The risks associated with pregnancy in women aged 35 years or older

The obstetric risks of adverse outcome during pregnancy in women aged > or =35 years were quantified using a retrospective analysis of data from 385 120 singleton pregnancies in the North West Thames Region, UK, between 1988 and 1997. A comparison of pregnancy outcome was made on the basis of maternal age at delivery: 18-34 years (n = 336 462), 35-40 years (n = 41 327) and women aged > 40 years (n = 7331). Women aged <18 years (n = 5246) were excluded from the study. Data are presented as percentages of 18-34 year old women, 35-40 year old and > 40 year old women, with adjusted odds ratios (OR) according to age group. Pregnant women aged 35-40 years were at increased risk of: gestational diabetes, OR = 2.63 [99% confidence interval (CI) 2.40-2.89]; placenta praevia = 1.93 (1.58-2.35); breech presentation = 1.37 (1.28-1.47); operative vaginal delivery = 1.5 (1.43-1.57); elective Caesarean section = 1.77 (1.68-1.87); emergency Caesarean section = 1.59 (1.52-1.67); postpartum haemorrhage = 1.14 (1.09-1.19); delivery before 32 weeks gestation = 1.41 (1.24-1.61); birthweight below the 5th centile = 1.28 (1.20-1. 36); and stillbirth = 1.41 (1.17-1.70). Women aged >40 years had higher OR for the same risks. Pregnant women aged >/=35 years are at increased risk of complications in pregnancy compared with younger women.     

Paternal age and birth defects: how strong is the association?

BACKGROUND: Although the association between maternal age and the risks of birth defects has been well studied, the evidence from population data linking paternal age with birth defects was limited and inconsistent. METHODS: We conducted a population-based retrospective cohort study of 5,213,248 subjects from the 1999-2000 birth registration data of the USA. Multiple logistic regressions were used to estimate the independent effect of paternal age on all birth defects and 21 specific defects groups after adjusting for potential confounding of maternal age, race, education, marital status, parity, prenatal care initiation, maternal smoking and alcohol drinking during pregnancy. RESULTS: A total of 77,514 (1.5%) birth defects were recorded in the study cohort. The adjusted odds ratios were 1.04 (1.01, 1.06), 1.08 (1.04, 1.12), 1.08 (1.02, 1.14) and 1.15 (1.06, 1.24), respectively, for infants born to fathers 30-35, 40-44, 45-49 and over 50 years (test for trend, P = 0.0155), when compared with those infants born to fathers aged 25-29 for any birth defect. Advanced paternal age was associated with increased risks of heart defects, tracheo-oesophageal fistulaoesophageal atresia, other musculoskeletal/integumental anomalies, Down's syndrome and other chromosomal anomalies. Fathers under 25 years of age were also at increased risks of spina bifida/meningocele, microcephalus, omphalocele/gastroschisis and other musculoskeletal/integumental anomalies. CONCLUSIONS: Infants born to older fathers have a slightly increased risk of birth defects. Young paternal age is also associated with slightly increased risk of several selected birth defects in their offspring. However, given the weak association, paternal age appears to play a small role in the aetiology of birth defects.     

Paternal age and congenital malformations

BACKGROUND: Spontaneous mutations in germ cells increase with male age, but an association between paternal age and congenital malformations is not well established. We conducted a population-based cohort study to estimate this association. METHODS: A study population of couples and their firstborn children were identified in the Danish Fertility Database between 1980 and 1996 (n = 71937). Diagnoses of congenital malformations in children were obtained by linkage to the nationwide hospital register (1980-1999). RESULTS: Overall, there were no differences in the prevalence of malformations as a function of paternal age. However, the prevalence of malformations of extremities and syndromes of multiple systems, as well as Down's syndrome, increased with increasing paternal age. For example, in comparison with fathers age 20-29 years, adjusted hazard ratio of syndromes of multiple systems was 1.15 [95% confidence interval (CI) 0.81-1.65] for age 35-39 years, 1.33 (95% CI 0.79-2.25) for age 40-44 years, 1.73 (95% CI 0.82-3.65) for age 45-49 years, and 3.20 (95% CI 1.37-7.48) for age > or = 50 years (test for trend P = 0.01). CONCLUSIONS: Our data suggest that advanced paternal age may be associated with an excess occurrence of some specific malformations. The association could be caused by mutations of the gametes in men induced by biological or environmental factors.     

