The impact of late pregnancy dating on the detection of fetal growth restriction at term.

INTRODUCTION: The inaccuracy of late pregnancy dating is often discussed, and the impact on diagnosis of fetal growth restriction is a concern. However, the magnitude and direction of this effect has not previously been demonstrated. In this study, we aimed to investigate the effect of late pregnancy dating by head circumference on the detection of late onset growth restriction, compared to first trimester crown-rump length dating. MATERIAL AND METHODS: This was a cohort study of 14 013 pregnancies receiving obstetric care at a tertiary center over a three-year period. Universal scans were performed at 12 weeks, including crown-rump length; at 20 weeks including fetal biometry; and at 36 weeks, where biometry, umbilical artery doppler and cerebroplacental ratio were used to determine the incidence of fetal growth restriction according to the Delphi consensus. For the entire cohort, the gestational age was first calculated using T1 dating; and was then recalculated using head circumference at 20 weeks (T2 dating); and at 36 weeks (T3 dating). The incidence of fetal growth restriction following T2 and T3 dating was compared to T1 dating using four-by-four sensitivity tables. RESULTS: When the cohort was redated from T1 to T2, the median gestation at delivery changed from 40 + 0 to 40 + 2 weeks (p < 0.001). When the cohort was redated from T1 to T3, the median gestation at delivery changed from 40 + 0 to 40 + 3 weeks (p < 0.001). T2 dating resulted in fetal growth restriction sensitivity of 80.2% with positive predictive value of 78.8% compared to T1 dating. T3 dating resulted in sensitivity of 8.6% and positive predictive value of 27.7%, respectively. The sensitivity of abnormal CPR remained high despite T2 and T3 redating; 98.0% and 89.4%, respectively. CONCLUSIONS: Although dating at 11-14 weeks is recommended, late pregnancy dating is sometimes inevitable, and this can prolong the estimated due date by an average of two to three days. One in five pregnancies which would be classified as growth restricted if the pregnancy was dated in the first trimester, will be reclassified as nongrowth restricted following dating at 20 weeks, whereas nine out of 10 pregnancies will be reclassified as non-growth restricted with 36-week dating.

Early antenatal risk factors for births before arrival: An unmatched case-control study.

INTRODUCTION: Birth before arrival is associated with maternal morbidity and neonatal morbidity and mortality. Yet, timely risk stratification remains challenging. Our objective was to identify risk factors for birth before arrival which may be determined at the first antenatal appointment. MATERIAL AND METHODS: This was an unmatched case-control study involving 37 348 persons who gave birth at a minimum of 22+0 weeks' gestation over a 5-year period from January 2014 to October 2019 (IRAS project ID 222260; REC reference: 17/SC/0374). The setting was a large UK university hospital. Data obtained on maternal characteristics at booking was examined for association with birth before arrival using a stepwise multivariable logistic regression analysis. Data are presented as adjusted odds ratios with 95% confidence intervals. Area under the receiver-operator characteristic curves (C-statistic) were employed to enable discriminant analysis assessing the risk prediction of the booking data on the outcome. RESULTS: Multivariable analysis identified significant independent predictors of birth before arrival that were detectable at booking: parity, ethnicity, multiple deprivation, employment status, timing of booking, distance from home to the nearest maternity unit, and safeguarding concerns raised at booking by clinical staff. Our model demonstrated good discrimination for birth before arrival; together, the predictors accounted for 77% of the data variance (95% confidence interval 0.74-0.80). CONCLUSIONS: Information gathered routinely at booking may discriminate individuals at risk for birth before arrival. Better recognition of early factors may enable maternity staff to direct higher-risk women towards specialized care services at an early point in their pregnancy, enabling time for clinical and social interventions.

Multimodal Deep Learning for Predicting Adverse Birth Outcomes Based on Early Labour Data.

