Grand multiparity

INTRODUCTION — This topic will discuss issues related to grand multiparity. Solomon first introduced the term "grand multipara" or "dangerous multipara" in 1934 after observing that increasing parity was associated with an increased risk of pregnancy complications and maternal mortality increased steadily from the 5^th to the 10^th pregnancy [1].

DEFINITION — A reasonable definition of "grand multiparity" is a patient who has had ≥5 births (live or stillborn) at ≥20 weeks of gestation, with "great grand multiparity" defined as ≥10 births (live or stillborn) ≥20 weeks of gestation [2]. However, other definitions are also used. (See 'Variability in the definition of parity' below.)

Pregnancy losses under 20 weeks of gestation are considered abortions. Spontaneous and induced abortions are not counted toward parity but are counted toward gravidity (ie, the number of times a patient has been pregnant, including the current pregnancy [eg, primigravidas = patients in their first pregnancy; multigravidas = patients who have had more than one pregnancy]).

PREVALENCE — In the United States in 2019, 2.97 percent of live births were the fifth child in the family, 1.3 percent were the sixth child, and 1.2 percent were the seventh child and over [3]. Africa has the highest rate of grand multiparity, where the incidence in some countries is as high as 27 percent [4-7].

EPIDEMIOLOGY — Grand multiparas tend to be older than patients of lower parity. In addition, social, cultural, economic, and religious factors affect the prevalence of grand multiparity. These factors include marrying at a very early age, low income, Muslim or ultra-Orthodox Jewish religion, residence in a rural area, lack of formal education, lack of employment outside of the home, and lack of access to, or religious proscription of, contraception [5,8,9].

FACTORS AFFECTING THE RELATIONSHIP BETWEEN PARITY AND PREGNANCY OUTCOME — The relationship between obstetric complications and parity has been studied extensively, with inconsistent findings. In addition to the usual limitations of observational data, there are several reasons for the discordancy:

Variability in the definition of parity — There are discrepancies in the way clinicians define parity. A study that evaluated the definition of parity among obstetricians and midwives in London noted that 62 percent defined parity as pregnancies ≥24 weeks of gestation irrespective of outcome, 25 percent defined parity as pregnancies ≥24 weeks ending in live birth, and 13 percent defined parity by the number of pregnancies irrespective of outcome [10]. Only 21 percent of those surveyed described twin pregnancies as a single parous experience.

In addition, there is a discrepancy between the clinical definition of parity and the definition used by the United States National Center for Health Statistics (NCHS), an organization within the Centers for Disease Control and Prevention (CDC). The NCHS defines parity as the number of prior live births, excluding stillbirths and fetal deaths [11], while most clinical investigators in the United States have defined parity as the number of births (live births and stillbirths) ≥20 weeks of gestation. Other gestational age cut-offs to define a parous event (eg, birth after 28 weeks of gestation) are used in other parts of the world.

Finally, investigators have variably defined grand multiparity as a parity of four, five, six, seven, or eight. Thus, one study may report outcomes for patients para ≥6 compared with those <6, while another reports outcomes for patients para ≥5 compared with those <5 [12].

Variability in the definition of controls — Studies have compared grand multiparas with different referent groups, including patients of parity 1 [13,14], 1 to 3 [15], 2 to 3 [16,17], 2 to 4 [18-21], 1 to 4 [22], 1 to 6 [23], 2 to 6 [24], and the general obstetric population [25]. This makes it difficult to compare findings among studies.

Nonlinear relationship between parity and pregnancy outcome — The relationship between parity and birth outcome is not linear. In a cross-sectional analysis of births to patients of parity 0 to 8 in Australia between 1992 and 1997, multivariate analysis showed that the risk of pregnancy complications was highest in nulliparas, lowest in multiparas who had one to three deliveries, and intermediate in multiparas with four or more deliveries (for any obstetric complication: nulliparas OR 1.75, Para 1 to 3 OR 0.96-1.03, Para 4 to 8 OR 1.19-1.35) [13]. These findings suggest that the risk of obstetric complications associated with parity is bimodal.

