

Immaturit y. unqualified, or with mention of subsidiary ("ondition

17.152

1-i._'I

17, 1~2

lon .o

Postnatal asphyxia and atel('ctasis

IIi. it;:.!

Iti .B

12.:119

7:1.7

I nflu('n za and pnt'ullwni a

I 1.-11 Ii

11 . 1

777

6.8

IO.9U

111 .'1

i .946

72.R

B.·lflil

fl .5

5.1 ")9

tio.a :U

Con~enital

ddeets·

IlI·d .. finl'd conditions, adjustlJlt'nt

incllldin~

J)utrilional

ili a

1-

Birth injuries Accidents All other causes Tot a l, all ('auses

:\. ·1116

:u

1:1,090

1:1.1

-151

99.7WI

1111 1. 11

H .1l7 1

-\5 .0 --_._ --

-- - - - --- - - - ---*rnduu('s congenitaimalformatiolls (14,lY7), hc~ molytic dis,'a,."t' o f o('''}HHn (IJjVJj, lu"rnia and inll''ilillalllh . . lllU'lioll (fU~()). IWo. nalal disol dns arisin'( flOIli crrtain diS('a~('s or IIwthrr dUI inl( pn'fil:nanev (fI70 '), 11I '1U0I d,.Uli(' di ...· ..... · of Iww bOl n (:;:W) , c-y!!.tic fihrosis (:!+t), "nU'ntai IIt·rich·ncr·· · (IBI). nt·(lplamlS lIndt·,. :!P. da,'s (HI} I, inluIl1I d"f"(,1 (If 1l1U,(·!t· (iK ·, and ()IIU'I ("oIH.lititms fir pit· natal oli~in (;-)fi). (SOtltC't·: Vilal Sialilolin. of III(' L'lIilrd Sf ... , .. ,_ 1'*;..t..1

Comment

More than 30 of evl'l"y 100 cOIl("t'ptions in the United Statcs end either in thc death of thc fetus during pregnancy or in the death of the live-born infant before his first birthday. Congenital defects and prematurity lead all the known causes of this vast destruction of life. Recog nition of these losses as a public health challenge of the highest magnitude depends upon a reappraisal of attitudes toward thc relative social importance of life before hirth, in infancy and childhood, and during maturity. Advances in knowledge of genetics and reproduction and the growth of fetology as a lIIedical discipline hold promise of increasing the "accessibility" of the "patient" before birth. There arc some who regard prevt'ntion of prenatal mortality as a comparatiwly unimportant puhlic health ohjective. Implicit in this attitude is the bt'lit'f that the pursuit of this objective merely would result in the survival of a largt'r number of defective individuals. This argummt wOllld bc justifit'd only if we were to consider ourseivt's powerless to prevent congenital defects. Actually, however, the most promising opportunities for reduction of rt'productive

wastage Illay 1)(' foulld precisely in those programs ailllt'd at the pn'\"('lltion of congt'nital defects. Thus, with cOlltilllll'd improvement in the undl'l"standing of hUllIan heredity, geJl(·tic counseling of prospect in' parents can he exp('ctl'd to play an increasingly impor_ tant role ill prt"'('ntillg conccptions which produce dd('din' (,llliJryos. Likewise, the provision of more extensivc and more adequate prt'natal carl' may be {'x(>ected to result not only in the suni\'al of more products of gestation, but also ill the prevention of defects in these fdust's which arc associat{'d with drugs. Illedical and d.·ntal radiation , Rh incompatibility, ,·i .... s infections, and other discases of the mother during pregnancy. Most important. with the continued dev{·lopment of n·search at the molecular ll'vc\, the tillle may not he too distant at which man lIIay he capahle of controlling his biologic potential through " ('ugenic engint'crin~(' In the words of Tatum": " . . . we can fores{'e the efTcctive prevention and alleviation of developmental errors, such as congenital malformations, whether these arc due to gel]('tic dt'fects, to faulty gene expn·ssion or regulation, or indirectly related to gene acti"ity via hormone production or targ(·t organ receptivity . . . the ae-

