The term multifetal gestation includes twins, triplets, and higher-order multiples. Multiple births are increasing in the United States and account for a large proportion of neonatal morbidity and mortality. In addition, these pregnancies often present a challenge in management for the obstetrician
Twins can be classified as monozygotic, originating from the fertilization and subsequent division of one egg, or dizygotic, originating from the fertilization and development of two eggs. Approximately one third of twins are thought to be monozygotic in the United States. 
Twins can be further classified by their chorionicity. Dizygotic twins are almost always dichorionic, diamniotic. The chronicity of monozygotic twins depends on the timing of division of the fertilized egg. Dichorionic, diamniotic twins result if the fertilized egg splits 0-3 days after fertilization. This is thought to occur in approximately 20-30% of monozygotic twins. Monochorionic, diamniotic twins occur at days 4-8 after fertilization and account for approximately 70% of monozygotic twins. Monochorionic, monoamniotic twins are rare (1-5% of monozygotic twins) and result secondary to division 8-12 days postfertilization. Conjoined twins occur with division 13 days or later; this is extremely rare.
The etiology of monozygotic twinning is unknown. Dizygotic twins are thought to result from the ovulation of multiple follicles caused by elevations in serum gonadotropin levels. Hence, advanced maternal age is associated with an increased prevalence of twin birth.
The availability of assisted reproductive technology has contributed to the increase in multiple gestations seen over the past 20 years. During ovulation induction treatment, the ovaries are stimulated to produce several follicles, thus increasing the risk of multiple eggs being released and subsequently fertilized. The risk of multiple gestations during in-vitro fertilization is directly related to maternal age and number of embryos transferred. With two embryos transferred, the risk of a multiple gestation was found to be 22.7% and 19.7% for women aged 20-29 years and 30-34 years, respectively. This risk increased to 45.7% in women aged 20-29 years and 39.8% for women aged 30-34 years if 3 embryos were transferred. 
Dizygotic twinning can occur more frequently in some families. This is thought to be secondary to genetic factors leading to ovulation of several eggs during the menstrual cycle. In contrast, monozygotic twinning has not been shown to have a familial inheritance.
The incidence of multiple gestations varies by country due to regional variations in dizygotic twin rates; monozygotic twinning rates are fairly constant across nations. In Nigeria, the rate of twinning has been reported as high as 49 per 1000 births.  In contrast, in Japan, the rate of twinning is 1.3 per 1000 births.  The incidence of spontaneous twins is thought to be approximately 1 in 80 pregnancies.  For spontaneous triplets, the incidence is estimated at 1 in 8,000.  In the United States, the twin birth rate was 33.3 per 1,000 births in 2009.  This rate had risen 70% from 1980-2004 and is thought to be secondary to older maternal age at childbirth and the use of fertility treatment. The rate of triplet and higher order multiple births was 1.5 per 1,000 total births in 2009. This number had initially increased during the 1980s and 1990s but has since declined.
Twin birth rates in 2005-2006 for non-Hispanic whites were 36 per 1,000, for non-Hispanic blacks, 36.8 per 1,000, and for Hispanics, 21.8 per 1,000. Since 1990, rates have risen 57% for non-Hispanic whites, 38% for non-Hispanic blacks, and 21% for Hispanic women. 
As maternal age increases, the risk of dizygotic twinning also increases. This is thought to be due to increased levels of follicle-stimulating hormone with advancing maternal age.  From 1980-2006, twin birth rates rose 27% for mothers younger than 20 years compared with 80% for women in their thirties. In 2006, 20% of births to women aged 45-54 were twins, compared with approximately 2% of births to women aged 20-24 years.  This increase can also be attributed in part to the use of assisted reproductive technology.
Although the frequency of multiple gestations is lower than singleton gestations, multiple gestations account for a disproportionate share of neonatal morbidity and mortality. Much of this can be attributed to a higher rate of preterm delivery for multiple gestations. The mean gestational age at delivery is 35 weeks for twins, 32 weeks for triplets and 29 weeks for quadruplets.  As a result, 25% of twins and 75% of triplets require admission to the neonatal intensive care unit (NICU).  Neurologic outcomes also appear to be worse in multiple births. When matched for gestational age at delivery, infants born from multifetal pregnancies have an approximately 3-fold increase in cerebral palsy  (see the Gestational Age from Estimated Date of Delivery calculator). There is an approximate fivefold increased risk of stillbirth and sevenfold increased risk of neonatal death. 
Monochorionic gestations are at risk for twin twin transfusion syndrome (TTTS) which can occur about 15% of monochorionic pregnancies.  TTTS is thought to be caused by vascular anastomoses within the placenta causing one twin to become underperfused (the “donor” twin) and the other twin to show signs of overperfusion (the “recipient” twin). Pregnancies complicated by TTTS are at significantly increased risk of neonatal morbidity and mortality.
Maternal morbidity is also increased in a multifetal gestation. Women with multiples are more likely to be hospitalized with complications including preterm labor, preterm premature rupture of membranes, preeclampsia, placental abruption, pulmonary embolism, and postpartum hemorrhage. As a result, hospital costs are higher in these pregnancies. 
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Asha J Heard, MD, MPH, FACOG Assistant Professor of Obstetrics and Gynecology, Associate Residency Director, Director of Clinical Ultrasound, Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, Louisiana State University Health Sciences Center
Asha J Heard, MD, MPH, FACOG is a member of the following medical societies: American College of Obstetricians and Gynecologists, American Institute of Ultrasound in Medicine, Society for Maternal-Fetal Medicine
Disclosure: Nothing to disclose.
Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference
Disclosure: Received salary from Medscape for employment. for: Medscape.
Ronald M Ramus, MD Professor of Obstetrics and Gynecology, Director, Division of Maternal-Fetal Medicine, Virginia Commonwealth University School of Medicine
Ronald M Ramus, MD is a member of the following medical societies: American College of Obstetricians and Gynecologists, American Institute of Ultrasound in Medicine, Medical Society of Virginia, Society for Maternal-Fetal Medicine
Disclosure: Nothing to disclose.
Jordan G Pritzker, MD, MBA, FACOG Adjunct Professor of Obstetrics/Gynecology, Hofstra North Shore-LIJ School of Medicine at Hofstra University; Attending Physician, Department of Obstetrics and Gynecology, Long Island Jewish Medical Center; Medical Director, Aetna, Inc; Private Practice in Gynecology
Disclosure: Nothing to disclose.
Steven J Ralston, MD Associate Professor of Obstetrics and Gynecology, Harvard Medical School; Consulting Staff in Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, Beth Israel Deaconess Medical Center
Steven J Ralston, MD is a member of the following medical societies: American College of Obstetricians and Gynecologists, American Society of Law, Medicine & Ethics, Association of Professors of Gynecology and Obstetrics, Society for Maternal-Fetal Medicine
Disclosure: Nothing to disclose.
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