Aspirin exposure during the first 20 weeks of gestation and IQ at four years of age

The relationship between maternal aspirin use during the first 20 weeks of pregnancy and the child's IQ at 4 years of age was investigated in 19,226 pregnancies occurring from 1959 to 1966 in the Collaborative Perinatal Project. The mean IQ of children exposed to aspirin was 98.3, which was 2.1 points higher (95% confidence interval = 1.7, 2.6; P less than 0.0001) than that of unexposed children. Adjustment for multiple social, demographic, and other confounders reduced this difference to less than one point in favor of the aspirin exposed group, although statistical significance remained. Total days of exposure was used as an index of dose, and no dose-response relationship between aspirin use and IQ was found. The effect of prenatal aspirin exposure did not vary by infant sex. It is concluded that an adverse effect of aspirin exposure on IQ is unlikely.     

Sex ratio of fetuses during the second trimester of gestation

The authors have investigated the sex ratio of fetuses between the thirteenth and twenty-fourth menstrual weeks. The study material, consisting of 749 fetuses, was obtained through induced second trimester abortions. The sex ratio of the 749 specimens was 109. The ratio was 129 between the thirteenth and sixteenth weeks, 105.8 between the seventeenth and twentieth weeks, and 94 between the twenty-first and twenty-fourth weeks of pregnancy. The overall ratio was 112 among Caucasian and 107 among both Black and Central American populations.     

Comparative analysis of the infant EEG at gestation term 30-42 weeks

The research involved comparison of characteristics of the power spectrum, index, coherence of the EEG at preterm and full-term infants of the first month of life. 6 groups of children are surveyed: (1) 30-32, (2) 33-34, (3) 35-36, (4) 37-38, (5) 39-40, (6) 41-42 weeks of gestation; each group consisted of 10 children. Capacity of delta frequencies was high in the 5th group. Capacity of theta frequencies was high in the 3rd group. The index of theta frequencies was high in the 2nd, 3rd and 4th groups. Capacity of alpha frequencies was hagh in the 2nd group. The index of alpha frequencies was high in the 1st, 2nd and 3rd groups. Indexes and of beta1- and beta2-frequencies were higher in the 1st, 2nd and 4th groups. The maximum quantity of coherent delta, theta and alpha frequencies was in the 6th group. In the 2nd group, in comparison with 5th group, were more coherent delta frequencies in the occipital and occipital-central areas. The results obtained show that the spectrum of capacity, indexes and coherence of the EEG depend on term of gestation at the moment of birth but this dependence has nonlinear character.     

Neonatal outcome of fetuses with urinary tract abnormalities diagnosed by prenatal ultrasonography.

Between 1979 and 1986 an abnormality of the urinary tract was diagnosed by prenatal ultrasound examination in 93 fetuses. Postnatal investigation at a large teaching hospital showed a definite abnormality in 85 infants, 66 of whom were boys. An obstructed urinary tract, usually requiring surgery, was present in 46 infants. Other abnormalities included a multicystic kidney (in 15 infants), vesicoureteric reflux (in 9), prune-belly syndrome (in 5) and polycystic kidneys (in 5). Early recognition and treatment of urinary tract disorders in infants should be accompanied by informed prenatal counselling to minimize parents'' anxiety.     

The intestinal microflora during the first weeks of life

Bacterial colonization of the neonatal gastrointestinal tract begins during birth when the neonate comes into contact with the maternal cervical and vaginal flora. In infants delivered by Caesarean section, bacteria colonizing the neonate gastrointestinal tract are provided by the environment. The first bacteria encountered in the majority of healthy infants, are facultative anaerobes, which remain predominant during the first 2 weeks of life. Among them, Staphylococcus, Enterobacteriaceae and Streptococcus were the genera most commonly isolated from the newborn faecal flora at birth. Facultative anaerobic bacteria are followed closely by Bifidobacterium sp. Clostridium perfringens is present within 2 days with an increase incidence in newborns delivered by a Caesarean section. Clostridium perfringens seems to be the precursor for installation of other anaerobic putrefactive bacteria, as Bacteroides and other Clostridium sp. The impact of Caesarean section and the period and quality of hospitalization are mainly implicated in changes of the normal newborn flora. Feeding seems to modulate the colonization pattern. In humans, breast milk plays a role in passive immunization of the neonatal intestine, and contains factors that promote the growth of Bifidobacterium bifidum in the intestinal flora. Formula feeding seems to promote implantation and persistence of Clostridium perfringens, and clearly enhances intestinal colonization of C. difficile in newborns.     

