Acute Fetal Demise with First Trimester Maternal Infection Resulting from
                    Listeria monocytogenes
                    in a Nonhuman Primate Model

ABSTRACT Infection with Listeria monocytogenes during pregnancy is associated with miscarriage, preterm birth, and neonatal complications, including sepsis and meningitis. While the risk of these conditions is thought to be greatest during the third trimester of pregnancy, the determinants of fetoplacental susceptibility to infection, the contribution of gestational age, and the in vivo progression of disease at the maternal-fetal interface are poorly understood. We developed a nonhuman primate model of listeriosis to better understand antecedents of adverse pregnancy outcomes in early pregnancy. Four pregnant cynomolgus macaques ( Macaca fascicularis ) received a single intragastric inoculation between days 36 and 46 of gestation with 10 7 CFU of an L. monocytogenes strain isolated from a previous cluster of human listeriosis cases that resulted in adverse pregnancy outcomes. Fecal shedding, maternal bacteremia, and fetal demise were consistently noted within 7 to 13 days. Biopsy specimens of maternal liver, spleen, and lymph node displayed variable inflammation and relatively low bacterial burden. In comparison, we observed greater bacterial burden in the decidua and placenta and the highest burden in fetal tissues. Histopathology indicated vasculitis, fibrinoid necrosis, and thrombosis of the decidual spiral arteries, acute chorioamnionitis and villitis in the placenta, and hematogenous infection of the fetus. Vascular pathology suggests early impact of L. monocytogenes infection on spiral arteries in the decidua, which we hypothesize precipitates subsequent placentitis and fetal demise. These results demonstrate that L. monocytogenes tropism for the maternal reproductive tract results in infection of the decidua, placenta, and the fetus itself during the first trimester of pregnancy. IMPORTANCE Although listeriosis is known to cause significant fetal morbidity and mortality, it is typically recognized in the third trimester of human pregnancy. Its impact on early pregnancy is poorly defined. Here we provide evidence that exposure to L. monocytogenes in the first trimester poses a greater risk of fetal loss than currently appreciated. Similarities in human and nonhuman primate placentation, physiology, and reproductive immunology make this work highly relevant to human pregnancy. We highlight the concept that the maternal immune response that protects the mother from serious disease is unable to protect the fetus, a concept relevant to classic TORCH ( t oxoplasmosis, o ther, r ubella, c ytomegalovirus, and h erpes) infections and newly illuminated by current Zika virus outbreaks. Studies with this model, using the well-understood organism L. monocytogenes , will permit precise analysis of host-pathogen interactions at the maternal-fetal interface and have broad significance to both recognized and emerging infections in the setting of pregnancy.

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Androgen secretion in women with threatened miscarriage

Voprosy ginekologii akušerstva i perinatologii ◽

10.20953/1726-1678-2020-5-22-28 ◽

2020 ◽

Vol 19 (5) ◽

pp. 22-28

Author(s):

М.М. Amiraslanova ◽

◽

I.V. Kuznetsova ◽

E.P. Gitel ◽

◽

...

Keyword(s):

