Jessica McPherson

Association of duration of neuroprotective magnesium sulfate infusion with neonatal and maternal outcomes.

OBJECTIVE: To evaluate the association of duration of magnesium sulfate infusion with stillbirth or death, cerebral palsy, and select adverse maternal and neonatal outcomes. METHODS: This is a secondary cohort analysis of women randomized to receive magnesium sulfate within a previously reported Maternal-Fetal Medicine Units Network prospective clinical trial. The association of antenatal infusion of magnesium sulfate for less than 12 hours, 12–18 hours, and greater than 18 hours on maternal and perinatal outcomes was compared. The primary outcome was cerebral palsy of any severity or death. Secondary outcomes included cerebral palsy, death, and select maternal and neonatal outcomes. Stratified and logistic regression analyses were used. The models were adjusted for race, gestational age at birth, time since last magnesium sulfate, any magnesium sulfate at delivery, and eligibility criteria as appropriate. RESULTS: Of 933 women available for analysis, 356, 341, and 236 received antenatal magnesium sulfate infusion for a total of less than 12 hours, 12–18 hours, or greater than 18 hours, respectively. Any cerebral palsy or death occurred in 39 women (11.7%) who received magnesium sulfate less than 12 hours, 34 women (10.3%) who received 12–18 hours of magnesium sulfate, and 20 women (8.8%) who received greater than 18 hours of magnesium sulfate. There was no difference in death or cerebral palsy among groups (less than 12 hours as reference; adjusted odds ratio [OR] 1.03, 95% confidence interval [CI] 0.60–1.77 for 12–18 hours; adjusted OR 1.08, 95% CI 0.57–2.03 for greater than 18 hours). Select maternal adverse drug affects and neonatal morbidities were also similar across groups. CONCLUSION: The duration of antenatal magnesium sulfate infusion is not associated with risk of death or cerebral palsy. The optimal treatment duration needed for maximal neuroprotection remains unknown. LEVEL OF EVIDENCE: II

Maternal seizure disorder and risk of adverse pregnancy outcomes

OBJECTIVE We sought to estimate the association between maternal seizure disorder and adverse pregnancy outcomes. STUDY DESIGN We performed a retrospective cohort study of singleton, nonanomalous pregnancies. Women with self-reported seizure disorder were compared to women without medical problems. The primary outcome was intrauterine growth restriction (IUGR) <10th percentile. Secondary outcomes included IUGR <5th percentile, stillbirth, preeclampsia, and preterm delivery. A sensitivity analysis was performed using women who reported using antiepileptics to estimate the impact of disease severity on pregnancy outcomes. RESULTS Of 47,118 women, 440 reported a seizure disorder. Women with seizure disorder were not at increased risk of IUGR <10th percentile (adjusted odds ratio, 1.11; 95% confidence interval, 0.82-1.50), IUGR <5th percentile, stillbirth, preeclampsia, or preterm delivery. The results were similar in the sensitivity analysis of women taking antiseizure medications. CONCLUSION Our results suggest women with a seizure disorder are not at increased risk of IUGR, stillbirth, preeclampsia, or preterm delivery.

Impact of chorionicity on risk and timing of intrauterine fetal demise in twin pregnancies

OBJECTIVE We sought to estimate the association between chorionicity and intrauterine fetal demise (IUFD) of one or both fetuses in twin pregnancies. STUDY DESIGN In a retrospective cohort of twins undergoing anatomic survey, risk of IUFD in monochorionic and dichorionic twins was compared. The primary outcome was IUFD of one or both fetuses; secondary outcomes included nonanomalous fetal deaths. RESULTS Of 2161 twin pregnancies meeting inclusion criteria, 86 had at least 1 IUFD and 32 experienced a double fetal loss. Monochorionic pregnancies had an increased risk of a single demise (adjusted odds ratio, 1.69; 95% confidence interval, 1.04-2.75) and a double demise (adjusted odds ratio, 2.11; 95% confidence interval, 1.02-4.37). Of all double demises, 70% occurred <24 weeks. CONCLUSION Monochorionic twins carry an increased risk of fetal death compared to dichorionic twins. Double demise occurs primarily <24 weeks, regardless of chorionicity.

Association between Cerebral Palsy or Death and Umbilical Cord Blood Magnesium Concentration.

