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Seven breastfeeding mothers received lidocaine for local analgesia prior to a dental procedure. Effect of metformin on miscarriage in pregnant patients with polycystic ovary syndrome. In another group, which took cefuroxim while breastfeeding, mild side-effects were reported in just under 3% of the cases, which was no more frequently reported than in a control group with cefalexin. The low molecular weight (about 152 for the free base), moderate plasma protein binding, and long plasma half-life suggest that the drug will cross to the embryo­fetus. Surprisingly, the German Commission E (Blumenthal 1998) and the American Herbal Products Association (McGaffin 1997) contraindicate the use of ginger during pregnancy. The former are generally effective but carry the risk of uterine overstimulation and fetal asphyxia in cases of labor induction or augmentation. When a combination therapy with more than one antiepileptic is required, it must be individually decided whether the baby should be supplemented or even weaned to reduce the exposure. Azelaic acid the antibacterial, antiphlogistic and keratolytic azelaic acid is used in acne therapy. In a review evaluating 17 publications on the occurrence of pregnancies during isotretinoin therapy in Europe, Crijns (2011) reported a frequency of 0. Other possible effects are growth restriction, hepatosplenomegaly and thrombocytopenia (Dontigny 2008). Placebocontrolled trial of atenolol in treatment of pregnancy-associated hypertension. The milk:maternal serum ratios (range) for the parent drug and active metabolite were 0. Sequential use of thrombolytic agents for thrombosed mitral valve prosthesis during pregnancy. The animal data suggest high risk, but the very limited human pregnancy experience prevents an assessment of the embryo­fetal risk. There is no experience in pregnancy with gusperimus, a guanidine derivate, and with mizoribine, both used in the treatment of renal graft rejection. Cases (cardiovascular defects without known chromosome anomalies) were drawn from three Swedish health registers (N = 5015). In a surveillance study of Michigan Medicaid recipients involving 229,101 completed pregnancies conducted between 1985 and 1992, 467 newborns had been exposed to amitriptyline during the 1st trimester (F. The risk of adverse reproductive and developmental disorders due to occupational pesticide exposure: an overview of current epidemiological evidence. Only one structural anomaly, consisting of an absent septum pellucidum, was observed in the infants examined. In general, therapeutic doses should be adhered to , and herbal teas should not be used excessively. The disease-modifying drugs are intended to minimize the severity and frequency of the relapses as well as the extent of the disability progression. Successful pregnancy in a living-related kidney transplant recipient who received sirolimus throughout the whole gestation. After accidental treatment during the pregnancy, etanercept should be replaced, if at all possible. Christopher 2006, Garcia-Donaire 2005, Jain 2004), including a small prospective study with 49 children of 37 mothers with liver transplants (Jain 2003), and on the National Transplantation Registry established in 1991 by the drug manufacturers (Armenti 2005). High vitamin A intake in early pregnancy and major malformations: a multicenter prospective controlled study. The results of two large prospective studies in the smelter town Port Pirie (Australia) and in Boston showed no significant association between prenatal lead exposure and child intelligence during the preschool period (Bellinger 1991, McMichael 1988). A recent study from Taiwan investigated 68 healthy urban mothers, and mothers married to fishermen, in relation to fish intake (Chien 2006a). Following maternal combination therapy for glaucoma with timolol, dipivefrin and dorzolamide, as well as sporadic systemic administration of acetazolamide, no adverse effects were reported in a closely monitored baby (Johnson 2001). Thyroid function studies were not reported, but the neonatal examinations were normal (5).

