Large placental chorioangioma with maternal and perinatal morbidity.

INTRODUCTION: Placental chorioangioma is a benign placenta tumour. Majority of cases, the placental chorioangioma are small and no maternal and fetal complications. We highlight a case diagnosed with large placental chorioangioma with an intrapartum event associated with significant maternal and perinatal morbidity. METHOD: A 38-year-old woman, Gravida 3 Para 1, with one previous miscarriage, presented with preterm labour at 33 weeks gestation. Antenatally, she was referred to a feto-maternal specialist for finding a placental tumour size 12 × 10 cm. Features are consistent with placental chorioangioma with polyhydramnios. The anomaly scan was normal. Antenatal fetal surveillance with Doppler studies were normal. RESULTS: During this admission, corticosteroid was given together with a tocolytic agent and opioid analgesia. Unfortunately, the labour progressed, and the patient felt reduced in fetal movement. The cardiotograph showed suspicious tracing. We proceed with emergency caesarean delivery. The placenta was sent for histopathology assessment which confirmed a large placental chorioangioma. The baby was born with Apgar's score of 9 at 1 min, pH of 7.28 and lactate of 7.28 with anaemia and thrombocytopenia. The uterus developed intermittent uterine atony, and the uterotonic agent was given. She recovered well post-delivery. The baby was admitted to the neonatal intensive care unit (NICU) and received a blood product transfusion and discharged from NICU on day 15 of life. DISCUSSION: Large placental chorioangioma is associated with polyhydramnios, preterm labour, postpartum haemorrhage, fetal anaemia, fetal distress, fetal hydrops and possible perinatal death. Multidisciplinary team involvement with feto-maternal specialists, anaesthetic and neonatologists would improve the outcome of both mother and fetus.

The use of antenatal corticosteroids in preterm labour for the prevention of perinatal mortality in hospitals in Tanzania.

Background: Antenatal corticosteroids (ACS) are given to pregnant women at risk of preterm delivery to hasten the maturation of the lungs, lowering the risk of newborn respiratory distress syndrome (RDS) and perinatal mortality. Objective: The aim of this study was to determine whether exposure to ACS was associated with lower rates of perinatal mortality and RDS in preterm infants delivered by women with preterm labour. Methods: This is a secondary analysis of data from four hospitals in Mwanza, Tanzania. All singletons and twins born to women who were in preterm labour between July 2019 and February 2020 and delivered in-hospital between 24 and 34 weeks of gestation were included. Data were recorded from participants' medical records and analysed using STATA Version 14. Results: Over an eight-month period, 588 preterm infants were delivered to 527 women. One hundred and ninety (36.1%) women were given ACS. Infants who were exposed to ACS in utero had a lower rate of perinatal mortality (6.8% vs 19.1%) and RDS (12.3% vs 25.9%) compared to those not exposed to ACS. In adjusted multivariable models, ACS exposure was related to a lower risk of perinatal mortality, aRR 0.23 (95% CI 0.13 - 0.39), and RDS, aRR 0.45 (95% CI 0.30 - 0.68). Conclusion: ACS significantly reduced the risk of perinatal mortality and RDS among preterm infants exposed to ACS in utero and delivered by women in preterm labour. The use of ACS should be encouraged in low-resource settings where preterm birth is prevalent to improve perinatal outcomes.

Preterm birth in low-middle income Countries.

Preterm birth (PTB), remains a major cause of significant morbidity and mortality world-wide with about 12-15million preterm births occurring every year. Although the overall trend is decreasing, this is mainly in high-income countries (HIC). The rate remains high in low-and middle-income countries (LMIC) varying on average between 10 and 12% compared to 9% in HIC. The pathogenesis of PTB is complex and multifactorial. Attempts to reduce rates that have focused on PTB as a single condition have in general been unsuccessful. However, more recent attempts to phenotype PTB have resulted in targeted preventative approaches which are yielding better results. Prevention (primary or secondary) is the only approach that has been shown to make a difference to rates of PTB. These include identifying risk factors pre-pregnancy and during pregnancy and instituting appropriate measures to address these. In LMIC, although some approaches that have been shown to be effective in some HIC are adaptable, there is a need to involve stakeholders at all levels in utilizing evidence preferrably generated in LMIC to implement strategies that are likely to reduce the rate of PTB. In this review, we focus on prevention and how to involve policy makers in the process of applying evidence into policy that would reduce PTB in LMIC.

Prevalence of Bacterial Vaginosis and Its Association With Preterm Birth in a Tertiary Care Hospital in Chennai: A Cross-Sectional Study.

