Bias in the prenatal lung measurements in fetal congenital diaphragmatic hernia with intrauterine growth restriction.

OBJECTIVES: The failure of a fetus to develop to its full potential due to maternal or placental factors is known as intrauterine growth restriction (IUGR). Fetal head growth is usually preserved in that situation producing a potential discordance between head and body size. Our goal is to discover if IUGR has an impact on the prenatal ultrasound measurements taken to assess pulmonary development in congenital diaphragmatic hernia (CDH). METHODS: A retrospective chart review (IRB#2017-6361) was performed on all prenatally diagnosed CDH patients from 2007 to 2016. Patient demographics, fetal and neonatal anthropometric measurements, and fetal lung parameters were the main subjects of the data that were gathered. Fetal growth was assessed by the curves based on US data by Olsen et al. and by Peleg et al. Of 147 CDH patients, 19 (12.9 %) patients were diagnosed with IUGR before the 30th gestational week while there were 20 (13.6 %) patients after the 30th gestational week. RESULTS: Patients with IUGR and the observed-to-expected lung-to-head ratio (O/E LHR) less than 25 % had better survival rates both to discharge and date compared to non IUGR group (p=0.226, OR 2.25 95 % CI 0.60-1.08 and p=0.175, OR 2.40 95 % CI 0.66-1.17, respectively). Moreover, the ECMO need of the patients who had IUGR and O/E LHR less than 25 % was significantly less than the patients without IUGR (38.5 vs. 80.0 %, p=0.005). CONCLUSIONS: This study confirms that the intrauterine measurements to predict pulmonary hypoplasia in CDH patients are misleading in the presence of IUGR and cause an overestimation.

Fetal magnetic resonance imaging, ultrasound, and echocardiography findings in twin reversed arterial perfusion sequence.

BACKGROUND: Twin reversed arterial perfusion (TRAP) sequence is a rare complication of monochorionic multiple gestation pregnancies, in which the pump twin provides hemodynamic support to a nonviable co-twin (acardius). Fetal magnetic resonance imaging (MRI) is used to detect pump twin abnormalities, particularly brain ischemia, prior to fetal intervention to interrupt umbilical blood flow to the acardius. OBJECTIVE: To summarize the imaging findings of TRAP sequence pregnancies in a large series. MATERIALS AND METHODS: A single-center retrospective review was performed of all TRAP sequence pregnancies referred for fetal MRI (2004-2021). Fetal MRI, ultrasound, and echocardiography data were collected. RESULTS: Eighty-eight TRAP sequence pregnancies with MRI were included (mean gestational age, 19.8±2.8 weeks). Demise of the pump twin was noted in two pregnancies at the time of MRI. By MRI, 12% (10/86) of live pump twins had abnormalities, including 3% (3/86) with brain abnormalities and 9% (8/86) with extra-cranial abnormalities. By echocardiography, 7% (6/86) of pump twins had structural cardiac abnormalities. Three acardius morphological subtypes were identified by MRI: acephalus (55%, 48/88), anceps (39%, 34/88), and amorphous (7%, 6/88). The mean ultrasound acardius to pump twin ratio A/P ratio, calculated for each twin pair as the ratio of the acardius trunk (and head, if present) plus limb volume to the pump twin estimated fetal weight) differed among the three acardius subtypes (P=.03). The mean A/P ratio moderately correlated with pump twin cardiothoracic ratio and combined cardiac output (Pearson's r=0.45 and 0.48, respectively, both P<.001). CONCLUSION: Fetal MRI of TRAP sequence pregnancies found anomalies in a substantial number of pump twins. The three acardius subtypes differed in A/P ratio, which moderately correlated with the pump twin cardiothoracic ratio and combined cardiac output.

Fetoscopic laser photocoagulation versus expectant management for stage I twin-to-twin transfusion syndrome: A systematic review and meta-analysis.

