Alison Fraser

Association of young maternal age with adverse reproductive outcomes.

BACKGROUND Pregnancy in adolescence is associated with an excess risk of poor outcomes, including low birth weight and prematurity. Whether this association simply reflects the deleterious sociodemographic environment of most pregnant teenagers or whether biologic immaturity is also causally implicated is not known. METHODS To determine whether a young age confers an intrinsic risk of adverse outcomes of pregnancy, we performed stratified analyses of 134,088 white girls and women, 13 to 24 years old, in Utah who delivered singleton, first-born children between 1970 and 1990. Relative risk for subgroups of this study population was examined to eliminate the confounding influence of marital status, educational level, and the adequacy of prenatal care. The adjusted relative risk for the entire study group was calculated as the weighted average of the stratum-specific risks. RESULTS Among white married mothers with educational levels appropriate for their ages who received adequate prenatal care, younger teenage mothers (13 to 17 years of age) had a significantly higher risk (P < 0.001) than mothers who were 20 to 24 years of age of delivering an infant who had low birth weight (relative risk, 1.7; 95 percent confidence interval, 1.5 to 2.0), who was delivered prematurely (relative risk, 1.9; 95 percent confidence interval, 1.7 to 2.1), or who was small for gestational age (relative risk, 1.3; 95 percent confidence interval, 1.2 to 1.4). Older teenage mothers (18 or 19 years of age) also had a significant increase in these risks. Even though sociodemographic variables associated with teenage pregnancy increase the risk of adverse outcomes, the relative risk remained significantly elevated for both younger and older teenage mothers after adjustment for marital status, level of education, and adequacy of prenatal care. CONCLUSIONS In a study of mothers 13 to 24 years old who had the characteristics of most white, middle-class Americans, a younger age conferred an increased risk of adverse pregnancy outcomes that was independent of important confounding sociodemographic factors.

PATERNAL AND MATERNAL COMPONENTS OF THE PREDISPOSITION TO PREECLAMPSIA

BACKGROUND There is an inherited maternal predisposition to preeclampsia. Whether there is a paternal component, however, is not known. METHODS We used records of the Utah Population Database to identify 298 men and 237 women born in Utah between 1947 and 1957 whose mothers had had preeclampsia during their pregnancy. For each man and woman in the study group, we identified two matched, unrelated control subjects who were not the products of pregnancies complicated by preeclampsia. We then identified 947 children of the 298 male study subjects and 830 children of the 237 female study subjects who had been born between 1970 and 1992. These children were matched to offspring of the control subjects (1950 offspring of the male control group and 1658 offspring of the female control group). Factors associated with preeclampsia were identified, and odds ratios were calculated with the use of stepwise logistic-regression analysis. RESULTS In the group whose mothers had had preeclampsia (the male study group), 2.7 percent of the offspring (26 of 947) were born of pregnancies complicated by preeclampsia, as compared with 1.3 percent of the offspring (26 of 1973) in the male control group. In the female study group, 4.7 percent of the pregnancies (39 of 830) were complicated by preeclampsia, as compared with 1.9 percent (32 of 1658) in the female control group. After adjustment for the offsprings year of birth, maternal parity, and the offsprings gestational age at delivery, the odds ratio for an adult whose mother had had preeclampsia having a child who was the product of a pregnancy complicated by preeclampsia was 2.1 (95 percent confidence interval, 1.0 to 4.3; P=0.04) in the male study group and 3.3 (95 percent confidence interval, 1.5 to 7.5; P=0.004) in the female study group. CONCLUSIONS Both men and women who were the product of a pregnancy complicated by preeclampsia were significantly more likely than control men and women to have a child who was the product of a pregnancy complicated by preeclampsia.

