Advancing maternal age: Pregnancy outcomes and management

INTRODUCTION — 

Pregnancy in women of advanced maternal age (AMA) is generally considered to be ≥35 years at the estimated date of delivery. However, there is no universal definition of AMA, in part because the effects of increasing age occur as a continuum rather than as a threshold effect.

Individuals ≥35 years old are at increased risk of pregnancy complications [1-4]. Some of these complications appear to be related to the aging process alone, while others are largely related to coexisting factors (eg, multiple gestation, higher parity, medical conditions associated with aging, including hypertension and metabolic dysfunction), which are less likely to be observed in younger women. However, most women of advanced age will ultimately have good pregnancy outcomes and are able to cope with the physical and emotional stresses of pregnancy and parenting [1-3,5-11].

Outcomes and management of pregnancy in women of advanced age will be reviewed here. Reproductive concerns related to fertility in older women and advanced paternal age are discussed separately.

●(See "Advancing maternal age: Infertility evaluation and management".)

●(See "Effect of advanced paternal age on fertility and pregnancy".)

In this topic, when discussing study results, we will use the terms "woman/en" or "patient(s)" as they are used in the studies presented. We encourage the reader to consider the specific counseling and treatment needs of transgender and gender-expansive individuals.

DEFINITIONS

●Advanced maternal age – AMA has historically been defined as maternal age ≥35 years at the estimated date of delivery [12]. This threshold was initially chosen to balance the risk of detecting a fetal trisomy with the risk of causing a pregnancy loss with an invasive procedure (eg, amniocentesis). However, the age cut-off for AMA pregnancy is not uniformly defined, and most studies stratify AMA into individuals 35 to 39 years of age and those that are 40 years or greater.

●Very advanced maternal age – As there are progressive age-related risks with increasing age at the timing of pregnancy, a category of "very advanced maternal age" is sometimes used to include individuals ≥45 years although this too is not a uniformly defined threshold [13,14].

EPIDEMIOLOGY — 

Although some countries have reported a decline in birth rates across most age groups, there has been a notable shift to pregnancy at older maternal ages, particularly in resource-abundant countries [15-17].

In the United States, from 2021 to 2022, the mean age of mothers at first birth increased from 27.3 to 27.4 years [18]. Similarly, the birth rate also increased during this time for individuals 35 to 39 years (53.7 to 55.3 births per 1000 females), 40 to 44 years (12 to 12.6 births per 1000 females), and 45 to 49 years (0.9 to 1.1 births per 1000 females) (figure 1). For 2022, this translated to 10,542 infants born to individuals 45 to 54 years.

A shift to pregnancy at older maternal ages has also been reported in Canada, Sweden, and the Netherlands, where the mean age of first-time mothers in 2021 was 30, 29.8, and 30.3 years, respectively [17].

The increased occurrence of births at older maternal ages is due to a combination of factors, including:

●An increase in females aged 35 to 45 years [19].

●Later marriage and second marriage.

●Increased availability of reliable contraception. However, older females also have a high prevalence of contraceptive nonuse, resulting in unintended pregnancy [20].

●Increased availability of assisted reproductive technologies for older patients, allowing individuals to extend their reproductive options.

●Wider opportunities for education and career advancement. Maternal education is one of the strongest predictors of contraception use, timing of childbearing, and the total number of children a woman will bear. College-educated females have higher first birth rates in their 30s and lower birth rates in their 20s, thus illustrating the trend of delayed childbearing related to educational achievement and career opportunities. In surveys, females have cited a desire to achieve career, educational, financial, and personal goals, as well as stability in a marital relationship, before planning pregnancy [21].

OBSTETRIC OUTCOMES — 

While younger women are at risk for the same poor pregnancy complications as older women, the risk is increased with advancing age (figure 2) [22-31]. This increased risk is related to both the aging process and coexisting factors (eg, multiple gestation, higher parity, increased rate of comorbid conditions [diabetes mellitus, hypertension]), which are less likely to be observed in younger women.

Coexisting maternal medical conditions — The prevalence of medical illnesses, such as hypertension, diabetes, cancer, obesity, cardiovascular, renal, and autoimmune diseases increases with advancing maternal age. The two most common medical problems complicating pregnancy are hypertension (preexisting and pregnancy-related) and diabetes (pregestational and gestational). Both conditions are increased in older women, especially those with a higher body mass index (BMI).

Hypertension — Hypertension is the most common medical problem encountered in pregnancy and is particularly prevalent in older women. The odds of being diagnosed with chronic hypertension are twofold higher in women ≥35 compared with 30 to 34 years of age and fivefold higher in those ≥45 compared with 35 to 44 years [31,32].

The incidence of preeclampsia is also higher. In the general obstetric population, the risk of preeclampsia is 3 to 4 percent; this increases to 5 to 10 percent in women over 40 years and is as high as 35 percent in women over 50 years [33,34].

