Unexplained Intrauterine Death Research Articles

Comparison of causes and circumstances of intrauterine death in term and preterm pregnancies at a tertiary care center

Abstract Background: It is of extreme importance to identify the causes of fetal deaths, so that preventive strategies can be framed and more vigilant monitoring and prenatal surveillance can be undertaken. Objective: To determine the causes and circumstances of intrauterine death in term and preterm pregnancies and compare these causes. Materials and Methods: A cross-sectional observational study was undertaken. All the mothers underwent basic and targeted investigations as per the hospital protocol to identify the causes of intrauterine death (IUD). Basic investigations included complete hemogram, infective serology, and liver and renal function tests. Results: The stillbirth rate was 17.83%. It was comparable in males and females. Most cases were second gravida. Birth weight was significantly lower in preterm pregnancies compared to term pregnancies. Other characteristics were comparable. The most common risk factor was pregnancy-induced hypertension 49 cases (40.49%). The presence of pregnancy-induced hypertension was comparable in two groups. Unexplained IUD was significantly more in preterm pregnancy cases compared to the term pregnancy cases. Conclusion: The main causes of fetal mortality identified from this study include pregnancy-induced hypertension, severe anemia, abruptio placenta, and Rh isoimmunization.

Consanguineous marriages and poor pregnancy outcomes

Objective: To examine the influence of consanguineous marriage on pregnancy outcomes and highlight the factors, such as rural region residency, unemployment, and poor education. Methodology: This prospective study used a questionnaire for women in Babylon teaching hospital and some private clinics from the 1st of June 2021 to the 1st of July 2022. Randomly, 500 women were taken, 150 of them had history of consanguineous marriage. Results: Mean age of women was 30 years; 77% were rural, 4.1% were employed, 21.6% had congenital abnormalities, 8.8% experienced recurrent miscarriages, and 10.1% suffered unexplained intrauterine mortality. 350 had no history of consanguineous marriage, a mean age of 34, 46.6% resided in rural areas, 79.3% were employed, 8.2% had congenital abnormalities, 3.4% had recurrent miscarriages, and 4% experienced unexplained intrauterine mortality. Consanguinity and rural living (p=0.0001) and employment (p=0.0001) were substantially correlated. Consanguinity was correlated with congenital abnormalities (p=0.0001), recurrent miscarriage (p=0.022), and unexplained intrauterine death (p=0.036). Conclusion: Consanguineous marriage is prevalent in our region (30%), especially in rural areas and jobless groups, which increases prenatal abnormalities, miscarriage, and intrauterine mortality.

Prevalence of gestational diabetes mellitus and its association with various risk factors in a tertiary care hospital in tribal population of Jharkhand

Background: Gestational diabetes mellitus (GDM) is associated with hypertension, preeclampsia, stillbirth, macrosomia, unexplained intrauterine death, instrumental and traumatic delivery leading to both maternal and foetal injuries, and increased risk of maternal and neonatal infections. The present study was conducted at Rajendra Institute of Medical Sciences, Ranchi to determine the prevalence of Gestational Diabetes Mellitus(GDM) and its associated risk factors in tribal population of Jharkhand. Aims and Objectives: The aim of the study was to determine the prevalence of GDM and to analyze its association with various risk factors. Materials and Methods: Detailed history of all patients was taken with emphasis on genetic and family history and history of the previous pregnancies. All the patients were screened by the single step 75 gm 2 hours oral glucose tolerance test (OGTT) as recommended by the World Health Organization. GDM was diagnosed if 2 hours PG is ≥140 mg/dL. Results: Most patients of GDM were from upper middle class 45.45%, followed by lower middle class (27.27%) and upper lower class (18.18%). For the non-GDM patients, most patients were from upper lower class (55.055%), followed by upper middle (24.71%). The prevalence of GDM was 12.12 % in the tribal population as compared to non-tribal population (10.44 %). In present study, in majority (89.00 %) of study subjects, result of 75 gm OGTT was negative. Result of 75 gm OGTT was positive in only 11 out of 100 study subjects (11.00 %). Conclusion: Tribal population in Jharkhand has very poor access to health-care services of the state. This study is first of its kind in our state which will set as an eye opener to further deliver better health-care facilities at grassroot level in Jharkhand.

