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PubMed2002

Decisions about amniocentesis by advanced maternal age patients following maternal serum screening may not always correlate clinically with screening results: need for improvement in informed consent process.

We evaluated the prenatal diagnosis utilization patterns of advanced maternal age (AMA) patients who underwent serum screening to assess how screening results correlated with their decisions regarding amniocentesis. A 6-year review (1994-1999) of laboratory records identified 2,456 AMA patients who underwent multiple-marker serum screening. The relationship between screening results and patients' decisions on whether or not to undergo amniocentesis was assessed. Among the 841 AMA patients with positive screens, more than half (52%) declined amniocentesis. Of the 1,615 patients with negative serum screening results, 208 (13%) opted for amniocentesis. We concluded that decisions by AMA patients regarding amniocentesis may not always correlate clinically with maternal serum screening results. Possible explanations, including how the state of informed consent may or may not contribute to these decisions, are discussed. It is suggested that understanding the reasons for these decisions may identify opportunities for improving service delivery to all pregnant patients considering prenatal testing. Use of a questionnaire is proposed as one mechanism for gaining a clearer understanding of the possible factors contributing to AMA patient decisions.

Adult↗
PubMed2000

Healthy births and ongoing pregnancies obtained by preimplantation genetic diagnosis in patients with advanced maternal age and recurrent implantation failure.

Preimplantation genetic diagnosis (PGD) and subsequent embryo development was evaluated in 72 couples presenting at our centre for intracytoplasmic sperm injection (ICSI) due to severe male factor. The embryo biopsies were performed in Ca(2+)/Mg(2+)-free medium. These patients were further divided into those with advanced maternal age (AMA, n = 49) and those with recurrent implantation failure (RIF, n = 23). Fluorescence in-situ hybridization (FISH) was carried out on 329 blastomeres (91.3%) with probes for the X, Y, 13, 18 and 21 chromosomes. The chromosomal abnormality rate was 41.3% with no significant difference between the AMA and RIF groups. Aneuploidy accounted for the majority (72.8%) of chromosomal abnormalities. Out of 329 embryos, 84.2% had cleaved after 24 h and 15.1% had arrested. Embryos were transferred in 70 patients and 22 pregnancies were achieved (31.4% with an ongoing pregnancy rate of 28.5%). There were no significant differences between the pregnancy rates of the AMA and RIF groups (32.5 and 30% respectively). Therefore PGD should be offered to patients with AMA and RIF. Furthermore, the use of Ca(2+)/Mg(2+)-free medium during the blastomere biopsy facilitates the procedure, while further embryo cleavage, ongoing pregnancies and healthy births are possible.

Adult↗
PubMed1995

Ovarian activity during follicular-phase down regulation in in vitro fertilization is associated with advanced maternal age and a high recurrence rate in subsequent cycles.

PURPOSE: Previous reports have suggested that the ovarian response to leuprolide acetate is predictive of in vitro fertilization pregnancy rates. This study evaluated the outcome of in vitro fertilization cycles complicated by elevated estradiol levels during leuprolide acetate down regulation and the outcome of subsequent cycles in the same patients. METHODS: Two hundred fifty-two in vitro fertilization cycles were initiated utilizing leuprolide acetate down regulation beginning on cycle day 1. RESULTS: Seventy-four of these cycles had an elevated estradiol level at the time of the baseline scan (28%). This group of patients had a higher maternal age, a higher cycle cancellation rate (27.5 vs 16.3%), and a high rate of recurrence on subsequent cycles (63%). CONCLUSIONS: The pregnancy rate per retrieval was equivalent in the two groups. This suggests that patients with advanced maternal age or a history of failure to suppress in a previous cycle may benefit from alternate regimens of superovulation.

Adult↗
PubMed1993

Limb deficiencies, chorion villus sampling, and advanced maternal age.

