Endocrinologic diseases management during breastfeeding

Serrano Aguayo, Pilar; García de Quirós Muñoz, Juan Manuel; Bretón Lesmes, Irene; Cózar León, Maria Victoria
doi:10.1016/j.medcle.2014.04.001
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    "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">Frequently&#44; health care professionals have to treat endocrinological diseases in women during the breastfeeding period&#46; There are many scientific spaces dedicated to the treatment of endocrinological diseases during pregnancy&#44; in publications&#44; seminars and congresses&#46; However&#44; there are not many reviews on the treatment of these diseases during the breastfeeding period&#46; Sometimes&#44; endocrinologists have little information on the subject&#44; or search for information with special interest in sources that cannot be easily accessed&#44; or scattered sources&#46; It is not uncommon for endocrinologists to decide to suspend breastfeeding &#40;BF&#41; if they have doubts&#46; Although these approaches vary according to the training of the professional&#44; let us use Canada case as an example&#44; where 44&#37; of endocrinologists recommended suspending BF when treatment with antithyroid medication must be provided to a woman during breastfeeding&#46;<a class="elsevierStyleCrossRef" href="#bib0285"><span class="elsevierStyleSup">1</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">To obtain a proper answer&#44; it is necessary to ask the right question&#46; The immediate answer to the question &#8220;does this child need to take a certain amount of a certain drug&#63;&#8221; is <span class="elsevierStyleItalic">no</span>&#46; However&#44; if we take into consideration all the aspects of a decision&#44; the right question is&#58; are the risks of taking milk from his mother with a certain amount of a certain drug more serious and frequent for this child than those of artificial feeding&#63; What are the risks of giving up breastfeeding for this woman&#63; In order to answer these questions&#44; we must know the risks of artificial feeding and compare them with those of BF with a certain amount of the drug&#44; as well as the risks of breastfeeding or giving up breastfeeding for a woman with a certain endocrinopathy&#46; The purpose of this article is to provide information on those aspects&#46;</p><p id="par0015" class="elsevierStylePara elsevierViewall">Numerous research works document the advantages of BF for mothers&#44; children&#44; the family and society&#46;<a class="elsevierStyleCrossRef" href="#bib0290"><span class="elsevierStyleSup">2</span></a> That includes health&#44; nutritional&#44; immunological&#44; psychological&#44; social&#44; economical and environmental benefits in the short&#44; medium and long term&#46;<a class="elsevierStyleCrossRef" href="#bib0295"><span class="elsevierStyleSup">3</span></a> The advantages of BF are present both in poor and technologically advanced countries&#46;<a class="elsevierStyleCrossRef" href="#bib0300"><span class="elsevierStyleSup">4</span></a> Favouring a high rate of breastfeeding also implies large savings of health care resources&#46;<a class="elsevierStyleCrossRef" href="#bib0305"><span class="elsevierStyleSup">5</span></a></p><p id="par0020" class="elsevierStylePara elsevierViewall">The World Health Organization and the Spanish Paediatric Association recommend exclusive BF until 6 months of age&#44; and to continue BF&#44; along with other foods&#44; until the baby is at least 2 years old&#44; with no maximum time&#44; but as long as the mother and child want to continue&#46;<a class="elsevierStyleCrossRef" href="#bib0310"><span class="elsevierStyleSup">6</span></a></p><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">Prolactinoma</span><p id="par0025" class="elsevierStylePara elsevierViewall">An effective treatment of hyperprolactinaemia restores fertility&#44; and it is therefore of special interest for the management of prolactinoma during pregnancy and breastfeeding&#46;</p><p id="par0030" class="elsevierStylePara elsevierViewall">The probability of growth of microprolactinomas during pregnancy is very low&#44; and 1&#46;6&#8211;2&#46;4&#37; of patients show symptoms related to tumour growth &#40;headache&#41;&#44; although in some others &#40;4&#46;5&#37;&#41;&#44; an asymptomatic growth may be proved through imaging tests&#46;<a class="elsevierStyleCrossRef" href="#bib0315"><span class="elsevierStyleSup">7</span></a> For this reason&#44; and given the potential teratogenicity of the drugs&#44; we recommend suspending treatment with dopaminergic agents once the pregnancy is confirmed&#46; The proper treatment if there are symptoms of tumour growth is bromocriptine&#46; We do not recommend carrying out imaging or ophthalmologic tests in all cases&#44; but only if the patient mentions symptoms evidencing tumour growth&#46;<a class="elsevierStyleCrossRef" href="#bib0320"><span class="elsevierStyleSup">8</span></a></p><p id="par0035" class="elsevierStylePara elsevierViewall">As regards macroprolactinomas&#44; 37&#37; of cases present symptoms of tumour growth &#40;headache&#44; in general&#44; and only in some cases&#44; visual changes&#41;&#44; and an additional 17&#37; may present asymptomatic tumour growth&#44; which can be proved through imaging tests&#46; 34&#37; of patients may experience a reduction of the tumour&#46;<a class="elsevierStyleCrossRef" href="#bib0325"><span class="elsevierStyleSup">9</span></a> Treatment with bromocriptine during the 12 months prior to the pregnancy greatly reduces the possibility of tumour growth&#44; as well as having had previous pituitary surgery or radiotherapy&#46;<a class="elsevierStyleCrossRefs" href="#bib0320"><span class="elsevierStyleSup">8&#44;10</span></a> In most cases&#44; the symptoms of growth are resolved with bromocriptine treatment&#44; although in some cases&#44; pituitary surgery is necessary&#46; We recommend close clinical surveillance during pregnancy and performing imaging and visual tests if there were any symptoms of tumour growth&#44; which&#44; if confirmed&#44; may be treated with bromocriptine&#44; reserving surgery for cases not responding to this treatment&#46; For certain tumour locations&#44; it may be advisable to use bromocriptine without interruptions&#44; since the beginning of the pregnancy&#44; without waiting for symptoms of further tumour growth&#46;<a class="elsevierStyleCrossRef" href="#bib0330"><span class="elsevierStyleSup">10</span></a></p><p id="par0040" class="elsevierStylePara elsevierViewall">After the pregnancy&#44; there is frequently a decrease of prolactin levels &#40;PRL&#41;&#44; in relation to concentrations prior to the pregnancy&#44; with normalisation at 60&#37; of microprolactinomas and at 72&#37; of macroprolactinomas&#46;<a class="elsevierStyleCrossRef" href="#bib0335"><span class="elsevierStyleSup">11</span></a> In an additional 11&#37;&#44; the tumour is healed &#40;normalisation of prolactin and restored menstruation&#41;&#46; The reduction or disappearance of the tumour occurs in 27&#8211;35&#37; of cases&#46;<a class="elsevierStyleCrossRef" href="#bib0315"><span class="elsevierStyleSup">7</span></a></p><p id="par0045" class="elsevierStylePara elsevierViewall">PRL measurement is not useful for a follow-up of microprolactinoma or macroprolactinoma during pregnancy or breastfeeding&#46;<a class="elsevierStyleCrossRefs" href="#bib0320"><span class="elsevierStyleSup">8&#44;12</span></a></p><p id="par0050" class="elsevierStylePara elsevierViewall">BF was a concern in relation to potential tumour growth&#44; because suction stimulates prolactin release&#46; However&#44; there is no evidence that BF poses a risk of tumour growth&#44;<a class="elsevierStyleCrossRef" href="#bib0345"><span class="elsevierStyleSup">13</span></a> probably because the doubtful effect of suction over tumour cells is non-existent and is lower than the effect of the oestrogen stimulus received during pregnancy&#44; and because of the protection offered by hypoestrogenemia inherent to BF&#46; BF does not increase the recurrence of hyperprolactinaemia&#44; which is normalised in 68&#37; of patients with prolactinomas &#40;microprolactinomas and macroprolactinomas&#41; or functional hyperprolactinaemia after pregnancy&#46;<a class="elsevierStyleCrossRef" href="#bib0350"><span class="elsevierStyleSup">14</span></a> Therefore&#44; breastfeeding must be advised in all cases of prolactinoma&#46; No differences have been observed either in prolactin concentrations after breastfeeding based on the duration of breastfeeding&#46; In cases with complications during pregnancy&#44; there must be a strict follow-up&#44; but with no contraindication of breastfeeding initially&#46; If there is compression of the optic chiasm or other adjacent structures&#44; initiating treatment with a dopaminergic agonist will be recommended&#44; and the side effect will be suppression of BF&#46; The current consensus&#44; according to the <span class="elsevierStyleItalic">Pituitary Society</span> guidelines for the diagnosis and treatment of prolactinomas&#44; is that neither microprolactinomas nor macroprolactinomas with no compromise of space are an absolute or relative contraindication for BF&#46;<a class="elsevierStyleCrossRef" href="#bib0355"><span class="elsevierStyleSup">15</span></a> Treatment with dopamine agonists shall not be started until the end of BF&#46; It is not adequate to advise the mother to stop breastfeeding before the rest of women&#44; that is to say&#44; BF until at least 2 years old&#44; with no maximum&#46; Meanwhile&#44; a clinical follow-up will be performed&#44; and if there is any suspicion of tumour growth&#44; imaging tests shall be performed to confirm&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Diabetes mellitus</span><p id="par0055" class="elsevierStylePara elsevierViewall">The known benefits of breastfeeding are of special interest in children of women with diabetes mellitus &#40;DM&#41;&#44; both type 1 and 2 &#40;DM 2&#41;&#44; because a reduction on the incidence of these diseases in susceptible patients has been reported&#46;<a class="elsevierStyleCrossRefs" href="#bib0360"><span class="elsevierStyleSup">16&#8211;19</span></a> The longer duration of BF also protects mothers with gestational diabetes from DM 2&#58; BF is associated with a marked delay in the onset of DM 2<a class="elsevierStyleCrossRef" href="#bib0380"><span class="elsevierStyleSup">20</span></a> and a notable minor incidence of said disease&#46;<a class="elsevierStyleCrossRef" href="#bib0385"><span class="elsevierStyleSup">21</span></a> The screening for DM 2 in women who have had gestational diabetes is recommended from week 6 to 12 after delivery&#46;<a class="elsevierStyleCrossRef" href="#bib0390"><span class="elsevierStyleSup">22</span></a> It is not advisable to suppress BF to perform the test&#44; which has been the standard practice so far and is prejudicial to women&#44; because it deprives women from an important factor of protection against the development of DM 2&#46;</p><p id="par0060" class="elsevierStylePara elsevierViewall">BF allows the mother to enjoy an option of health&#44; such as breastfeeding&#44; in the context of the overload caused by chronic diseases&#46; Diabetic women have the capacity to breastfeed their children&#44; like the rest of women&#46; The <span class="elsevierStyleItalic">American Diabetes Association</span> recommends encouraging diabetic women to breastfeed&#46;<a class="elsevierStyleCrossRef" href="#bib0395"><span class="elsevierStyleSup">23</span></a></p><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Considerations for the treatment of diabetes during breastfeeding</span><p id="par0065" class="elsevierStylePara elsevierViewall">The frequency of complications in the delivery for diabetic women increases when the diabetes is not properly controlled&#46; But even in well controlled patients&#44; an excess of medical intervention leads to an increase in complications&#46; A large number of diabetic women&#44; regardless of their degree of metabolic control and the status of the foetus&#44; have induced deliveries&#44; which is associated with a higher rate of instrumented deliveries and caesarean sections&#46; Frequently&#44; the new-born is separated from the mother and admitted into the neonatal unit&#44; many times for observation only&#46; Very often&#44; the new-born receives dextrose solution or artificial formula to avoid potential hypoglycaemia &#40;the incidence of which is increased in children of diabetic women&#44; especially if they did not have a proper metabolic control&#41;&#44; therefore omitting the first step of prevention&#44; which is frequent breastfeeding and skin-to-skin contact with the mother&#46;<a class="elsevierStyleCrossRef" href="#bib0400"><span class="elsevierStyleSup">24</span></a> All of that leads to a delay of the first contact with the breast&#44; which is the most important factor for successful breastfeeding&#44; also for diabetic women&#46;<a class="elsevierStyleCrossRef" href="#bib0405"><span class="elsevierStyleSup">25</span></a> In conclusion&#44; diabetic mothers have more obstacles in the beginning of breastfeeding than non-diabetic mothers&#44; and their