Tracy Manuck

Outcomes of expectantly managed preterm premature rupture of membranes occurring before 24 weeks of gestation

OBJECTIVE: To assess contemporary outcomes in expectantly managed preterm premature rupture of membranes (PROM) before 24 weeks of gestation. METHODS: We analyzed all patients with singleton pregnancies and preterm PROM before 24 weeks of gestation from 2001 to 2007. Patients immediately electing delivery, delivering within 12 hours of preterm PROM, carrying anomalous fetus(es), or multiple gestations were excluded. Neonatal survival without major morbidities was the primary outcome. Data were analyzed with multivariable logistic regression and Cox regression models. Week-specific probability estimates for neonatal morbidity and mortality were calculated based on gestational age at the time of preterm PROM. RESULTS: One hundred fifty-nine women fulfilled study criteria. Median gestational age at preterm PROM for all patients was 21.4 (range 14.0–23.9) weeks of gestation. Median delivery gestational age was 24.7 (range 15.4–34.1) weeks. Forty-seven patients experienced either an intrauterine fetal demise, elected delivery after initial expectant management, or delivered before planned resuscitation. Of 112 newborns admitted to neonatal intensive care, 89 (56.0% of all neonates) survived; 43 (48.3% of survivors, 27.0% of all neonates) had no major neonatal morbidities. Morbidity probabilities decreased with increasing gestational age at the time of preterm PROM. Delivery gestational age was predictive of both neonatal morbidity and mortality. CONCLUSION: More than one half of women who achieved at least 12 hours of latency and elected expectant management had a surviving infant; nearly 50% of survivors had no major neonatal morbidity. These contemporary outcomes are valuable in counseling women with early preterm PROM. LEVEL OF EVIDENCE: III

Risk factors for unscheduled delivery in patients with placenta accreta

OBJECTIVE Patients with suspected placenta accreta have improved outcomes with scheduled delivery. Our objective was to identify risk factors for unscheduled delivery in patients with suspected placenta accreta. STUDY DESIGN This was a cohort study of women with antenatally suspected placenta accreta. Women who delivered prior to a planned delivery date were compared with women who had a scheduled delivery. Data were analyzed using a Student t test, χ(2), logistic regression, and survival analyses. Variables included in the analyses were episodes of antenatal vaginal bleeding, preterm premature rupture of membranes (PPROM), uterine contractions, prior cesarean deliveries, interpregnancy interval, parity, and patient demographic factors. A value of P < .05 was considered significant. RESULTS Seventy-seven women with antenatal suspicion for placenta accreta were identified. Thirty-eight (49.4%) had an unscheduled delivery. Demographics were similar between groups. Unscheduled patients delivered earlier (mean 32.3 vs 35.7 weeks, P < .001) and were significantly more likely to have had vaginal bleeding (86.8% vs 35.9%, P < .001) and uterine activity (47.4% vs 2.6%, P < .001). Each episode of antenatal vaginal bleeding was associated with an increased risk of unscheduled delivery (adjusted odds ratio, 3.8; 95% confidence interval, 1.8-7.8). Risk of earlier delivery was even greater when associated with PPROM (P < .001). CONCLUSION Among women with suspected placenta accreta, those with antenatal vaginal bleeding were more likely to require unscheduled delivery. This risk increases further in the setting of PPROM and/or uterine contractions. These clinical factors should be considered when determining the optimal delivery gestational age for women with placental accreta.

Maternal and fetal morbidity associated with uterine rupture of the unscarred uterus

OBJECTIVE We sought to report obstetric and neonatal characteristics and outcomes following primary uterine rupture in a large contemporary obstetric cohort and to compare outcomes between those with primary uterine rupture vs those with uterine rupture of a scarred uterus. STUDY DESIGN This was a retrospective case-control study. Cases were defined as women with uterine rupture of an unscarred uterus. Controls were women with uterine rupture of a scarred uterus. Demographics, labor characteristics, and obstetric, maternal, and neonatal outcomes were compared. Primary rupture case outcomes were also compared by mode of delivery. RESULTS There were 126 controls and 20 primary uterine rupture cases. Primary uterine rupture cases had more previous live births than controls (3.6 vs 1.9; P < .001). Cases were more likely to have received oxytocin augmentation (80% vs 37%; P < .001). Vaginal delivery was more common among cases (45% vs 9%; P < .001). Composite maternal morbidity was higher among primary uterine rupture mothers (65% vs 20%; P < .001). Cases had a higher mean estimated blood loss (2644 vs 981 mL; P < .001) and higher rate of blood transfusion (68% vs 17%; P < .001). Women with primary uterine rupture were more likely to undergo hysterectomy (35% vs 2.4%; P < .001). Rates of major composite adverse neonatal neurologic outcomes including intraventricular hemorrhage, periventricular leukomalacia, seizures, and death were higher in cases (40% vs 12%; P = .001). Primary uterine rupture cases delivering vaginally were more likely to ultimately undergo hysterectomy than those delivering by cesarean (63% vs 9%; P = .017). CONCLUSION Although rare, primary uterine rupture is particularly morbid. Clinicians must remain vigilant, particularly in the setting of heavy vaginal bleeding and severe pain.

