Uso de eutimizantes durante el embarazo y la lactancia / The use of mood regulators in pregnancy and breastfeeding

Se revisa el uso de eutimizantes durante el embarazo y la lactancia, analizando su efecto teratógenico, así como los síndromes perinatales descritos y los posibles efectos en el desarrollo del neonato. Los hallazgos de los últimos años sugieren que la lamotrigina es la opción más segura, aunque solo ha demostrado efectividad en la prevención de la depresión bipolar, y que el litio es más seguro que lo clásicamente considerado, mientras que el ácido valproico debe evitarse y no existe suficiente experiencia con carbamazepina. La decisión de tratar o no con un eutimizante dependerá de una cuidadosa valoración de cada caso, con sus antecedentes personales, teniendo en cuenta que el trastorno bipolar por sí mismo se asocia a complicaciones obstétricas y para el feto y que el embarazo y en particular el puerperio son momentos de máximo riesgo de descompensación. En la lactancia el litio parece menos tóxico que lo previamente supuesto y al igual que la lamotrigina puede usarse en casos concretos, mientras que no hay motivos para suspender la carbamazepina o el ácido valproico en niños expuestos a ellos intraútero

A review is presented on the use of mood stabilisers and hypnotics during pregnancy and lactation, analysing their teratogenic effect, as well as the associated perinatal syndromes and the possible effects on the development of the newborn child. Recent evidence suggests that lamotrigine is the safest drug, despite it has only shown to be effective in the prevention of bipolar depression. It is demonstrated that lithium is clearly safer than that classically reported, whereas valproic acid must be avoided, and there is not sufficient experience with carbamazepine. The decision to treat or not to treat with a mood stabiliser will depend on a careful assessment of each patient. This should take into account her psychiatric history, as well as the association of bipolar disorder itself with obstetric complications. Unfavourable outcomes for the foetus, and the maximum risk of acute episodes linked to pregnancy, and especially the puerperium, must also be considered. Lithium seems to be less toxic than previously supposed for breastfeeding infants and lamotrigine can be also be used in selected cases. There appears to be no reasons to withdraw carbamazepine or valproic acid if the infant was exposed in pregnancy

Uso de antidepresivos durante el embarazo y la lactancia / Antidepressant use during pregnancy and breastfeeding

En los últimos 20 años se ha estudiado extensamente la seguridad de los antidepresivos con respecto al riesgo de teratogénesis, síndromes perinatales, complicaciones posnatales del neurodesarrollo y lactancia. La metodología de los estudios tiene limitaciones y la conclusión provisional es que el riesgo de efectos secundarios de los antidepresivos es bajo y su uso está justificado en el embarazo, siempre que exista una indicación clínica

The last 20 years have seen an extensive examination of relevant research questions regarding the reproductive safety of antidepressants: risk of developing teratogenesis, neonatal adaptation syndromes and speech and neurodevelopmental disorders. The provisional conclusion is that the risk is small in absolute terms, therefore their use can be justified if there exists a clinical indication

Biological effects of anti-RANKL antibody administration in pregnant mice and their newborns.

Denosumab, a fully human monoclonal antibody that neutralizes receptor activator of nuclear factor-κB ligand (RANKL) and blocks osteoclast differentiation, has received approval in Japan for use as an anti-resorptive drug for osteoporosis and skeletal-related events (SREs) in patients with solid cancer. Denosumab is contraindicated during pregnancy, though the effects of blocking RANKL activity on pregnant mothers and their newborns are unclear. We used mice to investigate the effects of an anti-RANKL antibody on maternal and newborn health. Mothers injected with the anti-RANKL antibody had increased bone mass as compared with the controls, while osteoclast number and the level of tartrate-resistant acid phosphatase (TRAP) in serum were increased at the end of pregnancy. Newborn mice exposed to the antibody in utero were normally born, but showed increased bone mass and died within 48 h after birth. None of the newborns were found to have milk in their stomachs, suggesting that they died due to a maternal defect in lactation. Consistent with this, anti-RANKL antibody-injected mothers displayed impaired mammary gland development. However, fostering by healthy surrogate mothers rescued only 33% of the antibody-exposed newborns, suggesting that neonatal mortality was due, at least in part, to an intrinsic defect in the newborns. Our findings show that anti-RANKL antibody administration during pregnancy results in not only an undesirable increase in bone mass, but also has harmful effects on newborn survival.

Corticosteroid Injections: A Review of Sex-Related Side Effects.

Corticosteroid injections are used as a nonoperative modality to combat acute inflammation when conservative treatments fail. As female patients are regularly seen by orthopedic physicians, it is essential to identify and understand potential sex-related side effects. The aim of this article is to examine available literature for sex-related side effects of orthopedic-related corticosteroid injections. Although the incidence is low, sex-related side effects, such as abnormal menstruation, lactation disturbances, facial flushing, and hirsutism, are associated with corticosteroid injections. Physicians should be aware of these female-specific side effects and relay this information as part of the informed consent process. [Orthopedics. 2017; 40(2):e211-e215.].

