Fatal hepatitis E viral infection in pregnant women in Ghana: a case series

ABSTRACT: BACKGROUND: Viral infections during pregnancy can pose serious threats to mother and fetus from the time of conception to the time of delivery. These lead to congenital defects, spontaneous abortion and even death. The definitive diagnosis and management of pregnancy-related viral infections may be challenging especially in less resourced countries. CASE PRESENTATION: We present clinical and laboratory responses to the diagnosis and management of three cases of fulminant hepatitis secondary to Hepatitis E viral infection in pregnancy.Case 1 was a 31-year-old Ghanaian woman who presented with a week's history of passing dark urine as well as yellowish discoloration of the eyes. She subsequently developed fulminant hepatitis secondary to Hepatitis E viral infection, spontaneously aborted at 24 weeks of gestation and later died.Case 2 was also a 31-year-old Ghanaian woman who was admitted with a four-day history of jaundice. She had low grade fever, but no history of abdominal pain, haematuria, pale stool or pruritus. She next developed fulminant hepatitis secondary to Hepatitis E viral infection. However, she did not miscarry but died at 28 weeks of gestation.Case 3 was a 17-year-old Ghanaian woman who was referred to the tertiary health facility on account of jaundice and anaemia. She had delivered a live male infant at maturity of 32 weeks but noticed she was jaundiced and had a presentation of active disease 3 days prior to delivery. The baby was icteric at birth and on evaluation, had elevated bilirubin (mixed type) with normal liver enzymes. Hepatitis E virus infection was confirmed in both mother and baby. However, the jaundice and the hepatomegaly resolved in mother and baby after 5 and 12 days respectively. CONCLUSION: To the best of our knowledge, these are the first documented cases of fatal fulminant hepatic failures resulting from HEV infection in Ghana.     

Clinical and molecular description of the prenatal diagnosis of a fetus with a maternally inherited microduplication 22q11.2 of 2.5 Mb

Microduplications of 22q11.2 have been recently characterized as a new genomic duplication syndrome showing an extremely variable phenotype ranging from normal or mild learning disability to multiple congenital defects and sharing some overlapping features with DiGeorge/Velocardiofacial syndrome (DGS/VCFS). We report on the prenatal diagnosis of a 22q11.2 microduplication in a fetus with normal development that was referred for chromosomal analysis at 17 weeks of gestation because of advanced maternal age. Pregnancy was the result of an IVF-ICSI attempt after 4 years of infertility, mainly due to severe oligoasthenoteratospermia of the father. Amniocentesis was undertaken and cytogenetic analysis revealed an apparently normal male karyotype. Multiple Ligation-dependent Probe Amplification (MLPA) revealed a microduplication in the 22q11.2 chromosome region. Parental analysis showed that the 22q11.2 microduplication has been inherited from the otherwise healthy mother. Analysis with high resolution array-CGH showed that the size of the microduplication is 2.5 Mb and revealed the genes that are duplicated, including the TBX1 gene. The parents elected to continue with the pregnancy and the infant is now five months old and shows normal development.     

Reinfection after rubella and congenital polymalformation syndrome

A case is reported of a term newborn with intra uterine growth retardation and numerous malformations such as complex heart disease, abnormalities of distal limbs, cleft palate. Death occurred after two days. The diagnosis of rubella embryopathy was confirmed by the following criteria: a high level of rubella antibodies in mother and newborn (1/1000) an isolation of rubella virus from the infant's urine. Diagnosis of rubella after reinfection was documented by a high level of antibodies in the mother three years before this pregnancy. Other observations reported in literature confirm the extreme rarity of congenital rubella after reinfection.     

