\documentclass[10pt]{article}

\usepackage{fullpage}
\usepackage{setspace}
\usepackage{parskip}
\usepackage{titlesec}
\usepackage[section]{placeins}
\usepackage{xcolor}
\usepackage{breakcites}
\usepackage{lineno}
\usepackage{hyphenat}





\PassOptionsToPackage{hyphens}{url}
\usepackage[colorlinks = true,
            linkcolor = blue,
            urlcolor  = blue,
            citecolor = blue,
            anchorcolor = blue]{hyperref}
\usepackage{etoolbox}
\makeatletter
\patchcmd\@combinedblfloats{\box\@outputbox}{\unvbox\@outputbox}{}{%
  \errmessage{\noexpand\@combinedblfloats could not be patched}%
}%
\makeatother


\usepackage{natbib}




\renewenvironment{abstract}
  {{\bfseries\noindent{\abstractname}\par\nobreak}\footnotesize}
  {\bigskip}

\titlespacing{\section}{0pt}{*3}{*1}
\titlespacing{\subsection}{0pt}{*2}{*0.5}
\titlespacing{\subsubsection}{0pt}{*1.5}{0pt}


\usepackage{authblk}


\usepackage{graphicx}
\usepackage[space]{grffile}
\usepackage{latexsym}
\usepackage{textcomp}
\usepackage{longtable}
\usepackage{tabulary}
\usepackage{booktabs,array,multirow}
\usepackage{amsfonts,amsmath,amssymb}
\providecommand\citet{\cite}
\providecommand\citep{\cite}
\providecommand\citealt{\cite}
% You can conditionalize code for latexml or normal latex using this.
\newif\iflatexml\latexmlfalse
\providecommand{\tightlist}{\setlength{\itemsep}{0pt}\setlength{\parskip}{0pt}}%

\AtBeginDocument{\DeclareGraphicsExtensions{.pdf,.PDF,.eps,.EPS,.png,.PNG,.tif,.TIF,.jpg,.JPG,.jpeg,.JPEG}}

\usepackage[utf8]{inputenc}
\usepackage[ngerman,english]{babel}



\usepackage{float}








\begin{document}

\title{Cause for optimism in mild hypoxic ischaemic hypoxic encephalopathy}



\author[1]{William Curtin}%
\affil[1]{Penn State College of Medicine}%


\vspace{-1em}



  
  \date{May 26, 2024}


\begingroup
\let\center\flushleft
\let\endcenter\endflushleft
\maketitle
\endgroup








\sloppy


\textbf{Title Page}

\textbf{Cause for optimism in mild hypoxic ischaemic hypoxic
encephalopathy}

William M. Curtin, MD, corresponding author

Division of Maternal-Fetal Medicine, Department of Obstetrics and
Gynecology \& Pathology and Laboratory Medicine, Penn State College of
Medicine, Penn State Health, Milton S. Hershey Medical Center, Hershey,
PA, USA

wcurtin@pennstatehealth.psu.edu

Mail code H103

500 University Dr, PO Box 850

Hershey, PA 17033-0850

Maternal-Fetal Medicine, Rm C3620

Phone 717-531-8142/Option \#5

Fax 717-531-0947

\textbf{Acknowledgements:} none

\textbf{Disclosure of Interests:} The author has no conflicts nor
competing interests to disclose, financial or otherwise, in connection
with this manuscript\textbf{.}

\textbf{Contribution to Authorship:} Dr. Curtin alone completed review
of the T\selectlanguage{ngerman}örn et al. final manuscript entitled ``Outcomes in children
after mild neonatal hypoxic ischaemic encephalopathy: A population-based
cohort study'' The writings and opinions expressed in his mini
commentary are solely the work of Dr. Curtin.

\textbf{Details of Ethics Approval:} not applicable at our institution's
IRB as a commentary is not considered research and does not involve
human subjects.

\textbf{Funding:} Dr. Curtin neither received nor utilized any funds in
writing this mini commentary.

The objective of the study by Törn et al. was to determine if mild
hypoxic ischaemic encephalopathy (HIE) was associated with severe
neurological outcomes utilizing a population-based approach facilitated
by five linked Swedish national databases. The rationale given was that
while moderate to severe HIE is known to be associated with significant
neurological morbidity, long-term disability, and mortality in children,
less is known about mild HIE. The authors note that half of the cases of
HIE are mild and they cite a systematic review of 250 infants (Conway
JM, et al. \emph{Early human development} . 2018; 120:80-7) showing a
22\% prevalence of abnormal neurological outcomes in this disorder.
There is therefore potential for significant burden of disease in mild
HIE. Törn et al. chose a primary composite outcome that included
cerebral palsy, epilepsy, mental retardation and death in children with
mild HIE and non HIE cohorts followed up to 6 years of age. With a
median follow-up of 3.3 years of age, 17 of 414 (4.1\%) and 4786 of
504,661 (0.95\%), in the mild HIE and non HIE cohorts respectively, had
the composite outcome with an adjusted hazard ratio of 3.85 (95\% CI:
2.27-6.50)

In 1976 Sarnat and Sarnat reported clinical and EEG features of 21
neonates at term who experienced ischaemic-anoxic encephalopathy (Sarnat
HB et al. \emph{Arch Neurol.} 1976; 33:696--705). This temporal
classification divided the infants into three progressively
deteriorating stages. Fast forward to the current millennium and
Sarnat's original classification is used to differentiate between
infants with mild and moderate/severe HIE, the latter two categories
benefiting from therapeutic hypothermia (Jacobs SE et al. \emph{Cochrane
Database Syst Rev.} 2013, Issue 1. Art. No.: CD003311). Seven infants
with moderate or severe HIE is the number needed to treat (NNT) to
prevent one adverse neurological outcome.

Therapeutic hypothermia is not standard of care in mild HIE; however, in
a survey of neonatal clinicians from 35 countries the vast majority
would support a large randomized controlled trial to examine
neurodevelopmental outcomes (Singla M, et al. \emph{Neonatology.} 2022;
119:712-718). The results from this methodical Swedish cohort study
provide data that can be used to direct further research. The composite
outcomes in HIE are lower than expected, and one could infer similar
outcomes in high resource settings. The data are reassuring and will be
useful for clinicians in counseling and reassuring parents with infants
affected by mild HIE. Regarding a randomized controlled trial of
therapeutic hypothermia in mild HIE: it would appear, based on the data
provided by Törn et al., if we hypothesize this therapy would result in
a 50\% reduction in the composite outcome, the NNT would be
approximately 50. This compares unfavorably to the NNT of 7 in
moderate/severe HIE. Perhaps, further insight could be gained by review
of individual patient data, particularly with respect to antenatal and
neonatal course, imaging, EEG, and biochemical data in order to identify
a subset that might benefit from therapeutic hypothermia or other novel
therapy.

Word count: 490

\selectlanguage{english}
\FloatBarrier
\end{document}

