Chronic hypertension, perinatal mortality and the impact of preterm delivery: a population-based study.

OBJECTIVES: To estimate the association between chronic hypertension and perinatal mortality and to evaluate the extent to which risks are impacted by preterm delivery. DESIGN: Cross-sectional analysis. SETTING: United States, 2015-18. POPULATION: Singleton births (20-44 weeks of gestation). EXPOSURE: Chronic hypertension, defined as elevated blood pressure diagnosed before pregnancy or recognised before 20 weeks of gestation. MAIN OUTCOMES AND MEASURES: We derived the risk of perinatal mortality in relation to chronic hypertension from Poisson models, adjusted for confounders. The impacts of misclassification and unmeasured confounding were assessed. Causal mediation analysis was performed to quantify the impact of preterm delivery on the association. RESULTS: Of the 15 090 678 singleton births, perinatal mortality rates were 22.5 and 8.2 per 1000 births in chronic hypertensive and normotensive pregnancies, respectively (adjusted risk ratio 2.05, 95% CI 2.00-2.10). Corrections for exposure misclassification and unmeasured confounding biases substantially increased the risk estimate. Although causal mediation analysis revealed that most of the association of chronic hypertension on perinatal mortality was mediated through preterm delivery, the perinatal mortality rates were highest at early term, term and late term gestations, suggesting that a planned early term delivery at 37-386/7 weeks may optimally balance risk in these pregnancies. Additionally, 87% (95% CI 84-90%) of perinatal deaths could be eliminated if preterm deliveries, as a result of chronic hypertension, were preventable. CONCLUSIONS: Chronic hypertension is associated with increased risk for perinatal mortality. Planned early term delivery and targeting modifiable risk factors for chronic hypertension may reduce perinatal mortality rates. TWEETABLE ABSTRACT: Maternal chronic hypertension is associated with increased risk for perinatal mortality, largely driven by preterm birth.

Trends in operative vaginal delivery, 2005-2013: a population-based study.

OBJECTIVE: The objectives of this study were to determine temporal trends in forceps and vacuum delivery and factors associated with operative vaginal delivery. DESIGN: Retrospective cohort. SETTING: Population-based study of US birth records. POPULATION: US births from 2005 to 2013. METHODS: This study evaluated forceps and vacuum extraction during vaginal delivery in live-born, non-anomalous singleton gestations from ≥ 36 to < 42 weeks of gestation. The primary outcomes were vacuum, forceps and overall operative delivery. Obstetric, medical and demographic characteristics associated with operative vaginal delivery were analysed. Multivariable logistic regression models were developed to determine factors associated with forceps/vacuum use. RESULTS: A total of 22 598 971 vaginal deliveries between 2005 and 2013 were included in the analysis. In all, 1 083 318 (4.8%) were vacuum-assisted and 237 792 (1.1%) were by forceps. Both vacuum and forceps deliveries decreased over the study period; vacuum deliveries decreased from 5.8% in 2005 to 4.1% in 2013, and forceps deliveries decreased from 1.4% to 0.9% during the same period. The adjusted odds ratio for forceps delivery was 0.70 (95% CI 0.69-0.72) in 2013 with 2005 as a reference. For vacuum delivery the odds ratio was 0.68 (95% CI 0.67-0.69) comparing the same years. CONCLUSION: Forceps and vacuum deliveries decreased during the study period. Low rates of operative delivery pose a challenge for resident education and may limit the degree to which women have access to alternatives to caesarean delivery. Initiatives that allow future generations of obstetricians to develop expertise in performing operative deliveries in the setting of decreased volume are an urgent resident education priority. TWEETABLE ABSTRACT: Forceps and vacuum delivery decreased significantly in the USA from 2005 to 2013.

Neurodevelopmental outcomes in children in relation to placental abruption.

