Publications

Sci Rep. 2019 Sep 27;9(1):13962. doi: 10.1038/s41598-019-50417-4. PMID: 31562365; PMCID: PMC6764989.

Abstract

First-trimester placenta (<10 gestational weeks (GW)) develops in a low oxygen environment (≈2%). Early oxygen exposure can cause oxidative damage leading to pregnancy disorders. The aim of this work was to determine the major sources of placental superoxide during early pregnancy – more specifically before 10 GW – and to study redox adaptation to increased oxygen pressure after 12 GW. Our results show that NADPH oxidase (Nox) is the main source of superoxide in first-trimester chorionic villi. Its activity is higher before 10 GW and concomitant with the location on the syncytiotrophoblast apical pole of p47phox, the Nox organizer subunit. After the increase in pO₂ pressure (12-14 GW), the activities of the antioxidant enzymes SOD1, catalase and GPX1 are increased. The redox-sensitive MAPK pathways show increased phosphorylated-p38 expression, but no variation in the phosphorylation of stress-activated protein kinase/c-Jun NH2-terminal kinase (SAPK/JNK) during first trimester, suggesting a physiological redox adaptation, whilst ERK1/2 phosphorylation is higher after 12 GW. Nox is the major superoxide source in early pregnancy (<10 GW). Increased superoxide production at 7-9 GW is associated with p38 MAPK pathway activation, suggesting that it is involved in physiological placental function and healthy early development of the placenta, through MAPK pathways.

Clin Infect Dis. 2019 Sep 27;69(8):1385-1393. doi: 10.1093/cid/ciy1073.

BACKGROUND:

In sub-Saharan Africa, malaria in the first half of pregnancy is harmful for both the mother and her fetus. However, malaria in the first trimester of pregnancy, when women are usually not protected against malaria, has been little investigated. For the first time, we assessed the effects of malaria in the first trimester on maternal and birth outcomes using a preconceptional study design.

METHODS:

From June 2014 to March 2017, 1214 women of reproductive age were recruited and followed monthly until 411 became pregnant. The pregnant women were then followed from 5-6 weeks of gestation until delivery. Path analysis was used to assess the direct effect (ie, not mediated by malaria in the second or third trimester) of malaria in the first trimester on maternal anemia and poor birth outcomes. The cumulative effect of infections during pregnancy on the same outcomes was also evaluated.

RESULTS:

The prevalence of malaria infections in the first trimester was 21.8%. Malaria in the first trimester was significantly associated with maternal anemia in the third trimester (adjusted odds ratio 2.25, 95% confidence interval 1.11-4.55). While we did not find evidence of any direct effect of first trimester malaria infections on birth outcomes, their association with infections later in pregnancy tended to increase the risk of low birth weights.

CONCLUSIONS:

Malaria infections in the first trimester were highly prevalent and have deleterious effects on maternal anemia. They highlight the need for additional preventive measures, starting in early pregnancy or even before conception.

PLoS One. 2019 Sep 19;14(9):e0222864. doi: 10.1371/journal.pone.0222864. eCollection 2019.

BACKGROUND:

Malaria and schistosomiasis represent two of the most prevalent and disabling parasitic infections in developing countries. Few studies have evaluated the effect of maternal schistosomiasis and malaria in the peri-conceptional period on infant’s risk of infection.

METHODS:

In Benin, women were followed from the preconception period until delivery. Subsequently, their children were followed from birth to 3 months of age. Pre-pregnancy malaria, malaria in pregnancy (MiP)-determined monthly using a thick blood smear-and urinary schistosomiasis-determined once before pregnancy and once at delivery using urine filtration-were the main maternal exposures. Infant’s febrile infection (fever with respiratory, gastrointestinal and/or cutaneous clinical signs anytime during follow-up) was the main outcome. In a secondary analysis, we checked the relation of malaria and schistosomiasis with infant’s hemoglobin (Hb) concentration. Both effects were separately assessed using logistic/mixed linear regression models.

RESULTS:

The prevalence of MiP was 35.7% with 10.8% occurring during the 1st trimester, and the prevalence of schistosomiasis was 21.8%. From birth to 3 months, 25.3% of infants had at least one episode of febrile infection. In multivariate analysis, MiP, particularly malaria in the 1st trimester, was significantly associated with a higher risk of infant’s febrile infection (aOR = 4.99 [1.1; 22.6], p = 0.03). In secondary results, pre-pregnancy malaria and schistosomiasis were significantly associated with a lower infant’s Hb concentration during the first 3 months.

