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.

Circulating biomarkers associated with placental dysfunction and their utility for predicting fetal growth restriction.

Fetal growth restriction (FGR) leading to low birth weight (LBW) is a major cause of neonatal morbidity and mortality worldwide. Normal placental development involves a series of highly regulated processes involving a multitude of hormones, transcription factors, and cell lineages. Failure to achieve this leads to placental dysfunction and related placental diseases such as pre-clampsia and FGR. Early recognition of at-risk pregnancies is important because careful maternal and fetal surveillance can potentially prevent adverse maternal and perinatal outcomes by judicious pregnancy surveillance and careful timing of birth. Given the association between a variety of circulating maternal biomarkers, adverse pregnancy, and perinatal outcomes, screening tests based on these biomarkers, incorporating maternal characteristics, fetal biophysical or circulatory variables have been developed. However, their clinical utility has yet to be proven. Of the current biomarkers, placental growth factor and soluble fms-like tyrosine kinase 1 appear to have the most promise for placental dysfunction and predictive utility for FGR.

Risks of stillbirth, neonatal mortality, and severe neonatal morbidity by birthweight centiles associated with expectant management at term.

BACKGROUND: Determining the optimal time of birth at term is challenging given the ongoing risks of stillbirth with increasing gestation vs the risks of significant neonatal morbidity at early-term gestations. These risks are more pronounced in small infants. OBJECTIVE: This study aimed to evaluate the risks of stillbirth, neonatal mortality, and severe neonatal morbidity by comparing expectant management with delivery from 37+0 weeks of gestation. STUDY DESIGN: This was a retrospective cohort study evaluating women with singleton, nonanomalous pregnancies at 37+0 to 40+6 weeks' gestation in Queensland, Australia, delivered from 2000 to 2018. Rates of stillbirth, neonatal death, and severe neonatal morbidity were calculated for <3rd, 3rd to <10th, 10th to <25th, 25th to <90th, and ≥90th birthweight centiles. The composite risk of mortality with expectant management for an additional week in utero was compared with rates of neonatal mortality and severe neonatal morbidity. RESULTS: Of 948,895 singleton, term nonanomalous births, 813,077 occurred at 37+0 to 40+6 weeks' gestation. Rates of stillbirth increased with gestational age, with the highest rate observed in infants with birthweight below the third centile: 10.0 per 10,000 (95% confidence interval, 6.2-15.3) at 37+0 to 37+6 weeks, rising to 106.4 per 10,000 (95% confidence interval, 74.6-146.9) at 40+0 to 40+6 weeks' gestation. The rate of neonatal mortality was highest at 37+0 to 37+6 weeks for all birthweight centiles. The composite risk of expectant management rose sharply after 39+0 to 39+6 weeks, and was highest in infants with birthweight below the third centile (125.2/10,000; 95% confidence interval, 118.4-132.3) at 40+0 to 40+6 weeks' gestation. Balancing the risk of expectant management and delivery (neonatal mortality), the optimal timing of delivery for each birthweight centile was evaluated on the basis of relative risk differences. The rate of severe neonatal morbidity sharply decreased in the period between 37+0 to 37+6 and 38+0 to 38+6 weeks, particularly for infants with birthweight below the third centile. CONCLUSION: Our data suggest that the optimal time of birth is 37+0 to 37+6 weeks for infants with birthweight <3rd centile and 38+0 to 38+6 weeks' gestation for those with birthweight between the 3rd and 10th centile and >90th centile. For all other birthweight centiles, birth from 39+0 weeks is associated with the best outcomes. However, large numbers of planned births are required to prevent a single excess death. The healthcare costs and acceptability to women of potential universal policies of planned birth need to be carefully considered.

Real-time imaging as visual biofeedback in active second stage of labor among nulliparas: a randomized controlled trial.

