Mother's age and daughter's fecundity. An epidemiological analysis of late 19th to early 20th century family reconstitutions

Luc J Smitsa,c, Gerhard A Zielhuisa, Piet H Jongbloeta and Frans WA Van Poppelb

a Department of Epidemiology and Biostatistics, University Medical Center, Nijmegen, The Netherlands.
b Netherlands Interdisciplinary Demographic Institute, The Hague, The Netherlands.
c Department of Epidemiology, Universiteit Maastricht, Maastricht, The Netherlands.

Dr LJM Smits, Department of Epidemiology, Universiteit Maastricht, PO Box 616, 6200MD Maastricht, The Netherlands. E-mail: luc.smits{at}epid.unimaas.nl

Abstract

Background At both ends of the female reproductive span, the risk of reproductive problems is increased. We hypothesize that this is partly explained by inadequate maturation of oocytes (‘pre-ovulatory overripeness’). As this phenomenon has been shown to lead to gonadal anomalies in the offspring of animals, we tested the prediction that daughters of older and very young mothers more often suffer reproductive problems due to ovarian maldevelopment.

Methods We analysed family reconstitutions of 1907 women born in Rotterdam, the Netherlands, between 1873 and 1902. We defined several measures of fecundity based on numbers, birth rates and fates of offspring. We made use of general estimating equations (GEE), a statistical technique that allowed simultaneous analysis of different births per woman while controlling for various time-dependent or time-independent co-variables.

Results The results indicated an increased risk of childlessness (adjusted odds ratio (aOR = 2.6, 95% CI : 1.1–7.4), stillbirth (aOR = 2.5, 95% CI : 1.1–5.6) and multiple birth (aOR = 2.1, 95% CI : 0.8–5.4) for daughters of mothers of >=40 years as compared to daughters born to mothers of intermediate age (24–30 years). Daughters of mothers of <=20 years, on the other hand, did not appear to have reduced fecundity.

Conclusion The results point to a decreased fecundity of daughters of older mothers, but not of daughters of younger mothers. The inconsistency of the results with respect to the oocytal-maturation hypothesis points to the action of other causal or non-causal mechanisms.

Keywords Maternal age, fertility, infertility, female aetiology, cohort studies, retrospective studies, prenatal exposure, delayed effects, pregnancy in adolescence, multiple pregnancy, pregnancy outcome, fetal death aetiology, family planning

Accepted 1 November 2001

Age is an important determinant of women's pregnancy outcome. Both teenage and middle-aged gravidas run an increased risk of reproductive loss and congenital anomalies.1–5 Although it is clear that age per se is only a proxy for biological conditions underlying age-associated risks, the precise nature of these conditions is still controversial.

It has been hypothesized that reproductive failure at both ends of the reproductive span may be the effect of a defective maturational state of the egg cell at the time of release from the ovary (‘pre-ovulatory overripeness of the oocyte’).6,7 Animal experiments and human observational studies have shown that eggs released after a prolonged pre-ovulatory phase of the menstrual cycle run a high risk of developing chromosomal and non-chromosomal defects when they are fertilized.8 Prolonged pre-ovulatory phases are observed more often during the first years after the first menstruation,9 during the last years before menopause,9 and also during the first months after the end of an earlier pregnancy10 and in subfecund women.11

A specific effect of pre-ovulatory overripeness of the egg cell may be the maldevelopment of the sex glands of the conceptus, with, as a consequence, a decreased fecundity in the male and female offspring.8 We found earlier that women with mild or severe menstrual disorders were conceived more often at high maternal age and after short interpregnancy intervals.12 In another study, daughters of older and younger mothers showed a somewhat decreased monthly probability of conception.13 On the other hand, women with recurrent early pregnancy loss were not conceived clearly more often in high-risk situations for pre-ovulatory overripeness.14 Other authors found evidence for reduced sperm quality in men born to mothers over the age of 40.15

In the present study, we examined whether the fecundity of the daughter, defined as her ability to achieve undelayed pregnancies and carry these to the birth of healthy singletons, is related to the age of her mother at the time of her birth. To this end, we analysed the reproductive histories of 1907 women born during the late 19th to early 20th century in or around Rotterdam (The Netherlands). In view of emerging birth control practices in this population, our challenge was to sift, as much as possible, biological effects on fecundity from differences in reproductive behaviour.

