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parturition
- william s. craig (9 August 2003)
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Poor maternal and perinatal outcome with short interpregnancy interval
- Jai B Sharma, Monika Malhotra, St Thomas Hospital, London (10 August 2003)
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Interpregnancy interval and breast feeding
- angela m hamon (11 August 2003)
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Residual confounding and biased odds ratios
- Adam Jacobs (13 August 2003)
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too little DHEA
- James M. Howard (23 November 2003)
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Re: too little DHEA FULL VERSION
- James M. Howard (24 November 2003)
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Re: Re: too little DHEA New Support: Magnesium: JAMA. 2003; 290: 2669-2676
- James M. Howard (27 November 2003)
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Re: Re: Re: too little DHEA New Support: Caesarean section: Lancet 2003; 362: 1779-84
- James M. Howard (30 November 2003)
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william s. craig, retired obstetrician sudbury
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My wife and I married in 1960 an had babies in 1961, 1962, 1963 1964, and 1966. All normal deliveries. I rathe doubt if the birth frequency is an important factor in obstetric health. In Uganda frequent pregnancy prevented STDs. Competing interests: None declared |
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Jai B Sharma, Assistant Professor in Obst & Gynaecology All India Institute of Medical Sciences, New Delhi 110029, Monika Malhotra, St Thomas Hospital, London
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The article by Smith et al (1)is interesting but not surprising as is the experience of us all in India where early pregnancies in adoloscents and repeated pregnancies at short intervals play a havoc with their lives with very high maternal and perinatal mortality and morbidity. Nutritional anaemia plays a significant role in poor pregnancy outcome in India where anaemia complicates 72-96 percent of all pregnancies ( 2-4). As the women enter their pregnancies with florid anaemia or with poor iron stores they have poor pregnancy outcome ( 2). After the childbirth they all breastfeed putting an extra load on their iron stores and then they enter their next pregnancy even before their iron stores are fulfilled putting them at greater risk in their subsequent deliveries ( 2). This cycle must be broken if we want their iron stores to get any better. They need to improve their nutritional status and need to practice contraception to increase interpregnancy interval to improve pregnancy outcome which will be of vital importance for countries like India. Most women in India are vegetarian or occasionally meat eaters precluding it to be a factor in their nutrition. Refernces; 1. Smith GCJ,Pell JP,Dobbie R. Interpregnancy interval and risk of preterm birth and neonatal death: retrospective cohort study. BMJ 2003; 327:313 2. Sharma JB. Nutritional anaemia during pregnancy in non-industrialised countries. In studd JJ ( eds). Progress in Obstetrics and Gynaecology, Vol 15, Churchill Livingstone, Edinburgh, 2003 pages;103-122 3. Sharma JB,Soni D, Murthy NS, Malhotra M. Effect of dietary habits on prevalence of anaemia in pregnant women of Delhi. J Obstet Gynaecol Res 2003; 29; 73-78 4. Malhotra M, Sharma JB, Batra S, Sharma S, Murthy NS,Arora R. Maternal and perinatal outcome in varying degrees of anemia. Int J Gynecol Obstet 2002; 79: 93-100 Competing interests: None declared |
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angela m hamon, specilist registrar, obstetrics and gynaecology singleton hospital, sa2 8qa
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Breast feeding is associated with a longer interpregnancy interval. Could it have been that breast feeding protected many babies in the longer-interpregnancy-interval groups from neonatal death? Could it be that breast feeding affects the uterus or other organ(s) and protects against preterm delivery in future pregnancy? If this is the case, suggesting a longer interpregnancy interval without breast feeding may not be beneficial. Competing interests: None declared |
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Adam Jacobs, Director Dianthus Medical Limited, London SW19 3TZ
