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PEDIATRICS Vol. 110 No. 6 December 2002, pp. 1163-1168

Infant Mortality Among Singletons and Twins in the United States During 2 Decades: Effects of Maternal Age

Dawn P. Misra, MHS, PhD* and Cande V. Ananth, PhD, MPH{ddagger}

* Department of Health Behavior and Health Education, University of Michigan School of Public Health, Ann Arbor, Michigan
{ddagger} Section of Epidemiology and Biostatistics, Department of Obstetrics, Gynecology and Reproductive Sciences, University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School, New Brunswick, New Jersey

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   ABSTRACT
TOP
 ABSTRACT
INTRODUCTION
 METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 
Objective. Whereas it is well-established that maternal age has a U-shaped relationship with infant mortality among singletons, effects on the risk of mortality among multiple births remains unexplored. If there is a relationship, then assessment of maternal age may identify pregnancies and births that should be targeted by both clinical and public health interventions. The objective of this study was to characterize the relationship between maternal age and infant mortality in singleton and twin births in the United States.

Methods. A retrospective cohort study was conducted of all live births (singleton: n = 22 546 718; twin: n = 535 544) in the United States in 1985–1986, 1990–1991, and 1995–1996. Risks and relative risks for infant deaths by maternal age before and after adjustments for birth cohort, gravidity, birth weight, and gestational age were measured.

Results. Maternal age had a U-shaped association with mortality among singletons, with highest rates seen at extremes of age. Among twins, however, there was a steep and inverse relationship between age and mortality, with those born to young mothers experiencing the highest mortality rates. Seven percent of twin births resulted in an infant death for women who were younger than 20 years, 2.7% for those 30 to 34 years, and 2.0% for women 40 to 49 years. Even after adjustments for gravidity, birth weight, and gestational age, these trends persisted. Additional examination by timing of death indicated that this relationship was primarily a function of postneonatal rather than neonatal mortality.

Conclusions. The highest mortality among twins occurred to women who delivered in their teens and early 20s. The implications of these findings, both from a clinical and a public health perspective, deserve attention.

Key Words: multiple gestations • twins • infant mortality • postneonatal mortality • maternal age

Abbreviations: NCHS, National Center for Health Statistics • RR, relative risk • SIDS, sudden infant death syndrome


   INTRODUCTION
TOP
 ABSTRACT
 INTRODUCTION
METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 
Much attention has been paid recently to increasing rates of multiple births and the increased risk of adverse perinatal outcomes that accompany such births. The increase in multiple birth rates has been concentrated among older mothers, although increases have also been seen in women of all ages. Although it is well-established that maternal age has a U-shaped relationship with infant mortality among singletons,1 with numerous studies examining the effect of younger2–4 and older5–9 maternal age on perinatal outcomes, the effect of maternal age on the risk of infant mortality among multiple births has not been explored adequately. An assessment of the influence of maternal age on infant mortality among twins would be informative for a number of reasons. First, maternal age is an easily measured attribute so that clinicians, programmatic personnel, and policy makers can readily identify individuals and populations at risk. Even if mechanisms cannot be elucidated immediately, awareness of the association between maternal age and infant mortality could inform risk assessment of the individual woman as well as needs assessment from a population perspective. Second, whereas most of the variability in twin infant mortality is likely explained by birth weight and gestational age, other possible influences that can be ameliorated (eg, infant care practices) have been relatively unexplored. Although maternal age might be considered relatively immutable, it may serve as a proxy for other factors that may be modifiable if identified. Although twins are at increased risk of infant death compared with singletons across all maternal ages, overall as well as in both the neonatal and postneonatal periods,10 this does not mean that the risk of twin mortality is unvarying with maternal age. Learning how infant mortality in twins relates to maternal age may also provide clues to its causes and strategies for improvement.

We sought to characterize the relationship between maternal age and infant mortality among singleton and twin births. The possible explanations for this relationship were examined in relation to 1) differences in birth weight and gestational age-specific mortality and 2) differences in the distribution of birth weight and gestational age. Patterns of neonatal and postneonatal mortality in relation to maternal age among twins and singletons were also explored.


   METHODS
TOP
 ABSTRACT
 INTRODUCTION
 METHODS
RESULTS
 DISCUSSION
 REFERENCES
 
We used data from the 1985–1986, 1990–1991, and 1995–1996 US birth cohorts. These data were derived from the national linked birth/infant death data files that are assembled by the National Center for Health Statistics (NCHS) of the Centers for Disease Control and Prevention. The data included all registered births delivered in the 50 states and the District of Columbia. These natality and mortality data files, produced annually, include statistical data from birth and infant death certificates (up to 1 year) that are provided to the NCHS by the individual states, under the Vital Statistics Cooperative Program.10 The data conform to uniform coding specifications and have passed rigorous (statistical) quality checks. They have been edited and reviewed and form the basis for official US birth and death statistics. Using these 3 different birth cohorts enabled us to determine whether effects were consistent across cohorts, an important assumption to examine given the dramatic changes in both the maternal age distribution and twin birth rates during the past 2 decades. In the absence of effect modification by birth cohort, the analyses are combined but adjusted by birth cohort.

