ObjectiveTo examine the associations of antenatal corticosteroid (ACS) exposure with neurodevelopment in early childhood, and how these vary with gestational age at birth.DesignPopulation-based cohort study.SettingScotland, UK.Population285 637 singleton children born at 28-41 weeks' gestation, between 1st January 2011 and 31st December 2017, who underwent health reviews at 27-30 months of age.MethodsLogistic and linear regression analyses, stratified by gestation at birth (28-33, 34-36, 37-38 and 39-41 weeks' gestation), were used to evaluate the associations between ACS exposure and neurodevelopmental outcomes, and adjusted for maternal age, body mass index, diabetes, antenatal smoking, parity, neighbourhood deprivation, birth year, child sex and age at review.Main Outcome MeasuresPractitioner-identified concerns about any neurodevelopmental domain, and the average of five domain scores on neurodevelopmental milestones from the parent-rated Ages and Stages Questionnaire (ASQ-3).ResultsAfter adjustment for covariates, ACS exposure was associated with reduced neurodevelopmental concerns in children born at 28-33 weeks' gestation (OR = 0.79, 95% CI = 0.62-0.999) and with increased neurodevelopmental concerns in children born at 34-36 weeks' gestation (OR = 1.11, 95% CI = 1.01-1.21). No independent associations emerged in children born at later gestations. ACS exposure was not associated with ASQ-3 scores in any gestational age group.ConclusionsIn early childhood, ACS exposure was associated with statistically significantly reduced neurodevelopmental concerns in children born at 28-33 weeks' gestation, and with statistically significantly increased neurodevelopment concerns in children born at 34-36 weeks' gestation. However, the effect sizes of these associations were small. No independent associations were found between ACS exposure and neurodevelopment in term-born children.

ObjectiveTo describe perinatal and maternal outcomes of preterm prelabour rupture of membranes (PPROM) before 23 weeks' gestation in a national cohort.DesignProspective observational study.SettingNational population based cohort study with the UK Obstetric Surveillance System (UKOSS), a research infrastructure of all 194 obstetric units in the UK, 1 September 2019 to 28 February 2021.Participants326 women with singleton and 38 with multiple pregnancies with PPROM between 16+0 and 22+6 weeks+days' gestation.Main outcome measuresPerinatal outcomes of live birth, survival to discharge from hospital, and severe morbidity, defined as intraventricular haemorrhage grade 3 or 4, or requiring supplemental oxygen at 36 weeks' postmenstrual age, or both. Maternal outcomes were surgery for removal of the placenta, sepsis, admission to an intensive treatment unit, and death. Clinical data included rates of termination of pregnancy for medical reasons.ResultsPerinatal outcomes were calculated with all terminations of pregnancy for medical reasons excluded, and a worst-best range was calculated assuming that all terminations for medical reasons and those with missing data would have died (minimum value) or all would be liveborn (maximum value). For singleton pregnancies, the live birth rate was 44% (98/223), range 30-62% (98/326-201/326), perinatal survival to discharge from hospital was 26% (54/207), range 17-53% (54/326-173/326), and 18% (38/207), range 12-48% (38/326-157/326) of babies survived without severe morbidity. The rate of maternal sepsis was 12% (39/326) in singleton and 29% (11/38) in multiple pregnancies (P=0.004). Surgery for removal of the placenta was needed in 20% (65/326) and 16% (6/38) of singleton and twin pregnancies, respectively. Five women became severely unwell with sepsis; two died and another three required care in the intensive treatment unit.ConclusionsIn this study, 26% of women who had very early PPROM with expectant management had babies that survived to discharge from hospital. Morbidity and mortality rates were high for both mothers and neonates. Maternal sepsis is a considerable risk that needs more research. These data should be used in counselling families with PPROM before 23 weeks' gestation, and currently available guidelines should be updated accordingly.