Cause-Specific Stillbirth and Neonatal Death According to Prepregnancy Obesity and Early Gestational Weight Gain: A Study in the Danish National Birth Cohort.

Maternal obesity is associated with impaired fetal and neonatal survival, but underlying mechanisms are poorly understood. We examined how prepregnancy BMI and early gestational weight gain (GWG) were associated with cause-specific stillbirth and neonatal death. In 85,822 pregnancies in the Danish National Birth Cohort (1996–2002), we identified causes of death from medical records for 272 late stillbirths and 228 neonatal deaths. Prepregnancy BMI and early GWG derived from an early pregnancy interview and Cox regression were used to estimate associations with stillbirth or neonatal death as a combined outcome and nine specific cause-of-death categories. Compared to women with normal weight, risk of stillbirth or neonatal death was increased by 66% with overweight and 78% with obesity. Especially deaths due to placental dysfunction, umbilical cord complications, intrapartum events, and infections were increased in women with obesity. More stillbirths and neonatal deaths were observed in women with BMI < 25 and low GWG. Additionally, unexplained intrauterine death was increased with low GWG, while more early stillbirths were seen with both low and high GWG. In conclusion, causes of death that relate to vascular and metabolic disturbances were increased in women with obesity. Low early GWG in women of normal weight deserves more clinical attention.

The prevalence of abnormal Doppler's of the umbilical artery in a low-risk pregnant population in South Africa.

BackgroundThe assessment of fetal blood flow using Doppler waveform can be used to identify placental insufficiency, and hence is a tool to identify fetuses at risk of stillbirth due to fetal growth restriction (FGR). In South Africa the largest category of perinatal deaths is ‘unexplained intrauterine death’. The majority of the mothers are clinically healthy women. This study was performed to determine the prevalence of abnormal umbilical resistance indices (abnormal RI) to see if screening a low-risk pregnant population is worthwhile.MethodsA descriptive study across 9 sites in 8 provinces of South Africa was performed to determine the prevalence of abnormal RI of the umbilical artery in women classified as having a low-risk pregnancy. The study was conducted from 1st September 2017- February 2020.The pregnant women classified were screened using a continuous wave Doppler ultrasound apparatus (Umbiflow™) between 28 and 34 weeks’ gestation. Women with fetuses with an abnormal RI were referred to a high-risk clinic and were managed according to standard protocol. The outcomes of all the deliveries were recorded.FindingsUmbiflow™ screening of the umbilical artery was performed in 7088 women across nine sites; 919 (13·0%) fetuses had an abnormal RI. Absent end diastolic flow (AEDF) was found in 87 (1·2%) fetuses. The prevalence of small for gestational ages (SGA) babies was 23·1% in the normal RI group and was significantly higher in the abnormal RI group 32·1% (p<0·0001). There was a statistical difference in the perinatal mortality rate between the normal RI (9.8/1000) and abnormal RI group (21.4/1000) [RR 0·046; 95% CI -0·06–0·98].InterpretationThe prevalence of abnormal RI and AEDF in this screened low-risk population was about ten times higher than that previously recorded in high income countries. Continuous wave Doppler ultrasound screening detected previously undiagnosed growth restricted babies. The prevalence of AEDF warrants continuous wave Doppler ultrasound screening of the low-risk pregnant population in South Africa.FundingThis study was funded by the South African Medical Research Council (SAMRC) and the Council for Scientific and Industrial Research (CSIR)

Early Prophylactic Enoxaparin for the Prevention of Preeclampsia and Intrauterine Growth Restriction: A Randomized Trial