Pregnancy Outcomes ◽

First Trimester ◽

Total Testosterone ◽

Third Trimester ◽

Group Iii ◽

The Third ◽

Threatened Miscarriage ◽

Group I ◽

Androgen Secretion ◽

Group Ii

Objective. To assess androgen secretion and its possible effect on pregnancy in women with threatened miscarriage in the first trimester. Patients and methods. This prospective observational study included 120 pregnant women divided into four groups. Group I comprised 32 patients with threatened miscarriage and hyperandrogenism who received corticosteroids; Group II was composed of 28 patients with threatened miscarriage and hyperandrogenism who did not receive corticosteroids; Group III included 30 patients with threatened miscarriage and no hyperandrogenism; and Group IV comprised 30 women with normal pregnancy. Serum levels of dehydroepiandrosterone sulfate (DHEA-S), 17-hydroxyprogesterone (17-OHP), and total testosterone were measured on the following weeks of gestation: 5–8, 9–12, 13–18, 19–24, and 25–32. We also evaluated clinical outcomes of pregnancy. Results. We observed no significant differences in 17-ОНР and DHEA-S secretion between women from Group III and controls. Patients from Group II demonstrated higher hormone levels than controls; however, their dynamics of 17-ОНР and testosterone secretion was similar to that in women without hyperandrogenism, so their DHEA-S levels decreased and reached control values by the third trimester. Corticosteroids reduced 17-ONR secretion in the second and third trimesters and DHEA-S secretion in the third trimester. Women receiving corticosteroids demonstrated the poorest clinical pregnancy outcomes. Conclusion. Hyperandrogenism should be considered as one of the risk factors for poor pregnancy outcomes. Administration of corticosteroids to reduce androgen levels impairs normal dynamics of their secretion, does not improve pregnancy outcomes, and is potentially harmful; therefore, these drugs should not be used for such purposes. Key words: pregnancy, hyperandrogenism, corticosteroid therapy, pregnancy outcomes, pregnancy loss, androgen secretion, threatened miscarriage

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Chemotherapy administration directly into the fourth ventricle in a nonhuman primate model

Journal of Neurosurgery Pediatrics ◽

10.3171/2012.1.peds11410 ◽

2012 ◽

Vol 9 (5) ◽

pp. 530-541 ◽

Cited By ~ 5

Author(s):

David I. Sandberg ◽

M. Melissa Peet ◽

Mark D. Johnson ◽

Phaedra Cole ◽

Tulay Koru-Sengul ◽

...

Keyword(s):

Nonhuman Primate ◽

Fourth Ventricle ◽

Magnetic Resonance Images ◽

Nonhuman Primate Model ◽

Primate Model ◽

The Third ◽

Group I ◽

Ventricular Tumors ◽

Group Ii

Object The authors hypothesized that chemotherapy infusions directly into the fourth ventricle might potentially play a role in treating malignant fourth ventricular tumors. The study tested the safety and pharmacokinetics of short- and long-term infusions of methotrexate into the fourth ventricle in a new nonhuman primate model. Methods Six rhesus monkeys underwent posterior fossa craniectomy and catheter insertion into the fourth ventricle. In Group I (3 animals), catheters were externalized, and lumbar drain catheters were placed simultaneously to assess CSF distribution after short-term methotrexate infusions. In 2 animals, methotrexate (0.5 mg) was infused into the fourth ventricle daily for 5 days. Serial CSF and serum methotrexate levels were measured. The third animal had a postoperative neurological deficit, and the experiment was aborted prior to methotrexate administration. In Group II (3 animals), catheters were connected to a subcutaneously placed port for subsequent long-term methotrexate infusions. In 2 animals, 4 cycles of intraventricular methotrexate, each consisting of 4 daily infusions (0.5 mg), were administered over 8 weeks. The third animal received 3 cycles, and then the experiment was terminated due to self-inflicted wound breakdown. All animals underwent detailed neurological evaluations, MRI, and postmortem histological analysis. Results No neurological deficits were noted after intraventricular methotrexate infusions. Magnetic resonance images demonstrated catheter placement within the fourth ventricle and no signal changes in the brainstem or cerebellum. Histologically, two Group I animals, one of which did not receive methotrexate, had several small focal areas of brainstem injury. Two Group II animals had a small (≤ 1-mm) focus of axonal degeneration in the midbrain. Intraventricular and meningeal inflammation was noted in 4 animals after methotrexate infusions (one from Group I and all three from Group II). In all Group II animals, inflammation extended minimally into brainstem parenchyma. Serum methotrexate levels were undetectable or negligible in both groups, ranging from 0.00 to 0.06 μmol/L. In Group I, the mean peak methotrexate level in fourth ventricle CSF exceeded that in the lumbar CSF by greater than 10-fold. Statistically significant differences between fourth ventricle and lumbar AUC (area under the concentration-time curve) were detected at peaks (p = 0.04) but not at troughs (p = 0.50) or at all time collection points (p = 0.12). In Group II, peak fourth ventricle CSF methotrexate levels ranged from 84.62 to 167.89 μmol/L (mean 115.53 ± 15.95 μmol/L [SD]). Trough levels ranged from 0.06 to 0.55 μmol/L (mean 0.22 ± 0.13 μmol/L). Conclusions Methotrexate can be infused into the fourth ventricle in nonhuman primates without clinical or radiographic evidence of injury. Observed inflammatory and other histological changes had no clinical correlate. This approach may have pharmacokinetic advantages over current treatment paradigms. Further experiments are warranted to determine if fourth ventricular chemotherapy infusions may benefit patients with malignant fourth ventricular tumors.