Objectives Describe infant and maternal outcomes of a national cohort of women with preterm prelabour rupture of membranes (PPROM) under 23 weeks gestation. Design Prospective national population-based cohort study using the UK Obstetric Surveillance System (UKOSS). Setting All 194 obstetric units in the UK. Participants 330 women with singleton and 38 with multiple pregnancies and PPROM between 16+0 and 22+6 weeks gestation 1/9/19-28/2/21. Main outcome measures Infant outcomes: livebirth, survival to hospital discharge and severe morbidity, defined as intraventricular haemorrhage grade 3 or 4 and/or supplemental oxygen requirement at 36 weeks postmenstrual age. Maternal outcomes: surgery for placental removal; sepsis; admission to intensive treatment unit (ITU) and death. Methods All data including rates of termination of pregnancy for medical reasons (TFMR) were reported. Three rates were calculated for infant outcomes: i) all TFMR excluded; ii) assuming that all TFMR and those with missing data would have died; iii) assuming that all TFMR and those with missing data would be liveborn. Rates are presented as i (ii to iii). Results For singleton pregnancies the livebirth rate was 44% (30 to 62%), infant survival to discharge was 26% (16 to 54%) and 18% (12 to 49%) of infants survived without severe morbidity. Maternal sepsis rate was 12% for singleton and 26% for twin pregnancies. Surgery for placental removal was 20% and 14%, respectively. Five women became severely unwell with sepsis, 2 died and a further 3 required ITU care. Conclusions Although significant numbers of pregnancies with very early PPROM have favourable outcomes, morbidity and mortality rates in this cohort are high for mothers and infants. These data can be used in counselling families facing PPROM prior to 23 weeks gestation and to underpin research into the complex pathologies, including sepsis, related to this condition. Currently available guidelines should be updated accordingly.

ABSTRACTObjectivesFirst, to determine the uptake of prenatal exome sequencing (pES) and the diagnostic yield of pathogenic (causative) variants in a UK tertiary fetal medicine unit following the introduction of the NHS England Rapid Exome Sequencing Service for fetal anomalies testing (R21 pathway). Second, to identify how the decision to proceed with pES and identification of a causative variant affect perinatal outcomes, specifically late termination of pregnancy (TOP) at or beyond 22 weeks' gestation.MethodsThis was a retrospective cohort study of anomalous fetuses referred to the Liverpool Women's Hospital Fetal Medicine Unit between 1 March 2021 and 28 February 2022. pES was performed as part of the R21 pathway. Trio exome sequencing was performed using an Illumina next‐generation sequencing platform assessing coding and splice regions of a panel of 974 prenatally relevant genes and 231 expert reviewed genes. Data on demographics, phenotype, pES result and perinatal outcome were extracted and compared. Descriptive statistics and the χ‐square or Fisher's exact test were performed using IBM SPSS version 28.0.1.0.ResultsIn total, 72 cases were identified and two‐thirds of eligible women (n = 48) consented to trio pES. pES was not feasible in one case owing to a low DNA yield and, therefore, was performed in 47 cases. In one‐third of cases (n = 24), pES was not proposed or agreed. In 58.3% (14/24) of these cases, this was because invasive testing was declined and, in 41.7% (10/24) of cases, women opted for testing and underwent chromosomal microarray analysis only. The diagnostic yield of pES was 23.4% (11/47). There was no overall difference in the proportion of women who decided to have late TOP in the group in which pES was agreed compared with the group in which pES was not proposed or agreed (25.0% (12/48) vs 25.0% (6/24); P = 1.0). However, the decision to have late TOP was significantly more frequent when a causative variant was detected compared with when pES was uninformative (63.6% (7/11) vs 13.9% (5/36); P < 0.0009). The median turnaround time for results was longer in cases in which a causative variant was identified than in those in which pES was uninformative (22 days (interquartile range (IQR), 19–34) days vs 14 days (IQR, 10–15 days); P < 0.0001).ConclusionsThis study demonstrates the potential impact of identification of a causative variant by pES on decision to have late TOP. As the R21 pathway continues to evolve, we urge clinicians and policymakers to consider introducing earlier screening for anomalies, developing robust guidance for late TOP and ensuring optimized support for couples. © 2022 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Background Antenatal corticosteroids (ACS) are widely prescribed to improve outcomes following preterm birth. Significant knowledge gaps surround their safety, long-term effects, optimal timing and dosage. Almost half of women given ACS give birth outside the “therapeutic window” and have not delivered over 7 days later. Overtreatment with ACS is a concern, as evidence accumulates of risks of unnecessary ACS exposure. Methods The Consortium for the Study of Pregnancy Treatments (Co-OPT) was established to address research questions surrounding safety of medications in pregnancy. We created an international birth cohort containing information on ACS exposure and pregnancy and neonatal outcomes by combining data from four national/provincial birth registers and one hospital database, and follow-up through linked population-level data from death registers and electronic health records. Results and discussion The Co-OPT ACS cohort contains 2.28 million pregnancies and babies, born in Finland, Iceland, Israel, Canada and Scotland, between 1990 and 2019. Births from 22 to 45 weeks’ gestation were included; 92.9% were at term (≥ 37 completed weeks). 3.6% of babies were exposed to ACS (67.0% and 77.9% of singleton and multiple births before 34 weeks, respectively). Rates of ACS exposure increased across the study period. Of all ACS-exposed babies, 26.8% were born at term. Longitudinal childhood data were available for 1.64 million live births. Follow-up includes diagnoses of a range of physical and mental disorders from the Finnish Hospital Register, diagnoses of mental, behavioural, and neurodevelopmental disorders from the Icelandic Patient Registers, and preschool reviews from the Scottish Child Health Surveillance Programme. The Co-OPT ACS cohort is the largest international birth cohort to date with data on ACS exposure and maternal, perinatal and childhood outcomes. Its large scale will enable assessment of important rare outcomes such as perinatal mortality, and comprehensive evaluation of the short- and long-term safety and efficacy of ACS.

