Early Preterm Delivery Research Articles

The Impact of Mode of Delivery on Early Preterm Morbidity and Mortality [32K

INTRODUCTION: Whether the mode of delivery for early preterm infants influences the risk of adverse outcomes is an ongoing topic of debate. This study aims to determine whether cesarean delivery is independently associated with improved early preterm neonatal morbidity or mortality. METHODS: This is a retrospective cohort study of preterm deliveries at 22.0–29.0 weeks gestation between 2010 and 2015, excluding multiple gestations, intrauterine fetal demise, and induction terminations. The primary outcome was a neonatal morbidity composite (apgar <5 at 5 min, prolonged ventilation >28 days, IVH, NEC, coagulopathy, discharged on home ventilator support, or discharged with enteric feeding tube). The secondary outcome was neonatal death. Outcomes were compared between patients who underwent cesarean vs vaginal delivery. Patients were first matched for ethnicity (black v. other). Propensity scores were estimated utilizing logistic regression models adjusting for small for gestational age, gestational at delivery, and nulliparity. IRB approval was granted through Washington University. RESULTS: Of the 273 (56.9%) early preterm deliveries, 125 (45.8%) were cesarean deliveries and 148 (54.2%) were vaginal deliveries. After matching, there were 115 patients in each group. In vertex fetuses, there was no significant difference in neonatal mortality within 24 hours (aOR 1.48 CI 0.56, 3.90) or within 28 days of delivery (aOR 0.71 CI 0.27, 1.90) by mode of delivery. There was no difference in composite neonatal morbidity. CONCLUSION: In this propensity score analysis, the risk of neonatal death or neonatal morbidity was not significantly improved among early preterm neonates delivered by cesarean versus vaginal delivery.

Adverse pregnancy outcomes among women presenting at antenatal clinics in Ou\xe9less\xe9bougou, Mali

BackgroundIn sub-Saharan Africa, malaria continues to scourge the population and is the primary cause of morbidity and mortality in young children and pregnant women. As current preventative measures such as intermittent preventive treatment and use of insecticide-treated nets provide incomplete protection, several malaria vaccines are currently under development, including one to specifically prevent pregnancy malaria. Prior to conducting vaccine trials, it is important to obtain background information on poor pregnancy outcomes in the target population to establish a baseline.MethodsPregnant women presenting at community health care centers for antenatal care were recruited to the study. Gestational age was determined by ultrasound examination following recruitment. Antenatal care and pregnancy outcome information were collected during a visit 4–8 weeks post-delivery.ResultsOne thousand eight hundred fifty women completed the study, and analysis included 1814 women after excluding multiple gestations (n = 26) and missing/incomplete data (n = 10). The percentage (95% CI) of adverse pregnancy outcomes is as follows: miscarriage, 0.28% (0.04–0.52); stillbirth, 1.93% (1.30–2.56); early neonatal death, 1.65% (1.03–2.24); late neonatal death, 0.39%, (0.10–0.68); and preterm delivery (PTD), 4.74% (3.76–5.73). The percentages of early and late neonatal deaths and PTD were significantly higher (p < 0.01) in primigravid compared to multigravid women. In primigravidae, 3.1, 1.1 and 7.1% of pregnancies resulted in early neonatal death, late neonatal death and PTD, respectively, while these outcomes in multigravidae were 1.0, 0.1 and 2.7%, respectively. Major malformations were identified in 4 newborns.ConclusionsLow gravidity and young age predict perinatal death and PTD. The information collected here can be used as a baseline for adverse pregnancy outcomes in future vaccine trials in pregnant women.

Diagnostic Imaging and Outcomes for Nonobstetric Surgery During Pregnancy.

A surgical disease occurring during pregnancy can present a diagnostic dilemma due to the desire to make a timely and accurate diagnosis within the constraints of limiting radiation exposure to the fetus. However, required diagnostic imaging should be pursued when indicated and attempts made to minimize the radiation dose by utilizing abdominal shielding and low-dose protocols when feasible. When surgery is indicated due to disease processes, treatment should not be altered or delayed due to pregnancy as the evidence for adverse pregnancy outcomes including early pregnancy loss and preterm delivery are overall of low quality due to substantial confounding by the disease process itself.

