David N. Hackney

Perinatal outcomes in type 2 diabetic patients compared with non-diabetic patients matched by body mass index

Objective: Given that both type 2 diabetes and obesity are associated with adverse pregnancy outcomes and often coexist, we sought to determine if outcomes in type 2 diabetic patients are related to the presence of diabetes or to maternal obesity. Methods: This retrospective cohort study examined perinatal outcomes of type 2 diabetic and nondiabetic patients matched by prepregnancy body mass index January 2000 to July 2008. Chi-square, Fisher’s exact test, Mann-Whitney U and t-tests were used to compare groups. The association between type 2 diabetes and adverse perinatal outcomes was evaluated through logistic regression with adjustment for potential confounders. Results: 213 pairs of type 2 and non-diabetic patients were compared. Diabetic patients had overall worse composite pregnancy, delivery, fetal, and neonatal outcomes. Specifically, diabetic patients had higher rates of preeclampsia, poly- and oligohydramnios, cesarean delivery, shoulder dystocia, postpartum hemorrhage, preterm delivery, LGA infant, fetal anomaly, and neonatal hypoglycemia, hyperbilirubinemia, RDS, sepsis, intubation, and admission to the NICU. Diabetes remained a significant predictor of adverse delivery, fetal and neonatal composite outcomes when adjusted for confounders in logistic regression. Conclusions: Type 2 diabetic patients have a higher incidence of adverse perinatal outcomes than nondiabetic patients independent of obesity.

What Do We Know about the Natural Outcomes of Preterm Labour? A Systematic Review and Meta-Analysis of Women without Tocolysis in Preterm Labour

BACKGROUND Current knowledge of the natural outcomes of untreated women in preterm labour is both incomplete and outcomes vary significantly between the available studies. The aim of this study was to systematically review outcomes of preterm labour without tocolysis and determine if outcome variation could be accounted for by differences in study populations. Such data could potentially assist in the interpretation of intervention trials that do not include a no-treatment arm. METHODS Included studies reported outcomes of women in clinically diagnosed preterm labour without tocolytic treatment between 1950 and 2011. Studies that were limited to preterm prelabour rupture of membranes, recurrent preterm labour or in which the women without tocolysis represented a potentially biased subgroup, or were not tocolysed because of contraindications were excluded. Study quality, design, and population characteristics were abstracted. Outcomes included pregnancy prolongation and the proportion of women undelivered at 48-72 h, 7 days, and term. Study characteristics associated with differing odds of preterm birth were explored through logistic regression. RESULTS Three hundred and eighty-five citations were initially identified, of which 26 were included encompassing 1383 women. The percentage of patients who were undelivered at 48-72 hours was 62.8%, at 7 days 53.4% and 40.4% delivered at term, though the range was very wide. Characteristics associated with decreased odds of delivery were not consistent among reported outcome measures. CONCLUSIONS Most women without tocolysis do not deliver within 7 days, although the range is very wide. The majority of this variation is unrelated to reported differences in study design or reported population characteristics.

Is the Accuracy of Prior Preterm Birth History Biased by Delivery Characteristics

To assess the sensitivity of birth certificates to preterm birth history and determine whether omissions are randomly or systemically biased. Subjects who experienced a preterm birth followed by a subsequent pregnancy were identified in a regional database. The variable “previous preterm birth” was abstracted from birth certificates of the subsequent pregnancy. Clinical characteristics were compared between subjects who were correctly versus incorrectly coded. 713 subjects were identified, of whom 65.5% were correctly coded in their subsequent pregnancy. Compared to correctly coded patients, patients who were not correctly identified tended to have late and non-recurrent preterm births or deliveries that were secondary to maternal or fetal indications. A recurrence of preterm birth in the subsequent pregnancy was also associated with correct coding. The overall sensitivity of birth certificates to preterm birth history is suboptimal. Omissions are not random, and are associated with obstetrical characteristics from both the current and prior deliveries. As a consequence, resulting associations may be flawed.

Vaginal bleeding in early pregnancy and preterm birth: systemic review and analysis of heterogeneity

Objective. To systemically review published studies of vaginal bleeding and the risk of preterm birth (PTB) and explore sources of heterogeneity between them. Methods. The literature was searched for peer-reviewed articles from 1980 to 2009 in which the primary analysis was the risk of PTB among low-risk subjects with and without bleeding. Heterogeneity was assessed through I2 statistics, and sources of heterogeneity were explored through subgroup analyses and meta-regression. Results. 218 studies were initially identified, 64 reviewed and 23 included. The pooled Odds Ratio for PTB was 1.74, though significant heterogeneity was present (I2 = 49.7%). Meta-regression demonstrated a significant association between a studys incidence of bleeding and quality assessment and subsequent odds ratio, such that studies with a lower quality assessment or lower incidence of bleeding demonstrated an increased odds of PTB. Conclusions. Bleeding in early pregnancy is associated with an increased risk of PTB; however, excessive heterogeneity exists among published studies. The heterogeneity arises in part from differences in the reported incidence of bleeding within study populations. Presumably studies that identify bleeding in a larger percentage of subjects consequently dilute the magnitude of the risk.

