Effects of dietary energy intake during gestation and lactation on milk yield and composition of first, second and fourth parity sows

In order to determine the effects of a varied level of dietary energy intake during pregnancy and lactation on milk yield and composition, first, second and fourth parity sows (Large White x German Landrace) were provided with energy at a level of either: (i) 100% of ME requirement (MEreq) during pregnancy and lactation, (ii) 120% MEreq during pregnancy and 80% during lactation, and (iii) 80% MEreq during pregnancy and 120% during lactation. In spite of equal target levels feed analysis revealed that gestating first parity sows with 120/80 treatment combination and lactating sows of 80/120 treatment combination received 25, and 11-17% more digestible N than in the respective 100/100 treatment combination. Irrespective of this 120/80 sows responded with the highest milk DM, fat, and energy contents, and the lowest lactose concentrations whereas protein levels where not affected, irrespective of parity (p < 0.05). Milk yield of sows in 1st and 4th lactation was 85 and 106% of that in 2nd lactation, respectively. Average milk composition was 18.1% DM, 4.9% protein, 6.8% fat, 5.6% lactose, and 0.8% ash. Milk composition changes ceased at day 7 of lactation with a reduction of milk GE and protein, and an increase of lactose content. Concentrations of threonine, arginine, valine, leucine, tyrosine, phenylalanine, cystine, and tryptophan, as well as stearic, oleic, and linoleic acid were higher in colostrum than in milk at later lactation stages. In contrast, laurine, myristic, palmitic, and palmitoleic acids were lower concentrated in colostrum. In conclusion, these results illustrate the importance of body reserve mobilization for milk production in sows and indicate that low energy supply during gestation cannot be compensated by higher energy supply during lactation.     

Progress in the prevention and control of schistosomiasis and soil-transmitted helminthiasis

In the last two decades important progress has been made in the understanding the epidemiology and the disease burden of schistosomiasis and soil-transmitted nematodes infection. In addition, practical tools for disease control have been developed and a strategy for the prevention and control of morbidy of schistosomaisis and soil-transmitted nematodes infection has been endorsed by the World Health Organization. This paper presents the recent progress in the prevention and control of these infections: the estimates of chronic and subtle morbidity in high risk groups and the evidence that these chronic and severe sequelae of infections can be reversed by appropriate treatment; the use of anthelminthic drugs during pregnancy and lactation; the relevance to control morbidity due to these infections also in pre-school children; the efficacy of anthelminthic drugs and the possible threat of drug resistance; price, quality and accessibility of treatment by delivering drugs through the school system and ways of reaching also non-enrolled school-age children. Finally, the strategy, targets and recommendations of the World Health Organization for the control of schistosomiasis and soil-transmitted nematodes infection are described.     

Effects of dietary energy intake during gestation and lactation on milk yield and composition of first,second and fourth parity sows

Abstract

In order to determine the effects of a varied level of dietary energy intake during pregnancy and lactation on milk yield and composition, first, second and fourth parity sows (Large White × German Landrace) were provided with energy at a level of either: (i) 100% of ME requirement (MEreq) during pregnancy and lactation, (ii) 120% MEreq during pregnancy and 80% during lactation, and (iii) 80% MEreq during pregnancy and 120% during lactation. In spite of equal target levels feed analysis revealed that gestating first parity sows with 120/80 treatment combination and lactating sows of 80/120 treatment combination received 25, and 11 – 17% more digestible N than in the respective 100/100 treatment combination. Irrespective of this 120/80 sows responded with the highest milk DM, fat, and energy contents, and the lowest lactose concentrations whereas protein levels where not affected, irrespective of parity (p < 0.05). Milk yield of sows in 1st and 4th lactation was 85 and 106% of that in 2nd lactation, respectively. Average milk composition was 18.1% DM, 4.9% protein, 6.8% fat, 5.6% lactose, and 0.8% ash. Milk composition changes ceased at day 7 of lactation with a reduction of milk GE and protein, and an increase of lactose content. Concentrations of threonine, arginine, valine, leucine, tyrosine, phenylalanine, cystine, and tryptophan, as well as stearic, oleic, and linoleic acid were higher in colostrum than in milk at later lactation stages. In contrast, laurine, myristic, palmitic, and palmitoleic acids were lower concentrated in colostrum. In conclusion, these results illustrate the importance of body reserve mobilization for milk production in sows and indicate that low energy supply during gestation cannot be compensated by higher energy supply during lactation.     

