Our research

Melamed N, Weitzner O, Church P, Banihani R, Barrett J, Yang J, Wong J, Piedboeuf B, Shah PS; Canadian Neonatal Network (CNN); Canadian Preterm Birth Network (CPTBN); Canadian Neonatal Follow-Up Network (CNFUN) Investigators. Neonatal and Early Childhood Outcomes of Twin and Singleton Infants Born Preterm. J Pediatr. 2023 Nov;262:113377. Click here for full paper.

Lipworth H, Hiersch L, Farine D, Barrett JFR, Melamed N. Current Practice of Maternal-Fetal Medicine Specialists Regarding the Prevention and Management of Preterm Birth in Twin Gestations. J Obstet Gynaecol Can. 2021 Jul;43(7):831-838. Click here for full paper.

There is much uncertainty regarding the best ways to decrease the risk of preterm birth in twins, and guidelines published by different professional societies often provide conflicting recommendations. In the current study, we surveyed maternal-fetal medicine specialists across Canada. We found that there are differences between specialists regarding how twin pregnancies are managed by individual specialists, including recommendations for physical activity in pregnancy, monitoring of cervical length, and the use of cervical suture (cerclage) or progesterone in women with a short cervix. We recommended that efforts should be made to standardize recommendations for the prevention of preterm birth in twins.

Menzies R, Li ALK, Murphy KE, Shah PS, Horn D, Barrett J, Melamed N. Risk of singleton preterm birth after prior twin preterm birth: a cohort study. J Matern Fetal Neonatal Med. 2020 Nov;33(21):3602-3607. Click here for full paper.

It is unclear whether delivering twins preterm increases a mother’s risk of having another preterm birth in their next singleton pregnancy. Using data from 2 large tertiary centers in Toronto (Sunnybrook and Mount Sinai Hospital), we found that a previous preterm birth in a twin pregnancy increases the risk of preterm birth in a future singleton pregnancy, and that this risk is also related to how preterm the twins were.

Menzies R, Li ALK, Melamed N, Shah PS, Horn D, Barrett J, Murphy KE. Risk of singleton preterm birth after prior twin preterm birth: a systematic review and meta-analysis. Am J Obstet Gynecol. 2020 Aug;223(2):204.e1-204.e8.Click here for full paper.

There is uncertainty regarding the risk of preterm birth in singleton pregnancies following a preterm twin birth. We reviewed all of the published scientific papers that studied pregnancies with a previous twin birth followed by a singleton pregnancy. We pooled the results of these studies together, and found that if an individual delivers twins preterm, they have a higher risk of giving birth to their next single baby early. The earlier the preterm twin birth, the higher the odds of the next pregnancy being preterm.

Martinka D, Barrett J, Mei-Dan E, Zaltz A, Melamed N. Respiratory morbidity in late preterm twin infants. Arch Gynecol Obstet. 2019 Aug;300(2):337-345. Click here for full paper.

In ‘late-preterm’ (between 34 and 36 weeks) singleton pregnancies, it has been shown that providing antenatal corticosteroids to promote fetal lung maturation is beneficial. However, it has not been investigated in late-preterm twins. Using data from a large, international study, we found that in individuals at risk of delivering their babies late-preterm, the risk of their babies having problems with their lungs is similar to single baby pregnancies. This suggests that  care providers who consider corticosteroids during the late-preterm period for singleton pregnancies, may consider extending this practice to late-preterm twins as well.

Rosen H, Hiersch L, Freeman H, Barrett J, Melamed N. The role of serial measurements of cervical length in asymptomatic women with triplet pregnancy. J Matern Fetal Neonatal Med. 2018 Mar;31(6):713-719. Click here for full paper.

Abbasi N, Barrett J, Melamed N. Outcomes following rescue cerclage in twin pregnancies. J Matern Fetal Neonatal Med. 2018 Aug;31(16):2195-2201. Click here for full paper.

Sometimes, the cervix in a twin pregnancy dilates too early (25 weeks or less). It is uncertain whether inserting a cervical stitch (otherwise known as a rescue cerclage) versus a wait-and-see method results in better outcomes for the parent and baby. Therefore, we studied the medical records of individuals with twin pregnancies where the cervix was dilated too early in pregnancy. We compared those pregnancies with a cervical stitch inserted and those without. We found that a cervical stitch can prolong pregnancy and improve the outcomes of the babies in individuals with a dilated cervix before 25 weeks, compared to no cervical stitch.

Kibel M, Barrett J, Tward C, Pittini A, Kahn M, Melamed N. The natural history of preterm premature rupture of membranes in twin pregnancies. J Matern Fetal Neonatal Med. 2017 Aug;30(15):1829-1835. Click here for full paper.

In some pregnancies, the water breaks too early (called preterm premature rupture of membranes, or PPROM). There is uncertainty whether the characteristics of PPROM are different between twin and singleton pregnancies. Therefore, we studied the medical records of twin pregnancies at Sunnybrook, in the case where the water breaks too early. We found that even though the water breaks too early, in twin pregnancies it tends to break a little later compared to singletons. It also is associated with a shorter time between water break and birth. These pregnancies tend to be less likely to experience infections or placental abruption (the placenta peeling off the wall of the uterus) compared to singleton pregnancies.

Melamed N, Pittini A, Hiersch L, Yogev Y, Korzeniewski SJ, Romero R, Barrett J. Do serial measurements of cervical length improve the prediction of preterm birth in asymptomatic women with twin gestations? Am J Obstet Gynecol. 2016 Nov;215(5):616.e1-616.e14. Click here for full paper.

One way in which preterm birth is predicted is through measuring the length of the cervix via ultrasound. It is uncertain whether multiple measurements taken over the length of a pregnancy can improve the prediction of preterm birth in twins, compared to a single measurement taken in the middle of the pregnancy. Therefore, we studied the medical records of all twin pregnancies at Sunnybrook between 2012 and 2014. We found that taking frequent measurements of the cervix in a systematic way can increase the likelihood of detecting twin pregnancies at risk for preterm birth.