Development and validation of a multivariable prediction model of spontaneous preterm delivery and microbial invasion of the amniotic cavity in women with preterm labor

Early spontaneous preterm delivery is often associated with microbial invasion of the amniotic cavity and/or intraamniotic inflammation. The objective of the study was to develop and validate clinically feasible multivariable prediction models of spontaneous delivery within 7 days and microbial invasion of the amniotic cavity in women admitted with diagnose of preterm labor and intact membranes below 34 weeks. We used data from a cohort of women admitted from 2012 to 2018 with diagnosis of preterm labor below 34 weeks who had undergone amniocentesis to rule out microbial invasion of the amniotic cavity. The main outcome was spontaneous delivery within 7 days from admission. The secondary outcome was microbial invasion of the amniotic cavity, defined by a positive culture and/or 16S ribosomal RNA gene in the amniotic fluid. The sample (n= 358) was divided into derivation (2012-2016) and validation cohorts (2017-2018). Logistic regression models using a stepwise selection of variables were developed for the outcomes evaluated. We explored as predictive variables ultrasound cervical length measurement at admission, maternal C-reactive protein, gestational age, amniotic fluid glucose, and interleukin-6 (expressed as log units). Models were developed in the derivation cohort and applied to the validation cohort and diagnostic performance was calculated. The derivation cohort included 263 women and the validation cohort 95 women. One hundred five of the women (39%, 105 of 268) spontaneously delivered in the following 7 days and 68 (19%, 68 of 358) had microbial invasion of the amniotic cavity. For spontaneous delivery within 7 days after admission, 4 predictors were identified: cervical length at admission, gestational age, amniotic fluid glucose, and interleukin-6. The diagnostic performance of the model was assessed in the validation cohort using the receiver operating characteristic curve and showed an area under curve of 0.86 (95% confidence interval, 0.77-0.95) with a detection rate of spontaneous delivery within 7 days of 87%, a false-positive rate of 33%, a negative predictive value of 80%, and a negative likelihood ratio of 0.1908. For microbial invasion of the amniotic cavity, 2 independent predictors of the amniotic cavity were identified: amniotic fluid glucose and maternal C-reactive protein. The receiver operating characteristic curve and an area under curve in the validation cohort was 0.83 (95% confidence interval, 0.70-0.96) with a detection rate of 76%, a false-positive rate of 8%, a negative predictive value of 93%, and a negative likelihood ratio of 0.2591. In women with preterm labor, we propose 2 clinically feasible prediction models to classify as low vs high risk of spontaneous delivery within 7 days and of microbial invasion of the amniotic cavity. The models showed a high diagnostic performance and could be of value to optimize clinical management.

A new rapid bedside test to diagnose and monitor intraamniotic inflammation in preterm PROM using transcervically collected fluid

Microbial invasion of the amniotic cavity, a clinical condition present in approximately 50% of patients with preterm prelabor rupture of membranes, is often associated with intraamniotic inflammation, a risk factor for a short admission-to-delivery interval, early preterm delivery, and neonatal complications. We previously developed a transcervical amniotic fluid collector, the device that allows the collection of fluid noninvasively from the cervical canal when membrane rupture occurs. This study was designed to determine whether rapid analysis of an interleukin-8 concentration in fluid obtained noninvasively by the transcervical amniotic fluid collector can be used to assess the risk of intraamniotic inflammation. We also compared the diagnostic performance of this point-of-care test for interleukin-8 in transcervically obtained fluid to that of a white blood cell count determined in amniotic fluid retrieved by transabdominal amniocentesis. This prospective cohort study was conducted between October 2011 and April 2017. Fluid was retrieved through both transabdominal amniocentesis and the use of a transcervical amniotic fluid collector within 24 hours of amniocentesis in patients with a singleton pregnancy and preterm prelabor rupture of the membranes (16-35 weeks of gestation). Amniotic fluid obtained via amniocentesis was cultured for aerobic and anaerobic bacteria and genital mycoplasmas; a white blood cell count was also measured in amniotic fluid. Intraamniotic infection was diagnosed when microorganisms were identified by the cultivation of amniotic fluid. Intraamniotic inflammation was defined as an elevated amniotic fluid matrix metalloproteinase-8 concentration (>23 ng/mL) assayed by enzyme-linked immunosorbent assay. Interleukin-8 in cervical fluid obtained by the collector was measured by the point-of-care test that used a test strip and scanner based on the fluorescence immunochromatographic analysis in 2019. The diagnostic indices, predictive values, and likelihood ratios of the 2 different tests were calculated. First, interleukin-8 concentration ≥9.5 ng/mL in cervical fluid, determined by the point-of-care test, was at the knee of the receiver operating characteristic curve analysis and had a sensitivity of 98% (56/57; 95% confidence interval, 91-99.96%), specificity of 74% (40/54; 95% confidence interval, 60-85%), positive predictive value of 80% (56/70; 95% confidence interval, 72-86%), negative predictive value of 98% (40/41; 95% confidence interval, 85-99.6%), positive likelihood ratio of 3.79 (95% confidence interval, 2.41-5.96), and negative likelihood ratio of 0.02 (95% confidence interval, 0.003-0.17) in the identification of intraamniotic inflammation; a concentration of matrix metalloproteinase-8 >23 ng/mL by enzyme-linked immunosorbent assay had a prevalence of 51% (57/111). Second, a cervical fluid interleukin-8 concentration ≥9.5 ng/mL had significantly higher sensitivity than a transabdominally obtained amniotic fluid white blood cell count (≥19 cells/mm3) in the identification of intraamniotic inflammation (sensitivity: 98% [95% confidence interval, 91-99.96%] vs 84% [95% confidence interval, 72-93%]; P<.05; specificity: 74% [95% confidence interval, 60-85%] vs 76% [95% confidence interval, 62-87%); positive and negative predictive values: 80% [95% confidence interval, 72-86%] and 98% [95% confidence interval, 85-99.6%] vs 79% [95% confidence interval, 69-86%] and 82% [95% confidence interval, 71-89%]) and in the identification of intraamniotic inflammation/infection (gold standard: positive culture for bacteria or a matrix metalloproteinase-8 >23 ng/mL; sensitivity: 91% [95% confidence interval, 82-97%] vs 75% [95% confidence interval, 63-85%]; P<.05). The point-of-care test was predictive of intraamniotic inflammation, based on the determination of interleukin-8 in fluid retrieved by a transcervical amniotic fluid collector. Therefore, the analysis of cervically obtained fluid by such point-of-care test may be used to noninvasively monitor intraamniotic inflammation in patients with preterm prelabor rupture of membranes.

