Multiple Gestations: Basics and Beyond Shailesh Kore
INDEX
Page numbers followed by f refer to figure and t refer to table
A
Abortion 63
spontaneous 134
Abruptio placentae 52
Acardiac acephalus 94f
Acardiac amorphus 95f
Acardiac fetus 95f
Acardiac paracephalus 95f
Acardiac twin 48, 65, 65f, 93
American Congress of Obstetricians and Gynecologists Guidelines 77
American Society for Reproductive Medicine 134
Amniocentesis 36, 38
Amnions, count number of 22
Amniotic band syndrome 147
Amniotic fluid 125
assessment of 54
Amniotic sacs, the number of 45
Amniotomy 131
Amorphus acardiac twin 48f
Analgesia 119
Anemia 52, 57, 61
and pre-eclampsia, prevention and treatment of 27
Anesthesia 119
Anorectal malformations 147
Antenatal corticosteroids 77
Antepartum hemorrhage 52, 57, 61
Apnea 145
Assisted reproductive technology 59, 134
Atrial natriuretic peptide 85
Auscultation 19
B
Bipolar cord coagulation 71
Birth, timing of 29, 130
Brain natriuretic peptide 85
Breast tenderness 19
Breastfeeding 150
twins 149f
C
Cardiotocograph machine 119
Cardiovascular profile score 55
Central nervous system 71, 151
Cephalic twin, delivery of 122
Cervical cerclage 76
Cervical length 57
ultrasonic assessment of 47f
Chin-to-chin interlocking 127f
Chorionic peak sign 45
Chorionic villus sampling 35, 39, 41, 60
Chorionicity 16, 21-23, 25
determination of 21, 25f, 44, 53
Chronic lung disease 145
Clomiphene citrate 134
Congenital anomalies 27, 53, 68
Congenital heart disease 147
Congenital malformations 47, 147
Conjoined twins 48, 66, 69, 110, 147
types of 66f, 112f, 113t
Cord accidents 62
Cordocentesis 41
Count gestational sacs 22
Crohn's disease 150
Crown-rump length 26, 32, 86
D
Deflexion 125
Delivery 98, 136
mode of 118
route of 130
timing and mode of 81
Dichorionic diamniotic triplet 17
pregnancies 28
Dichorionic diamniotic twins 107
Dichorionic gestation 23f, 24t
Dichorionic placenta 31f
Dichorionic triamniotic triplet 17
pregnancy 23f, 141f
Dichorionic triplet pregnancies 17
Discordant growth 54
Discordant twins 48, 49f, 63, 79
Disimpaction maneuvers 127
Dizygotic twins 16, 59
Doppler myocardial performance index 55
Down's syndrome 27, 32, 33, 69, 135
Dye, use of 38
E
Embryo
count number of 22
reduction 46, 46f
transfer 157
Estimated fetal weight 48, 79
External cephalic version 123
External parasitic twins 66
F
Fatigue 19
Fertilization 17
Fetal
blood sampling 41
death 62
fibronectin 57
growth
discordance 146
restriction 28, 61
growth, assessment of 54
heart rate 121f, 131
magnetic resonance imaging 115
Medicine Foundation 33
medicine unit 55
monitoring 119
scalp electrodes 120f
surveillance 52, 57, 135
Fetopelvic disproportion 125
Fetoscopic laser ablation 88
Fetus
mapping of 36
ultrasonography of 85
Fluorescent in situ hybridization 39
Follicle stimulating hormone 2, 18, 134
Fused placental masses 24f
G
Gamete intrafallopian transfer 157
Genitourinary anomalies 147
Gestational diabetes 57, 61
mellitus 27, 61
Gestational sacs 22t
Glucocorticoids, role of 77
Gonorrheal infection 40
H
Higher order multiple gestations 8
management of 135
Home uterine activity monitoring 56
Human chorionic gonadotropin 155
Human menopausal gonadotropin 134
Hydramnios 20, 61
Hyperemesis gravidarum 61
Hypertensive disorders 52
Hypovolemia 84
I
In vitro fertilization 18, 79, 134, 155
Indian Council of Medical Research Guidelines 157
Infertility therapy 3, 134
Intermittent auscultation 120
Intracardiac needle injection 137f
Intracardiac potassium chloride 99
Intracranial hemorrhage 146
Intrapartum cardiotocograph of twins 121f
Intrauterine death 99
Intrauterine fetal demise 52
Intrauterine growth restriction 28, 73, 86, 146
Intrauterine insemination 18
Ipsilon sign 45, 46f
K
Kimball-Rand maneuver 127, 128f
L
Labor
management of 119, 121
third stage of 131
Laser therapy, complications of 90
Live birth
