Multifetal gestations twin, triplet, and higher order multifetal pregnancies

Hayes, MD, MSCP.INTERIM UPDATE: The content in this Practice Bulletin has been updated as highlighted or removed as necessary to reflecta limited, focused change to align with ACOG Commi

MS NO: ONG-21-658 INTERIM UPDATE Downloaded from http://journals.lww.com/greenjournal by BhDMf5ePHKav1zEoum1tQfN4a+kJLhEZgbsIHo4XMi0h ACOG PRACTICE BULLETIN CywCX1AWnYQp/IlQrHD3i3D0OdRyi7TvSFl4Cf3VC1y0abggQZXdtwnfKZBYtws= on 03/05/2024 Clinical Management Guidelines for Obstetrician–Gynecologists NUMBER 231 (Replaces Practice Bulletin Number 169, October 2016) Committee on Practice Bulletins—Obstetrics and the Society for Maternal-Fetal Medicine This Practice Bulletin was developed by the Committee on Practice Bulletins—Obstetrics and the Society for Maternal-Fetal Medicine with the assistance of Edward J Hayes, MD, MSCP INTERIM UPDATE: The content in this Practice Bulletin has been updated as highlighted (or removed as necessary) to reflect a limited, focused change to align with ACOG Committee Opinion 828, Indications for Outpatient Antenatal Fetal Surveil- lance, and to provide additional information on screening for fetal chromosomal abnormalities in a multifetal gestation Multifetal Gestations: Twin, Triplet, and Higher-Order Multifetal Pregnancies The incidence of multifetal gestations in the United States has increased dramatically over the past several decades For example, the rate of twin births increased 76% between 1980 and 2009, from 18.9 to 33.3 per 1,000 births (1) However, after more than three decades of increases, the twin birth rate declined 4% during 2014-2018 to 32.6 twins per 1,000 total births in 2018 (2) The rate of triplet and higher-order multifetal gestations increased more than 400% during the 1980s and 1990s, peaking at 193.5 per 100,000 births in 1998, followed by a modest decrease to 153.4 per 100,000 births by 2009 (3) The triplet and higher-order multiple birth rate was 93.0 per 100,000 births for 2018, an 8% decline from 2017 (101.6) and a 52% decline from the 1998 peak (193.5) (4) The long-term changes in the incidence of multifetal gestations has been attributed to two main factors: 1) a shift toward an older maternal age at conception, when multifetal gestations are more likely to occur naturally, and 2) an increased use of assisted reproductive technology (ART), which is more likely to result in a multifetal gestation (5) A number of perinatal complications are increased with multiple gestations, including fetal anomalies, preeclamp- sia, and gestational diabetes One of the most consequential complications encountered with multifetal gestations is preterm birth and the resultant infant morbidity and mortality Although multiple interventions have been evaluated in the hope of prolonging these gestations and improving outcomes, none has had a substantial effect The purpose of this document is to review the issues and complications associated with twin, triplet, and higher-order multifetal gestations and present an evidence-based approach to management Background multifetal gestations are six times more likely to give birth preterm and 13 times more likely to give birth before 32 Fetal and Infant Morbidity and weeks of gestation than women with singleton gestations (3) Mortality An increase in short-term and long-term neonatal Multifetal gestations are associated with increased risk of and infant morbidity also is associated with multifetal fetal and infant morbidity and mortality (Table 1) There is gestations Twins born preterm (less than 32 weeks of an approximate fivefold increased risk of stillbirth and a gestation) are at twice the risk of a high-grade intraven- sevenfold increased risk of neonatal death, which primarily tricular hemorrhage and periventricular leukomalacia is due to complications of prematurity (6) Women with when compared with singletons of the same gestational VOL 137, NO 6, JUNE 2021 OBSTETRICS & GYNECOLOGY e145 © 2021 by the American College of Obstetricians and Gynecologists Published by Wolters Kluwer Health, Inc Unauthorized reproduction of this article is prohibited Table Morbidity and Mortality in Multifetal Gestations Characteristic Singleton Twins Triplets Quadruplets Mean birth weight* 3, 285 g 2, 345 g 1,6 80 g 1, 419 g Mean gestational age*† 38 weeks 35 weeks 31 weeks 30.3 weeks Downloaded from http://journals.lww.com/greenjournal by BhDMf5ePHKav1zEoum1tQfN4a+kJLhEZgbsIHo4XMi0h Percentage less than 34 weeks of gestation z 2.1 19.5 63.1 82.6 CywCX1AWnYQp/IlQrHD3i3D0OdRyi7TvSFl4Cf3VC1y0abggQZXdtwnfKZBYtws= on 03/05/2024 Percentage less than 37 weeks of gestation z 8.2 60.3 8.3 7.4 28 — Rate of cerebral palsy (per 1,000 live births)§ 1.6 52.5 23.6 96.3¶ Infant mortality rate (per 1,000 live births) k 5.4 * National Center for Health Statistics, Division of Vital Statistics Natality public-use data 2016-2019, on CDC WONDER Online Database, October 2020 Available at: http://wonder.cdc.gov/natality-expanded-current.html Retrieved December 10, 2020 † Average obstetric estimate gestational age (weeks) z Martin JA, Hamilton BE, Osterman MJ, Driscoll AK Births: final data for 2018 Natl Vital Stat Rep 2019;68(13):1-47 §Petterson B, Nelson KB, Watson L, Stanley F Twins, triplets and cerebral palsy in births in Western Australia in the 1980s BMJ 1993;307:1239–43 k Luke B, Brown M The changing risk of infant mortality by gestation, plurality, and race: 1989-1991 versus 1999-2001 Pediatrics, 2006;118:2488–97 ¶ Quadruplet and quintuplet data combined age (7) This, in part, explains the increased prevalence of for increased screening and potential for interventions, cerebral palsy in multifetal gestations (8) determination of chorionicity in the first trimester or early second trimester in pregnancy is important for Multifetal gestations are associated with signifi- counseling and management of women with multifetal cantly higher costs, in the antenatal and neonatal periods, gestations in large part because of the costs associated with prematurity (9) The average first-year medical costs, Maternal Morbidity and Mortality including inpatient and outpatient care, are up to 10 times greater for preterm infants than for term infants (10) Medical complications are more common in women with multifetal gestations than with singleton gestations Chorionicity These include hyperemesis, gestational diabetes mellitus, hypertensive disorders of pregnancy, anemia, hemor- Ultrasonography can be used to determine fetal number, rhage, cesarean delivery, and postpartum depression estimated gestational age, chorionicity, and amnionicity (15–21) Although these complications are more com- The determination of chorionicity in multifetal gestations mon in women with multifetal gestations, the manage- is clinically important because of the increased risk of ment of these complications follows the same strategies complications in monochorionic pregnancies Assess- as with a singleton gestation ment of chorionicity is most accurate early in gestation, and its determination is optimal when ultrasonography is Women with multifetal gestations have an increased performed in the first trimester or early second trimester incidence of hypertensive conditions associated with pregnancy The occurrence of hypertensive complica- Compared with dichorionic twins, monochorionic tions is proportional to the total fetal number, with twins have a higher frequency of fetal and neonatal singletons at 6.5%, twins at 12.7%, and triplets at 20.0% mortality, as well as morbidities, such as fetal and (22) One study found that ART pregnancies were at congenital anomalies, prematurity, and fetal growth increased risk (relative risk [RR], 2.1) of developing mild restriction (11, 12) This trend also is seen in higher- or severe preeclampsia, even after controlling for mater- order multifetal gestations; for example, a triplet gesta- nal age and parity (23) tion that is fully monochorionic or has a monochorionic twin pair is at higher risk of complications than a triplet Preeclampsia not only occurs more frequently in gestation that is trichorionic (13, 14) women with twin pregnancies than in women with sin- gleton gestations, it tends to occur earlier in pregnancy Because of the increased rate of complications This results in a higher likelihood of complications, such associated with monochorionicity, as well as the need e146 Practice Bulletin Multifetal Gestations OBSTETRICS & GYNECOLOGY © 2021 by the American College of Obstetricians and Gynecologists Published by Wolters Kluwer Health, Inc Unauthorized reproduction of this article is prohibited Downloaded from http://journals.lww.com/greenjournal by BhDMf5ePHKav1zEoum1tQfN4a+kJLhEZgbsIHo4XMi0h as preterm delivery at less than 35 weeks of gestation have lower frequencies of pregnancy loss, antenatal CywCX1AWnYQp/IlQrHD3i3D0OdRyi7TvSFl4Cf3VC1y0abggQZXdtwnfKZBYtws= on 03/05/2024 (34.5% twins versus 6.3% in singletons) and abruptio pla- complications, preterm birth, low-birth-weight infants, centae (4.7% twins versus 0.7% singletons) (17) Multifetal cesarean delivery, and neonatal deaths, with rates similar gestation is considered a high risk factor for preeclampsia to those observed in women with spontaneously con- Therefore, low dose aspirin (81 mg/day) prophylaxis is ceived twin gestations (29) Multifetal reduction may recommended and should be initiated between 12 and 28 decrease the risk of preeclampsia in women with weeks of gestation (optimally before 16 weeks of gestation) higher-order multifetal gestations One study reported and continued daily until delivery (24) Women with that only 14% of 59 women with twin pregnancies re- higher-order multifetal gestations are more likely to develop maining after multifetal reduction developed preeclamp- preeclampsia but also to present in an atypical manner (25) sia compared with 30% of women with triplet If hemolysis, elevated liver enzymes, and low platelet count pregnancies (30) A meta-analysis of six retrospective (HELLP) syndrome develops before term, transfer to a ter- cohort studies including 7,398 participants (530 under- tiary care center may improve the outcome for the woman going multifetal reduction and 6,868 controls) showed and her fetus (26) that multifetal reduction from twins to a singleton before 15 weeks of gestation was associated with a lower risk of The likelihood of a multifetal gestation increases preterm birth and a higher birth weight when compared with maternal age, even outside of ART use The with expectant management (31) multiple birth ratio increases from 16.3 per 1,000 live births for women younger than 20 years to 71.1 per 1,000 In multifetal pregnancy reduction, the fetus(es) to be live births for women 40 years and older (3) Older reduced are chosen on the basis of technical consider- women also are more likely to have obstetric complica- ations, such as which is most accessible to intervention tions irrespective of fetal number, including gestational and chorionicity Monochorionicity can