Hypertension is associated with an increased risk of a variety of adverse maternal and fetal/neonatal outcomes, including superimposed preeclampsia, preterm birth, small-for-gestational-age infants, placenta abruption, and cesarean birth [27,35,36]. (See "Chronic hypertension in pregnancy: Prenatal and postpartum care".)

Diabetes mellitus — The prevalence of diabetes also increases with maternal age; the rates of both preexisting diabetes mellitus and gestational diabetes increase three- to sixfold in women ≥40 years compared with women 20 to 29 years [13,22,27,33,34]. The incidence of gestational diabetes in the general obstetric population is 3 percent, rising to 7 to 12 percent in women over 40 years, and 20 percent in women over 50 years [22,33,34].

Preexisting diabetes is associated with increased risks of congenital anomalies, perinatal mortality, and perinatal morbidity; the major complication of gestational diabetes is macrosomia and its sequelae [37]. (See "Preexisting (pregestational) diabetes: Preconception counseling, evaluation, and management" and "Gestational diabetes mellitus: Glucose management, maternal prognosis, and follow-up".)

Early pregnancy loss — Older women experience an increased rate of early pregnancy loss (table 1) [38]. These losses are both trisomic and euploid and primarily result from a decline in oocyte quality; changes in uterine and hormonal function may also play a role. Most losses occur between 6 and 14 weeks of gestation. (See "Pregnancy loss (miscarriage): Terminology, risk factors, and etiology", section on 'Risk factors'.)

In a large, well-documented series from Norway where early pregnancy losses were captured using multiple registries including the Medical Birth Register of Norway, the Norwegian Patient Register, and the induced abortion register, the risk of pregnancy loss was lowest in women 25 to 29 years (10 percent), and the rate rose rapidly after 30 years, reaching 53 percent in women ≥45 years [39]. Other population-based studies report pregnancy loss rates in individuals 35 to 44 years of age and >45 years of 40 percent and 60 to 65 percent, respectively [40,41]. In another study of 76,000 singleton pregnancies, pregnancy loss rates after 11 weeks of gestation for patients <35, 35 to 39, and ≥40 years were 1.2, 1.6, and 2.7 percent, respectively (figure 2) [42]. The lower rates of pregnancy loss in this study are likely attributed to its study design: only patients with singleton pregnancies who presented to their first prenatal visit between 11 0/7 and 13 6/7 weeks of gestation were included in the study. As most pregnancy losses occur before this period, these rates are lower than expected.

The risk of pregnancy loss in women of advanced age persists with advancing gestation even after confirmation of a live pregnancy (presence of fetal cardiac activity by transvaginal ultrasound) [43-45]. In one study of over 148,000 pregnancies conceived with assisted reproductive technology (ART), the pregnancy loss rate after demonstrated fetal cardiac activity at 7 weeks according to maternal age was: <33 years (9.9 percent), 33 to 34 years (11.4 percent), 35 to 37 years (13.7 percent), 38 to 40 years (19.8 percent), 41 to 42 years (29.9 percent), and >42 years (36.6 percent) [45].

Ectopic pregnancy — Ectopic pregnancy, a major source of maternal morbidity and mortality in early pregnancy, is also influenced by maternal age [41,46,47]. Maternal age ≥35 years is associated with a four- to eightfold increased risk of ectopic pregnancy compared with younger women (table 1) [41,46]. This is discussed in detail separately. (See "Ectopic pregnancy: Epidemiology, risk factors, and anatomic sites", section on 'Increasing age' and "Overview of maternal mortality", section on 'Younger and older maternal age'.)

Multiple gestation — Advancing maternal age is associated with an increased prevalence of twin pregnancy, which is related to both a higher risk of naturally conceived twins and a higher use of ART in older women. Interestingly, in contrast to singletons, the outcome of multiple pregnancies in older women is as good or better than the outcome in younger women [48]. This is discussed in detail separately. (See "Twin pregnancy: Overview", section on 'Risk factors'.)

Placenta previa — Placental previa occurs more frequently in older women. In one cohort study of hospital discharge data evaluating pregnancy outcomes in women ≥40 years, nulliparous women ≥40 years (4777 individuals) compared with nulliparous women 20 to 29 years had a 10-fold increased risk of placenta previa; however, the absolute risk was small (0.25 versus 0.03 percent) [27]. Further, in a subsequent meta-analysis of 24 cohort studies evaluating pregnancy outcomes in women ≥45 years, those ≥45 compared with <45 years had higher rates of placenta previa (adjusted odds ratio [aOR] 3.74, 95% CI 2.46-5.7; four studies) [49]. (See "Placenta previa: Epidemiology, clinical features, diagnosis, morbidity and mortality".)

Placenta abruption — While placenta abruption also appears to be increased in older women, multiparity accounts for a significant proportion of this excess risk, and there is no significant correlation between maternal age and abruption once adjusted for parity (and hypertension). (See "Acute placental abruption: Pathophysiology, clinical features, diagnosis, and consequences".)

