Hydroxychloroquine PK and exposure-response in pregnancies with lupus: the importance of adherence for neonatal outcomes

ObjectiveEvaluate the impact of pregnancy physiology and medication non-adherence on serum hydroxychloroquine (HCQ) pharmacokinetics (PK) and exposure-response in SLE.MethodsWe conducted a PK analysis using data from two observational pregnancy registries. We enrolled pregnant women with SLE taking HCQ at least 3 months prior to, and throughout pregnancy, and excluded those with multiple gestations. Using the PK model, we conducted dosing simulations and imputed 0%/20%/40%/60% non-adherence to evaluate the impact of adherence versus physiological changes on HCQ concentrations. We compared the effect of pregnancy-average non-adherent concentrations (≤100 ng/mL vs >100 ng/mL) on preterm birth using adjusted logistic regression.ResultsWe enrolled 56 women who had 61 pregnancies. By the third trimester, mean apparent HCQ clearance increased by 59.6%. At a dosage of 400 mg/day, fully adherent patients are expected to have HCQ concentrations ≤100 ng/mL only 0.3% of the time, compared with 24.2% when 60% of doses are missed. Persistently low HCQ concentrations throughout pregnancy were associated with a significantly higher odds of preterm birth, controlling for lupus nephritis and race (OR 11.2; 95% CI 2.3 to 54.2; p=0.003).ConclusionsWe observed significant changes in HCQ PK during pregnancy, resulting in a shortening in the drug’s half-life by 10 days; however, medication non-adherence had a more pronounced effect on HCQ exposure compared with physiological changes alone. Moreover, pregnant women with non-adherent HCQ concentrations had significantly higher rates of preterm birth. Accordingly, optimising adherence in pregnancy may be more clinically meaningful than adjusting HCQ dosage to account for physiological changes. PK modelling indicates that serum HCQ concentrations ≤100 ng/mL are suggestive of non-adherence regardless of trimester and may help identify pregnancies at risk for poor outcomes.

Conditions that increase the risk of cesarean-related blood transfusions: a single-center cohort study

Objective This study aimed to define the conditions that increase the possibility of receiving a blood transfusion in patients who had a cesarean section. Methods This study was conducted between January 2016 – May 2020 in a university hospital located in Konya, Turkey. Pregnant women undergoing cesarean section were included. Of 4303 eligible patients, 188 women were the transfused group and 4115 women were the non-transfused group. Logistic regression analysis was performed for potential confounding factors. Results A total of 4303 eligible patients were evaluated in this study. There were 4115 patients (95.6%) in the non-transfused group. The transfused group consisted of 188 patients (4.4%). The probability of transfusion was higher in pregnant women with placenta previa, placenta accreta spectrum, thrombocytopenia, preoperative anemia, macrosomia above 4500 g, and multiple gestations [adjusted OR values (95% CI); 10.58 (range 4.75–23.57), 7.75 (range 3.22–18.61), 7.85 (range 3.46–17.79), 5.71 (range 4.21–7.74), 4.22 (range 1.21-14.67) and 2.10 (range 1.18-3.72), respectively]. There was no increase in the possibility of transfusion in 4000–4500 gram macrosomia, uterine fibroids, preeclampsia, premature rupture of membranes, previous cesarean sections and gestational diabetes mellitus. Conclusion Placenta previa, placenta accreta spectrum, thrombocytopenia, preoperative anemia, macrosomia above 4500 g and multiple gestations increase the possibility of transfusion. Perioperative blood preparation is vital in such patients. Prevention of anemia during pregnancy is critical in reducing transfusions.

Multiple gestation and perinatal outcome in the Federal Medical Centre, Yenagoa, South-South, Nigeria: A 5-year review

Background: Multiple gestation occurs when the gravid uterus harbours more than one foetus. It is a high-risk pregnancy, because of the associated adverse pregnancy outcomes culminating in some cases, in a high rate of maternal and perinatal morbidity and mortality. Objective: To determine the incidence of multiple gestation, and maternal and perinatal outcomes associated with it at the Federal Medical Centre, Yenagoa, South-South, Nigeria, over a five-year period. Materials and Methods: This retrospective study was carried out between 1st January, 2016 and 31st December, 2020. Data were retrieved and entered into a pre-designed proforma, and analysed using IBM SPSS version 25.0. Results were presented in frequencies and percentages for categorical variables, and mean and standard deviation for continuous variables. Results: One hundred and sixty-three women had multiple gestation in the period under review, out of a total of 4,571 pregnancies, which represented a case incidence rate of 35.6 multiple gestations per 1,000 deliveries in the Centre. Incidence rates for twins and triplets were 32.5 and 3.5 per 1,000 deliveries, respectively. About 51.5% were unbooked for antenatal care in the index pregnancy. The most common (47.2%) complication was preterm delivery. There were 342 neonates from 163 multiple gestations. There was death of 20 (5.8%) babies. Conclusion: The significant maternal and perinatal morbidity and mortality associated with multiple gestation can be reduced by early diagnosis, specialized antenatal care, skilled intrapartum, postpartum and neonatal care in centres with a full complement of skilled obstetricians, anaesthetists and neonatologists.

