Penicillin Allergy in Pregnancy: A Practical Review for the Obstetrician.

Outpatient penicillin allergy evaluation during pregnancy and associated clinical outcomes

Association Between Interpregnancy Interval and Adverse Neonatal and Maternal Outcomes Stratified by Gestational Age in Previous Pregnancy in China

Impact of a Penicillin Allergy Educational Session on Clinical Practice

Existing data on the use of nonsteroidal anti-inflammatory drugs (NSAIDs) during late pregnancy is well established, providing assurance. However, the use of NSAIDs during early pregnancy remains inconclusive owing to conflicting findings on adverse neonatal outcomes as well as the limited data on adverse maternal outcomes. Therefore, we sought to investigate whether early prenatal exposure to NSAIDs was associated with neonatal and maternal adverse outcomes. We conducted a nationwide, population-based cohort study using Korea's National Health Insurance Service (NHIS) database with a mother-offspring cohort constructed and validated by the NHIS to include all live births in women aged 18 to 44 years between 2010 and 2018. We defined exposure to NSAIDs as at least two records of NSAID prescriptions during early pregnancy (first 90 days of pregnancy for congenital malformations and first 19 weeks for nonmalformation outcomes) and compared against three distinct referent groups of (1) unexposed, no NSAID prescription during the 3 months before pregnancy start to end of early pregnancy; (2) acetaminophen-exposed, at least two acetaminophen prescriptions during early pregnancy (i.e., active comparator); and (3) past users, at least two NSAID prescriptions before the start of pregnancy but no relevant prescriptions during pregnancy. Outcomes of interest were adverse birth outcomes of major congenital malformations and low birth weight and adverse maternal outcomes of antepartum hemorrhage and oligohydramnios. We estimated relative risks (RRs) with 95% CIs using generalized linear models within a propensity score (PS) fine stratification weighted cohort that accounted for various potential confounders of maternal sociodemographic characteristics, comorbidities, co-medication use, and general markers of burden of illness. Of 1.8 million pregnancies in the PS weighted analyses, exposure to NSAIDs during early pregnancy was associated with slightly increased risks for neonatal outcomes of major congenital malformations (PS-adjusted RR, 1.14 [CI, 1.10 to 1.18]) and low birth weight (1.29 [1.25 to 1.33]), and for maternal outcome of oligohydramnios (1.09 [1.01 to 1.19]) but not antepartum hemorrhage (1.05 [0.99 to 1.12]). The risks of overall congenital malformations, low birth weight, and oligohydramnios remained significantly elevated despite comparing NSAIDs against acetaminophen or past users. Risks of adverse neonatal and maternal outcomes were higher with cyclooxygenase-2 selective inhibitors or use of NSAIDs for more than 10 days, whereas generally similar effects were observed across the three most frequently used individual NSAIDs. Point estimates were largely consistent across all sensitivity analyses, including the sibling-matched analysis. Main limitations of this study are residual confounding by indication and from unmeasured factors. This large-scale, nationwide cohort study found that exposure to NSAIDs during early pregnancy was associated with slightly higher risks of neonatal and maternal adverse outcomes. Clinicians should therefore carefully weigh the benefits of prescribing NSAIDs in early pregnancy against its modest, but possible, risk of neonatal and maternal outcomes, where if possible, consider prescribing nonselective NSAIDs for <10 days, along with continued careful monitoring for any safety signals.

Modest reduction in adverse birth outcomes following the COVID-19 lockdown

Chorioamnionitis and its association with neonatal and maternal adverse outcomes in women with and without epidural analgesia administration

