Composite Perinatal Morbidity Research Articles

Comparing population-based fetal growth standards in a US cohort

BackgroundNo fetal growth standard is currently endorsed for universal use in the US. Newer standards improve upon the methodologic limitations of older studies but before adopting into practice, it is important to know how recent standards perform at identifying fetal under- or over- growth and predicting subsequent neonatal morbidity or mortality in US populations. ObjectiveTo compare classification of estimated fetal weight (EFW) that is <5th or 10th percentile or >90th percentile by six population-based fetal growth standards and the ability of these standards to predict a composite of neonatal morbidity and mortality. Study DesignWe used data from the Nulliparous Pregnancy Outcomes Study: Monitoring Mothers-to be (nuMoM2b) cohort, which recruited nulliparous women in the first trimester at eight U.S. clinical centers (2010-2014). EFW was obtained from ultrasounds at 16-21 and 22-29 weeks (n=9530 women). We calculated rates of fetal growth restriction (EFW <5th and 10th percentiles; FGR<5 and FGR<10) and EFW >90th percentile (EFW>90) from three large prospective fetal growth cohorts with similar rigorous methodologies: INTERGROWTH-21, World Health Organization (WHO) sex-specific and combined, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) race/ethnic-specific and unified, and the historical Hadlock (1991) reference. To determine whether differential classification of FGR or EFW>90 among standards was clinically meaningful, we then compared area under the curve (AUC) and sensitivity of each standard to predict SGA or LGA at birth, composite perinatal morbidity and mortality alone, and SGA or LGA with composite perinatal morbidity and mortality. ResultsThe standards classified different proportions of FGR and EFW>90 for ultrasounds at 16-21 (visit 2) and 22-29 (visit 3) weeks. At visit 2, the NICHD race/ethnic-specific, WHO sex-specific and WHO-combined identified similar rates of FGR<10 (8.4-8.5%) with the other two having lower rates, while NICHD race/ethnic-specific identified the highest rate of FGR<5 (5.0%) compared to the other references. At visit 3, WHO-sex-specific classified 9.2% of fetuses as FGR<10, while the other five classified a lower proportion: WHO-Combined 8.4%, NICHD-race/ethnic-specific 7.7%, INTERGROWTH 6.2%, Hadlock 6.1%, and NICHD unified 5.1%. INTERGROWTH classified the highest (21.3%) as EFW>90 while Hadlock classified the lowest (8.3%). When predicting composite perinatal morbidity and mortality in the setting of early-onset FGR, WHO had the highest AUC of 0.53 (0.51, 0.53) for FGR<10 at 22-29 weeks, but the AUCs were similar among standards (0.52). Sensitivity was generally low across standards (22.7-29.1%). When predicting SGA-BW with composite neonatal morbidity or mortality, for FGR<10 at 22-29 weeks, WHO-sex-specific had the highest AUC (0.64; 95% CI 0.60, 0.67) and INTERGROWTH had the lowest (AUC=0.58; 95% CI 0.55, 0.62), though all standards had low sensitivity (7.0-9.6%). ConclusionsDespite classifying different proportions of fetuses as FGR or EFW>90, all standards performed similarly in predicting perinatal morbidity and mortality. Classification of different percentages of fetuses as FGR or EFW>90 among references may have clinical implications in the management of pregnancies, such as increased antenatal monitoring for FGR or cesarean for suspected LGA. Our findings highlight the importance of knowing how standards perform in local populations, but more research is needed to determine if any standard performs better at identifying risk of morbidity or mortality.

Comparative Diagnostic Performance of Estimated Fetal Weight and Isolated Abdominal Circumference for the Detection of Fetal Growth Restriction.

To describe the comparative incidence, detection of small-for-gestational age (SGA), and composite perinatal morbidity (CPM) associated with diagnostic criteria of fetal growth restriction (FGR) by estimated fetal weight (EFW) <10% with those with isolated abdominal circumference (AC) measurements <10%. We performed a retrospective cohort study of 1587 patients receiving prenatal care and delivery at our institution. We included all patients with ultrasounds and delivery outcomes available, and excluded terminations, second trimester losses, and pregnancies without ultrasounds. EFW was calculated from Hadlock and use of the Duryea centiles, and AC from Hadlock's reference curves. We determined SGA at birth and defined CPM as birthweight less than 3% or birthweight less than 10% with neonatal morbidity. Of 1587 patients, 28 (1.8%) were classified as FGR by EFW <10%. Three of 12 patients with isolated AC <10% developed EFW <10% later in pregnancy (25%). The performance of each diagnostic criteria were comparable for the outcomes of SGA and CPM, with similar sensitivities, but with decreased specificity for SGA outcome, and an increased false positive rate for patients classified as FGR by isolated AC <10, with a tradeoff of decreased false negatives. Broadening the diagnosis of FGR to include patients with isolated AC <10 did not significantly increase the detection of pregnancies at risk for SGA or CPM. Our conclusions may be limited by a lack of statistical power given a low frequency of SGA and CPM.

