Dynamics of contraceptive practice amongst urban Indian women.

BACKGROUND: Most studies on knowledge, attitude and practice regarding contraceptives have been conducted in rural areas and urban slums. In this study, a mixed urban population was surveyed. SUBJECTS: Two thousand parous women from different social and educational backgrounds residing in the metropolis of Mumbai (Bombay), Maharashtra were included in the study. RESULTS: Fifty per cent of illiterates, semi-literates and highschool educated, and 80% of college-educated couples said that they had no gender preferences for their children, but actual practice belied this. Regardless of the level of education, 25%, 75% and 95% of all couples were sexually active by 6 weeks, 3 months and 6 months after childbirth. Awareness regarding the availability of various contraceptives increased with education; 20% of all graduate couples used condoms or the rhythm method immediately after marriage. After the birth of their first child, 80% of educated couples used spacing methods whereas even after the birth of their third child more than 50% of the uneducated did not. The major complaint of the intrauterine device users was menorrhagia and abdominal pain, while that of pill users was nausea, giddiness and headache. Spacing methods were popular among the educated, and terminal ones among the uneducated. Steroidal contraceptive pills were not popular with any group, regardless of the level of education. CONCLUSION: Education was the main variable in the decisions regarding the family size, spacing interval, contraceptive awareness, its use immediately after marriage and during the postpartum period.

Low-dose progestogen contraception and the nursing mother.

Breast feeding, though an important and efficient contraceptive method, suffers from one major limitation: the contraceptive protection it offers the nursing mother ends abruptly without giving any physical indication of the return of fertility. Barrier methods and progesterone-only hormonal contraceptives, either in the oral, implant or injectable form, appear to be the primary contraceptive alternative for the nursing mother today. They neither adversely affect lactation, nor does the minute quantity of progesterone (NET or LNG) transferred to the infant affect its growth and physical well-being. Puerperal insertion of IUD carries an inherent risk of pelvic inflammatory disease, high expulsion rates and menorrhagia, once menses resume. Combination contraceptives affect both the quality and quantity of breastmilk; hence they are not recommended. Sterilization is a permanent method and therefore useful only when the family has been completed.

Can chronic maternal drug therapy alter the nursing infant's hepatic drug metabolizing enzyme pattern?

This study was carried out to investigate whether minute quantities of maternal drugs ingested over an extended period of time by a breast-feeding infant can alter the activity pattern of the infant's hepatic drug metabolizing enzyme (HDME). The HDME activity patterns of 12 breast-fed infants whose mothers were not on drug therapy were compared with those of 11 infants whose mothers had been taking 30 micrograms levo-norgesterel daily for 90 to 195 days (oral contraceptives group) and of 10 infants whose mothers had been taking ethambutol and isoniazid daily since pregnancy (tuberculosis group). As 6 beta hydroxycortisol in urine is considered to be a good and acceptable reflector of HDME activity, it was estimated from the infants' urine using enzyme-linked immunosorbent assay (ELISA) technique. A comparison of the patterns between 90 days of age and 195 days of age of the infants in the control group and the two study groups indicated an increase from 36.6 ng/mL to 58.4 ng/mL at 195 days in the control group. An initial decrease from 36.6 ng/mL to 26.2 ng/mL was noted with commencement of maternal levo-norgesterel therapy, followed by a slow and steady rise to 47.8 ng/mL at 195 days of age, with a shift in the peak from 120 to 135 days of infants age in the oral contraceptive group. A suppressed pattern with decreased levels of 6 beta hydroxycortisol ranging from 19.3 ng/mL to 26.5 ng/mL at 195 days was found in the tuberculosis group. The data were analyzed by two-way analysis of variance (ANOVA) coupled with Duncan's Multiple range test. Both treatment group showed significant differences from the control group at the 0.050 level. The HDME plays an important role in determining the final outcome of any drug in humans, as it controls the metabolism of drugs. Hence, alterations in its activity caused by the transfer of maternal drugs over a prolonged period of time could pose a serious problem to nurslings when they require drugs for their own benefit.

Is time-interval between mini-pill ingestion and breastfeeding essential?

