Prediction of preterm birth in growth-restricted and appropriate-for-gestational-age infants using maternal PlGF and the sFlt-1/PlGF ratio-A prospective study.

OBJECTIVE: To assess the utility of placental growth factor (PlGF) levels and the soluble fms-like tyrosine kinase-1/placental growth factor (sFlt-1/PlGF) ratio to predict preterm birth (PTB) for infants with fetal growth restriction (FGR) and those appropriate for gestational age (AGA). DESIGN: Prospective, observational cohort study. SETTING: Tertiary maternity hospital in Australia. POPULATION: There were 320 singleton pregnancies: 141 (44.1%) AGA, 83 (25.9%) early FGR (<32+0 weeks) and 109 (30.0%) late FGR (≥32+0 weeks). METHODS: Maternal serum PlGF and sFlt-1/PlGF ratio were measured at 4-weekly intervals from recruitment to delivery. Low maternal PlGF levels and elevated sFlt-1/PlGF ratio were defined as <100 ng/L and >5.78 if <28 weeks and >38 if ≥28 weeks respectively. Cox proportional hazards models were used. The analysis period was defined as the time from the first measurement of PlGF and sFlt-1/PlGF ratio to the time of birth or censoring. MAIN OUTCOME MEASURES: The primary study outcome was overall PTB. The relative risks (RR) of birth within 1, 2 and 3 weeks and for medically indicated and spontaneous PTB were also ascertained. RESULTS: The early FGR cohort had lower median PlGF levels (54 versus 229 ng/L, p < 0.001) and higher median sFlt-1 levels (2774 ng/L versus 2096 ng/L, p < 0.001) and sFlt-1/PlGF ratio higher (35 versus 10, p < 0.001). Both PlGF <100 ng/L and elevated sFlt-1/PlGF ratio were strongly predictive for PTB as well as PTB within 1, 2 and 3 weeks of diagnosis. For both FGR and AGA groups, PlGF <100 ng/L or raised sFlt-1/PlGF ratio were strongly associated with increased risk for medically indicated PTB. The highest RR was seen in the FGR cohort when PlGF was <100 ng/L (RR 35.20, 95% CI 11.48-175.46). CONCLUSIONS: Low maternal PlGF levels and elevated sFlt-1/PlGF ratio are potentially useful to predict PTB in both FGR and AGA pregnancies.

Prediction of preterm birth in women with fetal growth restriction - Is the weekly change in sFlt-1/PlGF ratio or PlGF levels useful?

INTRODUCTION: To assess the rate of change in soluble fms-like tyrosine kinase-1/placental growth factor (sFlt-1/PlGF) ratio and PlGF levels per week compared to a single sFlt-1/PlGF ratio or PlGF level to predict preterm birth for pregnancies complicated by fetal growth restriction. MATERIAL AND METHODS: A prospective cohort study of pregnancies complicated by isolated fetal growth restriction. Maternal serum PlGF levels and the sFlt-1/PlGF ratio were measured at 4-weekly intervals from recruitment to delivery. We investigated the utility of PlGF levels, sFlt-1/PlGF ratio, change in PlGF levels per week or sFlt-1/PlGF ratio per week. Cox-proportional hazard models and Harrell's C concordance statistic were used to evaluate the effect of biomarkers on time to preterm birth. RESULTS: The total study cohort was 158 pregnancies comprising 91 (57.6%) with fetal growth restriction and 67 (42.4%) with appropriate for gestational age controls. In the fetal growth restriction cohort, sFlt-1/PlGF ratio and PlGF levels significantly affected time to preterm birth (Harrell's C: 0.85-0.76). The rate of increase per week of the sFlt-1/PlGF ratio (hazard ratio [HR] 3.91, 95% confidence interval [CI]: 1.39-10.99, p = 0.01, Harrell's C: 0.74) was positively associated with preterm birth but change in PlGF levels per week was not (HR 0.65, 95% CI: 0.25-1.67, p = 0.37, Harrell's C: 0.68). CONCLUSIONS: Both a high sFlt-1/PlGF ratio and low PlGF levels are predictive of preterm birth in women with fetal growth restriction. Although the rate of increase of the sFlt-1/PlGF ratio predicts preterm birth, it is not superior to either a single elevated sFlt-1/PlGF ratio or low PlGF level.

