Anne S Ersbøll

Treatment with oral beta-blockers during pregnancy complicated by maternal heart disease increases the risk of fetal growth restriction.

To investigate the effect on fetal growth of treatment with oral beta‐blockers during pregnancy in women with congenital or acquired heart disease.

Treatment of bacterial vaginosis in pregnancy in order to reduce the risk of spontaneous preterm delivery: a clinical recommendation

Bacterial vaginosis (BV) is characterized by a dysbiosis of the vaginal microbiota with a depletion of Lactobacillus spp. In pregnancy, prevalences between 7 and 30% have been reported depending on the study population and the definition. BV may be associated with an increased risk of spontaneous preterm delivery (sPTD). However, it is controversial whether or not BV‐positive pregnant women will benefit from treatment to reduce the risk of sPTD. We could not identify any good‐quality guideline addressing this issue. Consequently we aimed to produce this clinical recommendation based on GRADE.

Peripartum cardiomyopathy in Denmark: a retrospective, population-based study of incidence, management and outcome.

Population‐based European studies of peripartum cardiomyopathy (PPCM) are few. We aimed to estimate the nationwide incidence and outcome of PPCM in Denmark during 2005–2014.

Peripartum cardiomyopathy: a systematic literature review.

Peripartum cardiomyopathy (PPCM) is a rare but potentially fatal disease defined by heart failure towards the end of pregnancy or in the months following delivery. We aim to raise awareness of the condition and give the clinician an overview of current knowledge on the mechanisms of pathophysiology, diagnostics and clinical management.

Exercise in Pregnancy: First Trimester Risks.

Most national guidelines recommend moderate exercise during pregnancy, but this is not followed by the majority of pregnant women. Fear of exercise risks is among reported barriers. In contrast to most reviews focusing on late pregnancy risks, this review evaluates the association between exercise in the first trimester and the risk of miscarriage. A systematic review based on the EMBASE and PUBMED databases was conducted and 5 studies assessing the association between early pregnancy exercise and miscarriage were identified. Diverging findings were reported making no clear conclusion possible. New studies with participants included in the prepregnancy period are needed.

Bromocriptine for the treatment of peripartum cardiomyopathy: comparison of outcome with a Danish cohort

Impressive work by Dr Hilfiker-Kleiner et al. underlies the multicentre randomized controlled trial (RCT) that compared two different dosage regimens of the prolactin-inhibitor bromocriptine in 63 peripartum cardiomyopathy (PPCM) patients. The study design did not include a placebo arm and to address this, a subgroup with baseline left ventricular ejection fraction (LVEF) < 30% was compared with a subgroup from the American Investigations of PregnancyAssociated Cardiomyopathy (IPAC) study. Better outcome was noted in the bromocriptine study subgroup. However, only 1 woman out of 63 in the bromocriptine RCT was of African descent compared with 30% in the IPAC cohort. It has been demonstrated that women of African descent have worse outcomes of PPCM, and hence the outcome differences observed between the two cohorts may not be entirely ascribed to bromocriptine. A Danish PPCM cohort, in which 91% are Caucasian, may serve as a better comparator to the RCT study. We performed post hoc analyses of outcome in two Danish subgroups with baseline LVEF < 30%: 13 women treated with the prolactin-inhibitor cabergoline for 2 days to inhibit lactation and 23 women without bromocriptine or cabergoline treatment (Table 1). Full recovery rate was not significantly different between the bromocriptine treated women in the RCT and the Danish women without (v P = 0.56). This new comparison questions the effect of prolactin-inhibition in PPCM, despite our own previous suggestion that it may predict recovery. It is important to underline limitations of all these comparisons: numbers are small and study designs, patient catchment, and follow-up differ. Disadvantages of bromocriptine therapy include potentially increased thrombosis risk and cessation of breastfeeding, a serious consideration especially in developing countries. Our comparison does not reject a possible effect of bromocriptine, but it underscores the need for more data to establish an evidence base for routine use of bromocriptine in PPCM.

Changes in the pattern of paracetamol use in the periconception period in a Danish cohort.

Paracetamol is the most commonly used over‐the‐counter drug in pregnancy. It is generally considered to be safe, but prolonged antenatal exposure has been associated with offspring short‐ and long‐term morbidity. Our aim was to describe the pattern of paracetamol use with a focus on frequent ingestion (more than once a week), 3 months before and in early pregnancy. In this cohort, 8650 pregnant women responded to a web‐based clinical questionnaire that included questions about drug use. Paracetamol was the most used drug before and in early pregnancy (35.2% and 6.5% of respondents, respectively). The proportion of frequent users decreased from 3.9% before to 0.9% in early pregnancy. Frequent paracetamol use was associated with smoking, co‐morbidities, body mass index ≥25 kg/m2, unplanned pregnancy, no education and inability to understand Danish. A significant decrease in the proportion of women with any paracetamol use in early pregnancy was noted after access to large packs was restricted by legislation.

