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PubMed2004

Effect of advanced maternal age on early mortality among quadruplets and quintuplets.

OBJECTIVE: This study was undertaken to determine whether advanced maternal age has an impact on survival among quadruplets and quintuplets. STUDY DESIGN: A retrospective cohort study was performed on 1 448 quadruplets and 180 quintuplets delivered in the United States between 1995 and 1997. Infants of older mothers (> or =35 years old) were compared with those of younger ones (<35 years old) in terms of early mortality indices. Adjusted mortality probabilities were computed by yearly intervals of maternal age. RESULTS: The likelihood for neonatal (odds ratio [OR]=2.00, 95% CI=1.20-3.45), perinatal (OR=2.10, 95% CI=1.32-3.23), and infant mortality (OR=2.13, 95% CI=1.28-3.60) was significantly higher among younger mothers. For each unit decrease in maternal age, the odds of stillbirth, neonatal, perinatal, and infant death went up by 9%, 12%, 13%, and 12%, respectively, in a dose-dependent fashion (P for trend <.0001). CONCLUSION: We found increasing maternal age to be associated with favorable survival outcomes among quadruplets and quintuplets.

Adult↗
PubMed2005

Pregnancy outcomes in women of very advanced maternal age.

OBJECTIVE: To assess outcomes for pregnancies progressing beyond 20 weeks' gestation in women of very advanced maternal age. DESIGN: Retrospective cohort study. SETTING: Two tertiary level obstetric hospitals. POPULATION: Women aged 45 years or more at the time of delivery over a 10-year period from 1 January 1992 to 31 December 2001. METHODS: Information regarding maternal, pregnancy and neonatal outcomes was obtained from the medical records. For comparison, routinely collected data from the obstetric database was obtained for women aged 20-29 years. RESULTS: Seventy-seven pregnancies in 76 women aged 45 years and over were registered in the 10-year period. There were 74 liveborn singletons, two sets of liveborn twins and one set of twins stillborn at 20 weeks' gestation. Sixteen women were primiparous. Eighty-four percent of pregnancies were conceived naturally and 53% underwent prenatal chromosomal determination; 53% of women had no pre-existing medical problems, 13% had hypertensive disorders of pregnancy and 8% of women developed gestational diabetes. There were 10 preterm and six post dates deliveries. The Caesarean section rate was 49%, compared to 23% in the 20-29 years age group (P < 0.001). Ten percent of neonates were small for gestational age, and 8% were large for gestational age. Seventeen percent required admission to the special care nursery and 6% had congenital abnormalities. CONCLUSIONS: Maternal and neonatal outcomes in this series were generally good. There was a significantly increased rate of Caesarean section. Overall, this study is reassuring for women aged 45 and over who have good general health and a chromosomally normal fetus.

Cesarean Section↗
PubMed1991

Prenatal diagnosis in advanced maternal age. Amniocentesis or CVS, a patient's choice or lack of information?

Ninety-six women of advanced maternal age were interviewed about the way they obtained information on prenatal diagnosis and about how the decision was made as to what procedure was to be performed (transabdominal chorionic villus sampling (TA-CVS) or amniocentesis). In the CVS group, women visited their physician or midwife earlier in pregnancy (mean 7.1 weeks) than those in the amniocentesis group (mean 10.7 weeks). The availability of prenatal diagnosis was not mentioned during the first antenatal visit in 55 per cent of women from the amniocentesis group as opposed to 25 per cent from the TA-CVS group. Approximately 40 per cent of women eligible for prenatal diagnosis did not receive any information from the referring body prior to counselling at our centre. Only 29 per cent of women who underwent amniocentesis had actually chosen this procedure; 71 per cent were too late to undergo TA-CVS at 12 weeks. It is concluded that information to the patient must be improved in order to ensure early referral for prenatal diagnosis.

Adult↗
PubMedDate not supplied

Is routine amniocentesis for advanced maternal age still indicated?