OBJECTIVE This study aims to evaluate whether magnesium sulfate (MgSO4) infusion at the time of delivery or magnesium cord blood concentration is associated with cerebral palsy (CP) or death diagnosed by the age of 2 years. METHODS Secondary analysis of data from a randomized trial of MgSO4 versus placebo for prevention of CP or death among offspring of women with anticipated preterm delivery. This study cohort included singleton, nonanomalous fetuses, whose mothers received MgSO4 as neuroprophylaxis. The primary outcomes were CP or death diagnosed by the age of 2 years. RESULTS A total of 936 neonates (93 with CP or death, 843 controls) were included in the analysis. Infants in the group with CP or death had MgSO4 infusing at delivery at a similar frequency to that of controls (49 [52.7%] vs. 463 [54.9%], p = 0.68). Mean concentrations of cord blood magnesium, available for 596 neonates, also were not different between the two groups (2.7 ± 0.9 vs. 2.6 ± 0.9 mEq/L, p = 0.66, respectively). Multivariable analyses did not alter these findings. CONCLUSION Among the offspring of women exposed to MgSO4, in utero, neither MgSO4 infusion at the time of delivery nor magnesium cord blood concentration is associated with CP or death.

Adverse outcomes in twin pregnancies complicated by early vaginal bleeding.

OBJECTIVE We sought to estimate the risks of adverse pregnancy outcomes associated with early vaginal bleeding in twin pregnancies. STUDY DESIGN In a retrospective cohort study of consecutive twin pregnancies undergoing anatomic survey, we compared women who reported vaginal bleeding at <22 weeks to those who did not. Exclusion criteria included monoamniotic pregnancies, twin-to-twin transfusion syndrome, and placenta previa. Primary outcomes included preeclampsia, abruption, preterm premature rupture of membranes (PPROM), preterm birth <34 weeks, and intrauterine growth restriction. RESULTS Of 2106 pregnancies meeting inclusion criteria, 175 reported vaginal bleeding. Twin pregnancies with early vaginal bleeding had significantly higher risks of abruption, PPROM, and preterm birth compared to twin pregnancies without bleeding. The findings were similar when twin pairs were stratified by parity or maternal comorbidities. CONCLUSION Twin pregnancies complicated by vaginal bleeding in early pregnancy have an increased risk of abruption, PPROM, and preterm birth <34 weeks.

Genomics of Preterm Birth-Evidence of Association and Evolving Investigations

Preterm birth (PTB) is a large public health problem in the United States and worldwide. There is a clear genetic component to the pathogenesis of PTB, as evidenced by twin studies, heritability studies, and investigations from large population databases. Although numerous single nucleotide polymorphisms have been associated with PTB, results have been inconsistent and overall disappointing. With recent advances in genetic technology, investigations are moving beyond simple, more traditional candidate gene studies, and have expanded to encompass more exploratory analyses using high-throughput genetic techniques. Care should be taken to consider the potential impact of fetal genotype, the environment, and gene-drug interactions (pharmacogenomics) in addition to maternal genotype. Future research should capitalize on evolving analytic techniques, including pathway analyses and correlation of genetic and functional data to optimize discovery, increase knowledge regarding prematurity pathogenesis, and begin to develop novel therapeutic strategies.

Maternal obesity and neuroprotective magnesium sulfate

OBJECTIVE Given the association between risk of cerebral palsy and children born to obese women, the study aim was to estimate whether maternal obesity is associated with reduced effectiveness of conventional antenatal magnesium sulfate dosing for the prevention of cerebral palsy and death. STUDY DESIGN This is a secondary cohort analysis of a multicenter randomized clinical trial completed by the Maternal-Fetal Medicine Units Network. Women were included in the original trial if deemed high risk for preterm delivery in the subsequent 24 hours. The present study included singleton, nonanomalous fetuses that were randomized to and received magnesium sulfate with complete data available. Outcomes between obese (body mass index ≥30 kg/m(2)) and nonobese women were compared. A secondary analysis of outcomes between morbidly obese (body mass index ≥40 kg/m(2)) and nonmorbidly obese women was performed. The primary outcome was a composite of cerebral palsy or perinatal death before 15 months corrected age. Secondary outcomes included moderate to severe cerebral palsy or death, any cerebral palsy, moderate to severe cerebral palsy, and death. A logistic regression analysis was used to estimate the odds ratio of each outcome. Based on sample size, exposure rate (obesity) and an outcome rate of 10%, assuming an 80% power and a 0.05 alpha error, this study had sufficient power to detect a 2-fold increase in the primary outcome. RESULTS Of 1188 women randomized to receive magnesium sulfate, 806 were included in this analysis. After adjusting for gestational age at delivery, maternal obesity was not associated with an increased risk of cerebral palsy or death in children born to women who received magnesium sulfate. Women with morbid obesity had higher rates of the primary outcome and cerebral palsy in an unadjusted analysis but did not have increased risks after adjusting for gestational age at delivery. In analyses stratified on gestational age, morbidly obese women who delivered after 28 weeks had increased risks of children with cerebral palsy or death and cerebral palsy, although case numbers were small. CONCLUSION Among women receiving antenatal neuroprotective magnesium sulfate, maternal obesity is not associated with an increased risk of having a child with cerebral palsy or death.