BACKGROUND: A prolonged second stage of labor increases the risk of severe perineal laceration, postpartum hemorrhage, operative delivery, and poor Apgar score. The second stage is longer in nulliparas. Maternal pushing during the second stage of labor is an important contributor to the involuntary expulsive force developed by uterine contraction to deliver the fetus. Preliminary data indicate that visual biofeedback during the active second stage hastens birth. OBJECTIVE: This study aimed to evaluate if visual feedback focusing on the perineum reduced the length of the active second stage of labor in comparison with the control. STUDY DESIGN: A randomized controlled trial was conducted in the University Malaya Medical Centre from December 2021 to August 2022. Nulliparous women about to commence the active second stage, at term, with singleton gestation, reassuring fetal status, and no contraindication for vaginal delivery were randomized to live viewing of the maternal introitus (intervention) or maternal face (sham/placebo control) as visual biofeedback during their pushing. A video camera Bluetooth-linked to a tablet computer display screen was used; in the intervention arm, the camera was focused on the introitus, and in the control arm, on the maternal face. Participants were instructed to watch the display screen during their pushing. The primary outcomes were the intervention-to-delivery interval and maternal satisfaction with the pushing experience assessed using a 0-to-10 visual numerical rating scale. Secondary outcomes included mode of delivery, perineal injury, delivery blood loss, birthweight, umbilical cord arterial blood pH and base excess at birth, Apgar score at 1 and 5 minutes, and neonatal intensive care unit admission. Data were analyzed with the t test, Mann-Whitney U test, chi-square test, and Fisher exact test, as appropriate. RESULTS: A total of 230 women were randomized (115 to intervention and 115 to control arm). The active second stage duration (intervention-to-delivery interval) was a median (interquartile range) of 16 (11-23) and 17 (12-31) minutes (P=.289), and maternal satisfaction with the pushing experience was 9 (8-10) and 7 (6-7) (P<.001) for the intervention and control arm, respectively. Women randomized to the intervention arm were more likely to agree to recommend their management to a friend (88/115 [76.5%] vs 39/115 [33.9%]; relative risk, 2.26 [95% confidence interval, 1.72-2.97]; P<.001) and more likely to have less severe perineal injury (P=.018). CONCLUSION: Real-time viewing of the maternal introitus as visual biofeedback during pushing resulted in higher maternal satisfaction compared with the sham control of viewing the maternal face; however, the time to delivery was not significantly shortened.

Eye-masks and earplugs compared to headband in nulliparas on increasing spontaneous vaginal delivery: a randomized trial.

BACKGROUND: A majority of pregnant women experience sleep disruption during pregnancy, especially in the third trimester. Lack of sleep is associated with preterm birth, prolonged labor and higher cesarean section rate. Six or less hours of night sleep in the last month of pregnancy is associated with a higher rate of caesarean births. Eye-masks and earplugs compared to headband improve night sleep by 30 or more minutes. We sought to evaluate eye-mask and earplugs compared to sham/placebo headbands on spontaneous vaginal delivery. METHODS: This randomized trial was conducted from December 2019-June 2020. 234 nulliparas, 34-36 weeks' gestation with self-reported night sleep < 6 h were randomized to eye-mask and earplugs or sham/placebo headband (both characterized as sleep aids) to be worn each night to delivery. After two weeks, interim outcome data of the average night sleep duration and the trial sleep related questionnaire was answered through the telephone. RESULTS: Spontaneous vaginal delivery rates were 60/117(51.3%) vs. 52/117(44.4%) RR 1.15 95% CI 0.88-1.51 P = 0.30 for eye-mask and earplugs or headband respectively. At 2-weeks into the intervention period, the eye-mask and earplugs arm reported longer night sleep duration 7.0 ± 1.2 vs. 6.6 ± 1.5 h P = 0.04, expressed increased satisfaction with the allocated aid 7[6.0-8.0] vs. 6[5.0-7.5] P < 0.001, agreed they slept better 87/117(74.4%) vs. 48/117(41.0%) RR 1.81 95% CI 1.42-2.30 NNTb 4 (2.2-4.7) P < 0.001 and higher compliance median[interquartile range] 5[3-7] vs. 4[ 2-5] times per week of sleep aid use P = 0.002. CONCLUSION: Eye-mask and earplugs use at home in late third trimester do not increase the spontaneous vaginal delivery rate even though self-reported night sleep duration, sleep quality, satisfaction and compliance with allocated sleep aid were significantly better than for sham/placebo headband. Trial registration This trial was registered with ISRCTN on June 11, 2019 with trial identification number: ISRCTN99834087 .

HbA1c at term delivery and adverse pregnancy outcome.