Melamed N, Shah J, Yoon EW, Pelausa E, Lee SK, Shah PS, Murphy KE; Canadian Neonatal Network Investigators. The role of antenatal corticosteroids in twin pregnancies complicated by preterm birth. Am J Obstet Gynecol. 2016 Oct;215(4):482.e1-9. Click here for full paper

Information about the effects of medications for infant lung maturation is limited in twin pregnancies, due to the small number of people pregnant with twins who enroll in studies related to these medications. Therefore, we studied the medical records of preterm singletons and preterm twins who were admitted to neonatal intensive care units (NICUs) in Canada between 2010 and 2014. We found that giving pregnant people a course of medications called for lung maturation 1-7 days before birth in twins is associated with lowered risk of infant death, lung complications, and severe brain injuries. This is similar to what is found in single babies.

Melamed N, Pittini A, Hiersch L, Yogev Y, Korzeniewski SS, Romero R, Barrett J. Serial cervical length determination in twin pregnancies reveals 4 distinct patterns with prognostic significance for preterm birth. Am J Obstet Gynecol. 2016 Oct;215(4):476.e1-476.e11. Click here for full paper.

Women with a twin pregnancy are at increased risk for preterm birth and measuring the length of the cervix via ultrasound is a powerful way to predict it. Obstetricians frequently monitor cervical length in multiple gestations; yet, the optimal method to use the results of cervical length measurements has not been determined. Therefore, we studied the medical records of all individuals with twins at Sunnybrook between 2012-2014. We found that there are 4 patterns of shortening of the cervix, and each has a different risk for preterm birth.

Hiersch L, Rosen H, Okby R, Freeman H, Barrett J, Melamed N. The greater risk of preterm birth in triplets is mirrored by a more rapid cervical shortening along gestation. Am J Obstet Gynecol. 2016 Sep;215(3):357.e1-6. Click here for full paper.

The risk of preterm birth increases with more fetuses in the womb (twins, triplets etc.) However, it is uncertain whether there is a different rate at which the cervix shortens in twins versus triplet pregnancies. Therefore, we studied the medical records of twin and triplet pregnancies that underwent length measurements of the cervix from 16-32 weeks of pregnancy. We found that triplet pregnancies are associated with a faster cervical shortening and higher rate of preterm birth compared to twin pregnancies.

Kibel M, Asztalos E, Barrett J, Dunn MS, Tward C, Pittini A, Melamed N. Outcomes of Pregnancies Complicated by Preterm Premature Rupture of Membranes Between 20 and 24 Weeks of Gestation. Obstet Gynecol. 2016 Aug;128(2):313-320. Click here for full paper.

Preterm premature rupture of membranes (P-PROM) is associated with poorer outcomes for babies. It is not clear how to manage mothers who experience P-PROM very early in pregnancy (i.e., before 23-24 weeks, known as the ‘pre-viable period’), since these cases carry even greater risks because the baby may be born very early and the lack of fluid so early in pregnancy can affect lung development. We studied the outcomes of mothers of single or twin babies after P-PROM in the pre-viable period (between 20-24 weeks) who chose to continue with pregnancy. We found that nearly half (49%) of the babies survived, but the babies who survived and their mothers were at risk of serious poor outcomes. This study emphasized the need for individualized counseling to mothers with pre-viable P-PROM and for close surveillance at a tertiary pregnancy center.

Melamed N, Hiersch L, Gabbay-Benziv R, Bardin R, Meizner I, Wiznitzer A, Yogev Y. Predictive value of cervical length in women with twin pregnancy presenting with threatened preterm labor. Ultrasound Obstet Gynecol. 2015 Jul;46(1):73-81. Click here for full paper.

One challenge in managing preterm labour (PTL) is classifying true and false preterm labour – less than 15% of those who present in PTL will deliver within 7 days of presentation. To predict preterm delivery, cervical length screening is used, however there is only limited information regarding the accuracy of cervical length screening in twin pregnancies that present in threatened PTL. In this study, we compared the accuracy of cervical length screening in twin pregnancies with PTL to those with singleton pregnancies. The key findings are that  in women with PTL, the performance of cervical length screening as a test for the prediction of preterm delivery is similar in twin and singleton pregnancies. However, the optimal threshold of CL for the prediction of preterm delivery appears to be higher in twin pregnancies, mainly owing to the higher baseline risk for preterm delivery in these pregnancies.

Melamed N, Hiersch L, Gabbay-Benziv R, Bardin R, Meizner I, Wiznitzer A, Yogev Y. Predictive value of cervical length in women with twin pregnancy presenting with threatened preterm labor. Ultrasound Obstet Gynecol. 2015 Jul;46(1):73-81. Click here for full paper.

One challenge in managing preterm labour (PTL) is classifying true and false preterm labour – less than 15% of those who present in PTL will deliver within 7 days of presentation. To predict preterm delivery, cervical length screening is used, however there is only limited information regarding the accuracy of cervical length screening in twin pregnancies that present in threatened PTL. In this study, we compared the accuracy of cervical length screening in twin pregnancies with PTL to those with singleton pregnancies. The key findings are that  in women with PTL, the performance of cervical length screening as a test for the prediction of preterm delivery is similar in twin and singleton pregnancies. However, the optimal threshold of CL for the prediction of preterm delivery appears to be higher in twin pregnancies, mainly owing to the higher baseline risk for preterm delivery in these pregnancies.

Hiersch L, Ray JG, Barrett J, Berger H, Geary M, McDonald SD, Diong C, Gandhi S, Guan J, Murray-Davis B, Melamed N; DOH-NET (Diabetes, Obesity and Hypertension in Pregnancy Research Network). Maternal cardiovascular disease after twin pregnancies complicated by hypertensive disorders of pregnancy: a population-based cohort study. CMAJ. 2021 Sep 20;193(37):E1448-E1458.  Click here for full paper.