To investigate the outcomes of asymptomatic stage I twin-to-twin transfusion syndrome (stage I TTTS) among patients treated with fetoscopic laser photocoagulation (FLP) versus expectant management. Databases such as PubMed, Web of Science and Scopus were systematically searched from inception up to March 1st, 2022. The primary outcome was at least one fetal survival at birth and secondary outcomes included gestational age at delivery, preterm premature rupture of membranes < 32 weeks, preterm birth < 32 weeks, and single and dual fetal survival. Five studies were included in the meta-analysis. There was no significant difference in terms of at least one survival (odds ratio (OR) = 1.40, 95%CI= (0.26, 7.43), P = 0.70), single survival (OR = 0.87, 95%CI= (0.51, 1.48), P = 0.60) and dual survival (OR = 1.63, 95%CI= (0.74, 3.62), P = 0.23) among FLP and expectant groups. Gestational age at delivery (mean difference = 1.19, 95%CI= (-0.25, 2.63), P = 0.10), the risk of PTB<32 weeks (OR = 0.88, 95%CI= (0.50, 1.54), P = 0.65), and pPROM<32 weeks (OR = 1.80, 95% CI= (0.41, 7.98), P = 0.44) were also comparable between the groups. Routine FLP of the placental anastomoses before 26 weeks of gestation is unlikely to be beneficial among asymptomatic stable stage I TTTS patients without cervical shortening as the procedure does not offer a survival advantage compared with expectant management.

Effect of allograft patch closure on incidence of spinal inclusion cyst formation following open fetal myelomeningocele repair.

OBJECTIVE: The aim of this study was to evaluate the incidence of spinal inclusion cyst (sIC) formation after open fetal myelomeningocele (fMMC) repair and the effect of dural patch closure. METHODS: The authors conducted a retrospective review of patients who underwent open fMMC repair at their institution between March 2011 and June 2020. All patients met the criteria for intervention defined by the Management of Myelomeningocele Study (MOMS). The primary outcomes investigated were development of sIC and need for surgical intervention. Secondary outcomes included need for CSF diversion, extent of reversal of hindbrain herniation, and ambulatory status. RESULTS: Of 56 patients who underwent open fMMC repair, 52 had adequate spinal imaging for review. Twelve of these patients (23%) developed sIC (95% CI 0.11-0.35). Six patients experienced symptoms and required surgical detethering with sIC resection. Six additional patients had evidence of sIC on surveillance MRI but remained asymptomatic. The authors found a statistically significant relationship between the use of a dural allograft patch and sIC formation (p = 0.05). In terms of sIC development, there was no statistically significant difference between patients who underwent primary closure and those who received an allograft at the level of the fascia (p = 0.34) or skin (p = 0.26). The rate of hydrocephalus requiring CSF diversion was 52%. Interestingly, 98% of patients had improvement in extent of hindbrain herniation. Dural patch closure did not have any effect on the rate of progressive hydrocephalus (p = 0.33) or degree of reversal of hindbrain herniation (p > 0.99). CONCLUSIONS: This study suggested that children with prenatally repaired MMC are at higher risk for development of sIC and associated symptoms than those who undergo postnatal repair. The presentation of symptoms was also earlier in these patients than previously reported after postnatal repair. The use of a dural allograft patch appears to have a positive correlation with sIC formation. Future investigations evaluating the incidence of sIC after fetoscopic MMC repair, in which primary dural closure typically cannot be achieved and a dural patch is most often utilized, will be helpful in facilitating prenatal counseling for patients considering fetal intervention.

Solomon versus selective fetoscopic laser photocoagulation for twin-twin transfusion syndrome: A systematic review and meta-analysis.