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Successful pregnancy with isolated herpes simplex virus encephalitis: case report and review of the literature. An increased risk of major malformations was also reported in a cohort of Danish laboratory technicians with exposure to organic solvents (Zhu 2006). Regierer 2006, Mubarak 2002) and some with additional indications, have shown no teratogenic or fetotoxic effects with mostly continuous therapy. Systemic use of tacrolimus during pregnancy is acceptable in wellgrounded cases (Section 2. Systemic toxicity of local anesthetic agents correlates well with their anesthetic potency. Due to the risk of a fatal lactic acidosis, combination treatment with didanosine and stavudine should only be used in cases where no alternatives are available (Bristol-Myers Squibb 2001). More studies are needed before the true incidence of heparin-induced osteoporosis in pregnant women can be determined. The older antihistamines with sedating action have become less important and should be reserved during breastfeeding for special conditions. Because of the risk of embryo and fetal harm, the drug is classified as contraindicated in pregnancy. The risk for all kinds of cancers together were within the usual range, however, there was an increased risk for adenocarcinoma of the vagina and cervix at advanced ages, while melanomas occurred more frequently at younger ages (Verloop 2010). Vitamin C supplementation is not necessary during pregnancy, if the diet is balanced. The mother was hospitalized for preterm labor and appeared to be infected with the Dengue virus during pregnancy. Several publications report a transfer of lamivudine to human milk in biologically significant quantities. Short-term treatment with doxylamine or hydroxyzine is also acceptable during breastfeeding. The findings relating maternal preconceptual monitoring to increased risk of fetal death remain equivocal, and require ongoing investigation (Doyle 2000). Recommendations for counseling breastfeeding mothers who are taking an antipsychotic drug were listed in a 2013 reference (11). The more common daily intake of 2 mg of cyproterone acetate for acne therapy has not yet been studied. A meta-analysis of the side effects of antihypertensive drugs in lighter forms of hypertension found that the subgroup using -receptor blockers only displayed a trend towards a lower birth weight (see Magee 2011). A study of 101 pregnant women who were vaccinated, four in the first, and 89 in the third trimester, did not reveal developmental anomalies in the offspring up to ages 3­4 (Nasidi 1993). With sulbactam, the relative daily dose transmitted was a maximum of 1% (Foulds 1985). Among the synthetic polyaromatic, receptor-selective retinoids are adapalene, which is used for severe acne vulgaris and tazarotine for the treatment of psoriasis. There are no data on the breastfeeding period for dirithromycin, josamycin, midecamycin, spiramycin, troleandomycin, and the ketolide telithromycin. One healthy child was reported (Ojeda-Uribe 2013, Pham 2009) with the last abatacept infusion at 2. If amiodarone was applied, the development of a prenatal struma needs to be excluded by a sonogram, and the fetus and neonate should be checked for possible hypothyroidism. It has also been associated during pregnancy and lactation with reports of fetal and neonatal androgenization (Awang 1991). Further, women are obtaining elevated levels of lead from ayurvedic medicines produced in non-health-inspected sites and some cosmetics. In a human case series with 70 pregnancies, carried to term after termination attempts with mifepristone, various malformations, among them four children with club foot (Sitruk-Ware1998) were observed. When the rats were treated from before mating through gestation, doses as small as 0. Spontaneous abortion and the prophylactic effect of folic acid supplementation in epileptic women undergoing antiepileptic therapy. In addition, it has been repeatedly reported that individual psychological and technical support of the mother is as successful as prolactin-activating medication in resolving breastfeeding problems, or even with relactation (see, for example, Seema 1997).

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It is indicated as adjunctive treatment of chronic simple (open-angle) glaucoma, secondary glaucoma, and preoperatively in acute angle-closure glaucoma where delay of surgery is desired in order to lower intraocular pressure. Prophylactic use of danaparoid in high-risk pregnancy with heparin-induced thrombocytopaenia-positive skin reaction. In 1997, the results were published of a small case-control study of 31 women who received electrical shocks during pregnancy, matched with control subjects (Einarson 1997). However, clinicians are less likely to contact a Registry to report a normal pregnancy outcome than an abnormal one. The carbonic anhydrase inhibitor, acetazolamide, which is related to thiazide, is prescribed p. Re: "Congenital defects and electric bed heating in New York State: a register-based case-control study" (Letter; comment). Fallotsche Tetralogie nach Cumarineinnahme in der Frьhschwangerschaft ­ eine Embryopathie? However, if adefovir is used during nursing for the treatment of the maternal infection, there is a potential risk of serious toxicity for the nursing infant, such as the nephrotoxicity seen in adults. In a different subset of over 28,000 children examined 2 years later, also at 7 years of age, and with more control for possible confounders, the association between behavioral problems and cell phone use was confirmed. Sensory changes in the milk can lead to feeding problems (Sachs 2013, American Academy of Pediatrics 2012). Is antiretroviral therapy during pregnancy associated with an increased risk of preterm delivery, low birth weight, or stillbirth? Pharmacokinetics Alcohol is rapidly absorbed through mucosa of the mouth, stomach and upper duodenum where absorption is greatest (70­80%). Red clover (Trifolium pretense) is also used, but often contains coumadin, which can cause bleeding. The dermal administration of tacrolimus is not problematic because little is absorbed and only low serum concentrations are achieved. Safety of post-exposure rabies prophylaxis during pregnancy: a follow-up study from Guangzhou, China. A 1985 study found a possible association between the use of aspirin in early pregnancy and congenital heart disease (73). A