Clinical epidemiology of twin deliveries in The Gambia and Burkina Faso: Secondary analyses of PregnAnZI-2 clinical trial data

Clinical epidemiology of twin deliveries in The Gambia and Burkina Faso: Secondary analyses of PregnAnZI-2 clinical trial data | medRxiv /* */ /* */ <!-- <!-- /*! * yepnope1.5.4 * (c) WTFPL, GPLv2 */ (function(a,b,c){function d(a){return"[object Function]"==o.call(a)}function e(a){return"string"==typeof a}function f(){}function g(a){return!a||"loaded"==a||"complete"==a||"uninitialized"==a}function h(){var a=p.shift();q=1,a?a.t?m(function(){("c"==a.t?B.injectCss:B.injectJs)(a.s,0,a.a,a.x,a.e,1)},0):(a(),h()):q=0}function i(a,c,d,e,f,i,j){function k(b){if(!o&&g(l.readyState)&&(u.r=o=1,!q&&h(),l.onload=l.onreadystatechange=null,b)){"img"!=a&&m(function(){t.removeChild(l)},50);for(var d in y[c])y[c].hasOwnProperty(d)&&y[c][d].onload()}}var j=j||B.errorTimeout,l=b.createElement(a),o=0,r=0,u={t:d,s:c,e:f,a:i,x:j};1===y[c]&&(r=1,y[c]=[]),"object"==a?l.data=c:(l.src=c,l.type=a),l.width=l.height="0",l.onerror=l.onload=l.onreadystatechange=function(){k.call(this,r)},p.splice(e,0,u),"img"!=a&&(r||2===y[c]?(t.insertBefore(l,s?null:n),m(k,j)):y[c].push(l))}function j(a,b,c,d,f){return q=0,b=b||"j",e(a)?i("c"==b?v:u,a,b,this.i++,c,d,f):(p.splice(this.i++,0,a),1==p.length&&h()),this}function k(){var a=B;return a.loader={load:j,i:0},a}var l=b.documentElement,m=a.setTimeout,n=b.getElementsByTagName("script")[0],o={}.toString,p=[],q=0,r="MozAppearance"in l.style,s=r&&!!b.createRange().compareNode,t=s?l:n.parentNode,l=a.opera&&"[object Opera]"==o.call(a.opera),l=!!b.attachEvent&&!l,u=r?"object":l?"script":"img",v=l?"script":u,w=Array.isArray||function(a){return"[object Array]"==o.call(a)},x=[],y={},z={timeout:function(a,b){return b.length&&(a.timeout=b[0]),a}},A,B;B=function(a){function b(a){var a=a.split("!"),b=x.length,c=a.pop(),d=a.length,c={url:c,origUrl:c,prefixes:a},e,f,g;for(f=0;f<d;f++)g=a[f].split("="),(e=z[g.shift()])&&(c=e(c,g));for(f=0;f<b;f++)c=x[f](c);return c}function g(a,e,f,g,h){var i=b(a),j=i.autoCallback;i.url.split(".").pop().split("?").shift(),i.bypass||(e&&(e=d(e)?e:e[a]||e[g]||e[a.split("/").pop().split("?")[0]]),i.instead?i.instead(a,e,f,g,h):(y[i.url]?i.noexec=!0:y[i.url]=1,f.load(i.url,i.forceCSS||!i.forceJS&&"css"==i.url.split(".").pop().split("?").shift()?"c":c,i.noexec,i.attrs,i.timeout),(d(e)||d(j))&&f.load(function(){k(),e&&e(i.origUrl,h,g),j&&j(i.origUrl,h,g),y[i.url]=2})))}function h(a,b){function c(a,c){if(a){if(e(a))c||(j=function(){var a=[].slice.call(arguments);k.apply(this,a),l()}),g(a,j,b,0,h);else if(Object(a)===a)for(n in m=function(){var b=0,c;for(c in a)a.hasOwnProperty(c)&&b++;return b}(),a)a.hasOwnProperty(n)&&(!c&&!--m&&(d(j)?j=function(){var a=[].slice.call(arguments);k.apply(this,a),l()}:j[n]=function(a){return function(){var b=[].slice.call(arguments);a&&a.apply(this,b),l()}}(k[n])),g(a[n],j,b,n,h))}else!c&&l()}var h=!!a.test,i=a.load||a.both,j=a.callback||f,k=j,l=a.complete||f,m,n;c(h?a.yep:a.nope,!!i),i&&c(i)}var i,j,l=this.yepnope.loader;if(e(a))g(a,0,l,0);else if(w(a))for(i=0;i (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0];var j=d.createElement(s);var dl=l!='dataLayer'?'&l='+l:'';j.src='//www.googletagmanager.com/gtm.js?id='+i+dl;j.type='text/javascript';j.async=true;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-P4HH5NV'); Skip to main content Home About Submit ALERTS / RSS Search for this keyword Advanced Search Clinical epidemiology of twin deliveries in The Gambia and Burkina Faso: Secondary analyses of PregnAnZI-2 clinical trial data Joquina Chiquita Jones , Toussaint Rouamba , Joel D. Bognini , Bully Camara , Usman N Nakakana , Athanase M. Somé , Nathalie Beloum , Guétawendé J W Nassa , Fatoumata Sillah , Edmond Yabré Sawadogo , Madikoi Danso , Shashu Graves , Bai Lamin Dondeh , Diagniagou Lankoandé , Ebrahim Ndure , Yusupha Njie , Christian Bottomley , Umberto d’Alessandro , Halidou Tinto , Anna Roca , Helen Brotherton doi: https://doi.org/10.1101/2025.10.25.25338790 Joquina Chiquita Jones 1 Medical Research Council Unit The Gambia at London School of Hygiene and Tropical Medicine , Banjul, Gambia Find this author on Google Scholar Find this author on PubMed Search for this