Background The most common preventive cause of premature labour is ascending infections. This study was conducted to evaluate the association between bacterial vaginosis (BV) and preterm labour in antenatal women and determine the significance of using the Amsel criteria to screen for BV. Methods This was a hospital-based cross-sectional study conducted among 100 antenatal mothers in the second trimester attending the antenatal OPD at a tertiary care hospital in Chennai from October 2019 to September 2021 after obtaining clearance from the institutional ethics committee and written informed consent from the study participants. Data were entered in Excel (Microsoft Corporation, Redmond, WA) and analysed in SPSS (IBM Corp., Armonk, NY). Results According to the Amsel criteria, BV was detected in 21 women (21%). Neither maternal age nor parity had an effect on the study group. There was a statistically significant relationship (p < 0.05) between the mode of delivery, preterm labour, and the study group. Of the 21 positive BV cases, 95% were positive for clue cells and only 5% were positive for gram-negative bacteria. Consequently, BV was found to be associated with early labour. There is no association between BMI and BV (p > 0.005). Conclusion In the current study, BV was shown to be associated with preterm labour. Our study underscores the significance of the Amsel criteria as a valuable tool for screening BV in antenatal women.

Factors contributing to preterm birth in patients presenting at tertiary care hospitals in Punjab.

Objective: To determine the various causes and factors leading to preterm birth in women presenting at tertiary care hospitals. METHODS: The cross-sectional, prospective study was conducted from June 19, 2021, to January 19, 2022, at the Central Park Teaching Hospital, Lahore, Pakistan, in collaboration with other tertiary care teaching hospitals in Lahore, and comprised pregnant women aged 15-45 years with preterm birth. Demographic and obstetric data was collected. Depending on the factors contributing to preterm birth, the subjects were categorised as spontaneous labour group A, preterm prelabour rupture of membrane group B, and iatrogenic preterm birth group C. Data was analysed using SPSS 25. RESULTS: Of the 1,300 recorded births, 200(15.38%) were preterm. Group A had 86(43%) women with mean age 28.55±4.68 years, group B had 43(21,5%) women with mean age 27.14±3.25 years, and group C had 71(35.5%) women with mean age 28.28±3.74 years (p>0.05). There was significant difference among the groups with respect to body mass index (p=0.001) and parity (p=0.021). Vaginal and urinary tract infections were significantly higher in group A compared to the other groups (p<0.05). In group C, pre-eclampsia was the main reason for preterm birth 45(63.38%). Conclusion: Medically indicated preterm birth rate was found to be high, and pre-eclampsia was noted as the main cause in iatrogenic preterm birth.

Gestational diabetes mellitus aggravates adverse perinatal outcomes in women with intrahepatic cholestasis of pregnancy.

PURPOSE: To evaluate the effect of intrahepatic cholestasis of pregnancy (ICP) with gestational diabetes mellitus (GDM) on perinatal outcomes and establish a prediction model of adverse perinatal outcomes in women with ICP. METHODS: This multicenter retrospective cohort study included the clinical data of 2,178 pregnant women with ICP, including 1,788 women with ICP and 390 co-occurrence ICP and GDM. The data of all subjects were collected from hospital electronic medical records. Univariate and multivariate logistic regression analysis were used to compare the incidence of perinatal outcomes between ICP with GDM group and ICP alone group. RESULTS: Baseline characteristics of the population revealed that maternal age (p < 0.001), pregestational weight (p = 0.01), pre-pregnancy BMI (p < 0.001), gestational weight gain (p < 0.001), assisted reproductive technology (ART) (p < 0.001), and total bile acid concentration (p = 0.024) may be risk factors for ICP with GDM. Furthermore, ICP with GDM demonstrated a higher association with both polyhydramnios (OR 2.66) and preterm labor (OR 1.67) compared to ICP alone. Further subgroup analysis based on the severity of ICP showed that elevated total bile acid concentrations were closely associated with an increased risk of preterm labour, meconium-stained amniotic fluid, and low birth weight in both ICP alone and ICP with GDM groups. ICP with GDM further worsened these outcomes, especially in women with severe ICP. The nomogram prediction model effectively predicted the occurrence of preterm labour in the ICP population. CONCLUSIONS: ICP with GDM may result in more adverse pregnancy outcomes, which are associated with bile acid concentrations.

Non-invasive prediction model of histologic chorioamnionitis with preterm prelabour rupture of membranes.

