The effects of acebutolol alone and in combination with furosemide or hydralazine in experimentally induced hypertensive G-minipigs

Experimentally induced hypertensive G-minipigs were used for assessing the antihypertensive effects of acebutolol, a cardioselective beta-adrenergic blocking agent. In the acute experiment, six females were used. Acebutolol (3 mg/kg, i.v.) alone or in combination with furosemide (1 mg/kg, i.v.) or hydralazine (1 mg/kg, i.v.) was administered through an implanted catheter. In the chronic experiments, five females received oral acebutolol (100-200 mg/day). The blood pressure, heart rate, plasma renin activity (PRA) and plasma aldosterone concentration (PAC) were used as parameters. In the acute experiment, there were no marked changes in the blood pressure or heart rate during the nondosing period. Acebutolol alone caused a marked decrease in the blood pressure and heart rate. In the two combination tests, combined administration with acebutolol and furosemide had a greater effect on the blood pressure and heart rate than did acebutolol alone. A combined acebutolol and hydralazine regimen caused a slight reduction not only in the blood pressure, but also in the heart rate compared with acebutolol alone. PRA and PAC remained essentially constant, with minor fluctuations, throughout the nondosing period. Following the injection of acebutolol alone, PRA showed an elevation with a significant rise after three hours and PAC showed a tendency to increase. PRA and PAC generally tended to increase in the case of combined administration with furosemide or hydralazine, but these tendencies were less conspicuous than with acebutolol alone. On the other hand, chronic treatment with acebutolol produced a significant decrease in the heart rate from two weeks after the administration and in the blood pressure from four weeks.(ABSTRACT TRUNCATED AT 250 WORDS)     

Plasma insulin, carbohydrate, and free fatty acid changes in newly born infants of diabetic and non-diabetic mothers after loading with glucose, fructose, and galactose.

Changes in the concentration of blood glucose, fructose and galactose and their disappearance rate, concentration of plasma insulin, free fatty acids, blood lactate and pyruvate after intravenous glucose, fructose and galactose loads (1 g/kg) were studied in 23 infants of insulin treated diabetic mothers (IDM). The control group consisted of 42 infants of healthy mothers (IHM). The disappearance rate of these monosaccharides was higher in IDM that in IHM (P less than 0.01). All monosaccharides enhanced plasma insulin levels, but the plasma insulin concentration varied considerably. The highest insulin response with difference between IDM and IHM occurred after loading with glucose. Fructose was the least effective insulin stimulator which did not increase glucose levels. All monosaccharides decreased free fatty acid levels. Lactate levels and lactate:pyruvate ratio in IHM were increased after fructose loading. The results of this study suggest that galactose is of some physiological importance for maintaining glucose levels and that the islet apparatus of newborns of diabetic mothers is less loaded with galactose than with glucose.     

The epidemiology of white full-term infants with short crown-heel lengths for gestational ages at birth

Fetal growth retardation was diagnosed in 137 (7.8 percent) of 1,757 white full-term infants who had crown-heel lengths below the fifth percentiles for their gestational ages. The incidence of short infants was 121 (11.1 percent) among 1,093 mothers with high-risk pregnancies compared to 16 (2.4 percent) in 664 low-risk mothers (p less than 0.0001). There were four high-risk categories: spontaneous premature rupture of membranes (PROM), fetal conditions, complications of pregnancy, and adverse maternal practices. The incidence of short infants was significantly higher in each of the four high-risk categories than in the low-risk group. There were three other conditions that were present in all pregnancies that were associated with the frequency of short infants: maternal height, socioeconomic status of head of household, and sex of infant. A short maternal height (under 157.7 cm = 62 inches) was significantly associated with an increase in short infants among mothers who smoked cigarettes at any level during pregnancy and among mothers with PROM in combination with other risks, but not in the group of 664 low-risk mothers. Significantly more short girls than short boys were born to mothers who smoked ten or more cigarettes a day throughout pregnancy or who had multiple adverse maternal practices, but no statistically significant differences were noted among mothers who smoked fewer than ten cigarettes per day, among those with PROM as the only risk factor, or among those with medical or obstetrical complications. Moreover, those mothers who were in socioeconomic groups III and IV and had other risk factors had a significantly higher incidence of short infants than did similar mothers in socioeconomic groups I and II.     