Background: Preeclampsia (PE) and intrauterine growth restriction (IUGR) are major causes of maternal and perinatal morbidity and mortality. Previous studies have shown that intervention with low-dose aspirin resulted in a reduction in the occurrence of preterm PE. However, no data are currently available on the effect of low-molecular-weight heparin (LMWH) for the prevention of pregnancy complications in women enrolled at first trimester screening. Objective: We aimed to assess the effectiveness of LMWH in the prevention of PE, IUGR, fetal death, and abruptio placentae in women classified as high risk based on their medical history and in women selected by first trimester screening of PE. Study ­Design: This was a multicenter, randomized, open-label, parallel controlled trial in women without thrombophilia between 6.0 and 15.6 weeks of gestation. Inclusion criteria were severe PE or IUGR before 34 weeks of gestation and/or abruptio placentae or unexplained intrauterine death in a previous pregnancy; uterine artery mean pulsatility index Doppler >95th percentile and/or positive first trimester screening for PE. Pregnant women were randomly assigned to receive no intervention or LMWH until the 36th week of gestation. The primary composite outcome consisted of 1 or more of the following: development of PE, IUGR, abruptio placentae, and intrauterine fetal death. Results: A total of 278 pregnant women were randomly allocated to receive LMWH (n = 134) or no intervention (n = 144). Overall, 115 (41%) women experienced placental insufficiency complications, with no significant differences between the 2 arms: 50/144 (34.7%) in the LMWH arm and 43/134 (32%) in the control arm (p = 0.64, OR: 1.13, 95% CI: 0.68–1.85). Conclusion: LMWH did not reduce the incidence of placenta-mediated complications either in women with previous adverse obstetric history without thrombophilia or in women selected by first trimester screening for PE. Based on these results, we cannot recommend the use of LMWH alone in women at risk of placental complications.

Serum mannose-binding lectin (MBL) concentrations are reduced in non-pregnant women with previous adverse pregnancy outcomes.

Mannose-binding lectin (MBL) is an important component of the innate immunity, and it is responsible not only for opsonization of micro-organisms, but also for efferocytosis. The aim of this study was to investigate whether MBL concentrations and lectin complement pathway activity are altered in non-pregnant women with previous adverse pregnancy outcomes. Patients were divided into four groups on the basis of their history of pregnancy complications, including control patients who had uncomplicated pregnancies and term deliveries (control, n=33), and three groups of patients with a history of pregnancy complications, including preterm labour (n=29), recurrent miscarriage (n=19) or unexplained intrauterine foetal death (IUFD; n=17). All women enrolled in the study had an interval of three to six months following their previous pregnancy, and they agreed to have a blood sample taken. We found significantly higher MBL concentrations and functional activity of the lectin complement pathway in healthy controls who had previous uneventful term pregnancies (1341ng/mL; activity 100% (IQR: 62%-100%)), compared to women with the history of IUFD (684ng/mL, P=.008; activity 8.5% (IQR: 0%-97.8%), P=.011), recurrent miscarriage (524ng/mL, P=.022; activity 44% (IQR: 4%-83%), P=.011) or preterm labour (799ng/mL, P=.022; activity 62.5% (IQR: 0%-83%), P=.003). Our results suggest that inadequate function of the complement lectin pathway is associated with a higher risk of preterm labour, recurrent miscarriage and unexplained intrauterine foetal death.

The value of histopathology of the placenta in a tertiary referral hospital in South Africa

Background. Unexplained intrauterine death (IUD) remains the most common cause of perinatal death in babies of 24 weeks’ gestation. Results. The total sample ( N =822) comprised 60.9% live-birth placentas and 39.1% IUD placentas. In the IUD group, the cause of death was clinically unexplained in 55.9% of cases. Histopathology identified in this group included chorioamnionitis (CA) (34.5%), maternal vascular malperfusion (32.1%), abruptio placentae (31.5%), delayed villous maturation (17.8%) and toxoplasmosis, other agents, rubella, cytomegalovirus and herpes simplex (TORCH) infections (6.1%), most commonly syphilis. No pathology was found in only 2% of IUD cases. Among live births, preterm labour accounted for 41.9% of placental submissions, of which the cause was unknown in 46.2% of cases. Clinically indicated and histologically defined CA was poorly correlated. Conclusion. This study demonstrates the value of placental histopathology in cases of adverse perinatal outcome.

