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Leptin in reproduction and hypertension in pregnancy

Singh H, Almabhouh FA, Alshaikhli HSI, Hassan MJM, Daud S, Othman R, et al.

Reprod Fertil Dev, 2024 Jul;36.
PMID: 39038160 DOI: 10.1071/RD24060

Leptin has important roles in numerous physiological functions, including those in the regulation of energy balance, and in immune and reproductive systems. However, in the recent years, evidence has implicated it in a number of obesity-related diseases, where its concentrations in serum are significantly elevated. Elevated serum leptin concentrations and increased placental leptin secretion have been reported in women with hypertensive disorders of pregnancy. Whether leptin is responsible for this disorder remains to be established. Leptin injections in healthy rats and mice during pregnancy result in endothelial activation, increased blood pressure and proteinuria. A potential role for leptin in the pathogenesis of pre-eclampsia is hypothesised, particularly in women who are overweight or obese where serum leptin concentrations are often elevated. This review summarises pertinent information in the literature on the role of leptin in puberty, pregnancy, and hypertensive disorders of pregnancy. In particular, the possible mechanism that may be involved in leptin-induced increase in blood pressure and proteinuria during pregnancy and the potential role of marinobufagenin in this disease entity. We hypothesise a significant role for oxidative stress in this, and propose a conceptual framework on the events that lead to endothelial activation, raised blood pressure and proteinuria following leptin administration.

Matched MeSH terms: Hypertension, Pregnancy-Induced/metabolism; Hypertension, Pregnancy-Induced/physiopathology
Does palm oil vitamin E reduce the risk of pregnancy induced hypertension?

Mahdy ZA, Siraj HH, Khaza'ai H, Mutalib MS, Azwar MH, Wahab MA, et al.

Acta Medica (Hradec Kralove), 2013;56(3):104-9.
PMID: 24592747

In view of the high anti-oxidative potential oftocotrienol, the role of the tocotrienol-rich fraction (TRF) of palm oil in preventing pregnancy induced hypertension (PIH) was explored in a randomized double-blind placebo-controlled clinical trial in an urban teaching hospital. Healthy primigravidae were randomized to receive either oral TRF 100 mg daily or placebo, from early second trimester until delivery. Out of 299 women, 151 were randomized into the TRF arm and 148 into the placebo arm. A total of 15 (5.0%) developed PIH. Although there was no statistically significant difference in the incidence of PIH (4/151 or 2.6% in the TRF arm vs. 11/148 or 7.4% in the placebo arm, p = 0.058) between the two arms, there was a tendency towards a lower incidence of PIH in the TRF arm compared to the placebo arm. With TRF supplementation, the relative risk (RR) of PIH was 0.36 (95% CI 0.12-1.09). In conclusion, although TRF from palm oil does not statistically significantly reduce the risk of development of PIH in the population studied, the 64% reduction in incidence of PIH is substantial. The findings warrant further clinical trials, particularly in high risk populations.

Matched MeSH terms: Hypertension, Pregnancy-Induced/epidemiology; Hypertension, Pregnancy-Induced/prevention & control*
Fulltext Matrix metalloproteinase-9 and tissue inhibitors of metalloproteinases 1 and 2 as potential biomarkers for gestational hypertension

Ab Hamid J, Mohtarrudin N, Osman M, Andi Asri AA, Wan Hassan WH, Aziz R

Singapore Med J, 2012 Oct;53(10):681-3.
PMID: 23112021

Gestational hypertension (GH) is a common disorder during pregnancy that can progress to preeclampsia and cause various subsequent fatal complications. A cluster of enzymes, called matrix metalloproteinases (MMPs), and its specific inhibitors, tissue inhibitors of metalloproteinases (TIMPs), have been reported to be involved in the pathophysiology of GH. The purpose of this study was to examine circulating levels of MMP-9, TIMP-1 and TIMP-2 in pregnant women who had GH and those who were normotensive.