Record linkage between a prenatal diagnosis register and a congenital malformation register in the state of Victoria, Australia, has enabled further evaluation of the suggested association between limb deficiencies and early chorion villus sampling (CVS). We found 3 anomalies in this category after later CVS (i.e., 9 weeks and beyond), but our data suggest that advanced maternal age may be a risk factor for both terminal and all limb deficiencies. The data from Victoria are tabulated with data obtained from other registers. Different birth prevalence figures are obtained by different registers, therefore limiting comparisons between registers.

Adult↗
PubMed1998

Isolated mild fetal pyelectasis detected by transvaginal sonography in advanced maternal age.

OBJECTIVE: To evaluate the importance and evolution of isolated, mild fetal pyelectasis, detected in early pregnancy by high-resolution transvaginal sonography, and to determine its association with abnormal fetal karyotypes. METHODS: Transvaginal scan at 11-16 weeks' gestation and transabdominal ultrasound examinations at the time of amniocentesis (16-18 weeks) were performed in 1093 pregnant women undergoing genetic amniocentesis because of advanced maternal age. In 795 cases, transabdominal scans were repeated at 22-24 weeks. Women were excluded if they had a spontaneous abortion, chose to terminate their pregnancy, or declined amniocentesis. Each patient was screened for fetal pyelectasis, defined as an increase in anteroposterior renal pelvic diameter, using cutoff values related to various stages of pregnancy. RESULTS: Isolated fetal pyelectasis was detected at the first ultrasound examination in 56 women (5.1%) in early pregnancy, in 32 (2.9%) at the time of amniocentesis, and in 23 (2.9%) at 22-24 weeks' gestation. Two fetuses with diagnoses of mild pyelectasis at the first transvaginal ultrasound demonstrated abnormal karyotypes at amniocentesis. In one case, the pyelectasis disappeared at 22-24 weeks' gestation. CONCLUSION: This retrospective study shows that pyelectasis is more frequently detectable by high-resolution transvaginal sonography in the first half of pregnancy than in the second half. When detected in early pregnancy, the finding is frequently transient and not associated with an increased risk of abnormal fetal karyotypes.

Adult↗
PubMed1997

Causes of fetal death in women of advanced maternal age.

OBJECTIVE: To examine which causes of fetal death occur more often in older women and to determine whether these causes have changed significantly since the 1960 s and early 1970 s. METHODS: Data from the McGill Obstetrical Neonatal Database were used to calculate rates of specific causes of fetal death in women younger than 35 and in women 35 years or older. Among the 101,640 births between 1961 and 1995, there were 715 stillbirths and 822 neonatal deaths. The autopsy rate was 97% and categorization of the causes of fetal death remained consistent over this 34-year period. The rates of specific causes of fetal death per 10,000 total births were determined for an earlier period (1961-1974) and a later period (1978-1995). RESULTS: Compared with the 1961-1974 period, there was a 60% reduction in the rates of both fetal and neonatal deaths during 1978-1995 (P < .001). During 1961-1974, women 35 years or older were more likely than their younger counter-parts to have fetal death due to lethal congenital anomalies (odds ratio [OR] 3.2; 95% confidence interval [CI] 1.5, 6.5); this was no longer true in the 1978-1995 period. From 1978 to 1995, older women were at a statistically significant increased risk for "unexplained" fetal death (OR 2.2; 95% CI 1.3, 3.8); women 35 years of age or older had approximately one in 440 births end in unexplained fetal death, compared to one in 1000 births for women younger than 35. CONCLUSIONS: Advanced maternal age is no longer associated with an increased risk for fetal death due to congenital anomalies. However, older women have a significantly higher risk for unexplained fetal death. The identification of those maternal and fetal characteristics that contribute to unexplained fetal death and its prevention remain important challenges for contemporary obstetric practice.

Cause of Death↗
PubMed2002

Impact of advanced maternal age on pregnancy outcome.