Cardiotocography (CTG) is a widely used technique to monitor fetal heart rate (FHR) during labour and assess the health of the baby. However, visual interpretation of CTG signals is subjective and prone to error. Automated methods that mimic clinical guidelines have been developed, but they failed to improve detection of abnormal traces. This study aims to classify CTGs with and without severe compromise at birth using routinely collected CTGs from 51,449 births at term from the first 20 min of FHR recordings. Three 1D-CNN and LSTM based architectures are compared. We also transform the FHR signal into 2D images using time-frequency representation with a spectrogram and scalogram analysis, and subsequently, the 2D images are analysed using a 2D-CNNs. In the proposed multi-modal architecture, the 2D-CNN and the 1D-CNN-LSTM are connected in parallel. The models are evaluated in terms of partial area under the curve (PAUC) between 0-10% false-positive rate; and sensitivity at 95% specificity. The 1D-CNN-LSTM parallel architecture outperformed the other models, achieving a PAUC of 0.20 and sensitivity of 20% at 95% specificity. Our future work will focus on improving the classification performance by employing a larger dataset, analysing longer FHR traces, and incorporating clinical risk factors.

The impact of a universal late third-trimester scan for fetal growth restriction on perinatal outcomes in term singleton births: A prospective cohort study.

OBJECTIVE: To investigate perinatal mortality, morbidity and obstetric intervention following the introduction of a universal late third-trimester ultrasound scan for growth restriction. DESIGN: Prospective cohort study. SETTING: Oxfordshire (OUH), UK. POPULATION: Women with a non-anomalous singleton pregnancy undergoing pregnancy care and term delivery at OUH with an estimated due date (EDD) of birth between 1 January 2014 and 30 September 2019. METHODS: Universal ultrasound for fetal growth restriction between 35+0 and 36+6 weeks was introduced in 2016. The outcomes of the next 18 631 eligible term pregnancies were compared, adjusting for covariates and time, with the previous 18 636 who had clinically indicated ultrasounds only. 'Screen-positives' for growth restriction were managed according to a pre-determined protocol which included non-intervention for some small-for-gestational-age babies. MAIN OUTCOME MEASURES: Extended perinatal mortality, a composite of mortality or encephalopathy Grade II-III, and expedited birth. Other outcomes included composite adverse outcomes used elsewhere, detection of low birthweight and birth from 37+0 to 38+6 weeks. RESULTS: Extended perinatal deaths decreased 27% and severe morbidity decreased 33% but neither change was statistically significant (adjusted odd ratio [aOR] 0.53, 95% confidence interval [C1] 00.18-1.56 and aOR 0.71, 95% CI 0.31-1.63). Expedited births changed from 35.2% to 37.7% (aOR 0.99, 95% CI 0.92-1.06). Birthweight (<10th centile) detection using fetal biometry alone was 31.4% and rose to 40.5% if all abnormal scan parameters were used. CONCLUSION: Improvements in mortality and severe morbidity subsequent to introducing a universal ultrasound for growth restriction are encouraging but remain unclear. Little change in intervention is possible. The antenatal detection of low birthweight remains poor but improves where markers of growth restriction are used.

Abnormal umbilical artery pulsatility index in appropriately grown fetuses in the early third trimester: an observational cohort study.

