Statins Prevent the Deleterious Consequences of Placental Chemerin Upregulation in Preeclampsia.

BACKGROUND: Chemerin, an inflammatory adipokine, is upregulated in preeclampsia, and its placental overexpression results in preeclampsia-like symptoms in mice. Statins may lower chemerin. METHODS: Chemerin was determined in a prospective cohort study in women suspected of preeclampsia and evaluated as a predictor versus the sFlt-1 (soluble fms-like tyrosine kinase-1)/PlGF (placental growth factor) ratio. Chemerin release was studied in perfused placentas and placental explants with or without the statins pravastatin and fluvastatin. We also addressed statin placental passage and the effects of chemerin in chorionic plate arteries. RESULTS: Serum chemerin was elevated in women with preeclampsia, and its addition to a predictive model yielded significant effects on top of the sFlt-1/PlGF ratio to predict preeclampsia and its fetal complications. Perfused placentas and explants of preeclamptic women released more chemerin and sFlt-1 and less PlGF than those of healthy pregnant women. Statins reversed this. Both statins entered the fetal compartment, and the fetal/maternal concentration ratio of pravastatin was twice that of fluvastatin. Chemerin constricted plate arteries, and this was blocked by a chemerin receptor antagonist and pravastatin. Chemerin did not potentiate endothelin-1 in chorionic plate arteries. In explants, statins upregulated low-density lipoprotein receptor expression, which relies on the same transcription factor as chemerin, and NO release. CONCLUSIONS: Chemerin is a biomarker for preeclampsia, and statins both prevent its placental upregulation and effects, in an NO and low-density lipoprotein receptor-dependent manner. Combined with their capacity to improve the sFlt-1/PlGF ratio, this offers an attractive mechanism by which statins may prevent or treat preeclampsia.

Is Amniotic Fluid Level a Predictor for Syndromic Diagnosis in Robin Sequence?

OBJECTIVE: The purpose of this study was to determine whether gestational amniotic fluid level abnormalities were associated with postnatal syndromic status in a series of patients with Robin sequence (RS). DESIGN: Retrospective study of participants with RS at Boston Children's Hospital from 1967 to 2017. Participants were divided into syndromic and nonsyndromic groups. The primary predictor variable was postnatal syndromic diagnosis (yes/no). Additional predictor variables included gestational age at birth, birthweight, sex, presence of cleft palate, and other congenital anomalies. The primary outcome variable was amniotic fluid level (normal, oligohydramnios, or polyhydramnios). Descriptive statistics were computed and logistic regression was used to analyze amniotic fluid level as a predictor for syndromic diagnosis. Statistical significance was set at P < .05. RESULTS: Sixty-five (54%) syndromic and 56 (46%) nonsyndromic RS participants were included. An abnormal amniotic fluid level was seen significantly more frequently in the syndromic group (49.2% vs 25.0%; P = .001). Abnormal amniotic fluid level was associated with a 2.9-fold increased likelihood of a syndromic diagnosis (P = .007). Polyhydramnios, which was seen more frequently than oligohydramnios, predicted a 4.18 times increased likelihood of a syndromic diagnosis (P = .003). CONCLUSIONS: Abnormal amniotic fluid level, particularly polyhydramnios, is associated with an increased likelihood of a syndromic diagnosis in patients with RS.