Mothers with single pregnancies who have hypertensive disorders of pregnancy (HDP), such as preeclampsia, are at risk of future cardiovascular disease. Given the possible differences in the mechanism underlying HDP in twin pregnancies compared with singleton ones, it’s not clear if this association between HDP and future maternal cardiovascular disease is true in twin pregnancies. In agreement with our hypothesis, we found that twin mothers with HDP had lower risk of future cardiovascular disease than singleton mothers with HDP. Still, both types of mothers had a higher risk than those without HDP. These findings provide some reassurance to mothers with twins who experienced HDP.

Aviram A, Berger H, Abdulaziz KE, Barrett JFR, Murray-Davis B, McDonald SD, Geary M, Melamed N; for DOH-NET (Diabetes, Obesity and Hypertension in Pregnancy Research Network) and SOON (Southern Ontario Obstetrical Network) Investigators. Outcomes Associated With Hypertensive Disorders of Pregnancy in Twin Compared With Singleton Gestations. Obstet Gynecol. 2021 Sep 1;138(3):449-458. Click here for full paper.

It is unclear whether the outcomes of twin pregnancies complicated by hypertension and preeclampsia differ compared to singleton pregnancies. In this paper we compared singleton and twin data from BORN (Better Outcomes Registry & Network Ontario). The key findings of this paper show that although the risk of adverse maternal and neonatal outcomes is higher in twin compared with singleton pregnancies complicated by hypertension and preeclampsia, these findings may be related to the higher baseline risk of some of these outcomes in twin pregnancies compared to singleton pregnancies.

Proctor LK, Kfouri J, Hiersch L, Aviram A, Zaltz A, Kingdom J, Barrett J, Melamed N. Association between hypertensive disorders and fetal growth restriction in twin compared with singleton gestations. Am J Obstet Gynecol. 2019 Sep;221(3):251.e1-251.e8. Click here for full paper.

In singleton pregnancies there is a strong association between high blood pressure in pregnancy and fetal growth restriction. However, it is unclear whether this association is also present in twin pregnancies given the different mechanisms of high blood pressure and fetal growth restriction in twins compared with singletons. To address this question we reviewed the records of twin and singleton pregnancies from Sunnybrook. We found that the association between these 2 conditions in twin pregnancies is similar to that in singletons ONLY when the diagnosis of fetal growth restriction in twins is done using twin-specific growth charts. Our findings suggest that the use of a twin-specific growth chart (rather than the same growth charts used in singleton pregnancies) should be used to diagnose fetal growth restriction in twin pregnancies.

Aviram A, Giltvedt MK, Sherman C, Kingdom J, Zaltz A, Barrett J, Melamed N. The role of placental malperfusion in the pathogenesis of preeclampsia in dichorionic twin and singleton pregnancies. Placenta. 2018 Oct;70:41-49. Click here for full paper.

In singleton mothers, hypertensive disorders of pregnancy (HDP), such as preeclampsia, are thought to be caused by an abnormal placental function, most commonly due to insufficient blood supply to the placenta. This placental disease, which is called maternal vascular malperfusion (MVM), can be identified on a pathological examination of the placenta under a microscope after birth. In an attempt to better understand the mechanisms of HDP in twin pregnancies, we compared the placentas of mothers who experienced HDP in twin vs. singleton pregnancies. We found that placentas from mothers with HDP in a twin pregnancy were less likely to be small and have MVMs than those from mothers with HDP in a singleton pregnancy. These findings provide support to our hypothesis that HDP in twin mothers may be caused by different factors than in singleton mothers.

Hiersch L, Barrett J, Fox NS, Rebarber A, Kingdom J, Melamed N. Should twin-specific growth charts be used to assess fetal growth in twin pregnancies? Am J Obstet Gynecol. 2022 Jul;227(1):10-28. Click here for full paper.

Van Mieghem T, Lewi L, Slaghekke F, Lopriore E, Yinon Y, Raio L, Baud D, Dekoninck P, Melamed N, Huszti E, Sun L, Shinar S, Collaborators. Prediction of fetal death in monochorionic twin pregnancies complicated by Type-III selective fetal growth restriction. Ultrasound Obstet Gynecol. 2022 Jun;59(6):756-762.  Click here for full paper.

Shinar S, Xing W, Lewi L, Slaghekke F, Yinon Y, Raio L, Baud D, DeKoninck P, Melamed N, Huszti E, Sun L, Van Mieghem T; Collaborators. Growth patterns of monochorionic twin pregnancy complicated by Type-III selective fetal growth restriction. Ultrasound Obstet Gynecol. 2022 Mar;59(3):371-376. Click here for full paper.

Ashwal E, Hiersch L, Berger H, Aviram A, Zaltz A, Kingdom J, Barrett J, Melamed N. Pathologic Basis for the Definition of Discordant Growth in Dichorionic Twins. Fetal Diagn Ther. 2021;48(4):279-287. Click here for full paper.

Twin fetuses face an increased risk of suboptimal growth and fetal growth restriction. One of the measures that aids clinicians in identifying twin fetuses that might be affected by such suboptimal growth is the difference in the size of the 2 co-twins, known as the intertwin size discordance (and is calculated as the difference in the weight of the 2 twins, divided by the weight of the larger twin, and expressed as %). However, there is an ongoing debate regarding the threshold of size difference that should raise a concern. While some studies suggested that the size discordance is concerning only when it exceeds 20-25%, others suggested that even smaller differences may be indicative of suboptimal growth of the smaller twin. In the current study we attempted to answer this question using a novel approach. We identified the threshold of intertwin size discordance that is associated with suboptimal growth by examining the placentas of the smaller twins for evidence of placental insufficiency. Based on this unique approach, we found discordant growth in dichorionic twins should raise the concern of fetal growth restriction of the smaller twin only when the discordance is greater than 25%.

Hiersch L, Barrett J, Aviram A, Mei-Dan E, Yoon EW, Zaltz A, Kingdom J, Melamed N. Patterns of discordant growth and adverse neonatal outcomes in twins. Am J Obstet Gynecol. 2021 Aug;225(2):187.e1-187.e14. Click here for full paper.

