Association of birth outcome with subsequent fertility

Association of birth outcome with subsequent fertility Tor Bjerkedal and J. David Erickson Oslo, Nonoay, and Atlanta, Georgia The association between birth outcome and subsequent fertility was analyzed by using linked Norwegian birth certificates. All births of order 1, 2, and 3 which occurred during 1967 through 1974 were considered index births; there were approximately 207,000 index births of order 1, 165,000 of order 2, and 87,000 of order 3. The mothers' fertility after these index births was summarized with a life-table technique. Fertility was most pronounced if there were no survivors of an index birth, intermediate if there was one survivor, and lowest if both members of a set of twins survived. Advanced maternal age was associated with markedly reduced fertility. The sex of a surviving singleton had little effect on a mother's subsequent fertility. However, there was a sex-related difference if index twins survived; fertility was lower after the birth of unlike-sex twins and higher after the birth of like-sex twins. This probably reflects reproductive limitation rather than a differential fecundity for mothers of dizygotic and monozygotic twins. A comparison of fertility after births of like-sex and unlike-sex twins with one survivor may indicate that mothers of dizygotic twins were more fertile, but the number available for study was small. Reproduction among women who had two index births during 1967 through 1974 was examined separately. Fertility was most marked if neither of the first two infants survived and lowest where three survived (i.e., where one of the index births involved twins). If there were two survivors, the sex composition of the pair influenced fertility; fertility was greater if the two survivors were of the same sex and lower if they were of unlike sex. Since a woman who has an unfavorable outcome in one pregnancy will be at a higher risk of having an unfavorable outcome in a subsequent pregnancy, the higher fertility of such women will, to some degree, inflate the frequency of unfavorable outcomes in a population of births. (AM. J. OesTET. GYNECOL. 147:399, 1983.)

In the course of an examination of the effects of interpregnancy interval on birth outcome (stillbirth, neonatal death, birth weight) in a modern industrialized country, Norway, Erickson and BjerkedaJl found that mothers who have babies who do not survive tend to have increased subsequent fertility. Similar trends have been shown in England by Record and Arrnstrong,2 who also showed that the birth and survival of a malformed infant seems to inhibit subsequent fertility. Record and associates 3 have also shown that the survival of twins inhibits fertility. The reasons for heightened or lowered fertility after a particular birth outcome are probably manifold; however. in a modern population in which birth control is widely practiced, one would expect the wishes of parents to play a major role. Such factors as desired family size or an inclination for a particular sex distribution of offspring may be important influences. NatuFrom the Institute of Preventive Medicine, University of Oslo, and the Birth Defects Branch, Chronic Diseases Division, Cimters for Disease Control, Public Health Service, United States Department of Health and Human Services. Received for publication February 11, 1983. Revised Mav 2, 1983. Accepted Ma.v 19, 1983. Reprint requests:]. David Erickson, Birth Dejects Branch, Chronic Diseases Division, Centers for Disease Control, Public Health Service, United States Department of Health and Human Services, Atklnta, Georgia 30333.

raJ variations of fecundity may play a relatively minor role. The effect of an unfavorable birth outcome (particularly childhood death) on a woman's subsequent fertility has been a central concern of modern demography. 4 Such relationships can have enormous implications, since the balance of the forces of fertility and death determines the rate of population growth. The demographic literature is replete with discussions of theories such as "replacement strategies" (replacement of dead children) and "insurance strategies" (overproduction of children as "insurance" against expected death). Most of this work has focused on developing nations where mortality rates are high but declining rapidly and where the balance of forces are not now in equilibrium. Massive declines in infant and childhood mortality in the developed nations have made the survival of children the expected norm. In addition, the declines have resulted in changes in the relative importance of various causes of death. Whereas infection was once the leading cause of infant death, environmental and health care improvements have reduced its impact, and birth defects, including preterm deliveries and low birth weight, are now a major cause of infant and childhood death. Although the causes of birth defects are unknown, clearly a woman who has had an adversely affected child is at substantially increased risk of

399

400

Bjerkedal and Erickson Am

J

October 15, 1\li'tl Obster. GvnemL

Table I. Numbers of order 2 births following order 1 index births,* by year of index birth and years of follow· up, Norway, 1967 through 1975 Order I index births Year· of birth

I

'I,

No.

