Management of pregnancy complications in women of advanced maternal age

The average age of women at childbirth in high resource obstetric settings has been increasing steadily for approximately 30 years. Women aged 35 years or over have an increased risk of gestational hypertensive disease, gestational diabetes, placenta praevia, placental abruption, perinatal death, preterm labour, fetal macrosomia and fetal growth restriction. Unsurprisingly, rates of obstetric intervention are higher among older women. Of particular concern is the increased risk of antepartum stillbirth at term in women of advanced maternal age. In all maternal age groups, the risk of stillbirth is higher among nulliparous women than among multiparous women. Women of advanced maternal age (>40 years) should be given low dose aspirin in the presence of an additional risk factor for pre-eclampsia and offered serial ultrasounds for fetal growth and wellbeing. Given the increased risk of antepartum stillbirth, induction of labour from 39 weeks’ gestation should be discussed with woman.     

Advanced maternal age

The average age of women at childbirth in industrialised nations has been increasing steadily for approximately 30 years. Women aged 35 years or over have an increased risk of gestational hypertensive disease, gestational diabetes, placenta praevia, placental abruption, perinatal death, preterm labour, fetal macrosomia and fetal growth restriction. Unsurprisingly, rates of obstetric intervention are higher among older women. Of particular concern is the increased risk of antepartum stillbirth at term in women of advanced maternal age. In all maternal age groups, the risk of stillbirth is higher among nulliparous women than among multiparous women. Women of advanced maternal age (>40 years) should be given low dose aspirin (in the presence of an additional risk factor for pre-eclampsia) and offered serial ultrasounds for fetal growth and wellbeing; given the increased risk of antepartum stillbirth, induction of labour from 39 weeks’ gestation should be discussed with the woman.     

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.     

高龄孕妇的孕期管理

近年来,高龄孕产妇人数快速增长,随之而来的是孕产妇及新生儿发病率与死亡率增高。明确高龄孕产妇所存在的风险,完善孕前咨询评估,加强出生缺陷的筛查、诊断,加强对凶险性前置胎盘的管理,加强剖宫产术后阴道分娩(VBAC)的管理,是保障高龄孕产妇健康,降低出生缺陷儿发生率,提高产科质量的关键。     

高龄女性瘢痕子宫再妊娠

随着我国二孩政策的全面实施,以往因各种因素导致瘢痕子宫妊娠的高龄孕妇明显增多。鉴于高龄及各种病因导致的子宫瘢痕形成的特点不同,再次妊娠的时机、孕期监测及风险各有差异。文章仅就比较常见的瘢痕子宫再妊娠的上述相关问题进行讨论,希望为产科临床工作者提供参考。     

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 ≥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. (Am J Obstet Gynecol 1996;175:1563-8.)     

Anesthetic considerations in pregnant women at advanced maternal age

Objective: To evaluate anesthetic considerations in pregnancy for women at advanced maternal age (≥?40 years).

Methods: A retrospective cohort study of laboring women aged 40 years or above comparing women aged 40–44 years old with those aged ≥45 years, in a single, tertiary, university affiliated medical center.

Results: Overall, 39?006 women delivered in our institution during the study period, of them 376 (1%) were eligible for analysis: 278 (74%) were 40–44 years old (control group) and 98 (26%) were 45 years old and above (study group). No differences were found between the groups with regards to analgesia or anesthesia management during labor. Differences were found in obstetrical characteristics such as higher rates of primiparity, preeclampsia, need for magnesium sulphate therapy and chronic hypertension among parturients aged ≥45 years. Of note, parturients aged ≥?45 years had an approximately eight-fold risk for postpartum hemorrhage.

Conclusion: Anesthesia management of parturients aged 45 years and above is comparable to the management of women aged 40–44 years. However, parturients ≥45 are more susceptible to bleeding complications.     

Advanced maternal age

Delayed childbearing is a growing trend in developed countries. Between 1982 and 2012, the number of live births to UK women over 40 more than quadrupled. This accelerating demographic shift is of major clinical and public health concern, because advanced maternal age has consistently been associated with adverse pregnancy outcomes. Current evidence suggests increased risk of miscarriage, ectopic pregnancy and stillbirth. Most studies also report elevated maternal morbidity resulting from hypertensive disorders and gestational diabetes. Many questions remain unanswered regarding the underlying mechanisms. The contribution of age per sé versus co-morbidities is unclear, as is the age threshold at which increased risks become significant. Despite the increased risks, there are potential psychological and social advantages to delaying childbirth and absolute numbers of complications are small. Further studies are required to develop effective strategies to reduce poor outcomes and provide optimal care for pregnant women of advanced age.     