Subfertility reflects accelerated ovarian ageing

BACKGROUND: The aim of the study was to explore the extent to which accelerated ovarian ageing may lead to subfertility early in reproductive life and eventually cause early menopause. METHODS: The population studied (n = 2393) never used oral contraceptives, hormone replacement therapy or an intrauterine device. Logistic regression analyses were performed using age at menopause as proxy for accelerated ovarian ageing. Measures of ovarian ageing and subfertility were menstrual cycle irregularity, ever consulted a physician for fertility problems, nulliparity, uniparity, miscarriage(s) and time interval >5 years between birth of first and second child. RESULTS: For every 5 years later menopause, the probability of reporting menstrual cycle irregularity was reduced by 26% (OR = 0.74, 95% CI: 0.63-0.86); the probability of ever consulting a physician for fertility problems was reduced by 18% (OR = 0.82, 95% CI: 0.71-0.95); the probability of staying nulliparous was reduced by 22% (OR = 0.78, 95% CI: 0.64-0.96); the probability of being uniparous was reduced by 22% (OR = 0.78, 95% CI: 0.66-0.91); the probability of having a miscarriage was reduced by 11% (OR = 0.89, 95% CI: 0.79-1.01); the probability of a large time interval between birth of first two children was reduced by 27% (OR = 0.73, 95% CI: 0.61-0.89). CONCLUSIONS: Fertility problems are frequently followed by early menopause. The findings support the view that both are an expression of accelerated ovarian ageing.     

Maternal Prepregnancy Underweight and Risk of Early and Late Stillbirth in Black and White Gravidas

ObjectiveThe association between underweight and stillbirth remains poorly defined, especially across racial/ethnic sub-populations. We investigate the association of pre-pregnancy underweight on the risk for early and late stillbirth among black and white mothers.MethodsWe conducted analysis on the Missouri maternally linked data files covering the period 1989-1997 inclusive. Using body mass index (BMI), we categorized mothers as underweight (BMI >18.5) and normal weight (BMI = 18.5-24.9). By applying logistic regression modeling with adjustment for intracluster correlation, we estimated the risk for total, early (≤28 weeks of gestation), and late stillbirth (>28 weeks of gestation) among black and white mothers.ResultsA total of 1808 cases of stillbirth were registered. The rate of stillbirth among white mothers was 3.7 per 1000, while the rate among blacks was 7.1 per 1000. Underweight black mothers had comparable risk for total (OR, 0.9; 95% CI, 0.7-1.2), early (OR, 1.1; 95% CI, 0.8-1.5), and late stillbirth (OR, 0.8; 95% CI, 0.5-1.2) as compared to their normal-weight counterparts. By contrast, underweight white gravidas had a 30% reduced likelihood (OR, 0.7; 95% CI, 0.6-0.9) for late stillbirth as compared to normal-weight white mothers. However, the risks for total and early stillbirth among underweight white mothers were similar to those of normal-weight white mothers.ConclusionLow prepregnancy BMI has similar effects on fetal survival in both blacks and whites except for late stillbirth. The underweight white survival advantage over blacks in late pregnancy could probably be due to greater access for identified white at-risk groups to effective obstetrical interventions as previously reported.     

Paternal age and maternal age are risk factors for miscarriage; results of a multicentre European study

BACKGROUND: It is well known that miscarriage risk increases with age. However, studies usually investigate only maternal age effects. We investigated both maternal age and paternal age effects on miscarriage risk to provide insight into this frequent reproductive failure. METHODS: The last planned pregnancies (n = 3174) that ended in a birth or miscarriage were analysed in a retrospective population-based study on women aged 25-44 years in Denmark, Germany, Italy and Spain. Maternal and paternal ages were analysed together, using a single variable 'couple age' in a multivariate logistic regression analysis, with couples composed of a woman and a man both aged 20-29 years forming the reference group. RESULTS: After adjustment for various factors (e.g. reproductive history, country), we found that the risk of miscarriage was higher if the woman was aged > or = 35 years, as has already been reported in a number of studies. However, the increase in risk was much greater for couples composed of a woman aged > or = 35 years and of a man aged > or = 40 years. Potential source of bias (especially 'reproductive compensation') are discussed. CONCLUSIONS: The risk of an adverse pregnancy outcome is highest if both partners are advanced in age.     

