Development and internal validation of the multivariable CIPHER (Collaborative Integrated Pregnancy High-dependency Estimate of Risk) clinical risk prediction model.

BACKGROUND: Intensive care unit (ICU) outcome prediction models, such as Acute Physiology And Chronic Health Evaluation (APACHE), were designed in general critical care populations and their use in obstetric populations is contentious. The aim of the CIPHER (Collaborative Integrated Pregnancy High-dependency Estimate of Risk) study was to develop and internally validate a multivariable prognostic model calibrated specifically for pregnant or recently delivered women admitted for critical care. METHODS: A retrospective observational cohort was created for this study from 13 tertiary facilities across five high-income and six low- or middle-income countries. Women admitted to an ICU for more than 24 h during pregnancy or less than 6 weeks post-partum from 2000 to 2012 were included in the cohort. A composite primary outcome was defined as maternal death or need for organ support for more than 7 days or acute life-saving intervention. Model development involved selection of candidate predictor variables based on prior evidence of effect, availability across study sites, and use of LASSO (Least Absolute Shrinkage and Selection Operator) model building after multiple imputation using chained equations to address missing data for variable selection. The final model was estimated using multivariable logistic regression. Internal validation was completed using bootstrapping to correct for optimism in model performance measures of discrimination and calibration. RESULTS: Overall, 127 out of 769 (16.5%) women experienced an adverse outcome. Predictors included in the final CIPHER model were maternal age, surgery in the preceding 24 h, systolic blood pressure, Glasgow Coma Scale score, serum sodium, serum potassium, activated partial thromboplastin time, arterial blood gas (ABG) pH, serum creatinine, and serum bilirubin. After internal validation, the model maintained excellent discrimination (area under the curve of the receiver operating characteristic (AUROC) 0.82, 95% confidence interval (CI) 0.81 to 0.84) and good calibration (slope of 0.92, 95% CI 0.91 to 0.92 and intercept of -0.11, 95% CI -0.13 to -0.08). CONCLUSIONS: The CIPHER model has the potential to be a pragmatic risk prediction tool. CIPHER can identify critically ill pregnant women at highest risk for adverse outcomes, inform counseling of patients about risk, and facilitate bench-marking of outcomes between centers by adjusting for baseline risk.

Anal sphincter injury in vaginal deliveries complicated by shoulder dystocia.

INTRODUCTION AND HYPOTHESIS: Shoulder dystocia is an obstetric emergency that occurs in 0.2-3% of all cephalic vaginal deliveries. We hypothesized that because of the difficult nature of deliveries complicated by shoulder dystocia, the condition may be associated with anal sphincter injury. We sought to identify risk factors for obstetric anal sphincter injury in women with shoulder dystocia. METHODS: This retrospective analysis included all cases of shoulder dystocia from 2007 to 2011 at two large tertiary referral centers, in the USA and Ireland. Details of maternal demographics, intrapartum characteristics, and delivery outcomes in cases of shoulder dystocia were analyzed. Univariate and multivariate analyses were used to describe the association between shoulder dystocia and anal sphincter injury. RESULTS: There were 685 cases of shoulder dystocia, and the rate of shoulder dystocia was similar at both institutions. The incidence of anal sphincter injury was 8.8% (60 out of 685). The rate was 14% (45 out of 324) in nulliparas and 4.2% (15 out of 361) in multiparas. Women with sphincter injury were more likely to be nulliparous (75% [45 out of 60] vs 45% [279 out of 625]; p < 0.0001), have had an operative vaginal delivery (50% [30 out of 60] vs 36% [226 out of 625]; p = 0.03) and require internal maneuvers (50% [30 out of 60] vs 32% [198 out of 625], p = 0.004) than those with an intact sphincter. On multivariate regression analysis, these predictors of sphincter injury remained significant when adjusted for other risk factors. Episiotomy was negatively associated with sphincter injury on multivariate regression analysis. CONCLUSIONS: In a retrospective cohort of 685 women with shoulder dystocia, the risk of anal sphincter injury is 9%. Risk factors include nulliparity, operative vaginal delivery, and use of internal maneuvers, whereas episiotomy was found to have a protective effect against anal sphincter injury during cases of shoulder dystocia.