Effects of stage of pregnancy on variance components,daily milk yields and 305-day milk yield in Holstein cows,as estimated by using a test-day model

Pregnancy and calving are elements indispensable for dairy production, but the daily milk yield of cows decline as pregnancy progresses, especially during the late stages. Therefore, the effect of stage of pregnancy on daily milk yield must be clarified to accurately estimate the breeding values and lifetime productivity of cows. To improve the genetic evaluation model for daily milk yield and determine the effect of the timing of pregnancy on productivity, we used a test-day model to assess the effects of stage of pregnancy on variance component estimates, daily milk yields and 305-day milk yield during the first three lactations of Holstein cows. Data were 10 646 333 test-day records for the first lactation; 8 222 661 records for the second; and 5 513 039 records for the third. The data were analyzed within each lactation by using three single-trait random regression animal models: one model that did not account for the stage of pregnancy effect and two models that did. The effect of stage of pregnancy on test-day milk yield was included in the model by applying a regression on days pregnant or fitting a separate lactation curve for each days open (days from calving to pregnancy) class (eight levels). Stage of pregnancy did not affect the heritability estimates of daily milk yield, although the additive genetic and permanent environmental variances in late lactation were decreased by accounting for the stage of pregnancy effect. The effects of days pregnant on daily milk yield during late lactation were larger in the second and third lactations than in the first lactation. The rates of reduction of the 305-day milk yield of cows that conceived fewer than 90 days after the second or third calving were significantly (P<0.05) greater than that after the first calving. Therefore, we conclude that differences between the negative effects of early pregnancy in the first, compared with later, lactations should be included when determining the optimal number of days open to maximize lifetime productivity in dairy cows.     

Elevated leptin concentrations in pregnancy and lactation: possible role as a modulator of substrate utilization.

Energy needs are increased during pregnancy and lactation. These increased energy needs may be met through partitioning of nutrients for energy utilization which is under hormonal control. The objective of the present studies was to determine if changes in plasma leptin occurred during pregnancy and lactation and if the changes were related to prolactin. Plasma leptin and prolactin were measured longitudinally in 9 women through pregnancy and lactation. In a second study, leptin and prolactin were measured 4 days and 28 days postpartum in 21 lactating women. Mean plasma leptin during the three trimesters of pregnancy was significantly higher (29.3+/-2.8 ng/ml) when compared to mean leptin during the three time periods of lactation (19.3+/-3.2 ng/ml) and control groups (9.8+/-1.4 ng/ml). Plasma leptin was elevated early in pregnancy and remained elevated throughout pregnancy. In the second study, the mean plasma leptin in the lactating women was significantly higher 4 days postpartum (17.3+/-3.7 ng/ml) and 28 days postpartum (19.2+/-3.9 ng/ml) when compared to controls (11.6+/-1.2 ng/ml). Prolactin in the control subjects (24+/-4 ng/ml) was significantly lower than in the pregnant (202+/-16 ng/ml) and lactating (108+/-26 ng/ml) groups. Similar observations were made in the second study (controls 20+/-2 ng/ml; lactation 28 days 159+/-21 ng/ml). Leptin during lactation was lower than in pregnancy but higher than control subjects. Regression analysis suggested that BMI and prolactin can be used as predictors of leptin in pregnancy and lactation. The increase in leptin and prolactin early in pregnancy suggests an association between the two hormones. Results of the present studies and research done by other investigators presents a strong role for leptin during pregnancy and lactation. Leptin is regulated by factors other than adiposity especially in reproductive women leading to our hypothesis that there are leptin and prolactin mediated effects on substrates used for energy utilization during pregnancy and lactation.     

A clinical look at the problem of drugs in pregnancy and their effect on the fetus.

The first annual W. E. Upjohn Lecture concerned itself with the interrelationship between administration of drugs to the pregnant woman and fetal outcome. The epidemiology of drug intake (both prescribed and self-administered drugs) during pregnancy is reviewed, using data derived from several surveys conducted both in the United States and in Scotland. The complexities of establishing a causal relationship between drug intake during pregnancy and effects upon the fetus are considered. Special emphasis is given to the adverse effects of aspirin and cigarette smoking. The shortage of data is critical and the need for further research is stressed.     