BACKGROUND: The aim of this study is to identify risk factors associated with histological chorioamnionitis (HCA) and develop a predictive model for antepartum assessment of the risk of PPROM with HCA. METHODS: This study retrospectively analyzed pregnant women who experienced PPROM between 25 + 0 and 35 + 0 weeks of gestational age. The women were divided into two groups based on the presence or absence of HCA. Univariate and multivariate logistic regression analyses were conducted to identify maternal risk factors and develop a clinical prediction model for HCA. The model's discrimination and consistency were evaluated using receiver operating characteristic (ROC) and calibration curves. RESULTS: Seventeen thousand one hundred forty-six (17,146) pregnant women were screened, and 726 (4.23 %) had PPROM. Out of the 286 subjects with PPROM, 160 developed HCA. The maternal age of these subjects ranged from 18 to 43 years (30.0 ± 5.4), while their gestational age (GA) ranged from 25 + 0 to 35 + 0 weeks (31.6 ± 2.0). The average GA at delivery was 32.2 ± 2.0 (weeks).Compared with the non-HCA group, the expectant time > 48 h, GA at delivery > 32 weeks, twin pregnancy, HGB (<110 g/Lg/L), degree of LGB (IIb-III), and WBC (>9.5 × 109 /L) were significantly more than in the PPROM with HCA group. The results show that the best model was obtained by leave-one-out logistic regression (AUC = 0.785, CA = 0.741, F1 = 0.739, Precision = 0.740, Recall = 0.741). In the validation set, logistic regression also achieved good results (AUC = 0.710, CA = 0.671, F1 = 0.654, Precision = 0.683, Recall = 0.671). Combining the previous analysis, we found that the prognostic model constructed using the core six features had the best predictive effect. CONCLUSIONS: Six features were associated with the occurrence of chorioamnionitis. These features were used to construct a diagnostic model that can accurately predict the probability of chorioamnionitis occurrence and provide a beneficial tool for the prevention and management of PPROM with HCA.

Relationship between prolonged gestation and nifedipine pharmacokinetics in long-term tocolysis.

In this study, we examined the pharmacokinetics of nifedipine and investigated the maternal and foetal background factors that prolong pregnancy in pregnant women undergoing long-term tocolysis. This prospective observational study included 38 pregnant women hospitalised for threatened preterm labour and treated with nifedipine extended-release tablets in combination with an intravenous ritodrine infusion. Maternal plasma nifedipine concentrations were determined using high-performance liquid chromatography. All patients were administered 20 or 40 mg/dose of nifedipine every 6 h at the time of blood sampling. The plasma trough concentration (Ctrough ) was 22.6 ± 17.3 ng/mL, the maximum plasma concentration (Cmax ) was 30.9 ± 15.3 ng/mL and the time to maximum concentration (Tmax ) was 1.70 ± 1.10 h, as determined using noncompartmental analysis (NCA). The area under the curve for drug concentration (AUCtau ) was 152.3 ± 91.8 mg/L・h, and oral clearance (CL/F) was 0.17 ± 0.08 L/h. Using logistic regression analyses, we identified the factors that predicted term delivery from 37 weeks to <42 weeks of gestation. Gestational age at admission and the AUCtau of nifedipine can predict term delivery. The AUCtau of nifedipine is a valuable regulatory predictor of term delivery in pregnant women undergoing long-term tocolysis.

Mendelian randomization reveals systemic lupus erythematosus and rheumatoid arthritis and risk of adverse pregnancy outcomes.

BACKGROUND: The effect of systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) on adverse pregnancy outcomes is a controversial topic. This study aimed to use Mendelian randomization (MR) analysis to assess the causal relationship between SLE, RA and adverse pregnancy outcomes. METHODS: Genetic variants for SLE and RA, as well as adverse pregnancy outcomes, were derived from pooled statistics from large public genome-wide association studies. Several methods, such as inverse variance weighting (IVW), MR-Egger, weighted median and MR-Pleiotropic Residuals Sum and Outliers, were employed to estimate two-sample causality. RESULTS: Genetic prediction of SLE was associated with higher odds of preterm labour [odds ratio (OR) 1.03, 95 % confidence interval (CI) 1.01-1.05; p = 0.008]. RA was associated with higher odds of preterm labour (OR 1.03, 95 % CI 1.01-1.06; p = 0.009), pre-eclampsia or eclampsia (OR 1.04, 95 % CI 1.01-1.07; p = 0.005), and poor fetal growth (OR 1.08, 95 % CI 1.04-1.12; p = 2.91 × 10-5). The results of bidirectional MR analysis did not indicate that SLE was associated with spontaneous abortion, pre-eclampsia or eclampsia, preterm rupture of membranes, or poor fetal growth (p-value for IVW 0.13-0.97). CONCLUSIONS: This study found a genetic association between SLE and the risk of preterm labour, and highlights the importance of perinatal care and monitoring for patients with SLE. Furthermore, RA was found to be associated with a wide range of adverse outcomes, including preterm labour, pre-eclampsia or eclampsia, and poor fetal growth; as such, there is a need for more intensive therapeutic interventions and prenatal monitoring.

