Effects of advanced maternal age on pregnancy

INTRODUCTION — There is no universal definition of advanced reproductive age in women, in part because the effects of increasing age occur as a continuum, rather than as a threshold effect. Fertility clearly declines with advancing age, especially after the mid-30s, and women who conceive are at greater risk of pregnancy complications [1-4]. However, studies have generally observed that most women over 45 years of age [5-10] or over 50 years of age [1-3,11] have good pregnancy outcomes and are able to cope with the physical and emotional stresses of pregnancy and parenting [11].

The effects of a woman's age on pregnancy will be reviewed here. Reproductive concerns related to management of pregnancy and fertility in older women and advanced paternal age are discussed separately.

●(See "Management of pregnancy in patients of advanced age".)

●(See "Evaluation and management of infertility in females of advancing age".)

●(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. However, we encourage the reader to consider the specific counseling and treatment needs of transgender and gender diverse individuals.

EPIDEMIOLOGY — Although some countries have reported a decline in birth rates across most age groups, the birth rates in older women have risen [12]. Nine percent of first births in the United States were to women ≥35 years of age, which is a 23 percent increase from 2000 [13]. The mean age of first-time mothers in high resource countries has increased as well: United States (mean age 26.3), Canada (mean age 29.6 years), Sweden (mean age 28.3 years), and the Netherlands (28.7 years) [13-16].

The increased occurrence of births at older maternal ages is due to the increased population of women aged 35 to 45, as well as later marriage, second marriage, the availability of better contraceptive options, and wider opportunities for further education and career advancement. Maternal education is one of the strongest predictors of use of contraception, timing of childbearing, and the total number of children a woman will bear. College educated women tend to have low first birth rates when in their 20s, but higher first birth rates in their 30s, thus illustrating the trend of delayed childbearing related to educational achievement and career opportunities. In surveys, women have cited a desire to achieve career, educational, financial, and personal goals, as well as stability in a marital relationship, before planning pregnancy [17].

However, older women also have a high prevalence of contraceptive nonuse resulting in unintended pregnancy [18]. Although women under age 25 have the highest rate of unintended pregnancy, women ≥35 years have the highest proportion of unintended pregnancies ending in abortion [19].

EARLY PREGNANCY ISSUES — Older women are at risk for the same pregnancy complications as younger women, but their risk is higher for some of these problems.

Spontaneous abortion (pregnancy loss) — Older women experience an increased rate of spontaneous abortion (figure 1 and figure 2) [20]. 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. The vast majority of 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 miscarriage was lowest in women ages 25 to 29 (10 percent), and the rate rose rapidly after the age of 30, reaching 53 percent in women ages 45 or older [21].

The risk of eventual spontaneous abortion in women of advanced age is significant despite demonstration of fetal cardiac activity by transvaginal ultrasound [22-24]. As an example, in one study of over 148,000 ART pregnancies, 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) [24]. This shows that the increased rate of pregnancy loss was not confined to blighted ova.

Ectopic pregnancy — Ectopic pregnancy, a major source of maternal mortality and morbidity in early pregnancy, is influenced by maternal age and race and/or ethnicity [25-27]. Maternal age ≥35 years is associated with a four- to eightfold increased risk of ectopic pregnancy compared with younger women (table 1) [25,26]. The ectopic pregnancy mortality is greatly influenced by both advanced maternal age and race [27].

●(See "Ectopic pregnancy: Epidemiology, risk factors, and anatomic sites".)

●(See "Overview of maternal mortality", section on 'Race and ethnicity'.)

Chromosomal abnormalities — Karyotype analysis from spontaneous abortions, pregnancy terminations, genetic amniocenteses, and live born and stillborn infants shows a steady increase in the risk of aneuploidy as a woman ages (table 2 and table 3 and table 4) [28,29]. The most common aneuploidy is autosomal trisomy. The biological basis for this observation 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 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 [30-35].

Theoretically, preimplantation selection of chromosomally and morphologically normal embryos could increase the chances of successful implantation and ongoing pregnancy, as well as avoid chromosomally abnormal births. Despite the high number of aneuploid embryos which are excluded from transfer by this procedure, data from randomized trials and controlled studies have shown that preimplantation selection neither improve 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 advanced maternal age 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 risk of autism spectrum disorders in offspring [36]. 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 [37-40]. Historically, an increase in congenital anomalies with advancing maternal age has been attributed to the recognized 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, in particular, seem to increase with maternal age independent of aneuploidy.