The aim of this study was to compare the pregnancy outcome and delivery complications in women 40 years or older (cases) to that of women 20 to 30 years old (controls). Over a 5-year period, 319 cases had a singleton delivery in our institution. These women were compared with 326 controls. Parity was significantly higher in cases compared with controls (3.2 vs. 1.8). Advanced maternal age, compared with younger age, was associated with significantly higher rates of preterm delivery (16.0 vs. 8.0%), cesarean delivery (CS) (31.3 vs. 13.5%), and the occurrence of one or more antepartum complications (29.5 vs. 16.6%). When the two groups were subdivided according to parity, rates of preterm delivery, CS, preeclampsia, gestational diabetes, chronic hypertension, and labor induction were each significantly higher among older multiparas compared with control multiparas. However, only preterm delivery, CS rates, and uterine fibroids were found to be significantly higher in older nulliparous compared with young nulliparous women. We conclude that multiparous women at least 40 years old have a higher antepartum complication rate including intrauterine fetal death compared with younger women.

Cesarean Section↗
PubMed1998

Effect of very advanced maternal age on pregnancy outcome and rate of cesarean delivery.

OBJECTIVE: To determine outcomes of pregnancies in women at least 44 years of age and to determine factors predicting cesarean delivery in these patients. METHODS: Between January 1988 and December 1995, 109 women at least 44 years old delivered in our medical center. These women were matched to a group of 309 women 20-29 years of age. Multiple logistic regression analysis was used to evaluate the association between maternal age and outcome variables, controlling for possible confounding factors. Based on the logistic regression, a predictive model was calculated for cesarean delivery and validated prospectively in a separate group of 30 consecutive women at least 44 years old, who delivered during the first 8 months of 1996. RESULTS: Very advanced maternal age, compared with younger age, was associated with a significantly higher rate of medical complications (hypertensive disorder and diabetes) (odds ratio [OR] 2.5; 95% confidence interval [CI] 1.5, 4.1; P < .001), instrument-assisted vaginal delivery (OR 7.5; 95% CI 2.2, 25.0; P < .004), and cesarean delivery (OR 7.3; 95% CI 2.2, 16.7; P < .001). The incidences of preterm labor, premature rupture of membranes, emergency cesarean delivery, meconium-stained amniotic fluid, small for gestational age newborns, and 5-minute Apgar scores of 7 or lower were not influenced by maternal age. The regression model showed an increased risk for cesarean delivery associated with age of at least 44 years (OR 7.3; 95% CI 2.2, 16.7), primiparity (OR 3.5; 95% CI 1.3, 9.8), infertility treatment (OR 3.6; 95% CI 1.5, 8.8), and egg donation (OR 19.5; 95% CI 6.1, 62.2), with positive and negative predictive values of 94 and 86%, respectively. CONCLUSION: Maternal age of at least 44 years is associated with medical complications in pregnancy and more interventions during labor. However, overall pregnancy outcomes are favorable. Cesarean delivery can be predicted accurately based on maternal age, parity, and infertility treatment.

Adult↗
PubMed2005

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.

Adult↗
PubMed2005

A randomized trial comparing alternative approaches to prenatal diagnosis counseling in advanced maternal age patients.

Prenatal diagnosis (PND) is offered routinely as part of pregnancy care to a large number of women at increased risk of fetal anomalies. Despite an extraordinary growth in the use of PND and significant resource allocation, few studies have examined outcomes of PND counseling, and virtually no research has evaluated the relative efficacy of various approaches to genetic counseling. This study was a randomized trial that compared which counseling methods - individual, group, and use of a decision aid - are effective in PND counseling for women of advanced maternal age (>/=35 years) and their partners. Three hundred and fifty-two women and 225 partners completed pre- and post-intervention questionnaires assessing changes in knowledge, decisional conflict, state anxiety, satisfaction, use of PND, and pregnancy outcomes. All participants showed a significant increase in knowledge and a decrease in decisional conflict post intervention. Those in the group intervention showed a significantly greater increase in knowledge than those in the individual counseling intervention. While high levels of satisfaction were reported by all, those in individual counseling were significantly more satisfied than those receiving group counseling or the decision aid. This study has shown unique benefits with each type of intervention such that women and their partners preferred individual genetic counseling, while they learned best in group-counseling sessions, and experienced the least decisional conflict regarding genetic testing with a decision aid.