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Investigating the relationship between factors such as interpregnancy interval and adverse outcomes is fraught with problems of confounding, and Smith et al deserve credit for taking a wide range of confounding factors into account in their analysis. However, I am not sure I agree with their conclusion that residual confounding is unlikely. First, it is not clear how adjustment for maternal age was done. The relationship between maternal age and adverse outcomes is non-linear, as both very young and very old mothers are at increased risk of adverse outcomes. Adjusting for age as a continuous linear variable would therefore be inappropriate. A better approach would be to adjust for age in categories, such as 5-year age bands, or to include both linear and quadratic terms for age. Perhaps Smith et al could clarify which approach they used. Second, adjustment for socioeconomic variables was, if I understand correctly, based solely on postcode of residence. This is a crude measure of socioeconomic deprivation, as it cannot be assumed that all women living in the same postcode area will be of equal socioeconomic status. This crude socioeconomic measure cannot adjust fully for socioeconomic status, meaning that residual confounding remains a real possibility. I am also concerned about the choice of reference category used for calculating odds ratios. The authors do not state their rationale for using an interpregnancy interval of 18–23 months as the reference category. If their primary hypothesis was that an interpregnancy interval of less than 6 months would be associated with adverse outcomes, then surely a more appropriate reference category would have been all women with interpregnancy intervals of 6 months or greater. This would have given greater statistical power. Moreover, the 18–23 months category was associated with the lowest rates of adverse outcomes of all the categories. If this was a post-hoc reason for its choice as the reference category, then this will have the effect of biasing the odds ratios for the 1–6 months category towards greater values. Competing interests: None declared |
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James M. Howard, independent biologist 1037 North Woolsey Avenue, Fayetteville, Arkansas 72701-2046, U.S.A.
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DHEA, which is produced by the mother for herself and her fetus, is reduced following a first birth. If a pregnancy does occur before sufficient rebound of DHEA in the mother, there is insufficient DHEA for proper growth and development of the fetus. The reduced DHEA may also cause problems for the mother. Competing interests: None declared |
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James M. Howard, independent biologist 1037 North Woolsey Avenue, Fayetteville, Arkansas 72701-2046, U.S.A.
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"Interpregnancy Interval and Risk of Preterm Birth and Neonatal Death" (Smith, et al., BMJ 2003; 327: 313 ) Explanation May be Due to Reduced DHEA Postpartum Following a First Pregnancy (Copyright 2003, James Michael Howard, Fayetteville, U.S.A.) Smith, et al., conclude in their report in the British Medical Journal that: "A short interpregnancy interval is an independent risk factor for preterm delivery and neonatal death in the second birth." (The abstract is available below.) I suggest these "adverse obstetric outcomes" result from a single phenomenon which should not go unacknowledged vis-à- vis the tremendous burdens in emotional suffering and medical costs. These conditions may be ameliorated by monitoring low levels of, and supplementation with, dehydroepiandrosterone (DHEA) in women who become pregnant again, soon after a first pregnancy. DHEA has been determined to decline in women "only after a first pregnancy" for remain low sometimes up to 150 months (J Clin Endocrinol Metab. 1987; 64: 111-8). This finding was repeated: "A previous paper in this journal reported that first pregnancy was followed by a marked decrease in dehydroepiandrosterone sulfate (DH[E]AS) and dehydroepiandrosterone (DH[E]A) levels. We report here confirmatory observations from cross-sectional measurements in 460 women. In premenopausal subjects (n = 306), the mean DH[E]AS level was 21% lower (P = 0.005) and the mean DH[E]A level was 32% lower (P less than 0.001) in parous than in nulliparous women." (J Clin Endocrinol Metab. 