Tracking progress on the health status and service delivery outcomes for neonates and children in the Metro West geographic service area of the Cape Metropole, 2010 - 2015

Background. Monitoring the health status of populations of children is one of the building blocks of the health system. The provision of an indicator dashboard with disaggregated data that are collected over time can be used to gauge the performance of the health system, guide the allocation of resources and prioritise health interventions within districts. Objectives. To determine neonatal and child mortality, morbidity and health service outcomes over a 6-year period in the Metro West geographic service area (GSA) of the Cape Town metropole. Methods. A dashboard with key indicators was developed using existing data. Results. From 2010 to 2015, there was a decrease in the perinatal mortality rate from 31.7 to 24.8 per 1 000 deliveries, and the early neonatal and neonatal mortality rates from 7.8 and 8.6 to 7.0 and 8.2 per 1 000 live births, respectively. The main obstetric causes of early neonatal deaths were antepartum haemorrhage (22 - 24%) and unexplained intrauterine death (13 - 16%); the main neonatal causes were immaturity (17 - 34%), congenital abnormalities (23 - 29%) and hypoxia (23 - 26%). Under-five mortality decreased in 2013 from 25 to 22 per 1 000 live births, with the main causes being neonatal conditions (32%), pneumonia (25%), congenital abnormalities (9%), injuries (8%) and diarrhoea (8%). Fifty percent of child deaths were out of hospital, with pneumonia and diarrhoea accounting for more than half of these. There was an improvement in health service coverage rates in 2015: immunisation <1 year old (99%); measles second dose (85%), pneumococcal third dose (100%) and rotavirus second dose (100%); maternal antiretroviral coverage (90%); HIV testing in mothers (93%); HIV DNA polymerase chain reaction testing in babies (97%); and a decrease in HIV transmission (2%). Exclusive breastfeeding coverage rates at 14 weeks, and vitamin A supplementation at 12 - 59 months, were only 30% and 44%, respectively, across the GSA. Conclusion. There was a decrease in perinatal, early neonatal, infant and under-five mortality in Metro West over the 6 years. Further reductions in under-five mortality will require focusing on interventions to reduce neonatal and out-of-hospital deaths across the service delivery platform. Home visits to at-risk mothers and infants by community health workers could prevent out-of-hospital deaths and improve exclusive breastfeeding and vitamin A coverage. This will require increasing the number of community health workers and broadening their scope of practice.

Stillbirth and intrauterine fetal death: role of routine histopathological placental findings to determine cause of death.

Placental abnormalities are a common cause of death in stillbirth, ranking second only to unexplained deaths, though there is wide variation in the proportion attributed to placental disease. In clinical practice, interpretation of the significance of placental findings is difficult, since many placental features in stillbirths overlap with those in live births. Our aim was to examine objectively classified placental findings from a series of > 1000 autopsies following intrauterine death in order to evaluate the role of placental histological examination in determining the cause of death. As part of a larger study evaluating several aspects of autopsy findings in intrauterine death, a dedicated database was used to collate antenatal and postmortem examination details for all cases examined between 2005 and 2013 at two tertiary specialist centers in London, UK. Histological findings for placentas were evaluated in relation to the final cause of death. Among 1064 intrauterine deaths, 946 (89%) cases had the placenta submitted for examination as part of the autopsy. Of these, 307 (32%) cases had the cause of death assigned to abnormalities of the placenta, cord or membranes. Around one third of stillbirths (≥ 24 weeks) had some isolated placental histological abnormality identified, many of uncertain significance, a significantly greater proportion than in cases of second-trimester intrauterine fetal demise (P < 0.0001). The cause of death was ascending infection in 176/946 (19%) cases, peaking at 22 weeks' gestation, with significantly more black mothers having ascending infection compared with other ethnicities (P < 0.0001). Maternal vascular malperfusion was the largest category of placental abnormalities in stillbirth, with peak prevalence in the early third trimester. There were 18 (2%) cases with specific histological abnormalities, including chronic histiocytic intervillositis and massive perivillous fibrin deposition. Placental pathologies represent the largest category of cause of intrauterine death. Placental histological examination is the single most useful component of the autopsy process in this clinical setting. A minority of cases are associated with specific placental pathologies, often with high recurrence rates, that can be diagnosed only on microscopic examination of the placenta. Many deaths remain unexplained, although placental histological lesions may be present which are of uncertain significance. A rigorous, systematic approach to placental pathology research and classification may yield better understanding of the significance of placental findings and reduce the rate of unexplained intrauterine deaths. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.

