Expanded prenatal phenotype of ALG12-associated congenital disorder of glycosylation including bilateral multicystic kidneys.

Congenital disorders of glycosylation (CDG) are a group of rare autosomal recessive genetic disorders caused by pathogenic variants in genes coding for N-glycosylated glycoproteins, which play a role in folding, degrading, and transport of glycoproteins in their pathway. ALG12-CDG specifically is caused by biallelic pathogenic variants in ALG12. Currently reported features of ALG12-CDG include: developmental delay, hypotonia, failure to thrive and/or short stature, brain anomalies, recurrent infections, hypogammaglobulinemia, coagulation abnormalities, and genitourinary abnormalities. In addition, skeletal abnormalities resembling a skeletal dysplasia including shortened long bones and talipes equinovarus have been seen in more severe neonatal presentation of this disorder. We report on a case expanding the phenotype of ALG12-CDG to include bilateral, multicystic kidneys in a neonatal demise identified with homozygous pathogenic variants in the ALG12 gene at c.1001del (p.N334Tfs*15) through clinical trio exome sequencing.

Left-Handedness in Obstetrics and Gynecology: A Nationwide Survey of U.S. Trainees and Educators.

OBJECTIVE: This study aimed to evaluate the views and influence of left-handedness among obstetrics and gynecology (OBGYN) trainees and educators and to identify perceived obstacles in training by left-handed (LH) trainees. STUDY DESIGN: An online survey was sent to the U.S. Obstetrics and Gynecology training programs. All participants were asked questions on hand preference for various medical and nonmedical activities, as well as on demographics. Participant responses to handedness and their role as a learner or educator directed them toward further questions. Trainees were surveyed on their experience and outlook as a LH physician in OBGYN. Educators were surveyed on their experience and attitudes in working with LH trainees. LH educators were also surveyed on their experience as a LH physician, similar to the LH trainees. Chi-square or Fisher's exact analysis was used as appropriate, with p-value <0.05 considered statistically significant. RESULTS: Responses were received from 21 training programs, totaling 304 individuals. Participants included 205 learners (156 right handed and 49 left handed), and 99 faculty (82 right handed and 17 left handed). A lack of LH surgical instrument availability (93.6%) and difficulty using right-handed (RH) instruments (83%) were notable obstacles reported by LH learners. The majority of LH learners (57.4%) did not consider their handedness to be disadvantageous but did note added difficulty when training under RH mentors when compared with training under LH mentors (66%). In contrast to LH educators, RH educators endorsed added difficulty in instructing operative procedures to LH learners (32.1 vs. 13.3%, p = 0.012). CONCLUSION: LH trainees face unique challenges during their OBGYN training. Educators would benefit from guidance on how best to manage these trainees. Educators should work to adapt surgical and procedural techniques to accommodate LH trainees. KEY POINTS: · LH learners reported more difficulty in training under RH mentors.. · RH mentors reported increased difficulty in educating LH trainees.. · Neither trainees nor educators considered being LH a significant disadvantage..

Diagnosis and Management of Acute Pancreatitis in Pregnancy.

Acute pancreatitis is rare in pregnancy; however, the associated morbidity and mortality make prompt diagnosis and appropriate management essential. 1,2 Although most cases are mild and improve with limited interventions, severe cases require a multidisciplinary approach in a critical care setting. The main principles of management include identification of an etiology to guide therapy, fluid resuscitation, electrolyte repletion, early nutritional support, and pain management. Antibiotics are not indicated for prophylaxis and should be reserved for cases with a suspected infectious process. Surgical management is indicated in select cases. Management in pregnant patients has few differences which are outlined below.

Maternal Nutrition and Fetal/Infant Development.

Nutrition in pregnant mothers has long been known to be an important determinant of fetal/maternal outcomes. In general, the typical American diet shows opportunities for improvement. The intake of fruits, vegetables, whole grains, and fiber may be below recommended levels, but the relative proportion of sodium, fats, and carbohydrates seems high. In this review, we present current evidence on how the fetal/neonatal outcomes may be altered by maternal nutrition at the time of conception, fetal nutrition in utero, contribution of maternal dietary factors in fetal outcomes, weight gain during pregnancy, diabetes during pregnancy, fetal growth restriction (FGR), maternal nutritional status during later pregnancy, and pregnancy in adolescent mothers.

Clinical Stratification of Pregnant COVID-19 Patients based on Severity: A Single Academic Center Experience.