1990; 70: 1651-3). I suggest these low levels of DHEA are directly connected with "adverse obstetric outcomes" in pregnancies of short intervals following a first pregnancy. In order to understand the connection of this low DHEA with "adverse obstetric outcomes," in pregnancies following first pregnancies without sufficient time for DHEA to rebound, I have to explain two ideas about DHEA. In 1985, I copyrighted my explanation of the "fight or flight" mechanism. I suggested that the major adrenal steroid, dehydroepiandrosterone (DHEA), was "selected" by evolution because it "optimizes" replication and transcription of DNA. Therefore, DHEA is involved in every tissue, especially nervous tissue, the brain. It follows that DHEA in sufficiently available levels will be involved in increasing, or optimizing, aggression between combatants. Combatants who fight to death or maiming reduce the probability of continuance of a species. DHEA levels would be positively involved in "impulses" or "motivation." I suggest the other major adrenal steroid, cortisol, was selected by evolution to counteract the effects of DHEA. As you may know, cortisol is the "stress" hormone, produced when we experience stress. I suggest cortisol levels are negatively involved in impulses or motivation. The ratio of cortisol to DHEA will be directly tied to our personalities as well as actions. When cortisol is high, we flee, when DHEA is high, we fight. Cortisol antagonizes the effects of DHEA and the ratio of cortisol to DHEA is important in many physiological phenomena, including obstetric outcomes. Too much cortisol for extended periods, especially in low DHEA conditions, may produce very negative effects in all tissues. Also, one should know that the very abundant source of DHEA in our blood exists as a "sulfated" form. This is known as DHEAS or DHEAsulfate. The active molecule, DHEA, is derived from DHEAS. Now, this is not well known. Therefore, sometimes, when DHEAS levels are measured and found to be high, this literally indicates that abundant DHEA is readily available. However, sometimes when DHEAS levels are measured as high, this also may mean that DHEA is not being produced from DHEAS. Since this is not well known, one has to look at the pattern of this ratio and interpret it in terms of potential pathology. So, sometimes high DHEAS may indicate negative or adverse conditions. I suggest this is the case in the following citations which connect high levels of DHEAS with preterm delivery. Mazor, et al., reported that "Maternal plasma DHEA-S concentrations were significantly higher in women with preterm labor who delivered preterm than in those who delivered at term." (Arch Gynecol Obstet. 1996; 259: 7-12). Now, if DHEAS is working normally, the relationship of cortisol ratio becomes important as an indication that cortisol is too high and antagonizing the effects of DHEA. (Remember the connection of cortisol to DHEA above.) Yoon, et al., found this in 1998: "An elevation in fetal plasma cortisol but not dehydroepiandrosterone sulfate was followed by the onset of spontaneous preterm labor in patients with preterm premature rupture of the membranes." (Am J Obstet Gynecol. 1998; 179: 1107-14). Smith, et al., also found: "They [the women of the study] were also shorter, less likely to be married, and more likely to be aged less than 20 years at the time of the second birth, to smoke, and to live in an area of high socioeconomic deprivation." I suggest all of these may be connected with higher levels of testosterone in these women. It is my hypothesis that testosterone exerts negative effects on the availability of DHEA. Therefore, these findings also may fit my explanation of low DHEA. It is my hypothesis that women of higher testosterone are increasing in percentage within our population. This suggests that premature births should be increasing and this is, indeed, the case. Black women produce more testosterone than white women. This may be why more black women exhibit these "adverse obstetric outcomes" more than white women. I suggest the "adverse obstetric outcomes" connected with a short interval between a first pregnancy and a subsequent pregnancy may result from insufficient DHEA in the mother. These conditions may be ameliorated by monitoring low levels of, and supplementation with, dehydroepiandrosterone (DHEA) in women who become pregnant again, soon after a first pregnancy. British Medical Journal 2003; 327: 313. Interpregnancy interval and risk of preterm birth and neonatal death: retrospective cohort study. Smith GC, Pell JP, Dobbie R. OBJECTIVE: To determine whether a short interval between pregnancies is an independent risk factor for adverse obstetric outcome. DESIGN: Retrospective cohort study. SETTING: Scotland. SUBJECTS: 89 143 women having second births in 1992-8 who conceived within five years of their first birth. MAIN OUTCOME MEASURES: Intrauterine growth restriction (birth weight less than the 5th