In utero exposure to famine and subsequent fertility: The Dutch Famine Birth Cohort Study

OBJECTIVES: We hypothesized that if prenatal caloric restriction due to nutritional deprivation had affected development of the organs responsible for producing and regulating female reproductive hormones, a woman's fertility would be impaired. METHODS: Women born in Amsterdam from August 1, 1944, through April 15, 1946, a period encompassing a severe 5-month famine, were identified (n = 700; 85% response rate). Date of birth and vital status of all offspring were ascertained by home interview between 1987 and 1991. Famine exposure was inferred from the mother's date of birth. RESULTS: Of the study participants, 74 (10.6%) had no children. The remainder reported 1334 off-spring (1294 singletons, 20 pairs of twins), of whom 14 were stillborn and 22 died in the first 7 days of life. There was no detectable effect of famine exposure on age at menarche, the proportion having no children, age at first delivery, or family size. An excess of perinatal deaths occurred among offspring of famine-exposed women, particularly those exposed in their third trimester. CONCLUSIONS: Acute famine exposure in utero appears to have no adverse consequences for a woman's fertility. The excess perinatal mortality in the second generation is unexplained and should be confirmed by other studies.     

Decrease in calcitonin-containing cells in truncus arteriosus

Parkinson's disease mortality was analyzed in Italy for the period from 1951 through 1987. The adjusted mortality was 4.27 and 2.77/100,000 population, respectively, for men and women. Adjusted rates increased in both sexes (63% increase in men and 80% in women in 1983 through 1987 vs 1951 through 1952). Age-specific mortality increased in subjects aged over 75 years and decreased in those under 64 years. The analysis by birth cohorts demonstrated higher rates in the cohorts born between 1890 and 1910 than in those born before and after that period. Even if these changes in Parkinson's disease mortality might reflect better case ascertainment and the increase of life expectancy of patients with Parkinson's disease, there is some evidence that the temporal variation is associated with the changing experiences of different birth cohorts.     

Maternal sensitivity during infancy and subsequent life events relate to attachment representation at early adulthood.

A prospective longitudinal research study of 86 prematurely born children from birth to age 18 years provided empirical evidence for continuity from infancy experience to representations of attachment at age 18 years. Young adults whose representation of attachment was dismissing had been objectively observed during infancy, 16–17 years earlier, to receive less sensitive maternal care than those infants who were later judged at early adulthood to have secure or preoccupied representations. Infancy experience alone did not differentiate young adults with secure representations from those with preoccupied representations. Rather, adverse life events through age 12, particularly parental divorce, reduced the likelihood of secure representations and increased the likelihood of preoccupied representations. The absence of adverse life events did not increase the likelihood of security for those who had not experienced early sensitive caregiving. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Characterization and amino acid sequence analysis of a new oxyimino cephalosporin-hydrolyzing class A beta-lactamase from Serratia fonticola CUV

Recent follow-up studies have provided convincing evidence that the foundations of chronic airflow obstruction (CAO) are laid in utero and early childhood. Men born in Hertfordshire and Derbyshire, England, were more likely to have impaired lung function at 60-70 years of age if they had been lighter at birth and if they had had lower respiratory tract infection (LRTI) in the first 2 years of life. Furthermore, they were more likely to have died from chronic obstructive pulmonary disease if they had been lighter at 1 year of age. These findings suggest that impairment of pulmonary growth in utero and early childhood, as a consequence of undernutrition and LRTI, plays an important part in the development of CAO in late adult life. This may be of particular importance for the future respiratory health of developing nations as the additive effects of smoking take hold.     

The Dutch famine and schizophrenia spectrum disorders

In the Dutch Hunger Winter at the end of World War II a combination of circumstances created the conditions of a natural experiment. Unlike other famines, the Dutch famine struck at a precisely circumscribed time and place, and in a society able to document the timing and severity of the nutritional deprivation as well as the effects on fertility and health. Because the Dutch maintained comprehensive military and health records, it was possible to compare the incidence of neurodevelopmental disorders in adulthood for birth cohorts exposed versus those unexposed to prenatal famine. We have conducted several studies guided by the hypothesis that prenatal micronutrient deficiencies can cause neurodevelopmental schizophrenia or related personality disorders. In this paper we shall summarize our previous work and combine the outcome data of the different studies. Early prenatal famine was found to be specifically and robustly associated with each of three conditions: (1) congenital anomalies of the central nervous system, (2) schizophrenia, and (3) schizophrenia spectrum personality disorders. We found that the greatest increase in the risk of schizophrenia spectrum disorder- schizophrenia plus spectrum personality disorder- occurred among males born in the famine cities in December 1945 (relative risk = 2.7; 95% confidence interval = 1.5-5.1). Persons born in December 1945 were generally conceived at the absolute peak of the famine (March-April 1945). In the hope that the associations we have found may offer clues to the aetiology of schizophrenia, we are currently tracing and examining the cases of schizophrenia after prenatal exposure to famine.     