CONGENITAL SYPHILIS IN CALIFORNIA

Routine serologic tests for syphilis (as required by California law governing prenatal examination) and penicillin therapy during pregnancy for infected mothers have been major factors in the prevention of congenital syphilis in California during the past ten years. In 1940 one of each 822 infants had the disease, as indicated by morbidity reports of congenital syphilis in infants under the age of one year. In 1950 the ratio was one in 8,148. To determine why congenital syphilis continues to occur, a study of the 134 cases reported over a two-year period was made with the cooperation of local health officers and practicing physicians. It showed that in 76 per cent of cases the mother did not consult a physician prior to delivery or reported so late in pregnancy that the infant was born before adequate penicillin therapy could be given. In another 15 per cent syphilis developed in the mother during pregnancy after a negative reaction to a prenatal serologic test. The other 9 per cent of cases were due to various factors, such as infectious relapse or reinfection in previously adequately treated mothers. The study indicated that most cases occur in the lower socioeconomic population groups. Seventy-four per cent of cases were in infants delivered in county hospitals.     

Effect of ABO Incompatibility on Pregnancy-Induced Rh Isoimmunization

The protective effect of ABO incompatibility between mother and fetus in respect of pregnancy-induced Rh isoimmunization has been recognized for approximately 20 years. Many have tacitly assumed that this protection was absolute and that when an infant was born with Rh hemolytic disease of the newborn, who was also ABO-incompatible with its mother, there must have been a previous ABO-compatible pregnancy in which the mother was initially sensitized. It has also been assumed that pregnancy-induced Rh isoimmunization could not occur if the father was AB and the mother O. Data are presented to show that both of these assumptions are not universally true. In a detailed study of a large number of families with pregnancy-induced Rh iso-immunization, nine families were found in which sensitization occurred and in which ABO incompatibility was present in every pregnancy. In addition, three families are documented in which pregnancy-induced Rh immunization had occurred and in which the father was AB and the mother O.     

Congenital cutaneous candidiasis associated with maternal peripartum candidemia

BackgroundCutaneous congenital candidiasis (CCC) is a rare condition consisting of invasive fungal infection of the epidermis and dermis that mostly affects preterm infants. Maternal vaginal candidiasis is present in half of the cases, although the occurrence of invasive candidiasis during pregnancy or peripartum period is exceptional.Case reportWe present the case of a full-term infant that was born by vacuum-assisted vaginal delivery to an apparently healthy 33 year-old woman with no history of intravenous drug use or vaginal candidiasis during pregnancy. The newborn showed a diffuse maculopapular rash with respiratory distress and bilateral interstitial lung infiltrates, requiring nasal continuous positive airway pressure support. Blood cultures obtained from the mother due to intrapartum fever yielded Candida albicans. Cultures of vaginal discharge and neonate skin also yielded C. albicans with the same in vitro susceptibly pattern. No alternative source for candidemia was identified. The clinical course after starting a systemic antifungal therapy was favorable in both the mother and the neonate, with clearance of candidemia and resolution of the skin lesions.ConclusionsCCC must be considered in full-term newborns with maculopapular rash at birth or during the first days of life. The absence of alternative sources for bloodstream infection in the present case suggests a potential etiopathogenic relationship between CCC and maternal candidemia. It is reasonable to rule out postpartum candidemia when CCC is suspected.     

Programs of mass and selective screening of pregnant women in prenatal studies. Screening of alpha fetoprotein in the blood serum of the mother]

The total of 38479 echography studies and 25147 alpha-fetoprotein estimations in mother blood serum have been performed upon prenatal screening. 445 congenital developmental defects are revealed. AFP base and limiting values (2.5 MoM and 0.5 MoM) are found. AFP values and echocardiography results in the nor and in genetic syndromes of multiple congenital developmental defects are compared. It is found that AFP values are higher than MoM or only slightly higher than Me in the same syndromes. The different level of AFP for the same syndromes appeared to be associated with the phenomenon of overlapping due to the clinical polymorphism and type of injury of the nervous system and with the extent of changes in placenta, amniotic fluid and umbilical cord were revealed in 99% of syndromes. The increased AFP level can be considered as a marker to detect signs of the genetic syndromes. Low AFP level peculiar to aneuploidy appeared to be normal or increased. The AFP test can be used as a marker of changed embryogenesis.     