Comparing Obstetric and Perinatal Outcomes Following Elective and Emergency Cervical Cerclage in Singleton and Multiple Pregnancies in a Tertiary Care Perinatal Centre.

Objective: To compare the success, failure rates and perinatal outcomes following emergency and elective cervical cerclage in singleton and twin pregnancies at a tertiary care perinatal centre over half a decade. Methods: All pregnant women, both with singleton and twin pregnancies, who had cervical cerclage between June 2014 and May 2019 were included in the retrospective study. Success rates, failure rates, maternal complications and perinatal outcomes were compared in both groups. Results: There were 129 women enrolled in the study, 48 in the emergency and 81 in the elective group. A significantly greater number of multiparous women were in the elective group (97.5% versus 68.7%; p-value < 0.001). Twins were nearly four times more in the emergency group as compared to  the elective group. The mean cervical length at time of cerclage was 2.05 cm and 1.5 cm; (p-value < 0.001) respectively in the elective and emergency groups. Almost half of the women in the emergency group had bulging membranes. (52.2%). Following cerclage, mean gestational age at delivery was similar in both groups. However, more women in the elective group delivered at or beyond 34 weeks in comparison to the emergency groups (71% versus 53.3%. P-value 0.05). Preterm labour leading to preterm births was almost twice in the emergency group than elective group (49% versus 22%, P-value 0.002). Rates of maternal chorioamnionitis were similar in both groups. The overall live birth rates were comparable (81.3% versus 84.4% P-value 0.85) in both the groups. These results were also seen on doing subgroup analysis of elective versus emergency cerclage in singleton pregnancies only. Failure rates were also similar in both groups (18.7% versus 15.6%, P-value 0.85) Composite neonatal morbidity was more in the emergency group than in the elective group (35.5 versus 14%, P-value 0.01). Conclusion: Live birth rates and failure rates were comparable following elective and emergency cerclage both overall and in singleton pregnancies. Maternal chorioamnionitis and neonatal sepsis  rates were similar in both the groups. However, composite neonatal morbidity was higher in the emergency cerclage group.

Study of Cervical Mucus Cytology and Serum Inflammatory Biomarkers in Preterm Labour Compared to Term Pregnancy Cases in a Tertiary Care Center of Western Uttar Pradesh (UP), India.

PURPOSE: The onset of labor prior to 37 weeks of gestation is preterm labor. Incidence ranges from 5% to 7% of live births in developed countries, but higher in developing countries (10-13%). Preterm birth is a major threat in perinatal health care, as well as a risk factor for neurological impairment and disability. Considering that infection is the major risk factor for preterm labor in rural areas, this study was performed to assess the cytological changes in the cervical mucus of normal-term and preterm labor cases. METHOD: A hospital-based cross-sectional observational study was conducted in the Department of Obstetrics and Gynecology at a tertiary care center in western Uttar Pradesh (UP), India. The sample size calculated was 90. The neutrophil-to-lymphocyte ratio (NLR) in cervical mucus, along with serum inflammatory biomarkers such as CRP and serum alkaline phosphatase, were compared in both groups. RESULT: The incidence of preterm labor increased with an increase in parity, and progression to preterm delivery is faster in the higher parity group. C-reactive protein (CRP) (p value = < 0.001) and serum alkaline phosphatases (taking 220IU/L as the cutoff value), as well as the NLR (p value < 0.001) in cervical mucus in preterm labor, are significantly higher than those in term labor cases, which can be used to predict preterm labor. CONCLUSIONS: Higher levels of serum alkaline phosphatase (> 220 IU/L) and CRP positivity can be used as prognostic markers. Using a cutoff value of 5 for the NLR in the cervical mucus of preterm labor patients proved to be a highly accurate predictor (82.2%) for preterm labor diagnosis.

Signature precursor and mature microRNAs in cervical ripening during gestational diabetes mellitus lead to pre-term labor and other impediments in future.