author on this site Toussaint Rouamba 2 Institut de Recherche en Sciences de la Santé (IRSS) – Unité de recherche Clinique de Nanoro (URCN) , Nanoro, Burkina Faso 3 Centre de Recherche en Epidémiologie, Biostatistique Et Recherche Clinique, Ecole de Santé Publique, Université Libre de Bruxelles , Bruxelles, Belgium Find this author on Google Scholar Find this author on PubMed Search for this author on this site Joel D. Bognini 2 Institut de Recherche en Sciences de la Santé (IRSS) – Unité de recherche Clinique de Nanoro (URCN) , Nanoro, Burkina Faso Find this author on Google Scholar Find this author on PubMed Search for this author on this site Bully Camara 1 Medical Research Council Unit The Gambia at London School of Hygiene and Tropical Medicine , Banjul, Gambia Find this author on Google Scholar Find this author on PubMed Search for this author on this site Usman N Nakakana 1 Medical Research Council Unit The Gambia at London School of Hygiene and Tropical Medicine , Banjul, Gambia 4 Gates Foundation , Seattle, USA Find this author on Google Scholar Find this author on PubMed Search for this author on this site Athanase M. Somé 2 Institut de Recherche en Sciences de la Santé (IRSS) – Unité de recherche Clinique de Nanoro (URCN) , Nanoro, Burkina Faso Find this author on Google Scholar Find this author on PubMed Search for this author on this site Nathalie Beloum 1 Medical Research Council Unit The Gambia at London School of Hygiene and Tropical Medicine , Banjul, Gambia Find this author on Google Scholar Find this author on PubMed Search for this author on this site Guétawendé J W Nassa 2 Institut de Recherche en Sciences de la Santé (IRSS) – Unité de recherche Clinique de Nanoro (URCN) , Nanoro, Burkina Faso Find this author on Google Scholar Find this author on PubMed Search for this author on this site Fatoumata Sillah 1 Medical Research Council Unit The Gambia at London School of Hygiene and Tropical Medicine , Banjul, Gambia Find this author on Google Scholar Find this author on PubMed Search for this author on this site Edmond Yabré Sawadogo 2 Institut de Recherche en Sciences de la Santé (IRSS) – Unité de recherche Clinique de Nanoro (URCN) , Nanoro, Burkina Faso Find this author on Google Scholar Find this author on PubMed Search for this author on this site Madikoi Danso 1 Medical Research Council Unit The Gambia at London School of Hygiene and Tropical Medicine , Banjul, Gambia Find this author on Google Scholar Find this author on PubMed Search for this author on this site Shashu Graves 1 Medical Research Council Unit The Gambia at London School of Hygiene and Tropical Medicine , Banjul, Gambia 5 Sherwood Forest Hospitals NHS Foundation , UK Find this author on Google Scholar Find this author on PubMed Search for this author on this site Bai Lamin Dondeh 1 Medical Research Council Unit The Gambia at London School of Hygiene and Tropical Medicine , Banjul, Gambia Find this author on Google Scholar Find this author on PubMed Search for this author on this site Diagniagou Lankoandé 2 Institut de Recherche en Sciences de la Santé (IRSS) – Unité de recherche Clinique de Nanoro (URCN) , Nanoro, Burkina Faso Find this author on Google Scholar Find this author on PubMed Search for this author on this site Ebrahim Ndure 1 Medical Research Council Unit The Gambia at London School of Hygiene and Tropical Medicine , Banjul, Gambia Find this author on Google Scholar Find this author on PubMed Search for this author on this site Yusupha Njie 6 London School of Hygiene and Tropical Medicine , London, United Kingdom Find this author on Google Scholar Find this author on PubMed Search for this author on this site Christian Bottomley 6 London School of Hygiene and Tropical Medicine , London, United Kingdom Find this author on Google Scholar Find this author on PubMed Search for this author on this site Umberto d’Alessandro 1 Medical Research Council Unit The Gambia at London School of Hygiene and Tropical Medicine , Banjul, Gambia Find this author on Google Scholar Find this author on PubMed Search for this author on this site Halidou Tinto 2 Institut de Recherche en Sciences de la Santé (IRSS) – Unité de recherche Clinique de Nanoro (URCN) , Nanoro, Burkina Faso