This meta-analysis aims to compare the perinatal outcome of twin-twin transfusion syndrome (TTTS) pregnancies undergoing selective versus vascular equator (Solomon) fetoscopic laser photocoagulation (FLP). We performed a systematic search in PubMed and Web of Science from inception up to 25 July 2021. Studies comparing the Solomon and selective techniques of FLP for treatment of TTTS pregnancies were eligible. Random-effects or fixed-effect models were used to pool standardized mean differences (SMD) and log odds ratio. Seven studies with a total of 1664 TTTS pregnancies (n = 671 undergoing Solomon and n = 993 selective techniques) were included. As compared to the selective FLP, Solomon was associated with a lower risk of recurrent TTTS compared to the selective technique (Log odds ratio [OR]: -1.167; 95% credible interval [CrI]: -2.01, -0.33; p = 0.021; I2 : 67%). In addition, Solomon was significantly associated with a higher risk of placental abruption than the selective technique (Log [OR]: 1.44; 95% CrI: 0.45, 2.47; p = 0.012; I2 : 0.0%). Furthermore, a trend for the higher risk of preterm premature rupture of membranes was observed among those undergoing Solomon (Log [OR]: 0.581; 95% CrI: -0.43, 1.49; p = 0.131; I2 : 17%). As compared to selective FLP, the Solomon technique for TTTS pregnancies is associated with a significantly lower recurrence of TTTS; however, it significantly increases the risk of placental abruption.

Fetoscopic Multilayer, Dural Patch Closure Technique for Intrauterine Myelomeningocele Repair: 2-Dimensional Operative Video.

Myelomeningocele (MMC) is the most common open neural tube defect associated with long-term survival. In 2011, The Management of Myelomeningocele Study (MOMS) trial demonstrated that fetal repair for MMC reduced the rate of shunted hydrocephalus and improved developmental, motor, and ambulation outcomes at 30 mo compared to postnatal intervention.1 Recent studies have demonstrated the safety and feasibility of fetoscopic MMC repair as well as reduction in preterm birth, lower risk of uterine dehiscence, and the option of vaginal delivery with this approach compared to open fetal repair.2-4 The patient is a 25-yr-old female, G4 P2, who presented at 20 wk's gestation with ultrasound findings concerning for MMC and Chiari II malformation. These findings were further corroborated with fetal magnetic resonance imaging. After extensive prenatal counseling in a multidisciplinary fashion and discussion regarding risks and benefits of prenatal closure of the MMC, the patient chose to undergo prenatal repair and surgical consent was obtained. At 25 wk's gestation, the patient underwent a fetoscopic multilayer closure with dural patch repair using a standardized, 3-port, carbon dioxide insufflation technique for the intrauterine treatment of MMC without any postoperative complications. The duration of the entire procedure was 275 min. At 36 wk's and 1 d's gestational age, the patient had a spontaneous vaginal delivery, resulting in a healthy male newborn. The surgical site was well healed without complications, and follow-up radiographic imaging was reassuring. This edited, 2-dimensional operative video highlights the key steps of the fetoscopic closure with follow-up postnatal clinical and radiographic outcomes.

Prospective, randomized, double-blind, placebo-controlled evaluation of the Pharmacokinetics, Safety and Efficacy of Recombinant Antithrombin Versus Placebo in Preterm Preeclampsia.

BACKGROUND: Despite expectant management, preeclampsia remote from term usually results in preterm delivery. Antithrombin, which displays antiinflammatory and anticoagulant properties, may have a therapeutic role in treating preterm preeclampsia, a disorder characterized by endothelial dysfunction, inflammation, and activation of the coagulation system. OBJECTIVE: This randomized, placebo-controlled clinical trial aimed to evaluate whether intravenous recombinant human antithrombin could prolong gestation and therefore improve maternal and fetal outcomes. STUDY DESIGN: We performed a double-blind, placebo-controlled trial at 23 hospitals. Women were eligible if they had a singleton pregnancy, early-onset or superimposed preeclampsia at 23 0/7 to 30 0/7 weeks' gestation, and planned expectant management. In addition to standard therapy, patients were randomized to receive either recombinant human antithrombin 250 mg loading dose followed by a continuous infusion of 2000 mg per 24 hours or an identical saline infusion until delivery. The primary outcome was days gained from randomization until delivery. The secondary outcome was composite neonatal morbidity score. A total of 120 women were randomized. RESULTS: There was no difference in median gestational age at enrollment (27.3 weeks' gestation for the recombinant human antithrombin group [range, 23.1-30.0] and 27.6 weeks' gestation for the placebo group [range, 23.0-30.0]; P=.67). There were no differences in median increase in days gained (5.0 in the recombinant human antithrombin group [range, 0-75] and 6.0 for the placebo group [range, 0-85]; P=.95). There were no differences between groups in composite neonatal morbidity scores or in maternal complications. No safety issues related to recombinant human antithrombin were noted in this study, despite the achievement of supraphysiological antithrombin concentrations. CONCLUSION: The administration of recombinant human antithrombin in preterm preeclampsia neither prolonged pregnancy nor improved neonatal or maternal outcomes.