Matched MeSH terms: Hypertension, Pregnancy-Induced/blood*; Hypertension, Pregnancy-Induced/diagnosis
Association between pregnancy induced hypertension and low birth weight; a population based case-control study

Rahman LA, Hairi NN, Salleh N

Asia Pac J Public Health, 2008;20(2):152-8.
PMID: 19124309 DOI: 10.1177/1010539507311553

The purpose of this study was to investigate the association between pregnancy-induced hypertension and low birth weight. A population-based case control study was conducted. Antenatal mothers who attended the government health centers in the district of Kuala Muda, Kedah, Malaysia from June 2003 to May 2004 were recruited. Cases were 312 mothers who delivered low birth weight babies, and controls were 312 mothers who delivered normal birth weight babies. Face-to-face interviews using a structured questionnaire and a review of medical records were carried out. After controlling for important confounders such as gestational age at delivery, maternal age, ethnicity, education, parity, and previous history of abortion, pregnancy-induced hypertension was found to be an independent risk factor (adjusted odds ratio = 5.06; 95% confidence interval: 2.63, 9.71) for low birth weight. There was a significant association of pregnancy-induced hypertension with low birth weight. Women who delivered low birth weight babies were 5 times more likely to have had pregnancy-induced hypertension.

Matched MeSH terms: Hypertension, Pregnancy-Induced*
Tissue kallikrein and kininogen levels in fetoplacental tissues from normotensive pregnant women and women with pregnancy-induced hypertension

Mohamed M, Larmie ET, Singh HJ, Othman MS

Eur J Obstet Gynecol Reprod Biol, 2007 Sep;134(1):15-9.
PMID: 17050061

An imbalance of vasoconstrictor and vasodilator substances in the placenta has been postulated in the pathogenesis of pregnancy-induced hypertension (PIH). There is however little information available on the kallikrein-kinin system (KKS) in women with PIH. The aim of this study therefore was to determine tissue kallikrein and kininogen levels and their distribution patterns in fetoplacental tissues from both normotensive pregnant (NTP) women and women with PIH.

Matched MeSH terms: Hypertension, Pregnancy-Induced/physiopathology*
High-Sensitivity Cardiac Troponin I Levels in Normal and Hypertensive Pregnancy

Ravichandran J, Woon SY, Quek YS, Lim YC, Noor EM, Suresh K, et al.

Am J Med, 2019 03;132(3):362-366.
PMID: 30503877 DOI: 10.1016/j.amjmed.2018.11.017

PURPOSE: The purpose of this study was to examine the association of circulating concentrations of high-sensitivity cardiac troponin I (hs-cTn) in the various trimesters of pregnancy in patients with and without hypertension.
METHODS: This was a prospective cross-sectional study of pregnant and postnatal women aged between 18-35 years with no coexisting diseases. Serum samples were analysed for hs-TnI.
RESULTS: A total of 880 women (mean age = 29.1 years [standard deviation = 5.1 years]) were recruited with 129 (14%), 207 (24%), and 416 (47%) patients in the first, second, and third trimesters, respectively. Ninety (10%) participants were recruited in the postnatal period. During pregnancy 28 (3%) patients were classified as having pregnancy-induced hypertension and 10 (1%) as preeclampsia. High-sensitivity cardiac troponin I was measurable in 546 (62%) participants with a median of 1 ng/L (range 0 to 783 ng/L). Troponin concentrations were above the 99th percentile in 19 (2%) individuals. Patients with pregnancy-induced hypertension and preeclampsia had higher concentrations of hs-TnI (median 11 ng/L [interquartile range (IQR) 6 to 22 ng/L] vs 12ng/L [IQR 3 to 98 ng/L] vs 1 ng/L [IQR 0 to 1 ng/L]). In logistic regression modeling hs-cTnI concentration remained an independent predictor of pregnancy-induced hypertension or preeclampsia in both unadjusted and adjusted models (odds ratio 9.3 [95% confidence interval 5.8 to 16.3] and 11.5 [95% confidence interval 6.3 to 24.1], respectively, per doubling of hs-TnI concentrations).
CONCLUSIONS: Cardiac troponin measured using a high-sensitivity assay is quantifiable in the majority of young pregnant women with 2% of individuals having concentration above the 99th percentile sex-specific threshold. Patients with pregnancy-induced hypertension or preeclampsia had higher cardiac troponin concentrations. Cardiac troponin was a strong independent predictor of pregnancy-induced hypertension or preeclampsia in pregnant and postnatal women.