breastfeeding may be easier if the circumstances benefiting the success of BF for any mother&#8211;child are ensured&#46; Diabetes itself is not an obstacle to BF&#44; and the factors associated with failure of same are the same than those for non-diabetic women&#46;<a class="elsevierStyleCrossRef" href="#bib0410"><span class="elsevierStyleSup">26</span></a> Together with the general information on breastfeeding that the mother should receive during the pregnancy&#44; it may be useful to add information regarding breastfeeding in the event of caesarean section and separation of the new-born&#46; Providing the additional support that diabetic mothers may require is associated to a higher rate of successful breastfeeding&#46;<a class="elsevierStyleCrossRef" href="#bib0415"><span class="elsevierStyleSup">27</span></a></p><p id="par0070" class="elsevierStylePara elsevierViewall">The excretion of lactose in urine &#40;lactosuria&#41; is a fact at the end of the pregnancy and the first days of the puerperium&#44; until the child takes a good amount of milk&#44; and also when the production of milk exceeds what the child takes&#46; It may lead to a diagnosis error in diabetic women&#44; because it can be detected as glucose in urine<a class="elsevierStyleCrossRef" href="#bib0420"><span class="elsevierStyleSup">28</span></a> when reagent strips are used&#46;</p><p id="par0075" class="elsevierStylePara elsevierViewall">Insulin needs decrease in relation to those prior to pregnancy&#44;<a class="elsevierStyleCrossRef" href="#bib0425"><span class="elsevierStyleSup">29</span></a> and it is therefore important to pay attention to capillary blood sugar levels monitoring&#44; adjust the insulin dose and make adjustments in the diet&#46; It is practical to advise the mother to have a snack available to eat when she notices symptoms of hypoglycaemia&#44; which are more frequent during breastfeeding and shortly after&#46;</p><p id="par0080" class="elsevierStylePara elsevierViewall">Breastfeeding diabetic mothers must take into consideration the increase in the requirement of nutrients&#44; just like any other breastfeeding women&#46; The distribution of food during the day is important&#44; to anticipate potential hypoglycaemia during the child&#39;s feeding&#44; or shortly after&#44; which also requires adjustments in the insulin dose&#46; The beginning of supplementary feeding and delactation require new adjustments in the diet and insulin&#44; which must be made individually&#46;</p><p id="par0085" class="elsevierStylePara elsevierViewall">Lactogenesis and the let-down reflex may be delayed due to independent factors to the delay in the first contact with the breast and less frequent suction&#46;<a class="elsevierStyleCrossRef" href="#bib0430"><span class="elsevierStyleSup">30</span></a></p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Compatibility of commonly used drugs to treat diabetes with breastfeeding</span><p id="par0090" class="elsevierStylePara elsevierViewall">The American Academy of Paediatrics &#40;AAP&#41; has periodically published guidelines on the compatibility of drugs with BF to help doctors in the decision making&#46; Until 2001&#44; these guidelines consisted of lists of drugs classified according to their potential effects on breastfeeding or the child&#44; and the longest one was the list of drugs usually compatible with BF&#46; In the last edition of 2013&#44;<a class="elsevierStyleCrossRef" href="#bib0435"><span class="elsevierStyleSup">31</span></a> it recommends assessing each case individually&#44; based on the more extensive and permanently updated information&#44; available through LactMed&#44;<a class="elsevierStyleCrossRef" href="#bib0440"><span class="elsevierStyleSup">32</span></a> an Internet database included in TOXNET&#44; of National Library of Medicine of the U&#46;S&#46;A&#46;<ul class="elsevierStyleList" id="lis0005"><li class="elsevierStyleListItem" id="lsti0005"><span class="elsevierStyleLabel">1&#46;</span><p id="par0095" class="elsevierStylePara elsevierViewall">Insulin&#58; a large peptide that does not get to the milk&#44; and even if it did&#44; it would be destroyed in the child&#39;s gastrointestinal tract&#46;<a class="elsevierStyleCrossRef" href="#bib0445"><span class="elsevierStyleSup">33</span></a> It poses no risks for the infant &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia></li><li class="elsevierStyleListItem" id="lsti0010"><span class="elsevierStyleLabel">2&#46;</span><p id="par0100" class="elsevierStylePara elsevierViewall">Antidiabetic medication&#58;<ul class="elsevierStyleList" id="lis0010"><li class="elsevierStyleListItem" id="lsti0015"><span class="elsevierStyleLabel">a&#41;</span><p id="par0105" class="elsevierStylePara elsevierViewall">Sulphonylureas&#58; Tolbutamide is considered safe and the AAP includes it in the list of medications compatible with breastfeeding&#46;<a class="elsevierStyleCrossRef" href="#bib0450"><span class="elsevierStyleSup">34</span></a> Glibenclamide &#40;or glyburide&#41; and glipizide are not significantly transferred to the milk&#44; and there have not been hypoglycaemias in the children studied&#46; Therefore&#44; it is also considered compatible with breastfeeding&#46;<a class="elsevierStyleCrossRef" href="#bib0455"><span class="elsevierStyleSup">35</span></a> There are no data on humans regarding glimepiride&#44; but studies on rodents have demonstrated the significant transfer to milk&#44; and elevated plasma levels in offspring&#46; Therefore&#44; it is better to avoid it&#46; There are no data regarding the remaining drugs&#46;</p></li><li class="elsevierStyleListItem" id="lsti0020"><span class="elsevierStyleLabel">b&#41;</span><p id="par0110" class="elsevierStylePara elsevierViewall">Thiazolidinediones &#40;pioglitazone and rosiglitazone&#41;&#46; There are no data in humans&#46;</p></li><li class="elsevierStyleListItem" id="lsti0025"><span class="elsevierStyleLabel">c&#41;</span><p id="par0115" class="elsevierStylePara elsevierViewall">Metiglinides &#40;repaglinide and nateglinide&#41;&#46; There are no data in humans&#46; Studies in animals show that they can be transferred to the milk and induce hypoglycaemia in the offspring&#46;</p></li><li class="elsevierStyleListItem" id="lsti0030"><span class="elsevierStyleLabel">d&#41;</span><p id="par0120" class="elsevierStylePara elsevierViewall">Biguanides&#58; Metformin is considered safe&#46; It is transferred to the milk in a clinically insignificant amount&#46;<a class="elsevierStyleCrossRef" href="#bib0460"><span class="elsevierStyleSup">36</span></a></p></li><li class="elsevierStyleListItem" id="lsti0035"><span