BackgroundPreterm birth is a global health priority. Using a progestogen during high-risk pregnancy could reduce PTB and adverse neonatal outcomes. MethodsSystematic review of randomised trials comparing vaginal progesterone, intramuscular 17hydroxyprogesterone caproate (17-OHPC), or oral progesterone with control, or with each other, in asymptomatic women at risk of preterm birth. We identified published and unpublished trials that completed primary data collection before July 30, 2016 (12 months before data collection began) by searching MEDLINE, Embase, CINAHL, the Maternity and Infant Care Database, and relevant trial registers between inception and July 30, 2019. Trials of progestogen to prevent early miscarriage or immediately-threatened preterm birth were excluded. Individual participant data were requested from investigators of eligible trials. Outcomes included preterm birth, early preterm birth, and mid-trimester birth. Adverse neonatal sequelae associated with early births were assessed using a composite of serious neonatal complications, and individually. Adverse maternal outcomes were investigated as a composite and individually. Individual participant data were checked and risk of bias assessed independently by two researchers. Primary meta-analyses used one-stage generalised linear mixed models that incorporated random effects to allow for heterogeneity across trials. FindingsInitial searches identified 47 eligible trials. Individual participant data were available for 30 of these trials. An additional trial was later included in a targeted update. Data were therefore available from a total of 31 trials (11,644 women and 16,185 offspring). Trials in singleton pregnancies included mostly women with previous spontaneous preterm birth or short cervix. Preterm birth before 34 weeks was reduced in such women who received vaginal progesterone (nine trials, 769 women; relative risk [RR] 0•78, 95% CI 0•68-0•90), 17-OHPC (five trials, 3,053 women; 0•83, 0•68-1•01), and oral progesterone (two trials, 183 women; 0•60, 0•41-0•90). Results for other birth and neonatal outcomes were consistently favourable, but less certain. A possible increase in maternal complications was suggested, but this was uncertain. We identified no consistent evidence of treatment interaction with any participant characteristics examined, although analyses within subpopulations questioned efficacy in women who did not have a short cervix. Trials in multifetal pregnancies mostly included women without additional risk factors. For twins, vaginal progesterone did not reduce preterm birth before 34 weeks (eight trials, 2046 women: RR 1•01, 95% CI 0•84-1•20) nor did 17-OHPC for twins or triplets (eight trials, 2253 women: 1•04, 0•92-1•18). Preterm premature rupture of membranes was increased with 17-OHPC exposure in multifetal gestations (rupture <34 weeks RR 1•59, 95% CI 1•15-2•22), but we found no consistent evidence of benefit or harm for other outcomes with either vaginal progesterone or 17-OHPC InterpretationVaginal progesterone and 17...

In women at low risk of preterm birth, CL predicts spontaneous preterm birth. However, its isolated use as a screening tool has limited value due to low sensitivity.

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Objective To evaluate the long‐term outcomes of children born to women with a short cervix and otherwise low risk for preterm birth, after antenatal exposure to vaginal progesterone vs placebo. Methods This was a follow‐up study of the Triple P trial, which randomized 80 low‐risk women with a short cervix (≤ 30 mm) at 18–22 weeks' gestation to progesterone (n = 41) or placebo (n = 39). At 2 years of corrected age, children were invited for a neurodevelopmental assessment, using the Bayley Scales of Infant and Toddler Development, third edition (BSID‐III), and a neurological and physical examination by an assessor blinded to the allocated treatment. Parents filled out the Ages and Stages Questionnaire, the Child Behavior Checklist (CBCL) and a general‐health questionnaire. The main outcome of interest was mean BSID‐III cognitive and motor scores. Additionally, a composite score of mortality and abnormal developmental outcome, including BSID‐III ≤–1 SD, CBCL score in the clinical range and/or parental reported physical problems (at least two operations or at least two hospital admissions in the previous 2 years), was evaluated. Our sample size, dictated by the original sample of the Triple P trial, provided 80% power to detect a mean difference (MD) of 15 points (1 SD) between groups for the BSID‐III tests. Results Of the 80 children born to the randomized women, one in the progesterone group and two in the placebo group died in the neonatal period. Follow‐up data were obtained for 59/77 (77%) children and BSID‐III outcomes in 57 children (n = 28 in the progesterone group and n = 29 in the placebo group) born at a median gestational age of 38 + 6 weeks (interquartile range (IQR), 37 + 3 to 40 + 1 weeks) with a median birth weight of 3240 g (IQR, 2785–3620 g). In the progesterone vs placebo groups, mean BSID‐III cognitive development scores were 101.6 vs 105.0 (MD, –3.4 (95% CI, –9.3 to 2.6); P = 0.29) while mean motor scores were 102.4 vs 107.3 (MD, –4.9 (95% CI, –11.2 to 1.4); P = 0.13). No differences were seen between the two groups in physical (including genital and neurological examination), behavioral and health‐related outcomes. Conclusion In this sample of children born to low‐risk women with a short cervix at screening, no relevant differences in neurodevelopmental, behavioral, health‐related and physical outcomes were found between offspring exposed to vaginal progesterone and those exposed to placebo. © 2020 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

In women with a short cervix, who are otherwise low risk, we could not show a significant benefit of progesterone in reducing adverse neonatal outcome and PTB.

BackgroundWomen with a short cervical length in mid-trimester pregnancy have a higher risk of preterm birth and therefore a higher rate of neonatal mortality and morbidity. Progesterone can potentially decrease the number of preterm births and lower neonatal mortality and morbidity. Previous studies showed good results of progesterone in women with either a history of preterm birth or a short cervix. However, it is unknown whether screening for a short cervix and subsequent treatment in mid trimester pregnancy is effective in low risk women.Methods/DesignWe plan a combined screen and treat study among women with a singleton pregnancy without a previous preterm birth. In these women, we will measure cervical length at the standard anomaly scan performed between 18 and 22 weeks. Women with cervical length ≤ 30 mm at two independent measurements will be randomly allocated to receive either vaginal progesterone tablets or placebo between 22 and 34 weeks. The primary outcome of this trial is adverse neonatal condition, defined as a composite outcome of neonatal mortality and severe morbidity. Secondary outcomes are time to delivery, preterm birth rate before 32, 34 and 37 weeks, days of admission in neonatal intensive care unit, maternal morbidity, maternal admission days for preterm labour and costs. We will assess growth, physical condition and neurodevelopmental outcome of the children at two years of age.DiscussionThis study will provide evidence for the usefulness and cost-effectiveness of screening for short cervical length at the 18-22 weeks and subsequent progesterone treatment among low risk women.Trial registrationNetherlands Trial Register (NTR): NTR207

Objectives To assess the effect of implementation of a newly developed e-learning module on the quality of cervical-length measurements. Methods

A cut-off value of 30 mm for CL was used to include women in a randomized clinical trial that was embedded in a cohort study. We suggest that the use of a predefined cut-off value for a short cervix influences the distribution of the CL measurements. Since the measurement is not blinded, preference of assessors for the control or intervention arms may have introduced selection bias. This might have resulted in fewer measurements around the cut-off value. Other trials using similar designs could benefit from this observation and take precautions to avoid selection bias. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.