A study was conducted on four alternate days over an eight-day period in a group of 12 healthy, 20-35 year old exclusively breast feeding women who were interested in weaning their infants. On each study day the women ingested 150 micrograms levonorgestrel. Maternal blood and milk samples were collected at 2, 4, 6, and 8 hr intervals after LNG ingestion on the 1st, 3rd, 5th, and 8th day. A time-dependent decrease in maternal serum and increase in breast milk levels of LNG were observed. Maintaining a time interval between mini-pill intake and breastfeeding results in higher levels of LNG in breast milk, thereby exposing the infant to a bolus of LNG in a "single-delayed" feed.

PIP: In India over an 8-day period, 12 healthy, lactating women aged 20-35 (body mass index, 21-23) who took a mini-pill with 150 mcg levonorgestrel (LNG) (Microlut) daily provided blood and breast milk samples over increasing time intervals between LNG ingestion and sample-taking. The researchers wanted to determine whether a time interval between maternal LNG ingestion and breast feeding delivers less LNG to the breast milk and the infant. Regardless of the time interval, about 10% of the LNG in the blood was transferred to the breast milk. The observed LNG levels in the breast milk were higher than the expected LNG levels, except at a 2-hour interval. Maternal sera LNG levels decreased as the time intervals increased (1198 pg/ml at 2 hours, 995 at 4 hours, 476 at 6 hours, and 340 at 8 hours), while the LNG levels in breast milk increased (100, 180, 250, and 330 pg/ml, respectively). The researchers explained the decrease in maternal levels by metabolism of LNG by the mother's liver, but they could not account for the increase of LNG in the breast milk. These findings show that maintaining a time interval between maternal ingestion of LNG and breast feeding increases LNG in breast milk, exposing the infant to a bolus of LNG in one delayed feed.

At what 'infant-age' can levonorgestrel contraceptives be recommended to nursing mothers?

OBJECTIVE: Levonorgestrel (LNG), a low-dose progestin, does not affect lactation but like all drugs taken by breastfeeding mothers, it can be transferred to the infant via breast milk. How infants of various ages cope with this unwanted maternal drug would help in deciding when to recommend this method of contraception to breastfeeding mothers. METHODS: The study was conducted in 30 exclusively breastfeeding mothers and their 4-, 12- and 24-week-old infants. The mothers daily received 30 micrograms LNG over a five-week period, thus exposing their infants to maternal LNG for that period. RESULTS: Four-week-old infants could neither absorb nor metabolize LNG efficiently. Twelve-week-old infants could metabolize LNG more efficiently than absorb. Twenty-four-week-old infants could do both efficiently. CONCLUSION: It is safe to introduce LNG to breastfeeding mothers at 12 weeks postpartum.

A sensitive ELISA for 6 beta-hydroxycortisol in urine using enzyme penicillinase (beta-lactamase).

A sensitive and specific, enzyme labelled immunosorbent assay (ELISA) for 6 beta-hydroxycortisol in diluted urine using penicillinase was developed. 6 beta-Hydroxycortisol-21-hemisuccinate was conjugated with enzyme penicillinase. Antibody immobilized on a polyvinylchloride ELISA plate (Dynatech) was used for separation of bound from free ligand. The sensitivity of the assay was between 2.0-3.0 pg per well and recovery of 6 beta-hydroxycortisol from urine ranged between 85.0-108.0%. The assay is simple, rapid and precise.

ICMR Task Force Study on hormonal contraception. Transfer of norethisterone (NET) and levonorgestrel (LNG) from a single tablet into the infant's circulation through the mother's milk.

A single tablet of either of the three different types of oral contraceptive preparations, viz. "Gynovlar" containing 3000 micrograms norethisterone (NET) and 50 micrograms ethinyl estradiol (EE2) or "Ovral" containing 250 micrograms levonorgestrel (LNG) and 50 micrograms EE2, or a daily progestogen only type--"Minipill" containing 30 micrograms of LNG only, were administered to 40 normal lactating women on a random basis. The sampling schedule in all the three body fluids, i.e. the maternal sera, breast milk and the infant's sera, was kept in such a manner that the peak levels of the contraceptive steroids would be expected to be present in these fluids. The results of this study indicate that the transfer ratio of LNG or NET from the maternal sera to her breast milk was approximately 10% (6-34%) for Gynovlar, 9% (5-18%) for Ovral and 6% (2-34%) for Minipill. However, it was interesting to observe that whereas the transfer ratio of NET or LNG from breast milk to infant's sera was similar for combination pills--8% (3-23%) for Gynovlar and 12% (3-42%) for Ovral, it was significantly higher for progestogen only Minipills--38% (13-92%) for LNG. The precise reason for the higher transfer ratio of LNG from breast milk to infant's serum in Minipill users cannot be explained.