OBJECTIVE: To evaluate a policy of selective rather than routine use of amniocentesis for advanced maternal age. METHOD: A consecutive series of 359 pregnant women aged 38-47 underwent nuchal translucency measurement (NTM) at 10-14 weeks, maternal serum screening (MSS) by alpha-fetoprotein (AFP) and human chorionic gonadotropin (hCG) at 15-17 weeks, and second trimester ultrasound at 21-23 weeks. Women with NTM <3 mm, MSS-derived risk <1/250, and a normal second trimester sonography were considered at low risk and were suggested not to have an amniocentesis. RESULTS: Either the NTM or MSS test was positive in 130 women; 105 (81%) of them elected to have an amniocentesis, versus 122 (53%) of 229 in whom both tests were negative (p < 0.001). Nineteen (5%) of 359 patients had NTM > or =3 mm; all 7 cases of Down's syndrome were in this group; 122 (34%) of 359 patients had a MSS-derived risk > or =1/250; 6 of the 7 cases of Down's syndrome were in this group: Ten patients had an abnormal second trimester ultrasound, 1 of which had trisomy 18. Of the 219 patients with MSS-derived risk <1/250, a NTM <3 mm, and a normal second trimester ultrasound, none had a baby with a chromosomal abnormality (95% confidence interval: 0-1.4%). CONCLUSION: Amniocentesis may be offered on a selective rather than routine basis in women over 38, based upon the results of noninvasive screening tests.

Adult↗
PubMed2006

Changing attitudes towards non-invasive aneuploidy screening at advanced maternal age in a German tertiary care center.

OBJECTIVE: To evaluate attitudes towards non-invasive aneuploidy screening at advanced maternal age in a German tertiary care centre and to compare the rate of invasive testing over a period of four years. METHODS: A retrospective analysis of 2657 singleton pregnancies with targeted first and second trimester ultrasound examination at 11-14, 15-18 and 19-23 weeks' gestation. RESULTS: The number of patients at or beyond 35 years increased by 36 % over this period. Concomitant with an increasing proportion of first trimester examinations (+ 13 %), a decrease in 15-18 weeks' examinations (- 14 %), but no changes regarding the 19-23 weeks' examination were observed. A total of 78 (2.9 %) abnormal karyotypes were found and 92 % (56/61) of the cases with autosomal trisomy had sonographic markers suggestive of foetal aneuploidy. The proportion of diagnosed chromosomal abnormalities at 11-14 weeks increased from 14 % in the first half to 49 % in the second half of the study period (p < 0.01). We observed a significant decrease in the rate of invasive procedures, especially in women reassured by a normal ultrasound examination (54 % versus 37 %, p < 0.01). CONCLUSION: There is an increasing acceptance of first trimester targeted ultrasound examination with the potential advantage of an earlier diagnosis of foetal aneuploidy. Furthermore, we observed annually increasing numbers of women who used the results of the ultrasound examination to guide their final decision about invasive testing, rather than undergo genetic testing as a primary option.

Aneuploidy↗
PubMed1993

Mitotic errors in somatic cells cause trisomy 21 in about 4.5% of cases and are not associated with advanced maternal age.

The study of DNA polymorphisms has permitted the determination of the parental and meiotic origin of the supernumerary chromosome 21 in families with free trisomy 21. Chromosomal segregation errors in somatic cells during mitosis were recognized after analysis of DNA markers in the pericentromeric region and (in order to identify recombination events) along the long arm of chromosome 21. Mitotic errors accounted for about 4.5% (11 of 238) of free trisomy 21 cases examined. The mean maternal age of mitotic errors was 28.5 years and there was no association with advanced maternal age. There was no preference in the parental origin of the duplicated chromosome 21. The 43 maternal meiosis II errors in this study had a mean maternal age of 34.1 years-the highest mean maternal age of all categories of chromosomal segregation errors.

Adult↗
PubMed2003

The impact of advanced maternal age (> or = 40 years) on birth outcomes among triplets: a population study.

OBJECTIVE: The objective was to determine the impact of advanced maternal age on the birth outcomes of triplet gestations. STUDY DESIGN: A retrospective cohort study on 15,795 triplets born in the United States from 1995 to 1997. The generalized estimating equations framework was used to generate relative risks after capturing the effect of sibling correlations within triplet clusters. RESULTS: There was a 40% higher likelihood for stillbirths among older gravidas (> or = 40 years) as compared to younger mothers (20-29 years) although this was statistically non-significant. By contrast, we noted a significantly lower level of neonatal mortality (OR=0.36, 95% CI=0.19-0.67), perinatal mortality (OR=0.53; 95% CI=0.32-0.89) and infant mortality (OR=0.37; 95% CI=0.20-0.67) among older mothers. CONCLUSION: Our findings demonstrate a "shifting phenomenon" whereby a higher level of intra-uterine demise was compensated by a higher rate of extra-uterine survival among triplets born to older mothers.