centile for gestational age), extremely preterm birth (24-32 weeks), moderately preterm birth (33-36 weeks), and perinatal death. RESULTS: Women whose subsequent interpregnancy interval was less than six months were more likely than other women to have had a first birth complicated by intrauterine growth restriction (odds ratio 1.3, 95% confidence interval 1.1 to 1.5), extremely preterm birth (4.1, 3.2 to 5.3), moderately preterm birth (1.5, 1.3 to 1.7), or perinatal death (24.4, 18.9 to 31.5). They were also shorter, less likely to be married, and more likely to be aged less than 20 years at the time of the second birth, to smoke, and to live in an area of high socioeconomic deprivation. When the outcome of the second birth was analysed in relation to the preceding interpregnancy interval and the analysis confined to women whose first birth was a term live birth (n = 69 055), no significant association occurred (adjusted for age, marital status, height, socioeconomic deprivation, smoking, previous birth weight vigesimal, and previous caesarean delivery) between interpregnancy interval and intrauterine growth restriction or stillbirth. However, a short interpregnancy interval (< 6 months) was an independent risk factor for extremely preterm birth (adjusted odds ratio 2.2, 1.3 to 3.6), moderately preterm birth (1.6, 1.3 to 2.0), and neonatal death unrelated to congenital abnormality (3.6, 1.2 to 10.7). The adjusted attributable fractions for these associations were 6.1%, 3.9%, and 13.8%. The associations were very similar when the analysis was confined to married non-smokers aged 25 and above. CONCLUSIONS: A short interpregnancy interval is an independent risk factor for preterm delivery and neonatal death in the second birth. Competing interests: None declared |
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James M. Howard, independent biologist 1037 North Woolsey Avenue, Fayetteville, Arkansas 72701-2046, U.S.A.
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JAMA. 2003; 290: 2669-2676."Effect of Magnesium Sulfate Given for Neuroprotection Before Preterm Birth A Randomized Controlled Trial" C.A. Crowther, et al. "Conclusions: Magnesium sulfate given to women immediately before very preterm birth may improve important pediatric outcomes. No serious harmful effects were seen." I suggest Crowther, et al., may have added to my explanation of a connection of testosterone with prematurity. Now, some white women exist who produce more testosterone than others; this explanation should also include these white women, however, black mothers produce more testosterone than white mothers so this effect probably predominates within black women. As I pointed out above, black mothers produce more testosterone than white mothers (Cancer Causes Control. 2003; 14: 347-55). African-American men and women consume less magnesium than whites (Ethn Dis. 1998; 8:10-20). A study of "hypomagnesemia among ambulatory urban African Americans," mainly women patients, concluded that "The prevalence of hypomagnesemia among patients from this urban minority community exceeds that reported in previous studies of the general population." (J Fam Pract. 1999; 48: 636-9). Increased hypomagnesemia was associated with increased morbidity. African-American women consume less magnesium and/or exhibit more magnesium deficiency. Testosterone reduces magnesium in women: "In addition, a decrease in ionized Mg was found with increased testosterone levels." (Fertil Steril. 1998; 69: 958-62). So, women who consume less magnesium, who produce more testosterone may exhibit more hypomagnesemia. I suggest it is possible that magnesium administered to women prenatally may alter final effects of testosterone on availability of dehydroepiandrosterone and, therefore, "improve important pediatric outcomes." Competing interests: None declared |
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James M. Howard, independent biologist 1037 North Woolsey Avenue, Fayetteville, Arkansas 72701-2046, U.S.A.
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I suggest this report, again, Lancet 2003; 362: 1779-84, may represent "adverse obstetric outcomes" caused by low dehydroepiandrosterone (DHEA). That is, I suggest the Caesarean section may induce a condition of low DHEA in women that may adversely affect future pregnancies. Osorio, et al., reported in 2002 "We found a significant reduction in the concentrations of DHEA-S and IGF-1 on days 2 and 7 after surgery versus the preoperative values." (World J Surg. 2002 Sep; 26: 1079-82) Competing interests: None declared |
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