Updated investigations of the role of methylenetetrahydrofolate reductase in human neural tube defects

Folate supplementation appears to reduce the risk for neural tube defects (NTDs). Methylenetetrahydrofolate reductase (MTHFR) is a candidate gene in the folate metabolism pathway that has been extensively studied in different human populations. We examined the risk associated with having the thermolabile variant (TT) of MTHFR in a study of 175 American Caucasians with NTDs and their families. We found a significant association in patients compared with 195 unrelated controls [odds ratio (OR) = 2.13, 95% confidence interval (95% CI) = 1.11-4.09)], but not in mothers (OR = 1.29, 95% CI = 0.622-2.67) or in fathers (OR = 1.45, 95% CI = 0.681-3.09). We found no evidence for unequal transmission from parents to an affected child (p > 0.10). We failed to find a previously reported association for a combined haplotype for MTHFR and cystathionine beta-synthase, except in subjects with NTDs compared with 559 pooled controls (OR = 2.87, 95% CI = 1.03-8.03). We found no evidence for an association for a novel CA-repeat polymorphism identified in a gene closely linked to MTHFR (p > 0.10). Our studies continue to suggest that additional candidate genes other than MTHFR may be responsible for an increased risk to NTD in some American Caucasian families.     

Familial aggregation of endometriosis in a large pedigree of rhesus macaques

BACKGROUND: Endometriosis occurs in several non-human primate species that have menstrual cycles. This study investigated the prevalence and familial aggregation of endometriosis in one of those species, the rhesus macaque. METHODS: Between 1978 and 2001, 142 animals with endometriosis were identified from necropsy and surgical records and through the use of magnetic resonance imaging (MRI) at the Wisconsin National Primate Research Center, Madison, USA. All cases were used to build one large multigenerational pedigree and nine nuclear families comprising 1602 females in total. By 2002, the pedigrees contained 124 cases diagnosed at necropsy; 17 at surgery and three at MRI. Female animals that had died aged > or = 10 years without endometriosis, had both ovaries until at least 1 year prior to death, and had a full necropsy, were considered unaffected. RESULTS: The prevalence of endometriosis among necropsied animals aged > or = 10 years in the colony was 31.4% [95% confidence interval (CI) 26.9-35.9%]; prevalence increased with rising age and calendar age at death. Familial aggregation of endometriosis was strongly suggested by a significantly higher average kinship coefficient among affecteds compared with unaffecteds (P < 0.001) and a higher recurrence risk for full sibs (0.75; 95% CI 0.45-1.0) compared with maternal half sibs (0.26; 95% CI 0.10-0.41) and paternal half sibs (0.18; 95% CI 0.02-0.34). The segregation ratio among affected mothers (44.2%) was not significantly higher compared with unaffected mothers (36.6%). CONCLUSIONS: The results support familial aggregation of endometriosis in the rhesus macaque, and indicate that this is a promising animal model for the investigation of mode of inheritance, the location of potential genetic susceptibility loci and the influence of environmental factors.     

Omphalocele, advanced maternal age, and fetal morbidity outcomes

In this study we wanted to determine if the risk for adverse neonatal outcome among omphalocele-affected fetuses is increased among older gravidas. This was a retrospective cohort study on live-born infants with omphalocele delivered in New York State from 1983 through 1999. We compared infants of older (>or=35 years) with those of younger (<35 years) mothers with respect to the following fetal morbidity indices: low birth weight and very low birth weight, preterm and very preterm, and small for gestational age. We used adjusted odds ratios to approximate relative risks. Data on a total of 1,010 infants with omphalocele were analyzed. Mean gestational age and birth weight were similar in both maternal age categories: mean+/-standard deviation (SD) for infants with omphalocele born to older mothers=37.4 weeks+/-3.9 versus 38.0 weeks+/-5.1 for those of younger mothers (P=0.2); mean birth weights+/-SD for infants with omphalocele born to older mothers=2,813+/-871.1 versus 2,958+/-809.9 for those of younger mothers (P=0.08). Also, the two maternal age sub-groups did not differ with respect to the fetal morbidity outcome: low birth weight (OR=0.95; 95% CI=0.60-1.51), very low birth weight (OR=0.78; 95% CI=0.36-1.69), preterm (OR=0.95; 95% CI=0.58-1.57), very preterm (OR=0.73; 95% CI=0.34-1.58), and SGA (OR=1.00; 95% CI=0.44-2.27). Thus, advanced maternal age does not appear to be a risk factor for fetal morbidity outcomes among omphalocele-affected fetuses. This information is potentially useful in counseling affected parents.     