Gestational age assignment was predominantly based on the date of last menstrual period.11 Effects of maternal age on mortality were examined as both a continuous variable and a categorical predictor. Maternal age was categorized as 15 to 19 years, 20 to 24 years, 25 to 29 years, 30 to 34 years, 35 to 39 years, and 40 to 49 years. Birth weight was categorized as <1500 g, 1500 to 2499 g, 2500 to 3999 g, and >=4000 g; and gestational age was grouped as 20 to 27, 28 to 31, 32 to 34, 35 to 36, and >=37 completed weeks. Gravidity (number of previous pregnancies) was categorized at 1, 2, or 3+.

Infant mortality (up to first year) rates by maternal age were derived for singleton and twin births. Unadjusted relative risks (RR) for infant deaths were calculated for each maternal age stratum, with 25 to 29 years serving as the universal reference category. Multivariable logistic regression models were developed to derive adjusted odds ratios and 95% confidence intervals of infant deaths by age categories, after adjusting for birth cohorts (1985–1986, 1990–1991 and 1995–1996), gravidity (gravida 1, gravida 2, and gravida >=3), birth weight, and gestational age. Finally, we also examined the influence of maternal age on neonatal (first 28 days) and postneonatal (deaths between 28 and 365 days) deaths among twins.

We sequentially excluded missing data on gestational age (n = 457 216), missing birth weight (n = 12 187), or maternal age <15 or >50 years (n = 64 105) from the singleton cohort, leaving 22 546 718 births for analysis. Similarly, we excluded 11 128 births with missing data on gestational age, 955 with missing data on birth weight, and 703 births with mothers age <15 or >50 years. These exclusions left us with 535 544 twin births for analysis.


   RESULTS
TOP
 ABSTRACT
 INTRODUCTION
 METHODS
 RESULTS
DISCUSSION
 REFERENCES
 
The rate of twinning increased across the 3 cohorts for all strata of maternal age (Table 1), with a substantial increase among older mothers. Although the relative increase was not as large as in older mothers, births to mothers in their teens and 20s also had an increased likelihood of resulting in twins.


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  		TABLE 1. Rates of Twinning (Among Live Births) in Relation to Maternal Age: United States 1985–1986, 1990–1991, and 1995–1996 Birth Cohorts

 
As expected, the infant mortality rates were higher for twins than for singletons in all 3 cohorts across all maternal ages (Fig 1). Maternal age showed a U-shaped association with infant mortality among singletons across the 3 cohorts, with increased mortality at extremes of age (Fig 1). Among twins, however, there was a steep and inverse relationship between maternal age and mortality, with twins born to younger mothers experiencing the highest rates. As there did not seem to be much difference in the association between age and mortality across cohorts, we present the combined data from the 3 cohorts but adjusted for cohort effects on mortality. Among singletons, there was an increase in the rate of infant death for births to women in the 2 youngest age groups (15–19 and 20–24), as well as in the 2 oldest age groups (35–39 and 40–49), relative to women aged 25 to 29 years (Table 2). For twins, the increase in risk was evident only for the younger women (15–19 and 20–24); mortality rates were, however, lower among older women.



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  		Fig 1. Infant mortality rates (log scale) by maternal age for singletons (dashed lines) and twins (solid lines): United States 1985–1986 ({circ}), 1990–1991 ({triangleup}), and 1995–1996 ({square}) birth cohorts.

 

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  		TABLE 2. Distribution of Infant Deaths Among Singleton and Twin Births: United States 1985–1986, 1990–1991, and 1995–1996 Birth Cohorts Combined

 
We speculated that the effects of maternal age, particularly in twins, might be 1) confounded by differences in the distribution of birth weight/gestational age differences in birth weight and gestational age-specific mortality or 2) differences in separate birth weight/gestational age strata (ie, effect modification). We therefore computed RRs for maternal age and mortality among singletons and twins, stratified by either birth weight (Table 3) or gestational age (Table 4). As birth weight is more reliably reported than gestational age, we focus on the birth weight stratification but also provide results stratified on gestational age, similar to those of birth weight, in the tables. Table 3 presents RRs for maternal age and infant mortality in singletons and twins stratified by birth weight adjusted for cohort and gravidity. Young maternal age in singleton births does not have much effect on risk of infant death among the <1500 g and 1500 to 2499 g birth weight strata. However, young maternal age does seem to increase risk at birth weights of 2500 g and higher. Singletons born to the oldest mothers (40–49 years) showed an increased risk at birth weights >=1500 g. Singletons born to mothers in their 30s did not seem to be at lower or higher risk of infant mortality, regardless of birth weight, compared with the reference group (25–29 years). Among twin infants, those who were born to younger mothers were at increased risk in all birth weight categories, but there was a stronger age effect on mortality in the higher birth weight ranges. Therefore, the trend with birth weight was similar to what was observed for singletons (effect modified with increasing birth weight), but there was an increased risk in the <1500 g and 1500 to 2499 g birth weight groups in twins that was absent among singletons. The data suggest a protective effect of older maternal age (>=30 years) among twins across birth weight groups without any consistent patterns. Adjustment for gestational age had little effect on the RRs and did not alter the observed patterns (Table 4).


