Risks of stillbirth, neonatal mortality, and severe neonatal morbidity by birthweight centiles associated with expectant management at term.

BACKGROUND: Determining the optimal time of birth at term is challenging given the ongoing risks of stillbirth with increasing gestation vs the risks of significant neonatal morbidity at early-term gestations. These risks are more pronounced in small infants. OBJECTIVE: This study aimed to evaluate the risks of stillbirth, neonatal mortality, and severe neonatal morbidity by comparing expectant management with delivery from 37+0 weeks of gestation. STUDY DESIGN: This was a retrospective cohort study evaluating women with singleton, nonanomalous pregnancies at 37+0 to 40+6 weeks' gestation in Queensland, Australia, delivered from 2000 to 2018. Rates of stillbirth, neonatal death, and severe neonatal morbidity were calculated for <3rd, 3rd to <10th, 10th to <25th, 25th to <90th, and ≥90th birthweight centiles. The composite risk of mortality with expectant management for an additional week in utero was compared with rates of neonatal mortality and severe neonatal morbidity. RESULTS: Of 948,895 singleton, term nonanomalous births, 813,077 occurred at 37+0 to 40+6 weeks' gestation. Rates of stillbirth increased with gestational age, with the highest rate observed in infants with birthweight below the third centile: 10.0 per 10,000 (95% confidence interval, 6.2-15.3) at 37+0 to 37+6 weeks, rising to 106.4 per 10,000 (95% confidence interval, 74.6-146.9) at 40+0 to 40+6 weeks' gestation. The rate of neonatal mortality was highest at 37+0 to 37+6 weeks for all birthweight centiles. The composite risk of expectant management rose sharply after 39+0 to 39+6 weeks, and was highest in infants with birthweight below the third centile (125.2/10,000; 95% confidence interval, 118.4-132.3) at 40+0 to 40+6 weeks' gestation. Balancing the risk of expectant management and delivery (neonatal mortality), the optimal timing of delivery for each birthweight centile was evaluated on the basis of relative risk differences. The rate of severe neonatal morbidity sharply decreased in the period between 37+0 to 37+6 and 38+0 to 38+6 weeks, particularly for infants with birthweight below the third centile. CONCLUSION: Our data suggest that the optimal time of birth is 37+0 to 37+6 weeks for infants with birthweight <3rd centile and 38+0 to 38+6 weeks' gestation for those with birthweight between the 3rd and 10th centile and >90th centile. For all other birthweight centiles, birth from 39+0 weeks is associated with the best outcomes. However, large numbers of planned births are required to prevent a single excess death. The healthcare costs and acceptability to women of potential universal policies of planned birth need to be carefully considered.

Video Instruction for Pushing in the Second Stage: a randomized controlled trial.

BACKGROUND: The second stage of labor requires active patient engagement. Previous studies suggest that coaching can influence the second stage of labor duration. However, a standardized education tool has not been established, and patients face many barriers to accessing childbirth education before delivery. OBJECTIVE: This study aimed to investigate the effect of an intrapartum video pushing education tool on the second stage of labor duration. STUDY DESIGN: This was a randomized controlled trial of nulliparous patients with singleton pregnancies ≥37 weeks of gestation admitted for induction of labor or spontaneous labor with neuraxial anesthesia. Patients were consented on admission and block randomized in active labor to 1 of 2 arms in a 1:1 ratio. The study arm viewed a 4-minute video before the second stage of labor on what to anticipate in the second stage of labor and pushing techniques. The control arm received the standard of care: bedside coaching at 10 cm dilation from a nurse or physician. The primary outcome was second stage of labor duration. The secondary outcomes were birth satisfaction (using the Modified Mackey Childbirth Satisfaction Rating Scale), mode of delivery, postpartum hemorrhage, clinical chorioamnionitis, neonatal intensive care unit admission, and umbilical artery gases. Of note, 156 patients were needed to detect a 20% decrease in the second stage of labor duration with 80% power, 2-sided alpha level of .05, and 10% loss after randomization. Funding was provided by the Lucy Anarcha Betsy award from the division of clinical research at Washington University. RESULTS: Of 161 patients, 81 were randomized to standard of care, and 80 were randomized to intrapartum video education. Among these patients, 149 progressed to the second stage of labor and were included in the intention-to-treat analysis: 69 in the video group and 78 in the control group. Maternal demographics and labor characteristics were similar between groups. The second stage of labor duration was statistically similar between the video arm (61 minutes [interquartile range, 20-140]) and the control arm (49 minutes [interquartile range, 27-131]) (P=.77). There was no difference in mode of delivery, postpartum hemorrhage, clinical chorioamnionitis, neonatal intensive care unit admission, or umbilical artery gases between groups. Although the overall birth satisfaction score on the Modified Mackey Childbirth Satisfaction Rating Scale was similar between groups, patients in the video group rated their "level of comfort during birth" and "attitude of the doctors in birth" significantly higher or more positively than patients in the control group (P<.05 for both). CONCLUSION: Intrapartum video education was not associated with a shorter second stage of labor duration. However, patients who received video education reported a higher level of comfort and a more favorable perception of their physician, suggesting that video education may be a helpful tool to improve the birth experience.