父亲生育年龄与子女罹患精神分裂症的相关性分析

目的 探讨在汉族人群中生父生育年龄与子女罹患精神分裂症风险的相关性.方法 收集351例精神分裂症患者与199名健康志愿者进行病例对照研究.将患者生父母生育年龄分组,以26～30岁组作为参照组,分别对生父母生育年龄的不同组别进行分类变量的Logistic回归分析,并予被试年龄、性别、生母或生父生育年龄等进行校正.结果 校正后,与生育年龄在26~30岁的父亲相比,31~35岁、36~40岁、≥41岁3个年龄组父亲子女罹患精神分裂症的OR值分别为3.834、8.805和11.619(P<0.05);父亲生育年龄≤25岁时,子女罹患精神分裂症的OR值为0.877(P>0.05).生母各生育年龄组P值无统计学意义.结论 生父生育年龄与子女罹患精神分裂症显著相关;生父生育年龄越大,子女罹患精神分裂症的风险越高.推测这一风险作用的生物学机制是随着男性年龄的增长,生殖细胞的分化成熟过程中会不断积累新发突变或父系基因印迹异常.

Abstract：

Objective To investigate whether advanced paternal age is related to an increased risk of schizophrenia in Chinese Han population. Methods A case-control design study was performed. Three hundred and fifty-one patients with schizophrenia and 199 unrelated healthy volunteers were recruited. By using Logistic regression, paternal age was divided into five categories, and maternal age into four categories. Setting the paternal age of 26-30 years as reference, the OR, P values and 95% CI of the other paternal age categories were analyzed, respectively. The participant's sex, age and parental age at birth were used as covariants for adjusting confounding effects. Results The OR for schizophrenia in offspring whose paternal age at birth of 31-35 years, 36-40 years, and ≥41 years categories were 3.834, 8.805, and 11.619 respectively. The advanced maternal age had no significant effects on the risk for schizophrenia in offspring. Conclusion The advanced paternal age was associated with elevated risk for schizophrenia in offspring among a Han Chinese population. Putative biological mechanisms may include accumulated de novo mutations and alterations in epigenetic regulations with aging in spermatogenesis.     

Teenage pregnancy and congenital anomalies: which system is vulnerable?

BACKGROUND: Teenage pregnancy may be associated with some forms of congenital anomalies. The objective of this study was to identify the types of congenital anomalies associated with teenage pregnancy. METHODS: We carried out a retrospective cohort study of 5 542 861 nulliparous pregnant women younger than 35 years of age with a live singleton birth between 1995 and 2000 in the USA. RESULTS: Compared with adult pregnancy (20-34 years old), and after adjustment for confounding variables, teenage pregnancy (13-19 years old) was associated with increased risk of central nervous system anomalies [odds ratio (OR) 1.08; 95% confidence interval (CI): 1.01, 1.16], gastrointestinal anomalies (OR: 1.39; 95% CI: 1.31, 1.49) and musculoskeletal/integumental anomalies (OR: 1.06; 95% CI: 1.03, 1.10). The teenage pregnancy associated increase in risk for central nervous system anomalies was mainly attributable to anomalies other than anencephalus, spina bifida/meningocele and hydrocephalus and microcephalus; for gastrointestinal anomalies the risk was mainly attributable to omphalocele/gastroschisis; and for musculoskeletal/integumental anomalies the risk was mainly attributable to cleft lip/palate and polydactyly/syndactyly/adactyly. No increased risk was found for circulatory/respiratory anomalies, urogenital anomalies, or Down's syndrome. CONCLUSIONS: Teenage pregnancy increases the risks of congenital anomalies in central nervous, gastrointestinal and musculoskeletal/integumental systems.     

