Cause Of Preterm Birth Research Articles

Prevalence and factors associated with preterm births among postnatal mothers at Soroti Regional Referral Hospital, Eastern Uganda

BackgroundGlobally, prematurity is the leading cause of death in neonates and therefore a major contributor to the under 5-year mortality. The study assesses the prevalence and risk factors associated with preterm birth at a Regional Referral Hospital in Eastern Uganda. MethodsThis was a descriptive cross-sectional study conducted at a Regional Referral Hospital in Eastern Uganda. A questionnaire was used to capture data on maternal socio-demographic features, and obstetrical causes of preterm birth. Additional information was got from maternal medical records. In total, 350 mother-baby pairs were studied. Bivariate and multivariate logistic regression models were fitted so as to establish the factors associated with preterm birth. A p-value < 0.05 was considered statistically significant. ResultsPrevalence of preterm birth at Soroti Regional Referral Hospital was 24.6% (86/350). Factors associated with preterm birth included: Fewer than 3 antenatal attendances (aOR = 3.115, 95% CI [1.659–5.849], P = 0.038), twin gestation (aOR = 6.973, 95% CI [1.128–43.097], P = 0.016), antepartum hemorrhage (aOR = 4.743, 95% CI[806–12.458], P < 0.001) and PPROM (aOR = 18.902, 95% CI[7.267–49.167], P < 0.001). Maternal mid upper arm circumference (MUAC) measurement ≥24 cm was a protective factor against preterm birth (aOR = 0.155, 95% CI[0.0686–0.352], P < 0.001). ConclusionPreterm births in Soroti-RH in Eastern Uganda were associated with poor maternal nutrition status, low antenatal attendance, twin gestation, antepartum hemorrhage, and preterm premature rupture of membranes. Health education on proper nutrition and routine monthly antenatal visits by healthcare workers is important for early screening and detection of high risk pregnancies.

A Short Communication on All About to Know Preterm Birth

Preterm delivery, commonly referred to as premature birth, occurs when a baby is delivered before the full 37 weeks of pregnancy. The danger of death or permanent disability increases with the time of birth [1]. Throughout the whole pregnancy, a developing baby experiences significant growth, particularly in the latter few weeks and months. For instance, the latter weeks of pregnancy are necessary for the development of the brain, lungs, and liver [2]. Based on gestational age, preterm birth is divided into the following subcategories: (1) Extremely preterm (less than 28 weeks), (2) Very Preterm (28 to 32 weeks) and (3) Mid- to late-term pregnancy (32 to 37 weeks). A lifetime of difficulties, such as learning challenges and vision and hearing impairments, are a reality for many survivors. Preterm birth is a worldwide issue, although it is more common in Africa and southern Asia. Depending on where they are born, preterm newborns have a significantly different chance of surviving. For instance, more than 90% of kids born in low-income countries who are extremely preterm (less than 28 weeks) pass away during the first few days of life, but less than 10% of newborns born in high-income nations who are extremely preterm pass away [3]. There are many causes of preterm birth. The majority of preterm births are due to natural causes, but others are brought on by illnesses or other pregnancy issues that necessitate caesarean sections or early labour induction. Multiple pregnancies, infections, and chronic illnesses like diabetes and high blood pressure are among the causes, although frequently there is no clear explanation. Additionally, there may be a hereditary component [3]. Your baby could have more glaring difficulties from being born prematurely or very modest signs. Prematurity can show itself in the following ways: Small size, with an oversized head that is not proportional to it, Sharper-looking, less rounded features than those of a full-term baby because to a lack of fat reserve, Fine hair covering most of the body, Low body temperature brought on by a lack of body fat reserves, especially right after birth in the delivery room, Breathing that is laboured or respiratory discomfort, Feeding issues result from a lack of swallowing and sucking reflexes [4].