Psychological adaptation after peripartum cardiomyopathy: a qualitative study

BACKGROUND Peripartum cardiomyopathy (PPCM) is a rare and potentially life-threatening condition of heart failure affecting women with no previous heart disease in the last months of pregnancy and up to six months after childbirth. OBJECTIVE To explore womens experiences of the process of regaining psychological balance and wellbeing (i.e. psychological adaptation) after having experienced severe peripartum morbidity. DESIGN A qualitative exploratory research design was applied to guide the study. Data was collected through in-depth, semi-structured, face-toface telephone and e-mail interviews. Thematic analysis was applied in the data analysis. SETTING The study was a sub-study of a larger nationwide research study investigating the incidence and clinical outcome of peripartum cardiomyopathy in Denmark during a ten-year period of 2005-2014. PARTICIPANTS Through a criterion-based sampling strategy, 14 Danish women with peripartum cardiomyopathy were recruited for participation in the study. In relation to severity of disease, demographics and pregnancy related characteristic, the sample showed a wide range of diversity. FINDINGS The overarching theme of the thematic analysis was identified to be Recovering to a new normal after peripartum cardiomyopathy. The overarching theme was comprised by five main themes: Losing trust, Silence after chaos, Disrupted early mothering, Choices made for me and not by me, and Ability to mobilize inner resources. CONCLUSIONS Findings from this study suggest that women are vulnerable in the time after PPCM diagnosis and struggle to find psychological balance in their life. The need for professional psychological support was often unmet and the physical symptoms were foregrounded in the recovery period. After PPCM, follow-up on psychological wellbeing and morbidity should be offered to women routinely.

Appreciable uncertainty regarding benefits and risks in the treatment of bacterial vaginosis to prevent preterm birth

Sir, As part of his speeches, the Roman senator Cato the Elder frequently uttered “Carthago delenda est” (Carthage must be destroyed). Similarly, Lamont and colleagues frequently utter that the “wrong patients with the wrong diagnosis were given wrong antibiotics at the wrong gestational age.” We respect that Lamont and colleagues find it difficult to accept meta-analyses, which “cut a toe and a bit of a heel” to merge evidence from more publications, and we certainly cannot exclude the possibility that future research will change clinical practice. However, in contrast to Lamont and colleagues, we emphasize that not only statistical significance but also other aspects should be taken into consideration in the development of clinical recommendations (1). Using GRADE, we found that appreciable uncertainty exists regarding the magnitude of benefits from clindamycin treatment compared with the risks. Given that the relative risk reported in Figure 5 represents the truth (2), the number needed to treat was 45 bacterial vaginosis (BV)-positive pregnant women to avoid one spontaneous preterm delivery (sPTD) before gestational week 37. This relatively minor effect should especially be measured against the microbiological concerns for iatrogenic damage when clindamycin is administered to approximately 10–15% of Danish pregnant women. These concerns include resistance development of BV-associated bacteria, Clostridium difficile colitis, and yet unknown adverse effects to the microbiome (3). The major concern raised by Lamont and colleagues seems to relate to whether the intervention with clindamycin before 22 weeks’ gestation would significantly reduce the incidence of sPTD (4). We agree that had the cut-off been gestational week 22, then the difference in incidence of sPTD would have been statistically significant with respect to clindamycin. Regardless, according to GRADE, the overall level of evidence for the outcome sPTD was rated low for reasons given in Supporting Information Table 2 (2). Regarding the PREMEVA 1 study, we agree that the risk of bias may have increased since October 2014 when we conducted the literature search. At this time, the PREMEVA1 abstract had only been published for 10 months (5). We sent out official emails to the authors; however, none responded. We agree that it is worrisome that the PREMEVA1 study is not yet published and we, as Lamont and colleagues, can only speculate why. Could publication bias due to negative findings be disregarded? Finally, it should be emphasized that we cannot confirm from our analyses that treatment of BV reduces the rate of early preterm birth and low birthweight infants, nor could we find the evidence in the review and meta-analysis by Lamont et al. from 2011 (6). In conclusion, we do not agree that the concerns mentioned by Lamont and colleagues would change the clinical recommendations in the recent AOGS publication (2). The weak recommendation against clindamycin reflects that some experts might treat BV in pregnancy whereas the majority would not, as “weak recommendations for or against intervention are made when guideline authors believe that most informed people would choose the recommended course of action, but a substantial number would not.”