complicate the hypertension, gestational diabetes mellitus, and abruptio reduction procedure; if one fetus of a monochorionic placentae twin pair is reduced, the negative effects on the development of the other are unknown For this reason, Contribution of Assisted it is usually recommended that both fetuses of a Reproductive Technology monochorionic pair be reduced Over the past several decades, the increased use of ART Selective fetal termination is the application of the has led to a dramatic increase in the incidence of fetal reduction technique to an abnormal fetus that is part multifetal births (27) The specific ART techniques that of a multifetal gestation The risks of the procedure are may have the most significant effect on the increase of higher than those associated with multifetal reduction, multifetal pregnancies are IVF and controlled ovarian largely because of a later gestational age at the time of the hyperstimulation with gonadotropins According to the procedure (i.e., 18–22 weeks of gestation after diagnosis most recent data available from cycles completed in of an anomaly compared with 10–12 weeks of gestation 2017, 25.5% of pregnancies conceived with ART are based on fetal number alone) (32) The unintended loss twins and 0.9% are higher-order multifetal pregnancies rate of the pregnancy is increased when women with (28) Only recently has there been a decrease in the higher-order multifetal gestations undergo selective fetal higher-order multiple birth rate (1) Data from 2017 termination in comparison with women with twin gesta- showed substantial variations in single embryo transfer tions who undergo the procedure (11.1 % versus 2.4%, rates among states and territories, reflecting variations in respectively) (33) Despite the procedure-related loss embryo-transfer practices among fertility clinics, which rate, pregnancy prolongation also has been observed in might in part account for higher multiple birth from ART women who undergo selective fetal termination (34, 35) observed in some states and territories (28) Clinical Considerations Multifetal Reduction and Selective and Recommendations Fetal Termination < How is chorionicity determined? Multifetal reduction reduces the likelihood of spontane- ous preterm delivery and other neonatal and obstetric Fetal risk is largely dependent on chorionicity Therefore, complications by decreasing the number of fetuses A the chorionicity of a multifetal pregnancy should be Cochrane review found that women who underwent established as early in pregnancy as possible, and the pregnancy reduction from triplets to twins, as compared optimal timing for determination of chorionicity by with those who continued with triplets, were observed to VOL 137, NO 6, JUNE 2021 Practice Bulletin Multifetal Gestations e147 © 2021 by the American College of Obstetricians and Gynecologists Published by Wolters Kluwer Health, Inc Unauthorized reproduction of this article is prohibited Downloaded from http://journals.lww.com/greenjournal by BhDMf5ePHKav1zEoum1tQfN4a+kJLhEZgbsIHo4XMi0h ultrasonography is in the first trimester or early second < Are there routine prophylactic interventions CywCX1AWnYQp/IlQrHD3i3D0OdRyi7TvSFl4Cf3VC1y0abggQZXdtwnfKZBYtws= on 03/05/2024 trimester In one series, the reported sensitivity, specific- ity, and positive and negative predictive values for that can prolong pregnancy in women with prediction of chorionicity by ultrasonography at 14 multifetal gestations? weeks of gestation or less was shown to be 89.8%, 99.5%, 97.8%, and 97.5%, respectively (36) Overall, Routine prophylactic interventions including cerclage, chorionicity was determined correctly in 95% of cases hospitalization, bedrest, tocolytics, and pessary have not been proved to decrease neonatal morbidity or mor- When ultrasound assessment clearly shows two pla- tality, and therefore should not be used based solely on centas or differing fetal sex, the pregnancy is dichorionic If the indication of multifetal gestation Recommendations only one placenta is visualized, the best ultrasonographic regarding potential interventions for women with a multi- characteristic to distinguish chorionicity is the twin peak fetal gestation and a short cervix or other risk factors for sign The twin peak sign (also called the lambda or delta preterm birth can be found in ACOG Practice Bulletin sign) is a triangular projection of tissue with the same No 130, Prediction and Prevention of Preterm Birth echogenicity as the placenta that extends beyond the chorionic surface of the placenta and is indicative of a Prophylactic Cerclage dichorionic gestation (37) The management of complica- tions related to monochorionicity (eg, twin–twin transfusion Prophylactic cerclage placement in women with a twin syndrome, single fetal death, and monoamniotic gestation) gestation or a triplet gestation without a history of and timing of delivery are discussed in “Clinical Consider- cervical insufficiency has not been shown to be benefi- ations and Recommendations” later in this document cial (45–47) < Can adjunctive tests be used to predict spon- Routine Hospitalization and Bed Rest taneous preterm birth in women with multi- The use of bed rest with or without hospitalization has fetal gestations? been commonly recommended to women with multifetal gestations However, a Cochrane review demonstrated no Asymptomatic Women benefit from routine hospitalization or bed rest for women with an uncomplicated twin pregnancy (48) Thus, bed Several methods have been used in an attempt to further rest with or without hospitalization in women with multi- quantify the risk of spontaneous preterm birth when fetal pregnancies is not recommended because of the lack screening asymptomatic women with multifetal gesta- of benefit and the risk of thrombosis and deconditioning tions, including transvaginal ultrasonographic cervical associated with prolonged bed rest in pregnancy length, digital examination, fetal fibronectin screening, and home uterine monitoring There are no interventions Prophylactic Tocolytics that have been shown to prevent spontaneous preterm delivery in asymptomatic women with multifetal gesta- There is no role for the prophylactic use of any tocolytic tions identified to be at risk based on these screening agent in women with multifetal gestations, including the methods The routine use of these screening methods in prolonged use of betamimetics for this indication The asymptomatic women with multifetal pregnancies is not use of tocolytics to inhibit preterm labor in multifetal recommended (38) gestations has been associated with a greater risk of maternal complications, such as pulmonary edema (49, Symptomatic Women 50) In addition, prophylactic tocolytics have not been shown to reduce the risk of preterm birth or improve In symptomatic women, the positive predictive value of a neonatal outcomes in women with multifetal gestations fetal fibronectin test result or of a short cervical length (51–53) The administration of oral betamimetics, specif- alone is poor, and they should not be used exclusively to ically, did not reduce the incidence of preterm birth, low- direct management in the setting of acute symptoms (39) birth-weight newborns, or neonatal mortality in women Although several observational studies have suggested with multifetal gestations when compared with placebo that knowledge of fetal fibronectin status or cervical (54) Oral betamimetics have been associated with length in women with singleton gestations who present increased maternal and fetal cardiac stress and gestational with symptoms of preterm labor may help health care diabetes mellitus (55, 56) Recently, prolonged use of providers reduce the use of unnecessary resources, these betamimetics also has been associated with increased findings have not been consistently confirmed by ran- adverse maternal cardiovascular events, including death domized trials for use in singleton or in multiple gesta- (57) Based on the available evidence, prophylactic to- tions (40–44) colysis in women with multifetal gestations is not recommended e148 Practice Bulletin Multifetal Gestations OBSTETRICS & GYNECOLOGY © 2021 by the American College of Obstetricians and Gynecologists Published by Wolters Kluwer Health, Inc Unauthorized reproduction of this article is prohibited Downloaded from http://journals.lww.com/greenjournal by BhDMf5ePHKav1zEoum1tQfN4a+kJLhEZgbsIHo4XMi0h Prophylactic Pessary antiinflammatory drugs should be first-line treatment CywCX1AWnYQp/IlQrHD3i3D0OdRyi7TvSFl4Cf3VC1y0abggQZXdtwnfKZBYtws= on 03/05/2024 Although there is a dearth of large-scale randomized There is at present no high-quality evidence that pro- trials of multifetal gestations alone, data supporting these phylactic cervical pessary use in unselected multifetal conclusions come from trials that have included singleton pregnancies reduces the frequency of spontaneous pre- and multifetal gestations (67) Thus, in multifetal gesta- term birth or perinatal morbidity In a multicenter tions a brief course of tocolysis may be considered for up randomized trial, 813 women with twins between 16 to 48 hours in the setting of acute preterm labor, in order weeks and 20 weeks of gestation were randomized to an to allow corticosteroids to be administered Maternal Arabin cervical pessary or no pessary (58) In the pessary risks associated with tocolytic use include pulmonary group, at least one child of 53 women (13%) had poor edema perinatal outcome (defined as either stillbirth, periven- tricular leukomalacia, severe respiratory distress syn- Corticosteroids drome, bronchopulmonary dysplasia, intraventricular hemorrhage, necrotizing enterocolitis, proven sepsis, or Administration of antenatal corticosteroids to women neonatal death) compared with at least one child of 55 with singleton gestations at risk of delivery between 24 women (14%) in the control group (RR, 0.98; 95% CI, weeks and 34 weeks of gestation has been shown to 0.69–1.39) A meta-analysis that included this study as decrease the incidence of neonatal death, respiratory well as other studies of asymptomatic women with mul- distress syndrome, intraventricular hemorrhage, and tiple gestations at various cervical length cutoffs con- necrotizing enterocolitis (68) A Cochrane review con- cluded that prophylactic cervical pessary is not an cluded that although antenatal corticosteroids are benefi- effective intervention for reducing preterm birth and cial in singleton gestations, further research is required to adverse perinatal outcomes (59) Thus, based on avail- demonstrate an improvement in outcomes for multifetal able evidence, the use of prophylactic cervical pessary is gestations (68) However, based on the improved out- not recommended in multifetal pregnancies (58) comes reported in singleton gestations, the National Insti- tutes of Health recommends that, unless a < Does progesterone treatment decrease the risk contraindication exists, a course of antenatal corticoste- roids should be administered to all patients who