A systematic review and critical evaluation of quality of clinical practice guidelines on fetal growth restriction.

INTRODUCTION: To systematically identify and critically assess the quality of clinical practice guidelines (CPGs) on management fetal growth restriction (FGR). CONTENT: Medline, Embase, Google Scholar, Scopus and ISI Web of Science databases were searched to identify all relevant CPGs on FGR. SUMMARY: Diagnostic criteria of FGR, recommended growth charts, recommendation for detailed anatomical assessment and invasive testing, frequency of fetal growth scans, fetal monitoring, hospital admission, drugs administrations, timing at delivery, induction of labor, postnatal assessment and placental histopathological were assessed. Quality assessment was evaluated by AGREE II tool. Twelve CPGs were included. Twenty-five percent (3/12) of CPS adopted the recently published Delphi consensus, 58.3% (7/12) an estimated fetal weight (EFW)/abdominal circumference (AC) EFW/AC <10th percentile, 8.3% (1/12) an EFW/AC <5th percentile while one CPG defined FGR as an arrest of growth or a shift in its rate measured longitudinally. Fifty percent (6/12) of CPGs recommended the use of customized growth charts to assess fetal growth. Regarding the frequency of Doppler assessment, in case of absent or reversed end-diastolic flow in the umbilical artery 8.3% (1/12) CPGs recommended assessment every 24-48, 16.7% (2/12) every 48-72 h, 1 CPG generically recommended assessment 1-2 times per week, while 25 (3/12) did not specifically report the frequency of assessment. Only 3 CPGs reported recommendation on the type of Induction of Labor to adopt. The AGREE II standardized domain scores for the first overall assessment (OA1) had a mean of 50%. OUTLOOK: There is significant heterogeneity in the management of pregnancies complicated by FGR in published CPGs.

Clinical significance of umbilical artery intermittent vs persistent absent end-diastolic velocity in growth-restricted fetuses.

BACKGROUND: Umbilical artery absent end-diastolic velocity indicates increased placental resistance and is associated with increased risk of perinatal demise and neonatal morbidity in fetal growth restriction. However, the clinical implications of intermittent vs persistent absent end-diastolic velocity are unclear. OBJECTIVE: We compared umbilical artery Doppler velocimetry changes during pregnancy and neonatal outcomes between pregnancies with fetal growth restriction and intermittent absent end-diastolic velocity and those with persistent absent end-diastolic velocity. STUDY DESIGN: In this retrospective study of singletons with fetal growth restriction and absent end-diastolic velocity, umbilical artery Doppler abnormalities were classified as follows: intermittent absent end-diastolic velocity (<50% of cardiac cycles with absent end-diastolic velocity) and persistent absent end-diastolic velocity (≥50% of cardiac cycles with absent end-diastolic velocity). The primary outcome was umbilical artery Doppler progression to reversed end-diastolic velocity. Secondary outcomes included sustained umbilical artery Doppler improvement, latency to delivery, gestational age at delivery, neonatal morbidity composite, rates of neonatal intensive care unit admission, and length of neonatal intensive care unit stay. Outcomes were compared between intermittent absent end-diastolic velocity and persistent absent end-diastolic velocity. Multivariate logistic regression was used to adjust for confounders. A receiver operating characteristic curve was generated to assess the sensitivity and specificity of the percentage of waveforms with absent end-diastolic velocity in predicting the neonatal composite. The Youden index was used to calculate the optimal absent end-diastolic velocity percentage cut-point for predicting the neonatal composite. RESULTS: Of the 77 patients included, 38 had intermittent absent end-diastolic velocity and 39 had persistent absent end-diastolic velocity. Maternal characteristics, including age, parity, and preexisting conditions did not differ significantly between the 2 groups. Progression to reversed end-diastolic velocity was less common in intermittent absent end-diastolic velocity than in persistent absent end-diastolic velocity (7.9% vs 25.6%; odds ratio, 0.25; 95% confidence interval, 0.06-0.99). Sustained umbilical artery Doppler improvement was more common in intermittent absent end-diastolic velocity than in persistent absent end-diastolic velocity (50.0% vs 10.3%; odds ratio, 8.75; 95% confidence interval, 2.60-29.5). Pregnancies with intermittent absent end-diastolic velocity had longer latency to delivery than those with persistent absent end-diastolic velocity (11 vs 3 days; P<.01), and later gestational age at delivery (33.9 vs 28.7 weeks; P<.01). Composite neonatal morbidity was less common in the intermittent absent end-diastolic velocity group (55.3% vs 92.3%; P<.01). Neonatal death occurred in 7.9% of intermittent absent end-diastolic velocity cases and 33.3% of persistent absent end-diastolic velocity cases (P<.01). The differences in neonatal outcomes were no longer significant when controlling for gestational age at delivery. The percentage of cardiac cycles with absent end-diastolic velocity was a modest predictor of neonatal morbidity, with an area under the receiver operating characteristic curve of 0.71 (95% confidence interval, 0.58-0.84). The optimal percentage cut-point for fetal cardiac cycles with absent end-diastolic velocity observed at the sentinel ultrasound for predicting neonatal morbidity was calculated to be 47.7%, with a sensitivity of 65% and specificity of 85%. CONCLUSIONS: Compared with persistent absent end-diastolic velocity, diagnosis of intermittent absent end-diastolic velocity in the setting of fetal growth restriction is associated with lower rates of progression to reversed end-diastolic velocity, higher likelihood of umbilical artery Doppler improvement, longer latency to delivery, and higher gestational age at delivery, leading to lower rates of neonatal morbidity and death. Our data support using an absent end-diastolic velocity percentage cut-point in 50% of cardiac cycles to differentiate intermittent absent end-diastolic velocity from persistent absent end-diastolic velocity. This differentiation in growth-restricted fetuses with absent end-diastolic velocity may allow further risk stratification.

