Risk Factors and Short Term Morbidities Associated With Term-Small for Gestational Age Babies Delivered at Nepalgunj Medical College

Introduction: Small for gestational age (SGA) refers to birth weight of neonates less than 10th percentile for gestational age or 2nd standard deviation below the population norms on the growth charts. Aims: To identify common risk factors and common morbidities for small for gestational age babies. Methods: This is a cross sectional descriptive study and it has been conducted at Department of pediatrics, Nepalgunj Medical college which is a tertiary level teaching hospital located in western part of Nepal. All term small for gestational age neonates born during study period from January 2020 to December 2020 were included. Detailed baseline demographic and clinical profile has been collected and recorded in the predesigned Proforma. Results: The most common risk factors associated with small for gestational age babies in our study were maternal hypertension (14.6%) , maternal GDM(9.6%), Urinary Tract Infection (UTI) in 1st or 2nd trimester of pregnancy, maternal anemia, smoking, alcohol consumption, hypothyroidism and congenital heart disease. The most common short term complications associated with Small for gestational age babies were hypoglycemia and Meconium aspiration syndrome. Conclusion: The most common risk factors associated with Small for gestational age babies in our study were maternal hypertension, maternal Gestational diabetes Mellitus (GDM), Urinary Tract Infection in 1st or 2nd trimester of pregnancy, maternal anemia, smoking, alcohol consumption, hypothyroidism and congenital heart disease. The most common short term complications associated with Small for gestational age babies were hypoglycemia and Meconium aspiration syndrome (MAS).

Upregulation of Fibrinogen-Like 1 Expression Contributes to Reducing the Progression of Preeclampsia

Fibrinogen-like 1 (FGL1) is involved in liver injury and liver regeneration, but its role in placenta and preeclampsia (PE) remains unclear. We assessed FGL1 expression in serum and placenta from L-NAME-induced PE-like mouse and in women with (n = 38) and without (n = 42) PE. For the mouse study, pregnant C57Bl/6 mouse (n = 6/group) were subcutaneously administered L-NAME with or without FGL1 once daily starting on days 7–14 of pregnancy and were sacrificed on gestational day (GD) 20. Maternal body weight, blood pressure, and urinary protein were assessed during GDs 8–20. The weight and length of the placenta and fetus were assessed. The placental structure was evaluated using hematoxylin staining. In the human study, the sera of the pregnant women during the late trimester were assessed with enzyme-linked immunosorbent assays (ELISAs). FGL1 expression in human trophoblast cell lines under L-NAME stimulation was measured using Western blotting and immunofluorescence staining. The detected FGL1 protein levels in serum and placenta were both significantly upregulated in patients and mouse with PE compared with those in the non-PE groups. FGL1 treatment decreased maternal hypertension and proteinuria, decreased fetal weight in mouse with PE, downregulated proinflammatory cytokine (interleukin-1b and interleukin-6) levels, and maintained the balance between antiangiogenic (fms-like tyrosine kinase-1) and proangiogenic (placental growth factor) substances in the placenta. L-NAME-upregulated FGL1 expression was inhibited following overexpression of FoxO3a. In summary, FoxO3a reduction is a potential pathophysiological mechanism leading to upregulated placental FGL1 expression that may play a pivotal role in preventing PE progression.

Placenta mediates the effect of maternal hypertension polygenic score on offspring birth weight: a study of birth cohort with fetal growth velocity data

Background Low birth weight (LBW) and fetal growth restriction are associated with the development of cardio-metabolic diseases later in life. A recent Mendelian randomization study concluded that the susceptibility of LBW infants to develop hypertension during adulthood is due to the inheritance of hypertension genes from the mother and not to an unfavorable intrauterine environment. Therein, a negative linear association has been assumed between genetically estimated maternal blood pressure (BP) and birth weight, while the observed relationship between maternal BP and birth weight is substantially different from that assumption. As many hypertension genes are likely involved in vasculature development and function, we hypothesized that BP-increasing genetic variants could affect birth weight by reducing the growth of the placenta, a highly vascular organ, without overtly elevating the maternal BP. Methods Using a birth cohort in the Japanese population possessing time-series fetal growth velocity data as a target and a GWAS summary statistics of BioBank Japan as a base data, we performed polygenic score (PGS) analyses for systolic BP (SBP), diastolic BP, mean arterial pressure, and pulse pressure. A causal mediation analysis was performed to assess the meditation effect of placental weight on birth weight reduced by maternal BP-increasing PGS. Maternal genetic risk score constituted of only “vasculature-related” BP single nucleotide polymorphisms (SNPs) was constructed to examine the involvement of vascular genes in the mediation effect of placental weight. We identified gestational week in which maternal SBP-increasing PGS significantly decreased fetal growth velocity. Results We observed that maternal SBP-increasing PGS was negatively associated with offspring birth weight. A causal mediation analysis revealed that a large proportion of the total maternal PGS effect on birth weight was mediated by placental weight. The placental mediation effect was remarkable when genetic risk score was constituted of “vasculature-related” BP SNPs. The inverse association between maternal SBP PGS and fetal growth velocity only became apparent in late gestation. Conclusions Our study suggests that maternal hypertension genes are strongly associated with placental growth and that fetal growth inhibition is induced through the intrauterine environment established by the placenta.