Influencia de la oxitocina administrada durante el parto en el mantenimiento de la lactancia materna. Estudio preliminar / Influence of oxytocin administered during labor in maintaining. breastfeeding. Preliminary study

Introducción: El uso de la oxitocina (Oxt) durante el parto está tan generalizado que hay una tendencia a asumir que sus efectos son bien conocidos. El objetivo del presente estudio es determinar si la Oxt administrada durante el parto posee alguna influencia sobre el mantenimiento de la lactancia materna exclusiva (LME). Pacientes y métodos: Este trabajo forma parte de un estudio cuyo objetivo principal es valorar la influencia de la Oxt administrada durante el parto en los reflejos neonatales primitivos. Se trata de un estudio descriptivo observacional realizado en 20 díadas madre-hijo. Se incluyeron madres primigestas que no habían presentado complicaciones durante el embarazo y habían tenido un recién nacido a término sano fruto de un parto vaginal inducido o estimulado con Oxt. Se realizó una llamada telefónica a los 3 meses. Resultados: Las dosis de Oxt que recibieron durante el parto las madres que no mantenían LME al cabo de 1 y 3 meses fueron superiores a las que mantenían LME (p <0,05). Conclusión: La Oxt administrada durante el parto puede influir de forma negativa en el mantenimiento de la LME(AU)

Introduction: Synthetic oxytocin (Oxt) is the most commonly used drug to induce or augment labour contractions. The objective of the study is to evaluate the effect of Oxt used during labour on exclusive breastfeeding. Patients and methods: This job is part of an observational descriptive study which primary objective is to investigate the effect of intrapartum oxytocin administration on primitive neonatal reflexes. Twenty women with their first term pregnancies were studied. Inclusion criteria were: healthy primiparae with a single gestation at term and vaginal delivery induced or augmented with Oxt. Three months following the birth all mothers were contacted by telephone to assess feeding. Results: Women breastfeeding exclusively had received a significantly lower average dose of Oxt than those women who were not exclusively breastfeeding at 1 and 3 months postpartum (p<0.05). Conclusion: Synthetic Oxt used during labour may have negative influence on breastfeeding(AU)

Sudden loss of milk supply following high-dose triamcinolone (Kenacort) injection.

Endogenous corticosteroids are involved in breast development, initiation and maintenance of milk production. Animal studies have shown that exogenous corticosteroids diminish milk production and milk ejection. A high dose depot injection of triamcinolone resulted in dramatic reduction in milk production in an established lactation. Domperidone and frequent expression restored milk production. Lower dose depot injection of betamethasone into the shoulder joint did not noticeably reduce milk production.

Aspectos clínicos prácticos del uso de anticomiciales / Practical clinical issues on the use of antiseizure drugs

Con la aparición de nuevos antiepilépticos más seguros y mejor tolerados, la utilización de los fármacos anticomiciales para el tratamiento de los trastornos psiquiátricos ha experimentado un notable auge en la última década. Desde la introducción de la vigabatrina en 1992, el arsenal de anticonvulsivantes disponibles se ha incrementado rápidamente a razón de prácticamente un nuevo fármaco cada 1-2 años. La rápida llegada al mercado de un número ingente de fármacos dificulta la actualización de conocimientos por parte del psiquiatra, máxime si se tiene en cuenta quela aplicación de los nuevos anticomiciales al tratamiento de los distintos trastornos psiquiátricos se fundamenta en gran medida en la experiencia clínica más que en los ensayos clínicos, por lo que no existen posologías ni pautas de uso estandarizadas. Sin embargo, es necesario que el psiquiatra conozca las peculiaridades de cada uno de estos fármacos en relación con su manejo rutinario, así como en situaciones especiales como el embarazo o la insuficiencia hepática o renal. El presente artículo recoge algunas recomendaciones acerca de los aspectos prácticos del uso de estos medicamentos, la mayoría de las cuales deriva necesariamente de la experiencia adquirida a partir de los pacientes epilépticos (AU)

With the advent of new antiepileptics safer and better tolerated, the use of anti-seizure drugs in the treatment of psychiatric disorders has experienced a remarkable growth in the last decade. Since the introduction of vigabatrin, in 1992, the armoury of available anticonvulsants has increased rapidly at a rate of practically one drug every one or two years. The fast arrival to the market of such a huge number of drugs hampers the psychiatrist keeping updated, especially when taking into account that the use of new anticonvulsants to treat different psychiatric disorders is based, to a great extent, on clinical experience rather than on clinical trials and thus, no standardised posologies or guidelines for their use are available. Nevertheless, psychiatrists need to know the peculiarities of each of these drugs regarding their routine management, as well as in special situations as pregnancy or renal or hepatic insufficiency. This article gives some recommendations about practical issues on the management of these drugs, most of which are necessarily based on experience gained from epileptic patients (AU)

