Guideline No. 452: Diagnosis and Management of Intrahepatic Cholestasis of Pregnancy.

OBJECTIVE: To summarize the current evidence and to make recommendations for the diagnosis and management of intrahepatic cholestasis of pregnancy. TARGET POPULATION: Pregnant people with intrahepatic cholestasis of pregnancy. OPTIONS: Diagnosing the condition using fasting or non-fasting bile acids, classifying disease severity, determining what treatment to offer, establishing how to monitor for antenatal fetal wellbeing, identifying when to perform elective birth. BENEFITS, HARMS, AND COSTS: Individuals with intrahepatic cholestasis of pregnancy are at increased risk of adverse perinatal outcomes including preterm birth, neonatal respiratory distress and admission to a neonatal intensive care unit, with an increased risk of stillbirth when bile acid levels are ≥100 µmol/L. There is inequity in bile acid testing availability and timely access to results, along with uncertainly of how to treat, monitor. and ultimately deliver these pregnancies. Optimization of diagnostic and management protocols can improve maternal and fetal postnatal outcomes. EVIDENCE: Medline, PubMed, Embase, and the Cochrane Library were searched from inception to March 2023, using medical subject headings (MeSH) and keywords related to pregnancy, intrahepatic cholestasis of pregnancy, bile acids, pruritis, ursodeoxycholic acid, and stillbirth. This document presents an abstraction of the evidence rather than a methodological review. VALIDATION METHODS: The authors rated the quality of evidence and strength of recommendations using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. See Appendix A (Tables A1 for definitions and A2 for interpretations). INTENDED AUDIENCE: Obstetric care providers, including obstetricians, family physicians, nurses, midwives, maternal-fetal medicine specialists, and radiologists. SOCIAL MEDIA ABSTRACT: Intrahepatic cholestasis of pregnancy requires adequate diagnosis with non-fasting bile acid levels which guide optimal management and delivery timing. SUMMARY STATEMENTS: RECOMMENDATIONS.

Treatment of women with mild gestational diabetes mellitus decreases the risk of adverse perinatal outcomes.

AIMS: Glycemic thresholds used to diagnose gestational diabetes mellitus (GDM) are a continued subject of debate. Lower glycemic thresholds identify women with milder GDM for whom treatment benefit is unclear. We compared adverse maternal and neonatal outcomes in treated and untreated women with mild hyperglycemia. METHODS: We reviewed 11 553 patient charts from two tertiary care centers and included singleton pregnancies >32-week gestation. GDM was diagnosed using the one- or two-step 75 g oral glucose tolerance test (OGTT) depending on the center. All OGTT results were reviewed. Women with glycemic values falling between the thresholds of the two tests, referred to as intermediate hyperglycemic (IH), defined as FPG 5.1-5.2 mmol/L, 1 h PG 10.0-10.5 mmol/L, or 2 h PG 8.5-8.9 mmol/L at 75 g OGTT, were untreated at center A and treated at center B. RESULTS: There were 630 women with IH, 334 were untreated (center A) and 296 who were treated (center B). After adjusting for covariates, untreated IH women had significantly higher rates of gestational hypertension (aOR 6.02, P = 0.002), large for gestational age (LGA) (aOR 3.73, P < 0.001) and birthweights > 4000 g (aOR 3.35, P = 0.001). Our results indicate that treating 11 women with IH would prevent one LGA birth and treating 13 would prevent 1 birthweight > 4000 g. CONCLUSION: The diagnosis of GDM using the two-step OGTT fails to identify subgroups of women with mild hyperglycemia that would benefit from treatment to lower the risk for adverse maternal and neonatal outcomes. Treatment of women with mild hyperglycemia decreased the risk of LGA and birthweight >4000 g by 3-fold.

A late-preterm, early-term stratified analysis of neonatal outcomes by gestational age in placenta previa: defining the optimal timing for delivery.