Pregnancy Outcomes in HIV-Infected Women of Advanced Maternal Age

Abstract

Background: There is limited information on pregnancy outcomes in women with HIV who are of a more advanced maternal age.Methods: Data from a national observational study in Italy were used to evaluate the risk of nonelective cesarean section, preterm delivery, low birthweight, major birth defects, and small gestational age-adjusted birthweight according to maternal age (<35 and ≥35 years, respectively).Results: Among 1,375 pregnancies with live births, 82.4% of deliveries were elective cesarean sections, 15.8% were nonelective cesarean sections, and 1.8% were vaginal deliveries. Rates of nonelective cesarean section were similar among mothers ≥35 and <35 years (odds ratio [OR], 1.22; 95% CI, 0.90–1.65;P = .19). Preterm delivery and low birthweight were significantly more common among women ≥35 years in univariate but not in multivariate analyses. Newborns from women ≥35 and <35 years showed no differences inZ scores of birthweight, with a similar occurrence of birthweight <10th percentile (12.1% vs 12.0%; OR, 1.02; 95% CI, 0.71–1.46;P = .93). The overall rate of birth defects was 3.4% (95% CI, 2.4–4.4), with no differences by maternal age (≥35 years, 3.5%; <35 years, 3.3%; OR, 1.05; 95% CI, 0.56–1.98;P = .88).Discussion: In this study of pregnant women with HIV, older women were at higher risk of some adverse pregnancy outcomes, such as preterm delivery and low birthweight. The association, however, did not persist in multivariable analyses, suggesting a role of some predisposing factors associated with older age.     

Paternal age, stillbirths and mutation

Previous suggestions that accumulation of mutations in the germ line of ageing fathers causes an increased stillbirth rate were based on analyses of data which were heterogeneous for social variables whose effects were confounded with possible paternal age effects. This study was confined to the analysis of stillbirth rates of groups of women selected to be homogeneous for education, previous pregnancy outcomes, age, race and marital status. It is concluded that stillbirth rates do not increase with father's age independently of maternal variables. Neither accumulation of mutations in the paternal germ line nor other biological change associated with father's age can be inferred to cause an increase in risk of stillbirth with increasing paternal age.     

Maternal and offspring MTHFR gene C677T polymorphism as predictors of congenital atrial septal defect and patent ductus arteriosus

To observe the association of MTHFR gene C677T locus polymorphism with occurrence of congenital heart defects (CHDs), 21 patients with atrial septal defect (ASD), 35 patients with patent ductus arteriosus (PDA), one patient with both conditions combined, and their biological parents were collected as the case group. Another 104 normal individuals and their biological parents without a family history of birth defects were selected as the control group. MTHFR C677T genotypes of each sample were determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). The results showed for the occurrence of ASD, the odds ratio (OR) of TT genotype was 4.08 [95% confidence interval (95% CI) = 1.28-13.24] compared with CT genotype. For the occurrence of PDA, the ORs of TT were 3.44 (95% CI = 0.89-16.13) and 2.38 (95% CI = 0.92-6.14) compared with CC and CT genotypes, respectively. Author as meant? Compared with CC + CT genotype combination, the ORs of TT were 3.95 (95% CI = 1.38-11.44) and 2.60 (95% CI = 1.02-6.36) for ASD and PSD respectively. The results also had sex differences and the statistical significance was only observed in male ASD and female PDA. The ORs of T allele carriers were 2.29 (95% CI = 1.08-4.92) and 1.88 (95% CI = 1.02-3.47) compared with C allele for the occurrences of ASD and PDA respectively. The analysis of parents genotype showed that the OR of TT mothers was 2.31 (95% CI = 0.96-5.59, P < 0.05) compared with (CC + CT) for the occurrence of PDA in offspring. So this study could give a clue that MTHFR C677T locus variation was related with occurrence of ASD and PDA, and the carriers of TT genotype and T allele had higher risk of diseases. The mother carrying TT genotype was associated with occurrence of PDA in offspring.     