Gestational diabetes mellitus (GDM) is a pathological condition in which the placenta releases a hormone called human placental lactogen that prevents maternal insulin uptake. GDM is characterised by varying degrees of carbohydrate intolerance and is first identified during pregnancy. Around 5-17% of pregnancies are GDM pregnancies. Older or obese women have a higher risk of developing GDM during gestation. Hyperglycemia is a classic manifestation of GDM and leads to alterations in eNOS and iNOS expression and subsequently causes ROS and RNS overproduction. ROS and RNS play an important role in maintaining normal physiology, when present in low concentrations. Increased concentrations of ROS is harmful and can cause cellular and tissue damage. Oxidative stress is defined as an imbalance between pro-oxidant and antioxidant molecules that manifests due to hyperglycemia. miRNAs are short, non-coding RNAs that play a critical role in regulating gene expression. Studies have shown that the placenta expresses more than 500 miRNAs, which play a crucial role in trophoblast division, movement, and apoptosis. Latest research has revealed that hyperglycemic conditions and increased oxidative stress, characteristic of GDM, can lead to the dysregulation of miRNAs. The placenta also releases miRNAs into the maternal circulation. The secreted miRNAs are encapsulated in exosomes or vesicles. These exosomes interact with tissues and organs at distant sites, releasing their cargo intracellularly. This crosstalk between hyperglycemia, ROS and miRNA expression in GDM has detrimental effects on both foetal and maternal health. One of the complications of GDM is preterm labour. GDM induced iNOS expression has been implicated in cervical ripening, which in turn causes preterm birth. This article focuses on the speculations of oxidative and nitrative stress markers that lead to detrimental effects in GDM. We have also envisaged the role of non-coding miRNA interactions in regulating gene expression for oxidative damage. Graphical Abstract: Holistic view of miRNA in GDM. I)(A) Placenta as a metabolic organ that provides the foetus with nutrients, oxygen and hormones to maintain pregnancy. Human placental lactogen (hPL) is one such hormone that is released into maternal circulation. hPL is known to induce insulin resistance. (B) ß-cell dysfunction leads to reduced glucose sensing and insulin production. Insulin resistance, a characteristic of GDM, exacerbates insulin ß cell dysfunction leading to maternal hyperglycemia. Hyperglycemia leads to increased ROS and RNS production through several mechanisms. Consequently, GDM is characterised by increased oxidative and nitrative stress.II)Exposure to maternal hyperglycemia causes increased ROS and RNS production in trophoblast cells. Oxidative stress caused by hyperglycemia may lead to eNOS uncoupling, causing eNOS to behave as a superoxide producing enzyme. iNOS expression in trophoblast cells leads to increased NO production. iNOS-derived NO reacts with ROS to produce RNS, thereby increasing nitrosative stress. Expression of antioxidant defences are reduced. Hyperglycemia and oxidative stress may alter the expression of some miRNAs. Some miRNAs are upregulated while others are downregulated. Some miRNAs are secreted into maternal circulation in the form of exosomes. Oxidative stress markers, nitrative stress markers and circulating miRNAs are found to be increased in maternal circulation.

Validation of parental recall questionnaire to classify preterm delivery subtypes: Spontaneous preterm labour, preterm premature rupture of membranes and clinician-initiated preterm delivery.

BACKGROUND: Preterm delivery (PTD) includes three main presenting subtypes: spontaneous preterm labour (sPTL), preterm premature rupture of membranes (pPROM) and clinician-initiated preterm delivery (ciPTD). PTD subtype data are rarely available from birth registries and are onerous to derive from medical records. OBJECTIVES: To develop and test the validity of a questionnaire to classify PTD subtype based on birthing parent recall of labour and delivery events. METHODS: The questionnaire was sent in 2022 to 581 patients with PTD history documented in the LIFECODES study, a hospital-based birth cohort in Boston, Massachusetts. Eighty-two respondents reported 94 PTDs that could be linked to medical records. Data on PTD subtype were extracted from medical records as the reference standard. RESULTS: Medical records indicated 47 spontaneous (24 sPTL, 23 pPROM) and 47 ciPTD deliveries occurring a median eight years earlier. The sensitivity and specificity of the recall questionnaire were 88% (95% confidence interval: 68, 97%) and 89% (79, 95%) for sPTL; 96% (78, 100%) and 94% (86, 98%) for pPROM; and 83% (69, 92%) and 100% (92, 100%) for ciPTD, respectively. Greater time since pregnancy did not degrade the sensitivity or specificity of the parental recall questionnaire. CONCLUSIONS: Although derived from a modest sample, the moderate-to-high sensitivity and specificity of the parental recall questionnaire to classify sPTL, pPROM and ciPTD demonstrates its potential for large studies of PTD and for correction of misclassification bias. Future studies are required to test the questionnaire in a variety of populations.