A Randomized Trial of Prenatal n-3 Fatty Acid Supplementation and Preterm Delivery

(N Engl J Med. 2019;381(11):1035–1045) Although early preterm deliveries (before 34 wk of gestation) only comprise 20% of all preterm deliveries, they are more likely to result in neonatal death or childhood disability. The rate of preterm deliveries is rising around the world, and previous research has indicated a significant relationship between reduced fish consumption during pregnancy and higher preterm delivery rates. In this study, the investigators examined the connection between n-3 long-chain polyunsaturated fatty acid (PUFA) supplements and the percentage of pregnant women who experienced preterm delivery.

A Randomized Trial of Prenatal n-3 Fatty Acid Supplementation and Preterm Delivery

(Abstracted from N Eng J Med 2019;381:1035–1045) Preterm delivery (defined as delivery before 37 weeks' gestation) occurs in 15 million pregnancies each year. Of these, approximately 20% are early preterm deliveries, occurring before 34 weeks' gestation and accounting for the largest burden of neonatal death and childhood disability.

Compartmentalized profiling of amniotic fluid cytokines in women with preterm labor.

ObjectiveAmniotic fluid cytokines have been implicated in the mechanisms of preterm labor and birth. Cytokines can be packaged within or on the surface of extracellular vesicles. The main aim of this study was to test whether the protein abundance internal to and on the surface of extracellular vesicles changes in the presence of sterile intra-amniotic inflammation and proven intra-amniotic infection in women with preterm labor as compared to the women with preterm labor without either intra-amniotic inflammation or proven intra-amniotic infection.Study designWomen who had an episode of preterm labor and underwent an amniocentesis for the diagnosis of intra-amniotic infection or intra-amniotic inflammation were classified into three groups: 1) preterm labor without either intra-amniotic inflammation or proven intra-amniotic infection, 2) preterm labor with sterile intra-amniotic inflammation, and 3) preterm labor with intra-amniotic infection. The concentrations of 38 proteins were determined on the extracellular vesicle surface, within the vesicles, and in the soluble fraction of amniotic fluid.Results1) Intra-amniotic inflammation, regardless of detected microbes, was associated with an increased abundance of amniotic fluid cytokines on the extracellular vesicle surface, within vesicles, and in the soluble fraction. These changes were most prominent in women with proven intra-amniotic infection. 2) Cytokine changes on the surface of extracellular vesicles were correlated with those determined in the soluble fraction; yet the magnitude of the increase was significantly different between these compartments. 3) The performance of prediction models of early preterm delivery based on measurements on the extracellular vesicle surface was equivalent to those based on the soluble fraction.ConclusionsDifferential packaging of amniotic fluid cytokines in extracellular vesicles during preterm labor with sterile intra-amniotic inflammation or proven intra-amniotic infection is reported herein for the first time. The current study provides insights into the biology of the intra-amniotic fluid ad may aid in the development of biomarkers for obstetrical disease.

