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Improving Perinatal Outcomes in Twin and Multiple Pregnancy
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Improving Perinatal Outcomes in Twin and Multiple Pregnancy

A special issue of Journal of Clinical Medicine (ISSN 2077-0383). This special issue belongs to the section "Obstetrics & Gynecology".

Deadline for manuscript submissions: closed (31 December 2020) | Viewed by 60766

Special Issue Editors

Prof. Asma Khalil

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Guest Editor
Fetal Medicine Unit, Department of Obstetrics & Gynaecology, St George's University Hospitals NHS Foundation Trust, University of London, Blackshaw Road, London SW17 0QT, UK
Interests: twin pregnancy; discordant anomalies in twins; selective fetal growth restriction; monochorionic twin pregnancy; twin-to-twin transfusion syndrome; twin anaemia polycythaemia sequence
Special Issues, Collections and Topics in MDPI journals
Prof. Dr. Enrico Lopriore

E-Mail Website
Guest Editor
Department of Pediatrics, Division of Neonatology, Leiden University Medical Center, Leiden, The Netherlands
Interests: monochorionic twins; twin–twin transfusion syndrome; twin anaemia polycythaemia sequence; neonatal haematology; anaemia; thrombocytopenia
Special Issues, Collections and Topics in MDPI journals
Prof. Liesbeth Lewi

E-Mail Website
Guest Editor
Department of Gynaecology and Obstetrics, University of Leuven, Leuven, Belgium
Interests: twin pregnancy; monochorionic twin pregnancy; twin-to-twin transfusion syndrome; twin reversed arterial perfusion; monoamniotic twins; twin anaemia polycythaemia sequence
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Multiple pregnancies are a major public health concern due to the significantly higher health risks for both mothers and newborns, as well as the impact on healthcare costs. Despite advances in antenatal care and prenatal diagnosis, twins and multiples remain high-risk pregnancies with excess perinatal mortality and morbidity. Advanced maternal age and assisted reproduction have led to an increase in the number of multiple pregnancies worldwide. Multiple pregnancies are overrepresented in stillbirth, neonatal death, and admission to the neonatal unit. Moreover, the risk of cerebral palsy is 6–7 times higher in twin and higher-order multiple pregnancies. Despite recent reports of a 50% reduction in stillbirth in twin pregnancies in some countries, the risk of complications remains high. It is estimated that twin pregnancies cost about five times more than singletons, while higher order multiple pregnancies cost nearly 20 times as much.

Over the past few years, a number of studies on the topic have been published, helping to provide a better understanding of the natural history and perinatal outcomes. However, it is also clear that much remains to be learned. The Global Twins and Multiples Priority Setting Partnership have identified the 10 most important research questions related to the future health of multiples and their families in 2019. These included assessment of growth patterns, short- and long-term outcomes, antenatal risk factors, medical interventions to reduce complications, and measures to reduce admission to the neonatal unit. With this Special Issue, we hope to encourage submissions that discuss the current state-of-the-art, address ongoing knowledge gaps, and focus on ongoing controversies related to twin and multiple pregnancies.

Prof. Asma Khalil
Prof. Enrico Lopriore
Prof. Liesbeth Lewi
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Journal of Clinical Medicine is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • Twin pregnancy
  • Selective fetal growth restriction
  • Stillbirth
  • Triplet pregnancy
  • Preterm birth
  • Twin to twin transfusion syndrome
  • Prenatal diagnosis

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9 pages, 1129 KiB  
Article
Perinatal Outcomes of Small for Gestational Age in Twin Pregnancies: Twin vs. Singleton Charts
by Veronica Giorgione, Corey Briffa, Carolina Di Fabrizio, Rohan Bhate and Asma Khalil
J. Clin. Med. 2021, 10(4), 643; https://doi.org/10.3390/jcm10040643 - 08 Feb 2021
Cited by 16 | Viewed by 3213
Abstract
Twin pregnancies are commonly assessed using singleton growth and birth weight reference charts. This practice has led to a significant number of twins labelled as small for gestational age (SGA), causing unnecessary interventions and increased risk of iatrogenic preterm birth. However, the use [...] Read more.
Twin pregnancies are commonly assessed using singleton growth and birth weight reference charts. This practice has led to a significant number of twins labelled as small for gestational age (SGA), causing unnecessary interventions and increased risk of iatrogenic preterm birth. However, the use of twin-specific charts remains controversial. This study aims to assess whether twin-specific estimated fetal weight (EFW) and birth weight (BW) charts are more predictive of adverse outcomes compared to singleton charts. Centiles of EFW and BW were calculated using previously published singleton and twin charts. Categorical data were compared using Chi-square or McNemar tests. The study included 1740 twin pregnancies, with the following perinatal adverse outcomes recorded: perinatal death, preterm birth <34 weeks, hypertensive disorders of pregnancy (HDP) and admissions to the neonatal unit (NNU). Twin-specific charts identified prenatally and postnatally a smaller proportion of infants as SGA compared to singleton charts. However, twin charts showed a higher percentage of adverse neonatal outcomes in SGA infants than singleton charts. For example, perinatal death (SGA 7.2% vs. appropriate for gestational age (AGA) 2%, p < 0.0001), preterm birth <34 weeks (SGA 42.1% vs. AGA 16.4%, p < 0.0001), HDP (SGA 21.2% vs. AGA 13.5%, p = 0.015) and NNU admissions (SGA 69% vs. AGA 24%, p < 0.0001), when compared to singleton charts (perinatal death: SGA 2% vs. AGA 1%, p = 0.029), preterm birth <34 weeks: (SGA 20.6% vs. AGA 17.4%, p = 0.020), NNU admission: (SGA 34.5% vs. AGA 23.9%, p < 0.000). There was no significant association between HDP and SGA using the singleton charts (p = 0.696). In SGA infants, according to the twin charts, the incidence of abnormal umbilical artery Doppler was significantly more common than in SGA using the singleton chart (27.0% vs. 8.1%, p < 0.001). In conclusion, singleton charts misclassify a large number of twins as at risk of fetal growth restriction. The evidence suggests that the following twin-specific charts could reduce unnecessary medical interventions prenatally and postnatally. Full article
(This article belongs to the Special Issue Improving Perinatal Outcomes in Twin and Multiple Pregnancy)
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9 pages, 1432 KiB  
Article
Clinical Significance of Velamentous Cord Insertion Prenatally Diagnosed in Twin Pregnancy
by Hyun-Mi Lee, SiWon Lee, Min-Kyung Park, You Jung Han, Moon Young Kim, Hye Yeon Boo and Jin Hoon Chung
J. Clin. Med. 2021, 10(4), 572; https://doi.org/10.3390/jcm10040572 - 03 Feb 2021
Cited by 8 | Viewed by 6040
Abstract
Background: The purpose of this study was to evaluate the prevalence of velamentous cord insertion (VCI) and the actual association between pathologically confirmed VCI and perinatal outcomes in twins based on the chorionicity. Methods: All twin pregnancies that received prenatal care at a [...] Read more.
