ABSTRACT
The integrity of human fetal membranes is crucial for harmonious fetal development throughout pregnancy. Their premature rupture is often the consequence of a physiological phenomenon that has been exacerbated. Beyond all the implied biological processes, inflammation is of primary importance and is qualified as 'sterile' at the end of pregnancy. In this study, complementary methylomic and transcriptomic strategies on amnion and choriodecidua explants obtained from the altered (cervix zone) and intact fetal membranes at term and before labour were used. By cross-analysing genome-wide studies strengthened by in vitro experiments, we deciphered how the expression of toll-like receptor 4 (TLR4), an actor in pathological fetal membrane rupture, is controlled. Indeed, it is differentially regulated in the altered zone and between both layers by a dual mechanism: (1) the methylation of TLR4 and miRNA promoters and (2) targeting by miRNA (let-7a-2 and miR-125b-1) acting on the 3'-UTR of TLR4. Consequently, this study demonstrates that fine regulation of TLR4 is required for sterile inflammation establishment at the end of pregnancy and that it may be dysregulated in the pathological premature rupture of membranes.
Subject(s)
Extraembryonic Membranes/metabolism , MicroRNAs/metabolism , Toll-Like Receptor 4/metabolism , 3' Untranslated Regions , Cells, Cultured , Epigenome , Female , Fetal Membranes, Premature Rupture/physiopathology , Humans , Inflammation/physiopathology , Pregnancy , Toll-Like Receptor 4/genetics , TranscriptomeABSTRACT
INTRODUCTION: Preterm prelabor rupture of membranes (PPROM) occurs in 3% of pregnancies and is the main cause (~30%) of premature delivery. Home care seems to be a safe alternative for the management of patients with PPROM, who have a longer latency than those with PPROM managed with conventional hospitalization. We aimed to identify the risk factors associated with a shortened latency before delivery in women with PPROM managed as outpatients. MATERIAL AND METHODS: The design was a retrospective cohort study and the setting was a Monocentric Tertiary centre (Lille University Hospital, France) from 2009 to 2018. All consecutive patients in home care after PPROM at 24-36 weeks were included. For the main outcome measure we calculated the latency ratio for each patient as the ratio of the real latency period to the expected latency period, expressed as a percentage. The risk factors influencing this latency ratio were evaluated. RESULTS: A total of 234 patients were managed at home after PPROM. Mean latency was 35.5 ± 20.7 days, corresponding to an 80% latency ratio. In 196 (83.8%) patients the length of home care was more than 7 days. A lower latency ratio was significantly associated with oligohydramnios (p < 0.001), gestational age at PPROM (p = 0.006), leukocyte count at PPROM more than 12 × 109 /L (p = 0.025), and C-reactive protein concentration more than 5 mg/L at 7 days after PPROM (p = 0.046). Cervical length was not associated with a lower latency ratio. CONCLUSIONS: Women with PPROM managed with home care are stable. The main risk factor associated with a reduced latency is oligohydramnios. Outpatients with oligohydramnios should be informed of the probability of a shortened latency period.
Subject(s)
Fetal Membranes, Premature Rupture/physiopathology , Obstetric Labor, Premature/physiopathology , Outpatients , Prenatal Care , Adult , Cohort Studies , Female , France , Humans , Pregnancy , Pregnancy Outcome , Retrospective Studies , Risk Factors , Time FactorsABSTRACT
High throughput sequencing has previously identified differentially expressed genes (DEGs) and enriched signalling networks in human myometrium for term (≥37 weeks) gestation labour, when defined as a singular state of activity at comparison to the non-labouring state. However, transcriptome changes that occur during transition from early to established labour (defined as ≤3 and >3 cm cervical dilatation, respectively) and potentially altered by fetal membrane rupture (ROM), when adapting from onset to completion of childbirth, remained to be defined. In the present study, we assessed whether differences for these two clinically observable factors of labour are associated with different myometrial transcriptome profiles. Analysis of our tissue ('bulk') RNA-seq data (NCBI Gene Expression Omnibus: GSE80172) with classification of labour into four groups, each compared to the same non-labour group, identified more DEGs for early than established labour; ROM was the strongest up-regulator of DEGs. We propose that lower DEGs frequency for early labour and/or ROM negative myometrium was attributed to bulk RNA-seq limitations associated with tissue heterogeneity, as well as the possibility that processes other than gene transcription are of more importance at labour onset. Integrative analysis with future data from additional samples, which have at least equivalent refined clinical classification for labour status, and alternative omics approaches will help to explain what truly contributes to transcriptomic changes that are critical for labour onset. Lastly, we identified five DEGs common to all labour groupings; two of which (AREG and PER3) were validated by qPCR and not differentially expressed in placenta and choriodecidua.