Elevated amniotic fluid lactate predicts labor disorders and cesarean delivery in nulliparous women at term.

OBJECTIVE: We sought to assess amniotic fluid lactate (AFL) at diagnosis of spontaneous labor at term (≥37 weeks) as a predictor of labor disorders (dystocia) and cesarean delivery (CD). STUDY DESIGN: This was a single-institution, prospective cohort study of 905 singleton, cephalic, term (≥37 weeks) nulliparous women in spontaneous labor. A standard management of labor (active management of labor) including a standard oxytocin regimen up to a maximum dose of 30 mU/min was applied. AFL was measured using a point-of-care device (LMU061; ObsteCare, Stockholm, Sweden). Labor arrest in the first stage of labor was defined as the need for oxytocin when cervical dilatation was <1 cm/h over 2 hours and in the second stage of labor by poor descent and rotation over 1 hour. Standard statistical analysis included analysis of variance, Pearson correlations, and binary logistic regression. Unsupervised decision tree analysis with 10-fold cross-validation was used to identify AFL thresholds. RESULTS: AFL was normally distributed and did not correlate with age, body mass index, or gestation. Unsupervised decision tree analysis demonstrated that AFL could be divided into 3 groups: 0-4.9 mmol/L (n = 118), 5.0-9.9 mmol/L (n = 707), and ≥10.0 mmol/L (n = 80). Increasing AFL was associated with higher total oxytocin dose (P = .001), labor disorders (P = .005), and CD (P ≤ .001). Multivariable regression analysis demonstrated that women with AFL ≥5.0-9.9 mmol/L (odds ratio [OR], 1.6; 95% confidence interval [CI], 1.06-2.39) and AFL ≥10.0 mmol/L (OR, 1.72; 95% CI, 1.01-2.93) were independent predictors of a labor disorder. AFL ≥5.0-9.9 mmol/L did not predict CD but multivariable analysis confirmed that AFL ≥10.0 mmol/L was an independent predictor of CD (OR, 3.35; 95% CI, 1.73-6.46). AFL ≥5.0-9.9 mmol/L had a sensitivity of 89% in predicting a labor disorder and a sensitivity of 93% in predicting CD with a 97% negative predictive value. AFL ≥10.0 mmol/L was highly specific but lacked sensitivity for CD. There was no difference in birthweight of infants according to labor disorder and delivery method. CONCLUSION: AFL at diagnosis of labor in spontaneously laboring single cephalic nulliparous term women is an independent predictor of a labor disorder and CD. These data suggest that women with AFL between 5.0-9.9 mmol/L with a labor disorder may be amenable to correction using the active management of labor protocol.

Endometrial aspiration biopsy: a non-invasive method of obtaining functional lymphoid progenitor cells and mature natural killer cells.

The aim of this study was to compare the efficacy of endometrial aspiration biopsy (EAB) with the more traditional dilatation and curettage (D&C) for the procurement of lymphoid progenitor cells and uterine natural killer (NK) populations in endometrial tissue. This prospective observational study conducted in a tertiary referral university hospital examined endometrium obtained from 32 women admitted for laparoscopic gynaecological procedures. Each participant had endometrium sampled using both EAB and D&C. Both methods were assessed as a source of uterine NK and lymphoid progenitor cells. Similar proportions of mature CD45+CD56+ NK cells (range 25.4-36.2%) and CD45+CD34+ lymphoid progenitors (range 1.2-2.0%) were found in tissue obtained using both EAB and D&C. These cells were adequate for flow cytometric analysis, magnetic bead separation and culture. Colony formation by the CD34+ population demonstrated maturational potential. Tissues obtained via endometrial biopsy and D&C are equivalent, by analysis of uterine NK and lymphoid progenitor cells. The aim of this study was to compare two methods of endometrial sampling - endometrial aspiration biopsy and traditional dilatation and curettage - for the procurement of haematopoietic stem cells and uterine natural killer (NK) populations in endometrial tissue. Thirty-two women who had gynaecological procedures in a tertiary referral hospital participated in this study and had endometrial tissue collected via both methods. Similar populations of mature NK cells and haematopoietic stem cells were found in tissue obtained using both endometrial aspiration biopsy and dilatation and curettage. Tissue obtained via endometrial aspiration biopsy was adequate for the culture and growth of haematopoietic stem cells. We conclude that tissue obtained via endometrial biopsy and dilatation and curettage is equivalent, by analysis of uterine NK and haematopoietic stem cells using flow cytometry. This has implications for further more extensive study of endometrial haematopoietic stem cell populations, as these samples can be collected in a clinical setting without a requirement for general anaesthesia.