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Listeria Placental Infection

mBio ◽

10.1128/mbio.00949-17 ◽

2017 ◽

Vol 8 (3) ◽

Cited By ~ 15

Author(s):

José A. Vázquez-Boland ◽

Emilia Krypotou ◽

Mariela Scortti

Keyword(s):

Pregnancy Outcomes ◽

Bacterial Infections ◽

Medical Intervention ◽

Neonatal Infections ◽

Nonhuman Primate Model ◽

Primate Model ◽

Food Borne ◽

Fetal Complications ◽

Adverse Pregnancy ◽

Transplacental Infection

ABSTRACT The Gram-positive facultative intracellular bacterium Listeria monocytogenes is the causative agent of listeriosis, a severe food-borne infection. Pregnant women are at risk of contracting listeriosis, which can potentially lead to miscarriage, stillbirth, preterm birth, and congenital neonatal infections. While other systemic bacterial infections may result in adverse pregnancy outcomes at comparable frequencies, L. monocytogenes has particular notoriety because fetal complications largely occur in the absence of overt illness in the mother, delaying medical intervention. Here, we briefly review the pathophysiology and mechanisms of maternofetal listeriosis, discussed in light of a recent mBio report on Listeria transplacental infection in a nonhuman primate model.

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The Third Branch of the Main Trunk of the Left Coronary Artery in Cercopithecus aethiops sabaeus. Is the Nonhuman Primate Model Appropriate?

The Anatomical Record ◽

10.1002/ar.21445 ◽

2011 ◽

Vol 294 (9) ◽

pp. 1506-1510

Author(s):

Valentina Nikolić ◽

Zoran Blagojević ◽

Lazar Stijak ◽

Miloš Mališ ◽

Gordana Teofilovski Parapid ◽

...

Keyword(s):

Coronary Artery ◽

Nonhuman Primate ◽

Left Coronary Artery ◽

Cercopithecus Aethiops ◽

Nonhuman Primate Model ◽

Primate Model ◽

Main Trunk ◽

The Third ◽

Cercopithecus Aethiops Sabaeus

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Adverse Placental Perfusion and Pregnancy Outcomes in a New Nonhuman Primate Model of Gestational Protein Restriction

Reproductive Sciences ◽

10.1177/1933719117704907 ◽

2017 ◽

Vol 25 (1) ◽

pp. 110-119 ◽

Cited By ~ 9

Author(s):

Victoria H. J. Roberts ◽

Jamie O. Lo ◽

Katherine S. Lewandowski ◽

Peter Blundell ◽

Kevin L. Grove ◽

...

Keyword(s):

Nonhuman Primate ◽

Pregnancy Outcomes ◽

Protein Restriction ◽

Nonhuman Primate Model ◽

Primate Model ◽

Placental Perfusion

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High Hemoglobin Level is a Risk Factor for Maternal and Fetal Outcomes of Pregnancy in Chinese Women: A Retrospective Cohort Study

10.21203/rs.3.rs-793648/v1 ◽

2021 ◽

Author(s):

Lanlan Wu ◽

Ruifang Sun ◽

Yao Liu ◽

Zengyou Liu ◽

Hengying Chen ◽

...