Composite Perinatal Morbidity Metrics: Getting closer but still with challenges.

Composite Perinatal Morbidity Metrics: Getting closer but still with challenges.

Mode of delivery, perinatal outcome and neurodevelopment in uncomplicated monochorionic diamniotic twins: a single-center retrospective cohort study

BackgroundThere is no agreement on the effect of planned mode of delivery in the perinatal morbidity and neurodevelopment in uncomplicated monochorionic diamniotic as well as regarding the safest mode of delivery. In this paper we have aimed to analyze the impact of the mode of delivery in uncomplicated monochorionic diamniotic twins ≥ 32 weeks of gestation.Material and methodsThis study included 72 women, followed and attended at our department, with uncomplicated monochorionic diamniotic pregnancies who had a birth between 32.0 and 37.6 weeks of gestation from January 2012 to December 2018. Outcomes were recorded in women who underwent planned vaginal delivery (induced or spontaneous onset of labor), and women who underwent a planned cesarean section for any reason that excluded vaginal delivery. Primary outcomes included: (1) A composite of any of the following: neonatal death, 5-min Apgar score < 4, respiratory distress syndrome, bronchopulmonary dysplasia, sepsis, periventricular leukomalacia, intraventricular hemorrhage, and necrotizing enterocolitis. (2) Neurodevelopmental status at 2 years of corrected age.ResultsIn this period, 42 women (58.3%) had a planned vaginal delivery, and 30 women (41.7%) had a planned cesarean section. In the first group, 64.3% had a vaginal delivery. The rate of successful vaginal delivery was similar regardless the onset of labor. We did not find a higher composite perinatal morbidity in the planned vaginal delivery group (planned vaginal delivery: 3.6% vs. planned cesarean section: 8.3%, aOR 1.36, 95% CI 0.24–7.81). Considering the onset of labor, it was more frequent in the spontaneous subgroup (8.3% vs. 0%). The rate of neurodevelopmental impairment was higher in the planned cesarean section group, without reaching statistical significance [10.2% vs. 4.9%, aOR 1.53 (95% CI 0.37–6.29)].ConclusionsIn uncomplicated monochorionic diamniotic twins at ≥ 32 weeks of gestation, when the first twin is in vertex presentation, our results suggest that planned vaginal delivery is safe, with a successful outcome as well as high vaginal delivery rate.

Perinatal morbidity prediction utilizing ultrasonographic central adiposity measures compared to BMI in patients with BMI≥40

We observed that a 3-variable model of late 3rd trimester ultrasonographic (US) measures of central adiposity is superior to BMI alone in predicting cesarean delivery (CD) in patients with BMI≥40 kg/m2. As these patients are more likely to experience maternal and neonatal morbidity, we evaluated the predictive ability of these measurements as well as a new primary model for adverse perinatal outcomes and compared these to BMI alone. Planned secondary analysis of a single center prospective cohort study of patients with BMI≥40 at >36 weeks’ GA and viable singletons. Patients underwent a single study visit >36 weeks’ (blinded to clinicians) at which BMI and 19 US/anthropometric central adiposity measures were obtained by trained personnel. Exclusions were contraindications to vaginal birth or prior CD. For this analysis, the primary outcome was composite perinatal morbidity (maternal puerperal infection, umbilical cord arterial pH< 7.1, NICU admission and other neonatal morbidities, Table). Receiver operator characteristics (ROC) curves with area under the curve (AUC) assessed the original 3-variable model’s predictive ability for the composite; AUCs for BMI, the 3-variable model from the primary analysis, and a new best-fit forward selection (α =0.05) model for the composite were compared. From 2017-2020, 149 women (mean BMI 45.4±5.2) were enrolled. The rate of perinatal morbidity was 18%. Multivariable logistic regression retained only one measurement, minimum pre-peritoneal subxiphoid fat depth, that was significantly associated with the perinatal composite (Model 1), but was poorly predictive (AUC 0.64 95%CI 0.52-0.76). BMI had no predictive ability (AUC 0.49 [0.37-0.61]), while our original 3-variable model (Model 2) had poor prediction, similar to Model 1 (Table). In patients with BMI≥40, maternal US fat depth measurements are no more predictive of adverse perinatal outcome than BMI alone, itself a poor predictor. As perinatal outcome may reflect other maternal and labor characteristics, incorporating these into models may improve prediction.

