Managing pregnancy of unknown location based on initial serum progesterone and serial serum hCG: development and validation of a two-step triage protocol.

A uniform rationalized management protocol for pregnancies of unknown location (PUL) is lacking. We developed a two-step triage protocol based on presenting serum progesterone (step 1) and hCG ratio two days later (step 2) to select PUL at high-risk of ectopic pregnancy (EP).Cohort study of 2753 PUL (301 EP), involving a secondary analysis of prospectively and consecutively collected PUL at two London-based university teaching hospitals. Using a chronological split we used 1449 PUL for development and 1304 for validation. We aimed to select PUL as low-risk with high confidence (high negative predictive value, NPV) while classifying most EP as high-risk (high sensitivity). The first triage step selects low-risk PUL at presentation using a serum progesterone threshold. The remaining PUL are triaged using a novel logistic regression risk model based on hCG ratio and initial serum progesterone (second step), defining low-risk as an estimated EP risk <5%.On validation, initial serum progesterone ≤2nmol/l (step 1) selected 16.1% PUL as low-risk. Second step classification with the risk model M6P selected an additional 46.0% of all PUL as low-risk. Overall, the two-step protocol classified 62.1% of PUL as low-risk, with an NPV of 98.6% and a sensitivity of 92.0%. When the risk model was used in isolation (i.e. without the first step), 60.5% of PUL were classified as low-risk with 99.1% NPV and 94.9% sensitivity.The two-step protocol can efficiently classify PUL into being at high or low risk of complications

The association between vaginal bacterial composition and miscarriage: a nested case-control study

OBJECTIVE: To characterise vaginal bacterial composition in early pregnancy and investigate its relationship with first and second trimester miscarriages. DESIGN: Nested case-control study. SETTING: Queen Charlotte's and Chelsea Hospital, Imperial College Healthcare NHS Trust, London. POPULATION: 161 pregnancies; 64 resulting in first trimester miscarriage, 14 in second trimester miscarriage and 83 term pregnancies. METHODS: Prospective profiling and comparison of vaginal bacteria composition using 16S rRNA gene-based metataxonomics from 5 weeks gestation in pregnancies ending in miscarriage or uncomplicated term deliveries matched for age, gestation and body-mass index. MAIN OUTCOME MEASURES: Relative vaginal bacteria abundance, diversity and richness. Pregnancy outcomes defined as first or second trimester miscarriage, or uncomplicated term delivery. RESULTS: First trimester miscarriage associated with reduced prevalence of Lactobacillus spp.-dominated vaginal microbiota classified using hierarchical clustering analysis (65.6% vs. 87·7%; P=0·005), higher alpha diversity (mean Inverse Simpson Index 2.5 (95% confidence interval 1.8-3.0) vs. 1.5 (1.3-1.7), P=0·003) and higher richness 25.1 (18.5-31.7) vs. 16.7 (13.4-20), P=0·017), compared to viable pregnancies. This was independent of vaginal bleeding and observable before first trimester miscarriage diagnosis (P=0·015). Incomplete/complete miscarriage associated with higher proportions of Lactobacillus spp.-deplete communities compared to missed miscarriage. Early pregnancy vaginal bacterial stability was similar between miscarriage and term pregnancies. CONCLUSIONS: These findings associate the bacterial component of vaginal microbiota with first trimester miscarriage and indicate suboptimal community composition is established in early pregnancy. While further studies are required to elucidate the mechanism, vaginal bacterial composition may represent a modifiable risk factor for first trimester miscarriage

Factors to consider in pregnancy of unknown location

The management of women with a pregnancy of unknown location (PUL) can vary significantly and often lacks a clear evidence base. Intensive follow-up is usually required for women with a final outcome of an ectopic pregnancy. This, however, only accounts for a small proportion of women with a pregnancy of unknown PUL location. There remains a clear clinical need to rationalize the follow-up of PUL so women at high risk of having a final outcome of an ectopic pregnancy are followed up more intensively and those PUL at low risk of having an ectopic pregnancy have their follow-up streamlined. This review covers the main management strategies published in the current literature and aims to give clinicians an overview of the most up-to-date evidence that they can take away into their everyday clinical practice when caring for women with a PUL

Diagnostic protocols for the management of pregnancy of unknown location: a systematic review and meta-analysis

