new theme preterm

A collaboration between The University of Sheffield and
The University of Cape Town

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ABSTRACTS

Introduction: Preterm birth (PTB at <37 weeks gestation) is the leading cause of death worldwide in children under 5 years. Approximately 10.6% of live births (14.8 million infants) are born prematurely each year with 81% of preterm births in Asia and sub-Saharan Africa.

Introduction:
Preterm birth (PTB at <37 weeks gestation) is the leading cause of death worldwide in children under 5 years. Approximately 10.6% of live births (14.8 million infants) are born prematurely each year with 81% of preterm births in Asia and sub-Saharan Africa. Developing clinical guidelines to prevent PTB in LMIC settings, where the preterm birth rates are highest requires drawing on existing evidence that is largely reliant on research data gathered in high income settings. We sought to explore the extent to which systematic review evidence considers generalisability of findings to LMIC settings, and the settings in which primary data are gathered. 

Methods: 
A mapping review described the evidence across a range of interventions, implemented during pregnancy to prevent spontaneous PTB. Systematic searches of electronic databases identified 188 systematic reviews for inclusion. Data was abstracted and findings subject to a narrative synthesis. If reported, the countries where the primary studies were undertaken were classified using World Bank categories. 

Results: 
We included 188 systematic reviews addressing the following interventions: health care delivery and health systems (n=18), predicting risk of PTB (n=18), lifestyle changes (n=15), nutritional interventions (n=36) periodontal disease treatment (n=23), influenza vaccination (n=2), infection screening and treatment (18 reviews), cerclage (n=19), corticosteroids (n=10), cervical pessary (n=6) and progesterone (n=23). We found a lack of consistency between reviews on the effects on PTB and an absence of strong evidence supporting existing interventions in reducing PTB. 28% of reviews did not report the country where the primary studies were undertaken suggesting a poor understanding of the influence of context on PTB outcomes. The proportion of studies undertaken in LMICs varied across intervention types. We found that there is very little data from low income countries, with most LMIC data derived from lower middle and middle income countries. 

Conclusions: 
This review describes the current evidence published over the last decade, on interventions to reduce the risk of PTB. We suggest an inverse care pattern of evidence with the least amount of evaluation occurring in those contexts where PTB rates are highest. The extent to which findings can be generalised to different contexts has been largely unexplored in the existing evidence reviews. The lack of data to support effective interventions in LMIC contexts has implications for the development of contextually relevant clinical guidelines. 

Background:  Preterm birth is a global and local public health challenge.  Sri Lanka toils to care for preterm babies.

Peiris T.D.P1, Jayaratne I.L.K1, Seneviratne R.de A2

1Family Health Bureau, Ministry of Health, Sri Lanka

2General Sir John Kothalawala Defence University, Sri Lanka

Background:  Preterm birth is a global and local public health challenge.  Sri Lanka toils to care for preterm babies.

Objective: To determine risk factors, immediate triggering factors and critical outcome predictors of preterm births and to assess coverage of essential interventions for preterm babies in a district in Sri Lanka.

Methods: Two unmatched case-control studies to determine risk factors and critical neonatal outcomes, a case-crossover study to identify triggering factors and two descriptive studies to assess coverage of essential newborn care interventions for preterms were carried out.

A preterm prediction score (PPS) was developed, validated and its feasibility was assessed in field.

Results: Population comprised of 75.1% late preterms. Main risk factors identified included: multiple pregnancy, bleeding during pregnancy, past preterm birth, recent stressful event, higher gravidity, PIH, unsatisfactory oral hygiene.

Immediate triggers were disturbed sleep and travelling by three-wheeler.

Main risk factors for critical outcomes included; abnormal APGAR, birth weight <2000, antenatal bleeding, stressful event, PPROM and frequent sexual intercourse. Magnesium sulfate and treated dental caries were protective factors.

Magnesium sulfate and kangaroo mother care were unsatisfactory among recommended interventions.

A low coverage was found for maternal abdomen delivery, delayed cord clamping, temperature measurement, vitamin K & breastfeeding counselling and delayed weighing.

PPS was identified as valid tool with a good predictive ability (AUC=0.746) feasible at field level.

Conclusions and Recommendations: Findings could be used to educate public and health professionals and preventive strategies should be formulated.

Keywords: Preterm birth, risk factor, triggering factor, neonatal outcome

Globally, around 11% of babies are born too soon and preterm birth (PTB) complications account for 35% of all newborn deaths. PTBs and deaths are inequitably distributed with higher rates in countries with limited resources, especially in sub-Saharan Africa and South Asia.