Severity of intrapartum fever and neonatal outcomes.

BACKGROUND: The few studies that have addressed the relationship between severity of intrapartum fever and neonatal and maternal morbidity have had mixed results. The impact of the duration between reaching maximum intrapartum temperature and delivery on neonatal outcomes remains unknown. OBJECTIVE: To test the association of severity of intrapartum fever and duration from reaching maximum temperature to delivery with neonatal and maternal morbidity. STUDY DESIGN: This was a secondary analysis of a prospective cohort of term, singleton patients admitted for induction of labor or spontaneous labor who had intrapartum fever (≥38°C). Patients were divided into 3 groups according to maximum temperature during labor: afebrile (<38°C), mild fever (38°C-39°C), and severe fever (>39°C). The primary outcome was composite neonatal morbidity (umbilical artery pH <7.1, mechanical ventilation, respiratory distress, meconium aspiration with pulmonary hypertension, hypoglycemia, neonatal intensive care unit admission, and Apgar <7 at 5 minutes). Secondary outcomes were composite neonatal neurologic morbidity (hypoxic-ischemic encephalopathy, hypothermia treatment, and seizures) and composite maternal morbidity (postpartum hemorrhage, endometritis, and maternal packed red blood cell transfusion). Outcomes were compared between the maximum temperature groups using multivariable logistic regression. Cox proportional-hazards regression modeling accounted for the duration between reaching maximum intrapartum temperature and delivery. RESULTS: Of the 8132 patients included, 278 (3.4%) had a mild fever and 74 (0.9%) had a severe fever. The incidence of composite neonatal morbidity increased with intrapartum fever severity (afebrile 5.4% vs mild 18.0% vs severe 29.7%; P<.01). After adjusting for confounders, there were increased odds of composite neonatal morbidity with severe fever compared with mild fever (adjusted odds ratio, 1.93 [95% confidence interval, 1.07-3.48]). Severe fevers remained associated with composite neonatal morbidity compared with mild fevers after accounting for the duration between reaching maximum intrapartum temperature and delivery (adjusted hazard ratio, 2.05 [95% confidence interval, 1.23-3.43]). Composite neonatal neurologic morbidity and composite maternal morbidity were not different between patients with mild and patients with severe fevers. CONCLUSION: Composite neonatal morbidity correlated with intrapartum fever severity in a potentially dose-dependent fashion. This correlation was independent of the duration from reaching maximum intrapartum temperature to delivery, suggesting that clinical management of intrapartum fever, in terms of timing or mode of delivery, should not be affected by this duration.

The association of fetal acidemia with adverse neonatal outcomes at time of scheduled cesarean delivery.