A case of congenital warfarin syndrome due to maternal drug administration during the pregnancy

Warfarin, which is used for anticoagulant therapy, rarely produces congenital warfarin syndrome characterized with hypoplastic nose, stippled epiphyses, and skeletal abnormalities when ingested during pregnancy. Here, we present a male infant, whose mother was treated with warfarin because of a prosthetic heart valve replacement after rheumatic heart disease, with signs of warfarin embryopathy. The mother's first pregnancy at 12 weeks gestation resulted in abortus due to warfarin toxicity. Subsequently, she delivered two healthy girls after her treatment had changed to low molecular heparin during pregnancy periods. We want to emphasize that risk-benefit ratio should be well weighed by both obstetricians and cardiologists when considering warfarin therapy for a woman at childbearing age.     

TOXOPLASMOSIS—The Protean Manifestations of the Condition and Their Significance in Pregnancy and in Newborn Infants

Toxoplasmosis is a relatively common and generally mild parasitic infection which can, however, produce fatal and crippling complications under certain conditions — particularly when a human fetus or a newborn infant is infected. In this instance, the infection is the result of a spread of the acquired disease which may occur in the mother in the last six months of pregnancy. Although the infection of adults can be dangerous and fatalities have been reported, the danger to the nervous system, eyes and other structures of the newborn infant can be devastating—blindness, brain damage and mental deficiency, particularly as the result of an obstruction to the flow of circulating cerebrospinal fluid within the brain.This report covers a number of differing features of the disease which have been described separately by other authors in specialty journals and in the foreign literature. If present, these signs should suggest toxoplasmosis, particularly in pregnancy, in the newborn infant and in still-born infants.Early diagnosis is of paramount interest in view of the poor response which may be obtained in the treatment of subacute and chronic phases of the illness. Difficulties in diagnosis stem from the manifestations of toxoplasmosis which closely resemble the symptoms of other infectious diseases.The clinical laboratory diagnosis is made by the isolation of the organism or by the demonstration of immune protein in the patient''s serum.     

Unilateral bowing of long bones and multiple congenital anomalies in a child born to a mother with gestational diabetes

We report on a new-born girl with multiple congenital anomalies consisting of major skeletal anomalies restricted to the left side, cleft palate, ventricular and atrial septal defect, retromicrognathia, short neck, dysplastic low-set ears and large birth weight. The left-side bony anomalies include shortening and bowing of the femur and tibia, hypoplasia of the fibula, hip dislocation, clubfoot and mild shortening of the long tubular bones in the left arm with elbow dislocation. The pregnancy was complicated by insulin-dependent gestational diabetes mellitus in the mother. The radiographic features were not consistent with the diagnosis of campomelic dysplasia, kyphomelic dysplasia or other skeletal dysplasias characterized by bowing and shortening of the long bones. To our knowledge, the multiple congenital anomalies, including major skeletal malformations, present in our case have never been simultaneously reported until now. A maternal diabetes syndrome in this infant is probable. The occurrence of major congenital malformations in offspring of women with gestational diabetes is reviewed and discussed. We provide evidence that gestational diabetes mellitus could be teratogenic. We recommend a careful diabetic control in every woman with a history of gestational diabetes.     

Adoption of an additional infant by a Western lowland gorilla (Gorilla gorilla gorilla).

A 10-year-old Western lowland gorilla, already caring for her own 14-month-old son, adopted a female neonate. The infant's mother (aged 7 years, 4 months) showed no interest in the infant, and it is unclear whether she abandoned the infant or whether it was seized by the dominant foster-mother. The foster-mother gave more maternal attention to the adoptee than to her own son but gave both infants the same protection. She adjusted her forms of transport to the age of each infant. The subadult mother of the neonate did not seek contact with her offspring during the first 4 weeks and in fact showed more interest in the 14-month-old male infant. Interactions between the two mothers were rare. The foster-mother's own male infant died 2 months after she had adopted the female infant. She looked after the adopted infant for 1 year, but then lost interest so that the adoptee had to be separated.     

