Search

This article discusses a study that aimed to compare different predictors of pre-eclampsia with severe features (PSF) within two weeks. The study analyzed data from 18 US centers and looked at various factors such as maternal plasma biomarkers, blood pressure, and laboratory values. The results showed that a plasma ratio of sFlt-1/PlGF ≥11.5 MoM was independently associated with PSF and severe adverse perinatal outcomes. The study concluded that this plasma ratio can be used to predict the progression to PSF and severe adverse perinatal outcomes in hospitalized, hypertensive patients between 23-35 weeks of gestation. [Extracted from the article]

Background: Angiogenic imbalances, characterized by an excess of antiangiogenic factors (soluble fms-like tyrosine kinase 1) and reduced angiogenic factors (vascular endothelial growth factor and placental growth factor), contribute to the mechanisms of disease in preeclampsia. The ratio of soluble fms-like tyrosine kinase 1 to placental growth factor has been used as a biomarker for preeclampsia, but the cutoff values may vary with gestational age and assay platform., Objective: This study aimed to compare multiples of the median of the maternal plasma soluble fms-like tyrosine kinase 1 to placental growth factor ratio, soluble fms-like tyrosine kinase 1, placental growth factor, and conventional clinical and laboratory values in their ability to predict preeclampsia with severe features., Study Design: We conducted a cohort study across 18 United States centers involving hospitalized individuals with hypertension between 23 and 35 weeks' gestation. Receiver operating characteristic curve analyses of maternal plasma biomarkers, highest systolic or diastolic blood pressures, and laboratory values at enrollment were performed for the prediction of preeclampsia with severe features. The areas under the curve were compared, and quasi-Poisson regression models were fitted to estimate relative risks. The primary outcome was preeclampsia with severe features within 2 weeks of enrollment. Secondary outcomes were a composite of severe adverse maternal outcomes (elevated liver enzymes, low platelets count, placental abruption, eclampsia, disseminated intravascular coagulation, and pulmonary edema) and a composite of severe adverse perinatal outcomes (birth weight below the third percentile, very preterm birth [<32 weeks' gestation], and fetal or neonatal death)., Results: Of the 543 individuals included in the study, preeclampsia with severe features within 2 weeks was observed in 33.1% (n=180) of them. A receiver operating characteristic curve-derived cutoff of 11.5 multiples of the median for the soluble fms-like tyrosine kinase 1 to placental growth factor plasma ratio provided good sensitivity (90.6%), specificity (76.9%), positive predictive value (66.0%), negative predictive value (94.3%), positive likelihood ratio (3.91), negative likelihood ratio (0.12), and accuracy (81.4%) for preeclampsia with severe features within 2 weeks. This cutoff was used to compare test positive cases (≥ cutoff) and test negative cases (< cutoff). Preeclampsia with severe features (66.0% vs 5.7%; P<.001) and composites of severe adverse maternal (8.11% vs 2.7%; P=.006) or perinatal (41.3% vs 10.14%; P=.001) outcomes within 2 weeks were more frequent in test positive cases than in test negative cases. A soluble fms-like tyrosine kinase 1 to placental growth factor plasma ratio ≥11.5 multiples of the median was independently associated with preeclampsia with severe features (adjusted incidence rate ratio, 9.08; 95% confidence interval, 6.11-14.06; P<.001) and a composite of severe adverse perinatal outcomes (adjusted incidence rate