Identifying Risk Factors for Premature Birth in the UK Millennium Cohort Using a Random Forest Decision-Tree Approach

Prior research on causes of preterm birth has tended to focus on pathophysiological processes while acknowledging the role of socioeconomic indicators. The present research explored a wide range of factors plausibly associated with preterm birth informed by pathophysiological and evolutionary life history perspectives on gestation length. To achieve this, a machine learning ensemble classification data analysis approach, random forest (RF), was applied to the UK Millennium Cohort (18,201 births). The results highlighted the importance of socioeconomic variables and parental age in predicting preterm (before 37 completed weeks) and very preterm (before 32 weeks) birth. Infants born in households with low income and with young fathers had an increased risk of both very preterm and preterm birth. Maternal health and health problems during pregnancy were not found to be useful predictors. The best-performing algorithm was for very preterm birth and had 93% sensitivity and 100% specificity using six variables. Algorithms predicting preterm birth before 37 weeks showed increased error, with out-of-bag error rates of about 7% versus only 1% for those predicting very preterm birth. The poorer performance of algorithms predicting preterm births to 37 weeks of gestation suggests that some preterm birth may not result from pathology related to poor maternal health or social or economic disadvantage, but instead represents normal life-history variation.

Cervical pessary for preventing preterm birth in singleton pregnancies.

Cervical pessary for preventing preterm birth in singleton pregnancies.

Fetal macrophages assist in the repair of ruptured amnion through the induction of epithelial-mesenchymal transition.

The premature rupture of the amniotic sac, a condition referred to as a preterm prelabor rupture of membranes (pPROM), is a leading cause of preterm birth. In some cases, these ruptured membranes heal spontaneously. Here, we investigated repair mechanisms of the amnion, a layer of epithelial cells in the amniotic sac closest to the embryo. Macrophages migrated to and resided at rupture sites in both human and mouse amnion. A process called epithelial-mesenchymal transition (EMT), in which epithelial cells acquire a mesenchymal phenotype and which is implicated in tissue repair, was observed at rupture sites. In dams bearing macrophage-depleted fetuses, the repair of amnion ruptures was compromised, and EMT was rarely detected at rupture sites. The migration of cultured amnion epithelial cells in wound healing assays was mediated by EMT through transforming growth factor-β (TGF-β)-Smad signaling. These findings suggest that fetal macrophages are crucial in amnion repair because of their ability to induce EMT in amnion epithelial cells.

Inflammation in preterm birth: Novel mechanism of preterm birth associated with innate and acquired immunity

Preterm birth (PB) is the most-frequent complication occurring during pregnancy, with a significant impact on neonatal morbidity and mortality. Chorioamnionitis (CAM), the neutrophil infiltration into chorioamniotic membranes, is a major cause of PB. However, several cases of PB have also been reported without apparent pathogenic infection or CAM. Such cases are now attributed to “sterile inflammation.” The concept of sterile inflammation has already attracted attention in various diseases, like cardiovascular diseases, diabetes, and autoimmune diseases; recently been discussed for obstetric complications such as miscarriage, PB, gestational hypertension, and gestational diabetes. Sterile inflammation is induced by alarmins, such as high-mobility group box 1 (HMGB1), interleukins (IL-33 and IL-1α), and S100 proteins, that are released by cellular damage without apparent pathogenic infection. These antigens are recognized by pattern-recognition receptors, expressed mainly on antigen-presenting cells of decidua, placenta, amnion, and myometrium, which consequently trigger inflammation. In reproduction, these alarmins are associated with the development of various pregnancy complications, including PB. In this review, we have summarized the development of PB related to acute CAM, chronic CAM, and sterile inflammation as well as proposed a new mechanism for PB that involves innate immunity, acquired immunity, and sterile inflammation.

A multidisciplinary Prematurity Research Cohort Study.