Find this author on Google Scholar Find this author on PubMed Search for this author on this site Anna Roca 1 Medical Research Council Unit The Gambia at London School of Hygiene and Tropical Medicine , Banjul, Gambia 7 IS Global, Campus Hospital Clínic-Universitat de Barcelona , Barcelona 08036, Spain 8 ICREA, Pg. Lluís Companys 23 , Barcelona 08010, Spain Find this author on Google Scholar Find this author on PubMed Search for this author on this site Helen Brotherton 1 Medical Research Council Unit The Gambia at London School of Hygiene and Tropical Medicine , Banjul, Gambia 9 Victoria Hospital Kirkcaldy, NHS Fife , UK Find this author on Google Scholar Find this author on PubMed Search for this author on this site For correspondence: hbrotherton{at}mrc.gm Abstract Full Text Info/History Metrics Supplementary material Data/Code Preview PDF ABSTRACT Introduction Twins have higher risk of adverse clinical outcomes in all settings, but especially in low- and middle-income countries. This study aims to understand the clinical epidemiology of twins from varied West African settings, focusing on prevalence and determinants of twins, and adverse perinatal outcomes associated with twin deliveries. These context specific insights may help to inform public health and clinical approaches to improving health and survival of this vulnerable newborn group. Methods We conducted secondary analyses from the PregnAnZI-2 randomised clinical trial, which included data from pregnant women and their offspring who were delivered at eight peripheral health facilities in rural Burkina Faso and two urban health facilities in The Gambia. Logistic regression was used to identify associations between primary outcome (twin deliveries) and both risk factors and adverse outcomes and was informed by a novel conceptual framework. Results Data from 12,192 newborns born from 11,983 women were analysed. The average twinning rate was 35 per 1000 total births (95% CI: 32-39): 27 per 1000 total births (95% CI: 23-31) in The Gambia and 45 per 1000 total births (95% CI: 40-51) in Burkina Faso. Risk factors for twinning included maternal ethnicity and parity. Twins had increased risk of low birth weight (OR =17.2, 95% CI:13.90-21.30, P= <0.001), low 5-min Apgar score (proxy for intrapartum related asphyxia) (OR =4.28, 95% CI: 2.79-6.33, P <0.001), intrapartum stillbirth (OR=4.69, 95% CI:2.47-8.22, P<0.001), and hospitalisation during the neonatal period (OR =1.69 95% CI:1.10-2.47, P= 0.011). Neonatal mortality was four-fold higher for twins than singletons (OR =4.23, 95% CI: 2.40-7.50, P <0.001), and among twin deaths, the second twin was more likely to die compared to the first twin (OR=2.46, 95% CI :1.05-7.59, P=0.048). Conclusion Twins are an important contributor to stillbirth and neonatal morbidity and mortality in West Africa. Efforts to identify twin pregnancies early, with optimisation of antenatal and intrapartum management could improve outcomes for this vulnerable newborn group. Trial Registration NCT03199547: Clinicaltrials.gov. Registered on 23rd June 2017 INTRODUCTION Worldwide, twin births occur in 1 in 76 pregnancies, equivalent to 13.1 per 1000 live births.( 1 ) Sub-Saharan Africa (SSA) has the highest rates of twin births globally, ( 1 , 2 ) with significant regional variation ( 3 ) ranging from >18 per 1000 live births in West and Central Africa to 11-15 per 1000 live births in Southern African countries.( 1 ) Twin pregnancies are associated with a substantially higher risk of antenatal and perinatal adverse outcomes, including preterm birth, low birth weight (LBW), stillbirth, intrapartum-related asphyxia (IRA), and neonatal mortality, compared to singleton pregnancies.( 4 , 5 ) As a consequence, surviving twins face an increased risk of long-term morbidities and neurodevelopmental impairment( 6 ), with huge impact on individuals, families, and societies. Generic risk factors for twin pregnancies are well established and include maternal characteristics such as older age, multiparity, family history of twinning, and nutritional status, as well as lifestyle factors such as smoking.( 5 , 7 , 8 , 9 ) Other influences include socioeconomic status, assisted reproductive therapy, and race/ethnicity.