Authors: Shams El Arifeen1, Ahmed Ehsanur Rahman1, Julie Balen2, Shumona Sharmin Salam2, Shafiqul Ameen1, Bronwen Gillespie2, Caroline Anne Mitchell2Fiona Campbell2, Simon Dixon2, Tazeen Tahsina1, Clive Gray3, Quamrun Nahar1, Dilly Anumba2

 1 icddr,b, Bangladesh

2 University of Sheffield, UK

3 University of Cape Town, South Africa

 Globally, around 11% of babies are born too soon and preterm birth (PTB) complications account for 35% of all newborn deaths. PTBs and deaths are inequitably distributed with higher rates in countries with limited resources, especially in sub-Saharan Africa and South Asia. Achieving the ambitious 2030-SDG target of reducing neonatal mortality rate to ≤12 per 1,000 live births will, therefore, require better understanding and innovations related to prevention and management of preterm birth in high burden countries. We aim to prioritise research options related to the prevention and management of PTB in low and middle-income countries (LMICs) with a specific focus on Bangladesh and South Africa. We have adopted the validated Child Health and Nutrition Research Initiative (CHNRI) methodology to set research priorities in this area. This includes obtaining inputs from two different groups: (i) technical experts in newborn and PTB research in LMICs and globally, who will be responsible for identifying and scoring research questions based on specific criteria; and (ii) stakeholders from Bangladesh and South Africa, with direct knowledge and experience of PTB policies, programmes and practices, who will set a minimum threshold and allocate weights to the criteria/intermediate scores. The process is managed by investigators from the Universities of Sheffield, Pretoria, Cape Town and icddr,b. Following the steps, a consultative workshop was organized in Bangladesh to determine the context for the prioritization exercise, list technical experts and stakeholders. A similar workshop will be organized in South Africa. This CHNRI exercise will generate a list of top-ranked research questions related to prevention and management of PTB in LMICs, based on Research Priority Score and Average Expert Agreement for each research question. This list can then inform funding agencies, development partners and researchers to prioritize research needs and allocate resources based on globally relevant and locally contextualised evidence.

 

Background: One of the main roles of the placenta is to maintain fetal-maternal tolerance. HIV and/or antiretroviral (ARV) exposure may interfere with this tolerance but data are sparse. We characterized placental decidua T regulatory cells (Treg) from HIV-infected women who initiated ART late in pregnancy compared to uninfected controls.

Nadia Ikumi1, Nonzwakazi Bangani1, Michelle Barboure1, Berenice Alinde1, Bryan Gascon1, Lizette Fick1, Komala Pillay2, Landon Myer3, Thokozile Malaba3, Mohammed Lamorde4, Saye Khoo5, Heather B Jaspan1 and Clive M Gray1

1Division of Immunology, Institute of Infectious Disease and Molecular Medicine, University of Cape Town

2Division of Anatomical Pathology, University of Cape Town

3Division of Epidemiology and Biostatistics, School of Public Health and Family Medicine, University of Cape Town

4Infectious Diseases Institute, College of Health Sciences, Makerere University

5Institute of Translational Medicine, University of Liverpool

Background: One of the main roles of the placenta is to maintain fetal-maternal tolerance. HIV and/or antiretroviral (ARV) exposure may interfere with this tolerance but data are sparse. We characterized placental decidua T regulatory cells (Treg) from HIV-infected women who initiated ART late in pregnancy compared to uninfected controls.

Methods: Placentas of HIV-infected women were drawn from an ongoing study in which women commence ART at or after 28 weeks’ gestation (n=14) and HIV-uninfected controls (n=6). Lymphocytes obtained from the maternal decidua and villous tissue were characterised using flow cytometry and formalin fixed paraffin embedded tissue sections were phenotyped using immunofluorescence. Pathology scoring was based on the Amsterdam placental workshop group consensus statement.

 Results: A higher incidence of preterm deliveries was reported in HIV infected mothers, 75% were very preterm (28+0-31+6 weeks). The frequency of decidual CD4+ T cells was lower in placentas from HIV infected women vs controls (p=0.005) and similarly, total CD8+ T cells were significantly higher in the HIV infected group (p=0.006). The variable expression of CD4+TIGIT and CD4+CD45RA, within decidual membranes was higher in HIV infected women vs uninfected. We identified a series of decidual Treg subsets that were all CD3+CD4+CD127-CD25HiFoxP3++ with variable expression of CD39, CTLA4 and TIGIT. Highly suppressive Treg cells were more enriched in placentas from very preterm placentas in HIV infected women. Pathology indices including prolonged meconium exposure, cord vessel vasculitis and plasmacytic deciduitis were reported in higher frequency in placentas from HIV infected women, specifically in very preterm deliveries.

