Examination of Text Message Plans and Baseline Usage of Families Enrolled in a Text Message Influenza Vaccine Reminder Trial: Survey Study.

BACKGROUND: Mobile health (mHealth) is quickly expanding as a method of health promotion, but some interventions may not be familiar or comfortable for potential users. SMS text messaging has been investigated as a low-cost, accessible way to provide vaccine reminders. Most (97%) US adults own a cellphone and of those adults most use SMS text messaging. However, understanding patterns of SMS text message plan type and use in diverse primary care populations needs more investigation. OBJECTIVE: We sought to use a survey to examine baseline SMS text messaging and data plan patterns among families willing to accept SMS text message vaccine reminders. METHODS: As part of a National Institutes of Health (NIH)-funded national study (Flu2Text) conducted during the 2017-2018 and 2018-2019 influenza seasons, families of children needing a second seasonal influenza vaccine dose were recruited in pediatric primary care offices at the time of their first dose. Practices were from the American Academy of Pediatrics' (AAP) Pediatric Research in Office Settings (PROS) research network, the Children's Hospital of Philadelphia, and Columbia University. A survey was administered via telephone (Season 1) or electronically (Season 2) at enrollment. Standardized (adjusted) proportions for SMS text message plan type and texting frequency were calculated using logistic regression that was adjusted for child and caregiver demographics. RESULTS: Responses were collected from 1439 participants (69% of enrolled). The mean caregiver age was 32 (SD 6) years, and most children (n=1355, 94.2%) were aged 6-23 months. Most (n=1357, 94.3%) families were English-speaking. Most (n=1331, 92.8%) but not all participants had an unlimited SMS text messaging plan and sent or received texts at least once daily (n=1313, 91.5%). SMS text messaging plan type and use at baseline was uniform across most but not all subgroups. However, there were some differences in the study population's SMS text messaging plan type and usage. Caregivers who wanted Spanish SMS text messages were less likely than those who chose English to have an unlimited SMS text messaging plan (n=61, 86.7% vs n=1270, 94%; risk difference -7.2%, 95% CI -27.1 to -1.8). There were no significant differences in having an unlimited plan associated with child's race, ethnicity, age, health status, insurance type, or caregiver education level. SMS text messaging use at baseline was not uniform across all subgroups. Nearly three-quarters (n=1030, 71.9%) of participants had received some form of SMS text message from their doctor's office; most common were appointment reminders (n=1014, 98.4%), prescription (n=300, 29.1%), and laboratory notifications (n=117, 11.4%). Even the majority (n=64, 61.5%) of those who did not have unlimited plans and who texted less than daily (n=72, 59%) reported receipt of these SMS text messages. CONCLUSIONS: In this study, most participants had access to unlimited SMS text messaging plans and texted at least once daily. However, infrequent texting and lack of access to an unlimited SMS text messaging plan did not preclude enrolling to receive SMS text message reminders in pediatric primary care settings.

A Clinical Decision Support System for Motivational Messaging and Tobacco Cessation Treatment for Parents: Pilot Evaluation of Use and Acceptance.

BACKGROUND: Research is needed to identify how clinical decision support (CDS) systems can support communication about and engagement with tobacco use treatment in pediatric settings for parents who smoke. We developed a CDS system that identifies parents who smoke, delivers motivational messages to start treatment, connects parents to treatment, and supports pediatrician-parent discussion. OBJECTIVE: The objective of this study is to assess the performance of this system in clinical practice, including receipt of motivational messages and tobacco use treatment acceptance rates. METHODS: The system was evaluated at one large pediatric practice through a single-arm pilot study from June to November 2021. We collected data on the performance of the CDS system for all parents. Additionally, we surveyed a sample of parents immediately after the clinical encounter who used the system and reported smoking. Measures were: (1) the parent remembered the motivational message, (2) the pediatrician reinforced the message, and (3) treatment acceptance rates. Treatments included nicotine replacement therapy, quitline referral (phone counseling), and/or SmokefreeTXT referral (text message counseling). We described survey response rates overall and with 95% confidence intervals (CIs). RESULTS: During the entire study period, 8,488 parents completed use of the CDS: 9.3% (n = 786) reported smoking and 48.2% (n = 379) accepted at least one treatment. A total of 102 parents who smoke who used the system were approached to survey 100 parents (98% response rate). Most parents self-identified as female (84%), aged 25 to 34 years (56%), and Black/African American (94%), and had children with Medicaid insurance (95%). Of parents surveyed, 54% accepted at least one treatment option. Most parents recalled the motivational message (79%; 95% CI: 71-87%), and 31% (95% CI: 19-44%) reported that the pediatrician reinforced the motivational message. CONCLUSION: A CDS system to support parental tobacco use treatment in pediatric primary care enhanced motivational messaging about smoking cessation and evidence-based treatment initiation.