When twins are different sizes in the womb, this can be a risk factor for negative pregnancy outcomes. However, it is unclear whether the timing of the size difference and how fast the twins grow differently may affect the prognosis of the pregnancy. Therefore, we studied the medical records of all twin pregnancies at Sunnybrook between 2011 and 2020. We found that there are 4 distinct growth patterns among twins that are related to adverse outcomes. Multiple measurements seemed to be more informative than a single measurement of size difference.

Melamed N, Baschat A, Yinon Y, Athanasiadis A, Mecacci F, Figueras F, Berghella V, Nazareth A, Tahlak M, McIntyre HD, Da Silva Costa F, Kihara AB, Hadar E, McAuliffe F, Hanson M, Ma RC, Gooden R, Sheiner E, Kapur A, Divakar H, Ayres-de-Campos D, Hiersch L, Poon LC, Kingdom J, Romero R, Hod M. FIGO (international Federation of Gynecology and obstetrics) initiative on fetal growth: best practice advice for screening, diagnosis, and management of fetal growth restriction. Int J Gynaecol Obstet. 2021 Mar;152 Suppl 1(Suppl 1):3-57. Click here for full paper.

Fetal Growth Restriction (FGR) is defined as the failure of a fetus to reach its growth potential due to a pathological factor (most commonly, dysfunction of the placenta). FGR is a serious complication and can cause stillbirth, neonatal death, and short- and long-term complications. This study, performed through the FIGO (International Federation of Gynecology and Obstetrics), brought together worldwide leading experts to summarize the evidence-based recommendations evidence for how to diagnose and manage FGR, as well as indicates areas where research is needed to provide further recommendations. This article attempts to take into consideration the unique aspects of antenatal care in low-resource settings, through collaboration with authors and FIGO member societies from low-resource settings such as India, Sub-Saharan Africa, the Middle East, and Latin America.

Shinar S, Xing W, Pruthi V, Jianping C, Slaghekke F, Groene S, Lopriore E, Lewi L, Couck I, Yinon Y, Batsry L, Raio L, Amylidi-Mohr S, Baud D, Kneuss F, Dekoninck P, Moscou J, Barrett J, Melamed N, Ryan G, Sun L, Van Mieghem T. Outcome of monochorionic twin pregnancy complicated by Type-III selective intrauterine growth restriction. Ultrasound Obstet Gynecol. 2021 Jan;57(1):126-133. Click here for full paper.

Monochorionic diamniotic twins (babies that are identical and share a placenta but have two separate amniotic sacs) are at risk of several serious complications, one of which is selective fetal growth restriction (sFGR), where one of the babies is considerably smaller of the other. sFGR is classified into three types, of which type-III is the most severe and unpredictable type, where the smaller twin is at risk of sudden demise. The goal of this study (1/3 in a series of studies on this topic) was to describe and quantify the risk of fetal demise in these cases. The overall rate of fetal demise was 8.2%. The risk decreased with gestational age: it was 8.1% before 16 weeks, which decreased to <2% after 28 weeks, and to <1% after 33 weeks. In most cases, delivery was scheduled for 32 weeks.

Hiersch L, Okby R, Freeman H, Rosen H, Nevo O, Barrett J, Melamed N. Differences in fetal growth patterns between twins and singletons. J Matern Fetal Neonatal Med. 2020 Aug;33(15):2546-2555. Click here for full paper.

It is uncertain whether the slowing of growth of twins observed in the womb during the third trimester is a normal physiologic adaptation or an abnormality reflecting failure of the placenta to support 2 babies. We used data of all twin pregnancies born in Sunnybrook. We discovered that twin fetus growth slows down at around 26 weeks of pregnancy, and that some body parts such as the abdomen are affected more than others.

Weiner E, Kahn M, Giltvedt K, Kibel M, Sherman C, Kingdom J, Barrett J, Melamed N. Nonpresenting Dichorionic Twins and Placental Vascular Malperfusion. Obstet Gynecol. 2017 Jun;129(6):1109-1117. Click here for full paper.

Kibel M, Kahn M, Sherman C, Kingdom J, Zaltz A, Barrett J, Melamed N. Placental abnormalities differ between small for gestational age fetuses in dichorionic twin and singleton pregnancies. Placenta. 2017 Dec;60:28-35. Click here for full paper.

It has been found that twin fetuses grow slower during the third trimester compared with single-fetuses. However, it is unclear whether the smallness of twin fetuses is due to factors related to the placenta, which is the case when singleton growth is restricted in the womb. Therefore, we studied the medical records of the smallest babies born at Sunnybrook (both twins and single babies) between 2002 and 2015.  We compared twins to singletons and looked at the difference between negative outcomes in these groups. We discovered that what makes a baby grow slowly in a twin pregnancy may be different from what does this in a singleton pregnancy and may suggest that smallness in a twin pregnancy is not as serious as smallness in a single baby pregnancy.

Melamed N, Yogev Y, Glezerman M. Effect of fetal sex on pregnancy outcome in twin pregnancies. Obstet Gynecol. 2009 Nov;114(5):1085-1092. Click here for full paper.

It is uncertain whether there is a relationship between the sex of the fetuses and the outcome of the pregnancy in twin pregnancies. Therefore, we studied all twin pregnancies with babies in separate amniotic sacs between 1995-2006. We compared the outcomes of pregnancies with male-male twins, male-female twins, and female-female twin pairs. We found pregnancies with a female co-twin had better outcomes than those with a male co-twin.

Danon D, Melamed N, Bardin R, Meizner I. Accuracy of ultrasonographic fetal weight estimation in twin pregnancies. Obstet Gynecol. 2008 Oct;112(4):759-64. Click here for full paper.