 Conclusions: The T cell phenotype in the maternal decidua appears to have a predominantly adult systemic footprint while the villous tissue mirrors foetal cells. There are unique and multiple Treg signatures in the placenta which appear to be associated with pre-term birth and may be influenced by HIV and or ART exposure.

Background: Intrauterine infections and unculturable vaginal bacteria has been suggested to play an important role in causing preterm birth (PTB). Inflammation during pregnancy has also been implicated in altering the homeostatic mechanisms for the developing foetus thereby leading to poor pregnancy outcomes.

Muchaneta Gudza-Mugabe1,2,6*, Enock Havyarimana1, Shameem Jaumdally1, Katie Lennard1, Andrew Tarupiwa2, Fortunate Mugabe4, Rooyen Mavenyengwa3 Lindi Masson1, Heather Jaspan1,5.

Authors’ affiliations: 
1University of Cape Town, South Africa

2National Microbiology reference laboratory, Zimbabwe

3University of Zimbabwe

4Harare Central Hospital, Zimbabwe

5Seattle Children’s Research Institute, USA

6 Letten Foundation Research Centre

Background:
Intrauterine infections and unculturable vaginal bacteria has been suggested to play an important role in causing preterm birth (PTB). Inflammation during pregnancy has also been implicated in altering the homeostatic mechanisms for the developing foetus thereby leading to poor pregnancy outcomes

Objective: Our objectives was to characterize the vaginal microbiota and immune factors of women who experienced preterm deliveries (delivery <37 weeks; n=42) compared to women who experienced term deliveries (n=202).

Methodology: Vaginal swabs were collected from pregnant women between 13-35 weeks of gestational age at referral hospitals in Harare, Zimbabwe. The 16SrRNA gene V4 region was PCR amplified and sequenced on the Illumina Miseq. Data was analysed using QIIME, UPARSE, and custom R scripts for downstream analysis. Cytokine concentrations were measured using Luminex

Results:
Three clusters of microbial community state types (CST) were evident:  CST1 (Lactobacillus. iners-dominated), CST2 (L. crispatus-dominated), CST3 (Mixed Gardnerella vaginalis-dominated). There were no differences in alpha and beta diversity between the preterm and term groups (p = 0.47 and p=0.939) respectively. Although there was no evidence of clustering of the two groups with any CST, the relative abundance of L. iners was most predictive of preterm birth using a random forest model. Low IL-13 (adj. p<0.001) and FGF-basic protein were significantly associated with preterm birth after controlling for possible risk factors such as pregnancy induced hypertension, maternal age, BV status and  HIV.

Conclusion:
In agreement with previous studies, L. iners, the dominant Lactobacillus in vaginas of black women, was found most predictive of PTB in this cohort, while low growth factors and Th2 cytokines factors were also associated with PTB.

Key words: Lactobacillus, CST., Gardnerella vaginalis, Preterm birth, microbiota, vagina

Background: Technological advances such as surfactant and intensive care have increased the survival of extremely low birth weight (ELBW) babies. The costs of these interventions are high. Equity and distributive justice considerations should guide provision of such services.

Setting: In 2015 a situation analysis of South Africa’s Western Cape province government’s neonatal services (597 beds, 12400 admissions) showed significant variation in care practices and outcomes for ELBW babies by hospital and region. Overall survival of babies born less than 1000g birth weight was 620/1000 live births.

Intervention:  A service-wide consultative, iterative, and evidence-led process of standardisation of interventions for ELBW babies across all perinatal care pathways was undertaken.

Outcome: The table shows the main gains that standardisation achieved for equity and distributive justice.

Intervention

Equity

Distributive justice

Babies likely to be born between 27 and 32 weeks’ gestation are moved in utero to tertiary centres for delivery where possible

Babies born below 27 weeks gestation and/or 800g are not eligible for surfactant or invasive ventilation

 

Levels of intervention are higher for inborn than outborn babies

 

Stratification of intervention levels by birth weight and/or gestation accords with hospital level

Care pathways that do not have the physical resources to meet the minimum standard have been flagged for priority interventions

Senior staff take responsibility for protocol-related decision-making and support of midwives and medical staff across all care pathways

 

Conclusion: A standard protocol was agreed and endorsed by managers and clinicians, setting the scene for improved equity and distributive justice in a middle income African health system.