Timing and cause of perinatal mortality for small-for-gestational-age babies in South Africa: critical periods and challenges with detection.

BackgroundLittle information exists on timing and cause of death for small-for-gestational-age (SGA) babies in low-and-middle-income-countries (LMICs), despite evidence from high-income countries suggesting critical periods for SGA babies. This study explored the timing and cause of stillbirth and early neonatal mortality (END, <7 days) by small-for-gestational age in three provinces in South Africa. In South Africa, the largest category of perinatal deaths is unexplained stillbirth, of which up to one-quarter have intra-uterine growth restriction.MethodsSecondary analysis of the South African Perinatal Problems Identification Program (PPIP) database allowed for the analysis of gestational age at death and clinically confirmed diagnosis of stillbirth and early neonatal death (END) (>1000 g and >28 weeks) across gestation. Comparisons by province, size-for-gestational-age, gestational age groups, and maternal condition at death were performed. The provinces investigated were: Western Cape (fortnightly antenatal care visits from 32 to 38 weeks), Limpopo and Mpumalanga (no antenatal care visits between 32 to 38 weeks).ResultsThere were 528,727 births in the study period and 8111 stillbirths and 5792 early neonatal deaths. Similar timing of deaths across gestation was seen for the three provinces with the greatest proportion of deaths for SGA babies at 33–37 weeks (stillbirths 52.9 %; END 43.3 %; p < 0.05). SGA babies had a greater proportion of deaths due to hypertension (SGA22.9 %; AGA 18.6 %; LGA 18.6 %; p < 0.05) and intrauterine growth restriction (SGA 6.8 %; AGA 1.7 %; LGA 1.4 %; p < 0.05). No increase was seen in poor maternal condition for SGA babies and 54.9 % of deaths had a healthy mother. Of mothers that were healthy the greatest proportion of SGA stillbirths were due to unexplained intrauterine death (53.9 %).ConclusionThere was a peak in stillbirths for SGA babies 33–37 weeks in all provinces. Detecting SGA is further complicated as in most cases the mother is healthy. Further research into Umbiflow Doppler velocimetry use in low-risk populations is warranted and may be a viable strategy to increase current detection of SGA babies at risk of mortality in LMICs.

Impact Assessment of Endocrine Disruptors on Sudden Intrauterine and Infant Death Syndromes

Background and Objectives: The endocrine disruptors (EDs) are able to interfere with the endocrine system, mimicking or antagonizing the hormonal activity. They can persist in the environment, due to their degradation resistance. The aim of our research has been to analyze the possible link between unexplained intrauterine and infant mortality and chronic exposure to EDs. Materials and Methods: We have investigated 16 cases of sudden intrauterine unexplained death syndrome (SIUDS) and 8 cases of sudden infant death syndrome (SIDS), collected over a 3-year period (2012-2014). Brain samples were submitted to chemical analysis of 25 EDs, consisting in a liquid-solid extraction procedure, followed by a purification step and by a gas chromatography-mass spectrometry analysis. Results: The analytical method to detect the presence of EDs in brain samples has been successfully applied to SIUDS and SIDS victims. At the level of the brainstem, the frequent association between the hypoplasia of the facial/parafacial complex and the hypoplasia of the raphe system has been ascertained. In particular, the hypodevelopment of the parafacial nucleus, consisting of ‘pre-inspiratory’ neurons with the main function of hierarchical modulation of breathing circuitry, appears an exclusive finding of unexplained stillbirths. Conclusions: The environmental EDs have been found able to cross the placental barrier, reaching also the brain nuclei assigned to the control of vital functions. This is consistent with literature data that report the presence of these selected pollutants in other human tissue. For this reason, environmental EDs should be searched during autopsy in order to establish a possible correlation with unexplained intrauterine and infant deaths.