Keyword(s):

Pregnancy Outcomes ◽

Chinese Women ◽

Adverse Pregnancy Outcomes ◽

Multivariate Logistic Regression ◽

Third Trimester ◽

Low Birth Weight Infants ◽

The Third ◽

Increased Risk ◽

Adverse Pregnancy ◽

Multivariable Adjustment

Abstract Background To examine the association of hemoglobin (Hb) levels during gestation with the risk of selected adverse pregnancy outcomes in Chinese women. Methods A total of 1911 singleton mothers were included. Hb levels were measured during the second (16-18th weeks) and third (28-30th weeks) trimesters of pregnancy, and pregnancy outcomes were followed. Statistical analysis was performed using multivariate logistic regression. Results After multivariable adjustment, Hb levels > 130 g/L in the second trimester increased the risk of low-birth-weight infants (LBW) (odds ratio [OR], 2.54; 95% confidence interval [CI], 1.12–5.77). In the third trimester of gestation, compared with women whose Hb levels between 110–119 g/L, women with Hb levels > 130 g/L had an increased risk of LBW (OR, 2.17; 95% CI, 1.05–4.48) and small-for-gestational-age infants (SGA) (OR, 1.98; 95% CI, 1.04–3.78). In addition, maternal Hb levels of < 110 g/L or > 130 g/L at the second week that were restored vs not restored in the third trimester decreased the risk of preterm birth (PTB) by 80% (95% CI, 0.07–0.58) and 86% (95% CI, 0.03–0.84), respectively. Conclusion Maternal Hb > 130 g/L was associated with increased risk of adverse pregnancy outcomes. Reduction of PTB risk was observed with correction of Hb level during the third trimester.

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Association Between Gestational Weight Gain in Women With Gestational Diabetes Mellitus and Adverse Pregnancy Outcomes: a Retrospective Cohort Study

10.21203/rs.3.rs-379454/v1 ◽

2021 ◽

Author(s):

Ping Shi ◽

Aimin Liu ◽

Xiaoyan Yin

Keyword(s):

Preterm Birth ◽

Relative Risk ◽

Pregnancy Outcomes ◽

Retrospective Cohort ◽

Caesarean Delivery ◽

Third Trimester ◽

Gestational Weight ◽

The Third ◽

Adverse Pregnancy ◽

In Pregnancy

Abstract Purpose: To examine the association between gestational weight gain (GWG) in women with gestational diabetes mellitus (GDM) and adverse pregnancy outcomes (APOs).Methods: This retrospective cohort study enrolled women with GDM and singleton live birth pregnancies who delivered between January 2010 and December 2020. Univariable and multivariable logistic regression analyses were used to determine the association between GWG outside the Institute of Medicine (IOM) guidelines and APOs.Results: Overall, 1606 women with GDM fulfilled the inclusion criteria. After adjusting for confounders, total GWG above IOM guidelines in pregnancy was associated with an increased risk of caesarean delivery [adjusted odds ratio (aOR)=1.34, 95% confidence interval (CI): 1.04-1.72], hypertensive disorders of pregnancy (HDP) (aOR=2.00, 95% CI: 1.28-3.12), preeclampsia (aOR=2.06, 95% CI: 1.01-3.12), macrosomia (aOR=1.55, 95% CI: 1.13-2.13) and LGA (aOR=1.83, 95% CI: 1.43-2.10), and a decreased risk of premature rupture of membrane (PROM) (aOR=0.46, 95% CI: 0.36-0.60) and preterm birth (aOR=0.35, 95% CI: 0.26-0.44); total GWG below IOM guidelines in pregnancy was associated with an increased relative risk of preterm birth (aOR=1.96, 95% CI: 1.44-2.66) and SGA (aOR=1.32, 95% CI: 1.11-1.50) and a decreased relative risk of macrosomia (aOR=0.35, 95% CI: 0.23-0.53). Further, in both second and third trimesters of pregnancy, GWG above IOM guidelines was found to be associated with a high risk of HDP (aOR=2.55, 95% CI: 1.86-3.38; aOR=1.93, 95% CI: 1.08-2.98), preeclampsia (aOR=2.28, 95% CI: 1.21-3.81; aOR=2.17, 95% CI: 1.35-4.37), macrosomia (aOR=1.20, 95% CI: 1.02-1.82; aOR=2.02, 95% CI: 1.51-2.64) and LGA (aOR=1.65, 95% CI: 1.36-2.04; aOR=1.88, 95% CI: 1.62-2.18). GWG above IOM guidelines in the third trimester of pregnancy also increased the risk of caesarean delivery (aOR=1.48, 95% CI: 1.16-2.34). While GWG below IOM guidelines in both second and third trimesters of pregnancy was associated with a decreased relative risk of macrosomia (aOR=0.66, 95% CI: 0.52-0.78; aOR=0.52, 95% CI: 0.39-0.63). In addition, GWG below IOM guidelines in the third trimester of pregnancy was associated with an increased relative risk of preterm birth (aOR=1.52, 95% CI: 1.12-2.05) and SGA (aOR=1.21, 95% CI: 1.10-1.69).Conclusion: GWG, outside the IOM guidelines has increased risks of APOs among women with GDM, implying that careful surveillance for GWG during different stages of pregnancy is warranted.