Subject(s)
Fetal Membranes, Premature Rupture/genetics , Labor Stage, First/physiology , Myometrium/metabolism , Adult , Base Sequence/genetics , Delivery, Obstetric/classification , Female , Fetal Membranes, Premature Rupture/physiopathology , Gene Expression/genetics , Gene Expression Regulation, Developmental/genetics , High-Throughput Nucleotide Sequencing , Humans , Labor Onset , Labor, Obstetric/genetics , Labor, Obstetric/physiology , Parturition , Placenta , Pregnancy , RNA-Seq , Sequence Analysis, RNA/methods , Transcriptome/genetics , Exome SequencingABSTRACT
OBJECTIVE: To identify factors at admission associated with a latency < 7 days after Preterm premature rupture of membranes (PPROM) between 22 and 32 weeks of gestation in singleton pregnancies. MATERIAL AND METHODS: A retrospective comparative study of all women with singleton pregnancies admitted for PPROM to an academic tertiary center during the 5-year period of 2015-2019. Women who gave birth < 7 days and ≥ 7 day after PPROM were compared. We determined risk at admission associated with a latency < 7 days after PPROM by logistic regression and identified high-risk subgroups by classification and regression tree (CART) analysis. RESULTS: Among 174 eligible births, 76 (44%) women gave birth < 7 days after PPROM and 98 (56%) later. The two groups had similar maternal baseline and obstetric characteristics. In multivariate analysis, the following variables reported at admission were independently associated with a latency < 7 days: painful uterine contractions (aOR 3.9, 95%CI 1.1-7.4), cervical length < 20 mm (aOR 2.4, 95%CI 1.2-4.8), and C reactive protein ≥ 10 mg/L (aOR 2.4, 95% CI 1.3-4.8). Women with painful uterine contractions and cervical length at admission < 20 mm were at highest risk of latency < 7 days (rate: 91%). Conversely, the women at lowest risk were those without uterine contractions, with a cervical length ≥ 20 mm, and C-reactive protein < 10 mg/L at admission (rate: 22%). CONCLUSION: Our results may be helpful in determining criteria at admission for selecting women eligible for outpatient care after an initial hospitalization.
Subject(s)
Fetal Membranes, Premature Rupture/etiology , Gestational Age , Risk Factors , Adult , Female , Fetal Membranes, Premature Rupture/diagnosis , Fetal Membranes, Premature Rupture/physiopathology , Humans , Paris/epidemiology , Pregnancy , Retrospective Studies , Tertiary Care Centers/organization & administration , Tertiary Care Centers/statistics & numerical dataABSTRACT
OBJECTIVE: No information exists about whether acute histologic chorioamnionitis (acute-HCA) is more advanced and severe, and intra-amniotic inflammation is more frequent and intense according to outside in neutrophil migration within the same chorio-decidua. The objective of current study is to examine this issue. MATERIALS AND METHODS: We included 106 singleton preterm-births (gestational age at delivery: 20-34 weeks) due to either preterm-labor or preterm-PROM in the context of acute chorio-deciduitis. Study-population was divided into 3 groups according to outside-in neutrophil migration within chorio-decidua as follows: 1) group-1: 'inflammation restricted to the decidua' (n = 22); 2) group-2: 'inflammation restricted to the MT of chorion and the decidua' (n = 31); 3) group-3: 'inflammation in the CT of chorion' (n = 53). We examined the frequency of inflammation in each placental compartment beyond chorio-decidua (i.e., amnion, umbilical cord, and chorionic-plate), and total grade (1-8) of acute-HCA. Moreover, the frequency of intra-amniotic infection (defined as positive amniotic-fluid culture for aerobic and anaerobic bacteria and genital mycoplasmas) and intra-amniotic inflammation (defined as amniotic fluid WBC ≥ 19 cells/mm3), and an intra-amniotic inflammatory response gauged by amnioticfluid WBC count (cells/mm3) were examined in 50 amniotic fluid samples within 7 days of birth. RESULTS: Amnionitis, funisitis and chorionic plate inflammation were more frequent (each for P < 0.01) and median total grade of acute-HCA was increased (P < 0.001) according to outside-in neutrophil migration within chorio-decidua (group-1vs.group-2vs.group-3). Moreover, intra-amniotic infection and inflammation were more frequent (each-for P < 0.05) and median amniotic-fluid WBC count was increased (P < 0.01) according-to outside-in neutrophil-migration within chorio-decidua (group-1 vs. group-2 vs. group-3). CONCLUSION: Acute-HCA is more advanced and severe, and intra-amniotic inflammation is more frequent and intense according to outside in neutrophil migration within the same chorio-decidua. This finding suggests that what is now acute chorio-deciduitis should be subdivided.