Adult↗
PubMed1997

Advanced maternal age and perinatal outcome: oocyte recipiency versus natural conception.

OBJECTIVE: To compare perinatal outcome in older oocyte recipients with that in women of advanced maternal age who conceived without assisted reproductive technologies. METHODS: We performed a retrospective cohort study of 46 oocyte recipients and 49 women who conceived without assisted reproductive technologies. The obstetric courses in singleton and multiple gestations in the two groups of women were compared. RESULTS: Among singleton pregnancies, a comparable obstetric course was noted between the groups. Fifty percent of the oocyte recipients experienced multiple gestations, resulting in an increased risk for placenta previa, premature rupture of membranes, preterm labor and delivery, glucose intolerance of pregnancy, pregnancy-induced hypertension, and cesarean delivery. However, only the risks for pregnancy-induced hypertension and cesarean delivery were significantly increased in the pregnancies of oocyte recipients with multiple gestations. CONCLUSIONS: Perinatal complications in women receiving oocyte donation may be related to their higher incidence of multiple gestation.

Age Factors↗
PubMed2004

Comparison of blastocyst transfer with or without preimplantation genetic diagnosis for aneuploidy screening in couples with advanced maternal age: a prospective randomized controlled trial.

BACKGROUND: It is generally accepted that the age-related increased aneuploidy rate is correlated with reduced implantation and a higher abortion rate. Therefore, advanced maternal age (AMA) couples are a good target group to assess the possible benefit of preimplantation genetic diagnosis for aneuploidy screening (PGD-AS) on the outcome after assisted reproductive technology (ART). METHODS: A prospective randomized controlled clinical trial (RCT) was carried out comparing the outcome after blastocyst transfer combined with PGD-AS using fluorescence in situ hybridization (FISH) for the chromosomes X, Y, 13, 16, 18, 21 and 22 in AMA couples (aged > or =37 years) with a control group without PGD-AS. From the 400 (200 for PGD-AS and 200 controls) couples that were allocated to the trial, an oocyte pick-up was performed effectively in 289 cycles (148 PGD-AS cycles and 141 control cycles). RESULTS: Positive serum HCG rates per transfer and per cycle were the same for PGD-AS and controls: 35.8% (19.6%) [%/per embryo transfer (per cycle)] and 32.2% (27.7%), respectively (NS). Significantly fewer embryos were transferred in the PGD-AS group than in the control group (P<0.001). The implantation rate (with fetal heart beat) was 17.1% in the PGD-AS group versus 11.5% in the control group (not significant; P=0.09). We observed a normal diploid status in 36.8% of the embryos. CONCLUSIONS: This RCT provides no arguments in favour of PGD-AS for improving clinical outcome per initiated cycle in patients with AMA when there are no restrictions in the number of embryos to be transferred.

Adult↗
PubMedDate not supplied

Utilization of prenatal cytogenetic diagnosis in women of advanced maternal age in Australia, 1979-1982.

This paper reports the results of a complete national survey to measure utilization rates of prenatal cytogenetic diagnosis (P.C.D.) in women of advanced maternal age in Australia. P.C.D. has been available throughout Australia for the last decade. Every laboratory in Australia providing a P.C.D. service for the years 1979-1982 took part in this study. Utilization rates (both National and State rates) by ages of mothers, are presented. Big interstate differences exist. The 1982 National P.C.D. utilization rate for pregnant women who were 40 years of age and over was 38.8 per cent, and this rate has shown an average annual increase of 9 per cent. In those four States which offered P.C.D. to pregnant women of 35 years or over the median utilization rate was 20 per cent. These Australian rates indicate an under-utilization of P.C.D. services with (in 1982) 50-80 per cent of 'at risk' women not being tested. Factors which influence this are discussed.

Adult↗
PubMed1996

Ultrasonographically adjusted midtrimester risk of trisomy 21 and significant chromosomal defects in advanced maternal age.