are at of preterm birth in women with multifetal risk of delivery within days and who are between 24 gestations? weeks and 34 weeks of gestation, irrespective of the fetal number (69) For information on administration of ante- Progesterone treatment does not reduce the incidence of natal steroids at the threshold of viability, see Obstetrics spontaneous preterm birth in unselected women with Care Consensus 6, Periviable Birth Administration of twin or triplet gestations and, therefore, is not recom- corticosteroids to pregnant women during the periviable mended (60–66) The administration of 17a-hydroxypro- period who are at risk of preterm delivery within days gesterone caproate to women with triplet gestations did is linked to a family’s decision regarding resuscitation not reduce neonatal morbidity or prolong gestation (64) and should be considered in that context (70) In addition, another randomized trial found that its use in women with triplet gestations was associated with a sig- Regularly scheduled repeat courses or serial courses nificantly increased rate of midtrimester fetal loss (63) (more than two) are not recommended A single repeat Recommendations regarding vaginal progesterone for course of antenatal corticosteroids should be considered women with a multifetal gestation and a short cervix in women with a gestation of less than 34 weeks, who can be found in ACOG Practice Bulletin No 130, Pre- have an imminent risk of preterm delivery within the next diction and Prevention of Preterm Birth days, and whose prior course of antenatal corticoste- roids was administered more than 14 days previously < How is preterm labor managed in women with Rescue-course corticosteroids could be provided as early as days from the prior dose, if indicated by the clinical multifetal gestations? scenario Tocolytics Magnesium Sulfate for Fetal Neuroprotection Tocolytic therapy may provide short-term prolongation of pregnancy, which enables the administration of Several large studies have been performed to examine antenatal corticosteroids as well as transport to a tertiary whether intravenous magnesium sulfate administered care facility, if indicated The overall evidence suggests before preterm delivery would decrease the incidence that when tocolysis is used for short-term pregnancy of death and cerebral palsy (71–73) Although none of prolongation, calcium channel blockers or nonsteroidal these studies showed improvement in the primary VOL 137, NO 6, JUNE 2021 Practice Bulletin Multifetal Gestations e149 © 2021 by the American College of Obstetricians and Gynecologists Published by Wolters Kluwer Health, Inc Unauthorized reproduction of this article is prohibited Downloaded from http://journals.lww.com/greenjournal by BhDMf5ePHKav1zEoum1tQfN4a+kJLhEZgbsIHo4XMi0h combined outcome, several meta-analyses of these ran- individual fetus The distribution of NT measurements CywCX1AWnYQp/IlQrHD3i3D0OdRyi7TvSFl4Cf3VC1y0abggQZXdtwnfKZBYtws= on 03/05/2024 domized trials concluded that prenatal administration of does not differ significantly between singletons and magnesium sulfate reduced the occurrence of cerebral twins, and standard cutoffs used in singleton gestations palsy (74–76) The accumulated available evidence sug- can also be used in twin gestations (84) Experience is gests that magnesium sulfate reduces the severity and limited with triplet gestations, but studies suggest that risk of cerebral palsy in surviving infants if administered nuchal translucency measurement is feasible, and screen- when birth is anticipated before 32 weeks of gestation, ing using only maternal age and nuchal translucency has regardless of fetal number Hospitals that elect to use been validated for the detection of Down syndrome and magnesium sulfate for fetal neuroprotection should trisomy 18 (85) Of note, in one study of monochorionic develop uniform and specific guidelines for their depart- twin pregnancies, a nuchal translucency value above the ments regarding inclusion criteria, treatment regimens, 95th percentile had a 38% positive predictive value for concurrent tocolysis, and monitoring in accordance with later development of severe twin–twin transfusion syn- one of the larger trials (71–73, 77) drome, further complicating first-trimester genetic screening in monochorionic gestations (86) < How is prenatal screening for fetal chromo- Cell-free DNA screening can be performed in twin somal abnormalities in women with multifetal pregnancies (78) Overall, performance of screening for gestations different than for singleton trisomy 21 by cell-free DNA in twin pregnancies is pregnancies? encouraging, but the total number of reported affected cases is smaller than in singleton pregnancies Given All women with multifetal gestations, regardless of age, the small number of affected cases, it is difficult to deter- are candidates for routine screening for fetal chromo- mine an accurate detection rate for trisomy 18 and 13 somal abnormalities No method of fetal chromosomal Twin fetuses in a single pregnancy each contribute dif- abnormality screening that includes a serum sample is ferent amounts of cell-free DNA into the maternal circu- as accurate in twin gestations as it is in singleton preg- lation It is possible that a fetus with a chromosomal nancies; this information should be incorporated into pre- abnormality would contribute less fetal DNA, therefore test counseling for patients with multiple gestations masking the aneuploid test result Recent studies have Further, there are no data available for serum screening suggested that sensitivity for trisomy 21 with cell-free for higher-order multiple gestations such as triplets and DNA in twin pregnancies may be similar to singletons quadruplets Analysis of the risks and benefits of screen- when a test result is returned; however, there is a higher ing or diagnostic testing in patients carrying multiple rate of test failure (87, 88) fetuses is complex, given the lower effectiveness of screening and how the prenatal identification of a single In multifetal gestations, if a fetal demise, vanishing aneuploid fetus might affect the pregnancy management twin, or anomaly is identified in one fetus, there is a (78) significant risk of an inaccurate test result if serum- based aneuploidy screening or cell-free DNA is used Presumably, monozygotic twins have the same This information should be reviewed with the patient genetic information in both fetuses and will reflect a and diagnostic testing should be offered single test result, although monozygotic twins discordant for karyotype have been described (79, 80) In a dizy- < What issues arise in prenatal diagnosis of fetal gotic twin pregnancy, a screen positive test infers that at least one of two fetuses is at increased risk of a chromo- chromosomal abnormalities in women with somal abnormality multifetal gestations? First-trimester, quad, and sequential or integrated Amniocentesis and CVS can be performed in women screening are options available to screen twin gestations, with a multifetal gestation who desire definitive testing although few data on test performance are available from for genetic anomalies The procedure-associated preg- prospective studies (81) Second-trimester serum screen- nancy loss rates for both tests are similar (reported at 1– ing of twin gestations can identify approximately 60% of 1.8%) and are slightly increased compared with loss rates fetuses affected with trisomy 21 at a 5% screen positive reported in women with singleton gestations (89–91) rate (82) A meta-analysis suggests that first trimester Chorionic villus sampling has the advantage that it can combined screening in twin gestations has a detection be performed earlier in gestation rate of 89% with a false-positive rate of 5.4%, which is similar to singleton gestations (83) However, there are technical difficulties that may be encountered when performing amniocentesis and CVS in Although serum screening evaluates the pregnancy women with multifetal gestations There is a risk of as a whole, the NT measurement directly evaluates the sampling error of approximately 1% in women with e150 Practice Bulletin Multifetal Gestations OBSTETRICS & GYNECOLOGY © 2021 by the American College of Obstetricians and Gynecologists Published by Wolters Kluwer Health, Inc Unauthorized reproduction of this article is prohibited Downloaded from http://journals.lww.com/greenjournal by BhDMf5ePHKav1zEoum1tQfN4a+kJLhEZgbsIHo4XMi0h multifetal gestations who undergo CVS (92) Genetic increases with the number of gestational sacs: 36% for CywCX1AWnYQp/IlQrHD3i3D0OdRyi7TvSFl4Cf3VC1y0abggQZXdtwnfKZBYtws= on 03/05/2024 amniocentesis, which typically is performed at 15 weeks twins, 53% for triplets, and 65% for quadruplets (102) of gestation or beyond, has a lower chance of this com- plication A complex counseling issue arises in the pres- In the second trimester and third trimester, up to 5% ence of a monochorionic twin gestation, in which case of twins and 17% of triplets undergo death of one or the likelihood of discordance in the karyotype is low, and more fetuses (103) Chorionicity influences the rate of patients may opt for having a karyotype analysis per- loss, predicts outcome in the survivor, and guides man- formed on a single fetus In this situation, it is important agement Monochorionic–diamniotic twins have an to discuss the accuracy of determining chorionicity by increased risk of stillbirth compared with dichorionic– ultrasonography diamniotic twins (104–106) Subsequent to the demise of one twin after 14 weeks of gestation, the risk of death When a chromosomal abnormality is diagnosed, in the co-twin is 15% in monochorionic gestations and counseling should include a discussion of options for 3% for dichorionic gestations (106) The risk of neuro- pregnancy management if only one fetus is found to be logic abnormality in the surviving twin is greater in affected These options include terminating the entire monochorionic gestations (18%) versus dichorionic ges- pregnancy; selective reduction of the affected fetus; and tations (1%) (107, 108) Although death of a co-twin in a continuing the pregnancy without any intervention monochorionic pregnancy in the late second trimester or early third trimester is associated with significant mor- < Are multifetal gestations with discordant fetal bidity and mortality in the other fetus, immediate deliv- ery of the co-twin has not been demonstrated to be of growth at risk of adverse outcomes? benefit (109) Therefore, in monochorionic twin gesta- tions in which death of one fetus is identified before 34 Discordant fetal growth in women with multifetal weeks of gestation, management should be based on the gestations is most commonly defined as a 20% difference condition of the mother or surviving fetus In the absence in estimated fetal weight between the larger and smaller of another indication, delivery before 34 weeks of gesta- fetus (93, 94) This growth discordance ratio is calculated tion is not recommended (110) Care should be