BACKGROUND: There are no obvious thresholds at which the risk of adverse pregnancy outcomes increases as a result of maternal hyperglycemia. HbA1c level which is representative of average blood glucose levels over the last 2-3 months is not as strongly predictive of adverse outcome compared to blood glucose values of oral glucose tolerance test. Data is sparse on the predictive value of HbA1c at term just prior to delivery on adverse outcome. We sought to evaluate HbA1c taken on admission for delivery at term on adverse outcomes of Cesarean delivery and large (≥ 90th centile) for gestational age (LGA) infants. METHODS: A prospective cross-sectional study was conducted in a university hospital in Malaysia from December 2017-August 2018. 1000 women at term whose deliveries were imminent were enrolled. Blood were drawn and immediately sent for HbA1c analysis at our hospital laboratory. Primary outcomes were Cesarean delivery and LGA. RESULTS: On crude analyses, Cesarean births (vs. vaginal births) were associated with significantly higher HbA1c (%) levels 5.4[5.2-5.7] vs. 5.3[5.1-5.6] P = < 0.001 but not for LGA vs. non-LGA 5.4[5.1-5.6] vs. 5.3[5.1-5.6] P = 0.17. After controlling for significant confounders identified on crude analysis (diabetes in pregnancy, parity, ethnicity, body mass index (BMI), previous cesarean, labor induction, Group B streptococcus (GBS) carriage and birth weight), HbA1c is independently predictive of Cesarean birth, adjusted odds ratio (AOR) 1.47 95% CI 1.06-2.06 P = 0.023 per HbA1c 1% increase. Following adjustment for significant confounders (BMI, predelivery anemia [hemoglobin < 11 g/dl] and GBS carriage), the impact of raised HbA1c level on LGA is AOR 1.43 95% CI 0.93-2.18 P = 0.101 per HbA1c 1% increase and non-significant. CONCLUSION: Raised HbA1c level at term births in the general pregnant population is independently predictive of Cesarean delivery after adjustment for potential confounders including diabetes in pregnancy.

Digital insertion of Foley catheter 16F versus 22F versus 28F in unripe cervix labor induction: A randomized trial.

AIM: To explore digital insertion in dorsal recumbent position of 16F, 22F, or 28F catheter bores on insertion failure, duration, and pain in unripe cervix labor induction. METHODS: A randomized trial was performed in a University hospital in Malaysia. Term women scheduled for labor induction, Bishop score ≤ 5, singleton, cephalic presentation, intact membrane, and reassuring pre-induction fetal heart rate tracing were recruited. Women with known gross fetal anomaly, allergy to latex and inability to consent or language difficulty were excluded. Participants were randomized to 16F, 22F, or 28F Foley catheter. Primary outcome was insertion failure and main secondary outcomes were insertion duration and pain (assessed by a Visual Numerical Rating Scale [VNRS] 0-10, higher score more pain). Analysis is done by analysis of variance (ANOVA), Kruskal-Wallis, and chi square test across the three arms and by t test and Mann-Whitney U test for pair wise comparisons. RESULTS: One hundred twenty-seven participants' data were analyzed. The insertion failure 7/43(16%) versus 4/42(10%) versus 5/42(12%), p = 0.64, insertion duration median [IQR] 2.8 [1.8-4.8] versus 2.8 [1.7-3.7] versus 2.8 [1.7-4.3] min, p = 0.68 and insertion pain VNRS mean {SD} 4.2 {2.5} versus 3.4 {2.3} versus 3.6 {2.2}, p = 0.26, insertion to delivery interval 26.0 {9.7} versus 25.6 {9.1} versus 22.8 {7.4} h, p = 0.45, and spontaneous vaginal delivery 20/43 (45%) versus 23/42(55%) versus 25/42(60%), p = 0.48 for 16F versus 22F versus 28F arms, respectively. Pairwise comparisons were not different. CONCLUSION: Foley catheter 16F versus 22F versus 28F resulted in similar digital insertion performance in the dorsal recumbent position for unripe cervix labor induction. CLINICAL TRIAL REGISTRATION: https://doi.org/10.1186/ISRCTN21224268.

Foley catheter and controlled release dinoprostone versus foley catheter labor induction in nulliparas: a randomized trial.