The influence of birthweight on mortality and severe neonatal morbidity in late preterm and term infants: an Australian cohort study.

Background: The aim of this study was to detail incidence rates and relative risks for severe adverse perinatal outcomes by birthweight centile categories in a large Australian cohort of late preterm and term infants. Methods: This was a retrospective cohort study of singleton infants (≥34+0 weeks gestation) between 2000 and 2018 in Queensland, Australia. Study outcomes were perinatal mortality, severe neurological morbidity, and other severe morbidity. Categorical outcomes were compared using Chi-squared tests. Continuous outcomes were compared using t-tests. Multinomial logistic regression investigated the effect of birthweight centile on study outcomes. Findings: The final cohort comprised 991,042 infants. Perinatal mortality occurred in 1944 infants (0.19%). The incidence and risk of perinatal mortality increased as birthweight decreased, peaking for infants <1st centile (perinatal mortality rate 13.2/1000 births, adjusted Relative Risk Ratio (aRRR) of 12.96 (95% CI 10.14, 16.57) for stillbirth and aRRR 7.55 (95% CI 3.78, 15.08) for neonatal death). Severe neurological morbidity occurred in 7311 infants (0.74%), with the highest rate (19.6/1000 live births) in <1st centile cohort. There were 75,243 cases of severe morbidity (7.59% livebirths), with the peak incidence occurring in the <1st centile category (12.3% livebirths). The majority of adverse outcomes occurred in infants with birthweights between 10 and 90th centile. Almost 2 in 3 stillbirths, and approximately 3 in 4 cases of neonatal death, severe neurological morbidity or other severe morbidity occurred within this birthweight range. Interpretation: Although the incidence and risk of perinatal mortality, severe neurological morbidity and severe morbidity increased at the extremes of birthweight centiles, the majority of these outcomes occurred in infants that were apparently "appropriately grown" (i.e., birthweight 10th-90th centile). Funding: National Health and Medical Research Council, Mater Foundation, Royal Australian College of Obstetricians and Gynaecologists Women's Health Foundation - Norman Beischer Clinical Research Scholarship, Cerebral Palsy Alliance, University of Queensland Research Scholarship.

Prevalence of Preterm Birth and Perinatal Outcomes in a Tertiary Hospital in Malaysia.

Background Preterm birth (PTB) is defined as neonates that are born alive >22 weeks of gestation and <37 weeks of gestation. Because of the immaturity of different organ systems, 14.84 million newborns worldwide are born prematurely, which is the largest contributing factor to mortality and morbidity. Although studies have been conducted in this field, the magnitude of PTB is a major issue in most developing countries including Malaysia. Objective To assess the prevalence of PTB and the perinatal outcome among women delivered in a tertiary university hospital in Malaysia.  Methods This was a cross-sectional study evaluating all singleton live births weighing>500g and delivered at >22+1 weeks of gestation between January 2015 and December 2019 in Universiti Malaya Medical Centre (UMMC), Kuala Lumpur, Malaysia. Data were collected from the hospital's recorded birth registry. The primary outcome was the PTB rate. Data were entered and analysed using Statistical Product and Service Solutions (SPSS) (version 28.0; IBM SPSS Statistics for Windows, Armonk, NY). Results A total of 26,022 singleton live births were reported for the period 2015-2019. PTB rates showed a sharp 6% decrease from 2015 to 2016, after which the trend was inconsistent until 2019. The risk of preterm babies being admitted to the neonatal intensive care unit (NICU) or the ward compared to the risk of neonatal mortality increases for babies of identified sex, delivered via caesarean, and with a birth weight between 2 and 3 kgs. Babies born at a gestational age between 22+1 and 33+6 have a higher risk of neonatal mortality compared to late preterm babies. Conclusions The PTB incidence trend was inconsistent from 2015 to 2019 in a tertiary university hospital in Malaysia, with a far higher prevalence compared to national data. The high NICU admission and mortality rates among preterm infants mean urgent strategies and policies are needed to improve perinatal outcomes.

Pipelle Endometrial Sampling With a Full Bladder Compared With Standard Care: A Randomized Controlled Trial.