Protraction or arrest disorders and cesarean birth — Women ≥35 years of age are more likely than younger women to experience protraction and arrest disorders and be delivered by cesarean [8,13,27,32,33,50-52]. The reasons for these higher rates are unclear but include an increased prevalence of medical complications, labor induction, and fetal malposition, as well as a lower threshold among both patients and physicians for performing a cesarean birth. Maternal request for cesarean birth is also becoming more common, particularly among older gravidae [53]. (See "Cesarean birth on patient request".)

In a United States cohort study of over 78,000 singleton births between 2003 and 2012, the proportion of women undergoing a primary cesarean birth increased with age for both primiparous and multiparous women; women with a prior cesarean birth were excluded from the study [52]. By years of age, the primary cesarean birth rate for women 25 to 34 years, 35 to 39 years, 40 to 44 years, 45 to 49 years, and ≥50 years was 20, 26, 31, 36, and 61 percent, respectively. For comparison, during a similar period, the overall primary cesarean birth rate for singleton births in the United States was approximately 22 percent [54].

When specific indications for cesarean birth are evaluated, older women appear to have an increased risk of labor abnormalities. The almost linear increase in the relationship between maternal age and uterine dysfunction is a continuous effect throughout the childbearing years [55-57]. Contemporary studies on the effect of age on the length of the first stage of labor have not reported consistent findings, while the length of the second stage appears to increase with increasing age [57,58].

By contrast, older women who undergo a trial of labor after a previous cesarean birth appear to be at increased risk of both failed trial of labor and uterine rupture [59,60]. (See "Choosing the route of delivery after cesarean birth".)

Severe maternal morbidity and mortality

●Severe morbidity – Women ≥35 years of age are at an increased risk of severe maternal morbidity. Representative studies are as follows:

•In a population-based study of nearly 830,000 singleton births from the state of Washington, the overall rate of severe maternal morbidity across all age groups was 1.6 per 100 deliveries [61]. Women ≥40 compared with 25 to 29 years had an eightfold increased risk of amniotic fluid embolism and threefold increased risk of obstetric shock; women 45 to 49 years had a 16-fold increased risk of renal failure and nearly fivefold increased risk of both obstetric intervention and admission to the intensive care unit. When the groups were stratified by age and compared with reference women 25 to 29 years, the adjusted overall risk difference for women 40 to 44 years, 45 to 49 years, and 50 or greater was 0.9, 1.6, 6.4 percent, respectively. The adjusted risk analysis controlled for maternal race, education, smoking status, marriage status, insurance type, parity, body mass index, assisted conception, neonatal sex, congenital anomalies, and medical conditions, including diabetes and hypertension.

•In a retrospective cohort analysis of nearly 37 million deliveries between 2006 and 2015, women 45 to 54 years compared with 25 to 29 years had nearly 3.5 times the risk of severe maternal morbidity and had the highest rates of cesarean birth, preeclampsia, postpartum hemorrhage, gestational diabetes, thrombosis, and hysterectomy in adjusted analyses [62].

•In a cohort study evaluating outcomes of almost 700 individuals giving birth at advanced maternal ages, patients ≥48 years (median: 49 years; age range: 48 to 61 years) compared with ≤47 years (median: 31 years; age range 16 to 46 years) had a sixfold increase in the risk of requiring blood transfusion and a 33-fold increase in intensive care unit admission; data were controlled for multiple gestations [13].

●Mortality – Maternal mortality, defined by the World Health Organization as "the death of a woman while pregnant or within 42 days of termination of pregnancy, irrespective of the duration and site of the pregnancy, from any cause related to or aggravated by the pregnancy or its management, but not from accidental or incidental causes" [63], is a key indicator of the health and well-being of a society.

In the United States, the maternal mortality rate (MMR) has increased considerably during past decades and is currently the highest among resource-abundant countries. One contributing factor is the higher rate of births to older women (figure 3). Maternal mortality is discussed in detail separately. (See "Overview of maternal mortality" and "Approaches to reduction of maternal mortality in resource-limited settings".)

Subsequent maternal medical conditions — Pregnancy at AMA may impact subsequent health as the woman continues to age, both because of changes from the pregnancy itself and because of the increased risk of pregnancy-related complications that negatively affect health. In an observational study using data from the United States Women's Health Initiative, women who had their last pregnancy at ≥40 compared with <40 years had a trend toward increased risk of hemorrhagic stroke (hazard ratio 1.5, 95% CI 1-2.1) [64]. Additionally, preeclampsia, which is more common in women of advancing maternal age, is a risk factor for subsequent cardiovascular disease [65].

Pregnancy at AMA also appears to be associated with a higher risk of pelvic organ prolapse [66]. This is discussed separately. (See "Pelvic organ prolapse in females: Epidemiology, risk factors, clinical manifestations, and management", section on 'Risk factors'.)