individ- by determining the difference in the estimated fetal ualized for each patient, and consultation with a weight between the two fetuses, divided by the weight physician with training in maternal–fetal medicine is of the larger fetus recommended In the event that a twin pregnancy is diagnosed late enough that chorionicity cannot be es- Whether growth-discordant multifetal gestations— tablished, management should be guided by individual- without a structural anomaly, aneuploidy, discordant ized assessment of fetal growth, growth discordance, and infection, oligohydramnios, or fetal growth restriction— other indicators of fetal well-being are at increased risk of adverse outcomes is debatable Several studies that examined this population have < What is the role of antepartum fetal surveil- shown that multifetal gestations with discordant but appropriate-for-gestational-age growth are not at lance in dichorionic pregnancies? increased risk of fetal or neonatal morbidity and mortality (95–98) However, multifetal gestations with discordant Once chorionicity has been established in the first or growth and pregnancies with at least one growth- early second trimester, ultrasound examination between restricted fetus have been observed to be associated with 18 weeks and 22 weeks of gestation allows for a survey a 7.7-fold increased risk of major neonatal morbidity of fetal anatomy, amniotic fluid, placentation, and (99) Moreover, growth-restricted twins have higher peri- growth Fetal growth in uncomplicated twin pregnancies natal mortality and morbidity rates when compared with occurs at a similar rate as singletons until approximately age-matched singletons (100) Thus, although there is no 28–32 weeks of gestation, when the growth rate of twins clear evidence of increased neonatal morbidity or mor- slows (111) For women with dichorionic twin gesta- tality with twin discordance alone, fetal growth restric- tions, there are no evidence-based recommendations on tion (or other abnormalities, such as fetal anomalies or the frequency of fetal growth scans after 20 weeks of oligohydramnios) in the setting of discordance may be a gestation; however, it seems reasonable that serial ultra- risk factor for adverse perinatal outcomes sonographic surveillance be performed every weeks in the absence of evidence of fetal growth restriction or < How is the death of one fetus managed? other pregnancy complications (112) In the first trimester, a substantial number of women with A recent systematic review by the Global Obstetrics multifetal gestations undergo spontaneous reduction of Network (GONet) Collaboration provided weekly still- one or more fetuses, commonly referred to as the “van- birth data for twins managed expectantly after 34 weeks ishing twin” (101) The probability of this reduction VOL 137, NO 6, JUNE 2021 Practice Bulletin Multifetal Gestations e151 © 2021 by the American College of Obstetricians and Gynecologists Published by Wolters Kluwer Health, Inc Unauthorized reproduction of this article is prohibited Downloaded from http://journals.lww.com/greenjournal by BhDMf5ePHKav1zEoum1tQfN4a+kJLhEZgbsIHo4XMi0h of gestation (113) The risk of stillbirth increased in all The criterion for diagnosis of twin–twin transfusion CywCX1AWnYQp/IlQrHD3i3D0OdRyi7TvSFl4Cf3VC1y0abggQZXdtwnfKZBYtws= on 03/05/2024 twins with advancing gestational age, and it was signif- syndrome with ultrasonography is a monochorionic– icantly greater in monochorionic than dichorionic twins diamniotic twin gestation with oligohydramnios (maxi- In dichorionic twins, stillbirth rates were as follows: mum vertical pocket less than cm) in one sac and polyhydramnios (maximum vertical pocket greater than c 0.8 per 1,000 at 35 0/7 to 35 6/7 weeks cm) in the other sac It is essential to rule out other eti- ologies, such as selective fetal growth restriction or fetal c 1.5 per 1,000 at 36 0/7 to 36 6/7 weeks discordance for structural, genetic, or infectious disor- ders There is no evidence that routine assessment with c 3.4 per 1,000 at 37 0/7 to 37 6/7 weeks umbilical artery Doppler is beneficial in the absence of growth or fluid discordance Once the diagnosis of twin– c 10.6 per 1,000 at 38 0/7 to 38 6/7 weeks twin transfusion syndrome has been made, the prognosis depends on gestational age and severity of the syndrome In monochorionic diamniotic twins the stillbirth Staging is commonly performed via the Quintero staging rates were as follows: system, and interventions including laser coagulation, amnioreduction, or selective reduction by radiofrequency c 0.9 per 1,000 at 34 0/7 to 34 6/7 weeks ablation may be considered in collaboration with a cli- c 2.8 per 1,000 at 35 0/7 to 35 6/7 weeks nician with expertise in twin–twin transfusion syndrome c 4.5 per 1,000 at 36 0/7 to 36 6/7 weeks diagnosis and management (125, 126) c 9.6 per 1,000 at 37 0/7 to 37 6/7 weeks Because of higher stillbirth risks in monochorionic- The optimal gestational age for initiation of surveil- diamniotic twins and the potential for severe clinical lance in pregnant individuals with uncomplicated dichor- consequences for the surviving twin, initiation of antena- ionic twins is not known However, for patients with tal fetal surveillance is typically recommended at 32 0/7 uncomplicated dichorionic twin pregnancies, weekly ante- weeks of gestation (114–116) natal fetal surveillance may be considered at 36 0/7 weeks of gestation (114–116) For patients with a dichorionic Monoamniotic Twins twin pregnancy complicated by maternal or fetal disorders such as fetal growth restriction, antenatal fetal surveillance The “natural” incidence of monoamniotic twins is in should be individualized and may be considered upon 10,000 However, the incidence may be increased for diagnosis, or at a gestational age after which delivery women who undergo in vitro fertilization using zona would be considered for abnormal testing (117) manipulation (127) Perinatal mortality is increased in monoamniotic twins with estimates ranging from 12% < How are the complications caused by mono- to 23% (128, 129) For patients with monoamniotic twin pregnancies, antenatal fetal surveillance should be indi- chorionic placentation managed? vidualized in consultation with maternal–fetal medicine Although many clinicians offer early inpatient manage- Women with monochorionic pregnancies are followed ment (beginning at 24–28 weeks of gestation) with daily more closely than those with dichorionic pregnancies fetal surveillance, regular assessment of fetal growth, and because of the higher risk of developing complications in delivery between 32 weeks and 34 weeks of gestation, pregnancy, including twin–twin transfusion syndrome, twin the optimal management of these patients remains uncer- anemia-polycythemia syndrome, fetal anomalies, and still- tain (130–132) birth (106, 118) The Society for Maternal-Fetal Medicine has developed checklists to assist in management of mono- Rare Complications chorionic gestations (119) Because of the increased risk of congenital cardiac disease, fetal echocardiogram is recom- Acardiac twin pregnancy is a complication unique to a mended at 18–22 weeks in monochorionic pregnancies monochorionic gestation that is characterized by a fetus (119, 120) Twin to twin transfusion syndrome occurs in lacking a normally developed heart and head It occurs in approximately 10–15% of monochorionic–diamniotic approximately 1% of monochorionic twins (133) The pregnancies and results from the presence of arteriove- acardiac fetus is able to survive in utero because of pla- nous anastomoses in a monochorionic placenta In the cental anastomoses shunting blood flow from the “pump affected pregnancy, there is an imbalance in the fetal– twin.” The pump twin can develop a high cardiac output placental circulations, whereby one twin transfuses the state and subsequent cardiac failure, which results in other It usually presents in the second trimester Serial intrauterine or neonatal demise in approximately 50% ultrasonographic evaluation is recommended approximately of cases (134) These rare conditions can be managed every weeks beginning at approximately 16 weeks of in collaboration with a clinician with expertise in gestation in monochorionic gestations to monitor for twin- to-twin transfusion syndrome (121–124) e152 Practice Bulletin Multifetal Gestations OBSTETRICS & GYNECOLOGY © 2021 by the American College of Obstetricians and Gynecologists Published by Wolters Kluwer Health, Inc Unauthorized reproduction of this article is prohibited Downloaded from http://journals.lww.com/greenjournal by BhDMf5ePHKav1zEoum1tQfN4a+kJLhEZgbsIHo4XMi0h complicated twin gestation management, such as a cesarean delivery did not significantly decrease the risk CywCX1AWnYQp/IlQrHD3i3D0OdRyi7TvSFl4Cf3VC1y0abggQZXdtwnfKZBYtws= on 03/05/2024 maternal–fetal medicine specialist of fetal or neonatal death or serious neonatal morbidity, as compared with planned vaginal delivery (2.2% and Conjoined twinning is a rare anomaly, with an 1.9%, respectively; OR [with planned cesarean delivery], incidence of in 50,000 to in 100,000 births (135) 1.16; 95% CI, 0.77–1.74; P5.49) (142) Therefore, in Once the diagnosis is reached, it is imperative that a diamniotic twin pregnancies at 32 0/7 weeks of gestation complete workup be undertaken to determine shared or later with a presenting fetus that is vertex, regardless anatomy, which guides management and determines of the presentation of the second twin, vaginal delivery is prognosis (136) Even with many reports in the lay press a reasonable option and should be considered, provided of successful separations, of those conjoined twinning that an obstetrician with experience in managing a non- cases diagnosed in utero, there is only an 18% survival vertex presenting second twin is available (143) rate of one twin from ultrasonographic diagnosis to suc- cessful separation (137) The optimal route of delivery for women with higher- order multifetal gestations remains unknown Small obser- < Are there special considerations for timing vational studies have suggested that similar perinatal out- comes can be obtained for women (with uncomplicated and route of delivery in women with multifetal triplet pregnancies and a presenting fetus that is vertex) who gestations? undergo planned trial of labor compared with those who undergo planned cesarean delivery Thus, in the presence of Although, on average, women with twin pregnancies obstetricians with experience in vaginal delivery of multiple give birth at approximately 36 weeks of gestation, gestations, a planned vaginal delivery of triplets can be preterm fetuses remain at significant risk of complica- considered (144–146) tions of prematurity (138) The risk of perinatal mor- tality begins to increase again in twin pregnancies at Women with one previous low transverse cesarean approximately 38 weeks of gestation (139) Based on delivery, who are otherwise appropriate candidates for these data, and in the absence of large randomized twin vaginal