Untreated Mothers Research Articles

523. PLACENTAL ANTIOXIDANT ENZYMES IN RAT PREGNANCY SHOW ZONE- AND STAGE-DEPENDENT VARIATION

Placental oxidative stress plays a key role in the pathophysiology of placenta-related disorders including preeclampsia. Protection from oxidative stress is provided by antioxidant enzymes which inactivate reactive oxygen species (ROS). The rat placenta consists of two major zones, the junctional (JZ) and labyrinth (LZ), and because only the LZ grows in late gestation we hypothesized it generates more ROS and thus requires greater antioxidant protection. Our previous studies on expression of the antioxidants superoxide dismutase (SOD)-1, SOD-2 and catalase support this hypothesis. Here, we extend these observations to include mRNA expression of SOD-3 and thioredoxin reductases (Txnrd-1, -2, -3) and activities of SOD, hydrogen peroxide (H2O2) scavenging and xanthine oxidase (XO). Placental oxidative damage was assessed by measurement of F2-isoprostanes and TBARS concentrations. We also measured the effects of maternal dexamethasone treatment, since glucocorticoid excess is known to induce oxidative damage in other tissues. Placentas were collected from untreated mothers on days 16 and 22 (term=day 23) and on day 22 after dexamethasone treatment from day 13 (1 μg/ml drinking water). SOD-3, Txnrd-1, -2, and -3 mRNAs were measured in JZ and LZ by qRT-PCR. F2-isoprostanes were measured by GC-MS and kit assays were used to measure TBARS and the activities of SOD, H2O2 scavenging and XO. In both placental zones, expression of SOD-3 and Txnrd-1 mRNAs and H2O2 scavenging activity decreased from day 16 to 22, whereas XO activity increased. Dexamethasone treatment increased H2O2 scavenging in both zones, but had no effect on SOD or XO activities or antioxidant mRNA expression. Despite predicted increases in placental ROS generation in late pregnancy and after dexamethasone, neither F2-isoprostanes nor TBARS were increased. These and our previous data suggest that endogenous protection against oxidative stress is abundant in the rat placenta and provides protection against potential oxidative insults including glucocorticoid excess.

Thyroid Disorders of Neonates Born to Mothers with Graves' Disease

Maternal hyperthyroidism implies the risk of thyroid abnormalities in the newborn. We describe retrospectively the clinical presentation, treatment and follow up of 28 children born of hyperthyroid mothers. Patients were subdivided as follows: Group A (neonatal hyperthyroidism) (n=9): born from eight hyperthyroid mothers and one thyroidectomized mother. Children born from untreated mothers consulted between 1 and 7 days of life, while those born from treated mothers consulted between 8 and 17 days. Eight needed treatment. All remitted completely. Group B (primary hypothyroidism) (n=14): born from treated mothers, detected by neonatal screening. Eleven had transient hypothyroidism and three needed treatment. Group C (hypothalamic-pituitary hypothyroidism) (n=5): born from uncontrolled hyperthyroid mothers and found during follow up (age 9-28 days). The infants were treated with thyroid hormone, and recovered before 8 months of life. Every child born from a mother with autoimmune thyroid disease needs paediatric endocrinological assessment for detection of possible thyroid disorders.

British HIV Association and Children's HIV Association guidelines for the management of HIV infection in pregnant women 2008

Top of page Abstract Introduction 1.0 Summary of recommendations 2.0 Scenarios: interventions to reduce mother-to child transmission of HIV 3.0 Background: UK prevalence of HIV in pregnancy and risk of transmission 4.0 Antenatal HIV testing 5.0 Preconception and fertility management in men and women infected with HIV 6.0 Sexual health of HIV-positive pregnant women 7.0 Psychosocial issues 8.0 Viral load and resistance 9.0 Management of HIV-related complications in pregnancy 10.0 Antiretroviral therapy in pregnancy: efficacy 11.0 Antiretroviral therapy in pregnancy: toxicity 12.0 Antiretroviral therapy and pregnancy: pharmacokinetics 13.0 Obstetric management of pregnancy and delivery 14.0 Pregnancy in women with HIV-2 infection 15.0 HIV and hepatitis B and C coinfections 16.0 Management of infants born to HIV-infected mothers 17.0 Infant feeding and HIV transmission during breastfeeding References Appendix

