Improvement in fetal pulmonary hypertension and maturity after reversal of ductal constriction: prospective cohort study.

OBJECTIVES: To test the hypotheses that estimated mean pulmonary arterial pressure (MPAP) decreases and pulmonary vascular maturation, assessed by the ratio of pulmonary arterial flow acceleration time to ejection time (AT/ET ratio), increases after reversal of fetal ductus arteriosus constriction by reducing maternal intake of the causal agent (prostaglandin inhibitors, such as polyphenol-rich foods or non-steroidal anti-inflammatory drugs), and that these effects are independent of gestational age, which are inferences not yet demonstrated in the clinical setting. METHODS: This was a prospective cohort study comparing Doppler echocardiographic ductal flow dynamics, MPAP and pulmonary arterial flow AT/ET ratio in third-trimester fetuses (≥ 28 weeks' gestation) with ductus arteriosus constriction, at the time of diagnosis and after 2 weeks of reduced maternal intake of prostaglandin inhibitors either by suspending the use of pharmacological agents with potential for prostaglandin inhibition or by restricting the consumption of polyphenol-rich foods. MPAP was estimated using the Dabestani equation (MPAP = 90 - (0.62 × AT)), and pulmonary vascular maturity was assessed using the AT/ET ratio, according to reported validation studies. Student's t-test was used for comparison of variables at diagnosis with those after reversal of ductal constriction. Change in MPAP and pulmonary AT/ET ratio between the two assessments was compared with the expected change in the same gestational period in normal fetuses based on reference curves of MPAP and pulmonary AT/ET ratio constructed in normal fetuses from healthy pregnant women at 19-37 weeks' gestation, encompassing the same gestational age range as the study group (28-37 weeks). RESULTS: Seventy pregnancies with fetal ductus arteriosus constriction were included in the study. After 2 weeks of reduced maternal intake of prostaglandin inhibitors, normalization of mean systolic (change from 1.86 ± 0.34 m/s at diagnosis to 1.38 ± 0.41 m/s; P < 0.001) and diastolic (change from 0.41 ± 0.11 m/s to 0.21 ± 0.065 m/s; P < 0.001) ductal velocities and of mean pulsatility index (change from 1.99 ± 0.20 to 2.55 ± 0.42; P < 0.001) was demonstrated. MPAP decreased between the assessments (change from 66.7 ± 6.90 mmHg at diagnosis to 54.5 ± 6.70 mmHg after 2 weeks; P < 0.001) and mean pulmonary AT/ET ratio increased (change from 0.20 ± 0.06 to 0.33 ± 0.07; P < 0.001). Change in MPAP between diagnosis and after 2 weeks of reduced maternal intake of prostaglandin inhibitors was -12.2 ± 0.30 mmHg, which was 5.3-times higher than that in 305 normal fetuses over 2 weeks during the same gestational period (-2.3 ± 0.19 mmHg) (P < 0.001), and change in pulmonary AT/ET ratio between the two assessments was 0.13 ± 0.08, which was 8.7-times higher than that in normal fetuses in the same gestational period (0.015 ± 0.08) (P < 0.001). CONCLUSIONS: Resolution of fetal ductal constriction is followed by a fall in MPAP and by an increase in pulmonary vascular maturity, to a significantly greater degree than is observed in normal fetuses in the same gestational-age period. © 2021 International Society of Ultrasound in Obstetrics and Gynecology.

Dilated cardiomyopathy due to premature ductus arteriosus constriction.

Herein, we present the first case of dilated cardiomyopathy due to premature constriction of the ductus arteriosus. A fetal echocardiography showed narrowing in the ductus arteriosus, and colour Doppler flow mapping could not identify blood flow through the ductus. Neonatal echocardiography revealed a left ventricular dilated cardiomyopathy, and the cardiomyopathy had fully resolved at 6 months of age.

Congenital tracheobronchial stenosis.

Congenital tracheobronchial stenosis is a rare disease characterized by complete tracheal rings that can affect variable lengths of the tracheobronchial tree. It causes high levels of morbidity and mortality both due to the stenosis itself and to the high incidence of other associated congenital malformations. Successful management of this complex condition requires a highly individualized approach delivered by an experienced multidisciplinary team, which is best delivered within centralized units with the necessary diverse expertise. In such settings, surgical correction by slide tracheoplasty has become increasingly successful over the past 2 decades such that long-term survival now exceeds 88%, with normalization of quality of life scores for patients with non-syndrome-associated congenital tracheal stenosis. Careful assessment and planning of treatment strategies is of paramount importance for both successful management and the provision of patients and carers with accurate and realistic treatment counseling.