OBJECTIVE: The aim of this study was to determine if appropriately grown fetuses (those that are not small-for-gestational-age) with a raised umbilical artery pulsatility index (>95th centile) in the mid third trimester are at increased risk of placental dysfunction and adverse outcome. METHODS: This is a 5-year retrospective cohort study using routinely collected data. Inclusion criteria were singleton, non-anomalous pregnancies having a growth scan with umbilical artery Doppler velocimetry between 28 + 0 and 33 + 6 weeks' gestation. Small-for-gestational-age fetuses were excluded. Cases were classified as group 1 (those with an umbilical artery pulsatility index >95th centile at any scan during target window) or group 2 (those where the umbilical artery pulsatility index was ≤95th centile at all scans). p-Values and odds ratios were calculated. Logistic regression was used to compute odds ratios adjusted for baseline estimated weight z-score, gestational age at delivery, and labor induction. RESULTS: After exclusions, there were 202 pregnancies in group 1 and 7950 in group 2. Differences in baseline characteristics between the groups include age (median age was 30 for group 1 and 32 for group 2, p < .001), smoking (group 1 were more likely to smoke, p < .001) and labor induction (more common in group 1, p = .03). Among those delivering ≥34 + 0, group 1 were more likely to be small-for-gestational-age and have an abnormal cerebro-placental ratio at the final scan (OR 6.76, CI 4.23-10.80 and OR 5.07, CI 3.37-7.63 respectively), and to develop features of growth restriction (OR 9.85, CI 6.27-15.49). Group 1 were also more likely to deliver <37 + 0 weeks' gestation (OR 1.71, CI 1.13-2.58) and to have birthweight <10th or <3rd centile (OR 5.26, CI 3.65-7.58 and OR 6.13, CI 3.00-12.54 respectively). These associations remained significant when adjusted for estimated weight at the initial scan. CONCLUSIONS: These data suggest that raised umbilical artery pulsatility index in an appropriately grown fetus at 28 + 0 to 33 + 6 weeks' gestation is associated with subsequent development of growth restriction markers and an increased risk of moderate and severe small-for-gestational-age at birth. This is independent of the estimated weight of these babies at the index scan.

Do specific maternal sensations experienced in late pregnancy correlate to a breech presenting baby? Evaluation of a simple maternal questionnaire.

OBJECTIVES: To investigate the effectiveness of a structured questionnaire completed at 36 weeks gestation in predicting breech presentation. DESIGN: Questionnaire-based study. SETTING: Tertiary NHS Foundation Trust. PARTICIPANTS: Women attending for a universally offered 36-week fetal growth scan. INTERVENTION: Completion of a previously designed maternal questionnaire detailing sensation of fetal movements during the past week, immediately before a routine growth scan. RESULTS: Between September 01, 2018 and September 30, 2019, 2341 questionnaires were handed out and 2053 were returned. Analysis was performed in 1938 (94.4%) completed questionnaires. Recorded presentation was breech in 109 (5.6%), transverse/oblique in 15 (0.8%), and cephalic in 1814 (93.6%). Women "thinking their baby was breech" had a high positive likelihood ratio, at 11.8 (95% CI 7.4-19.1), but poor sensitivity (27.3%). "Feeling kicks low down or near the bladder" was sensitive for non-cephalic presentation (76.3%) but with poor specificity (48.9%). The questions "kicks low" ("no") (P = 0.013, aOR 2.18 [1.18-4.04]) and 'thinks cephalic ("no")' (P = 0.001, aOR 0.12 (0.04-0.43) were independent risk factors for a non-cephalic presentation. CONCLUSIONS: The questions posed in this questionnaire could aid the detection of breech presentation, but do not perform better than published data on palpation. Missing a breech presentation near term through palpation alone is well reported. Combining the concept of palpation to exclude breech presentation and these questions may help focus a clinician and improve both palpation skills and breech detection. As a minimum, a woman who believes her baby is breech should be taken seriously.

Prenatal diagnosis of PERCHING syndrome caused by homozygous loss of function variant in the KLHL7 gene.

AIMS: A couple were referred for prenatal genetic testing at 31 weeks' gestation due to the presence of mild polyhydramnios and multiple central nervous system (CNS) abnormalities, including borderline ventriculomegaly, possible delayed sulcation, an enlarged cisterna magna and a small area of calcification around the posterior horns. Testing was initiated to identify any underlying genetic cause. MATERIALS AND METHODS: Rapid trio exome sequencing (ES) was performed on DNA extracted from parental blood samples and amniotic fluid. RESULTS: A pathogenic homozygous nonsense variant in KLHL7 (NM_001031710.2) associated with PERCHING syndrome (#617055) was identified. CONCLUSION: Whilst there are detailed descriptions of the many postnatal phenotypes seen in these patients, there are few reports of features identified during pregnancy. This report is the first published prenatal diagnosis of PERCHING syndrome and provides further information on the associated fetal phenotypes.