( 1 , 10 , 11 ) However, specific determinants for twinning within West African populations remain poorly explored, despite their importance in guiding targeted public health strategies aimed at early identification of twin pregnancies and optimising maternity care. This is particularly important if West Africa, a sub-region with both high twinning rates and the highest global neonatal mortality rates, is to achieve the sustainable development goal target of reducing avoidable neonatal mortality by 2030.( 12 ) Understanding the clinical epidemiology of this group of vulnerable newborns in West Africa is crucial to delivering appropriate antenatal and intrapartum care to women with twin pregnancies in-order to improve twin outcomes.( 5 , 13 ) This study aims to examine the clinical epidemiology of twins from varied settings in West Africa. Specifically, we aim to determine the prevalence of twin births, identify risk factors associated with twinning, and quantify the adverse perinatal outcomes associated with twins. METHODS Study design This is a secondary data analysis of the PregnAnZI-2 trial ( clinicaltrials.gov ref: NCT03199547 ), which was a phase III, double-blind, placebo-controlled randomised clinical trial conducted in The Gambia and Burkina Faso between 2017 and 2021. Intra-partum azithromycin or placebo were administered to women in labour to assess the effect on a composite primary outcome of neonatal mortality or infection.( 14 ) The whole trial cohort was included in this secondary study as the intervention was not associated with reductions in neonatal mortality or sepsis and would not influence twinning rates due to intrapartum timing of administration.( 15 ) Setting The PregnAnZI-2 trial was conducted at two urban government health facilities in The Gambia: Bundung Maternal Child Health Hospital (BMCHH) and Serekunda Health Centre (SHC). The two sites manage approximately 7000 deliveries per year.( 14 ) Approximately 84% of deliveries in The Gambia occur at health facilities.( 16 ) At the time of data collection, SHC lacked the capacity to provide emergency obstetric care and women requiring an emergency caesarean section were referred to the Kanifing General Hospital, ∼3.4 kilometres (Km) distance away. BMCHH provided emergency obstetric care and had a neonatal unit capable of providing WHO level 2 small and sick newborn care. Women experiencing complications of labour and unwell neonates were occasionally referred to the tertiary level obstetric department and national neonatal referral unit at the Edward Francis Small Teaching Hospital in Banjul, ∼15.5 Km distance away. In Burkina Faso, women were recruited at eight peripheral health facilities in the districts of Nanoro and Yako. Approximately 94% of deliveries in Burkina Faso occur at health facilities.( 17 ) The eight combined health facilities conducted ∼3800 deliveries annually, with antenatal, intrapartum and postnatal care available at primary care level. All mothers and newborns requiring specialised obstetric or neonatal hospital care were referred to the Saint Camille hospital in CRUN (25 Km average distance). The neonatal mortality rate (NMR) at study onset was the same in both countries (25/1000 live births), ( 18 ) with stillbirth rates of 21 per 1000 total births in The Gambia and 20 per 1000 total births in Burkina Faso.( 19 ) Participants Participants were pregnant women ≥ 16 years old who consented to take part in the PregnAnZI-2 trial and attended a study site for delivery. Women were excluded if they had a known acute or chronic condition (including HIV infection), planned caesarean section, severe congenital malformation detected in-utero, intra-uterine death, macrolide allergy or had taken a drug known to prolong QT interval during the preceding 2 weeks.