Worldwide, 10% of babies are born preterm, defined as a live birth before 37 weeks of gestation. Preterm birth is the leading cause of neonatal death, and survivors face lifelong risks of adverse outcomes. New approaches with large sample sizes are needed to identify strategies to predict and prevent preterm birth. The primary aims of the Washington University Prematurity Research Cohort Study were to conduct three prospective projects addressing possible causes of preterm birth and provide data and samples for future research. Pregnant patients were recruited into the cohort between January 2017 and January 2020. Consenting patients were enrolled into the study before 20 weeks' gestation and followed through delivery. Participants completed demographic and lifestyle surveys; provided maternal blood, placenta samples, and cord blood; and participated in up to three projects focused on underlying physiology of preterm birth: cervical imaging (Project 1), circadian rhythms (Project 2), and uterine magnetic resonance imaging and electromyometrial imaging (Project 3). A total of 1260 participants were enrolled and delivered during the study period. Of the participants, 706 (56%) were Black/African American, 494 (39%) were nulliparous, and 185 (15%) had a previous preterm birth. Of the 1260 participants, 1220 (97%) delivered a live infant. Of the 1220 with a live birth, 163 (14.1%) had preterm birth, of which 74 (6.1%) were spontaneous preterm birth. Of the 1220 participants with a live birth, 841 participated in cervical imaging, 1047 contributed data and/or samples on circadian rhythms, and 39 underwent uterine magnetic resonance imaging. Of the 39, 25 underwent electromyometrial imaging. We demonstrate feasibility of recruiting and retaining a diverse cohort in a complex prospective, longitudinal study throughout pregnancy. The extensive clinical, imaging, survey, and biologic data obtained will be used to explore cervical, uterine, and endocrine physiology of preterm birth and can be used to develop novel approaches to predict and prevent preterm birth.

Association between Preterm Premature Rupture of Membranes and Vitamin D Levels in Maternal Plasma and Umbilical Cord Blood of Newborns: A Prospective Study

Background: Preterm premature rupture of membranes (PPROM) is a major cause of preterm birth. There are few reports on vitamin D deficiency associated with PPROM. We aimed to investigate the association between PPROM and vitamin D levels in maternal plasma and the umbilical cord blood of newborns. Methods: This prospective study included 355 pregnant women who delivered live infants between March 2017 and December 2018 at a medical center. Vitamin D levels were measured in the maternal plasma at the first, second, third trimesters of pregnancy and just before delivery, and in the umbilical cord blood of newborns at birth. In addition, we evaluated the pregnancy and neonatal outcomes according to vitamin D status. Results: The rate of PPROM in the vitamin D deficiency group (25(OH)D &lt;20 ng/mL) was higher than in the non-deficiency group (25(OH)D ≥20 ng/mL) (p = 0.003). Vitamin D levels were significantly lower in the PPROM group than non-PPROM group in maternal plasma [at the first (p = 0.020) and second trimesters (p = 0.029), just before delivery (p = 0.015)], and in the cord blood of newborns (p = 0.006). Multiple logistic regression analysis showed that the odds ratio of PPROM by the increase of 1ng/mL of vitamin D levels in the cord blood of newborns was 0.907 (95% confidence interval 0.836–0.983) after adjustment for other confounders (age, gravidity, parity, and body mass index). Conclusions: Vitamin D deficiency has a significant association with PPROM. Our study would aid in understanding the mechanism of prevention of PPROM associated with vitamin D deficiency as well as reduction in preterm births.

Prophylactic administration of human amniotic fluid stem cells suppresses inflammation-induced preterm birth via macrophage polarization.

Ascending inflammation from the vagina is a major cause of preterm birth. Currently, this condition-especially when uncontrolled-has no effective treatment. Human amniotic fluid stem cells (hAFSCs) are mesenchymal stem cells known to exert potent anti-inflammatory effects in animal models of perinatal diseases, such as periventricular leukomalacia, myelomeningocele, and neonatal sepsis. However, hAFSC therapy for inflammation-induced preterm birth has not been tested. In order to determine the therapeutic effect of hAFSC transplantation, we employed a preterm mouse model of ascending infection; this model was constructed by administering lipopolysaccharide to pregnant mice. We investigated the preterm birth rate and evaluated the inflammation of tissues, which is related to progressive infections, such as those involving the cervix, placenta, and lavage cells, using real-time qPCR. Further, we tracked the fluorescence of fluorescently labeled hAFSCs using an in vivo imaging system, and hAFSC aggregation was evaluated using immunohistochemistry analysis. We also investigated the presence of multiple types of peritoneal macrophages via flow cytometry analysis. Finally, we performed sphere culturing and co-culturing to determine the therapeutic effects of hAFSCs, such as their anti-inflammatory effects and their potential to alter macrophage polarization. We found that hAFSC administration to the peritoneal cavity significantly reduced inflammation-induced preterm birth in the mouse model. The treatment also significantly suppressed inflammation of the placenta and cervix. Transplanted hAFSCs may have aggregated with peritoneal macrophages, switching them from an inflammatory to an anti-inflammatory type. This property has been reported in vivo previously, but here, we examined the effect in vitro. Our findings support the hypothesis that hAFSCs suppress inflammation and reduce preterm birth by switching macrophage polarity. This study is the first to demonstrate that hAFSCs are effective in the treatment and prevention of inflammation-induced preterm birth.

