Does anti-HPA-1a affect birthweight in fetal and neonatal alloimmune thrombocytopenia?
Margaret McKelvy
Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, Weill Cornell Medicine, New York, New York, USA
Search for more papers by this authorSrishti Tyagi
Norton College of Medicine, SUNY Upstate Medical University, Syracuse, New York, USA
Search for more papers by this authorEmilie Vander Haar
Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, Weill Cornell Medicine, New York, New York, USA
Search for more papers by this authorMadhavi Lakkaraja
Department of Pediatrics, Fred Hutchinson Cancer Center, Department of Pediatrics, University of Washington School of Medicine, Seattle, USA
Search for more papers by this authorTim Tomy
Department of Pediatrics, Hurley Medical Center, Flint, Michigan, USA
Search for more papers by this authorAmihai Rottenstreich
Department of Obstetrics and Gynecology, Laboratory of Blood and Vascular Biology, Rockefeller University, New York, New York, USA
Division of Maternal- Fetal Medicine, Department of Obstetrics and Gynecology, Zucker School of Medicine at Hofstra/Northwell, New York, New York, USA
Search for more papers by this authorRick Kapur
Department of Experimental Immunohematology, Sanquin Research, and Landsteiner Laboratory, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands
Search for more papers by this authorHuiying Zhi
Department of Pathology, Versiti Blood Center of Wisconsin, Blood Research Institute, Milwaukee, Wisconsin, USA
Search for more papers by this authorDebra Newman
Department of Pathology, Versiti Blood Center of Wisconsin, Blood Research Institute, Milwaukee, Wisconsin, USA
Search for more papers by this authorNina Scatz-Siemers
Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, New York, USA
Search for more papers by this authorCorresponding Author
James Bussel
Department of Pediatrics, Weill Cornell Medicine, New York, New York, USA
Correspondence
James Bussel, Department of Pediatrics, Weill Cornell Medicine, 525 E 68th St, Suite M-706, New York, NY 10002, USA.
Email: [email protected]
Search for more papers by this authorMargaret McKelvy
Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, Weill Cornell Medicine, New York, New York, USA
Search for more papers by this authorSrishti Tyagi
Norton College of Medicine, SUNY Upstate Medical University, Syracuse, New York, USA
Search for more papers by this authorEmilie Vander Haar
Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, Weill Cornell Medicine, New York, New York, USA
Search for more papers by this authorMadhavi Lakkaraja
Department of Pediatrics, Fred Hutchinson Cancer Center, Department of Pediatrics, University of Washington School of Medicine, Seattle, USA
Search for more papers by this authorTim Tomy
Department of Pediatrics, Hurley Medical Center, Flint, Michigan, USA
Search for more papers by this authorAmihai Rottenstreich
Department of Obstetrics and Gynecology, Laboratory of Blood and Vascular Biology, Rockefeller University, New York, New York, USA
Division of Maternal- Fetal Medicine, Department of Obstetrics and Gynecology, Zucker School of Medicine at Hofstra/Northwell, New York, New York, USA
Search for more papers by this authorRick Kapur
Department of Experimental Immunohematology, Sanquin Research, and Landsteiner Laboratory, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands
Search for more papers by this authorHuiying Zhi
Department of Pathology, Versiti Blood Center of Wisconsin, Blood Research Institute, Milwaukee, Wisconsin, USA
Search for more papers by this authorDebra Newman
Department of Pathology, Versiti Blood Center of Wisconsin, Blood Research Institute, Milwaukee, Wisconsin, USA
Search for more papers by this authorNina Scatz-Siemers
Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, New York, USA
Search for more papers by this authorCorresponding Author
James Bussel
Department of Pediatrics, Weill Cornell Medicine, New York, New York, USA
Correspondence
James Bussel, Department of Pediatrics, Weill Cornell Medicine, 525 E 68th St, Suite M-706, New York, NY 10002, USA.
Email: [email protected]
Search for more papers by this authorAbstract
Background
Fetal and neonatal alloimmune thrombocytopenia (FNAIT) ensues from parental incompatibility for platelet alloantigens with maternal sensitization. HPA-1a/1b incompatibility is the most common cause of FNAIT in Caucasians. Placental villitis and lower birthweight in FNAIT suggest anti-HPA-1a may have effects beyond inducing thrombocytopenia.
Objectives
Does FNAIT secondary to anti-HPA-1a result in smaller newborns and, the corollary, does antenatal management of FNAIT increase birthweight?
Study design
Birthweights of 270 FNAIT-affected newborns from a randomized clinical trial and a NAITbabies.org survey (135 paired siblings) were compared with those of published controls and treated to untreated FNAIT-affected siblings. Birthweights were converted to percentiles to account for gestational age, sex, and role of birth order in birth weight. Body weights of FNAIT-affected and -unaffected pups in a mouse FNAIT model were analyzed.
Results
Untreated siblings in both the clinical trial and NAITbabies.org cohorts were not small, compared with normal controls. However, treated siblings in both cohorts had significantly higher birthweight percentiles compared with their previous untreated affected sibling. After accounting for gestational age, sex, and birth order, increased birthweight percentile in treated compared with the untreated siblings remained significant in both cohorts. FNAIT-affected neonatal mice had lower bodyweights than FNAIT-unaffected pups.
Conclusions
Untreated FNAIT-affected newborns were not small; however, treatment of FNAIT-affected pregnancies increased newborn birthweights despite corrections to account for other factors that might have influenced the results. High dose IVIG is believed to “block” FcRn and lower maternal anti-HPA-1a levels, and thus increase birthweights by reducing levels of maternal anti-HPA-1a and reducing placental villitis.
CONFLICT OF INTEREST STATEMENT
James Bussel is a paid consultant for Rallybio LLC, Janssen Pharmaceuticals, UCB, and Argenx. The remaining authors report no conflict of interest.
Supporting Information
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pbc30835-sup-0002-TableS1.docx14.3 KB | Supporting Information |
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