Maternal thyroid hormone concentration during late gestation is associated with foetal position at birth

Objective  To evaluate whether there is an association between maternal thyroid hormone and foetal cephalic head position at term gestation.
Context  Rotation and flexion of the head enables the foetus to negotiate the birth canal. Low-normal range thyroid hormone concentrations in euthyroid pregnant women constitute a risk of infant motor abnormality. We hypothesized that low normal maternal thyroid hormone levels are associated with increased risk of abnormal foetal position at delivery.
Design  In 960 healthy Dutch women with term gestation and cephalic foetal presentation, thyroid parameters [foetal T4 (FT4), TSH and thyroid peroxidase antibody] were assessed at 36 weeks of gestation, and related to foetal head position (anterior cephalic vs. abnormal cephalic) and delivery mode (spontaneous vs. assisted delivery).
Results  Women presenting in anterior position ( n  = 891) had significantly higher FT4 levels at 36 weeks of gestation than those with abnormal cephalic presentation ( n  = 69). There were no between-group differences for TSH. Regression analyses indicated that the risk of abnormal head position decreased as a function of increasing FT4 [single odds ratio (OR) = 0·87, 95% confidence intervals (CI) 0·77–0·98; multivariate OR = 0·88, 95% CI 0·72–0·99)]. A similar inverse relationship between maternal FT4 and risk of assisted delivery was obtained (OR = 0·86, 95% CI 0·79–0·95; OR = 0·91, 95% CI 0·84–0·98).
Conclusion  The lower the maternal FT4 concentration at 36 weeks of gestation, the higher the risk of abnormal cephalic foetal presentation and assisted delivery.     

Maternal thyroid function during pregnancy and puerperal period

It has been noted that hypothyroidism in pregnant women can adversely affect the children's subsequent psychoneurotic development. Also, transient elevation of serum free thyroxine is occasionally seen in the first trimester of normal pregnancy. However, normal thyroid function during pregnancy and the puerperal period has not been clearly defined in Japan. The aim of this study was to assess maternal thyroid function during pregnancy and puerperal period in Japan. The concentrations of thyroid stimulating hormone (TSH), free triiodo-thyronine (free T(3)), free thyroxine (free T(4)) and thyroid binding capacity (TBC) of 522 normal pregnant and puerperal women (119 in the first trimester; 132 in the second trimester; 135 in the third trimester and 136 in the early puerperium) were measured by electrochemiluminescence immunoassay. We compared the measured data with those of healthy nonpregnant control. Twenty-six (21.8%) of 119 women in the first trimester had lower TSH levels and 23 (16.9%) of 136 women in the early puerperium had higher TSH levels than the normal range of healthy nonpregnant controls. Free T(3) gradually decreased during pregnancy, although it remained within the normal control range. Eight (6.7%) of 119 women in the first trimester had high free T(4) levels, which gradually decreased during pregnancy. Sixty (44.4%) of 135 women in the third trimester had low free T(4) levels. The values of TBC in the second trimester increased compared with the first trimester and did not change in the third trimester and decreased after delivery. There were no correlations between maternal TSH and levels of thyroid hormones (free T(3) or free T(4)), except for TSH and free T(4) in the first trimester. In conclusion, we showed that maternal thyroid function, especially TSH and free T(4), changed during the course of pregnancy. In assessing the thyroid function associated with pregnancy, one needs to keep in mind the tendency toward low free T(4) levels in the third trimester and high TSH levels in the early puerperal period.     