●The US National Birth Defects Prevention Study (NBDPS) is a population-based case control study that assessed the association between congenital anomalies and maternal age, adjusted for race/ethnicity, body mass index, folic acid use, gravidity, education, smoking, and parental age difference [41]. The study included 20,377 case infants and 8169 control infants and excluded infants with recognized or strongly suspected chromosomal abnormalities or single gene disorders. Compared with the reference group of women 25 to 29 years of age, offspring of women ≥40 years of age were at increased risk of several types of cardiac defects (aOR 2.2-2.9), as well as for esophageal atresia (aOR 2.9, 95% CI 1.7-4.9), hypospadias (aOR 2.0; 95% CI 1.4-3.0), and craniosynostosis (aOR 1.6, 95% CI 1.1-2.4).

●In the FASTER trial, the 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 (odds ratios for women ≥35 compared with women <35 ranged from 1.4 to 1.7) [37]. 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 [39].

●Lastly, an in depth analysis of all pregnancy outcomes (livebirths, stillbirths, and terminations) within a geographically confined region of Texas revealed the risk for all nonchromosomal congenital anomalies increased with advancing maternal age [38]. Fetuses of women 20 to 24 years of age had a congenital malformation rate of 3.5 percent, which was lower than the rate in women 35 to 39 years and ≥40 years (4.4 and 5.0 percent, respectively). Cardiac anomalies were notably increased, as well as clubfoot and congenital diaphragmatic hernia.

Results worldwide have not been consistent with all of these findings [42,43]. Differences in study design, case definition, and potential confounders may play a role in these discrepancies [41].

LATE PREGNANCY ISSUES

Impact of older age cohort — Some obstetric complications in older women appear to be related to the aging process alone, while others are largely related to coexisting factors such as multiple gestation, higher parity, and chronic medical conditions, which are less likely to be observed in younger women. Both may contribute to increased pregnancy-related maternal morbidity that is reported in older women. In a population-based study of nearly 830,000 singleton births from Washington State, women ages ≥40 years had an eightfold increased risk of amniotic fluid embolism and threefold increased risk of obstetric shock compared with women age 25 to 29 years; the overall rate of severe maternal morbidity across all age groups was 1.6 per 100 deliveries [44]. Women in the age 45 to 49 category 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 age 25 to 29 years, the adjusted overall risk difference was 0.9 percent for women age 40 to 44 years, 1.6 percent for women age 45 to 49 years, and 6.4 percent for women age 50 or greater. For women ≥50 years, the rate of severe maternal morbidity was greater than the rate of mortality or serious morbidity of their children. Of note, 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. Similarly, a retrospective cohort analysis of nearly 37 million deliveries between 2006 and 2015 reported that women ages 45 to 54 years had nearly 3.5 times the risk of severe maternal morbidity (compared with women ages 25 to 29) and had the highest rates of cesarean delivery, preeclampsia, postpartum hemorrhage, gestational diabetes, thrombosis, and hysterectomy in adjusted analysis [45].

Short interpregnancy interval, defined as time from one birth to the next conception, may further increase the risk of adverse maternal events for older women. In a population-based cohort study of over 148,000 pregnancies comparing maternal and perinatal outcomes at various birth intervals, the risk of severe maternal morbidity or mortality was increased for women age 35 or older (at time of index birth) who had 6-month interpregnancy intervals compared with 18-month intervals but not for women age 20 to 34 years giving birth at the same time intervals [46]. For women in the younger cohort, six-month interpregnancy intervals were more associated with adverse fetal and neonatal outcomes, particularly spontaneous preterm delivery. Based on this study, for women age 35 and older at index birth, we discuss the increased maternal risks with short (six-month) birth intervals, that risks associated with inter-birth intervals of 12 to 24 months appeared comparable to the risk nadir reported at 18 months, and that an interpregnancy interval of 12 months may reasonably balance concerns for age-related fertility decline and increased risk of chromosomal anomaly and concerns for maternal and fetal well-being. However, all counseling and shared decision making should respect the patient's plans for repeat pregnancy, including those with shorter birth intervals.

A detailed discussion of interpregnancy interval is presented separately. (See "Interpregnancy interval: Optimizing time between pregnancies".)