Neonatal brachial plexus injury: comparison of incidence and antecedents between 2 decades.

OBJECTIVE: We sought to compare the incidence and antecedents of neonatal brachial plexus injury (BPI) in 2 different 5-year epochs a decade apart following the introduction of specific staff training in the management of shoulder dystocia. STUDY DESIGN: All infants with BPI were prospectively identified during 2004 through 2008. Injuries were correlated with maternal details and intrapartum events and compared with the earlier series. RESULTS: Of 41,828 deliveries during 2004 through 2008, 72 infants with BPI were identified (1.7/1000), compared to 54 cases (1.5/1000) from 1994 through 1998 (P = .4); 9 injuries (12.5%) were persistent from 2004 through 2008, compared with 10 (18.5%) earlier (P = .4). There were no significant differences between the 2 time periods with respect to maternal parity, obesity, or prolonged pregnancy, although the cesarean section rate had increased from 10.7 to 18.4%. CONCLUSION: Despite training in the management of shoulder dystocia and a rising institutional cesarean section rate, the incidence of BPI has remained unchanged compared with 10 years earlier.

Saving Mothers' Lives: Reviewing maternal deaths to make motherhood safer: 2006-2008. The Eighth Report of the Confidential Enquiries into Maternal Deaths in the United Kingdom.

In the triennium 2006-2008, 261 women in the UK died directly or indirectly related to pregnancy. The overall maternal mortality rate was 11.39 per 100,000 maternities. Direct deaths decreased from 6.24 per 100,000 maternities in 2003-2005 to 4.67 per 100,000 maternities in 2006­2008 (p = 0.02). This decline is predominantly due to the reduction in deaths from thromboembolism and, to a lesser extent, haemorrhage. For the first time there has been a reduction in the inequalities gap, with a significant decrease in maternal mortality rates among those living in the most deprived areas and those in the lowest socio-economic group. Despite a decline in the overall UK maternal mortality rate, there has been an increase in deaths related to genital tract sepsis, particularly from community acquired Group A streptococcal disease. The mortality rate related to sepsis increased from 0.85 deaths per 100,000 maternities in 2003-2005 to 1.13 deaths in 2006-2008, and sepsis is now the most common cause of Direct maternal death. Cardiac disease is the most common cause of Indirect death; the Indirect maternal mortality rate has not changed significantly since 2003-2005. This Confidential Enquiry identified substandard care in 70% of Direct deaths and 55% of Indirect deaths. Many of the identified avoidable factors remain the same as those identified in previous Enquiries. Recommendations for improving care have been developed and are highlighted in this report. Implementing the Top ten recommendations should be prioritised in order to ensure the overall UK maternal mortality rate continues to decline.

Identification of a myometrial molecular profile for dystocic labor.

BACKGROUND: The most common indication for cesarean section (CS) in nulliparous women is dystocia secondary to ineffective myometrial contractility. The aim of this study was to identify a molecular profile in myometrium associated with dystocic labor. METHODS: Myometrial biopsies were obtained from the upper incisional margins of nulliparous women undergoing lower segment CS for dystocia (n = 4) and control women undergoing CS in the second stage who had demonstrated efficient uterine action during the first stage of labor (n = 4). All patients were in spontaneous (non-induced) labor and had received intrapartum oxytocin to accelerate labor. RNA was extracted from biopsies and hybridized to Affymetrix HuGene U133A Plus 2 microarrays. Internal validation was performed using quantitative SYBR Green Real-Time PCR. RESULTS: Seventy genes were differentially expressed between the two groups. 58 genes were down-regulated in the dystocia group. Gene ontology analysis revealed 12 of the 58 down-regulated genes were involved in the immune response. These included (ERAP2, (8.67 fold change (FC)) HLA-DQB1 (7.88 FC) CD28 (2.60 FC), LILRA3 (2.87 FC) and TGFBR3 (2.1 FC)) Hierarchical clustering demonstrated a difference in global gene expression patterns between the samples from dystocic and non-dystocic labours. RT-PCR validation was performed on 4 genes ERAP2, CD28, LILRA3 and TGFBR3 CONCLUSION: These findings suggest an underlying molecular basis for dystocia in nulliparous women in spontaneous labor. Differentially expressed genes suggest an important role for the immune response in dystocic labor and may provide important indicators for new diagnostic assays and potential intrapartum therapeutic targets.