number of 6
weight 29, 61, 134
Lower segment cesarean section 127
Lung maturation 77
Luteinizing hormone 2
M
Magnesium sulfate 77
Magnetic resonance imaging 53, 104, 108
Membranes, preterm premature rupture of 27
Middle cerebral artery-peak systolic velocity 86
Monochorionic diamniotic triplet 17
pregnancies 28
Monochorionic diamniotic twin 107, 108
pregnancy 22t
Monochorionic monoamniotic entangled umbilical cord 63f
Monochorionic monoamniotic pregnancy 50
Monochorionic monoamniotic triplet 17
pregnancies 28
Monochorionic monoamniotic twin 108, 109
pregnancies 28
Monochorionic placenta 32f
Monochorionic polyhydramnios 62f
Monochorionic triamniotic triplets 17
Monochorionic twin pregnancies 17
Monozygotic and dizygotic twins 17t
Monozygotic twinning 112f
mechanism of 60f, 111f
outcome of 17f
Monozygotic twins 16, 17, 59
Multifetal gestation, maternal complications of 57
Multifetal pregnancy 52
reduction 139
Multifetal reduction 136, 156
Multiple births, rate of 11t
Multiple fetuses 134
Multiple gestations 11, 12t, 16, 26, 31, 33, 35, 38, 44, 52, 59, 68, 73, 106, 118, 133, 139, 145, 148, 155
epidemiology of 1, 5
Multiple intrauterine gestations, assessment of 3
Multiple pregnancies 27, 36, 55, 133f
N
National Institute for Health and Care 29, 74, 134
Nausea 19
Necrotizing enterocolitis 146
Neonatal consequences of multiple gestations 145
Neonatal intensive care unit 77, 151
Neural tube defect 80, 147
Non-cephalic twin, delivery of 122
Non-invasive prenatal testing 33
role of 33
Nonsteroidal anti-inflammatory drugs 78
Nonstress test 48
Normal fetal circulation 93
Northern Survey of Twin and Multiple Pregnancy 7
Nuchal translucency 32
measurement of 32f
O
Obesity 9
Observable gestational sacs, number of 45
Omphalopagus 66
Oral contraceptives 3, 14
use of 3
Ovarian stimulation 3
Ovarian tumor 20
Ovulation induction 18, 134
Oxytocin 131
P
Patent ductus arteriosus 145
Perinatal asphyxia 146
Perinatal mortality 62
Placental malformations 147
Polycystic ovarian syndrome 3, 18
Polyhydramnios 52
Postpartum hemorrhage 61, 62, 123, 131
Post-procedural loss rates 38, 41
Pregnancy
fatty liver of 57, 61
hypertensive disorders of 57, 61
induced hypertension 19, 27
Prenatal chorionicity 87f
Preterm labor 52
prevention and treatment of 28
Progesterone 75
Pump twin 95
Q
Quadruplet pregnancy, neonatal outcomes of 137t
R
Renin-angiotensin system 85
Respiratory distress syndrome 145
S
Selective feticide
indications 87
procedure 88
Separate placental masses 24
Septostomy 87
Severe hydrops 95
Simultaneous visualization technique 38
Single embryo transfer policy 156
Single umbilical artery 147
Spontaneous twinning 17
Spontaneously occurring multiple gestations, 16
Stuck twin 47
T
Therapeutic amniocentesis 62
Thromboplastin theory 103
Tracheo-esophageal fistula 69
Transabdominal chorionic villus sampling 40f
Transcervical chorionic villus sampling 40f
Transvaginal chorionic villus sampling 40
Transvaginal sonography 28
Trap
complication of 95
sequence 94, 147
Trichorionic triplets 17
Tricuspid regurgitation 33
Triplet pregnancies 8
types of 17
Trophoblastic disease 102
Twins
anemia polycythemia sequence 85, 100, 142, 147, 148
delivery of 122
embolization syndrome 147
frequency of 59
gestational sac diamniotic dichorionic 45f
interlocking of 125
live births 6
maternities 8
peak sign 23, 31f
pregnancy 8, 99, 103, 131t
complications of 60, 61t
intrapartum management of 131
types of 16, 59
reversed arterial perfusion 36, 48, 61, 108, 148
sequence 92, 100
to-twin transfusion 80
syndrome 48, 55, 61, 64, 69, 84, 84f-85f, 87, 87f, 100, 107, 124, 142, 147, 148
Two-puncture technique 37
V
Vaginal breech delivery 123
Vanishing twin 45, 59
syndrome 106
Velamentous cord insertion 147
Vomiting 19
Y
Yolk sacs
count number of 22
numbers of 45
Z
Zavanelli maneuver 127
Zygosity 16, 21
×
Chapter Notes