class="elsevierStyleLabel">e&#41;</span><p id="par0125" class="elsevierStylePara elsevierViewall">Peptide analogues similar to glucagon-like-peptide 1&#58; exenatide and liraglutide&#46; There are no studies on humans&#46; However&#44; their pharmacokinetic characteristics make it less likely for them to cause undesirable effects on breastfed children&#46; They are peptides with high molecular weight&#44; and therefore scarce transfer to breast milk can be expected&#46; To achieve their therapeutic effect&#44; they require subcutaneous route&#44;<a class="elsevierStyleCrossRef" href="#bib0465"><span class="elsevierStyleSup">37</span></a> since they are destructed in the digestive tract &#40;also the child&#39;s&#44; assuming there were significant amount in the breast milk&#44; which is highly unlikely&#41;&#46; In mice&#44; the transfer of exenatide to milk is scarce&#44; according to the manufacturer&#39;s data sheet&#46; In addition&#44; liraglutide joins plasma proteins&#44; making it improbable to be transferred to milk in significant amounts&#46;</p></li><li class="elsevierStyleListItem" id="lsti0040"><span class="elsevierStyleLabel">f&#41;</span><p id="par0130" class="elsevierStylePara elsevierViewall">There are no data published for dipeptidyl peptidase inhibitors&#46;</p></li><li class="elsevierStyleListItem" id="lsti0045"><span class="elsevierStyleLabel">g&#41;</span><p id="par0135" class="elsevierStylePara elsevierViewall">Acarbose&#58; only 2&#37; of the dose is absorbed in the mother&#39;s gastrointestinal tube&#44; which makes it improbable for the drug to reach the child through the milk&#46;</p></li><li class="elsevierStyleListItem" id="lsti0050"><span class="elsevierStyleLabel">h&#41;</span><p id="par0140" class="elsevierStylePara elsevierViewall">Miglitol&#58; There are limited data indicating that it is scarcely excreted in milk &#40;according to the manufacturer&#44; 0&#46;02 of a 100<span class="elsevierStyleHsp" style=""></span>mg dose&#41; and it is improbable that it affects the child&#46;</p></li></ul></p></li><li class="elsevierStyleListItem" id="lsti0055"><span class="elsevierStyleLabel">3&#46;</span><p id="par0145" class="elsevierStylePara elsevierViewall">Calcium antagonists&#58; diltiazem&#44; verapamil&#44; nifedipine&#44; nicardipine&#46; Its transfer to milk is insignificant&#46; The AAP includes them in the list of medications compatible with breastfeeding&#46;<a class="elsevierStyleCrossRef" href="#bib0450"><span class="elsevierStyleSup">34</span></a></p></li><li class="elsevierStyleListItem" id="lsti0060"><span class="elsevierStyleLabel">4&#46;</span><p id="par0150" class="elsevierStylePara elsevierViewall">Angiotensin converting enzyme inhibitors&#58; enalapril&#44; captopril&#46; Its transfer to milk is scarce&#44; but given the extreme sensibility of the neonatal kidney&#44; its use in the first month of life is not advisable&#46; The AAP includes them in the list of medications compatible with breastfeeding&#46;</p></li><li class="elsevierStyleListItem" id="lsti0065"><span class="elsevierStyleLabel">5&#46;</span><p id="par0155" class="elsevierStylePara elsevierViewall">Alfametildopa&#58; It is transferred to the milk in insignificant amounts&#46; The AAP includes them in the list of medications compatible with breastfeeding&#46;</p></li><li class="elsevierStyleListItem" id="lsti0070"><span class="elsevierStyleLabel">6&#46;</span><p id="par0160" class="elsevierStylePara elsevierViewall">Beta blockers&#58; propranolol&#44; labetalol and metoprolol are considered compatible with breastfeeding&#46; Acebutolol and atenolol&#44; for which hypotension and bradycardia in infants has been described&#44; are not compatible&#46;</p></li><li class="elsevierStyleListItem" id="lsti0075"><span class="elsevierStyleLabel">7&#46;</span><p id="par0165" class="elsevierStylePara elsevierViewall">Antiplatelets&#58;<ul class="elsevierStyleList" id="lis0015"><li class="elsevierStyleListItem" id="lsti0080"><span class="elsevierStyleLabel">a&#41;</span><p id="par0170" class="elsevierStylePara elsevierViewall">Acetylsalicylic acid is considered as posing some risk in the classification of the AAP&#44; although it must be noted that studies carried out and the effects described in infants have been obtained with high doses of salicylate&#44; and it is unlikely that low doses of antiplatelets cause problems in infants&#46; However&#44; there are no dose&#8211;response studies&#44; and since Reye&#39;s syndrome may appear with low doses of acetylsalicylic acid&#44; its use cannot be recommended for breastfeeding women&#46;</p></li><li class="elsevierStyleListItem" id="lsti0085"><span class="elsevierStyleLabel">b&#41;</span><p id="par0175" class="elsevierStylePara elsevierViewall">Clopidogrel and ticlopidine&#58; these are drugs considered &#8220;not so safe&#8221; during breastfeeding&#46;<a class="elsevierStyleCrossRef" href="#bib0445"><span class="elsevierStyleSup">33</span></a> There are no data on its transfer to milk&#44; and although no adverse events have been described in infants&#44; they are powerful and irreversible platelet aggregation inhibitors&#46; Thus&#44; small quantities in the milk could&#44; in theory&#44; have lasting effects on infants&#46; Therefore&#44; the decision to use one of these drugs&#44; instead of acetylsalicylic acid&#44; must be made with caution and carefully assessing the risk&#47;benefit ratio&#44; until we have more data to help us with the decision-making on the subject&#46;</p></li></ul></p></li><li class="elsevierStyleListItem" id="lsti0090"><span class="elsevierStyleLabel">8&#46;</span><p id="par0180" class="elsevierStylePara elsevierViewall">Hypolipidemic agents&#58;<ul class="elsevierStyleList" id="lis0020"><li class="elsevierStyleListItem" id="lsti0095"><span class="elsevierStyleLabel">a&#41;</span><p id="par0185" class="elsevierStylePara elsevierViewall">Statins&#58; there is no relevant information on the use of these drugs during breastfeeding&#46; There is only some information published on pravastatin&#44;<a class="elsevierStyleCrossRef" href="#bib0470"><span class="elsevierStyleSup">38</span></a> and although the levels in milk are low&#44; the generalised consensus is that due to the possibility of altering the child&#39;s lipid metabolism&#44; statins should not be used during breastfeeding&#46;</p></li></ul></p></li><li class="elsevierStyleListItem" id="lsti0100"><span class="elsevierStyleLabel">9&#46;</span><p id="par0190" class="elsevierStylePara elsevierViewall">Resins &#40;cholestiramine&#44; colestipol&#41;&#46; Since they are not absorbable by the gastrointestinal tube of