Evaluating 2 year outcome in twins < or = 30 weeks gestation at birth: a regional perinatal unit's experience.

With improved technology in assisted reproductive medicine, there has been an absolute increase in the numbers of twin pregnancies with an associated increase in perinatal mortality and morbidity. This increase in perinatal mortality and morbidity is largely due to a higher incidence of delivering preterm as compared to singletons. Twin pregnancies have their unique complications that include abnormal placental communication and discordant growth which are associated with perinatal mortality and morbidity. The objectives of this study were two-fold: i) to determine if the morbidity/mortality outcome at 18-24 months corrected age seen in a cohort of twins born between 24-30 weeks gestation was significantly different as compared to singleton preterm infants of the same gestation; and ii) to determine and evaluate any differences between monochorionic (MC) and dichorionic (DC) twins. Twins 24-30 weeks gestation at birth born between 01/01/97-30/06/99 were identified and prospectively followed to 18-24 months corrected age (c.a.). They were matched with a singleton infant of the same gender and within 1 week of the same gestation. Obstetrical, neonatal and neurodevelopmental data were gathered and analyzed. The primary outcome was death or the presence of a severe neurodevelopmental deficit at 18-24 months corrected age. Of the 56 sets of twins identified, 52 sets were followed prospectively with 101 infants available for matching. In this cohort, twin pregnancies had a lower incidence of pregnancy-induced hypertension and premature rupture of membranes than singletons (p < 0.05). The two groups were comparable in neonatal characteristics. The incidence of death or severe disability was 29.7% in twins vs. 22.8% in singletons (p = 0.337, Fisher's exact test). The major area of defect was in the cognitive category for both groups, 9.9% vs. 7.9% respectively. MC twins made up 35.6%; DC twins 64.4%. Twin to twin transfusion syndrome (TTTS) occurred in 6.9%. Discordant growth occurred more frequently in MC pregnancies (p = 0.016). MC twins tended to be more premature, lower in birth weight, and experience neonatal morbidity in the form of patent ductus arteriosus and sepsis (p < 0.05) as compared to DC twins. However, the primary outcome of death or severe neurodevelopmental deficit at 18-24 months c.a. was not significantly different between the two groups, 38.9% (MC) vs. 24.6% (DC), (p = 0.173, Fisher's exact test). Neurodevelopmental morbidity or mortality in twins with TTTS was 42%. Mortality and severe neurodevelopmental morbidity were not signif cantly higher in twins as compared to singletons in this cohort. However, the trend is slightly higher in twins, which may have clinical significance. Though not statistically significant, the incidence of 38.9% in adverse outcome wth MC twins may be clinically significant. With the number of twins steadily increasing, further monitor ng is required to determine future directions in intervention and research. Early recognition of monochorionicity remains essential to optimize care and neurodevelopment for these infants.     

Expression of estrogen receptors in the efferent ductule of male sheep fetuses during gestation

There is as yet no report about the developmental changes of estrogen receptors (ERs) in the male reproductive system of the sheep fetus. In the present study, the testis, efferent ductule, and epididymis of sheep fetuses were collected at days 70, 90, and 120 of gestation and in the newborn lamb. ER alpha (ERalpha) and ER beta (ERbeta) were detected by immunohistochemistry. The results showed that ERbeta staining was negative in all of the examined tissues throughout gestation, whereas ERalpha immunoreactivity was only located in the nuclei of the efferent ductule epithelium. In addition, both ERalpha staining intensity and the number of ERalpha-positive cells were higher at day 90 of gestation, compared with that at day 70 and at birth. These results suggest that estrogen may play important roles in efferent ductule development in sheep fetuses.     