delivery, may be considered candidates trials that demonstrate a clearly optimal time for deliv- for trial of labor after cesarean delivery (147–151) ery, the following recommendations for timing of Delivery may be complicated by the need for internal delivery seem reasonable for women with uncompli- fetal manipulation or emergent cesarean delivery cated twin gestations (109, 140): Women with multifetal gestations also are at increased risk of uterine atony, postpartum hemorrhage, and c Women with uncomplicated dichorionic–diamniotic emergent hysterectomy (152) The administration of twin gestations can undergo delivery at 38 0/7–38 6/7 neuraxial analgesia in women with multifetal gesta- weeks of gestation tions facilitates operative vaginal delivery, external or internal cephalic version, and total breech extraction c Women with uncomplicated monochorionic–diamniotic (143) twin gestations can undergo delivery between 34 0/7 weeks and 37 6/7 weeks of gestation Summary of Recommendations c Women with uncomplicated monochorionic–mono- and Conclusions amniotic twin gestations can undergo delivery at 32 0/7–34 0/7 weeks of gestation The following recommendations and conclusions are based on good and consistent scientific evidence (Level A): The optimal route of delivery in women with twin gestations depends on the type of twins, fetal presenta- < There is no role for the prophylactic use of any to- tions, gestational age, and experience of the clinician performing the delivery A twin gestation in and of itself colytic agent in women with multifetal gestations, is not an indication for cesarean delivery Women with including the prolonged use of betamimetics for this monoamniotic twin gestations should be delivered by indication cesarean birth to avoid an umbilical cord complication of the non-presenting twin at the time of the initial twin’s < Progesterone treatment does not reduce the incidence delivery (130) of spontaneous preterm birth in unselected women Women with diamniotic twin gestations whose with twin or triplet gestations and, therefore, is not presenting fetus is in a vertex position are candidates recommended for a vaginal birth (141) A randomized trial of women with uncomplicated diamniotic twin pregnancies between 32 0/7 weeks and 38 6/7 weeks of gestation with a vertex presenting fetus demonstrated that planned VOL 137, NO 6, JUNE 2021 Practice Bulletin Multifetal Gestations e153 © 2021 by the American College of Obstetricians and Gynecologists Published by Wolters Kluwer Health, Inc Unauthorized reproduction of this article is prohibited Downloaded from http://journals.lww.com/greenjournal by BhDMf5ePHKav1zEoum1tQfN4a+kJLhEZgbsIHo4XMi0h < Serial ultrasonographic evaluation is recommended < For patients with a dichorionic twin pregnancy com- CywCX1AWnYQp/IlQrHD3i3D0OdRyi7TvSFl4Cf3VC1y0abggQZXdtwnfKZBYtws= on 03/05/2024 approximately every weeks beginning at approxi- plicated by maternal or fetal disorders such as fetal mately 16 weeks of gestation in monochorionic ges- growth restriction, antenatal fetal surveillance should tations to monitor for twin-to-twin transfusion be individualized and may be considered upon syndrome diagnosis, or at a gestational age after which delivery would be considered for abnormal testing The following recommendations and conclusions are based on limited or inconsistent scientific evidence < Women with uncomplicated monochorionic– (Level B): monoamniotic twin gestations can undergo delivery < Women who underwent pregnancy reduction from at 32 0/7–34 0/7 weeks of gestation triplets to twins, as compared with those who continued < Women with monoamniotic twin gestations should be with triplets, were observed to have lower frequencies of pregnancy loss, antenatal complications, preterm delivered by cesarean birth to avoid an umbilical cord birth, low-birth-weight infants, cesarean delivery, and complication of the non-presenting twin at the time of neonatal deaths, with rates similar to those observed in the initial twin’s delivery women with spontaneously conceived twin gestations < In diamniotic twin pregnancies at 32 0/7 weeks of < The chorionicity of a multifetal pregnancy should be gestation or later with a presenting fetus that is vertex, established as early in pregnancy as possible, and the regardless of the presentation of the second twin, optimal timing for determination of chorionicity by vaginal delivery is a reasonable option and should be ultrasonography is in the first trimester or early sec- considered, provided that an obstetrician with expe- ond trimester rience in managing a nonvertex presenting second twin is available < Routine prophylactic interventions including cerclage, < The administration of neuraxial analgesia in women hospitalization, bedrest, tocolytics, and pessary have not been proved to decrease neonatal morbidity or with multifetal gestations facilitates operative vaginal mortality, and therefore should not be used based delivery, external or internal cephalic version, and solely on the indication of multifetal gestation total breech extraction < Unless a contraindication exists, a course of antenatal References corticosteroids should be administered to all patients Martin JA, Hamilton BE, Osterman MJ Three decades of who are at risk of delivery within days and who are twin births in the United States, 1980-2009 NCHS Data between 24 weeks and 34 weeks of gestation, irre- Brief 2012(80):1–8 (Level II-3) spective of the fetal number Martin JA, Osterman MJ Is twin childbearing on the < Magnesium sulfate reduces the severity and risk of decline? Twin births in the United States, 2014-2018 NCHS Data Brief 2019(351):1–8 (Level II-3) cerebral palsy in surviving infants if administered when birth is anticipated before 32 weeks of gesta- Martin JA, Hamilton BE, Ventura SJ, Osterman MJ, Kir- tion, regardless of fetal number meyer S, Mathews TJ, et al Births: final data for 2009 Natl Vital Rep 2011;60:1–70 (Level II-3) < Women with one previous low transverse cesarean Martin JA, Hamilton BE, Osterman MJ, Driscoll AK delivery, who are otherwise appropriate candidates Births: final data for 2018 Natl Vital Stat Rep 2019; for twin vaginal delivery, may be considered candi- 68(13):1–47 (Level II-3) dates for trial of labor after cesarean delivery Blondel B, Kaminski M Trends in the occurrence, deter- The following recommendations and conclusions are based minants, and consequences of multiple births Semin Peri- primarily on consensus and expert opinion (Level C): natol 2002;26:239–49 (Level III) < All women with multifetal gestations, regardless of Scher AI, Petterson B, Blair E, Ellenberg JH, Grether JK, Haan E, et al The risk of mortality or cerebral palsy in age, are candidates for routine screening for fetal twins: a collaborative population-based study Pediatr Res chromosomal abnormalities 2002;52:671–81 (Level II-3) < The optimal gestational age for initiation of surveil- Rettwitz-Volk W, Tran TM, Veldman A Cerebral mor- bidity in preterm twins J Matern Fetal Neonatal Med lance in pregnant individuals with uncomplicated 2003;13:218–23 (Level II-3) dichorionic twins is not known However, for patients with uncomplicated dichorionic twin pregnancies, Yokoyama Y, Shimizu T, Hayakawa K Prevalence of weekly antenatal fetal surveillance may be considered cerebral palsy in twins, triplets and quadruplets Int J at 36 0/7 weeks of gestation Epidemiol 1995;24:943–8 (Level II-3) Bromer JG, Ata B, Seli M, Lockwood CJ, Seli E Preterm deliveries that result from multiple pregnancies associated e154 Practice Bulletin Multifetal Gestations OBSTETRICS & GYNECOLOGY © 2021 by the American College of Obstetricians and Gynecologists Published by Wolters Kluwer Health, Inc Unauthorized reproduction of this article is prohibited Downloaded from http://journals.lww.com/greenjournal by BhDMf5ePHKav1zEoum1tQfN4a+kJLhEZgbsIHo4XMi0h with assisted reproductive technologies in the USA: a cost 24 Low-dose aspirin use during pregnancy ACOG Commit- CywCX1AWnYQp/IlQrHD3i3D0OdRyi7TvSFl4Cf3VC1y0abggQZXdtwnfKZBYtws= on 03/05/2024 analysis Curr Opin Obstet Gynecol 2011;23:168–73 tee Opinion No 743 American College of Obstetricians (Cost-benefit) and Gynecologists Obstet Gynecol 2018;132:e44–52 (Level III) 10 Institute of Medicine Preterm birth: causes, conse- quences, and prevention Washington, DC: National 25 Hardardottir H, Kelly K, Bork MD, Cusick W, Campbell Academies Press; 2007 (Level III) WA, Rodis JF Atypical presentation of preeclampsia in high-order multifetal gestations Obstet Gynecol 1996;87: 11 Geipel A, Berg C, Katalinic A, Plath H, Hansmann M, 370–4 (Level III) Germer U, et al Prenatal diagnosis and obstetric out- comes in triplet pregnancies in relation to chorionicity 26 Sibai BM Diagnosis, controversies, and management of BJOG 2005;112:554–8 (Level II-3) the syndrome of hemolysis, elevated liver enzymes, and low platelet count Obstet Gynecol 2004;103:981–91 12 Glinianaia SV, Obeysekera MA, Sturgiss S, Bell R Still- (Level III) birth and neonatal mortality in monochorionic and dichor- ionic twins: a population-based study Hum Reprod 2011; 27 Multifetal pregnancy reduction Committee Opinion No 26:2549–57 (Level II-3) 719 American College of Obstetricians and Gynecolo- gists Obstet Gynecol 2017;130:e158–63 (Level III) 13 Bajoria R, Ward SB, Adegbite AL Comparative study of perinatal outcome of dichorionic and trichorionic iatro- 28 Sunderam S, Kissin DM, Zhang Y, Jewett A, Boulet SL, genic triplets Am J Obstet Gynecol 2006;194:415–24 Warner L, et al Assisted reproductive technology surveil- (Level II-3) lance - United States, 2017 MMWR Surveill Summ 2020;69(SS-9):1–20 (Level II-3) 14 Kawaguchi H, Ishii K, Yamamoto R, Hayashi S, Mitsuda N Perinatal death of triplet pregnancies by chorionicity 29 Dodd JM, Dowswell T, Crowther CA Reduction of the Perinatal Research Network Group in Japan Am J Obstet number of fetuses for women with a multiple pregnancy Gynecol 2013;209:36.e1–7 (Level II-3) Cochrane Database of Systematic Reviews 2015, Issue 11 Art No.: CD003932 doi: 10.1002/14651858 15 Sivan E, Maman E, Homko CJ, Lipitz S, Cohen S, Schiff CD003932.pub3 (Systematic Review and Meta-Analysis) E Impact of fetal reduction on the incidence of gestational diabetes Obstet Gynecol 2002;99:91–4 (Level II-3) 30 Smith-Levitin M, Kowalik A, Birnholz J, Skupski DW, Hutson JM, Chervenak FA, et al Selective reduction of 16 Schwartz DB, Daoud Y, Zazula P, Goyert G, Bronsteen multifetal pregnancies to twins improves outcome over R, Wright D, et al Gestational diabetes mellitus: meta- nonreduced triplet gestations Am J Obstet Gynecol bolic and blood glucose parameters in singleton versus 1996;175:878–82 (Level III) twin pregnancies Am J Obstet Gynecol 1999;181:912– (Level II-2) 31 Jin B, Huang Q, Ji M, Yu Z, Shu J Perinatal outcomes in dichorionic diamniotic twins with multifetal pregnancy 17 Sibai BM, Hauth J, Caritis S, Lindheimer MD, MacPher- reduction versus expectant management: a systematic son C, Klebanoff M, et al Hypertensive disorders in twin review and