FETAL/NEONATAL OUTCOMES

Fetal abnormalities

Chromosomal abnormalities — The risk of aneuploidy steadily increases as a woman ages, as demonstrated by karyotype analyses from tissue of pregnancy losses and terminations, genetic amniocenteses, and liveborn and stillborn infants [67].

The most common aneuploidy is autosomal trisomy. The age-related risks of being diagnosed with a fetus with trisomy 21, trisomy 18, trisomy 13, as well as some sex chromosome aneuploidy, are shown in the table (table 2). Other chromosomal imbalances (eg, partial deletion or duplication) and rare chromosomal abnormalities do not appear to be age related. The biologic basis for the increase in autosomal trisomy is that oocytes reach prophase I during the fetal period (five months postfertilization) and remain aligned on the metaphase plate until the oocyte is stimulated to divide, just prior to ovulation. Age-related errors appear to increase the risk of nondisjunction, leading to unequal chromosome products at the completion of division. These age-related errors may be related to cumulative oxidative stress, depletion in the number of normal oocytes available for maturation, and shortening of oocyte telomeres [68-73].

Theoretically, preimplantation selection of chromosomally and morphologically normal embryos could increase the chances of successful implantation and ongoing pregnancy, as well as avoid the birth of neonates with chromosomal abnormalities. Despite the high number of aneuploid embryos that are excluded from transfer by this procedure, data from randomized trials and controlled studies have shown that preimplantation selection neither improves the implantation rate nor the rate of live birth but decreases multiple gestation rates. (See "Preimplantation genetic testing", section on 'Advanced maternal age'.)

Gene abnormalities — There are sparse data on the effect of AMA on single gene disorders and epigenetic events other than in the setting of assisted reproduction. Epidemiologic studies have reported an association between advanced maternal and paternal age and the risk of autism spectrum disorders in offspring [74]. Although not proven as an independent risk factor for autism, parental age should be examined in large, population-based birth cohorts that have carefully examined potential confounders. (See "Autism spectrum disorder (ASD) in children and adolescents: Terminology, epidemiology, and pathogenesis", section on 'Parental age'.)

Congenital malformations — The risk of having a child with a congenital anomaly may increase with increasing maternal age [22,75-77]. Historically, an increase in congenital anomalies with advancing maternal age has been attributed to the increase of aneuploidy with advancing maternal age and the association of aneuploid fetuses with structural anomalies. However, several analyses have suggested that the risk of nonchromosomal anomalies also increases as women age. Cardiac anomalies seem to increase with maternal age independent of aneuploidy. Representative studies include the following:

●In a meta-analysis of 72 retrospective studies from multiple countries, maternal age >35 years was associated with an increased risk of nonchromosomal congenital anomalies (risk ratio [RR] 1.31, 95% CI 1.07-1.61), and increased further at age >40 years (RR 1.44, 95% CI 1.25-1.66) [78]. The risk of selected abnormalities at age >40 included the following: cleft lip/palate (RR 1.57), circulatory system (RR 1.94), digestive system (RR 2.16), and omphalocele (RR 2.57).

●In the US National Birth Defects Prevention Study (NBDPS), a population-based case-control study that assessed the association between congenital anomalies and maternal age and including 20,377 case infants and 8169 control infants, women ≥40 compared with 25 to 29 years were at increased risk of several types of cardiac defects (adjusted odds ratio [aOR] 2.2-2.9), as well as for esophageal atresia (aOR 2.9, 95% CI 1.7-4.9), hypospadias (aOR 2; 95% CI 1.4-3), and craniosynostosis (aOR 1.6, 95% CI 1.1-2.4) [79]. The study excluded infants with recognized or strongly suspected chromosomal abnormalities or single gene disorders outcome data and adjusted for race/ethnicity, body mass index, folic acid use, gravidity, education, smoking, and parental age

●In a prospective analysis of a randomized trial database evaluating the impact of maternal age on obstetric outcomes, rates of major congenital anomalies for offspring of women <35, 35 to 39, and ≥40 years of age were 1.7, 2.8, and 2.9 percent, respectively (aOR 1.4 to 1.7, 95% CI 1.1 to 2.4) [22]. Given the large size of this trial, the authors considered an OR >2 to be clinically significant, and none of these mathematically significant Ors reached this level of clinical relevance [76].

Low birth weight and preterm birth — AMA is responsible for a substantial proportion of the increased rate of low birth weight (LBW) infants and preterm birth (PTB) [1,14,22,34,80-84]. These risks have been illustrated in several population-based studies:

●In a prospective population-based Swedish cohort study including over 173,000 healthy nulliparous women with singleton pregnancies, those ages 35 to 40 compared with 20 to 24 years had a higher risk of very LBW (odds ratio [OR] 1.9); moderate LBW (OR 1.7); very preterm birth (OR 1.7); moderately preterm birth (OR 1.2); and small for gestational age infant (OR 1.7), after adjusting for smoking, history of infertility, and other medical conditions [81].