OBJECTIVE: Placental abruption has a profound impact on perinatal mortality, but implications for neurodevelopment during childhood remain unknown. We examined the association between abruption and neurodevelopment at 8 months and 4 and 7 years and evaluated the extent to which these associations were mediated through preterm delivery. DESIGN: Secondary analysis of a multicenter prospective cohort study. SETTING: Multicenter US National Collaborative Perinatal Project (1959-76). POPULATION: Women that delivered singleton live births. METHODS: Analyses of IQ scores were based on marginal structural models (MSM) to account for losses to follow-up. We also carried out a causal mediation analysis to evaluate if the association between abruption and cognitive deficits was mediated through preterm delivery, and performed a sensitivity analysis for unobserved confounding. MAIN OUTCOME MEASURES: We evaluated cognitive development based on the Bayley scale at 8 months (Mental and Motor Scores), and intelligent quotient (IQ) based on the Stanford-Binet scale at 4 years and the Wechsler Intelligence Scale for Children at 7 years. RESULTS: The confounder and selection-bias adjusted risk ratio (RR) of abnormal 8-month Motor and Mental assessments were 2.35 (95%CI 1.39, 3.98) and 2.03 (95%CI 1.13, 3.64), respectively, in relation to abruption. The associations at 4 years were attenuated and resolved at 7 years. The proportion of children with abruption-associated neurological deficits mediated through preterm delivery ranged from 27 to 75%. Following adjustment for unobserved confounding the proportion mediated through preterm delivery was attenuated. CONCLUSION: The effect of abruption on neurodevelopmental outcomes appears restricted to an effect that is largely mediated through preterm delivery. TWEETABLE ABSTRACT: Increased risk of cognitive deficits in relation to abruption appears to be mediated through preterm delivery.

Serious maternal complications in relation to severe pre-eclampsia: a retrospective cohort study of the impact of hospital volume.

OBJECTIVE: We examined rates of serious maternal complications in relation to severe pre-eclampsia based on the delivering hospital's annualised volume. DESIGN: Retrospective cohort study. POPULATION AND SETTING: Singleton deliveries (n = 25 782 235) in 439 hospitals in the USA. METHODS: Annualised hospital volume was categorised as 25-500, 501-1000, 1001-2000 and >2000. MAIN OUTCOME MEASURES: Rates of in-hospital maternal death and serious maternal complications, including puerperal cerebrovascular disorders, pulmonary oedema, disseminated intravascular coagulation, acute renal, heart and liver failure, sepsis, haemorrhage and intubation in relation to severe pre-eclampsia. We derived adjusted risk ratio (RR) and 95% confidence interval (CI), from hierarchical Poisson regression models. RESULTS: Severe pre-eclampsia was associated with an 8.7-fold (95% CI 7.6, 10.1) risk of composite maternal complications, with similar RRs across levels of hospital volumes. However, compared with hospitals with low annual volume (<2000), maternal mortality rates in relation to severe pre-eclampsia were lower in high volume hospitals. The rates of serious maternal complications were 410.7 per 10 000 to women who delivered in hospitals with a high rate of severe pre-eclampsia (≥2.12%) and 584.8 per 10 000 to women who delivered in hospitals with low severe pre-eclampsia rates (≤0.41; RR 1.75, 95% CI 1.24, 2.45). CONCLUSIONS: While the risks of serious maternal complications in relation to severe pre-eclampsia was similar across hospital delivery volume categories, deaths showed lower rates in large delivery volume hospitals than in smaller volume hospitals. The risk of complications was increased in hospitals with low compared with high severe pre-eclampsia rates. TWEETABLE ABSTRACT: Hospital volume had little impact on the association between severe pre-eclampsia and maternal complications.

Gestational diabetes in the United States: temporal changes in prevalence rates between 1979 and 2010.