The Effects of Pregnancy and Feeding on the Insulin and Glucose Concentrations in Blood of Ewes in Late Pregnancy

In 8 experimental ewes on normal diet the influence of pregnancy and feeding on insulin and glucose in the blood was studied. A reduction in insulin concentration was found as pregnancy advanced. Blood glucose fluctuated, but during late pregnancy the blood glucose level was significantly lower in twin–pregnant ewes than in ewes pregnant with 1 fetus. No increase in insulin concentration was demonstrated in twin–pregnant ewes after feeding, on the contrary an increase was found in ewes pregnant with 1 fetus. A limited effect of feeding on the glucose concentration was observed, especially compared to the reference range. A positive correlation was obtained between the concentration of glucose and insulin in the blood.     

A comparison of Chinese traditional and Western medical approaches for the treatment of mild hypertension

We compared the efficacy of Chinese traditional treatment for mild hypertension with that of a standard Western medical regimen in a group of 50 well-matched patients (24 allocated to Western medicine and 26 to Chinese traditional medicine) with mild hypertension (diastolic blood pressure 90-104 mmHg). Those receiving Western therapy were treated in a stepped-care fashion with dihydrochlorothiazide and atenolol. Those in the Chinese traditional therapy group received one of two mixtures of nine herbs and other ingredients, depending on symptoms at initial evaluation. Blood pressure dropped significantly in both groups after only a few days on therapy. After 19 days on treatment, the group receiving Western therapy had a fall in blood pressure from 168.2/96.3 mmHg to 137.3/76.7 mmHg (p less than 0.01), while those on Chinese traditional therapy fell from 168.2/95.9 mmHg to 146.4/80.5 mmHg (p less than 0.01). The fall in blood pressure was significantly greater, however, in those given Western therapy. The relief of existing symptoms or development of possible drug side effects was similar in both groups, except for nocturia, occurring more often in the group treated with Western therapy. We conclude that Western therapy is more effective in reducing blood pressure as compared with Chinese traditional therapy, but effective control of blood pressure in mild hypertensives is possible with either form of treatment.     

Relationships between pregnancy spacing,sex of infants,maternal age,and birth order,and neonatal and post‐neonatal mortality in Bangladesh

Abstract

The relationships between length of the interpregnancy interval, outcome of the pregnancy preceding the interval, sex of the infants, pregnancy order, maternal age, and maternal history of previous child deaths and neonatal and postneonatal mortality were explored in a rural Bangladeshi population using a multiple regression analysis. Specific interactions between the interpregnancy interval, outcome of the pregnancy preceding the interval, sex of the infants, and history of previous child deaths were examined. An inverse relationship was observed between postneonatal mortality and the length of the interpregnancy interval when the pregnancy preceding the interval was a surviving infant. No such trend was observed for neonatal mortality. Post‐neonatal mortality rates among children whose mothers had experienced two or more previous child deaths were essentially the same as that for infants whose mothers had experienced 0–1 child deaths when the interpregnancy intervals were more than 24 months. Although female infants have a lower neonatal mortality than male infants, the neonatal mortality rate for female infants conceived less than twelve months following a male infant birth was higher than for a male infant conceived less than twelve months following another male infant birth. Post‐neonatal mortality is consistently higher for female compared to male infants in all interval categories.     