Ultrasound predictors of adverse outcome in pregnancy complicated by pre-existing and gestational diabetes.

INTRODUCTION: Ultrasound assessment of fetuses subjected to hyperglycemia is recommended but, apart from increased size, little is known about its interpretation, and the identification of which large fetuses of diabetic pregnancy are at risk is unclear. Newer markers of adverse outcomes, abdominal circumference growth velocity and cerebro-placental ratio, help to predict risk in non-diabetic pregnancy. Our study aims to assess their role in pregnancies complicated by diabetes. MATERIAL AND METHODS: This is a retrospective analysis of a cohort of singleton, non-anomalous fetuses of women with pre-existing or gestational diabetes mellitus, and estimated fetal weight at the 10th centile or above. Gestational diabetes was diagnosed by selective screening of at risk groups. A universal ultrasound scan was offered at 20 and 36 weeks of gestation. Estimated fetal weight, abdominal circumference growth velocity, presence of polyhydramnios, and cerebro-placental ratio were evaluated at the 36-week scan. A composite adverse outcome was defined as the presence of one or more of perinatal death, arterial cord pH less than 7.1, admission to Neonatal Unit, 5-minute Apgar less than 7, severe hypoglycemia, or cesarean section for fetal compromise. A chi-squared test was used to test the association of estimated fetal weight at the 90th centile or above, polyhydramnios, abdominal circumference growth velocity at the 90th centile or above, and cerebro-placental ratio at the 5th centile or below with the composite outcome. Logistic regression was used to assess which ultrasound markers were independent risk factors. Odds ratios of composite adverse outcome with combinations of independent ultrasound markers were calculated. RESULTS: A total of 1044 pregnancies were included, comprising 87 women with pre-existing diabetes mellitus and 957 with gestational diabetes. Estimated fetal weight at the 90th centile or above, abdominal circumference growth velocity at the 90th centile or above, cerebro-placental ratio at the 5th centile or below, but not polyhydramnios, were significantly associated with adverse outcomes: odds ratios (95% confidence intervals) 1.85 (1.21-2.84), 1.54 (1.02-2.31), 1.92 (1.21-3.30), and 1.53 (0.79-2.99), respectively. Only estimated fetal weight at the 90th centile or above and cerebro-placental ratio at the 5th centile or below were independent risk factors. The greatest risk (odds ratio 6.85, 95% confidence interval 2.06-22.78) was found where both the estimated fetal weight is at the 90th centile or above and the cerebro-placental ratio is at the 5th centile or below. CONCLUSIONS: In diabetic pregnancies, a low cerebro-placental ratio, particularly in a macrosomic fetus, confers additional risk.

Late pregnancy ultrasound parameters identifying fetuses at risk of adverse perinatal outcomes: a protocol for a systematic review of systematic reviews.

INTRODUCTION: Stillbirths and neonatal deaths are leading contributors to the global burden of disease and pregnancy ultrasound has the potential to help decrease this burden. In the absence of high-Grading of Recommendations Assessment, Development and Evaluation (GRADE) evidence on universal obstetric ultrasound screening at or close to term, many different screening strategies have been proposed. Systematic reviews have rapidly increased over the past decade owing to the diverse nature of ultrasound parameters and the wide range of possible adverse perinatal outcomes. This systematic review will summarise the evidence on key ultrasound parameters in the published literature to help develop an obstetric ultrasound protocol that identifies pregnancies at risk of adverse perinatal outcomes at or close to term. METHODS: This study will follow the recent Cochrane guidelines for a systematic review of systematic reviews. A comprehensive literature search will be conducted using Embase (OvidSP), Medline (OvidSP), CDSR, CINAHL (EBSCOhost) and Scopus. Systematic reviews evaluating at least one ultrasound parameter in late pregnancy to detect pregnancies at risk of adverse perinatal outcomes will be included. Two independent reviewers will screen, assess the quality including the risk of bias using the ROBIS tool, and extract data from eligible systematic reviews that meet the study inclusion criteria. Overlapping data will be assessed and managed with decision rules, and study evidence including the GRADE assessment of the certainty of results will be presented as a narrative synthesis as described in the Cochrane guidelines for an overview of reviews. ETHICS AND DISSEMINATION: This research uses publicly available published data; thus, an ethics committee review is not required. The findings will be published in a peer-reviewed journal. PROSPERO REGISTRATION NUMBER: CRD42021266108.