Prenatal and postnatal MRI findings in open spinal dysraphism following intrauterine repair via open versus fetoscopic surgical techniques.

PURPOSE: The purpose of the study is to examine MRI findings of the brain and spine on prenatal and postnatal MRI following intrauterine repair of open spinal dysraphism (OSD) by open hysterotomy and fetoscopic approaches. MATERIALS AND METHODS: This study is a single-center HIPAA-compliant and IRB-approved retrospective analysis of fetal MRIs with open spinal dysraphism from January 2011 through December 2018 that underwent subsequent prenatal repair of OSD. RESULTS: Sixty-two patients met inclusion criteria: 47 underwent open repair, and 15 underwent fetoscopic repair, with an average gestational age of 22.6 ± 1.4 weeks at initial MRI. On postnatal MRI, spinal cord syrinx was seen in 34% (16/47) of patients undergoing open versus 33.3% (5/15) undergoing fetoscopic repair (P = 0.96). Postnatally, there was no significant difference in hindbrain herniation between the open versus fetoscopic repair groups (P = 0.28). Lateral ventricular size was significantly larger in the open (20.9 ± 6.7 mm) versus the fetoscopic repair (16.1 ± 4.9 mm) group (P = 0.01). CONCLUSION: Though lateral ventricular size in the open repair group was larger than the fetoscopic repair group, this can likely be explained by initial selection criteria used for fetoscopic repair. Other postoperative imaging parameters on postnatal MRI were not significantly different between the two groups.

Fetal somatic growth trajectory differs by type of congenital heart disease.

BackgroundThe growth trajectories of common measurements, including estimated fetal weight (EFW), head circumference (HC), and abdominal circumference (AC), in fetuses with congenital heart disease (CHD) have not been described for different cardiac lesions. We hypothesized that (i) fetuses with CHD have differential growth in utero, and (ii) different categories of CHD demonstrate different in utero growth curves.MethodsWe performed a retrospective observational cohort study of pregnancies with known fetal CHD seen from January 2000 to June 2013. For analysis, the infants were divided into single ventricle (SV), biventricular conotruncal, d-transposition of great arteries (d-TGA), biventricular septal defects (SD; including atrial, ventricular, and atrioventricular SD), and all others (Other).ResultsA total of 194 newborns met inclusion criteria. There was significant differential growth of EFW in all CHD types, except d-TGA, starting with low z-scores before 25 weeks gestation, improving toward normal around 30-32 weeks gestation, and then again differential growth with advancing gestation. SV and SD groups had significant differential growth of HC starting early in gestation and linearly progressing negative z-scores with advancing gestation.ConclusionWe observed differences in the fetal growth curves throughout gestation for the major categories of CHD, including significant differential growth in even "simple" CHD, such as SD.

Sonographic markers associated with adverse neonatal outcomes among fetuses with gastroschisis: an 11-year, single-center review.