BRCA1-positive patients are small for gestational age compared with their unaffected relatives

The BRCA1 gene is thought to exert its main function early in life. We, therefore, studied the effects of BRCA1 mutations on birth weight and birth length. This was carried out by comparing 33 women with and without mutations. Birth weight and length were obtained from a self-administered questionnaire. BRCA1 mutations carriers had a significantly lower birth weight (P = 0.0041) compared with non-carriers, after adjustment for gestational age. They were also significantly shorter at birth compared with their unaffected relatives (P = 0.0060), after adjustment for gestational age. The BRCA1 gene thus seems to influence the carriers in utero. The findings could imply that humans heterozygotic for the BRCA1 mutations may be influenced by the mutations during development in utero.     

The development of allergy in high-risk children

BACKGROUND: It is uncertain as to what extent the development of allergic disease in childhood is predictable during early infancy. A number of environmental factors have been suspected of increasing the risk of acquiring allergy, but the evidence is conflicting. OBJECTIVE: To observe the development of atopy and allergic disease in a cohort of high-risk children so as to determine the importance of certain environmental factors and to study the relationship between early and later manifestations. METHODS: A cohort of infants, all at high risk of allergy, was followed up from birth to the age of 7 years. In half, selected at random, cow's milk protein was avoided for 4 months. Skin-prick tests were performed and serum IgE measured in infancy and at 7 years, when an AlaTOP test was also performed. RESULTS: Skin sensitivity to egg in the first year of life was strongly associated with eczema, asthma, mite sensitivity and serum IgE at the age of 7 years, when mother's atopic history was associated with AlaTOP status, father's atopic history with skin sensitivity, and male sex with both. Maternal smoking during pregnancy was associated positively with IgE at 3 months and negatively with skin sensitivity at 7 years. The development of allergy was unrelated to infant feeding method or number of older siblings. CONCLUSION: Allergic disease in childhood is to a large degree determined before birth or during infancy.     

Twenty-year dynamics of serum cholesterol levels in the middle-aged population of eastern Finland

BACKGROUND: In cross-sectional analyses, serum cholesterol levels differ among different age groups. However, secular time trends in cholesterol levels can be seen across age groups in a population. A birth cohort analysis provides useful information on the combined effect of age and time on changes in serum cholesterol levels. OBJECTIVE: To analyze the 20-year dynamics of serum total cholesterol levels in relation to age, sex, birth cohort, time period, mortality rate, and changes in the intake of saturated fats. DESIGN: Cross-sectional measurements of serum total cholesterol levels in five independent population surveys done in 1972, 1977, 1982, 1987, and 1992. SETTING: Kuopio and North Karelia provinces in eastern Finland. PATIENTS: Random sample of 16,711 men and 17,542 women 25 to 64 years of age. Persons in the oldest birth cohort were born in 1913; persons in the youngest birth cohort were born in 1967. MEASUREMENTS: Total serum cholesterol levels and daily intake of dietary fat. RESULTS: Between 1972 and 1992, mean cholesterol levels decreased with time in each age group and for both sexes. According to the cross-sectional data, cholesterol levels increased with age and increased more steeply in women than in men. Contrary to these data, cholesterol levels in birth cohorts did not increase with age. Cholesterol levels did not change at all within birth cohorts of women and started to decrease after 45 years of age in birth cohorts of men. Cholesterol levels in the youngest birth cohorts (persons 25 to 29 years of age) entering the study each study year were markedly lower than levels in the same age group in the previous survey of risk factors. Daily intake of saturated fat decreased markedly between 1972 and 1992. Most of this decrease could be explained by change in intake of liquid dairy products and spreadable fats. In both sexes, changes in saturated fat intake were correlated with the time period, whereas the association with age was weak. CONCLUSIONS: In this Finnish population, total serum cholesterol levels are more closely associated with birth cohort than with age. Changes in dietary intake of saturated fat over time may account for changes in cholesterol levels. This finding suggests that community-based strategies for preventing cardiovascular disease can affect most of the population.     