Early menarche is associated with insulin resistance in advanced maternal age before delivery

Abstract

Purpose: With the wide implementation of the universal two-child policy in China, the number of pregnant women in advanced maternal age (AMA) will increase gradually. We aimed to assess the association between age at menarche (AAM) and insulin resistance (IR) before delivery in AMA. Methods: A total of 80 pregnant women in AMA were consecutively enrolled before delivery in Zhongda hospital. Pregnant women were stratified into early menarche group and late menarche group according to the age of regular menstruation (about 13?years). At delivery, serum glucose and lipid levels were measured. IR was calculated by the method of homeostasis model assessment 2(HOMA2). Results: The fasting blood insulin (17.68(9.72–36.71) and 10.35(7.76–15.10), respectively; p?=?.006) and HOMA-IR (2.08(1.18–4.37) and 1.24(0.89–1.78), respectively; p?=?.005) were higher in early menarche group than in late menarche group. AAM was inversely associated with HOMA-IR in AMA (r=??0.27, p?=?.014). In the multivariable analysis, AAM in late menarche group was negatively related to the level of HOMA-IR compared to those in early menarche group (β=??2.275, p≤.0001). Conclusions: Taken together, our findings suggest that AAM was inversely associated with HOMA-IR in AMA. Furthermore, pregnant women in AMA with early menarche might have higher HOMA-IR levels than those with late menarche.

Clinical trial registration: Chinese Clinical Trial Registry (No. ChiCTR-RRC-16008714), retrospectively registered     

Outcomes of IVF cycles coupled with PGS by aCGH of embryos from donor and autologous oocytes,transferred after vitrification to women of advanced maternal age

It is well documented that aneuploidy rate in preimplantation embryos increases with the mother’s age, and at the same time the number of oocytes diminishes. Consequently, for patients of advanced maternal age two options are available to overcome these limitations: use of oocytes from young donors, or use of own oocytes coupled with preimplantation genetic screening (PGS) for 24 chromosomes. However, it is not clear which strategy might be more effective. The aim of this retrospective study was to evaluate outcomes of IVF cycles coupled with transfer of vitrified embryos from donor or autologous oocytes, both with or without PGS. Our results demonstrate that while after PGS clinical pregnancy, twin pregnancy and spontaneous abortion rates are similar for embryos from donor and autologous oocytes, these rates are dramatically worse in all cycles without PGS. Therefore, PGS can be recommended as a screening method to all patients of advanced maternal age even when donor oocytes are used.     

Impact of advanced maternal age on neonatal survival of twin small-for-gestational-age subtypes

AIM: We examined the impact of advanced maternal age (>40 years old) on the survival of twin small-for-gestational-age (SGA) infants, that is, infants who were smaller in size than was expected for the baby's sex, genetic heritage, and gestational age. METHODS: The present study was a retrospective cohort study on twin live births in the USA from 1995 to 1998 inclusive. Two categories of SGA babies were defined: discordant (when only one of a twin pair was SGA) and concordant (when both were SGA). Otherwise, the twin pair was appropriate-for-gestational-age (AGA) concordant. RESULTS: 192,195 twin pairs were analyzed. The incidence of SGA discordance and concordance was 11.8% and 3.9%, respectively. The occurrence of both SGA subtypes tended to decrease with increasing maternal age. The unadjusted risk for neonatal mortality increased when both twins were affected (15.8: 22.8 and 56.6 per 1000 among AGA concordant, SGA discordant and SGA concordant twins; P-value for trend < 0.0001). Using maternal-age-specific AGA babies as reference, the adjusted risk for neonatal mortality climbed progressively with advancing maternal age in a dose-dependent pattern, being lowest among teenagers and highest in mothers aged > or =40 years. CONCLUSIONS: SGA discordance and concordance declined with advancing maternal age. In contrast, neonatal mortality of both SGA subtypes worsened with the increase in maternal age compared with that of the age-specific AGA infants. These findings are potentially useful to care providers in counseling older women, a group that is progressively increasing in size and is most susceptible to twining.     