Propofol allows precise quantitative arterial spin labelling functional magnetic resonance imaging in the rat.

Functional magnetic resonance imaging (fMRI) techniques highlight cerebral vascular responses which are coupled to changes in neural activation. However, two major difficulties arise when employing these techniques in animal studies. First is the disturbance of cerebral blood flow due to anaesthesia and second is the difficulty of precise reproducible quantitative measurements. These difficulties were surmounted in the current study by using propofol and quantitative arterial spin labelling (QASL) to measure relative cerebral blood volume of labelled water (rCBV(lw),) mean transit time (MTT) and capillary transit time (CTT). The ASL method was applied to measure the haemodynamic response in the primary somatosensory cortex following forepaw stimulation in the rat. Following stimulation an increase in signal intensity and rCBV(lw) was recorded, this was accompanied by a significant decrease in MTT (1.97+/-0.06s to 1.44+/-0.04s) and CTT (1.76+/-0.06s to 1.39+/-0.07s). Two animals were scanned repeatedly on two different experimental days. Stimulation in the first animal was applied to the same forepaw during the initial and repeat scan. In the second animal stimulation was applied to different forepaws on the first and second days. The control and activated ASL signal intensities, rCBVlw on both days were almost identical in both animals. The basal MTT and CTT during the second scan were also very similar to the values obtained during the first scan. The MTT recorded from the animal that underwent stimulation to the same paw during both scanning sessions was very similar on the first and second days. In conclusion, propofol induces little physiological disturbance and holds potential for longitudinal QASL fMRI studies.

Comparison of the contractile properties, oxidative capacities and fibre type profiles of the voluntary sphincters of continence in the rat.

The external urethral sphincter (EUS) and external anal sphincter (EAS) are the principal voluntary striated muscles that sustain continence of urine and faeces. In light of their common embryological origin, shared tonic sphincteric action and synchronized electrical activity in vivo, it was expected that they would exhibit similar physiological and structural properties. However, the findings of this study using paired observations of both sphincters isolated from the rat show clearly that this is not the case. The anal sphincter is much more fatigable than the urethral sphincter. On completion of a fatigue protocol, the amplitude of the last twitch of the EAS had declined to 42 +/- 3% of the first twitch, whereas the last twitch of the EUS was almost identical to that of the first (95 +/- 3%). Immunocytochemical detection of myosin heavy-chain isoforms showed that this difference was not due to the presence of more slow-twitch oxidative type 1 fibres in the EUS compared with the EAS (areal densities 4 +/- 1% and 5 +/- 1%, respectively; P = 0.35). In addition, the fatigue difference was not explained by a greater contribution to force production by fast oxidative type 2A fibres in the urethral sphincter. In fact, the anal sphincter contained a higher areal density of type 2A fibres (56 +/- 5% vs. 37 +/- 4% in the EUS, P = 0.017). The higher oxidative capacity of the EUS, measured histochemically, explained its fatigue resistance. These results were surprising because the fatigue-resistant urethral muscle exhibited faster single-twitch contraction times compared with the anal sphincter (56 +/- 0.87 ms vs. 72.5 +/- 1.16 ms, P < 0.001). Neither sphincter expressed the type 2X myosin isoform but the fast-twitch isoform type 2B was found exclusively in the EUS (areal density 16 +/- 2%). The type 2B fibres of the EUS were small (diameter 19.5 +/- 0.4 mum) in comparison to typical type 2B fibres of other muscles. As a whole the EUS is a more oxidative than glycolytic muscle. In conclusion, analysis of the twitch mechanics and fatigue of two sphincters showed that the EUS contained more fatigue-resistant muscle fibres compared with the EAS.