Effect of long-term lead exposure on hematology, blood biochemistry, and growth curves in monkeys

A total of 90 monkeys (Macaca fascicularis), comprising four study cohorts born over a seven-year period, were hand reared and dosed orally with lead or vehicle according to one of several protocols, in most cases from birth to 9-14 years. Blood lead concentrations of lead-exposed groups ranged from 10 to 90 micrograms/dl depending on dose and age. Routine hematology and blood biochemistry analyses were performed regularly. Comparison of treated groups at various ages to the appropriate control group revealed no strong indication of lead-related effects. In addition, body weight increase was modeled from days 30-3500 of age in subset of this larger group, including 52 monkeys exposed to vehicle or lead during development according to one of four regimens: vehicle, lead from birth onward, lead to 400 days of age, or lead beginning at 300 days of age. No effect of lead on body weight was found. These results suggest that lead exposure beginning early in life and continuing for as long as 14 years resulted in no overt toxicity, as measured by these parameters.     

Human physiological adaptability through the life sequence

Changes in organ function from birth to old age were investigated from published data. In essence, the observations of Shock and colleagues on maximal breathing capacity, vital capacity, glomerular filtration rate, renal plasma flow, basal metabolic rate (BMR), ulnar nerve conduction velocity, cardiac index, and intracellular water (ICW) for the age period 30 to 85 years were extended to the time of birth. There were two principal findings. First, with the exception of BMR and ICW, these functional indices increased from a low point at birth to a maximum between 3 and 20 years of age and then after 30 years declined progressively to 85 years; BMR declined from a maximum in infancy and ICW peaked at about 30 years and then declinded. Second, the coefficient of variation increased regularly from birth to old age. Because the peak of organ function coincided with the period of minimal mortality, the curve of organ function across the life sequence was considered to represent changes in adaptive capacity. Supporting evidence from studies of physical fitness, thermoregulation, and seasonal change of mortality was considered. It was concluded that these shifts in adaptive capacity between birth and old age were fundamental baselines for investigations of the epidemiology of health.     

A prospective cohort study on the survival experience of under five children in rural western India

OBJECTIVE: To study the role of birth weight, nutrition, immunization and other medical as well as social factors in determining child survival. DESIGN: A prospective cohort study. SETTING: 45 villages in Shirur Development Block in Pune District in Maharashtra. METHODS: A cohort of 4129 children were followed from birth till 5 years of age. Weight and length/height of the child was measured at birth and at 3 monthly home visits. Information was also obtained on common childhood morbidities, immunization status and other bio-medical factors. Cause of death was ascertained by verbal autopsy. RESULTS: The neonatal, infant and underfive mortality was rates were estimated to be 37, 60 and 79 per 1000 live births, respectively. Diarrhea and ARI contributed to the major mortality burden. The Kaplan Meier Survival curve showed a sharp fall in the neonatal period, a less rapid decline in the post-neonatal period followed by a marginal fall in the post-infancy period till 5 years age. Girls had a better survival in the early neonatal period but the trend reversed in the late neonatal period. Normal birth weight children had better survival curves compared to low birth weight children. Survival improved with increasing birth order. Multivariate analysis revealed that birth weight, immunization status, and mother's and child's nutritional status influenced infant and under five mortality. CONCLUSION: Birth weight continues to exert its influence not only on survival/mortality in early life but even as late as 5 years of age. Strategies to improve child survival should include immunization and breastfeeding.     

Prophylactic psychotherapy of addiction (author''s transl)

In a cohort of 50,282 pregnancies 19 children with cardiovascular defects were born to 1042 women who received female hormones during early pregnancy (18.2 per 1000). Among 49,240 children not exposed in utero to these agents there were 385 with cardiovascular malformations (7.8 per 1000). Six children with cardiovascular defects were born to a sub-group of 278 women who used oral contraceptives during early pregnancy (21.5 per 1000). After the data were controlled for a wide variety of potentially confounding factors by multivariate methods, the association between in utero exposure to female hormones and cardiovascular birth defects was statistically significant.     

Cohort differences in cognitive aging and terminal decline in the Seattle Longitudinal Study.