Health management of ewes during pregnancy

The objectives of health management of ewes during pregnancy are as follows: (i) successful completion of pregnancy at term, (ii) birth of healthy and viable lambs, with optimal birth and potential weaning bodyweight, (iii) optimum milk production during the subsequent lactation and (iv) improved management in relation to drug residues in animal products. Knowledge of the physiological background of pregnancy in ewes: changes, mechanisms and interactions, during pregnancy is important for the overall health management of ewes during pregnancy. Health management of pregnant ewes includes diagnosis of pregnancy and evaluation of the number of foetuses borne, which will support strategies for subsequent management of the flock. Nutritional management of ewes depends upon the stage of lactation and specifically aims to (i) prevention of pregnancy toxaemia and other metabolic diseases during the peri-partum period, (ii) formation of colostrum in appropriate quantity and quality, (iii) production of lambs with normal future birth bodyweight and (iv) support of increased milk yield during the subsequent lactation. At the end of lactation, udder management of pregnant ewes includes its clinical examination, culling of ewes considered unsuitable for lactation and, possibly, the intramammary administration of antibiotics; objectives of that procedure are (i) to cure infections which have occurred during the previous lactation and (ii) to prevent development of new mammary infection during the dry period. Management of abortions includes the correct and timely diagnosis of the causative agent of the disorder, as well as the strategic administrations of chemotherapeutic agents, aiming to prevent abortions in flocks with confirmed infection with an abortifacient agent, especially if no appropriate vaccinations had been carried out before the mating season. During the final stage of pregnancy, health management of ewes includes administration of appropriate anthelmintic drugs, aiming to eliminate gastrointestinal helminthes (thus, increasing production output of ewes) and preventing the built-up of parasitic burdens in the environment (thus, reducing infection of lambs during their neonatal period). Vaccinations of pregnant ewes aim to protect these animals, as well as their offspring, especially against diseases which are a frequent cause of neonatal mortality (e.g., clostridial infections). Health management also aims to prevent the main metabolic disorders of pregnant ewes (i.e., pregnancy toxaemia and hypocalcaemia), as well as to monitor flocks for development of these disorders. Health management of pregnant ewes is completed with application of husbandry practices before the start of the lambing season. Finally, in some cases, health management may include induction and synchronisation of lambings, which is a management or therapeutic procedure.     

Antifungal Therapy in Pregnancy and Breastfeeding

Antifungal therapy during pregnancy and lactation is challenging because of a lack of data on efficacy and safety, coupled with reports of teratogenicity. Although the Food and Drug Administration pregnancy category provides guidance regarding a drug’s potential fetal risks, limitations such as lack of a specific toxic dose or predisposing pregnancy trimester thwart its application. Central to the selection of optimal antifungal therapy are exploration of the literature and assessment of patient-specific factors, including awareness of effects on the pharmacokinetics of antifungal agents that result from physiologic changes during pregnancy. Topical azoles are favored for superficial fungal infections during pregnancy and lactation, whereas amphotericin B is preferred for invasive fungal infections. Data regarding the use of antifungal agents by breastfeeding women are lacking. More studies are needed, particularly with newer antifungals, to better guide clinicians in selecting optimal antifungal therapy that will provide benefit to the mother without harm to the fetus.     

Changes in endogenous urea recycling and the handling of renal urea in pregnant and lactating Sardi sheep kept on a constant feeding level

The kinetics of endogenous urea were compared during the last month of pregnancy, lactation, and a nonpregnant, nonlactating control period in Sardi sheep kept on a constant feed level. Urea entry rate estimated by injections of [14C]urea rose by 36% during pregnancy. Renal urea excretion was reduced by 40% during pregnancy and by 28% during lactation. Consequently, fractional urea recycling was greater during pregnancy and, to some extent, during lactation than during the control period. In a second series of experiments, glomerular filtration rate increased by 48% and urea filtration rate rose by 17% during pregnancy. During lactation, both glomerular filtration rate and urea filtration rate were close to control levels. It appears that the decreased renal urea excretion during pregnancy and lactation was due mainly to increased tubular reabsorption of urea. Rumination time increased by 15% during pregnancy. Rumen ammonia concentration was elevated in both pregnant and lactating ewes above the control period level. The results suggest that Sardi sheep possess a high potential for the conservation of nitrogen during pregnancy and lactation periods.     

