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Effect of maternal age and parity on the risk of uteroplacental bleeding disorders in pregnancy.

OBJECTIVE: To examine the risk of placental abruption, placenta previa, and uterine bleeding of unknown etiology in relation to advanced maternal age and parity in a large, population-based study. METHODS: Data for this study were derived from the Nova Scotia Atlee perinatal provincial data base, Canada, an ongoing project on human reproduction. Women who delivered between 1980 and 1993 (n = 123,941) in the province of Nova Scotia were included in the study, with the exception of pregnancies resulting in multiple births (n = 2859) and those missing data on maternal age or parity (n = 14). Multivariable logistic regression models based on the method of generalized estimating equations were used to generate odds ratios after adjustment for multiple confounders. RESULTS: The frequency of abruption was increased slightly among younger women (relative risk [RR] 1.3, 95% confidence interval [CI] 1.0-1.7), compared with women ages 25-29 years, but there was no increase with advancing maternal age. In contrast, the risk of placenta previa increased dramatically with advancing maternal age, with women older than 40 years having a nearly ninefold greater risk than women under the age of 20, after adjustment for potential confounders, including parity. Uterine bleeding of unknown etiology was not associated with advanced maternal age, except for a slight increase among women over 40 (RR 1.3, 95% CI 1.0-1.6). The risk of placenta previa and placental abruption was increased with higher parity among younger women only, but uterine bleeding of unknown etiology was more weakly associated with higher parity. In addition, an analysis of the joint effects of age and parity on placental abruption indicated a strong parity effect for women under 30 years, whereas the risk of placenta previa increased with increasing parity up to age 35 years. Uterine bleeding of unknown etiology also indicated a parity effect that was restricted to women under 25 years. CONCLUSION: Multiparity is associated with the risk of placenta previa and, to a lesser extent, placental abruption, but not with other uterine bleeding. Increasing maternal age is associated independently with the risk of placenta previa, but not with either of the other two conditions. Finally, the increased risks of uteroplacental bleeding disorders with advanced parity among the younger women (ie, 20-25 years, parity 3+) may reflect effects of close pregnancy spacing, or confounding by unmeasured factors that characterize women who have many pregnancies at a relatively young age. Overall, the findings suggest that the three uteroplacental bleeding disorders do not share a common etiology in relation to maternal age and parity, and that placenta previa is linked to aging of the uterus and the effects of repeated pregnancies.

Abruptio Placentae↗

Endometritis after cesarean: the effect of age.

In this study, we compared the rate of endometritis after cesarean section in two age groups. The first group consisted of patients who were 17 years old or younger (teenage group) and the second group of patients were 35 years of age or older (advanced maternal age group). Patients in each group were matched for length of labor, length of rupture of membranes, and the use of prophylactic antibiotics. In the teenage group, 18 of 41 (43.9%) developed endometritis compared with 6 of 41 (14.6%) in the advanced maternal age group (P < 0.003). This study supports the concept that young age is a risk factor for endometritis after cesarean section.

Adolescent↗

Prenatal diagnosis in Finland.

In Finland the local authorities are responsible for the provision of prenatal diagnostic services for the communities or the community pays for the visits of its citizens to the larger hospitals. The local authorities have autonomy in making the policies for prenatal diagnosis, which leads to an uneven availability of the services, i.e. availability of ultrasound (US) screening, maternal serum screening, and age limits for fetal chromosome studies due to advanced maternal age. The municipalities receive Government aid for health care. In all areas, US screening and screening for fetal chromosome anomalies either by advanced maternal age only or maternal serum screening are arranged. Families with special problems are sent to five university hospitals for prenatal diagnostic services. To make possible the prenatal diagnosis of the autosomal recessive diseases belonging to the Finnish disease heritage, a special effort has been made on their molecular genetics. The uptake level of ultrasound screening is on average 90%. In cases of abnormal findings, the patients are referred to central or university hospitals for further examinations. The uptake of amniocentesis (AC) or chorionic villus sampling (CVS) due to advanced maternal age is 50-85%. The high numbers come from southern and urban parts of the country. The uptake for maternal serum screening is probably of the similar or of even higher order. In addition to the public services, private prenatal diagnosis, US, maternal serum screening, AC and CVS are available in all parts of Finland.