OBJECTIVE: To examine age-period-cohort effects on trends in gestational diabetes mellitus (GDM) prevalence in the US, and to evaluate how these trends have affected the rates of stillbirth and large for gestational age (LGA)/macrosomia. DESIGN: Retrospective cohort study. SETTING: USA, 1979-2010. POPULATION: Over 125 million pregnancies (3 337 284 GDM cases) associated with hospitalisations. METHODS: Trends in GDM prevalence were examined via weighted Poisson models to parse out the extent to which GDM trends can be attributed to maternal age, period of delivery, and maternal birth cohort. Multilevel models were used to assess the contribution of population effects to the rate of GDM. Log-linear Poisson regression models were used to estimate the contributions of the increasing GDM rates to changes in the rates of LGA and stillbirth between 1979-81 and 2008-10. MAIN OUTCOME MEASURES: Rates and rate ratios (RRs). RESULTS: Compared with 1979-1980 (0.3%), the rate of GDM has increased to 5.8% in 2008-10, indicating a strong period effect. Substantial age and modest cohort effects were evident. The period effect is partly explained by period trends in body mass index (BMI), race, and maternal smoking. The increasing prevalence of GDM is associated with a 184% (95% CI 180-188%) decline in the rate of LGA/macrosomia and a 0.75% (95% CI 0.74-0.76) increase in the rate of stillbirths for 2008-10, compared with 1979-81. CONCLUSIONS: The temporal increase in GDM can be attributed to period of pregnancy and age. Increasing BMI appears to partially contribute to the GDM increase in the US. TWEETABLE ABSTRACT: The increasing prevalence of GDM can be attributed to period of delivery and increasing maternal age.

The effect of maternal haematocrit on offspring IQ at 4 and 7 years of age: a secondary analysis.

OBJECTIVE: To determine whether maternal haematocrit during pregnancy is associated with offspring IQ. DESIGN/SETTING/POPULATION: A secondary analysis of the Collaborative Perinatal Project, which enrolled women between 1959 and 1966 at 12 university hospitals in the United States. METHODS: We evaluated the relation between maternal haematocrit and IQ at 4 and 7 years of age. Linear and log-linear regression models were used to adjust for possible confounders. Marginal structural models with stabilised weights were used to account for selection bias due to children lost to follow up. MAIN OUTCOME MEASURES: Offspring IQ at 4 and 7 years of age. RESULTS: Of 35 959 patients, 1521 (4.2%) had moderate anaemia, 13 769 (38.3%) had mild anaemia, 18 227 (50.7%) had a normal haematocrit, and 2442 (6.8%) had a high haematocrit. The mean IQ at 4 and 7 years was significantly lower in the moderate and mild anaemia groups than in the normal haematocrit group (92.3 and 94.7 versus 100.6, respectively, P < 0.01, at 4 years; and 90.2 and 93.4 versus 99.1 at 7 years, P < 0.01). The high haematocrit group had a significantly higher mean IQ (104.5 at 4 years; 103.2 at 7 years) when compared with the normal haematocrit group (P < 0.01). Women with moderate anaemia were more likely to have children with IQ of 70-84 at 4 years (RR 1.22, 95% CI 1.08-1.38) and <70 at 7 years (RR 1.59, 95% CI 1.14-2.23). Women with a high haematocrit were more likely to have children with an IQ ≥120 at 7 years (RR 1.22, 95% CI 1.08-1.39). CONCLUSIONS: Maternal haematocrit is associated with offspring IQ at 4 and 7 years of age. TWEETABLE ABSTRACT: There is a nonlinear relation between maternal haematocrit and offspring IQ at 4 and 7 years of age.

Infant mortality in the United States.

The infant mortality rate (IMR) of 6.0 per 1000 live births in the United States in 2013 is nearly the highest among developed countries. Moreover, the IMR among blacks is >twice that among whites-11.11 versus 5.06 deaths per 1000 live births.This higher IMR and racial disparity in IMR is due to a higher preterm birth rate (11.4% of live births in 2013) and higher IMR among term infants. The United States also ranks near the bottom for maternal mortality and life expectancy among the developed nations-despite ranking highest in the proportion of gross national product spent on health care. This suggests that factors other than health care contribute to the higher IMR and racial disparity in IMR. One factor is disadvantaged socioeconomic status. All of the actionable determinates that negatively impact health-personal behavior, social factors, heath-care access and quality and the environment-disproportionately affect the poor. Addressing disadvantaged socioeconomic status by improving access to quality health care and increasing social expenditures would have the greatest impact on the USA's IMR and racial disparity in IMR.

Signs and symptoms associated with early pregnancy loss: findings from a population-based preconception cohort.