Function and Safety of SlowflowHD Ultrasound Doppler in Obstetrics.

SlowflowHD is a new ultrasound Doppler imaging technology that allows visualization of flow within small blood vessels. In this mode, a proprietary algorithm differentiates between low-speed flow and signals attributed to tissue motion so that microvessel vasculature can be examined. Our objectives were to describe the low-velocity Doppler mode principles, to assess the bone thermal index (TIb) safety parameter in obstetric ultrasound scans and to evaluate adherence to professional guidelines. To achieve the latter goals, we retrospectively reviewed prospectively collected ultrasound images and video clips from pregnancy ultrasound scans at >10 wk of gestation over 4 mo. We used a custom-built optical character recognition-based software to automatically identify all images and video clips using this technology and extract the TIb. Overall, a total of 185 ultrasound scans performed by three fetal medicine physicians were included, of which 60, 54 and 71 scans were first-, second- and third-trimester scans, respectively. The mean (highest recorded) TIb values were 0.32 (0.70), 0.23 (0.70) and 0.32 (0.60) in the first, second, and third trimesters, respectively. Thermal index values were within recommended values set by the World Federation for Ultrasound in Medicine and Biology American Institute of Ultrasound in Medicine and British Medical Ultrasound Society in all scans.

Improving diagnostic accuracy in pregnancy with individualised, gestational age-specific reference intervals.

BACKGROUND AND AIMS: Investigations in pregnancy should be interpreted using pregnancy-specific reference intervals (RIs). However, because of the progressive nature of pregnancy, even pregnancy-specific RIs may not be equally representative at different gestations. We proposed that gestational age-specific RIs may increase diagnostic accuracy over those with fixed limits. MATERIALS AND METHODS: The trajectory of platelets was mapped in 32,778 pregnant women, using 116,798 results. Then we evaluated the accuracy with which a low measurement in early pregnancy (<3rd centile) predicted thrombocytopaenia at term, compared to the existing limit (<150 × 109/L). RESULTS: Platelets fell by 14.8% between 8 and 40 weeks. Platelets below the 3rd centile before 20 weeks predicted thrombocytopaenia at term (<100 × 109/L) with a significantly greater degree of accuracy than a fixed limit (AUC 0.86 vs. 0.76, p = 0.004). CONCLUSION: Pregnancy-specific RIs can be defined using routinely collected hospital data, and the abundance of such freely available data enables a detailed investigation of temporal changes throughout gestation. Individualised RIs offer improved accuracy profiles, over and above those already derived specifically from pregnant populations. Clinicians should consider how this may be used to improve diagnostic accuracy for biomarkers used in current clinical practice, and those yet to be defined.

White blood cells in pregnancy: reference intervals for before and after delivery.