Adult↗
PubMed2001

Triple marker screening for fetal chromosomal abnormalities in Korean women of advanced maternal age.

The purpose of this article is to assess the value of maternal serum triple marker screening of alpha-fetoprotein (AFP), human chorionic gonadotropin (hCG), and unconjugated estriol (uE3) for the prenatal diagnosis of fetal chromosomal abnormalities in Korean women of advanced maternal age. Maternal sera were collected from 458 pregnant Korean women aged 35 between 15 and 20 weeks gestation before amniocentesis. A patient- specific second trimester risk for fetal Down's syndrome was calculated using the median values for AFP, hCG, uE3 and maternal age. Twelve fetal chromosomal abnormalities were identified. These included six cases of trisomy 21, one case of 46,XY/47,XY,+21, two cases of trisomy 18, one case of trisomy 13, and two cases of 45, X. A cutoff level of 1:200 detected 85.7% (6/7) of the cases of Down's syndrome and 20% (1/5) of the other aneuploidies, with a 27.3% false positive rate. However, a cutoff level of 1:270 did not result in any gains in detecting Down's syndrome or other aneuploidies at the expense of a false positive rate of 34.3%. Second trimester triple marker testing is an effective screening tool for detecting fetal Down's syndrome in Korean women > or = 35 years old. However, it is not an effective screening tool for non-Down's chromosomal abnormalities.

Adult↗
PubMed1999

Prevalence and significance of isolated fetal choroid plexus cysts detected in early pregnancy by transvaginal sonography in women of advanced maternal age.

This study examines the prevalence of isolated fetal choroid plexus cysts (CPCs) detected in early pregnancy by transvaginal sonography in an increased genetic risk population and their association with abnormal fetal karyotype. A prospective study was performed on 1692 pregnant women (>37 years) who underwent transvaginal scan at 11-16 weeks' gestation before genetic amniocentesis. The prevalence of isolated CPCs in our population was 1.48 per cent. An abnormal fetal karyotype was found in one case (4 per cent). It was concluded that if fetal CPCs are apparently isolated, genetic amniocentesis is not mandatory and additional risk factors such as advanced maternal age should be the main indication for fetal karyotyping.

Adult↗
PubMed1997

Increased trinucleotide repeat instability with advanced maternal age.

Nucleotide repeat instability is associated with an increasing number of cancers and neurological disorders. The mechanisms that govern repeat instability in these biological disorders are not well understood. To examine genetic aspects of repeat instability we have introduced an expanded CAG trinucleotide repeat into transgenic mice. We have detected intergenerational CAG repeat instability in transgenic mice only when the transgene was maternally transmitted. These intergenerational instabilities increased in frequency and magnitude as the transgenic mother aged. Furthermore, triplet repeat variations were detected in unfertilized oocytes and were comparable with those in the offspring. These data show that maternal repeat instability in the transgenic mice occurs after meiotic DNA replication and prior to oocyte fertilization. Thus, these findings demonstrate that advanced maternal age is an important factor for instability of nucleotide repeats in mammalian DNA.

Adenine↗
PubMed2000

The practical importance of pedigree analysis in women considering invasive prenatal diagnosis for advanced maternal age or abnormal serum screening tests.

