Early neonatal mortality is modulated by gestational age, birthweight and fetal heart rate abnormalities in the low resource setting in Tanzania – a five year review 2015–2019

Background: Early Neonatal mortality (ENM) (\u3c7days) remains a signifcant problem in low resource settings. Birth asphyxia (BA), prematurity and presumed infection contribute signifcantly to ENM. The study objectives were to determine: frst, the overall ENM rate as well as yearly ENM rate (ENMR) from 2015 to 2019; second, the infuence of decreasing GA (\u3c37weeks) and BW (\u3c2500g) on ENM; third, the contribution of intrapartum and delivery room factors and in particular fetal heart rate abnormalities (FHRT) to ENM; and fourth, the Fresh Still Birth Rates (FSB) rates over the same time period. Methods: Retrospective cohort study undertaken in a zonal referral teaching hospital located in Northern Tanzania. Labor and delivery room data were obtained from 2015 to 2019 and included BW, GA, fetal heart rate (FHRT) abnormalities, bag mask ventilation (BMV) during resuscitation, initial temperature, and antenatal steroids use. Abnormal outcome was ENM\u3c7days. Analysis included t tests, odds ratios (OR), and multivariate regression analysis. Results: The overall early neonatal mortality rate (ENMR) was 18/1000 livebirths over the 5 years and did not change signifcantly comparing 2015 to 2019. Comparing year 2018 to 2019, the overall ENMR decreased signifcantly (OR 0.62; 95% confdence interval (CI) 0.45–0.85) as well as infants ≥37weeks (OR 0.45) (CI 0.23–0.87) and infants \u3c37weeks (OR 0.57) (CI 0.39–0.84). ENMR was signifcantly higher for newborns \u3c37 versus ≥37weeks, OR 10.5 (p\u3c0.0001) and BW \u3c2500 versus ≥2500g OR 9.9. For infants \u3c1000g / \u3c28weeks, the ENMR was ~588/1000 livebirths. Variables associated with ENM included BW - odds of death decreased by 0.55 for every 500g increase in weight, by 0.89 for every week increase in GA, ENMR increased 6.8-fold with BMV, 2.6-fold with abnormal FHRT, 2.2-fold with no antenatal steroids (ANS), 2.6-fold with moderate hypothermia (all \u3c0.0001). The overall FSB rate was 14.7/1000 births and decreased signifcantly in 2019 when compared to 2015 i.e., 11.3 versus 17.3/1000 live births respectively (p=0.02). Conclusion: ENM rates were predominantly modulated by decreasing BW and GA, with smaller/ less mature newborns 10-fold more likely to die. ENM in term newborns was strongly associated with FHRT abnormalities and when coupled with respiratory depression and BMV suggests BA. In smaller newborns, lack of ACS exposure and moderate hypothermia were additional associated factors. A composite perinatal approach is essential to achieve a sustained reduction in ENMR

Distribution of HPV genotypes in cervical intraepithelial lesions and cervical cancer in Tanzanian women

<p>Abstract</p> <p>Background</p> <p>Infection with human papillomavirus (HPV) is associated with uterine cervical intraepithelial neoplasia (CIN) and invasive cancers (ICC). Approximately 80% of ICC cases are diagnosed in under-developed countries. Vaccine development relies on knowledge of HPV genotypes characteristic of LSIL, HSIL and cancer; however, these genotypes remain poorly characterized in many African countries. To contribute to the characterization of HPV genotypes in Northeastern Tanzania, we recruited 215 women from the Reproductive Health Clinic at Kilimanjaro Christian Medical Centre. Cervical scrapes and biopsies were obtained for cytology and HPV DNA detection.</p> <p>Results</p> <p>79 out of 215 (36.7%) enrolled participants tested positive for HPV DNA, with a large proportion being multiple infections (74%). The prevalence of HPV infection increased with lesion grade (14% in controls, 67% in CIN1 cases and 88% in CIN2-3). Among ICC cases, 89% had detectable HPV. Overall, 31 HPV genotypes were detected; the three most common HPV genotypes among ICC were HPV16, 35 and 45. In addition to these genotypes, co-infection with HPV18, 31, 33, 52, 58, 68 and 82 was found in 91% of ICC. Among women with CIN2-3, HPV53, 58 and 84/83 were the most common. HPV35, 45, 53/58/59 were the most common among CIN1 cases.</p> <p>Conclusions</p> <p>In women with no evidence of cytological abnormalities, the most prevalent genotypes were HPV58 with HPV16, 35, 52, 66 and 73 occurring equally. Although numerical constraints limit inference, findings that 91% of ICC harbor only a small number of HPV genotypes suggests that prevention efforts including vaccine development or adjuvant screening should focus on these genotypes.</p