Marijuana Use and Perinatal Outcomes Among Obstetric Patients in a Southern California Safety Net Hospital [22K

INTRODUCTION: Recreational marijuana use is increasing and poses a risk to both mother and the fetus. We aimed to assess marijuana use and perinatal outcomes in the local obstetric population at our hospital. METHODS: An IRB approved retrospective chart review identified a cohort of women with singleton gestations who delivered at LAC/USC hospital between 2015 and 2018. Women with self-reported marijuana use were compared with a control group. Demographic characteristics, maternal and perinatal outcomes were evaluated. Associations between these factors and marijuana use were assessed with univariate and multivariate regression. RESULTS: Of 2792 women who delivered during the study period, 151 (5.4%) had documented marijuana use. Compared to 192 non-users, marijuana users were more likely to be younger, non-Hispanic, undomiciled, unemployed and use other illicit substances. Marijuana users entered prenatal care later (14.2 vs. 22.1 weeks, P&lt;.001), were more likely to have preeclampsia (P=.046) and cesarean delivery (P=.01) and had infants with average birth weight 106 grams less (P=.02) than controls. After adjusting for confounders, marijuana use was not significantly associated with preterm birth or composite perinatal morbidity, but remained associated with 4.1-fold greater likelihood of delivering a small for gestational age (SGA) infant (95% CI 1.95-8.74). CONCLUSION: At a safety net hospital, antepartum marijuana use is significantly associated with SGA at birth. Marijuana users have higher maternal morbidity including preeclampsia and cesarean delivery, and are more likely to enter prenatal care later and report poly-substance use. Healthcare disparities associated with marijuana use make this a population of critical interest.

Pre- and postnatal brain hemodynamics in pregnancies at term: correlation with Doppler ultrasound, birthweight, and adverse perinatal outcome

Purpose To elucidate the correlation between pre- and postnatal cerebral Doppler in pregnancies close to term and to explore whether they are associated with perinatal outcome. Materials and methods Prospective study on singleton pregnancies at 36–37 weeks of gestation. The primary outcome was a composite score of perinatal morbidity, while secondary outcomes were adverse intra-partum outcome and abnormal acid–base status. All pregnancies underwent ultrasound assessment of umbilical artery (UA), middle cerebral artery (MCA), uterine arteries (UtAs) pulsatility index (PI), and cerebroplacental ratio (CPR). At birth, neonatal MCA PI was measured 72 h from delivery and correlated with prenatal Doppler, primary and secondary outcomes. Fisher’s test and multivariate logistic regression analysis were used to analyze the data. Results One hundred and sixty-six fetuses with both pre- and postnatal Doppler assessment of the MCA were included in the study. The risk of composite perinatal morbidity was higher in fetuses (OR: 5.7, 95% CI 2.2–14.6) and newborns (OR: 4.1, 95% CI 1.8–9.6) with fetal MCA PI < 10th centile. Likewise, the incidence of abnormal acid–base status was higher both in fetuses (20 versus 4.2%, p = .026) and newborns (17.1 versus 3.2%, p = .001) with a low MCA PI before and at birth, respectively. At logistic regression analysis, fetal and neonatal MCAPI were independently associated with composite perinatal morbidity and abnormal acid–base status, but not with adverse intra-partum outcome. In small for gestational age (SGA) fetuses, the incidence of composite perinatal morbidity was higher in fetuses and new-borns presenting compared to those not presenting with an MCA PI < 10th centile (61.5 versus 20%, p = .003 and 52.6% versus 7.1%, p = .008, respectively), while such association was lost when considering non-SGA fetuses. Conclusion A low MCA PI is associated with adverse perinatal outcome in pregnancies at term and tends to persist after birth.

Diagnostic Accuracy of Doppler Ultrasound in Predicting Perinatal Outcome in Appropriate for Gestational Age Fetuses: A Prospective Study.

