Late paternity and stillbirth risk.

BACKGROUND: The role of paternal ageing on the incidence of some genetic diseases in offspring depends on the hypothesis that spontaneous mutations accumulate due to continuous cell divisions during spermatogenesis. We examined the effect of paternal age on the complex multifactorial character, stillbirth. METHODS: In 3,619,647 Italian singletons born in 1990-1996 we evaluated stillbirth risk as a function of paternal ageing by means of multiple logistic regression models, which included maternal age and family education, as categorical covariates and interactions. The categorical risk was estimated for mothers and fathers beyond threshold ages of 35 and 40 years, respectively. RESULTS: Stillbirth risk increases with paternal ageing in mothers > or =30 years old, and maternal age and family education modify the impact. In families with low education, the risk accounts for odds ratio (OR) 1.015 [95% confidence interval (CI) 1.01-1.02] in mothers aged 30-34 years, and for OR 1.032 (95% CI 1.02-1.04) in mothers aged > or =35 years; in families with higher education the risk accounts for OR 1.008 (95% CI 1.00-1.02) and OR 1.025 (95% CI 1.01-1.04), respectively, in mothers aged 30-34 and > or =35 years. In these latter families, for mothers aged <35 and fathers > or =40 years the risk accounts for OR 1.12 (95% CI 1.00-1.25). CONCLUSIONS: The effect of paternal ageing on stillbirth risk is revealed in mothers aged > or =30 years and is modified by family education. In mothers aged 30-34 years from families with high education, the increase imputable to paternal ageing might be indicative of a genetic component.

Changes in twinning rate: Italy 1950-1996.

BACKGROUND: In the wide-ranging debate about the potential monitors of population fertility, twinning rate has been considered a candidate. In the developed countries, a decline in spontaneous twinning rate began around 1950 and continued until the late 1970s. The decrease in mean maternal age at delivery and the number of children per family have been considered as possible reasons for the decrease. The rise in twinning rates, which began in the 1980s, is probably due to the spread of assisted reproduction, at least for older mothers. METHODS: The temporal trend in twinning rate and the relationship with maternal age at delivery and birth order in the Italian population were analysed. RESULTS: The recent increase in twinning rate can be mainly attributed to the recourse to assisted reproduction techniques, as demonstrated by the twinning frequency among older primiparae. The twinning rate recently observed in young mothers approximates to the value of the 1950s, which is assumed to represent a 'natural' fertility condition. CONCLUSIONS: On the assumption that twinning is an indicator of fertility, and hence of population fitness, the present data seem to suggest that natural fertility has been slightly increasing in the Italian population.

Sex differential patterns in perinatal deaths in Italy.

In industrialized countries, male excess is generally found in early deaths, despite the overall decrease in mortality. We studied the association between sex and some factors generally considered crucial for babies' survival, such as mother's age and education, birth order, and gestational age, in order to gain insight into the causes underlying the persisting higher vulnerability of male sex in early life. The analysis was performed on babies dying during the perinatal period. These were subdivided into those who were stillborn and those who died during the first week of extrauterine life. A higher male excess among babies dying during the neonatal period than among those who were stillborn was always found in all classes of all factors. The finding of such generalized male overmortality in the early extrauterine period of life, together with the patterns shown by the temporal sex ratio in stillbirths and in early deaths, supports the hypothesis of a postponement of male risk from late fetal into neonatal life.

Sex ratio at reproductive age: changes over the last century in the Italian population.

The radical improvement in living conditions experienced in Italy during the last century caused a reduction in male extra-mortality during the prereproductive years. As a consequence, a progressive increase in the sex ratio at the beginning of the reproductive age (15-19 years) occurred, so that in recent times the sex ratio in the young adult population has approached the almost constant value of 1.06 observed at birth. We calculated that the sex composition would be the same in newborns and in young adults in about one generation: obviously, we have to assume that the sex differentials in mortality and migration are constant over time. The 1:1 equilibrium between sexes, which maximizes reproductive success, occurred in the 15-19 age group at the beginning of the century and shifted to the 30-35 age group in the 1990s. We compared the 1993-1995 sex ratios in different age groups in European Union countries and observed that in Italy as well as in other Mediterranean countries the numerical equality between sexes is reached at 30-35 years of age, while in north-central Europe it is reached later, approximately at the end of reproductive life.

Natural selection and reproductive behavior in Italy, 1930-1993.

