Reproductive and developmental toxicity assessment of palbociclib, a CDK4/6 inhibitor, in Sprague-Dawley rats and New Zealand White rabbits.

Palbociclib is a selective inhibitor of the cyclin-dependent kinase (CDK) 4/6, approved for the treatment of breast cancer. We assessed the potential effects of oral administration of palbociclib on reproduction and development. There were no effects on female or male fertility indices; however, in the male there was seminiferous tubule degeneration in the testes and secondary findings in the epididymides, lower testicular and epididymal weights, sperm density and motility. Palbociclib was not teratogenic in rats or rabbits; however, in the presence of maternal toxicity (lower maternal body weight gain and food consumption), low fetal body weights were observed in rats and small forepaw phalanges were noted in rabbits. There were, however, no adverse effects on the F1 generation in a pre- and post-natal developmental toxicity study in the rat.

Gestational weight gain in women with systemic lupus erythematosus.

Objective The objective of this study was to estimate the proportion of pregnant women with systemic lupus erythematosus meeting Institute of Medicine guidelines for gestational weight gain and determine correlates of adherence to guidelines. Methods Singleton, live births in the Hopkins Lupus Pregnancy Cohort 1987-2015 were included. Pre-pregnancy weight was the weight recorded 12 months prior to pregnancy/first trimester. Final weight was the last weight recorded in the third trimester. Adherence to Institute of Medicine guidelines (inadequate, adequate, or excessive) was based on pre-pregnancy body mass index. Fisher's exact test and analysis of variance determined factors associated with not meeting guidelines. Stepwise selection estimated predictors of gestational weight gain. Results Of the 211 pregnancies, 34%, 24% and 42% had inadequate, adequate and excessive gestational weight gain, respectively. In exploratory analyses, differences in Institute of Medicine adherence were observed by pre-pregnancy body mass index, race, elevated creatinine during pregnancy and pre-pregnancy blood pressure. Odds of inadequate and excessive gestational weight gain increased 12% with each 1 kg/m2 increase in pre-pregnancy body mass index. Lower maternal education was associated with increased odds of inadequate and excessive gestational weight gain. Conclusions As in the general population, most women with systemic lupus erythematosus did not meet Institute of Medicine guidelines. Our results identified predictors of gestational weight gain to aid in targeted interventions to improve guideline adherence in this population.

Ethnicity and gestational diabetes in New York City, 1995-2003.

OBJECTIVE: To characterise the patterns of occurrence of gestational diabetes among a wide range of ethnic groups that reside in New York City. DESIGN: Birth records and hospital discharge data were linked to more accurately assess the risk of gestational diabetes by ethnicity, compare risk in US-born to foreign-born women, and assess time trends. SETTING: New York City. POPULATION: All singleton live births occurring between 1995 and 2003. METHODS: Multivariable binomial regression analysis of ethnicity and gestational diabetes, yielding adjusted risk ratios with non-Hispanic white women as the referent. MAIN OUTCOME MEASURE: Diagnosis of gestational diabetes on birth certificate or in hospital discharge. RESULTS: Adjusted relative risks (aRRs) were modestly elevated for African-Americans and sub-Saharan Africans and somewhat higher (<2.0) for non-Hispanic Caribbeans, Hispanic Caribbeans, Central Americans, and South Americans. The aRR was 4.7 (95% CI = 4.6-4.9) for South Central Asians (with an absolute gestational diabetes risk of 14.3%), 2.8 (95% CI = 2.7-3.0) among South-East Asian and Pacific Islanders, and 2.3 (95% CI = 2.2-2.4) among East Asians. Among South Central Asians, the greatest risks were found for women from Bangladesh (aRR = 7.1, 95% CI = 6.8-7.3). Foreign-born women consistently had higher risk than US-born women. Risk for gestational diabetes increased over time among South Central Asians, some Hispanic groups, and African-Americans. CONCLUSIONS: Risk of gestational diabetes appears to vary markedly among ethnic groups, subject to potential artefacts associated with screening and diagnosis. These differences would have direct implications for health care and may suggest aetiologic hypotheses.