The accuracy of ultrasounds to estimate fetal weight in twins that are growth restricted is unclear, as the formulas used to estimate fetal growth are based on singleton pregnancies. In this paper we compared ultrasounds performed on twin pregnancies to those performed on singleton pregnancies. We then analyzed both the whole group and only those with fetal growth restriction or major size differences between twins. The key finding of this paper is that the accuracy of the ultrasonographic estimated fetal weight seems to be lower for twin gestations than for singleton gestations, especially for second twins. These data should be considered by clinicians when making decisions based on ultrasonographic characteristics.

Lipworth H, Amir K, Arruda I, Fockler M, Jung E, Po L, Barrett J, Melamed N. A new care pathway to optimize gestational weight gain in twin pregnancies. Am J Obstet Gynecol MFM. 2023 Aug;5(8):101018. Click here for full paper.

Lipworth H, Barrett J, Murphy KE, Redelmeier D, Melamed N. Gestational weight gain in twin gestations and pregnancy outcomes: a systematic review and meta-analysis. BJOG. 2022 May;129(6):868-879. Click here for full paper.

Lipworth H, Melamed N, Berger H, Geary M, McDonald SD, Murray-Davis B, Murphy KE,  Redelmeier DA, Yoon EW, Barrett JFR, Ram M; Diabetes, Obesity, and Hypertension In Pregnancy Research Network Investigators. Maternal weight gain and pregnancy outcomes in twin gestations. Am J Obstet Gynecol. 2021 Nov;225(5):532.e1-532.e12. Click here for full paper.

Lipworth H, Melamed N, Berger H, Geary M, McDonald SD, Murray-Davis B, Murphy KE, Redelmeier DA, Yoon EW, Barrett JFR, Ram M; Diabetes, Obesity, and Hypertension In Pregnancy Research Network Investigators. Maternal weight gain and pregnancy outcomes in twin gestations. Am J Obstet Gynecol. 2021 May 10:S0002-9378(21)00547-0. Click here for full paper.

Peer-reviewed, scientific research papers about the optimal weight gain in twin pregnancies are limited. As a result, the international organizations that defines optimal weight gain in pregnancy (the Institute of Medicine) has only published interim recommendations for twins. Therefore, we aimed to identify the optimal range of weight gain in twin pregnancies. We studied the medical records of all twin pregnancies followed at Sunnybrook between 2000 and 2014. We studied the weight gain of twin pregnancies that had positive outcomes, and found that this weight gain was similar to the recommendations from the Institute of Medicine, except for those who were classified with an obese pre-pregnancy body mass index. For this group, our data showed a lower optimal weight gain range. Also, we found weight gain outside of recommendations was associated with negative outcomes such as preterm birth, low birth weight, and preeclampsia.

Ram M, Berger H, Lipworth H, Geary M, McDonald SD, Murray-Davis B, Riddell C, Hasan H, Barrett J, Melamed N; DOH-Net (Diabetes, Obesity and Hypertension in Pregnancy Research Network) and SOON (Southern Ontario Obstetrical Network) Investigators. The relationship between maternal body mass index and pregnancy outcomes in twin compared with singleton pregnancies. Int J Obes (Lond). 2020 Jan;44(1):33-44. Click here for full paper.

In singleton pregnancies, maternal body mass index (BMI) has been shown to be related to the risk of pregnancies complications. However, it remains unclear whether this relationship is also present in twins given the higher baseline risk of many of these complications in twins. Using provincial data from Ontario, we discovered that being classified as underweight (low BMI) during pregnancy is associated with an increased risk of preterm birth especially in twin pregnancies. At the same time, we found that the association of obesity with pregnancy complications is weaker in twin pregnancies than in singleton pregnancies.

Aviram A, Barrett J, Mei-Dan E, Yoon EW, Melamed N. A prediction tool for mode of delivery in twin pregnancies-a secondary analysis of the Twin Birth Study. Am J Obstet Gynecol. 2023 Nov 17:S0002-9378(23)02032-X. Click here for full paper.

Anabusi S, Aviram A, Melamed N, Asztalos E, Naeh A, Zaltz A, Barrett J, Mei-Dan E. Mild neonatal morbidity in twins by planned mode of delivery: a secondary analysis of the Twin Birth Study. Am J Obstet Gynecol MFM. 2023 Jul;5(7):100973. Click here for full paper.

Hochler H, Tevet A, Barg M, Suissa-Cohen Y, Lipschuetz M, Yagel S, Aviram A, Mei-Dan E, Melamed N, Barrett JFR, Fox NS, Walfisch A. Trial of labor of vertex-nonvertex twins following a previous cesarean delivery. Am J Obstet Gynecol MFM. 2022 Jul;4(4):100640. Click here for full paper.

Amikam U, Hiersch L, Barrett J, Melamed N. Labour induction in twin pregnancies. Best Pract Res Clin Obstet Gynaecol. 2022 Mar;79:55-69. Click here for full paper.

Aviram A, Barrett JFR, Melamed N, Mei-Dan E.Mode of delivery in multiple pregnancies. Am J Obstet Gynecol MFM. 2021 Aug 25:100470. Click here for full paper.

Whether twins should be born vaginally or via cesarean section has been the subject of debate over many years. The Twin Birth Study (TBS), a large, randomized controlled trial provided the groundwork for evidence-based recommendations, though further questions were left out of the scope of this study. The current recommendations are:

• A trial of labor in dichorionic-diamniotic (DCDA) or monochorionic-diamniotic (MCDA) twin pregnancies in which the first twin is head-down, at 32 weeks’ gestation or beyond
• DCDA twins should be delivered no later than 37-38 weeks of gestation
• MCDA twins no later than 36-37 weeks of gestation
• monochorionic-monoamniotic (MCMA) twins no later than 32-34 weeks of gestation
• Breech extraction done by a competent healthcare provider seems to offer the higher chance of a successful vaginal delivery of the second twin, compared with external cephalic version.
• For very preterm, low-birthweight twins, there is no clear recommendation for mode of delivery, however most studies do not show a benefit of cesarean section over a trial of labour
• A trial of labor seems safe in those with a previous cesarean delivery.
• Cesarean section is likely beneficial for twin gestation with: breech first twin, MCMA twins, and higher order multiple gestation.
• In all multiple gestations, the delivery should be undertaken by an experienced practitioner competent in those deliveries.