●In a subsequent prospective population-based study from Sweden evaluating outcomes in women at more advanced ages, rates of PTB <32 weeks for women 20 to 29, 40 to 44, and ≥45 years of age were 1.01, 1.8, and 2.24 percent, respectively, after adjustment for confounders (eg, multiple gestation, smoking, parity, maternal comorbidities) [82].

●In a population-based Canadian series evaluating the impact of delayed childbirth on obstetric outcomes, women aged ≥35 compared with <35 years had an increased rate of LBW (at weights <2500 to <1000 grams: OR 1.1 to 1.6) and PTB (at gestational ages <37 to <30 weeks: OR 1.1 to 1.3) [80].

●In a population-based study from the United States evaluating outcomes associated with older maternal age at first birth, women ≥40 compared with 20 to 24 years had a higher rate of delivering an LBW infant, and this risk increased progressively with each five-year increase in maternal age (adjusted OR 2.3, 95% CI 1.6-3.4) [83]. The maternal age effect on both very LBW and PTB was similar (OR 1.8 for the oldest compared with the youngest group).

However, data are conflicting, and at least one study has reported that AMA may not independently increase the risk of LBW or PTB. In a Finnish birth register study of over 124,000 children born between 1987 and 2000, there was no relationship between AMA and LBW or PTB when in-family models were evaluated (ie, children born to the same mother at different maternal ages), although a small increased risk was reported for between-family models (ie, children born to different mothers at different ages) [85]. One possible explanation is the presence of factors not accounted for in the model that increase the risk of both giving birth at an older age and increase the risk of LBW or PTB. Further studies are needed to determine if this finding can be replicated and if the information applies to women beyond Finland.

Smoking has also been associated with LBW and PTB in all age groups, but the risk is particularly high in older smokers [86].

Perinatal mortality

●Fetal death – Women ≥35 years of age compared with younger women are at increased risk of stillbirth. In a meta-analysis of cohort studies evaluating risk factors for stillbirth in resource-abundant countries, maternal age ≥35 years was associated with a 65 percent increase in the odds of stillbirth (effect size 1.65, 95% CI 1.61-1.71; six studies) and the risk increased with increasing maternal age (ie, higher at 40 than at 35 years) [87]. In an analysis of over five million nonanomalous singleton gestations in the United States not included in the meta-analysis, the risk of stillbirth for women <35, 35 to 39 years, and ≥40 years was 3.73, 6.41, and 8.65 per 1000 ongoing pregnancies, respectively [88]. The increased risk of stillbirth is most notable after approximately 37 weeks of gestation and sharply increases at 40 weeks of gestation (figure 4) [88,89].

The excess perinatal mortality experienced by older women is largely due to nonanomalous fetal deaths, which are often unexplained, even after controlling for risk factors such as hypertension, diabetes, antepartum bleeding, smoking, and multiple gestation [1,82,88,90-97]. Nevertheless, the absolute risk of stillbirth in resource-abundant countries is small, even at very advanced maternal ages. In the prospective population-based study from Sweden evaluating outcomes in women at more advanced ages described above (see 'Low birth weight and preterm birth' above), the absolute risk of perinatal death (defined as an intrauterine fetal death ≥28 weeks of gestation or death of the liveborn child within the first 28 days of life) in women ≥40 and ≥45 years was 1.1 percent (343 deaths/31,662 deliveries) and 1.7 percent (20 deaths/1205 deliveries), respectively; data were adjusted for confounders such as parity, congenital malformations, smoking, and maternal disease [82]. By comparison, the absolute risk of perinatal death in offspring of women 20 to 29 years was 0.6 percent (5246 deaths/876,361 deliveries).

Smoking has also been associated with increased perinatal mortality in all age groups, but the risk is particularly high in older smokers [98,99].

●Neonatal death – In contrast to the increased risk of stillbirth with increasing maternal age, the risk of neonatal death among preterm infants is lower for older compared with younger women. In a population-based cohort study of over 12,000 neonates <33 weeks of gestation admitted to neonatal intensive care units in Canada, neonatal mortality progressively decreased with increasing maternal age (age 26 to 30 years: 7.4 percent, 31 to 40 years: 6.5 percent, 41 to 54 years: 6.1 percent; aOR 0.92, 95% CI 0.86-0.96) [100]. This may have been due to differences in underlying factors (eg, higher use of prenatal steroids and cesarean birth, lower rates of substance use disorders) in older women.

PREPREGNANCY COUNSELING — 

As with all women contemplating pregnancy, those of advancing age should be counseled to optimize their health (eg, achieve a normal body mass index [BMI; when possible], avoid smoking and alcohol, take a folic acid supplement) and seek prepregnancy counseling. Issues specific to the prepregnancy office visit in women ≥35 years are discussed here; details related to the prepregnancy visit in women of all ages are presented separately. (See "The prepregnancy office visit".)