Background: The purpose of this study was to evaluate the prevalence of velamentous cord insertion (VCI) and the actual association between pathologically confirmed VCI and perinatal outcomes in twins based on the chorionicity. Methods: All twin pregnancies that received prenatal care at a specialty clinic for multiple pregnancies, from less than 12 weeks of gestation until delivery in a single institution between 2015 and 2018 were included in this retrospective cohort study. Results: A total of 941 twins were included in the study. The prevalence of VCI in dichorionic (DC) twins and monochorionic diamniotic (MCDA) twins was 5.8% and 7.8%, respectively (p = 0.251). In all study population, the prevalence of vasa previa and placenta accreta spectrum was higher in VCI group than that of non-VCI group (p = 0.008 and 0.022). In MCDA twins with VCI, birth weight, 1 and 5-min Apgar score were lower than DC twins with VCI (p = 0.010, 0.002 and 0.000). There was no significant association between VCI and selective fetal growth restriction (p = 0.486), twin-to-twin transfusion syndrome (p = 0.400), and birth-weight discordance (>20% and >25%) (p = 0.378 and 0.161) in MCDA twins. Conclusion: There was no difference in the incidence of VCI in twins based on the chorionicity. Moreover, VCI was not a risk factor for adverse perinatal outcomes excepting vasa previa and placenta accreta spectrum, which had a high incidence in twins with VCI. Full article
(This article belongs to the Special Issue Improving Perinatal Outcomes in Twin and Multiple Pregnancy)
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10 pages, 552 KiB  
Article
Clinical Utility of Increased Nuchal Translucency at 11–13 Weeks of Gestation in Twin Pregnancies Based on the Chorionicity
by SiWon Lee, Hyun-Mi Lee, You Jung Han, Moon Young Kim, Hye Yeon Boo and Jin Hoon Chung
J. Clin. Med. 2021, 10(3), 433; https://doi.org/10.3390/jcm10030433 - 23 Jan 2021
Cited by 2 | Viewed by 1935
Abstract
To assess clinical implications of increased nuchal translucency (INT) in twin pregnancies based on the chorionicity. This was a retrospective review of the twin pregnancies who underwent first trimester ultrasound with nuchal translucency (NT) measurement at 11–13 weeks of gestation from January 2006 [...] Read more.
To assess clinical implications of increased nuchal translucency (INT) in twin pregnancies based on the chorionicity. This was a retrospective review of the twin pregnancies who underwent first trimester ultrasound with nuchal translucency (NT) measurement at 11–13 weeks of gestation from January 2006 to December 2014. Data were collected using the OB database and the chart review. Pregnancy outcomes, including gestational weeks at the delivery, abnormal fetal karyotypes, fetal structural anomalies, and twin-specific complications, were analyzed. A total of 1622 twin pregnancies with INT ≥ 95th percentile in one or both fetuses were identified. In all twin pregnancies with INT, abnormal fetal karyotypes were identified in 17 (8.6%) patients (odds ratio = 13.28, CI = 5.990–29.447, p = 0.000) and twin-specific complications were identified in 23 (11.6%) patients (odds ratio = 2.398, CI = 1.463–3.928, p = 0.001) compared to those with normal NT. Among the INT group, when the groups were subdivided into monochorionic (MC) and dichorionic (DC) pregnancies, 14.8% and 29.6% of the MC pregnancies had structural anomalies in one or both fetuses (odds ratio = 5.774, 95% CI = 1.445–23.071, p = 0.01) and twin-specific complications (odds ratio = 4.379, 95% CI = 1.641–11.684, p = 0.03), respectively, compared to DC pregnancies with 2.9% for structural anomalies and 8.8% for twin-specific complications. The prevalence of abnormal fetal karyotypes was not statistically different in patients with INT when compared between MC and DC pregnancies (p = 0.329). INT was associated with a higher rate of twin-specific complications and fetal structural anomalies in MC twin pregnancies rather than abnormal fetal karyotype. Therefore, NT measurement in MC twin pregnancies can be a useful tool for predicting adverse pregnancy outcomes. Appropriate counseling and surveillance based on the chorionicity are imperative in the prenatal care of twin pregnancies. Full article
(This article belongs to the Special Issue Improving Perinatal Outcomes in Twin and Multiple Pregnancy)
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14 pages, 1312 KiB  
Article
Uncomplicated Monochorionic Twins: Two Normal Hearts Sharing One Placenta
by Ximena Torres, Mar Bennasar, Laura García-Otero, Raigam J. Martínez-Portilla, Brenda Valenzuela-Alcaraz, Fátima Crispi, Anna Goncé, Eduard Gratacós, Francesc Figueras and Josep M. Martínez
J. Clin. Med. 2020, 9(11), 3602; https://doi.org/10.3390/jcm9113602 - 09 Nov 2020
Cited by 7 | Viewed by 3175
Abstract
Cardiovascular dysfunction has been reported in complicated monochorionic diamniotic (MCDA) pregnancies; however, little is known whether hemodynamic changes occur in uncomplicated MCDA twins. A prospective observational study was conducted including 100 uncomplicated MCDA twins matched by gestational age to 200 low-risk singletons. Echocardiography [...] Read more.