Tracheal Atresia with Segmental Esophageal Duplication: An Unusual Anatomic Arrangement.

An unusual anatomic configuration of segmental tracheal agenesis/atresia with esophageal duplication on autopsy in a fetus that demised in utero at 29 weeks is reported. The mother was scanned initially for a cardiac anomaly at 20 weeks and on follow-up scan at 27 weeks had polyhydramnios and underwent amnioreduction. The final autopsy diagnosis was vertebral, ano-rectal, cardiac, tracheoesophageal, renal, and limb malformations (VACTERL). We discuss the autopsy findings along with the embryological mechanisms and compare the configuration with Floyd's classification for tracheal agenesis. The difficulties in prenatal diagnosis are discussed.

Tracheal agenesis with tracheoesophageal fistulae: fetal MRI diagnosis with confirmation by ultrasound during an ex utero intrapartum therapy (EXIT) delivery and postdelivery MRI.

Tracheal agenesis is a rare and essentially lethal anomaly with divergent prenatal imaging findings depending on the presence or absence of a tracheoesophageal fistula. All prenatally diagnosed cases of tracheal agenesis reported to date have not had a tracheoesophageal fistula and presented with thoracoabdominal findings similar to congenital high airway obstruction syndrome. We present the case of a 32-week gestation fetus with rapid onset of polyhydramnios and no persistent findings of congenital high airway obstruction syndrome that was ultimately diagnosed with tracheal agenesis plus tracheoesophageal fistula by fetal MRI. Additionally, we present the novel uses of intraoperative US during a staged ex utero intrapartum therapy delivery and postdelivery MRI, facilitated by proximity within the neonatal ICU, to confirm diagnosis and direct patient management while minimizing unnecessary investigations.

Agreement between umbilical vein volume blood flow measurements obtained at the intra-abdominal portion and free loop of the umbilical cord.

OBJECTIVE: The umbilical vein (UV) is a single vessel and theoretically the volume of blood flowing through it should be equal whether it is measured at the intra-abdominal portion (IA) or a free loop of the umbilical cord (FL). However, the reported values vary considerably depending on the technique and site of measurement. Our objective was to investigate the correlation and agreement between UV volume blood flows (Q(uv)) measured at the IA and FL. METHODS: Blood flow velocities and inner diameter of the UV were measured cross-sectionally at the IA and FL in 131 pregnant women at 22-24 weeks' gestation, and in 53 of them longitudinally at 4-weekly intervals until delivery. For each sampling site, the Q(uv) was calculated as: 0.5 x time-averaged maximum velocity x pi x (UV diameter/2)(2). RESULTS: The mean Q(uv) measured at the IA (61.5 +/- 23.3 mL/min) and FL (60.7 +/- 17.6 mL/min) cross-sectionally in 131 fetuses at 22-24 weeks of gestation were similar, but the bivariate correlation between them was not strong (r = 0.38; P < 0.0001) and the intraclass correlation coefficient (ICC) was 0.37 (95% CI, 0.21-0.51). When the agreement between 131 pairs of Q(uv) measurements was tested with Bland-Altman analysis, the mean of the ratio IA-Q(uv)/FL-Q(uv) was found to be 1.05 (i.e. IA-Q(uv) exceeded FL-Q(uv) on average by 5%) with 95% limits of agreement of 0.31-1.78. In the longitudinal analysis of 232 pairs of Q(uv) measurements from 53 fetuses at 22-40 weeks, the mean Q(uv) obtained at the IA and FL were similar, i.e. 164 +/- 87 (range, 25-484) mL/min vs. 159 +/- 82 (range, 30-470) mL/min, and the correlation between them, assessed after grouping the observations in five different gestational age groups of 4-week intervals, was slightly better (r = 0.45-0.62; P < 0.0001). The ICC for the Q(uv) measurements obtained at the two sites ranged from 0.38 to 0.54. The mean of the ratio IA-Q(uv)/FL-Q(uv) was 1.07 (i.e. IA-Q(uv) exceeded FL-Q(uv) on average by 7%), with 95% limits of agreement of 0.39-1.75. CONCLUSION: Average Q(uv) measured at the IA and FL was similar, but the agreement between individual pairs of measurements was not good enough to be able to use them interchangeably. Therefore, any clinical application of Q(uv) measurement would require standardization of the technique, strict adherence to methodology and use of appropriate reference ranges for it to be useful.

