Abstract
During pregnancy, 17β-estradiol (E2) and progesterone (P) plasma concentrations increase up to 100-fold. The fetus is exposed to these increasing amounts of E2 and P. Within 1 d after delivery, E2 and P concentrations fall to nonpregnancy concentrations in the mother and the infant. Extremely premature infants are cut off from the placental supply of E2 and P at a very early developmental stage, and therefore they suffer from this deprivation for a longer period than infants born at term. Nothing is known about the consequences of this deprivation. The purpose of this study was to investigate how intrauterine concentrations of E2 and P could be maintained after birth. In 13 infants with a median gestational age of 26.4 wk (24.1-28.7), a phospholipid-stabilized soybean oil emulsion available for parenteral nutrition that contains different amounts of E2 and P was continuously administered, starting within the first postnatal hours. The supplementation was continued as long as venous access was indicated but not longer than 6 wk (median 20 d, 12-44). To maintain intrauterine plasma concentrations of 2000-6000 pg/mL E2 and 300-600 ng/mL P, 2.30 mg·kg-1·d-1 E2 (1.13-3.42 mg·kg-1·d-1) and 21.20 mg·kg-1·d-1 P (11.23-27.36 mg·kg-1·d-1) were needed. We conclude that supplementation of E2 and P to maintain intrauterine concentrations in extremely premature infants is possible intravenously. The infants in this study are enrolled in a randomized, controlled pilot study to evaluate the potential benefits of E2 and P supplementation.
Similar content being viewed by others
Log in or create a free account to read this content
Gain free access to this article, as well as selected content from this journal and more on nature.com
or
Abbreviations
- E2:
-
17β-estradiol, pg/mL × 3.671 = pmol/L
- P:
-
progesterone, ng/mL × 3.18 = nmol/L
- ELBW:
-
extremely low birth weight
- DES:
-
diethylstilbestrol
- EIA:
-
enzyme immunoassay
- ID/GC-MS:
-
isotope dilution/gas chromatography-mass spectrometry
References
Tulchinsky D, Hobel CJ, Yeager E, Marshall JR 1972 Plasma estrone, estradiol, estriol, progesterone, and 17 - hydroxyprogesterone in human pregnancy: I-normal pregnancy. Am J Obstet Gynecol 112: 1095–1100.
Kenny FM, Angsusingha K, Stinson D, Hotchkiss J 1973 Unconjugated estrogens in the perinatal period. Pediatr Res 7: 826–831.
Hercz P, Ungar L, Siklos P, Farquharson RG 1988 Unconjugated 17 beta-oestradiol and oestriol in maternal serum and in cord vein and artery blood at term and preterm delivery. Eur J Obstet Gynecol Reprod Biol 27: 7–12.
Tayama C, Ichimaru S, Ito M, Nakayama M, Maeyama M, Miyakawa I 1983 Unconjugated estradiol, estriol and total estriol in maternal peripheral vein, cord vein, and cord artery serum at delivery in pregnancies with intrauterine growth retardation. Endocrinol Jpn 30: 155–162.
Herruzo AJ, Mozas J, Alarcon JL, Lopez JM, Molina R, Molto L, Martos J 1993 Sex differences in serum hormone levels in umbilical vein blood. Int J Gynaecol Obstet 41: 37–41.
Scommegna A, Burd L, Bieniarz J 1972 Progesterone and pregnenolone sulfate in pregnancy plasma. Am J Obstet Gynecol 113: 60–65.
Sippell WG, Becker H, Versmold HT, Bidlingmaier F, Knorr D 1978 Longitudinal studies of plasma aldosterone, corticosterone, deoxycorticosterone, progesterone, 17-hydroxyprogesterone, cortisol, and cortisone determined simultaneously in mother and child at birth and during the early neonatal period: I-spontaneous delivery. J Clin Endocrinol Metab 46: 971–985.
Hercz P 1985 Quantitative changes in steroid and peptide hormones in the maternal-fetoplacental system between the 28th-40th weeks of pregnancy. Acta Med Hung 42: 29–39.
Siler-Khodr TM 1992 Endocrine and paracrine function of the human placenta. In: Polin RA, Fox WW (eds) Fetal and Neonatal Physiology. WB Saunders, Philadelphia, 74–85.
