TY - JOUR

T1 - Semaglutide and pregnancy

AU - Skov, Kenneth

AU - Mandic, Ida Nikoline

AU - Nyborg, Kathinka Marie

PY - 2023

Y1 - 2023

N2 - To the editorsSemaglutide is marketed for the treatment of diabetes and weight loss, and has been proposed for a host of other indications.1 It has even been suggested for the treatment of subfertility related to diabetes, overweight, and polycystic ovary syndrome (PCOS).2 Thus, increasing use among fertile women and even women planning pregnancy could be expected in the future. However, there is a paucity of data concerning semaglutide and human pregnancy outcomes. The manufacturer even discourages use within 2 months of planned pregnancy.3 Here, we describe a case of semaglutide exposure in early pregnancy. The authors are in possession of a written consent form for both mother and child signed by the mother.A 31-year-old woman pregnant with her second child was referred at gestational week (GW) 12 to counseling at the fetal medicine unit, due to off-label treatment with semaglutid for PCOS. She was treated with semaglutid 0.5 mg/week for 6 months, increasing to 1 mg/week a month before conception. The last injection was administered at GW 3 + 4. During treatment, she lost 27 kg and had a body mass index of 29 at the time of conception. Apart from PCOS, she received levothyroxine for uncomplicated myxoedema but was otherwise healthy.All routine prenatal screenings in the first and second trimesters were normal. At GW 35, the growth scan showed an estimated fetal weight within the normal range (+11%). Tests for gestational diabetes were normal both during the present and previous pregnancy. Total weight gain was 35 kg, equally gained with approximately 1 kg/week throughout the pregnancy. Two months after delivery, she resumed semaglutide treatment. At that time, she was still 20 kg above her weight at conception.She delivered a girl child by vaginal birth at GW 41 + 5. Birthweight was 5.230 g (+38%) and labor was complicated by shoulder dystocia. Postnatal pediatric examination revealed hypoglycemia but she was otherwise healthy. There were no signs that macrosomia was due to gestational diabetes. Besides difficulty in initiating breastfeeding, the postnatal period was uneventful. At 6 months of age, the child was developing normally.To our knowledge, this is the first case of pregnancy exposed to semaglutide described in the literature. The mother was treated up until GW 3 + 4. Due to the very long half-life of semaglutide (approximately 1 week), the pregnancy is considered to have been exposed for several weeks after cessation of therapy. Preclinical animal studies suggest a higher risk of early pregnancy loss and reduced fetal weight, probably due to maternal weight loss.3 Cessation of semaglutide for obesity is associated with significant weight gain in nonpregnant individuals.4In our case, the mother was treated for PCOS with lower doses than used for obesity. Nevertheless, she experienced massive weight loss during treatment and significant weight gain, not only in the third trimester but throughout the entire pregnancy after the treatment was discontinued. We suspect that maternal weight gain and fetal macrosomia is at least partly due to rebound weight gain associated with cessation of semaglutide. When assessing pregnant women treated with semaglutide, both the unknown risk of untoward pregnancy outcomes and the significant risk of rebound weight gain must be considered.

AB - To the editorsSemaglutide is marketed for the treatment of diabetes and weight loss, and has been proposed for a host of other indications.1 It has even been suggested for the treatment of subfertility related to diabetes, overweight, and polycystic ovary syndrome (PCOS).2 Thus, increasing use among fertile women and even women planning pregnancy could be expected in the future. However, there is a paucity of data concerning semaglutide and human pregnancy outcomes. The manufacturer even discourages use within 2 months of planned pregnancy.3 Here, we describe a case of semaglutide exposure in early pregnancy. The authors are in possession of a written consent form for both mother and child signed by the mother.A 31-year-old woman pregnant with her second child was referred at gestational week (GW) 12 to counseling at the fetal medicine unit, due to off-label treatment with semaglutid for PCOS. She was treated with semaglutid 0.5 mg/week for 6 months, increasing to 1 mg/week a month before conception. The last injection was administered at GW 3 + 4. During treatment, she lost 27 kg and had a body mass index of 29 at the time of conception. Apart from PCOS, she received levothyroxine for uncomplicated myxoedema but was otherwise healthy.All routine prenatal screenings in the first and second trimesters were normal. At GW 35, the growth scan showed an estimated fetal weight within the normal range (+11%). Tests for gestational diabetes were normal both during the present and previous pregnancy. Total weight gain was 35 kg, equally gained with approximately 1 kg/week throughout the pregnancy. Two months after delivery, she resumed semaglutide treatment. At that time, she was still 20 kg above her weight at conception.She delivered a girl child by vaginal birth at GW 41 + 5. Birthweight was 5.230 g (+38%) and labor was complicated by shoulder dystocia. Postnatal pediatric examination revealed hypoglycemia but she was otherwise healthy. There were no signs that macrosomia was due to gestational diabetes. Besides difficulty in initiating breastfeeding, the postnatal period was uneventful. At 6 months of age, the child was developing normally.To our knowledge, this is the first case of pregnancy exposed to semaglutide described in the literature. The mother was treated up until GW 3 + 4. Due to the very long half-life of semaglutide (approximately 1 week), the pregnancy is considered to have been exposed for several weeks after cessation of therapy. Preclinical animal studies suggest a higher risk of early pregnancy loss and reduced fetal weight, probably due to maternal weight loss.3 Cessation of semaglutide for obesity is associated with significant weight gain in nonpregnant individuals.4In our case, the mother was treated for PCOS with lower doses than used for obesity. Nevertheless, she experienced massive weight loss during treatment and significant weight gain, not only in the third trimester but throughout the entire pregnancy after the treatment was discontinued. We suspect that maternal weight gain and fetal macrosomia is at least partly due to rebound weight gain associated with cessation of semaglutide. When assessing pregnant women treated with semaglutide, both the unknown risk of untoward pregnancy outcomes and the significant risk of rebound weight gain must be considered.

KW - case report

KW - malformations

KW - overweight

KW - PCOS

KW - pregnancy

KW - risk pregnancy

KW - semaglutide

KW - untoward fetal outcome

U2 - 10.1002/ijgo.15092

DO - 10.1002/ijgo.15092

M3 - Journal article

C2 - 37688299

AN - SCOPUS:85170554300

VL - 163

SP - 699

EP - 700

JO - International Journal of Gynecology & Obstetrics

JF - International Journal of Gynecology & Obstetrics

SN - 0020-7292

IS - 2

ER -