Is there a therapeutic role for fetoscopic surgery in the prenatal treatment of gastroschisis? A feasibility study in sheep.

BACKGROUND/PURPOSE: Gastroschisis is a malformation of the anterior abdominal wall that consists of a right paraumbilical defect with bowel loops bathed in the amniotic fluid. The prognosis relies mainly on morbidity attributable to intrauterine bowel loss or postpartum bowel dysfunction. The purpose of this study was to evaluate a potential role for fetoscopic surgery in severely affected fetuses with this condition. METHODS: Employing fetoscopy, we created a laparoschisis model in eight fetal sheep between 74-92 days of gestation; median 86.5 days). Twenty to 31 days after fetoscopic creation of fetal laparoschisis, a second procedure was scheduled in six survivors of the first surgery with the goal of assessing the potential for fetoscopic intervention in this condition. RESULTS: In the six survivors, macroscopic intestinal changes achieved by this animal model resembled those of human fetuses with gastroschisis. Whereas fetoscopic enlargement of the defect within the abdominal wall was feasible, in none of the fetuses was return of herniated abdominal viscera followed by abdominal closure possible using fetoscopic instrumentation. Furthermore, any attempt to return the herniated viscera into the fetal abdomen resulted in immediate and severe hemodynamic compromise of the fetoplacental circulation by stretching of the intra-abdominal umbilical arteries and vein. CONCLUSION: Minimally invasive fetoscopic enlargement of the defect within the abdominal wall is feasible in sheep fetuses with iatrogenic laparoschisis. This approach might benefit human fetuses with gastroschisis considered at high risk for bowel loss by constriction at the defect site. In contrast, return of herniated abdominal viscera followed by abdominal closure is limited by physiological constraints and seems currently not feasible with current fetoscopic instrumentation.

Ductus venosus shunting in growth-restricted fetuses and the effect of umbilical circulatory compromise.

OBJECTIVE: To determine the degree of ductus venosus (DV) shunting in fetuses with intrauterine growth restriction (IUGR) and the effect of various degrees of umbilical circulatory compromise. METHODS: This was a cross-sectional observational study. Sixty-four fetuses with IUGR (estimated weight < or = 2.5(th) percentile) underwent ultrasound examination. The diameter, velocity, and blood flow were determined in the DV and intra-abdominal umbilical vein (UV), and the fraction of shunting and DV : UV diameter ratios were calculated. Placental compromise was classified according to either normal umbilical artery (UA) pulsatility index (PI), UA-PI > 97.5(th) percentile, or absent or reversed end-diastolic flow velocity (A/REDV). Regression analysis was used to construct mean values, and SD scores were used to determine differences compared with a reference population (n = 212) after ln- or power-transformation. RESULTS: In the 64 growth-restricted fetuses, the average DV shunting was 39% compared with 25% in the reference group (overall P < 0.0001). The corresponding values in the subgroups with normal UA-PI, UA-PI > 97.5(th) percentile, and A/REDV were 31%, 35%, and 57%, respectively. Fetuses with IUGR and normal UA-PI (SD score: mean, 0.48; 95% CI, 0.04-0.92) did not shunt significantly more than did the reference fetuses (SD score: mean, 0.0; 95% CI, - 0.15 to 0.15), but those with UA-PI > 97.5(th) percentile (SD score: mean, 0.85; 95% CI, 0.41-1.29), and particularly those with A/REDV (SD score: mean, 1.56; 95% CI, 1.0-2.12) did shunt significantly more. With more DV shunting, these fetuses distributed correspondingly less umbilical blood to the liver, one of the mechanisms being a lower perfusion pressure as reflected in the lower DV blood velocity (P < 0.0001). CONCLUSIONS: DV shunting is higher and the umbilical blood flow to the liver is less in fetuses with IUGR, particularly in those with the most severe umbilical hemodynamic compromise.

Umbilical vein constriction at the umbilical ring: a longitudinal study.