Associations Between Methylation of Paternally Expressed Gene 3 (PEG3), Cervical Intraepithelial Neoplasia and Invasive Cervical Cancer.

Cytology-based screening for invasive cervical cancer (ICC) lacks sensitivity and specificity to discriminate between cervical intraepithelial neoplasia (CIN) likely to persist or progress from cases likely to resolve. Genome-wide approaches have been used to identify DNA methylation marks associated with CIN persistence or progression. However, associations between DNA methylation marks and CIN or ICC remain weak and inconsistent. Between 2008-2009, we conducted a hospital-based, case-control study among 213 Tanzania women with CIN 1/2/3 or ICC. We collected questionnaire data, biopsies, peripheral blood, cervical scrapes, Human papillomavirus (HPV) and HIV-1 infection status. We assessed PEG3 methylation status by bisulfite pyrosequencing. Multinomial logistic regression was used to estimate odds ratios (OR) and confidence intervals (CI 95%) for associations between PEG3 methylation status and CIN or ICC. After adjusting for age, gravidity, hormonal contraceptive use and HPV infection, a 5% increase in PEG3 DNA methylation was associated with increased risk for ICC (OR = 1.6; 95% CI 1.2-2.1). HPV infection was associated with a higher risk of CIN1-3 (OR = 15.7; 95% CI 5.7-48.6) and ICC (OR = 29.5, 95% CI 6.3-38.4). Infection with high risk HPV was correlated with mean PEG3 differentially methylated regions (DMRs) methylation (r = 0.34 p<0.0001), while the correlation with low risk HPV infection was weaker (r = 0.16 p = 0.047). Although small sample size limits inference, these data support that PEG3 methylation status has potential as a molecular target for inclusion in CIN screening to improve prediction of progression. Impact statement: We present the first evidence that aberrant methylation of the PEG3 DMR is an important co-factor in the development of Invasive cervical carcinoma (ICC), especially among women infected with high risk HPV. Our results show that a five percent increase in DNA methylation of PEG3 is associated with a 1.6-fold increase ICC risk. Suggesting PEG3 methylation status may be useful as a molecular marker for CIN screening to improve prediction of cases likely to progress

Benefits and risks of antiretroviral therapy for perinatal HIV prevention.

CAPRISA, 2016.Abstract available in pdf

Pregnant women&apos;s beliefs, expectations and experiences of antenatal ultrasound in Northern Tanzania