BACKGROUND: Gastroschisis complicates 1 in 2000 births and is readily identifiable during prenatal ultrasound scans. Outcomes in fetuses that are affected by gastroschisis vary widely from stillbirth or neonatal death to uncomplicated surgical correction, which makes prenatal counseling challenging. OBJECTIVE: The goal of our study was to identify sonographic markers that are associated with perinatal death and morbidity that include significant bowel injury, necrotizing enterocolitis, and the need for bowel resection in fetuses with gastroschisis. STUDY DESIGN: We identified a cohort of fetuses that were diagnosed with gastroschisis from 2003-2014. Sonographic markers that were reviewed included growth restriction, abdominal circumference, oligohydramnios, bowel dilation, and gastric bubble characteristics. We evaluated these markers both at diagnosis and near delivery. Four adverse perinatal outcomes were assessed: perinatal death, necrotizing enterocolitis, need for bowel resection, and a composite of significant bowel injury, which included a diagnosis of bowel atresia or necrosis at the time of surgical exploration. Logistic regression was performed to calculate odds ratios and 95% confidence intervals for each marker and outcome. RESULTS: One hundred seventy-seven patients were identified, and 154 of these patients met inclusion criteria after exclusions for delivery <24 weeks gestation, other associated anomalies, lethal karyotype, or lost to follow-up evaluation. Markers at the time of diagnosis (median gestational age, 21 weeks [25th,75th interquartile range, 19, 24 weeks]) that were associated with perinatal death were abdominal circumference <5th percentile (odds ratio, 5.56; 95% confidence interval, 1.25-24.76), abnormal gastric bubble (odds ratio, 11.20; 95% confidence interval, 2.15-58.33), and abnormal stomach location (odds ratio, 17.1; 95% confidence interval, 2.99-97.85). An abnormal stomach location (odds ratio, 5.53; 95% confidence interval, 1.03-29.72) before delivery was associated with perinatal death. Gastric dilation before delivery (odds ratio, 4.36; 95% confidence interval, 1.10-17.34)] was associated with the need for bowel resection. CONCLUSION: Early sonographic markers of increased perinatal mortality rates include abdominal circumference <5th percentile and an abnormal gastric bubble.

The GoMo study: a randomized clinical trial assessing neonatal pain with Gomco vs Mogen clamp circumcision.

OBJECTIVE: Our objective was to compare the pain/stress levels of newborns among the 2 most common circumcision techniques after resident-wide education. STUDY DESIGN: The study period of this randomized control trial was October 2012 through March 2014. Following informed consent, full-term males from uncomplicated singleton pregnancies were randomized to Gomco (n=137) or Mogen (n=137) devices. Resident-wide education for an obstetrics and gynecology residency program at a single institution was performed to ensure standardized training. All infants received a subcutaneous ring block before the procedure and oral sucrose intraoperatively. The primary outcome was neonatal pain assessed physiologically by salivary cortisol levels (enzyme-linked immunosorbent assay) and clinically by a validated neonatal pain score (crying, requires increased oxygen administration, increased vital signs, expression, sleeplessness [CRIES]). Secondary outcomes were immediate complications, duration of procedure, and short-term outcomes as reported by mothers and pediatricians. A sample size of 274 (accounting for 20% loss of follow-up) was determined sufficient to detect a mean difference of 1.22 µg/dL in cortisol levels (Gomco, SD±3.34; Mogen, SD±0.81) with 80% power, P=.05 level of significance. RESULTS: A total of 251 infants completed the protocol. There were no significant differences in maternal or neonatal demographics including preoperative heart rate and mean arterial pressure. In the Mogen circumcision, the percentage change of cortisol was significantly lower than Gomco (279.1±498.15 vs 167.75±272.22; P=.049). There were no differences in postoperative CRIES scores. Postoperative heart rate was higher in infants undergoing Gomco circumcision than Mogen circumcision (138.7±16.5 vs 133.4±17.5; P=.015) as was mean arterial blood pressure (63.3±9.2 vs 60.4±8.6; P=.012). Mogen circumcisions were shorter (7.00±2.97 vs 3.65±1.84 minutes; P<.001). There were no significant differences in bleeding complications. A total of 168 maternal surveys were completed, with 98.7% maternal satisfaction in Gomco vs 98.9% in Mogen. There were no reports of bleeding after discharge or circumcision revisions in either group to date. CONCLUSION: Mogen clamp is associated with less neonatal pain physiologically by significantly lower percentage change in salivary cortisol, lower heart rate, and mean arterial blood pressure. There was no difference in CRIES scores. Mogen clamp circumcision duration is significantly shorter than Gomco clamp. Both methods demonstrate satisfactory maternal and pediatrician short-term follow-up.