Insulin Downregulates the Expression of ATP-binding Cassette Transporter A-I in Human Hepatoma Cell Line HepG2 in a FOXO1 and LXR Dependent Manner.

ATP-binding cassette transporter A-I (ABCA1) is an ubiquitously expressed protein whose main function is the transmembrane transport of cholesterol and phospholipids. Synthesis of ABCA1 protein in liver is necessary for high-density lipoprotein (HDL) formation in mammals. Thus, the mechanism of ABCA1 gene expression regulation in hepatocytes are of critical importance. Recently, we have found the insulin-dependent downregulation of other key player in the HDL formation-apolipoprotein A-I gene (J. Cell. Biochem., 2017, 118:382-396). Nothing is known about the role of insulin in the regulation of ABCA1 gene. Here we show for the first time that insulin decreases the mRNA and protein levels of ABCA1 in human hepatoma cell line HepG2. PI3K, p38, MEK1/2, JNK and mTORC1 signaling pathways are involved in the insulin-mediated downregulation of human ABCA1 gene. Transcription factors LXRα, LXRß, FOXO1 and NF-κB are important contributors to this process, while FOXA2 does not regulate ABCA1 gene expression. Insulin causes the decrease in FOXO1, LXRα and LXRß binding to ABCA1 promoter, which is likely the cause of the decrease in the gene expression. Interestingly, the murine ABCA1 gene seems to be not regulated by insulin in hepatocytes (in vitro and in vivo). We suggest that the reason for this discrepancy is the difference in the 5'-regulatory regions of human and murine ABCA1 genes.

Pediatric Practices' Perceptions of Text Message Communication with Families: An American Academy of Pediatrics (AAP), Pediatric Research in Office Settings (PROS) Study.

Background: Text messages can be an effective and low-cost mechanism for patient reminders; however, they are yet to be consistently integrated into pediatric primary care. Objective: The aim of this study was to explore pediatric primary care clinician and staff perceptions of pediatric office text message communication with families. Methods: As part of the National Institutes of Health-funded Flu2Text randomized controlled trial of second-dose influenza vaccine text message reminders, we conducted 7 focus groups and 4 individual interviews in July-August 2019 with primary care pediatric clinicians and staff (n = 39). Overall, 10 Pediatric Research in Office Settings (PROS) pediatric practices in 10 states were selected using stratified sampling. Semi-structured discussion guides included perspectives on possible uses, perceived usefulness, and ease of use of text messages; practices' current text messaging infrastructure; and perceived barriers/facilitators to future use of texting. Two investigators independently coded and analyzed transcripts based on the technology acceptance model using NVIVO 12 Plus (intercoder reliability, K = 0.86). Results: Overall, participants were supportive of text reminders for the second-dose influenza vaccine, other vaccines, and appointments and perceived texting as a preferred method of communication for caregivers. Health information privacy and patient confidentiality were the main concerns cited. Only respondents from practices with no internal appointment text message reminder system prior to the study expressed concerns about technology implementation logistics, time, and cost. Conclusion: Text message reminders, for various uses, appear to be well accepted among a group of geographically widespread pediatric practices after participation in a trial of influenza vaccine text message reminders. Privacy, confidentiality, and resource barriers need to be addressed to facilitate successful implementation.

Adiponectin Stimulates Apolipoprotein A-1 Gene Expression in HepG2 Cells via AMPK, PPARα, and LXRs Signaling Mechanisms.