meta-analysis Medicine (Baltimore) 2020; versus singleton gestations National Institute of Child 99:e20730 (Systematic Review and Meta-Analysis) Health and Human Development Network of Maternal- Fetal Medicine Units Am J Obstet Gynecol 2000;182: 32 Berkowitz RL, Stone JL, Eddleman KA One hundred 938–42 (Level II-3) consecutive cases of selective termination of an abnormal fetus in a multifetal gestation Obstet Gynecol 1997;90: 18 Luke B, Brown MB Contemporary risks of maternal 606–10 (Level III) morbidity and adverse outcomes with increasing maternal age and plurality Fertil Steril 2007;88:283–93 (Level II- 33 Eddleman KA, Stone JL, Lynch L, Berkowitz RL Selec- 3) tive termination of anomalous fetuses in multifetal preg- nancies: two hundred cases at a single center Am J Obstet 19 Conde-Agudelo A, Belizan JM, Lindmark G Maternal Gynecol 2002;187:1168–72 (Level II-3) morbidity and mortality associated with multiple gesta- tions Obstet Gynecol 2000;95:899–904 (Level II-3) 34 Lust A, De Catte L, Lewi L, Deprest J, Loquet P, Dev- lieger R Monochorionic and dichorionic twin pregnan- 20 Sheard C, Cox S, Oates M, Ndukwe G, Glazebrook C cies discordant for fetal anencephaly: a systematic review Impact of a multiple, IVF birth on post-partum mental of prenatal management options Prenat Diagn 2008;28: health: a composite analysis Hum Reprod 2007;22: 275–9 (Level III) 2058–65 (Level III) 35 Lynch L, Berkowitz RL, Stone J, Alvarez M, Lapinski R 21 Bailit JL Hyperemesis gravidarium: epidemiologic find- Preterm delivery after selective termination in twin preg- ings from a large cohort Am J Obstet Gynecol 2005;193: nancies Obstet Gynecol 1996;87:366–9 (Level III) 811–4 (Level II-3) 36 Lee YM, Cleary-Goldman J, Thaker HM, Simpson LL 22 Day MC, Barton JR, O’Brien JM, Istwan NB, Sibai BM Antenatal sonographic prediction of twin chorionicity The effect of fetal number on the development of hyper- Am J Obstet Gynecol 2006;195:863–7 (Level II-3) tensive conditions of pregnancy Obstet Gynecol 2005; 106:927–31 (Level II-3) 37 Finberg HJ The “twin peak” sign: reliable evidence of dichorionic twinning J Ultrasound Med 1992;11:571–7 23 Lynch A, McDuffie R Jr, Murphy J, Faber K, Orleans M (Level III) Preeclampsia in multiple gestation: the role of assisted reproductive technologies Obstet Gynecol 2002;99:445– 51 (Level II-3) VOL 137, NO 6, JUNE 2021 Practice Bulletin Multifetal Gestations e155 © 2021 by the American College of Obstetricians and Gynecologists Published by Wolters Kluwer Health, Inc Unauthorized reproduction of this article is prohibited Downloaded from http://journals.lww.com/greenjournal by BhDMf5ePHKav1zEoum1tQfN4a+kJLhEZgbsIHo4XMi0h 38 Reichmann JP Home uterine activity monitoring: an evi- 53 Ashworth MF, Spooner SF, Verkuyl DA, Waterman R, CywCX1AWnYQp/IlQrHD3i3D0OdRyi7TvSFl4Cf3VC1y0abggQZXdtwnfKZBYtws= on 03/05/2024 dence review of its utility in multiple gestations J Reprod Ashurst HM Failure to prevent preterm labour and deliv- Med 2009;54:559–62 (Level III) ery in twin pregnancy using prophylactic oral salbutamol Br J Obstet Gynaecol 1990;97:878–82 (Level I) 39 Berghella V, Saccone G Fetal fibronectin testing for reducing the risk of preterm birth Cochrane Database of 54 Yamasmit W, Chaithongwongwatthana S, Tolosa JE, Systematic Reviews 2019, Issue Art No.: CD006843 Limpongsanurak S, Pereira L, Lumbiganon P Prophylac- doi: 10.1002/14651858.CD006843.pub3 (Systematic tic oral betamimetics for reducing preterm birth in women Review and Meta-Analysis) with a twin pregnancy Cochrane Database of Systematic Reviews 2015, Issue 12 Art No.: CD004733 doi: 10 40 Joffe GM, Jacques D, Bemis-Heys R, Burton R, Skram B, 1002/14651858.CD004733.pub4 (Systematic Review Shelburne P Impact of the fetal fibronectin assay on and Meta-Analysis) admissions for preterm labor Am J Obstet Gynecol 1999;180:581–6 (Level II-3) 55 Fletcher SE, Fyfe DA, Case CL, Wiles HB, Upshur JK, Newman RB Myocardial necrosis in a newborn after 41 Giles W, Bisits A, Knox M, Madsen G, Smith R The long-term maternal subcutaneous terbutaline infusion for effect of fetal fibronectin testing on admissions to a ter- suppression of preterm labor Am J Obstet Gynecol 1991; tiary maternal-fetal medicine unit and cost savings Am J 165:1401–4 (Level III) Obstet Gynecol 2000;182:439–42 (Cost-benefit) 56 Gabriel R, Harika G, Saniez D, Durot S, Quereux C, Wahl 42 Grobman WA, Welshman EE, Calhoun EA Does fetal P Prolonged intravenous ritodrine therapy: a comparison fibronectin use in the diagnosis of preterm labor affect between multiple and singleton pregnancies Eur J Obstet physician behavior and health care costs? A randomized Gynecol Reprod Biol 1994;57:65–71 (Level II-3) trial Am J Obstet Gynecol 2004;191:235–40 (Level I) 57 Food and Drug Administration FDA drug safety commu- 43 Ness A, Visintine J, Ricci E, Berghella V Does knowl- nication: new warnings against use of terbutaline to treat edge of cervical length and fetal fibronectin affect man- preterm labor Silver Spring (MD): FDA; 2011.Available agement of women with threatened preterm labor? A at: http://www.fda.gov/drugs/drugsafety/ucm243539.htm randomized trial Am J Obstet Gynecol 2007;197:426 Retrieved January 31, 2014 (Level III) e1–7 (Level I) 58 Liem S, Schuit E, Hegeman M, Bais J, de Boer K, Bloe- 44 Plaut MM, Smith W, Kennedy K Fetal fibronectin: the menkamp K, et al Cervical pessaries for prevention of impact of a rapid test on the treatment of women with preterm birth in women with a multiple pregnancy (ProT- preterm labor symptoms Am J Obstet Gynecol 2003; WIN): a multicentre, open-label randomised controlled 188:1588–93; discussion 1593–5 (Level I) trial Lancet 2013;382:1341–9 (Level I) 45 Dor J, Shalev J, Mashiach S, Blankstein J, Serr DM 59 Conde-Agudelo A, Romero R, Nicolaides KH Cervical Elective cervical suture of twin pregnancies diagnosed pessary to prevent preterm birth in asymptomatic high- ultrasonically in the first trimester following induced ovu- risk women: a systematic review and meta-analysis Am lation Gynecol Obstet Invest 1982;13:55–60 (Level I) J Obstet Gynecol 2020;223:42–65.e2 (Systematic Review and Meta-Analysis) 46 Rebarber A, Roman AS, Istwan N, Rhea D, Stanziano G Prophylactic cerclage in the management of triplet preg- 60 Rouse DJ, Caritis SN, Peaceman AM, Sciscione A, Thom nancies Am J Obstet Gynecol 2005;193:1193–6 (Level EA, Spong CY, et al A trial of 17 alpha- II-3) hydroxyprogesterone caproate to prevent prematurity in twins National Institute of Child Health and Human 47 Moragianni VA, Aronis KN, Craparo FJ Biweekly ultra- Development Maternal-Fetal Medicine Units Network sound assessment of cervical shortening in triplet preg- N Engl J Med 2007;357:454–61 (Level I) nancies and the effect of cerclage placement Ultrasound Obstet Gynecol 2011;37:617–8 (Level III) 61 Norman JE, Mackenzie F, Owen P, Mactier H, Hanretty K, Cooper S, et al Progesterone for the prevention of 48 Crowther CA, Han S Hospitalisation and bed rest for preterm birth in twin pregnancy (STOPPIT): a rando- multiple pregnancy Cochrane Database of Systematic mised, double-blind, placebo-controlled study and meta- Reviews 2010, Issue Art No.: CD000110 doi: 10 analysis Lancet 2009;373:2034–40 (Level I) 1002/14651858.CD000110.pub2 (Meta-analysis) 62 Combs CA, Garite T, Maurel K, Das A, Porto M 17- 49 Wilkins IA, Lynch L, Mehalek KE, Berkowitz GS, Ber- hydroxyprogesterone caproate for twin pregnancy: a kowitz RL Efficacy and side effects of magnesium sulfate double-blind, randomized clinical trial Obstetrix Collab- and ritodrine as tocolytic agents Am J Obstet Gynecol orative Research Network Am J Obstet Gynecol 2011; 1988;159:685–9 (Level I) 204:221.e1–221.e8 (Level I) 50 Samol JM, Lambers DS Magnesium sulfate tocolysis and 63 Combs CA, Garite T, Maurel K, Das A, Porto M Failure pulmonary edema: the drug or the vehicle? Am J Obstet of 17-hydroxyprogesterone to reduce neonatal morbidity Gynecol 2005;192:1430–2 (Level II-3) or prolong triplet pregnancy: a double-blind, randomized clinical trial Obstetrix Collaborative Research Network 51 Cetrulo CL, Freeman RK Ritodrine HCL for the preven- [published erratum appears in Am J Obstet Gynecol tion of premature labor in twin pregnancies Acta Genet 2011;204:166] Am J Obstet Gynecol 2010;203:248.e1– Med Gemellol 1976;25:321–4 (Level III) (Level I) 52 O’Leary JA Prophylactic tocolysis of twins Am J Obstet Gynecol 1986;154:904–5 (Level III) e156 Practice Bulletin Multifetal Gestations OBSTETRICS & GYNECOLOGY © 2021 by the American College of Obstetricians and Gynecologists Published by Wolters Kluwer Health, Inc Unauthorized reproduction of this article is prohibited Downloaded from http://journals.lww.com/greenjournal by BhDMf5ePHKav1zEoum1tQfN4a+kJLhEZgbsIHo4XMi0h 64 Caritis SN, Rouse DJ, Peaceman AM, Sciscione A, Mo- 75 Conde-Agudelo A, Romero R Antenatal magnesium sul- CywCX1AWnYQp/IlQrHD3i3D0OdRyi7TvSFl4Cf3VC1y0abggQZXdtwnfKZBYtws= on 03/05/2024 mirova V, Spong CY, et al Prevention of preterm birth in fate for the prevention of cerebral palsy in preterm infants triplets using 17 alpha-hydroxyprogesterone caproate: a less than 34 weeks’ gestation: a systematic review and randomized controlled trial Eunice Kennedy Shriver metaanalysis Am J Obstet Gynecol 2009;200:595–609 National Institute of Child Health and Human Develop- (Meta-analysis) ment (NICHD), Maternal-Fetal Medicine Units Network (MFMU) Obstet Gynecol 2009;113:285–92 (Level I) 76 Costantine MM, Weiner SJ Effects of antenatal exposure to magnesium sulfate on neuroprotection and mortality in 65 Durnwald CP, Momirova V, Rouse DJ, Caritis SN, Peace- preterm infants: a meta-analysis Eunice Kennedy Shriver man AM, Sciscione A, et al Second trimester cervical National Institute of Child Health and Human Develop- length and risk of preterm birth in women with twin ges- ment Maternal-Fetal Medicine Units Network Obstet Gy- tations treated with 17-alpha hydroxyprogesterone cap- necol 2009;114:354–64 (Meta-analysis) roate Eunice Kennedy Shriver National Institute of Child Health and Human Development Maternal-Fetal 77 Magnesium sulfate before anticipated preterm birth for Medicine Units Network J Matern Fetal Neonatal Med neuroprotection Committee Opinion No 455 American 2010;23:1360–4 (Level II-3) College of Obstetricians and Gynecologists Obstet Gyne- col 2010;115:669–71 (Level III) 66 Wood S, Ross S, Tang S, Miller L, Sauve R, Brant R Vaginal progesterone to prevent preterm birth in multiple 78 Rose NC, Kaimal AJ, Dugoff L, Norton ME Screening pregnancy: a randomized controlled trial J Perinat Med for fetal chromosomal abnormalities ACOG Practice Bul- 2012 doi: 10.1515/jpm-2012-0057 (Level I) letin No 226 American College of Obstetricians and Gynecologists Obstet Gynecol 2020;136:e48–69 (Level 67 Haas DM, Quinney SK, Clay JM, Renbarger JL, Hebert III) MF, Clark S, et al Nifedipine pharmacokinetics are influ- enced by CYP3A5 genotype when used as a preterm labor 79 Rock KR, Millard S, Seravalli V, McShane C, Kearney J, tocolytic Obstetric-Fetal Pharmacology Research Units Seitz E, et al