Regression of fetal cerebral abnormalities by primary cytomegalovirus infection following hyperimmunoglobulin therapy

To assess the effects of maternal and intra-amniotic hyperimmunoglobulin (HIG) infusions among cytomegalovirus (CMV) infected fetuses with ultrasound abnormalities following a primary CMV infection. The subjects were fetuses with CMV-associated cerebral and other ultrasound abnormalities. Three mothers were treated with HIG infusions during pregnancy and two were untreated. Fetal ventricle size, organ echodensity and placental thickness were measured by ultrasound before and after HIG infusions. The children were evaluated between 3 and 7 years of age. The ventriculomegaly of all three fetuses of HIG-treated mothers regressed and the ascites, hepatic echodensities, periventricular echodensities, and intestinal echodensities disappeared. Their sensorial, mental and motor development was normal at 4, 4.7, and 7 years of age. In contrast, both infants born of untreated mothers had signs and symptoms of severe CMV cerebropathy. The outcomes of the infants born to HIG-treated mothers support the efficacy of HIG as a treatment for CMV-infected fetuses with ultrasound cerebral abnormalities.

In utero exposure to HAART induces oxidative stress in adult mice offsprings

Use of nucleoside analogue reverse transcriptase inhibitors (NRTI) during pregnancy reduces HIV infection among newborns and prevents vertical transmission of the virus. The fact that alterations in fetal environment can have long‐term consequences on metabolic and endocrine pathophysiology in adult life raises concern about long‐term safety of uterine exposure to NRTI. Since NRTI can induce mitochondrial toxicity and oxidative stress, we hypothesize that infants exposed to NRTI in utero may be at increased risk of oxidative stress‐associated diseases in adult life. To test our hypothesis, pregnant mice were treated with the NRTI, combivir, two weeks before mating, during mating, pregnancy, delivery and lactation. After weaning the pups also received combivir for two additional weeks. The untreated control mothers received the vehicle, apple juice. Our data indicates that 3 months after birth, the adult offsprings of NRTI‐treated mice had significantly higher levels of blood glucose, total cholesterol and calculated LDL‐cholesterol and reduced levels of hepatic and plasma glutathione, as compared to age‐matched offsprings born to control mothers (p<0.05). Since oxidative stress is implicated in pathophysiology of insulin resistance and diabetes, studies are being conducted to address the effects of oxidative stress on glucose metabolism and mitochondrial toxicity in adult offspring. [Supported by grants in part by the Clinical Research Center of Hawaii (P20 RR011091) and the U.S. Public Health Service grants from the RCMI Program (G12 RR003061)].

Diversity of risk of mother‐to‐child HIV‐1 transmission according to feeding practices, CD4 cell count, and haemoglobin concentration in a South African cohort

To estimate the probabilities of intrapartum and postpartum HIV-1 mother-to-child-transmission according to various feeding practices (formula feeding, exclusive breastfeeding, or mixed-feeding) and to other mother and infant covariates. We used the promotion time model extended to multiple exposures to study the probability of infection attributable to each transmission occasion. Blood samples from 551 infants from Durban (South Africa) born to HIV-1 positive untreated mothers between 1995 and 1998 were sequentially tested until 15 months. The probability of infection attributable to in utero and intrapartum transmission was 21.88% (18.71-25.20) and was not significantly associated with the feeding practice. The probability of infection attributable to postnatal transmission through exclusive breastfeeding was negligible -0.7% (0-2.5) for 6 months of exclusive breastfeeding-- in comparison with that observed with mixed-feeding -6.15% (3.16-9.57) for 6 months of mixed-feeding. Maternal CD4 cell count and gestational age were significant predictors of intrapartum transmission probability while maternal CD4 cell count and maternal haemoglobin concentration were significant predictors of postpartum transmission probability. Decisions about appropriate infant feeding practices should take into account the difference in postpartum transmission risk between exclusive and mixed-feeding. Mixed-feeding should be all the more avoided that mothers have poor immunological statuses and low haemoglobin concentrations.