VolulIle toO

Reproductive wastage

Numbt'!" :J

tivities of harlllful dOlllillant genes could in theory he repressed as desired, or inactive genes could 1)(' turned back on as needed, even in ut('l'O at nitical )lniods of dl'velopnlen1." Since deviations in structure, function, or tillling arc respollsible for much of the fetal and infant loss, efforts at r('(luction of this loss inevitably lIIust involve not only the quantity but the quality of human rcproduction. Appendix

Estimates of the weekly attntlOn ratc within a cohort of conceptions lIlay he made on the hasis of fetal death rates obtained from sc\'pral independent studies in the United States; national tabulations of live births by period of gestation"'; and national tabulations of illfant deaths from all causes and from prelllaturity, by wceks of age. l l Erhardt's'" extrapolations of ft'tal death ratcs, based on thc experience of private obstetric patients in New York City, eonform fairly closely with the loss curves subsequently developed hy Shapiro and associates':! and French and Bierman"; the formt'r ratios are used in the illustrations prl'sented. Live births by period of g(' station have bcen calculated from the I %~ natality data of thc

National Ccnter for Health Statistics by distrihu ting the hirths of lin known length of gestation in accordancc with the distribution of hirths of known gestation. Infant deaths among the live born of I('ss than ~o weeks' gestation have heen calculated in slIch a manner that the slim of these deaths has heen forced to agrce with the total numb('r of infant deaths attributed to prematurity, un4ualified or with mention of suhsidiary condition. I t has becn assuml'd that all of the live horn of less than 20 wecks' gestation die during infancy; the corresponding mortality ratios have been estimated at 90 per cent for live births of 20 to 27 weeks' gcstation, 20 per cent for 2H to 31 weeks, 8 per cent for :~2 to 35 weeks, 3 pCI' c('nt for 36 weeks, and D.5 per cent for 37 to 39 weeks. The deaths in these cohorts of prematures then were distrihuted by age so as to agrec with thc known distribution of these deaths by week-of-age intcrval. The result of these calculations is a modification of Erhardt's'" estimatcs of fetal loss to reflect the death of the live-born infants of all pcriods of gestation over an interval cxtending 92 wceks heyond conception.

REFERENCES

I. Carr, D.: Ohst. & GYl1{'C . 26: 308, 1965. 2. Waxman. S.: Rl"marks at Hawaiian Medical Association Meeting, May IB, 1967. 3. Marden, Philip M., et al.: j. Pediat. 64: 357, 1964. 4. McDonald, Alison D.: Brit. J. Prev. & Soc, Ml"d . 15: 4.1961. 5. Bierman, .Jessie M., et at. : Pub. Health Rep. 78: 1I :~9, 196]. 6. World Hl'alth Organizalion: Epidcm. Vital Statistics Rep. 19: 6, 1966. 7. Potter, Edith L. : Defective Babies Who Die Before Birth, in Birth Dl'fects, Philadelphia, 1963, J. B. Lippincott Company. R. Shapiro, Sam, et al.: Am. J. Pub. Health 55: 2, 1965. 9. Tatum, E. L.: Molecular Biology, Nucleic

447

10. 11. 12. 13. 14.

Acids, and the Future of Medicine, presented at Reflections on Research and the Future of Medicine Symposium, Columbia University College of Physicians and Surgeons and Merck, Sharp and Dohme Research Laboratories, May 26, 1966. Vital Statistics of the United States, 1964, Volume I. Natality. United States Department of Health, Education, and Welfare. Vital Statistics of the United States, 1964, Volume II. Mortality. United States Department of Health, Education, and Welfare. Erhardt, Carl L.: Am. J. Pub. Health 53: 9, 1963. Shapiro, Sam, et al.: Milbank Mem. Fund Quart. XL: 7, 1962. French, F ., and Biennan, J.: Pub. Health Rep. 77:835, \962 .