Elective Delivery at Term after a Previous Unexplained Intra-Uterine Fetal Death: Audit of Delivery Outcome at Tygerberg Hospital, South Africa.

ObjectivesTo assess the delivery outcome in a pregnancy with a previous unexplained intra-uterine death by elective induction of labour at term.MethodsAn audit of the pregnancy outcome of all women within the catchment area with a current singleton pregnancy; and a previous unexplained or unexplored singleton fetal demise ≥24 weeks (or 500 grams birth weight if gestation unknown) after planned routine induction of labour at full term (39-40 weeks).ResultsDuring the audit period, 306 patients with a previous intra-uterine fetal death were referred for further management. Of these, 161 had a clear indication for earlier intervention and were excluded from the protocol. Of the remaining 145 patients, 9 met further exclusion criteria and there were 2 patients who defaulted. Forty-two of the remaining study patients (with no known previous medical problems) developed complications during their antenatal course that necessitated a change in clinical management and earlier (<39 weeks) delivery. Of the remaining 92 patients in the audit, 47 (51%) went into spontaneous labour before their induction date; all 92 women delivered without major complications. There were no intra-uterine deaths prior to induction.ConclusionsCareful follow up at a high risk clinic identifies new or concealed maternal or fetal complications in 29% of patients with a previous intra-uterine death and no obvious maternal or fetal disease in the index pregnancy. When all risks are excluded and the pregnancy allowed to progress to full term (39-40 weeks) before an induction is offered, 50% will go into spontaneous labour.

Clinical spectrum of fetal long QT syndrome: a single-center experience

Objective: A considerable proportion of unexplained intrauterine fetal deaths are attributed to long QT syndrome (LQTS) susceptibility. Additionally, the estimated prevalence of LQTS in newborns is 1 in 2000. Still, prenatal diagnosis of LQTS is very rare. The aim of this study was to assess the frequency of prenatal diagnosis of LQTS at our institution, present the cases, compare our findings with the existing literature and propose a possible screening approach.Methods: We searched our fetal database between 2006 and 2013 for cases with suspected diagnosis of LQTS.Results: During the investigation period around 26 000 fetuses were evaluated and three cases of suspected fetal LQTS identified. Two cases of familial LQTS had no or mild intrauterine manifestation of the condition, the third fetus had a de-novo mutation with severe, early-onset disease.Conclusions: LQTS continues to be a challenging prenatal diagnosis. In fetuses who present with complex arrhythmias, a high degree of suspicion is required, and close surveillance and timely delivery in the presence of a multidisciplinary team are necessary. For asymptomatic cases or screening purposes, routine fetal heart rate registration and detailed assessment of cases with a low for gestational age baseline may be an option.

The genetic autopsy

To assess the relevance of perinatal and pediatric autopsies in genetic and metabolic diseases. Genetic investigations are an important component of fetal autopsies. Despite the advances in imaging diagnosis, the autopsy can identify abnormalities not seen on ultrasound or MRI, as confirmed in recent comparative studies. This is crucial in the diagnosis of syndromic conditions in which the information may be essential to determine the syndrome. Genetic tests may also have a role in the investigation of intrauterine growth restriction and unexplained stillbirth. New techniques have increased the diagnostic yield, even in cases of macerated fetuses.The genetic autopsy is not limited to fetal loss. Genetic abnormalities underlie many cases presenting as sudden unexpected death in infancy, childhood and adolescence, and the need to obtain appropriate samples for genetic analysis applies not only to fetal autopsies. Fetal autopsies are still the gold standard in diagnosis of fetal abnormalities. Genetic studies are an important component, not only in cases of congenital malformations, but also in unexplained intrauterine death and sudden unexpected death in infancy, as well as in children and adults.