BACKGROUND: Fetal acidemia at the time of a scheduled cesarean delivery is generally unexpected. In the setting of reassuring preoperative monitoring, the duration of fetal acidemia in this scenario is presumably brief. The neonatal sequelae and risks associated with brief fetal acidemia in this setting are unknown. OBJECTIVE: We aimed to assess whether fetal acidemia at the time of a scheduled prelabor cesarean delivery is associated with adverse neonatal outcomes. STUDY DESIGN: This was a retrospective cohort study of singleton, term, nonanomalous, liveborn neonates delivered by scheduled cesarean delivery that was performed under regional anesthesia from 2004 to 2014 at a single tertiary care center with a universal umbilical cord gas policy. Neonates born to laboring gravidas and those whose cesarean delivery was performed for nonreassuring fetal status were excluded. All included patients had reassuring preoperative fetal monitoring. The primary outcome was a composite adverse neonatal outcome that included neonatal death, encephalopathy, therapeutic hypothermia, seizures, intubation, and respiratory distress. This outcome was compared between patients with and those without fetal acidemia (umbilical artery pH <7.2). A multivariable logistic regression was used to adjust for confounders. Cases of fetal acidemia were further characterized as respiratory, metabolic, or mixed acidemia based on additional umbilical cord gas values. Secondary analyses examining the association between the type of acidemia and neonatal outcomes were also performed. RESULTS: Of 2081 neonates delivered via scheduled cesarean delivery, 252 (12.1%) had fetal acidemia at the time of delivery. Acidemia was more common in breech neonates and in neonates born to gravidas with obesity and gestational diabetes mellitus. Compared with fetuses with normal umbilical artery pH, those with fetal acidemia were at a significantly increased risk for adverse neonatal outcome (adjusted relative risk, 2.95; 95% confidence interval, 2.03-4.12). This increased risk was similar regardless of the type of acidemia. CONCLUSION: Even a brief period of mild acidemia is associated with adverse neonatal outcomes at the time of a scheduled cesarean delivery despite reassuring preoperative monitoring. Addressing modifiable intraoperative factors that may contribute to fetal acidemia at the time of a scheduled cesarean delivery, such as maternal hypotension and prolonged operative time, is an important priority to potentially decrease neonatal morbidity in full-term gestations.

Impact of Using Abdominal Circumference Independently in the Diagnosis of Fetal Growth Restriction.

OBJECTIVE: Society for Maternal-Fetal Medicine guidelines for diagnosing fetal growth restriction (FGR) have broadened the definition to include abdominal circumference (AC) <10th percentile for gestational age (GA) regardless of estimated fetal weight (EFW). We aimed to compare the ability of three definitions of FGR to predict small for gestational age (SGA) neonates and adverse outcomes. METHODS: We performed a secondary analysis of a prospective cohort of patients who underwent assessment of fetal growth between GA of 26 and 36 weeks. We compared three definitions of FGR: EFW <10th percentile; AC <10th percentile; either EFW or AC <10th percentile. The primary outcome was successful prediction of neonatal SGA. Secondary outcomes included a composite adverse neonatal outcome (CANO). We further compared these definitions of FGR using area under receiver operative curves (AUC) to measure their discriminatory abilities. RESULTS: About 1054 women met inclusion criteria. Ninety-one (8.6%) had EFW <10th percentile, 122 (11.6%) had AC <10th percentile, and 137 (12.9%) had either EFW or AC <10th percentile. SGA was seen in 139 (13.2%); CANO was seen in 139 (13.2%). Ability for detecting neonatal SGA was significantly better when the definition included both EFW or AC <10th percentile compared to either variable independently. The AUC were: 0.74, 0.73, 0.69; P = .0003. There was no statistical significance in ability for predicting CANO (AUC 0.51, 0.51, 0.50; P = .7447). CONCLUSIONS: Addition of AC as a criterion for diagnosing FGR improves our ability to predict neonatal SGA compared to using EFW alone. All three definitions were poorly predictive of neonates at risk for adverse outcomes.

The Impact of Mode of Delivery on Maternal and Neonatal Outcomes during Periviable Birth (22-25 Weeks).