OBJECTIVE: To compare insertion failure rates for Pipelle endometrial sampling with a full bladder compared with the standard process (not taking into account bladder status) without cervical manipulation. METHODS: A single-masked randomized trial was conducted in a single tertiary care center from July 2021 to January 2022. Two hundred fourteen participants aged 18 years or older who were scheduled for outpatient Pipelle endometrial sampling were randomized: 107 each to having a full bladder (by oral water intake) or standard process (without delayed sampling and bladder status not taken into account). Women with known cervical stenosis, gynecologic malignancy, uterine anomalies, leiomyoma distorting the uterine cavity, acute cervicitis, urge bladder dysfunction, intense anxiety, need for anesthesia or analgesic before the procedure, positive pregnancy test, or previous failed office endometrial sampling were excluded. The primary outcome was the insertion failure rate of endometrial sampling at first attempt. Secondary outcomes were pain during procedure, satisfaction score, analgesia use, procedure duration, and need for cervical manipulation. Factoring in a baseline insertion failure rate of 30.0%, relative risk of 0.45, α of 0.05, 80.0% power, and a dropout rate of 10.0%, we needed 107 participants in each arm. RESULTS: The insertion failure rate was significantly lower in the full bladder group compared with standard process: 25 of 107 (23.4%) compared with 45 of 107 (42.1%) (relative risk 0.56, 95% CI, 0.37-0.84; number needed to treat to benefit 6.0, 95% CI, 3.20-15.70). Pain score (median) during the procedure (interquartile range) was 4 (3-6) compared with 5 (3-8) ( P =.004); patient satisfaction score was 8 (7-9) compared with 7 (4-8) ( P <.001); and mean±SD procedure duration was 3.0±2.4 compared with 4.7±2.9 minutes ( P <.001) for the full bladder and standard process arm, respectively. Other secondary outcomes of cervical laceration, analgesia use, and adequacy of endometrial tissue for histopathologic assessment were not significantly different between groups. CONCLUSION: Pipelle endometrial sampling with a full bladder reduces the initial insertion failure rate, procedure-related pain, and duration of sampling and increases patient satisfaction compared with the standard process. CLINICAL TRIAL REGISTRATION: ISRCTN, ISRCTN33938192.

Five-minute Apgar score and risk of neonatal mortality, severe neurological morbidity and severe non-neurological morbidity in term infants - an Australian population-based cohort study.

Background: The aim of this study was to ascertain risks of neonatal mortality, severe neurological morbidity and severe non-neurological morbidity related to the 5-min Apgar score in early term (37+0-38+6 weeks), full term (39+0-40+6 weeks), late term (41+0-41+6 weeks), and post term (≥42+0 weeks) infants. Methods: This was a retrospective cohort study of 941,221 term singleton births between 2000 and 2018 in Queensland, Australia. Apgar scores at 5-min were categorized into five groups: Apgar 0 or 1, 2 or 3, 4-6, 7 or 8 and 9 or 10. Gestational age was stratified into 4 groups: Early term, full term, late term and post term. Three specific neonatal study outcomes were considered: 1) Neonatal mortality 2) Severe neurological morbidity and 3) Severe non-neurological morbidity. Poisson multivariable regression models were used to determine relative risk ratios for the effect of gestational age and Apgar scores on these severe neonatal outcomes. We hypothesized that a low Apgar score of <4 was significantly associated with increased risks of neonatal mortality, severe neurological morbidity and severe non-neurological morbidity. Findings: Of the study cohort, 0.04% (345/941,221) were neonatal deaths, 0.70% (6627/941,221) were infants with severe neurological morbidity and 4.3% (40,693/941,221) had severe non-neurological morbidity. Infants with Apgar score <4 were more likely to birth at late term and post term gestations and have birthweights <3rd and <10th percentiles. The adjusted relative risk ratios (aRRR) for neonatal mortality and severe neurological morbidity were highest in the Apgar 0 or 1 cohort. For infants in the Apgar 0 or 1 group, neonatal mortality increased incrementally with advancing term gestation: early term (aRRR 860.16, 95% CI 560.96, 1318.94, p < 0.001); full term (aRRR 1835.77, 95% CI 1279.48, 2633.91, p < 0.001); late term (aRRR 1693.61, 95% CI 859.65, 3336.6, p < 0.001) and post term (aRRR 2231.59, 95% CI 272.23, 18293.07, p < 0.001) whilst severe neurological morbidity decreased as gestation progressed: early term (aRRR 158.48, 95% CI 118.74, 211.51, p < 0.001); full term (aRRR 112.99, 95% CI 90.56, 140.98, p < 0.001); late term (aRRR 87.94, 95% CI 67.09, 115.27, p < 0.001) and post term (aRRR 52.07, 95% CI 15.17, 178.70, p < 0.001). Severe non-neurological morbidity was greatest in the full term, Apgar 2-3 cohort (aRRR 7.36, 95% CI 6.2, 8.74, p < 0.001). Interpretation: A 5-min Apgar score of <4 was prognostic of neonatal mortality, severe neurological morbidity, and severe non-neurological morbidity in infants born >37 weeks' gestation with the risk greatest in the early term cohort. Funding: National Health and Medical Research Council and Mater Foundation.