PURPOSE: To evaluate Foley catheter and controlled release dinoprostone insert compared to foley catheter alone on induction to delivery interval and maternal satisfaction. METHODS: A randomized trial was conducted in a university hospital in Malaysia from December 2018 to May 2019. Term nulliparas with unfavorable cervix (Bishop score ≤ 5) scheduled for labor induction were randomized to Foley catheter and controlled release dinoprostone insert simultaneously or Foley catheter alone. Primary outcomes were induction to delivery interval (hours) and maternal satisfaction on birth experience (assessed by 11-point Visual Numerical Rating Scale VNRS 0-10, higher score more satisfied). RESULTS: Induction to vaginal delivery intervals was mean ± standard deviation 22.5 ± 10.4 vs. 35.1 ± 14.9 h, P = < 0.001 but maternal satisfaction on birth experience was not significantly different median[interquartile range] VNRS 8[7-9] vs. 8[7-9], P = 0.12 for Foley catheter-controlled-release dinoprostone and Foley catheter alone arms, respectively. Cesarean delivery rates were 35/102(34.3%) vs. 50/101(49.5%), P = 0.02 RR 0.7 95% CI 0.5-0.9 NNTb 6.3 95% CI 3.5-39.4, pain score at 6 h after catheter insertion 5[2-8] vs. 1[1-3], P < 0.001, Bishop score at trial devices removal 9[9-10] vs. 8[7-9], P = 0.001, requirement for oxytocin induction or augmentation 39/102(38.2%) vs. 76/101(75.2%) NNTb 3 95% CI 2.0-4.1, P < 0.001 and amniotomy rates 73/99(73.7%) vs. 81/95(85.3%), P = 0.052 RR 0.9 85% CI 0.8-1.0 in Foley catheter-controlled-release dinoprostone and Foley catheter alone arms respectively. CONCLUSION: In nulliparas with unripe cervixes at term, combined Foley catheter and controlled release dinoprostone vaginal insert compared to Foley catheter alone reduces the induction to vaginal delivery interval and cesarean delivery rate but satisfaction was not significantly increased. CLINICAL TRIAL REGISTRATION: ISRCTN2282883, 03/12/2018, "prospectively registered" ( https://doi.org/10.1186/ISRCTN12282883 ).

Prophylactic metformin after antenatal corticosteroids (PROMAC): a double blind randomized controlled trial.

BACKGROUND: Antenatal corticosteroids (ACS) are increasingly used to improve prematurity-related neonatal outcome. A recognized and common adverse effect from administration of antenatal corticosteroid is maternal hyperglycemia. Even normal pregnancy is characterized by relative insulin resistance and glucose intolerance. Treatment of maternal hyperglycemia after ACS might be indicated due to the higher risk of neonatal acidosis which may coincide with premature birth. Metformin is increasingly used to manage diabetes mellitus during pregnancy as it is effective and more patient friendly. There is no data on prophylactic metformin to maintain euglycemia following antenatal corticosteroids administration. METHODS: A double blind randomized trial. 103 women scheduled to receive two doses of 12-mg intramuscular dexamethasone 12-hour apart were separately randomized to take prophylactic metformin or placebo after stratification according to their gestational diabetes (GDM) status. First oral dose of allocated study drug was taken at enrolment and continued 500 mg twice daily for 72 hours if not delivered. Six-point blood sugar profiles were obtained each day (pre- and two-hour post breakfast, lunch and dinner) for up to three consecutive days. A hyperglycemic episode is defined as capillary glucose fasting/pre-meal ≥ 5.3 mmol/L or two-hour post prandial/meal ≥ 6.7 mmol/L. Primary outcome was hyperglycemic episodes on Day-1 (first six blood sugar profile points) following antenatal corticosteroids. RESULTS: Number of hyperglycemic episodes on the first day were not significantly different (mean ± standard deviation) 3.9 ± 1.4 (metformin) vs. 4.1 ± 1.6 (placebo) p = 0.64. Hyperglycemic episodes markedly reduced on second day in both arms to 0.9 ± 1.0 (metformin) vs. 1.2 ± 1.0 (placebo) p = 0.15 and further reduced to 0.6 ± 1.0 (metformin) vs. 0.7 ± 1.0 (placebo) p = 0.67 on third day. Hypoglycemic episodes during the 3-day study period were few and all other secondary outcomes were not significantly different. CONCLUSIONS: In euglycemic and diet controllable gestational diabetes mellitus women, antenatal corticosteroids cause sustained maternal hyperglycemia only on Day-1. The magnitude of Day-1 hyperglycemia is generally low. Prophylactic metformin does not reduce antenatal corticosteroids' hyperglycemic effect. TRIAL REGISTRATION: The trial is registered in the ISRCTN registry on May 4 2017 with trial identifier https://doi.org/10.1186/ISRCTN10156101 .