Adiponectin is an adipose tissue hormone, participating in energy metabolism and involved in atherogenesis. Previously, it was found that adiponectin increases expression of the APOA1 (apolipoprotein A-1) gene in hepatocytes, but the mechanisms of this effect remained unexplored. Our aim was to investigate the role of adiponectin receptors AdipoR1/R2, AMP-activated protein kinase (AMPK), nuclear peroxisome proliferator-activated receptor alpha (PPARα) and liver X receptors (LXRs) in mediating the action of adiponectin on hepatic APOA1 expression in human hepatoma HepG2 cells. The level of APOA1 expression was determined by RT-qPCR and ELISA. We showed that the siRNA-mediated knockdown of genes coding for AdipoR1, AdipoR2, AMPK, PPARα, and LXRα and ß prevented adiponectin-induced APOA1 expression in HepG2 cells and demonstrated that interaction of PPARα and LXRs with the APOA1 gene hepatic enhancer is important for the adiponectin-dependent APOA1 transcription. The results of this study point out to the involvement of both types of adiponectin receptors, AMPK, PPARα, and LXRs in the adiponectin-dependent upregulation of the APOA1 expression.

Text Message Reminders for the Second Dose of Influenza Vaccine for Children: An RCT.

BACKGROUND AND OBJECTIVES: Among children requiring 2 influenza doses in a given season, second dose receipt nearly halves the odds of influenza. Nationally, many children do not receive both needed doses. This study sought to compare the effectiveness of text message reminders with embedded interactive educational information versus usual care on receipt and timeliness of the second dose of influenza vaccine. METHODS: This trial took place over the 2017 to 2018 and 2018 to 2019 influenza seasons among 50 pediatric primary care offices across 24 states primarily from the American Academy of Pediatrics' Pediatric Research in Office Settings practice-based research network. Caregiver-child dyads of children 6 months to 8 years in need of a second influenza vaccination that season were individually randomized 1:1 into intervention versus usual care, stratified by age and language within each practice. Intervention caregivers received automated, personalized text messages, including educational information. Second dose receipt by April 30 (season end) and by day 42 (2 weeks after second dose due date) were assessed using Mantel Haenszel methods by practice and language. Analyses were intention to treat. RESULTS: Among 2086 dyads enrolled, most children were 6 to 23 months and half publicly insured. Intervention children were more likely to receive a second dose by season end (83.8% versus 80.9%; adjusted risk difference (ARD) 3.8%; 95% confidence interval [0.1 to 7.5]) and day 42 (62.4% versus 55.7%; ARD 8.3% [3.6 to 13.0]). CONCLUSIONS: In this large-scale trial of primary care pediatric practices across the United States, text message reminders were effective in promoting increased and timelier second dose influenza vaccine receipt.

Electronic Health Record-Embedded, Behavioral Science-Informed System for Smoking Cessation for the Parents of Pediatric Patients.

BACKGROUND: Helping parents quit smoking is a public health priority. However, parents are rarely, if ever, offered tobacco use treatment through pediatric settings. Clinical decision support (CDS) systems developed for the workflows of pediatric primary care may support consistent screening, treatment, and referral. OBJECTIVES: This study aimed to develop a CDS system by using human-centered design (HCD) that identifies parents who smoke, provides motivational messages to quit smoking (informed by behavioral science), and supports delivery of evidence-based tobacco treatment. METHODS: Our multidisciplinary team applied a rigorous HCD process involving analysis of the work environment, user involvement in formative design, iterative improvements, and evaluation of the system's use in context with the following three cohorts: (1) parents who smoke, (2) pediatric clinicians, and (3) clinic staff. Participants from each cohort were presented with scenario-based, high-fidelity mockups of system components and then provided input related to their role in using the CDS system. RESULTS: We engaged 70 representative participants including 30 parents, 30 clinicians, and 10 clinic staff. A key theme of the design review sessions across all cohorts was the need to automate functions of the system. Parents emphasized a system that presented information in a simple way, highlighted benefits of quitting smoking, and allowed direct connection to treatment. Pediatric clinicians emphasized automating tobacco treatment. Clinical staff emphasized screening for parent smoking via several modalities prior to the patient's visit. Once the system was developed, most parents (80%) reported that it was easy to use, and the majority of pediatricians reported that they would use the system (97%) and were satisfied with it (97%). CONCLUSION: A CDS system to support parental tobacco cessation in pediatric primary care, developed through an HCD process, proved easy to use and acceptable to parents, clinicians, and office staff. This preliminary work justifies evaluating the impact of the system on helping parents quit smoking.

Autism Spectrum Disorder Screening During the COVID-19 Pandemic in a Large Primary Care Network.