Congenital Abnormalities↗

Twin gestation in older women: antepartum, intrapartum complications, and perinatal outcomes.

OBJECTIVE: The aim of this study is to present pregnancy and perinatal outcomes of twin gestations in older women and compare them with that for younger women. STUDY DESIGN: We conducted a retrospective cohort study of twin pregnancies in our department between 1988 and 2003. The women were classified into two groups by maternal age: women of age 35 years and older (study group) and women less than 35 years (control group). Population characteristics, complications during pregnancy and delivery, and neonatal outcomes were assessed. The Student's t-test, chi2 test, Fisher exact test, and binary logistic regression analysis were used to examine the relationship between maternal age and the different variables. RESULTS: A total of 238 twin pregnancies were enrolled (study group, 57 women; control group, 181 women). Spontaneous conceptions were significantly higher in the control group (P < 0.001), while conceptions after in vitro fertilization (IVF) were significantly higher in study group (P < 0.001). Mean figures of gestational age at delivery and birth weight for the older group did not differ significantly from the younger group. Although the antepartum and intrapartum complications were more common in the study group, they were not statistically significant compared to the control group. This was also true for the perinatal outcomes. Only the very low birth weight (VLBW < 1,500 g) rate was significantly higher in the study group. The number of perinatal deaths was similar on comparison by maternal age. CONCLUSIONS: Based on our study, advanced maternal age at twin gestation does not seem to affect significantly pregnancy complications and perinatal outcomes. VLBW was the only unfavorable perinatal outcome related to advanced maternal age.

Adult↗

Descriptive epidemiology of Down's syndrome in Estonia.

The aim of the study was to investigate the livebirth prevalence of Down's syndrome (DS) in Estonia during the past 14 years, create a DS database and observe the effectiveness of prenatal screening. This is a population-based descriptive study. The study subjects were children with DS diagnosis born between the years 1990 and 2003. We collected data from genetic centres in Estonia, from the databases of DS support groups, from institutions for disabled children and from the registers of family doctors/paediatricians. Prenatal screening for chromosomal anomalies for women aged >or=35 years was started in Estonia in 1995. Therefore, we divided the DS children into two groups: 112 born between 1990 and 1994 comprise group I, and 127 born between 1995 and 2003 comprise group II. Group II was further divided into two subgroups: IIa, from 1995 to 1998, when screening of advanced maternal age (>or=35 years) commenced, and IIb, from 1999 to 2003, when screening of second trimester maternal serum for younger women commenced. Prenatally, 68 cases of DS were diagnosed between 1995 and 2003 in the whole of Estonia, and all of these pregnancies were terminated. This represents 34.9% of all delivered and prenatally detected DS cases from this period. The overall livebirth prevalence was 1.17 per 1000 livebirths. The livebirth prevalence in group I was 1.25 and in group II was 1.09 per 1000 livebirths. The second trimester maternal serum screening with advanced maternal age screening was more effective than advanced maternal age screening alone. The livebirth prevalence in group IIa was 1.22 and in group IIb 0.99 per 1000 livebirths. Overall, regular trisomy was found in 90.4%, translocation in 6.3% and mosaicism in 2.9%. The overall male to female sex ratio of DS was 1.09.

Adult↗

Effect of arsenite, maternal age, and embryonic sex on spina bifida, exencephaly, and resorption rates in the splotch mouse.

BACKGROUND: This study examines interactions of a mutation in Pax3, embryonic sex, advanced maternal age, and arsenite exposure in the splotch (Sp) mouse model, with the aim of describing gene-environment interactions for neural tube defects and embryonic lethality. METHODS: Splotch heterozygous C57BL/6J mice were crossed to produce offspring of three genotypes with a common maternal genotype that were exposed to either sodium arsenite on gestational day (GD) 8.0, or advanced maternal age (dams older than 12 months). Embryos were extracted on GD 12 and genotyped for both Pax3 and sex. RESULTS: Arsenite treatment was a significant contributor to both exencephaly and spina bifida. Advanced maternal age resulted in a high exencephaly rate in Sp/Sp female embryos (but not other genotypes) and a high overall resorption rate. Arsenite treatment and advanced maternal age resulted in elevated sex ratios (male:female) for heterozygous and wild-type embryos. The sex ratio was highest for wild-type embryos and was lowered as the number of mutant Pax3 alleles increased. The sex ratio was not significantly different from 1.0 for splotch homozygotes. Control litters had spina bifida rates that were 95% in homozygous, 6% in heterozygous, and 0% in wild-type embryos. CONCLUSIONS: If arsenite produces exencephaly by inactivating the Pax3 protein, then the fact that the exencephaly rate was increased in Sp/Sp embryos with no functional Pax3 indicates that arsenite may either induce this defect through additional pathways, or may alter the response via modifier genes. Genetic and environmental factors contributed to the determination of murine sex ratios, with female embryos being more susceptible to loss.

