Background: Multiple gestation has a higher incidence of preterm birth(PTB), especially in the presence of a short cervix. Objectives: To perform a systematic review and network meta-analysis(NMA) evaluating the effect of progesterone, cerclage, cervical pessary and their combination as treatments for preventing PTB<34 weeks. Search strategy: PubMed, MEDLINE, Cochrane Library, EMBASE, Web of Science, BVS, Scopus, and grey literature were explored. Selection criteria: We included randomized controlled trials that compared an intervention with a control group or another intervention to prevent PTB in women with a twin pregnancy and a short cervix<40mm. Data collection and Analysis:Studies were checked for trustworthiness. We presented summary relative effect sizes(Odds Ratios) for each possible pair of interventions and we used the surface under the cumulative ranking curves(SUCRA) to rank all interventions. Main Results: A total of 20 studies participated in NMA. We found no evidence that the combined treatment of pessary and vaginal progesterone reduced the risk of spontaneous PTB <34 weeks when compared to no intervention(OR 0.68; 95%CI 0.16 to 2.9). Also, pessary(OR 0.78; 95%CI 0.49 to 1.3), vaginal progesterone(OR 0.79; CI95% 0.45 to 1.4) and injectable 17-OH progesterone alone(OR 0.85; CI95% 0.26 to 2.8) did not show a statistically significant reduction in spontaneous PTB. For overall PTB<34 weeks, findings were similar. Conclusions: We found no evidence that progesterone, cervical pessary, cerclage or their combination reduce PTB<34 weeks. There is an urgent need for randomized trials assessing these treatments in women with a multiple pregnancy and a short cervix.

Objective: To identify the association between cervical length (CL) and gestational age at birth. Design: Prospective cohort study. Setting: Seventeen Brazilian reference hospitals. Population: A cohort of 3139 asymptomatic singleton pregnant women who participated in the screening phase of a Brazilian multicenter randomized controlled trial (P5 trial). Methods: Transvaginal ultrasound (TVU) to measure CL was performed from 18 to 22+6 weeks. Women with CL ≤ 30 mm received vaginal progesterone (200 mg/day) until 36 weeks’ gestation. Main Outcome Measures: Area under receive operating characteristic curve (AUC), sensitivity, specificity, Kaplan-Meier curves for preterm birth (PTB), number needed to screen (NNS). Results: CL ≤25mm was associated with extremely severe, severe, moderate and late PTB, whereas a CL 25–30mm was directly associated with late sPTB. The AUC to predict sPTB<28 weeks was 0.82 and for sPTB<34 weeks was 0.67. Almost half of the sPTB occurred in nulliparous women and CL ≤30mm was associated with sPTB <37 weeks (OR = 7.84; 95%CI = 5.5–11.1). The NNS to detect one sPTB <34 weeks in women with CL ≤25mm is 121 and 248 screening tests are necessary to prevent one sPTB <34 weeks using vaginal progesterone prophylaxis. Conclusions: CL measured by TVU is associated with sPTB <34 weeks. Women with CL ≤30mm are at increased risk for late sPTB. Funding: Bill & Melinda Gates Foundation [OPP1107597], the Brazilian Ministry of Health, and the Brazilian National Council for Scientific and Technological Development (CNPq) [401615/20138]. Keywords: cervical length; number needed to screen; preterm birth; short cervix.

The SARS-CoV-2 pandemic scenario in Africa - What should be done to address pregnant women needs? A commentary.Charles M’poca Charles 1,2,*† ; Emefa Modey Amoah 3†; Kadidiatou Raissa Kourouma4; Luis Guilhermo Bahamondes2 ; José Guilherme Cecatti2 ; Nafissa Bique Osman 5,6,; Philip Govule 7; Abdou Karim Diallo8; Jahit Sacarlal 9 ; Rodolfo de Carvalho Pacagnella 2.1 Provincial Health Administration - DPS Manica, Manica Province, Mozambique.2 University of Campinas, School of Medicine, Department of Obstetrics and Gynecology, 101 Alexander Fleming st, Campinas, São Paulo, Zip code: 13083-970, Brazil.3 University of Ghana, Department of Population Family and Reproductive Health, Accra, Ghana.4 National Institute of Public Health of Côte d’Ivoire, Abidjan, Côte d’Ivoire.5 Eduardo Mondlane University, Faculty of Medicine, Department of Obstetrics and Gynecology, 706 Salvador Allende st, Maputo, Mozambique.6 Maputo Central Hospital, Department of Obstetrics and Gynecology, Agostinho Neto st, Maputo, Mozambique.7 University of Ghana, School of Public Health, Department of Epidemiology and Disease control, Accra, Ghana.8 Clinique Gynécologique et Obstétricale de l’Hôpital Aristide Le Dantec, Dakar, Senegal.9 Eduardo Mondlane University, Faculty of Medicine, Department of Microbiology, 706 Salvador Allende st, Maputo, Mozambique.† Co-First authorship*Corresponding author:Charles M’poca Charles, Provincial Health Administration - DPS Manica, Manica Province, Mozambique.Email: [email protected] number: +258 825483741 / +55 19 98198-7713Shortened running title: The SARS-CoV-2 pandemic in Africa & pregnant women.Keywords: SARS-CoV-2, COVID-19, Africa, Low and middle-income countries, network, severe maternal morbidity.The SARS-Cov-2 (COVID-19) virus causes an infectious and multisystem disease first diagnosed in China in December 2019.1Having evolved rapidly with an exponential increase in the number of cases and deaths worldwide, COVID-19 was declared a pandemic by the WHO in mid-March 2020. Although in most Sub-Saharan African countries the pandemic is in its initial phase, as of 8 September 2020, the cumulative total cases of COVID-19 in the African Region exceeded one million and it is now at 1 315 073 confirmed cases with 31 725 deaths.2The advent of the pandemic has exhibited the weaknesses of health systems in different settings, testing capacity and strategy being more evident in low and middle-income countries (LMICs).3The growing number