l

I

2

I

I

·1

I

I

I

I

7

I

8

5,660 5,849 6,005 5,842 .5,924 5,858 5,167

12,359

21,105

40,305

27,328

12,960

5,439

2,2:, I

853

272

6.2

16.8

40.0

58.7

69.6

7!'!.5

78.9

80.8

82.1

2.141 2,247 1,808 1,701 1,541 U52 972 797

Total 199.72.5 Life-table cumulative percentage

3,961 4,352 4.632 4,.571 4,844 4.968

2,302 2,512 2.637 2,701 2JlOR

1,240 1,336 1.447 I ,416

6

3,251 3,290 2,960 2,814 2,771 2,368 1,938 1.713

23,691 25,196 25,231 25,057 25,943 25,747 24.674 24.186

1967 1968 1969 1970 1971 1972 1973 1974

I

Order 2 bzrths by yerm of follow-up (No.)

723 798 730

414 439

Total order 2 birth' 19.964 20,823 20,219 19,045 17.888 14,346

272

8,077 2.510 122,872

*Index births used in this table were singletons who survived infancy. Table II. :r\umbers of index births, by category of outcome and order of birth, Norway, 1967 through 1974

Singleton, alive* Singleton. deadt Twinst. like sex, 2 alive Twins. unlike sex. 2 alive Twins, like sex, I alive, I dead Twins, unlike sex, I alive. I dead Twins, both sexes, 2 dead Total

199.72.5 [J,273 917 382 115 54 177

1.59,958 3,450 906 456 87 27 !00

83.840 2,042 .'i87 311

206,64:1

164,984

85,90H

:\4

18 56

*Alive-live-born and survived infancv. tDead-stillborn or died in infancy. :j:Numbers of twin pairs. having adversely affected infants in subsequent pregnancies. The present investigation describes the association between birth outcome and subsequent fertility in contemporary Norway and focuses on the number of survivors of an index birth as the main variable. The data set used is unusual because it offers the possibility of large-scale record linkage. I. ·' The motivation for this study is not that of demographers concerned with population growth, even though they should find the data of considerable interest. Rather, the interest is in developing background information about influences on fertility which are selectiYely modified by birth outcome, with a view to later investigation of the risks of women having babies with birth defects and other unfortunate pregnancy outcomes in more than one pregnancv. Methods and material

In Norway. law requires that the outcomes of all pregnancies lasting 16 weeks or more be reported to

the Medical Birth Registry. 6 This routine, established in 1967, places responsibility for reporting on attending midwives and physicians. Since the national identification number of the mother appears on the reports, fertility histories can be reconstructed from them. The histories are complete except for induced abortions and fetal deaths that occur before 16 weeks of gestation. For this study each birth of order l, 2, or 3 which was reported during the period 1967 through 1974 was an index birth, and its outcome was considered an index outcome. The mother's fertility patterns after various categories of index outcomes were compared. In addition, fertility patterns were assessed for women whose first and second births were reported to the registry during 1967 through 1974. The fertility assessment made here is based on intervals between the dates of the index births and the dates of conception (through 1975) of the subsequent pregnancies reported to the registry by the end of 1976. There were 8 years of follow-up for women who had

Birth outcome and subsequent fertility

Volume 147 Number4

1st PREGNANCY INDEX BIRTHS

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3rd PREGNANCY INDEX BIRTHS

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,.....

~--',:;...---

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,/·.-·-·-·--:::= _____ _

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70

a.

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401

2345678

Years

Years

0

2

3

4

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Fig. l. Cumulative percentage of women having a subsequent birth, by years to conception following

various index outcomes of first-, second-, and third-order index births, Norway, 1967 through 1975. their index births registered in I967, but only I year for those whose index births occurred in I974. To summarize these data with varying lengths of followup, we used a life-table technique similar to one described by Cutler and Ederer. 7 The association between the following index outcomes and subsequent fertility were assessed: (l) number of survivors; for singletons, whether survived infancy (not stillborn or dead within first year of life); for twins, the mortality status of each child; (2) the order of the index birth, restricted to first, second, and third; for second-order index births, an additional analysis was made for women whose first and second pregnancies were reported to the registry; (3) whether single or twin birth; (4) sex; for twins, sex composition of the pair; (5) age of mother (defined as the number of years' difference between the year of the index birth and the year of the mother's birth), divided into three categories: ::si9, 20 to 34, and ~35 years. Results