( 20 ) All offspring (stillbirths and livebirths) of recruited women were included in this secondary analysis. Assisted conception methods (e.g., In-vitro fertilisation) were not available at the study sites or governmental health facilities in either country at the time of study, so participants are assumed to all have spontaneous conceptions. Outcome measures The primary outcome was a binary variable (yes/no) for whether a newborn was a twin. Twins were compared to singletons in our analyses, with the exclusion of triplet deliveries (three newborns). Due to the absence of routine antenatal scanning in our setting, it was not possible to determine twin or triplet pregnancies in which an in-utero demise occurred prior to enrolment, hence twin deliveries instead of twin pregnancies were considered. Study procedures Pregnant women provided written informed consent during antenatal care, which was verbally confirmed during labour and prior to enrolment. Trained research nurses collected socio-demographic and clinical data prospectively as soon as possible after enrolment using the antenatal card, partograph and delivery notes as source documents.( 20 ) Data of interest included: maternal obstetric history; intrapartum events and delivery details; and perinatal outcome of stillbirth or live birth. Stillbirths were all classed as intrapartum in timing as women were only enrolled following confirmation of labour and measurement of foetal heart rate using a hand-held foetal doppler. Newborns who were unable to sustain breathing at delivery were resuscitated by health facility staff according to the Helping Babies Breathe protocol, with Apgar scores prospectively determined by health facility staff. Stillbirths were assigned by health facilities staff using clinical criteria (lack of breathing and heart rate) and verified by research staff. Birthweight was measured using calibrated digital scales, and easily recognisable congenital malformations were determined by trained research clinicians prior to discharge with post-hoc classification as per ICD-11 system.( 21 ) Birth outcomes for each twin partner were independently recorded. Active and passive surveillance were conducted to collect data on health outcome. All mothers and newborns underwent a detailed clinical assessment by a trained research clinician or paediatrician 4-24h after delivery and prior to health facility discharge. Discharge or referral to other health facilities was at the discretion of the health facility staff. Between discharge and 28 postnatal days, mothers were encouraged to contact the trial clinical team or visit a study health facility if they or their babies were unwell (passive surveillance), with travel expenses to encourage attendance for in-person review by the research team. In The Gambia, a trained research nurse conducted a home visit at day 28 to collect morbidity and mortality data and give clinical support when necessary (active surveillance). In Burkina Faso, women and their infants attended study health facilities at 28 days, with home visits by a field worker in the event of non-attendance. The decision to admit mothers and newborns during the follow-up period was made by trained research clinicians or paediatricians, based on their clinical judgement. Data management and statistical analysis Data were collected electronically using encrypted mobile and computer devices at all study sites and uploaded to a study specific Research Electronic Data capture (REDCap) database. Data consistency checks and validation were conducted as per PregnANZI-2 trial procedures.( 14 ) All analyses were conducted with Stata version 17.0 (Statacorp). Descriptive analyses were performed to determine the prevalence rates for all independent variables and adverse outcomes for the total cohort, with stratification according to plurality (singleton versus twin delivery). Twinning rates were computed by dividing the number of twin births by the total number of births and multiplying the outcome by 1000. We developed a novel conceptual framework based on biotoxicological plausibility and existing evidence for risk factors for twin pregnancy and impact of twinning on delivery outcome ( Figure 1 ). This framework was used to select independent variables for logistic regression to identify pre-conception and conception risk factors for twins versus singletons, expressed as crude odds ratios, with 95% confidence intervals to represent degree of certainty, and p values. For categorical variables, the baseline category was chosen to reflect either a “normal pregnancy and delivery” (e.g., normal birth