臀先露及肩先露者剖宫产时取胎的临床体会

目的：探讨臀先露及肩先露者剖宫产时取胎的方法,减少或避免新生儿股骨骨折和髋关节脱位的发生。方法以顺胎体滑出方向用力行臀牵引方法取胎。结果臀先露及肩先露剖宫产者436例中发生新生儿骨折者2例,发生率为0．46％。结论行臀牵引取胎时避免暴力,顺胎体滑出方向用力可减少新生儿股骨骨折及髋关节脱位的发生。     

Neonatal thyroid screening results are related to gestational maternal thyroid function

Objective To study the relationship between maternal thyroid function at each pregnancy trimester and neonatal screening results. Background Overt maternal thyroid dysfunction during gestation is associated with poor neonatal thyroid function. However, research on the relationship between suboptimal maternal thyroid function (assessed at three trimesters) and neonatal thyroid screening outcome is scarce. Design/Patients Prospective follow‐up study during three trimesters of gestation in 886 Dutch Caucasian healthy pregnant women followed from 12‐week gestation until term delivery (>37 weeks) and their neonates. Measurements The relation between neonatal data from the Congenital Hypothyroidism (CH) screening and maternal thyroid determinants [TSH, FT4 and thyroid peroxidase (TPO)‐Ab] assessed at 12‐, 24‐ and 36‐week gestation. Results Boys have lower screening TT4 levels and their mothers have higher TSH levels at 24‐ and 36‐week gestation. Higher maternal TSH levels (>97·5th percentile, as defined in 810 women without TPO‐Ab at 12 weeks) at one or more times during pregnancy (O.R: 2·26, 95% CI: 1·20–4·29) and lower gestational age (O.R: 1·22, 95% CI: 1·05–1·41) are independently related to lower screening TT4 levels. Conclusions Maternal thyroid function during gestation is related to neonatal TT4 at screening. The finding of both lower neonatal TT4 levels in boys and higher TSH levels in mothers carrying boys is worthy of further investigation, as both observations may be meaningfully related.     

Maternal nutrition during gestation and blood pressure in later life

OBJECTIVE: To assess the link between maternal diet during pregnancy and blood pressure of the offspring. DESIGN: Follow-up study. SETTING: A university hospital in Amsterdam, The Netherlands. PARTICIPANTS: People born at term as singletons between November 1943 and February 1947. MAIN OUTCOME MEASURE: Blood pressure at adult age. RESULTS: Adult blood pressure was not associated with protein, carbohydrate or fat intake during any period of gestation. We found, however, after adjustment for sex that the systolic blood pressure decreased by 0.6 mmHg (0.1-1.1) for every 1% increase in protein/carbohydrate ratio in the third trimester. This association was present both in people who had been exposed to the famine during gestation as well as in those who had not been exposed. The association between protein/carbohydrate ratio in the third trimester and adult blood pressure was furthermore independent of maternal weight gain and final weight, and birth weight [increase for every 1% increase in protein/carbohydrate ratio 0.6 mmHg (0.0-1.2)]. Adjustment for adult characteristics such as body mass index, smoking and socio-economic status did not affect the observed association appreciably [adjusted increase 0.5 mmHg (0.0-1.0)]. CONCLUSION: Adult blood pressure seems to be affected by small variations in the balance of macro-nutrients in the maternal diet during gestation rather than by relatively large variations in the absolute amounts.     

Maternal serum hepcidin is low at term and independent of cord blood iron status

Objectives: Hepcidin is the key regulator of iron homeostasis. The aims of this study were to determine serum hepcidin concentrations and reference ranges in pregnant women and cord blood of newborns at term and to evaluate the associations between hepcidin concentrations and iron status parameters. Methods: A total of 191 pregnant women–newborn pairs were studied in Kuopio University Hospital, Finland. The measured parameters were serum hepcidin, ferritin, transferrin receptor, transferrin saturation, red cell indices, and erythropoietin. Results: The hepcidin concentration in pregnant women was significantly lower than in cord blood at term [geometric mean concentration (GMC) (95% confidence intervals) in pregnant women 10.7 ng/mL (8.5–13.4 ng/mL) vs. GMC of cord blood hepcidin 69.3 ng/mL (55.3–86.8 ng/mL), P < 0.001, adjusted analysis of variance]. Hepcidin was undetectable in 12% of mothers. Hepcidin concentration in pregnant women was the lowest in those who had the lowest iron status. However, maternal hepcidin concentration was not associated with cord blood hepcidin or iron status markers. Hepcidin concentration in cord blood was associated with cord blood iron status, but not with maternal iron status. Conclusions: At term pregnancy, hepcidin concentrations are very low, allowing maximal availability of iron for the fetus. Maternal and cord blood hepcidin levels were independently associated with either maternal or cord blood iron status.     