OBJECTIVE: Our purpose was to determine whether normal midtrimester ultrasonography results reduces the risk of fetal Down syndrome and any clinically significant chromosomal defects in pregnancies with advanced maternal age and to develop risk tables on the basis of age and ultrasonographic results. STUDY DESIGN: Biometry data were obtained in 4079 women between 15 and 24 weeks undergoing amniocentesis for maternal age. Expected values of humerus, femur, both combined, and abdominal circumference based on biparietal diameter were generated from a normal group. Observed/expected values of each parameter and nuchal thickness > or = 6 mm was used to screen for Down syndrome and any clinically significant chromosome defects. Receiver-operator characteristic curves were used to determine threshold screening values for each parameter. By use of stepwise logistic regression the optimal measurements for detection of chromosome anomalies were established. An abnormal ultrasonography result was defined as either abnormal biometry choroid plexus cysts or a structural defect. RESULTS: The finding of shortened humerus (observed/expected < 0.90), abnormal nuchal thickness, or an anatomic defect had the highest sensitivity for Down syndrome detection, 70.6%, p < 0.0001, whereas a short humerus, small abdominal circumference, (observed/expected < 0.92), or an anatomic defect had a sensitivity of 46.7%, p < 0.0001, for any significant chromosome defect. With a normal ultrasonography the risk of Down syndrome in a 39-year-old woman falls from 1:100 to < 1:292. CONCLUSION: A normal ultrasonography substantially reduces the risk of Down syndrome and any chromosome abnormality. This information is useful in counseling women who decline amniocentesis on the basis of maternal age.

Biometry↗
PubMed1983

Genetic counseling before prenatal diagnosis for advanced maternal age: an important medical safeguard.

Genetic counseling before amniocentesis has been advocated by many geneticists with little evidence to support their contention. Records of patients referred exclusively for advanced maternal age were evaluated for additional diagnostic information obtained from the genetic counseling process that could place these patients at additional risks for previously unsuspected fetal abnormalities. A significant number of patients (43.3%) were at additional risk or had significant concerns regarding one or more hereditary or congenital disorders requiring extensive genetic counseling. The results of the present study provide a scientific basis for the consideration of genetic counseling as a standard part of all prenatal diagnostic procedures.

Adult↗
PubMed1983

The frequency and mutation rate of balanced autosomal rearrangements in man estimated from prenatal genetic studies for advanced maternal age.

The frequencies of balanced chromosome rearrangements were estimated from three series of advanced maternal-age prenatal genetic studies, and were compared to the frequencies that had been estimated from consecutive newborn surveys. In the maternal-age prenatal studies, the frequencies were: Robertsonian translocations, 0.11%; reciprocal translocations, 0.17%; and inversions, 0.12%. The total frequency of balanced rearrangements in the prenatal genetic studies performed with banding (0.40%, or 1 in 250) was twice that in the consecutive newborn surveys performed without banding (0.19%, or 1 in 526). The difference was limited to inversions and reciprocal translocations; the frequency of Robertsonian translocations was similar in the prenatal series and the newborn surveys. Both familial and de novo rearrangements were more common than anticipated. The de novo cases provided a mutation rate estimate of 4.3 per 10,000 gametes per generation (compared with 1.78 to 2.2 per 10,000 gametes in other surveys). These higher estimates may more reliably approximate the true mutation rate and frequencies of balanced rearrangements in the newborn population than do the newborn surveys.

Chromosome Aberrations↗
PubMed2005

Changing demographics of advanced maternal age (AMA) and the impact on the predicted incidence of Down syndrome in the United States: Implications for prenatal screening and genetic counseling.

This study documents the changes in the percentages of advanced maternal age (AMA) pregnancies in the United States and in Washington State, underlying demographic factors, the impact on the predicted incidence of Down syndrome, and its impact on Down syndrome screening. Data on births in the United States from 1933 to 2002 were obtained from publications and the website of the National Center for Health Statistics. Data for Washington State were obtained from the website of the Washington State Department of Health. Information on births at Swedish Medical Center was obtained from hospital records. The percentage of AMA pregnancies in the US was about 14% before World War II, dropped steadily to about 5% in the 1970s and rose since the 1980s to about 14% in 2002. AMA Fractions are greatest among non-Hispanic Caucasians and Asian/Pacific Islanders, women who have college education and beyond, and are married. However, since 1980, the AMA Fractions have increased across all racial/ethnic groups, educational levels, and married and unmarried women. In Washington State in 2001, the overall AMA Fraction was about 14%, but there was considerable variation in the AMA Fraction across counties. In 1980, AMA pregnancies accounted for about 25% of pregnancies with Down syndrome in the United States. In 2002, AMA pregnancies accounted for more than 50% of Down syndrome pregnancies. Given the current AMA Fraction, offering amniocentesis to women of age 35 and above would result in one in seven pregnant women undergoing amniocentesis. Based on likelihood ratios, AMA as a screening strategy for Down syndrome is significantly inferior to combined serum and sonographic screening.