Hypoglycemia of squirrel monkey neonates: implications for infant survival

Neonatal deaths are a serious problem in breeding colonies of squirrel monkeys. Seriously ill neonates in our colony are always hypoglycemic on presentation. To determine normal glucose values for squirrel monkey infants of various ages, serum glucose determinations were done at 1, 3, 7, 10, 14 days and 1 month of age using a standard laboratory test for serum glucose. Glucose concentration increased from a low of 49 +/- 3 mg/dl (Mean +/- SEM) at 1 day (n = 21) to 109 +/- 4 mg/dl at 1 month of age (n = 17). Glucose values for 1, 3 and 7 day-old infants were significantly lower than 1 month-old infants (P less than .05). To provide a time-averaged indication of blood glucose, glycosylated hemoglobin (GHb) measurements were made at 1 day, 1 week, 2 weeks, 1 month, 2 months, 1 year of age and in adults (greater than 3 years of age). GHb values ranged from 2.6% +/- 0.1 for 1 day old infants (n = 13) to 4.0 +/- 0.2 for adults (n = 10) with a steady increase during the first 2 months of life. Animals 1 year of age and younger had significantly lower glycosylated hemoglobin than adults. These studies indicate that blood glucose concentration is significantly lower in squirrel monkey neonates than in older infants, juveniles and adults. Maternal rejection, trauma, and associated problems occur commonly in socially reared squirrel monkeys. The marginal hypoglycemic state of these infants places them at high risk for clinical hypoglycemia as a sequel to such perturbations.     

他克莫司对大鼠血糖的影响及其作用机制

目的 观察不同浓度的他克莫司对大鼠血糖的影响.方法 选取雄性SD大鼠30只,体重70～85g,随机等分为三组.A组大鼠为他克莫司加五脂胶囊组,每日给予他克莫司(普乐可复Astellas Ireland Co.,Ltd生产)2 mg/kg和五酯软胶囊(四川光大制药有限公司生产)0.2粒/kg;B组为他克莫司组,每日给予他克莫司2 mg/kg;C组为对照组,每日给予同等量生理盐水,三组大鼠均在空腹时灌胃给药,用药1h后喂食.用药时间为5个月.每月监测大鼠他克莫司血药浓度和空腹血糖.结果 在用药的1～5个月期间,A组大鼠他克莫司血药浓度均明显高于B组.在用药的第1个月和第2个月,三组大鼠空腹血糖无明显差异(P＞0.05),用药第3个月后,A、B两组大鼠血糖均明显高于对照组(P＜0.01),A组大鼠血糖略高于B组,二者之间差异并无统计学意义(P＞0.05);用药第4、5个月后A、B两组大鼠的血糖持续升高,并且A组大鼠血糖明显高于B组(P＜0.01);A组的胰岛素分泌指数和敏感指数均明显低于C组(P＜0.01).结论 他克莫司通过减少胰岛素的分泌、增加胰岛素抵抗导致大鼠血糖升高,这种升血糖作用呈时间依赖性和浓度依赖性.     

Plasma prolactin responses to acute changes in central blood volume in man

The present study examined the relationship between plasma prolactin (PRL) and central blood volume (CBV) in man. 6 adult males lay in a lower body pressure box at a thermoneutral ambient temperature (27 degrees C) on three occasions. On each occasion a 70-min control period was followed by a 20-min exposure to a lower body pressure of either 0 mm Hg, -20 (lower body negative pressure; LBNP), or +10 mm Hg (lower body positive pressure; LBPP), followed by a 60-min recovery period. Blood was drawn and urine collected at 30-min intervals. Blood pressure and heart rate were monitored at 30-min intervals during control and recovery periods and at 10-min intervals during lower body pressure exposure. Neither 0 mm Hg, LBNP, nor LBPP altered plasma osmolality, sodium, or potassium levels. Increasing CBV by LBPP increased systemic blood pressure (p less than 0.01) but had no effect on heart rate, plasma PRL, or urine osmolality. LBNP, in contrast, increased heart rate (p less than 0.05). Half of the subjects undergoing LBNP developed presyncopal symptoms, characteristic of a vasovagal reaction which includes precipitous hypotension. Subjects developing these symptoms tended to exhibit an increase in plasma PRL and an increase in urine osmolality. Asymptomatic subjects demonstrated no change in plasma PRL or urine osmolality. In addition, subjects exhibiting a PRL response to LBNP had a higher control period plasma PRL baseline (231%) than did asymptomatic subjects. These data suggest that while plasma PRL levels are not sensitive to nonhypotensive changes in CBV, they do respond to hypotensive decreases in CBV and/or its associated nausea.(ABSTRACT TRUNCATED AT 250 WORDS)     

Maternal vitamin D intake and mineral metabolism in mothers and their newborn infants.