Introduction: Midtrimester prelabor rupture of membranes (PROM) between 16 and 24 weeks of gestational age is a major obstetric complication with high rates of perinatal morbidity and mortality. Amnioinfusion has been proposed in women with midtrimester PROM to target oligohydramnios and subsequently enhance pulmonary development and perinatal outcomes. Material and Methods: The purpose of this study was to perform a systematic review and meta-analysis including all randomized clinical trials investigating amnioinfusion versus no intervention in women with PROM between 16+0 and 24+0 weeks of gestational age. Databases Central, Embase, Medline, ClinicalTrials.gov and references of identified articles were searched from inception of database to December 2021. The primary outcome was perinatal mortality. Secondary outcomes included neonatal, maternal, and long-term developmental outcomes as defined in the core outcome set for preterm birth studies. Summary measures were reported as pooled relative risk (RR) or mean difference with corresponding 95% confidence interval (CI). Results: Two studies (112 patients, 56 in the amnioinfusion group and 56 in the no intervention group) were included in this review. Pooled perinatal mortality was 66.1% (37/56) in the amnioinfusion group compared with 71.4% (40/56) in no intervention group (RR 0.92, 95% CI: 0.72–1.19). Other neonatal and maternal core outcomes were similar in both groups, although due to the relatively small number of events and wide CIs, there is a possibility that amnioinfusion can be associated with clinically important benefits and harms. Long-term healthy survival was seen in 35.7% (10/28) of children assessed for follow-up and treated with amnioinfusion versus 28.6% (8/28) after no intervention (RR 1.30, 95% CI: 0.47–3.60, “best case scenario”). Conclusions: Based on these findings, the benefits of amnioinfusion for midtrimester PROM <24 weeks of gestational age are unproven, and the potential harms remain undetermined.

To assess the association between vaginal microbiome (VMB) composition and recurrent early spontaneous preterm birth (sPTB)/preterm prelabour rupture of membranes (PPROM).

A 2018 Cochrane review found that omega-3 supplementation in pregnancy was associated with a risk reduction of early preterm birth of 0.58; prompting calls for universal supplementation. Recent analysis suggests the benefit may be confined to women with a low baseline omega-3 fatty acid status. However, the contemporary omega-3 fatty acid status of pregnant women in the UK is largely unknown. This is particularly pertinent for women with a previous preterm birth, in whom a small relative risk reduction would have a larger reduction of absolute risk. This study aimed to assess the omega-3 fatty acid status of a UK pregnant population and determine the association between the long-chain omega-3 fatty acids and recurrent spontaneous early preterm birth. A total of 283 high-risk women with previous early preterm birth were recruited to the prospective observational study in Liverpool, UK. Additionally, 96 pregnant women with previous term births and birth ≥39 +0  weeks in the index pregnancy provided a low-risk population sample. Within the high-risk group we assessed the odds ratio of recurrent early preterm birth compared with birth at ≥37 +0  weeks of gestation according to plasma eicosapentaenoic acid plus docosahexaenoic acid (EPA+DHA) at 15–22 weeks of gestation. Our participants had low EPA+DHA; 62% (143/229) of women with previous preterm birth and 69% (68/96) of the population sample had levels within the lowest two quintiles of a previously published pregnancy cohort. We found no association between long-chain omega-3 status and recurrent early preterm birth ( n  = 51). The crude odds ratio of a recurrent event was 0.91 (95% CI 0.38–2.15, p  = 0.83) for women in the lowest, compared with the highest three quintiles of EPA+DHA. In the majority of our participants, levels of long-chain omega-3 were low; within the range that may benefit from supplementation. However, levels showed no association with risk of recurrent early spontaneous preterm birth. This could be because our population levels were too low to show benefit in being omega-3 “replete”; or else omega-3 levels may be of lesser importance in recurrent early preterm birth.

