Bi-allelic Mutations in PKD1L1 Are Associated with Laterality Defects in Humans.

Disruption of the establishment of left-right (L-R) asymmetry leads to situs anomalies ranging from situs inversus totalis (SIT) to situs ambiguus (heterotaxy). The genetic causes of laterality defects in humans are highly heterogeneous. Via whole-exome sequencing (WES), we identified homozygous mutations in PKD1L1 from three affected individuals in two unrelated families. PKD1L1 encodes a polycystin-1-like protein and its loss of function is known to cause laterality defects in mouse and medaka fish models. Family 1 had one fetus and one deceased child with heterotaxy and complex congenital heart malformations. WES identified a homozygous splicing mutation, c.6473+2_6473+3delTG, which disrupts the invariant splice donor site in intron 42, in both affected individuals. In the second family, a homozygous c.5072G>C (p.Cys1691Ser) missense mutation was detected in an individual with SIT and congenital heart disease. The p.Cys1691Ser substitution affects a highly conserved cysteine residue and is predicted by molecular modeling to disrupt a disulfide bridge essential for the proper folding of the G protein-coupled receptor proteolytic site (GPS) motif. Damaging effects associated with substitutions of this conserved cysteine residue in the GPS motif have also been reported in other genes, namely GPR56, BAI3, and PKD1 in human and lat-1 in C. elegans, further supporting the likely pathogenicity of p.Cys1691Ser in PKD1L1. The identification of bi-allelic PKD1L1 mutations recapitulates previous findings regarding phenotypic consequences of loss of function of the orthologous genes in mice and medaka fish and further expands our understanding of genetic contributions to laterality defects in humans.

Unintended Live Births Following Second Trimester Pregnancy Termination by Labor Induction.

OBJECTIVE: To determine the incidence of live births following labor induction for pregnancy termination in 16-22-week pregnancies. This information is important in order to be able to adequately counsel a pregnant woman regarding the options for pregnancy termination. STUDY DESIGN: We con- ducted a retrospective study over a 10-year period of all pregnancies that underwent labor induction for pregnan- cy termination between 16 and 22 gestational weeks. The indications for pregnancy termination included fetal anomalies and pregnancy complications. RESULTS: Over the 10-year period 94 patients under- went labor induction for pregnancy termination and were included in the study. There were 14 unintended live births. The gestational age at termination was significantly higher in the unintended live births as com- pared to stillbirths, 21.03±0.65 weeks vs. 20.28±1.15 weeks (p<0.05). In fetuses with trisomy 21 the unintended live births were more common. CONCLUSION: Unintended live birth following labor induction between 16 and 22 weeks' gestation occurs in about 15% of cases; however, the duration of heart beat is <2 hours in the majority of cases. The incidence of live birth was more common in more advanced pregnancies but did not differ by the method of induction or duration of labor.

Elevated delta OD 450 due to transient abnormal myelopoiesis in a Down syndrome fetus with hepatosplenomegaly on ultrasound.

Transient abnormal myelopoiesis (TAM) is a relatively common finding in children with Down syndrome but has also been diagnosed prenatally, most often presenting with fetal hepatosplenomegaly. We report a case of TAM with hepatosplenomegaly found on ultrasound and associated with an increased amniotic fluid Δ OD 450 value. TAM is most commonly transient but can be associated with fatality and therefore should be considered in the differential diagnosis when fetal hepatosplenomegaly is found on ultrasound. Amniocentesis with chromosomal analysis and a Δ OD 450 may aid in diagnosing TAM and predicting the severity of the liver involvement.

Discrepancy in placental echogenicity: a sign of twin anemia polycythemia sequence.

Twin anemia polycythemia sequence (TAPS) is a form of twin-to-twin transfusion syndrome that occurs very rarely and may not be diagnosed until after delivery. The condition leads to increased risk of perinatal morbidity and mortality. We present two cases of monochorionic diamniotic twins, in which the diagnosis of TAPS was made after documenting a discrepancy in the echodensities of the two portions of the placenta. Postnatal hemoglobin differences between the twins confirmed the diagnosis of TAPS. On the basis of these two cases, it appears that the heterogeneity in placental echogenicity is a sign of TAPS and Doppler measurement of middle cerebral artery peak systolic velocity is helpful for early diagnosis and management with timely delivery.

Maternal obesity: Perinatal implications.

Over the previous three decades, the prevalence and growth of overweight and obese status has risen relentlessly in both the general population and pregnant women. This rise is seen in both higher pre-pregnancy body mass index measurements along with excessive weight gain during pregnancy. Maternal obesity has been shown to exacerbate co-morbidities such as insulin resistance, pregnancy induced hypertension, and infectious states in parturient mothers. These changes have been shown to subsequently increase rates of fetal anomalies and affect fetal growth, as well as various aspects of the delivery such as rates of instrumented vaginal deliveries and an increase in delivery by cesarean section. Maternal obesity increases fetal birth weight, influences the delivery room resuscitation of the neonate by increasing the need for respiratory support, and increases the risk of neonatal hypoxic ischemic encephalopathy. This review also looks at recent studies revealing the strong association between maternal and offspring obesity and other long-term neurodevelopmental outcomes of offspring.