Tumour-specific HMG-CoAR is an independent predictor of recurrence free survival in epithelial ovarian cancer.

BACKGROUND: Our group previously reported that tumour-specific expression of the rate-limiting enzyme in the mevalonate pathway, 3-hydroxy-3-methylglutharyl-coenzyme A reductase (HMG-CoAR) is associated with more favourable tumour parameters and a good prognosis in breast cancer. In the present study, the prognostic value of HMG-CoAR expression was examined in tumours from a cohort of patients with primary epithelial ovarian cancer. METHODS: HMG-CoAR expression was assessed using immunohistochemistry (IHC) on tissue microarrays (TMA) consisting of 76 ovarian cancer cases, analysed using automated algorithms to develop a quantitative scoring model. Kaplan Meier analysis and Cox proportional hazards modelling were used to estimate the risk of recurrence free survival (RFS). RESULTS: Seventy-two tumours were suitable for analysis. Cytoplasmic HMG-CoAR expression was present in 65% (n = 46) of tumours. No relationship was seen between HMG-CoAR and age, histological subtype, grade, disease stage, estrogen receptor or Ki-67 status. Patients with tumours expressing HMG-CoAR had a significantly prolonged RFS (p = 0.012). Multivariate Cox regression analysis revealed that HMG-CoAR expression was an independent predictor of improved RFS (RR = 0.49, 95% CI (0.25-0.93); p = 0.03) when adjusted for established prognostic factors such as residual disease, tumour stage and grade. CONCLUSION: HMG-CoAR expression is an independent predictor of prolonged RFS in primary ovarian cancer. As HMG-CoAR inhibitors, also known as statins, have demonstrated anti-neoplastic effects in vitro, further studies are required to evaluate HMG-CoAR expression as a surrogate marker of response to statin treatment, especially in conjunction with current chemotherapeutic regimens.

Central representation of the inferior rectal nerve of the rat.

PURPOSE: Obstetric injury to the pudendal nerve contributes significantly to fecal incontinence. The inferior rectal nerve, a terminal branch of the motor division of the pudendal nerve, innervates the external anal sphincter. Animal models have been developed to establish the scientific basis of sacral neuromodulation. The aims of this study were to determine the spinal location of inferior rectal nerve motoneurons projecting to the external anal sphincter and whether the inferior rectal nerve carries sensory fibers. METHODS: Ten female virgin Wistar rats were used; 7 underwent bilateral inferior rectal nerve section and application of the neuronal tracer fluorogold. Five days later dorsal root ganglia L5 to S2 and the lumbosacral spinal cord were harvested and stained for activating transcription factor 3, a molecular marker of nerve injury. Three animals were used to confirm the specificity of activating transcription factor 3 nuclear labeling as a marker of axotomy. RESULTS: Fluorogold-labeled motoneurons were found exclusively at L6 in the dorsomedial sections of Onuf's nuclei (left and right), which contained 30 +/- 9 motoneurons with a median diameter of 28.3 microm (24.4-31.0) (25th-75th centiles). Double-labeled sensory neurons (fluorogold-labeled cytoplasm and activating transcription factor 3-labeled nuclei) were found in dorsal root ganglia L6 to S2 and were smaller in diameter (20.5 microm (17.8-26.7); median (25th-75th centiles)) than motoneurons (P < .0,001). CONCLUSIONS: The external anal sphincter receives both motor and sensory innervation from the inferior rectal nerve. Activating transcription factor 3 nuclear staining may prove useful for quantifying the degree of nerve injury in animal models of fecal incontinence.

Comparative analysis of international cesarean delivery rates using 10-group classification identifies significant variation in spontaneous labor.

OBJECTIVE: Cesarean section (CS) rates continue to rise throughout the developed world. The aim of this study was to highlight variations in obstetric populations and practices and to identify variations in CS rates in different institutions. STUDY DESIGN: Data from 9 institutional cohorts (total, 47,402; range, 1962-7985) from 9 different countries were examined using a 10-group classification system based on 4 characteristics of every pregnancy, namely single/multiple, nulliparity/multiparity, multiparity with CS scar, spontaneous/induced labor onset and term (>or=37 weeks) gestation. RESULTS: Overall CS rates correlated with CS rates in singleton cephalic nullipara (r = 0.992; P < .001). Whereas CS rates in induced labor were similar, greatest institutional variation were seen in spontaneously laboring multiparas (6.7-fold difference) and nulliparas (3.7-fold difference). CONCLUSION: Ten-group analysis of international obstetric cesarean practice identifies wide variations in women in spontaneous cephalic term labor, a low-risk cohort amenable to effective intrapartum corrective intervention.