Subject(s)
Cell Movement/physiology , Chorioamnionitis/blood , Neutrophils/physiology , Severity of Illness Index , Acute Disease , Adult , Amnion/metabolism , Amniotic Fluid , Chorion/metabolism , Decidua/metabolism , Female , Fetal Membranes, Premature Rupture/physiopathology , Humans , Infant, Newborn , Inflammation , Leukocyte Count , Obstetric Labor, Premature/physiopathology , Pregnancy , Premature Birth/physiopathologyABSTRACT
Using a novel in vitro model system combining biochemical/histologic with bioengineering approaches has provided significant insights into the physiology of fetal membrane weakening and rupture along with potential mechanistic reasons for lack of efficacy of currently clinically used agents to prevent preterm premature rupture of the membranes (pPROM) and preterm births. Likewise, the model has also facilitated screening of agents with potential for preventing pPROM and preterm birth.
Subject(s)
Extraembryonic Membranes/metabolism , Fetal Membranes, Premature Rupture/metabolism , Fetal Membranes, Premature Rupture/prevention & control , Extraembryonic Membranes/physiopathology , Female , Fetal Membranes, Premature Rupture/physiopathology , Granulocyte-Macrophage Colony-Stimulating Factor/metabolism , Humans , Infant, Newborn , Models, Biological , Pregnancy , Premature Birth/prevention & control , Progesterone/metabolism , Thioctic Acid/metabolism , Thrombin/metabolism , Tumor Necrosis Factor-alpha/metabolismABSTRACT
AIM: To investigate the role of thrombospondin motifs 9 (ADAMTS9) in preterm premature rupture of membranes (pPROM). MATERIALS AND METHODS: ADAMTS9 levels were measured in amnion cells from 24 patients of different groups (preterm vs. full-term birth, with vs. without PROM). ADAMTS9 was suppressed in human amnioblasts to investigate its effects on embryonic membrane cells and inflammation-induced cell damage. Pregnant mouse models were used to assess whether inflammation regulates ADAMTS9 by upregulating TNF-α and IL-6, contributing to the preterm birth occurrence. KEY FINDINGS: We found that ADAMTS9 protein and gene expression levels significantly differed among various groups (pPROM > full-term PROM > preterm non-PROM > full-term non-PROM). After ADAMTS9 suppression in human amnioblast WISH cells, TNF-α- and IL-6-induced apoptosis was decreased. In addition, TNF-α, IL-6, and ADAMTS9 protein and gene expression levels were increased in the embryos of mice treated with LPS compared with controls. In agreement, the rate of preterm birth was higher in the LPS group compared with controls. SIGNIFICANCE: Taken together, these in vitro and in vivo findings suggest that TNF-α and IL-6 secreted by macrophages during inflammation regulate ADAMTS9 and induce pPROM.
Subject(s)
ADAMTS9 Protein/physiology , Fetal Membranes, Premature Rupture/physiopathology , Interleukin-6/physiology , Tumor Necrosis Factor-alpha/physiology , ADAMTS9 Protein/genetics , Adult , Animals , Apoptosis , Cell Line , Female , Gene Knockdown Techniques , Gestational Age , Humans , Inflammation/physiopathology , Interleukin-6/genetics , Macrophages/metabolism , Male , Mice , Mice, Inbred C57BL , Placenta/chemistry , Pregnancy , Premature Birth/physiopathology , RNA, Messenger/analysis , THP-1 Cells , Tumor Necrosis Factor-alpha/genetics , Up-RegulationABSTRACT
Introduction: We aimed to compare the amniotic fluid interleukin (IL)-6 concentrations measured using the automated electrochemiluminescence immunoassay method and ELISA, and to establish an IL-6 concentration cut-off value for intra-amniotic inflammation (IAI) in preterm prelabor rupture of membranes (PPROM), which can be used in the automated electrochemiluminescence immunoassay method.Materials and methods: A total of 120 women with PPROM were included in this study. Amniotic fluid samples were obtained through transabdominal amniocentesis. IL-6 concentrations were assessed using both the automated electrochemiluminescence immunoassay method and ELISA, the current gold standard. IAI was defined as an amniotic fluid IL-6 concentration of ≥2600 pg/mL measured using ELISA.Results: A correlation between both assays was found (Spearman's rho = 0.97; p < .0001). Based on the receiver-operating characteristic curve for the identification of IAI (area under the curve = 0.99), a cut-off value of ≥3000 pg/mL was selected for the automated electrochemiluminescence immunoassay method with a sensitivity of 88%, specificity of 99%, positive predictive value of 97%, negative predictive value of 96%, and likelihood ratio of 76.Conclusions: For amniotic fluid IL-6 concentrations assessed using the automated electrochemiluminescence immunoassay method, a cut-off value of 3000 pg/mL was indicated for diagnosing IAI in women with PPROM.