Nonreassuring fetal status during trial of labor after cesarean.

OBJECTIVE Concern for uterine rupture has led to the decline in vaginal births after cesarean. Nonreassuring fetal status (NRFS) may precede uterine rupture. The objective of this study was to estimate the risks of uterine rupture, uterine dehiscence, and adverse fetal outcomes associated with NRFS during trial of labor after cesarean (TOLAC). STUDY DESIGN In a retrospective cohort study of the previously reported Maternal-Fetal Medicine Units Network prospective cohort cesarean registry, we compared women undergoing repeat cesarean for NRFS after TOLAC to those requiring repeat cesarean for other intrapartum indications. Exclusion criteria included women with a prior cesarean who underwent elective or indicated repeat cesarean or women with a multiple gestation. Primary outcomes included uterine rupture or dehiscence. Secondary outcomes included 5-minute Apgar score <7 and neonatal intensive care unit admission. Planned subanalyses for term and preterm deliveries were performed. Stratified and logistic regression analyses were used. RESULTS Of 17,740 women undergoing TOLAC, 4754 (26.8%) had a failed vaginal birth after cesarean. Of those, NRFS was the primary indication for cesarean in 1516 (31.9%). Women with NRFS as the primary indication for repeat cesarean were at increased risk of uterine rupture (adjusted odds ratio, 3.32; 95% confidence interval, 2.21-5.00), uterine dehiscence (adjusted odds ratio, 1.70; 95% confidence interval, 1.09-2.65), 5-minute Apgar score <7, and neonatal intensive care unit admission compared to women with other primary indications. CONCLUSION Women attempting TOLAC who require repeat cesarean for NRFS are at increased risk of uterine rupture and uterine dehiscence.

Association of Maternal Obesity with Child Cerebral Palsy or Death.

Objective The primary aim of this study was to determine if there is an association between maternal obesity and cerebral palsy or death in children. Study Design This is a retrospective cohort analysis of a randomized controlled clinical trial previously performed by the Maternal‐Fetal Medicine Units Network. Women in the original trial were included if at high risk for preterm delivery. The present study included singletons enrolled in the original study with complete data. Obese and nonobese women were compared. A secondary analysis comparing class 3 obese or classes 1 to 2 obese women to nonobese women was performed. The primary outcome was a composite of cerebral palsy or perinatal death. Results In this study, 1,261 nonobese, 339 obese, and 69 morbidly obese women were included. When adjusted for gestational age at delivery and magnesium exposure, there was no association between maternal obesity and child cerebral palsy or death. In the analysis using obesity severity categories, excess risk for adverse outcome appeared confined to the class 3 obese group. Conclusion In women at high risk of delivering preterm, maternal obesity was not independently associated with child cerebral palsy or death. The association in unadjusted analysis appears to be mediated by preterm birth among obese patients.

Labor progression in teenage women.

OBJECTIVE Compare labor progression in first and second stages in women < 18 years with those ≥18 years. STUDY DESIGN Retrospective cohort study of consecutive women at term that reached the second stage of labor between 2004 and 2008. The first stage in women < 18 years was compared with women ≥18 years. Average labor curves were constructed and median time spent to progress 1 cm in dilation and total time from 4 to 10 cm was estimated. Time spent pushing and total duration of second stage were compared between groups. Analyses were then stratified by parity. RESULTS There was no significant difference in progress of the first stage of labor between women < 18 years and those ≥18 years. In the second stage, nulliparous teenage women were less likely to have a duration > 60 or 120 minutes. CONCLUSION Laboring women < 18 years should be managed with the same expectations of labor as women ≥18 years.