weight, non-extremes of parity) or the most prevalent grouping (e.g., ethnicity). An adjusted logistic regression model was developed for each independent variable found to have p<0.2 on unadjusted regression. In-order to avoid over adjusting for multiple variables on the same causal pathway ( 22 ), each model included only variables occurring before or at the same timepoint as the independent variable of interest. As ethnicity and country are co-linear with no overlap, we chose to adjust for ethnicity only to provide more granular insights to risk factors for twinning. Statistical significance was defined as p<0.05. Download figure Open in new tab Figure 1. Conceptual Framework to understand development of twinning and impact of twin pregnancies on perinatal outcomes Underlined variables indicate data available for analysis in this study Assisted reproduction methods including pre-conception therapies and invitro fertilization RESULTS In total, 11,983 pregnant women and their 12,192 offspring were included in the analyses: 3.5% (428/12,192) were twins and 96.5% (11,764/12,192) were singletons ( Figure 2 ). Overall, the average twinning rate for the two countries was 35 per 1000 total births (95% CI: 32-39): 27 per 1000 total births (95% CI: 23-31) in The Gambia and 45.4 per 1000 total births (95% CI: 40-51) in Burkina Faso (p 4 (aOR 1.66, 95% CI 1.24-2.23), and primiparous women had reduced odds of twin birth (aOR 0.30, 95% CI 0.17-0.51). Younger maternal age (aOR 0.46, 95% CI 0.21-0.89) was associated with reduced odds of twins compared to women aged 20-35yrs. Maternal ethnicity of Gurunsi was associated with increased odds of having a twin compared to Mossi (aOR 1.69, 95% CI 1.09-2.62), with other ethnicities associated with reduced odds of twinning, such as Fula (aOR 0.55, 95% CI 0.35-0.81), Jola (aOR 0.54, 95% CI 0.33-0.84) and Mandinka (aOR 0.61, 95% CI 0.46-0.79) ( Table 1 ). Overall, 14.3% (13/91) of intrapartum stillbirths and 12.7% (18/142) of neonatal deaths occurred in twins. Out of the twins who were either stillborn or died, 26% (8/31) were twin 1 and 74% (23/31) were twin 2 (cOR 3.1, 95% CI 1.41-7.55, p =0.007). There was a 4-fold higher odds of intrapartum stillbirth (cOR 4.69, 95% CI: 2.47-8.22, p <0.001) and neonatal mortality (cOR 4.23, 95% CI 2.55-5.70, p <0.001) for twins compared to singletons ( Table 2 ). 21.9% (253/1156) of all LBW neonates in the cohort were twins and, compared to singletons, twins had 17-fold higher odds of being LBW (cOR 17.22, 95% CI 14.05-21.16, p <0.001). Twins were also more likely to have a low Apgar score at 1 minute (cOR 1.78, 95% CI 1.17-2.59, p =0.004) and 5 minutes (cOR 4.28, 95% CI: 2.79-6.33, p <0.001), be born by caesarean section (cOR 1.88, 95% CI 1.08-3.05, p = 0.016), and be admitted to hospital during the neonatal period (cOR 1.69, 95% CI 1.10-2.47, p =0.011). View this table: View inline View popup Download powerpoint Table 1. Pre-conception and conception factors associated with twinning in The Gambia and Burkina Faso View this table: View inline View popup Download powerpoint Table 2. Adverse perinatal outcomes associated with twin deliveries at health facilities in The Gambia and Burkina Faso Download figure Open in new tab Figure 2. Participants and perinatal outcomes for singleton and twins born at health facilities in The Gambia and Burkina Faso a) Of live-born twins who died, 66.7% (12/18) had the same mother (twin pairs) and 33.3% (6/18) had different mothers. DISCUSSION This large health-facility based study underlines the importance of optimising management of twin pregnancies and deliveries in West Africa, with twins making a substantial contribution to poor perinatal and neonatal outcomes such as intrapartum stillbirths, neonatal mortality, intra-partum related asphyxia, LBW and hospital admission. We identified significant sub-regional variation in twinning rates in West Africa, being higher in Burkina Faso compared to The Gambia. Maternal factors associated with twinning in our cohort included age, parity and ethnicity. The overall twinning rate in our West African cohort (35 per 1000 total births) is similar to findings from other health facility-based studies in the region, such as Nigeria (32.5 per 1000 total births)( 23 ) and Ghana (33.4 per 1000 total births),( 24 ), or countries from other Sub-Saharan regions such as Ethiopia (37.7 per 1000 total births)( 25 ). These rates are considerably higher than population-based surveillance studies of twinning across SSA (17 per 1000 total births),( 2 ) as well as in rural Gambia (15– 16.7 per 1000 births),( 7 , 26 ) and Burkina Faso (19.7-29.6 per 1000 livebirths).