OBJECTIVE: To assess the impact of the COVID-19 pandemic on screening for autism spectrum disorder (ASD) and screening equity among eligible children presenting for well-child care in a large primary care pediatric network, we compared rates of ASD screening completion and positivity during the pandemic to the year prior, stratified by sociodemographic factors. METHODS: Patients who presented for in-person well-child care at 16 to 26 months between March 1, 2020 and February 28, 2021 (COVID-19 cohort, n = 24,549) were compared to those who presented between March 1, 2019 and February 29, 2020 (pre-COVID-19 cohort, n = 26,779). Demographics and rates of completion and positivity of the Modified Checklist for Autism in Toddlers with Follow-up (M-CHAT/F) were calculated from the electronic health record and compared by cohort using logistic regression models. RESULTS: Total eligible visits decreased by 8.3% between cohorts, with a greater decline in Black and publicly insured children. In the pre-COVID-19 cohort, 89.0% of eligible children were screened at least once, compared to 86.4% during the pandemic (P < 0.001). Significant declines in screening completion were observed across all sociodemographic groups except among Asian children, with the sharpest declines among non-Hispanic White children. Sociodemographic differences were not observed in screen-positive rates by cohort. CONCLUSIONS: Well-child visits and ASD screenings declined across groups, but with different patterns by race and ethnicity during the COVID-19 pandemic. Findings regarding screen-completion rates should not be interpreted as a decline in screening disparities, given differences in who presented for care. Strategies for catch-up screening for all children should be considered.

Differentiation of human macrophages with anaphylatoxin C3a impairs alternative M2 polarization and decreases lipopolysaccharide-induced cytokine secretion.

Anaphylatoxin C3a is a small signaling polypeptide that is generated during complement activation. C3a is involved in the regulation of various innate and adaptive immune system processes; however, the role of C3a in macrophage differentiation and polarization is poorly elucidated. Here we showed that C3a impairs alternative M2 polarization of human macrophages and suppressed CD206, IL1Ra and CCL22 expression. C3a leads to a decrease of nuclear receptor PPARγ expression via the ERK1/2 signaling pathway, resulting in repressed PPARγ-dependent activation of CD36, FABP4 and LXRα genes and blunted response to an LXR ligand TO901317. Using small interfering RNA and agonist/antagonist approaches we showed that C3a decreases CD206, IL1Ra and CCL22 transcription at least partly in a PPARγ-dependent manner in M2 macrophages. Moreover, C3a impairs efferocytosis by M2 macrophages and inhibits their migratory activity. By contrast, macrophages treated with C3a during differentiation show blunted response to lipopolysaccharide stimulation owing to downregulation of TLR4 and lipid raft content. At the same time, differentiation of macrophages with C3a does not change M1 polarization in interferon gamma (IFNγ) and IFNγ + lipopolysaccharide-treated macrophages. These data provide a novel role of complement system and C3a in the regulation of M2 macrophage polarizations and suggest crosstalk between C3a, TLR4, PPARγ and LXR signaling pathways.

Innovation in the pediatric electronic health record to realize a more effective platform.

Commercial electronic health records (EHRs) were first developed to automate business processes. As EHRs developed, design principles focused on transferring existing paper-based documentation to comparable electronic forms. In addition, a strong industry focus on adult healthcare settings and quality measures has limited attention and resources for high priority EHR functionality needed for the unique health care of children. The objective of this paper is to provide a review of innovation in the EHR, that includes a variety of established and emerging technologies that may help realize a more effective EHR in child health settings. A more effective EHR would serve as an electronic hub. Existing EHR infrastructure could provide the foundation upon which new technologies and approaches branch and extend, enabling more rapid and customizable innovation to better meet shifting stakeholder and end-user needs. Among many areas for improvement, key goals of innovation could include technology that relieves ambulatory primary care clinician documentation burden, identifies needs, and supports improved care coordination and outcomes, focused on the following key areas: identification of child and family care needs, decision support, documentation, care coordination, and family communication.

Regulation of Apolipoprotein A-I Gene Expression in Human Macrophages by Oxidized Low-Density Lipoprotein.