ratio, 9.42; 95% confidence interval, 6.36-14.53; P<.001) but not with a composite of severe adverse maternal outcomes (adjusted incidence rate ratio, 2.20; 95% confidence interval, 0.95-5.54; P=.08). The area under the curve for the soluble fms-like tyrosine kinase 1 to placental growth factor plasma ratio in multiples of the median (0.91; 95% confidence interval, 0.89-0.94) for preeclampsia with severe features within 2 weeks was significantly higher (P<.001 for all comparisons) than either plasma biomarker alone or any other parameter with the exception of absolute soluble fms-like tyrosine kinase 1 to placental growth factor plasma ratio values., Conclusion: A soluble fms-like tyrosine kinase 1 to placental growth factor plasma ratio ≥11.5 multiples of the mean among hospitalized patients with hypertension between 23 and 35 week's gestation predicts progression to preeclampsia with severe features and severe adverse perinatal outcomes within 2 weeks., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Importance: Compared with early cord clamping (ECC), umbilical cord milking (UCM) reduces delivery room cardiorespiratory support, hypoxic-ischemic encephalopathy, and therapeutic hypothermia in nonvigorous near-term and full-term infants. However, UCM postdischarge outcomes are not known., Objective: To determine the 2-year outcomes of children randomized to UCM or ECC at birth in the Milking in Nonvigorous Infants (MINVI) trial., Design, Setting, and Participants: A secondary analysis to evaluate longer-term outcomes of a cluster-randomized crossover trial was conducted from January 9, 2021, to September 25, 2023. The primary trial took place in 10 medical centers in the US, Canada, and Poland from January 5, 2019, to June 1, 2021, and hypothesized that UCM would reduce admission to the neonatal intensive care unit compared with ECC; follow-up concluded September 26, 2023. The population included near-term and full-term infants aged 35 to 42 weeks' gestation at birth who were nonvigorous; families provided consent to complete developmental screening questionnaires through age 2 years., Intervention: UCM and ECC., Main Outcomes and Measures: Ages and Stages Questionnaire, 3rd Edition (ASQ-3) and Modified Checklist for Autism in Toddlers, Revised/Follow-Up (M-CHAT-R/F) questionnaires at ages 22 to 26 months. Intention-to-treat analysis and per-protocol analyses were used., Results: Among 1730 newborns from the primary trial, long-term outcomes were evaluated in 971 children (81%) who had ASQ-3 scores available at 2 years or died before age 2 years and 927 children (77%) who had M-CHAT-R/F scores or died before age 2 years. Maternal and neonatal characteristics by treatment group were similar, with median birth gestational age of 39 (IQR, 38-40) weeks in both groups; 224 infants (45%) in the UCM group and 201 (43%) in the ECC group were female. The median ASQ-3 total scores were similar (UCM: 255 [IQR, 225-280] vs ECC: 255 [IQR, 230-280]; P = .87), with no significant differences in the ASQ-3 subdomains. Medium- to high-risk M-CHAT-R/F scores were also similar (UCM, 9% [45 of 486] vs ECC, 8% [37 of 441]; P = .86)., Conclusions and Relevance: In this secondary analysis of a randomized clinical trial among late near-term and full-term infants who were nonvigorous at birth, ASQ-3 scores at age 2 years were not significantly different between the UCM and ECC groups. Combined with previously reported important short-term benefits, this follow-up study suggests UCM is a feasible, no-cost intervention without longer-term neurodevelopmental risks of cord milking in nonvigorous near-term and term newborns., Trial Registration: ClinicalTrials.gov Identifier: NCT03631940.