Reduced somatosensory cortical activation in experimental models of neuropathic fecal incontinence.

PURPOSE: Alteration in cortical awareness may be the underlying abnormality in patients with neuropathic fecal incontinence. The cortical effects of inferior rectal nerve injury were determined using somatosensory evoked cortical potential recordings in an experimental model of neuropathic fecal incontinence. METHODS: Eighteen female virgin Wistar rats were assigned equally to one of three groups: an unoperated control group, a nerve crush group (positive control), and a nerve balloon compression group. Four weeks following the injury, all animals underwent somatosensory evoked cortical potential recordings. Following this, the inferior rectal nerve was harvested, resin-embedded, sectioned (1 microm thickness), and axonal counts and axonal cross-sectional areas were analyzed using Scion Image software. RESULTS: Somatosensory evoked cortical potentials were reduced in the nerve crush and balloon compression groups compared with controls (P = 0.024, P = 0.03, respectively). The inferior rectal nerve was harvested in 14 of the 18 animals (4 control, 5 nerve crush, 5 balloon compression). There were no differences in median inferior rectal nerve total axonal counts (P = 0.69) or in the frequency distribution of axonal cross-sectional area between groups (control vs. nerve crush and control vs. balloon compression: P = 0.92, P = 0.17, respectively). CONCLUSIONS: Somatosensory evoked cortical potential amplitude is reduced following crush or compression injury to the inferior rectal nerve. In neuropathic fecal incontinence, alteration in cortical awareness may be the result of processing modification at a central and not peripheral level.

Effect of second vaginal delivery on anal function in patients at risk of occult anal sphincter injury after first forceps delivery.

PURPOSE: The study was designed to determine the effect of further vaginal delivery on anal sphincter function in women after apparently uncomplicated primiparous forceps delivery. METHODS: Fifty-two secundigravid women whose first child was forceps-assisted were compared with a control group of 20 women who had undergone spontaneous first vaginal delivery. Both groups were studied antenatally and again at 12 weeks after second delivery using a standardized bowel function questionnaire, endoanal ultrasound, and anal manometry. The primary outcome was fecal incontinence score after second delivery. RESULTS: Before second delivery, 20 of 52 (39 percent) of the forceps group and 3 of 20 (15 percent) control subjects (P = 0.103) reported minor alteration in fecal incontinence. Endoanal ultrasound was more frequently abnormal (38/52 (73 percent) vs. 6/20 (30 percent); P = 0.002), and median anal canal squeeze (71 vs. 104 mmHg; P = 0.004) and resting pressures (43 vs. 58 mmHg; P = 0.004) were lower in the forceps group. There was no difference in continence score between first and second delivery for the forceps group (P = 0.19) group or control subjects (P = 0.18). However, 10 of 38 (26 percent) women with an abnormal endoanal ultrasound after first forceps delivery developed new or worsening symptoms after second delivery. CONCLUSIONS: One-quarter of women with occult anal sphincter injury after first forceps delivery experienced some minor alteration in fecal continence after the second delivery.

Can neonatal TSH screening reflect trends in population iodine intake?