●Adverse outcomes – As maternal age increases, the risk of adverse obstetric and neonatal/fetal outcomes increases. Individuals should be aware of these risks and consider this in their reproductive health plans.(See 'Obstetric outcomes' above and 'Fetal/neonatal outcomes' above.)

The risk for adverse outcomes should be assessed by considering not only their age but also the presence or absence of concomitant risk factors (eg, hypertension, diabetes, obesity, previous pregnancy complicated by growth restriction, or preterm birth).

●Interpregnancy interval – We counsel women ≥35 years that short (ie, 6 to 18 months) interpregnancy intervals (ie, time from one birth to the next conception) may increase the risk of adverse pregnancy outcomes more so than their younger counterparts and that interpregnancy intervals of 12 months may reasonably balance these risks with the increasing risks of age-related fertility decline and chromosomal anomalies.

In a population-based cohort study of over 148,000 pregnancies comparing maternal and perinatal outcomes at various birth intervals, women ≥35 years (at time of index birth) who had 6- compared with 18-month interpregnancy intervals had an increased risk of severe maternal morbidity or mortality (0.62 versus 0.26 percent; adjusted risk ratio [aRR] 2.39, 95% CI 2-2.8) [101]. A significant difference was not observed in women 20 to 34 years old giving birth at the same time intervals.

A detailed discussion of interpregnancy interval is presented separately. (See "Interpregnancy interval: Optimizing time between pregnancies", section on 'Older individuals'.)

●Issues related to parenting – Increasing maternal age may be associated with improved health and development for young children. In one observational study of longitudinal cohorts evaluating health and development of children up to 5 years of age, increasing maternal age was associated with improved outcomes such as frequency of unintentional injuries, immunization rates, language development, and social development [102]. Children of older parents have also described several benefits, including the devotion, patience, and attention of their parents, as well as their emotional and financial stability [103,104].

By contrast, older parents should also be aware of the various issues related to their age on offspring, such as possibly being mistaken as grandparents, the increased possibility of parental death or serious illness while the child is young or an adolescent, the increased possibility that the young adult child will become a caregiver to aging parents, and generational issues.

MANAGEMENT

Routine prenatal care — Routine prenatal assessments for patients of all ages are described separately. (See "Prenatal care: Initial assessment" and "Prenatal care: Second and third trimesters".)

The goal of such care is to help minimize maternal risks and to recognize and treat maternal and fetal complications, many of which (eg, hypertension, diabetes, small for gestational age) are increased in individuals of AMA [27,35,36]. (See "Treatment of hypertension in pregnant and postpartum patients" and "Preeclampsia: Antepartum management and timing of delivery".)

Issues specific to AMA — In addition to routine prenatal assessments (see 'Routine prenatal care' above), the following management suggestions apply to patients ≥35 years of age at the estimated date of delivery.

Role of first-trimester ultrasound — For women ≥35 years, we obtain an ultrasound in the first trimester. This allows for accurate determination of the estimated date of delivery (to aid in timing of delivery) and early detection of a multiple gestation and/or congenital anomaly, which are both increased in women of advancing age. (See 'Timing of delivery and role of labor induction' below and 'Multiple gestation' above.)

The role of ultrasound during the initial prenatal assessment is discussed in more detail separately. (See "Prenatal care: Initial assessment", section on 'Ultrasound examination'.)

Evaluation for fetal abnormalities — All pregnant patients, regardless of age, should be offered testing for fetal abnormalities.

●Evaluation for fetal aneuploidy includes either noninvasive screening (typically with cell-free DNA) or diagnostic testing with an invasive procedure (ie, chorionic villus sampling, amniocentesis). (See "Prenatal care: Initial assessment", section on 'Aneuploidy screening and diagnosis' and "Prenatal care: Second and third trimesters", section on 'Offer screening or diagnostic testing for trisomy 21 and other genetic disorders'.)

Noninvasive prenatal screening to measure cell-free DNA in maternal blood has emerged as the most common option for fetal aneuploidy screening because it has both higher sensitivity and a lower false-positive rate than serum biochemical marker/ultrasound screening (table 3), and does not impose an inherent risk to the pregnancy like invasive diagnostic testing [105]. Guidance regarding screening and diagnostic testing are presented separately. (See "Prenatal screening for common fetal aneuploidies: Cell-free DNA test" and "Down syndrome: Overview of prenatal screening", section on 'Choice of screening test in singleton pregnancies' and 'Society guideline links' below.)

●Ultrasound examination to assess for significant structural anomalies can sometimes be performed in the first trimester and is routinely performed during the second trimester. (See "Prenatal care: Initial assessment", section on 'Fetal anomaly screening' and "Prenatal care: Second and third trimesters", section on 'Offer screening for fetal anomalies'.)

