"Doing something" about the cesarean delivery rate.

There is a general consensus that the cesarean delivery rate in the United States is too high, and that practice patterns of obstetricians are largely to blame for this situation. In reality, the US cesarean delivery rate is the result of 3 forces largely beyond the control of the practicing clinician: patient expectations and misconceptions regarding the safety of labor, the medical-legal system, and limitations in technology. Efforts to "do something" about the cesarean delivery rate by promulgating practice directives that are marginally evidence-based or influenced by social pressures are both ineffective and potentially harmful. We examine both the recent American Congress of Obstetricians and Gynecologists (ACOG)/Society for Maternal-Fetal Medicine Care Consensus Statement "Safe Prevention of Primary Cesarean Delivery" document and the various iterations of the ACOG guidelines for vaginal birth after cesarean delivery in this context. Adherence to arbitrary time limits for active phase or second-stage arrest without incorporating other clinical factors into the decision-making process is unwise. In a similar manner, ever-changing practice standards for vaginal birth after cesarean driven by factors other than changing data are unlikely to be effective in lowering the cesarean delivery rate. Whether too high or too low, the current US cesarean delivery rate is the expected result of the unique demographic, geographic, and social forces driving it and is unlikely to change significantly given the limitations of current technology to otherwise satisfy the demands of these forces.

Can the optimal cervical length for placing ultrasound-indicated cerclage be identified?

OBJECTIVE: To assess a continuum of cervical length (CL) cut-offs for the efficacy of ultrasound-indicated cerclage in women with previous spontaneous preterm birth (PTB). METHODS: This was a planned secondary analysis of a multicenter randomized clinical trial of ultrasound-indicated cerclage for the prevention of PTB in high-risk women. The efficacy of cerclage for preventing recurrent PTB < 35, < 32 and < 24 weeks' gestation was assessed using multivariable logistic regression analysis. Odds ratios (ORs) and CIs were estimated for a range of CL cut-offs using bootstrap regression. The 2.5(th) and 97.5(th) percentiles of bootstrapped ORs determined the CIs. Results were illustrated using smoothed curves superimposed on estimated ORs by CL cut-off. RESULTS: Of 301 women with a CL < 25 mm, 142 underwent ultrasound-indicated cerclage and 159 did not have cerclage placement. The few cases with CL < 10 mm limited the evaluation to CL cut-offs between < 10 mm and < 25 mm. For PTB < 35 weeks, ORs in women with a cerclage and CL < 25 mm were statistically significantly lower than in those without cerclage, and efficacy was maintained at smaller CL cut-offs. Results were similar for PTB < 32 weeks. For PTB < 24 weeks, results differed, with ORs increasing toward unity (no benefit), with wide CIs, for CL cut-offs between < 10 mm and < 15 mm, attributed to the small number of births < 24 weeks. CONCLUSIONS: The efficacy of ultrasound-indicated cerclage in women with previous spontaneous PTB varies by action point CL cut-off and by PTB gestational age of interest. Cerclage significantly reduces the risk of PTB < 35 and < 32 weeks, at CL cut-offs between < 10 mm and < 25 mm, with the greatest reduction at shorter CL, affirming that women with prior spontaneous PTB and a short CL are appropriate candidates for ultrasound-indicated cerclage. Copyright © 2015 ISUOG. Published by John Wiley & Sons Ltd.

Fetal heart rate patterns at 20 to 24 weeks gestation as recorded by fetal electrocardiography.

INTRODUCTION: With advancing technology it has become possible to accurately record and assess fetal heart rate (FHR) patterns from gestations as early as 20 weeks. The aim of our study was to describe early patterns of FHR, as recorded by transabdominal fetal electrocardiogram according to the Dawes-Redman criteria. Accordingly, short-term variability, basal heart rate, accelerations and decelerations were quantified at 20-24 weeks gestation among women with uncomplicated pregnancies. METHODS: This study was conducted in a subset of participants enrolled in a large prospective pregnancy cohort study. Our final data set consisted of 281 recordings of women with good perinatal outcomes who had undergone fetal electrocardiographic assessment as part of the Safe Passage Study. RESULTS: The success rate of the recordings was 95.4%. The mean frequency of small and large accelerations was 0.5 and 0.1 per 10 min, respectively and that of small and large decelerations 0.3 and 0.008 per 10 min, respectively. The mean and basal heart rates were both equal to 148.0 bpm at a median gestation of 161 days. The mean short term variation was 6.2 (SD 1.4) ms and mean minute range 35.1 (SD 7.1) ms. CONCLUSION: The 20-24-week fetus demonstrates FHR patterns with more accelerations and decelerations, as well as higher baseline variability than was anticipated. Information from this study provides an important foundation for further, more detailed, studies of early FHR patterns.