Effects of coexisting medical conditions — The prevalence of medical and surgical illnesses, such as cancer; cardiovascular, renal, and autoimmune disease; and obesity increases with advancing age. For this reason, women ≥35 years of age can expect to experience two- to threefold higher rates of hospitalization, cesarean delivery, and pregnancy-related complications than their younger counterparts [37,47-55]. Smoking has been associated with increased perinatal morbidity and stillbirth in all age groups, but the risk is particularly high in older smokers [56-58]. (See "Cigarette and tobacco products in pregnancy: Impact on pregnancy and the neonate".)

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 who are overweight.

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 two- to fourfold higher in women ≥35 years of age than in women 30 to 34 years of age and for women ≥45 years compared with those 35 to 44 years [55,59]. The incidence of preeclampsia in the general obstetric population is 3 to 4 percent; this increases to 5 to 10 percent in women over age 40 and is as high as 35 percent in women over age 50 [60,61].

Maternal and fetal morbidity and mortality related to hypertensive disorders during pregnancy can be reduced with careful monitoring and appropriately timed intervention, but with an increase in preterm birth, small for gestational age infants, and cesarean delivery [51,62,63]. (See "Treatment of hypertension in pregnant and postpartum patients" and "Preeclampsia: Antepartum management and timing of delivery".)

Diabetes mellitus — The prevalence of diabetes increases with maternal age; the rates of both preexisting diabetes mellitus and gestational diabetes increase three- to sixfold in women 40 years of age or older compared with women aged 20 to 29 [37,51,60,61,64]. The incidence of gestational diabetes in the general obstetric population is 3 percent, rising to 7 to 12 percent in women over age 40, and 20 percent in women over age 50 [37,60,61].

Preexisting diabetes is associated with increased risks of congenital anomalies, perinatal mortality, and perinatal morbidity, while the major complication of gestational diabetes is macrosomia and its sequelae [65]. (See "Pregestational (preexisting) diabetes: Preconception counseling, evaluation, and management" and "Gestational diabetes mellitus: Glucose management and maternal prognosis".)

Placental problems — The prevalence of placental problems, such as abruptio placenta and placenta previa, is higher among older women. Multiparity accounts for significant proportion of the excess risk in both disorders. In fact, there is no significant correlation between maternal age and abruption when parity and hypertension are taken into account. (See "Acute placental abruption: Pathophysiology, clinical features, diagnosis, and consequences".)

In contrast, age, as well as parity, appear to be independent risk factors for placenta previa. Nulliparous women ≥40 years of age have a 10-fold increased risk of placenta previa compared with nulliparous women age 20 to 29 years, although the absolute risk is small (0.25 versus 0.03 percent) [51]. (See "Placenta previa: Epidemiology, clinical features, diagnosis, morbidity and mortality".)

Perinatal morbidity — Advanced maternal age is responsible for a substantial proportion of the increased rate of low birth weight (LBW) and preterm delivery (PTD) observed in the past several years [1,37,61,66-71]. These risks were illustrated in several population-based studies:

●A prospective population-based Swedish cohort study restricted to healthy nulliparous women (n = 173,715) delivering singletons compared birth outcome in women age 35 to 40 with those 20 to 24 years [67]. Demographic characteristics, smoking, history of infertility, and other medical conditions were taken into account when calculating risk. After adjusting for these factors, older age was associated with a significantly higher risk of LBW and PTD: very LBW (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).

A subsequent prospective population-based study from Sweden evaluated outcome in women at more advanced ages and confirmed the increased risk of PTD in older women, after adjustment for confounders such as multiple gestation, smoking, parity, and maternal medical disease [68]. This series included over 32,000 women ≥40 years of age. The rates of PTD <32 weeks for women 20 to 29, 40 to 44, and ≥45 years of age were 1.01, 1.80, and 2.24 percent, respectively.

●A population-based Canadian series compared birth weight and PTD rates between women aged ≥35 and those under age 35 years [66]. Among older mothers, birth weight was slightly, but significantly, lower in every group (<2500 g, <1500 g, <1250 g, <1000 g) (OR 1.1 to 1.6), as was the rate of PTD (<37, <35, <32, and <30 weeks of gestation) (OR 1.1 to 1.3).

●A population-based study from the United States reported adjusted odds ratios for delivering a LBW infant increased progressively with each five-year increase in maternal age, reaching 2.3 (95% CI 1.6-3.4) in women ≥40 years versus those aged 20 to 24 years [69]. The maternal age effect on both very LBW and PTD was similar (OR 1.8 for the oldest compared with the youngest group).