OBJECTIVE: The objective of our study was to compare the maternal and neonatal complications of periviable birth by the delivery route. STUDY DESIGN: A retrospective cohort study of periviable deliveries (220/7-256/7weeks) from 2013 to 2020 at a tertiary teaching institution was conducted. Deliveries were grouped by the mode of delivery. Excluded deliveries included pregnancy termination, anomaly, or undesired neonatal resuscitation. The primary composite maternal outcome included death, intensive care admission, sepsis, surgical site infection, unplanned operation, or readmission. Secondary outcomes included maternal blood loss, length of stay, neonatal survival, bronchopulmonary dysplasia (BPD), intraventricular hemorrhage (IVH), necrotizing enterocolitis (NEC), patent ductus arteriosus (PDA), and retinopathy of prematurity (ROP). Outcomes were compared using Student's t-test, Wilcoxon-Mann-Whitney and Chi-squared tests. Relative risk (RR) and 95% confidence intervals were calculated with log-binomial regression. p-Values <0.05 were considered significant. Demographic and intervention variables associated with the outcome and the exposure were included in an adjusted relative risk (aRR) model. Subgroup analyses of singleton pregnancies and 220/7 to 236/7 weeks deliveries were conducted. RESULTS: After exclusion, 230 deliveries were included in the cohort. Maternal characteristics were similar between cohorts. For the primary outcome, cesarean delivery was associated with a trend toward increased maternal morbidity (22.6 vs. 10.7%, RR = 2.11 [1.03-4.43], aRR = 1.95 [0.94-4.03], p-value 0.07). Administration of magnesium sulfate, antenatal corticosteroids, and tocolytics were similar between cohorts. Neonatal survival to discharge was not different between the groups (54/83, 65.1% vs. 118/191, 61.8%, aRR = 0.93 [0.77-1.13]). Among the 172 neonates discharged alive, there was no difference in BPD, IVH, NEC, PDA, ROP, or intact survival. CONCLUSION: Periviable birth has a high rate of maternal morbidity with a trend toward the highest risk among women undergoing cesarean delivery. These risks should be included in shared decision-making. KEY POINTS: · Periviable birth has high maternal morbidity (19%) and is highest after cesarean delivery (23%).. · Route of delivery does not impact neonatal survival or intact neonatal survival.. · Head entrapment is rare during vaginal breech delivery..

The Impact of a Multidisciplinary Opioid Use Disorder Prenatal Clinic on Breastfeeding Rates and Postpartum Care.

OBJECTIVE: To evaluate the hypothesis that patients with opioid use disorder (OUD), who receive prenatal care in a multidisciplinary, prenatal OUD clinic, have comparable postpartum breastfeeding rates, prenatal and postpartum visit compliance, and postpartum contraceptive use when compared with matched controls without a diagnosis of OUD. STUDY DESIGN: This was a retrospective, matched, cohort study that included all patients who received prenatal care in a multidisciplinary, prenatal OUD clinic-Clinic for Acceptance Recovery and Empowerment (CARE)-between September 2018 and August 2020. These patients were maintained on opioid agonist therapy (OAT) throughout their pregnancy. CARE patients were matched to controls without OUD in a 1:4 ratio for mode of delivery, race, gestational age ± 1 week, and delivery date ± 6 months. The primary outcome was rate of exclusive breastfeeding at maternal discharge. Secondary outcomes included adherence with prenatal care (≥4 prenatal visits), adherence with postpartum care (≥1 postpartum visit), postpartum contraception plan prior to delivery, and type of postpartum contraceptive use. Conditional multivariate logistic regression was used to account for possible confounders in adjusted calculations. RESULTS: A total of 210 patients were included (42 CARE and 168 matched controls). Despite having lower rates of adequate prenatal care, 40 CARE patients (95%) were exclusively breastfeeding at discharge resulting in CARE patients being significantly more likely to be breastfeeding at discharge (adjusted relative risk (aRR): 1.28, 95% confidence interval [CI]: 1.05-1.55). CARE patients and controls demonstrated no difference in postpartum visit compliance (86 vs. 81%, aRR: 1.03, 95% CI: 0.76-1.40) or effective, long-term contraception use (48 vs. 48%; aRR: 0.81, 95% CI: 0.36-1.84). CONCLUSION: In the setting of multidisciplinary OUD prenatal care during pregnancy, patients with OUD were more likely to be breastfeeding at the time of discharge than matched controls, with no difference in postpartum visit compliance or effective, long-term contraception. KEY POINTS: · Women with OUD are more likely to breastfeed when engaged in a multidisciplinary prenatal clinic.. · Women with OUD had no difference in LARC use when engaged in a multidisciplinary prenatal clinic.. · Women with OUD had no difference in postpartum visit rate in a multidisciplinary prenatal clinic..

Prediction of Large-for-Gestational-Age Neonates by Different Growth Standards.

OBJECTIVE: Compare the accuracy of the Hadlock, the NICHD, and the Fetal Medicine Foundation (FMF) charts to detect large-for-gestational-age (LGA) and adverse neonatal outcomes (as a secondary outcome). METHODS: This is a secondary analysis from a prospective study that included singleton non-anomalous gestations with growth ultrasound at 26-36 weeks. LGA was suspected with estimated fetal weight > 90th percentile by the NICHD, FMF, and Hadlock charts. LGA was diagnosed with birth weight > 90th percentile. We tested the performance of these charts to detect LGA and adverse neonatal outcomes (neonatal intensive care unit admission, Ph < 7.1, Apgar <7 at 5 minutes, seizures, and neonatal death) by calculating the area under the curve, sensitivity, specificity, positive predictive value, and negative predictive value. RESULTS: Of 1054 pregnancies, 123 neonates (12%) developed LGA. LGA was suspected in 58 (5.5%) by Hadlock, 229 (21.7%) by NICHD standard, and 231 (22%) by FMF chart. The NICHD standard (AUC: .79; 95% CI: .75-.83 vs. AUC .64; 95%CI: .6-.68; p = < .001) and FMF chart (AUC: .81 95% CI: .77-.85 vs. AUC .64; 95%CI: .6-.68; p = < .001) were more accurate than Hadlock. The FMF and NICHD had higher sensitivity (77.2 vs. 72.4 vs. 30.1%) but Hadlock had higher specificity for LGA (97.5 vs. 88.5 vs. 85.4%). All standards were poor predictors for adverse neonatal outcomes. CONCLUSIONS: The NICHD and the FMF standards may increase the detection rate of LGA in comparison to the Hadlock chart. However, this may increase obstetrical interventions.

