History Of Previous Preterm Birth Research Articles

A descriptive study on the risk factors of preterm birth with its maternal and fetal outcomes at a tertiary care hospital

Background: India contributes to greatest number of preterm births all over the world. The global annual prevalence of preterm birth ranges from 9-12%. It is the most common indication for antenatal hospitalization and is the leading cause for under-five mortality. Aims and objectives were to study the incidence, risk factors, clinical presentation, effectiveness of timely intervention and, maternal and fetal outcomes of preterm birth. Methods: A Prospective hospital based cross-sectional study was done from February 2021 to February 2022. Results: The incidence of preterm labour in the study was 24%. Majority of cases presented with symptoms of UTI (47%), vaginal discharge (43%) and leaking per vagina (13%). Infections were the most common aetiology, 40% of cases had positive urine and vaginal swab culture. The most common neonatal complications were respiratory distress syndrome (7%) and neonatal sepsis (7%), others included seizures (2%), birth asphyxia (1%), enterocolitis (1%), hypoxic ischemic encephalopathy (1%), intracranial hemorrhage (1%), meningitis (1%) and pulmonary hemorrhage (1%). 5% of neonatal deaths were noted. Conclusions: Urogenital infections were the commonest etiology for the onset of preterm labour, followed by gestational hypertensive disorders, previous history of preterm birth and anaemia in pregnancy. We conclude that in established preterm labour, aggressive management with antenatal corticosteroids, Magnesium sulphate for neuroprotection when indicated, antibiotic coverage and use of tocolytics with early in-utero transfer of mother to centres with equipped neonatal care units will improve the neonatal outcome.

Prediction of spontaneous preterm birth using CCL2 and CXCL10 in maternal serum of symptomatic high-risk pregnant women: a prospective cohort study

IntroductionCCL2 and CXCL10 are putative biomarkers for the prediction of spontaneous preterm birth. This study evaluates these markers in a cohort of pregnant high-risk women.Material and methodsIn our prospective study, we included 109 women with signs of preterm labor between 20 + 0 and 31 + 6 weeks of gestation. Inclusion criteria were regular (< 3/30 min) or painful contractions, cervical length < 25 mm or a history of previous preterm birth (PTB). Blood samples were obtained upon first admission to our clinic. Biomarker concentrations were measured using pre-coated sandwich immunoassays (ELISA). Primary study outcome was spontaneous preterm birth < 34 weeks, secondary outcome was delivery < 37 weeks or within seven days after study inclusion.ResultsSixteen women (14.7%) delivered < 34 weeks and twenty women between 34 + 0 and 36 + 6 weeks (18.4%). Six patients (5.5%) gave birth within seven days after study admission. CXCL10 showed higher medium serum levels in women with PTB < 34 weeks (115 pg/ml compared to 61 pg/ml ≥ 34 weeks; p < 0.001) and < 37 weeks (103 pg/ml vs. 53 pg/ml; p < 0.001). In contrary, lower CCL2 serum levels were associated with PTB < 34 weeks (46 pg/ml vs. 73 pg/ml; p = 0.032) and birth within 7 days (25 pg/ml vs. 73 pg/ml; p = 0.008). The CXCL10/CCL2-ratio further improved the predictive model with a ROC-AUC of 0.83 (95% CI 0.73–0.93, p < 0.001) for delivery < 34 weeks. These corresponds to a sensitivity, specificity and positive predictive value of 0.67, 0.86 and 0.43 at a cut-off of 2.2.ConclusionLow maternal serum CCL2 levels are associated with a higher risk of preterm delivery within seven days. High CXCL10 serum levels are more associated with a high risk for preterm birth < 34 weeks. Elevated CXCL10/CCL2-ratio is showing the best predictive performance.Trial registration number (DRKS-ID)DRKS00010763, Registration date: September 02, 2016.

Role Of Low Dose Aspirin In Preventing Preterm Birth In Patients With Previous History Of Preterm Delivery

Objective: Preterm birth (PTB) occurs between 24-37 weeks of gestation. The important risk factor for PTB is a previous PTB and currently progesterone is used for the management of recurrent spontaneous PTB. Some studies have shown good outcomes but recent studies revealed that the use of vaginal progesterone was not related to a decreased likelihood of PTB or neonatal adverse effects. Thus, the controversy in the literature suggests multiple underlying pathological mechanisms involved in the progression of PTB. This study aims to determine the role of low-dose aspirin in the prevention of preterm birth in patients with a previous history of preterm delivery. Methodology: In this randomized controlled trial, a total of 172 patients fulfilling the inclusion criteria were selected from the inpatient and outpatient departments. Patients were divided randomly into two groups (group A and group B), using random number tables. In Group A, low-dose aspirin (75mg) was given while group B was taken as a control group. Patients were called every 8 weeks in the outpatient department for the assessment of compliance and side effects of the drug. The data were entered and analyzed by using SPSS v25.0. Chi-square was used to compare the two groups for incidence of preterm birth. Relative risk (along with a 95% confidence interval) for the decrease in the incidence of preterm birth with the use of aspirin was calculated. Results: The age of participants included in the study was 18 to 40 years. The mean age of patients in group A was 33.85±5.210 years and in group B was 32.86±4.139 years. The mean fetal birth weight in group A was 2281.1962±363.125 grams and in group B was 2271.4344±374.797 grams. In the low-dose aspirin group, 10(11.6%) had preterm birth and 31(36.0%) in the control group with a p-value of 0.001, which is statistically significant. The risk of having preterm birth with low-dose aspirin was 1.801 times less than controls. Conclusion: aspirin in low dose given before 14 weeks of gestation decrease spontaneous preterm birth as compared to the control group in a woman with a history of previous preterm birth which was spontaneous

Risk Scoring Systems for Preterm Birth and Their Performance: A Systematic Review.