Objectives: To determine whether rate of severe intraventricular hemorrhage (IVH) or death among preterm infants receiving placental transfusion with UCM is noninferior to delayed cord clamping (DCC)., Methods: Noninferiority randomized controlled trial comparing UCM versus DCC in preterm infants born 28 to 32 weeks recruited between June 2017 through September 2022 from 19 university and private medical centers in 4 countries. The primary outcome was Grade III/IV IVH or death evaluated at a 1% noninferiority margin., Results: Among 1019 infants (UCM n = 511 and DCC n = 508), all completed the trial from birth through initial hospitalization (mean gestational age 31 weeks, 44% female). For the primary outcome, 7 of 511 (1.4%) infants randomized to UCM developed severe IVH or died compared to 7 of 508 (1.4%) infants randomized to DCC (rate difference 0.01%, 95% confidence interval: (-1.4% to 1.4%), P = .99)., Conclusions: In this randomized controlled trial of UCM versus DCC among preterm infants born between 28 and 32 weeks' gestation, there was no difference in the rates of severe IVH or death. UCM may be a safe alternative to DCC in premature infants born at 28 to 32 weeks who require resuscitation., (Copyright © 2023 by the American Academy of Pediatrics.)

Background: Delayed cord clamping and umbilical cord milking provide placental transfusion to vigorous newborns. Delayed cord clamping in nonvigorous newborns may not be provided owing to a perceived need for immediate resuscitation. Umbilical cord milking is an alternative, as it can be performed more quickly than delayed cord clamping and may confer similar benefits., Objective: We hypothesized that umbilical cord milking would reduce admission to the neonatal intensive care unit compared with early cord clamping in nonvigorous newborns born between 35 and 42 weeks' gestation., Study Design: This was a pragmatic cluster-randomized crossover trial of infants born at 35 to 42 weeks' gestation in 10 medical centers in 3 countries between January 2019 and May 2021. The centers were randomized to umbilical cord milking or early cord clamping for approximately 1 year and then crossed over for an additional year or until the required number of consented subjects was reached. Waiver of consent as obtained in all centers to implement the intervention. Infants were eligible if nonvigorous at birth (poor tone, pale color, or lack of breathing in the first 15 seconds after birth) and were assigned to umbilical cord milking or early cord clamping according to their birth hospital randomization assignment. The baseline characteristics and outcomes were collected following deferred informed consent. The primary outcome was admission to the neonatal intensive care unit for predefined criteria. The main safety outcome was hypoxic-ischemic encephalopathy. Data were analyzed by the intention-to-treat concept., Results: Among 16,234 screened newborns, 1780 were eligible (905 umbilical cord milking, 875 early cord clamping), and 1730 had primary outcome data for analysis (97% of eligible; 872 umbilical cord milking, 858 early cord clamping) either via informed consent (606 umbilical cord milking, 601 early cord clamping) or waiver of informed consent (266 umbilical cord milking, 257 early cord clamping). The difference in the frequency of neonatal intensive care unit admission using predefined criteria between the umbilical cord milking (23%) and early cord clamping (28%) groups did not reach statistical significance (modeled odds ratio, 0.69; 95% confidence interval, 0.41-1.14). Umbilical cord milking was associated with predefined secondary outcomes, including higher hemoglobin (modeled mean difference between umbilical cord milking and early cord clamping groups 0.68 g/dL, 95% confidence interval, 0.31-1.05), lower odds of abnormal 1-minute Apgar scores (Apgar ≤3, 30% vs 34%, crude odds ratio, 0.72; 95% confidence interval, 0.56-0.92); cardiorespiratory support at delivery (61% vs 71%, modeled odds ratio, 0.57; 95% confidence interval, 0.33-0.99), and therapeutic hypothermia (3% vs 4%, crude odds ratio, 0.57; 95% confidence interval, 0.33-0.99). Moderate-to-severe hypoxic-ischemic encephalopathy was significantly less common with umbilical cord milking (1% vs 3%, crude odds ratio, 0.48; 95% confidence interval, 0.24-0.96). No significant differences were observed for normal saline bolus, phototherapy, abnormal 5-minute Apgar scores (Apgar ≤6, 15.7% vs 18.8%, crude odds ratio, 0.81; 95% confidence interval, 0.62-1.06), or a serious adverse event composite of death before discharge., Conclusion: Among nonvigorous infants born at 35 to 42 weeks' gestation, umbilical cord milking did not reduce neonatal intensive care unit admission for predefined criteria. However, infants in the umbilical cord milking arm had higher hemoglobin, received less delivery room cardiorespiratory support, had a lower incidence of moderate-to-severe hypoxic-ischemic encephalopathy, and received less therapeutic hypothermia. These data may provide the first randomized controlled trial evidence that umbilical cord milking in nonvigorous infants is feasible, safe and, superior to early cord clamping., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Alpha thalassemia major (ATM) is a hemoglobinopathy that usually results in perinatal demise if in utero transfusions (IUTs) are not performed. We established an international registry (NCT04872179) to evaluate the impact of IUTs on survival to discharge (primary outcome) as well as perinatal and neurodevelopmental secondary outcomes. Forty-nine patients were diagnosed prenatally, 11 were diagnosed postnatally, and all 11 spontaneous survivor genotypes had preserved embryonic zeta-globin levels. We compared 3 groups of patients; group 1, prenatally diagnosed and alive at hospital discharge (n = 14), group 2, prenatally diagnosed and deceased perinatally (n = 5), and group 3, postnatally diagnosed and alive at hospital discharge (n = 11). Group 1 had better outcomes than groups 2 and 3 in terms of the resolution of hydrops, delivery closer to term, shorter hospitalizations, and more frequent average or greater neurodevelopmental outcomes. Earlier IUT initiation was correlated with higher neurodevelopmental (Vineland-3) scores (r = -0.72, P = .02). Preterm delivery after IUT was seen in 3/16 (19%) patients who continued their pregnancy. When we combined our data with those from 2 published series, patients who received ≥2 IUTs had better outcomes than those with 0 to 1 IUT, including resolution of hydrops, delivery at ≥34 weeks gestation, and 5-minute appearance, pulse, grimace, activity, and respiration scores ≥7. Neurodevelopmental assessments were normal in 17/18 of the ≥2 IUT vs 5/13 of the 0 to 1 IUT group (OR 2.74; P = .01). Thus, fetal transfusions enable the survival of patients with ATM and normal neurodevelopment, even in those patients presenting with hydrops. Nondirective prenatal counseling for expectant parents should include the option of IUTs., (Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)