Methods

Data
The data were collected in collaboration with the ‘Historical Sample of the population of the Netherlands’ (HSN), a Dutch foundation that is compiling a database containing data on a half per cent of Dutch natives born between 1812 and 1922.16 Comparable databases can be found in Canada and Sweden. The principal sources of HSN data collection are the municipal vital registration data, which include birth-, marriage-, and death registries, the municipal population registries, and personal cards. An advantageous feature of the HSN is its ability to follow women irrespective of domestic migrations.

Daughters included in this study were born between 1873 and 1902 in Rotterdam or one of its neighbouring villages (Kralingen, Charlois, and Delfshaven, which were annexed by Rotterdam between 1886 and 1895). Daughters who never married or who married after age 44 were not included in the study. Since the follow-up process for each subject was very time-consuming we decided to actively select daughters born to mothers of low, intermediate, or advanced age, as restricted by the following limits: <=20 years (risk category), 24–30 years (reference category), and >=40 years (risk category), respectively. These groups were expected to provide sufficient contrast with respect to maternal age-associated risk of oocytal overripeness. Because daughters of young mothers were expected to be mostly firstborn and daughters of older mothers to be mostly second or later children, there was a possibility of poorly controllable confounding if birth rank turned out to be a determinant of one of the reproductive outcomes. Therefore, we restricted the sample to firstborns for daughters of younger mothers and their reference group, and to higher ranks for daughters of older mothers and their reference group.

All daughters were followed for as long as possible from their wedding until ultimately 49 years of age. Only the daughters' first marriages were considered. Principal reasons for end of follow-up (other than complete follow-up) were divorce, death of daughter, death of husband, and administrative loss. If necessary, daughters and their families were followed through the whole country of the Netherlands, unless source material was untraceable or destroyed. Data were collected on both liveborn and stillborn children.

Between the end of the 19th and the beginning of the 20th century, significant secular changes took place in fertility and infant mortality in the Netherlands. Infant mortality decreased from 21% in 1890 to 5% in 1930.17 The mean number of children dropped from 7 for Dutch marriages contracted in 1890 to 4.5 for those contracted in 1916 (wife's age at wedding <=25 years) (The Netherlands).18 In Rotterdam, the percentage of childless marriages increased from 7% (marriages in 1890) to 13% (marriages in 1916).19 Considerable differences in both fertility and infant mortality existed between groups with different religious denominations or socioeconomic status, or who inhabited different regions.19–23 Generally, the fertility differentials between groups (such as the higher fertility among Roman Catholics and Calvinists) and over time (fertility in subsequent marriage cohorts declined) can be more plausibly ascribed to differences in birth control behaviour than to differences in fecundity.19,21 Therefore, in order to be able to control for these disturbing influences, we collected information on a number of probable determinants of birth control behaviour (‘Co-variables’).

During the 19th century, the population of Rotterdam exhibited a remarkable growth (a near triplication between 1811 and 1879). This population increase was largely attributable to immigration, and natural growth played a significant role only at the end of the century.24 Due to this development, genetic heterogeneity was high and the probability of genetic disease due to inbreeding relatively low.

Outcome measures
To measure fecundity, we defined a number of outcome measures referring to ‘fecundability’ or quality of the offspring. We defined childlessness as the absence of live-or stillbirths in daughters who were married before age 31 and whose marriage lasted until at least age 45. The interval between wedding and first pregnancy was calculated as (date of first birth—gestational length)—date of wedding (in days), where gestational length was assumed to be 266 days for live births and 252 days for stillbirths. Daughters with negative wedding-to-first-pregnancy intervals and daughters without any live-or stillborn children were excluded, as were daughters with wedding-to-first-pregnancy intervals that exceeded the duration of marriage. Interpregnancy intervals were calculated as the difference, in days, between two successive births (henceforth indicated by b1, being the first birth, and b2, being the second birth), minus a gestational length of 266 days if b2 was a live birth, and 252 days if it was a stillbirth. Interpregnancy intervals partly or fully falling outside marriage were excluded from analysis. For all fecundability measures, we considered a multiple birth as one birth.