Outpatient vs inpatient Foley catheter induction of labor in multiparas with unripe cervixes: A randomized trial.

INTRODUCTION: Multiparous labor inductions are typically successful, and the process can be rapid, starting from a ripened cervix with a predictable response to amniotomy and oxytocin infusion. Outpatient Foley catheter labor induction in multiparas with unripe cervixes is a feasible option as the mechanical process of ripening is usually without significant uterine contractions and well tolerated. Labor contractions can be initiated by amniotomy and titrated oxytocin infusion in the hospital for well-timed births during working hours as night birth are associated with adverse events. We sought to evaluate outpatient compared with inpatient Foley catheter induction of labor in multiparas for births during working hours and maternal satisfaction. MATERIAL AND METHODS: A randomized trial was conducted in the University of Malaya Medical Center. A total of 163 term multiparas (no dropouts) with unripe cervixes (Bishop score ≤5) scheduled for labor induction were randomized to outpatient or inpatient Foley catheter. Primary outcomes were delivery during "working hours" 08:00-18:00 h and maternal satisfaction on allocated care (assessed by 11-point visual numerical rating score 0-10, with higher score indicating more satisfied). CLINICAL TRIAL REGISTRATION: ISRCTN13534944. RESULTS: Comparing outpatient and inpatient arms, delivery during working hours were 54/82 (65.9%) vs. 48/81 (59.3%) (relative risk 1.1, 95% CI 0.9-1.4, p = 0.421) and median maternal satisfaction visual numerical rating score was 9 (interquartile range 9-9) vs. 9 (interquartile range 8-9, p = 0.134), repectively. Duration of hospital stay and membrane rupture to delivery interval were significantly shorter in the outpatient arm: 35.8 ± 20.2 vs. 45.2 ± 16.2 h (p = 0.001) and 4.1 ± 2.9 vs. 5.3 ± 3.6 h (p = 0.020), respectively. Other maternal and neonatal secondary outcomes were not significantly different. CONCLUSIONS: The trial failed to demonstrate the anticipated increase in births during working hours with outpatient compared with inpatient induction of labor with Foley catheter in parous women with an unripe cervix. Hospital stay and membrane rupture to delivery interval were significantly shortened in the outpatient group. The rate of maternal satisfaction was high in both groups and no significant differences were found.

Glycemic control following two regimens of antenatal corticosteroids in mild gestational diabetes: a randomized controlled trial.

PURPOSE: To compare 3 consecutive days of hyperglycemic response following antenatal dexamethasone regimens of 12-mg or 6-mg doses 12 hourly in diet-controlled gestational diabetes. METHODS: A randomized controlled trial was carried out in a university hospital in Malaysia. Women with lifestyle-controlled gestational diabetes scheduled to receive clinically indicated antenatal corticosteroids (dexamethasone) were randomized to 12-mg 12 hourly for one day (2 × 12-mg) or 6-mg 12-hourly for two days (4 × 6-mg). 6-point (pre and 2-h postprandial) daily self-monitoring of capillary blood sugar profile for up to 3 consecutive days was started after the first dexamethasone injection. Hyperglycemia is defined as blood glucose pre-meal ≥ 5.3 or 2 h postprandial ≥ 6.7 mmol/L. The primary outcome was a number of hyperglycemic episodes in Day-1 (first 6 BSP points). A sample size of 30 per group (N = 60) was planned. RESULTS: Median [interquartile range] hyperglycemic episodes 4 [2.5-5] vs. 4 [3-5] p = 0.3 in the first day, 3 [2-4] vs. 1 [0-3] p = 0.01 on the second day, 0 [0-1] vs. 0 [0-1] p = 0.6 on the third day and over the entire 3 trial days 7 [6-9] vs. 6 [4-8] p = 0.17 for 6-mg vs. 12-mg arms, respectively. 2/30 (7%) in each arm received an anti-glycemic agent during the 3-day trial period (capillary glucose exceeded 11 mmol/L). Mean birth weight (2.89 vs. 2.49 kg p < 0.01) and gestational age at delivery (37.7 vs. 36.6 weeks p = 0.03) were higher and median delivery blood loss (300 vs. 400 ml p = 0.02) was lower in the 12-mg arm; all other secondary outcomes were not significantly different. CONCLUSION: In gestational diabetes, 2 × 12-mg could be preferred over 4 × 6-mg dexamethasone as hyperglycemic episodes were fewer on Day-2, fewer injections were needed and the regimen was completed sooner. CLINICAL TRIAL REGISTRATION: http://www.isrctn.com/ISRCTN16613220 .