A Comparison of Nifedipine Versus a Combination of Nifedipine and Sildenafil Citrate in the Management of Preterm Labour.

Background Preterm delivery is a significant contributor to neonatal and infant morbidity and mortality. Preventive methods are preferable to treatment protocols for reducing perinatal mortality and morbidity. The calcium channel blocker nifedipine has the potential to be employed as a tocolytic, whereas the phosphodiesterase inhibitor sildenafil citrate promotes smooth muscle relaxation. Objective This study aims to examine the tocolytic effect of nifedipine in combination with sildenafil citrate in managing preterm labour (PTL). Methods After approval from the ethical board, 160 patients fulfilling the selection criteria were enrolled in the study from the outpatient and emergency department of obstetrics and gynaecology, University of Lahore, Pakistan. After taking written informed consent, their demographic profile, i.e., name, age, gestational age at presentation, parity, and expected date of delivery was noted. Patients were randomly assigned in a 1:1 ratio to two study groups (Group A: sildenafil citrate + nifedipine) and (Group B: nifedipine) using a computer-generated random number table to obtain a trial sequence. In group A, each patient was given nifedipine 20 mg orally, followed by 10 mg orally every eight hours for 48 hours and vaginal administration of sildenafil citrate, 25 mg at eight-hour intervals, for 48 hours. In group B, females were given nifedipine 20 mg orally, followed by 10 mg orally every 8 hours for 48 hours. They were kept admitted for 72 hours. SPSS Statistics version 21.0 (IBM Corp. Released 2012. IBM SPSS Statistics for Windows, Version 21.0. Armonk, NY: IBM Corp.) was used to enter and analyse the collected data. Mean and standard deviation was calculated for quantitative variables like age, gestational age at presentation, gestational age at delivery, and BMI. Frequency and percentage were calculated for parity and preterm delivery. Results The study involved 160 patients, with the average age in Group A being 29.60±4.9 years and in Group B being 30.96±4.98 years. In terms of gestational age at delivery, Group A had an average of 34.16±1.7 weeks, while Group B had an average of 33.5±1.8 weeks (p-value<0.05). Preterm delivery was observed in 68.5% of Group A and 41.3% of Group B, with a significant p-value of 0.001. The study also discovered that the duration of prolonged pregnancy was significantly higher in Group A compared to Group B, with averages of 14.96±10.37 days and 10.24±8.97 days, respectively (p-value=0.002). Conclusion The results of this study suggest that the combination of sildenafil citrate and nifedipine may offer a promising new approach to improving pregnancy outcomes in cases of PTL. In the present study, sildenafil citrate plus nifedipine showed a significant effect in the management of PTL and prolongation in mean gestational age at delivery.

New medicines for spontaneous preterm birth prevention and preterm labour management: landscape analysis of the medicine development pipeline.

BACKGROUND: There are few medicines in clinical use for managing preterm labor or preventing spontaneous preterm birth from occurring. We previously developed two target product profiles (TPPs) for medicines to prevent spontaneous preterm birth and manage preterm labor. The objectives of this study were to 1) analyse the research and development pipeline of medicines for preterm birth and 2) compare these medicines to target product profiles for spontaneous preterm birth to identify the most promising candidates. METHODS: Adis Insight, Pharmaprojects, WHO international clinical trials registry platform (ICTRP), PubMed and grant databases were searched to identify candidate medicines (including drugs, dietary supplements and biologics) and populate the Accelerating Innovations for Mothers (AIM) database. This database was screened for all candidates that have been investigated for preterm birth. Candidates in clinical development were ranked against criteria from TPPs, and classified as high, medium or low potential. Preclinical candidates were categorised by product type, archetype and medicine subclass. RESULTS: The AIM database identified 178 candidates. Of the 71 candidates in clinical development, ten were deemed high potential (Prevention: Omega-3 fatty acid, aspirin, vaginal progesterone, oral progesterone, L-arginine, and selenium; Treatment: nicorandil, isosorbide dinitrate, nicardipine and celecoxib) and seven were medium potential (Prevention: pravastatin and lactoferrin; Treatment: glyceryl trinitrate, retosiban, relcovaptan, human chorionic gonadotropin and Bryophyllum pinnatum extract). 107 candidates were in preclinical development. CONCLUSIONS: This analysis provides a drug-agnostic approach to assessing the potential of candidate medicines for spontaneous preterm birth. Research should be prioritised for high-potential candidates that are most likely to meet the real world needs of women, babies, and health care professionals.