Cold compared with room temperature compress on the repaired primiparous perineum following injury at normal vaginal delivery: a randomized controlled trial.

BACKGROUND: The perineum is typically injured at the first vaginal birth. The application of a cold compress to the perineal repair site can reduce pain; however, the effect usually dissipates after a couple of hours. Repeated applications may be needed for sustained analgesia. However, the medium-term effect of repeated applications of cold compress on the perineal repair site on the recovery of sexual function and perineal healing is not known. OBJECTIVE: This study aimed to evaluate repeated applications of cold vs room temperature (placebo control) compress to the repaired primiparous perineum on pain upon movement. STUDY DESIGN: A randomized controlled trial was conducted in a university hospital in Malaysia from May 2022 to February 2023. A total of 224 women with a repaired episiotomy or spontaneous second-degree tear sustained at normal delivery were randomized as follows: 113 to frozen gel pack and 111 to room temperature gel pack, as wound compress. The compress was applied to the perineal repair site at 3 timepoints: immediately after repair, and at 4 and 8 hours after delivery, for 20 minutes at each application. The primary outcomes were pain during movement at 12 and 24 hours after delivery, scored using the 0 to 10 numerical rating scale. The secondary outcomes include duration of hospital stay; analgesic consumption; recovery and functional metrics of reestablishing flatus, mobilization, and urination, breastfeeding; maternal satisfaction with the allocated compress; and after hospital discharge for up to 6 weeks after birth through telephone interview, analgesic consumption, perineal pain, resumption of vaginal sex, and women's perception of perineal wound healing. RESULTS: The median (interquartile range) of pain at movement scores were 4 (4-5) vs 5 (4-5) (P=.018) at 12 hours and 2 (1-3) vs 2 (2-3) (P=.173) at 24 hours after birth for cold vs room temperature compress, respectively. Maternal satisfaction scores were 8 (7-9) vs 7 (6-8) (P=.119), oral analgesic for perineal pain while at the postnatal ward was taken by 94 of 113 (83.2%) vs 85 of 109 (78.0%) (relative risk, 1.07; 95% confidence interval, 0.94-1.21), and time to the first satisfactory breastfeeding episode was 11.6 (7.9-15.5) vs 13.0 (8.0-20.7) hours (P=.303) for cold vs room temperature compress, respectively. At 2 weeks telephone follow-up, analgesic intake and perineal pain were not different. At 6 weeks, analgesic intake, perineal pain, resumption of vaginal sex, exclusive breastfeeding, and maternal perception of perineal healing were not different. CONCLUSION: Intermittent cold compress in the first 8 hours to the repaired perineum reduces pain at 12 hours but the effect attenuates by 24 hours. Maternal satisfaction with their allocated compress was not different. There was no suggestion of harm or benefit on the other secondary outcomes.

Routine vaginal examination to assess labor progress at 8 compared to 4 hours after early amniotomy following Foley balloon ripening in the labor induction of multiparas: a randomized trial.

