Right and left ventricular 24-segment sphericity index is abnormal in small-for-gestational-age fetuses.

OBJECTIVE: Fetuses with growth restriction have been reported to have an abnormal sphericity index (SI), which is indicative of the shape of the ventricular chambers of the heart. Our aim was to evaluate the SI for 24 transverse segments distributed from base to apex of the right (RV) and left (LV) ventricles to determine whether, in small-for-gestational-age (SGA) fetuses, the SI is abnormal at locations other than the basal segment. METHODS: We evaluated 30 SGA fetuses between 25 and 37 weeks of gestation. SI was computed for both ventricles by dividing the end-diastolic mid-basal-apical length by each of 24 end-diastolic transverse segmental widths, from base (Segment 1) to apex (Segment 24). For each ventricle, the Z-score and centile for the SI from each of the 24 segments were computed using the mean and SD from published equations. The 24-segment method, defining abnormal SI as values < 10th centile or > 90th centile, was compared with that of using only the basal segment by chi-square analysis to determine the number of fetuses identified with an abnormal SI. RESULTS: In 23 of the 30 (77%) SGA fetuses, at least one of the 24 transverse segments in one or both ventricles had an abnormal SI; in 17% of cases, both ventricles were affected, in 23% of cases only the RV was involved and in 37% of cases only the LV was involved. Compared with the 24-segment model, significantly fewer fetuses with an abnormal SI were identified using only basal Segment 1, from the RV base (58%, 7/12; P < 0.01) or only Segment 12, in the mid portion of the RV (50%, 6/12; P < 0.005). Combining measurements of Segment 1 and Segment 12 from the RV identified 83% of fetuses with at least one abnormal SI and was not significantly different from using the 24-segment model. Similarly, significantly fewer fetuses with an abnormal SI were identified using only LV basal Segment 1 (63%, 10/16; P < 0.006) or only Segment 12, in the mid portion of the LV (75%, 12/16; P < 0.03), when compared with the 24-segment model. Combining measurements of both LV Segment 1 and Segment 12 identified 81% (13/16) of fetuses with an abnormal SI and was not significantly different from using the 24-segment model. CONCLUSION: The 24-segment SI of RV and LV provides a comprehensive method with which to examine the shape of the ventricular chambers and identifies more SGA fetuses with an abnormal SI than are identified using only the basal segment SI. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.

A new method to assess fetal head descent in labor with transperineal ultrasound.

OBJECTIVES: To assess the feasibility and reproducibility of measuring fetal head station and descent during labor using transperineal ultrasound (TPU) imaging, to compare the evaluation of fetal station through digital examinations with concurrent TPU assessments, and to assess its utility in distinguishing patients whose pregnancy will result in spontaneous vaginal delivery from those who will require operative vaginal delivery or Cesarean section for failure to progress. METHODS: TPU and digital examinations were performed in 88 term laboring patients with a singleton fetus in cephalic presentation. Using TPU imaging, head descent was quantified by measuring the angle between the long axis of the pubic symphysis and a line extending from its most inferior portion tangentially to the fetal skull. Intraobserver and interobserver variability were calculated using variance component analysis. TPU imaging was used to measure the angle of head descent during the second stage of labor in 23 of the women. RESULTS: Analysis of replicated measurements on 75 subjects, by the same observer at approximately the same time, yielded an average SD (intraobserver variability) of approximately 2.9 degrees for the measurement of angle of head descent on TPU examination. A separate variance component analysis on a subset of 15 assessments for which measurements were repeated by a second observer, with two to four replicate measurements obtained by each, yielded an interobserver error estimate of 1.24 degrees. A significant linear association was found between clinical digital assessments and measurement of angle of head descent by TPU examination (P < 0.001). An angle of at least 120 degrees measured during the second stage of labor was always associated with subsequent spontaneous vaginal delivery. In six pregnancies ending in Cesarean section the mean angle of descent measured at last TPU examination was only 108 degrees. CONCLUSIONS: The angle of head descent measured by TPU imaging provides an objective, accurate and reproducible means for assessing descent of the fetal head during labor.