Walking activity at estrus and subsequent fertility in dairy cows

Poor detection of estrus, still a major problem in the dairy industry, has prompted the development of electronic estrous detection technologies. One of the features of estrous behavior is a marked increase in walking activity. The objectives of the present study were to evaluate the effects of various management factors on walking activity increase at estrus, and the relationship between this trait and fertility. Data from 5883 artificial inseminations (AI) conducted in two high-producing dairy herds were analyzed. Detection of estrus was performed using a pedometer system. Of the total AI investigated, 2072 (35.2%) resulted in pregnancy. The following data were recorded for each animal at AI: herd, lactation number, milk production (average for the 3 days prior to AI), lactation stage (early, mid, and late lactation), previous estrous synchronization (cloprostenol or progesterone releasing intravaginal device [PRID] for animals showing estrus within 7 days of treatment), season (warm versus cool period), insemination number following parturition, inseminating bull, inseminator, and pedometer measurements. Variables were screened for associations with walking activity by analysis of variance (ANOVA) through generalized linear model procedures (PROC GLM). Increased parity and milk production, and insemination during the warm period were associated with lower pedometer measurements. No significant effects of the herd, estrous synchronization, and lactation stage were observed. The link between walking activity and fertility was determined by applying logistic regression models. We detected no significant effects of herd, milk production, estrous synchronization, lactation stage, and inseminator on pregnancy rate. A higher lactation and insemination number, and insemination during the warm period were negatively correlated with the pregnancy rate. The likelihood of pregnancy was greater when semen from one of the bulls was used and when physical activity at estrus was increased. Our findings indicate that cow and management factors contribute intensely to walking activity at estrus, and also reveal a close link between increased walking activity and fertility.     

The effect of exogenous prolactin on lactation performance of first-litter sows given protein-deficient diets during the first pregnancy

Twenty-four sows were used to study the effects of dietary protein restriction during pregnancy and exogenous porcine prolactin (pPRL) during late pregnancy and throughout lactation on lactation performance. Eight sows were given a protein-adequate diet containing 179 g crude protein (CP)kg⁻¹ during their first pregnancy while the remaining 16 sows received the same amount of a diet containing 80 g CP kg⁻¹. Eight of the sows given 80 g CP kg⁻¹ during pregnancy were injected with 15 mg pPRL i.m. twice daily at 08:00 and 20:00 between day (d) 102.1 (±0.3) of pregnancy and weaning after their first lactation. Pregnant sows offered the low protein diet gained significantly less body weight during gestation and tended to eat less in the subsequent lactation than sows given the protein-adequate diet. Dietary protein had no significant effect on birth weight, milk yield, milk composition or growth rate of the litter during lactation. Neither dietary protein intake during pregnancy nor exogenous prolactin affected the concentrations of plasma glucose, serum insulin, urea or non-esterified fatty acid (NEFA) during lactation. The concentration of lactose in plasma during lactation was unaffected by treatment, but at d 105 of pregnancy, plasma lactose levels were greater in sows which had received exogenous prolactin (32.4 vs. 6.2 mg l⁻¹, P < 0.05). The concentrations of RNA and DNA in mammary tissue biopsies were unaffected by either dietary protein or pPRL. The concentration of RNA and DNA increased between d 70 and 90 from 0.66 to 2.77 mg g⁻¹ and from 0.54 to 1.19 mg g⁻¹, respectively. Thereafter, RNA increased to 4.40 mg g⁻¹ at d 14 of lactation whilst DNA concentration remained at a similar level of 0.90 mg g⁻¹.Milk yield of sows between d 5 and 8 and between d 19 and 22 of lactation was reduced from 8.36 to 7.00 kg day⁻¹ and from 10.74 to 8.22 kg day⁻¹, respectively, in sows given pPRL. The protein content of colostrum from sows treated with pPRL was reduced from 164 to 104 g kg⁻¹ whereas the fat content increased from 47 to 127 g kg⁻¹. These results indicate that the administration of exogenous pPRL during late pregnancy and throughout lactation initiated lactogenesis prematurely and reduced subsequent milk yield during established lactation.     

