Relevance of augmented kisspeptin signaling through H364 KISS1R in central precocious puberty.

Understanding the pathophysiology of idiopathic central precocious puberty (ICPP) is essential, in view of its consequences on reproductive health and metabolic disorders in later life. Towards this, estimation of circulating levels of the neuropeptides, viz; Kisspeptin (Kp-10), Neurokinin B (NKB) and Neuropeptide Y (NPY), acting upstream to Gonadotropin-Releasing Hormone (GnRH), has shown promise. Insights can also be gained from functional studies on genetic variations implicated in ICPP. This study investigated the pathophysiology of ICPP in a girl by exploring the therapeutic relevance of the circulating levels of Kp-10, NKB, NPY and characterizing the nonsynonymous KISS1R variant, L364H, that she harbours, in a homozygous condition. Plasma levels of Kp-10, NKB and NPY before and after GnRH analog (GnRHa) treatment, were determined by ELISA. It was observed that GnRHa treatment resulted in suppression of circulating levels of Kp-10, NKB and NPY. Further, the H364 variant in KISS1R was generated by site directed mutagenesis. Post transient transfection of either L364 or H364 KISS1R variant in CHO cells, receptor expression was ascertained by western blotting, indirect immunofluorescence and flow cytometry. Kp-10 stimulated signalling response was also determined by phospho-ERK and inositol phosphate production. Structure-function studies revealed that, although the receptor expression in H364 KISS1R was comparable to L364 KISS1R, there was an enhanced signalling response through this variant at high doses of Kp-10. Thus, elevated levels of Kp-10, acting through H364 KISS1R, contributed to the manifestation of ICPP, providing further evidence that dysregulation of Kp-10/KISS1R axis impacts the onset of puberty.

Outcomes in neonates born to mothers with COVID-19 during the second wave in India.

COVID-19 pandemic has affected all age groups globally including pregnant women and their neonates. The aim of the study was to understand outcomes in neonates of mothers with COVID-19 during the first and second waves of COVID-19 pandemic. A retrospective analysis of 2524 neonates born to SARS-CoV-2-infected mothers was conducted during the first wave (n = 1782) and second wave (n = 742) of the COVID-19 pandemic at five study sites of the PregCovid registry in Maharashtra, India. A significant difference was noted in preterm birth, which was higher in the second wave (15.0%, 111/742) compared to the first wave (7.8%, 139/1782) (P < 0.001). The proportion of neonates requiring NICU admission was significantly higher in the second wave (19.0%, 141/742) as compared to that in the first wave (14.8%, 264/1782) (P < 0.05). On comparing regional differences, significantly higher neonatal complications were reported from Mumbai metropolitan region (P < 0.05). During the second wave of COVID-19, birth asphyxia and prematurity were 3.8- and 2.1-fold higher respectively (P < 0.001). Neonatal resuscitation at birth was significantly higher in second wave (3.4%, 25/742 vs 1.8%, 32/1782) (P < 0.05). The prevalence of SARS-CoV-2 infection in neonates was comparable (4.2% vs 4.6%) with no significant difference between the two waves. CONCLUSION: Higher incidence of adverse outcomes in neonates born to SARS-CoV-2-infected mothers in the second wave of COVID-19 as compared to the first wave. TRIAL REGISTRATION: PregCovid study is registered with the Clinical Trial Registry of India (CTRI/2020/05/025423, Registered on 28/05/2020). WHAT IS KNOWN: • The second wave of COVID-19 was more lethal to pregnant women than the first wave. Newborns are at risk of developing complications. WHAT IS NEW: • Birth asphyxia, prematurity, and neonatal resuscitation at birth were significantly higher in the second wave as compared to those in the first wave of the COVID-19 pandemic in India.

Protocol for a prospective, hospital-based registry of pregnant women with SARS-CoV-2 infection in India: PregCovid Registry study.

INTRODUCTION: Pregnant women are at increased risk of contracting COVID-19 due to several factors and therefore require special attention. However, the consequences of the COVID-19 pandemic on pregnant women and their newborns remain uncharted. The PregCovid registry aims to document the impact of SARS-CoV-2 infection on pregnant, postpartum women and their newborns. The aim of the registry is also to determine mother-to-child transmission of SARS-CoV-2 infection in India. METHODS AND ANALYSIS: PregCovid is a hospital-based registry for capturing information of pregnant, postpartum women with COVID-19 and their newborns in India. Medical case records of pregnant and postpartum women with a laboratory-confirmed diagnosis of COVID-19 will be captured in real-time using an online electronic patient record software. The data analysis will be carried out for symptoms, the severity of COVID-19, pregnancy complications, maternal morbidity and mortality, neonatal complications, mother-to-child transmission, etc. Data analysis will be carried out for different waves of the COVID-19 pandemic for rapid response and developing strategies well in advance to manage pregnant women infected with SARS-CoV-2. The evidence generated from the registry will be regularly shared with the appropriate authorities for policy decisions. Thus, the registry data may be useful for planning the strategies for better management of pregnant women with COVID-19. ETHICS AND DISSEMINATION: The study has been approved by the Institutional Ethics Committees of all the participating study sites under the Medical Education and Drugs Department, Government of Maharashtra, Topiwala National Medical College & BYL Nair Charitable Hospital, Mumbai and ICMR-National Institute for Research in Reproductive and Child Health, Mumbai, India. The results from this study will be disseminated with local, state, and national health authorities, collaborators and the general population on the study website (https://pregcovid.com) as well as dissemination through scientific meetings and publications. TRIAL REGISTRATION NUMBER: CTRI/2020/05/025423.