Placental characteristics and reduced risk of maternal breast cancer.

BACKGROUND: Women who have preeclampsia during pregnancy are at reduced risk of subsequent breast cancer. We examined whether other markers of reduced placental size or function, including increased blood pressure during pregnancy, predict a reduction in maternal breast cancer. METHODS: The Child Health and Development Studies is a 40-year follow-up of pregnant women enrolled in the Kaiser Permanente health plan between 1959 and 1967. We identified 3804 white women for whom data were available on placental examinations and other study variables. As of 1997, 146 women had developed invasive breast cancer. Proportional hazards models were used to estimate associations of breast cancer with markers of placental function. All statistical tests were two-sided. RESULTS: A blood pressure increase between the second and third trimesters exhibited a linear relationship with breast cancer rate, with the highest quartile showing a 51% reduction (95% confidence interval [CI] = 20% to 70%) that was not explained by preeclampsia. Smaller placental diameter was independently associated with a reduced breast cancer rate; the association increased with age at first pregnancy (P =.008). Maternal floor infarction of the placenta was associated with a 60% reduction in breast cancer rate (95% CI = 12% to 82%). In combination, placental risk factors were associated with a reduction in the breast cancer rate of as high as 94% (95% CI = 80% to 98%). CONCLUSIONS: Smaller placentas, maternal floor infarction of the placenta, and increasing blood pressure during pregnancy were associated with reduced maternal breast cancer. In the case of smaller placental diameter, the larger reduction observed with older age at first pregnancy suggests a process in which promotion of an existing lesion is blocked. Elucidating the mechanisms for these associations could provide clues to breast cancer prevention and treatment.

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.

Effect of maternal smoking and coffee consumption on the risk of having a recognized Down syndrome pregnancy.

To evaluate the possible effects of maternal smoking and caffeine or coffee consumption on the occurrence of a recognized pregnancy with Down syndrome, the authors analyzed data from a case-control study of 997 liveborn infants or fetuses with Down syndrome ascertained in California from 1991 to 1993 and 1,007 liveborn controls without a birth defect. Interviews with mothers covered demographic information, pregnancy, and medical history, with detailed questions on the use of tobacco, alcohol, and caffeinated beverages. All analyses were age-adjusted. High alcohol consumption (> or =4 drinks/week) in the first month of pregnancy was associated with reduced risk for a recognized Down syndrome conceptus (odds ratio (OR) = 0.54; 95% confidence interval (CI): 0.34, 0.85). Maternal smoking during the periconceptional period was not associated with risk of recognized Down syndrome (OR = 1.04; 95% CI: 0.79, 1.37), but maternal consumption of four or more cups of coffee per day was inversely associated (OR = 0.63; 95% CI: 0.41, 0.96). In multivariate analysis, a significant interaction between coffee drinking and smoking was observed. The inverse association remained only for nonsmoking mothers who drank four or more cups of coffee per day (OR = 0.48; 95% CI: 0.28, 0.82). These results suggest that among nonsmoking mothers, high coffee consumption is more likely to reduce the viability of a Down syndrome conceptus than that of a normal conceptus.

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. Mother's 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 mother's daily consumption of more than three cups of coffee (OR = 6.02; 95% CI = 1.2-29.7) and with mother's 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. Mother's 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.

Levels of maternal serum alpha-fetoprotein (AFP) in pregnant women and subsequent breast cancer risk.

High maternal serum alpha-fetoprotein (AFP) levels during pregnancy may be instrumental in reducing the subsequent risk of breast cancer. This hypothesis was tested in a nested case-control study using stored frozen sera accrued between 1959 and 1966 by the University of California at Berkeley Child Health and Development Studies (CHDS) group from a cohort of pregnant women. Cases with histologically confirmed breast cancer were identified from California Cancer Registry files covering their date of enrollment in the CHDS until 1994. Controls were selected from the CHDS cohort by using randomized recruitment. Third-trimester maternal serum AFP levels were analyzed by using both a radioimmunoassay and an immunoenzymatic method. After controlling for multiple confounders in logistic regression models, the authors found an inverse association between high levels of maternal serum AFP (top quartile) during the index pregnancy and the risk of breast cancer. The protective effect of high levels of maternal serum AFP varied by age at first full-term pregnancy (age 20 years or less: odds ratio (OR) = 0.43, 95% confidence interval (CI) 0.28-0.65; age 21-23 years: OR = 0.62, 95% CI 0.41-0.92). After age 27 years, the estimated risk exceeded unity (OR = 1.67, 95% CI 1.14-2.45). These study findings suggest that some of the protection against breast cancer conferred by early first full-term pregnancy may result from high levels of maternal serum AFP. After age 27 years, a high maternal serum AFP level is not protective and may increase risk.