Factors associated with preterm births in sacred heart hospital, Lantoro, Abeokuta, Ogun state

This research was carried out to ascertain the factors associated with preterm births in Sacred Heart Hospital, Lantoro, Abeokuta, Ogun State, Nigeria. The Objectives were to assess the Knowledge of mothers on the causes of preterm labour during ANC, assess causes of preterm birth in Sacred Heart Hospital, Lantoro, Abeokuta, determine the socio-demographic factors that influence preterm delivery in mothers attending Sacred Heart Hospital, Lantoro, Abeokuta and Investigate the possible options to the management of preterm labour. The significance of this study is to empower clients and health care professionals to understand and prevent preterm births, minimize the complications of preterm births and give better care to premature babies. Nurses could educate pregnant women based on the findings of this study to avoid practices that predispose them to preterm births. Early detection and prompt treatment of disease conditions associated with premature births. It will also serve as a base-line for future studies. Research design was retrospective/cross sectional study. Data was collected from the records of women who delivered in the hospital between January 2016 and December 2018. Sample size was determined by the use of Cochran’s formula to select 162 respondents from the ANC using self–structured questionnaire. Quantitative data was collected using abstract form questionnaire with 4 sections on socio-demographic, knowledge of causes of preterm births, preterm delivery among respondents and available options for the management of preterm births. Findings from the analysis revealed that 62% of nursing mothers have heard of preterm births, 57.1% have poor knowledge of causes. Majority (89.3%) were married and from monogamous homes (89.3%). Previous preterm births (78.6%) and pre-eclampsia (82.1%), the highest risk factor. Eighty-nine percent of mothers had babies with low apgar score while 80% had slow development. Almost all mothers (100%) opted for Kangoro Mother Care. Recommendations were made based on the findings that nurses should update their knowledge and skills on the causes, prevention and special care of preterm babies so as to guide the mothers aright thereby reducing infant morbidity and mortality associated with premature births.

MiR-195-5p facilitates the proliferation, migration, and invasion of human trophoblast cells by targeting FGF2.

Preeclampsia (PE), the most significant adverse exposure to cardiovascular risk during pregnancy, is one of the three major factors contributing to maternal and fetal mortality and the leading cause of preterm birth. Recently, various miRNAs have been reported to participate in PE occurrence and development. Nevertheless, the regulatory impact of miR-195-5p in PE is still indistinct. Quantitative realtime-PCR (qRT-PCR), western blot, and fluorescence in situ hybridization (FISH) assay were performed to examine miR-195-5p and FGF2 expressions in PE serum samples or HTR-8/SVneo and TEV-1 cells. CCK8, flow cytometry, wound scratch, and transwell assays were conducted to determine cell viability, cycle, apoptosis, migration, and invasion. Dual-luciferase reporter assay unveiled the relationship between miR-195-5p and FGF2. Migration-related and invasion-related protein expressions were measured by western blot assay. miR-195-5p was prominently downregulated while FGF2 was increased in serum samples from PE patients and hypoxia-treated human trophoblast cells. FGF2 was predicted as a downstream target of miR-195-5p and targeted association was verified by dual-luciferase reporter assay. Functional experiments elaborated that miR-195-5p could facilitate trophoblast cell proliferation and metastasis but hinder cell cycle and apoptosis. Inversely, overexpressing of FGF2 could reverse the effects of miR-195-5p on trophoblast cell growth. miR-195-5p was decreased in PE serum samples and cell lines, serving as a potential biomarker in protecting PE exacerbation by targeting FGF2.