Matched MeSH terms: Hypertension, Pregnancy-Induced/blood
Fulltext Vascular endothelial growth factor expression in placenta of hypertensive disorder in pregnancy

Azliana AF, Zainul-Rashid MR, Chandramaya SF, Farouk WI, Nurwardah A, Wong YP, et al.

Indian J Pathol Microbiol, 2018 1 13;60(4):515-520.
PMID: 29323064 DOI: 10.4103/IJPM.IJPM_376_16

INTRODUCTION: Hypertensive disorder in pregnancy (HDP) represents the most common medical complication in pregnancy. It is the leading cause of maternal and perinatal mortality and morbidity. Vascular endothelial growth factor (VEGF) stimulates vascular endothelial cell growth, survival, and proliferation, and they are known to be expressed in human placenta. The aim of this study was to determine the VEGF expression in the placenta of hypertensive and normotensive patients.
MATERIALS AND METHODS: This is a retrospective, cross-sectional study from January 1, 2015 to December 31, 2015. A total of 30 placentae comprised of 15 hypertensive and 15 normotensive cases were assessed. VEGF expression in placenta was assessed by immunohistochemistry, and the number of syncytial knots was counted.
RESULTS: Our study showed an increased syncytial knot formation in the placenta of hypertensive mothers. VEGF expression was seen in syncytiotrophoblasts of 14 of the hypertensive cases (14/15, 93.3%), while only two of the normotensive cases were positive (2/15, 13.3%). There were no statistically significant differences in VEGF expression in other placenta cells, that is, cytotrophoblasts (P = 1.0), decidual cells (0.1394), maternal endothelial cells (0.5977), and fetal endothelial cells (P = 1.0).
CONCLUSIONS: This study showed an increased number of syncytial knots is a consistent histological finding in the placenta of patient with HDP. VEGF expression was significantly increased in syncytiotrophoblasts in placenta of hypertensive group, and it could be used as a biomarker for hypertension.

Matched MeSH terms: Hypertension, Pregnancy-Induced/pathology*
A pilot study to determine whether progestogen supplementation using dydrogesterone during the first trimester will reduce the incidence of gestational hypertension in primigravidae

Zainul Rashid MR, Lim JF, Nawawi NH, Luqman M, Zolkeplai MF, Rangkuty HS, et al.

Gynecol Endocrinol, 2014 Mar;30(3):217-20.
PMID: 24552449 DOI: 10.3109/09513590.2013.860960

Gestational hypertension (GH) remains one of the main causes of high maternal and perinatal morbidity and mortality worldwide with the highest incidence among primigravidae of about 10%-15%. However, it was noted that the incidence of GH in primigravidae who conceived following assisted reproductive technique (ART) or intrauterine insemination (IUI) supplemented with dydrogesterone during the first trimester was low.

Study site: Obstetrics and Gynecology
Department, Pusat Perubatan Universiti Kebangsaan Malaysia PPUKM

Matched MeSH terms: Hypertension, Pregnancy-Induced/ethnology; Hypertension, Pregnancy-Induced/epidemiology; Hypertension, Pregnancy-Induced/physiopathology; Hypertension, Pregnancy-Induced/prevention & control*
Fulltext Oral nifedipine versus intravenous labetalol for acute blood pressure control in hypertensive emergencies of pregnancy: a randomised trial

Raheem IA, Saaid R, Omar SZ, Tan PC

BJOG, 2012 Jan;119(1):78-85.
PMID: 21985500 DOI: 10.1111/j.1471-0528.2011.03151.x

To compare oral nifedipine with intravenous labetalol in their rapidity to control hypertensive emergencies of pregnancy.