Induction of labour from 39 weeks in low-risk multiparas with ripe cervixes: A randomised controlled trial.

BACKGROUND: Induction of labour (IOL) in low-risk nulliparas at 39 weeks reduces caesarean delivery. Multiparas with ripe cervixes typically have vaginal delivery within eight hours. Delivery at night and weekend are associated with higher maternal and neonatal mortality. AIMS: To evaluate IOL in full-term multiparas with ripe cervixes to achieve delivery at normal working hours and improve maternal satisfaction. METHODS: A randomised trial was performed in a tertiary hospital in Malaysia. Low-risk multiparas with ripe cervixes (Bishop score ≥6) were recruited at 38+4 -40+0  weeks, then randomised to planned labour induction at 39+0  weeks or expectant care. Primary outcomes were delivery during 'normal working hours' 09:00-17:00 hours, Monday-Friday and patient satisfaction by visual numerical rating scale. RESULTS: For IOL (n = 80) vs expectant care (n = 80) arms respectively, primary outcomes of delivery at normal working hours was 27/80 (34%) vs 29/78 (37%), relative risk (RR) 0.9, 95% CI 0.5-1.7, P = 0.41, patient satisfaction was 8.0 ± 1.8 vs 7.8 ± 1.6, P = 0.41; presentation for spontaneous labour or rupture of membranes were 27/80 (34%) vs 70/79 (89%), RR 0.4, 95% CI 0.3-0.5, P < 0.001; and for labour induction 52/80 (65%) vs 15/79 (19%), RR 3.4, 95% CI 2.1-5.5, P < 0.001. Caesarean delivery was 8/80 (10%) vs 4/79 (5%), RR 2.0, 95% CI 0.62-6.3, P = 0.25; and mean birthweight was 3.1 ± 0.3 vs 3.3 ± 0.4 kg, P = 0.06 for IOL vs expectant care, respectively. CONCLUSION: Labour induction in low-risk multiparas does not increase births during working hours or improve patient satisfaction. Antenatal clinic visits and non-birth hospitalisation were significantly reduced.

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.

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.

Two different regimens of outpatient Foley catheter induction of labor in nulliparas: A randomized trial.

OBJECTIVES: To evaluate expectant compared to immediate return to hospital upon outpatient Foley catheter expulsion predicated on maternal satisfaction and amniotomy-titrated oxytocin infusion to delivery interval. METHODS: This randomized trial was conducted in a tertiary university hospital in Malaysia from September 2020 to February 2022. A total of 330 nulliparous women at term with unripe cervices (Bishop score ≤5), singleton viable fetus in cephalic presentation, reassuring preinduction fetal heart rate tracing and intact membranes who underwent planned outpatient Foley catheter induction of labor (IOL) were included. Women were randomized to expectant or immediate return to hospital if the Foley was spontaneously expelled at home before their scheduled hospital admission the following day. Primary outcomes were amniotomy-titrated oxytocin infusion to delivery interval and maternal satisfaction on the induction process (assessed by 0-10 visual numerical rating scale [VNRS]). RESULTS: Amniotomy-titrated oxytocin infusion to delivery interval was 8.7 ± 4.1 versus 8.9 ± 3.9 h, P = 0.605 (mean difference - 0.228 95% CI: -1.1 to +0.6 h) and maternal satisfaction VNRS score was median (interquartile range) 8 (7-9) versus 8 (7-9), P = 0.782. Early return to hospital rates were 37/165 (22.4%) versus 72/165 (43.6%), RR 0.51 (95% CI: 0.37-0.72), P ≤ 0.001, Cesarean delivery rates were 80/165 (48.5%) versus 80/165 (48.5%), RR 1.00 (95% CI: 0.80-1.25), P = 1.00 and duration of hospital stay was 54.4 ± 22.9 versus 56.7 ± 22.8 h, P = 0.364 for the expectant versus immediate return groups respectively. CONCLUSION: In outpatient Foley catheter IOL, expectant compared to immediate return to hospital following Foley dislodgement results in similarly high maternal satisfaction. The amniotomy-titrated oxytocin to delivery duration is non-inferior with expectant management.

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.