A Comparative Study of the Effectiveness of Transdermal Nitroglycerine Patches and Oral Nifedipine in Prolongation of Pregnancy in Women With Preterm Labour.

Backgrounds A significant contributor to newborn morbidity and mortality is preterm birth. Several techniques have been employed to identify patients at risk of premature labour. However, these predictors are not always effective because of their multifactorial aetiology. Preterm labour can be suppressed largely through tocolysis. This study compared the effectiveness and safety of transdermal nitroglycerine and oral nifedipine in preventing premature labour. Methods This study was done at Acharya Vinoba Bhave Rural Hospital, Sawangi, Wardha, Maharashtra, from December 2020 to November 2022, on 130 women presenting with preterm labour pains between 28 and 37 weeks of gestational age. All the women selected were randomized into two equal groups by using the envelope method. Sixty-five women were given a nitroglycerine patch (Group A), and the rest (65 women) were given an oral nifedipine tablet (group B). The variables studied were mean days of prolongation of pregnancy, treatment outcome, steroid coverage, along with feto-maternal outcomes among both groups. Results The percentage of women whose pregnancy was prolonged for at least 48 hours in the nitroglycerine group was 75.3%, and in the nifedipine group it was 93.8%. Failure to achieve tocolysis, defined as delivery within 48 hours, was seen significantly more in the nitroglycerine group (24.6%) than in the nifedipine group (6.1%). The overall foetal outcomes were comparable in both groups. Conclusion Oral nifedipine was found to be superior to transdermal nifedipine patches in terms of efficacy and safety in the management of preterm labour, with a better side effect profile.

Chorioamnionitis secondary to Ureaplasma parvum infection: a case report.

Objectives: Ureaplasma species are the most frequently isolated microorganisms in cases of spontaneous preterm labor, premature rupture of the membranes, or chorioamnionitis. Case presentation: A woman at 28+6 weeks of gestation with no apparent history of interest presented at the hospital with contractions. Upon suspicion of chorioamnionitis, the patient was admitted for a low segment transverse cesarean section, which was completed without any complications. The patient was discharged at 7 days. The newborn remained stable and showed no clinical signs of infection. However, on suspicion of chorioamnionitis, empirical treatment with intravenous ampicillin (2 g every 6 h) and gentamicin (5 mg/kg once daily) was initiated. Samples of pharyngeal/tonsillar, ear, and anal/rectal exudates were collected. At 24 h, all samples were positive for Ureaplasma parvum. Empirical treatment was suspended, and treatment with intravenous azithromycin was initiated (12 mg once daily). Endocervical and placental exudates were also positive for U. parvum. Fifty-two days after birth, the newborn was discharged. Conclusions: The relationship between Ureaplasma spp. colonization and perinatal disease seem to be clear. However, the high frequency of vaginal Ureaplasma spp. colonization and high rates of term labor among pregnant women with this colonization make further studies necessary.

LPCAT1 levels in the placenta, the maternal plasma and the fetal plasma do not predict fetal lung responses to glucocorticoids in a sheep model of pregnancy.

INTRODUCTION: Lysophosphatidylcholine acyltransferase 1 (LPCAT1) is important for saturated phosphatidylcholine (Sat-PC) production in the lung. Sat-PC is a critical component of pulmonary surfactant, which maintains low alveolar surface tension, facilitating respiration. Previous studies have reported an association between maternal and fetal LPCAT1 levels and neonatal lung function. Using a sheep model of pregnancy, we investigated a potential correlation between glucocorticoid-induced lung maturation and LPCAT1 mRNA and/or protein levels in the fetal lung, the placenta, the fetal plasma, and the maternal plasma. METHODS: Eighty seven single pregnant ewes received maternal intramuscular injections of betamethasone. A sub-group of five animals had both maternal and fetal catheters installed to allow for sequential sampling from both plasma compartments. Lambs were surgically delivered under terminal anaesthesia between 2 and 8 days after initial ANS treatment, at a gestational age of 121-123 days. Lambs were ventilated for 30 min to determine functional lung maturation before being euthanized for necropsy and sample collection. Fetal lung, placenta, and fetal and maternal plasma samples were used to analyse LPCAT1 gene expression and protein levels. RESULTS: The expression of LPCAT1 mRNA in the fetal lung was significantly corelated to Sat-PC levels at 8 days (R2 = 0.23, p < 0.001) and lung maturation status overall (gas exchange efficiency as determined by measurements of lamb PaCO2 during ventilation, R2 = 0.20, p < 0.001). Similarly, fetal lung LPCAT1 mRNA was also significantly correlated with the individual durability of ANS effects on fetal lung maturation (R2 = 0.20, p < 0.001). Although ANS therapy altered LPCAT1 mRNA expression in the placenta, observed changes were independent of fetal lung maturation outcomes. Neither maternal nor fetal plasma LPCAT1 levels were changed by ANS therapy over the period, including in analysis of serial maternal and fetal samples from chronically catheterised animals. DISCUSSION: LPCAT1 expression in the fetal lung was associated with the durability of glucocorticoid effects on fetal lung maturation. However, LPCAT1 expression in the placenta, the fetal plasma, and the maternal plasma was neither associated with, nor predictive of fetal lung maturation after glucocorticoid treatment in a sheep model of pregnancy.