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.

Passive and active maternal smoking as measured by serum cotinine: the effect on birthweight.

To determine how maternal exposure to environmental tobacco smoke affects birthweight, maternal sera obtained from 3529 pregnant women around 27 weeks gestation were analyzed for cotinine, a metabolite of nicotine. Based on cotinine levels, nonsmokers were divided into those exposed to environmental tobacco smoke (2-10 ng/mL) and those unexposed (< 2 ng/mL), and smokers were divided into tertiles. Compared with unexposed nonsmokers' infants, infants of exposed nonsmokers averaged 45 g less (P = .28) after adjustment for confounders, and smokers' infants averaged 78, 191, and 233 g less for the first, second, and third cotinine tertiles, respectively. Birthweight decreased 1 g for every nanogram per milliliter of cotinine increase (P < .001).

Black-white differences in serum cotinine levels among pregnant women and subsequent effects on infant birthweight.

OBJECTIVES: Higher levels of serum cotinine (a metabolite of nicotine) have been found in Black smokers than in White smokers even after self-reported cigarette dose was controlled. It is unknown whether higher cotinine levels in Black pregnant smokers may increase the risk of delivering an infant of reduced birthweight. METHODS: We analyzed serum cotinine levels of 374 Black and 829 White women who smoked during pregnancy and who delivered between April 1964 and April 1967. Racial differences in the relationship between cotinine and birthweight were examined. RESULTS: Cotinine levels were 27.4 ng/mL higher in Black smokers after cigarette dose and confounding variables were controlled. Blacks had higher cotinine levels than Whites at each dose. No significant racial differences in the rate of decrease in birthweight per nanogram of cotinine per milliliter were found. CONCLUSIONS: Our results confirm previous research showing higher cotinine levels at each smoking dose in Black smokers than in White smokers. Because there was no difference in the rate of decrease in birthweight due to cotinine, our results suggest that cigarette smoking among Blacks may have a greater effect on birthweight than it does among Whites.

Thyroid antibodies as a risk factor for Down syndrome and other trisomies.

To test whether the presence of thyroid antibodies in a parent is a risk factor for meiotic nondisjunction, we measured the levels of thyroid antibodies in serum samples drawn during early pregnancy from 101 gravidas who delivered a child with a trisomy, from 11 gravidas who had had a trisomic child in a previous pregnancy, and from 44 of their husbands. For each case mother, three controls were randomly selected from the same population and matched for age, race, sex of the child, and hospital of birth. Cases and controls came from two longitudinal populations, the Child Health and Development Studies (CHDS) and the national Collaborative Perinatal Project (CPP), together comprising more than 70,000 live births. All cases with both a definite diagnosis of trisomy-Down syndrome (DS) or other-and available serum were included. Overall, there was no association between the presence of thyroid antibodies in a mother and a trisomy in her offspring (odds ratio [OR] = .98, confidence interval [CI] = .54-1.85). The lack of association was seen in all three subgroups (DS only, other trisomies, and DS in a previous pregnancy), in all ethnic groups, and in the age groups of white mothers either less than 30 years of age (OR = .80, CI = .40-1.6) or greater than or equal to 30 years of age (OR = 1.26, CI = .82-1.9). In the CHDS population, case fathers, as compared with control fathers, did not have a higher prevalence of thyroid antibodies.(ABSTRACT TRUNCATED AT 250 WORDS)

The California Child Health and Development Studies of the School of Public Health, University of California at Berkeley.