Background: Gestational age (GA) is a key determinant of newborn survival and long-term impairment. Accurate estimation of GA facilitates timely provision of essential interventions to improve maternal and newborn outcomes. Menstrual based dating, ultrasound based dating, and neonatal estimates are primarily used for assessing GA; all of which have some strength and weaknesses that require critical consideration.

Authors: Shumona Sharmin Salam1, Nazia Binte Ali2, Ahmed Ehsanur Rahman2, Tazeen Tahsina2, Md. Irteja Islam2, Afrin Iqbal2, DM Emdadul Hoque2, Samir Kumar Saha3, Shams El Arifeen2 

1Department of Oncology and Metabolism, University of Sheffield, United Kingdom

2Maternal & Child Health Division, icddr,b, Dhaka 1212, Bangladesh

3 Department of Microbiology, Dhaka Shishu (Children’s) Hospital, Dhaka 1207, Bangladesh

Background: Gestational age (GA) is a key determinant of newborn survival and long-term impairment. Accurate estimation of GA facilitates timely provision of essential interventions to improve maternal and newborn outcomes. Menstrual based dating, ultrasound based dating, and neonatal estimates are primarily used for assessing GA; all of which have some strength and weaknesses that require critical consideration.  Last menstrual period (LMP) is simple, low-cost self-reported information, recommended by World Health Organization for estimating GA but has issues of recall mainly among poorer, less educated women and women with irregular menstruation, undiagnosed abortion, and spotting during early pregnancy. Several studies have noted that about 20-50% of women cannot accurately recall the date of LMP. The goal of this study is therefore to improve recall of LMP and by doing so increase the accuracy of LMP based GA assessment in a rural population of Bangladesh where antenatal care-seeking, availability and utilization of USG is low.

Methods:We are conducting a 4-parallel arm, superiority, community based cluster randomized controlled trial comparing three interventions to improve recall of GA with a no intervention arm. The interventions include (i) counselling and paper based calendar (ii) counselling and cell phone based SMS alert system (iii) counselling and smart-phone application. The trial is being conducted among 3360 adolescent girls and recently married women in Mirzapur sub-district of Bangladesh.

Discussion: Enrolment of study participants continued from January 24, 2017 to March 29, 2017. Data collection and intervention implementation is ongoing and will end by December, 2019. Data analysis will measure efficacy of interventions in improving the recall of LMP date among enrolled participants. Results will be reported following CONSORT guidelines. The innovative paper and e-platform based interventions, if successful, can provide substantial evidence to scale-up in low resource settings where m-Health initiatives are proliferating in policy and implementation.

Trial Registration: ClinicalTrials.gov NCT02944747. The trial has been registered before starting participant enrolment on 24 October 2016.

Keywords: Gestational age, LMP, recall, preterm birth, Bangladesh, mobile phone, m-Health

Aim: To develop, implement and evaluate family-centred interventions to promote parental involvement in caregiving in a Neonatal Intensive Care Unit.

Skene C, Gillespie S*, Gerrish K, Bayliss P, Price F, Pilling E.

 

Sheffield Teaching Hospitals NHS, Foundation Trust, UK. University of Sheffield, Sheffield, NIHR Sheffield Clinical Research Facility for Experimental Medicine, UK, Sheffield Children’s Hospital NHS Foundation Trust, UK. 

* Presenting author

 

Aim: To develop, implement and evaluate family-centred interventions to promote parental involvement in caregiving in a Neonatal Intensive Care Unit.

Methodology: A participatory action research approach was used to implement two changes in practice a) improved skin-to-skin contact b) unlimited parental presence at the cot-side. The changes were underpinned by a family-centred philosophy of care and education. Data were collected from staff using a questionnaire, focus groups and interviews, and from parents using focus groups and interviews. Qualitative data were analysed using Framework and quantitative data analysed using descriptive and t-test statistics.

Findings: Changes in practice were successfully implemented. Nurses reported positively on improvements in Family Centred Care; most notably information-sharing with parents, providing family support, enabling parental participation in care and improved competence supporting parents in care-giving. These changes were reflected in parental feedback.

Conclusion: Understanding the context of the neonatal unit can support cultural change when change is actively facilitated and owned by the staff concerned. Acknowledging parents as the main caregiver can be challenging for nurses and they require support and education to enable them to manage the changes necessary to provide Family-Centred Care.

