Roberta E. Christianson

Congenital heart disease in a cohort of 19,502 births with long-term follow-up.

The Child Health and Development Studies are longitudinal studies of pregnancy and the normal and abnormal development of the offspring. Women who were membres of the Kaiser Foundation Health Plan entered the study in early pregnancy, and their children were examined frequently until the youngest child in the study was 5 years old. This is a more intensive follow-up than hitherto reported. Of the 19,044 live-born children, 163 had definite and another 31 had possible congenital heart disease; the crude incidence rates per 1,000 live births were 8.8 for definite congenital heart disease and 10.4 for definite plus possible congenital heart disease. The incidence rate of congenital heart disease was 7.9 percent among all stillborn fetuses subjected to autopsy and 10.2 percent among those in this group with autopsies evaluated as being detailed enough to detect heart disease. Among the live-born children with congenital heart disease, 21 died in the neonatal period and 22 died in later infancy and childhood; about half the deaths were judged to have been due to heart disease. About 30 percent of the children with congenital heart disease had associated severe anomalies of other systems. In the whole cohort, 50 children had diagnosed chromosomal abnormalities (2.63/1,000 live births) and about 30 percent of them had congenital heart disease. Among the group of 163 children with definite congenital heart disease, the diagnosis was made in 46 percent by age 1 week, in 88.3 percent by age 1 year and 98.8 percent by age 4 years.

Anomalies in Down syndrome individuals in a large population-based registry

In a population of close to 2.5 million infants born from 1983 to 1993 registered in the California Birth Defects Monitoring Program, we compared the prevalence of structural birth defects among 2,894 infants with Down syndrome (DS) with that of infants without DS. Among 61 defects uniformly ascertained in affected and unaffected infants, 45 were significantly more common in DS, with atrioventricular canal (risk ratio = 1,009), duodenal atresia (risk ratio = 265), and annular pancreas (risk ratio = 430) being the most common. Most defects of blastogenesis and most midline defects were either nonsignificantly associated or not observed in infants with DS. Theories on the pathogenesis of defects in trisomies must account for the lack of and for the presence of specific defects.

Studies on blood pressure during pregnancy. I. Influence of parity and age.

Routine prenatal visit blood pressure measurements were used to examine the differences in blood pressure by age and parity in a cohort of 6,662 white gravidas. Both age and parity were observed to have significant effects on blood pressure during pregnancy. For a given age, nulliparas were observed to have higher mean blood pressures than parous gravidas, irrespective of the inclusion or exclusion of gravidas who were diagnosed to have hypertensive disorders during their pregnancies.

Maternal risk factors and major associated defects in infants with down syndrome

More than 50% of infants with Down syndrome have associated defects that cause considerable morbidity and mortality. We evaluated the hypothesis that the trisomic genome interacts with environmental factors to increase the risk for specific associated defects. We evaluated risk factors present during early pregnancy in a multiracial population of 687 infants with Down syndrome. Mothers cigarette smoking was associated with the grouped cardiac defects [odds ratio (OR)=2.0; 95% confidence interval (CI) = 1.2-3.2]. When adjusted for other cardiac defects and maternal race, the following specific defects were associated with smoking: atrioventricular canal (OR = 2.3; 95% CI = 1.2-4.5), tetralogy of Fallot (OR = 4.6; 95% CI = 1.2-17.0), and atrial septal defects without ventricular septal defect (OR = 2.2; 95% CI = 1.1-4.3). Hirschsprung disease was associated with mothers daily consumption of more than three cups of coffee (OR = 6.02; 95% CI = 1.2-29.7) and with mothers fever (OR = 3.4; 95% CI = 0.7-16.4), but the number of cases was small. Use of alcohol was not associated with any defect. Mothers race, age, parity, income, or education did not confound the associations. Results suggest that environmental factors can modify the occurrence of associated anomalies in the embryo with Down syndrome.

Prenatal DDT Exposure and Testicular Cancer: A Nested Case-Control Study

ABSTRACT The authors examined maternal serum levels of DDT-related compounds in relation to sons risk of testicular cancer 30 years later. Fifteen of 9,744 live-born sons were diagnosed with germ cell testicular cancer and had maternal serum samples. Cases were matched to three controls on race and birth year. Maternal serum DDT-related compounds, measured in the early postpartum, were associated with her sons risk of testicular cancer. Despite low statistical power, we observed that mothers of cases had a significantly higher ratio of p,p′-DDT (1,1,1-trichloro-2,2-bis(p-chlorophenyl)ethane) to p,p′-DDE (1,1′-dichloro-2,2′-bis(p-chlorophenyl)ethylene) and lower o,p′-DDT (1,1,1-tricholoro-2-(p-chlororphenyl)-2-(o-chlorophenyl)ethane). These findings are consistent with earlier exposure to DDT and with slower p,p′-DDT elimination among mothers of cases. Whether these associations could be direct, or operate via other pathways is unknown. Further research on interindividual differences in DDT metabolism could provide clues to testicular cancer etiology.

Fetal deaths in Mexican-American, black, and white non-Hispanic women seeking government-funded prenatal care.

Hispanics of Mexican origin constitute the largest minority population in the Southwestern United States, yet little is known about their reproductive health. This study assessed ethnic differentials in fetal mortality at 20 or more weeks gestation and identified the social and behavioral predictors associated with this outcome among low-income Hispanic, black non-Hispanic and white non-Hispanic women. Records were used of 80,431 patients attending federally funded prenatal care clinics in California from 1984 through 1989. The fetal death rate per 1,000 liver births and fetal deaths was 7.8 for Hispanic, 8.4 for white non-Hispanic and 20.5 for black non-Hispanic women. These rates indicated favorable reproductive outcomes for Mexican Americans despite their social risk profile. An analysis of stillbirths by gestational age showed that Hispanic women stood a significantly lower risk of short-gestational stillbirths than non-Hispanics. In contrast, Hispanic women had a higher proportion of term stillbirths. Hispanic acculturation was a significant predictor of short-term gestation fetal deaths only. The inability to pay for health care was a strong predictor of fetal deaths for all ethnic groups, underscoring the need to ensure adequate access to maternity care for low-income women.