Pregnant individuals are likely to need antibiotics during the peripartum period. For pregnant individuals who report a history of penicillin allergy, non-β-lactam antibiotics are often administered. Compared with first-line β-lactam antibiotics, alternative antibiotics can be less effective, more toxic, and more costly. It remains unclear if being labeled with a penicillin allergy is associated with adverse maternal and neonatal outcomes. We conducted a retrospective cohort study of all pregnant patients who delivered a viable singleton between 24 and 42 weeks of gestation at a large academic hospital from 2013 to 2021. We compared patients who had a documented penicillin allergy history in their electronic medical record versus those who did not and examined whether there were significant differences in maternal outcomes and neonatal outcomes. Bivariable and multivariable analyses were performed. Of 41,943 eligible deliveries included in the analysis, 4,705 (11.2%) patients had a penicillin allergy history documented in their electronic medical record and 37,238 (88.8%) did not. Even after adjusting for potential confounders, patients with a documented penicillin allergy had a higher risk of postpartum endometritis (adjusted odds ratio [aOR]: 1.46; 95% confidence interval [CI]: 1.01-2.11) and a higher risk of their neonates having a postnatal hospital stay lasting more than 72 hours (aOR: 1.10; 95% CI: 1.02-1.18). There were no significant differences seen in the other maternal and neonatal outcomes in both bivariable and multivariable analyses. Pregnant patients who are labeled as having a penicillin allergy are more likely to have postpartum endometritis, and neonates born to mothers who are labeled as having a penicillin allergy are more likely to have a postnatal hospital stay lasting more than 72 hours. There were no other significant differences seen in pregnant patients and their newborns whether they were labeled as having a penicillin allergy history or not. However, pregnant individuals with a penicillin allergy documented in their medical record were significantly more likely to receive alternative non-β lactam antibiotics, and may have benefitted from having more details of their allergy history available as well as proper allergy verification with testing. · It is unclear whether pregnant individuals labeled with penicillin allergies have worse obstetric outcomes.. · These individuals were significantly more likely to have endometritis and their newborns hospitalized for >72 hours.. · They were significantly more likely to receive alternative non-β lactam antibiotics than those without documented allergies..

Anaemia in pregnancy is a global health problem with associated maternal and neonatal morbidity and mortality. We aimed to investigate the association between maternal haemoglobin concentrations during pregnancy and the risk of adverse maternal and neonatal outcomes. In this prospective, observational, multinational, INTERBIO-21st fetal study conducted at maternity units in Brazil, Kenya, Pakistan, South Africa, and the UK, we enrolled pregnant women (aged ≥18 years, BMI <35 kg/m2, natural conception, and singleton pregnancy) who initiated antenatal care before 14 weeks' gestation. At each 5±1 weekly visit until delivery, information was collected about the pregnancy, as well as the results of blood tests taken as part of routine antenatal care, including haemoglobin values. The outcome measures were maternal (gestational diabetes, pregnancy-induced hypertension, and preterm premature rupture of membranes) and neonatal outcomes (small for gestational age, preterm birth, and acute respiratory distress syndrome). Between Feb 8, 2012, and Nov 30, 2019, 2069 women (mean age 30·7 years [SD 5·0]) had at least one routinely haemoglobin concentration measured at 14-40 weeks' gestation, contributing 4690 haemoglobin measurements for the analysis. Compared with a haemoglobin cutoff of 110 g/L, the risk was increased more than two-fold for pregnancy-induced hypertension at haemoglobin concentrations of 170 g/L (risk ratio [RR] 2·29 [95% CI 1·19-4·39]) and higher, for preterm birth at haemoglobin concentrations of 70 g/L (RR 2·04 [95% CI 1·20-3·48]) and 165 g/L (RR 2·06 [95% CI 1·41-3·02]), and for acute respiratory distress syndrome at haemoglobin concentrations of 165 g/L (RR 2·84 [95% CI 1·51-5·35]). Trimester-specific results are also presented. Our data suggests that the current WHO haemoglobin cutoffs are associated with reduced risk of adverse maternal and neonatal outcomes. The current haemoglobin concentration cutoffs during pregnancy should not only consider thresholds for low haemoglobin concentrations that are associated with adverse outcomes but also define a threshold for high haemoglobin concentrations given the U-shaped relationship between haemoglobin concentration and adverse neonatal and maternal outcomes. Bill & Melinda Gates Foundation.

Refining the clinical definition of active phase arrest of dilation in nulliparous women to consider degree of cervical dilation as well as duration of arrest

