Hypertensive Disorders of Pregnancy and Risk of Early Brain Abnormalities on Magnetic Resonance Imaging at Term among Infants Born at ≤32 Weeks' Gestational Age.

OBJECTIVE: To evaluate the proximal effects of hypertensive disorders of pregnancy (HDP) on a validated measure of brain abnormalities in infants born at ≤32 weeks' gestational age (GA) using magnetic resonance imaging at term-equivalent age. STUDY DESIGN: In a multisite prospective cohort study, 395 infants born at ≤32 weeks' GA, underwent 3T magnetic resonance imaging scan between 39 and 44 weeks' postmenstrual age. A single neuroradiologist, blinded to clinical history, evaluated the standardized Kidokoro global brain abnormality score as the primary outcome. We classified infants as HDP-exposed by maternal diagnosis of chronic hypertension, gestational hypertension, pre-eclampsia, or eclampsia. Linear regression analysis identified the independent effects of HDP on infant brain abnormalities, adjusting for histologic chorioamnionitis, maternal smoking, antenatal steroids, magnesium sulfate, and infant sex. Mediation analyses quantified the indirect effect of HDP mediated via impaired intrauterine growth and prematurity and remaining direct effects on brain abnormalities. RESULTS: A total of 170/395 infants (43%) were HDP-exposed. Adjusted multivariable analyses revealed HDP-exposed infants had 27% (95% CI 5%-53%) higher brain abnormality scores than those without HDP exposure (P = .02), primarily driven by increased white matter injury/abnormality scores (P = .01). Mediation analyses showed HDP-induced impaired intrauterine growth significantly (P = .02) contributed to brain abnormality scores (22% of the total effect). CONCLUSIONS: Maternal hypertension independently increased the risk for early brain injury and/or maturational delays in infants born at ≤32 weeks' GA with an indirect effect of 22% resulting from impaired intrauterine growth. Enhanced prevention/treatment of maternal hypertension may mitigate the risk of infant brain abnormalities and potential neurodevelopmental impairments.

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.

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.

Should We Stitch-Close the Fetoscopic Percutaneous Access? A Case-Series of Laparotomy to Trans-Amniotic Membrane Suturing for Intrauterine Port Placement in Fetoscopic Surgery for Twins.

INTRODUCTION: Maternal laparotomy-assisted fetoscopic surgery for in-utero myelomeningocele repair has shown that a trans-amniotic membrane suture during fetoscopic port placement can reduce postsurgical complications. Fetoscopic laser photocoagulation (FLP) for complex twins is typically performed percutaneously without a transmembrane stitch. However, in scenarios without a placental-free window, maternal laparotomy may be used for recipient sac access. Here, we present the outcomes of our series of laparotomy-assisted FLP cases, including a trans-amniotic membrane suturing of the fetoscopic port. METHODS: Retrospective series of twin-twin transfusion syndrome or twin anemia-polycythemia sequence (TAPS) cases treated at 2 fetal centers that underwent maternal laparotomy to FLP from September 2017 to January 2023. We recorded preoperative and operative characteristics, as well as pregnancy and neonatal outcomes. RESULTS: During the study period, 9 maternal laparotomy to FLP cases were performed. Two were excluded for prior percutaneous FLP in the pregnancy. The remaining seven utilized a maternal laparotomy to trans-amniotic membrane stitch with confirmation of proper suture placement under ultrasound guidance, and all surgeries were performed with a single 10 F Check-Flo® cannula. Mean gestational age (GA) at surgery was 19.1 weeks (range 16 weeks 4 days-23 weeks 3 days), with delivery occurring at a mean GA of 35.0 weeks (range 32 weeks 0 days-37 weeks 1 day), resulting in a mean latency of 15.8 weeks, significantly longer than what is reported in the literature and our own data (mean latency for percutaneous FLP 10.2, 95% CI 9.9-10.5). Furthermore, all cases underwent iatrogenic delivery before labor onset, with the lone delivery prior to 34 weeks due to concern for post-laser TAPS. CONCLUSION: This case series of laparotomy to FLP with trans-amniotic stitch, demonstrated no cases of spontaneous preterm birth and a longer-than-expected latency from surgery to delivery. Larger studies are warranted to investigate this approach.

Twin-twin transfusion syndrome recipient with arterial calcification and heterozygous variant in ABCC6: Evidence of a gene-environment interaction?