Objective: Determine effect of at least 60 s delayed cord clamping (DCC) on postpartum hemorrhage and maternal estimated blood loss (EBL) in very low birth weight (VLBW) cesarean deliveries when compared to early cord clamping (ECC)., Study Design: Retrospective study of VLBW infants at birth. Maternal pre- and post-operative hemoglobin, EBL, and neonatal outcomes were collected., Results: In total, 620 VLBW infants (DCC = 166, ECC = 454) born to 545 mothers (DCC = 155, ECC = 390) were included. Maternal PPH between DCC was 8% versus ECC was 10% p = 0.52. There were no differences in estimated blood loss or rate of maternal blood transfusion between groups. The post-operative hemoglobin was lower in infants receiving ECC compared to DCC (10.4 [9.4-11.5] versus 10.8 [10.1-11.9] g/dl, p = 0.01). In comparing pre-operative to post-operative hemoglobin there was no difference between DCC and ECC (-1.2 [-2.0 to -0.3] versus -1.2 [-2.1 to -0.6] g/dl, p = 0.46)., Conclusion: DCC of at least 60 s did not increase maternal bleeding complications during VLBW cesarean delivery. To our knowledge, this retrospective study is the largest sample size to date of preterm cesarean deliveries to support maternal safety regarding bleeding complications after delayed cord clamping., (© 2022. The Author(s), under exclusive licence to Springer Nature America, Inc.)

BACKGROUND: Among women with hypertensive disorders of pregnancy, biomarkers may stratify risk for developing preeclampsia with severe features (sPE). METHODS: Across 18 U.S. centers, we prospectively measured the ratio of serum soluble fms-like tyrosine kinase 1 (sFlt-1) to placental growth factor (PlGF) in pregnant women hospitalized between 23 and 35 weeks of gestation. The primary outcome was predicting sPE, and secondary outcomes included predicting adverse outcomes within 2 weeks. The prognostic performance of the sFlt-1:PlGF ratio was assessed by using a derivation/validation design. RESULTS: A total of 1014 pregnant women were evaluated; 299 were included in the derivation cohort and 715 in the validation cohort. In the derivation cohort, the median sFlt-1:PlGF ratio was 200 (interquartile range, 53 to 458) among women who developed sPE compared with 6 (interquartile range, 3 to 26) in those who did not (P<0.001). The discriminatory ratio of ≥40 was then tested in the validation cohort and yielded a 65% positive (95% confidence interval [CI], 59 to 71) and a 96% negative (95% CI, 93 to 98) predictive value for the primary outcome. The ratio performed better than standard clinical measures (area under the receiver-operating characteristic curve, 0.92 versus <0.75 for standard-of-care tests). Compared with women with a ratio <40, women with a ratio ≥40 were at higher risk for adverse maternal outcomes (16.1% versus 2.8%; relative risk, 5.8; 95% CI, 2.8 to 12.2). CONCLUSIONS: In women with a hypertensive disorder of pregnancy presenting between 23 and 35 weeks of gestation, measurement of serum sFlt-1:PlGF provided stratification of the risk of progressing to sPE within the coming fortnight. (Funded by Cedars-Sinai Medical Center and Thermo Fisher Scientific; ClinicalTrials.gov NCT03815110.)

Background: In contrast to the frequent occurrence of localized herpes simplex virus (HSV) infections during pregnancy, disseminated disease has rarely been reported., Case: A 21-year-old woman in the 27th week of gestation developed a catastrophic illness characterized by fever, progressive pneumonia, respiratory failure, leukopenia, disseminated intravascular coagulation (DIC), anicteric hepatitis, septic shock and acute renal failure. Initial studies for an infectious etiology were negative. In spite of empiric broad-spectrum antimicrobial therapy, her condition continued to deteriorate. Sparse vesicular skin lesions suggestive of HSV infection subsequently appeared. Despite initiation of acyclovir therapy, the patient died. HSV type 2 was cultured from a skin vesicle, and at autopsy there was extensive necrosis of the liver and lung with immunohistochemical stains positive for HSV antigen., Conclusion: In the third trimester of pregnancy, HSV can occasionally disseminate in immunocompetent women. A clinical syndrome of unexplained fever, pneumonia, anicteric hepatitis, leukopenia and DIC without mucocutaneous lesions should prompt investigation and possible treatment for disseminated HSV infection.