Introduction: Nowadays, the risk stratification of preterm birth (PTB) and its prediction remain a challenge. Many risk factors associated with PTB have been identified, and risk scoring systems (RSSs) have been developed to face this challenge. The objectives of this systematic review were to identify RSSs for PTB, the variables they consist of, and their performance. Materials and methods: Two databases were searched, and two authors independently performed the screening and eligibility phases. Records studying an RSS, based on specified variables, with an evaluation of the predictive value for PTB, were considered eligible. Reference lists of eligible studies and review articles were also searched. Data from the included studies were extracted. Results: A total of 56 studies were included in this review. The most frequently incorporated variables in the RSS included in this review were maternal age, weight, history of smoking, history of previous PTB, and cervical length. The performance measures varied widely among the studies, with sensitivity ranging between 4.2% and 92.0% and area under the curve (AUC) between 0.59 and 0.95. Conclusions: Despite the recent technological and scientifical evolution with a better understanding of variables related to PTB and the definition of new ultrasonographic parameters and biomarkers associated with PTB, the RSS's ability to predict PTB remains poor in most situations, thus compromising the integration of a single RSS in clinical practice. The development of new RSSs, the identification of new variables associated with PTB, and the elaboration of a large reference dataset might be a step forward to tackle the problem of PTB.

Nonsurgical periodontal treatment during pregnancy and rates of preterm birth

Periodontitis during pregnancy is associated with an increased risk of preterm birth (<37 weeks of gestation) or low birthweight (<2500 g) offspring. Beyond periodontal disease, the risk of preterm birth varies both by previous history of preterm birth and in association with social determinants prevalent among vulnerable and marginalized populations. This study hypothesized that the timing of periodontal treatment during pregnancy and/or social vulnerability measures modified the response to dental scaling and root planing for the treatment of periodontitis and prevention of preterm birth. This study aimed to determine the association of timing of dental scaling and root planing for gravidae with a diagnosed periodontal disease on the rates of preterm birth or low birthweight offspring among subgroups or strata of gravidae as part of the Maternal Oral Therapy to Reduce Obstetric Risk randomized controlled trial. All participants in the study had clinically diagnosed periodontal disease and differed by the timing of the periodontal treatment (dental scaling and root planing at <24 weeks [per protocol] or after delivery) or by baseline characteristics. Although all participants met the well-accepted clinical criteria for periodontitis, not all participants acknowledged a priori that they had periodontal disease. This was a per-protocol analysis of data from 1455 participants of the Maternal Oral Therapy to Reduce Obstetric Risk trial evaluating dental scaling and root planing on the risk of preterm birth or low birthweight offspring. Adjusted multiple logistic regression to control for confounders was used to estimate associations comparing the timing of periodontal treatment in pregnancy to receiving treatment after pregnancy (referent control) on rates of preterm birth or low birthweight among subgroups of gravidae with known periodontal disease. Study analyses were stratified, and the associations with the following characteristics-body mass index, self-described race and ethnicity, household income, maternal education, recency of immigration, and self-acknowledgment of poor oral health, were explored. Dental scaling and root planing during the second or third trimester of pregnancy were associated with an increased adjusted odds ratio of preterm birth among those at the lower body mass index strata (18.5 to <25.0 kg/m2) (adjusted odds ratio, 2.21; 95% confidence interval, 1.07-4.98), but not among individuals who were overweight (body mass index of 25.0 to <30.0 kg/m2; adjusted odds ratio, 0.68; 95% confidence interval, 0.29-1.59) or obese (body mass index of ≥30 kg/m2; adjusted odds ratio, 1.26; 95% confidence interval, 0.65-2.49). There was no significant difference in pregnancy outcomes related to the other evaluated variables: self-described race and ethnicity, household income, maternal education, immigration status, or self-acknowledgment of poor oral health. In this per-protocol analysis of the Maternal Oral Therapy to Reduce Obstetric Risk trial, dental scaling and root planing had no preventive benefit against adverse obstetrical outcomes and were associated with increased odds of preterm birth among individuals at lower body mass index strata. There was no significant difference in the occurrence of preterm birth or low birthweight after dental scaling and root planing periodontitis treatment concerning other analyzed social determinants of preterm birth.