This qualitative study explored pregnant women&apos;s beliefs, expectations and experiences of the recently introduced antenatal ultrasound service in BomaNg&apos;ombe hospital, Tanzania. Thematic analysis of 25 semi-structured interviews and 41 questionnaires was employed. The majority of women desired ultrasonography despite many not understanding the procedure or purpose. Patient&apos;s expectations included discovering fetal position, fetal sex and pregnancy problems. However, women frequently over-estimated the capacity of ultrasound, and had significant fears of harm. One sixth of questionnaire respondents said they did not want ultrasonography. Nonetheless since the service was introduced no woman has declined, and numerous interviewees believed scans were obligatory. Despite fears, some women reported enjoyment of ultrasound. Interviewees believed ultrasound would increase antenatal care (ANC) attendance. An informed consent policy and an education campaign are needed to reduce fears and maximise uptake and health gains. The effects of ultrasound availability on timely ANC uptake, including amongst women not currently accessing ANC, should be further researched.Cette étude qualitative a exploré les croyances, les attentes et les expériences des femmes enceintes par rapport aux services de l&apos;ultrason prénatal qui ont été nouvellement introduits dans l&apos;hôpital BomaNg&apos;ombe, en Tanzanie. Nous avons employé l&apos;analyse thématique de 25 interviews semi-structurées et 41 questionnaires. La plupart des femmes avaient besoin de l&apos;ultrasonographie malgré le fait que beaucoup d&apos;entre elles ne comprenaient pas la procédure ou l&apos;intention. Les attentes des patientes comprenaient la découverte de la position fœtale, le genre fœtal et les problèmes de la grossesse. Pourtant, les femmes ont souvent surestimé la capacité de l&apos;ultrason et elles avaient beaucoup du mal. Une sixième des interviewées à travers les questionnaires ont déclaré qu&apos;elles ne voulaient pas l&apos;ultrasonographie. Néanmoins, depuis que le service a été mis en place, aucune femme n&apos;a refusé et plusieurs interviewées ont cru que les écogrammes étaient obligatoires. Malgré les craintes, quelques femmes ont déclaré qu&apos;elles aiment l&apos;ultrason. Les interviewées ont cru que l&apos;ultrason va augmenter la fréquentation aux services prénatals (FSP). Une politique du consentement éclairé et une campagne éducative sont nécessaires pour réduire les craintes et pour tirer au maximum la captation et les rapports de la santé. Il faut approfondir des études sur les effets de la disponibilité sur la captation opportun de la FSP, y compris chez les femmes qui ne profitent pas actuellement de la FSP

Maternal outcome in multiple versus singleton pregnancies in Northern Tanzania: A registry-based case control study

Objective: To compare maternal outcome of multiple versus singleton pregnancies at a tertiary hospital in Tanzania. Methods: A case control study was designed using maternally linked data from Kilimanjaro Christian Medical Centre (KCMC) medical birth registry for the period of 2000–2010. A total of 822 multiple gestations (cases) were matched with 822 singletons (controls) with respect to maternal age at delivery and parity. The odds ratio (ORs) with 95% confidence intervals (CIs) for adverse maternal outcome between singleton and multiple gestations were computed in a multivariable logistic regression model. Results: Of the 33 997 births, there were 822 (2.1%) multiples. Compared with singletons, women with multiple gestations had increased risk for preeclampsia (OR 2.6; 95%CI: 1.7–3.9), preterm labour (OR 5.6; 95%CI: 4.2–7.4), antepartum haemorrhage (OR 1.6; 95%CI: 1.1–2.3), anaemia (OR 2.0; 95%CI: 1.6–2.6) and caesarean section (OR 1.5; 95%CI: 1.4–1.7). In addition, there were six maternal deaths among women with multiple gestations, of which all were attributed to postpartum haemorrhage. This accounted for a case fatality rate of 15.8%. Conclusions: Multiple gestations are associated with adverse maternal outcomes. Close follow-up and timely interventions may help to prevent poor outcomes related to multiple gestations. These findings suggest the needs for clinicians to counsel women with multiple gestations during prenatal care regarding the potential risks

Neonatal Mortality is Modulated by Gestational Age, Birthweight and Fetal Heart Rate Abnormalities in the Low Resource Setting in Tanzania – a Five Year Review 2015-2019