Cardiovascular dysfunction has been reported in complicated monochorionic diamniotic (MCDA) pregnancies; however, little is known whether hemodynamic changes occur in uncomplicated MCDA twins. A prospective observational study was conducted including 100 uncomplicated MCDA twins matched by gestational age to 200 low-risk singletons. Echocardiography was performed at 26–30 weeks gestation and cord blood B-type natriuretic peptide (BNP) was measured at delivery. In both groups, z-scores for echocardiographic parameters were within normal ranges; however the monochorionic group had larger atrial areas (mean (standard deviation) right atria-to-heart ratio: 17.0 (2) vs. 15.9 (1); p = 0.018; left atria-to-heart ratio: 17.0 (3) vs. 15.8 (2); p < 0.001) and signs of concentric hypertrophy (right relative wall thickness: 0.66 (0.12) vs. 0.56 (0.11); p < 0.001; left relative wall thickness: 0.69 (0.14) vs. 0.58 (0.12); p < 0.001). Longitudinal function was increased in twins, leading to higher tricuspid annular plane systolic excursion (6.9 mm (0.9) vs. 5.9 mm (0.7); p < 0.001) and mitral annular plane systolic excursion (4.9 mm (0.8) vs. 4.4 mm (1.1); p < 0.001. BNP levels at birth were also higher in MCDA twins (median [interquartile range]: 20.81 pg/mL [16.69–34.01] vs. 13.14 pg/mL [9.17–19.84]; p < 0.001). Thus, uncomplicated MCDA fetuses have normal cardiac shape and function, but signs of cardiac adaptation were identified by echocardiographic and biochemical parameters, when compared with singletons. Full article
(This article belongs to the Special Issue Improving Perinatal Outcomes in Twin and Multiple Pregnancy)
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10 pages, 239 KiB  
Article
Are Twin Pregnancies Complicated by Weight Discordance or Fetal Growth Restriction at Higher Risk of Preeclampsia?
by Veronica Giorgione, Amar Bhide, Rohan Bhate, Keith Reed and Asma Khalil
J. Clin. Med. 2020, 9(10), 3276; https://doi.org/10.3390/jcm9103276 - 13 Oct 2020
Cited by 20 | Viewed by 2732
Abstract
Studies have reported controversial findings on the association between fetal growth restriction (FGR) or intertwin weight discordance and the risk of hypertensive disorders of pregnancy (HDP) in twin pregnancies. The aim of this study was to investigate the association between twin growth disorders [...] Read more.
Studies have reported controversial findings on the association between fetal growth restriction (FGR) or intertwin weight discordance and the risk of hypertensive disorders of pregnancy (HDP) in twin pregnancies. The aim of this study was to investigate the association between twin growth disorders and HDP. Twin pregnancies resulting in two live births at St George’s Hospital between 2000 and 2019 were included. FGR or small-for-gestational-age (SGA) at birth was assessed using singleton and twin reference charts. Intertwin discordance [(large birthweight − small birthweight)/(large birthweight) × 100%)] was calculated. Logistic regression models were performed. SGA (aOR 2.34, 95% CI 1.60–3.44, p < 0.001), intertwin discordance ≥25% (aOR 2.10, 95% CI 1.26–3.49, p = 0.004) and their co-existence (aOR 2.03, 95% CI 1.16–3.54, p = 0.013) were significantly associated with HDP. After adjusting for the known maternal risk factors of HDP and the intertwin discordance, SGA (using the twin charts) was the strongest independent risk factor associated with HDP (aOR 2.12, 95% CI 1.40–3.22, p < 0.001) and preeclampsia (aOR 2.34, 95% CI 1.45–3.76, p < 0.001). This study highlights that the presence of at least one SGA twin is significantly associated with HDP during pregnancy. Therefore, maternal blood pressure should be closely monitored in twin pregnancies complicated by SGA with or without intertwin discordance. Full article
(This article belongs to the Special Issue Improving Perinatal Outcomes in Twin and Multiple Pregnancy)
12 pages, 865 KiB  
Article
Performance of Antenatal Diagnostic Criteria of Twin-Anemia-Polycythemia Sequence
by Becky Liu, Erkan Kalafat, Amar Bhide, Basky Thilaganathan and Asma Khalil
J. Clin. Med. 2020, 9(9), 2754; https://doi.org/10.3390/jcm9092754 - 26 Aug 2020
Cited by 6 | Viewed by 2507
Abstract
This study aims to elicit the validation performance of different diagnostic criteria and to evaluate the disease course and perinatal outcomes of pregnancies complicated by twin anemia polycythemia sequence (TAPS). Monochorionic diamniotic (MCDA) twin pregnancies who received serial middle cerebral artery (MCA) peak [...] Read more.