Association between lower uterine wall thickness measured at 18–22 weeks of gestation and risk of Preterm Birth: a prospective cohort study

BackgroundPreterm labour prediction has been relied on history of previous preterm birth and cervical length of current pregnancy. However, universal cervical length measurement has some limitation. We aim to find a surrogate marker of cervical length to close the gap in preterm prevention program and lower uterine wall thickness seems promising. We generate the nomogram of lower uterine wall thickness during 18–22 weeks of gestation and evaluate the accuracy of LUW thickness as a predictor of preterm delivery before 37 weeks.MethodsThis prospective cohort study included 524 Thai singleton pregnant women at 18–22 weeks of gestation between November 2016 and October 2017. After signing informed consent, transabdominal ultrasonography was performed to examine fetal anatomical structures and to measure LUW thickness. The results were blinded to the caregivers. The outcomes of all pregnancies were followed. The LUW thickness at 10th percentiles was established and was correlated with the outcomes of pregnancy. The performance of LUW thickness at 10th percentile as a predictor of preterm delivery was calculated. The intra-observer and inter-observer reliability of measurement were assessed by intraclass correlation coefficient and Bland-Altman plot.ResultsOf the 524 pregnant women, 64 (12.2%) delivered before 37 weeks of gestation. The reference value of lower uterine wall thickness at 18–22 weeks was established. Mean and 10th percentile of LUW thickness were 6.2 and 4.5 mm respectively. The inter-observer and intra-observer variation of measurement were small (intraclass correlation coefficient = 0.926 and 0.989 respectively). Using LUW thickness at less than 4.5 mm as a predictor of preterm delivery, we found a 2.37 folds increased risk of preterm delivery after adjustment of other factors (p = 0.037). Sensitivity, specificity, positive predictive value and negative predictive value were 14% (95% CI: 6.64–25.02), 92.8% (95% CI: 90.06–95.12), 22.5% (95% CI: 12.66–36.76) and 88% (95% CI: 86.92–89.08) respectively.ConclusionsThe measurement of LUW thickness by transabdominal ultrasonography is feasible and reproducible. The risk of delivery before 37 weeks of gestation is increased significantly if the LUW thickness at 18–22 weeks is less than 4.5 mm.Trial registrationThe study protocol was approved by institutional ethical committee (COA No. Si 657/2016).

Prevalence of preterm birth and perinatal outcome: A rural tertiary teaching hospital-based study.

Preterm birth is defined as births before 37 weeks of gestational age. Preterm birth is a major challenge in obstetric health care and leading cause of perinatal mortality and long-term morbidity. Complications arising from preterm births are the leading cause of deaths among children less than 5 years of age. Seventy-five percent of them could be saved with current, cost-effective interventions. The rate of preterm births worldwide is 5-18% with the developing countries accounting for the maximum deaths. This study was undertaken to evaluate the prevalence of preterm births and risk factors associated with it among women delivered at a rural tertiary teaching hospital in Telangana and further assess its impact on perinatal outcome. This was a retrospective case control study conducted at Mediciti Institute of Medical Sciences from January 2019 to December 2019. Of the 1243 deliveries during the study period, 135 births that occurred at <37 weeks were taken as cases and 248 term neonates were taken as control group. Data were collected retrospectively through review of prenatal and hospital delivery records. Data were collected and tabulated as shown in the results. Statistical analysis was done using Microsoft Excel. Frequency and percentage of each parameter were calculated and analyzed. The risk estimates were analyzed between the cases and controls by calculating the odds ratio, 95% confidence interval, and P value. P Value of <0.05 was considered significant. The prevalence rate of preterm birth was 10.86%. History of previous preterm birth (OR = 4.88, C.I: 1.50-15.87, P = 0.0084), previous LSCS (OR = 2.16, C.I: 1.36-3.44, P = 0.001), inter-pregnancy interval <12 months (OR = 2.78, C.I: 1.13-6.84, P = 0.026), hypertension (OR = 3.10, C.I: 1.78-5.42, P = 0.0001), PROM (OR =0.73, C.I: 2.36-9.49, P < 0.0001), Oligohydramnios (OR = 3.58, C.I: 1.29-9.9, P = 0.01), and multiple pregnancy (OR = 24.09, C.I: 3.09-187.46, P = 0.0024) were found to be significant risk factors for preterm birth. Though the NICU admission rate was high (52%), neonatal outcome was found to be satisfactory. Some of the risk factors that contributed to preterm birth were modifiable. Preventive strategies addressing the risk factors such as hypertension, oligohydramnios, and also improving health care quality to pregnant women will reduce the prevalence of preterm births and outcomes.

17-alpha hydroxyprogesterone caproate for the prevention of recurrent preterm birth among singleton pregnant women with a prior history of preterm birth: a systematic review and meta-analysis of six randomized controlled trials.

To perform a systematic review and meta-analysis of all randomized controlled trials (RCTs) that investigated the clinical benefits of 17-alpha hydroxyprogesterone caproate (17OHPC) in the prevention of recurrent preterm birth (PTB) among singleton pregnant women with a previous history of PTB. We searched four major databases up till April 2021 and assessed the risk of bias in the included studies. We meta-analyzed various maternal-neonatal endpoints (n=18) and pooled them as mean difference or risk ratio (RR) with 95% confidence interval (CI) using the random-effects model. Six RCTs met the inclusion criteria, comprising 2,573 patients (17OHPC=1,617, control=956). RCTs revealed an overall low risk of bias. The rates of PTB <35 weeks (n=5 RCTs; RR, 0.77; 95% CI, 0.63–0.93; P=0.008), PTB <32 weeks (n=3 RCTs; RR, 0.68; 95% CI, 0.51–0.91; P=0.009), neonates with low birth weight (<2.5 kg) at delivery (n=3 RCTs; RR, 0.63; 95% CI, 0.5–0.79; P<0.001), and neonatal death (n=4 RCTs; RR, 0.41; 95% CI, 0.20–0.84; P=0.02) were significantly reduced in the 17OHPC group compared with the control group. Moreover, 17OHPC treatment correlated with a significantly decreased rate of retinopathy (n=2 RCTs; RR, 0.42; 95% CI, 0.18–0.97; P=0.004). However, there were no significant differences in the rates of neonatal intensive care unit admission, cesarean delivery, and other preterm-related complications between both the groups. Among singleton pregnant women with a prior history of PTB, 17OHPC may favorably decrease the risks of recurrent PTB and reduce the rate of neonatal death.