single dose of tiaprofen 300 mg was given to three mothers in one study published only as an abstract. An endodermal sinus tumor diagnosed in pregnancy: case report and review of the literature. Over the course of the pregnancy, the hemoglobin level drops by 20 g/L, primarily because of the increase in blood volume. Vasoactive drugs in obstetrics: a review of data obtained by Doppler and color Doppler methods. This way of calculating can make sense in the case of a single dose with active ingredients that have a short half-life. A milk/ plasma ratio of 1 assumes that the levels are the same in both plasma and milk. Maternal ingestion of acetylsalicylic acid inhibits fetal and neonatal prostacyclin and thromboxane in humans. There is no evidence that maintenance therapy with intravenous or oral tocolytic drugs, given after a period of acute preterm contractions, will prolong gestational age (Roos 2013, Dodd 2012). Armodafinil is a lipophilic agent that is extensively metabolized to apparently inactive metabolites. Transport of methylmercury and inorganic mercury to the fetus and breast-fed infant. To summarize, the state of the data on the risk of birth defects and spontaneous abortion through occupational exposure to anesthetic gases is reassuring, while the effects on other developmental disorders need further studies. The influence of chlorpyrifos was independent of the contribution of neighbourhood characteristics to adverse neurobehavioral development (Lovasi 2011). Women, who needed insulin in addition to metformin for blood glucose control, were described separately. There is insufficient data on the breastfeeding period for the glycylcycline, tigecycline. Among 158 women who had also taken clomiphene after conception, there were malformations in eight children (5. Significant differences were noted in the increased rate of premature births when compared to the controls.

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Possible West Nile virus transmission to an infant through breast-feeding ­ Michigan, 2002. The opiate analgesics with no information on drug transfer into milk should not be used while breastfeeding. The most common total dose was 800 g, with a range from 200 to 16,000 g (four tablets daily for 20 days). However, because of the very limited human pregnancy experience with atypical antipsychotics, the American College of Obstetricians and Gynecologists does not recommend the routine use of these agents in pregnancy, but a risk benefit assessment may indicate that such use is appropriate (1). There are no data on the milk transfer of flupirtin, meptazinol, tilidine, tapentadol and ziconotide. Microcephaly (especially with phenytoin and with antiepileptic combination therapy). There are insufficient data to evaluate cilazapril, fosinopril, lisinopril, moexipril, perindopril, ramipril, spirapril, trandolapril and zofenopril. Azathioprine use during pregnancy: unexpected intrauterine exposure to metabolites. The results of this study have to be viewed with some reservation, one reason being the small numbers of cases. With 13 babies who took part in a comparative study with nortriptyline, no sertraline was found in the serum (detection limit 2 g/L) but in some children, desmethylsertraline was detected, with a maximum of 6 g/L (Lanza di Scalea 2009, Wisner 2006). However, no data on dose or length of treatment were reported, and no conclusions about causal association can be made on the basis of these results (Ito 1993). Radiation safety in the treatment of patients with thyroid diseases by radioiodine 131I: practice recommendations of the American Thyroid Association. National Institute of Child Health and Human Development Neonatal Research Network: Adverse neonatal outcomes associated with antenatal dexamethasone versus antenatal betamethasone. Single doses of 100­200 mg/kg, representing abuse ingestions of aspartame, resulted in peak phenylalanine plasma levels ranging from 20 to 49 micro-mol/dL (2,25). Newer case reports and a retrospective analysis of 379 pregnancies with pre-existing diabetes, did not observe any increased risk of congenital malformations: 93/379 were treated continuously with glibenclamide or metformin. The studies to date on general toxicity and on mutagenic and carcinogenic potential do not permit a conclusive judgment (Liebl 2000, Rimkus 1994). Sodium perchlorate also blocks the transport to the breast, where iodine accumulates (Janssen 2001). In another study, vecuronium was recommended, as it seems to have less side effects on fetal cardiac function than pancuronium (Watson 1996). Increased risk of miscarriage following overdose periconceptually or in early pregnancy, and of preterm birth, low birth Drugs During Pregnancy and Lactation. They also point to the group of intrauterine-exposed Hiroshima victims comprising not even 1,000 survivors, and to the data of the experience of exposed children in Hiroshima. Klinger (2001) examined 21 children ophthalmologically, and Cimaz (2004) examined six children by funduscopy and electroretinogram. In contrast, a study by Smith (2011) found no difference in cognitive abilities between infants of mothers who abused amphetamines during pregnancy compared to a control group; although a slight effect on fine motor performance was observed at 1 year of age, this was no longer present at 3 years of age. Low-dose aspirin exerts its beneficial effects in these disorders by irreversible inactivation of platelet cyclooxygenase, resulting in a greater inhibition of thromboxane A 2 synthesis than that of prostacyclin production. Alprazolam, chlordiazepoxide, diazepam and oxazepam were the primary substances recorded. Details regarding the pregnancy outcomes of the remaining two women who were bitten earlier in pregnancy, at 16 and 22 weeks, were not provided (Handel 1994, Russell 1979). The use of acetazolamide in idiopathic intracranial hypertension during pregnancy. In one woman who had applied minoxidil topically to her scalp at least twice a day, brain, heart and vascular malformations were diagnosed in her fetus. It should be applied extremely carefully, and only in combination with monitoring of uterine activity and fetal heart rate. Argatroban and dabigatran etexilate are univalent direct thrombin inhibitors that bind only to the active site of thrombin (Di Nisio 2005). Another case of exposure to epoprostenol from the twenty-third week of gestation showed a course without postpartum complications.