OBJECTIVE: It has been suggested that constriction of the umbilical vein (UV) at the umbilical ring has hemodynamic effects. We aimed to determine the occurrence and extent of such constriction in serial observations. METHODS: This was a prospective longitudinal study of UV velocities at the umbilicus measured at approximately 4-week intervals between 19 and 42 weeks' gestation in 129 low-risk singleton pregnancies. Each participant was examined three to five times. Multilevel modeling was used to construct the reference ranges and to test associations between variables. RESULTS: Gestational age-specific reference percentiles of UV velocities at the umbilicus were established based on 469 observations. Fetuses were able to alter the UV velocities considerably during the second half of pregnancy, signifying a varying degree of UV constriction. Of a total of 129 fetuses, 56 (43.4%) never had high UV blood velocity (i.e. > 46 cm/s, the highest quartile), 42 (32.6%) fetuses had high UV blood velocity on one occasion and 31 (24.0%) fetuses on two or more occasions. In 36 (27.9%) fetuses the UV velocity at the umbilical ring was > 300% of the mean gestational age-specific reference value at the intra-abdominal section on at least one occasion. Constriction of the UV at the umbilical ring did not affect the pulsatility of the umbilical artery, and was not associated with adverse perinatal outcome in this study. CONCLUSIONS: Low-risk fetuses may well constrict the UV at the abdominal wall with velocities extending over wide ranges on one or more occasions during the second half of pregnancy. Rather than being a risk for complications, the constriction seems to be part of physiological development and possibly a regulatory mechanism.

The midsagittal view of the fetal brain: a useful landmark in recognizing the cause of fetal cerebral ventriculomegaly.

AIM: To evaluate the positive predictive value of the midsagittal view of the fetal brain in recognizing the cause of ventriculomegaly diagnosed with traditional axial scan. METHODS: Fifty-eight pregnant women, referred to our Center following a generic diagnosis of ventriculomegaly have been evaluated: 38 had marked and 20 had borderline ventriculomegaly. The fetal brain was scanned by the midsagittal view using a transabdominal probe in fetuses in breech presentation or transverse lie and a transvaginal probe in fetuses in cephalic presentation. The possible cause of ventriculomegaly was postulated by combining the findings of the corpus callosum/cavum septi pellucidi complex with those of the posterior fossa. The prenatal diagnoses were compared with the anatomical specimens of aborted fetuses or with postnatal neuroimaging. RESULTS: The prenatal diagnoses were confirmed in 54/58 cases (PPV 93.1%). In the marked ventriculomegaly group, one case of partial agenesis of the corpus callosum was mistaken for a complete agenesis. In the group of borderline ventriculomegaly, two cases of partial agenesis of the corpus callosum were confused with a complete agenesis, while one case of suspected isolated ventriculomegaly was diagnosed after birth as partial agenesis of the corpus callosum. CONCLUSIONS: The sagittal scan of the fetal brain is a useful source of information and allows the contemporary view of both corpus callosum and posterior fossa, where various typical sonographic findings are present in ventriculomegaly.

Is fetal cerebral vascular resistance affected by the presence of nuchal cord(s) in the third trimester of pregnancy?

OBJECTIVE: To assess whether fetal cerebral vascular resistance is affected by the presence of nuchal cord(s) in the third trimester. METHODS: A set of 115 patients with well-established dates and singleton, appropriate for gestational age (GA), non-anomalous fetuses with nuchal cord(s) diagnosed with prenatal color Doppler imaging, between 28 and 41 weeks and 115 controls matched for GA, were studied. Patients with hypertension, diabetes and autoimmune conditions were excluded. Doppler indices were obtained from the umbilical artery (UA) and the fetal middle cerebral artery (MCA) upon initial diagnosis of the nuchal cord. RESULTS: Of 115 GA-matched pairs of pregnancies, 103 fetuses had a single nuchal cord and 12 a double nuchal cord. No significant differences were noted in patient age, gravidity, parity, sonographically estimated fetal weight (SEFW), and growth centile at ultrasonographic diagnosis. Mean UA systolic/diastolic ratio (S/D) was 2.28 +/- 0.32 and 2.36 +/- 0.33 (P = 0.03) and UA resistance index (RI) 0.55 +/- 0.06 and 0.57 +/- 0.06 (P = 0.02) among study and controls, respectively. Mean fetal MCA S/D and RI did not differ significantly between the two groups (fetal MCA S/D 5.01 +/- 1.28 and 5.04 +/- 1.71 (P = 0.86), and mean fetal MCA RI 0.78 +/- 0.06 and 0.78 +/- 0.05 (P = 0.88)). No significant differences were noted in GA at delivery, incidence of meconium-stained amniotic fluid, birth weight, mode of delivery, neonatal gender, 1 and 5 minute Apgar scores, or UA pH and base excess, between study and control patients. CONCLUSION: Fetal cerebral vascular resistance is not affected by the presence of nuchal cord(s) in the third trimester of pregnancy.

Idiopathic constriction of the fetal ductus arteriosus.