The auditory threshold in a school-age population is related to iodine intake and thyroid function.

The aim of this study was to determine the relationship between auditory capacity and urinary iodine, taking into account thyroid volume and function, in a population of school-age children. Audiometry was carried out in 150 children (ages 6-14 years), together with measurements of thyroid volume, thyrotropin (TSH), free T3, free T4, thyroglobulin, antiperoxidase and anti-TSH receptor antibodies, as well as iodine in a casual urine sample. Children with a TSH >5 microU/mL were excluded from the study. In the children with palpable goiter, there was an inverse relation between the auditory threshold at all frequencies and ioduria. Children with thyroglobulin values >10 ng/mL had a higher auditory threshold at all frequencies. In the children with palpable goiter and ioduria <100 microg/L, the levels of thyroglobulin and ioduria and the age accounted for 75% of the decibel (dB) variance at 2000 (Hertz), with similar results at other frequencies. The children with a thyroid sized at the >95th percentile had an odds ratio of 3.86 (95% confidence interval: 2.59-5.10) of having a threshold >20 dB. The results warn that iodine prophylaxis is needed to prevent not only goiter but also other iodine-deficiency disorders, such as involvement of the auditory threshold in school-age children.     

Maternal serum resistin at 11 to 13 weeks' gestation in normal and pathological pregnancies

The objective was to examine maternal serum levels of resistin at 11 to 13 weeks' gestation in normal and pathological pregnancies. Serum resistin, pregnancy-associated plasma protein A (PAPP-A), and uterine artery pulsatility index (PI) at 11 to 13 weeks were measured in 480 singleton pregnancies, including 240 with normal outcome, 60 that subsequently developed preeclampsia (PE), 60 that developed gestational diabetes mellitus (GDM), 60 that delivered large for gestational age (LGA) neonates, and 60 that delivered small for gestational age (SGA) neonates. Each value in both the normal and pathological outcome groups was expressed as a multiple of the expected normal median (MoM), and the median MoM values in the outcome groups were compared. In the PE group, compared with the controls, there were an increase in median resistin (1.22 MoM, P = .003) and uterine artery PI (1.25 MoM, P < .0001) and a decrease in serum PAPP-A (0.72, P < .0001). There was no significant association between serum resistin with either uterine artery PI (P = .415) or serum PAPP-A (P = .290). In the SGA, LGA, and GDM groups, serum resistin MoM was not significantly different from that of the controls (P = .415, P = .702, and P = .549, respectively). In pregnancies that develop PE, maternal serum resistin concentration at 11 to 13 weeks is increased in a manner not related to altered placental perfusion or function. In pregnancies complicated by the development of GDM or delivery of SGA or LGA neonates, serum resistin is not significantly altered.     

Maternal hypothyroxinaemia during the first half of gestation in an iodine deficient area with endemic cretinism and related disorders