Apolipoprotein A-I (ApoA-I) is a key component of reverse cholesterol transport in humans. In the previous studies, we demonstrated expression of the apoA-I gene in human monocytes and macrophages; however, little is known on the regulation of the apoA-I expression in macrophages during the uptake of modified low-density lipoprotein (LDL), which is one of the key processes in the early stages of atherogenesis leading to formation of foam cells. Here, we demonstrate a complex nature of the apoA-I regulation in human macrophages during the uptake of oxidized LDL (oxLDL). Incubation of macrophages with oxLDL induced expression of the apoA-I gene within the first 24 hours, but suppressed it after 48 h. Both effects depended on the interaction of oxLDL with the TLR4 receptor, rather than on the oxLDL uptake by the macrophages. The oxLDL-mediated downregulation of the apoA-I gene depended on the ERK1/2 and JNK cascades, as well as on the NF-κB cascade.

Neoadjuvant therapy of BRCA1-driven ovarian cancer by combination of cisplatin, mitomycin C and doxorubicin.

BACKGROUND: Cisplatin, mitomycin C and anthracyclines demonstrate high activity in BRCA1-deficient tumors. This study aimed to evaluate the efficacy of the triplet combination of these drugs in BRCA1-driven high-grade serous ovarian carcinomas (HGSOCs). METHODS: Ten HGSOC patients with germ-line BRCA1 mutation received neoadjuvant chemotherapy (NACT) consisting of mitomycin C 10 mg/m2 (day 1), doxorubicin 30 mg/m2 (days 1 and 8) and cisplatin 80 mg/m2 (day 1), given every 4 weeks (MAP regimen). The comparator group included 16 women, who received standard NACT combination of paclitaxel 175 mg/m2 and carboplatin (6 AUC), given every 3 weeks (TCbP scheme). RESULTS: None of the patients treated by the MAP scheme demonstrated complete pathologic response in ovaries, while 4 women showed absence of tumor cells in surgically excised omental specimens. When chemotherapy response scores (CRS) were considered, poor responsiveness (CRS 1) was not observed in the MAP group, but was common for the TCbP regimen (6/16 (38 %) for ovaries and 5/16 (31 %) for omentum; p = 0.05 and 0.12, respectively). Median treatment-free interval (TFI) was not reached in women treated by the MAP, but was 9.5 months for the TCbP scheme (p = 0.1). The rate of the recurrence within 1 year after the completion of the treatment was 4/10 (40 %) for the MAP and 10/13 (77 %) for the TCbP (p = 0.1). CONCLUSIONS: The attempt to intensify NACT by administering combination of 3 drugs did not result in high rate of complete pathologic responses. However, there was a trend towards higher efficacy of the MAP regimen versus conventional TCbP scheme with regard to CRS and clinical outcomes.

Vaccine hesitancy and influenza beliefs among parents of children requiring a second dose of influenza vaccine in a season: An American Academy of Pediatrics (AAP) Pediatric Research in Office Settings (PROS) study.

To receive adequate protection against influenza, some children 6 months through 8 y old need two doses of influenza vaccine in a given season. Currently, only half of those receiving the first dose receive a second. Our objective was to assess vaccine hesitancy and influenza disease and vaccine knowledge, attitudes, and beliefs among caregivers of children who received the first of their two needed doses. As part of a national-randomized control trial of second dose text-message influenza vaccine reminders (2017-2018 season), a telephone survey collected caregiver and index child demographic information. Each child had received the first of two needed influenza vaccine doses. Caregivers completed a measure of general vaccine hesitancy - the five-question Parent Attitudes About Childhood Vaccines Survey Tool (PACV-5) - and questions about influenza infection and vaccine. We assessed associations between participant demographic characteristics, vaccine hesitancy, and influenza beliefs and calculated the standardized proportion of caregivers endorsing each outcome using logistic regression. Analyses included responses from 256 participants from 36 primary care practices in 24 states. Some caregivers (11.7%) reported moderate/high vaccine hesitancy and many had misperceptions about influenza disease and vaccine. In multivariable models, no single variable was consistently associated with inaccurate knowledge, attitudes, and beliefs. These results demonstrate that caregivers whose children received the first dose of influenza vaccine may still be vaccine hesitant and have inaccurate influenza beliefs. Pediatricians should consider broadly addressing inaccurate beliefs and promoting vaccination even after caregivers agree to the first dose.

Insulin downregulates C3 gene expression in human HepG2 cells through activation of PPARγ.

