Methylphenidate in Pregnancy: A Multicenter, Prospective, Comparative, Observational Study.

INTRODUCTION: Methylphenidate is a central nervous system stimulant medicinally used in the treatment of attention-deficit disorder with or without hyperactivity (ADD/ADHD). Data on its use in human pregnancy are limited. The primary objective of the study was to evaluate the risk of major congenital anomalies after pregnancy exposure to methylphenidate for medical indications. METHODS: In a prospective, comparative, multicenter observational study performed in 4 participating Teratology Information Services (in Jerusalem, Berlin, Newcastle upon Tyne, and Toronto) between 1996 and 2013, methylphenidate-exposed pregnancies were compared with pregnancies counseled for nonteratogenic exposure (NTE) after matching by maternal age, gestational age, and year at initial contact. RESULTS: 382 methylphenidate-exposed pregnancies (89.5% in the first trimester) were followed up. The overall rate of major congenital anomalies was similar between the groups (10/309 = 3.2% [methylphenidate] vs 13/358 = 3.6% [NTE], P = .780). The rates of major congenital anomalies (6/247 = 2.4% [methylphenidate] vs 12/358 = 3.4% [NTE], P = .511) and cardiovascular anomalies (2/247 = 0.8% [methylphenidate] vs 3/358 = 0.8% [NTE], P = .970) were also similar after exclusion of genetic or cytogenetic anomalies and limiting methylphenidate exposure to the period of organogenesis (weeks 4-13 after the last menstrual period). There was a higher rate of miscarriages and elective terminations of pregnancy in the methylphenidate group. Significant predictors for the miscarriages using Cox proportional hazards model were methylphenidate exposure (adjusted hazard ratio [HR] = 1.98; 95% CI, 1.23-3.20; P = .005) and past miscarriage (adjusted HR = 1.35; 95% CI, 1.18-1.55; P < .001). CONCLUSIONS: The present study suggests that methylphenidate does not seem to increase the risk for major malformations. Further studies are required to establish its pregnancy safety and its possible association with miscarriages.

Hip arthroplasty with high chromium and cobalt blood levels--Case report of a patient followed during pregnancy and lactation period.

Metal-on-metal arthroplasty may lead to elevated blood chromium (Cr) and cobalt (Co) levels (>7 µg/l). Since carcinogenic, mutagenic, and teratogenic effects have been suggested, there is concern of pregnancy hazards for women with this condition. The 34-year-old patient has had a unilateral hip replacement for seven years. Before her pregnancy high Cr (47 µg/l) and Co (103 µg/l) blood concentrations were measured, but she did not develop any symptoms. A male infant was delivered after 41 weeks with first degree hypospadias. His levels were increased at 3 weeks of age: 14 µg/l (Cr) and 20 µg/l (Co), but decreased by 9 weeks to 6.7 µg/l (Cr) and 10.0 µg/l (Co). Maternal levels at delivery were 25 µg/l (Cr) and 51 µg/l (Co). The child was fully breast-fed and developed normally. An association between hypospadias and Cr/Co has to be considered speculative. The otherwise favorable outcome of this case may be reassuring for pregnant and breast-feeding patients with metal-on-metal hip replacements.

Case report: High chromium and cobalt levels in a pregnant patient with bilateral metal-on-metal hip arthroplasties.

BACKGROUND: Metal-on-metal bearings frequently are used in young patients leading to the concern that disseminated metals such as chromium (Cr) and cobalt (Co) as the main constituents could affect pregnancies. CASE DESCRIPTION: We describe a 41-year-old patient with bilateral metal-on-metal hip arthroplasties, a recurrent pseudotumor, and extremely high blood levels (Cr 39 µg/L, Co 138 µg/L) at 12 gestational weeks. At different gestational weeks, maternal blood, aspirate of the pseudotumor, and amniotic fluid were analyzed for Cr and Co. Therapy with chelating agents was not recommended because the mother showed no symptoms of toxicity and the safety of chelating therapy during pregnancy is not established. At 38 weeks of gestation, a healthy male infant was delivered with elevated Cr and Co cord blood levels. At the age of 8 weeks, the infant's Cr was comparable to the cord blood level, whereas the Co decreased considerably without treatment. At the age of 14 weeks, the infant's development was seemingly uneventful and no signs of toxicity were obvious. LITERATURE REVIEW: Carcinogenic, mutagenic, and teratogenic potentials of these metals have been suggested. However, we found no published clinical observations in context with pregnancies of women with hip arthroplasties using metal-on-metal implants. To our knowledge, this is the first report of such high levels of Cr and Co in a human pregnancy. PURPOSES AND CLINICAL RELEVANCE: Although we cannot generalize from one case, the seemingly uneventful outcome of this pregnancy may reassure colleagues when counseling patients with high ion levels whether to carry a pregnancy to term.

Pregnancy outcome after paternal exposure to azathioprine/6-mercaptopurine.

There are only few studies with conflicting results on pregnancy outcome after paternal exposure to azathioprine or 6-mercaptopurine. In our study, pregnancy outcome of 115 prospectively followed pregnancies after paternal exposure to azathioprine or 6-mercaptopurine is compared to a control group of 341 pregnancies. The rate of major malformations was not increased (3.0% in exposed versus 2.2% in the control group). There was no specific pattern of birth defects and no indication for chromosomal aberrations in the exposed group. We observed a higher rate of elective terminations of pregnancy in the exposed group and a non-significant increase of spontaneous abortions (cumulative incidence 19% versus 13%, respectively). Further prospective studies are required to address the question of a possibly increased risk for spontaneous abortion.