The gestational foundation of sex differences in development and vulnerability.

Despite long-standing interest in the role of sex on human development, the functional consequences of fetal sex on early development are not well-understood. Here we explore the gestational origins of sex as a moderator of development. In accordance with the focus of this special issue, we examine evidence for a sex differential in vulnerability to prenatal and perinatal risks. Exposures evaluated include those present in the external environment (e.g., lead, pesticides), those introduced by maternal behaviors (e.g., alcohol, opioid use), and those resulting from an adverse intrauterine environment (e.g., preterm birth). We also provide current knowledge on the degree to which sex differences in fetal neurobehavioral development (i.e., cardiac and motor patterns) are present prior to birth. Also considered are contemporaneous and persistent sex of fetus effects on the pregnant woman. Converging evidence confirms that infant and early childhood developmental outcomes of male fetuses exposed to prenatal and perinatal adversities are more highly impaired than those of female fetuses. In certain circumstances, male fetuses are both more frequently exposed to early adversities and more affected by them when exposed than are female fetuses. The mechanisms through which biological sex imparts vulnerability or protection on the developing nervous system are largely unknown. We consider models that implicate variation in maturation, placental functioning, and the neuroendocrine milieu as potential contributors. Many studies use sex as a control variable, some analyze and report main effects for sex, but those that report interaction terms for sex are scarce. As a result, the true scope of sex differences in vulnerability is unknown.

Effect of maternal zinc supplementation on the cardiometabolic profile of Peruvian children: results from a randomized clinical trial.

Zinc is an essential micronutrient for the development of the fetal renal, cardiovascular and metabolic systems; however, there is limited evidence of its effects on the postnatal cardiometabolic function. In this study, we evaluated the effect of maternal zinc supplementation during pregnancy on the cardiometabolic profile of the offspring in childhood. A total of 242 pregnant women were randomly assigned to receive a daily supplement containing iron+folic acid with or without zinc. A follow-up study was conducted when children of participating mothers were 4.5 years of age to evaluate their cardiometabolic profile, including anthropometric measures of body size and composition, blood pressure, lipid profile and insulin resistance. No difference in measures of child cardiometabolic risk depending on whether mothers received supplemental zinc during pregnancy. Our results do not support the hypothesis that maternal zinc supplementation reduces the risk of offspring cardiometabolic disease.

Women's response to fetal choroid plexus cysts detected by prenatal ultrasound.

OBJECTIVES: To determine maternal responses to detection of a minor structural variant, the choroid plexus cyst (CPC), in their fetus on prenatal ultrasound. STUDY DESIGN: We interviewed 34 pregnant women with an isolated CPC detected on mid-pregnancy ultrasound about their objective experience at diagnosis, emotional response and subsequent reactions. Audiotaped, transcribed responses were evaluated by two independent raters and analyzed qualitatively and quantitatively. RESULTS: All women reported negative emotional responses including shock, distress, fear and decreased attachment, despite counseling by 82% of providers that the CPC was probably benign. Three women underwent amniocentesis purely for reassurance after CPC detection. Most (79%) sought information beyond what their physician provided, frequently on the internet. One half of women reported that intense negative responses were temporary. However, weeks after diagnosis, 62% continued to believe that the CPC presented some danger to their baby. CONCLUSIONS: Detection of CPC prenatally can evoke profound, negative maternal emotional responses despite accurate provider counseling. Practitioners should consider these responses when counseling parents about these and other structural variants of unclear functional significance.

Choroid plexus cysts do not affect fetal neurodevelopment.

OBJECTIVE: To determine whether an isolated finding of a choroid plexus cyst (CPC) during routine ultrasound is associated with altered fetal growth or development. STUDY DESIGN: Prospective, case-control study comparing 35 CPC cases to 67 controls. Neurobehavioral development assessment included 50 min long serial recordings of heart rate, motor activity and their interrelation at 24, 28, 32 and 36 weeks gestation. Growth measurement was based on three ultrasound evaluations of femur length, biparietal diameter, head circumference and abdominal circumference at initial exam, 28 and 36 weeks. RESULTS: Longitudinal analyses revealed no differences in fetal heart rate, variability or accelerations; the number or duration of fetal movements or total motor activity; nor fetal movement-fetal heart rate coupling. CPC cases had slightly smaller head and abdominal circumferences at 28 weeks, but these differences had disappeared by 36 weeks. CPC detection was more common when routine exams were conducted earlier (18.8 versus 19.5 weeks; P<0.01). CONCLUSION: Despite the presumption that CPCs with normal karyotypes are benign variants, little empirical support exists. These results indicate that CPCs detected by prenatal ultrasound do not pose or reveal a threat to fetal development.