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In a case series of over 100 pregnant women who had angiography with fluorescein, no indication of undesirable fetal effects was seen (Halperin 1990). Similar associations of parental prenatal smoking suggest child blood pressure is not influenced by intrauterine effects. The therapy for acromegaly is an exception for which there is currently no general recommendation. Serum sertraline and N-desmethylsertraline levels in breast-feeding mother­baby pairs. Sources of calcium and magnesium; helps to relieve anxiety, restlessness, insomnia, and irritable skin. Lighter prematures displayed less emotional control and motor activity as well as greater shyness at 2 years of age (corrected age) (Pesonen 2009). No toxic effect on the infant has been demonstrated as yet, plus due to its limited oral bioavailability, is this to be expected. In these patients prolonged neuromuscular blockade requiring respiratory assistance may occur after administration of succinylcholine (Cherala 1989). A 200 g dose of misoprostol has been associated with increased uterine artery resistance indices by Doppler ultrasound, suggesting that perfusion reduction could underlie the disruption-type malformations (Yip 2000). A reproductive study in rats examined the effect of oral albendazole (0, 10, or 20 mg/kg/day) administered on gestational days 9­11. In each of these cases, the mother was also treated with other chemotherapeutic agents. Those that are used therapeutically include the non-fluorinated prednisone, prednisolone, and methylprednisolone, as well as deflazacort, hydrocortisone and prednyliden; and the fluoridated substances amcinonide, beclomethasone, betamethasone, budesonide, cloprednol, dexamethasone, flunisolide, flumetasone, fluocortolone, fluticasone, mometasone, and triamcinolone. Long-term safety of biologics in the treatment of moderate-to-severe plaque psoriasis: review of current data. Anesthesia with isoflurane for a caesarean delivery is well-tolerated by the fetus. Oxytocin should be applied with extreme caution for induction or augmentation of labor, and only in combination with careful monitoring of maternal uterine contractions and the fetal heart rate. The risk for coumarin embryopathy is small, particularly when therapy is discontinued prior to 6 weeks postconception or smaller doses. Methimazole pharmacology in man: studies using a newly developed radioimmunoassay for methimazole. A specific teratogenic effect cannot be clearly deduced from this publication and from other case descriptions which mostly comprise healthy newborns (Pons 1991, Lim 1990). A 1997 report described an open, retrospective survey on the use of antihypertensives in 398 consecutive pregnant women who attended an antenatal hypertension clinic from 1980 to 1995 (27). Statistical methods for estimating the probability of spontaneous abortion in observational studies. A 1987 retrospective report described the use of amantadine, starting before conception in four women, one of whom had a probable molar pregnancy (4). However, lamivudine and zidovudine are medications that are preferred in pregnancy because of extensive experience. However, direct contact of the breastfed baby with the area of the treated skin should be avoided. Autopsy of the 2190-g female fetus revealed a liver acetaminophen concentration of 250 mcg/g of tissue. Pivmecillinam and adverse birth and neonatal outcomes: a population-based cohort study. The male infant, delivered by cesarean section 20 hours later, died at 14 days of age secondary to intracranial hemorrhage, a complication thought to be caused by prematurity and unrelated to the thrombolytic therapy. Duration of effect > 36 hours Cushing threshold dose: 20 mg/day Cushing threshold dose: 0­40 mg/daily. Trazodone Trazodone has prominent sedative effects and is often prescribed in low doses as a hypnotic agent. Transfer of 131I into human breast milk and transfer coefficients for radiological dose assessments. Guidelines regarding antidote use, and hence availability may differ across units, and it is therefore advisable to obtain advice from a national or regional specialist poisons service as soon as possible. The effect of ampicillin administration on urinary estriol and serum estradiol in the normal pregnant patient.