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  		TABLE 3. RR (95% CI) for Infant Deaths in Relation to Maternal Age and Birth Weight Categories in Singleton and Twin Births: United States, 1985–1986, 1990–1991, and 1995–1996 Birth Cohorts Combined

 

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  		TABLE 4. RR (95% CI) for Infant Deaths in Relation to Maternal Age and Gestational Age Categories in Singleton and Twin Births: United States, 1985–1986, 1990–1991, and 1995–1996 Cohorts

 
Finally, we examined patterns of neonatal and postneonatal mortality with regard to maternal age among twins (Table 5). The patterns seen for overall infant mortality in twins are mirrored in the postneonatal mortality rates but not for the neonatal mortality rates. The neonatal mortality rates varied little with maternal age for twins. For twins who were born to younger mothers, there was a very small elevation in risk of neonatal mortality but a decreased risk for older mothers was not evident. As with infant mortality, postneonatal mortality was associated inversely with maternal age for twins.


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  		TABLE 5. RR (95% CI) for Neonatal and Postneonatal Deaths in Relation to Maternal Age in Twin Births: United States, 1985–1986, 1990–1991, and 1995–1996 Birth Cohorts Combined

 

   DISCUSSION
TOP
 ABSTRACT
 INTRODUCTION
 METHODS
 RESULTS
 DISCUSSION
REFERENCES
 
The increase in multiple-gestation births has been widely reported. It is often assumed that the increased utilization of infertility treatments is a result of the increased proportion of women who are delaying childbirth into their 30s and 40s. Although such women are more likely to experience a multiple birth, the rate of twins has also been rising for younger women (Table 1), yet little attention has been given to any possible influence of mother’s age on risk in twin gestations. As noted in a recent article that compared risk factors for preterm delivery among twins and singletons,12 little work has examined the role of social factors in predicting the outcome of twin gestations. The few studies that have examined social factors do not indicate a strong role for these factors in the outcomes of multiple-gestation pregnancies. Most of what we know about maternal age is based on studies that have excluded twins and higher order multiples. In studies of singletons, both younger and older maternal age has been reported to increase the risk of adverse perinatal outcomes, suggesting a U-shaped association.2–9

Among twin gestations, we found that increasing maternal age was strongly associated with declines in infant mortality. This was in sharp contrast to the U-shaped association among singletons seen in our data (Fig 1). A similar effect was noted across all 3 cohorts that were examined (1995–1996, 1990–1991, 1985–1986). We postulated that this effect might be explained by differences in birth weight or gestational age-specific mortality or by differences in the distribution of birth weight and gestational age. Rolett and Kiely12 recently reported an excess risk of preterm birth (<35 weeks) in twins who were born to adolescent mothers that was significantly greater than the increased risk for singletons who were born to adolescents. Similarly, Cheung et al13 found that maternal age was negatively related to preterm birth in twins but positively related to preterm birth in singletons. Our results, however, do not support differences in birth weight or gestational age as the explanation for the maternal age trends. When we examined whether these trends differed according to time of death, we found that maternal age had little influence on neonatal mortality. This was not surprising, given the patterns seen for preterm and low birth weight infants, the group most likely to die during the neonatal period. In contrast, the postneonatal mortality trends by maternal age in twins mirrored the trends seen for the overall infant mortality rates.

Maternal age is not a simple construct and is regarded by some as a social factor and by others as a biological one. Our objective here was to examine how maternal age related to infant outcomes in twin gestations in the United States. Our findings of a decreased risk for infant mortality in twins but not among singletons with older mothers can be interpreted as indicating that maternal age may serve as a proxy for needed resources or risk factors in a twin birth more strongly than in a singleton birth. Alternatively, one could argue that the factors that increase risk for singletons who are born to older mothers are less frequent in twin gestations. What differences might there be between a young mother and an older mother both giving birth to twins? It is likely that there are socioeconomic differences. Younger mothers may be more likely to be less affluent, less educated, and employed in positions with higher demands and lower control over their environment as compared with older women who give birth to twins. From a social perspective, these differences might have a greater impact in a more vulnerable twin as compared with a singleton gestation.

