Teen Pregnancy and Risk of Premature Mortality

Key Points Question What is the risk of premature mortality from 12 years of age onward in association with teen pregnancy? Findings In this population-based cohort study of 2.2 million female teenagers, the risk of premature death was 1.9 per 10 000 person-years among those without a pregnancy, 4.1 per 10 000 person-years among those with 1 pregnancy, and 6.1 per 10 000 person-years among those with 2 or more pregnancies. Meaning This study suggests that teen pregnancy may be a readily identifiable marker for subsequent risk of premature mortality in early adulthood.


Introduction
2][3][4][5] In the US, the leading causes of death among females aged 1 to 19 years are unintentional injury, suicide, and homicide; unintentional injury, cancer, and suicide are the leading causes among those aged 20 to 44 years. 6Although direct deaths during teen pregnancy and childbirth are rare 7 -predominantly from hemorrhage, hypertensive disorders, or sepsis 8 -teen pregnancy may be a marker of adverse life experiences preceding and/or during the formative teen years.For example, there is a doseresponse association of exposure to adverse childhood experiences (ACEs)-such as sexual and emotional abuse, parental divorce or separation, or income decline 9 -with subsequent teen pregnancy, 10,11 substance use, 12 and suicide. 13ACEs are also associated with premature mortality. 9,14,15e aforementioned studies reporting on the outcomes of teen pregnancies were limited by small sample sizes, self-reported outcomes later in life, incomplete data about induced abortion, and lack of information about cause of death.Population-based data within a universal health care system, like that in Canada, can capture all teen pregnancies with minimal selection bias, including hospital live births, stillbirths, and miscarriages or ectopic pregnancies, as well as drug-and procedure-induced abortions. 16,17The present study evaluated the rate of premature mortality from 12 years of age onward in association with the number of teen pregnancies, including the age at and nature of the teen pregnancy (ie, birth, miscarriage, or ectopic pregnancy contrasted with induced abortion), as well as the cause of death. 4

Methods
This population-based cohort study was conducted among all females who were alive at 12 years of age from April 1, 1991, to March 31, 2021, residing in the province of Ontario, Canada, and thus eligible for the universal Ontario Health Insurance Plan (OHIP).The index date for cohort entry was their 12th birthday.The use of the deidentified data in this project is authorized under section 45 of Ontario's Personal Health Information Protection Act and does not require review by a research ethics board or informed consent.This report followed the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) reporting guideline for cohort studies.
All datasets were linked using unique encoded identifiers and analyzed at ICES (eTable 1 in Supplement 1).ICES is an independent, not-for-profit organization that houses diagnostic, procedural, and sociodemographic data for Ontario residents.Data at ICES are linked deterministically and include hospitalizations, emergency department visits, census data, and births and deaths and capture induced abortions of a procedural and pharmaceutical nature 17 (eTable 2 in Supplement 1).

Study Exposures
The main study exposure was the number of teen pregnancies experienced between 12 and 19 completed years, categorized as 0 (the referent), 1, or 2 or more teen pregnancies.The teen pregnancy date was the recorded date of either a live birth, stillbirth, induced abortion, or miscarriage.This exposure was treated as a time-varying covariate because an individual could accumulate teen pregnancies over time.
A secondary exposure was the nature of the teen pregnancy between 12 and 19 years of age: no teen pregnancy (referent); teen pregnancy ending spontaneously in a live birth, stillbirth, miscarriage, or ectopic pregnancy; or teen pregnancy otherwise ending in an induced abortion. 16The justification for this approach is that a teen pregnancy ending in induced abortion has been associated with a higher future risk of nonlethal self-harm. 18Another secondary exposure was the age at which a female experienced her first pregnancy, namely, 12 to 15, 16 to 17, or 18 to 19 years, each relative to no teen pregnancy.