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Concentration and kinetic studies of intravenous acyclovir in serum and breast milk of a patient with eczema herpeticum. X-ray studies of the skull and wrists revealed normal bone structure and density without abnormal calcifications. A further case report describes an infant breastfed for 18 weeks, who developed completely unremarkably up to age 5. An apparently normal infant was born to a woman who had been treated with capecitabine and oxaliplatin during the first trimester of 2. The rapid dispersal of the newer inhalation anesthetics (sevoflurane, desflurane) leads to a more rapid normalization of the uterine tone after the operation is finished (Yoo 2006). The short-acting benzodiazepines (half-life 6­24 hours) are available as sedatives and hypnotics. The estimated amount of acyclovir ingested by the infant consuming 1000 mL/day of milk was about 1 mg (67). All three children were delivered prematurely, and two of them had neonatal anemia. Using insurance data, a Taiwanese study identified 2,497 women who used zolpidem during pregnancy and compared them with a control group. The synthetic antifibrinolytics, tranexamic acid and p-aminomethyl-benzoic acid, are used therapeutically for treatment of coagulopathies with increased 2. Off-label use of misoprostol for this indication may be the first choice in a low resource setting, but there remains a need for large randomized trials to further elucidate the relative effectiveness and risks of various dosages (Hofmeyr 2013). Thyroid hormones should not be given together with thyrostatics, because higher dosages of thyrostatics would then be necessary. The induction of lung maturation with a threatening premature birth is currently carried out with a one-time betamethasone cycle between the twenty-fourth (achievement of viability) and the thirty-fourth week of pregnancy. Pregnancy outcome after gestational exposure to erythromycin ­ a population-based register study from Norway. All three cases were associated with anaphylaxis and two resulted in premature deliveries, suspected by one author as being be due to a "post anaphylactic reaction. No abnormal feeding habits or behavior changes were noted on later evaluation, presumably after the effects of the narcotic had dissipated. When pyrimethamine is given in early pregnancy, it should be supplemented with folic acid, see also Chapter 2. Another case described an infant who developed diarrhea following repeated rectal administration of mesalazine to his mother. She delivered a normal infant (details not provided) that had normal growth and development at 6 months of age. Single parenteral administration of methylergometrine in the delivery room is apparently unproblematic for the breastfed infant, and may be used if it is really indicated. A number of studies and reviews indicate the complexity of evaluations of the effects of 2. Transfer of ampicillin into fetus and amniotic fluid from maternal plasma in late pregnancy. Treatment should be the same as for the nonpregnant patient, and may involve administration of an antidote such as atropine or pralidoxime. The single case of gross overdose is suggestive of an association between amitriptyline, perphenazine, or both, and malformations, but without confirming evidence no conclusions can be determined. With external and systemic administration of acyclovir or valacyclovir, breastfeeding is permitted. A healthy 2670-g female infant was delivered, but the gestational age was not specified. No evidence of impaired fertility or fetal harm was observed in either species at doses up to 100 times the human dose (assumed to be based on weight). Nitrous oxide is an ideal inhalation anesthetic for small surgical procedures during pregnancy. The clinical significance of the drug level in milk to the nursing infant at either time is unknown but is probably nil. Histologic abnormalities of placental tissues in Fabry disease: a case report and review of the literature.


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The glucuronidation capacity of the liver is limited at birth and increases gradually by 2­6 months of age. Carbamazepine, phenobarbital, primidone, phenytoin, felbamate, oxcarbazepine and topiramate are inducers of the hepatic cytochrome P450­3A4 enzyme system. Pregnancy outcome after gestational exposure to the new macrolides: a prospective multi-center observational study. When there has been significant exposure, this is not an indication for termination of pregnancy, and additional prenatal diagnostic tests are not required. However, the frequency of facial dysmorphism was significantly higher in the group exposed to carbamazepine as compared to their non-exposed siblings (60 versus 25%). Microcephaly and mental retardation is observed, above all, after doses >200 mGy between gestational weeks 10 and 17. Coordinators of World Association of Perinatal Medicine Prematurity Working Group: Guideline for the use of antenatal corticosteroids for fetal maturation. Adverse effects of isotretinoin: A retrospective review of 1,743 patients started on isotretinoin. In contrast with propranolol and sotalol, atenolol exposure during gestation did not increase the motor activity or cause poor performance in rat offspring (2). It has to be stressed that folding of the neural walls and closure of the neural tube (neural tube formation) takes place between about 22 and 28 days post-conception ­ i. Among these are regular lifting of heavy burdens, constant squatting or bending over, extreme stretching or bending, continuous standing or sitting without a break, and contact with poisonous or infectious materials, or with openly radioactive substances. Association between reported venlafaxine use in early pregnancy and birth defects, national birth defects prevention study, 1997­2007. Toxic effects need to be considered more with very young