This study aims to elicit the validation performance of different diagnostic criteria and to evaluate the disease course and perinatal outcomes of pregnancies complicated by twin anemia polycythemia sequence (TAPS). Monochorionic diamniotic (MCDA) twin pregnancies who received serial middle cerebral artery (MCA) peak systolic velocity (PSV) measurements without non-TAPS-related demise or major anomalies were included. Course of disease, antenatal intervention, additional ultrasound features, and perinatal outcomes were compared between each criteria and onset. Forty-nine cases of TAPS and 203 non-TAPS controls were identified. The incidence of TAPS was 19.2%, 15.7%, 7.8%, and 6.3% for ΔPSV MoM > 0.373, ΔPSV MoM > 0.5, traditional, and Delphi consensus criteria, respectively (p < 0.001). The incidence of antenatal intervention was 55.1, 62.5, 75.0, and 87.5%, respectively. Furthermore, cases detected according to the Delphi consensus criteria had a higher rate of progression or intervention compared to cases detected with ΔPSV MoM > 0.373 (87.0 vs. 59.0%, p = 0.037). TAPS had a significantly higher birth weight discordance than uncomplicated MCDA twins (25.3 vs. 7.3%, p < 0.001). Application of four different diagnostic criteria for TAPS leads to significant differences in the incidence, severity, and antenatal intervention. The Delphi criteria identified more severe cases likely to require intervention, and the delta PSV > 0.373 criteria identified milder cases, without a significant impact on neonatal outcomes. Full article
(This article belongs to the Special Issue Improving Perinatal Outcomes in Twin and Multiple Pregnancy)
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9 pages, 637 KiB  
Article
Notching and Pulsatility Index of the Uterine Arteries and Preeclampsia in Twin Pregnancies
by Stephanie Springer, Mariella Polterauer, Maria Stammler-Safar, Harald Zeisler, Heinz Leipold, Christof Worda and Katharina Worda
J. Clin. Med. 2020, 9(8), 2653; https://doi.org/10.3390/jcm9082653 - 15 Aug 2020
Cited by 3 | Viewed by 2822
Abstract
Increased uterine artery Doppler indices have been shown to be associated with preeclampsia and adverse pregnancy outcomes in singleton and twin pregnancies. At 20–22 weeks of gestation, we assessed the use of notching, the highest, lowest, and mean pulsatility index (PI), and the [...] Read more.
Increased uterine artery Doppler indices have been shown to be associated with preeclampsia and adverse pregnancy outcomes in singleton and twin pregnancies. At 20–22 weeks of gestation, we assessed the use of notching, the highest, lowest, and mean pulsatility index (PI), and the combination of notching and PI of the uterine arteries to screen for preeclampsia. This was done in a cohort of 380 twin pregnancies. The results showed that the combination of notching and the highest PI above the 95th centile of the uterine arteries gives the best screening characteristics for preeclampsia in twin pregnancies. We calculated sensitivities for preeclampsia for notching, highest PI, and the combination of notching and the highest PI of 50%, 45% and 91%, with specificities of 96%, 96% and 93%, respectively. The present findings demonstrate that notching, increased highest PI, and the combination of notching and the highest PI of the uterine arteries is associated with an increased risk of preeclampsia in twin pregnancies. We observed the highest sensitivity and specificity by using the combination of notching and the highest PI of the uterine arteries. Full article
(This article belongs to the Special Issue Improving Perinatal Outcomes in Twin and Multiple Pregnancy)
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11 pages, 405 KiB  
Article
The Association Between Hypertension in Pregnancy and Preterm Birth with Fetal Growth Restriction in Singleton and Twin Pregnancy: Use of Twin Versus Singleton Charts
by Erkan Kalafat, Aisha Abiola, Basky Thilaganathan, Amar Bhide and Asma Khalil
J. Clin. Med. 2020, 9(8), 2518; https://doi.org/10.3390/jcm9082518 - 05 Aug 2020
Cited by 15 | Viewed by 3084
Abstract
Objective: To compare the rates of fetal growth restriction (FGR) in singleton and twin pregnancies using singleton and twin-specific birthweight standards. Methods: The study included liveborn twin and singleton pregnancies between January 2000 and January 2019. Hypertensive disorders of pregnancy (HDP) included gestational [...] Read more.
Objective: To compare the rates of fetal growth restriction (FGR) in singleton and twin pregnancies using singleton and twin-specific birthweight standards. Methods: The study included liveborn twin and singleton pregnancies between January 2000 and January 2019. Hypertensive disorders of pregnancy (HDP) included gestational hypertension and pre-eclampsia. The study outcomes were FGR or small-for-gestational-age (SGA) at birth as assessed using singleton and twin reference charts. Results: The analysis included 1473 twin and 62,432 singleton pregnancies. In singleton pregnancies the risk of PTB <34 weeks without HDP (OR 2.82, p < 0.001), delivery ≥34 weeks with HDP (OR 2.38, p < 0.001), and PTB <34 weeks with HDP (OR 13.65, p < 0.001) were significantly higher in the pregnancies complicated by FGR compared to those without. When selective fetal growth restriction (sFGR) was assessed using the singleton standard, the risk of PTB <34 weeks without HDP (OR 1.03, p = 0.872), delivery ≥34 weeks with HDP (OR 1.36, p = 0.160) were similar in the pregnancies complicated by sFGR compared to those without, while the risk of PTB <34 weeks with HDP (OR 2.41, p = 0.025) was significantly higher in the pregnancies complicated by sFGR compared to those without. When sFGR was assessed using the twin-specific chart, the risk of PTB <34 weeks without HDP (OR 3.55, p < 0.001), delivery ≥34 weeks with HDP (OR 3.17, p = 0.004), and PTB <34 weeks with HDP (OR 5.69, p < 0.001) were significantly higher in the pregnancies complicated by sFGR compared to those without. The stronger and more consistent association persisted in the subgroup analyses according to chorionicity. The strength of association in dichorionic twin pregnancies resembles that of the singletons more closely and consistently when the FGR was diagnosed using the twin-specific charts. Conclusion: FGR in twin pregnancies has a stronger and more consistent association with HDP and PTB when using twin-specific rather than singleton charts. This study provides further evidence supporting the use of twin-specific charts when assessing fetal growth in twin pregnancies. Full article
(This article belongs to the Special Issue Improving Perinatal Outcomes in Twin and Multiple Pregnancy)
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11 pages, 277 KiB  
Article
Vaginal Progesterone Has No Diabetogenic Potential in Twin Pregnancies: A Retrospective Case-Control Study on 1686 Pregnancies
by Klara Rosta, Katharina Al-Bibawy, Maria Al-Bibawy, Wilhelm Temsch, Stephanie Springer, Aniko Somogyi and Johannes Ott
J. Clin. Med. 2020, 9(7), 2249; https://doi.org/10.3390/jcm9072249 - 15 Jul 2020
Cited by 1 | Viewed by 1763
Abstract
Background: In this study, we aimed to investigate the incidence of gestational diabetes mellitus (GDM) in women who carried twin pregnancies and received vaginal progesterone. Methods: In this retrospective cohort study, 203 out of 1686 women with twin pregnancies received natural progesterone (200 [...] Read more.