JAMA Network Open | Pediatrics
Teen Pregnancy and Risk of Premature Mortality

Study Outcomes
The primary study outcome was all-cause mortality starting at 12 years of age (eTable 2 in Supplement 1).A secondary outcome was all-cause mortality starting at 20 years of age (additional analysis 1 in eTable 2 in Supplement 1).For this latter outcome, women were followed up from 20 years of age onward, with individuals who died prior to 20 years of age excluded.Mortality details were further expanded by assessing the nature of the death-noninjury related, injury related of an unintentional nature, and injury related of an intentional nature-captured by the vital statistics dataset up to December 2018 (eTable 2 in Supplement 1).

Statistical Analysis
Baseline characteristics contrasted females with teen pregnancy vs no teen pregnancy between 12 and 19 years of age using standardized differences, with a value greater than 0.10 indicating an important difference. 19Unadjusted and adjusted hazard ratios (HRs) for all-cause mortality from 12 years of age (time zero) onward were generated using a Cox proportional hazards regression model, with age as the timescale (main model).A participant was censored at the end of provincial health coverage (as might occur with migration out of the province) or the end of the study period of March 31, 2022.Thus, 1 year of follow-up would be possible for a woman whose 20th birthday was on March 31, 2021, and longer for anyone whose 20th birthday was before that date.The number of teen pregnancies between 12 and 19 years of age was treated as a time-varying exposure.Hazard ratios were adjusted for each woman's year of birth (as a continuous calendar year value [eg, 1985, 1986,   1987, etc In the separate Cox proportional hazards regression models of the nature of the pregnancy (no teen pregnancy and teen pregnancy ending spontaneously or not 16,18 ) and the age at teen pregnancy (no teen pregnancy, 12-15, 16-17, or 18-19 years), the earliest teen pregnancy was chosen as the index exposure event.In the assessment of the nature of the premature death (noninjury related, unintentional injury, or intentional injury), a cause-specific hazard model was used, censoring on the competing risk of the other causes of death.Of all fatal intentional injuries among those who did or did not have a teen pregnancy, a breakdown was provided for those due to self-harm (International
In the assessment of all-cause mortality from 20 years of age onward (additional analysis 1), the cohort was restricted to women alive at their 20th birthday who had consistent OHIP eligibility between 12 and 19 years of age.In the Cox proportional hazards regression model, HRs were adjusted for each woman's year of birth, number of comorbidity ADGs at 9 to 11 years of age, area-level educational attainment less than high school when the teen was 20 years of age, income quintile at 20 years, and rural residence at 20 years.Statistical significance was set at a 2-sided P < .05.
Those who experienced a teen pregnancy were more likely to reside in the lowest neighborhood income quintile and in an area with less completion of a high school education.Females with a teen  4).Among those with a teen pregnancy, noninjury-related premature mortality was more common (incidence rate, 2.0 per 10 000 person-years [95% CI, 1.8-2.2 per 10 000 personyears]) than either unintentional (incidence rate, 1.0 per 10 000 person-years [95% CI, 0.9-1.2 per 10 000 person-years]) or intentional (incidence rate, 0.4 per 10 000 person-years [95% CI, 0.3-0.5 per 10 000 person-years]) deaths from injury.Those who had a teen pregnancy before 16 years of age had the highest incidence rate of premature death and a corresponding AHR of 2.00 (95% CI, 1.68-2.39)(Table 5).were due to assault (ICD-9 codes E960-E969; ICD-10CA codes X85-Y09 and Y87.1).For females with a teen pregnancy, 134 of fatal intentional injuries (74.4%) were due to self-harm and 46 (25.6%) were due to assault.This analysis is limited to the assessment of deaths up to December 2018, the last available date for death certificate data.

Discussion
In this population-based cohort study of 2.2 million females followed up within a universal health care system, the risk of premature death by approximately 31 years of age was 1.5 times higher among those who had 1 teen pregnancy and 2.1 times higher among those with at least 2 teen pregnancies.The associated risk was higher if the teen pregnancy ended in a miscarriage or birth (ie, spontaneously) and for deaths due to injury.A teen pregnancy before 16 years of age had the highest associated risk of premature death.