To elucidate the role of Doppler ultrasound in predicting perinatal outcome in appropriate for gestational age (AGA) fetuses at term. Prospective study carried out in a dedicated research ultrasound clinic. The inclusion criterion was AGA fetuses, defined as those with an estimated fetal weight between the 10th and 90th percentile, at 36 + 0-37 + 6 weeks of gestation. The primary outcome was a composite score of adverse perinatal outcome including either adverse intrapartum events or abnormal acid-base status at birth. Secondary outcomes were the individual components of the primary outcome. The Doppler parameters explored were umbilical artery (UA) PI, middle cerebral artery (MCA) PI, uterine arteries (UtA) PI and cerebroplacental ratio (CPR). Attending clinicians were blinded to Doppler findings. Logistic regression and ROC curve analyses were used to analyze the data. 553 AGA fetuses were included. There was no difference in mean UA PI (p = 0.486), MCA PI (p = 0.621), CPR (p = 0.832) and UtA PI (p = 0.611) between pregnancies complicated by composite perinatal morbidity compared to those not complicated by composite perinatal morbidity. In pregnancies complicated by adverse intrapartum outcome, the mean MCA PI (1.47 ± 0.4 vs 1.61 ± 0.4, p = 0.0039) was lower compared to the control group, while there was no difference in UA PI (p = 0.758), CPR (p = 0.108), and UtA PI (p = 0.177). Finally, there was no difference in any of the Doppler parameters explored between AGA fetuses with abnormal acid-base status at birth compared to those without abnormal acid-base status at birth. In the logistic regression analysis, UA PI, MCA PI, CPR, UtA PI, EFW and AC percentiles were not independently associated with composite adverse outcome, adverse intrapartum outcome or abnormal acid-base status at birth in non-SGA fetuses. The diagnostic performance of all of these Doppler parameters for predicting composite adverse outcome, adverse intrapartum outcome and abnormal acid-base status was poor. Cerebroplacental and maternal Doppler is not associated with or predictive of adverse pregnancy outcome in AGA fetuses close to term.

355: sIUGR in monochorionic diamniotic twins: Is it discordance >25%, EFW < 10th percentile or both?

Selective intrauterine growth restriction (sIUGR) is a common but inconsistently defined complication of monochorionic diamniotic (MCDA) twins. We sought to compare two definitions of sIUGR: 1) Estimated fetal weight (EFW) discordance > 25th percentile plus EFW < 10th percentile in the smaller twin. 2) Only one of these criteria. This is a retrospective cohort study of MCDA twin gestations that had surveillance ultrasounds (US) at our center between 2012 and 2018. We compared sIUGR pregnancies with EFW discordance > 25th percentile plus EFW < 10th percentile for the smaller twin (Group 1) to those with only one of these criteria (Group 2). Women with uncertain chorionicity, twin to twin transfusion syndrome, fetal anomalies, or less than 4 serial US exams were excluded. Routine US was performed biweekly from 16 weeks gestational age (GA) until delivery. The primary outcome was composite perinatal morbidity and mortality (Table 2). Pregnancy characteristics including Gratacos type, indication for delivery and mode of delivery were also compared between groups. Of 293 MCDA pregnancies that met inclusion criteria, sIUGR developed in 66 (22.5%); 42 women followed at our center for the entire pregnancy. Among these women, 18 (42.8%) were in Group 1 and 24 (36.4%) were in Group 2 (8 with discordance > 25%, 16 with EFW < 10th percentile). Maternal age, race, parity, and BMI were similar between groups (Table 1). Women in Group 1 were diagnosed with sIUGR at an earlier GA (22.2 [18.3, 27.0] vs. 28.6 [25.0, 32.0] weeks, p = 0.004). They were also more likely to have Gratacos type II or III (50.0% vs. 4.2 %, p = 0.001) and deliver due to deterioration of fetal status (55.6% vs. 4.2%, p = 0.001). The composite outcome occurred more frequently in Group 1 (44.7% vs. 13%, p = 0.001). sIUGR neonates with discordance of EFW > 25th percentile plus EFW < 10th percentile have more perinatal complications than those with only one criterion. Increased US surveillance may be beneficial in these pregnancies.View Large Image Figure ViewerDownload Hi-res image Download (PPT)

Maternal and perinatal outcomes in women undergoing expectant management of early-onset pre-eclampsia: A retrospective cohort study

Background. Expectant management of early-onset pre-eclampsia, with the aim of improving perinatal outcomes, may increase the risk of maternal morbidity. Objective. To study the maternal and perinatal outcomes and their association with various risk factors in women undergoing expectant management for early-onset pre-eclampsia. Methods. A retrospective cohort study was carried out in a tertiary centre in south India between April 2014 and June 2015. We studied 201 women with singleton pregnancies with pre-eclampsia diagnosed between 28 and 34 weeks’ gestation. Demographic data, medication and treatment details, and delivery data were extracted from maternal charts. The primary outcomes were: (i) composite maternal outcomes, defined as the development of any of eclampsia, abruptio placentae, pulmonary oedema or renal failure; and (ii) perinatal mortality. Logistic regression was used to assess the independent association risk factors with primary outcomes, after adjusting for other variables. Results. Sixty-nine women (34.3%) had one or more of the composite adverse maternal outcomes, and there were 74 (36.8%) cases of perinatal mortality. The presence of imminent symptoms (odds ratio (OR)=2.35) and multiparity (OR=2.31) were associated with composite adverse maternal outcomes, whereas low birth weight and breech vaginal delivery were associated with perinatal mortality. Perinatal mortality was higher in women with pre-eclampsia diagnosed between 28 and 30 weeks. Gestational age at diagnosis was not found to be associated with composite adverse maternal outcomes or perinatal morbidity. Conclusion. Expectant management in early-onset pre-eclampsia can be safely considered without increasing maternal risk, after thorough counselling about outcomes, based on the available neonatal facilities in low-resource settings.