Genetic counselling prior to prenatal diagnosis subserves several functions, one of them to put the planned prenatal test into the wider context of the personal and familial medical history. Even though considered a pivotal part of counselling, little is known about the informational yield and practical relevance of a comprehensive pre-test pedigree analysis. This is particularly true for patients who do not consider prenatal diagnosis for a specific heritable disorder with a high recurrence risk in the ongoing pregnancy, but for a moderate risk for conditions such as Down syndrome that mostly arise de novo. We analysed the informational yield of pedigree analysis for such patients through a retrospective analysis of 1356 consecutive genetic counselling sessions. All cases were referred for advanced maternal age or an abnormal result upon triple serum marker screening. 148 cases (10.9%) were classified as having a significant and previously unknown genetic or teratologic risk factor for the fetus that was uncovered through pedigree analysis. Of these cases, 55% could be recommended a specific prenatal test covering the previously unknown genetic risk factor.

Abnormalities, Drug-Induced↗
PubMed1996

Advanced maternal age and the risk of Down syndrome characterized by the meiotic stage of chromosomal error: a population-based study.

The identification of DNA polymorphisms makes it possible to classify trisomy 21 according to the parental origin and stage (meiosis I [MI], meiosis II [MII], or postzygotic mitotic) of the chromosomal error. Studying the effect of parental age on these subgroups could shed light on parental exposures and their timing. From 1989 through 1993, 170 infants with trisomy 21 and 267 randomly selected control infants were ascertained in a population-based, case-control study in metropolitan Atlanta. Blood samples for genetic studies were obtained from case infants and their parents. Using logistic regression, we independently examined the association between maternal and paternal age and subgroups of trisomy 21 defined by parental origin and meiotic stage. The distribution of trisomy 21 by origin was 86% maternal (75% MI and 25% MII), 9% paternal (50% MI and 50% MII), and 5% mitotic. Compared with women <25 years of age, women > or = 40 years old had an odds ratio of 5.2 (95% confidence interval, 1.0-27.4) for maternal MI (MMI) errors and 51.4 (95% confidence interval, 2.3-999.0) for maternal MII (MMII) errors. Birth-prevalence rates for women > or = 40 years old were 4.2/1000 births for MMI errors and 1.9/1000 for MMII errors. These results support an association between advanced maternal age and both MMI and MMII errors. The association with MI does not pinpoint the timing of the error; however, the association with MII implies that there is at least one maternal-age related mechanism acting around the time of conception.

Adult↗
PubMed2006

Advanced maternal age as an indication for preimplantation genetic diagnosis (PGD)--the need for more judicious application in clinically assisted reproduction.

BACKGROUND: Pre-implantation genetic diagnosis (PGD) is often recommended for routine screening of chromosomal aneuploidy in older women undergoing clinical assisted reproduction, even though its prognostic value on this group of patients is rather ambiguous. What is needed is a clear set of ethical guidelines in the marketing of this technically complex and expensive procedure to patients who are neither suffers nor carriers of serious genetic diseases. METHODS: Professional counseling would be required to enable an informed decision from the patient. Differences in the prognostic value of PGD for different medical indications must be clearly presented to the patient and they must also be told that PGD is not a completely 'fool-proof' means of preventing birth defects. What may be detected are some genetic syndromes and conditions associated with cytogenetic abnormalities. RESULTS: The patient must be made aware that the results of previous studies have demonstrated that the overwhelming majority of chromosomally abnormal oocytes and embryos either fail to fertilize or implant, and therefore have a relatively low chance of resulting in a live birth with chromosomal defects. Statistical data, particularly the concept of relative risk must clearly be presented to the patient without exaggerating the risk of birth defects. The patient must also be rightfully informed that PGD carries a small risk of damaging the embryo, which could compromise chances of conception. CONCLUSIONS: PGD should be judiciously indicated for advanced maternal age in clinically assisted reproduction. Other diagnostic options that may be cheaper, and which also possess a high level of accuracy should be presented first to the patient i.e. amniocentesis, chorionic villus biopsy and ultrasonargraphy.

Aneuploidy↗
PubMed2006

Advancing paternal age and autism.