Effect of interleukin-6 polymorphism on risk of preterm birth within population strata: a meta-analysis

BackgroundBecause of the role of inflammation in preterm birth (PTB), polymorphisms in and near the interleukin-6 gene (IL6) have been association study targets. Several previous studies have assessed the association between PTB and a single nucleotide polymorphism (SNP), rs1800795, located in the IL6 gene promoter region. Their results have been inconsistent and SNP frequencies have varied strikingly among different populations. We therefore conducted a meta-analysis with subgroup analysis by population strata to: (1) reduce the confounding effect of population structure, (2) increase sample size and statistical power, and (3) elucidate the association between rs1800975 and PTB.ResultsWe reviewed all published papers for PTB phenotype and SNP rs1800795 genotype. Maternal genotype and fetal genotype were analyzed separately and the analyses were stratified by population. The PTB phenotype was defined as gestational age (GA) < 37 weeks, but results from earlier GA were selected when available. All studies were compared by genotype (CC versus CG+GG), based on functional studies.For the maternal genotype analysis, 1,165 PTBs and 3,830 term controls were evaluated. Populations were stratified into women of European descent (for whom the most data were available) and women of heterogeneous origin or admixed populations. All ancestry was self-reported. Women of European descent had a summary odds ratio (OR) of 0.68, (95% confidence interval (CI) 0.51 – 0.91), indicating that the CC genotype is protective against PTB. The result for non-European women was not statistically significant (OR 1.01, 95% CI 0.59 - 1.75). For the fetal genotype analysis, four studies were included; there was no significant association with PTB (OR 0.98, 95% CI 0.72 - 1.33). Sensitivity analysis showed that preterm premature rupture of membrane (PPROM) may be a confounding factor contributing to phenotype heterogeneity.ConclusionsIL6 SNP rs1800795 genotype CC is protective against PTB in women of European descent. It is not significant in other heterogeneous or admixed populations, or in fetal genotype analysis.Population structure is an important confounding factor that should be controlled for in studies of PTB.

Neonatal and early childhood outcomes following early vs later preterm premature rupture of membranes

OBJECTIVE Data regarding long-term outcomes of neonates reaching viability following early preterm premature rupture of membranes (PPROM; <25.0 weeks at rupture) are limited. We hypothesized that babies delivered after early PPROM would have increased rates of major childhood morbidity compared with those with later PPROM (≥25.0 weeks at rupture). STUDY DESIGN This was a secondary analysis of a multicenter randomized controlled trial of magnesium sulfate vs placebo for cerebral palsy prevention. Women with singletons and PPROM of 15-32 weeks were included. All women delivered at 24.0 weeks or longer. Those with PPROM less than 25.0 weeks (cases) were compared with women with PPROM at 25.0-31.9 weeks (controls). Composite severe neonatal morbidity (sepsis, severe intraventricular hemorrhage, periventricular leukomalacia, severe necrotizing enterocolitis, bronchopulmonary dysplasia, and/or death) and composite severe childhood morbidity at age 2 years (moderate or severe cerebral palsy and/or Bayley II Infant and Toddler Development scores greater than 2 SD below the mean) were compared. RESULTS A total of 1531 women (275 early PPROM cases) were included. Demographics were similar between the groups. Cases delivered earlier (26.6 vs 30.1 weeks, P < .001) and had a longer rupture-to-delivery interval (20.0 vs 10.4 days, P < .001). Case neonates had high rates of severe composite neonatal morbidity (75.6% vs 21.8%, P < .001). Children with early PPROM had higher composite severe childhood morbidity (51.6% vs 22.5%, P < .001). Early PPROM remained associated with composite severe childhood morbidity in multivariable models, even when controlling for delivery gestational age and other confounders. CONCLUSION Early PPROM is associated with high rates of neonatal morbidity. Early childhood outcomes at age 2 years remain poor compared with those delivered after later PPROM.

Pregnancy outcomes in a recurrent preterm birth prevention clinic.