The effect of customization and use of a fetal growth standard on the association between birthweight percentileand adverse perinatal outcome.

It has been proposed that correction of offspring weight percentiles (customization) might improve the prediction of adverse pregnancy outcome; however, the approach is not accepted universally. A complication in the interpretation of the data is that the main method for calculation of customized percentiles uses a fetal growth standard, and multiple analyses have compared the results with birthweight-based standards. First, we aimed to determine whether women who deliver small-for-gestational-age infants using a customized standard differed from other women. Second, we aimed to compare the association between birthweight percentile and adverse outcome using 3 different methods for percentile calculation: (1) a noncustomized actual birthweight standard, (2) a noncustomized fetal growth standard, and (3) a fully customized fetal growth standard. We analyzed data from the Pregnancy Outcome Prediction study, a prospective cohort study of nulliparous women who delivered in Cambridge, UK, between 2008 and 2013. We used a composite adverse outcome, namely, perinatal morbidity or preeclampsia. Receiver operating characteristic curve analysis was used to compare the 3 methods of calculating birthweight percentiles in relation to the composite adverse outcome. We confirmed previous observations that delivering an infant who was small for gestational age (<10th percentile) with the use of a fully customized fetal growth standard but who was appropriate for gestational age with the use of a noncustomized actual birthweight standard was associated with higher rates of adverse outcomes. However, we also observed that the mothers of these infants were 3-4 times more likely to be obese and to deliver preterm. When we compared the risk of adverse outcome from logistic regression models that were fitted to the birthweight percentiles that were derived by each of the 3 predefined methods, the areas under the receiver operating characteristic curves were similar for all 3 methods: 0.56 (95% confidence interval, 0.54-0.59) fully customized, 0.56 (95% confidence interval, 0.53-0.59) noncustomized fetal weight standard, and 0.55 (95% confidence interval, 0.53-0.58) noncustomized actual birthweight standard. When we classified the top 5% of predicted risk as high risk, the methods that used a fetal growth standard showed attenuation after adjustment for gestational age, whereas the birthweight standard did not. Further adjustment for the maternal characteristics, which included weight, attenuated the association with the customized standard, but not the other 2 methods. The associations after full adjustment were similar when we compared the 3 approaches. The independent association between birthweight percentile and adverse outcome was similar when we compared actual birthweight standards and fetal growth standards and compared customized and noncustomized standards. Use of fetal weight standards and customized percentiles for maternal characteristics could lead to stronger associations with adverse outcome through confounding by preterm birth and maternal obesity.

Growth restriction: identifying fetuses at risk

Purpose: Examine risks of intrauterine growth restriction (IUGR) and composite perinatal outcomes with estimated fetal weights (EFW) 10–20th%, and compare outcomes using umbilical artery Doppler (UAD).Materials and methods: Retrospective, cohort evaluating ultrasound (US) EFW 10–20th%, between 2002 and 2012. Cases were identified with EFW % 10–20. Controls, EFW >20th% were obtained for each case, matched by gestational age, and US date. Unadjusted and adjusted logistic regression was used for outcomes.Results: Seven hundred and sixty-seven cases met criteria with matched controls. Fetuses having EFW 10–20th% (GA 33.6 ± 3.7 weeks) had increased IUGR on follow up ultrasound (OR 26.5[10.2–68.7], p < .01), small for gestational age (SGA) (OR 9.2 [6.9–12.3], p < .01), neonatal intensive care unit (NICU) admissions (OR 2.4 [1.6–3.6], p < .01), and composite perinatal morbidity (OR 7.8 [6.0–10.1], p < .01) on adjusted analyses. Abnormal UAD in cases had greater rates of 5 min Apgar <7, NICU admission and composite morbidity (p < .05).Conclusions: Pregnancies with EFW 10–20th% at the time of initial US are at increased risk for developing IUGR and being SGA at birth, with more NICU admissions and composite perinatal outcomes; abnormal UAD evaluation in cases conveyed further increase in outcomes.

Perinatal and maternal morbidity and mortality after attempted operative vaginal delivery at midpelvic station.