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Glycated Albumin in Pregnancy: Reference Intervals Establishment and Its Predictive Value in Adverse Pregnant Outcomes

10.21203/rs.2.14443/v1 ◽

2019 ◽

Author(s):

Ying Dong ◽

Yanhong Zhai ◽

Jing Wang ◽

Xin Xie ◽

Chunhong Zhang ◽

...

Keyword(s):

Pregnancy Outcomes ◽

Predictive Value ◽

Glycated Albumin ◽

Late Pregnancy ◽

Reference Intervals ◽

Diabetic Patients ◽

Third Trimester ◽

The Third ◽

Adverse Pregnancy ◽

In Pregnancy

Abstract Background As one of the most common pregnant complications, the gestational diabetes mellitus (GDM) is associated with significant adverse pregnant outcomes and it is crucial to accurately monitor the glycemic states of GDM patients. The HbA1c which is a traditional long-term glycemic marker used in diabetic patients, is not recommended in GDM patients during pregnancy. Recently, many efforts have been focused on the alternative marker glycated albumin (GA) and its application in pregnancy during which profound physiological changes take place. Our objective was to determine the reference intervals (RIs) of GA in healthy Chinese pregnant women and to assess the predictive value of serum GA in adverse pregnant outcomes. Methods Totally 479 healthy subjects including 153 in the first trimester, 174 in the second trimester, and 152 in the third trimester were enrolled from March to July 2019, for the purpose of establishing the trimester-specific RIs of GA. The diagnostic value of GA for GDM patients was evaluated and compared with that of fasting plasma glucose (FPG) at 24-28 weeks of gestation. The association between GA in the late pregnancy and the adverse pregnant outcomes was analyzed retrospectively with the data collected from January to June 2018 at our hospital. Results The estimated RIs of GA in present study were 10.87-15.09 %, 10.04-13.50 %, and 9.78-13.03 % in the first, second, and third trimesters respectively. The areas under receiver operating characteristic (ROC) curves were 0.503 for GA and 0.705 for FPG. More importantly, the GA levels of the third trimester did not show significant changes in women with large-for-date birth weight, preterm delivery, postpartum hemorrhage or hypertension when compared in women with normal pregnancy outcomes. The exception was that the GDM patients who developed preeclampsia did have a lower GA level in their late pregnancy. Conclusions Our results show that the GA was continuously decreased as the gestational age went up. It has limited value in diagnosing GDM and predicting adverse pregnancy outcomes.

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Hemoglobin Concentration and Pregnancy Outcomes: A Systematic Review and Meta-Analysis

BioMed Research International ◽

10.1155/2013/769057 ◽

2013 ◽

Vol 2013 ◽

pp. 1-9 ◽

Cited By ~ 21

Author(s):

Bunyarit Sukrat ◽

Chumpon Wilasrusmee ◽

Boonying Siribumrungwong ◽

Mark McEvoy ◽

Chusak Okascharoen ◽

...