A Radiolabeled Oligonucleotide Ligation Assay Demonstrates the High Frequency of Nevirapine Resistance Mutations in HIV Type 1 Quasispecies of NVP-Treated and Untreated Mother–Infant Pairs from Uganda

This study explores the levels of NVP and AZT resistance mutations in untreated, NVP- or AZT-treated mother-infant pairs in Uganda. PCR-amplified reverse transcriptase (RT) gene fragments derived from PBMC samples of 85 mothers (10 AZT treated, 35 NVP treated, and 40 untreated) and their 52 infected infants (5 AZT, 9 NVP, and 38 untreated) were classified as subtype A (59%), D (29%), C (3%), and recombinant forms (9%) by population sequencing. Only 16% of the NVP-treated infected mothers and infants harbored either the K103N or the Y181C at 6 weeks postdelivery. The majority of these samples (n = 107) were then analyzed using a radiolabeled oligonucleotide ligation assay (OLA) specific for K70R, K103N, and Y181C, using nonstandard bases to accommodate sequence heterogeneity. By OLA, 43% of the NVP-treated group had K103N and/or Y181C mutations in their HIV-1 population, using >0.6% cutoff based on a comparative clonal analysis of clinical isolates. Surprisingly, an equal fraction of the untreated and NVP-treated mother-infant group had the K103N mutation in their HIV-1 population in the range of 0.6-5%. These findings suggest a relatively high frequency of K103N mutation in the drug-naive, subtype A and D infected Ugandan population as compared to the very low frequency of the Y181C and K70R mutation (<0.6%). The prevalence of the K103N mutations may be related to its low fitness cost and high genetic stability. The persistence of these mutations may reduce the effectiveness of subsequent NVP use in treatment or prevention of perinatal transmission.

Microbial manipulation of the rat dam changes bacterial colonization and alters properties of the gut in her offspring

The impact of an altered bacterial colonization on gut development has not been thoroughly studied, despite the increased risk of certain diseases with a disturbed microbiota after birth. This study was conducted to determine the effect of microbial manipulation, i.e., antibiotic treatment or Escherichia coli exposure, of the dam on bacterial colonization and gut development in the offspring. Pregnant rats were administered either broad-spectrum antibiotics 3 days before parturition or live nonpathogenic E. coli Culture Collection of University of Göteborg, Sweden type strain (CCUG 29300(T)) 1 wk before parturition and up to 14 days of lactation in the drinking water. Cecal bacterial levels, gut growth, intestinal permeability, digestive enzyme levels, and intestinal inflammation were studied in 2-wk-old rats. Pups from dams that were antibiotic-treated had higher densities of Enterobacteriaceae, which correlated with a decreased stomach growth and function, lower pancreatic protein levels, higher intestinal permeability, and increased plasma levels of the acute phase protein, haptoglobin, compared with pups from untreated mothers. Exposure of pregnant/lactating mothers to E. coli CCUG 29300(T), also resulting in increased Enterobacteriaceae levels, gave in the offspring similar results on the stomach and an increased small intestinal growth compared with the control pups. Furthermore, E. coli pups showed increased mucosal disaccharidase activities, increased liver, spleen, and adrenal weights, as well as increased plasma concentrations of haptoglobin. These findings indicate that disturbing the normal bacterial colonization after birth, by increasing the densities of cecal Enterobacteriaceae, appears to have lasting effects on the postnatal microflora, which affects gut growth and function.