( 2 , 27 ) This disparity may be attributed to under-reporting of twin births in population-based studies, which typically rely on maternal recall of complete birth histories and often exclude stillbirths.( 27 ) In contrast, our study prospectively collected data on all pregnancy outcomes within a clinical trial setting, providing a more accurate estimate of twinning prevalence among women delivering at West African health facilities. We also identified intra-regional variation in twinning prevalence, with a higher rate in Burkina Faso compared to The Gambia. Such regional variation is well documented, with West and Central African countries showing higher twinning rates compared to East and Southern Africa ( 2 ) and with substantial variability both between and within different West African countries.( 2 , 23 ) Our findings may also be partially explained by a higher proportion of women with parity > 4 in the Burkina Faso sub-cohort and genetic differences present in varying ethnicities, which is speculated to be important in driving twinning in African populations.( 2 ) With a four-fold increased odds of neonatal mortality, the contribution of twins to neonatal mortality in our cohort was significant (12.5%) and is consistent with previous studies. ( 7 , 27 ) The contribution of twins to neonatal mortality is now well evidenced from all African regions ( 2 , 5 , 27 , 28 , 29 ) and underlines the urgent need for global policy and programmes to prioritise early twin detection, enhanced antenatal monitoring and intrapartum management as a strategy to reduce avoidable stillbirths, IRA, and neonatal deaths. We had similar observations for intrapartum stillbirths. The prevalence of intrapartum stillbirth in our health facility-born twin cohort (13%) aligns with rates reported in Nigerian health facilities (10.8%)( 23 ) and is substantially lower than rates reported from East African twin studies (30%).( 28 ) The association between twin delivery and low Apgar scores observed in our study and others( 30 ) suggests that IRA is an important factor in the development of intrapartum stillbirth and neonatal mortality for twins. Foetal malpresentation (e.g., breech or transverse lie) of one or both twins occurs in up to 50% of twin deliveries in similar West African settings ( 23 ) and may be an important event in the development of IRA, intrapartum stillbirth and neonatal mortality in our twin cohort, although specific data on this is not available in our study. Other adverse outcomes which were more prevalent among twins in our cohort included LBW, birth by caesarean section and hospital admission. Our estimate of a 17-fold increased odds of LBW in twins is consistent with findings from other settings, ( 3 , 4 , 28 , 31 ) with nearly half of all twin pregnancies resulting in LBW in East Africa.( 28 ) LBW typically occurs in twins due to premature delivery, growth restriction, or both. However, we are unable to comment on the underlying cause of LBW in our cohort due to the lack of reliable gestational age data, an ongoing challenge in settings without routine first trimester ultrasound scans. We also observed a 2-fold increased odds of twin neonates born by emergency caesarean section, reflecting likely intrapartum complications, also observed in other health-facility West African twin studies.( 3 , 4 , 32 ) Higher parity ( > 3), maternal age 20-35yrs and specific maternal ethnicities were associated with increased odds of twinning in our study. Women aged 35y. This pattern is consistent with other SSA studies ( 2 , 5 ) and could be attributed to age-related changes in maternal gonadotrophin levels and decline in ovarian function at the end of the reproductive cycle.