OBJECTIVE: This study aimed to describe baseline characteristics of a cohort of pregnant women infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and determine if these correlate with disease severity and perinatal outcomes. STUDY DESIGN: This was a retrospective cohort trial conducted at the University of Texas Medical Branch Galveston, Texas. All pregnant women presented to our medical center, who were screened and tested positive for SARS-CoV-2 virus, were included. We stratified our study population in three groups: asymptomatic, symptomatic not requiring oxygen therapy, and patients requiring oxygen support to maintain oxygen saturation >94%. Relevant population characteristics, laboratory data, and maternal and neonatal outcomes were abstracted. A p-value <0.05 was considered statistically significant. RESULTS: Between March and July 2020, 91 women tested positive for SARS-CoV-2 upon admission to our labor and delivery unit. Among these, 61.5% were asymptomatic, 34.1% were symptomatic, and 4.4% required oxygen support. Our population was mainly Hispanic (80.2%), multiparous (76.9%), obese (70.3%), and with a median age of 27 years. Median gestational age at symptom onset or diagnosis was 36 weeks. Significant differences were found between gestational age and disease severity. Maternal characteristics including age, body mass index (BMI), and presence of comorbid conditions did not appear to influence severity of SARS-CoV-2 infection. Significant laboratory findings associated with increasing disease severity included decreasing hemoglobin and white blood cell count, lymphopenia, and increasing levels of inflammatory markers including CRP, ferritin, and procalcitonin. Maternal and neonatal outcomes did not differ among groups. No SARS-CoV-2 was detected by polymerase chain reaction testing in neonates of mothers with COVID-19. CONCLUSION: Pregnant patients with COVID-19 infection are predominantly asymptomatic. Patients appear to be at increased risk for more severe infection requiring oxygen support later in pregnancy. KEY POINTS: · The majority of pregnant patients with COVID-19 are asymptomatic and <1 in 20 require oxygen support.. · Women in the later stages of pregnancy may be at increased risk for severe infection.. · Anemia, leukopenia, CRP, ferritin, and procalcitonin are associated with increasing severity..

Lyophilization of human amniotic fluid is feasible without affecting biological activity.

BACKGROUND: Fetal swallowing of human amniotic fluid (hAF) containing trophic factors (TFs) promotes gastrointestinal tract (GIT) development. Preterm birth interrupts hAF swallowing, which may increase the risk of necrotizing enterocolitis (NEC). Postnatally, it is difficult to replicate fetal swallowing of hAF due to volume. We aimed to evaluate whether hAF lyophilization is feasible and its effect on hAF-borne TFs. METHODS: We collected hAF (n = 16) from uncomplicated pregnancies. hAF was divided into three groups: unprocessed control (C), concentration by microfiltration (F), and by dialysis and lyophilization (L). EGF, HGF, GM-CSF, and TGF-α were measured in each group by multiplex assay. Bioavailability of TFs was measured by proliferation and LPS-induced IL-8 production by intestinal epithelial cells FHs74. RESULTS: After dialysis/lyophilization, GM-CSF and TGF-α were preserved with partial loss of EGF and HGF. hAF increased cell proliferation and reduced LPS-induced IL-8 production compared to medium alone. Compared to control, dialysis/lyophilization and filtration of hAF increased FHs74 cell proliferation (p < 0.001) and decreased LPS-induced IL-8 production (p < 0.01). CONCLUSIONS: Lyophilization and filtration of hAF is feasible with partial loss of TFs but maintains and even improves bioavailability of TFs measured by proliferation and LPS-induced IL-8 production by FHs74.

Medicolegal Review of Methotrexate Administration to Viable Intrauterine Pregnancies.

Objective: To examine 3 legal cases in which physicians prescribed methotrexate to women with a viable intrauterine pregnancy, presumed to be ectopic, resulting in adverse fetal outcomes. Study Design: We conducted an electronic literature search for legal cases using the keywords "methotrexate" and "pregnancy" in the LexisNexis legal research engine as well as an Internet-wide search using the additional keyword "verdict." We manually searched the resultant list of identified cases and categorized the studies identified in the search by verdict, award amount, and outcome of the embryo exposed to methotrexate. Results: The monetary awards are typically greater when the embryo exposed to methotrexate lives and requires continuous medical and custodial care as compared to when the fetus dies in utero or shortly after birth. Conclusion: Physicians who, with all good intentions, prescribe methotrexate to women with a viable pregnancy, presumed to be ectopic, could find them-selves liable for an adverse fetal outcome. For the benefit of patients, their unborn offspring, and the liability exposure of the physician, it is important to be very cautious when prescribing methotrexate.

The Development of a Critical Care Resident Research Curriculum: A Needs Assessment.