External validation of prognostic models predicting pre-eclampsia: individual participant data meta-analysis.

BACKGROUND: Pre-eclampsia is a leading cause of maternal and perinatal mortality and morbidity. Early identification of women at risk during pregnancy is required to plan management. Although there are many published prediction models for pre-eclampsia, few have been validated in external data. Our objective was to externally validate published prediction models for pre-eclampsia using individual participant data (IPD) from UK studies, to evaluate whether any of the models can accurately predict the condition when used within the UK healthcare setting. METHODS: IPD from 11 UK cohort studies (217,415 pregnant women) within the International Prediction of Pregnancy Complications (IPPIC) pre-eclampsia network contributed to external validation of published prediction models, identified by systematic review. Cohorts that measured all predictor variables in at least one of the identified models and reported pre-eclampsia as an outcome were included for validation. We reported the model predictive performance as discrimination (C-statistic), calibration (calibration plots, calibration slope, calibration-in-the-large), and net benefit. Performance measures were estimated separately in each available study and then, where possible, combined across studies in a random-effects meta-analysis. RESULTS: Of 131 published models, 67 provided the full model equation and 24 could be validated in 11 UK cohorts. Most of the models showed modest discrimination with summary C-statistics between 0.6 and 0.7. The calibration of the predicted compared to observed risk was generally poor for most models with observed calibration slopes less than 1, indicating that predictions were generally too extreme, although confidence intervals were wide. There was large between-study heterogeneity in each model's calibration-in-the-large, suggesting poor calibration of the predicted overall risk across populations. In a subset of models, the net benefit of using the models to inform clinical decisions appeared small and limited to probability thresholds between 5 and 7%. CONCLUSIONS: The evaluated models had modest predictive performance, with key limitations such as poor calibration (likely due to overfitting in the original development datasets), substantial heterogeneity, and small net benefit across settings. The evidence to support the use of these prediction models for pre-eclampsia in clinical decision-making is limited. Any models that we could not validate should be examined in terms of their predictive performance, net benefit, and heterogeneity across multiple UK settings before consideration for use in practice. TRIAL REGISTRATION: PROSPERO ID: CRD42015029349 .

Effect of Prophylactic Negative Pressure Wound Therapy vs Standard Wound Dressing on Surgical-Site Infection in Obese Women After Cesarean Delivery: A Randomized Clinical Trial.

Importance: Obesity increases the risk of both cesarean delivery and surgical-site infection. Despite widespread use, it is unclear whether prophylactic negative pressure wound therapy reduces surgical-site infection after cesarean delivery in obese women. Objective: To evaluate whether prophylactic negative pressure wound therapy, initiated immediately after cesarean delivery, lowers the risk of surgical-site infections compared with standard wound dressing in obese women. Design, Setting, and Participants: Multicenter randomized trial conducted from February 8, 2017, through November 13, 2019, at 4 academic and 2 community hospitals across the United States. Obese women undergoing planned or unplanned cesarean delivery were eligible. The study was terminated after 1624 of 2850 participants were recruited when a planned interim analysis showed increased adverse events in the negative pressure group and futility for the primary outcome. Final follow-up was December 18, 2019. Interventions: Participants were randomly assigned to either undergo prophylactic negative pressure wound therapy, with application of the negative pressure device immediately after repair of the surgical incision (n = 816), or receive standard wound dressing (n = 808). Main Outcomes and Measures: The primary outcome was superficial or deep surgical-site infection according to the Centers for Disease Control and Prevention definitions. Secondary outcomes included other wound complications, composite of surgical-site infections and other wound complications, and adverse skin reactions. Results: Of the 1624 women randomized (mean age, 30.4 years, mean body mass index, 39.5), 1608 (99%) completed the study: 806 in the negative pressure group (median duration of negative pressure, 4 days) and 802 in the standard dressing group. Superficial or deep surgical-site infection was diagnosed in 29 participants (3.6%) in the negative pressure group and 27 (3.4%) in the standard dressing group (difference, 0.36%; 95% CI, -1.46% to 2.19%, P = .70). Of 30 prespecified secondary end points, 25 showed no significant differences, including other wound complications (2.6% vs 3.1%; difference, -0.53%; 95% CI, -1.93% to 0.88%; P = .46) and composite of surgical-site infections and other wound complications (6.5% vs 6.7%; difference, -0.27%; 95% CI, -2.71% to 2.25%; P = .83). Adverse skin reactions were significantly more frequent in the negative pressure group (7.0% vs 0.6%; difference, 6.95%; 95% CI, 1.86% to 12.03%; P < .001). Conclusions and Relevance: Among obese women undergoing cesarean delivery, prophylactic negative pressure wound therapy, compared with standard wound dressing, did not significantly reduce the risk of surgical-site infection. These findings do not support routine use of prophylactic negative pressure wound therapy in obese women after cesarean delivery. Trial Registration: ClinicalTrials.gov Identifier: NCT03009110.