Abnormalities, Drug-Induced↗

Effects of maternal age, parity, and smoking on the risk of stillbirth.

OBJECTIVE: To examine the effects of advanced maternal age, nulliparity, and smoking on risk of stillbirth as gestation advances, and to explore possible clinical mediators of these effects. DESIGN: A population based cohort study. SETTING: Sweden, 1983 to 1989. SUBJECTS: All singleton pregnancies of 28 weeks gestation or greater in Nordic citizens at least 20 years old (n = 638,242). MAIN OUTCOME MEASURES: Crude and adjusted risks of stillbirth; gestational age specific risks of stillbirth. RESULTS: Older women (35 years or older), smokers, and nulliparas had elevated risks of stillbirth. The elevated stillbirth risk in smokers was eliminated when women with intrauterine growth retardation, placental abruption, and placenta previa were excluded from the analysis. However, the higher risks in older women and nulliparas persisted even when the analysis excluded women with hypertension, diabetes, placental complications, or growth retardation. Over the course of the third trimester, the age related risk of stillbirth increased, the smoking related risk decreased, and the higher risk in nulliparas showed no clear trend with gestational age. CONCLUSIONS: The association between smoking and stillbirth is explained entirely by the higher incidence of growth retardation and placental complications in smokers. The clinical mediators of the associations of maternal age and parity with stillbirth remain unexplained. Gestational age is an important modifier of the effects of advanced maternal age and smoking on stillbirth risk.

Abortion, Spontaneous↗

Maternal height and age: risk factors for cephalopelvic disproportion in Zimbabwe.

Maternal age and stature are among several factors used to screen pregnant women for potential risk of labour complications. In a population-based case-control study in Harare, Zimbabwe, multivariate analysis was carried out to evaluate the importance of maternal age and height as risk factors for cephalopelvic disproportion (CPD). Using data abstracted from the medical records of 203 women with operative deliveries due to CPD and 299 women with normal unassisted vaginal deliveries, multiple logistic regression models were developed. Although maternal age < 18 years was not a significant risk factor in this study (perhaps because there were few women in this age group), advanced maternal age (> or = 35 years) was associated with a relative risk of 2.7 compared to women 20-34, after adjusting for other demographic and obstetric factors. Maternal height < 160 cm was associated with a twofold increased risk of CPD as compared to taller women.

Adolescent↗

Maternal age and placenta previa: a population-based, case-control study.

OBJECTIVE: Our purpose was to determine if advanced maternal age has an adverse effect on placenta previa independent of other risk factors. STUDY DESIGN: A population-based, case-control study was performed with North Carolina vital records from 1988 to 1990, individually matching controls to cases on maternal race, gravidity, parity, previous spontaneous or induced abortion, previous cesarean section, and gestational age at delivery. RESULTS: A multivariate analysis showed that women aged 34 years or older had a two to three times higher risk of placenta previa in relation to women < 20 years old. A clear dose-response pattern was observed with increasing age. CONCLUSION: Advancing maternal age appears to increase the risk of placenta previa independent of other factors.

Adult↗

Association between maternal age and the likelihood of a cesarean section: a population-based multivariate logistic regression analysis.