Stillbirths were defined as births that were filed in the death registry but not in the birth registry. In the Netherlands, stillborn children and liveborn children who died before notification were registered in the death registry only.25 Neonatal death was defined as death within 30 days after birth in children registered in the birth registry. Children whose vital follow-up was incomplete for this period were excluded. Postneonatal death was defined as death within 365 days after birth for children who survived the first 30 days of life. Again, children whose follow-up was incomplete during this period were excluded. In cases of multiple birth, the most favourable vital outcome within the multiple birth was maintained. Multiple births were excluded when the follow-up of one of the children was insufficient to evaluate vital outcome and all others met the criteria for stillbirth, neonatal death, or postneonatal death. Multiple births were defined as births that occurred on the same day or at most one day apart. Finally, in studying gender, stillbirths (whose gender was not consistently registered) and multiple births were excluded.

Co-variables
A number of variables were included in order to control for any confounding effects of socioeconomic status, daughter's religion, and residence after wedding. These three dimensions were expected to be the most important socio-demographic determinants of birth control behaviour in this population. Religious denominations were classified into four groups: Dutch Reformed, Roman Catholic, Calvinist, and other (including Jewish and no denomination). Places of residence after wedding were divided into Rotterdam, Amsterdam, The Hague, and other. Socioeconomic status was approximated by the occupations of the daughter's father and husband and brought into the analysis as a four-class variable: service class (professionals and high civil servants, enterpreneurs, supervisors, heads of departments, merchants, self-employed other than shopkeepers, middle and lower white collar workers, factory owners), artisans (artisans, shopkeepers, manufacturers, market gardeners), (semi-)skilled workers, unskilled labourers (unskilled labourers, factory workers, rural labourers, fishermen).

Because a number of occupations involved working away from home for several days, which could have had an impact on coital frequency and thus on fecundability outcomes, we included an additional variable that indicated occupations with high and low risk of temporary spousal separation. Classification into the diverse categories of religious denomination, place of residence, and occupation was always based on the first religious denomination, etc., after the wedding. To allow for changing effects of these three variables over time, we included interaction terms with wedding year (when analysing childlessness and wedding-to-first-pregnancy interval), year of b1 (when analysing pregnancy intervals), or year of index birth (when analysing all other outcome measures). Index birth was taken to mean the birth on the basis of which the outcome is determined.

Because interpregnancy intervals may be influenced by the presence and duration of breastfeeding, we included a variable indicating whether or not an interpregnancy interval started after a stillbirth or the birth of a child that died or left the family within one year. Year of b1 or birth of index child was included as a variable in order to control for secular changes in reproductive outcomes. While, in this study, maternal age was the determinant of primary interest, the length of the birth interval preceding the daughter's birth, a possible determinant of pre-ovulatory overripeness of the egg, was included as a potential confounder.

Other co-variables included in the multivariate analyses were daughter's age at wedding, b1 or index child (5-year classes), year of wedding (10-year classes), short interval before index pregnancy (<6 months, >=6 months), and birth rank of b1 (1, 2–4, >4). In Table 1Go, we have summarized, for each outcome measure, the variables that were evaluated as a potential confounder in the analysis.


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Table 1 Co-variables treated as potential confounders in analyses of various outcomes
 
Statistical methods
Some of the study outcomes were measured only once per daughter (childlessness and wedding-to-first-pregnancy interval), while others could be measured several times, dependent on the number of offspring. For this reason, different analytical strategies were followed. Odds ratios (OR) for childlessness were calculated by use of unconditional logistic regression. For the analysis of wedding-to-first-pregnancy interval, we categorized the number of months after wedding possibly needed to achieve a pregnancy (1–2, 3–6, 7–12, 13–24, >24 months) and created four dummies for these five periods (treating the first period as the reference period). We counted the number of daughters at risk of conception at the beginning of each period and the number of daughters conceiving within each period, separately for different maternal age groups. In a logistic regression analysis, we modelled the influence of maternal age on the daughter's risk of conceiving after wedding as follows: c/r = dum3_6 dum7_12 dum13_24 dum25 agemoth, where c = number of pregnancies within specific period, r = number at risk in specific period, dum3_6 ... dum25 = dummies for four periods (1 = dealing with this period, 0 = else), and agemoth = categorical variable indicating mother's age. The overall OR of the risk group versus the reference group is then given by exp(b), where b is the regression coefficient of the co-variable risk given by SAS. A prerequisite for this analysis is constancy of the OR of the risk group versus the reference group in all five periods. For the evaluation of confounding, the numbers at risk and conceiving within each period were further subdivided by confounder level and co-variables for the confounders were included in the model.