ICMR task force study on hormonal contraception. Transfer of levonorgestrel (LNG) administered through different drug delivery systems from the maternal circulation into the newborn infant's circulation via breast milk.

The transfer of levonorgestrel (LNG) from the maternal plasma via breast milk to the infant was studied in 38 fully lactating and breast-feeding women at 4-6 weeks postpartum, for a duration of 28 days. These volunteers were provided with LNG contraceptive treatment delivered through three, different routes of drug delivery system: (i) intrauterine devices impregnated with LNG (LNG-IUD); (ii) subdermal implant (Norplant (R)-2); and (iii) minipills (LNG 30 micrograms daily). On the first day after either the LNG-IUD (n = 14 women) or Norplant (R)-2 (n = 14 women) insertion, the maternal blood and breast milk samples were collected at 2, 4 and 8 hourly intervals. This was followed by daily collection of these samples as well as infant's blood from days 2 to 4 and thereafter on days 7, 14 and 28. For infant's blood samples from LNG minipill users (n = 10 women), only a single 4-hour sample was collected on the first day and no samples were collected on days 3 and 4. The rest of the schedule for collection of maternal blood and breast milk as well as infant's blood samples were the same in minipill users as for the other two treatment groups. The study revealed a lower LNG percentage transfer from maternal sera to breast milk--11.8 +/- 2, 7 +/- 2 and 8 +/- 1 and relatively higher percentage LNG transfer from breast milk to infant's sera--75 +/- 17, 68 +/- 20 and 32 +/- 3, in LNG-IUD, Norplant (R)-2 and minipill users, respectively. Therefore, LNG contraceptive steroid is transferred into the infant's circulation, the biological significance of which remains to be established.

Pharmacodynamic effects of levonorgestrel (LNG) administered either orally or subdermally to early postpartum lactating mothers on the urinary levels of follicle stimulating hormone (FSH), luteinizing hormone (LH) and testosterone (T) in their breast-fed male infants.

Pharmacodynamic effect of levonorgestrel (LNG) present in small amounts in infant's circulation has not yet been studied adequately. In our present study, nine women were taking oral minipills (LNG 30 micrograms daily) and 10 were using subdermal implants, Norplant(R)-2, during early postpartum period from four weeks to 15 weeks. These were healthy lactating women in age group 20 to 35 yrs, who had full-term normal delivery of male infants. Daily 4-hour urine samples (from 8 AM to 12 noon) were collected from four weeks onwards to 15 weeks for estimations by radioimmunoassays of follicle stimulating hormone (FSH), luteinizing hormone (LH) and testosterone (T) levels. No significant differences (P greater than 0.05) were found between geometric means of the total area under curve at weekly intervals for FSH, LH and T hormones between the male infants from control group (n=10) when compared with oral minipill or Norplant(R)-2 users. These results are reassuring for future sexual growth and development of children who are exposed to contraceptive steroids during their infancy; however, they do require further confirmation by long-term epidemiological studies incorporating monitoring and surveillance of such children.

ICMR Task Force Study on hormonal contraception. Biological activity of ethinyl estradiol present in the breast milk.

A study was conducted to compare the biological activity of the estrogenic component of the endogenous steroids in breast milk samples collected during various phases of lactation with those milk samples collected from women who were on estrogen therapy. The estrogenic biological activity in the milk sample was assessed by the immature mouse uterine weight gain assay. Milk samples collected during postpartum period from six different study groups, viz., control colostrum of 1-3 days and 4-6 days, transitional milk (10-20 days) and mature milk (1-3 months) were compared with colostrum and mature milk of women treated with Lynoral (ethinyl estradiol 0.1 mg) three times a day for three days. Estrogenic activity was observed only in animals injected with milk extracts of colostrum samples from both control and Lynoral-treated women; however, they were not significantly different from each other. Therefore it is not the exogenous estrogens, but the endogenous estrogen present in large quantities in the colostrum that is responsible for the biological activity.