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PROBLEM - Premature birth complicates 10%-12% of deliveries. Infection and inflammation are the most common etiologies and are associated with increased offspring morbidity and mortality. We hypothesize that lipopolysaccharide (LPS)-induced maternal inflammation causes direct placenta injury and subsequent injury to the fetal intestine.
METHOD OF STUDY - Pregnant C57Bl6 mice were injected intraperitoneally on day 15.5 with 100 μg/kg LPS or saline. Maternal serum, amniotic fluid, placental samples, and ileal samples of offspring were obtained assessed for inflammation and/or injury. Maternal placental ultrasounds were performed. Placental DNA was isolated for microbiome analysis.
RESULTS - Maternal injection with LPS caused elevated IL-1β, IL-10, IL-6, KC-GRO, and TNF. Placental tissue showed increased IL-1β, IL-6, and KC-GRO and decreased IL-10, but no changes were observed in amniotic fluid. Placental histology demonstrated LPS-induced increases in mineralization and necrosis, but no difference in placental blood flow. Most placentas had no detectable microbiome. Exposure to maternal LPS induced significant injury to the ilea of the offspring.
CONCLUSION - Lipopolysaccharide causes a maternal inflammatory response that is mirrored in the placenta. Placental histology demonstrates structural changes; however, placental blood flow is preserved. LPS also induces an indirect intestinal injury in the offspring that lasts beyond the neonatal period.
© 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
OBJECTIVE - To assess whether interpregnancy interval length after a pregnancy loss is associated with risk of repeat miscarriage.
METHODS - This analysis includes pregnant women participating in the Right From the Start (2000-2012) community-based prospective cohort study whose most recent pregnancy before enrollment ended in miscarriage. Interpregnancy interval was defined as the time between a prior miscarriage and the last menstrual period of the study pregnancy. Miscarriage was defined as pregnancy loss before 20 weeks of gestation. Cox proportional hazard models were used to estimate crude and adjusted hazard ratios and 95% CIs for the association between different interpregnancy interval lengths and miscarriage in the study pregnancy. Adjusted models included maternal age, race, parity, body mass index, and education.
RESULTS - Among the 514 study participants who reported miscarriage as their most recent pregnancy outcome, 15.7% had a repeat miscarriage in the study pregnancy (n=81). Median maternal age was 30 years (interquartile range 27-34) and 55.6% of participants had at least one previous livebirth (n=286). When compared with women with interpregnancy intervals of 6-18 months (n=136), women with intervals of less than 3 months (n=124) had the lowest risk of repeat miscarriage (7.3% compared with 22.1%; adjusted hazard ratio 0.33, 95% CI 0.16-0.71). Neither maternal race nor parity modified the association. Attempting to conceive immediately was not associated with increased risk of miscarriage in the next pregnancy.
CONCLUSION - An interpregnancy interval after pregnancy loss of less than 3 months is associated with the lowest risk of subsequent miscarriage. This implies counseling women to delay conception to reduce risk of miscarriage may not be warranted.
A 2240 gram boy was born at 33.2 weeks gestation with nonblanching, deeply erythematous plaques and papules on the back, flanks, and scalp (Figure 1). His mother was GBS positive and on antibiotic suppression for prior cutaneous MRSA and urinary tract infections. Intrapartum intravenous Penicillin G was administered, and the amniotic sac was artificially ruptured 4 hours prior to delivery to facilitate labor. The delivery was uncomplicated without concern for chorioamnionitis, but the patient initially required CPAP for respiratory distress with 1-minute and 5-minute Apgar scores of 7 and 8, respectively. A skin punch biopsy is shown (Figure 2).
OBJECTIVE - To systematically review studies reporting the risk of spontaneous abortion among pregnant women of typical reproductive potential with and without uterine leiomyomas.
DATA SOURCES - We searched PubMed, EMBASE, Web of Science, and ClinicalTrials.gov for publications from January 1970 to December 2016.
METHODS OF STUDY SELECTION - We excluded studies that did not use imaging to uniformly document leiomyoma status of all participants, did not have a comparison group without leiomyomas, or primarily included women seeking care for recurrent miscarriage, infertility care, or assisted reproductive technologies.