Introduction A 2018 Cochrane review found that omega-3 supplementation in pregnancy was associated with a risk reduction of early preterm birth of 0.58; prompting calls for universal supplementation. Recent analysis suggests the benefit may be confined to women with a low baseline omega-3 fatty acid status. However, the contemporary omega-3 fatty acid status of pregnant women in the UK is largely unknown. This is particularly pertinent for women with a previous preterm birth, in whom a small relative risk reduction would have a larger reduction of absolute risk. This study aimed to assess the omega-3 fatty acid status of a UK pregnant population and determine the association between the long-chain omega-3 fatty acids and recurrent spontaneous early preterm birth. Material and methods A total of 283 high-risk women with previous early preterm birth were recruited to the prospective observational study in Liverpool, UK. Additionally, 96 pregnant women with previous term births and birth >= 39(+0 )weeks in the index pregnancy provided a low-risk population sample. Within the high-risk group we assessed the odds ratio of recurrent early preterm birth compared with birth at >= 37(+0 )weeks of gestation according to plasma eicosapentaenoic acid plus docosahexaenoic acid (EPA+DHA) at 15-22 weeks of gestation. Results Our participants had low EPA+DHA; 62% (143/229) of women with previous preterm birth and 69% (68/96) of the population sample had levels within the lowest two quintiles of a previously published pregnancy cohort. We found no association between long-chain omega-3 status and recurrent early preterm birth (n = 51). The crude odds ratio of a recurrent event was 0.91 (95% CI 0.38-2.15, p = 0.83) for women in the lowest, compared with the highest three quintiles of EPA+DHA. Conclusions In the majority of our participants, levels of long-chain omega-3 were low; within the range that may benefit from supplementation. However, levels showed no association with risk of recurrent early spontaneous preterm birth. This could be because our population levels were too low to show benefit in being omega-3 "replete"; or else omega-3 levels may be of lesser importance in recurrent early preterm birth.

Background: Antenatal corticosteroid treatment (ACT) has been widely accepted as a safe, beneficial treatment which improves outcomes following preterm birth. It has been shown to reduce respiratory distress syndrome and neonatal mortality and is commonly used in threatened or planned preterm delivery, as well as prior to elective Caesarean-section at term. There are some concerns however, that in some cases, ACT is used in patients where clinical benefit has not been established, or may potentially increase harm. Many women who receive ACT do not deliver preterm and the long-term consequences of ACT treatment are unclear. This study aims to evaluate the benefits and harms of ACT using latest trial evidence to allow refinement of current practice. Methods: This study will compare ACT with placebo or non-treatment. Inclusion criteria are: Randomised Controlled Trials (RCT) comparing ACT vs. no ACT (with or without placebo) in all settings. Exclusion criteria are: non-randomised or quasi-randomised studies and studies comparing single vs. multiple courses of ACT. Main outcomes are to evaluate, for women at risk of preterm birth or undergoing planned Caesarean- section, the benefits and harms of ACT, on maternal, fetal, newborn, and long-term offspring health outcomes. The individual participant data (IPD) of identified RCTs will be collected and consecutively synthesised using meta-analysis with both a one-stage model where all IPD is analysed together and a two-stage model where treatment effect estimates are calculated for each trial individually first and thereafter pooled in a meta-analysis. Sub-group analysis will be performed to identify heterogeneous effects of ACT across predefined risk groups. Discussion: Co-opt is the Consortium for the Study of Pregnancy Treatments and aims to complete a robust evaluation of the benefits and harms of ACT. This IPD meta-analysis will contribute to this by allowing detailed interrogation of existing trial datasets. PROSPERO registration: CRD42020167312 (03/02/2020).