Pregnant women receiving daily supplements of 400 IU (10 microgram) of vitamin D2 from the 12th week of pregnancy had plasma calcium concentrations higher at 24 weeks but similar at delivery to those in control pregnant women who did not receive the supplements. Infants of the women receiving the supplements had higher calcium, lower phosphorus, and similar magnesium concentrations on the sixth day of life and a lower incidence of hypocalcaemia than infants of the control women. Plasma concentrations of 25-hydroxycholecalciferol, which showed a seasonal variation, were higher in mothers and infants in the treated group. Cord-blood calcium, magnesium, phosphorus, and 25-hydroxycholecalciferol concentrations correlated with maternal values at delivery. Breast-fed infants had higher calcium and magnesium and lower phosphorus and 25-hydroxycholecalciferol concentrations than artificially fed infants. A defect of dental enamel was found in a high proportion of infants (many of whom had suffered from hypocalcaemia) born to the control women. These results suggest that vitamin D supplementation during pregnancy would be beneficial for mothers, whose intake from diet and skin synthesis is appreciably less than 500 IU of vitamin D daily.     

Blood flow in the ovary and oviduct of rats after sympathetic denervation

The effect of sympathetic denervation on blood flow in the ovary and oviduct was studied in rats undergoing oestrous cycles or at Day 14 of pregnancy. The ovary and oviduct on one side were denervated by briefly freezing the ovarian vascular pedicle and the ovarian suspensory ligament. Blood flow was measured using 15 microns 57Co-labelled microspheres while the rats were under barbiturate anaesthesia. In cyclic rats denervation raised blood flow to the oviduct by 90% the next day (P less than 0.01) and 39% at 4-10 days (0.05 less than P less than 0.1). Blood flow to the ovary was not affected. Denervation on Day 13 of pregnancy raised blood flow in the oviduct 5-fold at Day 14 (P less than 0.01) and denervation on Day 7 raised blood flow 3-fold on Day 14 (P less than 0.05). Blood flow to the luteal and non-luteal components of the ovary was not affected. Sham-operation did not affect blood flow in the oviduct or ovary. It is concluded that sympathetic nerves exert tonic vasoconstrictor control on the vasculature of the oviduct but not on that of the ovary, and that these nerves do not regulate the major changes in blood flow that occur in ovaries in various physiological states.     

Ovine fetal coronary and cerebral vascular responses to forskolin

The time related hemodynamic responses to forskolin-elicited increases in cAMP were studied in the near-term fetus. Catheters and electrodes were inserted into 6 fetal sheep to measure arterial, venous and thoracic pressures, electrocorticogram, and electrocardiogram. At gestational day 134, experiments were performed to determine the effect of forskolin infusion (400 micrograms/ml at 1.03 ml/min for 5 min) on fetal blood pressure, coronary and cerebral blood flow and resistance. Blood flow measurements were made using 15 microns microspheres labelled with radioactive isotopes during the control period and at 0, 5, 10, 15, and 45 min after forskolin infusion. Forskolin infusion was always initiated during a high-voltage electrocortical epoch and was given twice in each animal. In each case, forskolin caused electrocortical activity to change from high-voltage state to an intermediate voltage state. Blood pressure fell significantly by the end of the infusion period and returned to control levels 10 min later. Fetal heart rate and coronary blood flow were immediately elevated by forskolin (P less than 0.01) whereas cerebral blood flow did not increase until 5 min later (P less than 0.01). Cerebral blood flow was still elevated (P less than 0.05) 45 min after the end of forskolin infusion, whereas coronary blood flow had returned to control levels. Both cerebral and coronary vascular resistance fell significantly in response to forskolin infusion (P less than 0.01). This effect lasted at least 15 min and had returned to control levels 45 min after forskolin had been terminated.     

Development of hypertension and uraemia after pyelonephritis in childhood: 27 year follow up.