BACKGROUND: A majority of studies examining the relationship between advancing maternal age and the likelihood of cesarean section (CS) use data from regional samples or from a limited number of medical institutions. This study uses population-based data from Taiwan to explore the relationship between maternal age and the likelihood of a CS. METHODS: The National Health Insurance Research Database (NHIRD) on registries of medical facilities and board-certified physicians and monthly claim summaries for inpatients were used. In total, 502 524 singleton deliveries were included in the study. Multivariate logistic regressions were performed with the presence of CS as the dependent variable and maternal age (<20, 20-29, 30-34 and >34 years) as the independent variable. The study controlled for maternal indications, institution characteristics, maternal requests and attending physician characteristics. RESULTS: CS rates for the age groups <20, 20-29, 30-34 and >34 years were 17.7, 27.4, 37.4 and 47.5%, respectively. The regression analyses consistently showed that the likelihood of a CS significantly increased with advancing maternal age within each category of complication after adjusting for medical institution characteristics and characteristics of the attending physician. CONCLUSIONS: This study found that, after adjusting for maternal indications, and healthcare institution and physician characteristics, there was a significant relationship between advancing maternal age and an increased likelihood of a CS. This finding, together with the high CS rate of 32.1% in Taiwan, one of the highest reported in the world today, highlights an imperative need to devise interventions to reduce the frequency of CSs.

Adult↗

Normal midtrimester (17-20 weeks) genetic sonogram decreases amniocentesis rate in a high-risk population.

OBJECTIVE: To evaluate a screening protocol using advanced maternal age, triple-marker screening, and genetic sonography. METHODS: We compared adverse chromosomal outcomes of pregnancy in 1556 women referred for increased risk of aneuploidy because of either advanced maternal age or triple-marker test results. Patients were counseled about the results of the triple-marker test and subsequent sonography, which led to a patient decision of whether to pursue amniocentesis. Fetal measurements and structural abnormalities were compared with chromosomal findings. When patients elected amniocentesis, karyotypes were obtained. RESULTS: Genetic sonography reduced the rate of amniocentesis by 61% overall and by 40% when compared with an alpha-fetoprotein profile alone. The sensitivity of sonography combined with the triple-marker screen for the detection of trisomy 21 was 87% compared with 91% for the triple-marker screen alone. CONCLUSIONS: This study confirmed that sonographic findings in a targeted population, in combination with other risk markers (advanced maternal age and triple-marker screening), can be used to assess the risk of aneuploidy. Biometry provides additional information for assessing the risk of aneuploidy. Combining advanced maternal age, serum triple-marker screening, and sonographic screening may provide better risk prediction for use in clinical counseling.

Amniocentesis↗

Wilms's tumour and aniridia: clinical and cytogenetic features.

A survey carried out to detect children with aniridia/Wilms's tumour syndrome identified 8 living and 3 dead children. The incidence of aniridia was found to be 1 in 43 among Wilms's tumour patients in the UK. The clinical features included complete bilaterial aniridia, cataracts, glaucoma, mental retardation, hyperkinesis, hypospadias, and undescended testes. A high incidence of bilateral tumours (36%), male sex, presentation at a young age, and advanced maternal age appeared to be associated with the syndrome. The 8 living children each had a deletion on the short arm of chromosome 11. In contrast, although 2 patients with sporadic aniridia without Wilms's tumour had other malformations, neither had genitourinary anomalies, and the only additional problems in patients with familial aniridia were cataracts. Among 49 children with Wilms's tumour without aniridia ony one had bilateral tumours. No chromosome abnormalities were detected in patients with familial aniridia, nor were they detected in patients with Wilms's tumour without aniridia or in those with sporadic aniridia without Wilms's tumour. While many infants with the Wilms's tumour/aniridia syndrome are clinically diagnosable at birth, chromosome analysis using the elongated chromosome method is especially valuable to confirm the diagnosis in girls with sporadic aniridia and in boys who lack the genitourinary malformations. The presence of an 11p13 deletion confirms the diagnosis of the Wilms's tumour/aniridia syndrome and indicates a very high risk for the development of Wilms's tumour.

Child, Preschool↗

Is delayed childbearing changing gene frequencies in Western populations?