Matched MeSH terms: Hypertension, Pregnancy-Induced/physiopathology; Hypertension, Pregnancy-Induced/prevention & control*
Fulltext Periodic assessment of plasma sFlt-1 and PlGF concentrations and its association with placental morphometry in gestational hypertension (GH) - a prospective follow-up study

Jeevaratnam K, Nadarajah VD, Judson JP, Nalliah S, Abdullah MF

BMC Pregnancy Childbirth, 2010;10:58.
PMID: 20920154 DOI: 10.1186/1471-2393-10-58

Hypertensive disorders in pregnancy contributes to about 12% of maternal deaths in Malaysia and similarly worldwide. Early detection and adequate management are preventable strategies. Biochemical markers of abnormal angiogenesis would be more specific in early detection than routine blood pressure and proteinuria measurements. The aim of this study was to estimate maternal plasma PlGF and sFlt-1 levels in pregnant women with gestational hypertension at three intervals of pregnancy and correlate these biomarker levels with placental morphometry.

Matched MeSH terms: Hypertension, Pregnancy-Induced/blood*; Hypertension, Pregnancy-Induced/pathology*
Thrombophilic mutations in pre-eclampsia and pregnancy-induced hypertension

Omar SZ, Qvist R, Khaing SL, Muniandy S, Bhalla S

J Obstet Gynaecol Res, 2008 Apr;34(2):174-8.
PMID: 18412778 DOI: 10.1111/j.1447-0756.2008.00755.x

The aim of the present study was to determine the existence or prevalence of thrombophilic markers such as Factor V Leiden, prothrombin G20210A, protein S, protein C, activated protein C and anti-thrombin in pre-eclampsia and pregnancy-induced hypertensive patients.

Matched MeSH terms: Hypertension, Pregnancy-Induced/blood; Hypertension, Pregnancy-Induced/genetics*
Quantitative analysis of fetal DNA in maternal plasma in gestational diabetes mellitus, iron deficiency anemia and gestational hypertension pregnancies

Zamanpoor M, Rosli R, Yazid MN, Husain Z, Nordin N, Thilakavathy K

J Matern Fetal Neonatal Med, 2013 Jul;26(10):960-6.
PMID: 23339569 DOI: 10.3109/14767058.2013.766710

OBJECTIVE: To quantify circulating fetal DNA (fDNA) levels in the second and third trimesters of normal healthy pregnant individuals and pregnant women with the following clinical conditions: gestational diabetes mellitus (GDM), iron deficiency anemia and gestational hypertension (GHT).
METHODS: The SRY gene located on the Y chromosome was used as a unique fetal marker. The fDNA was extracted from maternal plasma and the SRY gene concentrations were measured by quantitative real-time polymerase chain reaction (PCR) amplification using TaqMan dual labeled probe system.
RESULTS: No significant differences were observed in the mean fDNA concentration between normal and GDM pregnancy samples (p > 0.05) and also between normal and anemic pregnancy samples (p > 0.05) in both trimesters, but significant differences were observed between the third trimester normal and GHT pregnancy samples (p = 0.001). GDM and iron deficiency anemia do not affect the levels of fDNA in maternal plasma while GHT significantly elevates the levels of fDNA in maternal plasma.
CONCLUSIONS: Increased amount of circulating fDNA in maternal plasma could be used for early identification of adverse pregnancies. GDM and anemia do not affect the levels of fDNA in maternal plasma while GHT significantly elevates the levels of fDNA in maternal plasma. Hence, the elevated fDNA values could be used as a potential screening marker in pregnancies complicated with GHT but not with GDM and iron deficiency anemia.

Matched MeSH terms: Hypertension, Pregnancy-Induced/blood*; Hypertension, Pregnancy-Induced/genetics
Which and what headache were we treating? Epidural blood patch for atypical headache following obstetric epidural anaesthesia

Chiu CL, Chan YK

Int J Obstet Anesth, 2000 Oct;9(4):273-5.
PMID: 15321079 DOI: 10.1054/ijoa.2000.0397

We present a case of headache following epidural anaesthesia for caesarean section. The patient did not exhibit the classical features of post dural puncture headache and the cause was uncertain. The headache was complicated by post partum seizure and a history of pregnancy-induced hypertension. A diagnostic lumbar puncture had to be done to exclude meningitis as she had a raised white blood count. An epidural blood patch performed 12 days post partum resolved the headache immediately.