Anatomic relationship between the pubic symphysis and ischial spines and its clinical significance in the assessment of fetal head engagement and station during labor.

OBJECTIVE: To develop a geometric model from computed tomographic (CT) images in non-pregnant women that would objectively reflect clinical head station in laboring patients, against which to test the accuracy of digital examinations. METHOD: CT scans were performed in 70 non-pregnant women to determine, using a geometric model, which angle in a mid-sagittal transperineal ultrasound (TPU) image best coincided with the mid-point of a line drawn between the ischial spines (zero station). Using a geometric algorithm, TPU angles were then assigned for other clinical stations (-5 to + 5). Finally, clinical station was assessed by digital examination and simultaneous TPU assessments in 88 laboring patients to see how closely the clinical examination correlated with the station calculated from the above geometric model. RESULTS: The mean angle between the long axis of the symphysis pubis and the mid-point of the line connecting the two ischial spines for the 70 non-pregnant subjects was 99 degrees . The geometric model developed allowed us to build an algorithm to assign a specific set of theoretical angles to each computed station. Relationships between digitally assessed fetal head station, TPU angle for each station, and the geometrical model created with CT data, are reported. Clinical digital assessment of station correlated poorly with computed station, especially at stations below zero, where it could have greater clinical impact. CONCLUSION: The TPU angle of 99 degrees correlated with zero station, and each station above or below this station could be assigned a specific corresponding angle for reference.

Spontaneous factor XI inhibitors. Seven additional cases and a review of the literature.

Circulating anticoagulants are endogenous blood components that inhibit the action of clotting factors. In some inhibitor conditions this inactivation in the function of the hemostatic system may lead to life-threatening hemorrhagic diathesis. Inhibitors directed against factor XI are generally associated with little or no impairment of the hemostatic system. We analyzed all reported cases of spontaneous factor XI inhibitor in the international literature, as well as cases identified at the Yale--New Haven (Conn) Hospital between 1970 and 1980, considering clinical spectrum, diagnosis, and therapy.

In utero gene delivery by intraamniotic injection of a retroviral vector producer cell line in a nonhuman primate model.

In utero gene therapy (IUGT) offers the promise of treating a wide variety of genetic diseases before the development of disease manifestations. The most convenient and potentially easiest method of targeting the fetus is through injection into the amniotic cavity. For long-term correction of genetic defects, retroviral vectors have great potential as a tool for gene therapy strategies. However, retroviral vectors are limited by growth to low titers. In an attempt to increase the amount of vector particles delivered and assess the potential of intraamniotic administration, we injected a retroviral vector producer cell line encoding the lacZ gene into the amniotic fluid of a nonhuman primate model. After birth the infants were analyzed for vector-mediated transduction. Two of four fetuses were successfully transduced, with transgene expression detected in the esophagus, trachea, and stomach. In some sections of tissue, nearly 100% of the cells lining the lumen of these tissues were positive for transduction. Although successful, the limited number of tissues in which transduction was observed led to an in vitro analysis of the effects of amniotic fluid (AF). The presence of amniotic fluid inhibited transduction by 99%. AF affected both the transducing activity of the vector and the health of the packaging cells. The negative effects of AF were gestational age dependent; greater inhibition was observed from AF collected at later stages of pregnancy. The fact that transduction was successful despite these negative effects indicates that this approach is a promising strategy for gene therapy.

Unconjugated cortisol in human amniotic fluid: relationship to lecithin/sphingomyelin ratio.

A specific and thoroughly validated competitive protein binding radioassay has been developed for the measurement of unconjugated cortisol in human amniotic fluid. Cortisol levels rose throughout normal gestation from 8.6 +/- 0.8 ng/ml at less than 20 weeks to 19.8 +/- 1.5 ng/ml at 30-40 weeks. Levels were significantly higher in amniotic fluid samples having mature lecithin/sphingomyelin (L/S) ratios (greater than 2), and good correlation with individual cortisol values was obtained (r = 0.79; P less than 0.001). These results support the hypothesis that cortisol plays a role in fetal lung maturation.