Expression of estrogen receptors in the efferent ductule of male sheep fetuses during gestation

There is as yet no report about the developmental changes of estrogen receptors (ERs) in the male reproductive system of the sheep fetus. In the present study, the testis, efferent ductule, and epididymis of sheep fetuses were collected at days 70, 90, and 120 of gestation and in the newborn lamb. ER alpha (ER) and ER beta (ER) were detected by immunohistochemistry. The results showed that ER staining was negative in all of the examined tissues throughout gestation, whereas ER immunoreactivity was only located in the nuclei of the efferent ductule epithelium. In addition, both ER staining intensity and the number of ER-positive cells were higher at day 90 of gestation, compared with that at day 70 and at birth. These results suggest that estrogen may play important roles in efferent ductule development in sheep fetuses.     

Evaluation of Chlorpropamide in Chemical Diabetes diagnosed during Pregnancy

The intravenous glucose tolerance test (I.V.G.T.T.) was used to diagnose chemical diabetes during pregnancy in 180 women, 50 of whom subsequently received chlorpropamide therapy in a daily dosage of 100 mg; the remainder had no drug therapy.Preliminary work showed the I.V.G.T.T. to be reproducible in the second and third trimesters but not in the puerperium in normal pregnancy. Though intravenous glucose tolerance deteriorates between the second and third trimesters in women with no features of diabetes, a significant improvement occurs after a course of chlorpropamide in a daily dosage of 100 mg during pregnancy in chemical diabetes, but this treatment did not enhance the rate of return to normal glucose tolerance post partum.Plasma glucose and insulin studies showed no evidence of hypoglycaemia or hyperinsulinism in the mother at delivery or in the newborn when chlorpropamide had been used compared with a group receiving no such treatment. In the infants of the chlorpropamide-treated mothers there was a suggestion of an increased rate of glucose disposal in response to a glucose challenge, but no increase in birth weight.There were two fetal deaths in the 50 pregnancies of mothers treated with chlorpropamide, one being due to a mistaken premature delivery and the other to a diaphragmatic hernia. Thus chlorpropamide in a dose of 100 mg a day has been shown to reverse chemical diabetes diagnosed and treated in pregnancy without apparent risk to the fetus.     

The outcome of twin pregnancies complicated by single fetal death after 20 weeks of gestation.

A retrospective study involving 972 twin births was conducted to evaluate the maternal and fetal outcomes of twin pregnancies complicated by single fetal death. The incidence of single fetal death in twin pregnancies after 20 weeks was 3.3%. Preterm birth rates for 37 and 32 gestational weeks were 81.3% and 41.6% respectively. The median interval between the diagnosis of fetal death and the delivery was 11 days (range 1-27 days). Eighteen (56%) infants were delivered by cesarean and 14 (43%) vaginally. Twin-twin transfusion syndrome (TTTS) was the cause of single fetal death in 8 of 32 twin pregnancies (25%). Ten of the surviving co-twins were lost in the neonatal period (31.3%) and half of those neonatal deaths were due to TTTS. TTTS is the major contributor for perinatal mortality in same-sex twins complicated by single fetal death. The death of one twin in utero should not be the only indication for preterm delivery, and in case of severe prematurity with a stable intrauterine environment; expectant management may be advisable until fetal lung maturation ensues.     

Relationships among the concentrations of 25 inflammation-associated proteins during the first postnatal weeks in the blood of infants born before the 28th week of gestation

Background

Inflammation appears to be involved in processes leading to organ damage in preterm newborns, yet little is known about the relationships among elevated concentrations of inflammation-associated proteins in the blood of preterm newborns.

Methods

In this exploratory study, we used an electrochemiluminescence method to measure 25 proteins in blood obtained on postnatal day 1 (range 1-3), day 7 (range 5-8), and day 14 (range 12-15) from 939 children born before the 28th week of gestation and evaluated to what extent those whose concentration of each protein was elevated (defined as in the highest quartile for gestational age and day the specimen was obtained) also had an elevated concentration of every other protein the same day or on a day 1 or 2 weeks later (p < .0001).

