Effects of Plasmodium falciparum infection on umbilical artery resistance and intrafetal blood flow distribution: a Doppler ultrasound study from Papua New Guinea.

BACKGROUND: Doppler velocimetry studies of umbilical artery (UA) and middle cerebral artery (MCA) flow help to determine the presence and severity of fetal growth restriction. Increased UA resistance and reduced MCA pulsatility may indicate increased placental resistance and intrafetal blood flow redistribution. Malaria causes low birth weight and fetal growth restriction, but few studies have assessed its effects on uteroplacental and fetoplacental blood flow. METHODS: Colour-pulsed Doppler ultrasound was used to assess UA and MCA flow in 396 Papua New Guinean singleton fetuses. Abnormal flow was defined as an UA resistance index above the 90th centile, and/or a MCA pulsatility index and cerebroplacental ratio (ratio of MCA and UA pulsatility index) below the 10th centile of population-specific models fitted to the data. Associations between malaria (peripheral infection prior to and at ultrasound examination, and any gestational infection, i.e., 'exposure') and abnormal flow, and between abnormal flow and birth outcomes, were estimated. RESULTS: Of 78 malaria infection episodes detected before or at the ultrasound visit, 62 (79.5%) were Plasmodium falciparum (34 sub-microscopic infections), and 16 were Plasmodium vivax. Plasmodium falciparum infection before or at Doppler measurement was associated with increased UA resistance (adjusted odds ratio (aOR) 2.3 95% CI 1.0-5.2, P = 0.047). When assessed by 'exposure', P. falciparum infection was significantly associated with increased UA resistance (all infections: 2.4, 1.1-4.9, P = 0.024; sub-microscopic infections 2.6, 1.0-6.6, P = 0.051) and a reduced MCA pulsatility index (all infections: 2.6, 1.2-5.3, P = 0.012; sub-microscopic infections: 2.8, 1.1-7.5, P = 0.035). Sub-microscopic P. falciparum infections were additionally associated with a reduced cerebroplacental ratio (3.64, 1.22-10.88, P = 0.021). There were too few P. vivax infections to draw robust conclusions. An increased UA resistance index was associated with histological evidence of placental malaria (5.1, 2.3-10.9, P < 0.001; sensitivity 0.26, specificity 0.93). A low cerebroplacental Doppler ratio was associated with concurrently measuring small-for-gestational-age, and with low birth weight. DISCUSSION/CONCLUSION: Both microscopic and sub-microscopic P. falciparum infections impair fetoplacental and intrafetal flow, at least temporarily. Increased UA resistance has high specificity but low sensitivity for the detection of placental infection. These findings suggest that interventions to protect the fetus should clear and prevent both microscopic and sub-microscopic malarial infections. Trial Registration ClinicalTrials.gov NCT01136850. Registered 06 April 2010.

Factors associated with ultrasound-aided detection of suboptimal fetal growth in a malaria-endemic area in Papua New Guinea.

BACKGROUND: Fetal growth restriction (FGR) is associated with increased infant mortality rates and ill-health in adulthood. Evaluation of fetal growth requires ultrasound. As a result, ultrasound-assisted evaluations of causes of FGR in malaria-endemic developing countries are rare. We aimed to determine factors associated with indicators of abnormal fetal growth in rural lowland Papua New Guinea (PNG). METHODS: Weights and growth of 671 ultrasound-dated singleton pregnancies (<25 gestational weeks) were prospectively monitored using estimated fetal weights and birthweights. Maternal nutritional status and haemoglobin levels were assessed at enrolment, and participants were screened for malaria on several occasions. FGR was suspected upon detection of an estimated fetal weight or birthweight <10(th) centile (small-for-gestational age) and/or low fetal weight gain, defined as a change in weight z-score in the first quartile. Factors associated with fetal weight and fetal weight gain were additionally assessed by evaluating differences in weight z-scores and change in weight z-scores. Log-binomial and linear mixed effect models were used to determine factors associated with indicators of FGR. RESULTS: SGA and low weight gain were detected in 48.3% and 37.0% of pregnancies, respectively. Of participants, 13.8%, 21.2%, and 22.8% had a low mid-upper arm circumference (MUAC, <22 cms), short stature (<150 cms) and anaemia (haemoglobin <90 g/L) at first antenatal visit. 24.0% (161/671) of women had at least one malaria infection detected in peripheral blood. A low MUAC (adjusted risk ratio [aRR] 1.51, 95% CI 1.29, 1.76, P < 0.001), short stature (aRR 1.27, 95% CI 1.04, 1.55, P = 0.009), and anaemia (aRR 1.27, 95% CI 1.06, 1.51, P = 0.009) were associated with SGA, and a low body mass index was associated with low fetal weight gain (aRR 2.10, 95% CI 1.62, 2.71, P < 0.001). Additionally, recent receipt of intermittent preventive treatment in pregnancy was associated with increased weight z-scores, and anaemia with reduced change in weight z-scores. Malaria infection was associated with SGA on crude but not adjusted analyses (aRR 1.13, 95% CI 0.95, 1.34, P = 0.172). CONCLUSION: Macronutrient undernutrition and anaemia increased the risk of FGR. Antenatal nutritional interventions and malaria prevention could improve fetal growth in PNG.

HIV-1 and HIV-2 prevalence, risk factors and birth outcomes among pregnant women in Bissau, Guinea-Bissau: a retrospective cross-sectional hospital study.

