BackgroundIn 2005, the FDA cautioned that exposure to paroxetine, a selective serotonin reuptake inhibitor (SSRI), during the first trimester of pregnancy may increase the risk of cardiac malformations. Since then, the association between maternal use of SSRIs during pregnancy and congenital malformations in infants has been the subject of much discussion and controversy. The aim of this study is to systematically review the associations between SSRIs use during early pregnancy and the risk of congenital malformations, with particular attention to the potential confounding by indication.MethodsThe study protocol was registered with PROSPERO (CRD42018088358). Cohort studies on congenital malformations in infants born to mothers with first-trimester exposure to SSRIs were identified via PubMed, Embase, Web of Science, and the Cochrane Library databases through 17 January 2018. Random-effects models were used to calculate summary relative risks (RRs).ResultsTwenty-nine cohort studies including 9,085,954 births were identified. Overall, use of SSRIs was associated with an increased risk of overall major congenital anomalies (MCAs, RR 1.11, 95% CI 1.03 to 1.19) and congenital heart defects (CHD, RR 1.24, 95% CI 1.11 to 1.37). No significantly increased risk was observed when restricted to women with a psychiatric diagnosis (MCAs, RR 1.04, 95% CI 0.95 to 1.13; CHD, RR 1.06, 95% CI 0.90 to 1.26). Similar significant associations were observed using maternal citalopram exposure (MCAs, RR 1.20, 95% CI 1.09 to 1.31; CHD, RR 1.24, 95% CI 1.02 to 1.51), fluoxetine (MCAs, RR 1.17, 95% CI 1.07 to 1.28; CHD, 1.30, 95% CI 1.12 to 1.53), and paroxetine (MCAs, RR 1.18, 95% CI 1.05 to 1.32; CHD, RR 1.17, 95% CI 0.97 to 1.41) and analyses restricted to using women with a psychiatric diagnosis were not statistically significant. Sertraline was associated with septal defects (RR 2.69, 95% CI 1.76 to 4.10), atrial septal defects (RR 2.07, 95% CI 1.26 to 3.39), and respiratory system defects (RR 2.65, 95% CI 1.32 to 5.32).ConclusionsThe evidence suggests a generally small risk of congenital malformations and argues against a substantial teratogenic effect of SSRIs. Caution is advisable in making decisions about whether to continue or stop treatment with SSRIs during pregnancy.Electronic supplementary materialThe online version of this article (10.1186/s12916-018-1193-5) contains supplementary material, which is available to authorized users.

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Endophytic actinobacteria are one of the important pharmaceutical resources and well known for producing different types of bioactive substances. Nevertheless, detection of the novelty, diversity, and bioactivity on endophytic actinobacteria isolated from mangrove plants are scarce. In this study, five different mangrove plants, Avicennia marina, Aegiceras corniculatum, Kandelia obovota, Bruguiera gymnorrhiza, and Thespesia populnea, were collected from Beilun Estuary National Nature Reserve in Guangxi Zhuang Autonomous Region, China. A total of 101 endophytic actinobacteria strains were recovered by culture-based approaches. They distributed in 7 orders, 15 families, and 28 genera including Streptomyces, Curtobacterium, Mycobacterium, Micrococcus, Brevibacterium, Kocuria, Nocardioides, Kineococcus, Kytococcus, Marmoricola, Microbacterium, Micromonospora, Actinoplanes, Agrococcus, Amnibacterium, Brachybacterium, Citricoccus, Dermacoccus, Glutamicibacter, Gordonia, Isoptericola, Janibacter, Leucobacter, Nocardia, Nocardiopsis, Pseudokineococcus, Sanguibacter, and Verrucosispora. Among them, seven strains were potentially new species of genera Nocardioides, Streptomyces, Amnibacterium, Marmoricola, and Mycobacterium. Above all, strain 8BXZ-J1 has already been characterized as a new species of the genus Marmoricola. A total of 63 out of 101 strains were chosen to screen antibacterial activities by paper-disk diffusion method and inhibitors of ribosome and DNA biosynthesis by means of a double fluorescent protein reporter. A total of 31 strains exhibited positive results in at least one antibacterial assay. Notably, strain 8BXZ-J1 and three other potential novel species, 7BMP-1, 5BQP-J3, and 1BXZ-J1, all showed antibacterial bioactivity. In addition, 21 strains showed inhibitory activities against at least one “ESKAPE” resistant pathogens. We also found that Streptomyces strains 2BBP-J2 and 1BBP-1 produce bioactive compound with inhibitory activity on protein biosynthesis as result of translation stalling. Meanwhile, Streptomyces strain 3BQP-1 produces bioactive compound inducing SOS-response due to DNA damage. In conclusion, this study proved mangrove plants harbored a high diversity of cultivable endophytic actinobacteria, which can be a promising source for discovery of novel species and bioactive compounds.

Mangroves have unique intertidal ecosystems of the tropics, which possess prolific biodiversity of actinomycetes. 1 Recent discoveries 2,3 of new species of microorganisms from the ecosystems encouraged us to explore the bioactive secondary metabolites from endophytic actinomycetes isolated from mangrove plants. As a result, the cultured broth of the strain I07A-01824, an endophytic Streptomyces albidoflavus, isolated from the leaf of Bruguiera gymnorrhiza collected at Shankou, Guangxi Province, People's Republic of China, was found to show moderate inhibiting activity against Magnaporth grisea. By bioassayguided fractionation, antimycin A 18 (1) was purified by chromatographies. By analyzing the spectroscopic data (including 1D and 2D NMR), its chemical structure was identified to be the first naturally occurring antimycin with an acetoxy group at C-8 (Figure 1).The strain I07A-01824 identified as Streptomyces was isolated from the leaf of B. gymnorrhiza collected at Shankou, Guangxi Province, People's Republic of China. A stock culture of the strain I07A-01824 was maintained on yeast and malt extract with glucose (YMG) agar slant consisting of 0.4% yeast extract (Beijing Aoboxing Biotechnology, Beijing, China), 1% malt extract (Beijing Aoboxing Biotechnology), 0.4% glucose and 1.2% agar (pH 7.2). The stock culture was inoculated into 250 ml Erlenmeyer flasks containing 50 ml of seed medium consisting of 0.5% glucose, 0.5% yeast extract, 0.5% peptone, 0.5% beef extract (Beijing Aoboxing Biotechnology), 0.4% corn steep liquor (North China Pharmaceutical Corporation, Shijiazhuang City, China), 2% soluble starch, 1% soybean meal (Beijing Comwin Pharm-Culture, Beijing, China), 0.4% CaCO 3 and 0.002% CoCl 2 (pH 7.2). The flask culture was incubated on a rotary shaker (180 r.p.m.) at 28 1C for 36 h. The seed culture (50 ml) was transferred into each of 40 5-l Erlenmeyer flasks containing 1 l of the same seed medium. The fermentation was carried out at 28 1C for 72 h on a rotary shaker (180 r.p.m.).The fermentation broth (40 l) was filtered and the filtrate was extracted with EtOAc (40 l). The extract was dried with Na 2

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