OBJECTIVE--Determination of the long term incidence of uraemia, hypertension, and toxaemia in pregnancy associated with non-obstructive focal renal scarring after pyelonephritis in childhood 25-35 years earlier. DESIGN--27 Year follow up of patients with non-obstructive focal scarring identified from a retrospective review of intravenous urograms performed in childhood between 1951 and 1967. SETTING--Paediatric primary referral centre and urological clinic in tertiary referral centre. PATIENTS--30 Patients (mean age 33 (range 22-41] with non-obstructive focal renal scarring first detected between 1951 and 1967 and a history of febrile urinary tract infection. MAIN OUTCOME MEASURE--Hypertension and complications of renal damage. RESULTS--Three patients had developed end stage renal disease, seven had developed hypertension, two of 16 women had a history of toxaemia during pregnancy, and seven patients had undergone renal surgery during follow up. Of the 20 patients who had neither had renal surgery nor had end stage renal disease, all had a significantly lower glomerular filtration rate and renal plasma flow and higher diastolic blood pressure, mean arterial blood pressure, plasma renin activity, and serum beta 2 microglobulin concentration than 13 healthy age matched controls. Diastolic blood pressure and plasma renin activity were positively correlated (r = 0.50, p less than 0.05) and so were fractional sodium excretion and both systolic and diastolic blood pressures (r = 0.54, p less than 0.01, r = 0.51, p less than 0.01 respectively). The progress of renal damage was unrelated to the incidence of recurrent infections. CONCLUSIONS--Children with focal renal scarring due to pyelonephritis are at high risk of serious long term consequences. It is essential that they are given adequate attention and care during adolescence and pregnancy.     

链尿佐菌素加高糖高脂饮食复制大鼠2型糖尿病模型

目的链尿佐菌素加高糖高脂饮食诱导大鼠2型糖尿病模型的建立。方法SD雄性大鼠高糖高脂饲料喂养3周后,采血检测空腹血糖及血清胰岛素,按25mg/g体重剂量一次性腹腔内注射链尿佐菌素,3d后,行糖耐量实验,对糖耐量异常大鼠继续喂以高糖高脂饲料,在第2、第4周再两次采血检测糖尿病鼠空腹血糖及血清胰岛素。结果与对照组比较,高糖高脂喂养大鼠血清胰岛素明显上升（P〈0.01）,但血糖无变化（P〉0.05）,糖尿病鼠血糖及血清胰岛素均显著的高于对照组（P〈0.01）。结论高糖高脂喂养能致大鼠明显的高胰岛素血症,辅以小剂量一次性注射链尿佐菌素而造成的糖耐量异常,可成功复制出2型糖尿病大鼠模型。     

Effect on Neonatal Jaundice of Oestrogens and Progestogens Taken before and after Conception

Study of 182 newborn babies has shown that among bottle-fed infants the mean plasma bilirubin concentration was slightly but significantly higher (P <0·01) in those whose mothers had previously used steroid contraceptives. A similar finding was not noted among breast-fed infants.A further 16 infants whose mothers had received progestogen therapy during their pregnancy had a mean plasma bilirubin concentration which was significantly higher than each of the four other groups of infants studied (P <0·01). Icterus occasionally reached clinically important levels in these babies.     

Cell-mediated immune responses to Chlamydia trachomatis in mothers and infants

Cell-mediated immunity to Chlamydia trachomatis was studied in pregnant women with chlamydial infection of the cervix, in infants born vaginally to these women, and in infants presenting with chlamydial conjunctivitis. Uninfected pregnant women and their infants were studied as controls. McCoy cell cultures were used to isolate C. trachomatis from clinical specimens. Cell-mediated immunity was measured by lymphocyte proliferative responses in vitro to stimulation by chlamydial antigens. Chlamydial IgG antibody in serum specimens was detected by a microenzyme-linked immunosorbent assay technique. The mean lymphocyte proliferative responses to chlamydial antigens were greater in infected women than in uninfected women both during pregnancy and in the postpartum period. Lymphocyte responsiveness in infected pregnant women, however, was less than in postpartum women. Despite failure to detect chlamydial infection in exposed infants, lymphocyte proliferative responses were greater in umbilical cord blood and later in peripheral blood samples from neonates born to infected mothers than in infants born to uninfected mothers. These responses were also greater in infants with chlamydial conjunctivitis than in infants of uninfected mothers. These data suggest that cellular immune responses to chlamydial antigens are increased in infected mothers and infants and that infants may acquire chlamydial cell-mediated immunity transplacentally.     

