Helmuth Vorherr

Placental insufficiency in relation to postterm pregnancy and fetal postmaturity: Evaluation of fetoplacental function; management of the postterm gravida

As pregnancy extends post term, incidence of placental insufficiency, fetal postmaturity (dysmaturity), and fetal perinatal death increases rapidly as a consequence of reduced respiratory and nutritive placental function. Despite a compensatory fetoplacental respiratory reserve capacity, fetal distress is observed in about one third of postterm pregnancies. On a biochemical level, placental pathophysiology in postterm-postmaturity pregnancies is not well understood. Postmaturity is correlated with increased incidence of placental lesions, fetal hypoxia-asphyxia, intrauterine growth retardation, increased perinatal death, and neonatal morbidity. Early diagnosis of fetal postmaturity is difficult because currently applied test methods allow recognition only when placental insufficiency is far progressed. Therefore, in postterm gravidas with a favorable cervix, induction of labor should be considered; in older primigravidas, in whom fetal losses may be sevenfold increased, or in multiparas with a history of obstetric complications, pregnancy may require termination by cesarean section. Pregnancy may be allowed to continue under close supervision in cases of uncertainty of duration of gestation, in gravidas carrying small babies, in young primigravidas, and in multigravidas in whom placentofetal function tests are normal. As long as fetal scalp blood sampling during labor does not show fetal acidosis, despite abnormal fetal heart rate pattern and meconium release, vaginal delivery may be attempted when deemed possible within a few hours. In parturients attention must be paid to the extent of uterine activity and type of medication; lateral positioning of the gravida and maternal oxygen breathing, facilitating fetal oxygen supply, are important features. Because during bearing-down efforts placentofetal respiratory reserves of postterm gravidas may become further compromised, immediate delivery by forceps or vacuum extraction may be considered. After delivery the umbilical cord should not be clamped immediately in order to allow increased fetal blood supply and to counteract fetal hypovolemia. Dysmature newborn infants require special care by the neonatologist.

Factors influencing fetal growth

Fetal growth is exponential and during the last 20 weeks of gestation the fetus gains 95% of its weight. Genetic, nutritional, environmental, uteroplacental, and fetal factors have been suggested to influence fetal growth. Uteroplacental and umbilical blood flow and transplacental glucose and fetal insulin are major determinants of fetal growth. The role of the fetal pituitary (growth hormone) and thyroid in fetal growth is not well understood; human anencephalic or athyroid fetuses usually have no or only minor retardation of growth. Also, it is not clear whether placental lactogen or somatomedin or a somatostatin-like substance of the placenta and fetus influences fetal growth. From experiments on rats it may be assumed that a specific placental-fetal growth-promoting and growth-regulating factors(s) exists. Identification of such a placental-fetal growth factor(s) in humans might aid in the prevention, diagnosis, and treatment of fetal growth retardation.

Drug Excretion in Breast Milk

The extent of drug excretion from the plasma into breast milk depends on the drugs degree of ionization and the difference between plasma pH 7.4 and average milk pH 7. The molecular weight and solubility of the drug in fat and water are also factors. Only those drug molecules in free solution can leave the blood capillaries. The alveolar epithelium is most permeable for drugs during the colostral phase of milk secretion. Nonelectrolytes such as ethanol and tetracycline enter the milk by diffusion and may reach the same concentration as in the plasma. Most drugs ingested by nursing mothers are excreted in milk but adverse effects on the nursling are reported only rarely as the amounts that pass into breast milk are nontoxic. In only a few instances of therapeutic drug intake does milk concentration exceed 1% of the ingested amount. Also drugs secreted in milk may be in the form of ineffective metabolites. However some drugs passing into milk are very potent as the newborns hepatic and renal drug detoxification processes are undeveloped. Sulfonamides ingested by the mother may produce neonatal jaundice in premature nurslings. Antibiotics secreted in milk may sometines produce bacterial resistance in the infant. In infants born with hereditary enzyme deficiencies drugs in breast milk may cause idiosyncrasy. Maternal treatment with high doses of anticoagulants of the coumarin type may result in decreased prothrombin levels in the nursling. Metronidazole oral therapy for the mother yields high serum and milk levels of the drug that are hazardous to the infant. Thiouracil medication for the mother may possibly cause goiter in the breast-fed infant. Steroids contained in contraceptive pills in usual doses do not harm the infant. Larger amounts of sex steroids may cause infantile jaundice. Diminished lactation is most apt to be cuased by oral contraceptives if they are given early in the puerperium. Of laxatives only the anthraquinone or emodin alkaloids as in cascara sagrada senna rhubarb or aloe have been thought to cause diarrhea in the nursling. Nicotine from excessive smoking may decrease the milk yield and rarely have adverse symptoms in the infant been reported. Moderate alcohol intake by the mother is not harmful to the breast-fed infant. As radioactive iodine administered to the mother may pass into breast milk in sufficient amounts to injure the infants thyroid nursing should not take place when this is given or for 10 days thereafter. Antineoplastic drugs given as anticancer therapy may cause bone marrow depression in the nursing infant. In Turkey breast-fed infants have been poisoned after their mothers had eaten wheat treated with hexachlorobenzene intended for seed. Chlorophenothane (DDT) is not dangerous. Fluorine over 1 part per million in drinking water or given in vitamin tablets may cause dental mottling in the breast-fed baby. A hypersensitivity reaction has been observed in an infant after the mother had received 2.4 million units of penicillin. Bottle-feeding should be recommended for women taking high doses of drugs known or suspected of producing adverse effects in nursing infants.

Teratogenesis and carcinogenesis in rat offspring after transplacental and transmammary exposure to diethylstilbestrol.