Matched MeSH terms: Hypertension, Pregnancy-Induced
Maternal plasma soluble fms-like tyrosine kinase-1 and placental growth factor levels as biochemical markers of gestational hypertension for Malaysian mothers

Nadarajah VD, Min RG, Judson JP, Jegasothy R, Ling EH

J Obstet Gynaecol Res, 2009 Oct;35(5):855-63.
PMID: 20149032 DOI: 10.1111/j.1447-0756.2009.01037.x

To establish baseline levels of maternal plasma soluble fms-like tyrosine kinase-1 (sFlt-1) and placental growth factor (PlGF) among normotensive Malaysian mothers and to compare the marker levels between normotensives and mothers with gestational hypertension (GH).

Matched MeSH terms: Hypertension, Pregnancy-Induced/blood*
Fulltext "Postpartum morbidity--what we can do"

Zainur RZ, Loh KY

Med J Malaysia, 2006 Dec;61(5):651-6.
PMID: 17623974

Postpartum is a crucial period for a mother. During this period a mother is going through the physiological process of uterine involution and at the same time adapting to her new role in the family. Many postpartum complications occur during this period. Among the important obstetric morbidities are postpartum hemorrhage, pregnancy related hypertension, pulmonary embolism and puerperal sepsis. Common surgical complications are wound breakdown, breast abscess and urinary fecal incontinence. Medical conditions such as anemia, headache, backache, constipation and sexual problems may also be present. Unrecognized postpartum disorders can lead to physical discomfort, psychological distress and a poor quality of life for the mothers. Providing quality postnatal care including earlier identification of the problems (correction) and proper intervention will help the mother to achieve full recovery and restore her functional status back to the pre-pregnancy state sooner.

Matched MeSH terms: Hypertension, Pregnancy-Induced/therapy
Reflections on the maternal mortality millennium goal

Lawson GW, Keirse MJ

Birth, 2013 Jun;40(2):96-102.
PMID: 24635463 DOI: 10.1111/birt.12041

Nearly every 2 minutes, somewhere in the world, a woman dies because of complications of pregnancy and childbirth. Every such death is an overwhelming catastrophe for everyone confronted with it. Most deaths occur in developing countries, especially in Africa and southern Asia, but a significant number also occur in the developed world.

Matched MeSH terms: Hypertension, Pregnancy-Induced/mortality
Role of Palm Oil Vitamin E in Preventing Pre-eclampsia: A Secondary Analysis of a Randomized Clinical Trial Following ISSHP Reclassification

Aminuddin NA, Sutan R, Mahdy ZA

Front Med (Lausanne), 2020;7:596405.
PMID: 33553199 DOI: 10.3389/fmed.2020.596405

Background: Preeclampsia is a significant cause of maternal and perinatal mortality worldwide. Oxidative stress plays a key role in its pathophysiology, hence antioxidants such as tocotrienol may be preventive against preeclampsia. In 2018, the ISSHP revised the definition of preeclampsia. In accordance with the new definition, we report a secondary data analysis from a clinical trial comparing palm oil vitamin E in the form of tocotrienol-rich fraction (TRF) against placebo, in preventing preeclampsia. Method: A randomized double-blind controlled trial was conducted in 2002-2005 to assess the benefits of TRF in preeclampsia prevention. A total of 299 primigravidae were recruited. The intervention group was supplemented with TRF 100 mg daily in super-olein capsules, whereas the placebo group was prescribed super-olein capsules without TRF, beginning from 12 to 16 gestational weeks until delivery. The primary outcome measure was incidence of preeclampsia. Results: The total incidence of pregnancy induced hypertension (PIH) was 5%, whereas the incidence of preeclampsia was 2.3%. The odds of developing PIH (adjusted OR 0.254; 95% CI: 0.07-0.93; p-value 0.038) and preeclampsia (adjusted OR 0.030; 95% CI: 0.001-0.65; p-value 0.025) were significantly lower in the TRF arm compared to the placebo arm. Conclusion: Antenatal supplementation with palm oil vitamin E in the form of TRF is associated with significant reductions in the incidence of preeclampsia and PIH in a single urban tertiary hospital. Palm oil vitamin E deserves further scrutiny as a potential public health preventive measure against preeclampsia and PIH.

Matched MeSH terms: Hypertension, Pregnancy-Induced

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