Adult↗
PubMed1997

Chromosomal analysis in 894 induced abortuses from women of advanced maternal age in relation to gestational weeks and fetal sex ratio.

OBJECTIVE: To clarify the prenatal sex ratio, and types and frequencies of chromosome anomalies in relation to gestational weeks in women of advanced maternal age. METHODS: Chromosomal analysis was performed in 894 induced abortuses derived from elderly pregnant women 35 or more years of age. RESULTS: The embryonic sex ratio in the chromosomally normal (abnormal) gave a preponderance of females over males in lower gestational weeks [366/458 (63/73); 79.9 to 100 (86.3 to 100) in 4-10 weeks]; the reversal of dominancy in those from females to males occurred in the 11th gestational week [41/29(5/4); 141.4 to 100 (125.0 to 100) in 11-20 weeks]. The frequency of trisomy in females at 10 weeks of gestation was significantly high (7/28; 25%). CONCLUSIONS: This study showed that the existence of a difference of and a reversal of the sex ratio in gestational weeks. It was considered that there might be a lower viability of genetically handicapped males as compared to such females. However, the reversal of the sex ratio, such as that observed between 9th and 10th gestational weeks, might reflect events occurring after implantation.

Abortion, Induced↗
PubMed1989

Toward a better understanding of the "advanced maternal age" factor.

Women over the age of 30-35 are presumed to encounter more adverse pregnancy outcomes because of their reduced reproductive efficiency. In the vast majority of studies of advanced maternal age and pregnancy outcome, however, researchers have failed to control for important contextual differences surrounding the pregnancy and childbirth experiences of younger and older women. These contextual differences can account for a considerable portion of the differential results mistakenly ascribed to reproductive age. In this article are reviewed research findings that identify three such hidden factors: older women's increasing likelihood of chronic diseases that adversely affect pregnancy outcome; the altered medical management of middle-aged women's pregnancies and labors, with resultant iatrogenically caused complications; and demographic characteristics suggesting that midlife pregnancy in the past has been associated with poverty or subfertility and today is associated with healthy middle-class postponers.

Adult↗
PubMed1993

The need to reevaluate trisomy screening for advanced maternal age in prenatal diagnosis.

OBJECTIVES: Fluorescence in situ hybridization aneuploidy screening promises immediate results. To evaluate aneuploidy screening in prenatal diagnosis, the prenatal records at Oregon were reviewed. STUDY DESIGN: Karyotype reports of 7240 amniocentesis samples referred for advanced maternal age were retrospectively reviewed for numeric and structural chromosome abnormalities. RESULTS: The frequency of abnormal karyotypes was 2.5%; 1.4% were age-related trisomies and sex-chromosome aneuploids, and 1.1% were non-age-related abnormalities. The incidence of structural rearrangements was 0.9%, of which 70% were familial but not suspected on the basis of family history. CONCLUSIONS: Structural chromosome abnormalities were twice as common as previously reported, representing a significant unrecognized risk for subsequent pregnancies and other family members. Fluorescence in situ hybridization aneuploidy screening would not routinely detect structural chromosome abnormalities, which were twice as frequent as numeric aneuploidy at age 35 years. Routine use of fluorescence in situ hybridization for prenatal diagnosis should not be adopted without a prospective study of its accuracy, reliability, and impact on prenatal diagnosis.

Amniocentesis↗
PubMedDate not supplied

Effects of advanced maternal age on development of preimplantation mouse embryos obtained from delayed mating.

Rodent embryos resulting from delayed mating grow more quickly than those resulting from normal mating. To clarify the effects of maternal age on this enhanced growth and rapid differentiation of mouse embryos obtained from delayed mating, we studied normal (0 h after ovulation) and delayed mating (6 h after ovulation) subgroups in two different age groups (middle-aged, 9-11 months; elderly, 13-15 months), and compared the number of cells and the proportion of blastocyst formed (morphologically advanced blastocysts) among them. In middle-aged female mice, preimplantation embryos derived from delayed mating progressed more rapidly than their normally mated counterparts. The number of cells and the proportion of blastocyst formed among embryos from delayed mating were almost 3 h ahead of those of normal embryos. In the delayed mating subgroup from elderly mice, an enhanced rate of development was not observed. There was no difference in development of normally mated embryos from middle-aged females compared to each counterpart from elderly female mice. Preimplantation mouse embryonic development from delayed mating may be affected by advanced maternal age.

Animals↗