Association between morbidity among term newborns and low-risk caesarean delivery rates.

OBJECTIVE: To examine the association between county-level caesarean delivery (CD) rates among women at low risk and morbidity among term newborns. DESIGN: Cross-sectional study. SETTING: Population-based study of US county-level birth data from 2015 to 2017. POPULATION: Nulliparous women with term, singleton, vertex-presenting infants (NTSV) at low risk for morbidity. METHODS: The primary exposure was county-level CD rates. MAIN OUTCOME MEASURES: The outcome was morbidity among the low-risk NTSV cohort, categorised as severe (5-minute Apgar score of ≤3, assisted ventilation for ≥6 hours, severe neurologic injury or seizure, transfer or death) or moderate (5-minute Apgar score of <7 but >3, administration of antibiotics or assisted ventilation at delivery). We used linear regression models to determine the association between county NTSV CD and neonatal morbidity rates with cluster robust standard errors. RESULTS: The analysis included data from 2 753 522 births in 952 counties from all 48 states. The mean NTSV CD rate was 23.6% (standard deviation 4.8%). The median severe and moderate neonatal morbidity rates were 15.2 (interquartile range, IQR 9.4-23.6) and 52.5 (IQR 33.4-75.7) per 1000 births, respectively. In the unadjusted analysis using the risk-adjusted exposure and outcome, every percentage point increase in the CD rate of a county was associated with 0.6 (95% CI -0.9, -0.3) and 2.3 fewer (95% CI -3.4, -1.1) cases of severe and moderate neonatal morbidity per 1000 live births. After adjustment for other county factors, the relationships remained significant. These findings were tested in multiple sensitivity analyses. CONCLUSIONS: Lower county-level NTSV CD rates were associated with a small increase in morbidity among term newborns in the USA. TWEETABLE ABSTRACT: Lower county-level caesarean delivery rates were associated with an increase in morbidity among term newborns in the USA.

Functional effects of protein kinase C activation on the human cardiac Na+ channel.

The cardiac Na+ current plays an important role in determining normal and abnormal impulse propagation in the heart. We have investigated the effects of protein kinase C (PKC) activation on the recombinant human cardiac Na+ channel (hH1) following heterologous expression in Xenopus laevis oocytes. Phorbol 12-myristate 13-acetate (PMA), which directly activates PKC, reduced current amplitude at all test potentials (43 +/- 12% at -10 mV). In contrast to the rat brain IIA (rBIIA) channel, there was no apparent change in either macroscopic Na+ current decay or the voltage dependence of channel gating. Further experiments indicate that the effects of PMA were mediated by PKC activation: (1) an inactive stereoisomer, 4 alpha-PMA, had no effect; (2) preincubation with the protein kinase inhibitor chelerythrine prevented the PMA effects; and (3) a hydrolyzable diacylglycerol analogue, 1-oleoyl-2-acetyl-glycerol, also reduced current (22 +/- 5%). In addition, when the alpha 1B-adrenergic receptor was coexpressed with hH1, the alpha-receptor agonist methoxamine reduced hH1 current (45 +/- 10%), an effect that could be eliminated by chelerythrine preincubation. When a conserved consensus PKC site (serine 1503) in the III-IV interdomain linker thought to be responsible for the PKC effects on rBIIA was mutated, PMA still reduced Na+ current, but the magnitude of the effect was smaller compared with that for the wild-type channel. Similar findings were obtained with alpha 1-receptor stimulation following receptor coexpression with the mutant channel. We conclude that activation of PKC modulates the human cardiac Na+ channel by at least two mechanisms, one similar to that seen with rat brain channels, involving a conserved putative PKC site, and a second more specific to the cardiac isoform.