Congenital tuberculosis associated with maternal disseminated miliary tuberculosis

Untreated tuberculosis during pregnancy presents a serious risk for transmission of disease to the newborn and can result in adverse perinatal and obstetrical outcomes. Tuberculosis during pregnancy and congenital tuberculosis are infrequent conditions and are difficult to diagnose due the non-specificity of the symptoms. A case report is presented of a woman who had no children previously with disseminated miliary tuberculosis. Tuberculosis symptoms appeared immediately after birth of the first child, with a clinical diagnosis on the second month after childbirth, whereupon the patient died. The son, a premature infant, showed disease symptoms from the first day, with primary pulmonary complex and persistent atelectasis due to bronchial obstruction. The obstruction was due to thoracic lymphadenitis and coinfection with cytomegalovirus. The infant received standard treatment and his condition improved.     

Effect of maternal tobacco smoking or exposure to second-hand smoke on the levels of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) in urine of mother and the first urine of newborn

Tobacco smoking during pregnancy is associated with a variety of negative consequences not only for the mother, but also for the developing fetus. Many studies have shown that carcinogens contained in tobacco smoke permeate across the placenta, and are found in fetus. The aim of the study was to determine the prenatal exposure to tobacco-specific carcinogenic N-nitrosamines on the basis of measurements of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) in urine of smoking and second-hand smoke (SHS) exposed women and in the first urine of their newborns. A questionnaire documenting demographics and socio-economical data, smoking habits and exposure to SHS was completed by 121 delivering women near or at term. Maternal concentrations of cotinine and NNAL were measured in urine of the mother and the first urine of her newborn infant by liquid chromatography tandem mass spectrometry (LC/MS/MS). The mean concentration of cotinine was 439.2 ng/mg creatinine and NNAL concentration in urine of smoking women was 74.0 pg/mg creatinine, and for her newborn 78.6 pg/mg creatinine. Among mothers exposed to SHS, cotinine and NNAL mean concentration were 23.1 ng/mg creatinine, and 26.4 pg/mg creatinine. In newborns of SHS exposed mothers during pregnancy the mean concentration of NNAL was 34.1 pg/mg creatinine, respectively. Active tobacco smoking as well as passive exposure to smoking during pregnancy is an important source of tobacco specific N-nitrosamines to the fetuses as evidenced by increased concentrations of this carcinogen. Determination of NNAL in maternal urine samples can be a useful biomarker of prenatal exposure of newborn to carcinogenic nitrosamines.     

An attempted within-group infanticide in wild chimpanzees

Two high-ranking adult male chimpanzees (Pan troglodytes) of M group in the Mahale Mountains National Park, Tanzania, tried to get a newborn female infant of an adult female who was born in M group. The mother was not seen to mate with these adult males during the probable conception cycle of the infant, but she disappeared from the group during the later cycle, when she may have been inseminated by a male of one of the neighboring unit groups. The adult males failed to get the infant because the grandmother of the newborn and her female friend cooperated to protect the mother and infant from attacks by the males. The sexual selection hypothesis for infanticide by adult male chimpanzees holds for this observed case. The sudden disappearance of another infant, a healthy female, strongly suggests the killing of female infants too. Therefore, the asserted male-biased infanticide in chimpanzees appears to be less tenable.     

Fetal methotrexate and misoprostol exposure: the past revisited

BACKGROUND: Fetal aminopterin/methotrexate syndrome was described nearly 50 years ago when these agents were first used as abortifacients. Physicians essentially stopped using these agents when the associated anomalies were recognized. Over the last several years the use of methotrexate with or without misoprostol for management of ectopic pregnancy and medical terminations of pregnancy has increased. METHODS: A 23-year-old female sought a termination at eight weeks gestation. She was given methotrexate followed by misoprostol. RESULTS: The medical termination was unsuccessful. The patient elected to continue the pregnancy secondary to financial considerations. She presented at 39 weeks without intervening prenatal care. She was diagnosed with severe preeclampsia. At delivery the infant was hypotonic and growth restricted with multiple anomalies. CONCLUSIONS: Physicians are increasingly using methotrexate with or without misoprostol for treatment of ectopic pregnancies and medical terminations. Clinicians need to be aware of the characteristic teratologic effects of these two agents.     

Down-regulation of L-type calcium channel in pups born to 52 kDa SSA/Ro immunized rabbits.