We report a case of a twin-twin transfusion syndrome (TTTS) recipient who, after successful fetoscopic surgery, developed a large pericardial effusion and calcifications of the aorta and main pulmonary artery. The donor fetus never had cardiac strain and never developed cardiac calcifications. A heterozygous likely pathogenic variant in ABCC6 (c.2018T > C, p.Leu673Pro) was identified in the recipient twin. While TTTS recipient twins are at risk of arterial calcifications and right heart failure secondary to the disease, calcifications of the great vessels are also observed in generalized arterial calcification of infancy, a Mendelian genetic disorder with associated biallelic pathogenic variations in ABCC6 or ENPP1, which can result in significant pediatric morbidity or mortality. The recipient twin in this case had some degree of cardiac strain prior to TTTS surgery; however, the progressive calcification of the aorta and pulmonary trunk occurred weeks after TTTS resolution. This case raises the possibility of a gene-environment interaction and emphasizes the need for genetic evaluation in the setting of TTTS and calcifications.

Association of amnioinfusion volume at the time of surgery for twin-twin transfusion syndrome and latency to delivery.

OBJECTIVE: To evaluate the impact of amnioinfusion and other peri-operative factors on pregnancy outcomes in the setting of Twin-twin transfusion syndrome (TTTS) treated via fetoscopic laser photocoagulation (FLP). METHODS: Retrospective study of TTTS treated via FLP from 2010 to 2019. Pregnancies were grouped by amnioinfusion volume during FLP (<1 L vs. ≥1 L). The primary outcome was latency from surgery to delivery. An amnioinfusion statistic (AIstat) was created for each surgery based on the volume of fluid infused and removed and the preoperative deepest vertical pocket. Regression analysis was planned to assess the association of AIstat with latency. RESULTS: Patients with amnioinfusion of ≥1 L at the time of FLP had decreased latency from surgery to delivery (61 ± 29.4 vs. 73 ± 28.8 days with amnioinfusion <1 L, p < 0.001) and increased preterm prelabor rupture of membranes (PPROM) <34 weeks (44.7% vs. 33.5%, p = 0.042). Amnioinfusion ≥1 L was associated with an increased risk of delivery <32 weeks (aRR 2.6, 95% CI 1.5-4.5), 30 weeks (aRR 2.4, 95% CI 1.5-3.8), and 28 weeks (aRR 1.9, 95% CI 1.1-2.3). Cox-proportional regression revealed that AIstat was inversely associated with latency (HR 1.1, 95% CI 1.1-1.2). CONCLUSION: Amnioinfusion ≥1 L during FLP was associated with decreased latency after surgery and increased PPROM <34 weeks.

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.

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.

The Maternal Impact, Health Burden, and Postpartum Sequela in Triplet Pregnancies: A Retrospective Cohort.

OBJECTIVE: The aim of the study is to describe the maternal health burden and perinatal outcomes in triplet pregnancies, and identify the maternal and pregnancy indicators associated with increased perinatal morbidity and mortality. STUDY DESIGN: This is a retrospective cohort study of triplet pregnancies from 2007 to 2014. Maternal data were manually collected and assessed until 6 weeks postpartum, and neonatal data were assessed until hospital discharge or death. RESULTS: Eighty-two triplet pregnancies were identified with 246 babies born. Mean gestational age at delivery was 32.3 (standard deviation [SD] ± 3.6) weeks and average birth weight was 1,726 g (SD ± 500). There were 12 perinatal deaths and 25 (10.2%) infants diagnosed with a congenital anomaly. Prior preterm birth and nulliparity had a negative impact on gestational age at delivery (p = 0.016) as compared with prior full-term births. Pregnancy complications (preeclampsia or hypertensive disorders [46.3%], gestational diabetes [28%], postpartum hemorrhage [9.8%], and blood transfusions [8.5%]) also impacted gestational age at delivery (33.0 vs. 34.0 weeks, p = 0.031). Spontaneous conception, chorionicity, and maternal medical problems did not have an impact on median gestational age. CONCLUSION: Nulliparity and presence of pregnancy complications are pertinent to triplet outcomes. This study provides valuable information for anticipatory guidance and preconception counseling to patients considering artificial reproductive technology.

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.

Contemporary Outcomes of Patients with Isolated Bilateral Renal Agenesis with and without Fetal Intervention.

INTRODUCTION: Bilateral renal agenesis (BRA) is a lethal diagnosis, specifically meaning that natural survival beyond birth is not expected secondary to pulmonary hypoplasia. Limited contemporary data are available about intervention and the impact of restoring amniotic fluid volume in relation to the risk for lethal pulmonary hypoplasia and other factors that might influence survival in cases of fetal BRA. OBJECTIVE: We report the largest series of patients undergoing fetal intervention and postnatal care for BRA at a single comprehensive fetal center. METHODS: All patients with fetal BRA were reviewed from January 2004 to November 2017. Maternal and neonatal data were collected in an institutional review board-approved retrospective review. RESULTS: From 2014 to 2017, 20 singleton pregnancies with isolated fetal BRA were evaluated and 14 had amnioinfusion. Eight had serial infusions. Of those, there were 6 neonatal deaths. There were 2 neonatal survivors beyond 30 days; however, both died of sepsis on dialysis. One of these survivors received amnioinfusions by percutaneous approach and one via amnioport. There were no survivors to transplantation. CONCLUSION: Fetal intervention via amnioinfusion may promote pulmonary survivorship after birth, but postnatal survival remains poor. Future studies must place an emphasis on standardizing the postnatal approach to this patient population.