Nearly 200,000 birth order I singleton infants survived infancy during I967 through I974 (Table I). About I23,000 of these were followed by an order 2 birth in which conception took place during the period of follow-up (through I975). From the numbers presented, the summary fertility experience was computed with the life-table technique. This measure indicates that 6.2% of first births were followed by a second birth in which conception took place within 6 months of the first, I6.8% were followed by a second conception within I year, and so on (Table I). The life-table cumulative percentage increased only slightly after a follow-up period of 5 years, suggesting thatconception of a second child rarely takes place more than 5 years after the birth of a first child who survives. Because fertility levels changed dramatically over the

Table III. Numbers of women with both first- and second-order index births registered, by category of outcome, Norway, 1967 through 1974 Category of outcome

3 alive,* like sex 3 alive, unlike sex 2 alive, like sex 2 alive, unlike sex I alive 0 alive Total

No. 395 741 48,395

48,118 5,282

2:35

103,166

*Alive-live-born and survived infancy; three alive because of twins in either first or second birth (or both). years of the study, the life-table method provides only an average picture of Norwegian fertility. This may be seen most easily by considering the change over time in the proportion of first-order index births that were followed within 6 months by a second conception. In I967, 9.0% of eligible women (2,I41/23,69I, Table I) conceived their second child within 6 months of the birth of their first child; by I974, the comparable percentage was 3.3. The life-table figure of 6.2% is the intermediate between these two extremes and does not reflect the experience of any particular cohort, a matter of no concern if there have been no outcome-associated differential changes in fertility. In other words, interest is in relative rather than absolute patterns of fertility. To assess this, we compared the life-table fertility with the fertility following 1967 births for several types of index outcomes, and it was found that the life-table method yielded the same relative picture as did the use of I967 index births alone. Because there was no indication of substantial differences in relative fertility, the full set of data was used. This gave a larger sample, which is particularly important for the rarer types of index outcomes.

402

Bjerkedal and Erickson

October 15, 1983 Am.

100

100

90

90

.....----·--·

80

SINGLETON BOYS _, .....OR GIRLS, ALIVE / TWIN BOYS,

V.

70 -60

-60

Q)

Q)

....0 a.

0 50

a;

a.

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Q)

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.

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J. Obstet. Gvnecol.

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-;:::.7't__.

~· ........ ,~~,/.._TWINS, UNLIKE

30

.

20

·'

SEX, ALIVE

//.~--

10

;!':"

0~~--~--r--.--,-~~-r~

2

3

4

5

6

0

7

2

3

4

5

6

7

8

Years

Years

Fig. 2. Cumulative percentage of women having a subsequent birth, by years to conception following various outcomes of first and second births in women who had both first and second pregnancies reported to the registry, Norway, 1967 through 1975.

Fig. 3. Cumulative percentage of women having a subsequent birth, by sex and years to conception following various outcomes of first-order index births, Norway, 1967 through 1975.

Fertility patterns after various categories of index outcome. Various categories of index outcomes by order of birth are given in Table II. In addition, numbers are given in Table III for various combinations of index outcomes for women who had both first and second index births reported to the registry. Effect of number of survivors and birth order. The lifetable-derived fertility patterns by number of survivors (Fig. I) show that infertility was highest when there were no survivors of an index pregnancy, intermediate when there was one survivor, and lowest when there were two survivors. Furthermore, for a given number of survivors, fertility was greatest after first-order index births and lowest after third-order index births (Fig. 1). Fertility patterns for women whose first- and secondorder births were reported to the registry are found in Fig. 2. Here the fertility after the second-order birth was most pronounced if no children survived from the first two births; fertility after one survivor was slower to rise but ultimately reached the same level as that after no survivors. The lowest fertility was for those women who had three surviving children from their first two births (the numbers with four survivors-surviving twins from both first and second pregnancies-were too small for analysis). Effect of plurality and sex. From Fig. I it is apparent that fertility after twins was similar to that after singletons, once the numbers of survivors of the index births were taken into account. Thus, fertility after twins where neither survived was similar to that after singletons who did not survive; likewise, fertility was similar after index twins with one survivor and after

surviving singletons. However, if both twins survived, fertility was substantially reduced. These effects held for first-, second-, and third-order index births (Fig. I). Fertility after first-order index births by sex is presented in Fig. 3. When the index outcome was a surviving singleton, fertility patterns for boys and girls were so similar they were plotted as one curve; it was not possible to differentiate them on this scale graph. The same similarity of fertility following male and female births was found after order 2 and 3 pregnancies. Fertility after index outcomes of surviving twins differed with the sex composition of the pair; fertility after unlike-sex twins seemed lower than after like-sex twins. A similar pattern may be seen in Fig. 2 where fertility following a first- and second-order outcome of two survivors of the same sex was higher than fertility after two survivors of different sexes. Effect of age of mother. Fertility was much reduced at advanced maternal age. Women who first gave birth when they were ~ 19 or between 20 and 34 years of age had similar patterns (Fig. 4). On the other hand, women who first gave birth at ages ~35 had a much reduced propensity to conceive again. The effect of maternal age was not accounted for in the fertility curves shown in Figs. 1 and 2, and some small differences might have been apparent if an adjustment had been made. Comment

