A genomic autopsy identifies causes of perinatal death and provides options to prevent recurrence

Perinatal death, of a fetus or newborn, is a devastating event for families. Following nationwide multicentre recruitment, we assessed ‘genomic autopsy’ as an adjunct to standard autopsy for 200 families who experienced perinatal death, and provided a definite or candidate genetic diagnosis in 105 families. From this understudied cohort, half of the (candidate) diagnoses were phenotype expansions or novel disease genes, revealing previously unknown in-utero presentations of existing developmental disorders, and genomic disorders that are likely incompatible with life. Among the definite diagnoses, 43% were recessively or dominantly inherited, posing a 25% or 50% recurrence risk for future pregnancies. Ten families used their diagnosis for preimplantation or prenatal diagnosis of 12 pregnancies, facilitating the delivery of ten healthy newborns and management of two affected pregnancies. We emphasize the clinical importance of genomic investigations of perinatal death, with short turn-around times, enabling accurate counselling and options for families to prevent recurrence.

Which chart and which cut-point: deciding on the INTERGROWTH, World Health Organization, or Hadlock fetal growth chart

Objective To determine how various centile cut points on the INTERGROWTH-21st (INTERGROWTH), World Health Organization (WHO), and Hadlock fetal growth charts predict perinatal morbidity/mortality, and how this relates to choosing a fetal growth chart for clinical use. Methods We linked antenatal ultrasound measurements for fetuses > 28 weeks’ gestation from the British Columbia Women’s hospital ultrasound unit with the provincial perinatal database. We estimated the risk of perinatal morbidity/mortality (decreased cord pH, neonatal seizures, hypoglycemia, and perinatal death) associated with select centiles on each fetal growth chart (the 3rd, 10th, the centile identifying 10% of the population, and the optimal cut-point by Youden’s Index), and determined how well each centile predicted perinatal morbidity/mortality. Results Among 10,366 pregnancies, the 10th centile cut-point had a sensitivity of 11% (95% CI 8, 14), 13% (95% CI 10, 16), and 12% (95% CI 10, 16), to detect fetuses with perinatal morbidity/mortality on the INTERGROWTH, WHO, and Hadlock charts, respectively. All charts performed similarly in predicting perinatal morbidity/mortality (area under the curve [AUC] =0.54 for all three charts). The statistically optimal cut-points were the 39th, 31st, and 32nd centiles on the INTERGROWTH, WHO, and Hadlock charts respectively. Conclusion The INTERGROWTH, WHO, and Hadlock fetal growth charts performed similarly in predicting perinatal morbidity/mortality, even when evaluating multiple cut points. Deciding which cut-point and chart to use may be guided by other considerations such as impact on workflow and how the chart was derived.

Low Birthweight as a Risk Factor for Non-communicable Diseases in Adults

According to studies undertaken over the past 40 years, low birthweight (LBW) is not only a significant predictor of perinatal death and morbidity, but also increases the risk of chronic non-communicable diseases (NCDs) in adulthood. The purpose of this paper is to summarize the research on LBW as a risk factor for NCDs in adults. The Barker hypothesis was based on the finding that adults with an LBW or an unhealthy intrauterine environment, as well as a rapid catch-up, die due to NCDs. Over the last few decades, terminology such as thrifty genes, fetal programming, developmental origins of health and disease (DOHaD), and epigenetic factors have been coined. The most common NCDs include cardiovascular disease, diabetes mellitus type 2 (DMT2), hypertension (HT), dyslipidemia, proteinuria, and chronic kidney disease (CKD). Studies in mothers who experienced famine and those that solely reported birth weight as a risk factor for mortality support the concept. Although the etiology of NCD is unknown, Barry Brenner explained the notion of a low glomerular number (nGlom) in LBW children, followed by the progression to hyperfiltration as the physiopathologic etiology of HT and CKD in adults based on Guyton's renal physiology work. Autopsies of several ethnic groups have revealed anatomopathologic evidence in fetuses and adult kidneys. Because of the renal reserve, demonstrating renal function in proportion to renal volume in vivo is more difficult in adults. The greatest impact of these theories can be seen in pediatrics and obstetrics practice.

Criminal of Adverse Pregnant Outcomes: A Perspective From Thyroid Hormone Disturbance Caused by SARS-CoV-2

Nowadays, emerging evidence has shown adverse pregnancy outcomes, including preterm birth, preeclampsia, cesarean, and perinatal death, occurring in pregnant women after getting infected by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), but the underlying mechanisms remain elusive. Thyroid hormone disturbance has been unveiled consistently in various studies. As commonly known, thyroid hormone is vital for promoting pregnancy and optimal fetal growth and development. Even mild thyroid dysfunction can cause adverse pregnancy outcomes. We explored and summarized possible mechanisms of thyroid hormone abnormality in pregnant women after coronavirus disease 2019 (COVID-19) infection and made a scientific thypothesis that adverse pregnancy outcomes can be the result of thyroid hormone disorder during COVID-19. In which case, we accentuate the importance of thyroid hormone surveillance for COVID-19-infected pregnant women.