FIGO good practice recommendations on progestogens for prevention of preterm delivery.

Women at high risk of preterm birth (either a previous spontaneous preterm birth and/or sonographic short cervix) with a singleton gestation should be offered daily vaginal progesterone or weekly 17‐OHPC treatment to prevent preterm birth. Benefit is most significant in those with prior history of preterm birth and a short cervix. For women with a previous spontaneous preterm birth and a cervix ≥30 mm the effectiveness of progesterone is uncertain. In asymptomatic women with no prior history of previous preterm birth, no mid‐trimester loss, or no short cervical length, progesterone therapy is not recommended for the prevention of preterm birth. For those with unselected multiple pregnancies, progesterone therapy is not recommended for the prevention of preterm birth. Daily vaginal progesterone or weekly 17‐OHPC treatment can be used for the prevention of preterm birth. The preparation used should be decided by the woman and her clinician. There is no evidence of neurological or developmental benefit or harm in babies whose mothers use progestogens for preterm birth prevention antenatally.

Risk factors of early and late preterm birth

Preterm birth (PTB) is one of the major causes of morbidity in newborn. The aim of this study was to estimate the prevalence and to compare the associated risk factors of early and late PTB. This was a hospital-based cross sectional study conducted in 2016/2017. Women, 271, having PTB at 28-33+6 weeks period of gestation was taken as early PTB and 34-36+6 were taken as late PTB. Data was collected using semi-structured questionnaire, patients’ record book, adopting face- to - face interview technique and clinical examination. The annual prevalence of PTB was 7.25% of which 11% were &lt;28+0 weeks, early PTB was 32% and late PTB was 57%. Mother with school education were 2.0 times more likely to have early preterm births than those having higher education (P-value: 0.005, COR: 2.061,95% CI:1.234-3.441). Mothers with positive history of PTB in any of previous pregnancy was 10.7 times more likely to have early PTB in current pregnancy (P-value: &lt;0.001, COR: 10.677, 95% CI: 2.792 – 40.746). Both variables were found to have independent risk on early PTB in logistic regression analysis (education: P-value: 0.027, aOR: 2.973, 95% CI: 1.132- 3.047; previous history of PTB: P-value: 0.002, aOR: 9.191, 95% CI: 2.308 - 36.596). Early and late PTB have differential risk factors. Mothers with positive history of PTB and having lower level of education were more likely to have early PTB.

Comparison of the frequency of preterm births in patients treated with oral versus intramuscular progesterone with history of previous preterm birth

Background: Globally, it has proven that preterm birth is associated with perinatal mortality to the extent of &gt;75%, and &gt;50% of perinatal and long term morbidity. Oral progesterone are easy to take but are less effective because of first pass hepatic metabolism leading to variable plasma levels while intramuscular progesterone carries the risk of swelling and bruising at injection site. The aim was to find out frequency of preterm birth in patients treated with oral versus intramuscular progesterone.Methods: Randomized controlled trial conducted in the department of obstetrics and gynecology, Sir Ganga Ram hospital Lahore, Pakistan conducted from 5 October 2017 to 4 April 2018. This study involved 530 pregnant women with history of at least 1 previous preterm delivery presenting in antenatal clinic between 16-20 weeks of gestation. Group I received oral progesterone 10 mg tablet duphaston BD from 20 weeks till 37 weeks. Group II received intramuscular progesterone injection proluton depot 250 mg IM weekly from 16-20 weeks till 37 weeks.Results: The mean age of the patients was 27.52±4.57 years while the mean gestational age was 17.39±1.38 weeks. 47.5% of the patients were para 2 followed by para 3 (32.3%) and para 1 (20.2%). The mean gestational age at delivery was significantly higher among intramuscular group (36.14±2.23 versus 35.07±2.97 weeks; p=0.000). The frequency of preterm delivery was significantly lower in intramuscular group (24.9% versus 39.6%; p=0.000) as compared to oral group.Conclusions: Frequency of preterm delivery was significantly lower in patients treated with intramuscular progesterone (24.9% versus 39.6%; p=0.000) as compared to oral progesterone.