Results

On each of the 3 days assessed, elevated concentrations of 17 proteins were associated with elevated concentrations of 15 or more of the other 24 proteins. VEGF, VEGF-R1, VEGF-R2 were among these proteins, while IGFBP-1 was associated with 13 other proteins on day 7. An elevated concentration of eight proteins on day 1 predicted an elevated concentration of 10 or more proteins on day 7, while an elevated concentration of only two proteins on day 7 were associated with elevated concentrations of 10 or more proteins on day-14. Few associations were seen between days 1 and 14.

Conclusions/inferences

Inflammation is a diffuse process in ELGANs, with elevated concentrations of cytokines, chemokines, adhesion molecules, matrix metalloproteinases, a growth factor and its receptors, as well as a growth factor binding protein associated with each other the same day, as well as on subsequent days.     

Leptin values in placental cord blood of human newborns with normal intrauterine growth after 30-42 weeks of gestation

OBJECTIVE: To evaluate leptin values in placental cord blood of newborns with normal intrauterine growth after 30-42 weeks of gestation. DESIGN: Leptin, a protein encoded by the ob gene, plays an important role in the regulation of feeding behaviour and energy balance in rodents, primates and humans. The presence of leptin in human amniotic fluid and cord blood has recently been reported in human gestations at term and the possible role of leptin in human fetal growth suggested. However, little is known of leptin synthesis during human foetal development. Thus, the aim of our work was to measure leptin (RIA, Linco Research, Inc.) in placental cord blood of human newborns at different fetal ages. PATIENTS: One hundred and twenty-six healthy newborns with normal intrauterine growth were studied. Twenty-nine were preterm (15 males and 14 females; gestational age: 30-36 weeks) and 99 were at term (49 males and 48 females; gestational age: 37-42 weeks). RESULTS: Leptin values increase progressively throughout gestation from 1.30 +/- 0.53 ng/ml at 30 weeks of gestation to 7.98 +/- 4.96 ng/ml (mean +/- SD) at term, and correlate positively with birth weight (r = 0.56, p < 0. 005, n = 126), length (r = 0.37, p < 0.005, n = 126), BMI (r = 0.57, p < 0.005, n = 126), head circumference (r = 0.37, p < 0.005, n = 126), gestational age (r = 0.48, p < 0.005, n = 126) and placental weight (r = 0.38, p < 0.003, n = 59). Leptin values are statistically significantly lower (p < 0.005) preterm (median: 2.05 ng/ml; range: 0.7-8.3 ng/ml) than at term (median: 7.0 ng/ml; range: 1.1-28.1 ng/ml). Leptin values are also significantly (p < 0.005) higher in females (median: 7.2 ng/ml; range: 0.9-23.6 ng/ml, n = 62) than in males (median: 4.8 ng/ml; range: 0.7-28.1 ng/ml, n = 64), although there are no differences in weight (2,864 +/- 536 g in females vs. 2,937 +/- 744 g in males). Multiple regression analysis shows weight to be a positive sex-independent predictor of serum leptin values (p < 0.0005). Sex also proves to be a predictor of leptin, independently of weight and is higher in females than in males (p < 0.003). CONCLUSION: Leptin is present in placental human cord blood after 30-42 weeks of gestation. Newborn weight and sex are independent predictors of leptin values.     

Characterization of the major steroids present in amniotic fluid obtained between the 15th and 17th weeks of gestation

In pooled amniotic fluid obtained between the 15th and 17th weeks of gestation the concentration of free steroids and steroid glucuronides was found to be 40 micrograms/dl. The concentration of steroid monosulfates and disulfates was 19 micrograms/dl. About half of the characterized steroids are progesterone metabolites. The "fetal type" 3 beta-hydroxy-5-ene steroids were found exclusively in the sulfoconjugated form. Their concentration represents 20% of the total steroid content. The identification of two 15 beta-hydroxylated C21 steroids, 3 beta,15 beta,17 alpha-tridoxy-5-pregnen-20-one and 5-pregnene-3 beta,15 beta,17 alpha,20 alpha-tetrol isolated from mid-pregnancy amniotic fluid is reported here. Metabolites of cortisol and 17-deoxycorticosteroid metabolites had similar quantitative importance, 8.6 and 9.4%, respectively.     