Development of fetal movement--fetal heart rate coupling from 20 weeks through term.

This study documents the development of fetal heart rate (FHR) change in response to fetal movement (FM) in healthy fetuses from 20 weeks' gestational age through term. Thirty-one fetuses received 50 min of Doppler-based monitoring at 20, 24, 28, 32, 36 and 38-39 weeks. FHR and FM were continuously digitized. A coupling index was computed as the percentage of FMs associated with increases in FHR of 5 beats/min or more within -5 or +15 s of movement onset. The latency between FM onset and FHR change was also computed, as were the amplitude and duration of all movements. FM and FHR became more integrated with advancing gestation. Coupling increased and the latency between FM and FHR changes decreased. Maternal age, blood pressure and fetal sex did not affect FM-FHR coupling, but fetuses of women who reported greater stress in their daily lives and had faster heart rates displayed reduced coupling. These data suggest that the development of FM-FHR coupling reflects the development of the central nervous system during gestation, and that development may be affected by maternal factors.

In vitro fertilization and the family: quality of parenting, family functioning, and child psychosocial adjustment.

This study examined associations between homologous in vitro fertilization (IVF) and quality of parenting, family functioning, and emotional and behavioral adjustment of 3-7-year-old children. A cross-sectional survey was conducted in Taiwan with 54 IVF mother-child pairs and 59 mother-child pairs with children conceived naturally. IVF mothers reported a greater level of protectiveness toward their children than control mothers. Teachers, blind to condition, rated IVF mothers as displaying greater warmth but not overprotective or intrusive parenting behaviors toward their children. Teachers scored children of IVF as having fewer behavioral problems than control children. In contrast, IVF mothers reported less satisfaction with aspects of family functioning. Family composition moderated parenting stress: IVF mothers with only 1 child perceived less parenting stress than did those in the control group.

Measuring the ups and downs of pregnancy stress.

Despite substantial interest in the effects of stress on pregnancy, few instruments are available to measure pregnancy-specific stressors. Moreover, research has typically focused on the distressing, negative aspects of pregnancy. This report examines the reliability and validity of the Pregnancy Experience Scale (PES), a 41-item scale that measures pregnancy-specific daily hassles and uplifts. The PES was administered to two cohorts of low risk women at 24, 30, and 36 weeks (n = 52) or 32 and 38 weeks (n = 137). Women perceived their pregnancies to be significantly more intensely and frequently uplifting than hassling. Internal scale reliability was high (alpha = 0.91 to 0.95). Frequency and intensity scores for hassles and uplifts were stable over time (r's = 0.56 to 0.83) and patterns of convergent and discriminant validity emerged between the PES and existing measures of general affective intensity, daily stressors, depressive symptoms, and anxiety. These results indicate that (1) failure to measure pregnancy-specific stress will underestimate the degree to which pregnant women experience distress and (2) measurement of only the negative aspects of pregnancy will overestimate distress and fail to portray the degree to which women are psychologically elevated by their pregnancies. Measurement of hassles relative to uplifts may provide the most balanced assessment of pregnancy appraisal.

Environmental contamination by eggs of Toxocara species.

A study was conducted to determine the level of contamination with Toxocara spp. eggs in parks and playgrounds in several central Illinois communities. A total of 135 composite 50-g soil samples were collected from 23 parks and public places in three cities in central Illinois. Of these soil samples, 22 (16.3%) contained from one to thirteen Toxocara spp. eggs. A total of 40 fecal samples were collected from the same parks. Toxocara spp. eggs were found in two (5%) of the samples.

Ivermectin treatment of horses: effect on the distribution of lawns and roughs in horse pastures.

A study was carried out to assess the feasibility of determining the grazing patterns of horses bimonthly via aerial survey and standard cartographic techniques. The grazing patterns in pastures with equivalent stocking rates of horses treated bimonthly with 200 micrograms of ivermectin kg-1 or 10 mg of oxibendazole kg-1 was assessed using aerial survey mapping performed three times during a grazing season. The distribution patterns of lawns and roughs in pastures were similar at all times during the study. Aerial survey was determined to be a very efficient and objective method of determining the composition of pastures grazed by horses.

Persistent activity of doramectin and ivermectin against Ascaris suum in experimentally infected pigs.