History and prospects of perinatal mortality rate in Russia

Population reproduction is a priority task of social policy and a factor of Russias national security. The review presents the stages of recording the perinatal mortality indicator, which is closely related to the frequency of preterm birth. In the first stage, the criteria for registering preterm birth were 28 weeks of pregnancy, and in the second, since 2012, 22 weeks. At both stages, due to underreporting of low birth weight babies (their transfer to the miscarriage group), stillbirths, including full-term babies, prevailed in the preterm birth indicator structure. The authors of the article stressed that the main cause of preterm birth (including iatrogenic) is the formation of endotoxemia syndrome, or systemic effects of aggressive metabolites in the mother placenta fetus system. In this etiopathogenetic therapeutic means are methods of efferent therapy in the form of plasmapheresis, etc. These technologies in many obstetric pathologies (thrombophilia, preeclampsia, Rh-conflict, isthmic-cesmic and chronic placental insufficiency, etc.) sanitize the mother placenta fetus system and allow to prolong pregnancy with a reduction of perinatal mortality index. The authors cite their own data on the use of efferent therapy methods in 102 women presenting at 2228 weeks of pregnancy to the Perinatal Center of Saint Petersburg State Medical University from other institutions after unsuccessful treatment according to the Protocols for various obstetric complications. Pregnancies were prolonged by 215 weeks; all 123 children (20 twins, 1 triplet) were born alive, did not require long-term intensive care, survived and were not disabled. Six newborns died and the perinatal mortality rate was 48 : 1000, which is an order of magnitude lower than that quoted in the literature for similar pathologies and gestational ages. In conclusion of the article, it is suggested that in order to reduce perinatal mortality in Russia, all large institutions should arrange efferent therapy rooms to treat sick pregnant women using the safe, low-cost technologies developed by the authors, using domestic equipment.

The Bradykinin System Contributes to the Regulation of Prostaglandin-Endoperoxide Synthase 2 Expression in Human Amnion Fibroblasts: Implications for Term and Preterm Birth.

BackgroundBradykinin (BK) and its biologically active metabolite des-Arg9 bradykinin (DABK) play a pivotal role in inflammation. Since chorioamnionitis is the leading cause of preterm birth and prostaglandin E2 (PGE2) derived from the amnion is key to labor initiation, we investigated if bradykinin peptides are part of the regulatory network of PGE2 synthesis in human amnion at parturition.MethodsHuman amnion tissue was obtained from term and preterm birth for the study of the changes of the bradykinin system at parturition. Cultured primary human amnion fibroblasts, the major source of PGE2, were used to study the effects of bradykinin peptides on PTGS2 expression and PGE2 production as well as the effects of infection mediators on bradykinin receptors.ResultsBradykinin peptides and their receptors BDKRB1 and BDKRB2 were present in human amnion, and their abundance increased in term and preterm labor. However, transcripts of the genes encoding the bradykinin precursor and its proteolytic cleavage enzymes were hardly detectable in human amnion despite the increased abundance of bradykinin peptides in term and preterm labor, suggesting that there is an alternative source of bradykinin peptides for human amnion and their actions are enhanced in human amnion at parturition. In-vitro studies in cultured human amnion fibroblasts showed that both BK and DABK increased the expression of prostaglandin-endoperoxide synthase 2 (PTGS2), the rate-limiting enzyme in prostaglandin synthesis, and subsequent PGE2 production. These effects of BK and DABK were mediated through BDKRB2 and BDKRB1 receptors, respectively, with subsequent activation of the p38 and ERK1/2 pathways. Moreover, lipopolysaccharide (LPS) and serum amyloid A1 (SAA1), the important mediators of infectious inflammation, induced the expression of both BDKRB1 and BDKRB2 through toll-like receptor 4 (TLR4). Induction of BDKRB1 and BDKRB2 expression by LPS and SAA1 enhanced BK- or DABK-induced PTGS2 expression and PGE2 production in human amnion fibroblasts.ConclusionsThis study demonstrated for the first time that the human amnion is a target tissue of bradykinin peptides and the bradykinin system may be part of the regulatory network of PTGS2 expression and PGE2 production in human amnion fibroblasts at both term and preterm birth, which may be enhanced by infection.

Unsupervised Learning Applied to the Stratification of Preterm Birth Risk in Brazil with Socioeconomic Data.