Chromosomal findings in fetuses with prenatally diagnosed cysts of the choroid plexus

Summary Choroid plexus cysts were diagnosed in 25 out of 823 fetuses with prenatally diagnosed abnormalities (growth retardation/malformations). Among these, 5 revealed a chromosomal disorder (4 cases with trisomy 18 and one case with a translocation trisomy 21). Additional abnormalities, such as growth retardation, holoprosencephaly, hydrocephalus and club foot, were found in 6 out of the 20 fetuses with no chromosomal abnormality. All fetuses with a chromosomal disorder revealed further typical prenatally recognizable abnormalities. Our observation indicates that prenatally diagnosed choroid plexus cysts should be considered as an indication for prenatal chromosomal diagnosis, although the risk of there being an underlying chromosomal disorder is low in cases with no additional abnormalities.     

Relationship between incidence of milk fever and feeding of minerals during the last 3 weeks of gestation

This study evaluated whether differences in milk fever incidence among Swedish dairy herds could be explained partly by differences in mineral feeding during the last weeks of gestation. A case–control study was performed on dietary risk factors for a high incidence of milk fever at the herd level using information regarding feeding and management of the dry cows collected in a written questionnaire distributed by post in spring 2008. The study was conducted from September 2004 to August 2007. Data on the diets fed to dry cows, with an emphasis on the amounts of minerals (Ca, P, Mg and K) fed 3 weeks before calving and at calving, were obtained from 30 herds belonging to the 100 Swedish herds with the highest recorded incidence of veterinary treatment for milk fever (>8.8%) and from 22 herds with no recorded milk fever treatments. Multivariable logistic regression analysis showed that a linear increase in the total amount of K and less than 26 g of Mg/day fed to dry cows 3 weeks before calving was associated with an increased risk of high milk fever incidence. A large increase in the amount of dry matter (DM) fed (>3.1 kg DM extra per day at calving compared with 3 weeks before calving) was associated with a higher incidence of milk fever, but no differences were found for Ca or P intake. Breed composition, herd average milk yield and age composition of the herd did not explain any of the observed differences between the case and the control herds. The results indicate that differences in the frequency of milk fever among herds can be associated with differences in mineral feeding of the dry cows. A high amount of K in the diet may increase the risk of milk fever linearly, whereas Mg should probably be fed at a higher level than the current Nordic recommendation to prevent milk fever.     

Pregnancy outcome of women exposed to azathioprine during pregnancy

BACKGROUND: Azathioprine (AZP) interferes with nucleic acid synthesis and is teratogenic in animals. In view of the paucity of information on the use of AZP during pregnancy we investigated this subject in a prospective, controlled, multicenter study. Our objective was too determine whether exposure to AZP during pregnancy increases the risk for major malformations and to determine the effect on pregnancy outcome. METHODS: Pregnant women on AZP who contacted one of seven teratogen information services were compared to a cohort of pregnant women who contacted two of the seven teratogen information services and took nonteratogenic treatments during their pregnancy. RESULTS: Follow-up was completed on 189 women in the AZP group and compared to 230 women in the control group. The rate of major malformations did not differ between groups with six neonates in each; the AZP rate was 3.5% and the control group rate was 3.0% (p = .775; OR 1.17; CI: 0.37, 3.69). The mean birth weight and gestational age were lower in the AZP group (2,995 g vs. 3,252 g [p = .001, difference of mean: 257, 95% CI: 106.3, 408.1] and 37.8 weeks vs. 39.1 weeks [p = .001, difference of mean: 1.3, 95% CI: .5, 2.0], respectively). The AZP group had more cases of prematurity (21.4% vs. 5.2% [p < .001; OR 4.0; 95% CI: 2.0, 8.06]) and low birth weight (23% vs. 6.0% [p < .001; OR 3.81; 95% CI: 2.0, 7.2]). CONCLUSIONS: These results suggest that AZP (50-100 mg/day) does not triple the rate of birth defects; however, it is associated with lower birth weight, gestational age, and prematurity. Larger studies are needed to confirm these observations.     