Strengths and Limitations
This study has some strengths.It was completed within a universal health care system that captures all teen pregnancies resulting in a hospital live birth, stillbirth, or ectopic pregnancy, as well as drug-and procedure-induced abortions and miscarriages managed within an inpatient or ambulatory setting. 16,17[12] Published studies were also underpowered to detect deaths during adolescence and early adulthood, including subtypes of death by intentional vs unintentional injury.Prior studies were rarely completed within a universal health care system, such that teen pregnancies ending in druginduced abortion could not be completely ascertained nor with sufficient follow-up into adulthood.
This study also has some limitations.We could not identify gender in our administrative data sets, only biological sex at birth.We also did not explore race or ethnicity as a confounder of the association between teen pregnancy and premature mortality for several reasons.First, we did not possess a data source that accurately identifies race and ethnicity, especially among Canadian-born women.Second, we were unaware of the reasons why race and ethnicity would be associated with teen pregnancy or premature mortality beyond the known higher rates of economic disadvantage and structural racism experienced by certain racial and ethnic groups 20 and the ensuing health risks to an affected family, 21 including a higher likelihood of ACEs 22 and intergenerational teen pregnancies. 16Adversity during childhood is associated with a greater likelihood of teen pregnancy 10 and for developing a broad array of chronic physical and psychiatric disorders. 23Even so, future strategies aimed at reducing ACEs, teen pregnancies, or the risks of premature death should carefully consider race and ethnicity within the context of exposure to economic or social disadvantage.
In the present study, the overall large number of fatalities enabled the generation of precise risk estimates, including deaths associated with intentional and unintentional injury or mortality. 4Absolute risk differences could not be calculated from the Cox proportional hazards regression models given the time time-varying nature of the exposure. 24Although women with a teen pregnancy had a higher rate of self-harm history between 12 and 19 years of age than those without a teen pregnancy, we did not evaluate interpersonal violence, substance use, 25 or psychiatric illness. 11For example, in a French population-based cohort study comparing pregnant adolescents aged 12 to 18 years with age-matched nonpregnant adolescents, the HR for subsequent hospitalization for nonlethal self-harm was 3.1 (95% CI, 2.6-3.7). 18Hence, assessment of these and other prevalent outcomes should provide a powerful examination of important antecedent conditions that can compromise physical health and life expectancy. 26

Implications for Policy and Clinical Practice
Evidence suggests that higher ACE scores in early childhood are a major factor associated with premature death during adolescence and midadulthood. 9Although there is a need to identify and reduce factors associated with ACEs, 14,15,22,27 including family instability, poverty, crowded housing, and parental separation, these factors have typically been evaluated in research studies up to the preteen years. 9Because individuals who have a history of ACEs are also more likely to engage in sexual risk taking and to experience teenage pregnancy, 27 a teen pregnancy may be another time point for identifying some individuals at greater risk of premature mortality and morbidity to facilitate access to appropriate supports.Such individuals may need counseling and assistance in dealing with the lingering trauma of ACEs, access to positive role models, supports to remain in school, and opportunities to promote self-efficacy during and after their teen years. 28,29e present study included all recognized teen pregnancies in Ontario, as well as how the pregnancy ended.Deaths as a direct consequence of a procedural or pharmaceutical abortion are extremely rare. 17In a cohort study from France, the risk of hospitalization for nonlethal self-harm among teenagers was highest after induced abortion (HR, 3.5 [95% CI, 2.9-4.2]). 18In the present study, teenagers whose pregnancy ended in an induced abortion were at somewhat higher risk of premature mortality, whereas the risk was even higher for those with a pregnancy that ended spontaneously in a birth or miscarriage.Together, the age at first teen pregnancy, the cumulative number of pregnancies, and the outcome of a teen pregnancy might each inform the targeting of strategies for the prevention of premature mortality among females.