mother&#44; they do not transfer to the milk and&#44; therefore&#44; they are compatible with breastfeeding&#46; It should be taken into consideration that prolonged use may favour the deficit of fat-soluble vitamins in the mother&#46;</p></li><li class="elsevierStyleListItem" id="lsti0105"><span class="elsevierStyleLabel">10&#46;</span><p id="par0195" class="elsevierStylePara elsevierViewall">Fibrates&#58; there are no data published on its use during breastfeeding&#46;</p></li><li class="elsevierStyleListItem" id="lsti0110"><span class="elsevierStyleLabel">11&#46;</span><p id="par0200" class="elsevierStylePara elsevierViewall">Ezetimibe&#58; there are no data published on its use during breastfeeding&#46;</p></li></ul></p></span></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Thyroid alterations</span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Hyperthyroidism</span><p id="par0205" class="elsevierStylePara elsevierViewall">Treatment with antithyroid drugs&#44; such as propylthiouracil and methimazole&#44; is considered safe during breastfeeding&#46;<a class="elsevierStyleCrossRef" href="#bib0475"><span class="elsevierStyleSup">39</span></a> Both drugs are transferred to milk in small quantities&#46; However&#44; according to the latest data on hepatotoxicity with antithyroid drugs&#44; especially propylthiouracil&#44; it seems better to treat hyperthyroidism during breastfeeding with thioamides with the lowest possible dosage&#46; In any case&#44; as we say&#44; both are compatible with breastfeeding&#44; and there is no justification in withdrawing breastfeeding to begin treatment with antithyroid drugs&#44; or advising against breastfeeding to a mother who already needs them during pregnancy&#46; The risk to which the child would be exposed to with artificial breastfeeding is clearly higher than the risk of the use of these drugs by the mother&#46; The thyroid function and the intellectual development of children remain normal during the treatment of their mothers&#46; Even when the mother gets hypothyroidism caused by these drugs&#44; the thyroid function in the child remains normal&#46;<a class="elsevierStyleCrossRef" href="#bib0480"><span class="elsevierStyleSup">40</span></a> Maternal doses of metimazol &#40;tiamazol&#41; of up to 20<span class="elsevierStyleHsp" style=""></span>mg&#47;day are considered safe both on the short &#40;hormonal levels&#41; and long term &#40;psychomotor development&#41;&#46;<a class="elsevierStyleCrossRefs" href="#bib0475"><span class="elsevierStyleSup">39&#44;40</span></a></p><p id="par0210" class="elsevierStylePara elsevierViewall">With doses above 20<span class="elsevierStyleHsp" style=""></span>mg&#44; taking the drug just after breastfeeding and before the longest sleep period of the child &#40;for instance&#44; after the night feeding&#41; would minimise the exposure of the infant to the drug&#46; With higher doses&#44; in any case&#44; a thyroid hormones determination could be made on the child to continue with breastfeeding&#46;</p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Hypothyroidism</span><p id="par0215" class="elsevierStylePara elsevierViewall">Typical symptoms of hypothyroidism are fatigue&#44; somnolence&#44; feeling cold&#44; constipation&#44; anaemia&#59; in moderate or mild hypothyroidism&#44; they may go unnoticed&#44; because they are non-specific&#46; During the puerperium&#44; it may be confused with postpartum depression&#44; or simply with fatigue attributed to the delivery or care of a new-born&#46; In breastfeeding women&#44; in addition to all of the above&#44; it may cause a <span class="elsevierStyleItalic">decrease in the production of milk</span>&#44; sometimes as the only symptom&#46; Therefore&#44; if there is suspicion of true hypogalactia&#44; it is advisable to rule out the presence of hypothyroidism&#46; This is the extended belief among professionals treating breastfeeding couples&#46; The participation of thyroid hormones in the synthesis of milk is well-known&#46; However&#44; there are few medical publications documenting the effects of the thyroid function on the production of milk&#46;<a class="elsevierStyleCrossRef" href="#bib0485"><span class="elsevierStyleSup">41</span></a></p><p id="par0220" class="elsevierStylePara elsevierViewall">Treatment consists of the administration of thyroxine sodium at replacement doses&#44; which allow the mother to have normal concentrations of thyroid hormones&#46; The thyroid hormone is present in the milk of healthy women in small amounts&#46;<a class="elsevierStyleCrossRef" href="#bib0490"><span class="elsevierStyleSup">42</span></a> Its exogenous administration also allows this transfer to the milk&#44; also in small quantities&#44; so reduced that they would not be enough to treat a child suffering from hypothyroidism&#46; Therefore&#44; treatment with thyroxine at replacement doses is considered safe during breastfeeding&#46;</p><p id="par0225" class="elsevierStylePara elsevierViewall">It is important to remember that women with hypothyroidism frequently require an increase in the regular dose of thyroxine during pregnancy&#44; and a decrease of the dose prior to gestation&#44; after the delivery&#46; It is recommended to go back to the dose prior to the pregnancy after delivery&#44; without waiting for a determination of hormone levels&#44; and afterwards adjust the dose based on successive determinations&#46;</p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Thyroid disease with onset during puerperium</span><p id="par0230" class="elsevierStylePara elsevierViewall">It is treated individually because&#44; frequently&#44; women with previous unknown thyroid disease may develop it during the puerperium&#44; which affects her health and her child&#39;s health&#44; and it is important to take into consideration its diagnosis and treatment&#46;</p></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Postpartum thyroiditis</span><p id="par0235" class="elsevierStylePara elsevierViewall">It is considered as a variant of Hashimoto&#39;s thyroiditis which appears within the first year after delivery&#46; It affects 3&#8211;16&#37; of women<a class="elsevierStyleCrossRef" href="#bib0495"><span class="elsevierStyleSup">43</span></a> and up to 25&#37; of women with type 1 DM&#46;<a class="elsevierStyleCrossRef" href="#bib0500"><span class="elsevierStyleSup">44</span></a> The course is variable&#46; There may be a phase of temporary hyperthyroidism &#40;not always present&#41;&#44; sometimes followed by temporary hypothyroidism or&#44; more rarely&#44; permanent&#46; It may also appear with these phases in women with