Early screening for gestational diabetes in selected patients — Since the prevalence of diabetes increases with advancing maternal age, and type 2 diabetes may be recognized periconceptionally, screening older individuals (eg, ≥40 years, ≥35 years with a body mass index [BMI] ≥25 kg/m²) for gestational diabetes in the first trimester, as well as later in pregnancy, is reasonable. This is discussed in detail separately. (See "Gestational diabetes mellitus: Screening, diagnosis, and prevention".)

Low-dose aspirin in selected patients — For patients ≥35 years of age and at least one other moderate risk factor (eg, nulliparity, BMI >30 kg/m², family history of preeclampsia in a mother or sister), we recommend low-dose aspirin for preeclampsia prevention. This is consistent with the US Preventive Services Task Force (USPSTF) and American College of Obstetricians and Gynecologists (ACOG) guidelines (table 4) [12,106] and is discussed in detail separately. (See "Preeclampsia: Prevention", section on 'Selecting patients at high risk of developing preeclampsia'.)

Antepartum testing — As with all pregnant women, we emphasize the importance of fetal movement (either subjectively or by using a quantitative method [kick counts]), as a sign of fetal well-being and encourage reporting decreased fetal movement in a timely fashion. However, given women ≥35 years of age are at increased risk of stillbirth, we also perform antepartum testing for such patients. (See 'Perinatal mortality' above.)

In our practice, we obtain an ultrasound examination at 32 to 36 weeks of gestation to assess fetal growth and amniotic fluid volume; this is consistent with guidance from ACOG [12,107]. Risk factors, such as age (eg, 35 to 39 years, ≥40 years), parity, and other factors (eg, hypertension, diabetes, obesity) that might influence risk help to determine the optimal timing within this range [108].

We then perform antepartum testing (weekly or twice weekly) until delivery. If, at any point, antepartum testing is not reassuring, additional testing or induction of labor is warranted. (See "Fetal assessment: Overview of antepartum tests of fetal well-being" and "Decreased fetal movement: Diagnosis, evaluation, and management".)

Data regarding antepartum testing at AMA is limited, and whether antenatal testing in women ≥35 years can reduce the incidence of fetal demise or fetal injury is unclear. There are no randomized trials that have examined the efficacy of routine antepartum testing in patients ≥35 years. In a retrospective study of over 4400 pregnant patients with singleton gestations, AMA and non-AMA patients had a similar risk of stillbirth at ≥36 weeks gestation when patients ≥35 years were monitored with weekly biophysical profile testing starting at 36 weeks and induced by 41 weeks of gestation [109].

The role of antepartum fetal monitoring and planned delivery in the prevention of fetal death is reviewed separately. (See "Stillbirth: Incidence, risk factors, etiology, and prevention", section on 'Planned delivery at 39 weeks' and "Stillbirth: Incidence, risk factors, etiology, and prevention", section on 'Strategies for preventing a first stillbirth in the general obstetric population'.)

Timing of delivery and role of labor induction — The optimal gestational age for delivery of women of advancing age is unclear and older patients and their providers must balance the benefits of remaining pregnant at term and waiting for spontaneous labor against the risk of stillbirth. (See 'Perinatal mortality' above.)

In our practice, for women ≥35 years we favor delivery in the 39^th week of gestation. For women who are ≥35 years and primiparous, ≥40 years, or who have additional risk factors for stillbirth (eg, pre-existing diabetes, obesity), we more strongly favor induction in the 39^th week of gestation. However, the decision between induction and awaiting spontaneous labor is ultimately determined by shared decision-making after counseling regarding the risks and benefits and understanding the patient's preferences.

Women who decline induction are managed with twice weekly testing (see 'Antepartum testing' above) until spontaneous labor, nonreassuring testing, or 41 weeks of gestation (when induction is typically recommended for all individuals) is achieved [110]. We generally discourage waiting for spontaneous labor beyond 40 weeks of gestation, especially for those ≥40 years.

Our rationale is based on the following [88,111-116]:

●There is an increased risk of stillbirth beyond this gestational age. (See 'Perinatal mortality' above.)

In a national cohort study of over 829,000 births from 2000 through 2012, the risk of stillbirth after 37 weeks of gestation fell as the frequency of induction of labor increased [115].

●There is a low risk of neonatal morbidity/mortality at this gestational age.

In a randomized trial evaluating obstetric outcomes in 600 primigravid individuals ≥35 years, those undergoing labor induction between 39 0/7 and 39 6/7 weeks gestation compared with expectant management had similar neonatal outcomes, including birth weight <2500 grams, Apgar score of 4 to 7, umbilical-cord blood arterial pH <7.00, and neonatal intensive care unit admission [117]. The study was not adequately powered to assess the risk of perinatal mortality. In an earlier retrospective database review of over 700,000 deliveries between 37 and 43 weeks of gestation in Scotland from the time period of 1985 to 1996, the lowest cumulative probability of perinatal death was at 38 weeks of gestation [118]. Furthermore, in a retrospective study of over 26,000 births to women of AMA, delivery between 38 5/7 and 39 6/7 weeks optimized the neonatal intensive care unit admission rate, and newborn Apgar ≤6 [113]. Maternal third- and fourth-degree perineal laceration rates and cesarean birth rates were also optimized at these gestational ages.