Subject(s)
Amniotic Fluid/metabolism , Chorioamnionitis/diagnosis , Electrochemical Techniques/methods , Fetal Membranes, Premature Rupture/physiopathology , Immunoassay/methods , Interleukin-6/metabolism , Adult , Biomarkers/metabolism , Chorioamnionitis/etiology , Chorioamnionitis/metabolism , Enzyme-Linked Immunosorbent Assay , Female , Humans , Pregnancy , Retrospective Studies , Sensitivity and SpecificityABSTRACT
AIM: Given the scarcity of relevant reports, this study aimed to elucidate whether pregnancy can be prolonged by maintaining the amniotic fluid volume with continuous transabdominal amnioinfusion (TA) for patients with mid-trimester preterm premature rupture of membranes (PPROM) and oligoamnios. METHODS: We retrospectively examined patients who were managed during hospitalization at our department after developing PPROM between week 22 day 0 and week 25 day 6 of gestation and subsequent oligoamnios (amniotic fluid index [AFI] <5 cm) within 7 days after PPROM onset. Cases between 2006 and 2011 comprised the conventional management group (n = 14); cases administered continuous TA between 2012 and 2017 comprised the continuous TA group (n = 14). The primary outcome was the number of days between PPROM and delivery. The secondary outcomes were the proportion of normal amniotic fluid volume (AFI ≥ 5 cm) maintained between PPROM and delivery and the perinatal prognosis for the mother and infant. RESULTS: The continuous TA group had significantly more days between PPROM and delivery and a significantly higher proportion of days that a normal amniotic fluid volume was maintained during that period, regardless of antimicrobial agents administered. Although no significant differences in the perinatal prognosis of disease were found between groups, there was a decreasing trend of composite perinatal mortality and morbidity, and the incidence rates were reduced by half. CONCLUSION: Continuous TA for PPROM with oligoamnios may allow significant prolongation of the gestation period while maintaining the amniotic fluid volume and may lead to improved perinatal prognosis.
Subject(s)
Amniotic Fluid/physiology , Fetal Membranes, Premature Rupture/therapy , Infusions, Parenteral/methods , Oligohydramnios/therapy , Pregnancy Trimesters/physiology , Adult , Amnion/physiopathology , Delivery, Obstetric , Female , Fetal Membranes, Premature Rupture/etiology , Fetal Membranes, Premature Rupture/physiopathology , Gestational Age , Humans , Oligohydramnios/etiology , Oligohydramnios/physiopathology , Pregnancy , Pregnancy Outcome , Prognosis , Retrospective Studies , Treatment OutcomeABSTRACT
We examined the association between gastroschisis and preterm birth (PTB, <37 weeks) by subtype. The sample was drawn from singleton live births in California from 2007 to 2012 contained in a birth cohort file maintained by the California Office of Statewide Health Planning and Development (n = 2,891,965; 1,421 with gastroschisis). Relative risks (RRs) and 95% confidence intervals (CIs) were calculated for PTB by gestational age (<34, 34-36, and any <37 weeks) and by type (spontaneous labor with intact membranes, preterm premature rupture of the membranes [PPROM], provider initiated) and were adjusted for maternal characteristics. Over 44.5% of infants with gastroschisis were born preterm because of spontaneous etiologies; notably, 8.4% of infants with gastroschisis were born <34 weeks because of spontaneous etiologies (adjusted RRs 9.1-12.2). Overall, 53.7% of infants with gastroschisis were born preterm compared with only 6.9% of infants without gastroschisis (adjusted RR 15.2, 95% CI 13.6-19.5) and are at particularly high risk of spontaneous PTB. Nearly 9% of infants with gastroschisis delivered <34 weeks, regardless of preterm etiology, indicating that these infants are at great risk for PTB morbidities in addition to the complications from gastroschisis.