A Randomized Trial Comparing Skin Antiseptic Agents at Cesarean Delivery.

BACKGROUND: Preoperative skin antisepsis has the potential to decrease the risk of surgical-site infection. However, evidence is limited to guide the choice of antiseptic agent at cesarean delivery, which is the most common major surgical procedure among women in the United States. METHODS: In this single-center, randomized, controlled trial, we evaluated whether the use of chlorhexidine-alcohol for preoperative skin antisepsis was superior to the use of iodine-alcohol for the prevention of surgical-site infection after cesarean delivery. We randomly assigned patients undergoing cesarean delivery to skin preparation with either chlorhexidine-alcohol or iodine-alcohol. The primary outcome was superficial or deep surgical-site infection within 30 days after cesarean delivery, on the basis of definitions from the Centers for Disease Control and Prevention. RESULTS: From September 2011 through June 2015, a total of 1147 patients were enrolled; 572 patients were assigned to chlorhexidine-alcohol and 575 to iodine-alcohol. In an intention-to-treat analysis, surgical-site infection was diagnosed in 23 patients (4.0%) in the chlorhexidine-alcohol group and in 42 (7.3%) in the iodine-alcohol group (relative risk, 0.55; 95% confidence interval, 0.34 to 0.90; P=0.02). The rate of superficial surgical-site infection was 3.0% in the chlorhexidine-alcohol group and 4.9% in the iodine-alcohol group (P=0.10); the rate of deep infection was 1.0% and 2.4%, respectively (P=0.07). The frequency of adverse skin reactions was similar in the two groups. CONCLUSIONS: The use of chlorhexidine-alcohol for preoperative skin antisepsis resulted in a significantly lower risk of surgical-site infection after cesarean delivery than did the use of iodine-alcohol. (Funded by the National Institutes of Health and Washington University School of Medicine in St. Louis; ClinicalTrials.gov number, NCT01472549.).

External validity in perinatal research.

Recent studies are beginning to focus on the external validity of well conducted internally valid research. This review gives an overview of external validity, the dimensions involved and suggestions for when future intervention trials are designed, using examples from perinatal research. Finally, we remind the perinatal researcher that it is their duty to provide extensive details beyond those needed to establish internal validity. The latter would help clinicians to determine whether the intervention is applicable to their population.

Customized fetal growth standard compared with the INTERGROWTH-21st century standard at predicting small-for-gestational-age neonates.

INTRODUCTION: The INTERGROWTH-21st project (IG-21) was recently performed aiming to provide a universal benchmark for comparing fetal growth across different ethnicities. Our aim was to compare the IG-21 with a customized standard for predicting pregnancies at risk for neonatal small-for-gestational age (SGA) and adverse outcomes. MATERIAL AND METHODS: This was a prospective cohort study including singleton pregnancies presenting for fetal growth assessment between 26 and 36 weeks of gestation. Fetal growth restriction was defined as estimated fetal weight <10th centile for gestational age using IG-21 and a customized standard. Neonatal SGA was defined as birthweight <10th centile for gestational age by the Alexander chart. Primary outcome was the prediction of neonatal SGA. Secondary outcomes included a composite of adverse neonatal outcomes. The discriminatory ability of each growth standard was compared using area under receiver operating characteristic curves (AUC). RESULTS: Of 1054 pregnancies meeting the inclusion criteria, the incidence of neonatal SGA was 139 (13.2%), and a composite adverse neonatal outcome occurred in 300 (28.4%). The sensitivity of the customized standard (38.8%) was higher than that of IG-21 (24.5%) for predicting neonatal SGA, with AUC (95% CI) of 0.67 (0.63-0.71) for customized vs 0.62 (0.58-0.65) for IG-21; P = .003. Both standards were comparable in predicting the composite adverse neonatal outcomes: AUC (95% CI) 0.52 (0.50-0.55) for customized vs 0.51 (0.50-0.53) for IG-21; P = 0.25. CONCLUSIONS: Both growth standards had modest performance in detecting neonatal SGA and were poor at predicting short-term adverse neonatal outcome.