infants than with those above 2 months of age, or even with an older baby who is only breastfed once or twice a day. Long-term follow-up of children born to mothers with acute leukemia during pregnancy. Moreover, the carcinogenic and mutagenic potential of alglucerase has not been studied. Restricting the analysis to children of women with a diagnosis of affective disorder, the adjusted hazard ratio was 1. The available case studies on the administration of gadolinium complex in human beings (De Santis 2007, Marcos 1997) gave no indication of embryonic or fetal toxicity; however, a recent report has found high levels of gadolium +3 (the toxic form) in the placentae of about six% of women in a control population. A 1966 report described a mother with two infants with microcephaly, mental retardation, and motor dysfunction (10). Perinatal mortality in the Australian study was a result of stillbirths more often than neonatal deaths (5, 41). Among the children of more than 600 pregnant women with rheumatic diseases, who were recorded in various studies and case series (Cooper 2014, Diav-Citrin 2013, Costedoat-Chalumeau 2003), and who were mostly exposed to hydroxychloroquine, no appreciably elevated risk of malformations was observed. Gadopentetic acid excretion into the milk was measured in a single patient over an observation time of 33 hours, 0. Urinary chromium excretion during pregnancy and its relationship with intravenous glucose loading. In contrast, a Norwegian investigation with about 2,900 pregnancies with epilepsy found that women using antiepileptic drugs (1/3 of the cohort) displayed more frequently mild preeclampsia, premature delivery, and children with a birth weight <2,500 g, a head circumference below the 2. However, with multi-chemical exposure, establishing a cause-effect relationship is difficult. Thirteen outcomes were known, 12 of which resulted in healthy, full-term infants without birth defects. In a case series with 26 pregnancies no anomalies were noted in the offspring, among them four children who had been exposed to monotherapy (Kondo 1996). Air emissions of dioxin have been dramatically reduced by 90% and most Americans have low level exposures. A 1999 retrospective cohort study reported the outcomes of 312 pregnancies in 223 women treated for gestational hypertension (N = 80), preeclampsia (N = 19), chronic hypertension (N = 179), or superimposed preeclampsia on chronic hypertension (N = 34) (28). Primarily, the drugs evaluated were alprazolam, chlordiazepoxide, diazepam, and oxazepam. Both immunoglobulins and hyperimmune sera against specific infections are not, as far as we know today, embryotoxic (review in Briggs 2011). Cytomegalovirus remains viable in naturally infected breast milk despite being frozen for 10 days. In addition to the limitations described above, inter-individual variation in alcohol metabolism and susceptibility to teratogenic effects as a result of genetic polymorphisms in both mother and fetus are likely to significantly influence risk at the individual level (review Ramsay 2010).

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Comparisons were made for uterine and umbilicoplacental vascular impedance, fetal hemodynamics, and cardiac function. Subsequent prospective cohort and retrospective case-control studies showed more 2. Of the 13 men described, 9 fathered 15 children (10­13), including 1 who fathered a child while receiving therapy (10). Twelve of the infants in whom premature ductal closure was not reported were co-exposed to other medications (Jones 2010). In five women who had a definite response to the aspirin, no improvement in plasma volume or fetal welfare was demonstrated. A population based case-control study with some 31 exposed pregnant women did not demonstrate an increased risk of malformations (Czeizel 2004c). Reported malformations other than limb reduction defects after therapeutic dosing included: micrognathia, anomalous right mandible, left pes equinovarus (1 case); swelling of hands and feet (1 case); hypospadias (1 case); and bilateral anophthalmia (1 case) (8,12­14). Because aspartame is a source of phenylalanine, although a minor source, this should be considered by these women in their dietary planning. In the clonidine-group blood pressure was lower and the rate of instrumental delivery higher with no difference in fetal outcome. A further study of 49 methamphetamine exposed and 49 unexposed children between the ages of 3 and 4, found significantly lower neuropsychological scores in the exposed compared to the unexposed children (Chang 2009). Clonidine, moxonidine, and reserpine are no longer part of the armamentarium of antihypertensive management. Nitrates may be used in pregnancy provided they are used for the right indication. All digitalis glycosides are able to cross the placenta; the fetal placenta concentration corresponds to the maternal one. Intrauterine exposure to mild analgesics is a risk factor for development of male reproductive disorders in human and rat. Thirteen of fourteen fetuses treated with sotalol alone responded with a restoration of normal sinus rhythm, two had recurrences, and in one case the fetus died. A 2007 report described three hypertensive women exposed to amlodipine in the 1st trimester (3). As a consequence of these issues, study findings may be inaccurate and interpretation of the data difficult, particularly in terms of ascribing causality to a particular exposure. However, norethisterone acetate is significantly lower dosed in the products available today ­ rather than 10 mg, only in the range of 1 mg. From this, an average relative infant dose of 28% can be calculated (Sugawara 1999). No information was provided on the status of the newborns, but there were no differences between the groups in the fetal biochemical profile score (2). Their effectiveness is based essentially on a suppression of the plasma