Paola Astolfi

Birthweight by gestational age in preterm babies according to a Gaussian mixture model

Objective  To provide a statistically sound criterion for identifying implausibly large birthweights for gestational age.

Paternal Age and Preterm Birth in Italy, 1990 to 1998

Background: Advanced paternal age has been reported to impair pregnancy outcome. Here, we investigated the association of advanced paternal age with preterm birth by using a very large national data set. Methods: We analyzed data from 1990 to 1998 on Italian firstborn singletons to mothers 20–24 and 25–29 years of age (n = 1,510,823). Odds ratios for overall preterm (<37 weeks’ gestation), very preterm (<32 weeks), and moderate preterm (32–36 weeks) births were evaluated through logistic regression models in paternal age classes (20–24, 25–29, 30–34, 35–39, 40–44, 45–49, 50+ years) after adjustment for confounders. Nonparametric regression models were used to fit the effect of paternal ageing on the incidence of very preterm births. Results: Odds ratios increased with paternal age more rapidly for very preterm than for moderate preterm births; among 45- to 49-year-old fathers, odds ratios for very preterm births reached 1.91 (95% confidence interval = 1.08–3.38) and 1.72 (1.25–2.36), respectively, in 20- to 24- and 25- to 29-year-old mothers. Conclusions: This study confirms that paternal age contributes to the risk of preterm birth. The effect is stronger on very preterm births but also influences moderate preterm births.

Correlation Between Father's Age and Husband's Age: A Case of Imprinting

Analysis of the data from the tenth Italian census shows that women born to older fathers tend to marry older men. The correlations between the ages of the father and the husband in various situations were always found to be positive and significant when the age of the woman and her educational level were held constant. Correlation coefficients are higher in rural and economically less developed areas. Behavioural imprinting is suggested as a possible explanation. (EXCERPT)

Frequency and coverage of trinucleotide repeats in eukaryotes.

In the aim to assess whether the tri-repeat shortage reported in vertebrates affects specific motifs, such as those causing neuromuscular diseases in man, we detected approximate di-, tri- and tetra-repeats (STR) longer than 25 bases in human chromosomes 21 and 22, and in some model organisms (M. musculus, D. melanogaster, C. elegans, A. thaliana and S. cerevisiae). We found that overall STR are more represented in mouse and in man than in the other organisms. However, tri-repeats are less represented than di- and tetra- in man and mouse, but show intermediate values between di- and tetra- in the other organisms. In man, ACG shows the lowest both frequency and coverage, ATC the highest coverage and AAT the highest frequency. In general, coverage and frequency of tri-repeats are linearly related, except for ACC, ATC, AAG, AGG motifs in man and AAG, AGG in mouse, which exhibit unexpectedly long repeats. Often their copy numbers exceed that found responsible for the dynamic mutations, set at around 40. The shortage in frequency and coverage of tri- vs. di- and tetra-repeats observed in man and mouse can be ascribed to a subset of the remaining tri-repeat motifs, but among them those recognized as dynamically mutable (AAG, AGC and CCG) are not the least represented. Possible constraints in tri-repeat expansion seem to be structural and conserved along the evolutionary scale: a motif-specific relaxation of the relevant controls may be responsible for the occasional expansions found in mouse and man.

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.

Paternal HLA genotype and offspring sex ratio.

AbstractFor twenty years, W.H. James has been proposing that the sex hormone level of both parents could control at least a quota of the secondary sex ratio variation at the time of conception. Observations supporting this hypothesis have come from investigations on some diseases related to the human leukocyte antigen (HLA). In the present study on 1102 healthy Italian families, we investigated the potential effect on the offspring sex ratio of HLA-B alleles on the basis of a genetic model. We defined three subsets of HLA-B alleles and hypothesized a locus (L) with three alleles, LH, LN, LB15, on the basis of the positive, neutral, or negative effect on the testosterone level. According to the genetic model and the dominance relation LH > LB15> LN, six genotypic and three phenotypic classes (H, N, B15) can be expected. We found a significantly high number of daughters (66%) born to fathers carrying the B15 phenotype. This result suggests an effect of the HLA-B15 allele on the secondary sex ratio, mediated by a low testosterone level.