Conclusions
This cohort study suggests that teen pregnancy may be a readily identifiable marker for subsequent risk of premature mortality in early adulthood.Apparent protective factors for the prevention of adolescent pregnancy include a stable family, school and peer support, open communication with adult mentors or parents about contraception use, free access to contraception, and female empowerment to abstain from unwanted or unplanned intercourse. 16,30Some of the former factors, among others, may also reduce the risk of youth suicide and self-harm. 31It remains to be determined whether there is additive value in including teenage pregnancy in the prevention of premature mortality among young and middle-aged women.
Teen Pregnancy and Risk of Premature Mortality 0%] vs 30 669 [1.5%]), but no higher recorded proportion of comorbidities, including those of a physical or mental health nature.The median age at teen pregnancy was 18 years (IQR, 17-19 years), of whom 121 276 (74.3%) had 1 pregnancy and 41 848 (25.6%) had 2 or more pregnancies.Of all female teenagers who had a pregnancy, 60 037 (36.8%) JAMA Network Open.2024;7(3):e241833.doi:10.1001/jamanetworkopen.2024.1833(Reprinted) March 14, 2024 3/9 Downloaded from jamanetwork.comby guest on 03/26/2024 pregnancy had a higher proportion of self-harm history between 12 and 19 years of age than those without a teen pregnancy (8123 [5.In additional analysis 1, on resetting time zero to start at 20 years of age, the AHRs were largely unchanged (eTable 3 in Supplement 1).In additional analysis 2, further adjusting for time-varying mental health factors at 12 to 19 years of age, the AHRs were slightly more attenuated but remained significant after 1 teen pregnancy (1.31 [95% CI, 1.21-1.42])or at least 2 teen pregnancies (1.78 [95% CI, 1.59-1.99])(eTable 4 in Supplement 1).Relative to no teen pregnancy, the AHR for premature death was 1.41 (95% CI, 1.29-1.54)if the first teen pregnancy ended in an induced abortion and 2.10 (95% CI, 1.91-2.31)if it ended in a miscarriage or birth (Table 3).Table 1.Description of 163 124 Females Aged 12 to 19 Years Who Had a Teen Pregnancy in Ontario, Canada, Between 1991 and 2021 and of 2 079 805 Females Who Did Not a A standardized difference >0.10 indicates an important difference.b Percentage of the local population aged 25 to 64 years with no high school certificate, diploma, or degree.c Aggregated Diagnosis Groups were created by the d Mental ADGs refer to ADG No. 23 (Psychosocial: e Major physical ADGs refer to ADG No. 3 (Time f The percentage sum is more than 100% because a female may have had more than 1 teen pregnancy.g Of these 60 037 births, 59 485 (99.1%) were live births, 384 (0.6%) stillbirths, and 168 (0.3%) stillbirths and live births.JAMA Network Open | Pediatrics Teen Pregnancy and Risk of Premature Mortality JAMA Network Open.2024;7(3):e241833.doi:10.1001/jamanetworkopen.2024.1833(Reprinted) March 14, 2024 4/9 Downloaded from jamanetwork.comby guest on 03/26/2024

Table 2 .
Risk of Premature Mortality From 12 Years of Age Onward, in Association With the Number of Teen Pregnancies a Female Had Between 12 and 19 Years of Age (Main Model)

Table 3 .
Risk of Premature Mortality From 12 Years of Age Onward, in Association With How the Teen Pregnancy Ended Between 12 and 19 Years of Age a If more than 1 teen pregnancy occurred between 12 and 19 years of age, then the earliest one was considered.bAdjusted for each female's year of birth, number of

Table 4 .
Risk of Premature Mortality From 12 Years of Age Onward, in Association With Pregnancy Between 12 and 19 Years of Age, Further Specified by the Nature of the Death Adjusted for each female's year of birth, number of comorbidity Aggregated Diagnosis Groups at 9 to 11 years of age (Յ2, 3-4, 5-6, or Ն7 years), area-level educational attainment less than high school (when teen was 12 years of age), timevarying residential income quintile at 12 to 19 years of age, and time-varying rural residence at 12 to 19 years of age.

Table 5 .
Risk of Premature Mortality From 12 Years of Age Onward, in Association With the Age at Which a Female Experienced Her First Pregnancy Between 12 and 19 Years of Age b Adjusted for each female's year of birth, number of comorbidity Aggregated Diagnosis Groups at 9 to 11 years of age (Յ2, 3-4, 5-6, or Ն7), area-level educational attainment less than high school (when teen was 12 years of age), time-varying residential income quintile at 12 to 19 years of age, and timevarying rural residence at 12 to 19 years of age.