Subject(s)
Fetal Membranes, Premature Rupture/epidemiology , Gastroschisis/embryology , Pregnancy Complications/epidemiology , Premature Birth/epidemiology , Adolescent , Adult , California/epidemiology , Cohort Studies , Female , Fetal Membranes, Premature Rupture/physiopathology , Gastroschisis/complications , Gastroschisis/physiopathology , Gestational Age , Humans , Infant , Infant, Newborn , Pregnancy , Pregnancy Complications/physiopathology , Pregnancy Outcome/epidemiology , Premature Birth/physiopathology , Retrospective Studies , Risk Factors , Young AdultABSTRACT
OBJECTIVE: To evaluate the influence of perinatal inflammation on neurodevelopmental outcome of premature infants. STUDY DESIGN: From a retrospective cohort study of women with preterm labor with intact membranes or preterm prelabor rupture of membranes (PPROM) with an amniocentesis to rule out intra-amniotic inflammation (IAI) and microbial invasion of the amniotic cavity (MIAC), we evaluated neurodevelopmental outcome of their infants born between 24.0 and 34.0 weeks gestation. Women with clinical chorioamnionitis at admission were excluded. Neurodevelopmental outcome was screened with the Ages & Stages Questionnaire (ASQ)-3. We analyzed the relationship between an altered ASQ-3 and antenatal, intra-partum and post-partum factors related to perinatal inflammation. RESULT: Among 98 infants evaluated, 22% had an abnormal score. Amniotic fluid interleukin-6 levels and early-onset sepsis (EOS) were independent factors of an altered ASQ-3 with delivery <26.0 weeks being the strongest predictor. CONCLUSIONS: In premature infants, the presence of IAI, delivery <26.0 weeks and EOS were found to be independent factors of an altered ASQ-3.
Subject(s)
Amniotic Fluid/chemistry , Amniotic Fluid/microbiology , Chorioamnionitis/physiopathology , Infant, Premature/growth & development , Neurodevelopmental Disorders/epidemiology , Premature Birth/physiopathology , Adult , Amniocentesis , Bacteria/isolation & purification , Cohort Studies , Female , Fetal Membranes, Premature Rupture/physiopathology , Gestational Age , Humans , Interleukin-6/analysis , Obstetric Labor, Premature , Parturition , Pregnancy , Retrospective Studies , Yeasts/isolation & purificationABSTRACT
Head trauma may occur during delivery and can lead to a number of conditions. When an infant is injured during birth, the cause of injury is generally due to mechanical forces, such as compression, excessive or abnormal traction during delivery, and the use of forceps. A 39-year-old woman who was a primagravida (first pregnancy) with a gestational age of 26 weeks premature pregnancy was referred to a hospital in Tehran due to premature rupture of membranes (PROM) and fever. She arrived 2 h after rupture (noting that the rupture lasted for one week and then the baby was delivered). Antibiotics were given early on. After weak labour pain, vaginal examination revealed that the cervix was fully dilated and one of the feet of the foetus had come out of the cervix and was seen in the vagina. The foetus had died. The delivery staff used traction with force. Due to the age of the foetus, the head was relatively big and could not be delivered; the neck was thin and broken and the head separated from the body. The mother underwent a caesarean section to deliver the head of the foetus a week after PROM. The father of the dead newborn foetus sued the hospital and the staff responsible for the delivery. When medical professionals damage the trust between patients and their families and babies are injured children, they should be held accountable.
Subject(s)
Delivery, Obstetric/standards , Malpractice , Wounds and Injuries/complications , Adult , Delivery, Obstetric/legislation & jurisprudence , Female , Fetal Membranes, Premature Rupture/mortality , Fetal Membranes, Premature Rupture/physiopathology , Humans , Infant, Newborn , Iran , Pregnancy , Wounds and Injuries/psychologyABSTRACT
AIM: This study aimed to investigate the cause of respiratory distress syndrome (RDS) in neonates from singleton pregnancies with preterm premature rupture of membranes (pPROM) between 24+0 and 36+6 weeks by using regression analysis for various factors. METHODS: In 175 singleton pregnancies with pPROM, 95 cases of RDS (54,29%) were diagnosed. In all cases the following information was collected: latency period of PROM, gestational age at birth, Umbilical Artery Pulsatility Index (UA PI), Middle Cerebral Artery Pulsatility Index (MCA PI), fetal distress, antenatal steroids use, delivery type, pregnancy hypertension disease, gestational glucose intolerance or diabetes, neonatal laboratory parameters, gender, weight, Apgar score, and other neonatal complications. Logistic regression analysis was used to investigate the effect of variables on RDS. RESULTS: The results of logistic regression analysis showed that the following variables are closely correlated with RDS: female gender (OR=0.52; 95%CI:0.28-0,97), antenatal steroids use (OR=0,46; 95%CI:0,34-0,64), abnormal UA PI and MCA PI (OR=2.96; 95%CI:1,43-6,12) (OR=2.05; 95%CI:1,07-3,95), fetal distress (OR=2.33; 95%CI:1,16-4,71), maternal HGB (OR=0.69; 95%CI:0,5-0,96), and neonatal RBC, HGB (OR=0.32; 95%CI:0,19-0,55) (OR=0.75; 95%CI:0,65-0,88). CONCLUSIONS: The main RDS risk factors in premature neonates are gender, abnormal fetoplacental circulation, and fetal distress. The laboratory parameters such as lower RBC and HGB count are observed in infants with RDS.