Reconsidering the switch from low-molecular-weight heparin to unfractionated heparin during pregnancy.

Venous thromboembolic disease accounts for 9% of all maternal deaths in the United States. In patients at risk for thrombosis, common practice is to start prophylactic doses of low-molecular-weight heparin and transition to unfractionated heparin during the third trimester, with the perception that administration of neuraxial anesthesia will be safer while on unfractionated heparin, as spinal/epidural hematomas have been associated with recent use of low-molecular-weight heparin. In patients receiving prophylactic doses of unfractionated heparin, neuraxial anesthesia may be placed, provided the dose used is 5,000 units twice a day. The American Society of Regional Anesthesia and Pain Medicine guidelines recognize that the safety of neuraxial anesthesia in patients receiving more than 10,000 units per day or more than 2 doses per day is unknown, limiting the theoretical benefit of unfractionated heparin at doses higher than 5,000 units twice a day.

Characteristics of women with nausea and vomiting of pregnancy who chose to continue compassionate use of placebo after a randomised trial.

The placebo effect has not been characterised in pregnant women suffering from nausea and vomiting of pregnancy (NVP). Our aim was to characterise determinants of the placebo effect in women treated with placebo for NVP. We analysed data from a multicentre, double blind randomised controlled trial of Diclectin (delayed release doxylamine and pyridoxine) vs placebo for the treatment of NVP. A total of 127 women in the placebo arm and 130 in the active arm provided evaluable data for this analysis. Women who chose to continue placebo on a compassionate basis (n = 41) had significantly better improvement in symptoms of NVP and higher Wellbeing scores than those who did not ask to continue compassionate use. Results were similar in the active drug arm. The request to continue compassionate use of either placebo or active drug could be predicted by greater improvement in symptoms of NVP during the trial period.

Association between body mass index and pregnancy outcome in a randomized trial of cerclage for short cervix.

OBJECTIVE: To evaluate whether increasing body mass index (BMI) alters the efficacy of ultrasound-directed cerclage in women with a history of preterm birth. METHODS: This was a planned secondary analysis of a multicenter trial in which women with a singleton gestation and prior spontaneous preterm birth (17 to 33 + 6 weeks' gestation) were screened for a short cervix by serial transvaginal ultrasound evaluations between 16 and 22 + 6 weeks. Women with a short cervix (cervical length < 25 mm) were randomly assigned to cerclage or not. Linear and logistic regression were used to assess the relationship between BMI and continuous and categorical variables, respectively. RESULTS: Overall, in the screened women (n = 986), BMI was not associated with cervical length (P = 0.68), gestational age at delivery (P = 0.12) or birth at < 35 weeks (P = 0.68). For the cerclage group (n = 148), BMI had no significant effect. For the no-cerclage group (n = 153), BMI was associated with a decrease in gestational age at delivery, with an estimated slope of - 0.14 weeks per kg/m(2) (P = 0.03; including adjustment for cervical length). This result was driven primarily by several women with BMI > 47 kg/m(2) . CONCLUSION: In women at high risk for recurrent preterm birth, BMI was not associated with cervical length or gestational age at birth. BMI did not appear to adversely affect ultrasound-indicated cerclage.

Fetal sex-related dysregulation in testosterone production and their receptor expression in the human placenta with preeclampsia.

OBJECTIVE: To determine the effects of fetal sex on aromatase and androgen receptor (AR) expression in the placenta of normal and preeclamptic pregnancies. STUDY DESIGN: Placentae from preeclamptic (five female and six male fetuses) and healthy pregnancies (seven female and seven male fetuses) were examined by immunofluorescence, western blotting and quantitative reverse transcriptase PCR. RESULT: Placental AR levels were significantly higher (P<0.05) in placentae of both male and female fetuses compared with their respective sexes in normal pregnancies. The placental aromatase levels varied depending on fetal sex. If the fetus was female, aromatase levels were substantially higher (P<0.05) in preeclamptic than in normal placentae. If the fetus was male, the aromatase levels were significantly lower (P<0.05) in preeclamptic than in normal placentae. Placental aromatase levels were significantly higher (P<0.05) in male- than in female-bearing normal placentae. CONCLUSION: Dysregulation in androgen production and signaling in preeclamptic placentae may contribute to placental abnormalities, increasing the frequency of maternal-fetal complications associated with preeclampsia.

