Cardiac birth defects in a twin infant born to a woman with chronic myeloid leukemia on dasatinib.

Preclinical animal studies have demonstrated an association between maternal use of tyrosine kinase inhibitors and embryofetal toxicity; yet, multiple clinical case series have reported normal pregnancy outcomes and healthy infants in women on these medications during the course of their pregnancy. We describe a case of a woman with chronic myeloid leukemia who had taken the second-generation tyrosine kinase inhibitor dasatinib during the first 12 weeks of her dichorionic diamniotic twin pregnancy and subsequently delivered two low-birth weight infants, one with severe cardiac malformations and the other without apparent birth abnormalities. To our knowledge, this is the first reported case of fetal cardiovascular defects in an infant born to a woman on dasatinib during a twin pregnancy and supports current recommendations to avoid this medication during pregnancy. We also review relevant preclinical and clinical studies of tyrosine kinase inhibitor use during pregnancy and explore alternative therapeutic options for patients with chronic myeloid leukemia during pregnancy to aid clinicians in the appropriate management of these patients so as to minimize both maternal and fetal risks.

Impaired bone and muscle development in young people treated with antiepileptic drugs.

OBJECTIVE: Antiepileptic drugs (AEDs) are associated with reduced bone density, balance impairment, and increased fracture risk in adults. However, pediatric data are limited. Therefore, we aimed to examine bone, muscle, and balance outcomes in young patients taking AEDs. METHODS: We undertook a case-control study utilizing an AED exposure-discordant matched-pair approach. Subjects were aged 5-18 years with at least 12 months of AED exposure. Pairs were twins, nontwin siblings and first cousins, sex- and age-matched (to within 2 years), allowing for greater power than with unrelated control subjects. Dual energy x-ray absorptiometry (DXA), peripheral quantitative computed tomography (pQCT), and muscle force/balance were tested, with questionnaires were administered for bone health and epilepsy details. RESULTS: Twenty-three pairs were recruited, (median age 12.9 years [subjects] and 13.5 years [controls])-7 twin, 14 sibling, and 2 cousin pairs. Those taking AEDs had an increased prevalence of fractures (15 fractures in 8 subjects, compared with 4 fractures in 3 controls, p < 0.01). Trabecular volumetric bone mineral density (vBMD) measured by pQCT at the 4% site (tibia) was reduced by 14% (p = 0.03) in subjects. Subjects exerted a decreased maximum force compared to body weight (Fmax total/g) at the tibia. There were no differences seen in either bone mineral parameters measured by DXA or balance measures. SIGNIFICANCE: Young people taking AEDs reported more fractures and had reductions in tibial vBMD and lower limb muscle force compared to their matched controls. These findings suggest that further exploration of bone health issues of young patients on AED therapy is required. Longitudinal studies are required to confirm these changes in the muscle-bone unit and to further explore the clinical outcomes.

Common psychiatric disorders and caffeine use, tolerance, and withdrawal: an examination of shared genetic and environmental effects.

BACKGROUND: Previous studies examined caffeine use and caffeine dependence and risk for the symptoms, or diagnosis, of psychiatric disorders. The current study aimed to determine if generalized anxiety disorder (GAD), panic disorder, phobias, major depressive disorder (MDD), anorexia nervosa (AN), or bulimia nervosa (BN) shared common genetic or environmental factors with caffeine use, caffeine tolerance, or caffeine withdrawal. METHOD: Using 2,270 women from the Virginia Adult Twin Study of Psychiatric and Substance Use Disorders, bivariate Cholesky decomposition models were used to determine if any of the psychiatric disorders shared genetic or environmental factors with caffeine use phenotypes. RESULTS: GAD, phobias, and MDD shared genetic factors with caffeine use, with genetic correlations estimated to be 0.48, 0.25, and 0.38, respectively. Removal of the shared genetic and environmental parameter for phobias and caffeine use resulted in a significantly worse fitting model. MDD shared unique environmental factors (environmental correlation=0.23) with caffeine tolerance; the genetic correlation between AN and caffeine tolerance and BN and caffeine tolerance were 0.64 and 0.49, respectively. Removal of the genetic and environmental correlation parameters resulted in significantly worse fitting models for GAD, phobias, MDD, AN, and BN, which suggested that there was significant shared liability between each of these phenotypes and caffeine tolerance. GAD had modest genetic correlations with caffeine tolerance, 0.24, and caffeine withdrawal, 0.35. CONCLUSIONS: There was suggestive evidence of shared genetic and environmental liability between psychiatric disorders and caffeine phenotypes. This might inform us about the etiology of the comorbidity between these phenotypes.

Herceptin (trastuzumab) therapy in a twin pregnancy with associated oligohydramnios.

Herceptin (trastuzumab) is an adjuvant chemotherapy agent used in treatment of certain breast cancers. Limited information is available on the use of herceptin in pregnancy. This case is a twin pregnancy exposed to herceptin until 23 weeks' gestation. One twin had chronic renal failure develop, whereas the other twin did not.

[Fetal warfarin syndrome in twin pregnancy]. / Plodowy zespól warfarynowy w przebiegu ciazy blizniaczej.

We describe a pair of twins, whose mother was being treated by oral anticoagulant drugs, as a result of having received mitral heart valve implantation in the past. The male twins monochorionic, monoamniotic--but one infant showed the features of fetal warfarin syndrome. In the study we discussed the pharmacogentetics and individual variation in the human metabolism during treatment with warfarin-perinatal growth and prevalence of congenital malformations. We analysed the threats to the fetus and mother, connected with administration of anticoagulant drugs.

The relationship between stimulant medication and tics.