Long QT Syndrome–Associated Mutations in Intrauterine Fetal Death

Intrauterine fetal death or stillbirth occurs in approximately 1 out of every 160 pregnancies and accounts for 50% of all perinatal deaths. Postmortem evaluation fails to elucidate an underlying cause in many cases. Long QT syndrome (LQTS) may contribute to this problem. To determine the spectrum and prevalence of mutations in the 3 most common LQTS susceptible genes (KCNQ1, KCNH2, and SCN5A) for a cohort of unexplained cases. In this case series, retrospective postmortem genetic testing was conducted on a convenience sample of 91 unexplained intrauterine fetal deaths (mean [SD] estimated gestational age at fetal death, 26.3 [8.7] weeks) that were collected from 2006-2012 by the Mayo Clinic, Rochester, Minnesota, or the Fondazione IRCCS Policlinico San Matteo, Pavia, Italy. More than 1300 ostensibly healthy individuals served as controls. In addition, publicly available exome databases were assessed for the general population frequency of identified genetic variants. Comprehensive mutational analyses of KCNQ1 (KV7.1, LQTS type 1), KCNH2 (HERG/KV11.1, LQTS type 2), and SCN5A (NaV1.5, LQTS type 3) were performed using denaturing high-performance liquid chromatography and direct DNA sequencing on genomic DNA extracted from decedent tissue. Functional analyses of novel mutations were performed using heterologous expression and patch-clamp recording. The 3 putative LQTS susceptibility missense mutations (KCNQ1, p.A283T; KCNQ1, p.R397W; and KCNH2 [1b], p.R25W), with a heterozygous frequency of less than 0.05% in more than 10 000 publicly available exomes and absent in more than 1000 ethnically similar control patients, were discovered in 3 intrauterine fetal deaths (3.3% [95% CI, 0.68%-9.3%]). Both KV7.1-A283T (16-week male) and KV7.1-R397W (16-week female) mutations were associated with marked KV7.1 loss-of-function consistent with in utero LQTS type 1, whereas the HERG1b-R25W mutation (33.2-week male) exhibited a loss of function consistent with in utero LQTS type 2. In addition, 5 intrauterine fetal deaths hosted SCN5A rare nonsynonymous genetic variants (p.T220I, p.R1193Q, involving 2 cases, and p.P2006A, involving 2 cases) that conferred in vitro electrophysiological characteristics consistent with potentially proarrhythmic phenotypes. In this molecular genetic evaluation of 91 cases of intrauterine fetal death, missense mutations associated with LQTS susceptibility were discovered in 3 cases (3.3%) and overall, genetic variants leading to dysfunctional LQTS-associated ion channels in vitro were discovered in 8 cases (8.8%). These preliminary findings may provide insights into mechanisms of some cases of stillbirth.

An investigation of the stillbirths at a tertiary hospital in Limpopo province of South Africa.

Objective:To determine the stillbirth rate and identify the causal factors associated with it in a tertiary hospital.Methods:A retrospective review of records of women who had stillbirths at a tertiary hospital of the Limpopo Province was conducted. The study period was two years from January 1, 2009 to December 31, 2010. The hospital maternity registers were used to identify the women who gave birth during the study period. Data were collected using a data collection form designed for the study. The data collected included maternal age, parity, gestation, mode of delivery, obstetric complications, infant or foetal’s gender and weight; whether the birth was fresh stillbirth or macerated and cause of stillbirth.Results:There were 5597 deliveries during the two years period of the study. The hospital-based stillbirth rate was 38.4 per 1000 births, with 71% being macerated. The majority of women with stillborn infant in this study were in the age group (24%) 20-34 years, followed by (23%) aged 35 years and older. Nulliparity was associated with stillbirth. Unexplained intrauterine foetal death, hypertensive disease, placenta abruptio was the leading causes of stillbirth.Conclusion:In this study stillbirth rate seems to be unacceptably high, though less than those reported in other settings. The causal factors associated with it were identified as nulliparity, unexplained intrauterine foetal deaths, hypertensive disease, and placenta abruptio. Because of the high rate of stillbirths reported in this study, it is recommended that interventions be made to introduce fetal autopsies at the tertiary healthcare facilities and that an educational intervention aimed teaching pregnant women be instituted.