hypothyroidism due to previous Hashimoto&#39;s thyroiditis&#44; and in treatment with thyroxine&#44; if there is some non-destructive thyroid&#46; Most women do not require treatment&#46; Only women with more prominent symptoms of hyperthyroidism will require symptomatic treatment&#44; only with beta blockers &#40;propranolol&#44; labetalol or metoprolol&#44; all compatible with breastfeeding<a class="elsevierStyleCrossRef" href="#bib0505"><span class="elsevierStyleSup">45</span></a>&#41; and no antithyroid drugs&#46; If there were a postpartum thyroiditis with hypothyroidism during breastfeeding&#44; treatment with levothyroxine is indicated&#46; After 6 months of replacement treatment&#44; withdrawal may be attempted&#44; provided it has been proved that the patient will not be hypothyroid&#46;<a class="elsevierStyleCrossRef" href="#bib0510"><span class="elsevierStyleSup">46</span></a></p></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Graves&#8217; disease with onset during puerperium</span><p id="par0240" class="elsevierStylePara elsevierViewall">Hyperthyroidism is usually more symptomatic than postpartum thyroiditis&#44; with higher hormonal concentrations&#44; more enlargement of the thyroid gland&#44; and it may be accompanied by Graves&#8217; ophthalmopathy&#44; absent in thyroiditis&#46; A thyroid scintigram is not necessary in the differential diagnosis between both entities&#44; which would also require temporary suspension of BF &#40;<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>&#41;&#46; The differential diagnosis can be made based on clinical and hormone data&#46; In some cases&#44; it may not be easy initially&#44; but reassessing the patient in 3 or 4 weeks we can have sufficient data to differentiate them&#46; Hyperthyroidism of thyroiditis is usually improved&#44; while Graves&#8217; disease would have worsened or have no changes&#46; The levels for thyroid-stimulating antibodies are increased in Graves&#8217; disease&#44; but not in thyroiditis&#46;</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia></span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">Use of radioisotopes during breastfeeding<a class="elsevierStyleCrossRef" href="#bib0515"><span class="elsevierStyleSup">47</span></a></span><p id="par0245" class="elsevierStylePara elsevierViewall">The use of radioisotopes in breastfeeding women &#40;<a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a>&#41; may require a temporary or definitive cessation of breastfeeding&#44; depending on the dose and the isotope used&#44; to avoid exposing the child to radioactivity through the milk&#46; If there are diagnostic or therapeutic alternatives to the use of radioisotopes&#44; it would be preferable to use them&#44; or&#44; if possible&#44; delay the use the radioisotope &#40;for instance&#44; waiting until the end of breastfeeding for a definitive treatment of hyperthyroidism with I-131&#44; and meanwhile&#44; treating with antithyroid medication&#44; if necessary&#41;&#46; If it were really necessary&#44; a detailed list of times where it is recommended not to breastfeed is provided in <a class="elsevierStyleCrossRef" href="#tbl0020">Table 4</a>&#46; During these periods&#44; the mother can extract the milk and discard it&#44; to maintain proper production of milk&#44; or save it and give it to the child later&#44; after 10 half lives of the radioisotope have passed&#46; If possible&#44; extracting the milk beforehand would allow disposing of milk to feed the child during the period while direct breastfeeding is not recommended&#46;</p><elsevierMultimedia ident="tbl0015"></elsevierMultimedia><elsevierMultimedia ident="tbl0020"></elsevierMultimedia><p id="par0250" class="elsevierStylePara elsevierViewall">After the use of usual clinical doses&#44; it is not necessary for the mother to avoid close physical contact with her child&#46;</p></span><span id="sec0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0060">Iodine deficit</span><p id="par0255" class="elsevierStylePara elsevierViewall">The needs of the child exclusively fed with breast milk must be provided by his mother&#39;s milk&#46; With a milk intake of 150&#8211;200<span class="elsevierStyleHsp" style=""></span>ml per kilo of weight a day&#44; the concentration of iodine in milk shall be at least 100<span class="elsevierStyleHsp" style=""></span>&#956;g&#47;l to provide the 90<span class="elsevierStyleHsp" style=""></span>&#956;&#47;kg&#47;day of the iodine that the child needs&#46; The concentration of iodine in breast milk mainly depends on the mothers&#8217; iodine intake&#44; although the mammary gland has the capacity to make an active excretion and increase its concentration trying to ensure proper contribution&#44; even when there is an iodine deficiency&#46;</p><p id="par0260" class="elsevierStylePara elsevierViewall">To obtain an iodine concentration in breast milk above 100<span class="elsevierStyleHsp" style=""></span>&#956;g&#47;l&#44; the iodine estimated need for breastfeeding women is at least of 250<span class="elsevierStyleHsp" style=""></span>&#956;g&#47;day&#46;<a class="elsevierStyleCrossRef" href="#bib0520"><span class="elsevierStyleSup">48</span></a> In areas with iodine deficiency&#44; these special needs are not guaranteed with iodine-rich food&#44; such as iodised salt&#44; and it is recommended that the breastfeeding woman receives an additional supplement with at least 200<span class="elsevierStyleHsp" style=""></span>&#956;g of iodine a day in the form of potassium iodide with a pharmacological formulation&#46;<a class="elsevierStyleCrossRef" href="#bib0525"><span class="elsevierStyleSup">49</span></a></p></span></span><span id="sec0065" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Prolactin deficit</span><p id="par0265" class="elsevierStylePara elsevierViewall">Prolactin is essential for lactogenesis&#44; and its deficiency leads to postpartum agalactia&#46; It is usually presented in association with other pituitary deficiencies&#46; The most frequent causes are the destruction of the pituitary gland due to trauma&#44; inflammation&#44; tumours&#44; surgery&#44; radiation or infarction&#46; The diagnosis is usually known before a potential pregnancy&#44; which is usually not possible spontaneously&#46; Only in the event of isolated prolactin deficiency&#44; or onset of the deficiency during pregnancy&#44; delivery or puerperium&#44; a diagnosis would have to be made after the insufficient milk production appears&#46; This scenario is typical for Sheehan&#39;s syndrome&#44; and it is possible in lymphocytic hypophysitis &#40;which does not always lead to