Defining cerebral palsy: pathogenesis, pathophysiology and new intervention.

Cerebral palsy (CP) affects 2/1 000 live-born children. There are several antenatal factors, including preterm delivery, low birth weight, infection/inflammation, multiple gestations, and other pregnancy complications, that have been associated with CP in both the preterm and term infant, with birth asphyxia playing a minor role. Due to the increasing survival of the very preterm and very low birth weight infant secondary to improvements in neonatal and obstetric care, the incidence of CP may be increasing. The topics of neonatal encephalopathy and CP, as well as hypoxic-ischemic encephalopathy, are of vital importance to anyone who ventures to deliver infants. Criteria sufficient to define an acute intrapartum hypoxic event as sufficient to cause CP have been advanced previously by both the American College of Obstetricians and Gynecologists and the International Cerebral Palsy Task Force. This review will cover the progression toward defining the pathogenesis and pathophysiology of cerebral palsy. Four essential criteria were advanced as prerequisites if one is to propose that an intrapartum hypoxic-ischemic insult has caused a moderate to severe neonatal encephalopathy that subsequently results in CP. Importantly, all four criteria must be met: 1) evidence of metabolic acidosis (pH <7.0 and base deficit of 12 mmol/L or more); 2) early onset of severe or moderate neonatal encephalopathy in infants born at 34 or more weeks' gestation; 3) CP of the spastic quadriplegic or dyskinetic type, and 4) exclusion of other identifiable etiologies, such as trauma, coagulation disorders, infectious conditions, or genetic disorders. Other criteria that together suggest intrapartum timing are also discussed. The focus of this paper is to explore antenatal antecedents as etiologies of CP and the impact of obstetric care on the prevention of CP.

Are we optimizing gestational diabetes treatment with glyburide? The pharmacologic basis for better clinical practice.

Glyburide's pharmacokinetics (PK) and pharmacodynamics have not been studied in women with gestational diabetes mellitus (GDM). The objective of this study was to assess steady-state PK of glyburide, as well as insulin sensitivity, beta-cell responsivity, and overall disposition indices after a mixed-meal tolerance test (MMTT) in women with GDM (n = 40), nonpregnant women with type 2 diabetes mellitus (T2DM) (n = 26), and healthy pregnant women (n = 40, MMTT only). At equivalent doses, glyburide plasma concentrations were approximately 50% lower in pregnant women than in nonpregnant subjects. The average umbilical cord/maternal plasma glyburide concentration ratio at the time of delivery was 0.7 +/- 0.4. Insulin sensitivity was approximately fivefold lower in women with GDM as compared with healthy pregnant women. Despite comparable beta-cell responsivity indices, the average beta-cell function corrected for insulin resistance was more than 3.5-fold lower in women with glyburide-treated GDM than in healthy pregnant women. Women with GDM in whom glyburide treatment has failed may benefit from alternative medication or dosage escalation; however, fetal safety should be kept in mind.

Timing of mid-trimester cervical length shortening in high-risk women.

OBJECTIVE: To examine the natural history of cervical length shortening in women who had experienced at least one prior spontaneous preterm birth at between 17+0 and 33+6 weeks' gestation. METHODS: This was an analysis of prerandomization data from the multicenter Vaginal Ultrasound Cerclage Trial. Serial cervical length was measured by transvaginal sonography in 1014 high-risk women at 16+0 to 22+6 weeks. We performed survival analyses in which the outcome was cervical length shortening<25 mm and data were censored if this did not occur before 22+6 weeks' gestation. The incidence of cervical length shortening and the time to shortening were compared for women whose earliest prior preterm birth was in the mid-trimester, defined as <24 weeks, vs. those at weeks 24-33. Similar comparisons were performed based on each patient's most recent birth history. RESULTS: Time to cervical length shortening by survival analysis was significantly shorter (hazard ratio (HR)=2.2, P<0.0001) and the relative risk (RR) of shortening significantly higher (RR=1.8, P<0.0001) for women whose earliest prior spontaneous preterm birth was at <24 weeks. A larger effect was observed for women whose most recent birth was at <24 weeks (HR=2.8, P<0.0001; RR=2.1, P<0.0001). The observed hazard ratios remained significant after adjusting for confounders in a multivariable Cox proportional hazards model. CONCLUSION: Women with a prior spontaneous preterm birth at <24 weeks are at a higher risk of cervical shortening, and do so at a higher rate and at an earlier gestational age, than do women with a later preterm birth history.