Preterm prelabor rupture of membranes prior to early preterm delivery elevates the risk of later respiratory‐related hospitalizations in the offspring

Preterm prelabor rupture of membranes (PPROM) precedes 30%-40% of all preterm births. Early preterm delivery (<34 gestation weeks) is a well-established risk factor for short- and long-term respiratory morbidity in the offspring. We aimed to ascertain whether the presence of PPROM, before early preterm delivery, independently impacts long-term respiratory hospitalizations in the offspring. A population-based retrospective cohort analysis was performed including all singleton early preterm deliveries. Exposure was defined as the presence of PPROM. Hospitalizations of the offspring up to the age of 18 years involving respiratory-related morbidity were evaluated. A Kaplan-Meier survival curve and multivariable Cox regression model were used to assess the association. During the study period, 3309 early preterm deliveries met the inclusion criteria. In 22.4% of cases (n = 742), PPROM was documented. Rates of respiratory-related hospitalizations of the offspring up to the age of 18 years were significantly higher in the exposed group (12.5% vs 9.4% in the unexposed group, P = .023). The survival curve demonstrated significantly higher cumulative incidence of respiratory hospitalizations in the exposed group (logrank P = .018). In the Cox regression model controlled for gestational age, and other clinically relevant confounders - PPROM before early preterm deliveries was independently associated with an increased risk for long-term childhood respiratory-related hospitalizations in the offspring (adjusted hazard ratio 1.40, 95% confidence interval, 1.05-1.87, P = .021). Fetal exposure to PPROM before early preterm delivery was associated with an increased risk for long-term respiratory hospitalizations in the offspring.

Low-dose aspirin for the prevention of preterm delivery in nulliparous women with a singleton pregnancy (ASPIRIN): a randomised, double-blind, placebo-controlled trial

Preterm birth remains a common cause of neonatal mortality, with a disproportionately high burden in low-income and middle-income countries. Meta-analyses of low-dose aspirin to prevent pre-eclampsia suggest that the incidence of preterm birth might also be decreased, particularly if initiated before 16 weeks of gestation. ASPIRIN was a randomised, multicountry, double-masked, placebo-controlled trial of low-dose aspirin (81 mg daily) initiated between 6 weeks and 0 days of pregnancy, and 13 weeks and 6 days of pregnancy, in nulliparous women with an ultrasound confirming gestational age and a singleton viable pregnancy. Participants were enrolled at seven community sites in six countries (two sites in India and one site each in the Democratic Republic of the Congo, Guatemala, Kenya, Pakistan, and Zambia). Participants were randomly assigned (1:1, stratified by site) to receive aspirin or placebo tablets of identical appearance, via a sequence generated centrally by the data coordinating centre at Research Triangle Institute International (Research Triangle Park, NC, USA). Treatment was masked to research staff, health providers, and patients, and continued until 36 weeks and 7 days of gestation or delivery. The primary outcome of incidence of preterm birth, defined as the number of deliveries before 37 weeks' gestational age, was analysed in randomly assigned women with pregnancy outcomes at or after 20 weeks, according to a modified intention-to-treat (mITT) protocol. Analyses of our binary primary outcome involved a Cochran-Mantel-Haenszel test stratified by site, and generalised linear models to obtain relative risk (RR) estimates and associated confidence intervals. Serious adverse events were assessed in all women who received at least one dose of drug or placebo. This study is registered with ClinicalTrials.gov, NCT02409680, and the Clinical Trial Registry-India, CTRI/2016/05/006970. From March 23, 2016 to June 30, 2018, 14 361 women were screened for inclusion and 11 976 women aged 14-40 years were randomly assigned to receive low-dose aspirin (5990 women) or placebo (5986 women). 5780 women in the aspirin group and 5764 in the placebo group were evaluable for the primary outcome. Preterm birth before 37 weeks occurred in 668 (11·6%) of the women who took aspirin and 754 (13·1%) of those who took placebo (RR 0·89 [95% CI 0·81 to 0·98], p=0·012). In women taking aspirin, we also observed significant reductions in perinatal mortality (0·86 [0·73-1·00], p=0·048), fetal loss (infant death after 16 weeks' gestation and before 7 days post partum; 0·86 [0·74-1·00], p=0·039), early preterm delivery (<34 weeks; 0·75 [0·61-0·93], p=0·039), and the incidence of women who delivered before 34 weeks with hypertensive disorders of pregnancy (0·38 [0·17-0·85], p=0·015). Other adverse maternal and neonatal events were similar between the two groups. In populations of nulliparous women with singleton pregnancies from low-income and middle-income countries, low-dose aspirin initiated between 6 weeks and 0 days of gestation and 13 weeks and 6 days of gestation resulted in a reduced incidence of preterm delivery before 37 weeks, and reduced perinatal mortality. Eunice Kennedy Shriver National Institute of Child Health and Human Development.