Circulating Hepatitis B Virus RNA in Newborns from Carrier Mothers

Objective: Despite intermittent flares, progression of chronic infection with hepatitis B virus has generally been related to a decrease in replication levels. In our laboratory, this decrease has been found to be associated with a decline in circulating full-length transcripts (fRNA) and to a shift to truncated transcripts (trRNA). Monitoring fRNA and trRNA as markers allows a more detailed analysis of high or low or non-replicative HBV infection stages. Methods: Here, we determined circulating HBV RNA in newborns from a total of 69 HBsAg-positive carrier mothers with and without immunotherapy administered during the last 3 months of pregnancy. Results: In line with previous observations, serum HBV DNA in newborns was only found when their mothers had not been treated (7/23). HBV RNA measured as trRNA was detected both in the presence and in apparent absence of serum HBV DNA. fRNA (coexisting with HBV DNA and HBeAg) was detected only in newborns from untreated mothers (8/23) and was always combined with trRNA. In contrast, trRNA was found in newborns from both untreated (20/23) and treated mothers (26/46). Conclusions: Our data strongly suggest a direct intrauterine transmission of a low-replicative (unapparent) HBV infection stage. However, a feto-maternal transfer of trRNA (transfer of a marker) rather than transmission of the infectious virus cannot be excluded.

Effects of Selective Serotonin Reuptake Inhibitors and Venlafaxine During Pregnancy in Term and Preterm Neonates

Our goals were to (a) describe neonatal behavioral signs in a group of newborns exposed in utero to selective serotonin reuptake inhibitors or venlafaxine at the time of delivery, (b) compare the rate of neonatal behavioral signs, prematurity, and admission to specialized neonatal care between a group of exposed and unexposed newborns, and (c) compare the effects in exposed preterm and term newborns. This was a retrospective cohort study including mothers taking selective serotonin reuptake inhibitors or venlafaxine during the third trimester and mothers who were not taking any antidepressants, psychotropic agents, or benzodiazepines at the time of delivery of their newborns. Neonatal behavioral signs included central nervous, respiratory, and digestive systems, as well as hypoglycemia and the need for phototherapy. Seventy-six mothers taking antidepressants and 90 untreated mothers and their newborns were analyzed. Smoking, alcohol intake, and substance abuse were more frequent among treated mothers. In infants in the exposed group, signs involving the central nervous and the respiratory systems were often observed (63.2% and 40.8%, respectively). These signs appeared during the first day of life, with a median duration of 3 days for exposed newborns. The signs resolved in 75% of cases within 3 to 5 days for term and premature newborns, respectively. All exposed premature newborns presented behavioral manifestations compared with 69.1% of term exposed newborns. Median length of stay was almost 4 times longer for exposed premature newborns than for those who were unexposed (14.5 vs 3.7 days). Neonatal behavioral signs were frequently found in exposed newborns, but symptoms were transient and self-limited. Premature infants could be more susceptible to the effects of selective serotonin reuptake inhibitors and venlafaxine.

Perinatal Group B Streptococcal Infections and the New Guidelines

After completing this article, readers should be able to: 1. Describe the current literature on surveillance studies and patient outcomes regarding group B Streptococcus (GBS) disease. 2. Discuss the current perinatal GBS prevention guidelines. 3. Describe the limitations of the “limited evaluation” in assessing newborns at risk for GBS disease. 4. Delineate the proposed management of asymptomatic infants at risk for GBS disease, with the goal of decreasing unnecessary testing and avoiding prolonged hospitalization. Group B Streptococcus (GBS), also known as S agalactiae , is an encapsulated gram-positive bacterium that is a common inhabitant of the human gastrointestinal and genitourinary tracts. Despite recent reductions in incidence, it remains the most common cause of neonatal bacterial infections in most developed countries. The most desirable approach suggested to eliminate neonatal GBS infection is the use of GBS vaccines prior to or early in pregnancy. However, until effective GBS vaccines become available, screening pregnant women for GBS colonization and providing intrapartum antibiotic prophylaxis (IAP) will continue to be the mainstay for prevention of GBS infection in neonates, as suggested by the Centers for Disease Control and Prevention (CDC). A 70% decline in the rate of early-onset GBS disease followed the introduction of the first national consensus guidelines in 1996. In 2002, new national guidelines were released based on evidence that the screening-based strategy was superior to a risk factor-based strategy for preventing GBS infections in the neonate. As a result of many obstetricians adopting the screening-based strategy, CDC data from 2004 showed a further decline in the incidence of early-onset GBS infection to 0.34 cases per 1,000 live births. This surpasses the Healthy People 2010 objective of a reduction in the incidence of early-onset disease to 0.5 cases per 1,000 live births for all races. It should be mentioned that different countries may demonstrate different results, but …