STUDY QUESTION: What is the relationship between signs and symptoms of early pregnancy and pregnancy loss <20 weeks' gestation? SUMMARY ANSWER: Vaginal bleeding is associated with increased incidence of early pregnancy loss, with more severe bleeding and bleeding accompanied by lower abdominal cramping associated with greater incidence of loss; conversely, vomiting is associated with decreased incidence of early pregnancy loss, even in the setting of vaginal bleeding, while nausea alone is not. WHAT IS KNOWN ALREADY: Two previous cohort studies with preconception enrollment suggested that bleeding is associated with loss while nausea is inversely associated with loss though these studies were limited by small study size and reporting after loss ascertainment. No prior preconception cohort study has examined multiple signs and symptoms in relation to pregnancy loss. STUDY DESIGN, SIZE, DURATION: Population-based preconception cohort of 501 couples discontinuing contraception to try for pregnancy in 16 counties in Michigan and Texas, USA. Participants were followed daily until positive home pregnancy test or 12 months of trying without an hCG pregnancy; women who became pregnant were followed daily from 2 to 7 weeks post-conception. PARTICIPANTS, SETTING, METHODS: Three hundred and forty-seven women had a positive home pregnancy test denoting hCG pregnancy. Three hundred and forty-one women remained after excluding ineligible pregnancies. Women recorded daily from 2 to 7 weeks post-conception their signs and symptoms, including vaginal bleeding (none, spotting, light, moderate and heavy), lower abdominal cramping, nausea and vomiting. Pregnancy losses were ascertained by a subsequent negative home pregnancy test, clinical confirmation or onset of menses, depending on gestational age at loss; time-to-loss was measured in days post-conception. Cumulative incidence functions and 95% confidence intervals (CIs) were constructed for each sign or symptom, and hazard ratios (HRs) and 95% CIs for presence compared with absence of signs or symptoms were estimated using Cox proportional hazard models. MAIN RESULTS AND THE ROLE OF CHANCE: Women experienced lower abdominal cramping (85%), nausea (48%), vomiting (46%) and light/moderate/heavy vaginal bleeding (24%) during early pregnancy. Ninety-five (28%) women experienced a loss. Cumulative incidence of pregnancy loss varied by symptomatology: 19% for vomiting, 27% for lower abdominal cramping, 35% for nausea only, 52% for vaginal bleeding, 81% for vaginal bleeding with lower abdominal cramping. Incidence of pregnancy loss was increased among women with vaginal bleeding (HR: 3.62, 95% CI: 2.29-5.74) and among women with vaginal bleeding and lower abdominal cramping (HR: 5.03, 95% CI: 2.07-12.20). Incidence of pregnancy loss was decreased for women with vomiting (HR: 0.51, 95% CI: 0.30-0.86). In the setting of vaginal bleeding with lower abdominal cramping, vomiting reduced the incidence of pregnancy loss (HR: 0.24, 95% CI: 0.11-0.56). LIMITATIONS, REASONS FOR CAUTION: There were few losses beyond 14 weeks gestation; thus, the precision of our findings related to losses occurring after the first trimester is limited. WIDER IMPLICATIONS OF THE FINDINGS: By using sensitive home pregnancy tests, we are able to document and characterize the cumulative incidence of the earliest pregnancy losses, which constitute the majority of losses. The use of daily, prospective capture of signs and symptoms relative to ascertainment of pregnancy loss minimizes potential biases associated with reporting after rather than before a loss, which could potentially distort the relationship between signs and symptoms and pregnancy loss. The findings of our study suggest that it may be useful to develop prognostic models for pregnancy loss based on signs and symptoms. STUDY FUNDING/COMPETING INTERESTS: This study was supported by the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health (contract numbers N01-HD-3-3355; N01-HD-3-3356; N01-HD-3-3358). The authors have no conflict of interest to declare.

Measurement and validation of frailty as a predictor of outcomes in women undergoing major gynaecological surgery.