The results of this study can be interpreted as showing that in a modern society the outcome of one pregnancy has a profound effect on a woman's subsequent fertility. If an index baby is stillborn or dies in infancy,

Birth outcome and subsequent fertility

Volume 147 Number 4

another child is usually conceived soon afterward. This effect is similar regardless of whether the index birth is of a singleton or of twins who both die. There is a striking similarity of fertility following index births when they are categorized by the number of survivors. This is most clearly reflected in the data on fertility patterns after order 2 index births (Fig. 1). The patterns after index births of "dead" singletons and after twins of whom none survive are very similar. Patterns are also similar after surviving singletons and after twins with one survivor. However, patterns for the three classes do differ; fertility is highest after an index birth with no survivors, intermediate after one survivor, and lowest after two survivors. The fertility after second-order index births with no survivors is not much lower than that after first-order index births with survival, whereas fertility following second-order index births with survival is considerably reduced. This may indicate a tendency to desire twochild families. However, it should be noted that fertility after third-order index births with no survivors is higher than that subsequent to third-order index births with a survivor. One possible interpretation of this finding is that many third-order pregnancies (those following the second-order index births) are desired. There is speculation that women who bear dizygotic twins might be more fecund than other women. 2 • 8 • 9 Although this study may illuminate this issue, the results also illustrate problems which are encountered in attempting to make inferences about fecundity from data on fertility. Norwegian mothers of unlike-sex twins (which are all dizygotic) have lower subsequent fertility (Fig. 3) than mothers of like-sex twins (like-sex twins are a monozygotic and dizygotic mixture). In the absence of voluntary fertility limitation, this pattern could be taken as an indication of lower fecundity of mothers of dizygotic twins, which is at variance with the speculation. However, women who had two surviving unlike-sex babies from the first two pregnancies had lower subsequent fertility than women who had two surviving like-sex babies (Fig. 2). This pattern could arise from a tendency to desire no more than two children, if one is male and one is female. Since it is possible that there is a similar tendency after the birth of unlike-sex twins, any judgment about fecundity from these data is suspect. The assessment of the Norwegian data on those index outcomes with one survivor may provide the basis for a closer estimate of the relative fecundity of mothers of twins. Fertility after order 1 index births with one survivor was lowest after the birth of like-sex twins with one survivor, intermediate after the birth of a surviving singleton, and highest after the birth of dizygotic (unlike-sex) twins with one survivor. Limiting comparisons to these categories of index outcomes

403

100 90

80 70

-60 c:

C1l ~ 50 C1l

D.. 40

30

20 10 0~-o--.--.--.--,r--.--r-~

0

2345678

Years

Fig. 4. Cumulative percentage of women having a subsequent birth, by maternal age and years to conception following various index outcomes of first-order index births, Norway, 1967 through 1975.

should have removed most differences arising from intentional limitation of family size. Thus, these data might suggest that mothers of dizygotic twins have a higher degree of fecundity. The data do not, of course, provide incontrovertible evidence, since the numbers of unlike-sex twin index births with only one survivor were small (Table II). Fertility is markedly reduced at advanced maternal age. If maternal age had been taken into account in the life-table analyses, the patterns of fertility might have been slightly different. Such adjustments were not made, however, because they would have heightened the differences observed rather than reduced them. For example, because dizygotic twins tend to be born to older mothers, the mothers of dizygotic twins will be less inclined to reproduce again. Thus, adjustment for mother's age would have increased the fertility differential observed after the birth of like- and unlike-sex twins when both survived. A comment should be made on the effects of these selective fertility differentials on the frequency of unfavorable pregnancy outcome in a population of births. Women who have had an unfavorable pregnancy outcome (for example, a baby who was stillborn or who died during infancy) are known to be at higher risk of having an unfavorable pregnancy outcome in a subsequent pregnancy. In Norway, where voluntary limitation of fertility is practiced, these high-risk women have a higher fertility than do women whose babies survive. Thus, greater fertility in high-risk women will inflate, to some degree, the overall population level of unfavorable reproductive outcome. A parity effect on unfavorable reproductive outcome is well known from cross-sectional data:' The general pattern is lower rates