Paternal risk factors for isolated membranous ventricular septal defects

A case-control study using data from the Baltimore-Washington Infant Study (BWIS) examined possible paternal risk factors in the etiology of isolated membranous ventricular septal defects (VSD). There were 641 total VSD case infants and 3,549 randomly selected control infants ascertained between 1981 and 1989. Isolated membranous VSDs were identified in 499 cases. Socio-demographic factors (such as parental age and race), social habits, and medical conditions were analyzed by multiple logistic regression in order to estimate adjusted odds ratios (OR) and 95% confidence intervals (CI). Paternal age was not found to be a risk factor per se, but small positive associations were found for some social habits and maternal factors. Significant associations were found for paternal marijuana use (OR 1.36, 95% CI 1.05-1.76), African-American race of the infant (OR 1.34, 95% CI 1.09-1.65), and for cocaine use among older fathers (OR 3.92, 95% CI 1.30-11.86). These associations support a multifactorial etiologic hypothesis for isolated membranous VSDs and point to some interesting parental behavioral and medical considerations which may contribute to risk for this common birth defect. Am. J. Med. Genet. 71:42–46, 1997. © 1997 Wiley-Liss, Inc.     

The I,105V polymorphism in glutathione S-transferase P1, parental smoking and the risk for nonsyndromic cleft lip with or without cleft palate

Genetic variations in the detoxification enzyme glutathione S-transferase P1 (GSTP1) may modify the teratogenicity of lifestyles, such as smoking. We investigated the role of the I105V polymorphism in GSTP1, parental periconception smoking, and their interaction with nonsyndromic cleft lip with or without cleft palate (CL/P) risk in the offspring. The GSTP1 I105V polymorphisms were determined in Dutch non-consanguineous Caucasians comprising of 155 CL/P triads (mother, father, child) and 195 control triads. The analyses were also carried out on complete triads only (n=69 CL/P and n=95 controls). Transmission disequilibrium testing and logistic regression analyses were performed. Neither maternal nor paternal smoking increased CL/P risk; odds ratios (OR): 1.2, 95 confidence intervals (CI)=0.7-2.0 and OR: 1.0, 95% CI=0.6-1.6, respectively. Carriership of the polymorphic Val105 allele in mothers may increase CL/P risk, OR: 1.5, 95% CI=0.96-2.5. Children homozygous for the Val105 allele may show an increased risk of CL/P, OR: 2.2, 95% CI=0.8-6.4. Maternal smoking tended to increase CL/P risk in mothers and children carrying Val105 alleles, OR=1.9, 95% CI=0.9-4.0 and OR=2.2, 95% CI=0.98-4.9, respectively. The highest risk for CL/P in children carrying Val105 alleles with a smoking father was 1.7, 95% CI=0.8-3.5. The GSTP1 I105V polymorphism in mothers and/or children either alone or in combination with maternal smoking may contribute to CL/P risk. Although of borderline significance, these results may underline the importance of smoking cessation in the periconception period for the prevention of CL/P in future generations.     

Genetic epidemiological study of maternal and paternal transmission of alzheimer's disease

Recent evidence for mitochondrial mutations associated with Alzheimers disease (AD) suggests the possibility of maternal transmission of this illness. We investigated this hypothesis by examining, in a variety of ways, the risk of a primary progressive dementia (PPD) in the parents (n = 650) and siblings (n = 1,220) of 325 AD probands. The results did not support maternal transmission in AD: The mothers of AD probands were not at greater risk of PPD than the fathers or the sisters of AD probands; the offspring of affected mothers were not at greater risk than the offspring of affected fathers or families with no affected parent; and, after selecting those proband families with evidence for increased familial loading, such families did not more frequently have affected mothers than fathers. In contrast, the cumulative risk of PPD in fathers of AD probands, while similar to that of mothers, was significantly increased over the brothers of AD probands. In addition, the cumulative risk curve of PPD in the offspring of affected fathers was significantly higher than the offspring of no affected parents. While no evidence for maternal transmission in AD was observed, unexpectedly, we did find evidence of increased paternal transmission. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 88:378–382, 1999. © 1999 Wiley-Liss, Inc.     