Preterm birth (PTB) is a phenomenon that brings risks and challenges for the survival of the newborn child. Despite many advances in research, not all the causes of PTB are already clear. It is understood that PTB risk is multi-factorial and can also be associated with socioeconomic factors. Thereby, this article seeks to use unsupervised learning techniques to stratify PTB risk in Brazil using only socioeconomic data. Through the use of datasets made publicly available by the Federal Government of Brazil, a new dataset was generated with municipality-level socioeconomic data and a PTB occurrence rate. This dataset was processed using various unsupervised learning techniques, such as k-means, principal component analysis (PCA), and density-based spatial clustering of applications with noise (DBSCAN). After validation, four clusters with high levels of PTB occurrence were discovered, as well as three with low levels. The clusters with high PTB were comprised mostly of municipalities with lower levels of education, worse quality of public services—such as basic sanitation and garbage collection—and a less white population. The regional distribution of the clusters was also observed, with clusters of high PTB located mostly in the North and Northeast regions of Brazil. The results indicate a positive influence of the quality of life and the offer of public services on the reduction in PTB risk.

Antibiotic choice for the management of preterm premature rupture of membranes in Taiwanese women

Preterm premature rupture of membranes (PPROM) is one of the most common causes of preterm birth. Antibiotic treatment is recommended to prolong the pregnancy course and reduce fetal morbidity in women with PPROM. However, the guidelines for antibiotic selection are based on studies done years ago, mostly in Western countries, which may not reflect the geographic, temporal, and ethnic variation in microbial colonization and infection in other parts of the world. We aimed to understand whether the antibiotics recommended by the current guidelines were sufficient to eradicate the majority of pathogens involved. This is a single-center retrospective study at a tertiary medical center in Taiwan with patients recruited from January 1, 2017, to December 31, 2019. All patient included had a confirmed diagnosis of PPROM. In this study, we aimed to investigate which broad-spectrum antibiotic was most suitable for PPROM cases in Taiwan. 133 women were included, and 121 women had positive culture results. Most of the pregnant women had one positive result (35.5%). The most common pathogen was Lactobacillus species (27.8%), followed by Streptococcus species (12.9%) and Staphylococcus species (12.09%). The most appropriate antibiotic therapy for PPROM was a combination of 1 g azithromycin given orally on admission plus a third-generation cephalosporin administered intravenously in the first 48 hours and followed by amoxicillin 500 mg per os for another five days. This recommended antibiotic regimen for women with PPROM needs further study under a randomized clinical trial with a larger study population to evaluate its efficacy.

Association of maternal polycystic ovary syndrome and diabetes with preterm birth and offspring birth size: a population-based cohort study.

Association of maternal polycystic ovary syndrome and diabetes with preterm birth and offspring birth size: a population-based cohort study.

New approaches suggest term and preterm human fetal membranes may have distinct biomechanical properties

Preterm prelabour rupture of membranes is the leading cause of preterm birth and its associated infant mortality and morbidity. However, its underlying mechanism remains unknown. We utilized two novel biomechanical assessment techniques, ball indentation and Optical Coherence Elastography (OCE), to compare the mechanical properties and behaviours of term (≥ 37 weeks) and preterm (33–36 weeks) human fetal membranes from ruptured and non-ruptured regions. We defined the expression levels of collagen, sulfated glycosaminoglycans (sGAG), matrix metalloproteinase (MMP-9, MMP-13), fibronectin, and interleukin-1β (IL-1β) within membranes by biochemical analysis, immunohistochemical staining and Western blotting, both with and without simulated fetal movement forces on membrane rupture with a new loading system. Preterm membranes showed greater heterogeneity in mechanical properties/behaviours between ruptured and non-ruptured regions compared with their term counterparts (displacement rate: 36% vs. 15%; modulus: 125% vs. 34%; thickness: 93% vs. 30%; collagen content: 98% vs. 29%; sGAG: 85% vs 25%). Furthermore, simulated fetal movement forces triggered higher MMP-9, MMP-13 and IL-1β expression in preterm than term membranes, while nifedipine attenuated the observed increases in expression. In conclusion, the distinct biomechanical profiles of term and preterm membranes and the abnormal biochemical expression and activation by external forces in preterm membranes may provide insights into mechanisms of preterm rupture of membranes.