Experimental data and clinical observations suggest that delaying childbearing influences the biology of the mother-fetus relationship, with a negative effect on fetal development and predisposition to severe diseases such as type 1 diabetes. We reason that advanced maternal age may influence intrauterine selection, favoring genotypes that are more adapted to the intrauterine environment of less young women. In the present study we have investigated the relationship of maternal age to HP genotype and PGM1-Rh area (chromosome 1) that have been previously found to be associated with fertility and developmental parameters. HP phenotype was determined in 679 consecutive puerperae from the population of central Italy. PGM1 phenotype and Rh C phenotype were determined in 222 puerperae and 200 newborns. The HP 1,1 phenotype decreases and the HP 2,2 phenotype increases with maternal age. The proportion of phenotypes carrying both the Rh C and PGM1*1 alleles is much higher in puerperae older than 36 years than in puerperae of age 22 years. The frequency of the PGM1*1-Rh C haplotype increases and the frequency of the PGM1*2-Rh C haplotype decreases with maternal age. The changes in these genetic systems with advancing maternal age are similar in mothers and newborns. The delay of childbearing age, associated in Western countries with the fertility transition in addition to detrimental effects on intrauterine development and increased susceptibility to severe disorders, could bring about changes in the genetic composition of a population.

Adult↗

[Alternatives to amniocentesis for maternal age].

Screening strategies of Down's syndrome should be re-evaluated. Amniocentesis for advanced maternal age has been proposed in the 70's because no other screening test was available. Maternal serum screening and first trimester nuchal translucency are now well validated, including in women over 38. The sequential and independent use of different screening tests leads to a dramatic increase of the false positive rate and thus of iatrogenic fetal losses. Maternal age remains the major risk factor for chromosomal anomalies, but it should be included in risk calculation strategies (ideally combining serum screening and nuchal translucency), and not taken as an isolated information. These screening strategies require strict quality control and audit, which is currently better achieved with serum screening than ultrasound screening. A complete information about Down's syndrome screening strategies should be given to women, regardless of their age, and their personal choice should be respected. For women of advanced maternal age, a policy of selective rather than routine amniocentesis is likely to reduce the risk of iatrogenic fetal loss and yet to allow for a reasonable sensitivity.

Adult↗

Advanced parental age in maternal uniparental disomy (UPD): implications for the mechanism of formation.

Uniparental disomy (UPD) describes the inheritance of a pair of chromosomes from only one parent. Meiotic nondisjunction followed by trisomy rescue is considered to be the major mechanism of formation. A literature search for cases with whole chromosome UPD other than UPD 15 was performed. Information on parental age was available in 111 cases with maternal UPD and in 34 cases with paternal UPD. In 52 out of 74 cases with maternal heterodisomy, information on the time of nondisjunction was also available. Around two-thirds of these cases were due to a maternal meiosis I error. Compared with the mean maternal age of 30.0 years in Bavarian mothers, in the year 2000 an advanced mean maternal age of 34.8 years was found in cases with maternal heterodisomy (n=74; P<0.0001). Almost no difference in the mean maternal age was observed between meiosis I errors (35.56 years; n=30) and meiosis II errors (35.78 years; n=14). The mean maternal age was 31.46 years in cases with maternal isodisomy and a normal karyotype (n=24), and the mean paternal age was 31.48 years in cases with paternal isodisomy (n=28). The various mean parental ages in heterodisomic and isodisomic cases are considered to reflect strongly the different mechanisms of formation: trisomy rescue or gamete complementation, which implies a meiotic nondisjunction in maternal heterodisomic UPD, and postzygotic somatic reduplication in cases with paternal and maternal isodisomic UPD.

Adult↗

Determinants of altered anxiety after abnormal maternal serum alpha-fetoprotein screening.

With maternal serum alpha-fetoprotein testing, large numbers of previously "low-risk" patients are now considered high risk and are offered genetic testing. Anecdotally, these patients have been perceived as more highly anxious than other second-trimester patients referred for genetic testing because of advanced maternal age. Thus we have studied patient demographics, true genetic risks, the perceptions of risk, and state (situational) and trait (constitutional) anxiety for these patients and their partners. Significantly increased state anxiety was noted for mothers as compared with fathers both in the group of women referred for testing because of maternal serum alpha-fetoprotein levels and in those referred due to advanced maternal age. State anxiety was increased in the women referred for maternal serum alpha-fetoprotein levels as compared with women referred for advanced maternal age. True genetic risks were comparable between the groups. Some critics have argued that maternal serum alpha-fetoprotein screening engenders unnecessary anxiety. Our data show that patients undergoing genetic testing due to maternal serum alpha-fetoprotein levels have higher state anxiety than women undergoing testing because of advanced maternal age, but that indication is much less a factor than are partner differences. Therefore, increased anxiety after abnormal maternal serum alpha-fetoprotein testing results cannot be reasonably used as an argument against such testing.