Hormone levels during prostaglandin F 2 infusions for therapeutic abortion.

PIP: This study determines the effect of prostaglandins (PGs) on fetal-placental hormone production or luteal steroidogenesis early in pregnancy by measuring plasma levels of unconjugated estrone, 17-beta estradiol, estriol, progesterone, 17-hydroxyprogesterone, human chorionic gonadotropin (HCG), and human chorionic somatomammotropin (HCS) in 7 healthy women aged 15-30 years receiving PGF2alpha for therapeutic abortion. The patients were 7-20 weeks pregnant and were all from the Clinical Research Unit of the Yale-New Haven Hospital. 5 patients participated in a dose-response tolerance study in which the drug was given over a 12-hour period at predetermined dose levels from 25-200 mcg/minute. The remaining 2 patients received 50 mcg for 12 consecutive hours, and 2 6-hour periods respectively. Heparinized blood samples were collected prior to the beginning of the infusion, at least hourly during the infusion, and also 24 hours after the beginning of the study. Transabdominal and transcervical catheters were used to monitor intrauterine pressures. A definite decline in estradiol levels (from 50-70% of initial levels) was observed during the PGF2alpha infusions. Plasma levels of unconjugated estriol were found to decline earlier and more markedly than the estradiol levels. 17-hydroxyprogesterone was undetectable in all but 1 patient who was 7 weeks pregnant. There were no significant changes in HCG levels in 4 patients until abortion and or curettage was performed. HCS levels gradually declined in 3 patients during the infusion process. This study shows that PGF2alpha does not exert a luteolytic effect in terminating pregnancy from 7-20 weeks gestation, confirming the study of Wiqvist et.al. Further study of the 1st few weeks of gestation should be done before ruling out the possibility of luteolysis in humans.^ieng

Tight metabolic control of overt diabetes in pregnancy.

Seventy-three patients with overt diabetes were followed during pregnancy with tight control of carbohydrate metabolism and frequent measurement of glucose levels. During the last 12 weeks of pregnancy, mean plasma glucose levels averaged 108 mg/dl. Mean fasting plasma glucose levels averaged 98 mg/dl. Of the 73 patients, 77 per cent had mean plasma glucose levels of less than 120 mg/dl. Perinatal mortality rate was 4 per cent; this was corrected to 1.4 per cent when congenital anomalies incompatible with life were removed from consideration. Patients were allowed to go as close to term as possible, with 51 per cent being delivered at or beyond 38 weeks. Only two babies (2.8 per cent) were delivered because of deterioration of fetoplacental function test results. The results of this suggest that tight metabolic control may prevent some of the fetal morbidity associated with overt diabetes in pregnancy.

Echocardiographic studies of the human fetus: prenatal diagnosis of congenital heart disease and cardiac dysrhythmias.

During obstetrical ultrasound examinations, 200 M-mode and 35 real-time two-dimensional echocardiographic studies were performed on 180 fetuses of high-risk pregnancies. Fetal gestational ages ranged from 18 to 41 weeks. M-mode "sweeps" demonstrating mitral- and septal-aortic fibrous continuity were obtained in 115 studies. Paradoxic septal motion in 50 fetuses suggested relarive right ventricular volume loading. Congenital cardiac malformations were accurately diagnosed in a 34-week fetus with pulmonary atresia and hypoplastic right ventricle and in a 28-week fetus with a univentricular heart. Congenital complete atrioventricular block was diagnosed in a 28-week fetus and atrial flutter with variable atrioventricular block was diagnosed in a 38-week fetus. The use of echocardiographic studies to evaluate cardiac structure and rhythm in utero assists in counseling prospective parents and in planning postnatal management for their offspring.

Pregnancy and its outcome in women with and without surgical treatment of congenital heart disease.