Prevalence of Iron Deficiency Anemia Among Pregnant Women in Zawia, Libya

Background: anemia is the most nutritional disorders affecting pregnant women particularly iron deficiency anemia IDA.IDA threatened the mother islife and considered as an established risk factor for intrauterine growth retardation, leading on too poor neonatal health and perinatal death. Objective: the aim of the study was to estimate the prevalence of IDA in Zawia city according to their hemoglobin level, age, and education. Methods and materials: the study was carried out in different centers in Zawia city, it was comprised 82 pregnant women aged 19-42 years, at various stage of pregnancy, out of 82 women 54 fulfilled the criteria, pregnant women who weren’t have known about their hemoglobin, they were excluded. The data collected by using of a questioner including 30 questions were asked to participants face to face. Data analysis: after the date is collected it classified and analyzed to determine the percentage of pregnant women suffering from iron deficiency anemia. The data analyzed by using of Microsoft excel (2013). Results: the prevalence of anemia in the present study was 85.18%, This prevalence was almost consistent with studies conducted in ZAWIA city over the last years, from the current study it is evidence that pregnant women had poor knowledge regarding main risk of IDA as well as poor practices for IDA prevention.

Perinatal Death Surveillance and Response: A Secondary Analysis of Nepal’s Efforts

This paper presents Nepal’s experience regarding perinatal death surveillance and the country’s response in reducing preventable perinatal deaths. In developing this paper, evidence of perinatal mortality in Nepal is brought from secondary sources, mainly the assessment report of Maternal and Perinatal Death Surveillance and Response (MPDSR) system. As of 2019, this initiative has been implemented in 77 hospitals across Nepal. Challenges and barriers in implementing the MPDSR system need to be brought to attention, as the system is being scaled up to 110 hospitals. Data from the Perinatal Death Review revealed that 72% of the maternal deaths occurred during the post-partum period, due to (i) post-partum haemorrhage, (ii) hypertensive disorder, (iii) pregnancy-related infections, and (iv) non-obstetric causes. In 70% of the cases such deaths could have been prevented. Majority of perinatal deaths, at 71%, were stillbirths, mainly due to low child weight of less than 2500 grams. In conclusion, there is urgent need for the national guidelines for MPDSR system to be amended, additional and continued training provision to the health workforce, improvement in the coordination and feedback mechanism, and strengthening of the information management system. Key words: MPDSR system; Perinatal Death Review; Nepal; Perinatal Mortality; Stillbirth

Intra-Hepatic Cholestasis of Pregnancy and Its Consequences: A Review

Background: The most common cause of liver illness in pregnancy is intrahepatic cholestasis (IHCP). It has a varying incidence due to geographic variance; factors such as advanced age, multiple pregnancy, family history, and previous pregnancy cholestasis have demonstrated a higher prevalence in these patients. Cholestasis in pregnancy has an aetiology that is currently unknown. It usually occurs after ovarian hyperstimulation syndrome in early pregnancy and coincides with growing oestrogen levels in the second half of pregnancy [1]. The ABCB4 gene mutation is largely associated in a subtype of progressive familial intrahepatic cholestasis, where disease clustering in first-degree relatives increases hereditary predisposition. Itchy palms and soles with elevated liver enzymes and bile acids are the most common symptoms. Some of the reported maternal problems in these patients include preterm labour, HELLP syndrome, acute fatty liver of pregnancy, and postpartum haemorrhage [2]. There are no precise antenatal foetal monitoring tests that can predict foetal fatalities in the womb. To reduce perinatal death with expectant treatment beyond this gestation, it is recommended that a pregnancy be terminated near 36–37 weeks of pregnancy.

Benefits of not smoking during pregnancy for non-Aboriginal women and their babies in New South Wales, Australia: a record linkage study

BackgroundSmoking rates among pregnant women in New South Wales (NSW) have plateaued at 8-9%. To inform relevant smoking reduction efforts, we aimed to quantify the benefits of not smoking during pregnancy for non-Aboriginal NSW mothers and their babies. The benefits of not smoking during pregnancy for NSW Aboriginal mothers have previously been described. These data are important inputs in modelling health and economic impacts of smoking cessation interventions. MethodsThis population-based cohort study used linked-data from routinely collected data sets. Not smoking during pregnancy was the exposure of interest among all NSW non-Aboriginal women who became mothers of singleton babies in 2012-2016. Unadjusted and adjusted relative risks (aRR) were used to examine associations between not smoking during pregnancy and adverse outcomes including severe morbidity, inter-hospital transfer, perinatal death, preterm birth and small-for-gestational age. Population attributable fractions (PAFs) were calculated to quantify adverse perinatal outcomes avoided in the population if all mothers were non-smokers. ResultsCompared with babies born to mothers who smoked during pregnancy, babies born to non-smoking mothers had a lower risk of all adverse perinatal outcomes including perinatal death (aRR}=0.68, 95%CI 0.61-0.76), preterm birth (aRR=0.58, 95%CI 0.56-0.61) and small-for-gestational age (aRR=0.48, 95%CI 0.47-0.50). PAFs(%) were 3.9% for perinatal death, 5.6% for preterm birth and 7.3% for small-for-gestational-age. Compared with women who smoked during pregnancy (n=36,518), those who did not smoke (n=413,072) had a lower risk of suffering severe maternal morbidity (aRR=0.87, 95%CI 0.81-0.93) and being transferred to another hospital (aRR=0.92, 95%CI 0.86-0.99). ConclusionsMothers who reported not smoking during pregnancy had a small reduction in their risk of morbidity and of being transferred to another hospital whilst their babies had substantially reduced risks of all adverse perinatal outcomes. Results have implications for clinician training, clinical care standards, and performance management.