OBJECTIVE: Though no official guidelines address the issue of the optimal timing of delivery in placenta previa, common practice is to conduct delivery between 36 and 37 weeks gestation. Given the rising concerns regarding unnecessary premature deliveries, the objective of this study was to compare neonatal outcomes among pregnancies complicated by placenta previa delivered at the late-preterm period (35, 36 weeks) relative to the early-term period (37 and 38 weeks). METHODS: We conducted a retrospective, population-based, cohort study using the CDC's Linked Birth-Infant Death data files from the U.S. for the year 2004. We stratified the cohort according to gestational age and placenta previa status. Using 38 weeks gestation as reference controls, the effect of delivery in a pregnancy with placenta previa at 35, 36 and 37 weeks gestation on the risk of several neonatal outcomes was estimated using logistic regression analysis, adjusting for relevant confounders. RESULTS: We analyzed a total of 4 118 956 births, of which 5675 (0.1%) met inclusion criteria. Late-preterm delivery was associated with lower birthweight and increased adequacy of care. Relative to neonates born at 38 weeks, birth at 35, 36 and 37 weeks was associated with no greater odds of meconium passage, fetal distress, fetal anemia, neonatal seizures, increased ventilator needs, or infant death at 1 year. However, odds of 5-min APGAR scores <7 were greater at 35 and 36 weeks (aOR [95% CI]): 3.33 [1.71-6.47] and 2.17 [1.11-4.22], respectively; as were odds of NICU admission rates: 2.25 [2.01-2.50] and 1.57 [1.38-1.76], respectively. Conclusions: Barring maternal indications, early-term delivery in placenta previa is associated with fewer complications and no greater risk than late-preterm delivery. This information may be helpful in the development of future guidelines, which are currently needed to guide the management of these pregnancies.

Correlation of cord blood pH, base excess, and lactate concentration measured with a portable device for identifying fetal acidosis.

OBJECTIVE: To determine the effectiveness of portable lactate analyzers in identifying fetal acidosis by correlating arterial and venous lactate values from umbilical cord blood with lactate, pH, and base excess measurements from central laboratory analyzers. METHODS: We performed a prospective study using arterial and venous cord blood from 52 women with a singleton fetus delivered at term. We evaluated the correlation between the cord blood lactate concentration measured using two of the same portable devices (Lactate Plus, Nova Biomedical) with the result from a central laboratory analyzer. Analyses of the correlation between arterial lactate concentration measured on the portable device with arterial pH and base excess were then performed. RESULTS: We observed a median arterial pH of 7.24 (range 7.05 to 7.35) and a median arterial lactate concentration of 3.7 mmol/L (range 1.7 to 8.8 mmol/L). An excellent correlation was observed between lactate concentrations measured by the two portable devices (arterial R² = 0.98 and venous R² = 0.98), and between the portable device and the central laboratory analyzer (arterial R² = 0.94 and venous R² = 0.95). In our population, the optimal cut-offs to predict a pH < 7.20 or a base excess > -8.0 mmol/L were a lactate concentration of 4.9 mmol/L and 5.3 mmol/L, respectively, according to receiver operator characteristic analysis. With a lactate concentration > 4.9 mmol/L, the portable device had a sensitivity of 82% and a specificity of 90% to identify samples with an arterial pH < 7.20. CONCLUSION: Cord blood lactate concentration measured with a portable device is a good predictor of cord blood base excess and pH. Future studies should be designed to correlate scalp blood lactate measurements with clinical outcomes.

Objectif : Déterminer l'efficacité des analyseurs de lactate portatifs, pour ce qui est de l'identification de l'acidose fœtale, en mettant en corrélation les valeurs artérielle et veineuse du lactate constatées dans le sang de cordon ombilical et les mesures du lactate, du pH et de l'excès de bases révélées par les analyseurs du laboratoire central. Méthodes : Nous avons mené une étude prospective en utilisant le sang de cordon artériel et veineux prélevé chez 52 femmes qui ont connu une grossesse monofœtale s'étant soldée en un accouchement à terme. Nous avons évalué la corrélation entre la concentration en lactate du sang de cordon mesurée au moyen de deux exemplaires du même appareil portatif (Lactate Plus, Nova Biomedical) et le résultat obtenu au moyen d'un analyseur du laboratoire central. Nous avons par la suite procédé à des analyses de la corrélation entre la concentration artérielle en lactate mesurée au moyen de l'appareil portatif et les valeurs artérielles du pH et de l'excès de bases. Résultats : Nous avons constaté un pH artériel médian de 7,24 (plage : 7,05 - 7,35) et une concentration artérielle en lactate médiane de 3,7 mmol/l (plage : 1,7 - 8,8 mmol/l). Une excellente corrélation a été constatée entre les concentrations en lactate mesurées par les deux appareils portatifs (R2 artériel = 0,98 et R2 veineux = 0,98) et entre les concentrations mesurées par l'appareil portatif et par l'analyseur du laboratoire central (R2 artériel = 0,94 et R2 veineux = 0,95). Au sein de notre population, les seuils optimaux permettant de prédire un pH < 7,20 ou un excès de bases > −8,0 mmol/l ont été des concentrations en lactate de 4,9 mmol/l et de 5,3 mmol/l, respectivement, selon l'analyse de la fonction d'efficacité du récepteur. En présence d'une concentration en lactate > 4,9 mmol/l, l'appareil portatif comptait une sensibilité de 82 % et une spécificité de 90 % pour ce qui est de l'identification des prélèvements présentant un pH artériel < 7,20. Conclusion : La concentration en lactate du sang de cordon qui est mesurée au moyen d'un appareil portatif constitue un bon facteur prédictif pour ce qui est du pH et de l'excès de bases du sang de cordon. De futures études devraient être conçues de façon à pouvoir mettre en corrélation les concentrations en lactate dans le sang prélevé sur le cuir chevelu et les résultats cliniques.