Subject(s)
Fetal Membranes, Premature Rupture , Pregnancy Trimester, Second , Pregnancy Trimester, Third , Respiratory Distress Syndrome, Newborn , Adult , Female , Fetal Membranes, Premature Rupture/epidemiology , Fetal Membranes, Premature Rupture/etiology , Fetal Membranes, Premature Rupture/physiopathology , Humans , Pregnancy , Respiratory Distress Syndrome, Newborn/epidemiology , Respiratory Distress Syndrome, Newborn/etiology , Respiratory Distress Syndrome, Newborn/physiopathology , Retrospective Studies , Risk FactorsABSTRACT
OBJECTIVE: Identify which obstetrical diagnoses are associated with suboptimal antenatal betamethasone administration. METHODS: We present a retrospective, cohort study of patients who received betamethasone due to a risk for preterm delivery, between 7/2013 and 9/2016 at our institution. Details of betamethasone administration were recorded including the diagnosis leading to betamethasone. Optimal administration was defined as two doses of betamethasone given 24 hours apart, with delivery occurring at greater than 24 hours but less than seven days after completion of the second dose of betamethasone. Suboptimal administration included any betamethasone dosing that did not meet the optimal criteria. RESULTS: 428 patients were identified for the study with 20.1% of patients receiving optimal betamethasone. Patients presenting with hypertensive disorders of pregnancy (36.1%) and preterm premature rupture of membranes (PPROM) (22.1%) were more likely to receive optimal betamethasone, while patients presenting with preterm labor (PTL) (41.8%) and placental abruption (24.6%) were more likely to receive suboptimal betamethasone (p-value < 0.0001). Among PTL patients, those presenting with contractions and cervical dilation/short cervix (19.15%) were more likely to receive optimal betamethasone (p-value 0.0349). Optimal betamethasone decreased the incidence of respiratory distress syndrome (RDS) among 32.1 to 34 week neonates. CONCLUSION: Hypertensive disorders of pregnancy and PPROM are associated with optimal betamethasone, whereas PTL and placental abruption are associated with suboptimal betamethasone.
Subject(s)
Anti-Inflammatory Agents/therapeutic use , Betamethasone/therapeutic use , Fetal Membranes, Premature Rupture/prevention & control , Obstetric Labor, Premature/prevention & control , Practice Patterns, Physicians'/statistics & numerical data , Premature Birth/prevention & control , Respiratory Distress Syndrome, Newborn/prevention & control , Adolescent , Adult , Drug Utilization Review , Female , Fetal Membranes, Premature Rupture/physiopathology , Hospitals, Community , Humans , Infant, Newborn , Pregnancy , Pregnancy Outcome , Prenatal Care/statistics & numerical data , Respiratory Distress Syndrome, Newborn/physiopathology , Retrospective Studies , Young AdultABSTRACT
OBJECTIVE: To characterize clinical outcomes of infants born after previable rupture of membranes (pROM, < 23 weeks gestation and latency period ≥ 2 weeks) in relation to refractory hypoxic respiratory failure (rHRF). STUDY DESIGN: pROM neonates categorized as rHRF (FiO2 > 0.6 for ≥ 2 h) and treated (high frequency ventilation + inhaled nitric oxide) were compared with no rHRF group. Primary outcome was survival until discharge. Factors associated with rHRF and mortality were identified. RESULT: Overall, mortality and disability rates were 28% and 22%, respectively. Treated rHRF group (n = 32) had longer period of ROM, mortality was (31% vs. 14%; p = 0.20), with similar survival-without-disability (54% vs. 47%; p = 0.67). Higher gestational age at birth [1.57 (1.03,2.39)] and cesarean delivery [12.6 (1.22,125)] were associated with increased survival. CONCLUSION: Birth after pROM is associated with high rates of adverse outcomes, independent of latency period. Following treatment, rHRF infants may have similar long-term outcomes as those without rHRF.