Discordant anomalies and karyotype in a Network Am J Perinatol 2013;30:275–81 (Level III) monochorionic twin pregnancy: a call for comprehensive genetic evaluation Ultrasound Obstet Gynecol 2017;49: 68 Roberts D, Brown J, Medley N, Dalziel SR Antenatal 544–5 (Level III) corticosteroids for accelerating fetal lung maturation for women at risk of preterm birth Cochrane Database of 80 Ramsey KW, Slavin TP, Graham G, Hirata GI, Balaraman Systematic Reviews 2017, Issue Art No.: CD004454 V, Seaver LH Monozygotic twins discordant for trisomy doi: 10.1002/14651858.CD004454.pub3 (Systematic 13 J Perinatol 2012;32:306–8 (Level III) Review and Meta-Analysis) 81 Operative vaginal birth ACOG Practice Bulletin No 219 69 Effect of corticosteroids for fetal maturation on perinatal American College of Obstetricians and Gynecologists outcomes NIH Consens Statement 1994;12(2):1–24 Obstet Gynecol 2020;135:e149–59 (Level III) (Level III) 82 Garchet-Beaudron A, Dreux S, Leporrier N, Oury JF, 70 Antenatal corticosteroid therapy for fetal maturation Muller F Second-trimester Down syndrome maternal Committee Opinion No 713 American College of Obste- serum marker screening: a prospective study of 11,040 tricians and Gynecologists Obstet Gynecol 2017;130: twin pregnancies ABA Study Group, Clinical Study e102–9 (Level III) Group Prenat Diagn 2008;28:1105–9 (Level II-3) 71 Crowther CA, Hiller JE, Doyle LW, Haslam RR Effect of 83 Prats P, Rodríguez I, Comas C, Puerto B Systematic magnesium sulfate given for neuroprotection before pre- review of screening for trisomy 21 in twin pregnancies term birth: a randomized controlled trial Australasian in first trimester combining nuchal translucency and bio- Collaborative Trial of Magnesium Sulphate (ACTOMg chemical markers: a meta-analysis Prenat Diagn 2014;34: SO4) Collaborative Group JAMA 2003;290:2669–76 1077–83 (Systematic Review and Meta-Analysis) (Level I) 84 Cleary-Goldman J, D’Alton ME, Berkowitz RL Prenatal 72 Marret S, Marpeau L, Zupan-Simunek V, Eurin D, Lev- diagnosis and multiple pregnancy Semin Perinatol 2005; eque C, Hellot MF, et al Magnesium sulphate given 29:312–20 (Level II-3) before very-preterm birth to protect infant brain: the rand- omised controlled PREMAG trial PREMAG trial group 85 Sepulveda W, Wong AE, Casasbuenas A Nuchal trans- BJOG 2007;114:310–8 (Level I) lucency and nasal bone in first-trimester ultrasound screening for aneuploidy in multiple pregnancies Ultra- 73 Rouse DJ, Hirtz DG, Thom E, Varner MW, Spong CY, sound Obstet Gynecol 2009;33:152–6 (Level III) Mercer BM, et al A randomized, controlled trial of mag- nesium sulfate for the prevention of cerebral palsy Eunice 86 Sebire NJ, D’Ercole C, Hughes K, Carvalho M, Nico- Kennedy Shriver NICHD Maternal-Fetal Medicine Units laides KH Increased nuchal translucency thickness at Network N Engl J Med 2008;359:895–905 (Level I) 10-14 weeks of gestation as a predictor of severe twin- to-twin transfusion syndrome Ultrasound Obstet Gyne- 74 Doyle LW, Crowther CA, Middleton P, Marret S, Rouse col 1997;10:86–9 (Level II-3) D Magnesium sulphate for women at risk of preterm birth for neuroprotection of the fetus Cochrane Database of 87 Gil MM, Galeva S, Jani J, Konstantinidou L, Akolekar R, Systematic Reviews 2009, Issue Art No.: CD004661 Plana MN, et al Screening for trisomies by cfDNA testing doi: 10.1002/14651858.CD004661.pub3 (Meta-analy- of maternal blood in twin pregnancy: update of The Fetal sis) Medicine Foundation results and meta-analysis Ultra- sound Obstet Gynecol 2019;53:734–42 (Systematic Review and Meta-Analysis) VOL 137, NO 6, JUNE 2021 Practice Bulletin Multifetal Gestations e157 © 2021 by the American College of Obstetricians and Gynecologists Published by Wolters Kluwer Health, Inc Unauthorized reproduction of this article is prohibited Downloaded from http://journals.lww.com/greenjournal by BhDMf5ePHKav1zEoum1tQfN4a+kJLhEZgbsIHo4XMi0h 88 Galeva S, Gil MM, Konstantinidou L, Akolekar R, Nic- nancy: incidence and effect on outcome Am J Obstet CywCX1AWnYQp/IlQrHD3i3D0OdRyi7TvSFl4Cf3VC1y0abggQZXdtwnfKZBYtws= on 03/05/2024 olaides KH First-trimester screening for trisomies by Gynecol 2002;186:77–83 (Level II-3) cfDNA testing of maternal blood in singleton and twin pregnancies: factors affecting test failure Ultrasound Ob- 103 D’Alton ME, Simpson LL Syndromes in twins Semin stet Gynecol 2019;53:804–9 (Level II-2) Perinatol 1995;19:375–86 (Level III) 89 Agarwal K, Alfirevic Z Pregnancy loss after chorionic 104 Lee YM, Wylie BJ, Simpson LL, D’Alton ME Twin villus sampling and genetic amniocentesis in twin preg- chorionicity and the risk of stillbirth [published erratum nancies: a systematic review Ultrasound Obstet Gynecol appears in Obstet Gynecol 2008;111:1217] Obstet Gyne- 2012;40:128–34 (Meta-analysis) col 2008;111:301–8 (Level II-3) 90 Simonazzi G, Curti A, Farina A, Pilu G, Bovicelli L, 105 Morikawa M, Yamada T, Yamada T, Sato S, Cho K, Rizzo N Amniocentesis and chorionic villus sampling Minakami H Prospective risk of stillbirth: monochorionic in twin gestations: which is the best sampling technique? diamniotic twins vs dichorionic twins J Perinat Med Am J Obstet Gynecol 2010;202:365.e1–5 (Level II-3) 2012;40:245–9 (Level II-3) 91 Cahill AG, Macones GA, Stamilio DM, Dicke JM, Crane 106 Danon D, Sekar R, Hack KE, Fisk NM Increased still- JP, Odibo AO Pregnancy loss rate after mid-trimester birth in uncomplicated monochorionic twin pregnancies: a amniocentesis in twin pregnancies Am J Obstet Gynecol systematic review and meta-analysis Obstet Gynecol 2009;200:257.e1–6 (Level II-3) 2013;121:1318–26 (Meta-analysis) 92 Eddleman KA, Stone JL, Lynch L, Berkowitz RL Cho- 107 Hillman SC, Morris RK, Kilby MD Co-twin prognosis rionic villus sampling before multifetal pregnancy reduc- after single fetal death: a systematic review and meta- tion Am J Obstet Gynecol 2000;183:1078–81 (Level III) analysis Obstet Gynecol 2011;118:928–40 (Meta-analy- sis) 93 Talbot GT, Goldstein RF, Nesbitt T, Johnson JL, Kay HH Is size discordancy an indication for delivery of pre- 108 Ong SS, Zamora J, Khan KS, Kilby MD Prognosis for term twins? Am J Obstet Gynecol 1997;177:1050–4 the co-twin following single-twin death: a systematic (Level III) review BJOG 2006;113:992–8 (Meta-analysis) 94 Breathnach FM, McAuliffe FM, Geary M, Daly S, Hig- 109 Karageyim Karsidag AY, Kars B, Dansuk R, Api O, Unal gins JR, Dornan J, et al Definition of intertwin birth O, Turan MC, et al Brain damage to the survivor within weight discordance Perinatal Ireland Research Consor- 30 of co-twin demise in monochorionic twins Fetal tium Obstet Gynecol 2011 Jul;118(1):94–103 doi: Diagn Ther 2005;20:91–5 (Level III) 1097/AOG.0b013e31821fd208 (Level II-2) 110 Spong CY, Mercer BM, D’Alton M, Kilpatrick S, Black- 95 Lopriore E, Slaghekke F, Vandenbussche FP, Middeldorp well S, Saade G Timing of indicated late-preterm and JM, Walther FJ, Oepkes D Cerebral injury in monochor- early-term birth Obstet Gynecol 2011;118:323–33 ionic twins with selective intrauterine growth restriction (Level III) and/or birthweight discordance Am J Obstet Gynecol 2008;199:628.e1–5 (Level II-3) 111 Alexander GR, Kogan M, Martin J, Papiernik E What are the fetal growth patterns of singletons, twins, and triplets 96 Appleton C, Pinto L, Centeno M, Clode N, Cardoso C, in the United States? Clin Obstet Gynecol 1998;41:114– Graca LM Near term twin pregnancy: clinical relevance 25 (Level II-3) of weight discordance at birth J Perinat Med 2007;35:62– (Level II-3) 112 Corcoran S, Breathnach F, Burke G, McAuliffe F, Geary M, Daly S, et al Dichorionic twin ultrasound surveil- 97 Cohen SB, Elizur SE, Goldenberg M, Beiner M, Novikov lance: sonography every weeks significantly underper- I, Mashiach S, et al Outcome of twin pregnancies with forms sonography every weeks: results of the extreme weight discordancy Am J Perinatol 2001;18: Prospective Multicenter ESPRiT Study Am J Obstet Gy- 427–32 (Level II-3) necol 2015;213:551.e1–5 (Level II-2) 98 Kilic M, Aygun C, Kaynar-Tuncel E, Kucukoduk S Does 113 Cheong-See F, Schuit E, Arroyo-Manzano D, Khalil A, birth weight discordance in preterm twins affect neonatal Barrett J, Joseph KS, et al Prospective risk of stillbirth outcome? J Perinatol 2006;26:268–72 (Level II-3) and neonatal complications in twin pregnancies: system- atic review and meta-analysis Global Obstetrics Network 99 Yinon Y, Mazkereth R, Rosentzweig N, Jarus-Hakak A, (GONet) Collaboration BMJ 2016;354:i4353 (System- Schiff E, Simchen MJ Growth restriction as a determi- atic Review and Meta-Analysis) nant of outcome in preterm discordant twins Obstet Gy- necol 2005;105:80–4 (Level II-3) 114 Booker W, Fox NS, Gupta S, Carroll R, Saltzman DH, Klauser CK, et al Antenatal surveillance in twin pregnan- 100 Odibo AO, McDonald RE, Stamilio DM, Ural SH, Ma- cies using the biophysical profile J Ultrasound Med 2015; cones GA Perinatal outcomes in growth-restricted twins 34:2071–5 (Level II-3) compared with age-matched growth-restricted singletons Am J Perinatol 2005;22:269–73 (Level II-3) 115 Burgess JL, Unal ER, Nietert PJ, Newman RB Risk of late-preterm stillbirth and neonatal morbidity for mono- 101 Landy HJ, Keith LG The vanishing twin: a review Hum chorionic and dichorionic twins Am J Obstet Gynecol Reprod Update 1998;4:177–83 (Level III) 2014;210:578.e1–9 (Level II-2) 102 Dickey RP, Taylor SN, Lu PY, Sartor BM, Storment JM, 116 Russo FM, Pozzi E, Pelizzoni F, Todyrenchuk L, Bernas- Rye PH, et al Spontaneous reduction of multiple preg- coni DP, Cozzolino S, et al Stillbirths in singletons, di- chorionic and monochorionic twins: a comparison of risks e158 Practice Bulletin Multifetal Gestations OBSTETRICS & GYNECOLOGY © 2021 by the American College of Obstetricians and Gynecologists Published by Wolters Kluwer Health, Inc Unauthorized reproduction of this article is prohibited Downloaded from http://journals.lww.com/greenjournal by BhDMf5ePHKav1zEoum1tQfN4a+kJLhEZgbsIHo4XMi0h and causes Eur J Obstet Gynecol Reprod Biol 2013;170: 129 Roque H, Gillen-Goldstein J, Funai E, Young BK, Lock- CywCX1AWnYQp/IlQrHD3i3D0OdRyi7TvSFl4Cf3VC1y0abggQZXdtwnfKZBYtws= on 03/05/2024 131–6 (Level II-2) wood CJ Perinatal outcomes in monoamniotic gestations J Matern Fetal Neonatal Med 2003;13:414–21 (Level III) 117 Antepartum fetal surveillance Committee Opinion No 229 American College of Obstetricians and Gynecolo- 130 Baxi LV, Walsh CA Monoamniotic twins in contempo- gists Obstet Gynecol 2021;137:e116–27 (Level III) rary practice: a single-center study of perinatal outcomes J Matern Fetal Neonatal Med 2010;23:506–10 (Level III) 118 Hack KE, Derks JB, Elias SG, Franx A, Roos EJ, Voer- man SK, et al Increased perinatal mortality and morbidity 131 DeFalco LM, Sciscione AC, Megerian G, Tolosa J, Ma- in monochorionic versus dichorionic twin pregnancies: cones G, O’Shea A, et al Inpatient versus outpatient man- clinical implications of a large Dutch cohort study BJOG agement of monoamniotic twins and outcomes Am J 2008;115:58–67 (Level II-2) Perinatol 2006;23:205–11 (Level III) 119 Hoskins IA, Combs CA Society