All remaining outcomes were measured potentially more than once per daughter, which caused observations to be statistically correlated. Therefore we used the generalized estimation equations approach (GEE),26 a statistical method that is able to deal with correlated observations while allowing simultaneous control for both time-dependent and time-independent co-variates. Using GEE, we calculated OR for stillbirth, neonatal death, postneonatal death, multiple birth, and male gender. Interpregnancy interval was analysed as a continuous variable after transformation of the distribution of interpregnancy intervals into a normal distribution by taking the square root of the logarithm of the interval.

For all outcomes, we evaluated confounding by adding one potential confounder at a time to the model. If the OR altered with 10% or more, we maintained the factor in the model, otherwise we excluded it. In the analysis of interpregnancy interval, we kept a potential confounder in the model if its addition made the difference between the risk group and the referent group more than 1.1 times or less than 0.9 times as large (while keeping all other present co-variables constant). We never kept the potential confounder in the model if, both before and after its addition, the absolute difference between the mean pregnancy interval lengths of the compared groups was less than 14 days.

Results

Descriptive statistics and distributions of co-variables
Total numbers of daughters of young and old mothers were 444 and 434, and of their respective comparison groups, 446, and 583 (Table 2Go). Median follow-up was nearly equal across the groups; short follow-up lengths (<2 years) were mostly due to divorce or husband's departure (45%) or husband's death (24%). Young mothers' daughters differed considerably from the comparison group with respect to age at wedding, year of birth and year of wedding. Also, fathers and husbands of young mother's daughters were more often from low socioeconomic classes. Old mothers' daughters were born in earlier years than their comparison group, less often after short birth intervals, and more often after very long birth intervals.


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Table 2 Descriptive statistics and distribution of co-variables per study group
 
It should be noted that, in our study population, short and very long birth intervals preceding daughters' births are overrepresented relative to their distribution in the general population, because the population of the present study partly overlaps with that of another study in which we considered the influence preceding birth interval on daughters' fecundity.27 In that study we oversampled short (<14 months), long (>38 months) and intermediate (21–32 months) birth intervals for reasons similar to those for oversampling young and advanced maternal ages in the present study (see Methods). This is not expected to have influenced the validity of the results of the present study because, in the multivariate analysis, preceding birth interval was controlled for.

Reproductive outcomes
The distribution of reproductive outcomes within the study groups is shown in Table 3Go. As expected on the basis of the literature, the marital reproductive pattern is very dissimilar to that of natural fertility populations, the latter showing low childlessness rates and high numbers of births per marriage.28 The proportions of childless marriages, prenuptial conceptions, and number of births are comparable, though, to those found in earlier studies in contemporary populations in Rotterdam and the Netherlands.19,21 Infant mortality ranged from 6.5% to 8.9% (not in Table), which is comparable to data in the literature.22,25 There were no triple or higher order births in our sample, and the prevalence of (monozygotic plus dizygotic) twins was comparable to figures presented by others.29 Finally, the commonly observed small preponderance of male to female births is also visible in our sample.


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Table 3 Reproductive characteristics of the study groups
 
Multivariate analysis
In Table 4Go, the results of the multivariate analyses are displayed. The risk of childlessness was elevated for old mothers' daughters (OR = 2.6, 95% CI : 1.1–7.4), but not for young mothers' daughters (OR = 0.9, 95% CI : 0.5–1.8), as compared to their respective control groups. Among the confounders maintained in the logistic model (for old mothers' daughters) was short birth interval before the daughter's birth. Without controlling for this variable, the OR for old mothers' daughters was less than half the adjusted OR. (No notable changes occurred after introducing long preceding interval into the model.)


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Table 4 Multivariate analysis of reproductive outcome of daughters by maternal age at their birth
 
Within the group of daughters with one or more pregnancies, no clear decrease in fecundability was observed in young mothers' daughters: the OR for failure to conceive after wedding was 1.1 (95% CI : 0.8–1.4), and the difference in interpregnancy intervals was –1% (meaning that the mean interpregnancy interval was 1% shorter in young mothers' daughters than in their comparison group) (95% CI : –12 to –12%). In old mothers' daughters, fecundability even seemed to be increased, with an OR for wedding-to-first-pregnancy interval of 0.8 (95% CI : 0.6–1.1) and a difference in interpregnancy interval of –12% (95% CI : –23%–1%). The OR for wedding-to-first-pregnancy interval did not change much after restriction to pregnancies occurring within 1 or within 2 years after the wedding. The risk of stillbirth in the daughter's offspring was increased in old mothers' daughters (OR = 2.5, 95% CI : 1.1–5.6), but not in young mothers' daughters (OR = 1.1, 95% CI : 0.6–2.0). Short, and to a lesser degree, long preceding birth intervals were confounders due to an increased risk of stillbirth for daughters born after short birth intervals (who were better represented within the comparison group for old mothers' daughters), and a decreased risk for daughters born after long birth intervals (who were better represented among old mothers' daughters).