of COVID-19 cases has forced many countries to reorganise existing health services and reassign available healthcare professionals to combat COVID-19. In this regard, a number of service delivery points were closed due to the lack of healthcare providers.In response to the COVID-19 pandemic, many countries enforced lockdown restrictions that closed down schools, businesses, restaurants, markets, religious gatherings, and limited mass gatherings and border entry. The lockdowns in some contexts, led to the disruption or suspension of many essential health services including sexual and reproductive health (SRH) services, thus placing women of reproductive age under conditions of greater vulnerability and at risk of suffering devastating effects from COVID-19.4, 5In LMIC countries, the disruption in SRH services such as family planning, prevention and treatment of sexual transmitted infection (STI), safe abortion services, antenatal and postnatal consultations pose risks to women of reproductive age. The disruptions were generally associated with low coverage of the health network, weak diagnostic capacity for SARS-CoV-2 detection, shortage of trained healthcare personnel and reduced demand for services in the available health facilities due to stigma and fear of acquiring SARS-COV-2 infection.This situation has the potential to contribute negatively to the incidence of high risk pregnancy, near miss, maternal and perinatal deaths in these LMIC countries, with the consequent compromise of objective 3.1 of the WHO Sustainable Development Goals, 2030 agenda.6Although information on the clinical course of the disease and the consequences on maternal and perinatal health are still scarce, there is evidence that SARS-CoV-2 infection during pregnancy is associated with an increased risk of perinatal complications, including foetal distress, premature birth, perinatal death 7 and increased rate of admission to the intensive care unit and need for mechanical ventilation. 8, 9The risk of maternal and perinatal complications may be increased in pregnant women with underlying medical conditions, black pregnant women, and pregnant women from a disadvantaged social class and, in contexts with limited access to adequate healthcare services for COVID-19 management. 10, 11Although, the impact of COVID-19 on pregnant women was considered a secondary priority (12), studies involving pregnant women with respiratory diseases caused by other respiratory viruses in addition to recent data from studies of pregnant women with SARS-CoV-2 infection in middle and high-income countries, highlight the need to pay special attention to this group of women, especially in settings where healthcare services are strained.While global maternal deaths gradually declined between 2000 and 2017, disparities in patterns of mortality still exist with Sub-Saharan Africa region alone accounting for approximately 66% of deaths in the continent.13 Due to the increasing number of reported maternal death cases related to the COVID-19, mostly from LMIC, and deficiencies in reporting cases in those countries, the need for prospective monitoring of COVID-19 cases among pregnant women in the context of LMIC is needed now more than ever.As SARS COV-2 is a novel virus, knowledge of its impact on sexual and reproductive health (SRH) is now emerging. 14Therefore, to understand the dynamics of SARS-CoV-2 infection in its broad spectrum in the obstetric population of LMIC countries and to minimize the effects of the pandemic on maternal and perinatal health, it is essential to join forces among African researchers to generate evidence to better elucidate the magnitude of the problem. For this, the adoption of interinstitutional and multinational strategies is essential to optimize the allocation of scarce resources to fight the pandemic.In response to the SARS-COV-2 pandemic in sub Saharan Africa, domestic and regional level efforts have been undertaken by various partners in multiple sectors.15, 16 A critical component to complement these strategies is the setting up of multi-centre collaborative networks of African researchers to undertake surveillance studies of conditions related to maternal and neonatal morbidity associated with COVID-19 and interinstitutional support for the creation and implementation of care protocols. The building of a collaborative network to study the impact of COVID-19 on the obstetric population in Africa (African Network for fighting COVID-19 in pregnancy- ANCOVID-19) would enable a broad understanding of the pattern of disease evolution in different countries and different contexts, enabling a better understanding of the role of context-specific determinants in the evolution of infection by SARS-CoV-2 and strengthen measure to ensure access to essential reproductive health services during pandemics, lockdowns and easing of restrictions.Likewise, the implementation of robust surveillance systems and support to weaker systems by the stronger partnerships may favour the collection of standardised information on related maternal and perinatal morbidity. Continuous monitoring of the impact of the disease on maternal and perinatal health including strategies for remote monitoring of pregnant women through telephone calls and/or digital tools where available coupled with the sharing of clinical information will contribute to a better understanding of the dynamics of infection in this population and the moment of greatest vulnerability for the maternal and newborn health.Thus, we call on all researchers in Africa to join in a continental effort to combat COVID-19 and reduce its impacts on maternal and perinatal health in Africa. This would encourage the provision of routine maternal and newborn services during and post pandemic in Sub-Saharan Africa.