Clinical and Genetic Findings in a Series of Eight Families with Arthrogryposis.

The term "arthrogryposis" is used to indicate multiple congenital contractures affecting two or more areas of the body. Arthrogryposis is the consequence of an impairment of embryofetal neuromuscular function and development. The causes of arthrogryposis are multiple, and in newborns, it is difficult to predict the molecular defect as well as the clinical evolution just based on clinical findings. We studied a consecutive series of 13 participants who had amyoplasia, distal arthrogryposis (DA), or syndromic forms of arthrogryposis with normal intellectual development and other motor abilities. The underlying pathogenic variants were identified in 11 out of 13 participants. Correlating the genotype with the clinical features indicated that prenatal findings were specific for DA; this was helpful to identify familial cases, but features were non-specific for the involved gene. Perinatal clinical findings were similar among the participants, except for amyoplasia. Dilatation of the aortic root led to the diagnosis of Loeys-Dietz syndrome (LDS) in one case. The phenotype of DA type 5D (DA5D) and Escobar syndrome became more characteristic at later ages due to more pronounced pterygia. Follow-up indicated that DA type 1 (DA1)/DA type 2B (DA2B) spectrum and LDS had a more favorable course than the other forms. Hand clenching and talipes equinovarus/rocker bottom foot showed an improvement in all participants, and adducted thumb resolved in all forms except in amyoplasia. The combination of clinical evaluation with Next Generation Sequencing (NGS) analysis in the newborn may allow for an early diagnosis and, particularly in the DAs, suggests a favorable prognosis.

Sonographic fetal weight estimation in normal and overweight/obese healthy term pregnant women by gestation-adjusted projection (GAP) method.

PURPOSE: The objective of this study is to assess the ultrasound accuracy in fetal weight estimation related to the time distance between the actual weight recorded at delivery and the period of sonography among normal and overweight/obese pregnant women within 3 weeks prior birth at term. METHODS: Four-hundred and ninety patients with healthy pregnancy were studied in a cohort study. The absolute percent error in estimation was achieved by gestation-adjusted projection method from Hadlock model for weight calculation as measure of accuracy. The mean percentage error variation over the weeks was correlated to maternal body mass index (BMI, Kg/m(2)) at ultrasound. The relationship between BMI and ultrasound performance was assessed by linear regression. RESULTS: The overall proportion of supposed sonographic estimated fetal weight at birth within ±10 % of the birth weight significantly declines over the weeks (P = .016). The trend toward a progressive deterioration in ultrasound accuracy is not statistically significant for normal weight women (P = .272) but it is for over-weight/obese (P = .044). On univariate analysis, the absolute percent error and absolute error are positively related to BMI. CONCLUSIONS: Accuracy is related to the week at ultrasound scan with a gradual deterioration over the time and it worsens with increasing distance in days between the date of ultrasounds and delivery. The deterioration is greater for BMI ≥ 25.

Intrapartum fetal heart rate monitoring: evaluation of a standardized system of interpretation for prediction of metabolic acidosis at delivery and neonatal neurological morbidity.

OBJECTIVE: To assess the ability of the intrapartum fetal heart rate interpretation system developed in 2008 by the National Institute of Child Health and Human Development (NICHD) to predict fetal metabolic acidosis at delivery and neonatal neurological morbidity. METHODS: We analyzed the intrapartum fetal heart rate tracings of 314 singleton fetuses at ≥ 37 weeks using the NICHD three-tier system of interpretation: Category I (normal), Category II (indeterminate) and Category III (abnormal). Category II was further divided into Category IIA, with moderate fetal heart rate variability or accelerations, and Category IIB, with minimal/absent fetal heart rate variability and no accelerations. The presence and duration of the different patterns were compared with several clinical neonatal outcomes and with umbilical artery acid-base balance at birth. RESULTS: The mean values of pH and base excess decreased proportionally as tracings worsened (p < 0.001). The duration of at least 30 min for Category III tracings was highly predictive of a pH <7.00 and a base excess ≤-12 mmol/L. The same was true for the duration of Category IIB tracings that lasted for at least 50 min. CONCLUSIONS: Our study demonstrates that the interpretation of fetal heart rate tracings based on a strictly standardized system is closely associated with umbilical artery acid-base status at delivery.