Early amniotomy and early oxytocin for prevention of, or therapy for, delay in first stage spontaneous labour compared with routine care.

BACKGROUND: Caesarean section rates are over 20% in many developed countries. The main diagnosis contributing to the high rate in nulliparae is dystocia or prolonged labour. The present review assesses the effects of a policy of early amniotomy with early oxytocin administration for the prevention of, or the therapy for, delay in labour progress. OBJECTIVES: To estimate the effects of early augmentation with amniotomy and oxytocin for prevention of, or therapy for, delay in labour progress on the caesarean birth rate and on indicators of maternal and neonatal morbidity. SEARCH METHODS: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (31 May 2013), MEDLINE (1966 to 4 July 2013), Embase (1980 to 4 July 2013), CINAHL (1982 to 4 July 2013), MIDIRS (1985 to 4 July 2013) and contacted authors for data from unpublished trials. SELECTION CRITERIA: Randomized and quasi-randomized controlled trials that compared oxytocin and amniotomy with expectant management. DATA COLLECTION AND ANALYSIS: Three review authors extracted data independently. We stratified the analyses into 'Prevention Trials' and 'Therapy Trials' according to the status of the woman at the time of randomization. Participants in the 'Prevention Trials' were unselected women, without slow progress in labour, who were randomized to a policy of early augmentation or to routine care. In 'Treatment Trials' women were eligible if they had an established delay in labour progress. MAIN RESULTS: For the 2013 update, we identified and excluded one new clinical trial. This updated review includes 14 trials, randomizing a total of 8033 women. The unstratified analysis found early intervention with amniotomy and oxytocin to be associated with a modest reduction in the risk of caesarean section; however, the confidence interval (CI) included the null effect (risk ratio (RR) 0.89; 95% CI 0.79 to 1.01; 14 trials; 8033 women). In prevention trials, early augmentation was associated with a modest reduction in the number of caesarean births (RR 0.87; 95% CI 0.77 to 0.99; 11 trials; 7753). A policy of early amniotomy and early oxytocin was associated with a shortened duration of labour (average mean difference (MD) - 1.28 hours; 95% CI -1.97 to -0.59; eight trials; 4816 women). Sensitivity analyses excluding four trials with a full package of active management did not substantially affect the point estimate for risk of caesarean section (RR 0.87; 95% CI 0.73 to 1.05; 10 trials; 5165 women). We found no other significant effects for the other indicators of maternal or neonatal morbidity. AUTHORS' CONCLUSIONS: In prevention trials, early intervention with amniotomy and oxytocin appears to be associated with a modest reduction in the rate of caesarean section over standard care.

Early amniotomy and early oxytocin for prevention of, or therapy for, delay in first stage spontaneous labour compared with routine care.

