Zygosity, chorionicity and amnionicity.
Triplet pregnancies may result from various fertilization and division scenarios involving ovum and sperm. Triplets can be trizygotic, dizygotic and monozygotic. Zygosity in higher order multiples (quadruplets or more) also varies.
In any scenario where there is shared placentation, and hence vascular anastamoses in the placenta, there is an increased risk of complications due to this configuration.
The evaluation of the membranes (amnion and chorion) and placenta(s) after the birth is important in all multiple pregnancies, but it does not always help determine zygosity.
Epidemiology
Twins and triplets occur naturally in about 1 in 80 and 1 in 8,000 pregnancies, respectively. There are familial and genetic factors that contribute to the risk of having naturally occurring twins, which are most commonly nonidentical twins (fraternal; dizygotic) and occur due to multiple ovulation; therefore, the chance of having twins runs down the maternal line. There are some families (few) who have a pedigree of recurrent monozygotic twinning but this is rare.
Currently, multiple pregnancies account for about 3% of births and about 15% of infant mortality. In the developed world, multiple birth rates started declining in the 1959s reaching a nadir in the 1970s but rising since then. From the late 1990s while triplet rates began to decline, twin rates continued to rise.[2]
The incidence of multiple pregnancy, and in particular twin pregnancy, varies between populations and over time. The population differences are mainly due to variation in dizygous twinning as monozygous twinning rates remain relatively constant. Variation over time relates to changes in factors that are known to influence twinning rates.
Factors influencing twinning rates
Population variation
As there are familial/genetic factors involved in dizygotic twinning, there are variations by race, and hence parts of the world with Asians having the lowest rate (Japan has the lowest rate) and Europeans and most other populations intermediate rates, but some Africans very high rates (Nigeria has the highest rate)[3].
Maternal age
Women of an older age (35–39 years) are at higher risk of multiple pregnancy and this is thought to be due to a rise in the level of gonadotrophins with age, with maximum stimulation of follicles occurring at age 35–39 years. Delayed childbearing and the increased use of assisted reproductive therapy (ART) with advancing age also contributes to multiple pregnancy rates[3].
Parity
The chance of twinning has been noted to be associated with increasing parity. One theory is that women who are more fertile, and hence have many pregnancies, are more likely to conceive twins or more. Others think this is due to the maternal age effect[3].
Socioeconomic, constitutional and maternal lifestyle factors
In the literature, some studies suggest lower social class, greater maternal height, obesity, heavy smoking and possibly different dietary habits contribute to twinning rates, but there is conflicting evidence and these associations are not clear[3].
Family history
There is consistent evidence in the literature that if a first-degree relative has had twins, there is an increased chance of twinning, particularly dizygous twins. Twinning seems to run down the maternal line[3].
Oral contraceptive use
There is conflicting evidence whereby some studies suggest lower twinning rates with recent oral contraceptive use, some higher rates and some no association.
Assisted reproductive technology
Up to two-thirds of the increase in multiple gestations have been attributed to the use of in-vitro fertilization (IVF) and ovulation induction making ART the largest contributor to the rising multiple pregnancy rate. In Europe, a quarter of deliveries following IVF are multiple pregnancies[4]. The rates are even higher in the USA and Canada.
It is possible to reduce multiple pregnancy rates from ART by cautious use of ovulation induction agents and reducing embryo transfer number, but there are complex factors worldwide that affect the widespread adoption of single embryo transfer (SET) policies[5]. Furthermore, monozygotic twinning (70% of which will be monochorionic with shared placentation and highest risk) still occurs with ART and SET, particularly since the introduction of day 5 blastocyst transfer, which optimizes successful pregnancy rates. There are theories about why blastocyst transfer is associated with higher rates, but there is no definitive explanation[6].
Maternal risks
Multiple pregnancy is associated with increased incidence of all maternal complications (apart from post-term pregnancy and macrosomia), including hypertensive disorders (gestational hypertension and pre-eclampsia), gestational diabetes, obstetric cholestasis, antepartum hemorrhage, postpartum hemorrhage, and incidence and complications of operative delivery, Maternal mortality is more than double that of singleton pregnancy[7]. Women who have multiple pregnancy are at increased risk of postpartum depression and this has an impact on other children and the family.
Fetal risks
Fetal loss/miscarriage
There is a higher risk of fetal loss and miscarriage (pregnancy loss before 24 weeks gestation) in multiple pregnancy, with risks increasing with number of fetuses. The higher fetal loss rates are mainly explained by the increased risk of poor implantation, fetal abnormality (aneuploidy and structural), extreme preterm labor and in monochorionic twins, complications of shared placenta.
Fetal abnormality
Fetuses in multiple pregnancy are at increased risk of structural abnormalities and this is thought to be mainly due to abnormal cleavage in monozygotic twinning. In the majority of cases, only one fetus is affected. If more than one is affected (rare), the severity can be variable with one severely affected and another not as severely affected.
Fetuses in multiple pregnancy are not individually at increased risk of chromosomal abnormality, but the risk of chromosomal abnormality is higher because of the additive effect, i.e., because the more fetuses the more chance there is an abnormality, e.g., in twins it is doubled and in triplets it is tripled.
There are also abnormalities that are unique to multiple pregnancy, namely conjoined twins, acardiac twin in twin reversed arterial perfusion sequence.
Preterm birth
The most common complication for the fetus of multiple pregnancy is preterm delivery, which is associated with increased perinatal morbidity and mortality[8]. Up to 60% of twins deliver before 37 weeks’ gestation (10% before 32 weeks) and the rates are higher for triplets and higher orders, i.e., with increasing number of fetuses gestational age at delivery decreases. The vast majority of higher order multiples do not reach 34 weeks, let alone term. The causes of preterm birth fall into three categories: iatrogenic (clinically indicated), spontaneous preterm labor or premature rupture of the amniotic membranes. In twins, about 50% are iatrogenic, one-third after spontaneous preterm labor and 10% after premature rupture of the amniotic membranes[9].
Although only about 2–3% of births are multiples (mainly twins), up to 30% of admissions to neonatal units are multiples. It is important not to be complacent about this as although modern neonatal care has resulted in increased survival rates for extreme preterm babies, there has not been a dramatic effect on long-term outcomes, and it is now known that even late preterm and early term births are associated with more long-term morbidity than previously thought[10]. Some studies have suggested that preterm multiples have poorer outcome compared with weight and gestation-matched singletons.
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