for Maternal-Fetal Med- 132 Ezra Y, Shveiky D, Ophir E, Nadjari M, Eisenberg VH, icine special statement: updated checklists for manage- Samueloff A, et al Intensive management and early deliv- ment of monochorionic twin pregnancy Patient Safety ery reduce antenatal mortality in monoamniotic twin preg- and Quality Committee, Society for Maternal-Fetal Med- nancies Acta Obstet Gynecol Scand 2005;84:432–5 icine Am J Obstet Gynecol 2020;223:B16–20 (Level III) (Level III) 120 AIUM practice parameter for the performance of fetal 133 Sogaard K, Skibsted L, Brocks V Acardiac twins: path- echocardiography J Ultrasound Med 2020;39:E5-16 ophysiology, diagnosis, outcome and treatment Six cases (Level III) and review of the literature Fetal Diagn Ther 1999;14: 53–9 (Level III) 121 Emery SP, Bahtiyar MO, Dashe JS, Wilkins-Haug LE, Johnson A, Paek BW, et al The North American Fetal 134 van Gemert MJ, Umur A, van den Wijngaard JP, VanBa- Therapy Network Consensus Statement: prenatal manage- vel E, Vandenbussche FP, Nikkels PG Increasing cardiac ment of uncomplicated monochorionic gestations Obstet output and decreasing oxygenation sequence in pump Gynecol 2015;125:1236–43 (Level III) twins of acardiac twin pregnancies Phys Med Biol 2005;50:N33–42 (Level III) 122 Sueters M, Middeldorp JM, Lopriore E, Oepkes D, Kan- hai HH, Vandenbussche FP Timely diagnosis of twin-to- 135 Mutchinick OM, Luna-Munoz L, Amar E, Bakker MK, twin transfusion syndrome in monochorionic twin preg- Clementi M, Cocchi G, et al Conjoined twins: a world- nancies by biweekly sonography combined with patient wide collaborative epidemiological study of the Interna- instruction to report onset of symptoms Ultrasound Ob- tional Clearinghouse for Birth Defects Surveillance and stet Gynecol 2006;28:659–64 (Level III) Research Am J Med Genet C Semin Med Genet 2011; 157C:274–87 (Level II-3) 123 Royal College of Obstetricians and Gynaecologists Con- sensus views arising from the 50th Study Group: multiple 136 Spitz L, Kiely EM Conjoined twins JAMA 2003;289: pregnancy London: RCOG; 2006.Available at: http:// 1307–10 (Level III) www.rcog.org.uk/files/rcogcorp/uploadedfiles/Study- GroupConsensusViewsMultiplePregnancy.pdf Retrieved 137 Mackenzie TC, Crombleholme TM, Johnson MP, February 5, 2014(Level III) Schnaufer L, Flake AW, Hedrick HL, et al The natural history of prenatally diagnosed conjoined twins J Pediatr 124 Lewi L, Gucciardo L, Van Mieghem T, de Koninck P, Surg 2002;37:303–9 (Level III) Beck V, Medek H, et al Monochorionic diamniotic twin pregnancies: natural history and risk stratification Fetal 138 Refuerzo JS, Momirova V, Peaceman AM, Sciscione A, Diagn Ther 2010;27:121–33 (Level III) Rouse DJ, Caritis SN, et al Neonatal outcomes in twin pregnancies delivered moderately preterm, late preterm, 125 Simpson LL Twin-twin transfusion syndrome Society and term Am J Perinatol 2010;27:537–42 (Level II-3) for Maternal-Fetal Medicine [published erratum appears in Am J Obstet Gynecol 2013;208:392] Am J Obstet 139 Cheung YB, Yip P, Karlberg J Mortality of twins and Gynecol 2013;208:3–18 (Level III) singletons by gestational age: a varying-coefficient approach Am J Epidemiol 2000;152:1107–16 (Level 126 Stamilio DM, Fraser WD, Moore TR Twin-twin trans- II-3) fusion syndrome: an ethics-based and evidence-based argument for clinical research Am J Obstet Gynecol 140 Medically indicated late-preterm and early-term deliver- 2010;203:3–16 (Level III) ies ACOG Committee Opinion No 818 American Col- lege of Obstetricians and Gynecologists Obstet Gynecol 127 Slotnick RN, Ortega JE Monoamniotic twinning and zo- 2021;137:e29–33 (Level III) na manipulation: a survey of U.S IVF centers correlating zona manipulation procedures and high-risk twinning fre- 141 Hofmeyr GJ, Barrett JF, Crowther CA Planned caesarean quency J Assist Reprod Genet 1996;13:381–5 (Level III) section for women with a twin pregnancy Cochrane Data- base of Systematic Reviews 2015, Issue 12 Art No.: 128 Heyborne KD, Porreco RP, Garite TJ, Phair K, Abril D CD006553 doi: 10.1002/14651858.CD006553.pub3 Improved perinatal survival of monoamniotic twins with (Systematic Review and Meta-Analysis) intensive inpatient monitoring Obstetrix/Pediatrix Research Study Group Am J Obstet Gynecol 2005;192: 142 Barrett JF, Hannah ME, Hutton EK, Willan AR, Allen 96–101 (Level II-2) AC, Armson BA, et al A randomized trial of planned cesarean or vaginal delivery for twin pregnancy Twin Birth Study Collaborative Group [published erratum VOL 137, NO 6, JUNE 2021 Practice Bulletin Multifetal Gestations e159 © 2021 by the American College of Obstetricians and Gynecologists Published by Wolters Kluwer Health, Inc Unauthorized reproduction of this article is prohibited Downloaded from http://journals.lww.com/greenjournal by BhDMf5ePHKav1zEoum1tQfN4a+kJLhEZgbsIHo4XMi0h appears in N Engl J Med 2013;369:2364 N Engl J Med 148 Cahill A, Stamilio DM, Pare E, Peipert JP, Stevens EJ, CywCX1AWnYQp/IlQrHD3i3D0OdRyi7TvSFl4Cf3VC1y0abggQZXdtwnfKZBYtws= on 03/05/2024 2013;369:1295–305 (Level I) Nelson DB, et al Vaginal birth after cesarean (VBAC) attempt in twin pregnancies: is it safe? Am J Obstet Gy- 143 D’Alton ME Delivery of the second twin: revisiting the age- necol 2005;193:1050–5 (Level II-3) old dilemma Obstet Gynecol 2010;115:221–2 (Level III) 149 Varner MW, Thom E, Spong CY, Landon MB, Leveno 144 Grobman WA, Peaceman AM, Haney EI, Silver RK, Mac- KJ, Rouse DJ, et al Trial of labor after one previous Gregor SN Neonatal outcomes in triplet gestations after a trial cesarean delivery for multifetal gestation National Insti- of labor Am J Obstet Gynecol 1998;179:942–5 (Level II-2) tute of Child Health and Human Development (NICHD) Maternal-Fetal Medicine Units Network (MFMU) Obstet 145 Alamia V Jr, Royek AB, Jaekle RK, Meyer BA Pre- Gynecol 2007;110:814–9 (Level II-3) liminary experience with a prospective protocol for planned vaginal delivery of triplet gestations Am J Obstet 150 Myles T Vaginal birth of twins after a previous Cesarean Gynecol 1998;179:1133–5 (Level III) section J Matern Fetal Med 2001;10:171–4 (Level II-2) 146 Wildschut HI, van Roosmalen J, van Leeuwen E, Keirse 151 Miller DA, Mullin P, Hou D, Paul RH Vaginal birth after MJ Planned abdominal compared with planned vaginal cesarean section in twin gestation Am J Obstet Gynecol birth in triplet pregnancies Br J Obstet Gynaecol 1995; 1996;175:194–8 (Level II-3) 102:292–6 (Level III) 152 Francois K, Ortiz J, Harris C, Foley MR, Elliott JP 147 Sansregret A, Bujold E, Gauthier RJ Twin delivery after Is peripartum hysterectomy more common in multiple a previous caesarean: a twelve-year experience J Obstet gestations? Obstet Gynecol 2005;105:1369–72 Gynaecol Can 2003;25:294–8 (Level III) (Level II-3) e160 Practice Bulletin Multifetal Gestations OBSTETRICS & GYNECOLOGY © 2021 by the American College of Obstetricians and Gynecologists Published by Wolters Kluwer Health, Inc Unauthorized reproduction of this article is prohibited Downloaded from http://journals.lww.com/greenjournal by BhDMf5ePHKav1zEoum1tQfN4a+kJLhEZgbsIHo4XMi0h The MEDLINE database, the Cochrane Library, and the Published online on May 20, 2021 CywCX1AWnYQp/IlQrHD3i3D0OdRyi7TvSFl4Cf3VC1y0abggQZXdtwnfKZBYtws= on 03/05/2024 American College of Obstetricians and Gynecologists’ own internal resources and documents were used to Copyright 2021 by the American College of Obstetricians and conduct a literature search to locate relevant articles Gynecologists All rights reserved No part of this publication published between January 1990-October 2013 The may be reproduced, stored in a retrieval system, posted on the search was restricted to articles published in the Internet, or transmitted, in any form or by any means, elec- English language Priority was given to articles tronic, mechanical, photocopying, recording, or otherwise, reporting results of original research, although review without prior written permission from the publisher articles and commentaries also were consulted Abstracts of research presented at symposia and American College of Obstetricians and Gynecologists scientific conferences were not considered adequate for 409 12th Street SW, Washington, DC 20024-2188 inclusion in this document Guidelines published by organizations or institutions such as the National Multifetal gestations: twin, triplet, and higher-order multifetal Institutes of Health and the American College of pregnancies ACOG Practice Bulletin No 231 American Obstetricians and Gynecologists were reviewed, and College of Obstetricians and Gynecologists Obstet Gynecol additional studies were located by reviewing 2021;137:e145–62 bibliographies of identified articles When reliable research was not available, expert opinions from obstetrician–gynecologists were used Studies were reviewed and evaluated for quality according to the method outlined by the U.S Preventive Services Task Force: I Evidence obtained from at least one properly de- signed randomized controlled trial II-1 Evidence obtained from well-designed controlled trials without randomization II-2 Evidence obtained from well-designed cohort or case–control analytic studies, preferably from more than one center or research group II-3 Evidence obtained from multiple time series with or without the intervention Dramatic results in uncontrolled experiments also could be regarded as this type of evidence III Opinions of respected authorities, based on clinical experience, descriptive studies, or reports of expert committees Based on the highest level of evidence found in the data, recommendations are provided and graded according to the following categories: Level A—Recommendations are based on good and consistent scientific evidence Level B—Recommendations are based on limited or inconsistent scientific evidence Level C—Recommendations are based primarily on consensus and expert opinion VOL 137, NO 6, JUNE 2021 Practice Bulletin Multifetal Gestations e161 © 2021 by the American College of Obstetricians and Gynecologists Published by Wolters Kluwer Health, Inc Unauthorized reproduction of this article is prohibited Downloaded from http://journals.lww.com/greenjournal by BhDMf5ePHKav1zEoum1tQfN4a+kJLhEZgbsIHo4XMi0h This information is designed as an educational resource to aid clinicians in providing obstetric and gynecologic care, and use CywCX1AWnYQp/IlQrHD3i3D0OdRyi7TvSFl4Cf3VC1y0abggQZXdtwnfKZBYtws= on 03/05/2024 of this information is voluntary This information should not be considered as inclusive of all proper treatments or methods of care or as a statement of the standard of care It is not intended to substitute for the independent professional judgment of the treating clinician Variations in practice may be warranted when, in the reasonable judgment of the treating clinician, such course of action is indicated by the condition of the patient, limitations of available resources, or advances in knowledge or technology The American College of Obstetricians and Gynecologists reviews its publications regularly; 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