Adult↗

Frequencies of chromosomal abnormalities at amniocentesis: over 20 years of cytogenetic analyses in one laboratory.

Prenatal diagnosis of chromosomal disorders has been performed for more than 20 years, mainly for advanced maternal age. Chromosomal abnormality rates derived from second trimester amniocentesis have mainly come from a collection of small-scale studies from North America and Western Europe. Accurate risk estimates for chromosomal abnormalities are important tools for the physician or obstetrician who would need to make referrals to a prenatal genetic center. This paper presents amniocentesis rates of clinically significant cytogenetic abnormalities for various indications, including advanced maternal age, previous chromosomal abnormality, parental structural rearrangement and a family history of aneuploidy as defined in the text. These data come from a Canadian prenatal diagnosis laboratory with more than 20 years experience in second trimester cytogenetic analysis. They show that the overall frequency of chromosomal abnormalities for advanced maternal age (> or = 35 years) is 1.79%. In this group, 21% of all abnormalities are structural rearrangements (including markers) and less than half of all abnormalities are trisomy 21. The advanced maternal age specific risk of aneuploidies at second trimester is 1.24%. Recurrence risk for aneuploidy after a previous one is 1.29%. However, it is much higher (4.84%) for women of > or = 35 years. When a parent's brother, sister, nephew or niece is affected, the risk of occurrence of aneuploidies (0.24%) is not elevated. When there is a balanced translocation in one of the parents, the overall risk is 10.2% for unbalanced translocations and 37.3% for balanced translocations.

Amniocentesis↗

Correlation between indication for amniocentesis and the time of its performing.

OBJECTIVES: Prenatal diagnosis of fetal disorders is a very wide range of noninvasive and invasive methods. We use ultrasound examination and biochemical tests as screening tools in the low risk pregnancies. In a high risk pregnancy we perform invasive procedures to obtain definitive diagnosis. Amniocentesis is carried out in the first or in the early second trimester of pregnancy to determine: fetal karyotype, monogenic disorders, metabolic errors, the level of alpha-fetoprotein and acetylocholinesterase. DESIGN: The aim of our study was to determine the impact of the indication to amniocentesis on the time of performing the procedure. MATERIALS AND METHODS: We have analysed all the 721 amniocenteses carried out in the Department of Obstetrics in Gdansk in 1996-2002. Amniocenteses were performed due to: advanced maternal age in 553 cases, fetal malformation in current pregnancy in 39 cases, inherited disease in previous pregnancies in 80 cases, maternal balanced translocation in 6 cases, psychological reasons in 15 cases, inherited diseases in the family in 8 cases and serious obstetric history in 9 cases, abnormal results of triple test in 11 cases. The T-Student test was used for statistical analysis with the significance level p=0.05. RESULTS: The amniocentesis was performed in the 15th (from the 12th to the 26th) week of gestation. Amniocentesis performed because of: advanced maternal age in the 15th (from the 12th to the 25th); foetal malformation in current pregnancy in the 16th (from the 12th to the 26th); inherited disease in previous pregnancies in the 14th (from the 12th to the 18th); maternal balanced translocation in the 13th (from the 13th to the 14th); psychological reasons in the 15th (from the 13th to the 18th); inherited diseases in the family in the 15th (from the 13th to the 22nd); serious obstetric history in the 16th (from the 15th to the 17th); abnormal results of triple test in the 16th (from the 14th to the 19th). There is a statistical difference between time of performing amniocentesis because of advanced maternal age, fetal malformation in current pregnancy, maternal balanced translocation and other indications. CONCLUSION: In pregnancies with serious obstetric history--balanced translocation, inherited disease in previous pregnancies--women decided to perform amniocentesis earlier than in cases when advanced maternal age was the only indication for this procedure.

Adult↗