Newborn brachial plexus injuries: The twisting and extension of the fetal head as contributing causes.

The exact mechanism of the causation of brachial plexus injury (BPI) has long been a matter of controversy. It is our opinion that the twisting and the extension of the fetal head, during the labour and delivery process, will increase the stretching of the neck, thus contributing to the labour forces as the cause of BPI. Our opinions are offered to other researchers and readers for their consideration of how the labour forces can cause BPI.

Calcitonin gene-related peptide stimulates human villous trophoblast cell differentiation in vitro.

Calcitonin gene-related peptide (CGRP) is a multifunctional peptide present in both maternal and fetal circulations in pregnancy. Its receptors have been identified on human trophoblast cells, but the role of CGRP in trophoblast differentiation remains unknown. This study was designed to determine the effect of CGRP on the differentiation of villous trophoblasts isolated from normal human term placentae. The morphological and functional differentiation of the trophoblast cells were assessed by desmosomal protein immunofluorescent staining and the quantification of hCG, estrogen and progesterone secretion. Results showed that (i) exposure of villous trophoblast cells to CGRP led to a dose-dependent increase in intracellular cyclic adenosine monophosphate (cAMP) accumulation; (ii) immunofluorescent staining with antidesmosomal antibody was identified at the boundaries between aggregated cytotrophoblast cells, and these stainings disappeared when cells fused to form syncytiotrophoblast cells; (iii) the formation of multinucleated syncytiums in primary cultured cytotrophoblasts was stimulated by CGRP as evidenced by the changes in antidesmosomal staining; (iv) CGRP increases trophoblast hCG secretion in a time- and dose-dependent manner, and this secretion was blocked by CGRP antagonist, CGRP(8-37), and (v) both 17beta-estradiol (E(2)) and progesterone concentrations in the culture medium were increased by CGRP, and these increases were dose dependent. These observations suggest that CGRP may be involved in the morphological and functional differentiation of trophoblast cells, and these actions might be attributed to CGRP-induced intracellular cAMP accumulation.

Contrast sonography, video densitometry and intervillous blood flow: a pilot project.

PURPOSE: To examine the feasibility of constructing time-intensity (TI) curves from the intervillous space with an intravascular ultrasound contrast agent and computer assisted video densitometry. STUDY DESIGN: We sedated nine pregnant baboons, optimized the grey scale and color Doppler images of their placentas, and then fixed the transducers in place. For each injection of contrast, we recorded images on videotape without changing the ultrasound image processing functions. Video images were captured using a Macintosh personal computer equipped with a video-capture board using image analysis software (Image 1.4, W Rasband, NIH). For each injection, we sampled digitized images of a fixed region of interest at regular intervals. After computing the mean video density of each image, we used the sampling frequency to construct TI curves depicting any change over time as the contrast agents washed into and out of the intervillous space. RESULTS: Three of four agents tested produced changes in the video density of the placenta. TI curves were established using both grey scale and color Doppler signal augmentation. As expected, intra-arterial agents produced rapid accumulation and decay. Intravenous agents produced more protracted effects secondary to bolus dilution and transit through the right heart and pulmonary vascular bed. CONCLUSION: TI curves may be generated from the intervillous space with the use of a transpulmonary ultrasound contrast agent and video densitometry. If validated by further study, this may allow investigators to apply ultrasound and indicator-dilution theory to intervillous blood flow.

Local immunomodulation with CD4 and CD8 antibodies, but not cyclosporine A, improves osteogenesis induced by ADhBMP9 gene therapy.