A prospective, double-blinded cohort study using quantitative fetal fibronectin testing in symptomatic women for the prediction of spontaneous preterm delivery.

BACKGROUND: Spontaneous preterm birth (PTB) affects 6.5% of deliveries in Hong Kong. Quantitative fetal fibronectin (fFN) is under-utilised as a test for PTB prediction in Hong Kong. Our objective was to evaluate the effectiveness of quantitative fFN in predicting spontaneous PTB in women with symptoms of threatened preterm labour (TPTL) in our population. METHODS: A prospective, double-blinded cohort study of women with a singleton gestation and TPTL symptoms presenting to a tertiary hospital in Hong Kong between 24 + 0 to 33 + 6 weeks was performed from 1st October 2020 and 31st October 2021. Women with vaginal bleeding, ruptured membranes, and cervical dilation > 3 cm were excluded. The primary outcome was to test the characteristics of quantitative fFN in predicting spontaneous PTB < 37 weeks. Secondary outcome was to investigate the relationship between fFN value and time to PTB. Test characteristics of quantitative fFN at different thresholds were evaluated. RESULTS: 48 women with TPTL were recruited. All had fFN testing at admission with the results being concealed from the obstetrician managing the patient. 10 mothers had PTB (< 37 weeks' gestation). 7/48 (15%) had a subsequent PTB within 14 days from testing and 5 (10%) delivered within 48 h. The negative predictive value (NPV) of predicting delivery within 14 days was 97.3% and 100% when using a cut-off of < 50ng/ml and < 10ng/ml respectively. Using > 200 ng/ml as cut-off can also reliably predict delivery within 48 h - 7 days with positive predictive value PPV of 100%; as well as PTB before 37 weeks. CONCLUSIONS: Quantitative fFN has predictive value for spontaneous PTB prediction in symptomatic women in a Hong Kong population. fFN concentration could help clinicians rule out PTB and avoid unnecessary interventions and hospitalisation.

Progestogen maintenance therapy for prolongation of pregnancy after an episode of preterm labour: A systematic review and meta-analysis.

BACKGROUND: Evidence for progestogen maintenance therapy after an episode of preterm labour (PTL) is contradictory. OBJECTIVES: To assess effectiveness of progestogen maintenance therapy after an episode of PTL. SEARCH STRATEGY: An electronic search in Central Cochrane, Ovid Embase, Ovid Medline and clinical trial databases was performed. SELECTION CRITERIA: Randomised controlled trials (RCT) investigating women between 16+0 and 37+0 weeks of gestation with an episode of PTL who were treated with progestogen maintenance therapy compared with a control group. DATA COLLECTION AND ANALYSIS: Systematic review and meta-analysis were conducted. The primary outcome was latency time in days. Secondary neonatal and maternal outcomes are consistent with the core outcome set for preterm birth studies. Studies were extensively assessed for data trustworthiness (integrity) and risk of bias. MAIN RESULTS: Thirteen RCT (1722 women) were included. Progestogen maintenance therapy demonstrated a longer latency time of 4.32 days compared with controls (mean difference [MD] 4.32, 95% CI 0.40-8.24) and neonates were born with a higher birthweight (MD 124.25 g, 95% CI 8.99-239.51). No differences were found for other perinatal outcomes. However, when analysing studies with low risk of bias only (five RCT, 591 women), a significantly longer latency time could not be shown (MD 2.44 days; 95% CI -4.55 to 9.42). CONCLUSIONS: Progestogen maintenance therapy after PTL might have a modest effect on prolongation of latency time. When analysing low risk of bias studies only, this effect was not demonstrated. Validation through further research, preferably by an individual patient data meta-analysis is highly recommended.