HORMONAL CIRCADIAN AND CIRCANNUAL RYTHMS IN HUMAN INTRAUTERINE GROWTH RETARDATION

Cristina Maggioni*, Franz Halberg°, Germaine Cornelissen°

* I Clinica Ostetrico- Ginecologica- University of Milan, Italy

° Chronobiological Laboratories, University of Minnesota, Minneapolis USA

e-mail: cristina.maggioni@unimi.it

AIM Causes of intrauterine growth retardation (IUGR) involve many different factors. Maternal environment is the most important determinant of neonatal weight, accounting for more similarity in birth weight of siblings than does genetic affinity but others factors could mediate this pathological process that remains poorly understood.

We investigate if maternal hormonal circadian and circannual rhythms may be related to foetal growth.

METHODS. 25 subjects during the third trimester of pregnancy were evaluated.  Pregnancies were single and gestational age was ascertained by a precise menstrual history and a first trimester ultrasonography.

14 were healthy controls (CC) 11 were women with pregnancy complicated only by idiopathic IUGR . There were no congenital or chromosomal abnormalities.

None of the women were affected by medical diseases, or receiving drugs. The diagnosis of IUGR was made on a base of fetal growth rate pattern monitored by serial ultrasonographic measurements, which was below the 10th percentile and confirmed at birth

SETTING .  Obstetric unit. All subjects were hospitalized and submitted to the same regimen of life; blood was drawn at four hour interval (1 am, 5 am, 9 am, 1 pm, 5 pm 9 pm) immediately centrifuged and stored at -40°C..

We evaluate Progesterone, Estriol (E3), Melatonin, Prolactin, Cortisol, Aldosterone, Plasma Renin Activity (PRA), Dehydroepiandrosterone Sulfate (DHEA S), Atrial natriuretic peptide (ANP), Growth Hormone (GH).

RESULTS. Melatonin is of maternal origin and freely cross the placenta, estriol is almost totally of foetal origins, Dheas is of foetal origins but    represent the major source for Estriol production in foetal liver and placenta.

We detect statistically significant differences in hormonal circadian profiles in IUGR complicated pregnancy compared to normal for Estriol, DHEAS and blood pressure related hormones which maybe represent an attempt to ameliorate placental perfusion.

 Only E3 and DHEAS show a correlation with foetal weight and length .

We found also strong differences in yearly rhythms between CC and IUGR for melatonin and E3

The circadian amplitude is modulated by a yearly component in both groups. The amplitude of the circannual component differs with borderline statistical significance between the two groups for the case of the 01:00(P=0.067) and the 09:00 (P=0.087) values. Pregnancies complicated with IUGR show a statistically significant about-yearly component modulating the circadian MESOR of circulating melatonin.

Moreover, Melatonin and E3 24-hour average and the 24-hour and 12-hour amplitudes component are also modulated by an about half-yearly in IUGR. A circasemiannual (about half-yearly) component prominently characterizes body weight and length at birth of children with birth characteristics below usual norms. Differences between IUGR and uncomplicated pregnancies may involve an about-yearly and/or half- yearly rather than an about-daily variation. They may reflect associations not only with sunlight, temperature and societal schedules, which have a yearly pattern, but also associations with terrestrial magnetism, characterized by a half-yearly pattern of its disturbance.

CONCLUSIONS .  Geomagnetic influences  maybe  involved in the pathogenesis of intrauterine growth retardation or that IUGR  foetus may be more sensitive to geomagnetic disturbances. 

© Copyright 2008. All rights reserved. Contact to Victor Martynyuk: ubs@science-center.net  tel.: +38 050 6535592