Life span researchers have long been interested in how and why fundamental aspects of human ontogeny differ between cohorts of people who have lived through different historical epochs. When examined at the same age, later born cohorts are often cognitively and physically fitter than earlier born cohorts. Less is known, however, about cohort differences in the rate of cognitive aging and if, at the very end of life, pervasive mortality-related processes overshadow and minimize cohort differences. We used data on 5 primary mental abilities from the Seattle Longitudinal Study (Schaie, 2005) to compare both age-related and mortality-related changes between earlier born cohorts (1886–1913) and later born cohorts (1914–1948). Our models covary for several individual and cohort differences in central indicators of life expectancy, education, health, and gender. Age-related growth models corroborate and extend earlier findings by documenting level differences at age 70 of up to 0.50 SD and less steep rates of cognitive aging on all abilities between 50 and 80 years of age favoring the later born cohort. In contrast, mortality-related models provide limited support for positive cohort differences. The later born cohort showed steeper mortality-related declines. We discuss possible reasons why often reported positive secular trends in age-related processes may not generalize to the vulnerable segment of the population that is close to death and suggest routes for further inquiry. (PsycINFO Database Record (c) 2011 APA, all rights reserved)     

Cohort differences in disability and disease presence

Using the National Health Interview Surveys conducted from 1982 through 1993, this article examines cohort patterns in disability and disease presence for adults born between 1915 and 1959, at ages ranging from 30 to 69 years. In general, disability decreases for cohorts born between 1916 and the early 1940s (for men) or the early 1950s (for women), but begins to increase for cohorts born after those dates. Later-born cohorts have significantly lower levels of some diseases, most importantly cardiovascular diseases, arthritis, and emphysema. However, some diseases and conditions are more prevalent in later-born cohorts: asthma, musculoskeletal disorders, and orthopedic impairments. The results presented here indicate that adults born in the late 1940s and 1950s will be in better cardiovascular health but may be in worse musculoskeletal condition when they enter old age compared with current cohorts of older persons.     

Traumatic subdural pneumocephalus causing rise in intracranial pressure in the early phase of head trauma: report of two cases

The mortality rate is high and prognosis is worse among new-borns with prenatal diagnosis of heart malformation, mainly due to factors such as its association with other malformations, and a range of more severe diseases probably resulting from the predominance of the obstetric use of the four chamber view. In this study we retrospectively assessed the range of cardiopathies diagnosed by foetal echocardiography and their evolution, compared with previous years. From January 1994 to December 1995, 1173 foetal echocardiograms were performed at a gestation age of 24 weeks. Sixty-one foetuses (5.2%) had cardiac anomalies, structural in 56 and arrhythmia in 5. The risks and indications were maternal in 37%, foetal in 31%, familial in 17% and environmental in 15%. Three were false negatives (VSD:2; truncus arteriosus: 1). Five died in utero, and 18 were assessed after birth with a mean gestational age of 37 weeks and birth weight of 3 Kg, a caesarean section was performed in 9. All but one were born in central hospitals. Six children were operated on. Two children died, one after surgery. Compared with the four previous years of activity, indication due to foetal risk rose from 6 to 31%, the number of cases diagnosed with heart disease increased from 14 to 30 per year, and the mortality decreased from 59 to 11%. Despite this, we still observe that the vast majority of new-borns who are hospitalised due to a severe heart disease had no prenatal diagnosis, indicating the need to continue our educational policy in this field.     

Statistical analysis of data derived from clinical variables of plaque and gingivitis

BACKGROUND: Historical cohort studies in England have found that impaired fetal growth and lower respiratory tract infections in early childhood are associated with lower levels of lung function in late adult life. These relations are investigated in a similar study in Scotland. METHODS: In 1985-86 a follow up study was carried out of 1070 children who had been born in St Andrew's from 1921 to 1935 and followed from birth to 14 years of age by the Mackenzie Institute for Medical Research. Recorded information included birth weight and respiratory illnesses. The lung function of 239 of these individuals was measured. RESULTS: There was no association between birth weight and lung function. Pneumonia before two years of age was associated with a difference in mean forced expiratory volume in one second (FEV1) of -0.39 litres (95% confidence interval (CI) -0.67, -0.11; p = 0.007) and in mean forced vital capacity (FVC) of -0.60 litres (95% CI -0.92, -0.28; p < 0.001), after controlling for age, sex, height, smoking, type of spirometer, and other illnesses before two years. Similar reductions were seen in men and women. Bronchitis before two years was associated with smaller deficits in FEV1 and FVC. Asthma or wheeze at two years and older and cough after five years were also associated with a reduction in FEV1. CONCLUSIONS: The relation between impaired fetal growth and lower lung function in late adult life seen in previous studies was not confirmed in this cohort. The deficits in FEV1 and FVC associated with pneumonia and bronchitis in the first two years of life are consistent with a causal relation.     