The effect of age at smoking initiation on lung cancer risk

It has been assumed that a younger age at initiation of cigarette smoking is associated with an increased risk of lung cancer, but previous studies have not adjusted for two strong risk factors, the amount smoked and duration smoked. We used data from a population-based case-control study with 282 histologically confirmed lung cancer cases matched to 3,282 random controls to determine whether age at initiation of smoking plays an independent role in the occurrence of lung cancer. After controlling for age, sex, and amount of tobacco exposure, men who began to smoke before age 20 had a substantially higher risk of developing lung cancer [odds ratio (OR) = 12.7; 95% confidence interval (CI) = 6.39–25.2] compared with men who began smoking at age 20 or older (OR = 6.03; 95% CI = 2.82–12.9). For women, the heavy increase in risk continued until age 25 (OR = 9.97; 95% CI = 4.68–21.2) compared with women who began smoking at age 26 or older (OR = 2.58; 95% CI = 0.5312.4). There was no predisposition toward a specific histologic type of lung cancer. In this study, up to 52.4% of lung cancer cases in men and up to 73.0% of lung cancer cases in women could be attributed to this effect of early age of first smoking. (Epidemiology 1993; 4:444–448)

Pregnancy outcomes in female childhood and adolescent cancer survivors: a linked cancer-birth registry analysis.

OBJECTIVE To compare birth outcomes among female survivors of childhood and adolescent cancer who subsequently bear children, relative to those of women without a history of cancer. DESIGN Retrospective cohort study. SETTING Four US regions. PARTICIPANTS Cancer registries identified girls younger than 20 years who were diagnosed as having cancer from 1973 through 2000. Linked birth records identified the first live births after diagnosis (n = 1898). Comparison subjects were selected from birth records (n = 14 278). Survivors of genital tract carcinomas underwent separate analysis. MAIN EXPOSURE Cancer diagnosis at younger than 20 years. MAIN OUTCOME MEASURES Infant low birth weight, preterm delivery, sex ratio, malformations, mortality, and delivery method, and maternal diabetes, anemia, and preeclampsia. RESULTS Infants born to childhood cancer survivors were more likely to be preterm (relative risk [RR], 1.54; 95% confidence interval [CI], 1.30-1.83) and to weigh less than 2500 g (1.31; 1.10-1.57). For the offspring of genital tract carcinoma survivors, RRs were 1.33 (95% CI, 1.13-1.56) and 1.29 (1.10-1.53), respectively. There were no increased risks of malformations, infant death, or altered sex ratio, suggesting no increased germ cell mutagenicity. In exploratory analysis, bone cancer survivors had an increased risk of diabetes (RR, 4.92; 95% CI, 1.60-15.13), and anemia was more common among brain tumor survivors (3.05; 1.16-7.98) and childhood cancer survivors whose initial treatment was chemotherapy only (2.45; 1.16-5.17). CONCLUSIONS Infants born to female survivors of childhood and adolescent cancer were not at increased risk of malformations or death. Increased occurrence of preterm delivery and low birth weight suggest that close monitoring is warranted. Increased diabetes and anemia among subgroups have not been reported, suggesting areas for study.

Evaluation of record linkage between a large healthcare provider and the Utah Population Database

OBJECTIVE Electronically linked datasets have become an important part of clinical research. Information from multiple sources can be used to identify comorbid conditions and patient outcomes, measure use of healthcare services, and enrich demographic and clinical variables of interest. Innovative approaches for creating research infrastructure beyond a traditional data system are necessary. MATERIALS AND METHODS Records from a large healthcare systems enterprise data warehouse (EDW) were linked to a statewide population database, and a master subject index was created. The authors evaluate the linkage, along with the impact of missing information in EDW records and the coverage of the population database. The makeup of the EDW and population database provides a subset of cancer records that exist in both resources, which allows a cancer-specific evaluation of the linkage. RESULTS About 3.4 million records (60.8%) in the EDW were linked to the population database with a minimum accuracy of 96.3%. It was estimated that approximately 24.8% of target records were absent from the population database, which enabled the effect of the amount and type of information missing from a record on the linkage to be estimated. However, 99% of the records from the oncology data mart linked; they had fewer missing fields and this correlated positively with the number of patient visits. DISCUSSION AND CONCLUSION A general-purpose research infrastructure was created which allows disease-specific cohorts to be identified. The usefulness of creating an index between institutions is that it allows each institution to maintain control and confidentiality of their own information.