Background: In this study, we aimed to investigate the incidence of gestational diabetes mellitus (GDM) in women who carried twin pregnancies and received vaginal progesterone. Methods: In this retrospective cohort study, 203 out of 1686 women with twin pregnancies received natural progesterone (200 mg/day between gestational weeks 16 + 0 and 36 + 0) vaginally for ≥ 4 weeks. The control group consisted of 1483 women with twin pregnancies without progesterone administration. Pearson’s Chi squared test, Fisher’s exact test, and Student’s t-test was used to compare differences between the control and the progesterone-treated groups. A multivariate binary logistic regression was performed to assess relative independent associations on the dependent outcome of GDM incidence. Results: Vaginal progesterone treatment in twin pregnancies had no significant influence on developing GDM (p = 0.662). Higher pre-pregnancy BMI (OR 1.1; p < 0.001), GDM in previous pregnancy (OR 6.0; p < 0.001), and smoking during pregnancy (OR 1.6; p = 0.014) posed an increased risk for developing GDM. Conclusion: In twin pregnancies, the use of vaginal progesterone for the prevention of recurrent preterm delivery was not associated with an increased risk of GDM. Full article
(This article belongs to the Special Issue Improving Perinatal Outcomes in Twin and Multiple Pregnancy)
9 pages, 535 KiB  
Article
Both Low and High PAPP-A Concentrations in the First Trimester of Pregnancy Are Associated with Increased Risk of Delivery before 32 Weeks in Twin Gestation
by Aleksandra Saletra-Bielińska, Katarzyna Kosińska-Kaczyńska, Iwona Szymusik, Bartosz Kaczyński, Robert Brawura-Biskupski-Samaha, Szymon Kozłowski, Patrycja Jarmużek, Izabela Walasik and Mirosław Wielgoś
J. Clin. Med. 2020, 9(7), 2099; https://doi.org/10.3390/jcm9072099 - 03 Jul 2020
Cited by 1 | Viewed by 7366
Abstract
In twin gestation, the relationship between pregnancy associated plasma protein (PAPP-A) and perinatal outcome is unclear. The aim of the study was to determine if low and high concentrations of PAPP-A in the first trimester are related to perinatal outcome in twins. A [...] Read more.
In twin gestation, the relationship between pregnancy associated plasma protein (PAPP-A) and perinatal outcome is unclear. The aim of the study was to determine if low and high concentrations of PAPP-A in the first trimester are related to perinatal outcome in twins. A retrospective study was conducted. Medical data of women in twin pregnancies who delivered between 2013 and 2018 were analyzed. PAPP-A concentrations were measured between 10 + 0 and 13 + 6 weeks. The associations between low (<10th percentile) and high (>90th percentile) values of PAPP-A and pregnancy complications were analyzed. A total of 304 patients were included. PAPP-A <10th percentile was associated with a high risk of preterm delivery (OR 6.14; 95% CI 2.1–18), delivery <34 weeks (OR 2.39; 95% CI 1.1–5.1) or <32 weeks (OR3.06; 95% CI 1.4–6.8). Significant relations between PAPP-A >90th percentile and delivery <34 weeks (OR4.09; 95% CI 1.8–9.1) or <32 weeks (OR 2.83; 95% CI 1.2–6.6) were found. PAPP-A >90th percentile was related to high risk of intrauterine fetal demise (OR 10; 95% CI 2.4–42.5). Both low and high PAPP-A concentrations seem to be related to pregnancy outcome. Further research is needed to investigate evaluation of risk of pregnancy complications according to PAPP-A concentrations as a continuous variable. Full article
(This article belongs to the Special Issue Improving Perinatal Outcomes in Twin and Multiple Pregnancy)
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10 pages, 823 KiB  
Article
Amniodrainage-Induced Circulatory Dysfunction in Women Treated for Twin-To-Twin Transfusion Syndrome
by Patrick Greimel, Philipp Klaritsch, Holger Simonis, Bence Csapó, Maximilian Pohl and Daniel Schneditz
J. Clin. Med. 2020, 9(7), 2085; https://doi.org/10.3390/jcm9072085 - 02 Jul 2020
Cited by 2 | Viewed by 1928
Abstract
Twin-to-twin transfusion syndrome (TTTS) in monochorionic-diamniotic twin pregnancies usually requires fetoscopic laser ablation (FLA) followed by amniodrainage (AD). Perioperative maternal hemodynamic changes and hemodilution have been observed. Little is known about the underlying pathophysiology. We aimed to evaluate the impact of high volume [...] Read more.