Three-Dimensional Power Doppler Evaluation of Cerebral Vascular Blood Flow: A Novel Tool in the Assessment of Fetal Growth Restriction.

OBJECTIVES: To determine whether fetuses with fetal growth restriction (FGR) are more likely to have abnormal cerebral vascular flow patterns compared to fetuses who are appropriate for gestational age (AGA) when quantified by using 3-dimensional (3D) power Doppler ultrasound. METHODS: We conducted a prospective cohort study of singleton gestations presenting for growth ultrasound examination between 24 and 36 weeks' gestation. Patients with FGR (estimated fetal weight < 10th percentile) were enrolled and matched 1:1 for gestational age (±7 days) with AGA fetuses. A standardized 3D power Doppler image of the middle cerebral artery territory was obtained from each patient. The vascularization index (VI), flow index (FI), and vascularization-flow index (VFI) were calculated by the Virtual Organ computer-aided analysis technique (GE Healthcare, Milwaukee, WI). These indices were compared between FGR and AGA fetuses and correlated with 2-dimensional Doppler parameters. Neonatal outcomes were also compared with respect to the 3D parameters. RESULTS: Of 306 patients, there were 151 cases of FGR. There was no difference in the VI (6.0 versus 5.7; P = .65) or VFI (2.0 versus 1.8; P = .31) between the groups; however, the FI was significantly higher in FGR fetuses compared to AGA controls (33.9 versus 32.3; P = .009). There was a weak, but significant, negative correlation between the FI and both the middle cerebral artery pulsatility index (r = -0.34; P < .001) and cerebroplacental ratio (r = -0.29; P < .001). Within the FGR group, there was no difference in any of the 3D vascular indices with regard to neonatal outcomes. CONCLUSIONS: Three-dimensional power Doppler measurement of cerebral blood flow, but not the vascularization pattern, is significantly altered in FGR. This measurement may play a future role in distinguishing pathologic FGR from constitutionally small growth.

Sexual Dimorphism in Umbilical Vein Blood Flow During the Second Half of Pregnancy: A Longitudinal Study.

OBJECTIVES: To investigate gestational age-specific serial changes in umbilical vein (UV) volume blood flow during the second half of normal pregnancy and establish sex-specific reference ranges. METHODS: This work was a prospective longitudinal study of singleton low-risk pregnancies. The UV diameter and maximum blood flow velocity were serially measured by sonography at the intra-abdominal portion of the UV over 19 to 41 weeks. Umbilical vein volume blood flow was calculated and normalized for estimated fetal weight. RESULTS: One hundred seventy-nine women and their fetuses (87 male and 92 female) were included in the final analysis, and a total of 746 observations were used to construct sex-specific reference intervals. We found no statistically significant sex-specific differences in the UV parameters examined. However, the temporal development patterns of normalized UV volume blood flow appeared to differ between male and female fetuses during the second half of pregnancy, with crossovers at 24 and 32 weeks' gestation. CONCLUSIONS: Umbilical vein volume blood flow is similar among male and female fetuses in quantitative terms, but the pattern of gestational age-dependent temporal changes may be different, which may have important physiologic implications with regard to in utero development and maturation of the fetoplacental unit.

Gestational Weight Gain: Association with Adverse Pregnancy Outcomes.

Background It is unclear how adherence to the Institute of Medicine's (IOM) guidelines for weight gain affects pregnancy outcomes. Objective We investigated how weight gain outside the IOM's recommendations affects the risks of adverse pregnancy outcomes. Study Design We performed a secondary analysis of a prospective cohort study including singleton, nonanomalous fetuses. The risks of small for gestational age (SGA), macrosomia, preeclampsia, cesarean delivery, gestational diabetes, or preterm birth were calculated for patients who gained weight below or above the IOM's recommendations based on body mass index category. A time-to-event analysis was performed to account for gestational age at delivery. A Cox proportional model was fit to estimate hazard ratios accounting for possible confounders. Results Women who gained weight below recommendations were 2.5 times more likely to deliver SGA and twice as likely to deliver preterm. Normal-weight patients who gained below recommendations were 2.5 times more likely to deliver SGA and twice as likely to deliver preterm. Obese patients who gained inadequate weight were 2.5 times more likely to deliver SGA. Conclusion Among normal-weight patients, adhering to IOM recommendations may prevent growth abnormalities and preterm delivery. Among obese patients, a minimum weight gain requirement may prevent SGA infants.