Exposure to drugs during pregnancy has the potential to harm offspring. Teratogenic effects are the most feared adverse outcomes in newborns; however, a wide spectrum of less known, usually reversible and often acute, neonatal adverse events can also occur due to drug intake by mothers during pregnancy, particularly in close proximity to delivery. This narrative review is aimed at the description of drugs and drug classes for which licit maternal use in the predelivery period has been associated with neonatal non-teratogenic disorders. For each drug class, epidemiology, clinical features, biological mechanism and management of these adverse reactions have been discussed in detail. Although these adverse reactions have been described mainly for substances used illicitly for recreational purposes, several prescription drugs have also been involved; these include mainly psychotropic medications such as opioids, antidepressants, antiepileptics and antipsychotics. These effects can be partly explained by withdrawal syndromes (defined also as 'neonatal abstinence syndrome') caused by the delivery-related discontinuation of the drug disposition from the mother to the fetus, with symptoms that may include feeding disorders, tremors, irritability, hypotonia/hypertonia, vomiting and persistent crying, occurring a few hours to 1 month after delivery. Otherwise, neonatal neurological and behavioral effects can also be caused by a residual pharmacological effect due to an accumulation of the drug in the blood and tissues of the newborn, with various symptoms related to the toxic effects of the specific drug class, usually developing a few hours after birth. With few exceptions, validated protocols for the assessment and management of withdrawal or residual pharmacological effects of these drugs in neonates are often lacking or incomplete. Spontaneous reporting of these adverse reactions seems limited, although it might represent a useful tool for improving our knowledge about drug-induced neonatal syndromes.

This explorative study suggests that the class of PPIs could be involved in reports of muscular ADRs, rather than any other ADR, more frequently than any non-statin drug. Our results must be corroborated by further studies.

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The evaluation of the relationship between the use of antidiabetic drug and the occurrence of cancer is extremely challenging, both from the clinical and pharmacoepidemiological standpoint. This narrative review described the current evidence supporting a relationship between the use of antidiabetic drugs and the incidence of solid cancers. Areas covered: Data from pharmacoepidemiological studies on cancer incidence were presented for the main antidiabetic drugs and drug classes, including human insulin and insulin analogues, metformin, sulfonylureas, glinides, alpha-glucosidase inhibitors, thiazolidinediones, incretin mimetics, and sodium glucose co-transporter 2 inhibitors. The relationship between the use of antidiabetics and the incidence of solid cancer was described in strata by any cancer and by organ-specific cancer and by drug and by drug classes. Information supporting biological evidence and putative mechanisms were also provided. Expert opinion: The history of exploration of the relationship between antidiabetic drugs and the risk of solid cancers has showed several issues. Unrecognized biases and misinterpretations of study results have had important consequences that delayed the identification of actual risk and benefits of the use of antidiabetic drugs associated with cancer occurrence or progression. The lesson learned from the past should address the future research in this area, since in the majority of cases findings are controversial and confirmatory studies are warranted.

Vitamin D (VitD) is largely used in Italy, often inappropriately; thus, an evaluation of its safety is a crucial issue. This study analyses the adverse reactions (ARs) associated with the use of products containing VitD (VitDps) reported to the Italian National Pharmacovigilance and Phytovigilance networks. From March 2002 to August 2022, a total of 643 and 127 reports concerning 903 and 215 ARs were retrieved from Pharmacovigilance and Phytovigilance networks, respectively. Overall, 332 (29.6%) ARs were classified as serious, and the most described ones were hypercalcaemia, renal failure and tachycardia. Serious AR risk was significantly higher for subjects using more than four concomitant products (OR 2.44 [95% CI 1.30–4.60]) and VitD doses higher than 1000 IU/day (OR 2.70 [95% CI 1.30–5.64]). In Italy, there was a modest decrease in AR reporting, despite the slightly increased use of VitD during the COVID-19 pandemic. To the best of our knowledge, this is the first study describing all VitDps-related ARs observed in the Italian general population. Since underreporting is the main limitation of the safety reporting systems, the necessity to continue ARs monitoring, also using real-world data on VitDps prescription, use and outcome patterns is highlighted.