OBJECTIVE: Frailty is the loss of physical or mental reserve that impairs function, often in the absence of a defined comorbidity. Our aim was to determine whether a modified frailty index (mFI) correlates with morbidity and mortality in patients undergoing hysterectomy. DESIGN: Retrospective cohort study. SETTING: Hospitals across the USA participating in the National Surgical Quality Improvement Program (NSQIP). SAMPLE: Patients who underwent hysterectomy from 2008 to 2012. METHODS: An mFI was calculated using 11 variables in NSQIP. The associations between mFI and morbidity and mortality were assessed. Model fit statistics (c-statistics) were utilised to evaluate the ability of mFI to distinguish outcomes. MAIN OUTCOME MEASURE: Wound infection, severe complications and mortality. RESULTS: A total of 66 105 patients were identified. Wound complications increased from 2.4% in patients with an mFI of zero to 4.8% in those with mFI ≥ 0.5 (P < 0.0001). Similarly, severe complications increased from 0.98% to 7.3% (P < 0.0001), overall complications rose from 3.7% to 14.5% (P < 0.0001) and mortality increased from 0.06% to 3.2% (P < 0.0001) for patients with a frailty index of zero compared with those with an index of ≥ 0.5. Versus chance, the goodness-of-fit c-statistics suggested that mFI increases the ability to detect wound complications by 11.4%, severe complications by 22.0% and overall complications by 11.0%. CONCLUSIONS: The mFI is easily reproducible from routinely collected clinical data and predictive of outcomes in patients undergoing hysterectomy. Frailty may be useful in the preoperative risk assessment of women undergoing gynaecological surgery. TWEETABLE ABSTRACT: Frailty may be useful in the preoperative risk assessment of women undergoing gynaecological surgery.

Hospital variation in maternal complications following caesarean delivery in the United States: 2006-2012.

OBJECTIVE: To assess hospital variability in and patient and hospital factors associated with caesarean delivery (CD) complications. STUDY DESIGN: Population-based cohort. SETTING: United States delivery admissions. POPULATION: Women who underwent a CD between 2006 and 2012. METHODS: Hospital-specific random-effects log-linear regression models were developed to account for patient, obstetric, and hospital risk factors related to a composite complication outcome including infection, haemorrhage, surgical complications and prolonged hospital stay. Between-hospital variability in rates of CD complications was also estimated. MAIN OUTCOME MEASURE: Composite complication rate. RESULTS: Among 1 339 397 women who underwent CD in 457 hospitals, 6.4% (n = 85 838) experienced a complication. The most frequent complications were haemorrhage, transfusion, length of stay >7 days, and endometritis. Complications were strongly associated with the presence of obstetric factors and pre-existing medical conditions. Complication rates were 54% higher among black (8.8%) than white (5.7%) women (P < 0.001), and were more common in teaching (8.1%) than non-teaching (5.4%) hospitals (P < 0.001). In an adjusted model, the mean complication rate was 6.7%. A small proportion of hospitals (4.8%) had a complication rate greater than twice the mean (≥13.4%). Complications were strongly associated with the presence of obstetrical factors and pre-existing medical conditions. CONCLUSIONS: CD complication rates are strongly associated with patient and obstetric factors. While CD complication rates may be a quality metric of limited utility given the low rate of complications across most hospitals, a small number of hospitals demonstrate particularly high rates of complications. Review of CD complication rates may be an important aspect of quality assurance processes for these centres. TWEETABLE ABSTRACT: A small number of hospitals demonstrate particularly high rates of caesarean complications.

Clinical indication and timing of antenatal corticosteroid administration at a single centre.