Konnatale Syphilis trotz Mutterschaftsvorsorge? Eine Evaluierung von 14 Fällen

Congenital syphilis (CS) can be effectively avoided by adequate treatment of the mother during pregnancy. Nevertheless, in recent years, the Robert Koch Institute has reported 6-8 of CS cases per year. The aim of this study was to investigate cases of CS with regard to obstetrical history and results of maternal syphilis serology during pregnancy and postpartum. Between 1997 and 2001, a total of 14 cases of CS were diagnosed after birth in the Stuttgart laboratory. Information on clinical and serological data obtained during prenatal care and at birth had been provided by the treating gynaecologists and paediatricians. Furthermore, serum samples from 11 of the 14 mothers were investigated at the Stuttgart laboratory after birth and also retrospectively at the Herford laboratory. All mothers presented without clinical signs of syphilis. Delayed prenatal care was observed in 6 out of 14 cases. Eleven of the 14 mothers had a positive treponemal screening test. Treatment was initiated only in two of them. During pregnancy treponemal IgM and cardiolipin antibodies were detected in none of 9 and in 5 of 8 sera of untreated mothers, respectively. In contrast, maternal serum samples investigated after birth were all positive for cardiolipin antibodies and 7 of 10 serum samples were positive for TP IgM antibodies. Delayed or absent prenatal care and misinterpretation of syphilis serology (or laboratory failures) in the presence of latent syphilis are mostly responsible for the inadequate management of syphilis during pregnancy and thus the occurrence of CS.

Age at Which HIV Infection Can Be Detected in Infants

In St. Petersburg, Russia, we sought to describe the characteristics of active high-risk injection drug users (IDUs) to evaluate the associations between behavioral and demographic characteristics and HIV-1 infection and to describe 3 discrete recruitment methods. Active high-risk IDUs were recruited in 3 ways: through street outreach, at facilities serving IDUs, and by network-based chain referral. Recruits were screened, counseled, and tested for HIV-1. Sociodemographic and behavioral data were collected. HIV-1 prevalence was analyzed as a function of sociodemographic and behavioral variables. During the 10-month recruitment period, data from 900 participants were collected: median age was 24 years, and in the previous month, 96% used heroin and 75% shared needles with others. The baseline HIV prevalence was 30% (95% confidence interval [CI]: 27 to 33). Recruitment through social networks was the most productive strategy. HIV-positive individuals were younger, but none of the other sociodemographic or behavioral characteristics differed significantly by HIV status. The estimated HIV prevalence of 30% places St. Petersburg among the worst IDU-concentrated epidemics in Europe. Recruitment through network-based chain referral is a useful method for recruiting active IDUs. Sociodemographic and behavioral links to prevalent HIV infection remain to be elucidated.

Maternal panic disorder and congenital abnormalities: A population‐based case‐control study