Twin-to-twin transfusion syndrome (TTTS) in monochorionic-diamniotic twin pregnancies usually requires fetoscopic laser ablation (FLA) followed by amniodrainage (AD). Perioperative maternal hemodynamic changes and hemodilution have been observed. Little is known about the underlying pathophysiology. We aimed to evaluate the impact of high volume amniodrainage on intrauterine pressure, placental thickness and maternal blood characteristics. A total of 18 cases of TTTS were included in this prospective pilot study. All patients were treated with FLA and subsequent AD. Intrauterine pressure and placental thickness were assessed before, during and after amniodrainage. Maternal hemoglobin, hematocrit and serum albumin were measured at admission and 24 h after the intervention. Amniodrainage led to a decrease in mean intrauterine pressure (from 30.1 ± 8.1 mmHg to 17.6 ± 3.6 mmHg (p < 0.001)) and an increase in mean placental thickness (from 16.8 ± 6.4 mm to 31.83 ± 8.64 mm (p < 0.001)). There was a positive correlation between changes in placental thickness and the amount of amniodrainage during intervention (Pearson’s Rho 0.73; p = 0.001). Hematocrit decreased from 33.4 ± 3.8 (%) to 28.4 ± 3.5 (%), i.e., an increase in relative blood volume by 18 ± 10.2% (p < 0.001). Albumin decreased from 37.9 ± 0.9 g/L to 30.7 ± 2.2 g/L, i.e., an increase in relative plasma volume by 24 ± 8.1% (p < 0.001). Amniodrainage leads to uterine decompression, increased placental thickness and subsequent maternal hemodilution. We propose the term “amniodrainage-induced circulatory dysfunction” for these specific maternal hemodynamic changes in the treatment of twin-to-twin transfusion syndrome. Full article
(This article belongs to the Special Issue Improving Perinatal Outcomes in Twin and Multiple Pregnancy)
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10 pages, 2788 KiB  
Article
The Predictive Value of the Cervical Consistency Index to Predict Spontaneous Preterm Birth in Asymptomatic Twin Pregnancies at the Second-Trimester Ultrasound Scan: A Prospective Cohort Study
by Johannes van der Merwe, Isabel Couck, Francesca Russo, Xavier P. Burgos-Artizzu, Jan Deprest, Montse Palacio and Liesbeth Lewi
J. Clin. Med. 2020, 9(6), 1784; https://doi.org/10.3390/jcm9061784 - 08 Jun 2020
Cited by 8 | Viewed by 4173
Abstract
Novel transvaginal ultrasound (TVU) markers have been proposed to improve spontaneous preterm birth (sPTB) prediction. Preliminary results of the cervical consistency index (CCI), uterocervical angle (UCA), and cervical texture (CTx) have been promising in singletons. However, in twin pregnancies, the results have been [...] Read more.
Novel transvaginal ultrasound (TVU) markers have been proposed to improve spontaneous preterm birth (sPTB) prediction. Preliminary results of the cervical consistency index (CCI), uterocervical angle (UCA), and cervical texture (CTx) have been promising in singletons. However, in twin pregnancies, the results have been inconsistent. In this prospective cohort study of asymptomatic twin pregnancies assessed between 18+0–22+0 weeks, we evaluated TVU derived cervical length (CL), CCI, UCA, and the CTx to predict sPTB < 34+0 weeks. All iatrogenic PTB were excluded. In the final cohort of 63 pregnancies, the sPTB rate < 34+0 was 16.3%. The CCI, UCA, and CTx, including the CL was significantly different in the sPTB < 34+0 weeks group. The best area under the receiver operating characteristic curve (AUC) for sPTB < 34+0 weeks was achieved by the CCI 0.82 (95%CI, 0.72–0.93), followed by the UCA with AUC 0.72 (95%CI, 0.57–0.87). A logistic regression model incorporating parity, chorionicity, CCI, and UCA resulted in an AUC of 0.91 with a sensitivity of 55.3% and specificity of 88.1% for predicting sPTB < 34+0. The CCI performed better than other TVU markers to predict sPTB < 34+0 in twin gestations, and the best diagnostic accuracy was achieved by a combination of parity, chorionicity, CCI, and UCA. Full article
(This article belongs to the Special Issue Improving Perinatal Outcomes in Twin and Multiple Pregnancy)
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15 pages, 513 KiB  
Article
Post-Laser Twin Anemia Polycythemia Sequence: Diagnosis, Management, and Outcome in an International Cohort of 164 Cases
by Lisanne S.A. Tollenaar, Enrico Lopriore, Stefano Faiola, Mariano Lanna, Julien Stirnemann, Yves Ville, Liesbeth Lewi, Roland Devlieger, Anne Sophie Weingertner, Romain Favre, Sebastian R. Hobson, Greg Ryan, Carlota Rodo, Silvia Arévalo, Philipp Klaritsch, Patrick Greimel, Kurt Hecher, Manuela Tavares de Sousa, Asma Khalil, Basky Thilaganathan, Eric P. Bergh, Ramesha Papanna, Glenn J. Gardener, Andrew Carlin, Elisa Bevilacqua, Victorya A. Sakalo, Kirill V. Kostyukov, Mert O. Bahtiyar, Abigail Wilpers, Mark D. Kilby, Eleonor Tiblad, Dick Oepkes, Johanna M. Middeldorp, Monique C. Haak, Frans J.C.M. Klumper, Joost Akkermans and Femke Slaghekkeadd Show full author list remove Hide full author list
J. Clin. Med. 2020, 9(6), 1759; https://doi.org/10.3390/jcm9061759 - 05 Jun 2020
Cited by 19 | Viewed by 4742
Abstract
The aim of this study was to investigate the management and outcome in the post-laser twin anemia polycythemia sequence (TAPS). Data of the international TAPS Registry, collected between 2014 and 2019, were used for this study. The primary outcomes were perinatal mortality and [...] Read more.