Introduction: There is consensus that planned vaginal birth after caesarean (VBAC) is a clinically safe choice for the majority of women with a single previous lower segment caesarean delivery. Such choice is also supported by health economic modelling and may be a strategy used to limit further escalation of caesarean delivery rates and maternal morbidity associated with multiple caesarean deliveries.

Objective To review what is known about the relationship between stillbirth and inequalities from different disciplinary perspectives to inform stillbirth prevention strategies. Design Systematic review using the meta-narrative method. Setting Studies undertaken in the UK. Data sources Scoping phase: experts in field, exploratory electronic searches and handsearching. Systematic searches phase: Nine databases with no geographical or date restrictions. Non-English language studies were excluded. Study selection Any investigation of stillbirth and inequalities with a UK component. Data extraction and synthesis Three authors extracted data and assessed study quality. Data were summarised, tabulated and presented graphically before synthesis of the unfolding storyline by research tradition; and then of the commonalities, differences and interplays between narratives into resultant summary meta-themes. Results Fifty-four sources from nine distinctive research traditions were included. The evidence of associations between social inequalities and stillbirth spanned 70 years. Across research traditions, there was recurrent evidence of the social gradient remaining constant or increasing, fuelling repeated calls for action (meta-theme 1: something must be done). There was less evidence of an effective response to these calls. Data pertaining to socioeconomic, area and ethnic disparities were routinely collected, but not consistently recorded, monitored or reported in relation to stillbirth (meta-theme 2: problems of precision). Many studies stressed the interplay of socioeconomic status, deprivation or ethnicity with aggregated factors including heritable, structural, environmental and lifestyle factors (meta-theme 3: moving from associations towards intersectionality and intervention(s)). No intervention studies were identified. Conclusion Research investigating inequalities and stillbirth in the UK is underdeveloped. This is despite repeated evidence of an association between stillbirth risk and poverty, and stillbirth risk, poverty and ethnicity. A specific research forum is required to lead the development of research and policy in this area, which can harness the multiple relevant research perspectives and address the intersections between different policy areas. PROSPERO registration number CRD42017079228.

ObjectiveThe QUiPP algorithm combines cervical length, quantitative fetal fibronectin (qfFN) and medical history to quantify risk of preterm birth. We assessed the utility of QUiPP to inform preterm birth prevention treatment decisions.DesignA prospective cohort study with a subsequent impact assessment using the QUiPP risk of birth before 34 weeks’ gestation.SettingA UK tertiary referral hospital.SampleIn all, 119 women with previous spontaneous preterm birth (sPTB) or preterm premature rupture of membranes (PPROM) before 34 weeks’ gestation.MethodsCervical length and qfFN were measured at 19+0 to 23+0 weeks’ gestation. Clinical management was based on history and cervical length. After birth, clinicians were unblinded to qfFN results and QUiPP analysis was undertaken.Main outcome measuresPredictive statistics of QUiPP algorithm using 10% risk of sPTB before 34+0 weeks as treatment threshold.ResultsFifteen of 119 women (13%) had PPROM or sPTB before 34 weeks. Of these, 53% (8/15) had QUiPP risk of sPTB before 34+0 weeks above 10%. Applying this treatment threshold in practice would have doubled our treatment rate (20 versus 42%). QUIPP threshold of 10% had positive likelihood ratio (LR) of 1.3 (95% CI 0.76–2.18), and negative LR of 0.8 (95% CI 0.45–1.40) for predicting sPTB before 34+0 weeks.ConclusionsUse of the QUiPP algorithm in this population may lead to substantial increase in interventions without evidence that currently available treatment options are beneficial for this particular group.Tweetable abstractIndependent study finds that the QUiPP algorithm could lead to substantial increases in treatment without evidence of benefit.

The Midlands and North of England Stillbirth Study (MiNESS) was a case-control study of women who had a stillbirth or who had an ongoing pregnancy. During the set up phase questions were raised about whether interviewing women within six weeks of a stillbirth and recruiting women who were still pregnant into a “stillbirth” study was acceptable. This led to the research questions “whether it is appropriate to ask women who have recently experienced a stillbirth to participate in research?” and “whether it is appropriate to ask pregnant women to participate in a research project looking at factors associated with stillbirth.” This nested study aimed to describe the opinions of women approached to participate in MiNESS to explore their views and experiences of a research project focussed on stillbirth.