Frequency of Thrombocytopenia in Neonatal Sepsis

Objective: To determine the frequency of neonatal thrombocytopenia among patients presented with sepsis at tertiary care Hospital. Methodology: This cross-sectional study was conducted at the Department of pediatrics SKBZ/CMH Muzaffarabad, during six months from September 2018 to March 2019. All the diagnosed septic neonates, age < 28 days and either gender were included. Their basic demographic data like age and gender, along with their contact details were taken. The sample of blood was sent in blood culture bottles to hospital laboratory to confirm bacterial growth, that was diagnosed as sepsis. Blood sample was sent to the hospital also to diagnose thrombocytopenia. Reports were consulted by the pathologist. All the data were collected by a structured study proforma. All data were entered and analyzed with the help of SPSS version 22. Results: The mean age of patients was 8.92 ± 5.40 days with minimum and maximum age as 1 and 27 days. There were 117(47.56%) males and 129(52.44%) female cases. A total of 40(16.26%) cases had their maternal hypertension, 54(21.95%) neonates had gram + and 157(63.82%) neonates had Gram negative. A total of 63(25.61%) cases had thrombocytopenia while 183(74.39%) neonates were seen without thrombocytopenia. The frequency of thrombocytopenia was statistically insignificant according to gender and types of culture (p->0.05). Conclusion: It is concluded that frequency of thrombocytopenia in neonatal sepsis was found in a quarter of the cases. In neonatal sepsis, thrombocytopenia must be ruled out at patient’s presentation and must be treated as early as possible as thrombocytopenia is an independent risk factor for sepsis-associated mortality. Keywords: Incidence, thrombocytopenia, neonatal sepsis

Protective effects of Zingiber officinale extract on myocardium and placenta against labetalol-induced histopathological, immune-histochemical, and ultrastructural alterations in pregnant rats

Background Labetalol is an antihypertensive drug commonly used in obstetrics for both long-term treatment and the acute management of severe maternal hypertension. However, there have not been published articles about the effects of labetalol on the myocardium and the placenta. This study aimed to estimate the histological, immune-histochemical, and ultrastructural cardio- and placental-toxicity of labetalol administration and the effectiveness of ginger against this toxicity in pregnant rats. Labetalol was daily administrated orally with or without ginger at a dose of 300 mg/kg and 200 mg/kg, respectively, during the gestation days 6 to 20. Results In the labetalol-administrated group, the myocardium displayed histological and ultrastructure destructive changes and a significant increase in caspase-3 expression. Labetalol also decreased the placental weight compared with the control group, caused marked degeneration and disorganization of their architecture, and increased caspase-3 expression. Co-administration of ginger after labetalol highly ameliorates the adverse effect of labetalol on both cardiac and placental tissues. Conclusions It is concluded that ginger can mitigate cardiac and placental toxicity induced by labetalol administration into pregnant rats.

Protein Phosphatase 2A Activation via ApoER2 in Trophoblasts Drives Preeclampsia in a Mouse Model of the Antiphospholipid Syndrome

Rationale: Preeclampsia (PE) is a potentially life-threatening, placenta-based hypertensive disorder during pregnancy, and the antiphospholipid syndrome (APS) frequently leads to PE. APS pregnancies are also complicated by fetal demise and intrauterine growth restriction (IUGR). Objective: Here we determined how the circulating antiphospholipid antibodies (aPL) characteristic of APS alter placental trophoblast function to cause PE and also endanger the fetus. Methods and Results: Experiments were performed in mice, in cultured human trophoblasts, and in human placenta samples. Effects of aPL and IgG from healthy subjects were compared. Based on prior findings in culture, in vivo studies were done in mice deficient in apolipoprotein E receptor 2 (ApoER2) in trophoblasts. Endpoints in tissues and cells were determined by enzymatic assay, Q-PCR, ELISA or immunoblotting. Whereas in wild-type mice aPL caused maternal hypertension and proteinuria, fetal demise and IUGR, mice lacking trophoblast ApoER2 were protected. In culture aPL attenuated trophoblast proliferation and migration via an ApoER2-related protein complex comprised of the protein phosphatase PP2A, Dab2, and JIP4. Via trophoblast ApoER2 in mice and in culture, aPL stimulated PP2A activity, leading to MMP14 and HIF1alpha upregulation and increased soluble endoglin (sEng) production. HIF1alpha and sEng upregulation was related to PP2A desphosphorylation of PHD2. In mice PP2A inhibition prevented aPL-induced maternal hypertension and proteinuria, and fetal demise and IUGR. Placentas from APS patients displayed PP2A hyperactivation, PHD2 dephosphorylation and HIF1α upregulation, and these findings were generalizable to placentas of women with PE from causes other from APS. Conclusions: In APS pregnancies trophoblasts are the critical cell target of aPL, and via ApoER2-dependent PP2A activation, aPL cause PE through MMP14 upregulation and PHD2 dephosphorylation leading to HIF1 and sEng upregulation. Moreover, parallel processes may be operative in PE in non-APS patients. Interventions targeting PP2A may provide novel means to combat APS-related PE and PE unrelated to APS.