ObjectiveThe objective of this study was to compare the differences in neonatal and maternal adverse outcomes between low-risk full-term nulliparous (women giving birth for the first time) and low-risk full-term multiparous (women who have given birth previously) using a database from 18 hospitals.MethodsThe cohort study, conducting from January 2019 to December 2019, described the frequency of maternal and neonatal adverse outcomes in low-risk nulliparous women and multiparous women who labored at 37–41 weeks of gestation. The association between maternal parity and the risk of neonatal and maternal adverse outcomes were analyzed based on multivariate Poisson regression.ResultsOf the 75,033 live births during the study period, 49,935 (66.55%) met the inclusion criteria, including 44.18% of nulliparous women and 55.82% of multiparous women. After adjustment, the risk of maternal adverse outcomes was 0.56 times reduced in multiparous women compared to nulliparous women (aRR 0.56, 95% CI 0.52–0.65, 44% lower risk), and the incidence of complication interventions in multipara was lower than in nullipara (aRR 0.76, 95% CI 0.59–0.99). Macrosomia and low birth weight were the most common neonatal adverse outcomes in the two groups. There was no statistically significant difference in neonatal adverse outcomes between multipara and nullipara after controlling for confounders.ConclusionAmong low-risk women who delivered at 37–41 weeks of gestation, the risk of maternal adverse outcomes and the incidence of complication interventions in nulliparous women were higher than in multiparous women. There was no statistically significant difference in adverse neonatal outcomes between two groups after adjustment.

Objective The rate of preeclampsia with severe features has increased. Previous studies have shown elevated liver enzymes are an indicator of worsening hypertensive disease of pregnancy and adverse outcomes, therefore leading to their inclusion as a diagnostic criterion for severe features of preeclampsia. Despite this, there are limited data to support an aspartate aminotransferase (AST) or alanine aminotransferase (ALT) concentration ≥ two times the upper limit of normal as the critical point at which maternal harm from ongoing pregnancy exceeds neonatal harm from delivery. The objective of this study is to evaluate the association between elevated liver enzymes and maternal and neonatal outcomes among patients with preeclampsia with severe features. Methods Retrospective cohort study among hypertensive patients who delivered ≥23 weeks’ gestation at Oregon Health & Science University (October 2013–September 2018). Those with preeclampsia with severe features (including chronic hypertension with superimposed preeclampsia meeting criteria for severe features) were included after a screening of ICD-9 and ICD-10 codes and chart validation. The primary exposure was elevated liver enzymes prior to delivery, according to the American College of Obstetricians and Gynecologists’ criteria for severe features of preeclampsia: aspartate aminotransferase (AST) or alanine aminotransferase (ALT) ≥2x the upper limit of normal (above threshold liver function tests [LFTs]). Primary outcomes included adverse maternal and neonatal outcomes. Differences were analyzed by Chi-squared, Fisher’s exact, t-test, and logistic regression, with α = 0.05. Results Of 11,825 deliveries, 319 (2.7%) met inclusion criteria and had preeclampsia with severe features. Of these, 44 (13.8%) had above threshold LFTs. Adverse maternal outcomes were no different in those with above threshold LFTs compared to those with below threshold LFTs. The unadjusted odds of an adverse neonatal outcome were 2.08 times greater in patients with above threshold LFTs (95% CI: 1.04–4.14), and 2.43 times greater when adjusting for maternal characteristics (95% CI: 1.17–5.04) compared to those with below threshold LFTs. However, the association between above threshold LFTs and adverse neonatal outcomes became non-significant after adjustment for gestational age at delivery (OR: 1.54, 95% CI: 0.63–3.76). Conclusion Among patients with preeclampsia with severe features, above threshold LFTs are not independently associated with an increased risk of adverse maternal or neonatal outcomes. Adverse neonatal outcomes in patients with preeclampsia with severe features and above threshold LFTs are driven by earlier gestational age at delivery. Prospective studies are needed to guide delivery timing in patients with preeclampsia and elevated liver enzymes. Brief rationale The criteria for elevated liver function tests (greater than two times the upper limit of normal) are widely accepted among obstetricians to diagnose a severe feature of preeclampsia. However, these criteria are based on expert opinion and extrapolated from data on patients with HELLP syndrome. Since preterm delivery of the neonate is recommended for preeclampsia with severe features, the threshold used to define severe liver enzyme elevation has a direct impact on neonatal outcomes. Therefore, the goal of our study was to determine if patients with preeclampsia with severe features and a pre-delivery AST or ALT level ≥ two times the upper limit of normal have worse maternal and neonatal outcomes compared to those with an AST and ALT below this level.