A new policy for prenatal screening and diagnosis of Down syndrome for pregnant women with advanced maternal age in a public hospital

Objective.?Before April 2006, women with singleton pregnancy and advanced maternal age (AMA, 35 years and older) were offered either direct invasive tests or a variety of screening tests for Down syndrome (DS) with routine anomaly scan at 18–20 weeks. After April 2006, to reduce procedure-related fetal loss, invasive test was performed only for positive screening result or the presence of major fetal anomaly on ultrasound. We reviewed our 2-year experience after the policy change.

Methods.?Two-year data after policy change were compared to the 1-year historic control before policy change.

Results.?A total of 2257 eligible women were counselled in the 2 years after policy change. The uptake of screening was 96.7%. The overall detection rate for DS was 90% (18/20) at a false positive rate of 10.9%. The number of invasive tests performed to diagnose one case of DS was reduced 7-fold from 97 to 13.

Conclusions.?The number of direct invasive tests was markedly reduced. With effective DS screening policy, it is possible to do away with direct invasive testing for the majority of women with AMA.     

Psychological factors influencing choice of prenatal diagnosis in Chinese multiparous women with advanced maternal age

Objectives: To investigate the psychological predictors in Chinese multiparous pregnant women of advanced maternal age (AMA) for choosing aneuploidy screening or diagnostic testing.

Methods: A total of 84 pregnant women of AMA were consecutively enrolled from Renming Hospital, Wuhan University. All participants completed three questionnaires: Zung Self-Rating Anxiety Scale (SAS), Zung Self-Rating Depression Scale (SDS), and Pregnancy Stress Rating Scale (PSRS). Demographic information and the choice of noninvasive prenatal testing (NIPT) versus invasive prenatal diagnosis (PND) were also collected.

Results: Thirty-seven chose to have invasive PND, and 47 chose NIPT. Choosing invasive PND, as opposed to NIPT, was associated with lower educational background (χ²?=??2.269, p?=?.023), higher SAS scores (47.62?±?7.96 versus 44.21?±?6.10, p?=?.029), and higher SDS scores (50.41?±?9.80 versus 45.96?±?11.05, p?=?.058). Logistic regression analysis further showed that the decisive predictors for invasive PND are SAS (OR =1.106, p?=?.008) scores, scores of factor 3 in PSRS and the stress from changes of shape and motility (OR =0.471, p?=?.038). Subgroup analysis showed that women with previous negative pregnancy experience had higher scores in factor 2-stress (guarantee of maternal-fetal safety: 1.96?±?0.63 versus 2.49?±?0.65, p?=?.004) and total PSRS scores (1.60?±?0.4 versus 1.83?±?0.31, p?=?.044) than those without. Additionally, unemployment post pregnancy was associated with marginally significant higher PSRS scores (p?=?.083).

Conclusions: The decision for invasive PND might be swayed by anxiety and attenuated by pregnancy stress originating from worry about changes in fetal shape and motility (measured by SAS and factor 3 score of PSRS, respectively).     

Preeclampsia in twin gestations: Association with IVF treatments,parity and maternal age

Objective.?To identify maternal factors that increase the risk of preeclampsia in twin gestations and to investigate whether twins conceived by in vitro fertilization (IVF) lead to an increased risk of preeclampsia development.

Materials and methods.?A retrospective population-based cohort study of twin deliveries was performed. Maternal characteristics and perinatal outcomes were evaluated. Patients' data were obtained from a computerized database and analyzed using SPSS statistical package.

Results.?During the study period there were 2628 twin deliveries, and of these 3.1% had severe preeclampsia and 6.16% mild preeclampsia. Patients with severe preeclampsia were more likely to be primiparous, and to have significantly higher frequency of chronic hypertension, gestational diabetes mellitus (GDM), IVF treatments, cesarean delivery, preterm delivery and twin discordancy than in the normotensive patients. Chronic hypertension, pirimiparity, twin discordancy and maternal age were independent risk factors for the development of preeclampsia. In a multivariate regression model including IVF treatment, parity and maternal age as risk factors for preeclampsia, women younger than 35 years that conceived following IVF treatments had an independent risk factor for the development of preeclampsia.