The aim of this study was to investigate the management and outcome in the post-laser twin anemia polycythemia sequence (TAPS). Data of the international TAPS Registry, collected between 2014 and 2019, were used for this study. The primary outcomes were perinatal mortality and severe neonatal morbidity. Secondary outcomes included a risk factor analysis for perinatal mortality and severe neonatal morbidity. A total of 164 post-laser TAPS pregnancies were included, of which 92% (151/164) were diagnosed antenatally and 8% (13/164) postnatally. The median number of days between laser for TTTS and detection of TAPS was 14 (IQR: 7–28, range: 1–119). Antenatal management included expectant management in 43% (62/151), intrauterine transfusion with or without partial exchange transfusion in 29% (44/151), repeated laser surgery in 15% (24/151), selective feticide in 7% (11/151), delivery in 6% (9/151), and termination of pregnancy in 1% (1/151). The median gestational age (GA) at birth was 31.7 weeks (IQR: 28.6–33.7; range: 19.0–41.3). The perinatal mortality rate was 25% (83/327) for the total group, 37% (61/164) for donors, and 14% (22/163) for recipients (p < 0.001). Severe neonatal morbidity was detected in 40% (105/263) of the cohort and was similar for donors (43%; 51/118) and recipients (37%; 54/145), p = 0.568. Independent risk factors for spontaneous perinatal mortality were antenatal TAPS Stage 4 (OR = 3.4, 95%CI 1.4-26.0, p = 0.015), TAPS donor status (OR = 4.2, 95%CI 2.1–8.3, p < 0.001), and GA at birth (OR = 0.8, 95%CI 0.7–0.9, p = 0.001). Severe neonatal morbidity was significantly associated with GA at birth (OR = 1.5, 95%CI 1.3–1.7, p < 0.001). In conclusion, post-laser TAPS most often occurs within one month after laser for TTTS, but may develop up to 17 weeks after initial surgery. Management is mostly expectant, but varies greatly, highlighting the lack of consensus on the optimal treatment and heterogeneity of the condition. Perinatal outcome is poor, particularly due to the high rate of perinatal mortality in donor twins. Full article
(This article belongs to the Special Issue Improving Perinatal Outcomes in Twin and Multiple Pregnancy)
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16 pages, 889 KiB  
Article
Middle Cerebral Artery Doppler Velocimetry for the Diagnosis of Twin Anemia Polycythemia Sequence: A Systematic Review
by Clifton O. Brock, Eric P. Bergh, Kenneth J. Moise, Jr, Anthony Johnson, Edgar Hernandez-Andrade, Dejian Lai and Ramesha Papanna
J. Clin. Med. 2020, 9(6), 1735; https://doi.org/10.3390/jcm9061735 - 04 Jun 2020
Cited by 6 | Viewed by 3326
Abstract
Twin anemia polycythemia sequence (TAPS) is a rare complication of monochorionic diamniotic (MCDA) twins. Middle cerebral artery peak systolic velocity (MCA-PSV) measurements are used to screen for TAPS while fetal or neonatal hemoglobin levels are required for definitive diagnosis. We sought to perform [...] Read more.
Twin anemia polycythemia sequence (TAPS) is a rare complication of monochorionic diamniotic (MCDA) twins. Middle cerebral artery peak systolic velocity (MCA-PSV) measurements are used to screen for TAPS while fetal or neonatal hemoglobin levels are required for definitive diagnosis. We sought to perform a systematic review of the efficacy of MCA-PSV in diagnosing TAPS. Search criteria were developed using relevant terms to query the Pubmed, Embase, and SCOPUS electronic databases. Publications reporting diagnostic characteristics of MCA-PSV measurements (i.e., sensitivity, specificity or receiver operator curves) were included. Each article was assessed for bias using the Quality Assessment of Diagnostic Accuracy Studies II (QUADAS II) tool. Results were assessed for uniformity to determine whether meta-analysis was feasible. Data were presented in tabular form. Among publications, five met the inclusion criteria. QUADAS II analysis revealed that four of the publications were highly likely to have bias in multiple areas. Meta-analysis was precluded by non-uniformity between definitions of TAPS by MCA-PSV and neonatal or fetal hemoglobin levels. High-quality prospective studies with consistent definitions and ultrasound surveillance protocols are still required to determine the efficacy of MCA-PSV in diagnosing TAPS. Other ultrasound findings (e.g., placenta echogenicity discordance) may augment Doppler studies. Full article
(This article belongs to the Special Issue Improving Perinatal Outcomes in Twin and Multiple Pregnancy)
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13 pages, 1550 KiB  
Article
Prevalence of Gestational Diabetes in Triplet Pregnancies: A Retrospective Cohort Study and Meta-Analysis
by Marlene Hager, Johannes Ott, Deirdre Maria Castillo, Stephanie Springer, Rudolf Seemann and Sophie Pils
J. Clin. Med. 2020, 9(5), 1523; https://doi.org/10.3390/jcm9051523 - 18 May 2020
Cited by 4 | Viewed by 2121
Abstract
Background: Over the last decades, there has been a substantial increase in the incidence of higher-order multiple gestations. Twin pregnancies are associated with an increased risk of gestational diabetes mellitus (GDM). The literature on GDM rates in triplet pregnancies is scarce. Methods: A [...] Read more.