INTRODUCTION: Penicillin (PCN) allergy affects 10% of the U.S. population. The American College of Obstetricians and Gynecologists recommends PCN allergy testing in pregnancy when available. The objective of this study is to explore obstetric and allergy providers' knowledge and attitudes toward penicillin allergy testing and identify current barriers. METHODS: Single hospital system survey-based study of all obstetric and allergy providers. All obstetric and allergy providers were emailed an anonymous survey of their knowledge, current practice pattern, and perceived barriers to PCN allergy testing. Institutional review board approval was obtained for this study. RESULTS: From January 1, 2021 to July 31, 2022, 2,795 of 20,500 initial prenatal visits (14%) had a listed beta-lactam allergy. Of these 2,795 patients, 300 (11%) were referred for allergy testing. Fifty-four obstetric providers completed surveys. Thirty-nine percent of obstetric providers had never referred a patient for PCN allergy evaluation. Twenty-seven percent of obstetric providers self-identified lack of provider knowledge in testing process as a complete barrier to testing, and one-third of providers perceived lack of time in clinic to discuss referral as a barrier. Twenty-one allergy providers completed the survey. All allergy provider responders were willing to perform allergy testing in pregnant women, with 63% performing a direct oral challenge to confirm results. Forty-one percent of allergy providers preferred to defer testing until the third trimester. CONCLUSION: Allergy providers are willing and able to perform penicillin allergy testing in pregnancy, but testing is limited by obstetric provider referrals. Current barriers include obstetric provider knowledge about testing and resources to allow efficient discussion of testing benefits in clinic.

Background and Objectives: Mild gestational diabetes (GDM) refers to the gestational hyperglycemia, which does not fulfill the diagnostic criteria for GDM. The results of studies on adverse pregnancy outcomes among women with mild GDM are controversial. Therefore, the aim of this systematic review and meta-analysis was to investigate the impact of mild GDM on the risk of adverse maternal and neonatal outcomes.Methods: A thorough literature search was performed to retrieve articles that investigated adverse maternal and neonatal outcomes in women with mild GDM in comparison with non-GDM counterparts. All populations were classified to three groups based on their diagnostic criteria for mild GDM. Heterogeneous and non-heterogeneous results were analyzed using the fixed/random effects models. Publication bias was assessed using the Harbord test. DerSimonian and Laird, and inverse variance methods were used to calculate the pooled relative risk of events. Subgroup analysis was performed based on mild GDM diagnostic criteria. Quality and risk of bias assessment were performed using standard questionnaires.Results: Seventeen studies involving 11,623 pregnant women with mild GDM and 53,057 non-GDM counterparts contributed to the meta-analysis. For adverse maternal outcomes, the results of meta-analysis showed that the women with mild GDM had a significantly higher risk of cesarean section (pooled RR: 1.3, 95% CI 1.2–1.5), pregnancy-induced hypertension (pooled RR: 1.4, 95% CI 1.1–1.7), preeclampsia (pooled RR: 1.3, 95% CI 1.1–1.5) and shoulder dystocia (pooled RR: 2.7, 95% CI 1.5–5.1) in comparison with the non-GDM population. For adverse neonatal outcomes, the pooled relative risk of macrosomia (pooled RR = 0.4, 95% CI: 1.1–1.7), large for gestational age (pooled RR = 1.7, 95% CI: 1.3–2.3), hypoglycemia (pooled RR = 1.6, 95% CI: 1.1–2.3), hyperbilirubinemia (pooled RR = 1.1, 95% CI: 1–1.3), 5 min Apgar <7 (pooled RR = 1.6, 95% CI: 1.1–2.4), admission to the neonatal intensive care unit (pooled RR = 1.5, 95% CI: 1.1–2.1), respiratory distress syndrome (pooled RR = 3.2, 95% CI: 1.8–5.5), and preterm birth (pooled RR = 1.4, 95% CI: 1.1–1.7) was significantly increased in the mild GDM women as compared with the non-GDM population. However, the adverse events of small for gestational age and neonatal death were not significantly different between the groups. Analysis of composite maternal and neonatal outcomes revealed that the risk of those adverse outcomes in the women with mild GDM in all classifications were significantly higher than the non-GDM population. Also, the meta-regression showed that the magnitude of those increased risks in both composite maternal and neonatal outcomes was similar.Conclusion: The risks of sever adverse neonatal outcomes including small for gestational age and neonatal mortality are not increased with mild GDM. However, the increased risks of most adverse maternal and neonatal outcomes are observed. The risks have similar magnitudes for all mild GDM diagnostic classifications.

Adverse maternal and neonatal outcomes among women with preeclampsia with severe features <34weeks gestation with versus without comorbidity.

Effects of Women’s Weight Changes on Adverse Outcomes in a Second Pregnancy