To the Editor: The prenatal reflex DNA test described in our paper1.Wald NJ, Huttly WJ, Bestwick JP et al. Prenatal reflex DNA screeningfor trisomies 21, 18, and 13. Genet Med; e-pub ahead of print 9 November 2017.Google Scholar is a method of screening that has advantages over the recall method.2.Chitty L.S. Wright D. Hill M. et al.Uptake, outcome and costs of implementing non-invasive prenatal testing for Down’s syndrome into NHS maternity care: prospective cohort study in eight diverse maternity units.10.1136/bmj.i3426BMJ. 2016; 354: i3426Google Scholar,3.Public Health England. NHS public health functions agreement 2017-18. Service specification no.16. NHS Fetal Anomaly Screening Programme—screening for Down’s, Edwards’ and Patau’s Syndromes (Trisomy 21, 18 & 13). https://www.england.nhs.uk/wp-content/uploads/2017/05/serv-spec-16.pdf. Accessed 29 November 2017.Google Scholar In the recall method as described,3.Public Health England. NHS public health functions agreement 2017-18. Service specification no.16. NHS Fetal Anomaly Screening Programme—screening for Down’s, Edwards’ and Patau’s Syndromes (Trisomy 21, 18 & 13). https://www.england.nhs.uk/wp-content/uploads/2017/05/serv-spec-16.pdf. Accessed 29 November 2017.Google Scholar a combined test is carried out and women with a risk ≥1 in 150 receive a positive result; they are invited to return for counseling and offered either a second screening test based on a DNA analysis or an invasive diagnostic test—of course, without an obligation to accept either. Walker, in her letter,4.Walker C.L. Response to Wald et al.1:CAS:528:DC%2BC1cXhtVamsb7I10.1038/gim.2017.237Genet Med. 2018; 20: 1Google Scholar does not appear to fully accept the advantages of the reflex method. Reflex DNA screening results in a higher rate of detection (95% vs. 81%) of pregnancies with trisomy 21, 18, and 13 and a false-positive rate (0.02% vs. 2.4%) about a hundred times lower than the recall method. Consequently, the reflex method means fewer women with an unaffected pregnancy are given a positive screening result, while a high detection rate is maintained. A quantitative comparison of the two methods in respect of screening for trisomy 21 is given at http://www.wolfson.qmul.ac.uk/ReflexDNAversusRecallDNA. This shows that in 10,000 pregnancies screened by either the reflex or recall methods, respectively, the following numbers apply: (i) women recalled, 0 vs. 259; (ii) invasive diagnostic tests in unaffected pregnancies, 1.8 vs. 30.3; (iii) trisomy 21 pregnancies detected, 30.3 vs. 25.9; and (iv) odds of being affected given a positive result, 17:1 vs. 1:1. These advantages of the reflex method over the recall method are clear and, contrary to Walker’s opinion, involve no extrapolation. It is untenable to suggest that worrying women and their partners with the news of a positive screening result when this is completely unnecessary is good medical practice, or even ethical. Calling women back for another test when this can be avoided causes unnecessary harm and this is always wrong. It is not an issue that is relevant to patient autonomy or choice, which is, of course, important.Our responses to Walker’s four points are as follows. (i) The decision to be screened is an option that women can, of course, discuss with their partners; obtaining consent to reflex DNA screening is no different from obtaining consent to other screening tests. (ii) Notifying women that they have a positive screening result is obviously distressing. If this can be avoided without loss of efficacy it should be done. It is not a legitimate or ethical matter for research. (iii) The duty of health professionals is to offer the most effective and safe tests or interventions that are affordable. This is not paternalistic; it is the expected duty of care. There is no withholding of information, as Walker states in relation to reflex DNA screening, because consent is obtained for the reflex test incorporating all its components. The combined test itself has several components and no one argues that separate consent should be sought for each component (nuchal translucency measurement and two blood measurements). The concept underlying the reflex DNA test is to capture the advantages of a single screening test with several components instead of performing two separate sequential tests. (iv) Avoiding unnecessary harm without loss of efficacy is always a benefit and therefore not a valid research issue.While there is agreement about using the combined test followed by a DNA test in some women, there is disagreement on how this is done. Walker holds the view that there is merit in women being told that they have a positive combined test result, and then being recalled for counseling. Given that reflex DNA screening can avoid this step entirely, and deliver a test with an improved screening performance, we see no advantage in the recall strategy.We are puzzled by Walker’s view that avoiding the unnecessary reporting of false-positive results is not a self-evident benefit, and puzzled by her questioning the consequential reduced use of clinical resources, which was unambiguously clear to the midwives and clinicians involved. We are also at a loss to understand how Walker seems to lean toward the recall method, when the evidence so strongly favors the reflex method with the added benefit of avoiding needless worry among the women screened.Ethical declarationDisclosureN.J.W. is Director of Logical Medical Systems, which produces software for the interpretation of Down syndrome screening tests. The other authors declare no conflict of interest. To the Editor: The prenatal reflex DNA test described in our paper1.Wald NJ, Huttly WJ, Bestwick JP et al. Prenatal reflex DNA screeningfor trisomies 21, 18, and 13. Genet Med; e-pub ahead