Circulating Maternal sFLT1 (Soluble fms-Like Tyrosine Kinase-1) Is Sufficient to Impair Spiral Arterial Remodeling in a Preeclampsia Mouse Model

One driving factor for developing preeclampsia—a pregnancy disorder, often associated with poor spiral artery (SpA)-remodeling and fetal growth restriction—is the anti-angiogenic sFLT1 (soluble fms-like tyrosine kinase-1), which is found to be highly upregulated in preeclampsia patients. The sFLT1-mediated endothelial dysfunction is a common theory for the manifestation of maternal preeclampsia symptoms. However, the influence of sFLT1 on SpA-remodeling and the link between placental and maternal preeclampsia symptoms is less understood. To dissect the hsFLT1 (human sFLT1) effects on maternal and/or fetoplacental physiology in preeclampsia, sFLT1-transgenic mice with systemic hsFLT1 overexpression from midgestation onwards were used. SpA-remodeling was analyzed on histological and molecular level in placental/mesometrial triangle tissues. Maternal kidney and aorta morphology was investigated, combined with blood pressure measurements via telemetry. hsFLT1 overexpression resulted in maternal hypertension, aortic wall thickening, and elastin breakdown. Furthermore, maternal kidneys showed glomerular endotheliosis, podocyte damage, and proteinuria. preeclampsia symptoms were combined with fetal growth restriction already at the end of the second trimester and SpA-remodeling was strongly impaired as shown by persisted vascular smooth muscle cells. This phenotype was associated with shallow trophoblast invasion, delayed presence of uterine natural killer cells, and altered lymphatic angiogenesis. Overall, this study showed that circulating maternal hsFLT1 is sufficient to induce typical maternal preeclampsia-like symptoms in mice and impair the SpA-remodeling independent from the fetoplacental compartment, revealing new insights into the interaction between the placental and maternal contribution of preeclampsia.

Maternal and fetal characteristics and causes of stillbirth in a tertiary care hospital of Nepal: secondary analysis of registry-based surveillance data

ObjectivesStillbirth is one of the vital indicators of quality care. This study aimed to determine maternal-fetal characteristics and causes of stillbirth in Nepal.DesignSecondary analysis of single-centred registry-based surveillance data.SettingThe study was conducted at the Department of Obstetrics and Gynecology, Chitwan Medical College Teaching Hospital, a tertiary care hospital located in Bharatpur, Nepal.ParticipantsAll deliveries of intrauterine fetal death, at or beyond 22 weeks’ period of gestation and/or birth weight of 500 g or more, conducted between 16 July 2017 and 15 July 2019 were included in the study.Main outcome measuresThe primary outcome measure of this study was stillbirth, and the secondary outcome measures were maternal and fetal characteristics and cause of stillbirth.ResultsOut of 5282 institutional deliveries conducted over 2 years, 79 (1.5%) were stillbirths, which gives the stillbirth rate of 15 per 1000 births. Of them, the majority (75; 94.9%) were vaginal delivery and only four (5.1%) were caesarean section (p<0.0001). The proportion of the macerated type of stillbirth was more than that of the fresh type (58.2% vs 41.8%; p=0.13). Only half of the mothers who experienced stillbirth had received antenatal care. While the cause of fetal death was unknown in one-third of cases (31.6%; 25/79), among likely causes, the most common was maternal hypertension (29.1%), followed by intrauterine infection (8.9%) and fetal malpresentation (7.6%). Four out of 79 stillbirths (5%) had a birth defect.ConclusionHigh rate of stillbirths in Nepal could be due to the lack of quality antenatal care. The country’s health systems should be strengthened so that pregnancy-related risks such as maternal hypertension and infections are identified early on. Upgrading mothers’ hygiene and health awareness is equally crucial in reducing fetal deaths in low-resource settings.