Efectos de fármacos hipnóticos en el embarazo y la lactancia / Drugs hypnotics in pregnancy and lactation

La utilización de psicofármacos, especialmente hipnóticos y ansiolíticos puede ser necesaria en algunas mujeres gestantes y lactantes. No obstante la escasa información científica existente sobre el tema puede condicionar la correcta administración terapéutica. En parte es totalmente comprensible ya que no se pueden realizar, por cuestiones evidentemente éticas, ensayos clínicos en humanos que nos den alguna información sobre el tema. Lo mejor es conocer que existen algunas de estas sustancias que pueden utilizarse y que el control medico es imprescindible para garantizar la buena alud tanto de la madre como del feto. Por eso hemos creído necesaria la compilación de información acerca de la idoneidad de la administración de estos psicofármacos. Para poder aportar datos científicos contrastados hemos consultado tres organismos que han estudiado y dictado normas sobre estos temas, la FDA (food and drug administration) y la ADEC (australian drug evaluation committee) para el tema de la gestación, y la Escuela Andaluza de Salud Pública, para la lactancia (AU)

The use of psychotropics specially hypnotics and anxiolytics can be necessary in some pregnant and nursing women. Despite the lack of scientific information on the subject it can affect the correct therapeutic administration. The lack of information is understandable due to the impossibility to do, for ethical reasons, clinical tests in humans. The best thing is to know than some of these substances exist that they can be used and that medical control is essential to insure the good health of both the mother and of the fetus. For that reason we have believe necessary an information compilation about the suitability of the administration of these drugs. In order to be able to compare dictated scientific data we have consulted three agencies that have studied and dictated norms on these subjects, the FDA (food and drug administration), the ADEC (Australian Drug Evaluation Committee) in relation to pregnancy and Escuela Andaluza de Salud Pública in relation to breast feeding (AU)

[Effects of Maidang Rutong granule on l-dopa-induced galactozemia in rats].

OBJECTIVE: To study galactagogue effect of Maidang Rutong granule on the lactation rats. METHOD: The experiments were designed to observe the efficiency of Maidang Rutong granule on lactescence, serum prolactin, and morphology of mammary gland with rat galactozemia model established by injecting l-dopa. RESULT: Maidang Rutong granule showed significant enhancement for lactescence and the offspring's body weight. It could antagonize the decrease of serum prolactin and the atrophy of mammary gland induced by l-dopa. CONCLUSION: Maidang Rutong granule exhibited significant galactagogue effect on the l-dopa-induced galactozemia in rats.

Does continuing oral magnesium supplementation until delivery affect labor and puerperium outcome?

OBJECTIVE: To determine the labor and puerperal impact of continuing oral magnesium supplementation until delivery. STUDY DESIGN: Single-center study with matched controls. In 40 pairs of healthy women with vaginally delivered singleton pregnancies, matched for maternal age, race and parity, maternal and neonatal outcome endpoints were compared in those receiving continuous oral magnesium aspartate supplementation 15-30 mmol/d for at least 4 weeks until delivery (for constipation, calf cramps, preterm contraction without cervical effacement or additional tocolytics) versus non-supplemented controls. RESULTS: In the magnesium group labor was nonsignificantly longer (stage 1: 326.0+/-187.5 min versus 276.7+/-140.8 min, P = 0.19; stage 2: 52.0+/-44.5 min versus 43.5+/-44.0 min, P = 0.40) and maximum oxytocin dose nonsignificantly higher (14.5+/-9.4 [median 12.0; n=15] versus 10.5+/-6.9 [median 7.5] mU/min, P = 0.28; n = 10). Fewer women had afterpains (12 versus 20, P=0.11), required spasmolysis (3 versus 14, P = 0.005), or could breastfeed their infants exclusively at discharge (24 versus 34, P = 0.04). CONCLUSION: Continuing oral magnesium supplementation until delivery does not significantly prolong labor or increase the oxytocin requirement, but it significantly impairs breastfeeding competence.

Use of measures of disproportionality in pharmacovigilance: three Dutch examples.