Congenital heart block is considered a model of passively acquired autoimmune disease in which the mother generates anti-SSA/Ro and/or anti-SSB/La antibodies that cross the placenta and presumably injure the heart of developing fetus. CHB is accompanied by ECG abnormalities including AV block, sinus bradycardia, and ventricular dysfunction. Our previous data indicate that these abnormalities are caused by maternal autoantibody-mediated disturbance of L-type Ca channels. To investigate the consequence of chronic exposure of L-type Ca channels in newborn pups to maternal autoantibodies during pregnancy, we immunized female rabbits with human 52 kDa-SSA/Ro (Ro52) recombinant protein. ECG revealed that pups from the immunized group had varying degrees of conduction defects. In addition, I(CaL) density and protein were reduced in hearts of pups from the immunized group. Sera and purified IgG from immunized rabbits inhibited I(Ba) recorded from oocytes with expressed alpha(1C) and beta(2a) subunits of L-type Ca channel. Pups born to Ro52 immunized mothers exhibited down-regulation of L-type calcium channels in heart. The data provide new insight into the pathogenesis of congenital heart block.     

Congenital rubella affecting an infant whose mother had rubella antibodies before conception.

A woman who had had high titres of rubella antibodies some months before she became pregnant gave birth to an infant in whom congenital rubella was confirmed at 4 months. Rubella haemagglutination inhibition tests, complement fixation tests, and immunofluorescence tests with anti-human IgG were carried out on sera from the mother. Rubella antibody titres in sera obtained in March 1971, seven and a half months before conception, were equivalent to 400 units, which is usually taken as indicating good immunity. Rubella virus was isolated from the baby''s nose and throat in July 1973 but was not isolated from a cervical swab taken from the mother in December 1973; tests of her immunological competence did not show any definite abnormality. The presence of high levels of rubella haemagglutination inhibition antibodies does not invariably confer immunity or exclude the possibility of congenital rubella in a subsequent pregnancy.     

Dispermic origin of a 69,XXY triploid

Summary Triploidy, 69,XXY, was found in a newborn with multiple abnormalities. Conception had occurred shortly after the mother ceased taking an oral contraceptive. The infant carried a pair of 21s with giant satellites; of the parents, only the father carried a giant-satellited 21. This, together with the XXY constitution, suggested a dispermic origin of the triploidy.     

Maternal use of selective serotonin re-uptake inhibitors in early pregnancy and infant congenital malformations

BACKGROUND: Maternal use of selective serotonin re-uptake inhibitors (SSRIs) has recently been associated with an increased risk for certain malformations. METHODS: Using the Swedish Medical Birth Register, we identified women who had reported the use of SSRIs in early pregnancy and studied their infants, born between July 1, 1995 and the end of 2004. Congenital malformations were identified from that register, from the Register of Congenital Malformations, and from the Hospital Discharge Register. The effect of drug exposure was studied after adjustment for a number of identified maternal characteristics that could act as confounders. RESULTS: We identified 6,481 women who reported the use of SSRIs in early pregnancy and their 6,555 infants. There was no general increase in malformation risk. An increased risk for cystic kidneys was seen, but this was based on only nine malformed infants, and the pathology varied between these cases. An in-depth study of cardiovascular defects identified an association between such defects and notably ventricular and atrial septum defects and maternal use of paroxetine but not other SSRIs. No support for a postulated association between SSRI use and infant craniostenosis or omphalocele was found. CONCLUSIONS: Use of SSRIs in early pregnancy does not seem to be a major risk factor for infant malformations. The association between paroxetine use and infant cardiovascular defects may be a result of multiple testing, but is supported by other studies.     

Blood group and behavioral differences among dizygotic twins: A failure to replicate

Abstract

The relationship between the age of mother and pregnancy outcome is examined using the matched birth‐infant death data for Arkansas. Indicators of pregnancy outcome are examined in relation to measures of SES and access to health care. The hypothesis that the elevated rate of newborn mortality and morbidity among infants delivered by adolescents as a consequence of biologic immaturity is examined. The analysis suggests that the higher levels of obstetric risk observed among teenage mothers is an artifact of lower SES and inferior access to health care and not biological immaturity as previously assumed.