Introduction: We sought to determine the relationship of cervicovaginal fluid (CVF) cytokine and metabolite expression with spontaneous preterm birth (PTB, <37 week’s gestation) and delivery within 2 weeks (14 days) of presentation with symptoms of preterm labour.

Emmanuel Amabebe, Xiaoya He, Robyn Wood, Dilly Anumba

Department of Oncology and Metabolism, University of Sheffield, UK.

Introduction: We sought to determine the relationship of cervicovaginal fluid (CVF) cytokine and metabolite expression with spontaneous preterm birth (PTB, <37 week’s gestation) and delivery within 2 weeks (14 days) of presentation with symptoms of preterm labour.

Method: CVF from 97 (preterm=19, term=78) singleton women with threatened preterm labour studied between 19+0-36+6 weeks’ gestation were analysed for cytokine/chemokines by multiplexed bead-based immunoassay, while metabolites were quantified by enzyme-based spectrophotometry in a subset of 61 women (preterm=16, term=45). Overall, 10 women delivered within 14 days of sampling. Prevalence of targeted vaginal bacterial species was also determined for 70 women (preterm=14, term=66) by PCR.

Results: In addition to several correlations, certain cytokine-metabolite combinations were predictive of PTB, while others were predictive of delivery within 14 days of sampling (Table 1). Fusobacterium sp., Mubiluncus mulieris and Mycoplasma hominis were also detected in more preterm-delivered than term women (P<0.0001), while, M. curtisii was found in more term-delivered than preterm women (P<0.0001). The prevalence of GardnerellaBacteroides sp., and Lactobacillus sp. did not differ significantly between the groups.

Table 1. Predictive capacities of CVF cytokine-metabolite combinations for preterm birth within 14 days of sampling.

Biomarker combination

AUC, 95%CI

<37 weeks’ gestation

L/D-lactate ratio+Acetate+IL-6+TNF-r1

0.82, 0.65-0.93

Acetate+IL-6+TNF-r1

0.84, 0.67-0.94

Total lactate+Acetate+IL-6+TNF-r1

0.85, 0.69-0.95

Delivery within 14 days of sampling

Acetate/glutamate ratio+IL-6

0.82, 0.65-0.93

Total lactate+Acetate/glutamate ratio+IL-6

0.82, 0.66-0.93

L/D-lactate ratio+Acetate/glutamate ratio+IL-6

0.84, 0.67-0.94

AUC, area under the ROC curve; CI, confidence interval.

Conclusion: The combination of CVF metabolites and pro-inflammatory mediators which are indicators of host-microbial interactions related to preterm labour are able to distinguish symptomatic women at risk of imminent preterm birth and this can be tested in larger population for potential clinical utility.

Introduction: Spontaneous preterm birth (sPTB) remains a leading cause of neonatal mortality and morbidity worldwide, accounting for over 1 million deaths a year.

B.F. Narice, M.A. Martínez, D. Lázaro-Pacheco, E. Amabebe, I.U. Rehman and D.O. Anumba

Introduction: Spontaneous preterm birth (sPTB) remains a leading cause of neonatal mortality and morbidity worldwide, accounting for over 1 million deaths a year. The limited predictive value of current screening techniques calls for the development of more accurate and cost-effective non-invasive tools for sPTB. We employed Raman Spectroscopy, a technique which is based on the inelastic scattering of low-intensity monochromatic light, to assess the cervicovaginal fluid (CVF) in pregnant women as a predictive tool for sPTB.

Methods: High vaginal swabs were taken from mid-trimester asymptomatic high risk women with previous history of sPTB (n=21) and from mid- and third-trimester symptomatic women (n=25), and analysed with DXRTM Raman Microscope using PCA-LDA (Unscrambler X, CAMO). Results were then correlated with enzyme-based spectrophotometry and nuclear magnetic resonance spectroscopy (H1-NMR) and interpreted in the context of the clinical history of the patients, their cervical length measured by transvaginal ultrasound (TVS CL) and quantitative fetal fibronectin (fFN).

Results: Raman was capable of predicting sPTB with a sensitivity of 91% and a specificity of 64.7% in the asymptomatic group, and a sensitivity of 93.8% and specificity of 67% in the symptomatic group. Women who delivered prematurely had higher fFN values and shorter TVS CL than their term counterparts though differences in the asymptomatic group were not statistically significant. Consistent with previous H1-NMR data (Amabebe et al, 2016), acetate levels measured with Raman and spectrophotometry in women who delivered prematurely were significantly higher than in those who had a term delivery (p<0.05).