renin-angiotensinaldosterone system. Meta-analysis of the relation between silicone breast implants and the risk of connective-tissue diseases. There was no relationship between the defect and either acetaminophen or acetylcysteine due to the timing of exposure. Urapidil is recommended as an alternative to dihydralazine in the management of preeclampsia. If, however, the level is very low in the plasma, it will also be low in the milk, even though the milk plasma ratio is 1. The fetal thyroid stimulating hormone collected by umbilical cord puncture can provide information about the effect of the maternal 131I-therapy, also in still (compensated) euthyroid fetuses and gives indications for a possibly necessary postnatal thyroxin supplementation (Welch 1997). Niclosamide Niclosamide is an anthelmintic that is effective against tapeworms (cestodes). The symptoms are variable, consisting of mild hypotonia, weak crying, weak sucking and rarely, a ptosis and breathing insufficiency. Rotavirus vaccine effectiveness and case-control study on risk factors for breakthrough infections in Germany, 2010­2011. A Danish cohort study based on prescription registers identified 1606 women redeeming a prescription for pyrvinium (449 during first trimester).


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There was neither an indication of an increased risk of spontaneous abortion nor was a teratogenic effect demonstrable (Carlier 1998). These reviews concluded that while there is some evidence that exposure to pesticides contributes to male and female infertility, the evidence on spontaneous abortion, preterm birth, birth weight, stillbirth, and congenital malformations are inconsistent, and firm conclusions cannot be drawn, either for occupational exposure (gardening, farming, agriculture, horticulture, greenhouse work, etc. If chronic hepatitis B requires lamivudin or tenofovir therapy, breastfeeding seems acceptable after simultaneous hepatitis B immunization of the baby (Chapter 4. This effect is thought to be caused by pathophysiological changes in the placenta which limit uterine blood flow thereby causing fetal growth restriction. For specific treatments, the numbers of exposed pregnancies/live-born children/ spontaneous abortions/induced abortions/minor malformations were as follows: levodopa only: 38/29/3/7/3; pramipexole only: 12/9/3/0/0; rotigotine only: 2/2/0/0/0; ropinirole only: 3/2/0/1/0; levodopa combined with pramipexole: 3/3/0/0/0; levodopa combined with ropinirole: 1/1/0/0/0. One of the infants was evaluated at 4 months of age and appeared normal except for small size (weight 3rd percentile, head circumference 10th percentile). Developmental and peri-postnatal study in cynomolgus monkeys with belimumab, a monoclonal antibody directed against B-lymphocyte stimulator. Amiodarone given by three routes to terminate fetal atrial flutter associated with severe hydrops. Contrary to individual reports, newborn sepsis does not occur frequently after the induction of lung maturation with glucocorticoids. Both thiamazol and propylthiouracil result in a non-clinically significant exposure for the newborn infant. With chronic or intermittent excessive alcohol consumption (binge drinking), breastfeeding should be discontinued. Maternal blood and amniotic fluid levels of moxifloxacin, levofloxacin and cefixime. Johns wort (Hypericum perforatum) and breastfeeding plasma and breast milk concentrations of hyperforin for 5 mothers and 2 infants. The dipeptide compounds are hydrolyzed to the individual amino acids in the gut, and these, along with methanol, will be evaluated in later sections. Of the 17 women who had been given pudendal anesthesia with a dose of prilocaine limited to 200 mg, none developed symptomatic methemoglobinemia (Kirschbaum 1991). A study with pregnant rabbits found that, with doses producing maternal acidosis and electrolyte changes, acetazolamide produced a dose-related increase in axial skeletal malformations (7). In a double-blind, randomized study of neonatal jaundice prophylaxis, either antipyrine (N = 24), 300 mg/day or placebo (N = 24) was given from the 38th week of gestation until delivery (4). Most of the reported experience is with treatment after the first trimester of pregnancy. The critical exposure period for classical methotrexate embryopathy appears to be 6­8 weeks after conception (Hyoun 2012, Feldkamp 1993), although a susceptibility to conotruncal heart defects may occur with maternal methotrexate treatment a little earlier in pregnancy (Hyoun 2012). However, due to methodological irregularities, these results should be interpreted with necessary caution. Prenatal alcohol exposure patterns and alcohol-related birth defects and growth deficiencies: a prospective study. Ketamine Ketamine is a fast-acting injectable anesthetic that has a good analgesic effect and little effect on respiration. The reduced fetal growth appears to be related to increased vascular resistance in both the mother and the fetus and is a function of the length of drug exposure. An increased malformation risk is not expected for hydroxyethyl starch (Chapter 2. Tissue damage after irradiation of the uterus was suspected as the cause, especially if the radiotherapy took place before menarche. One year later, Gouraud (2012) provided a longer follow-up of six children exposed to tacrolimus through breastfeeding. The greatest risk for mitochondrial toxicity is exhibited in vitro for didanosine, stavudine, and zidovudine. This extremely limited transfer and the limited enteral absorption, do not lead to an expectation of any risk for a breastfed infant. Pregnancy may exacerbate existing disease or result in new disease manifestations, but the data suggest that treatment may reduce the risk of spontaneous abortion and bleeding complications. Both colostrum and milk had significantly higher concentrations than did maternal serum or plasma.