TABULATION, INTEGRATION, AND RESULTS - Two authors independently reviewed eligibility, extracted data, and assigned overall quality ratings based on predetermined criteria. Of 1,469 articles identified, nine were eligible. Five enrolled general obstetric populations and four included women undergoing amniocentesis. In five studies in general obstetric populations that included 21,829 pregnancies (1,394 women with leiomyomas and 20,435 without), only one adjusted for potential confounders. This meta-analysis revealed no increase in risk of spontaneous abortion among those with leiomyomas compared with those without (11.5% compared with 8.0%; risk ratio 1.16, 95% CI 0.80-1.52). When bias from confounding was estimated for nonadjusted studies, the aggregate calculated risk ratio was 0.83 (95% CI 0.68-0.98).
CONCLUSION - Leiomyoma presence was not associated with increased risk of spontaneous abortion in an analysis of more than 20,000 pregnant women. Failure of prior studies to adjust for confounders may have led to the common clinical belief that leiomyomas are a risk factor for spontaneous abortion.
Sickle cell disease (SCD) is associated with adverse pregnancy outcome. In women with SCD living in low-resource settings, pregnancy is associated with significantly increased maternal and perinatal mortality rates. We tested the hypothesis that implementing a multidisciplinary obstetric and hematology care team in a low-resource setting would significantly reduce maternal and perinatal mortality rates. We conducted a before-and-after study, at the Korle-Bu Teaching Hospital in Accra, Ghana, to evaluate the effect of a multidisciplinary obstetric-hematology care team for women with SCD in a combined SCD-Obstetric Clinic. The pre-intervention period was assessed through a retrospective chart review to identify every death and the post-intervention period was assessed prospectively. Interventions consisted of joint obstetrician and hematologist outpatient and acute inpatient reviews, close maternal and fetal surveillance, and simple protocols for management of acute chest syndrome and acute pain episodes. Primary outcomes included maternal and perinatal mortality rates before and after the study period. A total of 158 and 90 pregnant women with SCD were evaluated in the pre- and post- intervention periods, respectively. The maternal mortality rate decreased from 10 791 per 100 000 live births at pre-intervention to 1176 per 100 000 at post-intervention, representing a risk reduction of 89.1% (P = 0.007). Perinatal mortality decreased from 60.8 per 1000 total births at pre-intervention to 23.0 per 1000 at post-intervention, representing a risk reduction of 62.2% (P = 0.20). A multidisciplinary obstetric and hematology team approach can dramatically reduce maternal and perinatal mortality in a low-resource setting.
© 2017 Wiley Periodicals, Inc.
The prenatal environment is now recognized as a key driver of non-communicable disease risk later in life. Within the developmental origins of health and disease (DOHaD) paradigm, studies are increasingly identifying links between maternal morbidity during pregnancy and disease later in life for offspring. Nutrient restriction, metabolic disorders during gestation, such as diabetes or obesity, and maternal immune activation provoked by infection have been linked to adverse health outcomes for offspring later in life. These factors frequently co-occur, but the potential for compounding effects of multiple morbidities on DOHaD-related outcomes has not received adequate attention. This is of particular importance in low- or middle-income countries (LMICs), which have ongoing high rates of infectious diseases and are now experiencing transitions from undernutrition to excess adiposity. The purpose of this scoping review is to summarize studies examining the effect and interaction of co-occurring metabolic or nutritional stressors and infectious diseases during gestation on DOHaD-related health outcomes. We identified nine studies in humans - four performed in the United States and five in LMICs. The most common outcome, also in seven of nine studies, was premature birth or low birth weight. We identified nine animal studies, six in mice, two in rats and one in sheep. The interaction between metabolic/nutritional exposures and infectious exposures had varying effects including synergism, inhibition and independent actions. No human studies were specifically designed to assess the interaction of metabolic/nutritional exposures and infectious diseases. Future studies of neonatal outcomes should measure these exposures and explicitly examine their concerted effect.
PURPOSE - Data about maternal recall accuracy for classifying early pregnancy medication exposure are meager. Nonetheless, studies often rely on recall to evaluate potential impact of pharmaceuticals on the developing fetus.
METHODS - Right from the Start is a community-based pregnancy cohort that enrolled women from North Carolina, Tennessee, and Texas. A subset of 318 women participated in daily medication diaries initiated before conception (2006-2012). We examined nonsteroidal anti-inflammatory drugs (NSAIDs) as an example of a drug type that is difficult to study due to its intermittent and primarily over-the-counter use as well as its incomplete documentation in medical and pharmaceutical records. Selective serotonin reuptake inhibitors (SSRI) were assessed as a prescription medication comparator. Maternal recall of NSAID and SSRI use in early pregnancy was examined by comparing diary data (gold standard) to first-trimester interview.