Constriction of the ductus arteriosus in the fetus is well studied, but mostly secondary to maternal exposure to indomethacin or other non-steroidal anti-inflammatory medications, or structural cardiac lesions. We present a case of a fetus presenting with right ventricular hypertrophy secondary to an S-shaped ductus arteriosus with distal constriction diagnosed by pulsed Doppler imaging. A review of the recent English literature of similar cases is presented.

Circumferential abdominal skin defect possibly due to umbilical cord encirclement.

We report on a newborn black male twin with a distinctive circumferential abdominal skin defect who was identified through the Active Malformation Surveillance Program at the Brigham and Women's Hospital. There were no other malformations, and amniotic disruption was not present. Although it cannot be proven, we believe that this skin defect may have been caused by in utero encirclement of the abdomen by an umbilical cord.

A new in utero model for lateral facial clefts.

The etiopathogenesis behind the formation of atypical craniofacial facial clefts remains unknown. To test the hypothesis that physical restricting forces such as amniotic bands can lead to the formation of these unusual clefts in the postorganogenesis period, we have modified a previously reported fetal lamb model of amniotic band syndrome to examine the effects of these bands on craniofacial development. Five 70-day gestation fetal lambs (term, 140 days) were exposed via a maternal hysterotomy. In each animal, an attempt was made to create a lateral craniofacial cleft by applying a 2-0 nylon suture as a constriction band to the growing face. The sutures were attached to either the zygomatic arch or the infraorbital rim externally and then looped circumferentially into the oral commissure. Each suture was positioned so as to create either a Tessier type 5 or a Tessier type 7 cleft. Four of five fetal lambs survived to term. Both types of lateral facial clefts were effectively produced using this model. In each group, the presence of an intraoral constriction band led to the formation of macrostomia, with an average 7.4-mm lateral displacement of the oral commissure. In addition to these soft tissue changes, each animal also had partial bony clefting (i.e., a bony groove) induced by the pressure of the restriction band across the growing facial skeleton. In the two lambs with the Tessier type 7 cleft, incomplete bony clefts developed across the zygomatic arch. In three animals with bands placed across the medial infraorbital rim, significant infraorbital and malar bony clefts formed similar to a classic Tessier type 5 facial cleft. No evidence of tissue necrosis, maceration, or ulceration was noted in any animal. These data present, for the first time, evidence that the constriction of craniofacial growth by external forces such as a swallowed amnionic band can lead to the development of lateral facial clefting involving both soft tissue and bony elements. These malformations are likely due to a combination of directly tethering normal tissue migration and an increase in local pressure, which produces cellular ischemia and apoptosis. Furthermore, our data demonstrate that these clefts can occur later in fetal development during a period of facial growth rather than during the period of primary facial morphogenesis.

Meconium ileus and intestinal atresia in fetuses and neonates.

A collaborative study was performed to determine the different types and mechanisms of intestinal abnormalities during gestation. Cases had to fulfill one or more of the following three criteria: (1) meconium ileus, (2) intestinal stenosis or atresia, and (3) meconium peritonitis. Esophageal atresia, anorectal atresia, and abdominal wall defects were excluded. One hundred two cases were reviewed from the autopsies of 42 induced abortions, 22 stillborns, and the surgical findings in 38 neonates. Meconium ileus was detected mainly during the second trimester (28/38), and was associated with cystic fibrosis (15), fetal blood deglutition (4), infection (6), or multiple-abnormalities (10), in which three chromosomal aberrations were found. Intestinal stenosis or atresia was more commonly detected during the third trimester of gestation (46/56). Sixteen of the 30 duodenal malformations were associated with trisomy 21, whereas in the 26 small intestinal atresias, signs of distress or ischemia were most frequently detected. Only 8 of 25 meconium peritonitis cases were isolated. A total of 20 cystic fibrosis cases could be proved. In this series, functional abnormalities were observed predominantly in the second trimester and associated mainly with cystic fibrosis or amniotic fluid abnormalities. Anatomic lesions were commonly detected later on and associated with ischemic conditions, chromosomal aberrations, and even cystic fibrosis.

Enamel hypoplasia, bilateral cataracts, and aqueductal stenosis: a new syndrome?

We report on a 12-year-old girl who presented with generalized enamel hypoplasia, cataracts, and enlargement of the cerebral ventricles secondary to aqueductal stenosis. Previously described syndromes of enamel defects with or without cataracts were excluded on the basis of clinical criteria and appearance of the dentition. Metabolic conditions which could have caused cataracts were excluded clinically and by biochemical tests. The combination of signs in this patient may represent a new syndrome.