Increased use of operative vaginal delivery (i.e., forceps or vacuum application), of which 20% occurs at midpelvic station, has been advocated to reduce the rate of cesarean delivery. We aimed to quantify severe perinatal and maternal morbidity and mortality associated with attempted midpelvic operative vaginal delivery. We studied all term singleton deliveries in Canada between 2003 and 2013, by attempted midpelvic operative vaginal or cesarean delivery with labour (with and without prolonged second stage). The primary outcomes were composite severe perinatal morbidity and mortality (e.g., convulsions, assisted ventilation, severe birth trauma and perinatal death), and composite severe maternal morbidity and mortality (e.g., severe postpartum hemorrhage, shock, sepsis, cardiac complications, acute renal failure and death). The study population included 187 234 deliveries. Among women with dystocia and prolonged second stage of labour, midpelvic operative vaginal delivery was associated with higher rates of severe perinatal morbidity and mortality compared with cesarean delivery (forceps, adjusted odds ratio [AOR] 1.81, 95% confidence interval [CI] 1.24 to 2.64; vacuum, AOR 1.81, 95% CI 1.17 to 2.80; sequential instruments, AOR 3.19, 95% CI 1.73 to 5.88), especially with higher rates of severe birth trauma. Rates of severe maternal morbidity and mortality were not significantly different after operative vaginal delivery, although rates of obstetric trauma were higher (forceps, AOR 4.51, 95% CI 4.04 to 5.02; vacuum, AOR 2.70, 95% CI 2.35 to 3.09; sequential instruments, AOR 4.24, 95% CI 3.46 to 5.19). Among women with fetal distress, similar associations were seen for severe birth trauma and obstetric trauma, although vacuum was associated with lower rates of severe maternal morbidity and mortality (AOR 0.52, 95% CI 0.33 to 0.80). Associations tended to be stronger among women without a prolonged second stage. Midpelvic operative vaginal delivery is associated with higher rates of severe birth trauma and obstetric trauma, whereas overall rates of severe perinatal and maternal morbidity and mortality vary by indication and operative instrument.

Perinatal Outcomes in Pregnancies With a Low Fetal Fraction on Non Invasive Prenatal Testing [4N

INTRODUCTION: Placental-origin cell-free maternal DNA is known as the fetal fraction (FF). Low FF is a risk factor for aneuploidy, and may be a risk factor for poor perinatal outcome. Our objective was to evaluate the relation between low FF, and perinatal outcome. METHODS: This is a retrospective review of singleton pregnancies who had NIPT. We compared the maternal BMI, gestational age of delivery (GA), birth weight (BW), and composite perinatal morbidity (CPM) between patients with a FF &lt; 4% on NIPT (LFF), and those with a normal FF on their NIPT (NFF). The CPM was defined as the presence of any of the following complications: spontaneous abortion, hypertensive disorders of pregnancy, abruption, IUFD, preterm birth, low BW, NICU admission, or neonatal death. RESULTS: 256 patients were included. 28 (10.9%) had LFF, while 228 (89.1%) had NFF. Median age was 35-years, and median GA was 39 weeks. The rate of CPM in the entire cohort was 26.5%. Median BMI was significantly higher in the LFF group (27.4 vs. 22.1 kg/m2; p&lt; .001). There were no significant differences in CPM, gestational age at delivery or BW. Among the 28 patients in the LFF group, median FF in cases with CPM was significantly lower than in cases without CPM (2.0% vs. 3.2%; p=.04). CONCLUSION: There were no significant differences in obstetric outcomes between the two groups. Within the LFF group, lower FFs were associated with a higher rate of CPM. Larger studies are necessary to evaluate the association between uncommon outcomes and FF.

High dose antithrombin supplementation in early preeclampsia: A randomized, double blind, placebo-controlled study

IntroductionAntithrombin levels are often reduced in preeclampsia and infusion of antithrombin concentrates has been reported to prolong gestation in severe preeclampsia. We aimed to evaluate efficacy and safety of high-dose antithrombin (ATIII) supplementation in patients with single pregnancies and preeclampsia occurring before 30weeks of gestation. Materials and methodsIn November 2004 a double-blind, placebo-controlled trial (code KB033) was started in 13 Italian centers. The planned sample size was of 240 patients (intention-to-treat, ITT population) to detect a 30% relative risk reduction of the primary endpoint, composite perinatal morbidity. Eligible patients were randomized to high dose AT (3000IU/daily, ATIII Kedrion S.p.A., Italy), or placebo (1% glycine) for 7days or less until delivery, whichever came first. The per-protocol (PP) population was restricted to patients receiving at least two days of treatment. ResultsThe study was terminated by the sponsor in October 2007 after the enrolment of 38 evaluable patients – 20 randomized to high dose AT and 18 to placebo, 27 treated for 2days or more – out of 164 screened patients. Enrolment failures were mainly represented by requirement for immediate delivery and consent refusal (91 patients). The primary endpoint occurred in 15 of 38 patients (39.5%), with a relative risk in the AT arm of 0.85 (95% CI 0.42–1.75) and 0.79 (95% CI 0.30-2.11) in the ITT and PP populations, respectively. Living neonates in the two arms had similar weight at birth, Apgar scores, and duration of hospitalization in neonatal ICU. In mothers, AT supplementation was associated with reduced blood loss at delivery and with surrogate laboratory markers (LDH, d-dimer). ConclusionsThe results of this markedly underpowered trial, albeit suggestive of a potential maternal benefit, cannot support high-dose AT supplementation to improve fetal/neonatal outcomes in early preeclampsia.