Bjerkedal and Erickson

October I 5, I Hil:l

Am.

in second-order births than in first-order births and then increasing rates in orders 3, 4:, and so on. The results of this study suggest that at least part of the increase noted at the higher parities is due to the increased fertilitv of high-risk women. Finally. a comment seems warranted regarding the need for counseling of women who have had stillborn babies. Since many fetuses and babies are lost because of congenital malformations, the mothers need to be informed that they are at increased risk of having a malformed infant in the next pregnancy. This information needs to be transmitted promptly. since we have shown that these women tend to quickly become pregnant again. Indeed, more than half of the women who lost their first child became pregnant within l year of that loss. and about one third did so within 6 months.

REFERENCES I. Erickson,]. D., and Bjerkedal T.: Interpregnancy interval.

Association with birth weight, stillbirth and neonatal death, Epidemiol. Community Health, 32:124, 1978. Record, R. G., and Armstrong, E.: The influence of the birth of malformed child on the mother's further reproduction, Br.]. Prev. Soc. Med. 29:267. 1975. Record, R. G., Armstrong, E., and Lancashire, R. j.: A study of the fertility of mothers of twins, J. Epidemiol. Community Health 32:183, 1978. Preston, S. H.: Introduction, in The Effects of Infant and Child Mortality on Fenilitv, New York. 1978, Academic Press, Inc., pp: I· I 8. , Bakket.eig, L. S., and Hoffman, H. J.: Perinatal tnortality by birth order within cohorts based on sibship size. R. Med. .J. 2:693, 1979. Bjerkedal, T. · The medical birth registry of :'>lorwav. In Mednick, S. H .. and Baert. A. E.. editors: Prospective Longitudinal Research: An Empirical Basis for the Prevention of Psychosocial Disorders, published on behalf of the World Health Organization Regional Office of Europe. London, 1981, Oxford University Ptess, pp. 58-60. Cutler. S. J., and Ederer, F.: Maximum utilization of the life table method in analyzing survival, J. Chronic Dis. 8:699, 1958. Bulmer, M.G.: The effect of parental age. parity and duration of marriage on the twinningrate, Ann. Hum. Genet. 23:454. 1959. Allen, G., and Schacter, J.: Ease of conception in mothers of twins, Soc. Bioi. 18:18, 1971.

J. 2. 3. 4. 5. 6.

7.

We thank the staff of the Medical Birth Registry of Norway. University of Bergen; Rolv Skjaerven, Head of Data Processing; also A. N. Oppegaard, C. Tucker and S. Gentry.

J. Obstet. GynetoL

8. 9.

Picenadol (LY 150720) compared with meperidine and placebo for relief of post-cesarean section pain: A randomized double-blind study Donald M. Sherline, M.D. Augusta, Georgia Picenadol (LY 150720) is a racemic mixture of an N·methyl-4-phenylpiperidine derivative, with agonist-antagonist opiate properties. Preclinical animal pharmacology and toxicology studies demonstrated analgesic activity and a low order of toxicity. Clinical pharmacology studies have demonstrated its safety in man. Hospitalized post-cesarean section patients with postoperative pain were blindly given an intramuscular dose of picenadol, 25 mg, meperidine, 100 mg. or placebO. Analgesia and side effects of picenadol and meperidine were similar. (AM. J. Oesrer. GYNEGOL. 147:404, 1983.)

Picenadol (L Y 150720) is a racemic mixture of an N-methyl-4-phenylpiperidine derivative. 1 The d-optiFrom the Departments of Obstetrics and Gynecology, Rush Medical College and the Medical College of Georgin., and the Department of Anesthesiology, Medical College of Georgia. Received for publication January 31, 1983. Revised April18, 1983. Accepted May 31, 1983. Reprint Tequests: Dr. DoMld M. Sherline, Department of Obstetrics and Gynecology, Medical College of Georgia, Augusta, Georgia 30912.

404

cal isomer has potent opiate-like agonist actmty whereas the !-isomer has both weak agonist and antagonist activity. No other stereoisomer pair is known in which there is a similar differentiation of opiate activity. The theoretical advantages of such an agonist/ antagonist compound have been recognized for years. Obstetricians are accustomed to the concept of attempting to minimize both maternal respiratorv depression and fetal/newborn depression while at the same time