The human immunodeficiency virus (HIV) remains a leading cause of maternal morbidity and mortality in Sub-Saharan Africa. Prevention of mother-to-child transmission (PMTCT) has proven an effective strategy to end paediatric infections and ensure HIV-infected mothers access treatment. Based on cross-sectional data collected from June 2008 to May 2013, we assessed changes in HIV prevalence, risk factors for HIV, provision of PMTCT antiretroviral treatment (ART), and the association between HIV infection, birth outcomes and maternal characteristics at the Simão Mendes National Hospital, Guinea-Bissau's largest maternity ward. Among 24,107 women, the HIV prevalence was 3.3% for HIV-1, 0.8% for HIV-2 and 0.9% for HIV-1/2. A significant decline in HIV-1, HIV-2, and HIV-1/2 prevalence was observed over time. HIV infection was associated with age and ethnicity. A total of 85% of HIV-infected women received ART as part of PMTCT, yet overall treatment coverage during labour and delivery declined significantly for both mothers and infants. Twenty-two percent of infants did not receive treatment, and 67% of HIV-2-infected mothers and 77% of their infants received ineffective non-nucleoside reverse transcriptase inhibitors for PMTCT. Maternal HIV was associated with low birth weight but not stillbirth. Inadequate continuity of care and ART coverage present challenges to optimal PMTCT in Guinea-Bissau.

Correction: Stillbirths in urban Guinea-Bissau: A hospital- and community-based study.

[This corrects the article DOI: 10.1371/journal.pone.0197680.].

Correction: Political instability and supply-side barriers undermine the potential for high participation in HIV testing for the prevention of mother-to-child transmission in Guinea-Bissau: A retrospective cross-sectional study.

[This corrects the article DOI: 10.1371/journal.pone.0199819.].

Stillbirths in urban Guinea-Bissau: A hospital- and community-based study.

BACKGROUND: Stillbirth rates remain high in many low-income settings, with fresh (intrapartum) stillbirths accounting for a large part due to limited obstetrical care. We aimed to determine the stillbirth rate and identify potentially modifiable factors associated with stillbirth in urban Guinea-Bissau. METHODS: The study was carried out by the Bandim Health Project (BHP), a Health and Demographic Surveillance System site in the capital Bissau. We assessed stillbirth rates in a hospital cohort consisting of all deliveries at the maternity ward at the National Hospital Simão Mendes (HNSM), and in a community cohort, which only included women from the BHP area. Stillbirth was classified as fresh (FSB) if fetal movements were reported on the day of delivery. RESULTS: From October 1 2007 to April 15 2013, a total of 38164 deliveries were registered at HNSM, among them 3762 stillbirths (99/1000 births). Excluding deliveries referred to the hospital from outside the capital (9.6%), the HNSM stillbirth rate was 2786/34490 births (81/1000). During the same period, 15462 deliveries were recorded in the community cohort. Of these, 768 were stillbirths (50/1000). Of 11769 hospital deliveries among women from Bissau with data on fetal movement, 866 (74/1000) were stillbirths, and 609 (70.3%) of these were FSB, i.e. potentially preventable. The hospital FSB rate was highest in the evening from 4 pm to midnight (P = 0.04). In the community cohort, antenatal care (ANC) attendance correlated strongly with stillbirth reduction; the stillbirth rate was 71/1000 if the mother attended no ANC consultations vs. 36/1000 if she attended ≥7 consultations (P<0.001). CONCLUSION: In Bissau, the stillbirth rate is alarmingly high. The majority of stillbirths are preventable FSB. Improving obstetrical training, labour management (including sufficient intrapartum monitoring and timely intervention) and hospital infrastructure is urgently required. This should be combined with proper community strategies and additional focus on antenatal care.

Political instability and supply-side barriers undermine the potential for high participation in HIV testing for the prevention of mother-to-child transmission in Guinea-Bissau: A retrospective cross-sectional study.

BACKGROUND: The World Health Organization recommends HIV testing is included in routine screening tests for all pregnant women in order to prevent mother-to-child-transmission of HIV and reduce maternal morbidity and mortality. OBJECTIVES: To assess the proportion of women approached and tested for HIV at delivery and factors associated with non-testing at the maternity ward of the Simão Mendes National Hospital (HNSM) in Bissau, Guinea-Bissau. METHODS: We conducted a retrospective cross-sectional study among women presenting for delivery from June 2008 until May 2013. During the study period, national policy included opt-out HIV-testing at delivery. Modified Poisson regression models were used to examine the association of maternal characteristics with HIV testing. Time trends were determined using Pearson's χ2 test. RESULTS: Seventy-seven percent (24,217/31,443) of women presenting for delivery were counselled regarding PMTCT, of whom 99.6% (24,107/24,217) proceeded with HIV testing. The provision of opt-out HIV testing at labour increased from 38.1% (1,514/3973) in 2008 to 95.7% (2,021/2,113) in 2013, p<0.001. There were four distinct periods (two or more consecutive calendar months) when less than 50% of women delivering at HNSM were tested. Periods of political instability were significantly associated with not testing for HIV (adjusted prevalence ratio [APR] 1.79; 95% CI 1.73-1.84), as was a lower educational status (APR 1.05; 95% CI 1.00-1.10), admission during evenings/nights (APR 1.05; 95% CI 1.01-1.09) and on Sundays (APR 1.14; 95% CI 1.07-1.22) and Mondays (APR 1.12; 95% CI 1.05-1.19). CONCLUSIONS: Rapid scale-up of PMTCT HIV testing services and high testing coverage was possible in this resource-limited setting but suffered from regular interruptions, most likely because of test stock-outs. Establishing proper stock management systems and back-up plans for periods of political instability is required to ensure the maintenance of health system core functions and increase health system resilience.