OBJECTIVE: To determine how well antenatal corticosteroids (ACS) were timed, based on the indication for administration for women delivering preterm. DESIGN: Retrospective cohort study. SETTING: Tertiary medical centre. POPULATION: Six hundred and thirty women who had singleton preterm births between 24 and 34 weeks' gestational age. METHODS: Charts from 2006 to 2011 were reviewed for indications for ACS administration, which included premature rupture of membranes, threatened preterm labour, risk factors for spontaneous preterm birth such as short ultrasound cervical length, positive fetal fibronectin, and hypertensive disorders of pregnancy. Charts were reviewed for timing of ACS administration in relation to delivery. MAIN OUTCOME MEASURES: The primary outcome was optimal timing, defined as administration of ACS ≥ 24 hours to ≤ 7 days prior to delivery. RESULTS: Of 630 women who delivered preterm, 589 (93%) received ACS prior to delivery. ACS timing was optimal in 40% (238 of 589) of cases. Women with hypertensive disorders were most likely to have steroids optimally timed (62%). Asymptomatic women at increased risk for preterm delivery were less likely to receive optimally timed ACS (12%). The majority of women who received steroids >2 weeks prior to delivery (57%) received a second course. CONCLUSION: A majority of women who delivered preterm did not receive optimally timed ACS. Diagnostic tools that identified women at risk for preterm birth were not able to identify patients for appropriate steroid timing. Given the range of clinical scenarios in which patients are at increased risk for preterm delivery, further research is needed to assist clinicians in optimising steroid administration. TWEETABLE ABSTRACT: Optimal timing of antenatal steroids prior to delivery does not occur in most cases.

Effect of cervical cerclage on rate of cervical shortening.

OBJECTIVE: Although cerclage has been shown to reduce the risk of recurrent preterm birth in a high-risk patient population, the mechanism by which this occurs is not well understood. Our objective was to evaluate whether cerclage affects the rate of cervical shortening taking into account exposure to 17-hydroxyprogesterone and vaginal progesterone. METHODS: This was a retrospective cohort study of women who had serial cervical length measurements due to a history of spontaneous preterm delivery. Demographic data, obstetric history, progesterone administration, delivery information and serial cervical length measurements were collected. The rate of cervical shortening was compared in women with and without cerclage. Subgroup analyses were performed to compare rates of cervical shortening by indication for cerclage (history indicated vs ultrasound indicated) and outcome in the current pregnancy (cerclage vs no cerclage among those who delivered preterm). RESULTS: A total of 414 women were included of whom 32.4% (n = 134) had a cerclage. There was no difference in the rate of cervical shortening between the cerclage (0.8 mm/week) and no-cerclage (1.0 mm/week, P = 0.43) groups. The rates of cervical shortening among history-indicated and ultrasound-indicated cerclage groups were similar (0.9 vs 1.3 mm/week, respectively, P = 0.2). Among patients with a preterm delivery in the index pregnancy, the rates of cervical shortening among those with (1.31 mm/week) and without (1.28 mm/week, P = 0.78) cerclage were also similar. CONCLUSION: Cervical shortening among women with cerclage occurs at a similar rate to that among women without a cerclage, regardless of indication for cerclage or pregnancy outcome.

Vaginal progesterone in women with twin gestations complicated by short cervix: a retrospective cohort study.

OBJECTIVE: To determine whether the use of vaginal progesterone in twin gestations with a cervical length (CL) of ≤2.5 cm is associated with a reduced risk of preterm delivery. DESIGN: Retrospective cohort study. SETTING: Tertiary-care medical centre in New York City. POPULATION: Women with twin gestations undergoing sonographic cervical length screening. METHODS: Women with twin gestations with a CL of ≤2.5 cm between 16 and 32 weeks of gestation, and who delivered at our centre between 2010 and 2013, were included. We evaluated the impact of vaginal progesterone on the risk of preterm delivery using a Cox proportional hazard model, adjusted for potential confounding factors. We then performed a propensity score analysis using inverse probability of treatment weights to account for treatment selection bias and confounding. MAIN OUTCOME MEASURE: Delivery prior to 35 weeks of gestation. RESULTS: Of the 167 twin pregnancies analysed, 61 (35.7%) were treated with vaginal progesterone. The hazard ratio (HR) of delivery prior to 35 weeks of gestation in the vaginal progesterone group, compared with the no vaginal progesterone group, was 1.8 (95% confidence interval, 95% CI 1.5-3.1) in the unadjusted analysis, 1.4 (95% CI 0.7-3.2) following multivariable adjustment for confounding factors, and 1.5 (95% CI 1.1-2.3) using propensity score methods. CONCLUSION: Women with more risk factors for preterm delivery were more likely to be treated with vaginal progesterone. After statistically correcting for this with propensity score methods, we found that vaginal progesterone therapy in twin pregnancies with a CL ≤2.5 cm was associated with an increased risk of preterm delivery.