A Modified Murine Embryonic Stem Cell Test for Evaluating the Teratogenic Effects of Drugs on Early Embryogenesis

Mammalian fetal development is easily disrupted by exogenous agents, making it essential to test new drug candidates for embryotoxicity and teratogenicity. To standardize the testing of drugs that might be used to treat pregnant women, the U.S. Food and Drug Administration (FDA) formulated special grade categories, labeled A, B, C, D and X, that define the level of risk associated with the use of a specific drug during pregnancy. Drugs in categories (Cat.) D and X are those with embryotoxic and/or teratogenic effects on humans and animals. However, which stages of pregnancy are affected by these agents and their molecular mechanisms are unknown. We describe here an embryonic stem cell test (EST) that classifies FDA pregnancy Cat.D and Cat.X drugs into 4 classes based on their differing effects on primitive streak formation. We show that ~84% of Cat.D and Cat.X drugs target this period of embryogenesis. Our results demonstrate that our modified EST can identify how a drug affects early embryogenesis, when it acts, and its molecular mechanism. Our test may thus be a useful addition to the drug safety testing armamentarium.     

Effect of the Japanese diet during pregnancy and lactation or post-weaning on the risk of metabolic syndrome in offspring

We examined the effects on offspring of ingestion of the 1975 Japanese diet during pregnancy and lactation and after weaning in mice. Pregnant dams were divided into groups that were fed the Japanese diet or a control diet and raised until offspring were weaned. The offspring after weaning were further divided into groups that were raised on the Japanese diet or the control diet. Ingestion of the Japanese diet after weaning suppressed accumulation of visceral fat in offspring, and reduced the amount of lipids in serum and liver. This effect was weakened if the Japanese diet was only ingested during pregnancy and lactation. Therefore, it was suggested that ingestion of the Japanese diet of mothers during pregnancy and lactation weakens the lipid accumulation inhibitory effect of the Japanese diet in children.     

Ethical Implications in Vaccine Pharmacotherapy for Treatment and Prevention of Drug of Abuse Dependence

Different immunotherapeutic approaches are in the pipeline for the treatment of drug dependence. “Drug vaccines” aim to induce the immune system to produce antibodies that bind to drugs and prevent them from inducing rewarding effects in the brain. Drugs of abuse currently being tested using these new approaches are opioids, nicotine, cocaine, and methamphetamine. In human clinical trials, “cocaine and nicotine vaccines” have been shown to induce sufficient antibody levels while producing few side effects. Studies in humans, determining how these vaccines interact in combination with their target drug, are underway. However, although vaccines can become a reasonable treatment option for drugs of abuse, there are several disadvantages that must be considered. These include i) great individual variability in the formation of antibodies, ii) the lack of protection against a structurally dissimilar drug that produces the same effects as the drug of choice, and iii) the lack of an effect on the drug desire that may predispose an addict to relapse. In addition, a comprehensive overview of several crucial ethical issues has not yet been widely discussed in order to have not only a biological approach to immunotherapy of addiction. Overall, immunotherapy offers a range of possible treatment options: the pharmacological treatment of addiction, the treatment of overdoses, the prevention of toxicity to the brain or the heart, and the protection of the fetus during pregnancy. So far, the results obtained from a small-scale experiment using vaccines against cocaine and nicotine suggest that a number of important technical challenges still need to be overcome before such vaccines can be approved for clinical use.     

The influence of maternal nicotine exposure on neonatal lung metabolism. Protective effect of ascorbic acid.

The aim of the present study was to establish whether ascorbic acid supplementation (1 mg/kg/body mass/day) during pregnancy and lactation will prevent the effect of maternal nicotine exposure (1 mg/kg body weight/day) on neonatal lung carbohydrate, DNA and protein metabolism. The data show that the adult lung ascorbic acid content was reduced by 76% after exposure to nicotine. In contrast, maternal nicotine exposure during pregnancy and lactation has no effect on neonatal lung ascorbic acid content. However, ascorbic acid supplementation during pregnancy and lactation prevented the adverse effects of maternal nicotine exposure on neonatal lung carbohydrate, DNA and protein metabolism.     