Evidence for the Association Between STIs and Preterm Birth

Source: Gao R, Liu B, Yang W, et al. Association of maternal sexually transmitted infections with risk of preterm birth in the United States. JAMA Netw Open. 2021;4(11):e2133413. doi:10.1001/jamanetworkopen.2021.33413Investigators from multiple institutions conducted a retrospective study to assess the association between maternal sexually transmitted infections (STI) during pregnancy and premature birth. For the study, they reviewed data on birth certificates of children born by singleton birth between 2016 and 2019 in all 50 states and the District of Columbia. Data abstracted from birth certificates included demographic information, maternal pregnancy history, and estimated gestational age at birth. Also included on the birth certificates was a history of maternal infection with chlamydia, gonorrhea, and/or syphilis at the time of the diagnosis of pregnancy or during pregnancy. The primary study outcome was premature birth, defined as gestational age <37 weeks. Secondary outcomes included extremely premature birth (<28 weeks), very preterm birth (28-31 weeks), and moderately preterm birth (32-36 weeks). The association between maternal STI and these outcomes were assessed with logistic and multinomial regression, after adjustment for multiple confounders. Models that included any of the assessed STIs, and specific STIs were conducted. In addition, analyses stratified by maternal age or race/ethnicity were performed.Data on 14,373,023 singleton births were included in the analyses. The mean age of the mothers of these infants was 29 ± 5.8 years. A total 267,260 (1.9%) mothers had chlamydia, 43,147 (0.3%) had gonorrhea, and 16,321 (0.1%) had syphilis. Among the study newborns, 1,146,800 (8.0%) were born prematurely. In the multivariate model, any maternal STI was associated with an increased risk of premature birth (OR, 1.06; 95% CI, 1.05, 1.07); infection with chlamydia (OR, 1.03; 95% CI, 1.02, 1.04), gonorrhea (OR, 1.11; 95% CI, 1.08, 1.15), and syphilis (OR, 1.17; 95% CI, 1.11, 1.22) were each individually associated with an increased risk of premature birth. Maternal STI was associated with an increased risk of very premature birth (OR, 1.07; 95% CI, 1.03, 1.12), and moderately preterm birth (OR, 1.06; 95% CI, 1.05, 1.08), but not extremely premature birth (OR, 1.00; 95% CI, 0.95, 1.05). There was a small but statistically significant (P <0.001) increase in the risk of premature birth associated with maternal STI among women ≥35 years old (OR, 1.09), and those 25-34 years old (OR, 1.08), compared to those <25 years old (OR, 1.06). There was a statistically significant increased risk of premature birth associated with maternal STI among women who were white (OR, 1.10; 95% CI, 1.08, 1.13), Black (1.04; 95% CI, 1.02, 1.06) and Hispanic (OR, 1.06; 95% CI, 1.03, 1.09), but not Asian (OR, 1.01; 95% CI, 0.90, 1.13).The authors conclude that maternal infection with chlamydia, gonorrhea, or syphilis is associated with an increased risk of premature birth.Dr Von Kohorn has disclosed no financial relationship relevant to this commentary. This commentary does not contain a discussion of an unapproved/investigative use of a commercial product/device.The holy grail of neonatal-perinatal medicine is the prevention of adverse newborn outcomes, and, ultimately, the prevention of preterm birth. Intrauterine infection is thought to be a leading cause of preterm birth, although the precise contribution of specific STIs to preterm birth is unclear.1 The current study, a high-quality observational analysis of more than 14 million women with singleton pregnancies in the US, provides some of the best evidence to date that STIs—specifically chlamydia, gonorrhea, and syphilis—are associated with preterm birth. Still, the nature of the study leaves key questions unanswered.The authors of the accompanying editorial comments that some epidemiologists caution against considering interpreting near-even odds, such as those in the current study, as valid when the sample size is extremely large.2 Furthermore, observational studies, no matter how large, are subject to bias and cannot determine causation.3 Thus, it remains possible that pregnant women with STIs in this study, or in general, are systematically prone to preterm birth for reasons other than the STIs themselves. Perhaps most importantly, the current researchers did not seek to elucidate whether prevention or treatment of STIs is effective in preventing preterm birth. Recent observational data suggest that treatment of STIs in pregnancy is not effective in preventing preterm birth.4 The editorial authors state that they know of no randomized controlled trials that answer this question.2 A randomized trial of STI prevention to decrease preterm birth is intriguing. It is unclear how a randomized trial could be designed for treatment of STIs, since treatment is the standard of care in pregnancy.The best evidence to date indicates that STIs are associated with preterm birth. It remains unclear whether treatment of STIs is an effective intervention to prevent preterm birth.