This study was designed to see if immunosuppression achieved using local application of cyclosporine A (Cs. A) or CD4 and CD8 antibodies would improve bone formation following intramuscular injections of human BMP-4 and BMP-9 adenoviral vectors (ADhBMP4 and ADhBMP9) in Sprague-Dawley rats. Cs. A was injected into the thigh muscle. After 2 days, ADhBMP4, ADhBMP9, and the antibodies were separately injected into the left and right rear legs. At this time, the number of CD4+/CD3+ cells was significantly lower and the number of CD8+/CD3+ cells higher in the Cs. A group than in the control group (P < 0.01). The total number of white blood cells 3 days following injection of CD4 and CD8 antibodies was significantly lower than that before the injection (P < 0.01). At 4 weeks after the viral and antibody injections, mean bone volumes at the ADhBMP9 treatment sites were 0.29 +/- 0.01 cm3 in the viral control group, 0.17 +/- 0.03 cm3 in the Cs. A-ADhBMPs group, and 0.59 +/- 0.07 cm3 in the antibodies-ADhBMPs group. ADhBMP4 did not induce new bone formation in any group. This study demonstrates that local immunomodulation may improve the osteogenic potential of bone morphogenetic protein gene therapy in the clinical setting.

Stillbirth in obstetric practice: report of survey findings.

OBJECTIVE: Stillbirth affects a large portion of the population and results in mortality rates comparable to those of preterm delivery and sudden infant death syndrome combined. Despite the large burden, little information is available to offer patients regarding etiology, treatment or prevention for a subsequent pregnancy. METHODS: We surveyed a sample of Fellows of the American College of Obstetricians and Gynecologists to determine the practice patterns in the management of stillbirth. RESULTS: The majority of Fellows agreed on the definition of stillbirth; however, their approach to treatment and prevention varied. A majority of Fellows believed that research on understanding stillbirth was of national importance. CONCLUSIONS: A comprehensive educational effort to include current knowledge regarding causes and management, standardized diagnostic procedures, death registration and case review is recommended to improve obstetric care of those with a stillbirth.

Osteogenic potential of five different recombinant human bone morphogenetic protein adenoviral vectors in the rat.

Bone morphogenetic protein (BMP) adenoviral vectors for the induction of osteogenesis are being developed for the treatment of bone pathology. However, it is still unknown which BMP adenoviral vector has the highest potential to stimulate bone formation in vivo. In this study, the osteogenic activities of recombinant human BMP-2, BMP-4, BMP-6, BMP-7, and BMP-9 adenoviruses were compared in vitro, in athymic nude rats, and in Sprague-Dawley rats. In vitro osteogenic activity was assessed by measuring the alkaline phosphatase activity in C2C12 cells transduced by the various BMP vectors. The alkaline phosphatase activity induced by 2 x 10(5) PFU/well of BMP viral vector was 4890 x 10(-12) U/well for ADCMVBMP-9, 302 x 10(-12) U/well for ADCMVBMP-4, 220 x 10(-12) U/well for ADCMVBMP-6, 45 x 10(-12) U/well for ADCMVBMP-2, and 0.43 x 10(-12) U/well for ADCMVBMP-7. The average volume of new bone induced by 10(7) PFU of BMP vector in athymic nude rats was 0.37+/-0.03 cm(3) for ADCMVBMP-2, 0.89+/-0.07 cm(3) for ADCMVBMP-4, 1.02+/-0.07 cm(3) for ADCMVBMP-6, 0.24+/-0.05 cm(3) for ADCMVBMP-7, and 0.63+/-0.07 cm(3) for ADCMVBMP-9. In immunocompetent Sprague-Dawley rats, no bone formation was demonstrated in the ADCMVBMP-2, ADCMVBMP-4, and ADCMVBMP-7 groups. ADCMVBMP-6 at a viral dose of 10(8) PFU induced 0.10+/-0.03 cm(3) of new bone, whereas ADCMVBMP-9 at a lower viral dose of 10(7) PFU induced more bone, with an average volume of 0.29+/-0.01 cm(3).

Postpartum hemorrhagic shock resulting in thrombotic thrombocytopenic purpura-hemolytic uremic syndrome.