We studied the relaxation of natural selection affecting the newborn population in Italy between 1930 and 1993 due to the decrease in the stillbirth (mortality) rate and the simultaneous changes in women's reproductive behavior (strategies). Results show that, apart from a drastic overall reduction, the stillbirth rate has varied among different groups of neonates. The present stillbirth rate of less than 5 per thousand, observed in 8 of the 20 phenotypic classes defined on the basis of maternal age at delivery and neonate birth order, most likely represents an unavoidable biological or genetic cost. A 9 per thousand stillbirth rate, about twice the potential minimum, exists among neonates born to women delivering at advanced age (> or = 35): the risk they face at the first or, in adverse living conditions, the fourth pregnancy could, however, be decreased by a policy aimed at countering the tendency to delay maternity and improving antenatal care in economically disadvantaged areas of the country.

Reduced male births in major Italian cities.

The downward trend in the sex ratio at birth that has occurred in several countries over the last 30 years was postulated to signal a deterioration in environmental conditions, particularly unfavourable for male conception and fetus survival. In Italy, in contrast, an upward trend has been observed. Assuming that exposure to reproductive hazards occurs mainly in the major cities, we contrasted the 1970-1995 sex ratio trend for the metropolitan area (defined as the four provinces containing the largest Italian cities) with that for the non-metropolitan area (defined as the rest of the country). In the metropolitan area, the proportion of live-born males showed a negative trend significantly different from the positive trend observed in the rest of the country. Moreover, the stillbirth rate among males was constantly and significantly higher in the metropolitan area. Our results suggest that the decrease in the sex ratio at birth observed in the metropolitan area might be interpreted as a signal of increasing exposure to hazardous environmental conditions for male conceptions and neonates.

Risks of preterm delivery and association with maternal age, birth order, and fetal gender.

The risk of preterm delivery in a recent sample (1990-1994) of Italian liveborns was examined, taking into account child birth order, and maternal age and education in addition to the fetal gender. Univariate analyses showed that a higher risk was associated with male than female babies, with first- than second-born children, with older mothers, and with less educated mothers. The relative weights of the factors examined were evaluated through logistic regression analyses and the highest and the lowest risks were found to be associated with advanced maternal age and male fetal gender respectively. Our findings therefore suggest that biological factors associated more with advanced maternal age than with the male gender of the fetus may influence premature onset of labour.

Sex ratio and parental age gap.

We tested the hypothesis that a large age difference between parents can shift the sex ratio at birth in favor of males, as Manning et al. (1997) suggested in their analysis of English and Welsh data. Among children born in Lombardy (northern Italy) in 1990 and 1991, we observed an anomalous excess of males born to a particular subsample of parents with a wide age gap (> 15 yr) between them; in the overall sample the father-mother age gap does not significantly contribute to the determination of the child's sex.

Normal values of overnight albumin excretion rate in a sample of healthy Italian children and adolescents.

The aim of this study was to define normal values of albumin excretion rate (AER) in young people. We measured overnight timed AER (tAER, microgram/min) by a double-antibody radioimmunoassay in 281 healthy Italian children and adolescents (160 M and 121 F), aged 7-19 years. The frequency distribution of tAER deviated from normality, therefore percentiles were used: median and 95th percentile were 2.3 and 6.9 micrograms/min respectively. Log transformed tAER was not related to age or pubertal stage. "Borderline" AER refers to AER higher than normal 95th percentile in non-diabetic subjects but lower than microalbuminuria threshold level. Incipient nephropathy, expressed as "borderline" AER, has been reported in adult IDDM patients, and can be reversed by improving metabolic control. Because incipient diabetic nephropathy may be present in young IDDM patients without microalbuminuria, screening for AER should be recommended for pediatric diabetic patients, also before puberty, in order to detect early renal damage and the "borderline" AER state.

Radiologic progression in patients with juvenile chronic arthritis treated with methotrexate.

We investigated the rate of radiologic progression, as measured by carpal length, in 26 children with juvenile chronic arthritis who were treated with methotrexate. After 2 years of treatment, the carpal length was significantly more deteriorated in nonresponders in both the "better" wrist (P = .001) and the "worse" wrist (P = .005). These results show that methotrexate may have a "disease modifying" potential in juvenile chronic arthritis.

Natural selection in industrialized countries: a study of three generations of Italian newborns.