Background. Conducting research is expected from many clinicians' professional profile, yet many do not have advanced research degrees. Research training during residency is variable amongst institutions and research education needs of trainees are not well understood. Objective. To understand needs of critical care trainees regarding research education. Methods. Canadian critical care trainees, new critical care faculty, program directors, and research coordinators were surveyed regarding research training, research expectations, and support within their programs. Results. Critical care trainees and junior faculty members highlighted many gaps in research knowledge and skills. In contrast, critical care program directors felt that trainees were prepared to undertake research careers. Major differences in opinion amongst program directors and other respondent groups exist regarding preparation for designing a study, navigating research ethics board applications, and managing a research budget. Conclusion. We demonstrated that Canadian critical care trainees and junior faculty reported gaps in knowledge in all areas of research. There was disagreement amongst trainees, junior faculty, research coordinators, and program directors regarding learning needs. Results from this needs assessment will be used to help redesign the education program of the Canadian Critical Care Trials Group to complement local research training offered for critical care trainees.

The pattern of indeterminate human immunodeficiency virus test and follow-up evaluation in pregnant women.

We studied the pattern of indeterminate HIV serological tests among pregnant women with follow-up testing in the postpartum period. Medical records of pregnant women were reviewed over a 2-year period. Of 16,596 pregnant women, 127 (0.8%) had positive HIV enzyme-linked immunoassay (ELISA) result. With Western blot (WB) test, 54 (0.33%) were positive, 43 (0.26%) were negative, and 30 (0.18%) were indeterminate. One of the 30 women (3.3%) with indeterminate WB converted to positive WB during pregnancy. White and black women were more likely to have an unconfirmed positive ELISA (indeterminate or negative WB) than Hispanics ( P = 0.021). The positive WB rate for black women was significantly higher ( P < 0.001) than other racial/ethnic groups. The postpartum follow-up testing of 14 women with indeterminate WB varied between 4 to 20 weeks; 16 did not have any postpartum follow-up test. The common bands in indeterminate WB were P24, P18, and nonviral proteins. The pattern of indeterminate WB result and its follow-up was variable during pregnancy and postpartum period. There is a need for development of national standards of care for indeterminate WB mothers and their infants in the postpartum period. Additional studies are needed to determine the cause of indeterminate tests, reducing their occurrence in the testing process, and the optimum time for testing in the postpartum period.

Sequential one-pot combination of multi-component and multi-catalysis cascade reactions: an emerging technology in organic synthesis.

Creating sequential one-pot combinations of multi-component reactions (MCRs) and multi-catalysis cascade (MCC) reactions is a challenging task that has already emerged as a new technology in synthetic organic chemistry. Through one-pot sequential combination of MCRs/MCC reactions, the chemical products (fine chemicals, agrochemicals and pharmaceuticals) that add value to our lives can be produced with less waste and greater economic benefits. Within this Emerging Area, we describe our recent developments and designs for sequential one-pot MCRs/MCC reactions to facilitate their realization as biomimetics in organic chemistry.

Preterm premature rupture of membranes: clinical outcomes of late-preterm infants.

OBJECTIVE: To determine gestational age-specific neonatal outcomes of late preterm infants delivered as a consequence of premature rupture of membranes (PROM). METHODS: Retrospective cohort study of infants born to women delivered electively due to preterm PROM between 34(0/7) and 36(6/7) weeks of gestation. Neonatal outcomes were compared between those delivered at 34(0/7) to 34( 6/7) weeks, at 35(0/7) to 35(6/7) weeks, and at 36( 0/7) to 36(6/7) weeks. RESULTS: 192 infants were identified. The 34(0/7) to 34(6/7) week infants had significantly higher neonatal intensive care admission rate (72.5%) compared to those at 35( 0/7) to 35(6/7) weeks (22.8%) and at 36 to 36(6/7) weeks (17.8%) (P < .05). Neonatal respiratory distress syndrome was significantly higher at 34(0/7) to 34(6/7) weeks (35.4%) compared with 35(0/7) to 35(6/7) week and 36(0/7) to 36( 6/7) week infants (10.5% and 4.1%; P < .05). The longest hospitalization occurred in the 34(0/7) to 34(6/7) week infants (248.5 +/- 20.0 hours). CONCLUSION: Substantial short-term morbidity occurred in late preterm infants. The greatest number of complications affected infants born at 34(0/7) to 34(6/7) weeks.

Progesterone, but not 17-alpha-hydroxyprogesterone caproate, inhibits human myometrial contractions.