BACKGROUND: Vaginal examination to monitor labor progress is recommended at least every 4 hours, but it can cause pain and embarrassment to women. Trial data are limited on the best intensity for vaginal examination. Vaginal examination is not needed for oxytocin dose titration after an amniotomy has been performed and oxytocin infusion started. The Foley balloon commonly ripens the cervix without strong contractions. Amniotomy and oxytocin infusion are usually required to drive labor. OBJECTIVE: This study aimed to evaluate the first vaginal examination at 8 vs 4 hours after amniotomy-oxytocin after Foley ripening in multiparous labor induction. STUDY DESIGN: A randomized controlled trial was conducted from October 2021 to September 2022 at the University Malaya Medical Center, Kuala Lumpur, Malaysia. Multiparas at term were recruited at admission for labor induction. Participants were randomized to a first routine vaginal examination at 8 or 4 hours after Foley balloon ripening and amniotomy. Titrated oxytocin infusion was routinely commenced after amniotomy to initiate contractions. The 2 primary outcomes were the time from amniotomy to delivery (noninferiority hypothesis) and maternal satisfaction (superiority hypothesis). Data were analyzed using the Student t test, Mann-Whitney U test, and chi-square test (or Fisher exact test), as suitable for the data. RESULTS: A total of 204 women were randomized, 102 to each arm. Amniotomy to birth intervals were 4.97±2.47 hours in the 8-hour arm and 5.79±3.17 hours in the 4-hour arm (mean difference, -0.82; 97.5% confidence interval, -1.72 to 0.08; P=.041; Bonferroni correction), which were noninferior within the prespecified 2-hour upper margin, and the maternal satisfaction scores (11-point 0-10 numerical rating scale) with allocated labor care were 9 (interquartile range, 8-9) in the 8-hour arm and 8 (interquartile range, 7-9) in the 4-hour arm (P=.814). In addition, oxytocin infusion to birth interval difference was noninferior within the 97.5% confidence interval (-1.59 to 0.23) margin of 1.3 hours. Of the maternal outcomes, the amniotomy to first vaginal examination intervals were 3.9±1.8 hours in the 8-hour arm and 3.4±1.3 hours in the 4-hour arm (P=.026), and the numbers of vaginal examinations were 2.00 (interquartile range, 2.00-3.00) in the 8-hour arm and 3.00 (interquratile range, 2.00-3.25) in the 4-hour arm (P<.001). For the 8-hour arm, the first vaginal examination was less likely to be as scheduled and more likely to be indicated by sensation to bear down (P<.001), and the epidural analgesia rates were lower (13/102 participants [12.7%] in the 8-hour arm vs 28/102 participants [27.5%] in the 4-hour arm; relative risk, 0.46; 95% confidence interval, 0.26-0.84; P=.009). Other outcomes of the mode of delivery, indications for cesarean delivery, and delivery blood loss were not different. Neonatal outcomes were not different. CONCLUSION: Routine first vaginal examination at 8 hours compared with that at 4 hours was noninferior for the time to birth but did not improve maternal satisfaction.

The Relationship between Placental Shear Wave Elastography and Fetal Weight-A Prospective Study.

Background/Objectives: The utility of shear wave elastography (SWE) as an adjunct to ultrasound biometry and Doppler velocimetry for the examination of placental dysfunction and suboptimal fetal growth is unclear. To date, limited data exist correlating the mechanical properties of placentae with fetal growth. This study aimed to investigate the relationship between placental shear wave velocity (SWV) and ultrasound estimated fetal weight (EFW), and to ascertain if placental SWV is a suitable proxy measure of placental function in the surveillance of small-for-gestational-age (SGA) pregnancies. Methods: This prospective, observational cohort study compared the difference in placental SWV between SGA and appropriate-for-gestational-age (AGA) pregnancies. There were 221 women with singleton pregnancies in the study cohort-136 (61.5%) AGA and 85 (38.5%) SGA. Fetal biometry, Doppler velocimetry, the deepest vertical pocket of amniotic fluid, and mean SWV were measured at 2-4-weekly intervals from recruitment to birth. Results: There was no difference in mean placental SWV in SGA pregnancies compared to AGA pregnancies, nor was there any relationship to EFW. Conclusions: Although other studies have shown some correlation between increased placental stiffness and SGA pregnancies, our investigation did not support this. The mechanical properties of placental tissue in SGA pregnancies do not result in placental SWVs that are apparently different from those of AGA controls. As this study did not differentiate between constitutionally or pathologically small fetuses, further studies in growth-restricted cohorts would be of benefit.