Chlamydia trachomatis and Adverse Pregnancy Outcomes: Meta-analysis of Patients With and Without Infection

ObjectivesWe conducted a meta-analysis to determine the association between Chlamydia trachomatis and adverse perinatal outcomes.MethodsElectronic databases were searched between 1970 and 2013. Included studies reported perinatal outcomes in women with and without chlamydia. Summary odds ratios were calculated using fixed- and random-effects models. Study bias was assessed using a Funnel Plot and Begg’s test.ResultsOf 129 articles identified, 56 studies met the inclusion criteria encompassing 614,892 subjects. Chlamydia infection in pregnancy was associated with preterm birth (OR = 1.27, 95% CI 1.05, 1.54) with a large quantity of heterogeneity (I2 = 61%). This association lost significance when limiting the analysis to high-quality studies based on the Newcastle–Ottawa Scale. Chlamydia infection in pregnancy was also associated with preterm premature rupture of membranes (OR = 1.81, 95% CI 1.0, 3.29), endometritis (OR 1.69, 95% CI 1.20, 2.38), low birthweight (OR 1.34, 95% CI 1.21, 1.48), small for gestational age (OR 1.14, 95% CI 1.05, 1.25) and intrauterine fetal demise (OR 1.44, 95% CI 1.06, 1.94).ConclusionsThis review provides evidence that chlamydia in pregnancy is associated with a small increase in the odds of multiple adverse pregnancy outcomes. The literature is complicated by heterogeneity and the fact that the association may not hold in higher quality and prospective studies or those that use more contemporary nucleic acid testing.

Maternal outcomes following the initiation of an institutional delayed cord clamping protocol: an observational case–control study

Abstract Objective: The objective of this study is to evaluate maternal outcomes before and after implementation of an institutional delayed cord clamping (DCC) protocol. Study design: We performed a secondary analysis of a retrospective cohort study of deliveries occurring at <34 weeks at a tertiary care center in 2013–2014. About 139 women who underwent early cord clamping were compared with 130 women delivered after DCC protocol implementation. Maternal estimated blood loss (EBL) was the primary outcome of interest. Operative times, post-Cesarean decrease in hemoglobin (Hgb), and rates of post-partum hemorrhage and transfusion were also examined in bivariate and multivariable analyses. Results: About 75% of post-guideline deliveries had actual DCC. In regression analyses, only Cesarean delivery and multifetal gestation increased EBL. No trends were identified in EBL over time. In post-hoc analysis, the study had over 80% power to detect a difference in post-partum hemorrhage rates of 20%. Conclusion: An institutional DCC protocol for deliveries <34 weeks was not associated with an identifiable increase in adverse maternal outcomes.

Re-evaluation of the subgroup analysis from the Royal College of Obstetricians and Gynaecologists randomized controlled trial of cervical cerclage

History-indicated cervical cerclage is offered to patients who are at risk of spontaneous preterm birth (SPTB), though the indications are controversial. A common practice of offering cerclage after three prior SPTBs or midtrimester losses (MTLs) is based on findings of the subgroup analysis of the 1993 Royal College of Obstetricians and Gynaecologists (RCOG) randomized trial of cervical cerclage. The subgroup analysis was performed by repeating the primary analysis within individual subgroups, which can lead to erroneous conclusions. We repeated the subgroup analysis by evaluating the interaction between the characteristic of interest and treatment allocation in a regression model. The interaction between cerclage and any prior PTB as a binary variable was non-significant. Among subjects delivering at <37 weeks, there was a significant interaction between cerclage and prior PTBs as a continuous variable or ≥ 3 (p-values 0.04 and 0.03, respectively). There were no significant interactions between cerclage and the aforementioned outcomes among women who delivered at <33 weeks, though this may have been secondary to a smaller number of SPTB in this range. Our findings lend credence to the current recommendations regarding the use of history-indicated cerclage, though they remain subject to the inherent limitations of subgroup analyses.

Outcomes of Term Induction in Trial of Labor After Cesarean Delivery: Analysis of a Modern Obstetric Cohort.