Effect of solid meal on gastric emptying of,and glycemic and cardiovascular responses to,liquid glucose in older subjects

Gastric emptying is a determinant of the postprandial glycemic and cardiovascular responses to oral carbohydrate. We evaluated the effects of a solid meal on gastric emptying and the glycemic and cardiovascular responses to oral glucose in healthy older subjects. Ten subjects aged 72.1 +/- 1.9 yr were studied. Each subject had measurements of gastric emptying, blood glucose, serum insulin, blood pressure, and heart rate after ingestion of a 50-g glucose drink (300 ml) with (mixed meal) or without (liquid only) a solid meal (300 g ground beef). Gastric emptying of liquid was initially slightly more rapid (P < 0.05) after the mixed meal compared with liquid only at 5 min (92.0 +/- 1.5 vs. 96.0 +/- 1.3%) and much slower (P < 0.05) after 120 min. The time to peak blood glucose was less (39.0 +/- 4.0 vs. 67.5 +/- 10.3 min; P < 0.01) and blood glucose subsequently lower (P < 0.01) after the mixed meal. The increase in serum insulin was greater (P < 0.001) after the mixed meal. Blood pressure fell (P < 0.05) in the first 30 min, with no difference between the two meals. Increase in heart rate after both meals (P < 0.005), was greater (P < 0.05) after the mixed meal. The presence of a noncarbohydrate solid meal had discrepant effects on early and subsequent emptying of a nutrient liquid, which affects postprandial glycemia and increased heart rate.     

Fructose and glucose ingestion and muscle glycogen use during submaximal exercise

Substrate utilization after fructose, glucose, or water ingestion was examined in four male and four female subjects during three treadmill runs at approximately 75% of maximal O2 uptake. Each test was preceded by three days of a carbohydrate-rich diet. The runs were 30 min long and were spaced at least 1 wk apart. Exercise began 45 min after ingestion of 300 ml of randomly assigned 75 g fructose (F), 75 g glucose (G), or control (C). Muscle glycogen depletion determined by pre- and postexercise biopsies (gastrocnemius muscle) was significantly (P less than 0.05) less during the F trial than during C or G. Venous blood samples revealed a significant increase in serum glucose (P less than 0.05) and insulin (P less than 0.01) within 45 min after the G drink, followed by a decrease (P less than 0.05) in serum glucose during the first 15 min of exercise, changes not observed in the C or F trials. Respiratory exchange ratio was higher (P less than 0.05) during the G than C or F trials for the first 5 min of exercise and lower (P less than 0.05) during the C trial compared with G or F for the last 15 min of exercise. These data suggest that fructose ingested before 30 min of submaximal exercise maintains stable blood glucose and insulin concentrations, which may lead to the observed sparing of muscle glycogen.     

Prolactin response to sulpiride in non insulin dependent diabetes mellitus

Blood glucose, insulin and prolactin concentrations were determined before and after sulpiride injection (50 mg i.m.) in 20 non-insulin-dependent diabetic patients (10 with retinopathy and 10 without evidence of retinal damage) and 10 subjects with normal glucose tolerance. Prolactin response to sulpiride was significantly higher in diabetics than in controls (at 20 min., p less than 0.01; at 30 and 60 min., p less than 0.005; at 90 min., p less than 0.01; at 120 min., p less than 0.05). The sulpiride induced hyperprolactinemia did not influence blood glucose and plasma insulin levels in controls as well as in diabetic patients. Prolactin response to sulpiride was the same in diabetics with and in those without retinal changes. We conclude that acute hyperprolactinemia seems to have no influence on glucose homeostasis in normal and non insulin-dependent diabetic subjects.     

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.