Our determination that the (negative) association with maternal age is largely the result of postneonatal mortality suggests that understanding the influence of young maternal age on twin births may lie in an examination of the postneonatal causes of death. We were unable to do so with our data as the cause of death information is available only for the most recent cohort in our data set (1995–1996). Sudden infant death syndrome (SIDS) is the leading cause of death in the postneonatal period.14 In some studies, but not all, young maternal age has been identified as a risk factor for SIDS.15 Multiple-gestation infants are also at increased risk for SIDS.15 Furthermore, a number of infant care practices have been correlated with SIDS, most notably sleep position.15 A recent review on SIDS concluded that "the affected infants are not completely normal in development but possess some inherent weakness which may only become obvious when the infant is subjected to an unusual stress."15 Twins may be more vulnerable to SIDS, and this vulnerability may interact with maternal age through infant care behaviors. Injury is another leading cause of death during the postneonatal period. Certainly the stress of caring for 2 infants might affect risk for injury in an unequal manner for a young mother as compared with an older one. An older mother may be more likely to have sufficient resources to provide a safe home environment and may be more educated overall and with regard to safe infant care practices.

Although it is likely that the increased risk of mortality in infants who are born to younger mothers is related to socioeconomic differences, this should not deter clinicians and public health professionals from considering maternal age as an important factor in an assessment of risks and needs for women who are pregnant with twins. Unlike many putative risk factors, maternal age is easily and accurately measured. For example, although a number of studies have now concluded that the increased risk of adverse outcomes for singletons who are born to teenage mothers is attributable to social and not biological factors,4 clinical providers would correctly assess the average teenage prenatal patient as being at increased risk.

These data were somewhat limited in terms of covariates. Although education of the mother was recorded, its utility is dubious in an examination of maternal age, as young women may not have completed their education. Vital statistics data are necessarily limited in their scope, but only data such as these are likely to have sufficient numbers of outcomes to conduct analyses with adequate statistical power. Another limitation of our study pertains to the analysis of mortality among twins. Because mortality risk within a sibship is likely to be higher when 1 of the twins dies compared with 2 unrelated singleton infants, this introduces an intracluster correlation. Failure to adjust for this intracluster correlation will likely yield biased confidence intervals of the RRs, although the RRs themselves will remain unaffected.16 The extent of such a bias, however, would depend on the strength of the intracluster correlation. The US natality and mortality data files, unfortunately, do not identify twins within a sibship for us to adjust for the intracluster correlation during statistical analysis. Although the NCHS has recently released the matched multiple birth file that links multiple births to the same mother for 1995–1997, multiple births from the older cohorts (1985–1986 and 1990–1991) remain unlinked.

Communities with a high proportion of teen births would likewise assess needs as greater than those communities with lower rates of teen births. Although the proportion of live births that result in twins is lower among younger mothers, it is not negligible and has been increasing in the past 2 decades. If twins who are born to mothers who are younger than 20 years experienced infant mortality rates equal to twins who are born to 25- to 29-year-old mothers, our analyses suggest that there would be 229 fewer infant deaths with an attributable risk of 7.8%. For singletons, the attributable risk would be just one tenth of that in twins, approximately 0.78%. The increased risk for twin infants who are born to younger women needs to be examined more carefully by public health and clinical practitioners as well as by public health and clinical researchers.


   ACKNOWLEDGMENTS
 
The associations between maternal age and infant mortality in twins were identified through work on a perinatal health project in the Johns Hopkins Women’s and Children’s Health Policy Center and funded by Cooperative Agreement U93 MC 00101-04 from the Maternal and Child Health Bureau, Health Resources Services Administration, US Department of Health and Human Services.

We thank Adam Allston for assistance in producing the initial vital statistics tables that led the authors to identify the associations with maternal age.


   FOOTNOTES
 
Received for publication Jan 22, 2002; Accepted Jun 18, 2002.

Reprint requests to (D.P.M.) Department of Health Behavior and Health Education, University of Michigan School of Public Health, 1420 Washington Heights, M5015, Ann Arbor, MI 48109. E-mail: dmisra{at}umich.edu


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 DISCUSSION
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  4. Strobino DM, Ensminger ME, Kim YJ, Nanda J. Mechanisms for maternal age differences in birthweight. Am J Epidemiol.1995; 142 :504 –514[Abstract/Free Full Text]
  5. Kessler I, Lancet M, Borenstein R, Steinmetz A. The problem of the older primipara. Obstet Gynecol.1980; 56 :165 –169[Abstract/Free Full Text]
  6. Forman M, Meirik O, Berendes H. Delayed childbearing in Sweden. JAMA.1984; 252 :3153 –3159
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PEDIATRICS (ISSN 1098-4275). ©2002 by the American Academy of Pediatrics



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