Maternal panic disorder in pregnancy is the most common manifestation of anxiety disorders in Hungary. The association between panic disorder during pregnancy and structural birth defects, i.e., congenital abnormalities, was studied. The prevalence of maternal panic disorder in cases with different congenital abnormalities was compared to that of matched controls in the population-based Hungarian Case-Control Surveillance System of Congenital Abnormalities. Of 22,843 cases with congenital abnormalities, 210 (0.9%) had mothers with panic disorder during pregnancy compared to 187 (0.5%) of 38,151 controls (adjusted prevalence odds ratio [POR] 1.6; 95% CI, 1.3-2.0). Specific groups of congenital abnormalities were also assessed versus controls. Cases with isolated cleft lip with or without cleft palate (CL/P) (adjusted POR, 3.4; 95% CI, 1.3-9.0) and multiple congenital abnormalities (adjusted POR, 3.0; 95% CI, 1.2-7.2) were more likely to have had mothers with panic disorder during the study pregnancy. Notably, among mothers with panic disorders, the associations were found only in offspring of untreated mothers. A higher rate of isolated CL/P and multiple congenital abnormalities may be caused by the direct biological effect of panic disorder or by the interaction of maternal panic disorder and lifestyle factors. Antipanic drug treatment seems to have a protective effect for isolated CL/P and multiple congenital abnormalities. Birth Defects Research (Part A), 2006.

The Relationship of the Factor V Leiden Mutation and Pregnancy Outcomes for Mother and Fetus

Venous thromboembolism associated with pregnancy is the most common cause of maternal deaths and also is a significant cause of maternal morbidity. The most common genetic factor predisposing to thrombosis is the factor V Leiden (FVL) mutation. Retrospective studies have found a 10% to 25% increase in the risk of venous thromboembolism in pregnant women heterozygous for the FVL mutation. The present prospective, multicenter study was aimed at determining the risk conferred by the FVL mutation on pregnant women with no history of thromboembolism. Another goal was to assess the impact of maternal (or fetal) carriage of the FVL mutation on pregnancy outcomes. Screening of 4885 women who were seen at 13 clinical centers before 14 weeks gestation yielded 134 heterozygous carriers of the FVL mutation (2.7%). Whites were affected substantially more often than blacks or Hispanics. Of 4 women with pregnancy-related venous thromboembolism, 3 had pulmonary embolism, and one had deep venous thrombosis. None of these events occurred in women carrying the FVL mutation. The risk of adverse pregnancy outcomes did not differ significantly in mutation carriers and noncarriers. The findings in this prospective study indicate strongly that untreated mothers heterozygous for the FVL mutation are at low risk of thromboembolism (and prophylactic anticoagulant therapy is not indicated) providing that there are no evident risk factors for thrombosis.

A randomized trial of two postexposure prophylaxis regimens to reduce mother-to-child HIV-1 transmission in infants of untreated mothers

Single-dose nevirapine (NVP) prophylaxis to mother and infant is widely used in resource-constrained settings for preventing mother-to-child transmission (MTCT) of HIV-1. Where women do not access antenatal care or HIV testing, postexposure prophylaxis to the infant may be an important preventative strategy. This multicentre, randomized, open-label clinical trial (October 2000 to September 2002) in South Africa compared single-dose NVP with 6 weeks of zidovudine (ZDV), commenced within 24 h of delivery among 1051 infants whose mothers had no prior antiretroviral therapy. HIV-1 infection rates were ascertained at birth, and at 6 and 12 weeks of age. Kaplan-Meier survival methods were used to estimate HIV-1 infection rates in an intention-to-treat analysis. Overall, 6 week and 12 week MTCT probability was 12.8% [95% confidence interval (CI),10.5-15.0] and 16.3% (95% CI,13.4-19.2), respectively. At 12 weeks, among infants who were not infected at birth, 24 (7.9%) infections occurred in the NVP arm and 41 (13.1%) in the ZDV arm (log rank P = 0.06). Using multivariate analysis, factors associated with infection following birth were ZDV use [odds ratio (OR), 1.8; 95% CI,1.1-3.2; P = 0.032), maternal CD4 cell count < 500 x 10(6) cells/l (OR, 2.5; 95% CI,1.3-5.0; P = 0.007), maternal viral load > 50 000 copies/ml (OR, 3.6; 95% CI,2.0-6.2; P < 0.0001) and breastfeeding (OR, 2.2; 95% CI,1.3-3.8; P = 0.006). A single-dose of NVP given to infants offers protection against HIV-1 infection and should be a strategy used in infants of mothers with untreated HIV infection.