Although older mothers have more PTDs, their preterm neonates are not at increased risk of morbidity compared with preterm neonates of younger women. A population based cohort study of over 12,000 neonates <33 weeks of gestation admitted to Canadian NICUs observed a trend of higher rates of neonatal survival without morbidity with increasing maternal age (adjusted OR 1.047, 95% CI 1.001-1.095) [72].

In contrast to the studies listed above, at least one study has reported that advancing maternal age may not independently increase the risk of low birth weight or preterm delivery. In a Finnish birth register study of over 124,000 children born between 1987 and 2000, there was no relationship between advanced maternal age and low birth weight or preterm birth when in-family models were evaluated (ie, children born to 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), consistent with prior studies [73]. 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 low birth weight or preterm delivery. Further studies are needed to determine if this finding can be replicated and if the information applies to women beyond Finland.

Perinatal mortality

Fetal death — Large studies worldwide consistently report that older women (≥35 years of age) are at significantly increased risk of stillbirth compared with younger women. A systematic review and meta-analysis of these studies calculated that maternal age older than 35 years was associated with a 65 percent increase in the odds of stillbirth (effect size 1.65, 95% CI 1.61-1.71) compared with younger women [74]. The relative risk of stillbirth increased with increasing maternal age (ie, higher at age 40 than at age 35). The increased risk of stillbirth is most notable after approximately 37 weeks of gestation (figure 3) [75,76].

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 [1,68,75,77-84]. Nevertheless, the absolute risk of stillbirth in developed countries is small, even at very advanced maternal ages:

●A prospective population-based study from Sweden reported the absolute risk of an intrauterine fetal death ≥28 weeks of gestation or death of the live-born child within the first 28 days of life was 1.1 percent in women aged ≥40 years (343 deaths/31,662 deliveries) and 1.7 percent in women ≥45 years (20 deaths/1205 deliveries) after adjusting for confounders such as parity, congenital malformations, smoking, and maternal disease [68]. The absolute risk of fetal or neonatal death in offspring of women 20 to 29 years of age was 0.6 percent (5246 deaths/876,361 deliveries).

●An analysis of over five million nonanomalous singleton gestations in the United States found the risk of stillbirth at 37 to 41 weeks for primiparous women increased significantly with maternal age [75]. The risk of stillbirth for women under age 35, age 35 to 39 years old, and over 40 years old was 3.73, 6.41, and 8.65 per 1000 ongoing pregnancies, respectively. The increased risk of stillbirth with increasing age persisted after accounting for medical disease and race/ethnicity. The risk increased sharply at 40 weeks of gestation, which suggests that older women are "post-term" sooner than younger women.

The role of antepartum fetal monitoring and elective delivery in 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'.)

Neonatal death — In contrast to the increased risk of stillbirth with increasing maternal age, the risk of neonatal death among neonates born preterm is lower than in preterm infants of younger women. In the population based cohort study of neonates <33 weeks of gestation admitted to NICUs discussed above, neonatal mortality progressively decreased with increasing maternal age (adjusted OR 0.922, 95% CI 0.855-0.955) [72]. This may have been due to differences in underlying factors, such as higher use of prenatal steroids and cesarean delivery and lower rates of substance abuse, in older women.

Multiple gestation — Advancing 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 [85].

Labor and cesarean delivery — The optimum gestational age for delivery of women of advancing age is unclear. While some data support delivery in the 39^th week of gestation, which has not been associated with an increase in the risk of cesarean delivery and appears to be cost neutral [86-89], other strategies are reasonable [89]. (See "Management of pregnancy in patients of advanced age", section on 'Risks of stillbirth versus delivery'.)

Studies consistently report that women ≥35 years of age are more likely than younger women to experience labor dystocia [90] and be delivered by cesarean [8,51,59,60,64,91,92]. In a United States cohort study of over 78,000 singleton births between 2003 and 2012, the proportion of women undergoing a primary cesarean delivery increased with age for both primiparous and multiparous women (women with a prior cesarean delivery were excluded from study) [92]. By years of age, the primary cesarean delivery rate was 20 percent for women ages 25 to 34 years, 26 percent for women 35 to 39 years, 31 percent for women 40 to 44 years, 36 percent for women 45 to 49 years, and 61 percent for women ≥50 years. For comparison, the overall primary cesarean delivery rate for singleton births in the United States was approximately 22 percent during a similar time period [93].

