Irvin Emanuel

Perinatal factors and risk of breast cancer

A high level of endogenous estrogen in utero has been hypothesized to he a possible risk factor for breast cancer. We used information from two population-hosed case-control studies to investigate the relation between perinatal factors and risk of invasive breast cancer among women age 21–45 years (746 cases, 960 controls) and women age 50–64 years (401 cases, 439 controls). Breast cancer cases were ascertained through a population-based cancer registry, and controls were selected by random digit dialing. After adjustment for age, menopausal status, and maternal smoking, the birthweight-breast cancer association in women age 21–45 years followed a J-shaped curve, with women whose birthweight was less than 2,500 gm [odds ratio (OR) = 1.3; 95.4, confidence interval (CI) = 09–2.01 and 4,000 gm or more (OR = 1.7; 95% CI = 1.1–2.5) at increased risk. Women age 50–64 years who were 4,000 gm or more at birth appeared to be at slightly reduced risk of breast cancer (OR = 0.6; 95% CI = 0.3–1.1). With the exception of maternal smirking, there was little effect of other perinatal factors on breast cancer risk in either group. These results support the hypothesized association between intrauterine estrogen exposure and subsequent risk of breast cancer.

Intergenerational studies of human birthweight from the 1958 birth cohort. 1. Evidence for a multigenerational effect

Objective To investigate possible multigenerational influences on birthweight.

Early-life risk factors and the development of Alzheimer's disease

Objective: To investigate the association of early-life factors with AD. Background: The early-life environment and its effect on growth and maturation of children and adolescents are linked to many adult chronic diseases (heart disease, stroke, hypertension, and diabetes mellitus), and these effects are also linked to maternal reproduction. AD may have an early-life link. The areas of the brain that show the earliest signs of AD are the same areas of the brain that take the longest to mature during childhood and adolescence. A poor-quality childhood or adolescent environment could prevent the brain from reaching complete levels of maturation. Lower levels of brain maturation may put people at higher risk for AD. Methods: In a community-based case-control study (393 cases, 377 controls), we investigated the association of early-life factors and AD. Early-life variables include mother’s age at patient’s birth, birth order, number of siblings, and area of residence before age 18 years. Patient education level and apolipoprotein E (APOE) genotypes were also included in the analysis. Results: Area of residence before age 18 years and number of siblings are associated with subsequent development of AD. For each additional child in the family the risk of AD increases by 8% (OR = 1.08, 95% CI = 1.01 to 1.15). More controls compared with cases grew up in the suburbs (OR = 0.45, 95% CI = 0.25 to 0.82). APOE ε4 and the patient’s education level did not confound or modify the associations. Conclusions: The early-life childhood and adolescent environment is associated with the risk of AD.

Maternal health during childhood and later reproductive performance.

Literature concerning the relationship between the health of mothers during their own chilhood and subsequent reproductive performance is reviewed. The author concludes that there is substantial evidence of an indirect nature that intergenerational factors are important in several problems associated with pregnancy outcome. The geographic focus is worldwide.

Intergenerational studies of human birthweight from the 1958 birth cohort.

OBJECTIVE To ascertain whether maternal twinning influences the previously described association between the birthweight of singleton mothers and their infants. DESIGN AND SUBJECTS The association between the birthweight of singleton parents and their offspring and that between twin parents and their offspring was compared using data from the 23-year-old sample of the 1958 British national birth cohort. The numbers available for full comparison were 1027 female and 611 male singleton cohort members, and 26 female and 17 male twin cohort members and their first singleton livebirths. RESULTS Of the mothers who had been twins, half had been of low birthweight, and overall their mean weight was 700 g less than that of their singleton counterparts. Nevertheless, the mean birthweight of babies of twin mothers was 133 g, and of twin fathers 94 g, greater than of babies of corresponding singletons. For female, but not male, parents this difference persisted after adjustment for confounding variables. CONCLUSIONS We suggest two possible reasons for the difference between the weight of babies of twin and singleton mothers. Firstly, the growth of twins becomes retarded late in pregnancy, possibly after a period critical in determining long-term reproductive effects. Secondly, the twin survivors were of higher birthweight than the original twin cohort, whilst the singleton survivors were more representative of all singleton births, thus introducing a possible bias.Objective To ascertain whether maternal twinning influences the previously described association between the birthweight of singleton mothers and their infants.