Reproductive Outcomes following Laser Surgery for Twin-Twin Transfusion Syndrome.

BACKGROUND: There are limited studies describing future reproductive outcomes in women who have had selective fetoscopic laser photocoagulation (SFLP) for twin-twin transfusion syndrome (TTTS). OBJECTIVE: Our study aims to compare reproductive outcomes following monochorionic multiple gestational pregnancies complicated by TTTS requiring SFLP to those not requiring SFLP. METHODS: This is a retrospective cohort study that analyzed records of patients who were evaluated at the Cincinnati Fetal Center (2007-2014) for monochorionic multiple gestations. A questionnaire regarding reproductive, obstetric, gynecologic, and psychological outcomes following the index pregnancy was administered to consented participants by electronic distribution. The data was compared between pregnancies with prior SFLP versus no prior SFLP. RESULTS: There was a higher response rate in the SFLP group (219/474, 46.2%) versus the referent group (62/187, 33.2%). The median interval between the index pregnancy and survey completion was 74 months and 46 months in the SFLP and referent groups, respectively. Approximately 38 and 37% of the women in the SFLP and referent groups attempted conception after the index pregnancy with a >90% pregnancy success rate in both groups. Use of assisted reproductive technology was highly prevalent in both the index and subsequent pregnancies, with no significant difference between the groups. Over 60% of the women in each group did not attempt future pregnancy. Of those, approximately 1 in 3 cited the outcome of the index pregnancy as the primary reason for not pursuing future conception. There were no significant differences in selected maternal-fetal complications and new-onset gynecologic problems. More than 1 in 4 women in both groups were diagnosed with a mental health disorder following the index pregnancy. CONCLUSION: SFLP does not appear to be associated with adverse reproductive, obstetric, or gynecologic outcomes. The data may help facilitate evidence-based counseling for this patient population.

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.

Perinatal outcomes of single fetal survivor after fetal intervention for complicated monochorionic twins.

OBJECTIVE: To compare perinatal outcomes between acute single fetal demise following fetoscopic laser photocoagulation to planned selective reduction (SR) in complicated monochorionic twin pregnancies. METHODS: This was a secondary analysis of prospectively collected data in complicated monochorionic twin pregnancies from 2 fetal centers from 2011 to 2016. Group 1 included women undergoing fetoscopic laser photocoagulation for twin-twin transfusion syndrome (TTTS) who experienced a single fetal demise within 24 hours of the procedure. Group 2 consisted of women undergoing planned selective reduction (SR) with TTTS, and Group 3 SR for indications other than TTTS. RESULTS: Survival of the remaining co-twin at birth was highest in Group 1 (n = 77 patients; 95%) compared with that in Group 2 (n = 15; 80%) and Group 3 (n = 32; 78%; P = .047). The preterm premature rupture of membrane rate was higher in Group 1 (47%) compared with that in Group 2 (33%) and Group 3 (7%; P < .001). Group 1 had a lower gestational age at delivery and shorter procedure-to-delivery interval compared with the other 2 groups (P < .01). CONCLUSION: When single fetal demise occurs following fetoscopic laser photocoagulation, the surviving co-twin is more likely to survive to delivery but has higher PPROM rates and a shorter latency period compared with planned selective reduction for TTTS or other indications.

Hemodynamic adaptation to suboptimal fetal growth in patients with single ventricle physiology.

BACKGROUND: In fetuses with structurally normal heart and suboptimal fetal growth (SFG), umbilical artery vascular resistance increases as measured by umbilical artery pulsatility index (UA-PI). The objective of this study is to compare hemodynamic responses to SFG in fetuses with single ventricle (SV) and controls with structurally normal heart. METHODS: Fetal echocardiograms around 30 weeks of gestation were reviewed. UA-PI and middle cerebral artery pulsatility index (MCA-PI) were calculated. SFG was defined as a birth weight below 25th percentile for gestational age. RESULTS: Studies from 92 fetuses were reviewed-SV (n = 50) and controls (n = 42). The prevalence of SFG was higher in SV compared to controls (46% vs 21%, P = .02). In patients with normal heart and SFG, UAPI was significantly higher than normal controls (P = .003) suggesting increased placental vascular resistance. In SV with SFG there was no difference in UAPI compared to SV without SFG. There was no difference in MCA-PI between the groups. CONCLUSIONS: The hemodynamic response to SFG in SV varies from fetuses with structurally normal heart. The mechanism of SFG and the placental pathology may be distinct in SV.