OBJECTIVE Iodine deficiency is well known as the cause of several disorders such as endemic goitre and cretinism, along with a wide spectrum of psychoneurological development disorders including endemic mental deficiency and endemic cognitive deficiency, which are generally correlated to damage to the fetus. Such damage Is, by Inference, deemed a consequence either directly of iodine deficiency or of insufficient availability of thyroxine at the feto-placental unit level. Early pregnancy represents the crucial period for neurogenesis in the embryo. Several experimental studies have emphasized the direct role of maternal T4 in neurological embryo-genesis, before the onset of fetal thyroid function and, therefore, Its protective role In fetal thyroid failure. The objective of this study was to evaluate whether Iodine deficiency may Influence thyroid status of pregnant women throughout the first half of pregnancy. DESIGN Thyroid function tests including total and free T4 and T3, TBG and TSH along with urinary iodine excretion were measured In the serum of pregnant women from an iodine deficient endemic goitre area In north-eastern Sicily, at 8, 13 and 20 weeks of gestation. The times of sampling were chosen to correspond approximately to a period prior to, coincident with and after the onset of fetal thyroid function, respectively. SUBJECTS The longitudinal study was undertaken In 16 euthyroid pregnant women from the iodine deficient area in which major iodine deficiency disorders such as endemic cretinism and endemic cognitive deficiency In schoolchildren still persist (area A) and in 7 age matched volunteer pregnant women from a marginally iodine sufficient area (area B). MEASUREMENTS Hormones and TBG were measured using commercial kits. Urinary iodine was measured by an automated method. RESULTS The divergent changes In serum T4 and TBG with pregnancy progression induced a progressive TBG desaturation by T4 during the whole study period (from 22 to 17% in area A, ANOVA two-way F = 18-9, P<0.0001; from 33 to 20% in area B, F = 20.7, P<00005) in both areas. At 20 weeks, average FT4 levels were lower in area A than in area B (11.5±2.5 vs 14.3±2.4 pmol/l, t(= 2.7 P<0.01) and were below the normal range In 2/16 and borderline-low In 6/16 pregnant women. FT4 serum levels were Inversely related to TSH concentrations (r=?0.54, P<0.0001) which progressively increased, in area A, during the whole study period (F= 6.0, P<0.01) and were abnormally high in the two women with low FT4, but not In area B. Also in area A (F= 3.4, P<0.05) a significant T3/T4 molar ratio Increase was observed. CONCLUSIONS Iodine deficiency induces in early pregnancy a series of events (reduced synthesis of maternal T4, TBG desaturation by T4, critical decrease of FT4 levels with consequent TSH increase) responsible for overt or marginal biochemical hypothyroidism in about 50% of pregnant women. It is hypothesized that the Imbalance of maternal thyroid hormone homeostasis during pregnancy as a consequence of endemic iodine deficiency may be responsible for the impaired psychoneurological development observed In children from that area so appropriate Iodine and/or thyroxine prophylaxis to women In that region may prevent the neuro-behavloural, cognitive and motor compromise of the population.     

Oestrone, oestradiol-17beta and oestriol levels in human foetal plasma during gestation and at term

Marked rises in both unconjugated and sulphoconjugated estrone, estradiol-17-beta and estriol were observed in human fetal plasma between midgestation and term. Significant arterio-venous differences were found in the umbilical cord plasma. No consistent arterio-venous differences were found in the umbilical cord plasma. This indicates that all 3 estrogens are secreted from the placenta into the fetal circulation in the unconjugated form. Mean unconjugated estrogen (estrone + estradiol-17-beta + estriol) levels rose from 22.7 ng/ml at 17-20 weeks of gestation to 108.9 ng/ml at term in umbilical venous plasma and from 4.3 ng/ml to 23.3 ng/ml in umbilical arterial plasma. This represents a secretion rate of approximately 30 mg estrogen/day into the umbilical vein at term. Mean estrogen sulphate levels rose from 128 ng/ml to 313 ng/ml in the cord plasma during the same period. Of the 3 estrogens measured, estriol was quantitatively the major estrogen in fetal plasma. It consistently represented about 78% of the unconjugated fraction and 95% of the sulphate fraction at all stages of gestation. The method of delivery did not have a significant effect on the estrogen levels in uncomplicated pregnancies. Similar estrogen levels were found in fetal heart blood after either hysterotomy at spontaneous abortion at 16-20 weeks of gestation, and no significant differences were found for estrogen levels in cord plasma after elective Caesarean section at 38-39 weeks when compared with estrogen levels after normal delivery at term. A significant rise in fetal unconjugated estrogens at a time when fetal corticosteroids are increasing may be of physiological importance for fetal maturation in women.     

Maternal and neonatal thyroid function at birth in an area of marginally low iodine intake.