A study was conducted to investigate the persistent nematocidal activity of two avermectins against experimentally-induced infections of Ascaris suum in swine. Seventy-two nematode-free cross-bred pigs of similar bodyweight were randomly allotted to nine treatment groups of eight pigs each. Eight of the groups were treated with injectable solutions containing 300 microg of doramectin/kg (IM) or 300 microg of ivermectin/kg (SC) either 0 (same day), 7, 14, or 21 days prior to an oral challenge of 50000 embryonated A. suum eggs. The ninth group (control) was challenged in parallel without any avermectin treatment. At 41 or 42 days after challenge, pigs were euthanatized and adult and larval stages of A. suum were collected from the gastrointestinal tract of each pig and counted. Both avermectins significantly (P < 0.0002) reduced nematode counts when given on the day of challenge (0 days prior), and the efficacy was 100% and 97.5% for doramectin and ivermectin, respectively. Doramectin given 7 days prior to challenge significantly (P < 0.0001) reduced nematode counts, and the efficacy was 98.4%. For all other avermectin-treatment groups, nematode counts were not significantly reduced compared to those in control pigs. These data indicated that anthelmintic activity of ivermectin against A. suum persisted for less than 7 days and the activity of doramectin persisted for more than 7, but less than 14 days.

Controlled efficacy study of the bioequivalence of Strongid C and generic pyrantel tartrate in horses.

The bioequivalence of Strongid C and generic pyrantel tartrate was determined in a controlled study using 30 horses with naturally acquired endoparasitic infections. Three horses were randomly allocated to each of ten replicates based on quantitative nematode and ascarid egg counts and fecal larvae culture results. Horses within each replicate were randomly assigned to one of three treatment groups. Horses in Treatment Group 1 received only oats; horses in Treatment Group 2 received generic pyrantel tartrate pellets (2.65 mg pyrantel tartrate kg-1) mixed with oats; horses in Treatment Group 3 were fed Strongid C pellets (2.65 mg pyrantel tartrate kg-1) mixed with oats. Horses were treated daily for a 30 day continuous treatment period. At the termination of the study the horses were necropsied and endoparasites recovered, identified, and enumerated. In all instances, no significant difference (P > 0.05) in mean numbers of parasites recovered existed between horses treated with generic pyrantel tartrate and Strongid C. Numbers of gastrointestinal parasites recovered from horses treated with generic pyrantel tartrate or Strongid C were shown to be significantly different (P < 0.05) from numbers of gastrointestinal parasites recovered from non-treated controls for the large strongyles (Strongylus vulgaris, S. edentatus, and Triodontophorus spp.), small strongyles (Cyathostomum spp., Cylicocyclus spp., and Cylicostephanus spp.) and fourth-stage Parascaris equorum. Numbers of adult P. equorum recovered from horses treated with Strongid C were also significantly different (P < 0.05) from those from non-treated controls. Numbers of adult P. equorum recovered from horses treated with generic pyrantel tartrate were not significantly different (P = 0.0761) from those from non-treated controls. The determination of bioequivalence was based upon the 95% confidence interval of the difference between the mean number of parasites recovered from horses treated with generic pyrantel tartrate and the mean number of parasites recovered from horses treated with Strongid C. For all instances in which the numbers of parasites recovered from horses treated with either Strongid C or generic pyrantel tartrate were significantly different from the numbers of parasites recovered from non-treated controls, bioequivalence was demonstrated.

Clinical trial of moxidectin oral gel in horses.

A clinical trial carried out over 98 days was done to evaluate treatment of horses with moxidectin gel for efficacy as measured by (1) reduction in the production of parasite ova post treatment, (2) a comparison of the posttreatment parasite egg count suppression of moxidectin to ivermectin, and (3) assessment of the field safety, animal acceptance of the moxidectin formulation, and the utility of the moxidectin delivery device. One hundred and fifty Standardbred horses with naturally acquired parasite infections were used in the study. Moxidectin had more prolonged and greater suppressive influence than did ivermectin on reappearance and magnitude of strongyle egg counts post treatment. Differences were not observed between the capability of ivermectin or moxidectin to reduce and suppress low Parascaris equorum egg counts. Adverse reactions to treatments were not observed, and the utility of the moxidectin delivery syringe and animal acceptance of moxidectin treatment were satisfactory.

A comparison of the bioequivalence of 0.5% fenbendazole top dress pellets or 10% fenbendazole oral suspension against a spectrum of equine parasites.