●There are diminishing subsequent reproductive options for patients in this age group.

●Data do not support an association between induction of labor and an increased risk of cesarean birth [114,119].

In a meta-analysis of four trials including over 2500 pregnant women ≥35 years at term, those undergoing induction of labor compared with expectant management had similar rates of cesarean birth [120]. In another randomized trial not included in this meta-analysis and discussed above, those undergoing labor induction compared with expectant management had similar rates of cesarean birth [117]. This is discussed in more detail separately. (See "Induction of labor with oxytocin", section on 'Scheduled induction at 39 weeks'.)

SOCIETY GUIDELINE LINKS — 

Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: General prenatal care" and "Society guideline links: Prenatal genetic screening and diagnosis".)

SUMMARY AND RECOMMENDATIONS

●Definitions – Advanced maternal age (AMA) is generally considered to be maternal age ≥35 years at the estimated date of delivery; however, the age cut-off for AMA in pregnancy is not uniformly defined. Very advanced maternal age is a category that is sometimes used to describe individuals ≥45 years. (See 'Definitions' above.)

●Adverse outcomes

•Obstetric outcomes that occur with increased frequency in women of advanced age include early pregnancy loss, ectopic pregnancy, multiple gestation, placenta previa, protraction/arrest disorders, and cesarean birth. Severe maternal morbidity and maternal mortality are also increased (figure 3). (See 'Obstetric outcomes' above.)

•Fetal/neonatal outcomes that occur with increased frequency in women of advanced age include fetal chromosomal abnormalities (table 2) and some congenital anomalies; a substantial proportion of infants born to women of AMA have low birth weight (LBW) or are preterm. There is also an increased risk of perinatal mortality. (See 'Fetal/neonatal outcomes' above.)

●Prepregnancy counseling – As part of prepregnancy counseling, we counsel women ≥35 years that short interpregnancy intervals (ie, 6 to 18 months between one birth and the next conception) may increase the risk of adverse pregnancy outcomes more so than their younger counterparts. Interpregnancy intervals of 12 months may reasonably balance these risks with the increasing risks of age-related fertility decline and chromosomal anomalies. (See 'Prepregnancy counseling' above.)

●Management specific to AMA

•First-trimester ultrasound – For all women ≥35 years, we obtain an ultrasound in the first trimester to allow for accurate determination of the estimated date of delivery and early detection of a multiple gestation and/or congenital anomaly. (See 'Role of first-trimester ultrasound' above.)

•Testing for fetal aneuploidy –All pregnant patients, regardless of age, should be offered genetic screening for fetal abnormalities. Cell-free DNA screening has both higher sensitivity and a lower false-positive rate than serum biochemical marker/ultrasound screening. This is discussed separately. (See 'Evaluation for fetal abnormalities' above and "Prenatal care: Initial assessment", section on 'Aneuploidy screening and diagnosis'.)

•Role of early screening for gestational diabetes and low-dose aspirin for preeclampsia prevention – Selected women ≥35 years of age are candidates for early screening for gestational diabetes and low-dose aspirin for preeclampsia prevention. This is discussed in detail separately. (See 'Early screening for gestational diabetes in selected patients' above and "Gestational diabetes mellitus: Screening, diagnosis, and prevention", section on 'Targeted screening of individuals at high risk' and 'Low-dose aspirin in selected patients' above and "Preeclampsia: Prevention", section on 'Selecting patients at high risk of developing preeclampsia'.)

•Antepartum testing – We obtain an ultrasound examination at 32 to 36 weeks of gestation to assess fetal growth and amniotic fluid volume; this is consistent with guideline recommendations. We then perform antepartum testing (weekly or twice weekly) until delivery. Risk factors, such as age (eg, 35 to 39 years, ≥40 years), parity, and other factors (eg, hypertension, diabetes, obesity) might influence risk help to determine the optimal timing within this range. (See 'Antepartum testing' above.)

•Timing of delivery – For most pregnant women ≥35 years of age at the estimated date of delivery, we suggest induction of labor at 39 weeks of gestation (Grade 2C). However, some patients, particularly those who are 35 to <40 years of age, may reasonably opt for continued antepartum testing rather than induction of labor. We discuss both options and respect the patient's preference regarding timing and type of intervention. However, we generally discourage waiting for spontaneous labor beyond 40 weeks of gestation, especially for those ≥40 years. (See 'Timing of delivery and role of labor induction' above.)