Inadequate adjustment for maternal age — Many of the complications that have been associated with grand multiparity have also been independently associated with advanced maternal age [26]. Increasing maternal age is associated with increasing prevalence of comorbidities, such as type 2 diabetes, hypertension, and obesity, which also increase the risk of adverse pregnancy outcome. Thus, maternal age is an important confounder that must be accounted for to minimize bias in interpretation of results. (See "Effects of advanced maternal age on pregnancy".)

The importance of maternal age was illustrated in a retrospective cohort study that examined the birth outcomes of 4937 young (under 35 years of age) grand multiparas (parity ≥5) and over 83,000 young primiparas in Utah [14]. Young grand multiparas compared with young primiparas were at lower risk for "any intrapartum complication" (eg, placental abruption, placenta previa, intrapartum vaginal bleeding, umbilical cord prolapse, fetal distress, malpresentation, surgical delivery, instrumented delivery). In addition, young grand multiparas compared with older grand multiparas were also at lower risk for any intrapartum complication. However, the evidence is conflicting. In a prospective study including 426 young (ages 18 to 35) grand multiparous and "low-risk" primiparous patients in Sudan, young grand multiparas compared with primiparas had higher rates of postpartum hemorrhage, low birth weight, and infant neonatal intensive care unit admission; other maternal and neonatal complications were similar between groups [27].

Healthy person effect — Patients who have had obstetric complications in their first few pregnancies may be more likely to end childbearing before becoming grand multiparas compared with those who had uncomplicated pregnancies and deliveries. Thus, grand multiparas may represent a healthier group than patients of lower parity.

RISK OF PREGNANCY COMPLICATIONS — A multivariate analysis of parity and pregnancy outcome reported a significantly increased risk of "any obstetric complication" among patients of parity 4, 5, 6, and 7 to 8 when compared with primiparas [13]. The obstetric complications included antepartum hemorrhage, gestational diabetes, pregnancy-induced hypertension, prelabor rupture of membranes, threatened preterm labor, postpartum hemorrhage, and third-degree lacerations. There was a variable relationship between parity and the individual components of the composite outcome.

Grand multiparity probably increases the risk of the following complications, although findings are inconsistent across studies:

●Placental abnormalities, such as placenta previa and abruption [16,19-21,28-31]

●Postpartum hemorrhage [13,19,22,27]

●Macrosomia [15,17,19,20,23,24,32-34]

●Umbilical cord prolapse [35]

Data are not adequate to clearly support or refute an association between grand multiparity and:

●Cesarean delivery [6,34,36]

●Venous thromboembolic events [37]

●Gestational hypertension/preeclampsia [18,20,23,25,33,34,36,38-40]

●Pregestational/gestational diabetes [18,23,24,33,34,39-41]

●Malpresentation/operative delivery [16,17,19,20,24,25,28,30,33,40,42]

●Dysfunctional labor/prolonged labor [15-20,43]

●Preterm birth/low birth weight [6,27,34,40,44]

●Neonatal intensive care unit admission [13,20,27]

●Perinatal death [13,15,17-19,25,28,32,39,40,45]

●Amniotic fluid disorders (oligohydramnios, polyhydramnios) [36,46]

●Perineal lacerations [7,47]

Some problems with the available data are that most reports have not distinguished between chronic hypertension, gestational hypertension, and preeclampsia or between pregestational and gestational diabetes; many studies did not adjusted for confounders; and reports on the risk of perinatal death did not control for concurrent maternal medical problems.

Role of previous cesarean delivery — The route of previous deliveries is a key factor to consider when evaluating the risk of adverse pregnancy outcome. Large observational studies have consistently shown that patients who undergo multiple repeat cesarean deliveries are at increased risk of maternal morbidity, and the risk increases with the number of cesarean deliveries. The largest prospective study of maternal morbidity associated with multiple cesarean deliveries included 6201 first; 15,808 second; 6324 third; 1452 fourth; 258 fifth; and 89 sixth cesarean deliveries [48]. The odds of placenta previa and accreta progressively increased with the number of cesarean deliveries, and patients with placenta previa were at very high risk of also having placenta accreta (table 1 and table 2). The risk of peripartum hysterectomy at the fourth cesarean delivery was 1 in 40, increasing to 1 in 11 at the sixth cesarean delivery. (See "Repeat cesarean birth", section on 'Is there an unsafe number of repeat cesarean births?'.)