The effect of maternal obesity on sonographic fetal weight estimation and perinatal outcome in pregnancies complicated by fetal growth restriction.

Maternal obesity represents a challenge in the sonographic (US) assessment of fetal weight, and is a recognized risk factor for adverse pregnancy outcome. The objective of this secondary analysis of data from the Prospective Observational Trial to Optimize Pediatric Health in fetal growth restriction (FGR) Study (PORTO) was to describe the effect of maternal obesity on the accuracy of US in determining the estimated fetal weight (EFW) and the perinatal outcome of pregnancies affected by FGR. Between 2010 and 2012, 1,116 women with nonanomalous singleton pregnancies with an EFW in less than the tenth centile were recruited for the PORTO study. Maternal body mass index (BMI) was divided into five subcategories: normal (BMI < 24.9 kg/m(2) ), overweight (25-29.9), obese class 1 (30-34.9), obese class 2 (35-39.9), and obese class 3 (>40). The accuracy of the EFW was determined in women who delivered within 2 weeks of their last US scan. Perinatal outcomes were analyzed by BMI subcategory. Of the 1,074 patients with complete records, 691 (64%) were of normal weight, 258 (24%) were overweight, 93 (9%) were in obese class 1, 32 (3%) were in obese class 2, and none were in obese class 3. Overall, the EFW determined prior to delivery was within 6% of the actual birth weight in all BMI subcategories. Overweight and obese women delivered more commonly by cesarean section and at earlier gestational ages than did women with a normal BMI (p = 0.0008), resulting in lower birth weights (p = 0.0031) and significantly increased composite perinatal morbidity (p < 0.0001) and mortality (p = 0.0215) rates. US examination is reliable for assessing the weight of fetuses with FGR in overweight women. Maternal obesity, however, has a significant adverse effect on perinatal outcomes. Thus, health education should focus on awareness of this adverse effect, with optimization of prepregnancy weight as its main goal.

Outpatient cervical ripening by nitric oxide donors for prolonged pregnancy: a randomized controlled trial.

To assess whether outpatient cervical ripening at 41 0/7 weeks of gestation with the nitric oxide donor isosorbide mononitrate reduces cesarean delivery rates in nulliparous women with an unfavorable cervix. We recruited nulliparous pregnant women with a Bishop score less than 6 in a randomized, multicenter, double-blind, placebo-controlled trial. Women received 40 mg vaginal isosorbide mononitrate or a placebo at 41 0/7, 41 2/7, and 41 4/7 weeks of gestation. They returned home between visits. At 41 5/7 weeks of gestation, for women who had not yet given birth, labor was induced with oxytocin or prostaglandins, depending on cervical status. We needed 685 women per group to detect a 25% reduction in the cesarean delivery rate, the primary outcome measure, from 25% in the placebo group to 18.75% in the isosorbide mononitrate group (1-β=0.8, α=0.05, two-sided). The NOCETER (NO donors for reduction of CEsareans at TERm) trial was a negative study. The cesarean delivery rate was 27.3% (185/678) in the isosorbide mononitrate group and 27.2% (186/684) in the placebo group (relative risk 1.00, 95% confidence interval [CI] 0.84-1.19). None of the maternal secondary efficacy outcomes differed between groups. Side effects were more common among women receiving isosorbide mononitrate than in the placebo group (78.8% [534/678] compared with 27.9% [191/684], relative risk 2.82, 95% CI 2.49-3.20). Composite perinatal morbidity did not differ between groups. Outpatient cervical ripening with vaginal isosorbide mononitrate for prolonged pregnancy in nulliparous women does not reduce cesarean delivery rate. ClinicalTrials.gov, www.clinicaltrials.gov, NCT00930618.

