In this systematic review and meta-analysis of more than 1 million pregnant women, 47% had gestational weight gain greater than IOM recommendations and 23% had gestational weight gain less than IOM recommendations. Gestational weight gain greater than or less than guideline recommendations, compared with weight gain within recommended levels, was associated with higher risk of adverse maternal and infant outcomes.
OBJECTIVE
To determine whether the use of vaginal progesterone in asymptomatic women with a sonographic short cervix in the mid-trimester reduces the risk of preterm birth and improves neonatal morbidity and mortality.
STUDY DESIGN
Individual patient data meta-analysis of randomized controlled trials.
RESULTS
Five trials of high quality were included with a total of 775 women and 827 infants. Treatment with vaginal progesterone was associated with a significant reduction in the rate of preterm birth <33 weeks (RR 0.58, 95% CI 0.42–0.80), <35 weeks (RR 0.69, 95% CI 0.55–0.88) and <28 weeks (RR 0.50, 95% CI 0.30–0.81), respiratory distress syndrome (RR 0.48, 95% CI 0.30–0.76), composite neonatal morbidity and mortality (RR 0.57, 95% CI 0.40–0.81), birth weight <1500 g (RR 0.55, 95% CI 0.38–0.80), admission to NICU (RR 0.75, 95% CI 0.59–0.94), and requirement for mechanical ventilation (RR 0.66, 95% CI 0.44–0.98). There were no significant differences between the vaginal progesterone and placebo groups in the rate of adverse maternal events or congenital anomalies.
CONCLUSION
Vaginal progesterone administration to asymptomatic women with a sonographic short cervix reduces the risk of preterm birth and neonatal morbidity and mortality.
We aggregated coding variant data for 81,412 type 2 diabetes cases and
370,832 controls of diverse ancestry, identifying 40 coding variant association
signals (p<2.2×10−7): of these,
16 map outside known risk loci. We make two important observations. First, only
five of these signals are driven by low-frequency variants: even for these,
effect sizes are modest (odds ratio ≤1.29). Second, when we used
large-scale genome-wide association data to fine-map the associated variants in
their regional context, accounting for the global enrichment of complex trait
associations in coding sequence, compelling evidence for coding variant
causality was obtained for only 16 signals. At 13 others, the associated coding
variants clearly represent “false leads” with potential to
generate erroneous mechanistic inference. Coding variant associations offer a
direct route to biological insight for complex diseases and identification of
validated therapeutic targets: however, appropriate mechanistic inference
requires careful specification of their causal contribution to disease
predisposition.
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