Background Neonatal mortality (NM) remains a significant problem in low resource settings. Birth asphyxia (BA) and prematurity contribute significantly to NM. The study objectives were to determine first, the overall NM as well as yearly neonatal mortality rate from 2015 to 2019. Second, the impact of decreasing GA (\u3c37 weeks) and BW (\u3c2500 grams) on NM. Third, the contribution of intrapartum and delivery room (DR) factors and in particular fetal heart rate abnormalities (FHRT) on NM \u3c7 days. Methods Retrospective cohort study. Labor and delivery room data were obtained from 2015 to 2019 and included BW, GA, fetal heart rate (FHRT) abnormalities, bag mask ventilation (BMV) during resuscitation, initial temperature, antenatal steroids use. Outcome was binary i.e. either death \u3c 7 days or survival. Analysis included t tests, odds ratios (OR) and multiple logistic regression Results The overall neonatal mortality rate was 18/1000 livebirths over the five years. NM was significantly higher for newborns \u3c37 versus ≥37 weeks, OR 10.5 (p\u3c0.0001) and BW \u3c2500 versus ≥2500g OR 9.9 (p\u3c0.0001). For infants \u3c1000g / \u3c28 weeks, the neonatal mortality rate was ~ 588/1000 livebirths. Variables associated with NM included BW - odds of death decreased by 0.55 for every 500g increase in weight, by 0.89 for every week increase in GA, NM increased 6.8-fold with BMV, 2.6-fold with abnormal FHRT, 2.2 fold with no antenatal corticosteroid (ACS), 2.6-fold with moderate hypothermia (all \u3c0.0001). Conclusion NM rates was predominantly modulated by decreasing BW and GA, with smaller/ less mature newborns 10-fold more likely to die. NM in term newborns is strongly associated with FHRT abnormalities and when coupled with respiratory depression suggests BA. In smaller newborns, lack of ACS and moderate hypothermia were additional contributing factors. A composite perinatal approach is essential to achieve a sustained reduction in NM

Using fetal scalp stimulation with Doppler ultrasonography to enhance intermittent auscultation in low-resource settings: a diagnostic trial from Tanzania

Abstract Background Hypoxia during labor contributes to 2.2 million intrapartum and early neonatal deaths each year. An additional 0.6–1.0 million cases of life-long disability occur because of fetal hypoxia during labor. It is known that fetal heart rate changes in labor correspond to hypoxia and neurologic compromise, but a reliable, low-cost method for detecting these changes is not available. In this study we sought to compare the ability of a handheld Doppler device to detect accelerations as part of the fetal scalp stimulation test and to compare the diagnostic performance of routine intermittent auscultation with auscultation that is augmented with fetal scalp stimulation. Methods This non-randomized, pre- and post-diagnostic trial was conducted with 568 maternal-fetus pairs at Kilimanjaro Christian Medical Center in Moshi, Tanzania. The first objective was to determine whether a handheld Doppler device could detect fetal accelerations in labor with reasonable accuracy as compared with a cardiotocography machine. We performed the fetal scalp stimulation test on 50 fetuses during labor using both a handheld Doppler and a cardiotocography machine and compared the outcomes for correlation using the kappa correlation coefficient. During the second objective, two groups of laboring women were monitored either with intermittent auscultation alone per routine protocol (N = 251) or with intermittent auscultation augmented with fetal scalp stimulation per study protocol(N = 267). Diagnostic accuracy of the monitoring method was determined by comparing umbilical cord blood gases immediately after birth with the predicted state of the baby based on monitoring. The analyses included sensitivity, specificity, and positive and negative predictive values. Results The prevalence of fetal acidemia ranged from 15 to 20%. Adding the fetal scalp stimulation test to intermittent auscultation protocols improved the performance of intermittent auscultation for detecting severe acidemia (pH < 7.0) from 27 to 70% (p = 0.032). The negative predictive value of intermittent auscultation augmented with the fetal scalp stimulation test ranged from 88 to 99% for mild (pH < 7.2) to severe fetal acidemia. Conclusions The fetal scalp stimulation test, conducted with a handheld Doppler, is feasible and accurate in a limited resource setting. It is a low-cost solution that merits further evaluation to reduce intrapartum stillbirth and neonatal death in low-income countries. Trial registration ClinicalTrials.gov (NCT02862925)