BACKGROUND: The distribution of neonatal blood thyroid-stimulating hormone (TSH) concentrations has been used as an index reflecting population dietary iodine intake, with higher concentrations being indicative of lower iodine intake. We examined this distribution in neonates born in Ireland, where the pregnant population has shown a recent decline in urinary iodine (UI) excretion. Our objectives were to determine if any alteration was observed in the percentage of values > 5.0 mIU/L and whether a trend in neonatal blood TSH was apparent. METHODS: Samples drawn from the National Neonatal Screening Programme were assessed during the years 1995-2006 from winter (January n = 35,079) and summer (August n = 37,940) months, respectively, in view of the known seasonal variation in Irish dietary iodine intake. RESULTS: Apart from the first years studied (1995-1996), the proportion of individual blood TSH values >5.0 mIU/L did not exceed 3%, a value believed to be indicative of iodine deficiency. A significant declining trend in the proportion of blood TSH >5.0 mIU/L was observed in subsequent years (p < 0.01). While excluding severe iodine deficiency, these analyses failed to detect the slight but highly significant (p < 0.001) tendency toward increasing blood TSH within the 0-5.0 mIU/L interval in the study population between 1999 and 2006, which was greater in summer than in winter months (p < 0.001). CONCLUSIONS: These data support a link between fetal thyroid function and a fall in maternal iodine intake. While the findings of the proportion of blood TSH values >5.0 mIU/L exclude severe maternal or fetal iodine deficiency, a trend toward increasing TSH may provide an early indication of impending iodine deficiency. The findings assume greater importance in the context of declining UI reported from many developed countries even where the proportion of blood TSH values >5.0 mIU/L is <3%, thus excluding severe maternal and fetal iodine deficiency.

Internal anal sphincter defect influences continence outcome following obstetric anal sphincter injury.

OBJECTIVE: To date, little correlation has been found between the extent of anal sphincter injury defined by endoanal ultrasound and symptoms of postpartum fecal incontinence. To define this relationship, we assessed a large cohort of women following first recognized obstetric anal sphincter injury. STUDY DESIGN: In all, 500 consecutive women were studied at 3 months following primary repair of a first recognized obstetric anal sphincter injury sustained during vaginal delivery. Assessment included a standardized fecal incontinence questionnaire (modified Jorge-Wexner score), anal manometry, and endoanal ultrasound. Severe fecal incontinence was defined by a score greater than 9. Statistical significance of the relationship between symptoms and factors including age, parity, mode of delivery, and extent of sphincter injury (defined by endoanal ultrasound), was analyzed through multiple logistic regression. RESULTS: Increasing age (P = .006) and parity (P = .039), instrumental delivery (P < .001), an anal canal resting pressure of < or = 35 mm Hg (P = .047), and internal anal sphincter (IAS) injury (P = .002) were significantly related to the presence of fecal incontinence. With multivariate analysis, and adjusting for other factors, instrumental delivery (OR 3.1; 95% CI 1.2-7.9) and IAS defect thickness (partial thickness defect > 1 quadrant or full thickness defect; OR 5.1 95% CI 1.5-22.9) were predictive of severe incontinence, but external anal sphincter defects were not. CONCLUSION: Endosonographic evidence of IAS injury is predictive of fecal incontinence following obstetric anal sphincter injury. The presence of an IAS defect should be sought carefully if the anal sphincter is injured during vaginal delivery.

Outcome of second delivery after prior macrosomic infant in women with normal glucose tolerance.

OBJECTIVE: Our aim was to estimate the obstetric outcome of second delivery in women with normal glucose tolerance whose first fetus was macrosomic (fetal weight >/= 4,500 g). METHODS: Primiparas delivering a macrosomic infant during the years 1997-2000 were identified from a hospital computer database, and the obstetric outcome of a second delivery was analyzed up until June 2003. A control group (birth weight 3,000-3,500 g) served for comparison. RESULTS: Among 13,020 first pregnancies, 301 (2.3%) were macrosomic. A similar proportion in the macrosomic group, 156 of 301 (52%), and control group, 171 of 300 (57%), returned for second delivery (P = .252). Compared with controls, first macrosomic deliveries were characterized by higher rates of operative delivery, anal sphincter injury, and shoulder dystocia. At second delivery, 32% of neonates in the macrosomic group and 0.3% in the control group weighed 4,500 g or more (P < .001). More prelabor cesareans were performed in the macrosomic group compared with controls (27 of 156, 17.3%, compared with 8 of 171, 4.7%; P < .001). Among 104 women in the macrosomic group who labored after first vaginal delivery, 99% (103 of 104) delivered vaginally again compared with 44% (11 of 25) who labored after primiparous cesarean delivery (P < .001), which compares with 97% (146 of 150) and 77% (10 of 13), respectively, in the control group. CONCLUSION: Despite a one-third recurrence of macrosomia, first vaginal delivery of a macrosomic infant was associated with a high incidence of second vaginal delivery. Conversely, primiparous macrosomic cesarean delivery conveyed a high risk (56%) for repeat intrapartum cesarean whether macrosomia recurred or not. LEVEL OF EVIDENCE: II-2.