C3 is an acute phase protein, and thus its plasma concentration increases quickly and drastically during the onset of inflammation. Insulin plays a complex role in inflammation. Elevated level of plasma C3 was shown to correlate with heightened fasting insulin levels and insulin resistance and appears to be a risk factor for the cardiovascular disease and atherosclerosis. The main source of plasma C3 is liver. Nothing is known about effects of insulin on C3 gene expression and protein secretion by hepatocytes. In light of these data we asked if insulin is capable of regulating C3 production in hepatocytes. Here we show that insulin downregulates C3 gene expression in human hepatoma cells HepG2 through activation of PI3K, mTORC1, p38 and MEK1/2 signaling pathways. Transcription factors PPARα, PPARγ, HNF4α and NF-κB are important contributors to this process. Insulin activates PPARγ through PI3K/Akt/mTORC1 pathway, which results in PPARγ binding to DR4 and DR0 cis-acting elements within the C3 promoter and subsequent displacement of HNF4α and PPARα from these sites. As a result PPARα/NF-κB complex, which exists on C3 promoter, is broken down and C3 gene expression is downregulated. The data obtained can potentially be used to explain the molecular mechanism underlying the correlation between heightened level of plasma C3 and insulin resistance in humans.

Tumor necrosis factor α stimulates endogenous apolipoprotein A-I expression and secretion by human monocytes and macrophages: role of MAP-kinases, NF-κB, and nuclear receptors PPARα and LXRs.

Apolipoprotein A-I (ApoA-I) is the main structural and functional protein component of high-density lipoprotein. ApoA-I has been shown to regulate lipid metabolism and inflammation in macrophages. Recently, we found the moderate expression of endogenous apoA-I in human monocytes and macrophages and showed that pro-inflammatory cytokine tumor necrosis factor α (TNFα) increases apoA-I mRNA and stimulates ApoA-I protein secretion by human monocytes and macrophages. Here, we present data about molecular mechanisms responsible for the TNFα-mediated activation of apoA-I gene in human monocytes and macrophages. This activation depends on JNK and MEK1/2 signaling pathways in human monocytes, whereas inhibition of NFκB, JNK, or p38 blocks an increase of apoA-I gene expression in the macrophages treated with TNFα. Nuclear receptor PPARα is a ligand-dependent regulator of apoA-I gene, whereas LXRs stimulate apoA-I mRNA transcription and ApoA-I protein synthesis and secretion by macrophages. Treatment of human macrophages with PPARα or LXR synthetic ligands as well as knock-down of LXRα, and LXRß by siRNAs interfered with the TNFα-mediated activation of apoA-I gene in human monocytes and macrophages. At the same time, TNFα differently regulated the levels of PPARα, LXRα, and LXRß binding to the apoA-I gene promoter in THP-1 cells. Obtained results suggest a novel tissue-specific mechanism of the TNFα-mediated regulation of apoA-I gene in monocytes and macrophages and show that endogenous ApoA-I might be positively regulated in macrophage during inflammation.

First-trimester maternal serum matrix metalloproteinase-9 (MMP-9) and adverse pregnancy outcome.

OBJECTIVE: To investigate the potential value of maternal serum matrix metalloproteinase-9 (MMP-9) in first-trimester screening for preeclampsia and spontaneous early preterm delivery. METHODS: The concentrations of MMP-9, tumour necrosis factor soluble receptor-1 (TNF-R1), pregnancy-associated plasma protein-A (PAPP-A) and uterine artery pulsatility index (UA-PI) were measured at 11(+0) - 13(+6) weeks in cases of preeclampsia (n = 128), gestational hypertension (n = 88), small for gestational age (n = 296), spontaneous early preterm delivery (n = 57) and controls (n = 569). The distributions of measured metabolites and UA-PI in the control and adverse outcome groups were compared. Logistic regression analysis was used to determine the significant contributors in the prediction of adverse outcomes. RESULTS: The median MMP-9 was higher than controls in the preeclampsia (1.190 MoM) and preterm delivery (1.187 MoM) groups. In the preeclampsia group there was a significant association between serum MMP-9 and TNF-R1 (r = 0.523, P < 0.0001). Significant prediction of preeclampsia was provided by history and UA-PI, and prediction of preterm delivery was provided by history and neither was improved by the addition of MMP-9. CONCLUSION: In pregnancies developing preeclampsia, the increased level of MMP-9 and the good correlation with TNF-R1 suggest the presence of an underlying inflammatory process. In the pregnancies resulting in spontaneous preterm delivery the small increase in MMP-9 is not useful in the prediction of preterm delivery.