Histopathological analysis of the placental lesions in pregnancies complicated with IUGR and stillbirths in comparison with noncomplicated pregnancies

Placental factors and hypoxemia are the keys to intrauterine growth restriction (IUGR) and stillbirth. The aim of the study is to analyze histological changes in placentas of IUGR fetuses in pregnancies with no apparent etiologic factor and unexplained intrauterine fetal deaths. A total of 110 placentas were collected; 26 placentas of IUGR fetuses with no apparent cause, 58 placentas from unexplained intrauterine deaths over 20 weeks of gestation, and 26 placentas from uncomplicated pregnancies who delivered a healthy live baby. Microscopic examinations of placentas were performed for histopathological analyzes. Gestational age at delivery was 33.67±4.37 weeks, 29.15±8.36 weeks, and 39.0±1.52 weeks in women in group I, group II and group III, respectively (p<0.01). Infarction and intervillous thrombosis are significantly more frequent in placentas of Group I and group II. Chronic villitis occurred in 69%, 63% and 30% of group I, group II, and group III, respectively. Placental intravascular thrombi (Group I, 31% and group II, 26%), perivillous fibrin deposition and fibrinoid necrosis (65% in Group I and 53% in group II), infarction, intervillous thrombosis, chronic villitis, hemorrhagic endovasculitis, placental intravascular thrombi, perivillous fibrin deposition, fibrinoid necrosis, erythroblastosis and villous edema were found in the study group. The results reported here indicate that a relationship exists between morphological changes in the placentas of IUGR and intrauterine fetal deaths.

Low Birth Weight in Kuala Lumpur

Low birth weight babies are defined as those weighing under 2,500 g. They make 13.5% of all births at the Maternity Hospital, Kuala Lumpur but contribute to 74.8% of all deaths. They are most likely to be Indian babies and least likely to be Chinese. Among all 3 communities, the primigravidae tend to produce smaller babies than multiparae but this is also true for the Indian of parity more than 3. The Malay teenager is more likely to produce small babies than their older counterparts but not so with the Indian and Chinese. There are definite clinical factors associated with or causing the births of small babies and the lighter the baby, the more influential are these factors. Maternal hypertension, antepartum haemorrhage, multiple pregnancy and unexplained intrauterine death are the 4 outstanding associations with both low birth weight and perinatal death. Although the spontaneous (often premature) onset of labour was the commonest preceding factor, it was much less important in the lowest birth weight groups of babies and was a less important contributor to perinatal death.

Total perinatally related losses at Tygerberg Hospital – a comparison between 1986, 1993 and 2006

To determine the leading causes of perinatal deaths and to evaluate any changes, with the inclusion of placental histology. At perinatal mortality meetings, primary and final causes of death were assigned for the period 1 July 2006 - 30 June 2007. All singleton babies born to women residing in the metropolitan area serviced by Tygerberg Hospital were included in the prospective descriptive study. The total number of singleton births was 10 396. The total of perinatally related losses (TPRL) rate was 26.2 per 1,000 births. The leading primary obstetric causes of death were: infections (47 - 17.3%), spontaneous preterm labour (PTL) (41 - 15.1%), antepartum haemorrhage (APH) (40 - 14.7%), intra-uterine growth restriction (IUGR) (40 - 14.7%), fetal abnormality (31 - 11.4%), hypertensive disorders (25 - 9.2%), unexplained intra-uterine deaths (IUD) (20 - 7.4%), intrapartum hypoxia (12 - 4.4%) and maternal disease (9 - 3.3%). A total of 162 placentas were sent for histology; 58 reports changed the primary cause of death. The TPRL rate for singleton pregnancies was 26.2 per 1,000 births for the study period. The TPRL rates in 1986 and 1993 were 36.7 and 30.5 per 1,000 deliveries. Infection is now the leading primary cause of death, followed by spontaneous PTL, APH and IUGR. During the previous two study periods, APH was the leading primary cause of death, followed by spontaneous PTL. Unexplained IUDs ranked third in 1986, fourth in 1993 and seventh in this study because of the availability of placental histology. Placental histology reports changed 21.3% of the primary causes of death.