In the state of Connecticut, 233 women with congenital heart defects were prospectively followed up through 482 pregnancies that resulted in 372 infants who were examined frequently during their first 3 years of life. Approximately half of the women had undergone cardiac surgery and they were compared with the women without operation. There was no maternal mortality, and no patient had infective endocarditis, brain abscess or a cerebrovascular accident. The proportion of pregnancies resulting in live births did not differ significantly in mothers with and without cardiac surgery; the average live birth rate was 77 percent in all. However, the number and size of live-born infants was much greater in mothers who had become acyanotic as a result of reparative surgery than in the still cyanotic women, whether or not they had had palliative surgery. In cyanotic women, placental size was abnormally large in relation to birth weight, which was abnormally low. When the mothers were classified according to cardiac function, there was a significant difference between the number of infants born alive to mothers in good to excellent status and the number born to mothers in fair to poor condition. The latter had a significant increase in interrupted pregnancies as well as in cardiovascular complications during pregnancy. The total group had a 16.1 percent incidence rate of infants with congenital heart disease. This rate was corrected to 14.2 percent by removal of seven mothers, two with Noonan's syndrome, one with hypertrophic cardiomyopathy and four with a family history of congenital heart defects.

Fetal echocardiography. A tool for evaluation of in utero cardiac arrhythmias and monitoring of in utero therapy: analysis of 71 patients.

Fetal echocardiographic studies were performed in 71 patients referred for evaluation of cardiac rhythm disturbances at 24 to 40 weeks' gestation. After 2-dimensional echocardiographic study of cardiac structure was performed, M-mode echocardiograms were analyzed for measurement of cardiac rate, atrioventricular contraction sequence, atrioventricular valve motion, and duration of postectopic pauses. Arrhythmias were diagnosed in 59 patients. In 34 patients with isolated ectopic beats, the arrhythmia resolved during later pregnancy in 26 or within the first 5 days of life in 8. Six patients had mild sinus bradycardia and 8 had frequent sinus pauses; all 14 had resolution of the arrhythmia during pregnancy. Sustained arrhythmias occurred in 11 patients. Deaths occurred when there was associated fetal congestive heart failure (hydrops fetalis), structural heart disease, or both. M-mode echocardiography diagnosed supraventricular tachycardia in 3 fetuses. The echocardiogram was used thereafter for monitoring transplacental digoxin therapy.

Cytogenetic diagnosis using midtrimester fetal blood samples: application to suspected mosaicism and other diagnostic problems.

Cytogenetic studies on fetal blood cells obtained at 18-25 weeks gestation have provided information for decision making in 25 cases identified as being at high risk of having an abnormal fetus. In particular, in the 21 cases studied to consider the possibility of true mosaicism, confirmation in fetal blood was obtained in three, one of which presented as a pseudomosaic on the original amniotic fluid cell study. Fetal blood was also informative in two cases (one positive and the other negative) in which a diagnosis of the fragile X syndrome was being considered. Furthermore, when high risk pregnancies presented late in gestation (21-24 weeks), these methods allowed for a rapid cytogenetic diagnosis. The procedure has proved useful in most of these cases since the couples involved had indicated that they would probably have terminated the pregnancy without the reassurance of normal fetal lymphocyte studies. Since the technique carries a much higher risk of pregnancy loss than does amniocentesis, its use should only be considered when there are compelling indications.

Management of coarctation of the aorta during pregnancy.

In this report, we shall describe the instantaneous electronic monitoring of the fetal heart rate at 24 weeks' gestation. The mother was undergoing resection of coarctation of the aorta. Because the fetal heart rate reflects by physiological and pharmacologic events, monitoring this rate enabled the anesthesiologists and surgeons to make therapeutic intervention sooner and on a more rational basis.

Grief in the perinatal period.

The loss or threatened loss of an infant in the perinatal period is a tragic event. The practitioner often feels helpless in trying to ease the family's grief. Based on crisis intervention and grief theory, a protocol is suggested for preparing families and presenting them with the tragic news concerning their baby. Suggested interventions for the couple at the time of delivery and a discussion of the needs of other family members are presented. Preparing the family for discharge from the hospital and follow-up are also discussed.