Both perinatal and infant mortality in the daughter's offspring were not affected by high or low maternal age at the daughter's birth. A doubled risk of multiple birth was observed for old mothers' daughters, although the 95% CI included 1 (OR = 2.1, 95% CI : 0.8–5.4); young mothers' daughters did not exhibit an increased risk. Finally, the risk of male offspring was not determined by high nor by low maternal age at the daughter's birth.

Discussion

In Western Europe, the average age at which women start giving birth is rising steadily, and now lies between 27 and 29 years.30 In the Netherlands, the fertility rate of women between 40 and 44 years has almost doubled during the last 15 years.30 The health effects of increased age at first birth have recently attracted the attention of epidemiologists and policy makers.31 In the US, on the other hand, the serious health consequences of childbearing at the other end of the age spectrum are reason for concern: notwithstanding a decreasing trend since the early 1990s, still each year over 1 in every 20 US women between 15 and 19 years give birth to a child.32

In the present study, we have addressed the question of whether daughters born at either extreme of the maternal reproductive span more often face reduced fecundity than daughters born at a less extreme maternal age. We were driven by the hypothesis that ovarian maldevelopment may arise in the conceptus as an effect of pre-ovulatory overripeness of the egg cell, a condition presumed to occur more often at low or high maternal age.8 We found a positive association between high maternal age at daughter's birth and the risk of childlessness, stillbirth, and (possibly) twin birth, while no clear association was observed between any of the measured reproductive outcomes and low maternal age at daughter's birth. These findings suggest an adverse influence of high maternal age, but not of low maternal age, on the daughter's fecundity.

In an earlier study, we found that women with mild or severe menstrual cycle disorders were more often conceived by mothers of >=40 years, but not more often by teenage mothers.12 Menstrual cycle disorders often go with anovulation and low fecundability.33 The increased occurrence of childlessness in old mothers' daughters but not among young mothers' daughters, as found in the present study, is in agreement with these earlier observations. However, the intervals between marriage and first pregnancy and between pregnancies suggested no decreased (but rather increased) fecundability in old mothers' daughters. The cause of this inconsistency is not clear, but it indicates that the effect of advanced maternal age on the daughter's fecundability is an ‘all-or-nothing’ phenomenon, with no intermediate forms involving moderate reductions of fecundability.

In the light of our hypothesis, a puzzling observation is the absence of any effects of young maternal age on the daughter's fecundability and quality of her offspring. One possible cause of this is an inadequate choice of the upper age limit in the definition of low maternal age as a high-risk category for pre-ovulatory overripeness. We estimated the mean menarcheal age of the mothers of our study population to be 15 years,34 and the duration of menstrual irregularities thereafter to be approximately 5 years.35 However, as earlier menarche may be associated with faster achievement of cycle regularity36 and earlier wedding and reproduction,37 it is difficult to approximate the period of postmenarcheal menstrual irregularity by age only. In order to evaluate the sensitivity of the results to the choice of the age limits, we calculated adjusted OR with an upper limit of 18 instead of 20 years for low maternal age. This resulted in an OR of 1.8, (95% CI : 0.6–5.1) for childlessness; the risk of stillbirth, however, was not increased, nor were the values of the other outcomes. We also evaluated whether a higher age limit for high maternal age (42 years instead of 40 as the lower limit) led to more or further increased reproductive risks. This was not the case except for neonatal mortality, the OR of which increased to 1.6 (95% CI : 0.8–3.3).

We cannot exclude that some residual bias due to differential misclassification and uncontrolled confounding exists, because we were not able to control for all known (and unknown) potential confounders. This may be true in particular for the analysis of the effects of young maternal age, since this group showed greater socio-demographic differences with its comparison group than the advanced maternal age group.