OBJECTIVE: The aim was to determine whether progesterone (P4) or 17-alpha-hydroxyprogesterone caproate (17P) directly inhibit human uterine contractility in vitro and thereby clarify their mechanisms of action. STUDY DESIGN: Myometrial tissues were suspended in organ chambers and exposed for 2 to 20 hours to varying concentrations of P4 or 17P or solvent. Contractile activity was registered, stored, and analyzed. Dose response curves were then generated for P4 or 17P at various times. RESULTS: P4 significantly inhibited spontaneous contractility dose dependently. The inhibition was not blocked by RU486 but was reversible after washing. Surprisingly, 17P dose dependently stimulated contractility. HPLC and GC-MS methods were used to determine the detectable concentrations of progestins in the baths. CONCLUSION: P4, at concentrations equivalent to those present in the placenta and uterus, inhibit spontaneous myometrial contractility in vitro by nongenomic mechanisms.

Glyburide metabolism by placentas of healthy and gestational diabetics.

The aim of this investigation was to determine the metabolism of glyburide (GL) by microsomes prepared from placentas obtained from uncomplicated pregnancies (UP), women with gestational diabetics (GD) on a diabetic diet, and those on a diet and GL. Term placentas were obtained from UP and GD. Crude microsomal fractions were prepared by differential centrifugation and stored at -80 degrees C. The activity of the microsomes in metabolizing glyburide to the trans-4-hydroxycyclohexyl glyburide (THCGL) and cis-3-hydroxycyclohexyl glyburide (CHCGL) was determined and quantified using high-performance liquid chromatography-mass spectrometer (HPLC-MS). The activity of the placental microsomes varied widely between individual placentas in each group. The median values (pmol.mg (-1) P.min (-1)) for the rates of THCGL formation were 0.34, 0.3, and 0.23 for placentas of UP, GD on diet, and GD on GL and a diet, respectively. The median values for CHCGL formation were 0.13 for UP, 0.11 for GD on a diet, and 0.10 (pmol.mg (-1) P.min (-1)) for GD on GL and a diet. A pool of individual microsomal fractions from each group was prepared and its activity revealed the following: greater formation of THCGL in the UP (0.36 +/- 0.10) than GD (0.22 +/- 0.03) ( P = 0.058 for GD on a diet, 0.04 for GD on GL). There was greater formation of CHCGL in UP (0.26 +/- 0.04) than GD (0.12 +/- 0.003) ( P < 0.006). There was no difference in GD on a diet and GD on GL plus diet. We concluded that the apparent differences in the formation of metabolites may be statistically significant, but it is unlikely to be of physiological importance, given the sample size and other experimental factors. Therefore, a more comprehensive investigation is underway.

The validity of cervical dilation as an indication of true labor between 32 and 36 weeks 6 days of gestation.

OBJECTIVE: Cervical dilation with regular contraction traditionally has been used to differentiate between true and false labor. This diagnostic criterion has not been tested as most patients receive tocolytics. Our objective was to determine the time from admission to delivery in women with preterm contractions and advanced cervical dilation without tocolytics. STUDY DESIGN: We reviewed the records of patients with preterm labor on the basis of regular contractions and cervical dilation > or = 3 cm between 32 and 36 weeks 6 days of gestation. Chi-square analysis was performed for delivery at > 1 week. RESULTS: In the records, 68.8% of the patients remained pregnant at > 1 week without tocolysis. Between 32 and 34 weeks of gestation, the use of tocolysis did not help to prolong pregnancy > 1 week (81% vs 88%; alpha = .05; power = 0.65). CONCLUSION: Cervical dilation with preterm contraction cannot be used as an indication of true labor. More accurate methods to diagnose true preterm labor and direct management decisions are needed.

Hepatitis C in pregnancy.

Hepatitis C is the most common cause of chronic liver disease and liver transplantation, with 25,000 cases reported in the United States per year. By blood product screening, transfusion-related viral transmission has been virtually eliminated, and maternal fetal transmission is now one of the most important modes of transmission. Hepatitis C virus (HCV) infection is blood borne but only 25% of the infected pregnant women indicate a history of blood products transfusion or intravenous drug use. HCV transmission is 2- to 4-fold higher in women coinfected with HIV. Although cesarean delivery has not been shown to decrease perinatal transmission, it may have benefits in women with viremia at the time of delivery. During pregnancy, treatment of HCV is contraindicated, even though perinatal transmission is associated with a higher incidence of chronic liver disease. This review gives an update on the disease agent, risk factors, modes of transmission, diagnosis, treatment modalities, and perinatal issues that require further evaluation.