Conclusions: This pilot study suggests that Raman can accurately detect key molecular differences in the CVF of pregnant women based on birth outcome which may hold predictive value for sPTB.

Background: Pre-eclampsia complicates 2-15% of pregnancies worldwide. In a previous South African study, the prevalence of HIV was significantly lower (26.4%) in women with pre-eclampsia compared to controls (36.6%). We investigated the association between HIV and pre-eclampsia in South Africa, as well as outcomes of babies born to pre-eclamptic mothers.

Mpho Sikhosana1,2*, Lazarus Kuonza1, Clare Cutland2, Nkengafac Motaze2,4 Melinda Suchard2, 5

 1South African Field Epidemiology Training Programme, National Institute for Communicable Diseases, Division of the National Health Laboratory Service, South Africa, 2Centre for Vaccines and Immunology, National Institute for Communicable Diseases, Division of the National Health Laboratory Service, South Africa, 3Respiratory and Meningeal Pathogens Research Unit, Chris Hani Baragwanath Academic Hospital, University of the Witwatersrand 3Department of Global Health, Faculty of Medicine and Health Sciences, Stellenbosch University, 5Chemical Pathology, School of Pathology, Faculty of Health Sciences, University of the Witwatersrand

*Corresponding authors: Mpho Sikhosana, South African Field Epidemiology Training Programme, National Institute for Communicable Diseases, Division of the National Health Laboratory Service, South Africa. lsikhosana@gmail.com or Sikhosanam@nicd.ac.za

Background: Pre-eclampsia complicates 2-15% of pregnancies worldwide. In a previous South African study, the prevalence of HIV was significantly lower (26.4%) in women with pre-eclampsia compared to controls (36.6%). We investigated the association between HIV and pre-eclampsia in South Africa, as well as outcomes of babies born to pre-eclamptic mothers.

Methods: This case control study used secondary data from a cohort study investigating correlates of protection against invasive Group B Streptococcus disease. We defined a pre-eclamptic case as new onset of hypertension (>140mmHg systolic blood pressure and/or >90mmHg diastolic blood pressure) at or after 20 weeks gestation in a previously normotensive woman, coupled with proteinuria (rapid uranalysis >2+). A control was a participant without pre-eclampsia. Exclusion criteria included unknown or unrecorded HIV status or history of chronic hypertension. The association between pre-eclampsia and HIV status, body mass index and maternal age was assessed using logistic regression.

Results: We identified 573 cases and 600 controls from review of clinical notes. Of low birthweight infants (<2500g), 82 were born to controls while 298 were born to cases (p <0.001). Of 367 (31.3%) premature infants, most were born to cases compared with controls (47.6% vs 15.7%; p <0.001). HIV positivity was 24% and 30% amongst cases and controls respectively. After univariate analysis, HIV and maternal age were associated with pre-eclampsia. After multivariate analysis, HIV status remained negatively associated with pre-eclampsia (OR 0.7, p 0.01).

Conclusion: Pre-eclampsia is a major cause of prematurity and low birthweight in infants, with half of pre-eclamptic women delivering preterm, low birthweight infants. HIV status was negatively associated with pre-eclampsia, confirming previous studies. HIV infection may be a protective factor against development of pre-eclampsia. Immune mechanisms which may be responsible for such protection warrant further study.  

Keywords: HIV, pre-eclampsia, hypertension, maternal age, body mass index, immune

Background: Despite the recognized benefit of antiretroviral therapy (ART) for preventing and treating HIV, some studies have reported adverse birth outcomes with in utero ART exposure.

Vundli Ramokolo1,2, Ameena E. Goga1,3, Carl Lombard4, Tanya Doherty1,5, Debra J. Jackson5,6 and Ingunn M.S. Engebretsen2

 

1Health Systems Research Unit, South African Medical Research Council, Cape Town, South Africa

2Centre for International Health, Department of Global Public Health and Primary Health Care,

University of Bergen, Bergen, Norway

3Department of Paediatrics and Child Health, Kalafong Hospital, University of Pretoria, South Africa

4Biostatistics Unit, South African Medical Research

Council, Cape Town, South Africa

5School of Public Health, University of the Western Cape, Cape Town, South Africa;

6UNICEF, New York, New York

Background: 
Despite the recognized benefit of antiretroviral therapy (ART) for preventing and treating HIV, some studies have reported adverse birth outcomes with in utero ART exposure. We evaluated the effect of infant in utero HIV and ART exposure on preterm delivery (PTD), low birth weight (LBW), small for gestational age (SGA), and underweight for age (UFA) at 6 weeks.

