Advanced Maternal Age & Pregnancy Dr .Ashraf Fouda Ob/Gyn. Consultant Damietta General Hospital

Sources Up to date on-line 22/4/2009 The older obstetric patient 2008 : Mehrnoosh Aref-Adib Theresa Freeman-Wang Ifat Ataulla

Advanced Maternal Age Improvements in women’s general health have led to this term tending to be reserved for pregnancies in women at or over 40 years of age.

INTRODUCTION   Fertility clearly declines with advancing age, especially after the mid-30s, and Women who conceive are at greater risk of pregnancy complications

INTRODUCTION   With use of assisted reproductive techniques (ART), births have been reported in women as old as 66 years of age. The oldest woman to achieve a naturally conceived pregnancy was 57 years old.

Shift towards delayed child bearing is due to: Changing role of women in work {more career opportunities are available}. High female educational level. ↑ Contraceptive opportunities. ↑ Availability of ART → Sensation of women that they may achieve pregnancy and childbearing at any time.

Pregnancy at Advanced Maternal Age may be due to: 1- Late marriage. 2- Long period of primary infertility. 3- Delayed childbearing.

Proportion of babies born to mothers of varying age group, showing trend of increased percentage born to mothers in older age groups and fewer in younger mothers.

PREGNANCY For first births, the proportion to women : In the past quarter century, older women in the USA have accounted for an increasing proportion of total births: in 2005, 14 % of all births were to women ≥35 years of age . For first births, the proportion to women : 30-34 years has increased 3-fold, 35-39 years has increased 6-fold, and ≥40 years has increased 15-fold .

PREGNANCY   The mean age of first-time mothers in other developed countries is increasing: Canada (mean age 29.6 years), Sweden (mean age 28.3 years), and Netherlands (28.7 years).

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 Older women experience an increased rate of spontaneous abortion. These losses are both trisomic and euploid and primarily result from a: decline in oocyte quality; changes in uterine and hormonal function. The vast majority of losses occur between 6 and 14 weeks of gestation.

The calculated risk of spontaneous loss in each age group was : Spontaneous abortion The calculated risk of spontaneous loss in each age group was : <30 years of age (12 %), 30 to 34 years (15 %), 35 to 39 years (25 %), 40 to 44 years (51 %), ≥45 years (93 %).

Down Syndrome (Trisomy 21)

Down Syndrome (Trisomy 21)

Edward Syndrome (Trisosomy 18)

Preconceptional Risks and Management ↑Risk of anueploidy in oocyte: Definition: Abnormal number of chromosomes around the normal figure Causes: Non-dysjunction Robertosonian translocation

↑Risk of Anueploidy in Oocyte: Types: A) Monosomy: Absence of one homologous chromosome Autosomal monosomy is fatal. B) Trisomy: presence of 3 homologous chromosome.

↑Risk of Anueploidy in Oocyte: Management: ART with preimplantation genetic diagnosis. + Transfer only embryos with no genetic abnormalities.

Pre-implantation genetic diagnosis (PGD)

Ectopic pregnancy  Maternal age ≥35 years is associated with a 4-8 fold increased risk of ectopic pregnancy compared with younger women. This high risk likely reflects an accumulation of risk factors over time, such as: Multiple sexual partners, Pelvic infection, and Tubal pathology.

Congenital Malformations The risk of having a child with a congenital anomaly may increase with increasing maternal age. This is attributed to the recognized increase of aneuploidy with advancing maternal age and the association of aneuploid fetuses with structural anomalies.

Increased Risk for Down Syndrome

Congenital Malformations More recent analysis suggests that, as women age, the risk of non-chromosomal anomalies increases. Cardiac anomalies, in particular, seem to increase with maternal age independent of aneuploidy. Clubfoot and congenital diaphragmatic hernia were also increased.

Congenital Malformations Congenital malformation rate: 3.5%, in women 20-24 years of age 4.4% in women 35 to 39 years and 5% in women ≥40 years .

LATE PREGNANCY ISSUES Some obstetrical complications 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.

Effects of Coexisting Medical Conditions The prevalence of medical and surgical illnesses, such as: cancer and cardiovascular, renal, and autoimmune disease, increases with advancing age. So, women ≥35 years of age can expect to experience 2-3 fold higher rates of hospitalization, cesarean delivery, and pregnancy-related complications than their younger counterparts.

Smoking Smoking has been associated with increased perinatal morbidity and stillbirth in all age groups, but the risk is particularly high in older smokers.

Effects of Coexisting Medical Conditions The two most common medical problems complicating pregnancy are hypertension (preexisting and pregnancy related) and diabetes (pregestational and gestational).

Hypertension  Hypertension is the most common medical problem encountered in pregnancy and is particularly prevalent in older women. Chronic hypertension is 2-4 fold higher in women ≥35 years of age than in women 30 - 34 years of age.

Hypertension The incidence of preeclampsia in the general obstetric population is 3 - 4% Increases to: 5 - 10% in women over age 40 and is as high as 35 % in women over age 50.