CONCLUSION:

We evidenced the deleterious effect of maternal parasitic infections on infant’s health. Our results argue in favor of the implementation of preventive strategies as early as in the peri-conception.

Pan Afr Med J. 2019 Sep 16;34:30. doi: 10.11604/pamj.2019.34.30.20013. eCollection 2019.

Introduction:

Placental malaria (PM) is an important predictor of infant morbidity and mortality in sub-Saharan Africa. Although placental histology is the gold standard test to diagnose PM, the placenta impression smears remains widely used in epidemiological studies. This study is set to evaluate the performance of placental impression smears to detect PM in pregnant women in southern Benin.

Methods:

A cross-sectional analysis was performed on data collected in the framework a multicenter randomized clinical trial (Malaria in Pregnancy Preventive and Alternative Drugs). Samples from 491 pregnant women were examined in the district of Allada, Southern Benin. Plasmodium falciparum infections have been assessed in placental blood and placental biopsy.

Results:

Placental malaria detected by placenta impression smears and histology were prevalent in 11.4% and 10.8%, respectively. Sensitivity and specificity of placental impression smears were 90.6% and 98.4%. Among 55 pregnant women tested positive by placenta impression smears, 48 were positive by the histology, while 7 were negative (positive predictive value: 87.3%). Four hundred and twenty four (424) of the 429 tested negative by the placenta impression smears, were also negative according to histology whereas the rest (5 of 429) of the women were positive (negative predictive value: 98.8%).

Conclusion:

Placenta impression smear is an accurate and easy method for the diagnosis of placental malaria.

Abstract

Objective: To describe obstetrical care and in-hospital outcomes in very preterm triplet pregnancies in a European multiregional cohort.

Methods: Data from a prospective population-based study of very preterm births between 22 + 0 and 31 + 6 weeks of gestation in 19 regions from 11 European countries participating in the EPICE project in 2011/2012 were used to describe triplet pregnancies and compare them with twins and singletons.

Results: Triplets constituted 1.1% of very preterm pregnancies (97/8851) and 3.3% of very preterm live births (258/7900); these percentages varied from 0% to 2.6% and 0% to 6% respectively across the regions. In-hospital mortality after live birth was 12.4% and did not differ significantly from singletons or twins or by birth order. However, 28.9% of mothers with a triplet pregnancy experienced at least one neonatal death. Ninety percent of live-born triplets were delivered by cesarean. Vaginal delivery was associated with an Apgar score of less than 7, but not with in-hospital mortality.

Conclusions: The prevalence of very preterm triplets varies across European regions. Most triplets were born by cesarean and those born vaginally had lower Apgar scores. Overall, in-hospital mortality after live birth was similar to singletons and twins.

Clin Infect Dis. 2019 Sep 12. pii: ciz748. doi: 10.1093/cid/ciz748. [Epub ahead of print]

BACKGROUND:

In the context of global malaria elimination efforts, special attention is being paid to submicroscopic Plasmodium falciparum infections. In pregnant, sub-Saharan African women, such infections are more prevalent than microscopic infections, and are thought to have adverse effects on both mothers’ and newborns’ health. However, no study has studied the dynamics and determinants of these infections throughout pregnancy. Retard de Croissance Intra-uterin et Paludisme (RECIPAL), a preconception cohort study carried out in Benin between 2014 and 2017, represented a unique opportunity to assess this issue.

METHODS:

We used data from 273 pregnant Beninese women who were followed-up from preconception to delivery. We studied the dynamics of and factors influencing submicroscopic (and microscopic) P. falciparum infections during the 3 trimesters of pregnancy, using an ordinal logistic mixed model.

RESULTS:

The incidence rate of submicroscopic P. falciparum infections during pregnancy was 12.7 per 100 person-months (95% confidence interval [CI] 10.8-14.9), compared to 6.7 per 100 person-months (95% CI 5.5-8.1) for microscopic infections. The prevalences were highest in the first trimester for both submicroscopic and microscopic infections. After adjustment for potential confounding factors, we found that those of young age and those with a submicroscopic P. falciparum infection prior to pregnancy were at significantly higher risks of submicroscopic and microscopic infections throughout pregnancy, with a more pronounced effect in the first trimester of pregnancy.

CONCLUSIONS:

The first trimester of pregnancy is a particularly high-risk period for P. falciparum infection during pregnancy, especially for the youngest women. Malaria prevention tools covering the preconception period and early pregnancy are urgently needed to better protect pregnant women and their newborns.