Keyword(s):

Systematic Review ◽

Birth Weight ◽

Preterm Birth ◽

Low Birth Weight ◽

Gestational Age ◽

Pregnancy Outcomes ◽

Meta Analysis ◽

First Trimester ◽

Third Trimester ◽

The Third

Objective. To conduct a systematic review and meta-analysis of hemoglobin effect on the pregnancy outcomes.Methods. We searched MEDLINE and SCOPUS from January 1, 1990 to April 10, 2011. Observational studies addressing association between hemoglobin and adverse pregnancy outcomes were selected. Two reviewers independently extracted data. A mixed logistic regression was applied to assess the effects of hemoglobin on preterm birth, low birth weight, and small for gestational age.Results. Seventeen studies were included in poolings. Hemoglobin below 11 g/dL was, respectively, 1.10 (95% CI: 1.02–1.19), 1.17 (95% CI: 1.03–1.32), and 1.14 (95% CI: 1.05–1.24) times higher risk of preterm birth, low birth weight, and small for gestational age than normal hemoglobin in the first trimester. In the third trimester, hemoglobin below 11 g/dL was 1.30 (95% CI: 1.08–1.58) times higher risk of low birth weight. Hemoglobin above 14 g/dL in third trimester decreased the risk of preterm term with ORs of 0.50 (95% CI: 0.26–0.97), but it might be affected by publication bias.Conclusions. Our review suggests that hemoglobin below 11 g/dl increases the risk of preterm birth, low birth weight, and small gestational age in the first trimester and the risk of low birth weight in the third trimester.

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Serum Urea Acid and Urea Nitrogen Levels are Risk Factors for Maternal and Fetal Outcomes of Pregnancy: A Retrospective Cohort Study

10.21203/rs.3.rs-942069/v1 ◽

2021 ◽

Author(s):

Lanlan Wu ◽

Yao Liu ◽

Zengyou Liu ◽

Hengying Chen ◽

Siwen Shen ◽

...

Keyword(s):

Risk Factors ◽

Pregnancy Outcomes ◽

Large Population ◽

Adverse Pregnancy Outcomes ◽

Third Trimester ◽

Fetal Outcomes ◽

Urea Nitrogen ◽

Nitrogen Levels ◽

The Third ◽

Adverse Pregnancy

Abstract Background In recent years, results on the association between serum uric acid (UA) and pregnancy outcomes have been inconsistent, and the association between urea nitrogen (UN) and adverse pregnancy outcomes in normal pregnant women has not been reported. Thus, we examined the association of UA and UN levels during gestation with the risk of adverse pregnancy outcomes in a relatively large population. Methods A total of 1602 singleton mothers were included. Both UA and UN levels were collected and measured during the second (16–18th week) and third (28–30th week) trimesters of gestation respectively. Statistical analysis was performed using multivariate logistic regression. Results After adjustment, the highest quartile of UA in the third trimester increased the risk of premature rupture of membranes (PROM) and small for gestational age infants (SGA) by 48% (odds ratio [OR]: 1.48, 95% confidence interval [CI]: 1.04–2.10) and 99% (95% CI: 1.01–3.89) compared to those in the lowest quartile. The adjusted OR (95% CI) in the highest quartile of UN for the risk of SGA was 2.18 (95% CI: 1.16–4.13) and 2.29 (95% CI: 1.20–4.36) in the second and third trimester, respectively. In the second trimester, when UA and UN levels were both in the highest quartile, the adjusted OR (95% CI) for the risk of SGA was 2.51 (95% CI: 1.23–5.10). In the third trimester, when the group 1 (both indicators are in the first quartile) was compared, the adjusted ORs (95% CI) for the risk of SGA were 1.98 (95% CI: 1.22–3.23) and 2.31 (95% CI: 1.16–4.61) for group 2 (UA or UN is in the second or third quartile) and group 3 (both indicators are in the fourth quartile), respectively. Conclusions Higher UA and UN levels increased the risk of maternal and fetal outcomes. The simultaneous elevation of UA and UN levels was a high-risk factors for the development of SGA, regardless of whether they were in the second or third trimester.

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