The reasons for the high rate of operative delivery in older women are controversial, but include an increased prevalence of medical complications, induction of labor, and fetal malposition, as well as a lower threshold among both patients and physicians for performing a cesarean delivery. Maternal request for cesarean delivery is becoming more common, particularly among older gravidae [94]. (See "Cesarean birth on patient request".)

When specific indications for cesarean birth are evaluated, older women appear to have an increased risk of failure of labor to progress normally. The almost linear increase in the relationship between maternal age and uterine dysfunction is a continuous effect throughout the childbearing years [95-97]. 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 [97,98]. However, despite the impact of age on uterine function, a meta-analysis of five trials that included over 2600 women reported that induction of labor at term in women aged 35 years or older did not increase the cesarean delivery rate compared with women undergoing expectant management [99].

Older women who undergo a trial of labor after a previous cesarean delivery appear to be at increased risk of both failed trial of labor and uterine rupture [100,101]. (See "Choosing the route of delivery after cesarean birth".)

Maternal mortality — While maternal mortality is relatively rare, women 40 years or older are at a sixfold increased risk of maternal death when compared with women less than 20 years of age [102]. There is a further discrepancy when evaluating data by race and ethnicity; Black women are more than three times more likely to die during pregnancy than white women. White women 40 years of age or older have a pregnancy-related mortality ratio (PRMR) of 51.5 per 100,000 live births whereas Black women of the same age have a rate of 189.7 per 100,000 [102]. (See "Overview of maternal mortality", section on 'Race and ethnicity'.)

Additional discussions of maternal morbidity and mortality are available in related content.

●(See "Overview of maternal mortality".)

●(See "Approaches to reduction of maternal mortality in resource-limited settings".)

LATER ISSUES

Parenting — An observational study of longitudinal cohorts noted that increasing maternal age was associated with improved health and development for children up to 5 years of age [103]. Outcomes included frequency of unintentional injuries, immunization rates, language development, and social development. Children of older parents have described several benefits, including the devotion, patience, and attention of their parents, as well as their emotional and financial stability [104,105].

On the other hand, 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.

Medical — The experience of pregnancy at an advanced maternal age may impact subsequent health as the woman continues to age, both because of changes from the pregnancy itself and because of increased risk of pregnancy-related complications that negatively affect health. An observational study from the United States Women's Health Initiative reported a trend toward increased risk of hemorrhagic stroke in women who had their last pregnancy at ≥40 years of age compared with women who had their last pregnancy at age <40 years (hazard ratio 1.5, 95% CI 1.0-2.1) [106]. Additionally, preeclampsia, a risk factor for subsequent cardiovascular disease, is much more common in women of advancing maternal age [107]. In contrast, a study in Israeli women reported that women with late-age births (birth at age 45 years or older) had an approximately 40 percent lower mortality risk compared with women whose last birth was before age 35 [108]. This discrepancy suggests that factors other than reproductive age are involved. One possible explanation for the conflicting data is a two-hit hypothesis that proposes that both early life stressors and reproduction accelerate aging, and women who have both will be most affected [109]. More studies are needed to clarify these relationships.

MANAGEMENT — Management of infertility and pregnancy in older women is discussed separately. (See "Management of pregnancy in patients of advanced age".)

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: Female infertility" and "Society guideline links: General prenatal care".)

SUMMARY AND RECOMMENDATIONS

●Women should be informed that delaying childbearing until the mid-30s significantly increases the risk of infertility and of developing a chronic medical disease which might complicate pregnancy. (See 'Epidemiology' above.)

●Women contemplating pregnancy should be counseled to optimize their health (eg, achieve a normal body mass index and avoid smoking, recreational drugs, and alcohol) and seek preconceptional counseling. (See "The preconception office visit".)

●Pregnancy complications that occur with increased frequency in older gravidae include: ectopic pregnancy, spontaneous abortion, fetal chromosomal abnormalities, some congenital anomalies, placenta previa, gestational diabetes, preeclampsia, and cesarean delivery. Such complications may, in turn, result in preterm birth. There is also an increased risk of perinatal mortality. (See 'Early pregnancy issues' above and 'Late pregnancy issues' above.)