Interactions between breast-feeding, specific parental atopy, and sex on development of asthma and atopy

BACKGROUND: The influence of breast-feeding on the risk of developing atopy and asthma remains controversial. OBJECTIVE: To examine asthma and atopy outcomes by sex, reported specific parental history of atopy, and breast-feeding. METHODS: In a birth cohort, we examined childhood asthma and atopy (positive skin prick tests) by sex and breast-feeding in relation to maternal and paternal atopy. Interactions were explored in logistic regression models. RESULTS: For boys, breast-feeding (odds ratio [OR], 1.63; 95% CI, 0.93-2.87; P = .09) and maternal atopy (OR, 1.95; 95% CI, 0.93-4.08; P = .08) were each associated with atopy at age 13 years. Breast-feeding increased the risk for atopy among boys with paternal atopy (OR, 7.39; 95% CI, 2.21-24.66) compared with non-breast-fed boys with paternal atopy, but did not significantly further increase risk among subjects with maternal atopy. For girls, breast-feeding (OR, 0.74; 95% CI, 0.41-1.31) and maternal and paternal atopy were not independent risk factors for atopy at age 13 years. However, breast-feeding increased the risk for atopy in girls with maternal atopy (OR, 3.13; 95% CI, 1.20-8.14) compared with non-breast-fed girls with maternal atopy. There was no such effect among subjects with paternal atopy. Results for the outcome of asthma followed a similar pattern. CONCLUSION: The influence of breast-feeding on development of atopy and asthma differs by sex and by maternal and paternal atopy, and is most significant among subjects at lower baseline risk. CLINICAL IMPLICATIONS: Analyses of environmental risk factors for asthma and atopy should be stratified by specific parental atopy and sex.     

The population-based prevalence of achondroplasia and thanatophoric dysplasia in selected regions of the US

There have been no large population-based studies of the prevalence of achondroplasia and thanatophroic dysplasia in the United States. This study compared data from seven population-based birth defects monitoring programs in the United States. We also present data on the association between older paternal age and these birth defects, which has been described in earlier studies. The prevalence of achondroplasia ranged from 0.36 to 0.60 per 10,000 livebirths (1/27,780-1/16,670 livebirths). The prevalence of thanatophoric dysplasia ranged from 0.21 to 0.30 per 10,000 livebirths (1/33,330-1/47,620 livebirths). In Texas, fathers that were 25-29, 30-34, 35-39, and > or =40 years of age had significantly increased rates of de novo achondroplasia among their offspring compared with younger fathers. The adjusted prevalence odds ratios were 2.8 (95% CI; 1.2, 6.7), 2.8 (95% CI; 1.0, 7.6), 4.9 (95% CI; 1.7, 14.3), and 5.0 (95% CI; 1.5, 16.1), respectively. Using the same age categories, the crude prevalence odds ratios for de novo cases of thanatophoric dysplasia in Texas were 5.8 (95% CI; 1.7, 9.8), 3.9 (95% CI; 1.1, 6.7), 6.1 (95% CI; 1.6, 10.6), and 10.2 (95% CI; 2.6, 17.8), respectively. These data suggest that thanatophoric dysplasia is one-third to one-half as frequent as achondroplasia. The differences in the prevalence of these conditions across monitoring programs were consistent with random fluctuation. Birth defects monitoring programs may be a good source of ascertainment for population-based studies of achondroplasia and thanatophoric dysplasia, provided that diagnoses are confirmed by review of medical records.     

Increasing paternal age is associated with delayed conception in a large population of fertile couples: evidence for declining fecundity in older men. The ALSPAC Study Team (Avon Longitudinal Study of Pregnancy and Childhood)

The impact of male age on fecundity remains controversial. Here, a large population study was used to investigate the effect of paternal age on time to conception. All couples in the Avon Health district expecting a baby between 1 April 1991 and 31 December 1992 were eligible. Questionnaires completed by both the man and the woman at 18 weeks gestation covered specific fertility factors, e.g. parity, paternity, cohabitation and oral contraception; and non-specific factors, e.g. educational achievement, housing, cigarette smoking, alcohol consumption, obesity. Logistic regression was used to identify factors independently related to conception in < or =6 or < or =12 months. Of 8515 planned pregnancies, 74% were conceived in < or =6 months, 14% in the second 6 months and 12% after more than a year. Nine variables, including the age of the woman, were independently related to time to conception. After adjustment for these, the likelihood of conception within 6 or 12 months was lower in older men. Compared to men <25 years old, the adjusted odds ratios (95% confidence interval) for conception in < or =12 months were 0.62 (0.40, 0.98), 0.50 (0.31, 0.81) and 0.51 (0.31, 0.86) in men aged 30-34, 35-39 and > or =40 years respectively.