Predictors of cerclage failure in singleton pregnancies with a history of preterm birth and a sonographic short cervix

To identify predictors of ultrasound-indicated cerclage failure in singleton pregnancies for preventing extremely preterm birth. A retrospective cohort study included 96 singleton pregnancies with ultrasound-indicated McDonald cerclage in women with prior preterm birth (PTB) and cervical shortening. Descriptive statistics were calculated at baseline and logistic regression analyses were performed to identify the factors associated with cerclage failure. In all, 28 (29%) of them suffered preterm delivery at <28 weeks. Multivariate analysis identified cervical dilation, noncephalic presentation, and platelet-lymphocyte ratio (PLR) as independent predictors of cerclage failure (OR, 3.12, 95%CI, 1.01-9.66; OR, 5.81, 95%CI, 1.04-32.53; OR, 1.02, 95%CI, 1.01-1.03, respectively). The efficacy of these predictors was evaluated using a receiver operating characteristics. The area under the curve was 0.87 (95%CI: 0.78-0.96, P<0.001) with a sensitivity of 78.6% and specificity of 88.2%. Our findings indicated that cervical dilation, fetal presentation, and PLR were valuable predictors of cerclage failure in singleton pregnancies with a history of PTB and a sonographic short cervix. Theresultscan be potentially usedto assess the prognosis of patients after cerclage and alert clinicians to considerenhanced surveillance and administration of individuals at an increased risk.

The association between maternal and paternal race and preterm birth

Non-Hispanic black maternal race is a known risk factor for preterm birth. However, the contribution of paternal race is not as well established. We sought to evaluate the risk of preterm birth among non-Hispanic black, non-Hispanic white, and mixed non-Hispanic black and non-Hispanic white dyads. This was a population-based cohort study of all live births in the United States from 2015 to 2017, using live birth records from the National Vital Statistics System. Singleton, nonanomalous infants whose live birth record included maternal and paternal self-reported race as either non-Hispanic white or non-Hispanic black were included. The primary outcome was preterm birth at <37 weeks' gestation; secondary outcomes included preterm birth at <34 and <28 weeks' gestation and delivery gestational age (as a continuous variable). Data were analyzed using chi-square, t test, analysis of variance, and logistic regression. A Kaplan-Meier survival curve was also generated. There were 11,809,599 live births during the study period; 4,008,622 births met the inclusion criteria. Of included births, 291,647 (7.3%) occurred at <37 weeks' gestation. Using the convention of maternal race first followed by paternal race, preterm birth at <37 weeks' gestation was most common among non-Hispanic black and non-Hispanic black dyads (n=70,987 [10.8%]), followed by non-Hispanic black and non-Hispanic white (n=3137 [9.5%]), non-Hispanic white and non-Hispanic black (n=9136 [8.3%]), and non-Hispanic white and non-Hispanic white dyads (n=209,387 [6.5%]; P<.001 for trend). Births at <34 weeks' (n=74,474) and <28 weeks' gestation (n=18,474) were also more common among non-Hispanic black and non-Hispanic black dyads. Specifically, 24,351 (3.7%) non-Hispanic black and non-Hispanic black, 1017 (3.1%) non-Hispanic black and non-Hispanic white, 2408 (2.2%) non-Hispanic white and non-Hispanic black, and 46,698 non-Hispanic white and non-Hispanic white dyads delivered at <34 weeks' gestation, and 7988 non-Hispanic black and non-Hispanic black (1.2%), 313 (1.0%) non-Hispanic black and non-Hispanic white, 584 (0.5%) non-Hispanic white and non-Hispanic black, and 9589 (0.3%) non-Hispanic white and non-Hispanic white dyads delivered at <28 weeks' gestation. Non-Hispanic white and non-Hispanic white dyads delivered at a mean 38.8± standard deviation of 1.7 weeks' gestation, although non-Hispanic white and non-Hispanic black, non-Hispanic black and non-Hispanic white, and non-Hispanic black and non-Hispanic black dyads delivered at 38.6±2.0, 38.5±2.3, and 38.3±2.4 weeks' gestation, respectively (P<.001). Adjusted odds ratios for the association between maternal or paternal race and preterm birth were highest for non-Hispanic black and non-Hispanic black dyads at each gestational age cutoff: adjusted odds ratio, 1.60 (95% confidence interval, 1.11-1.19) (<37 weeks' gestation); adjusted odds ratio, 2.47 (95% confidence interval, 2.41-2.53) (<34 weeks' gestation); and adjusted odds ratio, 4.22 (95% confidence interval, 4.04-4.41) (<28 weeks' gestation) compared with the non-Hispanic white referent group. Models adjusted for insurance status, chronic hypertension, tobacco use during pregnancy, history of previous preterm birth, and male fetus. In the Kaplan-Meier survival analysis, non-Hispanic black and non-Hispanic black dyads delivered the earliest across the range of delivery gestational ages compared with all other combinations of dyads. Non-Hispanic black paternal race is a risk factor for preterm birth and should be considered when evaluating maternal a priori risk of prematurity. Future research should investigate the mechanisms behind this finding, including determining the contribution of factors, such as racism, maternal and paternal genetics, and epigenetics to an individual's risk of preterm birth.