BACKGROUND: Caesarean section rates are over 20% in many developed countries. The main diagnosis contributing to the high rate in nulliparae is dystocia or prolonged labour. The present review assesses the effects of a policy of early amniotomy with early oxytocin administration for the prevention of, or the therapy for, delay in labour progress. OBJECTIVES: To estimate the effects of early augmentation with amniotomy and oxytocin for prevention of, or therapy for, delay in labour progress on the caesarean birth rate and on indicators of maternal and neonatal morbidity. SEARCH METHODS: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (15 February 2012), MEDLINE (1966 to 15 February 2012), EMBASE (1980 to 15 February 2012), CINAHL (1982 to 15 February 2012), MIDIRS (1985 to February 2012) and contacted authors for data from unpublished trials. SELECTION CRITERIA: Randomized and quasi-randomized controlled trials that compared oxytocin and amniotomy with expectant management. DATA COLLECTION AND ANALYSIS: Three review authors extracted data independently. We stratified the analyses into 'Prevention Trials' and 'Therapy Trials' according to the status of the woman at the time of randomization. Participants in the 'Prevention Trials' were unselected women, without slow progress in labour, who were randomized to a policy of early augmentation or to routine care. In 'Treatment Trials' women were eligible if they had an established delay in labour progress. MAIN RESULTS: For this update, we have included a further two new clinical trials. This updated review includes 14 trials, randomizing a total of 8033 women. The unstratified analysis found early intervention with amniotomy and oxytocin to be associated with a modest reduction in the risk of caesarean section; however, the confidence interval (CI) included the null effect (risk ratio (RR) 0.89; 95% CI 0.79 to 1.01; 14 trials; 8033 women). In prevention trials, early augmentation was associated with a modest reduction in the number of caesarean births (RR 0.87; 95% CI 0.77 to 0.99; 11 trials; 7753). A policy of early amniotomy and early oxytocin was associated with a shortened duration of labour (average mean difference (MD) - 1.28 hours; 95% CI -1.97 to -0.59; eight trials; 4816 women). Sensitivity analyses excluding four trials with a full package of active management did not substantially affect the point estimate for risk of caesarean section (RR 0.87; 95% CI 0.73 to 1.05; 10 trials; 5165 women). We found no other significant effects for the other indicators of maternal or neonatal morbidity. AUTHORS' CONCLUSIONS: In prevention trials, early intervention with amniotomy and oxytocin appears to be associated with a modest reduction in the rate of caesarean section over standard care.

Early amniotomy and early oxytocin for prevention of, or therapy for, delay in first stage spontaneous labour compared with routine care.

BACKGROUND: Caesarean section rates are over 20% in many developed countries. The main diagnosis contributing to the high rate in nulliparae is dystocia or prolonged labour. The present review assesses the effects of a policy of early amniotomy with early oxytocin administration for the prevention of, or the therapy for, delay in labour progress. OBJECTIVES: To estimate the effects of early augmentation with amniotomy and oxytocin for prevention of, or therapy for, delay in labour progress on the caesarean birth rate and on indicators of maternal and neonatal morbidity. SEARCH STRATEGY: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (November 2008), MEDLINE (January 1970 to November 2008), EMBASE (1980 to November 2008), CINAHL (1982 to November 2008), MIDIRS (1985 to November 2008) and contacted authors for data from unpublished trials. SELECTION CRITERIA: Randomized and quasi-randomized controlled trials that compared oxytocin and amniotomy to expectant management. DATA COLLECTION AND ANALYSIS: Three authors extracted data independently. We stratified the analyses into 'Prevention Trials' and 'Therapy Trials' according to the status of the woman at the time of randomization. Participants in the 'Prevention Trials' were unselected women, without slow progress in labour, who were randomized to a policy of early augmentation or to routine care. In 'Treatment Trials' women were eligible if they had an established delay in labour progress. MAIN RESULTS: Twelve trials, including 7792 women, were included. The unstratified analysis found early intervention with amniotomy and oxytocin to be associated with a modest reduction in the risk of caesarean section; however, the confidence interval crossed unity and was compatible with no effect (risk ratio (RR) 0.89; 95% confidence interval (CI) 0.79 to 1.01). In Prevention trials, early augmentation was associated with a modest reduction in the number of caesarean births (RR 0.88; 95% CI 0.77 to 0.99). A policy of early amniotomy and early oxytocin was associated with a shortened duration of labour (mean difference - 1.11 hour). Sensitivity analyses excluding three trials with a full package of Active Management did not substantially affect the point estimate of the effect (RR 0.87; 95% CI 0.73 to 1.04). We found no other significant effects for the other indicators of maternal or neonatal morbidity. AUTHORS' CONCLUSIONS: In prevention trials, early intervention with amniotomy and oxytocin appears to be associated with a modest reduction in the rate of caesarean section over standard care.