prolactin deficiency&#41;&#46;</p><span id="sec0070" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Sheehan&#39;s syndrome</span><p id="par0270" class="elsevierStylePara elsevierViewall">This is the name given to an infarction of the pituitary gland due to a severe loss of blood during or after delivery&#46;<a class="elsevierStyleCrossRef" href="#bib0530"><span class="elsevierStyleSup">50</span></a> Despite the higher obstetric control in our area&#44; these cases still continue to exist&#46; It may be recognised in the first days after delivery due to symptoms as lethargy&#44; anorexia&#44; weight loss and agalactia&#46; Later&#44; there is a lack of menstruation and loss of body hair&#46; There are less severe forms that cannot be recognised until several years later&#46; Cases have been described which keep some of the hormones produced by the pituitary gland&#46; But the prolactin deficit is constant&#44; which leads to failure in the production of milk&#46;</p></span><span id="sec0075" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Lymphocytic hypophysitis</span><p id="par0275" class="elsevierStylePara elsevierViewall">It is a rare disease characterised by lymphocyte infiltration of the pituitary gland&#44; followed by destruction of pituitary cells&#46; A large proportion of cases occur at the end of the pregnancy or during the puerperium&#46;<a class="elsevierStyleCrossRef" href="#bib0535"><span class="elsevierStyleSup">51</span></a> The symptoms are headache and pituitary function deficit&#59; the hormones which are most frequently at deficit are the <span class="elsevierStyleItalic">adrenocorticotropic hormone</span> &#40;ACTH&#41; and the thyroid-stimulating hormone&#46; Sometimes there is hyperprolactinaemia&#44; but other times there is prolactin deficiency&#46;<a class="elsevierStyleCrossRef" href="#bib0540"><span class="elsevierStyleSup">52</span></a></p></span><span id="sec0080" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Isolated prolactin deficiency</span><p id="par0280" class="elsevierStylePara elsevierViewall">Isolated prolactin deficiency<a class="elsevierStyleCrossRef" href="#bib0545"><span class="elsevierStyleSup">53</span></a> is a rare entity with first clinical manifestation in the puerperium&#44; and it is agalactia&#46; Some of the cases described are associated with mutations of the genes <span class="elsevierStyleItalic">Pit-1</span> and <span class="elsevierStyleItalic">Prop</span>-<span class="elsevierStyleItalic">1</span>&#46;<a class="elsevierStyleCrossRefs" href="#bib0550"><span class="elsevierStyleSup">54&#44;55</span></a> Sometimes it is associated with ACTH deficiency&#46;</p><p id="par0285" class="elsevierStylePara elsevierViewall">When there is prolactin or oxytocin deficiency&#44; BF is not possible&#46; Synthetic prolactin was obtained for the first time in 1990&#46; Its exogenous administration restores BF in women with prolactin deficiency&#46;<a class="elsevierStyleCrossRef" href="#bib0560"><span class="elsevierStyleSup">56</span></a> There are synthetic hormones available in the market to replace each one of the hormonal deficits&#44; except prolactin&#44; which&#44; despite having been isolated and synthesised&#44; is not available for clinical use&#46;</p></span></span><span id="sec0085" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Funding</span><p id="par0290" class="elsevierStylePara elsevierViewall">The authors declare that they received no funding to carry out this work&#46;</p></span><span id="sec0090" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Conflict of interest</span><p id="par0295" class="elsevierStylePara elsevierViewall">The authors declare that there are no conflicts of interest&#46;</p></span></span>"
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        0 => array:2 [
          "identificador" => "sec0005"
          "titulo" => "Prolactinoma"
        ]
        1 => array:3 [
          "identificador" => "sec0010"
          "titulo" => "Diabetes mellitus"
          "secciones" => array:2 [
            0 => array:2 [
              "identificador" => "sec0015"
              "titulo" => "Considerations for the treatment of diabetes during breastfeeding"
            ]
            1 => array:2 [
              "identificador" => "sec0020"
              "titulo" => "Compatibility of commonly used drugs to treat diabetes with breastfeeding"
            ]
          ]
        ]
        2 => array:3 [
          "identificador" => "sec0025"
          "titulo" => "Thyroid alterations"
          "secciones" => array:7 [
            0 => array:2 [
              "identificador" => "sec0030"
              "titulo" => "Hyperthyroidism"
            ]
            1 => array:2 [
              "identificador" => "sec0035"
              "titulo" => "Hypothyroidism"
            ]
            2 => array:2 [
              "identificador" => "sec0040"
              "titulo" => "Thyroid disease with onset during puerperium"
            ]
            3 => array:2 [
              "identificador" => "sec0045"
              "titulo" => "Postpartum thyroiditis"
            ]
            4 => array:2 [
              "identificador" => "sec0050"
              "titulo" => "Graves&#8217; disease with onset during puerperium"
            ]
            5 => array:2 [
              "identificador" => "sec0055"
              "titulo" => "Use of radioisotopes during breastfeeding"
            ]
            6 => array:2 [
              "identificador" => "sec0060"
              "titulo" => "Iodine deficit"
            ]
          ]
        ]
        3 => array:3 [
          "identificador" => "sec0065"
          "titulo" => "Prolactin deficit"
          "secciones" => array:3 [
            0 => array:2 [
              "identificador" => "sec0070"
              "titulo" => "Sheehan&#39;s syndrome"
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            1 => array:2 [
              "identificador" => "sec0075"
              "titulo" => "Lymphocytic hypophysitis"
            ]
            2 => array:2 [
              "identificador" => "sec0080"
              "titulo" => "Isolated prolactin deficiency"
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          ]
        ]
        4 => array:2 [
          "identificador" => "sec0085"
          "titulo" => "Funding"
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        5 => array:2 [
          "identificador" => "sec0090"
          "titulo" => "Conflict of interest"
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        6 => array:1 [
          "titulo" => "References"
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    "fechaRecibido" => "2014-02-20"