BACKGROUND: White blood cells (WBC) are commonly measured to investigate suspected infection and inflammation in pregnant women, but the pregnancy-specific reference interval is variably reported, increasing diagnostic uncertainty in this high-risk population. It is essential that clinicians can interpret WBC results in the context of normal pregnant physiology, given the huge global burden of infection on maternal mortality. METHODS: We performed a longitudinal, repeated measures population study of 24,318 pregnant women in Oxford, UK, to map the trajectory of WBC between 8-40 weeks of gestation. We defined 95% reference intervals (RI) for total WBC, neutrophils, lymphocytes, eosinophils, basophils, and monocytes for the antenatal and postnatal periods. FINDINGS: WBC were measured 80,637 times over five years. The upper reference limit for total WBC was elevated by 36% in pregnancy (RI 5.7-15.0×109/L), driven by a 55% increase in neutrophils (3.7-11.6×109/L) and 38% increase in monocytes (0.3-1.1×109/L), which remained stable between 8-40 weeks. Lymphocytes were reduced by 36% (1.0-2.9×109/L), while eosinophils and basophils were unchanged. Total WBC was elevated significantly further from the first day after birth (similar regardless of the mode of delivery), which resolved to pre-delivery levels by an average of seven days, and to pre-pregnancy levels by day 21. INTERPRETATION: There are marked changes in WBC in pregnancy, with substantial differences between cell subtypes. WBC are measured frequently in pregnant women in obstetric and non-obstetric settings, and results should be interpreted using a pregnancy-specific RI until delivery, and between days 7-21 after childbirth. FUNDING: None.

Emergency cervical cerclage in twin and singleton pregnancies with 0-mm cervical length or prolapsed membranes.

INTRODUCTION: Cervical cerclage is controversial in twin pregnancies, although recent data from the USA supports its use where "physical examination-indicated". Limited data exist, however, in the extreme situation of 0-mm ultrasound-measured cervical length or even prolapsed membranes. This research compares the success of emergency cervical cerclage in multiple and singleton pregnancies. MATERIAL AND METHODS: This is a retrospective cohort study of all such cerclages performed at a tertiary hospital over a 15-year period. "Emergency" was where transvaginal ultrasound-assessed cervical length was 0 mm, with amniotic membranes at or beyond the external cervical os. Exclusion criteria were clinical or biochemical evidence of infection, regular contractions, bleeding, ruptured membranes, or gestation beyond 24+0  weeks. The primary outcome, or "success", was defined as birth >27+6  weeks of gestation, with the neonate alive 28 days later with no markers of adverse outcome (seizures, periventricular leukomalacia, intracranial hemorrhage more than Grade 2, or necrotizing enterocolitis). Demographic and cerclage variables were assessed against the primary outcome. Variables correlated with success were analyzed between multiple and singleton pregnancies. Comparison of all adverse outcomes was then adjusted using logistic regression. RESULTS: A total of 135 pregnancies were included (107 singletons and 28 multiples [all twins]). Success was achieved in 79 (58.5%; 57.9% in singletons, 60.7% in twins). Nulliparity, in utero transfer, symptoms, prolapsed membranes, and dilation more than 3 cm were predictors of failure, but twin pregnancy was not. After controlling for potential confounding variables, there was no significant difference in measures of success between singleton and twin pregnancies, apart from higher rates of neonatal unit admission. CONCLUSIONS: Emergency cervical cerclage, even in extreme situations, is as effective in twin pregnancies as it is in singletons.

Correction: The impact of a routine late third trimester growth scan on the incidence, diagnosis, and management of breech presentation in Oxfordshire, UK: A cohort study.

[This corrects the article DOI: 10.1371/journal.pmed.1003503.].

The Antenatal and Postnatal Consequences of Antenatal Exposure to Prolonged Low Dose Indomethacin.