Successful use of maternal blood in the management of severe hemolytic disease of the fetus and newborn due to anti-Kp(b).

BACKGROUND: The incidence of hemolytic disease of the fetus and newborn (HDFN) has decreased since the introduction of Rh immunoglobulin prophylaxis in Rh(D)-negative pregnant women. Thus, the relative incidence of rare alloantibody-related HDFN has increased. The lack of available maternally matched red blood cells for transfusion in these cases may create management difficulties. CASE: We report a case of anti-Kp(b) HDFN. Severe fetal anemia required intrauterine transfusion. Difficulty in obtaining Kp(b)-negative blood necessitated using the mother's donated RBCs. CONCLUSION: Severe HDFN with rare antibodies can be managed successfully using maternal blood.

Gestational Diabetes: Overview with Emphasis on Medical Management.

With the rising trend in obesity, the incidence of gestational diabetes mellitus (GDM) and perinatal complications associated with the condition are also on the rise. Since the early 1900s, much knowledge has been gained about the diagnosis, implications, and management of gestational diabetes with improved outcomes for the mother and fetus. Worldwide, there is variation in the definition of GDM, methods to screen for the condition, and management options. The International Association of Diabetes in Pregnancy Study Groups has published recommendations for a one-step approach to screen pregnant women for GDM, in order to develop outcome-based criteria that can be used internationally. However, management of GDM continues to be varied, and currently several options are available for treatment of hyperglycemia during pregnancy. A review of various aspects of GDM is discussed with a focus on the medical management during pregnancy, as practiced in the United States.

Severe lead poisoning caused by use of health supplements presenting as acute abdominal pain during pregnancy.

BACKGROUND: The public and some health care providers regard complementary and alternative medications as safe. There is no scientific basis for that belief, but there is evidence of poor quality control and toxicity of some remedies. CASE: A white pregnant woman presented with diffuse, acute abdominal pain ultimately diagnosed as lead poisoning due to the use of traditional Asian Indian health supplements. CONCLUSION: Use of traditional medicines may extend beyond the ethnic group in which the traditional medicine originated. When symptoms warrant, poisoning with lead or other heavy metals should be considered in the differential diagnosis.

Role of Maternal Thyroid-Stimulating Immunoglobulin in Graves' Disease for Predicting Perinatal Thyroid Dysfunction.

Objective To assess maternal thyroid-stimulating immunoglobulin (TSI) as a predictor of neonatal thyroid hyperthyroidism in pregnancies complicated by Graves' disease. Methods This is a 10-year retrospective study of patients with a history of Graves' disease and elevated TSI activity level defined as 1.3 times the normal. All subjects underwent cordocentesis for ultrasound findings of suspected fetal thyrotoxicosis (fetal tachycardia, oligohydramnios, hydrops, and thyromegaly). Neonatal diagnosis was made based on neonatal thyroid function testing or symptoms. Results Fourteen patients were included in the study, seven with active Graves' disease requiring antithyroid drug ("ATD group") and seven with iatrogenic hypothyroidism on levothyroxine ("levothyroxine group"). Four cases (57%) of neonatal thyrotoxicosis were diagnosed in the levothyroxine group compared with two cases (28%) in the ATD group. The lowest maternal TSI level at which a neonate did not develop hyperthyroidism was 2.6 for the levothyroxine group and 2.5 for the ATD group. The odds ratio of a neonate from the levothyroxine group developing hyperthyroidism compared with one from the ATD group is 3.3 (95% confidence interval: 0.4-30.7). Conclusion For patients with Graves' disease, those with iatrogenic hypothyroidism and TSI > 2.5 times the basal level are at the highest risk for neonatal thyrotoxicosis.

Deciduoma, a Large Intrauterine Mass of Deciduosis.

Deciduosis is the presence of ectopic decidual tissue outside the uterus, pelvic, or abdominal organs usually associated with pregnancy. It usually presents as smaller lesions but can be larger vascular lesions. Typically, these masses are detected incidentally during operative procedures. Our patient was referred at 14 weeks for a large intrauterine mass detected on ultrasound examination that was initially thought to be an acardiac twin. The mass was highly vascularized. However, since the patient was asymptomatic, she strongly desired to continue the pregnancy. The pregnancy was followed closely from 14 to 39 weeks with serial ultrasound examinations. The vascularity was documented to diminish overtime and the mass appeared to convolute as well. Due to the decrease in vascularity of the mass, the patient was allowed spontaneous vaginal delivery at term. Following delivery of the fetus and the placenta, the mass was easily extracted manually without any complications.

Extensive cervical prolapse during labor: a case report.