Hypertension 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, IUGR, and Cesarean delivery.

Diabetes mellitus The prevalence of diabetes increases with maternal age. The rates of both preexisting diabetes mellitus and gestational diabetes increase 3-6 fold in women ≥40 years, compared with women aged 20 - 29 years .

Diabetes Mellitus The incidence in the general obstetric population of gestational diabetes is 3% rising to: 7 to 12% in women over age 40, and 20% in women over age 50.

Diabetes Mellitus 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.

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.

Perinatal Morbidity Advanced maternal age is responsible for a substantial proportion of the increased rate of: low birth weight (LBW) and preterm delivery (PTD).

Perinatal Mortality The relative risk of stillbirth increases with increasing maternal age (ie, it is higher at age 40 than at age 35) and is most notable after about 37 weeks of gestation .

Perinatal Mortality The excess perinatal mortality is largely due to non-anomalous fetal deaths, which are often unexplained, even after controlling for risk factors such as: hypertension, diabetes, antepartum bleeding, smoking.

Multiple Gestation Advancing age is associated with an increased prevalence of twin pregnancy, It is related to both a higher risk of naturally-conceived twins and a higher use of ART in older women.

Multiple Gestation Interestingly, in contrast to singletons, the outcome of multiple pregnancies in older women is as good or better than the outcome in younger women .

Cesarean Delivery Older women are more likely to be delivered by cesarean than younger women The cesarean delivery rate in women: 50% at age 40 - 45 and 80 -100% at age over 50 years, The rate in the general obstetric population of the United States was about 25%.

Cesarean Delivery The reasons for the high rate of operative delivery in older women 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.

Cesarean Delivery Maternal request (cesarean on demand) is becoming more common, particularly among older gravidae. Older women appear to have an increased risk of cephalopelvic disproportion resulting in failure of labor to progress normally.

Dysfunctional Labor The linear increase in the relationship between maternal age and uterine dysfunction is a continuous effect throughout the childbearing years. Older women who undergo a trial of labor after a previous cesarean are at increased risk of both failed trial of labor and uterine rupture.

Maternal Mortality  Older women are at increased risk of maternal death, Only a small effect in developed countries since the risk of dying during childbirth is already very low in these areas.

Maternal Mortality  In the United States from 1991 to 1997, the risk maternal mortality for women: 35 - 39 years of age was more than twice that of women aged 25 - 29 years (21 per 100,000 live births); Over 40 years old, was 5 - fold higher (46 per 100,000 live births)

Maternal Mortality  In developing nations, however, maternal mortality remains a significant problem. Lack of adequate care contributes to these maternal losses, but increasing age and parity are also significant contributors.

Fetal Hazards 1- Higher incidence of: 2- ↑ Perinatal mortality rate Chromosomal abnormalities. (triosmy 21 → 1/350 after age of 35 yrs) . Congenital fetal malformation. Spontaneous abortion. IUGR. Preterm labor with all the hazards of prematurity. 2- ↑ Perinatal mortality rate

Maternal Hazards I) During pregnancy: 1- Higher incidence of PIH {Preeclampsia & eclampsia} Spontaneous abortion and its complications. Ectopic pregnancy & Vesicular mole 2-Diabetes and its complications (after age of 40yrs) 3-Abnormal placentaion (placental abruption, & placenta previa)

Maternal Hazards II) During Labor: Dysfunctional labor. Prolonged labor. Chorioamnionitis. Atonic PPH. Traumatic PPH.

III) During Puerperium: Maternal Hazards III) During Puerperium: Subinvolution of the uterus. Purperal sepsis. N.B: Important Note: Delayed childbearing :→ eliminate the protective effect of pregnancy against cancer ovary & cancer breast.

Pregnancy complications that occur with increased frequency in older gravidae include: Ectopic pregnancy, Spontaneous abortion, Fetal chromosomal abnormalities, Some congenital anomalies, Placental problems, Gestational diabetes, Pre-eclampsia, and Cesarean delivery.

Pre-pregnancy Counseling Women should be advised about the risks of Down syndrome and other aneuploidies. They should be made aware of: Available screening techniques, Their accuracy and effectiveness, as well as the Inherent risks of definitive testing with amniocentesis or chorionic villus sampling

Antenatal Care Reassurance and psychological support Pre-existing medical conditions must be taken into account, especially the risks of hypertension, diabetes and cardiovascular problems, which need a multidisciplinary approach to management.

Intrapartum and Delivery Health Careers should be aware of the increased frequency of severe complications that may threaten the health and life of the older obstetric patient

Despite the apparent risks of pregnancy, labour and delivery associated with increasing maternal age, It is important to know that the majority of women in this category have successful pregnancies and healthy children, and the risks are very small in absolute numbers. Good antenatal care, with appropriate and accurate information, can have a positive influence on the overall outcome.

The other face of the coin There can be advantages to delaying childbearing. The older age groups are often: Better educated, Financially more secure and, possibly, Emotionally better prepared for pregnancy.

The End!