Save Clear


Epidemiology of Multiple Gestations1

ShaileshKore,
Rashmi PatilRaydurg,
ChaitraThunga
 
INTRODUCTION
Over the past few decades, incidence of multiple gestations has increased steadily not only in developed countries but also in developing and underdeveloped countries. Apart from reasons related to increased use of ART, other reasons are also responsible for these changes. Since 1980, world witnessed sharp increase in incidence of twin as well as higher order pregnancy. This was probably because of increased use of ART technique, higher number embryo transfer, and also changes in the age distribution of women at child birth, with more women giving birth at older ages. Multiple births have huge impact on health care. Though with the medical and technological advances outcome of preterm and low-birth weight babies has improved, multiple gestations are still associated with increased risk of maternal and perinatal complications. Fortunately, since the last one decade, with more rational embryo transfer practices, though twin pregnancy incidence has remained high, incidence of higher order pregnancy has started declining.
The epidemiology of twinning is complex and, though not fully understood, there are certain factors which have definite bearing with occurrence of multiple gestations.
It is important to understand the changing epidemiology of multiple births, especially for women with advanced maternal age. Twin pregnancies are the result of a complex interaction of genetic and environmental factors. Twinning rate rose by 76% from 18.8 to 32.1 per 1000 live births in 2009. Since then, however, evolving infertility management has resulted in decreased rates of higher order multifetal births to its lowest level. Especially, rates of triplets are decreased by 10% from 153 per 100,000 births to 138 per 100,000 births in 2010.1 Frequency of monozygotic twin birth is relatively constant worldwide approximately one set per 250 births, incidence is generally independent of race, heredity, age, and parity. One exception is that zygotic splitting is increased following ART.2
 
RACIAL AND GEOGRAPHICAL FACTORS
Twin pregnancy incidence varies from country to country. Highest reported is in Nigeria and the lowest in Japan.3 In general, the dizygotic twinning rate is about 8/1000 in Caucasians, about twice as large in Negroes and less than half in mongoloids. The factors which influence the racial differences in dizygotic twinning incidence include genetic 2predisposition, levels of follicle-stimulating hormone (FSH) and undernourishment.4
Mothers of dizygotic twins have significantly higher basal FSH concentrations and FSH pulse frequency with consequent elevation of follicular phase estradiol, inhibin and luteinizing hormone (LH) concentrations. In the study by Martin et al., it was found that basal FSH concentration in women is significantly higher in populations with high twinning rates (e.g. Western Nigeria: 50/1000 maternities) compared to that in women from populations with low twinning rates.5
 
MATERNAL AGE
Dizygotic twinning frequency increases almost 4-fold between ages of 15 and 37 years,6 monozygotic rates being fairly constant. It is in this age range that maximal FSH stimulation increases the rate of multiple follicles developing.7 Rate of twinning increases dramatically with advancing maternal age because the use of ART is more likely in older women.8 Although paternal age has been linked to frequency of twinning, its affect is felt to be small.9 Bulmer et el. reported that if parity is held constant, rate of twinning is increased by 4-fold, or by 300%, between the ages 15 and 37 years.10
 
SOCIAL, CONSTITUTIONAL AND MATERNAL LIFESTYLE FACTORS
In women of lower social class in Nigeria,11 higher rates of twinning were observed, and this could be attributed to the different dietary habits. No consistent association between education and risk of twin pregnancies emerged from case-control study.12 Some association was found between greater maternal height and risk of dizygotic twins. Higher incidence of twins was seen in overweight women.13 Taller-heavier women had a twinning rate of 25–30% greater than short, nutritionally deprived women.14 Higher folate intake and plasma folate concentrations were associated with an increased rate of twinning in women undergoing in-vitro fertilization techniques.15 Nylander14 showed a definite increase gradient in the twinning rate related to greater nutritional status as reflected by maternal size. Ericson,16 Haggarty,17 Hasbargen18 have reported 40% increase in prevalence of twinning among women who have taken supplementary folic acid.
In two case-control studies conducted in Greece and Italy,12,19 authors reported that there is increased tendency of multiple gestations, both monzygotic and dizygotic, in women who are heavy smokers, but this finding was not statistically significant. Also the risk of multiple gestations tended to be higher in alcoholic women, consuming 15 or more alcoholic drinks per week.
 