Because our population exhibited signs of emerging birth control practice, we expected that differences in fecundability between the study groups would be more pronounced after restriction to daughters from earlier birth cohorts (who were expected to practise birth control less extensively). After confining the analysis to daughters born before 1888, we found that the risk of childlessness increased for old mothers' daughters (OR = 3.0), whereas the OR for young mothers' daughters went further down (to 0.5). However, the other fecundability measures did not change much after this restriction.

The precise mechanism underlying our observations is unclear. Although the higher risk of childlessness and stillbirth in daughters born at advanced maternal age could be the effect of ovarian maldevelopment in the female conceptus due to pre-ovulatory overripeness of the oocyte (the hypothesis which gave rise to this study), other mechanisms may be able to explain these findings even better.

First, post-(as opposed to pre-) ovulatory overripeness of the egg cell may also play a role in human reproductive failure38 and it has been observed to cause similar effects on the development of the sex glands as does pre-ovulatory overripeness.39 Therefore, it is likewise possible that post-ovulatory ageing also causes reduced fecundity in the offspring. The risk of post-ovulatory overripeness is thought to increase with decreasing coital frequency.40 The number of coital acts per week varies widely between couples but is known to decrease with the spouses' (mainly the wife's) ages and the duration of marriage.41,42 Post-ovulatory overripeness as the underlying mechanism would also explain the absence of an elevated risk of childlessness and stillbirth in young mothers' daughters.

Second, familial forms of subfertility have been described43 that can be attributable to shared genes, environment or constitution (e.g. body mass index). For subfecund mothers it will take longer to achieve or approximate a desired number of children, a situation that will increase their risk of birth after 40; the risk of their daughters being born to 40+ mothers will be equally increased. A similar mechanism may apply with respect to stillbirth for which familial forms have been described also.44 Like post-ovulatory overripeness of the egg cell, these mechanisms would also explain the absence of reproductive problems in young mothers' daughters.

There are also two other hypotheses, in addition to pre-and postovulatory overripeness, that refer to the quality of the egg cell in explaining developmental (especially genetic/chromosomal) defects. The first one states that egg cell quality may progressively deteriorate, as a result of accumulation of damage as the woman gets older.45 The second states that differences in egg cell quality already exist before birth, as a consequence of ‘gradients' in the fetal ovary during the formation of egg cells.46 During adulthood, high-quality egg cells would be selected first for maturation and ovulation. Consequently, as the woman gets older, only egg cells of progressively inferior quality would be left.47 Both hypotheses would explain a (gradual) increase in the risk of ovarian dysfunction in the daughter as the mother gets older, that is, if the imperfections carried by the egg cells in older women are similar to those seen in pre-and post-ovulatorily overripe ova.

In conclusion, this study provides evidence for the existence of a relationship of a woman's fecundity with advanced, but not with low, maternal age at her birth. In view of the inconsistency of the results and the plausibility of alternative explanations, it would be premature to conclude that the initially proposed mechanism of ovarian pathology due to pre-ovulatory overripeness of the egg cell underlies the associations.


KEY MESSAGES

  • We hypothesize that daughters born to mothers of either very young or advanced age have a higher risk of ovarian maldevelopment as a consequence of lower-quality oocytes.
  • In a historic cohort study, daughters of mothers of >=40 years were observed to have higher risks of childlessness, stillbirth and multiple birth.
  • Daughters of mothers of <=20 did not appear to have reduced fecundity.
  • Given the inconsistency of the results, other mechanisms than the one hypothesized may underly these observations.

 


A woman and child in the Netherlands at the beginning of the twentieth century (source: Nederlands Familiealbum)

Acknowledgments

This study was supported by Grant 900–561–064 from The Netherlands Organisation for Scientific Research. We wish to thank the Historical Sample of the Netherlands for collecting the data, Marco van Leeuwen and Ineke Maas for putting their occupational classification at our disposal (version Jan. 1997), and Huub Straatman for assistance in statistical modelling.