Hiersch L, Shah PS, Khurshid F, Masse E, Murphy K, McDonald SD, Carson G, Barrett J, Melamed N; Canadian Neonatal Network Investigators and the Canadian Preterm Birth Network Investigators. Mode of delivery and neonatal outcomes in extremely preterm Vertex/nonVertex twins. Am J Obstet Gynecol. 2020 Dec 9:S0002-9378(20)31368-5. Click here for full paper.

In cases of twins born very early in gestation, there is a concern that a vaginal delivery may be associated with an increased risk of birth trauma to the second twin, especially when the second twin is in breech presentation. We studied all very preterm twins born before 28 between 2010 and 2017 in level-3 NICUs across Canada. We found that in cases where the first twin was facing head-down but the second twin was breech, there was no difference in risk of negative outcomes for the babies if the patient has a vaginal birth or a cesarean birth. However, we found that nearly a third of the women who had a trial of vaginal delivery required urgent cesarean section for the second baby.

Aviram A, Lipworth H, Asztalos EV, Mei-Dan E, Melamed N, Cao X, Zaltz A, Hvidman L, Barrett JFR. Delivery of monochorionic twins: lessons learned from the Twin Birth Study. Am J Obstet Gynecol. 2020 Dec;223(6):916.e1-916.e9. Click here for full paper.

There is limited information about the recommended way to deliver monochorionic-diamniotic twins (twins that share a placenta). We used data collected from a large, international study comparing vaginal birth to cesarean birth in twin pregnancies. We concluded that in individuals with monochorionic twin pregnancies between 32 and 39 weeks, if the first baby is in head-down position, a planned cesarean birth does not raise or lower the risk of serious illness or death of the babies compared with vaginal birth.

Dougan C, Gotha L, Melamed N, Aviram A, Asztalos EV, Anabusi S, Willan AR, Barrett J, Mei-Dan E. Cesarean delivery or induction of labor in pre-labor twin gestations: a secondary analysis of the twin birth study. BMC Pregnancy Childbirth. 2020 Nov 17;20(1):702. Click here for full paper.

There has been uncertainty regarding whether an induction of labour or a planned cesarean delivery has better outcomes for the mother and baby. We used data collected from a large, international study comparing vaginal birth to cesarean birth in twin pregnancies. We concluded that in individuals with twin pregnancies between 32 and 39 weeks, both induction of labour and cesarean section prior to labour have similar outcomes for the health of the baby.

Aviram A, Lipworth H, Asztalos EV, Mei-Dan E, Cao X, Melamed N, Zaltz A, Anastasio HB, Berghella V, Barrett JFR. The worst of both worlds-combined deliveries in twin gestations: a subanalysis of the Twin Birth Study, a randomized, controlled, prospective study. Am J Obstet Gynecol. 2019 Oct;221(4):353.e1-353.e7. Click here for full paper.

It is uncertain how often a ‘combined twin delivery’ occurs (a birth in which the first twin is delivered vaginally and the second is delivered via emergency cesarean section). It is also uncertain what the risk factors and outcomes for this type of delivery are. Therefore, we used data collected from a large, international study comparing vaginal birth to cesarean birth in twin pregnancies. We found that if the second twin is lying sideways in the womb after the first twin has been delivered vaginally, this is a risk factor for the need to perform an emergency cesarean section for the second twin. When there is a need for a cesarean section for the second twin, this carries a higher risk of negative outcomes for the second baby.

Mei-Dan E, Dougan C, Melamed N, Asztalos EV, Aviram A, Willan AR, Barrett JFR. Planned cesarean or vaginal delivery for women in spontaneous labor with a twin pregnancy: A secondary analysis of the Twin Birth Study. Birth. 2019 Mar;46(1):193-200. Click here for full paper.

It is uncertain what the outcomes are of cesarean versus vaginal birth in twin pregnancies where patients arrive at the Birthing Unit in spontaneous labour. Using data from a large, international study, we found that in individuals with twin pregnancies who arrive to the Labour & Delivery department in active labour between 32 and 39 weeks of pregnancy, if the first twin is in head-down position, either a planned vaginal birth or planned cesarean birth are associated with similar outcomes.

Weiner E, Barrett J, Ram M, Lipworth H, Mizrachi Y, Bas Lando M, Melamed N. Delivery of the Nonpresenting Twin First: Rates and Associated Factors. Obstet Gynecol. 2018 Jun;131(6):1049-1056. Click here for full paper.

In a twin pregnancy, the twins are labelled “presenting” and “non-presenting” depending on their position in the womb. The “presenting” twin is lower down than the “non-presenting” twin, and is usually delivered first. In some cases, however, the non-presenting twin is delivered first. It is unclear how often this happens, and what the risks are for this event happening. Therefore, we studied all twins born between 2002 and 2016 at Sunnybrook where one twin was female and the other male. We wanted to study whether the twins ‘switched places’ between the time of ultrasound 2 weeks prior to birth and at the birth itself. We found in 6.8% of births, the twins switched places and the second twin was delivered first.

Rosen H, Barrett J, Okby R, Nevo O, Melamed N. Risk factors for obstetric anal sphincter injuries in twin deliveries: a retrospective review. Int Urogynecol J. 2016 May;27(5):757-62. Click here for full paper.

Sometimes during delivery, there are tears in the anal opening, called “obstetric anal sphincter injuries” or OASIS. The risk factors for these injuries are uncertain in twin pregnancies. Therefore, we studied the medical records of individuals with twin pregnancies who delivered vaginally at Sunnybrook between 2000-2014. We compared individuals who had injuries to their anal opening to those who did not. We found that individuals with twins who had birth assisted by forceps or vacuum were at higher risk of anal injuries.

Rosen H, Melamed N, Okby R, Nevo O, Barrett J. Is the risk of obstetric anal sphincter injuries increased in vaginal twin deliveries? J Matern Fetal Neonatal Med. 2016;29(10):1700-3. Click here for full paper.