Uterine blood flow during the first 3 weeks of pregnancy in dairy cows

Transrectal color Doppler sonography was used to compare changes in uterine blood flow between cyclic and early pregnant lactating dairy cows. Examinations were carried out in 53 multiparous lactating cows on days 3, 6, 9, 11, 13, 15, 18 and 21 (day 0=estrus). Fourteen cows were examined during the estrous cycle and thirty-nine cows after insemination with frozen/thawed sperm. Uterine blood flow was reflected by the time-averaged maximum velocity (TAMV) and the pulsatility index (PI) in the uterine artery ipsilateral to the corpus luteum. Twenty-one cows that were not pregnant on day 25 were excluded from the study. There was high inter-individual variability in PI- (CV: 22-62%) and TAMV-values (CV: 22-42%) at all examinations. In cyclic cows, TAMV values increased between days 13 and 18 and PI values decreased between days 15 and 21 (P<0.05). In pregnant cows (n=18), TAMV values increased from days 9 to 11 and then decreased to minimal values by day 18 (P<0.05). The PI values decreased between days 3 and 11 and then increased to maximum levels on day 18 (P<0.05). On day 21, both variables reached (P<0.05) values that did not differ (P>0.05) from those on day 11. The changes in TAMV were correlated with estrogen and progesterone concentrations (r=0.69 and -0.70, respectively; P<0.05) in cycling cows, but not in pregnant cows (P>0.05). The PI values did not correlate with steroid hormone levels (P>0.05). Differences in uterine blood flow between cycling and early pregnant cows were observed only on day 18 (P<0.05). The results show that in pregnant cows changes in uterine blood supply can be detected already in the second week after insemination; these changes do not occur in the second week of the cycle.     

Relationship of length of uterus in prepubertal pigs and number of corpora lutea and fetuses at 30 days of gestation

Relationships of the length of the uterus at one reproductive stage to the length at other stages and the effect on potential litter size were determined. In Experiment 1, the length of the uterus was measured in situ at 20, 60, or 100 days of age at laparotomy with 20 gilts in each of the three age groups. Forty days after the initial measurement, the uterus was again measured in situ, gilts were ovariectomized and hysterectomized, and associations among uterine measurements at the two different stages were determined. Correlations between uterine length in situ and between uterine length and weight 40 days later were all greater than 0.75 (P < 0.001). The length of one uterine horn increased from 13.9 cm at 20 days of age to 36.7 cm at 140 days of age (P < 0.01). In Experiment 2, 66 gilts were unilaterally hysterectomized and ovariectomized (UHOX) at 150 days of age and the ovary was weighed. Length of the one horn was measured in 36 gilts. At 10 days after first estrus, the length of the remaining uterine horn was measured at laparotomy and corpora lutea were counted in 53 gilts. In 15 of the 53 gilts the remaining uterine horn was removed to obtain uterine weights. At the second or third estrus, 38 gilts were mated and at Day 30 of gestation, 31 gilts were pregnant. The gilts were killed, and the length of the uterus measured and corpora lutea (CL) and fetuses were counted. The length of one uterine horn at 150 days of age was 70 cm with a range of 47–110 cm. At 10 days after first estrus, length had increased to a mean of 141 cm with a range of 86–194 cm and at 30 days of gestation the mean was 244 cm with a range of 186–311 cm. There were 12.2 CL at first estrus, which was not different from 12.4 CL at the second or third estrus. The mean number of fetuses in one horn at 30 days of gestation was 9.5 with 77% prenatal survival. Length of uterine horn at 150 days of age was correlated with uterine horn length (r = 0.56, P < 0.001) at 10 days after first estrus and number of live fetuses (r=0.39, P<0.05) at 30 days of gestation. At Day 10 after first estrus, uterine length was not correlated with the number of CL, whereas at Day 30 of gestation, the number of CL and uterine length were correlated with the number of live fetuses in those gilts with below the mean number of live fetuses, but not in those gilts with above the mean of live fetuses. The number of live fetuses (r=0.66, P < 0.001) and fetal survival (r=0.63; P < 0.001) were correlated with uterine horn length in pregnant UHOX gilts. Length of the prepubertal uterus gives an indication of postpubertal length and the potential litter size in pigs.