Prospective study of antibody to human papilloma virus type 16 and risk of cervical, endometrial, and ovarian cancers (United States)

Objective: Human papilloma virus (HPV) is frequently detectable in cancers of the cervix, vagina, and vulva, but its role in endometrial and ovarian cancers is less certain. This analysis aimed to examine the association of presence of HPV type 16 (HPV-16) antibodies with subsequent risk of cervical, endometrial, and ovarian cancers. Methods: In a prospective study enrolling over 15,000 pregnant women, pre-cancer sera from women who developed cervical (n = 83), endometrial (n = 34), and ovarian (n = 35) cancers were compared with sera from 172 control women frequency-matched by age group and race. Results: HPV-16 seropositivity (OR = 2.0, 95% CI 1.0–3.4) was associated with cervical cancer, with the association more prominent for cancers occurring within 10 years of serum sampling (OR = 2.3, 95% CI 1.0–5.3) than cancers occurring later (OR = 1.6, 95% CI 0.75–3.6). Overall, the associations between HPV-16 seropositivity and endometrial (OR = 1.6, 95% CI 0.64–3.8) and ovarian cancers (OR = 1.1, 95% CI 0.43–2.8) were not significant, although the odds ratios for those cancers occurring within 20 years after serum sampling were similar to that for cervical cancer (OR = 2.2 for both). Conclusions: Our results confirm that HPV-16 infection precedes the development of cervical cancer. Predictability of HPV-16 seropositivity for risk of other female cancers warrants further investigation.

Maternal meiosis II nondisjunction in trisomy 21 is associated with maternal low socioeconomic status

Purpose: We evaluated whether the association of socioeconomic risk factors for trisomy 21 differed by type of maternal meiotic error.Methods: We determined meiotic errors by DNA analysis for 150 trisomy 21 cases, and maternal lifetime exposures to low socioeconomic factors by questionnaire.Results: Mothers of meiosis II cases were significantly more likely to be exposed to four low socioeconomic factors than mothers of meiosis I cases (odds ratio = 9.50; 95% confidence interval = 1.8–49.8).Conclusion: Maternal lifetime exposure to poor socioeconomic environment is a risk factor for a trisomy 21, particularly if nondisjunction leads to a maternal meiosis II.

Maternal smoking, alcohol, and coffee use during pregnancy and son's risk of testicular cancer

It has been suggested that increased risk for testicular cancer occurring worldwide may be due to exposures during fetal development. Lifestyle or environmental exposures may be the most important predictors of risk. However, few studies have directly examined these exposures prospectively. The Child Health and Development Studies is a 40-year follow-up of 20,530 pregnancies occurring between 1959 and 1967. There were 20 cases of testicular cancer diagnosed through 2003 among sons with a maternal interview in early pregnancy. Cases were matched to three controls on birth year and race. Odds ratios and 95% confidence intervals were calculated with exact conditional logistic regression. Compared to controls, mothers of testicular cancer cases were more likely to drink alcohol (unadjusted odds ratio, 3.2; 95% confidence interval, 0.83-15.48 for above vs. below the median for controls) and less likely to drink coffee (unadjusted odds ratio, 0.19; 95% confidence interval, 0.02-1.02 for above vs. below the median). Case mothers were neither more nor less likely to smoke. Although low power may limit interpretation of negative results, the prospective design minimizes bias. In this cohort, maternal serum testosterone in pregnancy was previously reported to be lower in women who drank alcohol. Because populations with high testicular cancer risk also have lower maternal testosterone, we suggest that testosterone could play a role in explaining the higher risk of sons testicular cancer among mothers who drank alcohol during pregnancy.

Fetal Trisomy 21 and Maternal Preeclampsia

Background: Placental trophoblast shedding into maternal circulation has been hypothesized as a potential cause of preeclampsia. Because pregnancies with a trisomy 21 fetus also have high levels of fetal cells and cell-free fetal DNA in maternal circulation, we examined whether trisomy 21 pregnancies have a higher risk of preeclampsia than euploid pregnancies. Methods: We used 2 population-based databases. We identified 7763 pregnancies with a singleton trisomy 21-affected fetus and 15,293 matched euploid gestations from the U.S. Natality files for the period 1995–1999. The second database consisted of 665 pregnancies with fetal trisomy 21 and 987 euploid controls in a population-based Down syndrome study in California. In the latter study, women were interviewed by telephone regarding characteristics and pregnancy complications. Gestational hypertension and preeclampsia are the outcomes of this study. Results: The U.S. Natality files showed that in nulliparous women fetal trisomy 21 was associated with a reduced risk of pregnancy-induced hypertension (adjusted relative risk [aRR] = 0.67; 95% confidence interval [CI] = 0.53 to 0.85). Findings from the California study confirmed this association in nulliparous women, and further revealed that the decrease in overall risk of pregnancy-induced hypertension was mainly the result of a large reduction in the risk of preeclampsia (aRR = 0.19; CI = 0.04 to 0.88) rather than in gestational hypertension by itself (0.83; 0.37 to 1.84). Neither dataset showed these effects among multiparous pregnancies. Conclusion: Fetal trisomy 21 is associated with a reduced, rather than increased, risk of preeclampsia, specifically in nulliparous women.