Despite its many clinical applications, indomethacin is seldom used in pregnancy, principally because of concerns regarding the potential for constriction of the arterial duct. The aim of this study was to document adverse antenatal effects and postnatal outcomes after in utero exposure to low-dose indomethacin. We studied a retrospective cohort of pregnancies between 2005 and 2016 at the John Radcliffe Hospital, Oxford, UK, in which mothers at extremely high risk of preterm birth were treated as prophylaxis with indomethacin 25 mg, 12 hourly, before 29 weeks. Antenatal effects on the arterial duct and postnatal outcomes were analysed. Overall, 198 fetuses had in utero follow-up, and 13 (6.6%) had ductal constriction, all within 9 days of starting treatment. No ductal constriction was seen in pregnancies when therapy was started before 20 weeks, and all effects were reversed after cessation of therapy. An analysis of postnatal complications was possible in 181 neonates. There were eight (4.4%) neonatal deaths, all but one associated with extreme preterm birth. Seven (5%) patent ductus arteriosus cases occurred in the 140 neonates delivered after 28 weeks who were alive at discharge. Postnatal complications were not more common in neonates in whom antenatal ductal constriction had been demonstrated. In conclusion, fetuses exposed to prolonged low dose indomethacin have a low incidence of in utero complications; these complications can be diagnosed with ultrasound and are reversible. Adverse postnatal events are related to gestation at birth and do not appear more common.

The impact of individual sonographer variation on the detection of small for gestational age fetuses using a third trimester growth scan.

OBJECTIVES: Detection of small for gestational age (SGA) fetuses in a third trimester ultrasound could be affected by variation in sonographer performance. METHODS: Retrospective analysis of all singleton, non-anomalous ultrasound examinations between 35+0 -36+6 weeks gestation, in a single institution where a universal 36-week scan is offered. Screen positive was defined as estimated fetal weight (EFW) <10th centile; SGA was birthweight <10th centile. Individual sonographers' distributions of head circumference (HC), abdominal circumference (AC) and femur length (FL) were used to assess sonographers' screen positive rate (SPR), detection rate (DR) and true positive rate (TPR). Univariate and multivariate regression analysis was performed to assess the association between the sonographers' mean and SD (SD) for HC, AC, FL and their SPR, DR and TPR. RESULTS: There were 27 sonographers performing more than 50 examinations per year, a total of 5691 scans. The mean incidence of SGA was 10.0%. For an overall SPR of 9.4%, the overall DR was 43.8% (95% CI: 39.6% - 48.1%) and the overall TPR was 46.5% (95% CI: 42.9% - 50.2%). Higher AC scatter (SD difference up to 11.6 mm) was associated with higher SPR (P = 0.001). Lower mean FL (difference up to 3.6 mm) was associated with higher SPR (P = 0.003) and higher DR (P = 0.002). As a result, DR varied amongst different sonographers between 14.3% and 85.7% and TPR varied between 8.3% and 100.0%. CONCLUSIONS: Monitoring of individual AC and FL distributions is a simple and effective tool for institutional quality assurance.

Pregnancy-specific reference intervals for C-reactive protein improve diagnostic accuracy for infection: A longitudinal study.

BACKGROUND AND AIMS: Infections are a major cause of maternal mortality. C-reactive protein (CRP), a commonly-used inflammatory marker, is widely used to inform diagnosis, but the upper limit of normal in pregnancy is uncertain. We have defined trimester-specific reference intervals for CRP and evaluated their diagnostic accuracy for infection. MATERIALS AND METHODS: Development cohort: longitudinal study of pregnant women to determine 95% reference intervals. Evaluation cohort: diagnostic accuracy study to evaluate these intervals in 50 women with suspected intrauterine infection. RESULTS: In these 322 healthy pregnant women, CRP was substantially higher than in most non-pregnant populations. CRP was similar in each trimester, with an upper reference limit of 19 mg/L. CRP increased linearly with body mass index (p < 0.0001). The sensitivity and specificity of CRP for diagnosing chorioamnionitis were 73% and 86%, respectively. The overall diagnostic accuracy using the pregnancy-specific reference interval was significantly better than that of the existing standard (p = 0.03). CONCLUSIONS: CRP is a widely-used clinical tool in pregnancy, and a pregnancy-specific reference interval should be used to optimise diagnostic accuracy. Chorioamnionitis was used as an example of a localised infection with well-defined outcomes, but pregnancy-specific RIs for CRP should be considered in any clinical setting including pregnant women.