A reevaluation of the value of hCS determination in the management of prolonged pregnancy.

In an initial study at the Yale-New Haven Hospital human chorionic somatomammotropin levels were reported to have predictive significance for the antepartum diagnosis of the postmaturity syndrome. Expanded data from the same institution do not support the original findings.

Intrauterine transfusion utilizing ultrasound.

Thirty-seven intrauterine transfusions were performed on 17 severely Rh-sensitized women utilizing a technique entirely dependent upon ultrasound for needle insertion. The neonatal survival rate was 71%; 57% (4 of 7) of the hydropic fetuses and 80% (8 of 10) of those with no antenatal evidence of ascites survived. Twenty-five percent of the 12 neonatal survivors received their initial transfusion at 26.5 weeks or earlier. These results are comparable to the best of those in series relying on x-ray or fluoroscopy techniques for performing the procedure. Intrauterine transfusion continues to play an essential therapeutic role in the management of the severely affected erythroblastotic fetus. It is recommended that techniques relying on ultrasound be utilized in preference to those using x-ray to reduce radiation exposure in utero.

Use of hPL in the diagnosis of intrauterine growth retardation.

Measurements were taken of human placental lactogen (hPL) in 111 pregnant patients with subnormal uterine growth or complications often associated with IUGR and assessed as a measurement of growth retardation. The results of this study are presented here.

Ultrasound assessment of fetal intestinal development in the evaluation of gestational age.

A prospective ultrasound study was conducted in 289 uncomplicated pregnancies with gestational ages ranging from 16-40 weeks. Biometric measurements obtained included biparietal diameter (BPD), head and abdominal circumferences, measurements of long bones, and maximal transverse colon diameter. The pattern of small intestinal peristalsis, presence of colonic haustra, and progressive changes in the colon's intraluminal echogenicity were also evaluated. A high degree of correlation was found between gestational age and transverse colon diameter (in millimeters) (R2 = 0.859; P less than .0001), increasing colonic intraluminal echogenicity (R2 = 0.741; P less than .0001), and the appearance and progressive increase in small intestinal peristalsis (R2 = 0.726; P less than .0001). Colonic haustra were visualized in 87.5% after 30 weeks (specificity 100%, sensitivity 77.4%). A high degree of correlation with gestational age was also found if echogenicity and peristalsis were combined (R2 = 0.873; P less than .0001), and proved superior to that found with measurement of BPD (R2 = 0.655; P less than .0001) or femur length (R2 = 0.805; P less than .0001) after 28 weeks. Observations of progressive changes in small intestinal peristalsis and colonic intraluminal echogenicity, together with the development of colonic haustra and progressive increase in transverse colon diameter, allow one to estimate gestational age independent of standard biometry. This approach has particular utility in the third trimester, when sonographic estimation of gestational age is least accurate.

Fetal biparietal diameter as a predictor of a mature lecithin/sphingomyelin ratio.

The records of 148 patients who had undergone simultaneous determination of fetal biparietal diameter and lecithin sphingomyelin ratio were reviewed. The results of the lecithin sphingomyelin determination could not be predicted with an acceptable degree of accuracy utilizing the fetal biparietal diameter. When patients were grouped by maternal disease, no significant difference between diabetic and control patients was noted. Other subgroups were too small to allow a valid statistical comparison.

Endotoxin stimulates prostaglandin E2 production by human amnion.

The studies presented in this report were designed to evaluate whether bacterial endotoxin alters the rate of biosynthesis of prostaglandin E2 (PGE2) by human amnion. Amnion cells were established in primary monolayer culture from women undergoing elective cesarean sections. Endotoxin from Escherichia coli and Salmonella typhosa were incubated with amnion cells for 16 hours, and radioimmunoassay was used to measure PGE2 released into the media. Bacterial endotoxin demonstrated a concentration-dependent stimulatory effect on the rate of PGE2 synthesis by amnion cells. These observations suggest a mechanism for the onset of labor associated with intra-amniotic infection.