Subject(s)
Fetal Membranes, Premature Rupture/physiopathology , Hypoxia/physiopathology , Premature Birth/mortality , Respiratory Insufficiency/therapy , Canada , Cesarean Section/statistics & numerical data , Female , Gestational Age , High-Frequency Ventilation , Humans , Hypoxia/etiology , Infant, Newborn , Logistic Models , Male , Nitric Oxide/therapeutic use , Pregnancy , Respiratory Insufficiency/etiology , Retrospective StudiesABSTRACT
OBJECTIVE DATA: Preterm prelabor rupture of membranes occurs in 3% of all pregnancies. Neonatal benefit is seen in uninfected women who do not deliver immediately after preterm prelabor rupture of membranes. The purpose of this study was to evaluate whether the administration of progestogens in singleton pregnancies prolongs pregnancy after preterm prelabor rupture of membranes. STUDY: Searches were performed in MEDLINE, OVID, Scopus, EMBASE, ClinicalTrials.gov, and the Cochrane Central Register of Controlled Trials with the use of a combination of keywords and text words related to "progesterone," "progestogen," "prematurity," and "preterm premature rupture of membranes" from the inception of the databases until January 2018. We included all randomized controlled trials of singleton gestations after preterm prelabor rupture of membranes that were randomized to either progestogens or control (either placebo or no treatment). Exclusion criteria were trials that included women who had contraindications to expectant management after preterm prelabor rupture of membranes (ie, chorioamnionitis, severe preeclampsia, and nonreassuring fetal status) and trials on multiple gestations. We planned to include all progestogens, including but not limited to 17-α hydroxyprogesterone caproate, and natural progesterone. STUDY APPRAISAL AND SYNTHESIS METHODS: The primary outcome was latency from randomization to delivery. Metaanalysis was performed with the use of the random effects model of DerSimonian and Laird to produce relative risk with 95% confidence interval. Analysis was performed for each mode of progestogen administration separately. RESULTS: Six randomized controlled trials (n=545 participants) were included. Four of the included trials assessed the efficacy of 17-α hydroxyprogesterone caproate; 1 trial assessed rectal progestogen, and 1 trial had 3 arms that compared 17-α hydroxyprogesterone caproate, rectal progestogen, and placebo. The mean gestational age at time randomization was 26.9 weeks in the 17-α hydroxyprogesterone caproate group and 27.3 weeks in the control group. 17-α Hydroxyprogesterone caproate administration was not found to prolong the latency period between randomization and delivery (mean difference, 0.11 days; 95% confidence interval, -3.30 to 3.53). There were no differences in mean gestational age at delivery, mode of delivery, or maternal or neonatal outcomes between the 2 groups. Similarly, there was no difference in latency for those women who received rectal progesterone (mean difference, 4.00 days; 95% confidence interval, -0.72 to 8.72). CONCLUSION: Progestogen administration does not prolong pregnancy in singleton gestations with preterm prelabor rupture of membranes.
Subject(s)
17 alpha-Hydroxyprogesterone Caproate/therapeutic use , Fetal Membranes, Premature Rupture/drug therapy , Premature Birth/prevention & control , Progestins/therapeutic use , 17 alpha-Hydroxyprogesterone Caproate/administration & dosage , Female , Fetal Membranes, Premature Rupture/physiopathology , Humans , Pregnancy , Progestins/administration & dosage , Randomized Controlled Trials as Topic , Time FactorsABSTRACT
OBJECTIVE: To describe survival rate after preterm premature rupture of membranes (PPROM) before 25 weeks of gestation and compare neonatal morbidity and mortality among those born alive with a control group of infants born at a similar gestational age without premature rupture of membranes. METHODS: We conducted a retrospective single-centre study at Port-Royal maternity, from 2007 to 2015, comparing neonatal outcomes between liveborninfants exposed to PPROM prior to 25 weeks of gestation (WG) and a control group not exposed to premature rupture of the membranes. For each live-born child, the next child born after spontaneous labor without PPROM was matched for gestational age at birth, sex, and whether or not they received antenatal corticosteroid therapy. The primary endpoint was severe neonatal complications assessed by a composite endpoint including neonatal deaths, grade 3-4 HIV, bronchopulmonary dysplasia, leukomalacia and stade 3-4 retinopathies. RESULTS: Among 77 cases of very premature rupture of the membranes, 55 children were born alive. Among these, the average gestational age at birth was 28 WG and 1 day. The rate of severe neonatal complications did not differ between the two groups (43.6% in the PPROM group vs. 36.4%, P=0.44) and the survival rate at discharge was also similar in the two groups (85.5% vs. 83.6%, P=0.98). CONCLUSIONS: In our cohort and among livebirths after 24 WG, PPROM before 25 WG was not associated with an increased risk of morbidity and mortality compared to children born at the same gestational age after a spontaneous labor with intact membranes.