Induced abortion and subsequent outcome of pregnancy in a series of American women.

We studied the effect of induced abortion on outcome of subsequent pregnancy in a sample of 4896 parturients in Seattle, Washington, from July, 1972, through June, 1976. We used a matched-pair analysis for 571 women with histories of prior abortions. In addition to analyses involving all women with histories of induced abortions, separate analyses were done for 97 black women and 277 primiparas. Histories of prior induced abortions were not related to low birth weight, premature delivery, stillbirth, neonatal death, miscarriage or congenital malformations in subsequent pregnancies. The termination procedure and weeks of gestation at time of termination were not related to the later occurrence of low birth weight or premature delivery.

Intergenerational Factors in Pregnancy Outcome

In general, clinicians and epidemiologists studying reproductive outcomes seem to regard pregnancy merely as an acute situation lasting about 280 days. This common idea places attention primarily on events occurring during pregnancy itself, such as exposure to infectious and chemical agents, physiological and anatomical abnormalities, inadequate diet, abnormal weight gain, pregnancy-induced hypertension, abruptio placenta, and placenta previa. As a result there has been relatively little interest in intrinsic maternal host factors, with some exceptions such as maternal diabetes and other overt maternal chronic diseases. This contrasts with epidemiological studies of various chronic adult diseases, such as hypertension, coronary disease, and various cancers, where the disease is considered at least partly to be related to life-style factors accumulated over a long period of time. There is now substantial evidence that important maternal host factors that influence reproductive outcome are present by the time a woman’s first pregnancy occurs, and that some of these host factors are the end result of long-term processes probably occurring over more than one generation.

Intergenerational Factors in the Etiology of Anencephalus and Spina Bifida

To test the hypothesis that events and conditions early in womens lives influence their Future risk of producing babies with anencephalus and spina bifida, a case‐control study compared mothers of affected infants with mothers whose infants were normal.

ACCELERATED AGEING IN YOUNG MOTHERS OF CHILDREN WITH DOWN'S SYNDROME

Abstract For decades a consistent and dramatic increase in the incidence of Downs syndrome with increasing maternal age has been reported. While this relationship has overshadowed all other epidemiological findings, its significance in the aetiology of Downs syndrome has not yet been clarified. It is suggested that the underlying importance of this age relationship pertains to the process of biological ageing and its influence on the reproductive process. Mothers who give birth to a child with Downs syndrome at a chronologically early age may, in some respects, be characterised by an acceleration of the biological ageing process. In support of this hypothesis is the finding of increased prevalence of grey hair in young mothers of children with Downs syndrome. Furthermore, this hypothesis is consistent with previously published data on the biological characteristics of mothers of affected children.

Respiratory distress syndrome and maternal birth weight effects.

Objective To study traditional risk factors and the intergenerational risk factor maternal low birth weight (LBW) for respiratory distress syndrome (RDS) in infants in multiple ethnic groups. Methods The population-based database consists of hospital records linked to Washington state maternal and infant vital records. Four racial-ethnic groups were studied, whites, blacks, Native Americans, and Hispanics. Poisson regression models were used to estimate relative risks of various factors for RDS. Results Rates for RDS were whites 1.2%, blacks 1.9%, Native Americans 1.3%, and Hispanics 1.0%. Maternal LBW was associated with increased relative risk (RR) for RDS in whites (2.6, 95% confidence interval [CI] 1.6, 4.2) and blacks (3.3, 95% CI 1.9, 5.6) for infants born vaginally. Compared with mothers of normal infants, birth weights of mothers of infants with RDS and delivered vaginally were significantly lower in whites, blacks, and Native Americans. The association of maternal LBW with RDS persisted in blacks even when multiple risk factors were added to the model (RR 2.4; 95% CI 1.1, 5.1). Conclusion The association of maternal LBW with RDS is probably due in part to the association of maternal LBW with infant LBW and preterm birth. The strong persistent association of maternal LBW with RDS in blacks suggests that improvement of perinatal outcomes in that group will require improvement of long-term birth weight distribution.