Association of antenatal corticosteroids with morbidity and mortality among preterm multiple gestations: meta-analysis of observational studies

ObjectiveThis meta-analysis aimed to assess the efficacy of antenatal corticosteroids (ACS) on morbidity and mortality among preterm multiple pregnancies.MethodsThe PubMed, Embase, Web of Science and Cochrane Library databases were searched for studies investigating the outcomes among preterm multiple gestations following to ACS, from their inception to 1 November 2020. Two authors independently performed the study selection, risk of bias assessment and data extraction. The primary outcomes were respiratory distress syndrome (RDS) and mortality and secondary outcomes included intraventricular haemorrhage (IVH), periventricular leukomalacia (PVL), necrotising enterocolitis, retinopathy of prematurity and bronchopulmonary dysplasia. Pooled ORs were obtained using random effects models. Subgroup analyses were performed to explain heterogeneity by ACS completeness, administration-to-delivery intervals (≤7 days) and single or multicentre.ResultsA total of 16 observational studies with 36 973 newborns were included in the meta-analysis. ACS treatment was associated with a reduction in RDS (OR 0.66; 95% CI 0.54 to 0.82; I2=91.4%; p<0.001), mortality (OR 0.64; 95% CI 0.50 to 0.81; I2=85.9%; p<0.001), IVH (OR 0.67; 95% CI 0.54 to 0.83; I2=77.4%; p<0.001) and PVL (OR 0.65; 95% CI 0.47 to 0.92; I2=75.5%; p<0.001). Subgroup analyses showed ACS completeness, administration-to-delivery interval and multicentre study affected these associations.DiscussionACS may be beneficial for reducing the risks of RDS, mortality, IVH and PVL among preterm multiple gestations. The efficacy of ACS could be affected by ACS completeness and administration-to-delivery. More robust evidence on the efficacy of ACS treatment among multiple gestations is warranted.

Long-term follow-up of children exposed in-utero to progesterone treatment for prevention of preterm birth: study protocol of the AMPHIA follow-up

IntroductionPreterm birth is one of the main problems in obstetrics, and the most important cause of neonatal mortality, morbidity and neurodevelopmental impairment. Multiple gestation is an important risk factor for preterm birth, with up to 50% delivering before 37 weeks. Progesterone has a role in maintaining pregnancy and is frequently prescribed to prevent (recurrent) preterm birth and improve pregnancy outcomes in high-risk patients. However, little is known about its long-term effects in multiple gestations. The objective of this follow-up study is to assess long-term benefits and harms of prenatal exposure to progesterone treatment in multiple gestations on child development.Methods and analysisThis is a follow-up study of a multicentre, double-blind, placebo-controlled randomised trial (AMPHIA trial, ISRCTN40512715). Between 2006 and 2009 women with a multiple gestation were randomised at 16–20 weeks of gestation to weekly injections 250 mg 17α-hydroxyprogesterone caproate or placebo, until 36 weeks of gestation or delivery. The current long-term follow-up will assess all children (n=1355) born to mothers who participated in the AMPHIA trial, at 11–14 years of age, with internationally validated questionnaires, completed by themselves, their parents and their teachers.Main outcomes are child cognition and behaviourAdditional outcomes are death (perinatal and up to age 14), gender identity, educational performance and health-related problems. We will use intention-to-treat analyses comparing experimental and placebo group. To adjust for the correlation between twins, general linear mixed-effects models will be used.Ethics and disseminationAmsterdam UMC MEC provided a waiver for the Medical Research Involving Human Subjects Act (W20_234#20.268). Results will be disseminated through peer-reviewed journals and summaries shared with stakeholders, patients and participants. This protocol is published before analysis of the results.Trial registration numberNL8933.

Presentation of acute pulmonary edema in severe pre-eclamptic pregnant women: a case report

Pulmonary edema refers to an excessive accumulation of fluid in the pulmonary interstitial and alveolar spaces. It may occur in low risk pregnancies but one very important predisposing factor is association with pre-eclampsia. Acute pulmonary edema during pregnancy is very rare and occurs in 0.08% pregnancies. About 3% of severe pre-eclamptic patients develop acute pulmonary edema. Several risk factors have been identified: preeclampsia or eclampsia, use of tocolytic therapy, severe infection, cardiac disease, iatrogenic fluid overload, and multiple gestations. This case examines one such presentation and reviews some of the diagnostic possibilities.

Women with multiple gestations have an increased risk of development of hypertension in the future

Background Multiple gestations are associated with an increased incidence of preeclampsia. However, there exists no evidence for an association between multiple gestations and development of hypertension(HTN) later in life. This study aimed to determine whether multiple gestations are associated with HTN beyond the peripartum period. Methods In this retrospective nationwide population-based study, women who delivered a baby between January 1, 2007, and December 31, 2008, and underwent a national health screening examination within one year prior to their pregnancy were included. Subsequently, we tracked the occurrence of HTN during follow-up until December 31, 2015, using International Classification of Diseases-10th Revision codes. Results Among 362,821 women who gave birth during the study period, 4,944 (1.36%) women had multiple gestations. The cumulative incidence of HTN was higher in multiple gestations group compared with singleton group (5.95% vs. 3.78%, p < 0.01, respectively). On the Cox proportional hazards models, the risk of HTN was increased in women with multiple gestations (HR 1.35, 95% CI 1.19, 1.54) compared with those with singleton after adjustment for age, primiparity, preeclampsia, atrial fibrillation, body mass index, blood pressure, diabetes mellitus, high total cholesterol, abnormal liver function test, regular exercise, and smoking status. Conclusions Multiple gestations are associated with an increased risk of HTN later in life. Therefore, guidelines for the management of high-risk patients after delivery should be established.

Lesioni cutanee stellate e simmetriche in un gemello “rimasto solo”

The incidence of multiple pregnancy has increased, particularly because of the advances in assisted reproductive technologies. Multiple gestations are high risk pregnancies, especially the monochorionic ones. Two/thirds of initially twin pregnancies result in singles at birth, a condition defined as vanishing twin syndrome. The intrauterine death of one of the twins can cause direct fetal damage to the surviving one on several levels. The paper describes the case of a child born from twin pregnancy that was interrupted for one of the co-twins at early second trimester of gestation who presented with aplasia cutis congenita.