Thrombotic microangiopathies may be initiated by a number of antecedent events. When presented with postpartum hemorrhage and unexplained thrombocytopenia, it is prudent to consider microangiopathic hemolytic anemia in the differential diagnosis. A 25-year-old woman, gravida 2, para 1, had an uncomplicated repeat Cesarean delivery at 38 weeks' gestation. She subsequently had an exploratory laparotomy for hemoperitoneum resulting from a left uterine artery laceration. On postoperative day 3, she developed thrombotic chrombocytopenic purpura-hemolytic uremic syndrome and was treated with plasma exchange therapy and dialysis. It is critical that clinicians consider this potentially fatal disease in the differential diagnosis when hemorrhagic shock is associated with unexplained thrombocytopenia, so that appropriate and early treatment may lead to a favorable outcome.

Effects of L-type Ca(2+)-channel blockade, K(+)(ATP)-channel opening and nitric oxide on human uterine contractility in relation to gestational age and labour.

Relative uterine inactivity during pregnancy changes to vigorous rhythmic contractility during labour. We hypothesized that mechanisms involved in the regulation of uterine quiescence and contractility differ between term and preterm myometrium and in labour and non-labour states. Myometrial strips, prepared from biopsies taken at Caesarean section from labouring and non-labouring women preterm and at term, were mounted in organ chambers for isometric tension recording. Oxytocin (10(-9) mol/l) was added to maintain stable contractions, and effects of various inhibitors of uterine contractility were studied. The inhibitory effects of L-type Ca(2+)-channel blocker nifedipine and ATP-sensitive K(+)-channel opener pinacidil were greater in myometrium from the non-labour versus the labour group, both preterm and at term. In addition, pinacidil's effect was greater at term compared with preterm in the non-labour group. Mg(2+) and the nitric oxide donor sodium nitroprusside significantly inhibited contractility in all groups without significant differences with regard to labour or gestational age. Decreased inhibition of human uterine contractility by L-type Ca(2+)-channel blockers and K(+)(ATP)-channel openers in preterm and term labour may reflect changes in expression and activity of these channels. Effects of nitric oxide and Mg(2+) are not affected by gestational age or labour.

Cardiac disease and pregnancy.

The pregnant state imposes a supraphysiologic strain on the pregnant woman's cardiac performance through complex biochemical, electric, and physiologic changes affecting the blood volume, myocardial contractility, and resistance of the vascular bed. In the presence of underlying heart disease, these changes can compromise the woman's hemodynamic balance, her life, and that of her unborn child. Cardiac pathology represents a heterogeneous group of disorders, each with its own hemodynamic, genetic, obstetric, and social implications. Physicians caring for these women should actively address the issue of reproduction. Ideally, pregnancy should be planned to occur after optimization of cardiac performance by medical or surgical means. Once pregnancy is achieved, the concerted effort of a multidisciplinary team of obstetricians, cardiologists, anesthesiologists, nursing, social, and other services provides the best opportunity to carry the pregnancy to a successful outcome.

Teaching the Laufe-Piper forceps technique at cesarean delivery.

OBJECTIVE: To present a method of teaching forceps technique during cesarean delivery of breech-presenting infants using Laufe-Piper forceps and to evaluate its usefulness. STUDY DESIGN: For several years, residents at the University of Texas Medical Branch, Galveston, have learned and practiced Piper forceps technique during cesarean delivery. To assess their experience with this method, we mailed questionnaires to third- and fourth-year residents and recent graduates of the Galveston program. The same surveys were mailed to a control group of residents and recent graduates of two other programs where this teaching exercise is not practiced routinely. RESULTS: Responses were received from 32 (74%) study subjects and 63 (71%) controls. Demographic characteristics and experience with vaginal breech delivery were similar between the two groups. Respondents from the Galveston program noted greater annual use of forceps for vaginal delivery of cephalic-presenting infants (P = .012). They also rated themselves as more comfortable (P = .023) and more skilled (P = .006) with Piper forceps than controls. Of 53 respondents who had had previous experience with this teaching method, 47 noted that it provided a great or moderate educational benefit, and 36 strongly or moderately believed it gave them more confidence in using Piper forceps during vaginal breech delivery. Using multiple regression analysis, sex, overall level of experience, Piper forceps experience during vaginal delivery and overall forceps use were stronger determinants of self-rated comfort and skill than was experience with Laufe-Piper forceps during cesarean. CONCLUSION: Laufe-Piper forceps can be used for cesarean delivery of breech-presenting infants. This practice promotes confidence and skill for their use at vaginal delivery.