Retrospective analysis on the efficacy of corticosteroid prophylaxis prior to elective caesarean section to reduce neonatal respiratory complications at term of pregnancy: review of literature.

PURPOSE: Our purpose was to conduct a systematic review of the literature to determine whether synthetic pharmaceutical glucocorticoids (betamethasone and dexamethasone) are safe as well as effective in reducing neonatal respiratory morbidity at term of pregnancy prior to elective caesarean section. The overall incidence of respiratory disorders is estimated at 2.8%, and the main risk factors are gestational age and mode of delivery. Newborns delivered by elective caesarean section (CS after 37 weeks) are more susceptible to serious respiratory complications than babies born by vaginal delivery. Neonatal respiratory morbidity at term of pregnancy is low but not negligible. Further, it is increasing due to a drastic decline in trial of labour in those pregnant women who underwent a caesarean section in the past. Because prophylaxis is inexpensive, easy to administer, and safe, other studies should be conducted to confirm its effectiveness. METHODS: We conducted a systematic review of literature since 1965 on the discovery of action mechanisms, pharmaceutical development, proper dosage, and potential side effects of corticosteroids on the mother and offspring to extrapolate their efficacy as no clinical trial has directly demonstrated it. RESULTS: We extrapolated no negative effects on mother and foetus behaviour. CONCLUSIONS: Human studies suggest that corticosteroid administration may become a proper clinical indication prior to caesarean section in the reduction of neonatal respiratory problems.

A case report of Sheehan's syndrome with acute onset, hyponatremia and severe anemia.

Sheehan's syndrome is a well-known cause of panhypopituitarism secondary to pituitary apoplexy, that generally occurs after an intra- or postpartum bleeding episode characterized by severe hypertension or hemorrhagic shock. The diagnosis can be difficult and is often formulated after some years from the syndrome occurrence. We report the case of a woman with an early diagnosis of early-onset Sheehan's syndrome associated with severe hyponatremia following dystocic childbirth complicated by postpartum hemorrhage.

Reduction of the risk of cervical intraepithelial neoplasia in HIV-infected women treated with highly active antiretroviral therapy.

BACKGROUND AND AIM OF THE WORK: The purpose of our study was to determine whether highly active antiretroviral therapy (HAART) reduces the onset of cervical intraepithelial neoplasia (CIN) in HIV-positive women. METHODS: The study was designed to assess CIN incidence in a cohort of 101 HIV-positive women and to evaluate its relationship with ongoing antiretroviral therapy. The patients were screened through a combined Pap smear and colposcopic examination on a yearly basis. If any abnormalities were reported, the patients underwent targeted biopsy with histological confirmation of the diagnosis. RESULTS: During the follow-up period, 38 patients (37.6%) developed histologically verified CIN, including low-grade CIN in seven patients (6.9%) and high-grade CIN in 31 patients (30.4%). Over the study period, 43 patients (42.6%) were treated with HAART for at least 6 months, the average duration of treatment being 37 months. Analysis of HAART efficacy in preventing CIN onset, determined by the Cox regression model with a time-dependent covariate adjusted for the CD4 level at the first visit, showed that HAART significantly reduced the risk of developing CIN (hazard ratio, 0.3; p = 0.004). CONCLUSION: HIV-positive patients present a high incidence of CIN and of high-grade CIN in particular. HAART exhibits a protective action against the onset of cervical lesions.

Second-trimester maternal serum alpha-fetoprotein elevation and its association with adverse maternal/fetal outcome: ten years experience.

BACKGROUND: Alpha-fetoprotein (AFP) is the major serum protein in the embryonic stage and in the early fetal stage. The aim of this study was to determine any possible association between an "unexplained" elevation of maternal serum alpha-fetoprotein (MSAFP) levels in the second trimester of pregnancy and adverse maternal/fetal outcome. METHODS: A retrospective cohort study, was carried out in the University of Parma, by reviewing all triple tests that had been found positive for neural tube defect screening, showing an "unexplained" MSAFP elevation (> or =2.5 multiples of the median [MoM]), which could not be ascribed to any apparent reason. These results were compared with those of negative controls (MSAFP <2.5 MoM) in order to evaluate the course and outcome of pregnancy. Statistical analysis was performed by chi-square test, Fisher's exact test, Student's t-test, and odds ratio calculation. RESULTS: We reviewed 16,747 tests: 143 tests with high MSAFP levels were found, including 105 data already available. Out of them 21 tests were excluded from the study because of the presence of fetal malformations, chromosomal diseases, or late miscarriage. Among the 84 remaining pregnancies, 43 were significantly associated with increased rates of pregnancy pathology compared with the control group of 199 patients, with 25 complicated pregnancies. In addition, high MSAFP levels were correlated with a less favorable neonatal outcome in terms of low birth weight, Apgar score, and transfer to a neonatal intensive care unit. CONCLUSIONS: Unexplained elevation of MSAFP levels in the second trimester of pregnancy is associated with an adverse maternal/fetal outcome, possibly suggesting the need for a more strict management of pregnancies.