Family history is a predictor of current preterm birth

Reliable prediction of spontaneous preterm birth remains limited, particularly for nulliparous and multiparous women without a personal history of preterm birth. Although previous preterm birth is a risk factor for recurrent preterm birth, most spontaneous preterm births occur in women with no previous history of preterm birth. This study aimed to determine whether patients' self-reported maternal family history of preterm births among siblings and across 3 generations was an independent risk factor for spontaneous preterm births after controlling for potential confounders. This was a retrospective analysis of a prospectively acquired cohort using a comprehensive single, academic center database of deliveries from August 2011 to July 2017. The objective of the current analysis was to evaluate the risk of preterm birth among women with and without a family history of preterm birth. All subjects in the database were directly queried regarding familial history across 3 generations, inclusive of obstetrical morbidities. Index subjects with probable indicated preterm birth (eg, concurrent diagnosis of preeclampsia; hemolysis, elevated liver enzymes, and low platelet count; or placenta previa or placenta accreta) were excluded, as were nonsingleton pregnancies. Univariate and multivariate analyses with logistic regression were used to determine significance and adjusted relative risk. In this study, 23,816 deliveries were included, with 2345 (9.9%) born prematurely (<37 weeks' gestation). Across all subjects, preterm birth was significantly associated with a maternal family history of preterm birth by any definition (adjusted relative risk, 1.44; P<.001), and the fraction of preterm birth occurring in women with a positive family history increased with decreasing gestational age at which the index subjects of preterm birth occurred. For nulliparous women, a history in the subject's sister posed the greatest risk (adjusted relative risk, 2.25; P=.003), whereas for multiparous women with no previous preterm birth, overall family history was most informative (P=.003). Interestingly, a personal history of the index subject herself being born preterm presented the greatest individual risk factor (adjusted relative risk, 1.94; P=.004). Spontaneous preterm birth in the current pregnancy was significantly associated with a maternal family history of preterm birth among female relatives within 3 generations and notably sisters. The risk persisted among gravidae without a previous preterm birth, demonstrating the capacity for familial history to independently predict risk of spontaneous preterm birth even in the context of a negative personal history. This study provides evidence that self-reported maternal family history is relevant in a US population cohort and across more distant generations than has previously been reported.

Maternal cigarette smoking before and during pregnancy and the risk of preterm birth: A dose-response analysis of 25 million mother-infant pairs.

BackgroundMost of the women who smoke before pregnancy continue smoking during pregnancy, and some start to quit smoking after being pregnant, although existing guidelines for pregnancy recommend that women who smoke should quit smoking before pregnancy. Findings about the timing and intensity of maternal smoking, especially low-intensity smoking (1–9 cigarettes per day), and preterm birth are still inconsistent and ambiguous. This study aimed to examine the association of the timing of smoking and doses of smoking before pregnancy and during the first or second trimester of pregnancy with preterm birth in a large-scale population-based retrospective cohort study.Methods and findingsWe used nationwide birth certificate data from singleton mother–infant pairs in the United States National Vital Statistics System, 2011–2018. All adult women with live singleton births, without preexisting hypertension or diabetes, and with complete data on smoking and gestational age at delivery were included. Participants reported their smoking status (yes or no) and daily number of cigarettes consumed before and during each trimester of pregnancy. The outcome of interest was preterm birth, defined as a birth before 37 weeks of gestation. Logistic regression models were used to estimate the odds ratio (OR) with 95% confidence intervals (CIs) of preterm birth associated with smoking status and the number of cigarettes consumed, adjusting for maternal age, race/ethnicity, parity, education levels, prepregnancy BMI, previous history of preterm birth, marital status, infant sex, and initiation of prenatal care. This study included 25,623,479 women, with a mean age of 29 years (range 20–50 years); 13,742,486 (53.6%) participants were of non-Hispanic white ancestry, 5,971,598 (23.3%) of Hispanic ancestry, and 3,417,456 (13.34%) of non-Hispanic black ancestry. The prevalence of preterm birth was 9.3% (n = 2,378,398). We found that maternal smoking during pregnancy, even at a very low level of intensity, was associated with an increased risk of preterm delivery. The adjusted ORs (95% CI) of preterm birth for mothers who smoked 1–2, 3–5, 6–9, 10–19, and ≥20 cigarettes per day during the first trimester compared with mothers who did not smoke were 1.31 (1.29–1.33), 1.31 (1.30–1.32), 1.33 (1.31–1.35), 1.44 (1.43–1.45), and 1.53 (1.52–1.55), respectively (all P values < 0.001), whereas for those who smoked during the second trimester, the corresponding ORs were 1.37 (1.35–1.39), 1.36 (1.35–1.38), 1.36 (1.34–1.38), 1.48 (1.47–1.49), and 1.59 (1.58–1.61), respectively (all P values < 0.001). Furthermore, smokers who quit before pregnancy, regardless of smoking intensity, had a comparable risk of preterm birth with nonsmokers, although this was not the case when cessation occurred in the first or second trimester of pregnancy. The major limitation of this study is the self-reported information about smoking, which may be subject to information bias. In addition, we cannot rule out the possibility of residual confounding caused by unmeasured factors in an observational research design.ConclusionsIn this study, we observed that low-intensity cigarette consumption during either the first or second trimester of pregnancy, even as low as 1–2 cigarettes per day, was associated with an increased risk of preterm birth. These findings suggest that there is no safe level or safe trimester for maternal smoking during pregnancy. Women of reproductive age who smoke should be strongly encouraged and supported to quit smoking before pregnancy.