Fetal origins of adult cardiac disease: a novel approach to prevent fetal growth restriction induced cardiac dysfunction using insulin like growth factor.

BACKGROUND: Fetal growth restriction (FGR) is a risk factor for adult cardiovascular disease. Intraplacental gene transfer of human insulin-like growth factor-1 (IGF-1) corrects birth weight in our mouse model of FGR. This study addresses long term effects of FGR on cardiac function and the potential preventive effect of IGF-1. STUDY DESIGN: Laparotomy was performed on pregnant C57BL/6J mice at embryonic day 18 and pups were divided into three groups: Sham operated; FGR (induced by mesenteric uterine artery ligation); treatment (intraplacental injection of IGF-1 after uterine artery ligation). Pups were followed until 32 wk of life. Transthoracic echocardiography was performed starting at 12 wk. RESULTS: Systolic cardiac function was significantly impaired in the FGR group with reduced fractional shortening compared with sham and treatment group starting at week 12 of life (20 ± 4 vs. 31 ± 5 vs. 32 ± 5, respectively, n = 12 for each group; P < 0.001) with no difference between the sham and treatment groups. CONCLUSION: Intraplacental gene transfer of IGF-1 prevents FGR induced cardiac dysfunction. This suggests that in utero therapy may positively impact cardiac remodeling and prevent adult cardiovascular disease.

Use of an Amnioport to Maintain Amniotic Fluid Volume in Fetuses with Oligohydramnios Secondary to Lower Urinary Tract Obstruction or Fetal Renal Anomalies.

OBJECTIVE: We describe a technique to maintain amniotic fluid in fetuses with severe oligo-/anhydramnios secondary to lower urinary tract obstruction or fetal renal disease when urine production is inadequate to maintain a normal amniotic fluid volume (AFV). METHODS: An amnioport was inserted into the amniotic space. The catheter was secured to prevent dislodgment and tunneled to a subcutaneous reservoir. The reservoir was accessed as necessary, infusing normal saline to maintain AFV. Pregnancy continued until term or indicated delivery. RESULTS: Since 2010, 15 patients in this category were considered for an amnioport. Six chose comfort care and one elected percutaneous amnioinfusions. Nine amnioport procedures were performed in eight patients. There were no fetal deaths. All eight had successful restoration and maintenance of amniotic fluid. Delivery ranged from 9 to 96 days after placement (mean 63.7 days). One died due to unrecognized laryngeal web and another one died of pulmonary hypoplasia after preterm premature rupture of membranes. None of the remaining six had pulmonary hypoplasia. Three remain alive. DISCUSSION: Severe oligo-/anhydramnios in the second trimester secondary to fetal anomalies is almost uniformly lethal due to pulmonary hypoplasia without restoration of amniotic fluid. The amnioport procedure may allow pulmonary survival but commits families to postnatal care decisions regarding pulmonary and renal complications.

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.

Intrauterine fetal demise after prenatal diagnosis of congenital heart disease: assessment of risk.

OBJECTIVES: Elective deliveries in fetal congenital heart disease (CHD) attempt to balance fetal and neonatal risk with the goal of optimizing overall outcome. However, the magnitude of the risk for intrauterine fetal demise (IUFD) is unclear. This study aimed to (1) determine the rate of IUFD and (2) identify fetal risk factors associated with IUFD. METHODS: Retrospective review of pregnancies complicated by CHD between 1998 and 2010. Data were collected regarding pregnancy outcome, extracardiac anomalies (ECA), genetic and cardiac diagnoses, severity of valve regurgitation, gestational age at birth and birth weight. Fisher's exact test and odds ratios were used to compare outcomes between groups. RESULTS: A total of 501 pregnancies analyzed resulted in 445 live births, 22 IUFD, 16 terminations and 18 unknown outcomes. Amongst IUFD, 27% had a genetic diagnosis, 50% had an ECA and 27% had severe valve regurgitation. IUFD odds increased threefold with ECA and sevenfold with severe valve regurgitation. IUFD occurred in 1.2% without risk factors. CONCLUSIONS: IUFD in fetuses with CHD is associated with ECA, genetic syndromes and severe valve regurgitation. In absence of these fetal characteristics, the occurrence of IUFD is low, although it remains higher than in fetuses without CHD.