The risk of uterine rupture may be increased in grand multiparity and is known to be increased in any patient undergoing a trial of labor after cesarean delivery (TOLAC) (see "Choosing the route of delivery after cesarean birth"). A retrospective study reported the rate of uterine rupture during a trial of labor after a single previous cesarean was no higher than the background risk associated with TOLAC [49]. The authors identified six uterine ruptures among 1922 TOLACs (0.3 percent) in patients with ≥6 births and one previous cesarean. Other smaller series have reported mixed results [50-53]. It is difficult to determine the true risk of uterine rupture in these studies because of the low rate of this complication and differences in study methods and terminology. However, in a large, retrospective multicenter study including almost 5000 patients undergoing TOLAC after a single cesarean delivery, multiparous (parity 2 to 5) compared with grand multiparous (parity ≥6) patients had similar rates of uterine rupture (0.3 percent in both groups) [54].

LONG-TERM RISKS — Long-term follow-up studies suggest that grand multiparity may increase the likelihood of certain maternal health issues.

●Increased risk for pelvic organ prolapse – There is convincing evidence that the risk of pelvic organ prolapse increases with increasing parity [55-57]. As an example, in the Oxford Family Planning study, a prospective cohort study of more than 17,000 patients followed for 17 years, the risk of hospital admission for pelvic organ prolapse increased markedly after the first and second births compared with nulliparity (fourfold and eightfold increase, respectively) but increased less rapidly for subsequent births (ninefold increase after the third birth; 10-fold increase after the fourth birth) [57]. Among parous patients, 75 percent of prolapse cases can be attributed to pregnancy and childbirth [58]. Specific factors, such as forceps delivery, may be particularly important [59]. Patients with pelvic organ prolapse may present with symptoms related specifically to the prolapsed structures, such as a bulge or vaginal pressure, or with associated symptoms, including urinary, defecatory, or sexual dysfunction. (See "Pelvic organ prolapse in females: Epidemiology, risk factors, clinical manifestations, and management".)

●Increased risk for diastasis recti. (See "Rectus abdominis diastasis", section on 'Pregnancy'.)

●Variable effects on cancer risk – Grand multiparity has been consistently associated with a decreased risk of breast cancer, suggesting that multiple pregnancies and/or lactations are associated with changes protective against this disease [60-63]. Some studies have reported a decreased risk for endometrial [60,64,65] and ovarian [60,66] cancers, but not cervical cancer [67], but these data are less consistent [63].

Grand multiparity has also been associated with an increased risk of some cancers, such as the liver/biliary tract, but data are less consistent [60,68-70]. These findings require further investigation to better understand confounding factors, such as age, obesity, smoking, and duration of breastfeeding. (See "Endometrial carcinoma: Epidemiology, risk factors, and prevention" and "Epithelial carcinoma of the ovary, fallopian tube, and peritoneum: Incidence and risk factors" and "Factors that modify breast cancer risk in women", section on 'Reproductive factors'.)

●There are conflicting data about the impact of parity on the risk of osteoporosis [71], with some studies finding no increased risk of osteoporosis [71-77] and similar levels of postpartum bone mineral density [78], while other studies report an increased risk of femoral osteoporosis [79] or postmenopausal osteoporosis [77,79].

●Two reports have linked grand multiparity with left ventricular diastolic dysfunction [80,81]. A parity-associated decrease in HDL cholesterol levels has also been reported [82], suggesting an increased risk of cardiovascular disease among grand multiparas. These changes may be mediated by weight gain and risk of type 2 diabetes mellitus and modified by duration of lactation [83].

●Other outcomes have not been evaluated extensively in grand multiparous versus multiparous patients. Grand multiparity may increase permanent weight gain [84] and may increase risk of insulin resistance [85] and diabetes [6,41,86-89].

●A few studies have found an association between grand multiparity and psychiatric illness in adult offspring, including mood disorders [90,91] and suicide attempts [90,92]. More research is needed to understand this association.