Methods: 
We surveyed 6179 HIV-unexposed-uninfected (HUU) and 2599 HIV-exposed-uninfected (HEU) infants. HEU infants were stratified into 3 groups: ART, Zidovudine alone, and no antiretrovirals (None). The ART group was further stratified to explore pre- or  postconception exposure. Multivariable logistic regression evaluated effects of HIV and ARV exposure on the outcomes.

Results: 
We found higher odds of PTD, LBW, SGA, and UFA in HEU than HUU infants. HEU in the None group (adjusted odds ratio [AOR], 1.9; 95% confidence interval [CI], 1.2–3.0) or those whose mothers initiated ART preconception (AOR, 1.7; 95% CI, 1.1–2.5) had almost twice the odds of PTD than infants whose mothers started ART postconception, but no increased odds for other outcomes.

Conclusions:
There was an association between preconception ART and PTD. As ART access increases, pregnancy registers or similar surveillance should be in place to monitor outcomes to inform future policy.

Keywords. antiretroviral therapy; birth outcome; HIV; South Africa.

This paper builds on critical scholarship in global health to call for people-centred health systems research on preterm birth (PTB), with South Africa as a case study.

Contributors: Bronwen Gillespie, Shumona Salam, Siobhan Gillespie, Priya Soma-Pillay, Quamrun Nahar, Dilly Anumba, Julie Balen

This paper builds on critical scholarship in global health to call for people-centred health systems research on preterm birth (PTB), with South Africa as a case study. The World Health Organization (WHO) advises that PTB prevention and management requires improved access to quality maternity systems and services (WHO 2018). South Africa has reduced the maternal mortality ratio in public health hospitals by almost a third within seven years (Moodley et al. 2018) and neonatal mortality is in decline, albeit more slowly than investment would imply (Rhoda et al. 2018), signaling an important turnaround from earlier reports (HRW 2011, Chadwick et al 2014). Through a detailed literature review we found comprehensive recommendations for improvements in health systems and clinical procedures related to maternal and neonatal care (Pattinson 2014, DoH 2014, Rhoda et al, 2018). However, two interrelated cross-cutting issues that could benefit from further examination have emerged, namely: (i) disparities in service use (e.g. amongst adolescents, HIV patients, migrants, specific socioeconomic and geographic areas) and reproductive decision making, such as rates of unplanned pregnancies, in certain populations (Chersich et al 2017, STATS SA 2016); and (ii) the importance of quality of care, referring not just to care on the body but also the interpersonal interactions (WHO 2018, HRW 2011) and organizational relationships (Blaauw et al 2003, Gilson et al 2004) involved. Literature includes work on the influence of ‘voice’ in the mConnect system (Schneidermann 2018) and in the uptake of kangaroo mother care (Solomons and Rosant 2012), highlighting the importance of relational aspects of care. An approach to addressing PTB should therefore include a focus on social relations of care, or the interpersonal exchanges between patient and provider and the understandings that drive these, as well as on reproductive agency, both of which put women’s lived experience at the centre.

Background: South Africa has a high perinatal mortality rate, the Saving Babies Report (2012 – 2013) shows that district hospitals have the highest early neonatal mortality rate for babies under 2000g per level of care.

Background: South Africa has a high perinatal mortality rate, the Saving Babies Report (2012 – 2013) shows that district hospitals have the highest early neonatal mortality rate for babies under 2000g per level of care. Inadequate neonatal facilities, care plans, and monitoring were important avoidable factors in deaths from prematurity-related conditions. The national perinatal morbidity and mortality committee report (2014) emphasises the importance of CPAP, and recommends its availability in district hospitals.

Madwaleni District Hospital (1400 deliveries per year) is in the Amathole district of the rural Eastern Cape – where perinatal mortality and early neonatal death rates are well above the national average. Before June 2018 respiratory support was limited to nasal prongs or head box oxygen, and nursing care was provided by maternity unit midwives. Neonates requiring more support were referred to Nelson Mandela Academic Hospital in Mthatha (two hours by road). Transfers are challenging with few available beds, long ambulance waiting times, untrained ambulance staff, and inadequate equipment.

On 5 June 2018 Madwaleni opened a neonatal unit equipped with CPAP and dedicated neonatal unit nursing staff.

 Methods and Results: We conducted a retrospective audit of neonatal admissions before (January to May 2018) and after (June to October) the unit opening. While the incidence of neonates admitted remained unchanged (8% of live births); we transferred fewer neonates (four versus one), had fewer early neonatal deaths (four versus two) and utilised CPAP in five cases that would otherwise have been transferred.