OBJECTIVE We sought to compare rates of recurrent spontaneous preterm birth (PTB) and neonatal morbidity between women enrolled in a recurrent PTB prevention clinic compared to those receiving usual care. STUDY DESIGN This was a retrospective cohort study of women with a single, nonanomalous fetus and ≥1 spontaneous PTB <35 weeks. Women enrolled in a recurrent PTB prevention clinic were compared to those receiving usual care. The recurrent PTB prevention clinic was consultative and included 3 standardized visits. Usual-care patients were treated by their primary provider. The primary outcome was recurrent spontaneous PTB <37 weeks. RESULTS Seventy recurrent PTB prevention clinic and 153 usual-care patients were included. Both groups had similar pregnancy histories. Recurrent PTB prevention clinic patients had increased utilization of resources, had lower rates of recurrent spontaneous PTB (48.6% vs 63.4%, P = .04), delivered later (mean 36.1 vs 34.9 weeks, P = .02), and had lower rates of composite major neonatal morbidity (5.7% vs 16.3%, P = .03). CONCLUSION Women referred to a consultative recurrent PTB prevention clinic had reduced rates of recurrent spontaneous prematurity and major neonatal morbidity.

Progesterone receptor genotype, family history, and spontaneous preterm birth.

OBJECTIVE: To examine whether women with a personal or family history of preterm birth are more likely to have genetic variation in the human progesterone receptor (hPR). METHODS: Women with a singleton preterm birth at less than 37 weeks of gestation between 2002 and 2006 were identified from a prospectively collected clinical and biologic obstetric database (cases). Women in the control group were those with only term deliveries at or above 38 weeks of gestation. The Utah Population Database was queried for family history (first- or second-degree relative) of preterm birth. DNA was extracted from stored buffy coats and genotyped for six single nucleotide polymorphisms in the hPR. RESULTS: One hundred fifty-four patients (92 women in the preterm case group, 62 women in the term control group) were included. All were white or Hispanic. There were no statistical differences between white and Hispanic allele frequencies. Women in the preterm case group were more likely to carry the minor allele, G (minor allele frequency 0.29 compared with 0.18, P=.035) for rs471767, and were more likely to carry the GT haplotype across rs471767 and rs578029 compared with women in the term control group. Similar haplotype block variation was seen among women with preterm birth plus a family history of preterm birth. CONCLUSION: Allele and haplotype frequencies in the hPR are significantly different among women with preterm birth and women with preterm birth plus a family history of preterm birth. This suggests the hPR gene may be a candidate for association with preterm birth or familial preterm birth. LEVEL OF EVIDENCE: III

Admixture mapping to identify spontaneous preterm birth susceptibility loci in African Americans.

OBJECTIVE: Preterm birth is 1.5 times more common in African American (17.8%) than European American women (11.5%), even after controlling for confounding variables. We hypothesize that genetic factors may account for this disparity and can be identified by admixture mapping. METHODS: This is a secondary analysis of women with at least one prior spontaneous preterm birth enrolled in a multicenter prospective study. DNA was extracted and whole-genome amplified from stored saliva samples. Self-identified African American patients were genotyped with a 1,509 single nucleotide polymorphism (SNP) commercially available admixture panel. A logarithm of odds locus-genome score of 1.5 or higher was considered suggestive and 2 or higher was considered significant for a disease locus. RESULTS: One hundred seventy-seven African American women with one or more prior spontaneous preterm births were studied. One thousand four hundred fifty SNPs were in Hardy-Weinberg equilibrium and passed quality filters. Individuals had a mean of 78.3% to 87.9% African American ancestry for each SNP. A locus on chromosome 7q21-22 was suggestive of an association with spontaneous preterm birth before 37 weeks of gestation (three SNPs with logarithm of odds scores 1.50–1.99). This signal strengthened when women with at least one preterm birth before 35.0 (eight SNPs with logarithm of odds scores greater than 1.50) and before 32.0 weeks of gestation were considered (15 SNPs with logarithm of odds scores greater than 1.50). No other areas of the genome had logarithm of odds scores higher than 1.5. CONCLUSION: Spontaneous preterm birth in African American women may be genetically mediated by a susceptibility locus on chromosome 7. This region contains multiple potential candidate genes, including collagen type 1-&agr;-2 gene and genes involved with calcium regulation. LEVEL OF EVIDENCE: III

Magnesium sulfate, chorioamnionitis, and neurodevelopment after preterm birth.

To assess the neuroprotective effect of magnesium sulfate (MgSO4) in preterm children exposed to chorioamnionitis.

Risk factors associated with preterm birth after a prior term delivery

The objective of this study was to assess the presence of newly acquired preterm birth (PTB) risk factors among primiparous women with no prior history of PTB.