We have studied the impact of natural selection on the Italian population, analysing the relationship between stillbirth and three related variables: birth weight, birth order and maternal age. A progressive relaxation of selection with time has been demonstrated by the reduction of the Haldane index calculated with respect to the three variables.

Heterogeneous effects of natural selection on the Italian newborns.

We have studied the impact of natural selection through stillbirth on the Italian population, taking into account the socio-economic heterogeneity of the country. The results suggest that older age at delivery and lower cultural level of the mothers, indicators of critical biological and socio-economic conditions, even at present increase stillbirth risk. Moreover, in the less favourable environment of the southern regions, selection is still sex-specific.

Early selection and sex composition in Italy: a study at the regional level.

We have chosen four Italian regions with different degrees of industrialization and socioeconomic levels to study environmental differences in the sex ratio. The improvement in living and sanitary conditions during the last century has led to a progressive reduction in early male extramortality, and the sex ratio at birth has been almost unchanged at least to the first year of life and probably up to reproductive age. To investigate whether socioeconomic, cultural, or biological factors still influence the sex ratio at birth, we studied the stillbirth rate and the relations between newborn viability and sex composition as a function of maternal age and educational level. Our results suggest that in less favorable environments early selection against male newborns is almost twice that against female newborns when the mothers are the least favored for socioeconomic status, cultural level, and biological conditions (older than 39 years).

Factors affecting the sex ratio in humans: multivariate analysis of the Italian population.

Several studies have shown that the human secondary sex ratio is affected by a wide range of biological and environmental factors. Here, we describe a partitioning of the sex ratio variability as observed in the Italian population over the last two generations. This period has seen drastic changes in the environmental conditions of Italy. As a consequence, demographic and biological variables that can affect the sex ratio have also changed dramatically. In an attempt to isolate any specific effect, we used a stepwise multiple regression to analyze the covariation over time of the sex ratio and of relevant parameters, such as stillbirth rate, maternal age, firstborn proportion, and birth order. The results show that a quadratic function of the firstborn proportion and mother's age is a fairly good predictor of sex ratio values.

Sex ratio and selection by early mortality in humans: fifty-year analysis in different ethnic groups.

We studied the sex ratio (M/F) in representative populations of the main human ethnic groups, namely, US whites, US blacks, and Japanese. The data cover a period of over 50 years. For intra-ethnic comparison, we included analogous data on Italians. The populations studied show heterogeneous patterns: the US white and Italian populations are the most similar, with no drastic variations in live-birth sex ratio throughout the period. Comparison of sex ratio data for live-borns and 1-year-old infants yields a similar pattern in all groups; the differences between the two sex ratio values are constantly reducing. It can be hypothesized that in the near future the sex ratio observed at birth will be maintained up to reproductive age. If this value is stabilized by natural selection, as is likely, new relationships between the sex ratio and selection are expected to evolve in the populations of developed countries.

Sex ratio and natural selection in humans: a comparative analysis of two Caucasian populations.

In the course of the last century industrialized countries have experienced significant changes in mortality rates. Since the sex ratio of a population may be considered a function of, among other factors, differential mortality in the two sexes, it is expected to correlate with changes in sex-specific mortality rates. In this paper secular changes in the sex ratio at birth and after the action of relevant components of early selection (stillbirth, mortality within the first month and within the first year of life) have been studied in the Italian and in the USA White populations. The results can be summarized as follows. (i) In the past, extra male-specific mortality appeared to reduce the relatively large values of the sex ratio observed at birth, and this held true in both populations. (ii) In more recent times, male-specific mortality has been decreasing in all age groups, and the sex ratios before and after the action of early selection now tend to identical values. Therefore, it can be envisaged that in the near future the sex ratio observed at birth will be maintained up to the reproductive age. If the reproductive value is stabilized by natural selection, as is likely, new relationships between sex ratio and selection may be expected to develop in a relatively short time.

Genetic analysis of human obesity in an Italian sample.

An analysis of the genetic factors in obesity has been carried out on a sample of nuclear families from Aosta (N. Italy). The families consisted of the parents and sibs of all elementary school children considered to be obese during a preliminary screening and a similar sample of non-obese children and their nuclear families. The numbers of such families were 67 and 112, respectively. Several tests were applied in order to examine the genetic contribution to obesity, and in particular to investigate the presence of a dominant major gene. Our conclusions are that genetic factors are certainly present. Several analyses suggest the presence of a dominant major gene with weak effect.