Conclusion.?IVF treatments in primiparous patients and age younger than 35 years are independent risk factors for preeclampsia. Twin discordancy is an additional independent risk factor for the occurrence of preeclampsia.     

无创产前检测在高龄孕妇中检测胎儿非整倍体的临床应用

目的:探讨高通量测序(HTS)技术在高龄孕妇胎儿染色体非整倍体筛查中的临床应用。方法:2 090例单胎高龄孕妇行无创产前检测(NIPT),结果异常的孕妇再行羊膜腔穿刺,羊水细胞培养后染色体G320显带核型分析。结果:2 090例样本中,高通量基因测序提示22例胎儿染色体非整倍体高风险,19例孕妇自愿接受羊水产前诊断,其中16例羊水G带核型结果与NIPT测序结果一致,包括12例T21,2例T18,2例性染色体异常,阳性预测值为84.2%(16/19)。结论:对于拒绝接受介入性产前诊断的高龄孕妇,临床可推荐无创的高通量基因测序产前检测技术,进一步降低出生缺陷儿的发生率。     

The risks and outcome of pregnancy in an advanced maternal age in oocyte donation cycles

Abstract

The maternal age at the first and repeated deliveries constantly rises in developed countries due to current social trends that favor values of personal achievements upon procreation. Assisted reproduction technologies and especially the availability of oocyte donation programs extend the age of fecundity to the fifth and sixth decades of life. The ability to conceive and deliver at such age raises serious medical, moral, social and legal concerns regarding the health and welfare of the mother and child will be presented and discussed here.     

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.     

Psychosocial adjustment of couples to first-time parenthood at advanced maternal age: an exploratory longitudinal study

Objective: This study aimed to describe the psychosocial adjustment of primiparous women of advanced age and their partners (AMA group) compared to their younger counterparts (comparison group) from the third trimester of pregnancy to six months postpartum and to explore the psychosocial adjustment of the AMA group, depending on infertility history. Background: First-time parenthood at advanced maternal age (AMA) is a growing reproductive trend; however, few longitudinal studies have explored the psychosocial adjustment of couples from pregnancy to the first postpartum months, considering the distinct trajectories that precede this reproductive behaviour. Methods: Fifty-eight couples in the AMA group (≥35 years at the time of delivery) and 41 couples in the comparison group (20–34 years) were consecutively recruited in a Portuguese urban referral hospital. Both partners responded to the Brief Symptom Inventory-18, the EUROHIS-QoL-8 and the Dyadic Adjustment Scale – Revised during the third trimester of pregnancy (T1), at one month (T2) and six months postpartum (T3). Couples also completed visual analogue scales to assess parenting difficulty, competence and gratification at T2 and T3. Results: The psychosocial adjustment of the AMA group and the comparison group over time was more similar than different. Within the AMA group, perceived parenting difficulty decreased over time for previously infertile couples but remained stable for previously fertile couples. Conclusion: Healthcare providers should avoid stereotypical views and normalise the psychosocial adjustment over the transition to first-time parenthood at AMA. Antenatal psychoeducational interventions should promote realistic expectations about the demands of early parenting, especially among previously infertile couples.     

High-order multiple gestations

Infertility treatments have produced an increase in multiple gestations with twins accounting for 3.3% of births in the United States in 2002. Over that same time period, premature deliveries increased from 10.7% in 1992 to 12.1% in 2002. High-order multiple gestations have also increased, and virtually all of those deliver prematurely. Clinicians are facing the challenge of managing these complicated pregnancies. Neonatal outcome will primarily depend on the gestational age at delivery and the birth weight of the babies. Care is directed at aggressively and proactively preventing preterm delivery. Ultrasound assessments are made frequently to assess fetal anatomical abnormalities, nuchal translucency, fetal growth, cervical length, amniotic fluid, and biophysical profile. Stress reduction and activity reduction will decrease uterine activity, and tocolytic drugs are employed to decrease background contractions to reduce preterm labor (PTL). Fetal fibronectin testing helps predict risk of PTL, and magnesium sulfate tocolysis is used in aggressive dosing to arrest PTL if it occurs. Outcomes are presented and discussed. Successful outcomes are not only possible, but probable.