BACKGROUND: There is no international consensus on how to manage women with a pregnancy of unknown location (PUL). OBJECTIVES: To present a systematic quantitative review summarising the evidence related to management protocols for PUL. SEARCH STRATEGY: MEDLINE, COCHRANE and DARE databases were searched from 01/01/1984 to 31/01/2017. The primary outcome was accurate risk prediction of women initially diagnosed with a PUL having an ectopic pregnancy (high risk) as opposed to either a failed PUL or intrauterine pregnancy ((low risk). SELECTION CRITERIA: All studies written in the English language, that were not case reports or series that assessed women classified as having a PUL at initial ultrasound. DATA COLLECTION AND ANALYSIS: Forty-three studies were included. QUADAS-2 criteria were used to assess the risk of bias. We used a novel linear mixed effects model and constructed summary receiver operating characteristic (SROC) curves for the thresholds of interest. MAIN RESULTS: There was a high risk of differential verification bias in most studies. Meta-analyses of accuracy were performed on (i) single hCG cut-off levels, (ii) hCG ratio (hCG at 48 hours / initial hCG), (iii) single progesterone cut-off levels and (iv) the 'M4 model' (a logistic regression model based on the initial hCG and hCG ratio). For predicting an ectopic pregnancy, the AUCs (95% CI) for these four management protocols were: (i) 0.42 (0.00-0.99), (ii) 0.69 (0.57-0.78), (iii) 0.69 (0.54-0.81) and (iv) 0.87 (0.83-0.91), respectively. CONCLUSIONS: The M4 model was the best available method for predicting a final outcome of ectopic pregnancy. Developing and validating risk prediction models may optimise the management of PUL

The association between hyperemesis gravidarum and psychological symptoms, psychosocial outcomes and infant bonding: a two point prospective case control multi-centre survey study in an inner city setting

Objectives To assess if there is any association between hyperemesis gravidarum (HG), psychological morbidity and infant bonding and to quantify any psychosocial consequences of HG DesignTwo-point prospective case control, multi-centre survey study with antenatal and postnatal data collection SettingThree London hospitalsParticipantsPregnant women at ≤ 12 completed weeks gestation recruited consecutively over two years. Women with HG were recruited at the time of admission; controls recruited from a low risk antenatal clinic. 106 women were recruited to the cases group and 108 to the control. Response rates at antenatal data collection were 87% and 85% in the cases and control groups respectively. Postnatally, the response rate was 90% in both groups. Primary and secondary outcome measuresPrimary outcomes were; psychological morbidity in the antenatal and postnatal periods, infant bonding in the postnatal period and psychosocial implications of HG. Secondary outcomes were the effects of severity and longevity of HG and assessment of correlation between EPDS scores and maternal-to-infant bonding scores. ResultsAntenatally, 49% of cases had probable depression compared to 6% of controls (OR 14.4 (5.29,39.44). Postnatally, 29% of cases had probable depression versus 7% of controls (OR 5.2(1.65,17.21). There was no direct association between HG and infant bonding. 53% of women in the HG group reported needing four or more weeks of sick leave compared to 2% in the control group (OR 60.5 (95% CI 8.4;2535.6)). ConclusionsLong lasting psychological morbidity associated with HG was evident. Significantly more women in the cases group sought help for mental health symptoms in the antenatal period, however very few were diagnosed with or treated for depression in pregnancy or referred to specialist perinatal mental health services. HG did not directly affect infant bonding. Women in the cases group required long periods off work, highlighting the socioeconomic impact of HG

Validation and updating of risk models based on multinomial logistic regression

Background: Risk models often perform poorly at external validation in terms of discrimination or calibration. Updating methods are needed to improve performance of multinomial logistic regression models for risk prediction. Methods: We consider simple and more refined updating approaches to extend previously proposed methods for dichotomous outcomes. These include model recalibration (adjustment of intercept and/or slope), revision (re-estimation of individual model coefficients), and extension (revision with additional markers). We suggest a closed testing procedure to assist in deciding on the updating complexity. These methods are demonstrated on a case study of women with pregnancies of unknown location (PUL). A previously developed risk model predicts the probability that a PUL is a failed, intra-uterine, or ectopic pregnancy. We validated and updated this model on more recent patients from the development setting (temporal updating; n = 1422) and on patients from a different hospital (geographical updating; n = 873). Internal validation of updated models was performed through bootstrap resampling. Results: Contrary to dichotomous models, we noted that recalibration can also affect discrimination for multinomial risk models. If the number of outcome categories is higher than the number of variables, logistic recalibration is obsolete because straightforward model refitting does not require the estimation of more parameters. Although recalibration strongly improved performance in the case study, the closed testing procedure selected model revision. Further, revision of functional form of continuous predictors had a positive effect on discrimination, whereas penalized estimation of changes in model coefficients was beneficial for calibration. Conclusions: Methods for updating of multinomial risk models are now available to improve predictions in new settings. A closed testing procedure is helpful to decide whether revision is preferred over recalibration. Because multicategory outcomes increase the number of parameters to be estimated, we recommend full model revision only when the sample size for each outcome category is large

Does fetal growth in the first trimester correlate with the amount and duration of vaginal bleeding or abdominal pain? A preliminary study

status: publishe

Do pregnancy outcomes correlate with the amount and duration of vaginal bleeding or abdominal pain in the first trimester? A preliminary study

status: publishe