Efficacy of intramuscular progesterone in prevention of preterm birth in patients with history of preterm birth

Background: Preterm birth is associated with many adverse outcomes and is defined as birth of a baby before 37 weeks of gestation. Around 15 million babies born preterm around the world with survival rates at different gestational like less 23 week, 23 weeks, 24 weeks and 25 weeks are 0%, 15%, 55% and 80% respectively. Progesterone has shown to reduce the incidence of preterm birth. Objective of the study was to find out frequency of preterm birth in patients (with previous history of preterm birth) treated with intramuscular progesterone.Methods: It was randomized controlled trial conducted in the department of Obstetrics and Gynecology, Unit-I, Sir Ganga Ram Hospital Lahore, Pakistan conducted from October 2017 to April 2018. It included 530 pregnant women with history of at least 1 previous preterm delivery presenting in antenatal clinic between 16-20 weeks of gestation. The lottery method was employed to segregate patients in two groups. Patients received intramuscular progesterone injection proluton depot 250 mg intramuscular weekly from 16-20 weeks till 37 weeks and other group received placebo drug.Results: Mean age was 27.52±4.57 years while the mean gestational age was 17.39±1.38 weeks. The mean gestational age at delivery was significantly higher among intramuscular group (36.14±2.23 versus 35.07±2.97 weeks; p=0.000). The frequency of preterm delivery was significantly lower in intramuscular group (24.9% versus 39.6%; p=0.000) as compared to placebo group.Conclusions: Frequency of preterm delivery was significantly lower in patients treated with intramuscular progesterone (24.9% versus 39.6%; p=0.000) irrespective of patients age, parity, BMI and number of previous preterm deliveries.

Adherence rates and outcomes for 17-hydroxyprogesterone caproate use in women with a previous history of preterm birth

Progesterone has been used for preventing preterm birth with mixed results. The American College of Obstetricians and Gynecologists and Society for Maternal-Fetal Medicine recommended the use of 17-hydroxyprogesterone caproate for risk reduction of recurrent spontaneous preterm birth based on the results of a multicenter, randomized trial in the United States. However, recent literature lacks consensus for efficacy in the American population. In addition, partial adherence and outcomes thereof are underreported. Hence, the relationship between practical adherence to 17-hydroxyprogesterone caproate and outcomes were evaluated. The objective of this study was to evaluate the adherence to 17-hydroxyprogesterone caproate, defined as receipt of greater than 80% of intended injections, at an outpatient maternal-fetal medicine center and its effect on maternal and neonatal outcomes. This retrospective cohort study included women older than 18 years with a singleton gestation, history of spontaneous preterm birth who initiated 17-hydroxyprogesterone caproate weekly injections between 16 and 20 weeks' gestational age and delivered between the years 2014 and 2017. Women receiving 17-hydroxyprogesterone caproate injections outside of the clinic were excluded. The primary outcome of adherence and secondary outcomes of gestational age at delivery, birthweight, and neonatal outcomes were analyzed using descriptive data, independent t-test, Mann-Whitney U test, chi-square test, and Fisher exact test, where appropriate, with a P value <.05 being considered significant. Adherence to 17-hydroxyprogesterone caproate occurred in 38 of 92 (41.3%) women included in the study. At baseline, there was a difference in age between groups of adherent and nonadherent women (adherent: 30.8 years; nonadherent: 27.4 years; P=.002). The rate of spontaneous preterm birth less than 37, 35, and 32 weeks were not significantly different in those who were adherent vs nonadherent to 17-hydroxyprogesterone caproate. There were no differences in gestational age at delivery (adherent: 36.8±2.6 weeks; nonadherent: 36.5±3.8 weeks; P=.66), birthweight (adherent: 2776 g; nonadherent: 2709 g; P=.68), or composite neonatal morbidity (adherent: 18.4%; nonadherent: 20.4%; P=.86) between the adherent and nonadherent groups. Neonatal intensive care unit length of stay was 15.5 days in the adherent group compared with 15 days in the nonadherent group (P=.72). Real-world adherence to 17-hydroxyprogesterone caproate is suboptimal with less than half of women adherent to in-clinic administration. Adherence to 17-hydroxyprogesterone caproate was not associated with a difference in gestational age at delivery or birthweight compared with nonadherence. Further studies are needed to assess the outpatient administration and benefit of 17-hydroxyprogesterone caproate therapy.

The effect of early administration of rectal progesterone in IVF/ICSI twin pregnancies on the preterm birth rate: a randomized trial

BackgroundThe rate of multiple pregnancies in IVF/ICSI ranges from 20 to 30%. The incidence of preterm birth in multiple pregnancies is as high as 60% and is even higher in pregnancies conceived after IVF & ICSI. The effect of progesterone on prevention of preterm birth in twins is controversial. Our group has proven a positive effect in reduction of preterm birth, by starting progesterone from the mid-trimester, in exclusively IVF/ICSI singleton pregnancies but not twins. The purpose of our current study was to explore the effect of earlier administration of natural progesterone, in IVF/ICSI twin pregnancies starting at 11–14 weeks for prevention of preterm birth.MethodsThis is a double-blind, placebo controlled, single center, randomized clinical trial. Women with dichorionic twin gestations, having an IVF/ICSI trial were randomized to receive natural rectal progesterone (800 mg daily) vs placebo, starting early from 11 to 14 weeks. They also received oral and vaginal antimicrobial agents as part of our routine treatment for vaginitis and urinary tract infection. They were randomized regardless of cervical length and had no previous history of preterm birth or known Mullerian anomalies. The primary outcome was spontaneous preterm birth rate before 37 weeks. The secondary outcome was; spontaneous preterm birth before 34, 32, 28 weeks and neonatal outcome.ResultsA total of 203 women were randomized to both groups, final analysis included 199 women as 4 were lost to follow up. The base line characteristics as well as gestational age at delivery were not significantly different between the study and the placebo group (34.7 ± 3.6 vs 34.5 ± 4.5, P = 0.626). Progesterone administration was not associated with a significant decrease in the spontaneous preterm birth rates before 37 weeks (73.5% vs 68%, P = 0.551), before 34 (20.6% vs 21.6%, P = 0.649), before 32 (8.8% vs 12.4%, P = 0.46) & before 28 (4.9% vs 3.1%, P = 0.555) weeks.ConclusionsRectal natural progesterone starting from the first trimester in IVF/ICSI twin pregnancies did not reduce spontaneous preterm birth.Trial registrationThe trial was registered on 31 January 2014 at www.ISRCTN.com, number 69810120.