Allergy. 2019 Sep;74(9):1790-1793. doi: 10.1111/all.13787. Epub 2019 Apr 30.

Letter to the Editor

Matern Child Health J. 2019 Aug;23(8):1108-1116. doi: 10.1007/s10995-019-02747-y.

Objectives

Even during pregnancy women may suffer from violence. We estimated the prevalence of physical abuse during pregnancy, we analyzed the main risk factors and described the relationship between physical violence, psychological wellbeing and pregnancy outcome.

Methods

We used a national representative sample of births, in all public and private maternity units, in 2016 in France. Women were interviewed after delivery, on their living conditions and occurrence of physical violence at least once during pregnancy. The study of risk factors and pregnancy outcome was done with multivariable logistic regressions.

Results

Of 12,330 women included in the analysis 1.8% (95% CI 1.6-2.0) had been exposed to physical violence during pregnancy. Risk of violence was associated with the couple situation [women without a partner or in couple not cohabiting (OR 2.89, 95% CI 1.96-4.26)], household income (less than 3000 euros monthly), and state medical assistance coverage. Physical violence was more prevalent in case of a history of induced abortion or cannabis use during pregnancy. Psychological distress was more frequent with than without physical violence (e.g., 62% vs. 24% had a sadness period during pregnancy, p < 0.001). The risk of spontaneous preterm birth and transfer of the newborn to a neonatal intensive care unit were significantly higher among women experiencing physical violence during pregnancy compared to other women.

Conclusions for Practice

Main factors associated with increased risk of violence during pregnancy were socio-economics. The identification by caregivers of women exposed to violence during pregnancy needs to be improved to develop preventive and care strategies.

Sci Rep. 2019; 9: 11918. Published online 2019 Aug 15. doi: 10.1038/s41598-019-48427-3. PMCID: PMC6695383.

AbstrAct:

Adverse long-term cardiovascular (CV) consequences of PE are well established in women. However, the mechanism responsible for that risk remains unknown. Here, we mated wild-type female mice of the FVB/N strain to STOX1A-overexpressing mice to mimic severe PE and investigated the long-term consequences on the maternal cardiovascular system. Ultrasonography parameters were analyzed in mice before pregnancy and at 3 and 6 months post-pregnancy. At 6 months post-pregnancy, cardiac stress test induced by dobutamine injection revealed an abnormal ultrasonography doppler profile in mice with previous PE. Eight months post-pregnancy, the heart, endothelial cells (ECs) and plasma of females were analyzed and compared to controls. The heart of mice with PE showed left-ventricular hypertrophy associated with altered histology (fibrosis). Transcriptomic analysis revealed the deregulation of 1149 genes in purified ECs and of 165 genes in the hearts, many being involved in heart hypertrophy. In ECs, the upregulated genes were associated with inflammation and cellular stress. Systems biology analysis identified interleukin 6 (IL-6) as a hub gene connecting these pathways. Plasma profiling of 33 cytokines showed that, 8 of them (cxcl13, cxcl16, cxcl11, IL-16, IL-10, IL-2, IL-4 and Ccl1) allowed to discriminate mice with previous PE from controls. Thus, PE triggers female long-term CV consequences on the STOX1 mouse model.

Int J Pharm. 2019 Aug 15;567:118479. doi: 10.1016/j.ijpharm.2019.118479. Epub 2019 Jun 27.

Abstract

Controlled distribution of a drug by its association to a nanocarrier is a promising approach for the treatment of pregnancy disorders such as preeclampsia. For this application, tracking both the nanocarrier and the drug is necessary to ensure the safety of both the mother and the foetus. This study reports a method to visualize and quantify the uptake of liposomal formulations in placental tissue using florescent labelling and appropriate analytical tools. Lipoplexes were labelled with a fluorescent lipid, DOPE-NBD while the encapsulated siRNA was fluorescently labelled with rhodamine. Lipoplexes were incubated with villous placenta explants, explants were imaged with confocal microscopy, then DOPE-NBD was extracted from the explant and quantified by HPLC. Qualitative evaluation by confocal microscopy showed the presence of lipoplexes and siRNA into the outer layer of the placental explants, the syncytiotrophoblast. For quantitative evaluation, an HPLC method for the quantification of fluorescent lipid DOPE-NBD in placental tissue was developed and validated. The developed method was applied to quantify the DOPE-NBD uptake in the placental tissue. Increased amounts of DOPE-NBD were detected in placental explants when increasing the incubation concentration of lipoplexes. This study provides a method to evaluate the interactions between liposomal formulation and the placental barrier.