In some deliveries, there are interventions necessary for the safe delivery of the baby, such as forceps or vacuum extraction. These interventions are more common in vaginal twin deliveries. It is uncertain whether these interventions in twin pregnancies are associated with more injuries to the anal sphincter compared to singleton pregnancies. Therefore, we studied the medical records of individuals with twin and singleton pregnancies who delivered vaginally at Sunnybrook between 2000-2014. We compared the rate of injuries to the anal opening in individuals with twins to those with single baby pregnancies. We found that though individuals with twins required more assistance (with forceps and vacuum), those who had single baby pregnancies experienced more anal opening injuries, mainly due to twin births having earlier delivery.

Melamed N, Wong J, Asztalos E, Rosen H, Okby R, Barrett J. The Likelihood of Change in Fetal Presentation During the Third Trimester in Twin Pregnancies. Obstet Gynecol. 2015 Dec;126(6):1231-1236. Click here for full paper.

Sometimes near the end of a pregnancy, one or both twins flip their position from head-down to feet-down or vice-versa. We wanted to look at the likelihood that one of the twins would flip around between the time of ultrasound and the birth. We studied data collected from a large, international study comparing vaginal birth to cesarean birth in twin pregnancies. We found that the likelihood of the lower twin (Twin A) flipping around after 32 weeks is low when they are in the head-down position, but is much higher for the upper twin even in the third trimester.

Melamed N, Avnon T, Barrett J, Fox N, Rebarber A, Shah BR, Halperin I, Retnakaran R, Berger H, Kingdom J, Hiersch L. Gestational diabetes in twin pregnancies-a pathology requiring treatment or a benign physiological adaptation? Am J Obstet Gynecol. 2024 Jan 12:S0002-9378(24)00012-7.  Click here for full paper.

Berezowsky A, Ardestani S, Hiersch L, Shah BR, Berger H, Halperin I, Retnakaran R, Barrett J, Melamed N. Glycemic control and neonatal outcomes in twin pregnancies with gestational diabetes mellitus. Am J Obstet Gynecol. 2023 Dec;229(6):682.e1-682.e13. Click here for full paper.

Hiersch L, Shah BR, Berger H, Geary M, McDonald SD, Murray-Davis B, Guan J, Halperin I, Retnakaran R, Barrett J, Melamed N. Screening Accuracy of the 50 g-Glucose Challenge Test in Twin Compared With Singleton Pregnancies. J Clin Endocrinol Metab. 2022 Sep 28;107(10):2854-2864. Click here for full paper.

Hiersch L, Shah BR, Berger H, Geary M, McDonald SD, Murray-Davis B, Halperin I, Retnakaran R, Barrett J, Melamed N; for DOH-NET (Diabetes, Obesity and Hypertension in Pregnancy Research Network) and SOON (Southern Ontario Obstetrical Network) Investigators. Oral Glucose Tolerance Test Results in Pregnancy Can Be Used to Individualize the Risk of Future Maternal Type 2 Diabetes Mellitus in Women With Gestational Diabetes Mellitus. Diabetes Care. 2021 Aug;44(8):1860-1867. Click here for full paper.

In this study, we aimed to quantify how at-risk a mother with gestational diabetes was for future type 2 diabetes mellitus (T2DM). We utilized the results from abnormal oral glucose tolerance tests (OGTT) and the criteria for diagnosis of GDM. The key findings of this study are that the risk of future maternal T2DM increased with the number of abnormal OGTT values and was highest for women with three abnormal values. The risk of future T2DM was also affected by the type of OGTT abnormality. These results may inform providers caring for those with GDM, as individualized information regarding the future risk of T2DM can be provided based on the type and number of abnormal OGTT values, as well as the diagnostic criteria used for the diagnosis of GDM.

Zhao G, Murphy KE, Berger H, Shah BR, Halperin I, Barrett J, Melamed N. The screening performance of glucose challenge test for gestational diabetes in twin pregnancies: a systematic review and meta-analysis. J Matern Fetal Neonatal Med. 2021 Jul 29:1-11. Click here for full paper.

The screening approach for gestational diabetes, which is based on a 50g glucose challenge test, has been well validated in singleton pregnancies. Given the physiologic differences and greater increase in insulin resistance in twin pregnancies, the performance of this screening approach in twin pregnancies may differ. In this paper we summarized available literature regarding the performance of the screening test for gestational diabetes in twin pregnancies. The key finding of this paper is that there are no data on how accurate this test is for the diagnosis of gestational diabetes in twins. This means that we do not how many cases of gestational diabetes in twin pregnancies are being missed. Therefore, there is an urgent need to validate current screening approach for gestational diabetes in twin pregnancies. Developing twin-specific 75-g oral glucose tolerance test diagnostic thresholds for gestational diabetes based on the risk of future maternal diabetes: a population-based cohort study.

Hiersch L, Shah BR, Berger H, Geary M, McDonald SD, Murray-Davis B, Guan J, Halperin I, Retnakaran R, Barrett J, Melamed N; for DOH-NET (Diabetes, Obesity, Hypertension in Pregnancy Research Network), SOON (Southern Ontario Obstetrical Network) Investigators™. DEVELOPING twin-specific 75-g oral glucose tolerance test diagnostic thresholds for gestational diabetes based on the risk of future maternal diabetes: a population-based cohort study. BJOG. 2021 May 25. Click here for full paper.

The current diagnostic criteria for gestational diabetes in twins are identical to those used in singleton pregnancies. However, there are considerable in glucose metabolism between twin and singleton pregnancies, one of which relates to the greater need of glucose and other nutrients by the 2 fetuses in cases of twin pregnancies. Therefore, it may well be that different, twin-specific criteria are needed to optimize the diagnosis of gestational diabetes in twin pregnancies, in part to avoid over-diagnosis of gestational diabetes in twins. The current study is the first to develop such twin-specific diagnostic criteria for gestational diabetes based on a novel approach and a large provincial dataset. Gestational diabetes and fetal growth in twin compared with singleton pregnancies.