Lindsay R 1988 Sex steroids in the pathogenesis and prevention of osteoporosis. In: Riggs BL, Melton III J (eds) Osteoporosis: Etiology, Diagnosis and Management. Raven Press, New York, 333–358.
Pohlandt F 1994 Prevention of postnatal bone demineralization in very low-birthweight infants by individually monitored supplementation with calcium and phosphorus. Pediatr Res 35: 125–129.
Uchibori M, Kawashima S 1985 Effects of sex steroids on the growth of neuronal processes in neonatal rat hypothalamus-preoptic area and cerebral cortex in primary culture. Int J Dev Neurosci 3: 169–176.
Arimatsu Y, Hatanaka H 1986 Estrogen treatment enhances survival of cultured fetal rat amygdala neurons in a defined medium. Brain Res 391: 151–159.
Geola F, Frumar A, Tataryn I, Lu K, Hershman J, Eggena P, Sambhi M, Judd H 1980 Biological effects of various doses of conjugated equine estrogens in postmenopausal women. J Clin Endocrinol Metab 51: 620–625.
Judd H 1987 Efficacy of transdermal estradiol. Am J Obstet Gynecol 156: 1326–1331.
Radfar N, Ansusingha K, Kenny FM 1976 Circulating bound and free estradiol and estrone during normal growth and development and in premature thelarche and isosexual precocity. J Pediatr 89: 719–723.
Dvoracsek E, Kassai Z, Torok I, Balogh A 1990 Sexual steroid levels and their clinical significance in the early neonatal age. Acta Physiol Hung 76: 151–158.
Tulchinsky D, Okada DM 1975 Hormones in human pregnancy: IV-plasma progesterone. Am J Obstet Gynecol 121: 293–299.
Smith OW 1948 Diethylstilbestrol in the prevention and treatment of complications of pregnancy. Am J Obstet Gynecol 56: 821–834.
Dalton K 1962 Controlled trials in the prophylactic value of progesterone in the treatment of preeclamptic toxaemia. J Obstet Gynaecol 69: 463–468.
Dalton K 1968 Ante-natal progesterone and intelligence. Br J Psychiatry 114: 1377–1382.
Dalton K 1976 Prenatal progesterone and educational attainments. Br J Psychiatry 129: 438–442.
Reinisch JM 1977 Prenatal exposure of human foetuses to synthetic progestin and oestrogen affects personality. Nature 266: 561–562.
Herbst A, Ulfelder H, Poskanzer D 1971 Adenocarcinoma of the vagina: Association of maternal stilbestrol therapy with tumor appearance in young women. N Engl J Med 284: 878–881.
Jones L, Bern H 1977 Long-term effects of neonatal treatment with progesterone, alone and in combination with estrogen, on the mammary gland and reproductive tract of female BALB/cfC3H mice. Cancer Res 37: 67–75.
Tapanainen J, Penttinen J, Huhtaniemi I 1979 Effect of progesterone treatment on the development and function of neonatal rat adrenals and testes. Biol Neonate 36: 290–297.
Warner M, Yau L, Rosen J 1980 Long term effects of perinatal injection of estrogen and progesterone on the morphological and biochemical development of the mammary gland. Endocrinology 106: 823–832.
Levine S, Mullins R 1964 Estrogen administered neonatally affects sexual behavior in male and female rats. Science 144: 185–187.
Wudy SA, Wachter UA, Homoki J, Teller WM 1995 17 alpha-hydroxyprogesterone, 4-androstenedione, and testosterone profiled by routine stable isotope dilution/gas chromatography-mass spectrometry in plasma of children. Pediatr Res 38: 76–80.
Acknowledgements
The authors thank M. Schulz (Endocrinological Laboratory, Department of Obstetrics and Gynecology, University of Ulm) and M. Hartman (Steroid Laboratory, Department of Pediatrics, University of Ulm) for excellent technical assistance.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Trotter, A., Maier, L., Grill, HJ. et al. 17β-Estradiol and Progesterone Supplementation in Extremely Low-Birth-Weight Infants. Pediatr Res 45, 489–493 (1999). https://doi.org/10.1203/00006450-199904010-00006
Received:
Accepted:
Issue date:
DOI: https://doi.org/10.1203/00006450-199904010-00006
This article is cited by
-
Viable bacterial colonization is highly limited in the human intestine in utero
Nature Medicine (2020)
