Magnesium sulfate for preterm labor and preterm birth.

Approximately half of the more than 500,000 preterm births each year result from preterm labor. Tocolytic therapy continues to be the focus of treatment of these women. Although a variety of tocolytics are used in clinical practice, magnesium sulfate remains one of the most commonly used agents. Magnesium sulfate has also been the focus of recent research for its potential neuroprotective effects for neonates born preterm. Evaluation of 19 randomized clinical trials reveals that magnesium sulfate tocolysis does not reduce the frequencies of delivery within 48 hours, 7 days, or early/late preterm birth, and is not associated with improvements in newborn morbidities or mortality. No other tocolytic class resulted in improved newborn outcomes when compared with magnesium sulfate tocolysis. We conclude that it is appropriate to withhold tocolysis with magnesium sulfate or other agents from women presenting in preterm labor as newborn benefit has not been demonstrated with such treatment. If initiated to achieve time for antenatal corticosteroid administration, or for other acute reasons, treatment can be discontinued once these goals have been achieved or if labor subsides before then. Because brief pregnancy prolongation is unlikely to improve newborn outcomes after corticosteroid administration has been completed, it is appropriate to withhold magnesium sulfate tocolysis from women with recurrent preterm labor thereafter. If magnesium sulfate is given for neuroprotection, a protocol from one of the three major trials that have demonstrated benefits should be used.

Small fetal size before 20 weeks' gestation: associations with maternal tobacco use, early preterm birth, and low birthweight.

OBJECTIVE: The objective of the study was to determine whether small fetal size before 20 weeks' gestation is associated with preterm birth (PTB), low birthweight (LBW), and poor fetal growth. STUDY DESIGN: A total of 4405 singleton pregnancies at 10-19 weeks' gestation (GA) based on a known last menstrual period (LMP) were evaluated. Ultrasound-estimated GA (US-GA) was calculated based on crown-rump length at 10-13 weeks and by femur, head, and abdominal measurements from 14 to 19 weeks. The outcomes were compared between small (1-10 days smaller than LMP-GA) and large (0-10 days larger than LMP-GA) fetuses. RESULTS: At 10-19 weeks, small fetuses measured 2.7 days younger and were more likely to have mothers who smoked (P = .004). Small fetuses had no more PTB (11.4 vs 12.1%, P = .47) but did have more early PTB before 34 (5.4 vs 4.3%, P = .07) and before 32 weeks (4.1 vs 2.7%, P = .009). Small fetuses had lower birthweights (BWT), more frequent BWT below 2500 g (13.0 vs 8.6%), below 1500 g (4.0 vs 2.4%), and below 1000 g (2.9 vs 1.4%) as well as BWT below 2500 g at term (4.9 vs 2.3%) and BWT less than the 10th percentile (8.8 vs 3.7%), P < or = .003 for each. Small fetuses at 10-19 weeks also had less frequent macrosomia and were less frequently large for gestational age at birth (P < .0001 for each). These findings largely persisted in multivariable analyses. CONCLUSION: Small fetal size at 10-19 weeks is associated with tobacco use in pregnancy, early PTB, LBW, and poor fetal growth.

Nuclear progesterone receptors in the human pregnancy myometrium: evidence that parturition involves functional progesterone withdrawal mediated by increased expression of progesterone receptor-A.

CONTEXT: We examined whether human parturition involves functional progesterone withdrawal mediated by changes in myometrial expression of progesterone receptors (PRs)-A and -B. OBJECTIVE: Our objectives were to: 1) measure PR-A and PR-B protein levels in human pregnancy myometrium and determine whether the PR-A to PR-B ratio changes with advancing gestation and labor onset; and 2) determine how changes in the PR-A to PR-B ratio affect myometrial cell progesterone responsiveness. DESIGN: PR protein levels and cellular localization were measured by Western blotting and immunohistochemistry, respectively, in lower uterine segment uterine wall tissue from preterm (<37 wk; not laboring; n = 5) and term (37-40 wk; not in labor: n = 6; in labor: n = 5) cesarean delivery. The capacity for PR-A and PR-B, alone and in combination, to mediate genomic progesterone responsiveness measured by the activity of a progesterone-responsive reporter plasmid was examined by artificially modulating their levels in the PHM1-31 myometrial cell line. RESULTS: PR-A and PR-B immunostaining was detected only in the nucleus of myometrial cells. The PR-A to PR-B protein ratio was 0.49 +/- 0.082 (mean +/- sem) in preterm tissue; increased to 1.03 +/- 0.071 (P < 0.001) in nonlaboring term tissue; and increased further to 2.65 +/- 0.344 (P < 0.001) in laboring term tissue. Only PR-B mediated progesterone-induced transcriptional activity. PR-A had no effect alone but markedly decreased PR-B-mediated progesterone responsiveness. CONCLUSIONS: Functional progesterone withdrawal in human parturition may be mediated by an increase in the myometrial PR-A to PR-B ratio due to increased PR-A expression.