of print 9 November 2017.Google Scholar is a method of screening that has advantages over the recall method.2.Chitty L.S. Wright D. Hill M. et al.Uptake, outcome and costs of implementing non-invasive prenatal testing for Down’s syndrome into NHS maternity care: prospective cohort study in eight diverse maternity units.10.1136/bmj.i3426BMJ. 2016; 354: i3426Google Scholar,3.Public Health England. NHS public health functions agreement 2017-18. Service specification no.16. NHS Fetal Anomaly Screening Programme—screening for Down’s, Edwards’ and Patau’s Syndromes (Trisomy 21, 18 & 13). https://www.england.nhs.uk/wp-content/uploads/2017/05/serv-spec-16.pdf. Accessed 29 November 2017.Google Scholar In the recall method as described,3.Public Health England. NHS public health functions agreement 2017-18. Service specification no.16. NHS Fetal Anomaly Screening Programme—screening for Down’s, Edwards’ and Patau’s Syndromes (Trisomy 21, 18 & 13). https://www.england.nhs.uk/wp-content/uploads/2017/05/serv-spec-16.pdf. Accessed 29 November 2017.Google Scholar a combined test is carried out and women with a risk ≥1 in 150 receive a positive result; they are invited to return for counseling and offered either a second screening test based on a DNA analysis or an invasive diagnostic test—of course, without an obligation to accept either. Walker, in her letter,4.Walker C.L. Response to Wald et al.1:CAS:528:DC%2BC1cXhtVamsb7I10.1038/gim.2017.237Genet Med. 2018; 20: 1Google Scholar does not appear to fully accept the advantages of the reflex method. Reflex DNA screening results in a higher rate of detection (95% vs. 81%) of pregnancies with trisomy 21, 18, and 13 and a false-positive rate (0.02% vs. 2.4%) about a hundred times lower than the recall method. Consequently, the reflex method means fewer women with an unaffected pregnancy are given a positive screening result, while a high detection rate is maintained. A quantitative comparison of the two methods in respect of screening for trisomy 21 is given at http://www.wolfson.qmul.ac.uk/ReflexDNAversusRecallDNA. This shows that in 10,000 pregnancies screened by either the reflex or recall methods, respectively, the following numbers apply: (i) women recalled, 0 vs. 259; (ii) invasive diagnostic tests in unaffected pregnancies, 1.8 vs. 30.3; (iii) trisomy 21 pregnancies detected, 30.3 vs. 25.9; and (iv) odds of being affected given a positive result, 17:1 vs. 1:1. These advantages of the reflex method over the recall method are clear and, contrary to Walker’s opinion, involve no extrapolation. It is untenable to suggest that worrying women and their partners with the news of a positive screening result when this is completely unnecessary is good medical practice, or even ethical. Calling women back for another test when this can be avoided causes unnecessary harm and this is always wrong. It is not an issue that is relevant to patient autonomy or choice, which is, of course, important. Our responses to Walker’s four points are as follows. (i) The decision to be screened is an option that women can, of course, discuss with their partners; obtaining consent to reflex DNA screening is no different from obtaining consent to other screening tests. (ii) Notifying women that they have a positive screening result is obviously distressing. If this can be avoided without loss of efficacy it should be done. It is not a legitimate or ethical matter for research. (iii) The duty of health professionals is to offer the most effective and safe tests or interventions that are affordable. This is not paternalistic; it is the expected duty of care. There is no withholding of information, as Walker states in relation to reflex DNA screening, because consent is obtained for the reflex test incorporating all its components. The combined test itself has several components and no one argues that separate consent should be sought for each component (nuchal translucency measurement and two blood measurements). The concept underlying the reflex DNA test is to capture the advantages of a single screening test with several components instead of performing two separate sequential tests. (iv) Avoiding unnecessary harm without loss of efficacy is always a benefit and therefore not a valid research issue. While there is agreement about using the combined test followed by a DNA test in some women, there is disagreement on how this is done. Walker holds the view that there is merit in women being told that they have a positive combined test result, and then being recalled for counseling. Given that reflex DNA screening can avoid this step entirely, and deliver a test with an improved screening performance, we see no advantage in the recall strategy. We are puzzled by Walker’s view that avoiding the unnecessary reporting of false-positive results is not a self-evident benefit, and puzzled by her questioning the consequential reduced use of clinical resources, which was unambiguously clear to the midwives and clinicians involved. We are also at a loss to understand how Walker seems to lean toward the recall method, when the evidence so strongly favors the reflex method with the added benefit of avoiding needless worry among the women screened. Ethical declarationDisclosureN.J.W. is Director of Logical Medical Systems, which produces software for the interpretation of Down syndrome screening tests. The other authors declare no conflict of interest. DisclosureN.J.W. is Director of Logical Medical Systems, which produces software for the interpretation of Down syndrome screening tests. The other authors declare no conflict of interest. N.J.W. is Director of Logical Medical Systems, which produces software for the interpretation of Down syndrome screening tests. The other authors declare no conflict of interest.