Dystocia increases with advancing maternal age.

OBJECTIVE: The purpose of this study was to assess the influence of maternal age on obstetric indices of uterine efficiency in spontaneous nulliparous labor managed according to a standardized protocol in order to determine whether increasing maternal age is more commonly associated with dystocia. STUDY DESIGN: Information was collected prospectively and retrieved retrospectively from an obstetric database for a 5-year period on a consecutive series of nulliparas in spontaneous term (> or = 37 weeks' gestation) labor with singleton cephalic presentations. All women were managed according to an established Active Management protocol. Indices for dystocia, including need for oxytocin augmentation, prolonged labor (> 12 hr), instrumental delivery, and cesarean section were compared between 5 maternal age categories (< 20 years, 20-24, 25-29, 30-34, and > or = 35 years). RESULTS: The obstetric outcomes of 10,737 consecutive nulliparas in spontaneous term labor were analyzed for the 5 years 1998 to 2002. The incidences of oxytocin augmentation, prolonged labor, instrumental delivery, and intrapartum cesarean section including cesareans for dystocia all increased significantly and progressively with increasing maternal age. Mean gestational age and birth weight were similar in each age category. CONCLUSION: In a context of uniform labor management, all 4 indices of dystocia examined were increased progressively with maternal age, although oxytocin augmentation proved a generally effective intervention in all age categories. These findings have implications for the analysis of intervention rates by health care providers, particularly in developed countries where the proportion of older nulliparas is increasing.

Diagnosis and management of obstetric anal sphincter injury.

PURPOSE OF REVIEW: The purpose of this review is to outline optimum practice in diagnosis and management of obstetric anal sphincter injury. The review focuses briefly on prevention of the problem before outlining diagnosis of sphincter injury as well as immediate and long-term management of patients who have sustained such injuries. RECENT FINDINGS: Increasing vigilance is vital in order that sphincter injury is not overlooked; immediate radiological assessment may play a role in diagnosis. Optimum anal sphincter repair should be followed by oral laxative administration to maintain sphincter integrity. Biofeedback physiotherapy and sacral nerve stimulation show great promise in treatment of persistent symptoms. Optimum mode of delivery in future pregnancies is not clearly defined, and decisions should be individualized. SUMMARY: Because obstetric injury to the anal sphincter mechanism cannot always be prevented, efforts must focus on limiting its occurrence, documenting its severity and providing optimum therapy to women who have sustained it. Management includes routine postnatal review of at-risk women and antenatal assessment in future pregnancies to limit deterioration in continence after future deliveries.

The effect of regular antenatal perineal massage on postnatal pain and anal sphincter injury: a prospective observational study.

OBJECTIVE: Antenatal perineal massage has been shown to reduce the incidence of perineal tears in primiparous women. The aim of this study was to determine whether perineal massage impacts on primary prevention of symptomatic disruption of the fecal continence mechanism. METHODS: An observational study recruited two cohorts of women. The first, massage group (MG) chose to perform daily perineal massage from 34 weeks gestation, and the second, control group (CG) was asked to avoid massage. Perineal injury and postnatal pain were documented and all women were invited to attend at three months postpartum for continence assessment, anal manometry, and endoanal ultrasound. RESULTS: Of 179 women recruited, 100 were in the MG while 79 women were controls. Mode of delivery was not influenced by perineal massage. Although the impact did not reach statistical significance, women aged over 30 years in the MG were more likely to be delivered with an intact perineum than controls. Postnatal perineal pain was much reduced in the MG compared with the CG (p = 0.029). Of the women recruited, 136 (75.9%) returned for a postnatal continence assessment. Manometry pressures, continence scores, and endoanal ultrasound findings were similar in both groups. CONCLUSION: Antenatal perineal massage was found to significantly affect postnatal perineal pain scores although it did not impact on the incidence of intact perineum at delivery, postnatal continence scores, anal manometry pressures, or endoanal ultrasound findings.