Abstract Transplacental and transmammary exposure of tat offspring to diethylstilbestrol (DES) was studied in regard to potential teratogenesis and carcinogenesis. Pregnant and/or lactating rats received DES in oil subcutaneously. In females so exposed, abnormal development of the urogenital sinus (hypospadias and urethrovaginal cloaca formation) occurred. In exposed male offspring, hypospadias, phallic hypoplasia, inhibition of growth and descent of testes, as well as abnormalities of Wolffian derivatives, were observed. In 20–40 per cent of DES-exposed female offspring, vaginal adenosis, endometrial squamous metaplasia, and genital malignancy were encountered. Two DES-exposed offspring had a vaginal squamous carcinoma, one had an endometrial adenocarcinoma, and one had an ovarian adenocarcinoma. Vaginal squamous carcinomas may have originated in foci of squamous metaplastic epithelium of vaginal adenosis. None of the control rats developed genital malignancy.

Contraception after abortion and post partum: An evaluation of risks and benefits of oral contraceptives with emphasis on the relation of female sex hormones to thromboembolism and genital and breast cancer

Abstract Fertility (ovulation) returns promptly in patients after abortion. At 6 weeks post partum, about 5 per cent of nursing and 15 per cent of nonlactating women ovulate. About 10 to 20 per cent of mothers can conceive between Weeks 6 and 12 post partum even when they are nursing. Contraception, if desired, must be instituted immediately after abortion and not later than 4 to 5 weeks post partum. Literature reports regarding indications and potential hazards of contraceptives are inconsistent. In individual patients, pill intake can be related to hypertension, disturbance in liver function and carbohydrate metabolism, thromboembolic disease, decrease of milk yield in nursing mothers, or cancer of the reproductive organs. In mass studies, however, no definite cause-effect relationship has yet been established. Because female sex hormones and nonsteroid estrogens (diethylstilbestrol) in particular, may under some conditions induce or promote accelerated growth of breast or genital cancer, women with a family or personal history of such malignancies should not receive any type of female sex hormone.

Antimicrobial effect of chlorhexidine and povidone-iodine on vaginal bacteria

The antimicrobial potency of 4 per cent chlorhexidine gluconate was compared with that of 10 per cent povidone-iodine (1 per cent free iodine) on the vaginal bacteria of 150 premenopausal, non-pregnant women. From 30 of the women blood samples were taken before and at either 15, 30 or 60 minutes after vaginal cleansing with chlorhexidine for chlorhexidine analysis. Five minutes after applying either chlorhexidine or povidone-iodine almost 99 per cent of bacteria present on the lateral wall of the vagina were killed. Chlorhexidine was significantly more effective than povidone-iodine. Serosanguineous , mucoid or white-yellowish vaginal discharge did not alter the effectiveness of either antimicrobial agent. In contrast to povidone-iodine, vaginally applied chlorhexidine was not absorbed in measurable amounts (sensitivity of detection method: 0 X 1 mg/l) into the bloodstream. Chlorhexidine may therefore prove of value for treating vaginitis especially during pregnancy and also for combating microbes such as Group B streptococci which are potentially harmful to the newly-born child.

To breast-feed or not to breast-feed?

For the infants well-being, breastfeeding is preferable to formula-feeding, but for the mother, breast-feeding has both advantages and disadvantages. If breast-feeding is to be successful, the mother must want to nurse her baby. She also must be in good health and without a family history of breast cancer, maintain an adequate diet during both pregnancy and lactation, and not take drugs potentially dangerous to the baby. Other important factors include effective breast stimulation by suckling, adequate removal of milk, intact hypothalamic-hypophyseal function, and normal sympathetic-adrenal tone.

Para-Endocrine Tumor Activity with Emphasis on Ectopic ADH Secretion

Evidence has accumulated by biochemical, histologic, tissue incubation and tissue culture studies that some malignant tumors may synthesize substances which are either biologically and immunologically closely related to or identical with the respective natural hormone. Hormone measurements in blood and urine reflect the production rates in tumor tissue; ectopic hormone secretion by tumor cells is capable of raising respective plasma and urinary hormone concentrations several fold above normal. Hormone estimates (antidiuretic hormone, adrenocorticotrophic hormone, gonadotropins, etc.) in high risk subjects (heavy smokers, etc.) may contribute to early diagnosis of lung cancer and support therapeutic and prognostic evaluation of the cancer patient.

Rat mammary deoxyribonucleic acid synthesis during the estrous cycle, pregnancy, and lactation in relation to mammary tumorigenesis: its implication for human breast cancer.

Rat mammary DNA synthesis is greatly reduced during late pregnancy and lactation; this corresponds to the decreased incidence of induced mammary tumors by chemical carcinogens during these periods. The protective effects of pregnancy and lactation against mammary tumorigenesis of rats and human subjects may be explained by the prolonged phases of mitotic rest encountered during pregnancy and lactation.

Suckling-Induced Delay of Implantation and Increased Fecundity in Rats

In rats fertilized during the 1st or 2nd day postpartum (second consecutive pregnancy), suckling induces intrauterine blastocyst dormancy and delays implantation for 8-22 days. In spite of this relatively long time of blastocyst dormancy, associated with greatly reduced cellular metabolism, subsequent implantation and growth results in significantly larger litters (13.6 +/- 0.62; means +/- SE) than in primigravidas (10.4 +/- 0.89) or in rats with a second-spaced pregnancy (11.2 +/- 0.72). Enhanced fecundity in rats with second consecutive pregnancies may be attributed to increased ovarian blood supply of preceding gestation and/or to augmented pituitary FSH-LH secretion resulting in intensified ovarian gonadotropic stimulation for postpartum ovulation.