References

1 Jacono JJ, Jacono BJ, St. Onge M, Van Oosten S, Meininger E. Teenage pregnancy: a reconsideration. Can J Public Health 1992;83: 196–99.[ISI][Medline]

2 Croen LA, Shaw GM. Young maternal age and congenital malformations: a population-based study. Am J Public Health 1995;85:710–13.[Abstract]

3 Fretts RC, Usher RH. Causes of fetal death in women of advanced maternal age. Obstet Gynecol 1997;89:40–45.[Abstract/Free Full Text]

4 Fraser AM, Brockert JE, Ward RH. Association of young maternal age with adverse reproductive outcomes. N Engl J Med 1995;332:1113–17.[Abstract/Free Full Text]

5 Fretts RC, Schmittdiel J, McLean FH, Usher RH, Goldman MB. Increased maternal age and the risk of fetal death. N Engl J Med 1995; 333:953–57.[Abstract/Free Full Text]

6 Fugo NW, Butcher RL. Irregular menses; overripeness and fetal anomalies. J Reprod Med 1970;4:79–80.[Medline]

7 Jongbloet PH. The effect of pre-ovulatory overripeness of human eggs on development. In: Blandau RJ (ed.). Aging Gametes. Basel: S Karger AG, 1975, pp.300–29.

8 Smits LJ, Jongbloet PH, Zielhuis GA. Preovulatory overripeness of the oocyte as a cause of ovarian dysfunction in the human female. Med Hypotheses 1995;45:441–48.[CrossRef][ISI][Medline]

9 Vollman RF. The Menstrual Cycle. Major Problems in Obstetrics and Gynecology. Vol. 7. Philadelphia: WB Saunders Co., 1977.

10 Gray RH, Campbell OM, Zacur HA, Labbok MH, MacRae SL. Postpartum return of ovarian activity in nonbreastfeeding women monitored by urinary assays. J Clin Endocrinol Metab 1987;64: 645–50.[Abstract]

11 Wu CH. Ovulatory disorders and infertility in women with regular menstrual cycles. Curr Opin Obstet Gynecol 1990;2:398–404.[ISI][Medline]

12 Smits LJ, Willemsen WNP, Zielhuis GA, Jongbloet PH. Conditions at conception and risk of menstrual disorders. Epidemiology 1997;8: 524–29.[CrossRef][ISI][Medline]

13 Smits LJ, Zielhuis GA, Jongbloet PH, Bouchard G. The association of birth interval, maternal age and season of birth with the fertility of daughters: a retrospective cohort study based on family reconstitutions from nineteenth and early twentieth century Quebec. Paediatr Perinat Epidemiol 1999;13:408–20.[CrossRef][ISI][Medline]

14 Smits LJ, Nelen WLDM, Wouters MGAJ, Straatman H, Jongbloet PH, Zielhuis GA. Conditions at conception in women with recurrent miscarriage. Soc Biol 1998;45:143–49.[ISI][Medline]

15 St John JC, Cooke ID, Barratt CLR. Mitochondrial mutations and male infertility. Nature Med 1997;3:124–25.

16 Mandemakers K. Historical Sample of the Population of the Netherlands (HSN). Backgrounds, objectives, and international context. In: Marker HJ, Pagh K (eds). Yesterday. Proceedings from the 6th international conference of the Association of History and Computing. Odense: Odense University Press, 1994, pp.174–81.

17 Van Poppel F. Urban-rural versus regional differences in demographic behavior. The Netherlands, 1850–1960. J Urban Hist 1989;15: 363–98.[ISI]

18 Van Poppel FWA. De differentiële vruchtbaarheid in Nederland in historisch perspectief: de invloed van de sociale status. (The differential fertility in the Netherlands in a historical perspective: the influence of social status.) Bevolk Gezin 1974;2:223–47.

19 Sanders J. The Declining Birth Rate in Rotterdam; A Statistical Analysis of the Drop in the Number of Children in 24644 Rotterdam Families During the Last 50 years. The Hague: Martinus Nijhoff, 1931.

20 Van Poppel F. Religion and health: catholicism and regional mortality differences in nineteenth-century Netherlands. Soc Hist Med 1992;5: 229–52.[ISI][Medline]

21 Methorst HW. Differential fertility; birth rates and infant mortality in the Netherlands. Population (Special Memoir)1935, pp.3–70.

22 Van Poppel F. The relationship between socio-economic position and infant and childhood mortality in the Netherlands in the period 1850–1940. In: IUSSP International Population Conference, Manila 1981. Liege 1983, pp.649–89.

23 Van Poppel FWA. Late fertility decline in the Netherlands: the influence of religious denomination, socio-economic group and region. Eur J Population 1985;1:347–73.[ISI]

24 Van Dijk H. Rotterdam 1810–1880; aspecten van een stedelijke samenleving. (Rotterdam 1810–1880; aspects of an urban society.) Schiedam: Interbook International BV, 1976.