CONTEXT: Maternal and paternal ages are associated with neurodevelopmental disorders. OBJECTIVE: To examine the relationship between advancing paternal age at birth of offspring and their risk of autism spectrum disorder (ASD). DESIGN: Historical population-based cohort study. SETTING: Identification of ASD cases from the Israeli draft board medical registry. PARTICIPANTS: We conducted a study of Jewish persons born in Israel during 6 consecutive years. Virtually all men and about three quarters of women in this cohort underwent draft board assessment at age 17 years. Paternal age at birth was obtained for most of the cohort; maternal age was obtained for a smaller subset. We used the smaller subset (n = 132 271) with data on both paternal and maternal age for the primary analysis and the larger subset (n = 318 506) with data on paternal but not maternal age for sensitivity analyses. MAIN OUTCOME MEASURES: Information on persons coded as having International Classification of Diseases, 10th Revision ASD was obtained from the registry. The registry identified 110 cases of ASD (incidence, 8.3 cases per 10 000 persons), mainly autism, in the smaller subset with complete parental age data. RESULTS: There was a significant monotonic association between advancing paternal age and risk of ASD. Offspring of men 40 years or older were 5.75 times (95% confidence interval, 2.65-12.46; P<.001) more likely to have ASD compared with offspring of men younger than 30 years, after controlling for year of birth, socioeconomic status, and maternal age. Advancing maternal age showed no association with ASD after adjusting for paternal age. Sensitivity analyses indicated that these findings were not the result of bias due to missing data on maternal age. CONCLUSIONS: Advanced paternal age was associated with increased risk of ASD. Possible biological mechanisms include de novo mutations associated with advancing age or alterations in genetic imprinting.

Adult↗
PubMed2006

Induction of labor with misoprostol in pregnancies with advanced maternal age.

OBJECTIVE: The objective was to compare the efficacy and complications of intravaginal misoprostol application with oxytocin infusion for induction of labor in advanced aged pregnancies with a Bishop score of < 6. STUDY DESIGN: A hundred advanced aged (> or = 35 years) pregnant patients with a Bishop score of < 6 were randomized into two groups. The first group (50 patients) received 50 microg intravaginal misoprostol four times with 4 h intervals and the second group received oxytocin infusion for induction of labor starting from 2 mIU/min and was increased every 30 min with 2 mIU/min increments up to a maximum of 40 mIU/min. The time from induction to delivery, the route of delivery, fetal outcome, and maternal complications were recorded. Statistical analyses were performed using the Mann-Whitney U, Chi-squared and t tests to determine differences between the two groups. A p value < or = 0.05 was considered significant. RESULTS: Misoprostol was superior for induction of labor in advanced aged pregnancies with Bishop score of < 6, as the mean time from induction to delivery was 9.61 +/- 4.12 h and 11.46 +/- 4.86 h in the misoprostol and oxytocin groups respectively, with a significant difference between the groups (p = 0.04). The rate of vaginal delivery was higher in the misoprostol group (84.0%) than in the oxytocin group (80.0%), but the difference did not reach significance (p = 0.60). The rates of placental abruption and postpartum hemorrhage were similar in both groups and no cases of uterine rupture occurred. The 1- and 5-min mean Apgar scores were 6.98 +/- 1.17 to 9.08 +/- 0.99 and 6.88 +/- 1.81 to 9.00 +/- 1.35 in the misoprostol and oxytocin groups respectively, with no significant differences between the groups (p = 0.74, p = 0.83). No cases of asphyxia were present. The rate of admission to the neonatal intensive care unit was similar in both groups. CONCLUSION: Intravaginal misoprostol seems to be an alternative method to oxytocin in the induction of labor in advanced aged pregnant women with low Bishop scores, as it is efficacious, cheap, and easy to use. But large studies are necessary to clarify safety with regard to the rare complications such as uterine rupture.

Administration, Intravaginal↗