Reproductive outcomes in male childhood cancer survivors: a linked cancer-birth registry analysis

OBJECTIVE To compare the risk of reproductive and infant outcomes between male childhood cancer survivors and a population-based comparison group. DESIGN Retrospective cohort study. SETTING Four US regions. PARTICIPANTS Cancer registries identified males younger than 20 years diagnosed with cancer from 1973 to 2000. Linked birth certificates identified first subsequent live offspring (N = 470). Comparison subjects were identified from remaining birth certificates, frequency-matched on year and age at fatherhood, and race/ethnicity (N = 4150). MAIN EXPOSURE Cancer diagnosis before age 20 years. OUTCOME MEASURES Pregnancy and infant outcomes identified from birth certificates. RESULTS Compared with infants born to unaffected males, offspring of cancer survivors had a borderline risk of having a birth weight less than 2500 g (relative risk, 1.43 [95% confidence interval, 0.99-2.05]) that was associated most strongly with younger age at cancer diagnosis and exposure to any chemotherapy (1.96 [1.22-3.17]) or radiotherapy (1.95 [1.14-3.35]). However, they were not at risk of being born prematurely, being small for gestational age, having malformations, or having an altered male to female ratio. Overall, female partners of male survivors were not more likely to have maternal complications recorded on birth records vs the comparison group. However, preeclampsia was associated with some cancers, especially central nervous system tumors (relative risk, 3.36 [95% confidence interval, 1.63-6.90]). CONCLUSIONS Most pregnancies resulting in live births among partners of male childhood cancer survivors were not at significantly greater risk of complications vs comparison subjects. However, there remains the possibility that prior cancer therapy may affect male germ cells with some effects on progeny and on female partners.

All-Cause and Cause-Specific Mortality after Hypertensive Disease of Pregnancy

OBJECTIVE: To assess whether women with a history of hypertensive disease of pregnancy have increased risk for early adult mortality. METHODS: In this retrospective cohort study, women with one or more singleton pregnancies (1939–2012) with birth certificate information in the Utah Population Database were included. Diagnoses were categorized into gestational hypertension; preeclampsia; hemolysis, elevated liver enzymes, and low platelet count syndrome; and eclampsia. Women with more than one pregnancy with hypertensive disease (exposed) were included only once, assigned to the most severe category. Exposed women were matched one to two to unexposed women by age, year of childbirth, and parity at the time of the index pregnancy. The causes of death were ascertained using Utah death certificates and the fact of death was supplemented with the Social Security Death Index. Hazard ratios for cause-specific mortality among exposed women compared with unexposed women were estimated using Cox regressions adjusting for neonatal sex, parental education, preterm delivery, race–ethnicity, and maternal marital status. RESULTS: A total of 60,580 exposed women were matched to 123,140 unexposed women; 4,520 (7.46%) exposed and 6,776 (5.50%) unexposed women had died by 2012. All-cause mortality was significantly higher among women with hypertensive disease of pregnancy (adjusted hazard ratio [HR] 1.65, 95% confidence interval [CI] 1.57–1.73). Exposed womens greatest excess mortality risks were from Alzheimer disease (adjusted HR 3.44, 95% CI 1.00–11.82), diabetes (adjusted HR 2.80, 95% CI 2.20–3.55), ischemic heart disease (adjusted HR 2.23, 95% CI 1.90–2.63), and stroke (adjusted HR 1.88, 95% CI 1.53–2.32). CONCLUSION: Women with hypertensive disease of pregnancy have increased mortality risk, particularly for Alzheimer disease, diabetes, ischemic heart disease, and stroke.