Steroid Hormone Levels in Recipient Amniotic Fluid in Twin-Twin Transfusion Syndrome and Their Association with Preterm Delivery.

Preterm delivery following fetoscopic laser surgery (FLS) of twin-twin transfusion syndrome (TTTS) is associated with severe perinatal morbidity and mortality. The role of steroid hormones in amniotic fluid (AF) after FLS remains unknown. A prospective cohort study of consecutive case series of FLS for TTTS was performed from April 2012 to February 2017. Cases were divided into early (≤27 weeks) spontaneous preterm delivery (ED) and late delivery (LD; ≥34 weeks) following FLS and compared. AF supernatants were assessed for protein, estradiol, progesterone and cortisol levels (using the ELISA kit), and normalized to total protein levels to adjust for dilution. A total of 294 consecutive cases of FLS for TTTS in monochorionic-diamniotic twins were performed during the study period. AF was available in 44 ED patients and 50 LD patients. On logistic regression, ED was associated with higher normalized progesterone levels (odds ratio [OR]: 1.25; 95% confidence interval [CI]: 1.12-1.41), lower normalized cortisol (OR: 0.78; 95% CI: 0.64-0.96), and higher estradiol levels (OR: 1.3; 95% CI: 1.03-1.63). Elevated AF normalized progesterone and estradiol, and lower normalized cortisol levels were associated with ED. This novel finding requires further exploration to establish the molecular mechanism operational in pregnancies complicated by TTTS to potentially prevent early preterm birth after fetal surgery.

Early Preterm Preeclampsia Outcomes by Intended Mode of Delivery

(Am J Obstet Gynecol. 2019;220:100.e1–100.e9) There is a paucity of studies investigating the optimal mode of delivery for pregnant patients with preeclampsia with severe features, superimposed preeclampsia, eclampsia, or the syndrome of hemolysis, elevated liver enzymes, and low platelets in early preterm births. There is no consensus on this topic, which has not been investigated by any randomized controlled trials. To reduce the risk of maternal mortality and morbidity, early preterm delivery is often recommended when preeclampsia with severe features is diagnosed. This study aimed to compare maternal and neonatal outcomes by intended mode of delivery in pregnancies complicated by early preterm preeclampsia.

A comparison of risk factors for breech presentation in preterm and term labor: a nationwide, population-based case\u2013control study

PurposeTo determine if the common risks for breech presentation at term labor are also eligible in preterm labor.MethodsA Finnish cross-sectional study included 737,788 singleton births (24–42 gestational weeks) during 2004–2014. A multivariable logistic regression analysis was used to calculate the risks of breech presentation.ResultsThe incidence of breech presentation at delivery decreased from 23.5% in pregnancy weeks 24–27 to 2.5% in term pregnancies. In gestational weeks 24–27, preterm premature rupture of membranes was associated with breech presentation. In 28–31 gestational weeks, breech presentation was associated with maternal pre-eclampsia/hypertension, preterm premature rupture of membranes, and fetal birth weight below the tenth percentile. In gestational weeks 32–36, the risks were advanced maternal age, nulliparity, previous cesarean section, preterm premature rupture of membranes, oligohydramnios, birth weight below the tenth percentile, female sex, and congenital anomaly. In term pregnancies, breech presentation was associated with advanced maternal age, nulliparity, maternal hypothyroidism, pre-gestational diabetes, placenta praevia, premature rupture of membranes, oligohydramnios, congenital anomaly, female sex, and birth weight below the tenth percentile.ConclusionBreech presentation in preterm labor is associated with obstetric risk factors compared to cephalic presentation. These risks decrease linearly with the gestational age. In moderate to late preterm delivery, breech presentation is a high-risk state and some obstetric risk factors are yet visible in early preterm delivery. Breech presentation in extremely preterm deliveries has, with the exception of preterm premature rupture of membranes, similar clinical risk profiles as in cephalic presentation.