Background: Over the last decades, there has been a substantial increase in the incidence of higher-order multiple gestations. Twin pregnancies are associated with an increased risk of gestational diabetes mellitus (GDM). The literature on GDM rates in triplet pregnancies is scarce. Methods: A retrospective cohort study was performed to assess the prevalence of GDM in women with a triplet pregnancy. GDM was defined through an abnormal oral glucose tolerance test (OGTT). A meta-analysis of GDM prevalence was also carried out. Results: A cohort of 60 women was included in the analysis. Of these, 19 (31.7%) were diagnosed with GDM. There were no differences in pregnancy outcomes between women with and without GDM. In the meta-analysis of 12 studies, which used a sound GDM definition, an estimated pooled prevalence of 12.4% (95% confidence interval: 6.9–19.1%) was found. In a leave-one-out sensitivity analysis, the estimated GDM prevalence ranged from 10.7% to 14.1%. Conclusion: The rate of GDM seems increased in women with triplets compared to singleton pregnancies. However, GDM did not impact short-term pregnancy outcomes. Full article
(This article belongs to the Special Issue Improving Perinatal Outcomes in Twin and Multiple Pregnancy)
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14 pages, 764 KiB  
Article
Selective Fetal Growth Restriction in Dichorionic Twin Pregnancies: Diagnosis, Natural History, and Perinatal Outcome
by Nikolaos Antonakopoulos, Petra Pateisky, Becky Liu, Erkan Kalafat, Baskaran Thilaganathan and Asma Khalil
J. Clin. Med. 2020, 9(5), 1404; https://doi.org/10.3390/jcm9051404 - 09 May 2020
Cited by 10 | Viewed by 3750
Abstract
This study aims to evaluate the natural history, disease progression, and outcomes in dichorionic twins with selective fetal growth restriction (sFGR) according to different diagnostic criteria and time of onset. Dichorionic twins seen from the first trimester were included. sFGR was classified according [...] Read more.
This study aims to evaluate the natural history, disease progression, and outcomes in dichorionic twins with selective fetal growth restriction (sFGR) according to different diagnostic criteria and time of onset. Dichorionic twins seen from the first trimester were included. sFGR was classified according to the Delphi consensus, and was compared to the outcomes of those classified by the International Society of Ultrasound in Obstetrics and Gynecology (ISUOG) diagnostic criteria. Early sFGR occurred before 32-weeks, and late sFGR after 32-weeks. Disease progression, neonatal outcomes such as gestation at delivery, birthweight, neonatal unit (NNU) admission, and morbidities were compared. One-hundred twenty-three of 1053 dichorionic twins had sFGR, where 8.4% were classified as early sFGR, and 3.3% were late sFGR. Disease progression was seen in 36%, with a longer progression time (5 vs. 1 week) and higher progression rate (40% vs. 26%) in early sFGR. Perinatal death was significantly higher in the sFGR than the non-sFGR group (24 vs. 16 per 1000 births, p = 0.018), and those with early sFGR had more NNU admissions than late sFGR (p = 0.005). The ISUOG diagnostic criteria yielded a higher number of sFGR than the Delphi criteria, but similar outcomes. sFGR have worse perinatal outcomes, with early onset being more prevalent. Use of the Delphi diagnostic criteria can reduce over-diagnosis of sFGR and avoid unnecessary intervention. Full article
(This article belongs to the Special Issue Improving Perinatal Outcomes in Twin and Multiple Pregnancy)
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Review

Jump to: Research

19 pages, 340 KiB  
Review
Review of International Clinical Guidelines Related to Prenatal Screening during Monochorionic Pregnancies
by Lauren Nicholas, Rebecca Fischbein, Stephanie Ernst-Milner and Roshni Wani
J. Clin. Med. 2021, 10(5), 1128; https://doi.org/10.3390/jcm10051128 - 08 Mar 2021
Cited by 8 | Viewed by 4464
Abstract
We conducted a search for international clinical guidelines related to prenatal screening during monochorionic pregnancies. We found 25 resources from 13 countries/regions and extracted information related to general screening as well as screening related to specific monochorionic complications, including twin-twin transfusion syndrome (TTTS), [...] Read more.
We conducted a search for international clinical guidelines related to prenatal screening during monochorionic pregnancies. We found 25 resources from 13 countries/regions and extracted information related to general screening as well as screening related to specific monochorionic complications, including twin-twin transfusion syndrome (TTTS), selective fetal growth restriction (SFGR), and twin anemia-polycythemia sequence (TAPS). Findings reveal universal recommendation for the early establishment of chorionicity. Near-universal recommendation was found for bi-weekly ultrasounds beginning around gestational week 16; routine TTTS and SFGR surveillance comprised of regularly assessing fetal growth, amniotic fluids, and bladder visibility; and fetal anatomical scanning between gestational weeks 18–22. Conflicting recommendation was found for nuchal translucency screening; second-trimester scanning for cervical length; routine TAPS screening; and routine umbilical artery, umbilical vein, and ductus venosus assessment. We conclude that across international agencies and organizations, clinical guidelines related to monochorionic prenatal screening vary considerably. This discord raises concerns related to equitable access to evidence-based monochorionic prenatal care; the ability to create reliable international datasets to help improve the quality of monochorionic research; and the promotion of patient safety and best monochorionic outcomes. Patients globally may benefit from the coming together of international bodies to develop inclusive universal monochorionic prenatal screening standards. Full article
(This article belongs to the Special Issue Improving Perinatal Outcomes in Twin and Multiple Pregnancy)
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