Late childbearing and its impact on adverse pregnancy outcome: stillbirth, preterm delivery and low birth weight.

BACKGROUND The role of parental ageing on the incidence of adverse pregnancy outcome is based on increased morbidity and obstetric problems during pregnancy and delivery in old mothers, and on the accumulation of spontaneous harmful mutations for continuous cell divisions during spermatogenesis in old fathers. The aim of this study is to estimate the impact of paternal and maternal ageing on the risk of adverse pregnancy outcome. DATA AND METHODS From the group of 3,616,622 Italian singletons born in 1990-1996 we estimated the risks of stillbirth, preterm birth (<37 weeks of gestation) in live births, and low birth-weight (< 2.3 Kg) in live full-term births. The risks were estimated as a function of maternal and paternal ageing through logistic regression models, which included, as covariates, parity (1st, 2nd, > or =3rd) and family education (low, < or =8 years of schooling for both parents; high, >8 years for at least one parent). Parental ages were examined as quantitative (in one year classes) or categorical factors (in three classes: fathers 20-29, 30-39, > or =40; mothers 20-29, 30-34, > or =35). RESULTS AND CONCLUSIONS We found that, compared with 20-29-year old parents, mothers > or =30 years and fathers > or =40 years are at risk of adverse pregnancy outcome. The effects are more relevant for preterm births and greater in the least than in the most favourable birth conditions, i.e., in first-born children of less educated families than in second-born children of highly educated families. For the risk of a preterm delivery, the odds ratio is OR = 1.32 [1.28-1.36] in mothers aged 30-34 years, and OR=1.97 [1.88-2.07] in mothers 235 years in the least favourable conditions, and OR = 1.14 [1.10-1.18] and OR = 1.56 [1.22-1.27] respectively, in the most favourable conditions. The impact of paternal ageing is smaller but significant in fathers > or =40 years: for the risk of a preterm birth, the odds ratio is OR = 1.40 [1.33-1.47] in the least favourable conditions, and OR = 1.14 [1.08-1.21] in the most favourable conditions. This last, baseline risk might be indicative of a paternal genetic component associated with childbearing in advanced age.

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.

Trends in Childbearing and Stillbirth Risk: Heterogeneity among Italian Regions

Abstract: In Italy, as in all Western countries, the almost monotonic decline in fertility observed since the 1960s has been paralleled until the beginning of the 1980s by a decrease in maternal age at delivery. Since then, age at marriage and at childbearing has been increasing and marital fertility has continued to decrease. By 1994 Italy showed extreme values of low total fertility rate (1.22) and of high mean maternal age at delivery (29.7). For the period between 1960 and 1994 we identified five U-shaped patterns in maternal age at delivery corresponding to five geographical areas, which differ socioeconomically and culturally. Since it is well known that an increase in the maternal age is accompanied by an increase in the risk of unfavorable pregnancy outcome, we estimated the stillbirth risk run by older (>=35 years) mothers who delivered in 1994, with respect to their younger counterparts. The differences between the areas are reflected in the higher risk in southern compared to northern Italy: the maximum value occurred in Sicily (odds ratio 2.02, 95% confidence interval, 1.51-2.70) and the minimum value, even lower than in the north but not statistically significant, was found in Sardinia (odds ratio 1.25, 95% confidence interval, 0.81-1.91), known to be characterized by peculiar cultural and biological features.

PAST MALARIA, THALASSEMIA AND WOMAN FERTILITY IN SOUTHERN ITALY

The role of natural selection in maintaining the thalassemia polymorphism is examined in a southern Italy district, in the past affected by malaria endemia. The Haldanes hypothesis that the thalassemia heterozygotes enjoy more protection than the normal homozygotes against the risk of malaria infection, seems to be confirmed by this indirect study at population level. The higher number of children born of the women who lived in the highly endemic villages, where the highest proportion of heterozygotes occurs, supports the hypothesis that the woman fertility contributes to the thalassemia maintenance. The joint effects of the acquired and inherited immunities and of the reproductive compensation are assumed as the mechanisms through which malaria and thalassemia influence fertility.