The approval by the FDA of Rh immune globulin in 1968 led to a decrease in the incidence of Rh isoimmunization. As a result, fewer cases are seen by both the perinatologist and neonatologist. Prompt identification and early referral of the isoimmunized mother to a tertiary center will facilitate optimal management incorporating the latest techniques. In selected clinical situations, the less invasive technique of amniocentesis can be offered in place of fetal blood sampling for Rh D typing. In the anemic fetus requiring intrauterine transfusions, delivery is the goal once lung maturity is documented. As described elsewhere in the issue, recent improvements in neonatal care have facilitated management of complications not seen in the fetus but potentially critical in the neonate.

Since pathologic changes of the placenta have been found in preeclamptic pregnancies, a relationship between fetal-maternal hemorrhage and preeclampsia was investigated. Sixty-two women with singleton pregnancies in the third trimester were studied. Thirty-one of these women with preeclampsia were matched with 31 normotensive healthy pregnant women. Maternal serum levels of alpha-fetoprotein (MSAFP) and Kleihauer-Betke (KB) test were determined to reflect the degree of fetal-maternal hemorrhage. There were no significant differences in MSAFP levels, MSAFP to creatinine ratio, or the appearance of fetal cells as measured by the KB test between preeclamptic pregnancies and matched controls. Our data do not suggest that fetal-maternal hemorrhage is increased in pregnant women with preeclampsia.

Objective: We examined intraplacental color Doppler flow patterns and spectral Doppler flow velocity waveforms of villous arteries in pregnancies with intrauterine growth retardation., Study Design: A total of 192 uncomplicated pregnancies and 29 pregnancies with intrauterine growth retardation between 26 and 41 weeks' gestation were examined in this cross-sectional study. Intraplacental color Doppler flow findings and pulsatility indexes of umbilical and villous arteries were correlated with the presence of intrauterine growth retardation and multiple outcome variables. Villous arteries were identified by their intraplacental color Doppler flow image, and flow velocity waveforms were obtained by superimposition of pulse-wave Doppler., Results: (1) Intraplacental color Doppler flow signals from two or more villous arteries were detected in all 192 normal pregnancies but were undetectable in 8 of 29 fetuses with intrauterine growth retardation (27.6%, p < 0.0001). Absence of intraplacental color Doppler flow signals was associated with fetal distress in 6 of 8 cases (87.5%) and perinatal death in two cases (25.0%), compared with 3 of 21 (14.2%, p < 0.005) and 0 of 21 (not significant) cases of intrauterine growth retardation with detectable intraplacental color Doppler flow. Median Apgar scores at 1 minute were 5 and 8 (p < 0.05), respectively, and at 5 minutes were 8 and 8 (not significant), respectively. (2) Umbilical artery flow velocity waveforms were abnormal (> 95th percentile) in 8 of 21 cases of intrauterine growth retardation (38.0%) with detectable intraplacental color Doppler flow, including two cases with reversed end-diastolic flow. In contrast, the corresponding villous artery flow velocity waveforms were abnormal in only 1 of 21 cases (p < 0.04)., Conclusion: (1) Failure to detect intraplacental color Doppler flow signals is associated with intrauterine growth retardation and fetal distress. (2) Flow velocity waveforms of detectable villous arteries are usually normal in intrauterine growth retardation, even in the presence of extremely abnormal umbilical artery flow velocity waveforms.

Fetal medicine is a new discipline that emerged out of the expansion of modern technology. Evaluation of the fetus heretofore was not possible except by indirect methods. Pregnancy management focused primarily on the care of the mother with the expectation that the fetus would be an indirect beneficiary. Our present-day approach to pregnancy and prenatal evaluation has been altered by the introduction of new techniques such as ultrasound, amniocentesis, and CVS, which have made the fetus and its intrauterine environment accessible. Improvements in ultrasonographic equipment have allowed for better visualization of the fetus, earlier detection of structural anomalies, and facilitation of the performance of invasive procedures. The recent introduction of CVS represents a major step toward achieving the goal of early diagnosis. Prevailing experience has demonstrated that it is a relatively safe and reliable procedure with a low complication rate. Early amniocentesis may be considered as an alternative to CVS when the latter is not advisable, although future studies are needed to accurately estimate the procedure-related risks (Table 5). Transcervical endoscopy allows a more detailed appreciation of fetal anatomy, although its role in clinical practice remains to be defined. Biochemical markers such as alpha fetoprotein, unconjugated estriol, and hCG, alone and in combination, have been studied regarding their potential to predict chromosomal abnormalities. Today there is a changing trend in prenatal diagnosis with women requesting more information about their unborn child and expecting such information earlier in gestation. The goal of prenatal diagnosis has been directed toward earlier detection to reduce the anxiety of waiting and permit the safer option of first-trimester termination of pregnancy.