Study of Causes, Methods and Complications of Early and Late Miscarriage due to Intentional Abortion in Women referred to Health Centers covered by Shahid Beheshti University

Abstract Introduction: Induced abortion is a major threat to women’s fertility health. In particular, in developing countries and the societies where abortion is illegal, abortions are commonly carried out under unsanitary conditions, causing maternal complications, dangers to maternal health, and women’s future infertility. These consequences are especially evident in Iran where at least 80,000 illegal abortions are done annually. The current study aimed to examine the reasons for abortion, methods of abortion, and its short-term and long-term complications. Methods: This study, which adopted a descriptive design, was conducted among the women who had already carried out abortion and referred to one of the health, therapeutic, and educational centers affiliated with Shahid Beheshti University of Medical Sciences. The participants (N = 360) were selected the data were gleaned through a self-designed questionnaire and statistically analyzed using SPSS version 17. Results: The results of analyzing the data collected through the 369 questionnaires revealed that the mean age of participants was 26 years (SD = 7.2 years). The main reason for abortion was financial problems. With regard to marital status, 91.3% of the participants were married. Also, considering their job, 74.2% of the respondents were housewives, while 15.5% were employed in office jobs. Further, in 55.3% of the cases, abortion had been carried out as a result of the husband’s encouragement. The most common method of abortion was prescribing chemical medications, while the least popular method was intrauterine manipulations (with only 197 women reporting this abortion method). Moreover, 114 participants reported that they had accomplished curettage in a specialist physician’s office without anesthesia. The short-term complications of abortion included abdominal pain after abortion and incomplete abortion. On the other hand, long-term complications entailed visceral injury (1%), complications in the next pregnancy, bleeding in early pregnancy (10.7%), preterm delivery (7.9%), and ectopic pregnancy (7.4%). Conclusions: Scientific and religious education through appropriate procedures along with preventing unwanted pregnancy is a decisive factor in abortion.

Single nucleotide polymorphisms of Toll-like receptor-4 and of autophagy-related gene 16 like-1 gene for predisposition of premature delivery: A prospective study.

To investigate the impact of carriage of single nucleotide polymorphisms (SNPs) of the Toll-like receptor-4 (TLR4) and of autophagy-related gene 16-like-1 (ATG16L1) in preterm delivery (PTD).A prospective cohort of 145 pregnant women was studied. Women were prospectively followed-up until delivery. Genotyping for rs4986790 (Asp299Gly transition) and rs4986791 (Thr399Ile transition) of TLR4 and for rs2241880 of ATG16L1 was done by PCR-restriction fragment length polymorphism. The primary study endpoint was the impact of carriage of minor alleles of TLR4 on early PTD before gestational week 32. Associations with human chorionic gonadotrophin (hCG) were also analyzed. Peripheral blood mononuclear cells were isolated from 15 healthy women and stimulated for cytokine production.No difference in clinical characteristics was observed between women delivering full term and preterm. The frequency of early PTD was 25% among women carrying minor alleles of TLR4 and 6.8% among women carrying major alleles (P: .032). Odds ratios for PTD were 3.85 among women carrying the GG genotype of rs2241880 and major alleles of TLR4 and 0.26 among carriers of GG genotype and minor alleles of TLR4 (P: .030). The co-presence of GG genotype of rs2241880 and hCG above 70 U/L was an independent variable for PTD. Stimulated production of interleukin-6 was greater among women with GG genotypes of rs2241880.Minor alleles of SNPs of TLR4 predispose to early PTD. The GG genotype of rs2241880 of ATG16L1 is associated with PTD when hCG is supra-elevated.

Maternal and obstetric complications in fetal surgery for prenatal myelomeningocele repair: a systematic review.