Subject(s)
Fetal Membranes, Premature Rupture/physiopathology , Infant Mortality , Premature Birth/physiopathology , Female , Fetal Membranes, Premature Rupture/mortality , Gestational Age , Humans , Infant , Infant, Newborn , Infant, Premature , Live Birth , Male , Morbidity , Pregnancy , Pregnancy Outcome , Premature Birth/mortality , Retrospective Studies , Risk FactorsABSTRACT
Preterm birth, defined as birth occurring prior to 37 weeks gestation is a common obstetric complication affecting 8% of pregnancies and is associated with significant morbidity and mortality. Infection/inflammation has been implicated in both the aetiology of preterm birth itself and associated neonatal pulmonary and neurological morbidity. Treatment options are currently limited to prolongation of the pregnancy using cervical cerclage, pessaries or progesterone or administration of drugs including steroids to promote lung maturity and neuroprotective agents such as magnesium sulphate, the timing of which are highly critical. Although delivery is expedited in cases of overt infection, decisions regarding timing and mode of delivery in subclinical infection are not clear-cut. This review aims to explore the use of magnetic resonance imaging (MRI) in the antenatal assessment of pregnancies at high risk of preterm birth and its potential to guide management decisions in the future.
Subject(s)
Fetal Membranes, Premature Rupture/diagnostic imaging , Pregnancy, High-Risk , Premature Birth/prevention & control , Prenatal Diagnosis , Amniotic Fluid/diagnostic imaging , Amniotic Fluid/immunology , Amniotic Fluid/microbiology , Chorioamnionitis/diagnostic imaging , Chorioamnionitis/etiology , Chorioamnionitis/physiopathology , Chorioamnionitis/therapy , Female , Fetal Development , Fetal Membranes, Premature Rupture/microbiology , Fetal Membranes, Premature Rupture/physiopathology , Fetal Membranes, Premature Rupture/therapy , Humans , Magnetic Resonance Imaging , Oligohydramnios/diagnostic imaging , Oligohydramnios/etiology , Oligohydramnios/physiopathology , Oligohydramnios/therapy , Practice Guidelines as Topic , Pregnancy , Pregnancy Complications, Infectious/diagnostic imaging , Pregnancy Complications, Infectious/etiology , Pregnancy Complications, Infectious/physiopathology , Pregnancy Complications, Infectious/therapy , Premature Birth/epidemiology , Premature Birth/etiology , RiskABSTRACT
BACKGROUND: Despite the high prevalence of premature rupture of membranes (PROM) in low-resource settings, the preferred mode of delivery remains unclear. We compared the perinatal mortality in a prospective cohort of women with PROM after 28 weeks following vaginal or caesarean delivery at Mulago Hospital with the aim of adopting evidence based practice and improving patient care. METHODS: Between November 2015 and May 2016, 1455 women with PROM after 28 weeks of gestation and their newborns were prospectively followed from admission to discharge at Mulago Hospital. The primary outcome was perinatal mortality. Secondary neonatal outcomes included sepsis and admission to the Special Care Unit. Maternal outcomes included maternal deaths and complications. Outcomes were compared between women who had vaginal vs. caesarean delivery using multivariable logistic regression. All statistical tests were 2-sided with the level of statistical significance set at p < 0.05. RESULTS: The incidence of PROM was 12.1%. The perinatal mortality following PROM was 65 per 1000 live births. Of the 1425 women with PROM, 991 (69.5%) had vaginal delivery and 434 (30.5%) underwent Caesarean section. There was no statistical difference in perinatal mortality by the mode of delivery (vaginal vs. caesarean) in PROM (p = 0.12). The risk factors for perinatal mortality included chorioamnionitis, failure to administer corticosteroids in preterm PROM, gestational age (28-33 weeks), duration of drainage of liquor (24-48 hours), and presence of maternal complications. Caesarean delivery was associated with increased maternal postpartum infections, admission to the Special Care Unit and maternal death. CONCLUSION: In low resource settings, vaginal delivery is the preferred mode of delivery for PROM after 28 weeks gestation. It is associated with lesser maternal and perinatal morbidity when compared to caesarean delivery.