RESULTS - Sensitivity and specificity for recall of NSAID exposure were 78.6% and 62.3%, respectively (kappa statistic: 0.41), with 72.3% agreement for exposure classification. Sensitivity and specificity for recall of SSRI exposure were 77.8% and 99.0%, respectively (kappa statistic: 0.79), with 97.8% agreement.
CONCLUSIONS - Our findings suggest the validity of maternal recall varies with medication type and prospective data collection should be prioritized when studying early pregnancy drug exposures.
Copyright © 2016 Elsevier Inc. All rights reserved.
Staphylococcus aureus, a metabolically flexible gram-positive pathogen, causes infections in a variety of tissues. Recent evidence implicates S. aureus as an emerging cause of chorioamnionitis and premature rupture of membranes, which are associated with preterm birth and neonatal disease. We demonstrate here that S. aureus infects and forms biofilms on the choriodecidual surface of explanted human gestational membranes. Concomitantly, S. aureus elicits the production of proinflammatory cytokines, which could ultimately perturb maternal-fetal tolerance during pregnancy. Therefore, targeting the immunological response to S. aureus infection during pregnancy could attenuate disease among infected individuals, especially in the context of antibiotic resistance.
Published by Oxford University Press for the Infectious Diseases Society of America 2016. This work is written by (a) US Government employee(s) and is in the public domain in the US.
The aim of this propensity-matched cohort study was to evaluate the impact of prenatal SSRI exposure and a history of maternal depression on neonatal brain volumes and white matter microstructure. SSRI-exposed neonates (n=27) were matched to children of mothers with no history of depression or SSRI use (n=54). Additionally, neonates of mothers with a history of depression, but no prenatal SSRI exposure (n=41), were matched to children of mothers with no history of depression or SSRI use (n=82). Structural magnetic resonance imaging and diffusion weighted imaging scans were acquired with a 3T Siemens Allegra scanner. Global tissue volumes were characterized using an automatic, atlas-moderated expectation maximization segmentation tool. Local differences in gray matter volumes were examined using deformation-based morphometry. Quantitative tractography was performed using an adaptation of the UNC-Utah NA-MIC DTI framework. SSRI-exposed neonates exhibited widespread changes in white matter microstructure compared to matched controls. Children exposed to a history of maternal depression but no SSRIs showed no significant differences in brain development compared to matched controls. No significant differences were found in global or regional tissue volumes. Additional research is needed to clarify whether SSRIs directly alter white matter development or whether this relationship is mediated by depressive symptoms during pregnancy.
Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.
BACKGROUND - Pregnancy in women with sickle-cell disease (SCD) is associated with increased adverse outcomes. Findings on the association between SCD and adverse pregnancy outcomes are conflicting, and the results do not address whether these associations are similar in both low- and high-income countries.
OBJECTIVES - We conducted a systematic review and meta-analysis to evaluate pregnancy outcomes associated with SCD.
SEARCH STRATEGY - The MEDLINE database was searched using medical subject headings (MeSH) and keywords for articles on pregnancy outcomes in women with SCD.
SELECTION CRITERIA - We used full research articles published in English that compared women with SCD with women who did not have SCD, as controls.
DATA COLLECTION AND ANALYSIS - Data were abstracted and analysed using comprehensive Meta-analysis 2.2. The primary outcomes were intrauterine growth restriction and perinatal mortality. Secondary outcomes were rates of caesarean sections, pre-eclampsia, eclampsia, postpartum haemorrhage, maternal mortality, prematurity, and low birthweight. Random-effects models were used to calculate pooled odds ratios (ORs) with 95% confidence intervals (95% CIs).
MAIN RESULTS - Sixteen studies met all of the selection criteria and were included in the analysis. SCD was associated with intrauterine growth restriction (pooled OR 2.79, 95% CI 1.85-4.21), perinatal mortality (pooled OR 3.76, 95% CI 2.34-6.06), and low birthweight (pooled OR 2.00, 95% CI 1.42-2.83). SCD was also associated with an increased risk of pre-eclampsia (pooled OR 2.05, 95% CI 1.47-2.85), maternal mortality (pooled OR 10.91, 95% CI 1.83-65.11, P = 0.009), and eclampsia (pooled OR 3.02, 95% CI 1.20-7.58).
CONCLUSION - Pregnancy in women with SCD is associated with increased risks of adverse perinatal and maternal outcomes in both low- and high-income countries.
TWEETABLE ABSTRACT - This meta-analysis showed worse pregnancy outcomes in women with sickle-cell disease compared with controls.
© 2015 Royal College of Obstetricians and Gynaecologists.