Comparing prenatal and postnatal surgical repair techniques for myelomeningocele (MMC), in utero fetal surgery has increasingly gained acceptance and is considered by many specialized centers the first choice of treatment. Despite its benefits, as demonstrated in the Management of Myelomeningocele Study (MOMS), including reduced need for CSF shunting in neonates and improved motor outcomes at 30 months, there is still an ongoing debate on fetal and maternal risks associated with the procedure. Prenatal open hysterotomy, fetoscopic MMC repair techniques, and subsequent delivery by cesarean section are associated with maternal complications. The aim of this systematic review is to assess the available literature on maternal and obstetric complication rates and perinatal maternal outcomes related to fetal MMC repair. The authors identified references for inclusion in this review by searching PubMed and MEDLINE, with restrictions to English language, case series, case reports, clinical trials, controlled clinical trials, meta-analyses, randomized controlled trials, reviews, and systematic reviews. The rate of maternal and obstetric complications was analyzed based on studies focusing on this issue and presenting clear results on the matter. Of 1264 articles screened, 36 were included in this systemic review, whereof 11 were eligible for data analysis and comparison. The average overall rate of maternal and obstetric complications corresponds to 78.6%. The majority of the described events are obstetric complications, varying from chorioamniotic membrane separation in 65.6% of cases, oligohydramnios in 13.0% of cases, placental abruption in 5.0% of cases, spontaneous or preterm premature membrane rupture in 42.0% of cases, and early preterm delivery in 11.3% of cases due to uterine dehiscence, occurring in 0.9% of cases. The most common medical complications are development of pulmonary edema occurring in 2.8%, gestational diabetes in 3.7%, gestational hypertension/preeclampsia in 3.7%, and need for blood transfusions in 3.2% of cases. Limitations of the review arise from the lack of data in the current literature, with maternal and obstetric complications being underreported. Although the efforts of further advancement of intrauterine prenatal MMC repair aim to increase neonatal outcomes, maternal health hazard will continue to be an issue of crucial importance and further studies are required.

A Randomized Trial of Prenatal n−3 Fatty Acid Supplementation and Preterm Delivery

BackgroundPrevious studies have suggested that maternal supplementation with n−3 long-chain polyunsaturated fatty acids may reduce the incidence of preterm delivery but may also prolong gestation beyond term; however, more data are needed regarding the role of n−3 long-chain polyunsaturated fatty acids in pregnancy.MethodsWe performed a multicenter, double-blind, randomized trial in which women who were pregnant with single or multiple fetuses were assigned to receive either fish-oil capsules that contained 900 mg of n−3 long-chain polyunsaturated fatty acids (n−3 group) or vegetable-oil capsules that contained trace n−3 long-chain polyunsaturated fatty acids (control group) daily, beginning before 20 weeks of gestation and continuing to 34 weeks of gestation or delivery, whichever occurred first. The primary outcome was early preterm delivery, defined as delivery before 34 completed weeks of gestation. Other pregnancy and neonatal outcomes were also assessed.ResultsA total of 5544 pregnancies in 5517 women were randomly assigned at six centers in Australia; 5486 pregnancies were included in the primary analysis. Early preterm delivery occurred in the case of 61 of 2734 pregnancies (2.2%) in the n−3 group and 55 of 2752 pregnancies (2.0%) in the control group; the between-group difference was not significant (adjusted relative risk, 1.13; 95% confidence interval [CI], 0.79 to 1.63; P=0.50). There were no significant differences between the groups in the incidence of interventions in post-term (>41 weeks of gestation) deliveries, in adverse events, or in other pregnancy or neonatal outcomes, except that a higher percentage of infants born to women in the n−3 group than in the control group were very large for gestational age at birth (adjusted relative risk, 1.30; 95% CI, 1.02 to 1.65). Percentages of serious adverse events did not differ between the groups. Minor gastrointestinal disturbances were more commonly reported in the n−3 group than in the control group.ConclusionsSupplementation with n−3 long-chain polyunsaturated fatty acids from early pregnancy (<20 weeks of gestation) until 34 weeks of gestation did not result in a lower incidence of early preterm delivery or a higher incidence of interventions in post-term deliveries than control. (Funded by the Australian National Health and Medical Research Council and the Thyne Reid Foundation; ORIP Australian New Zealand Clinical Trials Registry number, ACTRN12613001142729.)

Polymorphism of the IL-1β, TNF, IL-1RA and IL-4 Cytokine Genes Significantly Increases the Risk of Preterm Birth.

Preterm birth is not only medical, but also a social problem. The global goal of medicine is prevention of preterm labor and identification of risk factors leading to preterm birth. The objective of our study was to find the association between polymorphic markers in the cytokine IL-1β, TNF-α, IL-1Ra, and IL-4 genes and development of preterm labor. The prospective study was conducted in 108 pregnant women with the risk of preterm birth. The main group consisted of 66 women whose pregnancy ended with preterm delivery despite the ongoing therapy. The comparison group included 42 women with the full-term delivery. The dominant T allele of the cytokine IL-1β gene polymorphism rs1143634 (3953C→T) was 7.6 times more common in women with preterm delivery vs. the comparison group (36.4 and 4.8%, respectively; RR, 1.802; 95% CI, 1.420-2.288; p < 0.05); its homozygous form was detected only in women with preterm delivery at the very early gestation age (less than 26 weeks). The dominant proinflammatory allele 2R of the IL-1 receptor antagonist gene (IL-1Ra) was 1.5 times more common in women with preterm delivery than in the comparison group (63.6 and 42.8%, respectively; RR, 1.400; 95% CI, 1.009-1.943; p < 0.05), which makes the 2R allele the risk factor for preterm birth. The 2R/2R and 2R/4R genotypes led to a very early and early preterm delivery, respectively. The combination of three or four proinflammatory genotypes was detected only in women with a very early preterm delivery, which confirms that the combination of several proinflammatory genotypes is an extremely unfavorable factor for the full-term pregnancy. Identification of genetic polymorphisms in the interleukin genes at the periconceptional stage will help to prevent the risk of preterm delivery, which will reduce the incidence of preterm births, as well as perinatal morbidity and mortality.