Amniotic fluid infection, inflammation, and colonization in preterm labor with intact membranes

The purpose of this study was to compare intraamniotic inflammation vs microbial invasion of the amniotic cavity (MIAC) as predictors of adverse outcome in preterm labor with intact membranes. Interleukin-6 (IL-6) was measured in prospectively collected amniotic fluid from 305 women with preterm labor. MIAC was defined by amniotic fluid culture and/or detection of microbial 16S ribosomal DNA. Cases were categorized into 5 groups: infection (MIAC; IL-6, ≥11.3 ng/mL); severe inflammation (no MIAC; IL-6, ≥11.3 ng/mL); mild inflammation (no MIAC; IL-6, 2.6-11.2 ng/mL); colonization (MIAC; IL-6, <2.6 ng/mL); negative (no MIAC; IL-6, <2.6 ng/mL). The infection (n = 27) and severe inflammation (n = 36) groups had similar latency (median, <1 day and 2 days, respectively) and similar rates of composite perinatal morbidity and mortality (81% and 72%, respectively). The colonization (n = 4) and negative (n = 195) groups had similar outcomes (median latency, 23.5 and 25 days; composite morbidity and mortality rates, 21% and 25%, respectively). The mild inflammation (n = 47) groups had outcomes that were intermediate to the severe inflammation and negative groups (median latency, 7 days; composite morbidity and mortality rates, 53%). In logistic regression adjusting for gestational age at enrollment, IL-6 ≥11.3 and 2.6-11.2 ng/mL, but not MIAC, were associated significantly with composite morbidity and mortality rates (odds ratio [OR], 4.9; 95% confidence interval [CI], 2.2-11.2, OR, 3.1; 95% CI, 1.5-6.4, and OR, 1.8; 95% CI, 0.6-5.5, respectively). We confirmed previous reports that intraamniotic inflammation is associated with adverse perinatal outcomes whether or not intraamniotic microbes are detected. Colonization without inflammation appears relatively benign. Intraamniotic inflammation is not simply present or absent but also has degrees of severity that correlate with adverse outcomes. We propose the designation amniotic inflammatory response syndrome to denote the adverse outcomes that are associated with intraamniotic inflammation.

Vaginal progesterone vs cervical cerclage for the prevention of preterm birth in women with a sonographic short cervix, previous preterm birth, and singleton gestation: a systematic review and indirect comparison metaanalysis

No randomized controlled trial has compared vaginal progesterone and cervical cerclage directly for the prevention of preterm birth in women with a sonographic short cervix in the mid trimester, singleton gestation, and previous spontaneous preterm birth. We performed an indirect comparison of vaginal progesterone vs cerclage using placebo/no cerclage as the common comparator. Adjusted indirect metaanalysis of randomized controlled trials. Four studies that evaluated vaginal progesterone vs placebo (158 patients) and 5 studies that evaluated cerclage vs no cerclage (504 patients) were included. Both interventions were associated with a statistically significant reduction in the risk of preterm birth at <32 weeks of gestation and composite perinatal morbidity and mortality compared with placebo/no cerclage. Adjusted indirect metaanalyses did not show statistically significant differences between vaginal progesterone and cerclage in the reduction of preterm birth or adverse perinatal outcomes. Based on state-of-the-art methods for indirect comparisons, either vaginal progesterone or cerclage are equally efficacious in the prevention of preterm birth in women with a sonographic short cervix in the mid trimester, singleton gestation, and previous preterm birth. Selection of the optimal treatment needs to consider adverse events, cost and patient/clinician preferences.

Universal Cervical Length Screening for Prediction and Prevention of Preterm Birth

Universal transvaginal ultrasound (TVU) cervical length (CL) screening represent a step forward in the campaign against preterm birth (PTB). Transvaginal ultrasound CL is a safe, acceptable, reproducible, and accurate screening test, with potentially widespread availability given its feasibility. For this screening to be effective, the ultrasounds should be done with proper TVU technique and with continuing quality assurance. Clinicians should refrain from screening different populations, at different gestational ages, and from stretching the definition of short CL to include measurements above 25 mm. A single TVU CL measurement at about 18 to 24 6/7 weeks can be offered to all singleton gestations. About 2% to 5% of these women will demonstrate a TVU CL of 20 mm or less and should be offered vaginal progesterone, either 200-mg suppository or 90-mg gel daily, until 36 weeks, being counseled that this intervention has been associated with about 45% decrease in PTB and neonatal benefits. Serial TVU CL measurements, about every 2 weeks and weekly if CL is 25 to 29 mm, can be offered between about 16 and 23 6/7 weeks to singleton gestations with a prior spontaneous PTB. In the 40% of these women who will develop a short TVU CL of less than 25 mm, cerclage should be offered, as it is associated with a significant 30% reduction in the risk of PTB less than 35 weeks and a 36% reduction in composite perinatal mortality and morbidity. Transabdominal CL screening has not been sufficiently studied and cannot be recommended. Results from just 1 trial offer promise for pessary as another effective intervention, which cannot be recommended yet until results are confirmed with another trial. Transvaginal ultrasound CL in multiples cannot be recommended yet, given lack of effective interventions in this population.