Chronic ingestion of ethanol or glucose solutions affects hypothalamic and limbic TRH metabolism in dams and their pups

The effect of chronic ethanol consumption during pregnancy and lactation on thyrotropin releasing hormone (TRH) metabolism was investigated in the hypothalamus and limbic areas of female rats and their weaned pups. Pregnant female rats received ethanol or isocaloric glucose solution during pregnancy either alone, or also during the 3 weeks of lactation. Thyrotropin (TSH) and corticosterone levels were measured in serum; TRH and TRH-gly concentrations were determined in hypothalamus, hippocampus, n.accumbens, frontal cortex and amygdala of dams and pups at 21 days after parturition. Ethanol or glucose consumption during pregnancy and lactation produced a decrease in TSH levels compared with control animals fed at libitum; water replacement during lactation normalized TSH levels only in glucose-fed dams. Pups from ethanol or pair-fed dams showed low weight and increased TSH levels compared with normal rats. Variations in TRH metabolism were detected in limbic areas. Chronic ethanol caused a decrease in the levels of TRH in the hippocampus and frontal cortex of dams. In contrast, glucose chronic ingestion increased TRH content specifically in n.accumbens and amygdala of dams. Most of the variations in TRH content of limbic areas of pups were not specific for glucose or ethanol treatment and correlated with the deleterious effect of the mother's thyroid condition, although some differences were observed depending on pup's gender. These results support the involvement of TRHergic neurons in the limbic system of the female rat exposed to alcohol or glucose during pregnancy and lactation.     

Metabolism of sheep adipose tissue during pregnancy and lactation. Adaptation and regulation.

1. Changes in the mean volume, the rate of fatty acid and acylglycerol glycerol synthesis, the activity of lipoprotein lipase and the numbers and affinities of insulin receptors of subcutaneous adipocytes are reported for sheep at different stages of pregnancy and lactation. In addition, the serum concentrations of insulin, progesterone, prolactin, choriomammotropin, somatotropin, glucose, acetate, L-lactate, glycerol and unesterified fatty acids are reported for these sheep. 2. A switch from lipid accumulation to net lipid mobilization accompanied by a decline in the capacity for lipid synthesis, occurred at the onset of the last third of pregnancy. Net lipid mobilization continued during lactation. 3. The changes that occurred in the serum concentrations of the various hormones listed above are discussed in relation to their possible roles in the modulation of adipose tissue metabolism in sheep during pregnancy and lactation. The observations are compared with those from previous studies on the hormonal control of adipose tissue metabolism in the rat during pregnancy and lactation.     

Prolactin-releasing peptide mRNA expression in mouse medulla remains relatively stable during pregnancy and lactation

We compared levels of prolactin-releasing peptide (PrRP) mRNA expression in mouse medulla at different stages of pregnancy and lactation. Mouse medulla samples were collected on days 6, 12 and 18 of pregnancy and lactation, respectively (six per group), for mRNA. Expression levels of PrRP mRNA in the medulla were measured by semi-quantitative RT-PCR, with glyceraldehyde 3-phosphate dehydrogenase as a control. PrRP mRNA was highly expressed in mouse medulla oblongata on day 6 of pregnancy (0.53), followed by 0.43 at lactation day 6, and 0.42 at lactation day 12. The expression level of PrRP mRNA on days 12 and 18 of pregnancy and day 18 of lactation shared the same value of 0.36. PrRP mRNA levels during lactation decreased slightly compared with that during pregnancy, but the differences between them were not significant. In summary, PrRP mRNA levels in the medulla oblongata remain relatively stable during pregnancy and lactation. This is evidence that medulla PrRP is not involved in the regulation of prolactin secretion.     

Adaptative decrease in expression of the mRNA for uncoupling protein and subunit II of cytochrome c oxidase in rat brown adipose tissue during pregnancy and lactation.

Uncoupling-protein (UCP) mRNA expression is decreased to 15% of virgin control levels between days 10 and 15 of pregnancy, and remains at these low values during late pregnancy and lactation. Abrupt weaning of mid-lactating rats causes a slight but significant increase in UCP mRNA. Expression of mRNA for subunit II of cytochrome c oxidase (COII) decreased to half that of virgin control in late pregnancy and during lactation. Whereas COII mRNA expression is in step with the known modifications of brown-fat mitochondria content during the breeding cycle of the rat, UCP mRNA expression appears to be diminished much earlier than the mitochondrial proton-conductance-pathway activity. On the other hand, the reactivity of brown fat to increase expression of UCP and COII mRNAs in response to acute cold or noradrenaline treatment is not impaired during lactation.