The Effect of the Cause of Delivery on Neonatal Outcomes in Early Preterm Deliveries

AbstractThe aim of this study was to evaluate the effect of causes of delivery on short-term neonatal morbidities and mortality in EPD (&lt; 34 gestational weeks). We retrospectively analysed the deliveries occurring between 23 + 0 and 33 + 6th gestational weeks at our tertiary center during 2014–2018. A total of 290 deliveries were evaluated, and 369 newborns [singletons (56.4%), twins (36.6%) and triplets (7.1%)] were included in the study. The causes of deliveries were defined as spontaneously preterm birth (n = 107, 29%), preterm premature rupture of membranes (PPROM) (n = 131, 35.5%) or iatrogenic preterm birth (n = 131, 35.5%). The rate of neonatal respiratory distress syndrome (RDS), patent ductus arteriosus, bronchopulmonary dysplasia (BPD), intraventricular haemorrhagia (IVH), necrotising enterocolitis, retinopathy of prematurity, neonatal resuscitation, sepsis and death were similar between groups. However; neonatal RDS, BPD, IVH and sepsis were found to be higher in cases with chorioamnionitis, which could be considered as subcategory of PPROM. Preterm deliveries have an adverse effect on perinatal outcomes. Also, such causes of labor might be related to varied neonatal morbidities. However, splitting to early preterm deliveries into subgroups, according to cause of delivery, did not provide further information to predict such complications except chorioamnionitis.

Characteristics and pregnancy outcomes across gestational diabetes mellitus subtypes based on insulin resistance.

This study aimed to determine the characteristics and pregnancy outcomes across different subtypes of gestational diabetes mellitus (GDM) based on insulin resistance. GDM subtypes were defined in 1813 pregnant women from a multicentre prospective cohort study, stratified according to insulin resistance, based on Matsuda index below the 50th percentile of women with normal glucose tolerance (NGT), during a 75g OGTT at 24-28weeks' gestation. GDM was diagnosed in 12.4% (n = 228) of all participants based on the 2013 WHO criteria. Compared with women with NGT (1113 [61.4%] of the total cohort) and insulin-sensitive women with GDM (39 [17.1%] women with GDM), women with GDM and high insulin resistance (189 [82.9%] women with GDM) had a significantly higher BMI, systolic BP, fasting plasma glucose (FPG), fasting total cholesterol, LDL-cholesterol and triacylglycerol levels in early pregnancy. Compared with women with NGT, insulin-sensitive women with GDM had a significantly lower BMI but similar BP, FPG and fasting lipid levels in early pregnancy. Compared with women with NGT, women with GDM and high insulin resistance had higher rates of preterm delivery (8.5% vs 4.7%, p = 0.030), labour induction (42.7% vs 28.1%, p< 0.001), Caesarean section (total Caesarean sections: 28.7% vs 19.4%, p = 0.004; emergency Caesarean sections: 16.0% vs 9.7%, p = 0.010), neonatal hypoglycaemia (15.4% vs 3.5%, p< 0.001) and neonatal intensive care unit admissions (16.0% vs 8.9%, p = 0.003). In multivariable logistic regression analyses using different models to adjust for demographics, BMI, FPG, HbA1c, lipid levels and gestational weight gain in early pregnancy, preterm delivery (OR 2.41 [95% CI 1.08, 5.38]) and neonatal hypoglycaemia (OR 4.86 [95% CI 2.04, 11.53]) remained significantly higher in women with GDM and high insulin resistance compared with women with NGT. Insulin-sensitive women with GDM had similar pregnancy outcomes as women with NGT. The need for insulin treatment during pregnancy and the rate of glucose intolerance in the early postpartum period were not significantly different among the GDM subtypes. GDM with high insulin resistance represents a more adverse metabolic profile with a greater risk of adverse pregnancy outcomes.