The Child Health and Development Studies are prospective longitudinal studies on medical and social aspects of pregnancies and on the health and development of children. Data have been assembled on about 20,000 pregnancies occurring in one hospital between 1959 and 1967, and on follow-up of the children through adolescence. A currently ongoing project updates certain vital statistics of the entire study population. The data assembled in this longitudinal study supported a wide range of research projects, several of which proved to be important for the health of mothers and children. Notwithstanding, subsets of the assembled data, with potential value for public health, have not yet been explored. The data archive has been made accessible to the research community at large so that other significant research topics can be investigated. In the following article, brief descriptions are given of the history and design of the Child Health and Development Studies, of the contents of the data archive, and of the major areas of research that have been explored. Procedures to obtain access to the data and to the user's manual are explained, and a bibliography is included.

Incidence of congenital anomalies among white and black live births with long-term follow-up.

The incidence of congenital anomalies at birth and accumulated to five years is presented for live-born children in a large prospective study. Congenital anomalies are not all diagnosable at birth; our data demonstrate that the incidence rate increases approximately three-and-one-halffold for Blacks and approximately fivefold for Whites between six days of age and five years of age. The incidence of congenital anomalies at birth was higher among Black children than White children, but there were no notable differences between the groups in incidence accumulated to age five years. At five years, the incidence rate of severe and moderate (but not trivial) congenital anomalies amounted to 15 per cent; for severe congenital anomalies, 4 per cent. Severe congenital anomalies diagnosed through age five years were observed to have a much higher incidence among children who weighted 2500 gm or less at birth than among those who were heavier.

The relationship between maternal smoking and the incidence of congenital anomalies.

The incidence of congenital anomalies among the offspring of women who never smoked, of those who were past smokers, and of those who smoked during pregnancy was examined for 14,735 children who were members of the Kaiser Foundation Health Plan, a prepaid medical care program in the San Francisco East Bay Area of California. The children were offspring of mothers enrolled in the Child Health and Development Studies, a longitudinal study of pregnancy and the normal and abnormal development of offspring. There were no significant differences in the incidence of congenital anomalies when smokers (all dose levels combined) were compared with those who had never smoked. While there was a slight decrease in the incidence of congenital anomalies among light smokers, a significant difference was observed when the incidence of congenital anomalies among the offspring of women who smoked 20 or more cigarettes daily was compared with that observed among the offspring of women who never smoked. The increase in incidence associated with heavy smoking occurred predominantly among male offspring and was attributed to anomalies classified as moderate. The incidences of two specific anomalies, inguinal hernia and strabismus, were observed to increase significantly when the mothers had smoked during pregnancy. A significant decrease was observed in the incidence of moderate musculo-skeletal anomalies among the male offspring of smokers. The differing nature of the various associations noted stresses the complexity of underlying causal mechanisms.

Gross differences observed in the placentas of smokers and nonsmokers.

Gross placental characteristics of 7651 smokers and nonsmokers are compared in light of the previous finding that placentas of smokers are heavier for the weight of their fetuses than are those of nonsmokers. Subchorionic fibrin deposits and placental calcification are more prevalent in the placentas of smokers than in those of nonsmokers. While mean placental weights and placental weight distributions for light and heavy smokers combined do not differ from those of nonsmokers, other placental measurements do differ. Smokers have thinner, rounder placentas than nonsmokers and the distance from the edge of rupture of the membranes to the placental margin is reduced among smokers. These findings are discussed in relation to placental changes observed at high altitudes and complications of pregnancy that differ for smokers and nonsmokers.

PIP: A previous large (7651) prospective study of smokers and nonsmokers revealed that the placentas of smokers are heavier for the weight of the fetus than placentas of nonsmokers. To expand on these findings, the present investigation examined gross differences observed in the placentas of smokers and nonsmokers from this large study population. This analysis is based on 5699 single, white live births and 1952 single, black live births. Morphologic assessment of the placentas immediately after birth showed the following. Subchorionic fibrin deposits and placental calcification were more prevalent in smoker placentas than in nonsmoker placentas. However, mean placental weights and placental weight distributions for light and heavy smokers combined did not differ from those of nonsmokers. Other placental measurements were different: smokers had thinner, rounder placentas than nonsmokers and the distance from edge of membrane rupture to the placental margin was reduced among the smokers. The striking similarity of placental changes observed at high altitudes and in conjunction with maternal smoking gives strong support to the hypothesis that hypoxia is contributing to the differences observed.

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.