OBJECTIVE: To evaluate outcomes of induction of labor, compared with expectant management, in women attempting trial of labor after cesarean delivery (TOLAC) in a large obstetric cohort. METHODS: We performed a secondary analysis of data from the Consortium on Safe Labor that included women with term (37 weeks of gestation or greater) singleton gestations and a history of one prior cesarean delivery who attempted TOLAC. Induction of labor was compared with expectant management by week of gestation from 37 to 40 weeks in both high- and low-risk cohorts. The primary outcome was failed TOLAC. Secondary outcomes included composite maternal morbidity (hysterectomy, transfusion, intensive care unit (ICU) transfer, venous thromboembolism, death), composite neonatal morbidity (5-minute Apgar score less than 5, cord pH less than 7.0, asphyxia, hypoxic ischemic encephalopathy, neonatal death), and neonatal ICU admission. Multivariate logistic regression was performed with adjustment for confounding factors. RESULTS: We identified 6,033 women attempting TOLAC of whom 1,626 (27.0%) underwent induction of labor and 4,407 (73.0%) did not. Compared with expectant management, induction was associated with an increased risk of failed TOLAC at 37–39 weeks of gestation but not at 40 weeks of gestation (37 weeks of gestation, 48.5% compared with 34.3%, adjusted odds ratio [OR] 1.53, 95% confidence interval [CI] 1.02–2.28]; 38 weeks of gestation, 47.0% compared with 33.0%, adjusted OR 1.74, 95% CI 1.29–2.34; 39 weeks of gestation, 45.6% compared with 29.8%, adjusted OR 2.16, 95% CI 1.76–2.67; 40 weeks of gestation, 37.9% compared with 29.4%, adjusted OR 1.21, 95% CI 0.90–1.66). Induction was associated with an increased risk of composite maternal morbidity at 39 weeks of gestation (adjusted OR 1.87, 95% CI 1.22–2.87) and neonatal ICU admission at 37 weeks of gestation (adjusted OR 2.51, 95% CI 1.62–3.90). Induction was not associated with an increased risk of neonatal morbidity. CONCLUSION: Induction of labor in women with one prior cesarean delivery, compared with expectant management, is associated with an increased risk of failed TOLAC. Apart from small increases in maternal morbidity at 39 weeks and neonatal ICU admission at 37 weeks of gestation, induction is not associated with an increased risk of severe maternal or neonatal morbidity. LEVEL OF EVIDENCE: II

Pregnancy outcomes of women with failure to retain rubella immunity.

Abstract Objective: We sought to explore the clinical variables associated with the loss of rubella immunity during pregnancy and to determine if these changes are linked to obstetrical complications. Methods: This is a case-control study in which women were identified whose rubella antibody titers were equivocal or non-immune and compared to those who had retained immunity. Two hundred and eighty-five cases were identified and compared to the same number of controls using Student’s t test, Mann–Whitney U-test or Fisher’s exact test. Univariate and multivariate logistic regressions were employed. Results: Subjects with diminished immunity were more likely to have public insurance and higher gravidity with a trend toward increased tobacco use. Diminished rubella immunity was not associated with adverse obstetrical outcomes, including preterm birth and pre-eclampsia and is likely not a risk factor for these pregnancy outcomes. Conclusion: While no adverse pregnancy outcomes were associated with a loss of rubella immunity, women with greater number of pregnancies appear to lose their immunity to rubella. This relationship needs to be explored further and if proven, revaccination prior to pregnancy may need to be addressed.

Determinants of the competing outcomes of intrauterine infection, abruption, or spontaneous preterm birth after preterm premature rupture of membranes

Abstract Objective: Patients with PPROM are at risk for a variety of outcomes, including chorioamnionitis (CA), placental abruption (PA), or preterm labor (PTL). Competing risk regression can analyze a cohort’s risk of individual outcomes while accounting for ongoing deliveries secondary to competing events. Methods: A secondary analysis of the subjects from MFMU BEAM study of neuroprotection after preterm birth (BEAM) with conservative PPROM management. Deliveries were categorized as: PA, CA, PTL, “elective” or “indicated”. The association between outcomes of PA, CA or PTL and clinical predictors of twins, ethnicity, parity, gestational age at rupture, bleeding, contractions, cervical dilation, preterm birth history, weight, and genitourinary infections were evaluated via competing risk regression. Result: 1970 subjects were included. The significance and directionality of predictors varied according to specific outcomes. Patients with twins had an increased PTL hazard (1.85) though reductions in CA- (0.66) or PA-specific (0.56) hazards. Decreased latency in African-Americans was almost entirely due to an increased CA hazard (1.44) without a significant association with PTL. Increasing gestational age at membrane rupture was associated with a decreasing hazard of CA although increasing hazard of PTL. Conclusions: For patients with PPROM, the hazards associated with different clinical predictors vary according to exact outcomes.