Purpose: To describe single center clinical experience with cervical pessary used for high-risk pregnant women who also had short cervix. We have focused on the techniques to optimize efficacy and minimize the risk of complications and side effects related to pessary insertion, removal, and pregnancy management.Methods: This is an audit from specialist preterm birth prevention clinic in Liverpool Women's Hospital, United Kingdom for the period between January 2013 and December 2017. We also conducted postal survey in November 2015 to evaluate women's experience with vaginal pessary.Results: Out of 235 women who were treated for short cervix, 129 (55%) had cervical pessary as a first line treatment. Overall, 50% of treated women reached term. 17 women (13%) needed additional treatment, 9 women had pessary reinserted (7%), and 53 (41%) had pessary removed before 36 weeks, mainly due to ruptured membranes. Significant vaginal discharge and pelvic discomfort were reported by 14 and 7% women, respectively. 89% of treated women would recommend the pessary treatment to others.Conclusions: Whilst the cervical pessary continues to be evaluated in clinical trials, our experience suggests that pessary is quite easy to insert and remove and is well tolerated by the women.

Objective To report perception of fetal movements in women who experienced a stillbirth compared with controls at a similar gestation with a live birth. Design Case–control study. Setting 41 maternity units in the UK. Participants Cases were women who had a late stillbirth ≥28 weeks gestation (n=291) and controls were women with an ongoing pregnancy at the time of the interview (n=733). Controls were frequency matched to cases by obstetric unit and gestational age. Methods Data were collected using an interviewer-administered questionnaire which included questions on maternal perception of fetal movement (frequency, strength, increased and decreased movements and hiccups) in the 2 weeks before the interview/stillbirth. Five fetal movement patterns were identified incorporating the changes in strength and frequency in the last 2 weeks by combining groups of similar pattern and risk. Multivariable analysis adjusted for known confounders. Primary outcome measure Association of maternally perceived fetal movements in relation to late stillbirth. Results In multivariable analyses, women who reported increased strength of movements in the last 2 weeks had decreased risk of late stillbirth compared with those whose movements were unchanged (adjusted OR (aOR) 0.18, 95% CI 0.13 to 0.26). Women with decreased frequency (without increase in strength) of fetal movements were at increased risk (aOR 4.51, 95% CI 2.38 to 8.55). Daily perception of fetal hiccups was protective (aOR 0.31, 95% CI 0.17 to 0.56). Conclusions Increased strength of fetal movements and fetal hiccups is associated with decreased risk of stillbirth. Alterations in frequency of fetal movements are important in identifying pregnancies at increased risk of stillbirth, with the greatest risk in women noting a reduction in fetal activity. Clinical guidance should be updated to reflect that increase in strength and frequency of fetal movements is associated with the lowest risk of stillbirth, and that decreased fetal movements are associated with stillbirth. Trial registration number NCT02025530 .