Functional abilities at age 4 years of children born before 29 weeks of gestation

OBJECTIVES: To assess the rate of impairment and disability among babies born very preterm and to investigate the association between such impairment and gestational age at birth. DESIGN: Cohort study of a geographically defined population of babies. SETTING: Oxford Regional Health Authority. SUBJECTS: All babies born alive before 29 weeks of gestation to mothers resident in the region during 1984-6. MAIN OUTCOME MEASURES: Survival rates and rates of impairment and disability among survivors at the age of 4 years. RESULTS: Of the 342 babies, half (170) survived to be discharged home. Of the 164 survivors to age 4 years, 153 (93%) were assessed. A total of 35 (23%; 95% confidence interval 16% to 30%) were severely disabled and only 54 (35%; 28% to 43%) were unimpaired. The risk of impairment and disability increased with decreasing gestational age at birth (p < 0.003). CONCLUSIONS: With the increasing survival rate among babies born before 29 weeks of gestation, we need urgently to establish reliable ways of monitoring the proportion of survivors who have a disability.     

Testicular cancer risk and maternal parity: a population-based cohort study

The aim was to study, in a population-based cohort design, whether first-born sons run a higher risk of testicular cancer than later born sons; to investigate whether this difference in risk was affected by birth cohort, age of the son, maternal age, interval to previous delivery and other reproductive factors; and, finally, to evaluate to what extent changes in women's parity over time might explain the increasing incidence of testicular cancer. By using data from the Civil Registration System, a database was established of all women born in Denmark since 1935 and all their children alive in 1968 or born later. Sons with testicular cancer were identified in the Danish Cancer Registry. Among 1015994 sons followed for 15981 967 person-years, 626 developed testicular cancer (443 non-seminomas, 183 seminomas). Later born sons had a decreased risk of testicular cancer (RR = 0.80, 95% CI = 0.67-0.95) compared with first-born sons. The RR was 0.79 (95% CI = 0.64-0.98) for non-seminomas and 0.81 (95% CI = 0.58-1.13) for seminomas. There was no association between testicular cancer risk and overall parity of the mother, maternal or paternal age at the birth of the son, or maternal age at first birth. The decreased risk of testicular cancer among later born sons was not modified by age, birth cohort, interval to the previous birth, sex of the first-born child, or maternal age at birth of the son or at first birth. The increased proportion of first-borns from birth cohort 1946 to birth cohort 1969 only explained around 3% of an approximated two-fold increase in incidence between the cohorts. Our data document a distinctly higher risk of testicular cancer in first-born compared with later born sons and suggest that the most likely explanation should be sought among exposures in utero. The increase in the proportion of first-borns in the population has only contributed marginally to the increase in testicular cancer incidence.     

Retinal arteriovenous malformation with fluctuating vision and ischemic central retinal vein occlusion and its sequelae: 25-year follow-up of a case

A comparison was made of the outcome of 73 neonates born with their birth weight of 500-999 gm in National Taiwan University Hospital during the period between January 1, 1993 and December 31, 1996 (Period II), with the outcome of 21 such neonates born between April 1, 1988 and October 31, 1992 (Period I). Exclusion criteria included parental refusal for resuscitation, and major anomalies. Data were collected via a predetermined record sheet. The incidences of the extremely-low-birth-weight infants were 23/10,173 (0.23%) and 81/13,835 (0.59%) in Periods I and II, respectively. Early neonatal mortality rate was significant decreased in Period II (43% versus 14%). The limit of viability was improved from gestational age of 26 weeks or 700 gm to gestational age of 24 weeks or 600 gm. The incidence of neonatal morbidity (80% versus 50%) and total survival rate (48% versus 60%) have not changed significantly as seen in this limited number of cases. This study concluded that, with the introduction of exogenous surfactant and modern neonatal care, early neonatal survival rate and the limit of viability were improved.