Spontaneous reporting systems for suspected adverse drug reactions (ADRs) remain a cornerstone of pharmacovigilance. In The Netherlands 'the Netherlands Pharmacovigilance Foundation Lareb' maintains such a system. A primary aim in pharmacovigilance is the timely detection of either new ADRs or a change of the frequency of ADRs that are already known to be associated with the drugs involved, i.e. signal detection. Adequate signal detection solely based on the human intellect (case by case analysis or qualitative signal detection) is becoming time consuming given the increasingly large number of data, as well as less effective, especially in more complex associations such as drug-drug interactions, syndromes and when various covariates are involved. In quantitative signal detection measures that express the extent in which combinations of drug(s) and clinical event(s) are disproportionately present in the database of reported suspected ADRs are used to reveal associations of interest. Although the rationale and the methodology of the various quantitative approaches differ, they all share the characteristic that they express to what extent the number of observed cases differs from the number of expected cases. In this paper three Dutch examples are described in which a measure of disproportionality is used in quantitative signal detection in pharmacovigilance: (i) the association between antidepressant drugs and the occurrence of non-puerpural lactation as an example of an association between a single drug and a single event; (ii) the onset or worsening of congestive heart failure associated with the combined use of nonsteroidal anti-inflammatory drugs and diuretics as an example of an association between two drugs and a single event (drug-drug interaction); and the (iii) (co)-occurrence of fever, urticaria and arthralgia and the use of terbinafine as an example of an association between a single drug and multiple events (syndrome). We conclude that the use of quantitative measures in addition to qualitative analysis is a step forward in signal detection in pharmacovigilance. More research is necessary into the performance of these approaches, especially its predictive value, its robustness as well as into further extensions of the methodology.

A comprehensive approach to evaluating nipple discharge.

While emphasis is justifiably placed on the importance of detecting breast masses during breast examination, the equally important need for accurate assessment of nipple discharge is often overlooked. Inspection and palpation for nipple discharge should be part of every breast examination. When detected, a critical analysis should be made of every nipple discharge, with the ultimate objective being differentiation between benign and malignant discharges. All nipple discharges can be defined by the physical characteristics of laterality, spontaneity, color, consistency, number of ducts involved, and duration. By correlating these characteristics with certain historical features (e.g., age, pregnancy, trauma, drugs), accurate determination of etiology can be made. A four-step approach is presented that offers a logical method for making the essential correlations. The sequence of the four relevant questions proposed gives the examiner a logical basis from which to assign clinical importance to each discharge. An algorithm is outlined that correlates diagnostic considerations with therapeutic actions.

Black breast milk due to minocycline therapy.

We report the unusual case of a 29-year-old female who developed black discoloration of breast milk 3 weeks after commencing oral minocycline therapy for acne vulgaris. Histochemical analysis of the breast milk revealed the presence of pigment particles within macrophages with iron staining characteristics. We propose that the pigment may represent an iron chelate of minocycline or one of its derivatives.

Usefulness of recombinant human prolactin for treatment of poor puerperal lactation in a rat model.

Recombinant human prolactin (r-hPRL) was produced by a line of murine C127 cells transfected with human PRL gene. To assess the biological efficacy of r-hPRL in vivo, we studied its influence on milk secretion using a rat model in which lactation was reduced by bromocriptine treatment. Puerperal rats were injected daily for 9 days after delivery with bromocriptine or bromocriptine plus r-hPRL, and lactational performance was assessed by weighing the pups. The concentrations of rat and human PRL in rat serum were measured by specific radioimmunoassays and the mammary glands were examined on postpartum day 10. Daily injection of bromocriptine (0.1 mg/rat) significantly reduced the endogenous level of rat PRL and impaired the weight gain of the pups. Administration of r-hPRL increased the serum level of human PRL. Daily injections of r-hPRL (50 micrograms/rat, twice a day) restored lactational performance and significantly increased the weight of the pups. The detrimental effect of bromocriptine on the mammary glands, assessed by both weight and histological appearance, was reversed by administration of r-hPRL. These results demonstrate that r-hPRL is biologically active in vivo and replacement therapy of r-hPRL is effective in improving the lactational performance in bromocriptine-treated rats, and also that r-hPRL may be useful for the treatment of women with poor lactation.

Can magnesium sulfate therapy impact lactogenesis?

This case report describes a patient who ingested magnesium sulfate (MgSO4) for approximately four days as a treatment for pregnancy-induced hypertension. Stage II lactogenesis was delayed until the tenth postpartum day at which point the patient's breasts became fully engorged. No explanation for this delay was found, other than the possibility that magnesium sulfate treatment impeded lactogenesis. Implications for professionals who care for lactating women are discussed.

Cimetidine-induced galactorrhea.

Various breast abnormalities have been described in patients treated chronically with cimetidine, but galactorrhea has been reported only twice in the medical literature. In both cases, there appeared to be an associated hyperprolactinemia. These problems could well represent a consequence of histamine2-receptor blockade. We report here a female patient with hepatic cirrhosis and portal hypertension who developed hyperprolactinemia and galactorrhea while on long-term cimetidine therapy. Both the hyperprolactinemia and the galactorrhea disappeared when the patient was switched to ranitidine, an alternative H2-receptor blocker. A review of the previous case reports and relevant literature is included.