Ashwal E, Berger H, Hiersch L, Yoon EW, Zaltz A, Shah B, Halperin I, Barrett J, Melamed N. Gestational diabetes and fetal growth in twin compared with singleton pregnancies. Am J Obstet Gynecol. 2021 Apr 17:S0002-9378(21)00454-3. Click here for full paper.

Gestational diabetes is associated with faster growth of the fetus in a singleton pregnancy, but may affect twins differently because they tend to grow slower during the third trimester, and are more likely to be affected by fetal growth restriction. Therefore, we studied all the medical records of twin pregnancies at Sunnybrook between 2011 and 2020. We found that twin pregnancies with gestational diabetes are less likely to be associated with accelerated fetal growth.

Hiersch L, Berger H, Okby R, Ray JG, Geary M, McDonald SD, Murray-Davis B, Riddell C, Halperin I, Hasan H, Barrett J, Melamed N; DOH-NET (Diabetes, Obesity and Hypertension in Pregnancy Research Network); SOON (Southern Ontario Obstetrical Network) Investigators. Gestational diabetes mellitus is associated with adverse outcomes in twin pregnancies. Am J Obstet Gynecol. 2019 Jan;220(1):102.e1-102.e8. Click here for full paper.

In singleton pregnancies, diabetes of pregnancy is associated with a risk of complications. In twins however, it is uncertain whether diabetes of pregnancy carries a similar risk for complications, in part due to the greater demands for glucose in the presence of two babies. We studied all twins and single babies born in Ontario between 2012-2016. We found that gestational diabetes in twin pregnancies was less likely to be associated with high blood pressure issues and certain negative outcomes for the baby, compared to in singleton pregnancies.

Hiersch L, Berger H, Okby R, Ray JG, Geary M, Mcdonald SD, Murry-Davis B, Riddell C, Halperin I, Hasan H, Barrett J, Melamed N; for DOH-NET (Diabetes, Obesity and Hypertension in Pregnancy Research Network) and SOON (Southern Ontario Obstetrical Network) Investigators™. Incidence and risk factors for gestational diabetes mellitus in twin versus singleton pregnancies. Arch Gynecol Obstet. 2018 Sep;298(3):579-587. Click here for full paper.

It is unclear whether the risk of diabetes of pregnancy, and how often it occurs, differs between singleton and twin pregnancies. We studied the medical records of all people who delivered either a single baby or twins in Ontario between 2012-2016. We found that twin pregnancies carry a higher risk for diabetes during pregnancy compared with singleton pregnancies. However, the effect of known risk factors for diabetes in pregnancy is similar to those who have singleton pregnancies.

Tward C, Barrett J, Berger H, Kibel M, Pittini A, Halperin I, Cohen H, Melamed N. Does gestational diabetes affect fetal growth and pregnancy outcome in twin pregnancies? Am J Obstet Gynecol. 2016 May;214(5):653.e1-8. Click here for full paper.

Twin pregnancies are at an increased risk for restricted fetal growth in the womb, which may be related to the shared resources by two babies. In addition, gestational diabetes (GDM) can cause accelerated fetal growth, so it is unclear whether this growth may counteract the restricted fetal growth in a twin pregnancy. Therefore, we studied the medical records of individuals with twin pregnancies who were checked in the clinic for gestational diabetes (diabetes of pregnancy) from 2003-2014. We found that there is a relationship between the severity of gestational diabetes and the twins growing to different sizes in the womb.

Yogev Y, Eisner M, Hiersch L, Hod M, Wiznitzer A, Melamed N. The performance of the screening test for gestational diabetes in twin versus singleton pregnancies. J Matern Fetal Neonatal Med. 2014 Jan;27(1):57-61. Click here for full paper.

Considering the differences between twin and singleton pregnancies with regards to weight and level of placental hormones, it is possible that the accuracy of the Glucose Challenge Test (that tests for gestational diabetes) may differ between twins and singletons. In this study, we compared the performance of two glucose tolerance tests (GCT and OGTT) in twin and singleton pregnancies. The main findings of this study are that the 50 g GCT appears to be associated with a higher false positive rate and a lower positive predictive value in twin compared with singleton pregnancies. The screening performance of glucose challenge test for gestational diabetes in twin pregnancies: a systematic review and meta-analysis.

Weitzner O, Barrett J, Murphy KE, Kingdom J, Aviram A, Mei-Dan E, Hiersch L, Ryan G, Van Mieghem T, Abbasi N, Fox NS, Rebarber A, Berghella V, Melamed N. National and international guidelines on the management of twin pregnancies: a comparative review. Am J Obstet Gynecol. 2023 Dec;229(6):577-598. Click here for full paper.

Mei-Dan E, Jain V, Melamed N, Lim KI, Aviram A, Ryan G, Barrett J(3). Guideline No. 428: Management of Dichorionic Twin Pregnancies. J Obstet Gynaecol Can. 2022 Jul;44(7):819-834.e1. Click here for full paper.

Hiersch L, Berger H, McDonald SD, Murray-Davis B, Abdulaziz KE, Geary M, Barrett J, Melamed N; for DOH-NET (Diabetes, Obesity, and Hypertension in Pregnancy Research Network) and SOON (Southern Ontario Obstetrical Network) Investigators. Maternal age and pregnancy outcomes in twin compared with singleton gestations. Int J Gynaecol Obstet. 2023 Aug;162(2):684-692. Click here for full paper.

Hiersch L, Attali E, Melamed N. Special considerations regarding antenatal care and pregnancy complications in dichorionic twin pregnancies. Am J Obstet Gynecol MFM. 2022 Mar;4(2S):100500. Click here for full paper.

Mashiach R, Anter D, Melamed N, Ben-Ezra M, Meizner I, Hamama-Raz Y. Psychological response to multifetal reduction and pregnancy termination due to fetal abnormality. J Matern Fetal Neonatal Med. 2013 Jan;26(1):32-5. Click here for full paper.