25 Tabeau E. Changing definitions in infant mortality: a case study of the Netherlands, 1843–1991. Bevolk Gezin 1994;1:79–107.

26 Liang KY, Zeger SL. Longitudinal data analysis using generalized linear models. Biometrika 1986;73:13–22.[ISI]

27 Smits LJ, Jongbloet PH, Zielhuis GA. Fecundity of daughters born after short, intermediate, or long birth intervals, an analysis of family reconstitutions from The Netherlands, 19th–Early 20th Century. Soc Biol 2000;47:18–33.[ISI][Medline]

28 Henry L. Some data on natural fertility. Eugenics Quarterly 1961;8:81–91.[ISI]

29 Parazzini F, Villa A, Moroni S, Tozzi L, Restelli S. The epidemiology of multiple pregnancies. Acta Genet Med Gemellol 1994;43:17–23.[Medline]

30 Council of Europe. Recent Demographic Developments in Europe, 2000. Strasbourg: Council of Europe Publishing, 2000.

31 Beets G, Dourleijn E, Liefbroer A, Henkens K. De timing van het eerste kind in Nederland en Europa. (The timing of the birth of the first child in the Netherlands and Europe.) Report to the Netherlands Department of Social Affairs, Netherlands Interdisciplinary Demographic Institute, The Hague, 2000.

32 Ventura SJ, Sally CC, Matthews TJ. Variations in teenage birth rates, 1991–98. National And State Trends, National Vital Statistics Reports. Vol. 48, no. 6, 2000.

33 Speroff L, Glass RH, Kase NG. Clinical Gynecologic Endocrinology and Infertility. Baltimore: Williams and Wilkins, 1994.

34 Bolk L. De menarche bij de Nederlandsche vrouw en de vervroeging ervan bij de jongste generatie. (Menarcheal age in Dutch women and its decrease in the youngest generation.) KNAW Verslagen, Wis-en Natuurkundige Afdeeling 1923;32:711–25.

35 Metcalf MG, Skidmore DS, Lowry GF, Mackenzie JA. Incidence of ovulation in the years after the menarche. J Endocrinol 1983;97: 213–19.[Abstract]

36 Apter D, Vihko R. Early menarche, a risk factor for breast cancer, indicates early onset of ovulatory cycles. J Clin Endocrinol Metab 1983; 57:82–86.[Abstract]

37 Sandler DP, Wilcox AJ, Horney LF. Age at menarche and subsequent reproductive events. Am J Epidemiol 1984;119:765–74.[Abstract]

38 Wilcox AJ, Weinberg CR, Baird DD. Post-ovulatory ageing of the human oocyte and embryo failure. Hum Reprod 1998;2:394–97.[CrossRef]

39 Witschi E. Overripeness of the egg as a cause of twinning and teratogenesis: a review. Cancer Res 1952;12:763–97.[ISI]

40 Butcher RL. Pre-ovulatory and post-ovulatory overripeness. Int J Gynaecol Obstet 1976:14:105–10.[Medline]

41 Udry JR, Deven FR, Coleman SJ. A cross-national comparison of the relative influence of male and female age on the frequency of marital intercourse. J Biosoc Sci 1982;14:1–6.[ISI][Medline]

42 James WH. Decline in coital rates with spouses' ages and duration of marriage. J Biosoc Sci 1983;15:83–87.[ISI][Medline]

43 Franks S. Polycystic ovary syndrome. N Engl J Med 1995;333: 853–61.[Free Full Text]

44 Schauer GM, Kalousek DK, Magee JF. Genetic causes of stillbirth. Semin Perinatol 1992;16:341–51.[ISI][Medline]

45 Volarcik K, Sheean L, Goldfarb J, Woods L, Abdul-Karim FW, Hunt P. The meiotic competence of in-vitro matured human oocytes is influenced by donor age: evidence that folliculogenesis is compromised in the reproductively aged ovary. Hum Reprod 1998;13:154–60.[Abstract]

46 Henderson SA, Edwards RG. Chiasma frequency and maternal age in mammals. Nature 1968;218:22–28.[ISI]

47 Te Velde ER. Disappearing ovarian follicles and reproductive ageing (letter). Lancet 1993:341:1125–26.[CrossRef][ISI][Medline]





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