‘Programming’ of orexigenic and anorexigenic hypothalamic neurons in offspring of treated and untreated diabetic mother rats

Exposure to maternal diabetes in utero (GD) may ‘program’ for obesity. Orexigenic neuropeptides, like neuropeptide Y (NPY) and agouti-related peptide (AGRP), and anorexigenic neuropeptides, like proopiomelanocortin (POMC) and alpha-melanocyte-stimulating hormone (MSH), are decisively involved in body weight regulation. We investigated consequences of GD and its treatment by pancreatic islet transplantation in rats for development of neuropeptidergic neurons in the arcuate hypothalamic nucleus (ARC) in weanling offspring. In GD, islet transplantation on d15 of pregnancy led to normalized blood glucose. Sham-transplanted GD mothers (TSGD) remained hyperglycemic. Twenty-one-day-old TSGD offspring developed hypothalamic ‘malorganization’. Despite of normal leptin and insulin levels in TSGD offspring, increased immunopositivity of NPY and AGRP appeared. TSGD offspring showed unchanged POMC, but decreased MSH-immunopositivity. In conclusion, untreated diabetes in pregnant rats leads to ‘malprogramming’ of hypothalamic neuropeptidergic neurons in offspring, probably contributing to later development of overweight. These acquired alterations are preventable by treatment of maternal GD.

The sequelae of untreated maternal hypothyroidism

The concept that gestational subclinical hypothyroidism could have deleterious effects on the intellectual outcome of progeny was championed more than three decades ago by Evelyn Man in a series of publications. Her studies lay fallow until the Spanish group directed by Morreale de Escobar and the Dutch group headed by Vulsma provided the rationale for her results. Although the findings of the Spanish and Dutch groups elucidated the pathophysiologic basis for Man's conclusions, questions remained regarding the reliability of her biochemical measurements and possible bias in patient selection. In view of the uncertainty surrounding the validity of Man's work, we decided to try to confirm her findings. Our initial goal was to obtain an estimate of the prevalence of subclinical hypothyroidism in an unselected population living in New England. We accomplished this with two separate prospective studies involving 12 000 pregnant women residing in Maine. We found that 2.3% had TSH concentrations of >6.0 mU/l and 0.3% had TSH values of >12 mU/l at 17 weeks' gestation. We next did a retrospective study, utilizing sera that had been stored at -20 degrees C for 8 years, obtained in week 17 of gestation from 25 000 women. We identified 62 women with subclinical hypothyroidism and 124 matched controls. Fourteen of the hypothyroid mothers had been diagnosed and treated before and during pregnancy on a dosage of thyroxine that was unchanged. WISC IQs of the offspring of the 124 control and 62 hypothyroid mothers were determined at 8+/-0.5 years. The mean and s.d. of IQs of the children of the 124 control and of the 14 treated hypothyroid mothers were significantly higher than those of the children of the 48 untreated hypothyroid women. More than twice as many children of the untreated mothers had IQs of >1 s.d. below the control mean, and four times as many of the children had IQs 2 s.d. below the control mean, as did the children of the controls. A comparison of the mean hormonal values of the treated and untreated mothers at 17 weeks showed no significant difference in any of the biochemical markers. We surmise that the circulating level of thyroxine was normal in the treated mothers at a critical time before 17 weeks' gestation, but by 17 weeks it was insufficient to meet the growing demands of pregnancy. Treatment should begin as early as possible in pregnancy with the goal of maintaining free thyroxine (FT(4)) in the upper half of the normal reference range and TSH in the lower half of the normal reference range. In view of these data, we believe that all pregnant women should be screened for hypothyroidism as early in pregnancy as possible (or even before conception). To be cost-effective, screening programs should be based on those designed for congenital hypothyroidism, in which filter-paper blood specimens are forwarded to regional laboratories for thyroid function determinations.