Clinical evidence supports the observation that stimulant drugs increase the severity of tics in 25% to 50% of patients with TS, and occasionally can precipitate TS in a patient who did not previously manifest symptoms of this disorder. As ADD is frequently associated with TS, the clinician is often faced with a dilemma. A conservative approach to the use of stimulant medication, stringent criteria for its use, adequate counseling of the child and parents, and a thorough cost-benefit analysis before initiating treatment are required. Behavior management and environmental manipulation can be useful techniques with the child with ADD, and should be tried before medication is considered.

Thyroid aplasia in male sibling of heterozygotic twins born to the hyperthyroid mother treated with propylthiouracil during pregnancy (case report).

UNLABELLED: A 30-year-old pregnant female was diagnosed to have thyrotoxicosis (TSH= 0.005 µU/ml) at 13th week of gestation. Propylthiouracil (PTU; 200 mg daily) was prescribed to her and four weekly follow ups by the endocrinologist and obstetrician were ensured. At each examination TSH, FT4 and FT3 levels were normal and she became symptom free. Repeated ultrasound examination throughout the pregnancy did not reveal any fetal abnormality. The lady normally delivered heterozygotic twins. Umbilical cord blood of the baby boy twin showed a high TSH (541 µU/ml; reference range 0.270 - 4.20 µU/ml). He was started on thyroxine therapy (50 µg once daily). Ultrasound reported the absence of the thyroid gland. One month later TSH was within normal range and thyroxine dose was adjusted to 25 µg once daily. Repeated ultrasound confirmed the absence of thyroid gland. TSH was repeatedly normal. The boy is currently doing well on thyroxine replacement therapy. The other non-identical twin was a healthy girl with normal thyroid function tests and always thereafter. This case report suggested that PTU could be a hazardous drug to the fetus, since the mother gave birth to a baby with thyroid aplasia. KEYWORDS: PTU, Thyroid aplasia, Thyrotoxicosis, TSH.

Twin preterm neonates with cardiac toxicity related to lopinavir/ritonavir therapy.

We report twin neonates who were born prematurely at 32 weeks of gestation to a mother with human immunodeficiency virus infection. One of the twins developed complete heart block and dilated cardiomyopathy related to lopinavir/ritonavir therapy, a boosted protease-inhibitor agent, while the other twin developed mild bradycardia. We recommend caution in the use of lopinavir/ritonavir in the immediate neonatal period.

Development of Churg-Strauss syndrome with severe multiple mononeuropathy after leukotriene receptor antagonist treatment in one of the monozygotic twins with asthma: case report.

Several cases of Churg-Strauss syndrome (CSS) have been reported in asthmatic patients treated with leukotriene receptor antagonists (LTRAs). It is not clear whether LTRA is a causative factor in the development of vasculitis. We present the case of a 26-year-old patient, who developed severe central and peripheral neuropathy after a short-term treatment with LTRA, followed by gastrointestinal perforation and bleeding. The patient was successfully treated with high-dose glucocorticoids, immunoglobulins, and cyclophosphamide. His monozygotic twin brother treated for asthma does not meet classification criteria for Churg-Strauss syndrome at the moment, but his condition is being monitored. Both asthma and rheumatology specialists should consider the possibility of CSS development in patients treated with LTRAs.

Foetal kidney maldevelopment in maternal use of angiotensin II type I receptor antagonists.

We report renal lesions observed in a foetus exposed throughout pregnancy to angiotensin II type I (AT 1) receptor antagonists. The mother suffered from essential hypertension and was treated with Cozaar (losartan 50 mg). Autopsy examination of the foetus revealed severe renal lesions, including tubular dysgenesis, hypertrophy of the endothelial and medial cells lining the arterial and arteriolar walls, hyperplasia of the juxtaglomerular apparatus and poorly developed vasa recta. Similar lesions have already been observed in foetuses of women treated with angiotensin-converting enzyme antagonists and also in foetuses and neonates of animals undergoing experimental blockade of the renin-angiotensin system. The purpose of this report is to describe structural lesions observed in the kidneys, and, particularly, vascular lesions. Our results suggest that the use of AT 1 receptor antagonists during pregnancy may have a severe deleterious effect on kidney development in the foetus.

[Congenital atrial flutter with hydrops fetalis caused by tocolytic therapy (author's transl)]. / Kongenitales Vorhofflattern mit Hydrops fetalis durch mütterliche Tokolytikamedikation.

A 31-year-old healthy woman received Ritodrine (Pre-Par) from the 26th week of gestation because of twin pregnancy. Three weeks before birth continous intravenous medication with the same drug was commenced because of premature uterine contractions. Five days later a heart rate of over 200/minute was noted in one of the twins. This tachycardia persisted until birth while the heart rate of the other twin remained normal. At 33 weeks monozygotic female twins were delivered after artifical rupture of membranes. One twin was normal, birth weight 1.6 kg. The other baby showed persistent atrial flutter, was hydropic (weight 2.75 kg) and suffered from gross cardiac failure. Atrial flutter was converted to sinus rhythm one hour after birth by DC-countershock. Digoxin was commenced, the child rapidly improved and now still remains in sinus rhythm six month later.

The development of adenocarcinoma of the endometrium in young women receiving long-term sequential oral contraception.

PIP: 4 cases of adenocarcinoma of the endometrium were reported in young women. All were using and had used for periods of 4-12 years a sequential oral contraceptive, Oracon, manufactured by Mead Johnson Laboratories. Ethinyl estradiol and mestranol, the 3 methyl ether of ethinyl estradiol, are 25 times more potent than diethylstilbestrol, which has recently been implicated in the development of vaginal adenocarcinoma in female offspring of women treated during pregnancy with it. A study is now in progress to determine whether long-term use of Oracon produces premalignant changes in the endometrium. Doctors with patients on similar sequential contraceptives should watch for abnormal vaginal bleeding.^ieng