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Randomized comparison of mefloquine-artesunate versus quinine in the treatment of multidrug-resistant falciparum malaria in pregnancy. Terbutaline, salbutamol and fenoterol are the drugs of choice for asthma control during breastfeeding. Even with uncomplicated caesarean section, uterine atony can lead to increased loss of blood, in this context the relaxant effect of the inhalation agents is unwanted. Spontaneous abortion among female employees and decreased birth weight in their offspring. At the age of 19 years, 84 of those exposed in utero were still able to be compared with 328 "controls": the low death rate in the betamethasone group (22% versus 35%) was not 2 Pregnancy 2. There was a higher risk for stillbirths with congenital anomalies (nine stillbirths with neural tube defects). Pregnancy outcomes of 22 pregnant women treated for Amanita phalloides ingestion compared with those of 40 non-exposed women, did not suggest any association between an increased risk of major congenital malformation or minor anomalies and mushroom toxicity (Tнmбr 1997). Additional data are needed to confirm these risks but, as with all drug use in pregnancy, routine use of acetaminophen should be avoided. It may also be considered as first-line therapy in neurological patients (European Association for the Study of the Liver 2012). They did not differ from the 96 controls (children born from mothers not treated) in gross or fine motor measures, hearing, vision or language, based on maternal response to questionnaires. There are published results on flupentixol for about 100 pregnancies (Reis 2008), which give no indication of an increased risk for malformations. Analysis of 629 pregnancy outcomes in transplant recipients treated with Sandimmun. Nordstrom (1978) studied spontaneous abortions, birth weight of offspring, and congenital defects in Swedish workers in and around a smelter. A double blind study of seven women exposed to domperidone, and nine women using a placebo while breastfeeding premature infants showed that with domperidone, the amount of milk could be increased by 49. Tomson (2009) analyzed about 300 pregnancies from case series and registries, and found four major malformations with monotherapy. Organophosphate pesticide exposure and neurodevelopment in young Mexican-American children. Exposure to nitrofurantoin during the first trimester of pregnancy and the risk for major malformations. Pregnancy outcome following gestational exposure to Echinacea: a prospective controlled study. A population-based case-control study of the safety of oral anti-tuberculosis drug treatment during pregnancy. The molecular weight (about 534) and elimination half-life (9­13 hours) suggest that the drug will be excreted into breast milk. With a steady dose, its level decreases during pregnancy to 40­50%, apparently due to increased renal excretion (Lуpez-Fraile 2009, Westin 2008, Tomson 2007). A study of pregnant women with borderline iodine intake suggested that, smoking in pregnancy may be a major etiological factor for thyroid enlargement in the newborn (Chanoine 1991). A pregnant patient with renal vein thrombosis successfully treated with low-dose, thrombolytic therapy: a case report. Most other investigations did not find teratogenic effects, either with untreated epilepsy or with grand mal seizures during pregnancy. Congenital malformations have been reported in infants exposed during pregnancy, but they do not appear to be related to the drug. A 1994 report described three pregnancies in two women who were being treated with amiodarone (16). Nine women were given intravenous alfentanil 50 g and then 10 g as needed during anesthesia in the postpartum period. The outcome of the infants exposed throughout gestation included six preterm (<37 weeks), three small-for-gestational-age (all with poor prenatal care), one of whom had a seizure on the first day, and two full-term but extremely drowsy infants.

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