Effects of Intrapartum Penicillin Prophylaxis on Intestinal Bacterial Colonization in Infants

Early-onset group B streptococcal (GBS) infections remain a leading cause of morbidity and mortality in infants. To prevent the vertical transmission of GBS and neonatal GBS infection, guidelines recommend intrapartum penicillin or amoxicillin prophylaxis. This intrapartum antibiotic prophylaxis (IAP) is suspected to favor colonization by antibiotic-resistant bacteria. However, the effects of this prophylaxis on the patterns of acquisition of gastrointestinal bacterial flora in infants have never been studied. We collected stool samples from 3-day-old infants born to mothers who received intrapartum amoxicillin (antibiotic-exposed group; n = 25) and to untreated mothers (non-antibiotic-exposed group; n = 25). The groups were matched for factors known to affect intestinal microbial colonization: gestational age, type of delivery, and type of feeding. Qualitative and quantitative differential analyses of the bacterial flora in stool samples were performed. Similar numbers of infants in the non-antibiotic-exposed and antibiotic-exposed groups were colonized by aerobic bacteria and amoxicillin-resistant enterobacteria (75 and 77%, respectively) (P = 0.79). In contrast, significantly fewer infants in the antibiotic-exposed group than in the non-antibiotic-exposed group were colonized by anaerobic bacteria, especially Clostridium (12 and 40%, respectively) (P < 0.05). Regarding intestinal bacterial colonization, the differences between antibiotic-exposed and non-antibiotic-exposed infants were remarkably few. The only statistically significant effect was the reduced initial bacterial colonization by Clostridium in the antibiotic-exposed group. In our study, the use of IAP did not favor colonization by beta-lactam-resistant bacteria. However, further evaluations are required to highlight the potential risks of the widespread use of antibiotics to prevent early-onset GBS infection.

PRODUCTIVITY STIMULATION IN STRAWBERRY BY APPLICATION OF PLANT BIOREGULATORS

Influence of several plant bioregulators (PBRs) on yield and growth of strawberry plants in two field experiments was evaluated. Experiments were carried out at the Research Institute of Pomology and Floriculture, Skierniewice, Poland, in the years 1997-2000. In the first experiment conducted from 1997 to 1999 three cultivars (‘Senga Sengana’, ‘Dukat’ and ‘Elkat’) were sprayed 3 times during the blooming time with new formulations of preparations containing 2-naphthoxyacetic acid (BNOA) and/or gibberellic acid (GA3). It was found that the tested cultivars responded differently to the applied PBRs. ‘Senga Sengana’ responded positively, while ‘Dukat’ and ‘Elkat’ did not. Among evaluated bioregulators the best results were obtained after the application of Betoxon Super 050 SL (salt of 2-naphthoxyacetic acid with triethanolamine). It resulted in increased yield (by 31.9%) and improved fruit quality. Fruits from treated plants were larger (by 11.6%) and firmer than those from the control ones. Application of the PBRs had no influence on the degree of fruit infection with grey mould. The second experiment was carried out in 2000. Its aim was to stimulate the vegetative growth (determined by formation of runners and daughter plants) of three strawberry cultivars which are poor in forming runners and therefore difficult to propagate (‘Selva’, ‘Mara des Bois’ and ‘Vikat’) by application (three times in mid summer) of several PBRs. The following PBRs were applied: Pomonit Super 05 SL (5% triethanolamine salt NAA), Paturyl 100 SL (10% BA), Gibrescol 10 MG (10% GA3), Promalin 3.6 SL (1.8% BA + 1.8% GA4+7) and ASAHI SL (trade name Atonik – 0.3% sodium para-nitro-phenolan + 0.2% sodium orto-nitrophenolan + 0.1% sodium 5-nitrogujakolan) – each of them in concentrations of 0.1% and 0.2%. The most simulative effect on daughter plants formation was established for Gibrescol 10 MG (0.2%) and Promalin 3.6 SL (0.2%), results being quite similar for both preparations. These treatments increased the number of daughter plants by almost 300% as compared with the untreated control mother plants.