A controlled test was conducted to assess the efficacy bioequivalence of a single dose of 0.5% fenbendazole (FBZ) top dress pellets to a 10% FBZ suspension formulation (Panacur suspension 10%, Hoechst Roussel Vet). Thirty horses with naturally-acquired parasite infections, in replicates of three, were used. Strongyle egg per gram counts were not significantly different (P>0.1) between groups pretreatment, but FBZ treated groups were significantly different from the control group post-treatment. At necropsy, which occurred seven to nine days post-treatment, two methods of nematode recovery were compared to assess whether a small aliquot can be used in a control test to determine efficacy against large as well as small strongyles. Both post mortem worm recovery techniques revealed similar efficacies of both formulations (>95%) against small and large strongyles, but large differences in the number of worms recovered. Six species of small strongyles comprised 96% of all the small strongyles recovered: Coronocyclus coronatus, Cylicocyclus insigne, Cylicostephanus longibursatus, Cylicocyclus brevicapsulatus, Cylicocyclus nassatus, and Cyathostomum catinatum. The results of this study demonstrated therapeutic bioequivalence between FBZ formulations and also the need to sample at least a 10% aliquot to accurately estimate number of large strongyles. No adverse reactions to treatment were detected.

Bacteriologic examination of equine fecal flora as a diagnostic tool for equine intestinal clostridiosis.

The fecal flora of 56 clinically healthy and 23 sick horses were examined bacteriologically for counts of Clostridium perfringens, molds, coliforms, alpha- and beta-hemolytic streptococci, and microbes belonging to genus Bacillus, as well as for the presence of Salmonella spp. Of the healthy horses, 85.7% had a C perfringens count less than 10(1) colony-forming units/g of feces. Of the healthy horses, lowest counts were found in race-horses. Of the sick horses, equine intestinal clostridiosis was diagnosed in 2 horses with large C perfringens counts (10(4) to 10(7) colony-forming units/g) and with acute diarrhea. The 7 isolates of C perfringens were identified as serotype A. Salmonella spp were not detected from any of the horses. The study indicated that diagnosing equine intestinal clostridiosis based on the determination of the fecal C perfringens count was suitable.

Anti-strongyle activity of a propylene glycol-glycerol formal formulation of ivermectin in horses (mares).

Four groups of 10 horses (mares) each were treated with a 1% solution of ivermectin (200 micrograms/kg of body weight) in a propylene glycol-glycerol formal base orally, a 1% solution of ivermectin (200 micrograms/kg) in a propylene glycol-glycerol formal base via nasogastric tube, a 1.87% paste of ivermectin (200 micrograms/kg) orally, or a 22.7% paste of oxibendazole (10 mg/kg) orally. Fecal examinations were done before treatment and on posttreatment days (PTD) 14, 28, 42, 56, and 70. Strongyle egg per gram counts and sugar flotation fecal examinations were performed. Results of fecal examinations before treatment were similar in all horses. All horses treated with ivermectin had similar percentages of reductions in mean strongyle egg per gram counts after treatment; 100% on PTD 14, 28, and 56 and 93.4% to 98.7% on PTD 70. All ivermectin treatment groups had 0 horses detected as passing strongyle eggs on PTD 14 and 28, 0 to 2 on PTD 42, 3 to 5 on PTD 56, and 8 to 9 on PTD 70. Horses treated with oxibendazole had 99.9%, 99.7%, 92.9% 78.6%, and 54.5% reductions in mean strongyle egg per gram counts and 5, 7, 8, 9, and 9 horses detected as passing strongyle eggs on PTD 14, 28, 42, 56, and 70, respectively. Adverse reactions to treatment were not observed.

Anthelmintic efficacy of avermectin B1a and dihydroavermectin B1a against ovine gastrointestinal nematodes in 1977.

In a critical study, 40 female mixed-breed lambs with experimental infections of Cooperia spp, Trichostrongylus colubriformis, Ostertagia circumcincta, T axei, and Haemonchus contortus were allocated to 8 groups in 1977. Groups 1 and 5 served as controls. Groups 2 to 4 were treated orally with avermectin B1a at dosage levels of 25, 50, and 100 micrograms/kg of body weight, respectively. Groups 6 to 8 were given oral dihydroavermectin B1a at dosage levels of 50, 100, and 200 micrograms/kg, respectively. The lambs were euthanatized and necropsied 6 days after treatment. The compounds were greater than 99% effective at all dosage levels.

Clinical observations in collies given ivermectin orally.