Correlation of transabdominal and transvaginal sonography for the assessment of uterocervical angle at 16–24 weeks’ gestation

The objective of this study was to determine the correlation between transabdominal (TAS) and transvaginal sonography (TVS) uterocervical angle (UCA) measurement in pregnant women with no history of previous preterm birth. A cross-sectional study involving singleton pregnancies between 16 and 24 weeks of gestation who underwent routine foetal anatomical scan was conducted. The TAS-UCA measurement was performed before voiding and with an empty bladder. A total of 256 women completed the sonography. The mean maternal age was 32 ± 6.68 years. The mean gestation age at the time of ultrasound assessment was 19 ± 1.71 weeks. The mean prevoid TAS-UCA was 119.74 ± 33.12° and the mean postvoid TAS-UCA was 110.73 ± 25.30°. There was a significant difference between prevoid and postvoid TAS-UCA measurement (p < .05). The mean TVS-UCA was 103.91 ± 26.42°. The Pearson correlation coefficients of prevoid and postvoid TAS-UCA with TVS-UCA were 0.438 and 0.601, respectively. In conclusion, the postvoid TAS-UCA has moderate correlation with TVS-UCA measurement and is better than the prevoid TAS-UCA in women with low risk for preterm birth.IMPACT STATEMENTWhat is already known on this subject? TVS is the gold standard for cervical length (CL) assessment for prediction preterm birth. However, TVS requires an experienced or trained sonographer and some women decline TVS because of the embarrassment and discomfort during examination. Several studies have demonstrated the correlation between TAS and TVS and suggested that TAS could be an alternative for CL screening. UCA has been reported as a new predictor of spontaneous preterm birth and is usually performed by TVS. Thus, it is interesting to evaluate whether TAS can be a substitute procedure for TVS in UCA measurement.What the results of this study add? TAS may be used as a substitute procedure for TVS and the postvoid TAS is more appropriate than prevoid TAS for UCA measurement.What the implications are of these findings for clinical practice and/or further research? TAS may be an alternative method for UCA measurement when TVS is unavailable or in pregnant women who decline TVS-UCA measurement. However, further study should be conducted to confirm the association between TVS-UCA and postvoid TAS-UCA before deciding to use postvoid TAS-UCA as a screening tool for preterm prediction.

The effects of progesterone therapy in pregnancy: vaginal and intramuscular administration

Aim This study was performed to evaluate the effects of vaginal versus intramuscular progesterone supplementations on the mood, quality of life, and metabolic changes in pregnant women with the history of previous preterm birth. Methods This study was conducted as a prospective, randomized, open label, clinical trial evaluated 100 pregnant women who referred for prenatal visit, with 16–17 weeks of gestation from September 2014 through October 2015. The mothers were then randomly allocated into two groups: the vaginal progesterone group to receive 400 mg cyclogest vaginal suppositories (Actavis, UK limited, England) once daily, and the intramuscular progesterone group to receive weekly intramuscular injections of 250 mg of 17-hydroxyprogesterone caproate (17-HPC) (Bayer Schering Pharma, Germany), starting from the 16th to the 35th weeks of pregnancy. Demographics, medical and obstetrical history, sleeping disturbances, alteration in sexual desire, nausea/vomiting, serum levels of fasting blood sugar (FBS), high-density lipoprotein (HDL), and low-density lipoprotein (LDL) were evaluated, first and 8 weeks later. Results About 11 (11.2%) screened positive for psychosocial disorders; 25 (25.5%) had sleep disturbance, 11 (11.2%) had alteration in sexual desire, and 29 (29.6%) had nausea/vomiting upon enrollment. After 2 months of receiving daily vaginal progesterone, there was a significant increase in the GHQ-28 score (p < .001), and rates of positive screening for psychosocial disorders (p = .001) in this group. No statistically significant differences were observed in the HDL levels (p = .06), LDL levels (p = .15), rates of impaired FBS (p = .08), nausea/vomiting (p = .2), sexual desire alteration (p = .56), and sleep disturbance (p = 1) in the participants who were randomized to this group. Conclusion Our results indicated that psychosocial disorders increased significantly at 24th week gestational age after 2 months of progesterone consumption in both groups which could show psychological impact of progesterone regardless of the route of consumption. This calls for higher psychological attention in these women.