    "fechaAceptado" => "2014-04-24"
    "NotaPie" => array:1 [
      0 => array:2 [
        "etiqueta" => "&#9734;"
        "nota" => "<p class="elsevierStyleNotepara" id="npar0010">Please cite this article as&#58; Serrano Aguayo P&#44; Garc&#237;a de Quir&#243;s Mu&#241;oz JM&#44; Bret&#243;n Lesmes I&#44; C&#243;zar Le&#243;n MV&#46; Tratamiento de enfermedades endocrinol&#243;gicas durante la lactancia&#46; Med Clin &#40;Barc&#41;&#46; 2015&#59;144&#58;73&#8211;79&#46;</p>"
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          "leyenda" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">DPP-4&#44; dipeptidyl peptidase 4&#59; GLP-1&#44; <span class="elsevierStyleItalic">glucagon-like peptide-1</span>&#59; ACE inhibitor&#44; angiotensin-converting enzyme inhibitor&#46;</p>"
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                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><tbody title="tbody"><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleItalic">Insulin</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Compatible&#46; It is destructed in the gastrointestinal tube of the infant&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="2" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="2" align="left" valign="top"><span class="elsevierStyleItalic">Sulphonylureas</span></td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Tolbutamide&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Compatible with breastfeeding&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Glibenclamide glyburide</span> and <span class="elsevierStyleItalic">glipizide</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Compatible with breastfeeding&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Glimepiride&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">There are no data in humans&#44; it is significantly transferred to milk in rodents&#46; It is best to avoid it&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Other sulfonylurea&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">There are no data&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="2" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleItalic">Thiazolidinediones</span> &#40;pioglitazone <span class="elsevierStyleItalic">and</span> rosiglitazone&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">There are no data in humans&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleItalic">Meglitinides</span> &#40;repaglinide <span class="elsevierStyleItalic">and</span> nateglinide&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">There are no data in humans&#46; It is significantly transferred to milk in rodents&#46; It is best to avoid it&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleItalic">Biguanides&#58;</span> metformin&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Compatible with breastfeeding&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleItalic">Alpha-glucosidase inhibitors</span> &#40;miglitol <span class="elsevierStyleItalic">and</span> acarbose&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Compatible with breastfeeding&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleItalic">DPP-4 inhibitors</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">There are no data&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleItalic">GLP-1 analogues</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">There are no data&#44; but they have elevated molecular weight and join proteins with binding affinity&#46; There is no oral bioavailability for the infant&#46; The effects on the infant are unlikely&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleItalic">Calcium antagonists&#58; nifedipine&#44; diltiazem&#44; verapamil&#46;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Compatible with breastfeeding&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleItalic">ACE inhibitors&#58; captopril&#44; enalapril</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Compatible with breastfeeding&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleItalic">Alfametildopa</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Safe&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleItalic">Propranolol&#44; labetalol&#44; metoprolol</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Compatible with breastfeeding&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleItalic">Atenolol</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Not safe&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleItalic">Clopidogrel and ticlopidine</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Not safe&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleItalic">Acetylsalicylic acid</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Compatible with breastfeeding in small doses &#40;antithrombotic&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleItalic">Statins</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">There are no data&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleItalic">Resins</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Compatible with breastfeeding&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleItalic">Fibrates</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">There are no data&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleItalic">Ezetimibe</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">There are no data&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
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          "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Compatibility of the most used drugs for diabetes mellitus with breastfeeding&#46;</p>"
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        "etiqueta" => "Table 2"
        "tipo" => "MULTIMEDIATABLA"
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        "tabla" => array:2 [
          "leyenda" => "<p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">TRAb&#44; thyroid releasing antibody&#46;</p>"
          "tablatextoimagen" => array:1 [
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                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Graves-Basedow&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Postpartum thyroiditis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">Clinical symptoms of evident &#40;florid&#41; hyperthyroidism&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Usually not very symptomatic&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">More elevated hormonal levels&nbsp;\t\t\t\t\t\t\n
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