BACKGROUND: An extensive, irreducible cervical prolapse during pregnancy is a rare condition and can lead to various complications, including severe cervical edema and dystocia in labor. Treatment options are very limited. CASE: A 33-year-old woman with spina bifida and a history of multiple intraabdominal operations and extensive intraperitoneal adhesions was admitted in labor at 36(6/7) weeks' gestation with an irreducible cervical prolapse. The cervical prolapse was reduced by topical application of concentrated magnesium sulfate. CONCLUSION: In active labor, a prolapsed cervix that is enlarged and edematous can be managed with a topical concentrated magnesium solution to prevent cervical dystocia and lacerations.

Impact of maternal obesity on very preterm infants.

OBJECTIVE: Infants born at less than 34 weeks' gestational age are at higher risk for morbidity and mortality. Data are limited on the impact of maternal obesity on the very preterm infant. This study reviewed whether maternal obesity further increases the intensive care needs of very preterm infants of less than 34 weeks' gestation. METHODS: Maternal and neonatal data for live-born singleton births of 23 0/7 to 33 6/7 weeks' gestation delivering in upstate New York were reviewed. BMI categorization followed the National Institutes of Health BMI classification that subdivides obesity into three ascending BMI groups. RESULTS: Records were obtained on 1,224 women, of whom 31.6% were classified with obesity. Despite similar mean gestational age (31 to 31.6 weeks, P = 0.57) and birth weight (1,488 to 1,569 g, P = 0.51) of the infants in the BMI categories, delivery room (DR) resuscitation was more common for infants of women with level III obesity (63.2%, P = 0.04) with a trend toward the continued need for assisted ventilation (54.7%, P = 0.06). CONCLUSIONS: Preterm infants of women with level III obesity were more likely to require DR resuscitation with a trend to continued need for ventilatory support beyond 6 hours of age. This could impact utilization of DR resources at delivering hospitals.

Antenatal course of a fetal intracranial arteriovenous fistula: a case report.

BACKGROUND: Intracranial arteriovenous fistulas (AVFs) are rare in childhood. AVFs in fetuses are very rare and usually not associated with the vein of Galen. These can be solitary or multiple and may be associated with aneurysms or AVMs. The presentation of an AVF depends on the age of the patient, site and size of the fistula, and any accompanying lesion. Neonates can present with cardiac failure and a cranial bruit, infants with cardiomegaly and cardiac failure, children with hydrocephalus, and adolescents and adults with headaches, seizures or intracranial hemorrhage. CASE: Ultrasound and Doppler flow studies revealed a large, vascular lesion in the left cerebral hemisphere that was consistent with an arteriovenous malformation or fistula. The fetus developed cardiomegaly and transient pleural effusion not hydrops. Planned cesarean section without manipulation of thefetal head was performed at 39 weeks. Embolization during the neonatal period completely ceased flow through the arteriovenous fistula. At 28 months of age the child was doing well and showed no developmental or neurologic deficits. CONCLUSION: Prenatal recognition of fistulas and malformations can result in a good outcome as long as thefetus does not develop cardiac failure. Knowledge of the presence of an extensive arteriovenous malformation orfistula prior to birth allows planned delivery and permits the parents and medical team to be prepared for treatment at a tertiary care center.

Prenatal diagnosis and management of fetal anemia secondary to a large chorioangioma.

BACKGROUND: Chorioangiomas are benign vascular tumors of the placenta. Complications occur when their size exceeds 5 cm. CASE: We report the use of peak systolic velocity in the middle cerebral artery, fetal hemoglobin levels in maternal circulation, and maternal serum alpha-fetoprotein levels in the diagnosis and management of fetal anemia in a patient with a large placental chorioangioma. CONCLUSION: Fetal hemoglobin levels in maternal circulation and abrupt elevations of middle cerebral artery peak velocity may be useful in detecting fetal anemia.

Possible maternal inheritance of a common obstructive urinary tract anomaly. Report of a case of a woman with multiple urinary tract infections and two sons with posterior urethral valves.

BACKGROUND: Posterior urethral valves (PUVs) are the most common cause of lower urinary tract obstruction in boys. Several prior reports have described PUV in siblings and twins, often with a variable phenotype. CASE: PUVs were found in two brothers. The first child had developmental delay, while the second had a branchial cleft cyst and an anteriorly rotated right ear. The children's mother had a history of numerous urinary tract infections of unknown etiology. CONCLUSION: Though most cases of PUV appear to be sporadic, there are reports that suggest a partial genetic etiology, as our case suggests.

Cystic fibrosis presenting as fetal anemia. A case report.

BACKGROUND: Cystic fibrosis in the fetus may present with meconium ileus, seen as dilated, hyperechogenic bowel on the prenatal ultrasound examination. Rarely does in utero bowel perforation occur with resulting peritoneal echogenicity, ascites or lack of bowel dilation. CASE: In a case of cystic fibrosis in a fetus, all three findings above occurred, as did anemia, most likely secondary to bleeding from perforated bowel. The anemia was detected following the finding of significantly elevated peak flow velocity in the middle cerebral artery (MCA). CONCLUSION: Fetuses with cystic fibrosis can develop anemia. MCA peak flow velocity measurements are helpful in detecting the anemia.