Early Initiation and Long-Term Use of Vaginal Progesterone may Cause Gestational Diabetes Mellitus.

Preterm birth (PTB) is an important cause of neonatal mortality and morbidity. Spontaneous PTB (sPTB) is the most common cause of PTB. In patients with a singleton pregnancy, progesterone treatment appears to reduce the rate of spontaneous preterm birth in those with a previous history of spontaneous preterm labor and/or cervical shortening in the current pregnancy. Progesterone therapies used for the prevention of sPTB may increase the risk of gestational diabetes mellitus (GDM) towards the end of pregnancy owing to their effects on carbohydrate metabolism. We aimed to show the effects of vaginal progesterone use, starting time, and duration of treatment on GDM. A retrospective cohort study was carried out in pregnant women 18 to 39 years old who came to our hospital between January 1, 2021, and August 31, 2021, and who had a 2-hour 75-g oral glucose tolerance test (OGTT) at 24 to 28 weeks of gestation. In a total of 540 patients, 68 were diagnosed with GDM based on at least one abnormal plasma glucose value at screening. The remaining 472 patients with normal plasma glucose levels were considered as the control group. The groups were compared in terms of age, parity, pre-pregnancy body mass index (BMI), smoking, gestational age, and vaginal progesterone use. Patients using vaginal progesterone with and without GDM were then compared again in terms of indications for vaginal progesterone use, initiation time of progesterone therapy, duration of progesterone use, and cervical length. The incidence of GDM in our study group was 12.5%. Despite the use of vaginal progesterone at a higher rate in the GDM group than in the control group (23.5 vs. 13.9%; p=0.07), it was not statistically significant. When we examined patients using progesterone as a subgroup analysis, the mean time to start vaginal progesterone treatment was 19.8±2.6 (14-24), and it was significantly earlier in the GDM group (18.1±2.0 vs. 20.2±2.6; p=0.007). Initiation of vaginal progesterone before 20 weeks of gestation was statistically significantly more frequent in the GDM group than the control group (68.8 vs. 39.4%; p=0.050 OR :3.3, 95%CI: 1.0-10.8). The mean duration of vaginal progesterone use was 50.0±15.6 days (28-90) and it was longer in the GDM group (57.8±13.4 vs. 48.1±15.6; p=0.027). Since the duration of vaginal progesterone use will be prolonged, there may be a risk of GDM, especially in patients who started vaginal progesterone before the 20th week of pregnancy. Even if the OGTT test performed between 24-28 weeks is normal, it should be kept in mind that these patients may have GDM in the later weeks of pregnancy, and repeating the OGTT test should be considered if necessary.

A Simple Method to Establish Sufficiency and Stability in Meta-Analyses: With Application to Fine Particulate Matter Air Pollution and Preterm Birth.

Fine particulate matter air pollution (PM2.5) is a potential cause of preterm birth. Inconsistent findings from observational studies have motivated researchers to conduct more studies, but some degree of study heterogeneity is inevitable. The consequence of this feedback is a burgeoning research effort that results in marginal gains. The aim of this study was to develop and apply a method to establish the sufficiency and stability of estimates of associations as they have been published over time. Cohort studies identified in a recent systematic review and meta-analysis on the association between preterm birth and whole-pregnancy exposure to PM2.5 were selected. The estimates of the cohort studies were pooled with cumulative meta-analysis, whereby a new meta-analysis was run for each new study published over time. The relative risks (RR) and 95% confidence interval (CI) limits needed for a new study to move the cumulative RR to 1.00 were calculated. Findings indicate that the cumulative relative risks (cRR) for PM2.5 (cRR 1.07, 95% CI 1.03, 1.12) converged in 2015 (RR 1.07, 95% CI 1.01, 1.14). To change conclusions to a null association, a new study would need to observe a protective RR of 0.93 (95% CI limit 1.02) with precision equivalent to that achieved by all past 24 cohort studies combined. Preterm birth is associated with elevated PM2.5, and it is highly unlikely that any new observational study will alter this conclusion. Consequently, establishing whether an observational association exists is now less relevant an objective for future studies than characterising risk (magnitude, impact, pathways, populations and potential bias) and interventions. Sufficiency and stability can be effectively applied in meta-analyses and have the potential to reduce research waste.