FIRST-DEGREE RELATIVES AND PARENTAL CONSANGUINITY
While consanguinity showed, though insignificant, yet positive association with dizygotic twins in Indian population, total and monozygotic twinning rate declined with closeness of consanguinity.20 In a study by Lichtenstein et al., they reported an increased risk of giving birth to twins in women who were themselves twins.21
It was also reported in that study that dizygotic mothers had an increased risk of giving birth to dizygotic twins, while monozygotic mothers had an increased risk of having monozygotic twins. Parisi et al. analyzed the incidence of twinning in the families of twins, and indicated that a propensity to monozygotic twinning, as well as to dizygotic twinning, may be inherited through the maternal line.22 They also found a paternal role in dizygotic, but not in monozygotic twinning. As a determinant of twinning, the family history of mother is more important than that of the father. White and Wyshak23 found that women who themselves were a dizygotic twins gave birth to twins at a rate of 1 set per 58 births. Women who were not a twin but whose husbands were a dizygotic twins, gave birth to twins at a rate of 1 set per 116 pregnancies. Painter et al.6 found potential linkage peaks with the long arm of chromosome 6 and also on chromosomes 7, 9 and 16.
 
REPRODUCTIVE HISTORY
A positive relationship has been seen between parity and frequency of dizygotic twinning.20 Conversely, Rao et al.20 in their study reported a negative corelation between monozygotic pregnancies and multiparity, while Olusanya24 found an 8-fold increase in multiple gestations 3when parity was 4 or less and 20-fold increase when parity was 5 or more compared with primiparas.
 
USE OF ORAL CONTRACEPTIVES
Several studies have been published on the relationship between use of oral contraceptives (OCs) and subsequent risk of multiple gestations after their discontinuation. Different studies in literature have shown conflicting results regarding relationship of the use of oral contraceptives and multiple gestations. Though some studies have shown decrease in risk of multiple gestations, particularly, in those women using pills for short duration, many more studies have quoted 3- to 6- fold increase in risk. This increase in risk is only for short period after discontinuation of OC due to rebound increase of pituitary gonadotropins. Hemon et al.25 reported lower fertility with higher incidence of chromosomal abnormalities among spontaneous abortions after OC discontinuation. Increased fecundity and higher rate of dizygotic twinning was reported in women who conceive within 1 month after stopping oral contraception but not during subsequent months.26 Paradox of declining fertility but increasing twinning with advancing maternal age can be explained by an exaggerated pituitary release of FSH in response to decreases negative feedback from impending ovarian failure.8
 
INFERTILITY THERAPY
Ovulation induction with clomiphene or FSH with chorionic gonadotropins remarkably enhances likelihood of multiple ovulations. Incidence of multifetal gestations in assisted reproductive technology is 14%. With clomiphene citrate treatment, it is 6.8–17%, and with gonadotropins, 18–53%. Risk of multiple gestations is 50% and 32% when gonadotropins were used for ovulation induction in hypogonadotropic women and normogonadotropic women respectively, while in oligomenorrhic women, chance is 18% as reported by Assessment of Multiple Intrauterine Gstations from Ovarian Stimulation (AMIGOS) and Pregnancy in Polycystic Ovary Syndrome (PPCOS II).27
 