 Conclusion: Madwaleni’s neonatal unit gives vulnerable babies access to improved medical and nursing care in a dedicated unit. Although the unit is new and numbers small, we believe that Madwaleni will assist in improving neonatal outcomes in our in district, alleviate strain on our referral centre, and can serve as a template for other small district hospitals around the country.

 

Introduction: Most recommendations on infection screening and antimicrobial therapy for the prevention of preterm birth (PTB) arise from research conducted in developed countries and cannot be generalised. Therefore, we propose a comprehensive systematic review of all available literature which specifically targets interventions in low-middle income countries (LMICs).

Chanzu-Ikumi*, B.F. Narice*, E. Amabebe, C. Gray, D.O. Anumba

*Contributed equally

Introduction: Most recommendations on infection screening and antimicrobial therapy for the prevention of preterm birth (PTB) arise from research conducted in developed countries and cannot be generalised. Therefore, we propose a comprehensive systematic review of all available literature which specifically targets interventions in low-middle income countries (LMICs).

Method: The initial scoping search will be conducted using Medline via Ovid, Web of Science and Scopus, and subsequently complemented with citation searching. Medical Subject Headings for the search strategy will include but not be limited to PTB, LMICs, infection screening, antibiotics, and pre-labour premature rupture of membranes (PPROM). Synonyms and truncation strategies will be used to optimise the engine search. Study selection will follow the PRISMA guidelines, and quality assessment will be performed using CASP checklists. Only primary research which explores measures to prevent or treat infections (Intervention) in pregnant women from LMICs (Participants) when compared to no or alternative intervention (Control) with the aim to reduce PTB or increase birthweight (Outcome) will be included. The search will be limited to human studies, but no data or language restriction will be applied.

Results: Selected studies will be grouped into 5 main themes: (1) antimalarial treatment, (2) congenital infection screening, (3) bacterial vaginosis treatment, (4) antibiotics for asymptomatic bacteriuria and (5) administration of antibiotics in the context of PPROM and PTB.

Conclusion: We hope this review will help us (1) better understand the impact that antenatal screening and treatment of infections has on gestational age and weight at birth in LMICs and (2) identify gaps in the existing literature to inform future high-quality primary studies in low resource settings which assess interventions to reduce infection-inflammation-associated PTB.

The purpose of this study was to describe the prevalence of HLA antibodies in serum of 30 mother-infant pairs six weeks post-partum.

DM Savulescu1, M Groome2, SCK Malfeld1, S Madhi2, A Koen2, S Jones2 and M Suchard1,3

  1. Centre for Vaccines and Immunology (CVI), National Institute for Communicable Diseases (NICD), a division of the National Health Laboratory Service, South Africa
  2. Respiratory and Meningeal Pathogens Research Unit (RMPRU), University of the Witwatersrand, South Africa
  3. Chemical Pathology, Faculty of Health Sciences, University of the Witwatersrand, South Africa

Human leukocyte antigens (HLA) are proteins responsible for presentation of peptide fragments to responding T lymphocytes. They are expressed on the surface of most cells in the human body. HLA-encoding genes are the most polymorphic genes in the human genome. The high HLA polymorphism may result in immune responses against antigens originating in another individual (alloimmunity), which may, in part, be mediated by antibodies against HLA proteins (HLA antibodies). During the late stages of pregnancy, women produce and transfer high amounts of antibodies, including HLA antibodies, to the fetus. However, very little is known about their specificity, transfer rate, role in pregnancy or their development in newborns.

The purpose of this study was to describe the prevalence of HLA antibodies in serum of 30 mother-infant pairs six weeks post-partum. We used Luminex technology that allows for detection of low levels of antibodies. We found 72% of babies and 80% of mothers to express HLA antibodies. 77% of HLA class I and 50% of HLA class II baby antibodies matched those of their mothers, suggesting that the remaining antibodies were self-made. In contrast, only 16 and 24% of the maternal HLA class I and HLA class II antibodies, respectively, were found in their babies. The most common sub classes of antibodies were HLA-B for class I in both groups, and DQA/B and DRB1 for class II in babies and mothers, respectively.

These findings contribute to our understanding of mother-to-fetus transfer and natural development of HLA antibodies in infants. We believe that this information is required as a baseline in clinical trials of infectious disease vaccines during pregnancy, and for designing maternal immunization-based vaccines against enveloped viral infections.