●There is some evidence that grand multiparity may be associated with later-life cognitive impairment [93] and Alzheimer's disease [94]. Researchers have identified differences in hippocampal volume by parity, with grand multiparas having higher rates of hippocampal atrophy compared with patients of lower parity [95]. These associations may be related to the role of estrogen on cognitive function, but additional research is needed in this area.

PATIENT COUNSELING — We counsel our patients that the maximum number of pregnancies that is safe for mother and baby is unclear, and factors other than obstetric issues need to be considered. Although having more than four or five deliveries has been associated with a number of obstetric complications, most patients who experience this number of births have similar birth outcomes when compared with patients of lower parity, especially in settings where contemporary obstetric care with adequate resources is readily available.

We believe most of the complications that have been associated with grand multiparity may actually be related to advanced maternal age and its associated comorbidities, and we review the relevant medical issues on a case-by-case basis. (See "Effects of advanced maternal age on pregnancy".)

Regardless of maternal age, in patients without underlying comorbidities, the fourth, fifth, or sixth deliveries do not appear to be independent risk factors for severe obstetric complications, except possibly placenta previa and abruption [16,19-21,28-31]. However, we counsel patients with more than one prior cesarean delivery of the clearly increased risk of placenta previa-accreta and associated morbidities with increasing number of cesarean births. (See "Placenta previa: Epidemiology, clinical features, diagnosis, morbidity and mortality" and "Placenta accreta spectrum: Clinical features, diagnosis, and potential consequences".)

Grand multiparous patients who are obese, prediabetic, and/or have a history of gestational diabetes mellitus may benefit from weight loss prior to conception. Whenever possible, preconception counseling addressing healthy lifestyle and pregnancy risks is indicated in this group [96].

PREGNANCY MANAGEMENT — Antepartum clinical care is similar for all multiparous patients, regardless of the number of previous deliveries.

In patients with a prior cesarean delivery, we do not advise against a trial of labor based on grand multiparity alone. (See "Choosing the route of delivery after cesarean birth".)

Intrapartum, providers should anticipate an increased risk of macrosomia, labor abnormalities, and postpartum hemorrhage. Thus, they should be prepared to manage labor abnormalities more common in this population (eg, failure to progress due to macrosomia or malposition) and complications such as shoulder dystocia and excessive bleeding after delivery. (See "Shoulder dystocia: Intrapartum diagnosis, management, and outcome" and "Overview of postpartum hemorrhage".)

SUMMARY AND RECOMMENDATIONS

●Although grand multiparity has been associated with a number of obstetric complications, most grand multiparas have similar birth outcomes when compared with patients of lower parity, especially in settings where modern obstetric care is readily available. (See 'Risk of pregnancy complications' above.)

●The maximum number of pregnancies that is safe for mother and baby is unclear, and factors other than obstetric issues need to be considered. Most of the complications that have been associated with grand multiparity may actually be confounded by advanced maternal age and its associated comorbidities. Thus, in patients without underlying comorbidity, grand multiparity does not appear to be an independent risk factor for severe obstetric complications, except for placenta previa, abruption, and postpartum hemorrhage. (See 'Risk of pregnancy complications' above and 'Factors affecting the relationship between parity and pregnancy outcome' above.)

●Patients who undergo multiple repeat cesarean deliveries are at increased risk of maternal morbidity, particularly placenta previa and accreta. The risk increases with the number of cesarean deliveries. However, a trial of labor after a single prior cesarean delivery in a grand multiparous woman does not appear to be associated with greater risks than a similar trial of labor in women of lower parity. (See 'Role of previous cesarean delivery' above.)

●Antepartum clinical care is similar for all multiparous patients, regardless of the number of previous deliveries. In patients with a prior cesarean delivery, we do not advise against a trial of labor based on grand multiparity alone. During labor, providers caring for grand multiparas should anticipate and be prepared to manage macrosomia (and shoulder dystocia), labor abnormalities (including dystocia related to macrosomia or malposition), and postpartum hemorrhage. (See 'Pregnancy management' above.)

●The long-term maternal effects of grand multiparity are not well established. The best evidence is for an increased risk of pelvic organ prolapse. (See 'Long-term risks' above.)