Pregnancy outcomes in women receiving growth hormone replacement therapy enrolled in the NordiNet® International Outcome Study (IOS) and the American Norditropin® Studies: Web-Enabled Research (ANSWER) Program

Beverly M K Biller, Charlotte Höybye, Paul Carroll, Murray B Gordon, Anna Camilla Birkegård, Nicky Kelepouris, Navid Nedjatian, Matthias M Weber, Beverly M K Biller, Charlotte Höybye, Paul Carroll, Murray B Gordon, Anna Camilla Birkegård, Nicky Kelepouris, Navid Nedjatian, Matthias M Weber

Abstract

Purpose: Data on the safety of growth hormone (GH) replacement therapy during pregnancy are limited. We report a combined analysis of data from pregnant women treated with GH while enrolled in two non-interventional, multicenter studies: NordiNet® International Outcome Study (IOS) and the American Norditropin® Studies: Web-Enabled Research (ANSWER) Program.

Methods: Pregnancy data were pooled from NordiNet® IOS and the ANSWER Program. Data were collected during routine clinic visits by participating physicians using a web-based system. Patients exposed to GH replacement therapy during pregnancy were included in the analysis.

Results: The study population included 40 female patients with typical causes of adult GH deficiency (GHD). Overall, there were 54 pregnancies. Of these, 47 were exposed to GH between conception and delivery. In 48.9% of pregnancies exposed to GH, the dose was > 0.6 mg/day. GH was continued past conception and then stopped during the first, second, and third trimester, in 27.7%, 17.0%, and 2.1% of pregnancies, respectively. In 29.8%, GH was continued throughout pregnancy, with an unchanged dose in most cases. Of the 47 GH-exposed pregnancies, 37 (78.7%) progressed to normal delivery. There were three adverse events reported in two pregnancies.

Conclusion: These real-world data suggest that there were no new safety signals related to GH exposure in women with GHD during pregnancy. These results are consistent with findings from previous studies reporting data in pregnancies exposed to GH at conception or throughout pregnancy. This observational study in additional pregnancies provides further evidence that GH exposure does not adversely affect pregnancy outcome.

Clinical trial registration: ClinicalTrials.gov NCT00960128 (date of registration: August 13, 2009) and NCT01009905 (date of registration: November 5, 2009).

Keywords: Adult growth hormone deficiency; Human growth hormone; IGF-I; Outcome; Pregnancy.

Conflict of interest statement

BMKB served as the PI of research grants to Massachusetts General Hospital from Novo Nordisk, OPKO, Novartis, and Strongbridge; and consults occasionally for Aeterna Zentaris, Ascendis, EMD Serono, Novo Nordisk, Pfizer, and Strongbridge. CH was a NordiNet® IOS investigator and has received lecture fees from Novo Nordisk, Pfizer and Sandoz, and is a member of the global steering committee for the PATRO study (Sandoz) and has consulted for Novo Nordisk and Ascendis. PC has received honoraria for participation in advisory boards for Shire, Pfizer, and Novo Nordisk. MBG reports research support from Camurus, Chiasma, Corcept, Crinetics, Ipsen, Novartis, Novo Nordisk, Opko, Pfizer, Strongbridge, and Teva; and has been a scientific consultant to Chiasma, Ipsen, and Novo Nordisk. ACB, and NN are employees of Novo Nordisk. NK is an employee of Novo Nordisk and has stocks in Novo Nordisk and Pfizer. MMW has received honoraria for participation in advisory boards and as a speaker from Novartis, Ipsen and Novo Nordisk, and research grants from Ipsen and Novartis.

© 2021. The Author(s).

Figures

Fig. 1
Fig. 1
Etiology of pituitary diseases. aOther causes of acquired GHD consisted of: GHD due to Sheehan syndrome, sarcoidosis, and unspecified GHD. GHD growth hormone deficiency
Fig. 2
Fig. 2
Growth hormone therapy in exposed pregnancies. a Growth hormone therapy during pregnancy. b Cumulative number of pregnancies exposed to growth hormone during pregnancy. c Growth hormone dose at conception. d Growth hormone dose during pregnancy. aUntil 14 days before delivery. bThe number of pregnancies cumulatively exposed at conception or with unknown exposure amounts to fewer than 47 because, in one pregnancy, growth hormone replacement therapy started in the first trimester. Exposure to growth hormone at conception, first trimester, second trimester, third trimester, or up to termination was defined as exposure before and after 2 weeks of each pregnancy stage (b). Growth hormone dose data were not available for five pregnancies, for which conception date was unknown (missing; b). cPatients not exposed corresponds to one patient who started growth hormone replacement therapy after conception (c). The growth hormone dose of this patient during pregnancy is also included in d
Fig. 3
Fig. 3
Growth hormone dose over time. a Pregnancies exposed to growth hormone only at conception. b Growth hormone replacement stopped during the first trimester. c Growth hormone replacement stopped during the second or third trimesters. d Pregnancies exposed to growth hormone throughout pregnancy. Spaghetti plots of each patient’s exposure to growth hormone throughout pregnancy. Each color line represents one patient. In b and c, lines that rise and then continue horizontally after the third trimester represent postpartum resumption of growth hormone replacement therapy. C conception, T1 end of first trimester, T2 end of second trimester, T3 end of third trimester

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