Thyroid function was evaluated in cord serum of healthy full-term newborns and compared to that of mothers immediately after parturition. The study was carried out in an area without overt iodine deficiency, but with a marginal iodine supply (less than 100 micrograms/day in 80% of women). The aim of the study was to delineate the interrelationships between the thyroid statuses of mother and child at birth. Maternal thyroid function was characterized at delivery by relative hypothyroxinemia; increased T3/T4 ratios, indicating preferential T3 secretion; slightly increased TSH levels within the normal range in 97% of women; increased serum thyroglobulin (TG) values, which were above normal in 60% of women; and also goiter formation in almost 10% of women. The findings indicated glandular stimulation and confirmed our earlier reports that pregnancy constitutes a stress for the maternal thyroid economy, enhanced by the limited availability of iodine in the diet. By contrast, newborns showed a strikingly distinct pattern: there was no relative hypothyroxinemia and free T4 levels were significantly higher than in the respective mothers (19.4 vs. 14.7 pmol/L; P less than 0.001). In spite of these differences, however, mean neonatal TSH and TG levels were significantly higher than maternal values, respectively 6.0 vs. 1.9 mU/L for TSH (P less than 0.001) and 70 vs. 40 micrograms/L for TG (P less than 0.001). Furthermore, neonatal TG and TSH levels increased in parallel and were highly correlated with maternal data, suggesting a regulatory link between both thyroid economies. The results suggested that the common regulatory link is the limited availability of the iodine supply. In conclusion, the present study demonstrates that even in conditions with a marginally low iodine intake, pregnancy constitutes a stimulus for both the maternal and newborn thyroids. Changes in both groups are associated and the abnormalities in TSH and TG are amplified in the newborns. The TSH and TG alterations at birth in full-term healthy newborns, associated with similar alterations in maternal thyroid function, provide evidence for a common stimulatory factor, relative iodine deficiency. The data emphasize the hypersensitivity of neonatal thyroid function to marginal iodine deficiency and point to the need to increase the iodine supply in groups at risk, such as women during pregnancy, and also newborns in the perinatal period.     

Maternal hypothyroidism during the first half of gestation compromises normal catabolic adaptations of late gestation in the rat

Female rats were mated and thyroidectomized on the same day. Some animals were kept without treatment and killed on day 12 or 21 of gestation (T). Others were subsequently treated daily with 1.8 micrograms L-T4/100 g BW for either the first 12 days and then not treated from that time until day 21 [T+T4(I+0)] or else not treated for the first 12 days and then treated from days 12-21 [T+T4(0+II)]. A final group received treatment during the entire 21-day study [T+T4(I+II)] and was used as the control. The net maternal body weight increased until day 12 of gestation in T+T4(I+II) rats, but not in T animals. On day 21 net maternal body weight was significantly lower in T and T+T4(0+II) than in T+T4(I+II) rats. Lipoprotein lipase activity in the lumbar fat pads increased from days 0 to 12 of gestation and decreased on day 21, whereas in the heart the change was in the opposite direction, and these changes were greater in T+T4(I+II) rats than in T rats. Incorporation of [U-14C]glucose administered in vivo into liver [14C]fatty acids or [14C]glycogen was significantly lower in T rats than in T+T4(I+II) on either the 12th or 21st day of gestation. The response of plasma triglyceride, glycerol, or beta-hydroxybutyrate levels to 24 h of starvation was similar in 12-day pregnant rats regardless of whether they were treated with T4, whereas on day 21 the change was greater in T+T4(I+II) or T+T4(I+0) animals than in T or T+T4(0+II) animals. Results show that maternal hypothyroidism during the first half of gestation impaired the anabolic events occurring during this phase and compromised the normal catabolic response during late gestation even when T4 treatment was restored. However, once maternal metabolic stores were built up normally during the first half of gestation, maternal hypothyroidism during late gestation did not affect the mother's normal metabolic adaptation, including the accelerated response to starvation.