The intergenerational predisposition to operative delivery

Objective To determine the risk of cesarean delivery for women who themselves were born via operative delivery. Methods A linked data base was constructed between the birth certificates of individuals born in Utah during 1947–1957 (parental cohort) and who subsequently became a parent of offspring born in Utah between 1970–1991 (off-spring cohort). Parental cohort women (cases) who had been delivered operatively (cesarean delivery, mid- or high for-ceps) as well as women who had a sibling delivered by an operative procedure were matched (1:2) with parental-cohort women born by spontaneous vaginal delivery (controls). Both cases and controls were selected based on having a record of at least one delivery in Utah during 1970–1991. Results Women who were delivered by cesarean were at increased risk of subsequently delivering their children by cesarean (odds ratio [OR] 1.41, 95% confidence interval [CI] 1.18–1.70; P < .001). Progressive risk was associated with parental delivery by mid- or high forceps (OR 1.72, 95% CI 1.20–2.47; P = .004), parental cesarean because of cephalopelvic disproportion alone (OR 1.83, 95% CI 1.16–2.88; P = .01), or parental cesarean for dysfunctional labor (OR 5.97, 95% CI 1.5–23.6; P < .001). The attributable risk for cesarean delivery to the contemporary population is 3.5%. Conclusion An intergenerational predisposition to cesarean delivery exists.

Maternal and neonatal outcomes for pregnancies before and after gastric bypass surgery.

Background:Interaction between maternal obesity, intrauterine environment and adverse clinical outcomes of newborns has been described.Methods:Using statewide birth certificate data, this retrospective, matched-control cohort study compared paired birth weights and complications of infants born to women before and after Roux-en-Y gastric bypass surgery (RYGB) and to matched obese non-operated women in several different groups. Women who had given birth to a child before and after RYGB (group 1; n=295 matches) and women with pregnancies after RYGB (group 2; n=764 matches) were matched to non-operated women based on age, body mass index (BMI) prior to both pregnancy and RYGB, mother’s race, year of mother/s birth, date of infant births and birth order. In addition, birth weights of 13 143 live births before and/or after RYGB of their mothers (n=5819) were compared (group 3).Results:Odds ratios (ORs) for having a large-for-gestational-age (LGA) neonate were significantly less after RYGB than for non-surgical mothers: ORs for groups 1 and 2 were 0.19 (0.08–0.38) and 0.33 (0.21–0.51), respectively. In contrast, ORs in all three groups for risk of having a small for gestational age (SGA) neonate were greater for RYGB mothers compared to non-surgical mothers (ORs were 2.16 (1.00–5.04); 2.16 (1.43–3.32); and 2.25 (1.89–2.69), respectively). Neonatal complications were not different for group 1 RYGB and non-surgical women for the first pregnancy following RYGB. Pregnancy-induced hypertension and gestational diabetes were significantly lower for the first pregnancy of mothers following RYGB compared to matched pregnancies of non-surgical mothers.Conclusion:Women who had undergone RYGB not only had lower risk for having an LGA neonate compared to BMI-matched mothers, but also had significantly higher risk for delivering an SGA neonate following RYGB. RYGB women were less likely than non-operated women to have pregnancy-related hypertension and diabetes.

Identifying clinical/translational research cohorts: ascertainment via querying an integrated multi-source database

BACKGROUND Ascertainment of potential subjects has been a longstanding problem in clinical research. Various methods have been proposed, including using data in electronic health records. However, these methods typically suffer from scaling effects-some methods work well for large cohorts; others work for small cohorts only. OBJECTIVE We propose a method that provides a simple identification of pre-research cohorts and relies on data available in most states in the USA: merged public health data sources. MATERIALS AND METHODS The Utah Population Database Limited query tool allows users to build complex queries that may span several types of health records, such as cancer registries, inpatient hospital discharges, and death certificates; in addition, these can be combined with family history information. The architectural approach incorporates several coding systems for medical information. It provides a front-end graphical user interface and enables researchers to build and run queries and view aggregate results. Multiple strategies have been incorporated to maintain confidentiality. RESULTS This tool was rapidly adopted; since its release, 241 users representing a wide range of disciplines from 17 institutions have signed the user agreement and used the query tool. Three examples are discussed: pregnancy complications co-occurring with cardiovascular disease; spondyloarthritis; and breast cancer. DISCUSSION AND CONCLUSIONS This query tool was designed to provide results as pre-research so that institutional review board approval would not be required. This architecture uses well-described technologies that should be within the reach of most institutions.