An oral liquid form of ivermectin was administered to 14 purebred Collies (12 rough coated, 2 smooth coated). All Collies were given ivermectin at dosages of 100 and then 200 micrograms/kg of body weight. Three of the dogs developed mild clinical signs of toxicosis (salivation, vomiting, confusion, ataxia, and tremors) with the 100 micrograms/kg dosage. After the 200 micrograms/kg dosage, 7 dogs (including 1 smooth-coated Collie) developed severe toxicosis (seizure-like activity, recumbency, nonresponsiveness, and coma). Because dogs that developed severe toxicosis were not retreated, only the 7 remaining dogs were given ivermectin at 600 micrograms/kg. Severe toxic signs were not observed in the dogs given the 600 micrograms/kg dosage, and only 1 of these 7 dogs developed severe toxicosis when given ivermectin at 2,500 micrograms/kg. Dogs that developed severe toxicosis were given supportive care while in the comatose state. All dogs recovered completely. The results indicated that Collies (including the smooth-coated Collies) have a wide range of sensitivity to ivermectin-induced toxicosis.

Evaluation of ivermectin for larvicidal effect in experimentally induced Parascaris equorum infections in pony foals.

A controlled test was carried out on 15 pony foals inoculated with 1,500 +/- 108.8 infective Parascaris equorum eggs. The foals were assigned to 3 treatment groups. Treatments given on postinoculation day 11 included 0.2 mg of ivermectin/kg of body weight, formulated as paste (n = 5), or liquid (n = 5), or no treatment (controls; n = 5). The foals were euthanatized on postinoculation day 25, and examined for larvae in the small intestine, lungs, and liver. Larvae were not found in foals treated with ivermectin liquid or paste, whereas significantly (P less than 0.05) higher mean numbers (960.9; range, 379 to 1,736) of 4th-stage larvae were found in the controls. Histologic and gross examination of lungs and liver revealed pathologic changes attributable to P equorum migration that were similar in all foals. Adverse reactions to treatment were not observed.

Efficacy of ivermectin against Dirofilaria immitis larvae in dogs 30 and 45 days after induced infection.

Forty-two Beagles, 14 to 15 weeks of age, were injected subcutaneously with 50 infective larvae of Dirofilaria immitis and were allotted by weight, within sex, to 6 treatment groups. Group 1 served as nonmedicated vehicle-treated controls; groups 2 through 5 were given an oral tablet form of ivermectin at dosages of 0.3 micrograms/kg, 1.0 micrograms/kg, 2.0 micrograms/kg, and 3.3 micrograms/kg at 30 days after inoculation; group 6 was given the 2.0 micrograms/kg dosage at 45 days after inoculation. Dogs were euthanatized and necropsied 154 days after treatment (day 139 for dogs in group 6) and examined for heartworms. On the numerical bases of helminths recovered in the groups, the efficacies for preventing heartworm maturation were 0% (group 2), 53.2% (group 3), 97.2% (group 4), 98.1% (group 5), and 63.8% (group 6). Drug-related adverse reactions were not detected.

Efficacy of an in-feed preparation of ivermectin against endoparasites and scabies mites in swine.

In 2 trials, the efficacy of an in-feed preparation of ivermectin was evaluated in 40 pigs naturally infected with endoparasites and Sarcoptes scabiei var suis. Treated pigs (n = 10 in each trial) were fed a ration containing 2 ppm ivermectin for 7 days, followed by consumption of a nonmedicated ration for the remainder of the trial. Control pigs (n = 10 in each trial) were fed a complete, nonmedicated ration for the duration of the trial. Pigs in trial A were monitored for 14 days after treatment; those in trial B were monitored for 35 days after treatment. In trial A, treatment efficacy of ivermectin was 100% against Ascaris suum, Physocephalus sexalatus, Oesophagostomum dentatum, O brevicaudum, Metastrongylus spp; 99.8% against Ascarops strongylina; 90.9% against Trichuris suis; and 13.1% against Macracanthorhynchus hirudinaceus. At the terminus of the trial, statistically significant (P less than 0.05) differences were observed between numbers of treated and control pigs infected with A suum, Ascarops strongylina, and Oesophagostomum spp. On posttreatment day 14, S scabiei were not found in any scrapings taken from treated pigs, but were found in scrapings from 3 of 10 control pigs. The number of infested pigs in the treatment group was not statistically different from the number of infested pigs in the control group. In trial B, treatment efficacy was 100% for A suum and Metastrongylus spp; 96.9% for Ascarops strongylina; and 76.9% for M hirudinaceus. At the terminus of the trial, statistically significant (P less than 0.05) differences were evident between numbers of treated and control pigs infected with A suum, Ascarops strongylina, and Metastrongylus spp.(ABSTRACT TRUNCATED AT 250 WORDS)