Integrated monitoring of fetal growth restriction by computerized cardiotocography and Doppler flow velocimetry.

OBJECTIVE: To investigate the correlations between Doppler flow velocimetry and computerized cardiotocography (cCTG) in fetal growth restriction. STUDY DESIGN: Fifty growth-restricted foetuses with abdominal circumference below the 10th percentile and no major abnormalities were studied. A total of 186 cCTG tracings (at least two per patient) analysed using the HP2CTG system were compared with the corresponding umbilical artery pulsatility index (PI), the PI ratio of umbilical artery to middle cerebral artery, and the ductus venosus systolic/atrial ratio. RESULTS: Worsening in umbilical artery Doppler velocimetry parameters was associated with a significant reduction of short- and long-term variability indices and accelerations. When end-diastolic umbilical artery flow was preserved, a reversed ratio between umbilical artery and middle cerebral artery PIs was not correlated with a worsening of cCTG parameters; in the presence of umbilical artery absent or reversed flow, ductus venosus Doppler velocimetry abnormalities were correlated with a significant reduction of variability. When end-diastolic umbilical artery flow was preserved, there was a progressive increase in variability indices and accelerations with advancing gestational age. In the more compromised fetuses this "maturation" process of cCTG patterns was not found. CONCLUSION: There is a strict correlation between Doppler velocimetry abnormalities and cCTG parameter deterioration, in particular between ductus venosus and variability.

Meconium-stained amniotic fluid and fetal oxygen saturation measured by pulse oximetry during labour.

BACKGROUND AND AIM OF THE WORK: The high false-positive rate of electronic fetal heart rate monitoring is the major obstacle to the correct prediction and diagnosis of intrapartum fetal distress. Fetal pulse oximetry is a safe and accurate indicator of fetal oxygenation. The aim of this study was to evaluate the clinical use of this technique for the diagnosis of fetal hypoxia and for prevention of fetal metabolic acidosis and asphyxia during labour, in the presence of meconium-stained amniotic fluid with or without abnormal fetal heart rate patterns, using a threshold value of 30% oxygen saturation. METHODS: Fetal blood oxygen saturation levels (SpO2) of 58 term fetuses with non-reassuring fetal status were measured during labour by fetal pulse oximetry. In 35 cases the amniotic fluid was stained with meconium at onset of labour. Mean SpO2 levels at the different stages of labour were matched against fetal heart rate patterns, the amniotic fluid status, and neonatal outcome. The 35 cases with meconium-stained amniotic fluid were compared with a control group of 28 pregnant women at term who had meconium-stained amniotic fluid during labour but were not monitored by pulse oximetry. RESULTS: When the fetal heart rate tracings were abnormal, mean SpO2values were significantly lower in the first 30 minutes of application and in the last 30 minutes of labour or before Cesarean section. Meconium-stained amniotic fluid was associated with lower SpO2values only when fetal heart monitoring showed a "non-reassuring" pattern. No cases were observed with severe neonatal acidosis, with Apgar score <7 at 5 minutes, or with other adverse neonatal events. In patients with meconium-stained amniotic fluid, neonatal outcomes were better in the group monitored by pulse oximetry versus the control group, although the differences were not statistically significant. CONCLUSIONS: Continued monitoring of fetal oxygen saturation combined with fetal heart rate monitoring may improve accuracy in the evaluation of fetal well-being. As a result, labour could be more safely managed in pregnancies with non-reassuring fetal status as measured by conventional methods, especially in the presence of meconium-stained amniotic fluid.