( 33 ) Our finding that twins were more likely to be born to women with increasing parity is consistent with previous studies from SSA,( 2 ) including The Gambia,( 7 ) and the Indian sub-continent.( 34 ) Similar to these studies, we identified that multiparous women have the highest odds of twins, independent of maternal age, and consistent with previous evidence that maternal age and parity have independent positive associations with twin births.( 5 ) Gambian ethnicities did not show any increased risk and had overall lower odds of twinning compared to the Mossi ethnic group in Burkina Faso. There is conflicting data on the influence of ethnicity on twinning in Gambian women, with reduced twinning rates in rural Mandinka populations historically reported,( 26 ) yet a more recent population-based rural study finding no ethnic predisposition.( 7 ) Our findings suggest that early (first trimester) targeted screening of multiparous women may enable early detection of twin pregnancies and provide a feasible strategy leading to optimised antenatal care, including foetal growth monitoring, promotion of maternal nutrition, and detection of obstetric complications known to be more prevalent in twin pregnancies (e.g., hypertensive disorders of pregnancy).( 28 ) Conclusion Twins represent a highly vulnerable neonatal population in The Gambia and Burkina Faso, with among the highest prevalence rates globally and a significantly increased risk of LBW, intrapartum stillbirth, IRA and neonatal mortality. Multiparous women from specific ethnic groups are at higher risk of twinning. There is an urgent need to implement systematic screening strategies for early detection of twin pregnancies, paired with high quality and context specific antenatal and intrapartum management. Strengthening these services is essential if the SDG target of reducing preventable neonatal mortality is to be achieved in West African countries by 2030. Data Availability Data may be obtained from a third party and are not publicly available. The clinical data has been collected following provision of informed consent under the prerequisite of strict participant confidentiality. Qualified researchers may request access with the Gambia Government/MRC Joint Ethics Committee. The review process and release of data will be facilitated by MRC Unit The Gambia ( http://www.mrc.gm/ ) through the Head of Governance at MRCG. Access will not be unduly restricted. DECLARATIONS Ethical approval The parent trial was approved by The Gambia Government/Medical Research Council Unit The Gambia (MRCG) Joint Ethics Committee, the Comité d’Ethique pour la Recherche en Santé (CERS) and the Ministry of Health of Burkina Faso, and the LSHTM Ethics Committee. All women provided written informed consent during antenatal care visits and were free to withdraw at any time. Authors’ contributions AR conceptualised this study with input from UdA, HB, AT, BC, JDB. Data collection was co-ordinated by BC, JDB and PregnAnZI-2 field teams in The Gambia and Burkina Faso. TR performed the analysis with full access to the data. JCJ drafted the initial manuscript with input from HB and AR. All authors contributed to the final version. AR gave oversight to the work as guarantor and accepts full responsibility for finished work and controlled the decision to publish. Declaration of competing interests None declared. Data sharing statement Data may be obtained from a third party and are not publicly available. The clinical data has been collected following provision of informed consent under the prerequisite of strict participant confidentiality. Qualified researchers may request access with the Gambia Government/MRC Joint Ethics Committee. The review process and release of data will be facilitated by MRC Unit The Gambia ( http://www.mrc.gm/ ) through the Head of Governance at MRCG. Access will not be unduly restricted. Funding The PregnAnZI-2 trial was funded by a grant from the UKRI under the Joint Global Health Trial Scheme (JGHT) (ref: MC_EX_MR/P006949/1) and the Gates Foundation (Ref:OPP1196513). The funders and study sponsor (MRCG) had no role in the study design, collection, analysis or interpretation of data, writing of article nor the decision to submit for publication. 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