CONCLUSION
Epidemiological observations show us that the causes of monozygotic and dizygotic twins are multi-factorial. Monozygotic twins are largely determined by genetic mechanisms as the frequency of monozygotic pregnancies over the time and in different areas are constant, and the trends in dizygotic pregnancies suggest that environmental factors play a role here. Maternal age and the hereditary components are the best-defined determinants of risk of multiple births, other determinants being race, parity and nutrition. Higher rates of neonatal problems and greater risk of complications of pregnancy and delivery are associated with multiple births.28 Thus, it is important to clarify the causes of this condition.
REFERENCES
  1. Martin JA, Hamilton BE, Ventura SJ, et al. Births: final data for 2010. Natl Vital Stat. 2012. pp. Rep 61(1).
  1. Aston K, Peterson C, Carrell D. Monozygotic twinning associated with assisted reproductive technologies: a review. Reproduction. 2008; 136(4):377.
  1. Golding J. Factors associated with twinning and other multiple birth, social and biological effects on perinatal mortality. Perinatal analysis. Bristol University, Bristol. 1990;3:21-66.
  1. Danforth DN Danforth's Obstetrics and Gynaecology. 6th edition, 1990. JB Lippincott Co.,  Philadelphia 
  1. Martin NG, Robertson DM, Chenevix Trench G, et al (1991b). Elevation of follicular phase inhibin and LH levels in mothers of DZ twins suggests non ovarian control of human multiple ovulation. Fertil Steril. 1991;56:469-74.
  1. Painter JN, Willemsen G, Nyholt D, et al. A genome wide linkage scan for dizygotic twinning in 525 families of mothers of dizygotic twins. Human Reprod. 2010;25(6):1569.
  1. Beemsterboer SN, Homberg R, Gorter NA, et al. The paradox of declining fertility but increasing twinning rates with advancing maternal age. Hum Reprod. 2006:21:1531.
  1. Ananth CV, Chauhan SP. Epidemiology of twinning in developed countries: Semin Perinatol. 2012: 36:156.
  1. Abel EL, Kruger ML. Maternal and paternal age and twinning in the United States, 2004-2008. J Perinat. 2012:40:237.
  1. Benirschke K. The biology of twinning in man. By MG Bulmer. Clarendon Press,  Oxford.  205 pp 1970. Teratology. 1971;4(2):213. doi:10.1002/tera.1420040214.
  1. Nylander PPS. The factors that influence twinning rates. Acta Genet Med Gemellol. 1981;30:189-202.
  1. Kapidaki M, Roupa Z, Sparos L, et al. Coffee intake and other factors in relation to multiple deliveries: a study in Greece. Epidemiology. 1995;6:294-8.
  1. Harlap S. Multiple births in former oral contraceptive users. Br J Obstet Gynaecol. 1979; 86:557-62.
  1. Nylander PP. Biosocial aspects of multiple births. J Biosoc Sci. 1971:3:29.
  1. Haggarty P, McCallum H, McBain H, et al. Effects of B vitamins and genetics on success of in-vitro fertilization—prospective cohort study. Lancet. 2006:367:1513.
  1. Ericson A, Kallen B, Alberg A. Use of multivitamin and folic acid in early pregnancy and multiple births in Sweden. Twin Res. 2001;4(2):63.
  1. Haggarty P, McCallum H, McBain H, et al. Effect of B vitamins and genetics on success of in vitro fertilization: prospective cohort study. Lancer. 2006;367(9521):1513.
  1. Hasbargen U, Lohse P, Thaler CJ. The number of dichorionic twin pregnancies is reduced by the common MTHFR 677C → T mutation. Hum Reprod. 2000;15(12):2659.
  1. Parazzini F, Chatenoud L, Benzi G, et al. Coffee and alcohol intake, smoking and risk of multiple pregnancy. Hum Reprod. 1996;11:2306-9.
  1. Rao PSS, lnbaraj SG, Muthurathnam S. Twinning rates in Tamil Nadu. J Epidemiol Community Health. 1983;37:117-20.
  1. Lichtenstein P, Otterblad Olausson P, Bengt Kallen AJ. Twin births to mothers who are twins: a registry based study. Br Med J. 1996;312:879-81.
  1. Parisi P, Gatti M, Prinzi G, et al. Familial incidence of twinning. Nature. 1983;304:626-8.
  1. White C, Wyshak G. Inheritance in human dizygotic twinning: N Engl J Med. 1964:271:1003.
  1. Olusanya BO, Solanke OA. Perinatal correlates of delayed childbearing in a developing country. Arch Gynecol Obstet. 2012;285(4):951.
  1. Hemon D, Berger C, Lazar P. Twinning following oral contraceptive discontinuation. Int J Epidemiol. 1981;10:319-28.
  1. Rothman KJ. Fetal loss, twinning and birthweight after oral contraceptive use. N Engl J Med. 1977: 297:468.
  1. Legro RS, Kunselman AR, Brzyski RG, et al. The pregnancy in polycystic ovarian syndrome ii trial: rationale and design of a double blind randomised trial of clomiphene citrate and letrozole for the treatment of infertility in women with polycystic ovarian syndrome. Contemp Clin Trials. 2012: 33:470.
  1. MacGillivray I. Twin pregnancy. In: Phillip EE, Barnes J, Newton M (eds). Obstetrics and Gynaecology. William Heinemann Medical Books,  London;  1986. pp. 248-53.