Despite extensive adverse publicity, tobacco use continues in approximately 25% of all pregnancies in the United States, overshadowing illicit drugs of abuse, including cocaine. The societal cost of maternal smoking is seen most readily in underweight newborns, in high rates of perinatal morbidity, mortality and Sudden Infant Death Syndrome and in persistent deficits in learning and behavior. We have designed animal models of nicotine exposure to prove that nicotine itself is a neuroteratogen, thus providing a causative link between tobacco exposure and adverse perinatal outcomes. In particular, nicotine infusion paradigms that, like the transdermal patch used in man, produce drug exposure without the confounds of other components of tobacco or of episodic hypoxic-ischemic insult, have enabled a mechanistic dissection of the role played by nicotine in fetal brain damage. Nicotine targets specific neurotransmitter receptors in the fetal brain, eliciting abnormalities of cell proliferation and differentiation, leading to shortfalls in the number of cells and eventually to altered synaptic activity. Because of the close regulatory association of cholinergic and catecholaminergic systems, adverse effects of nicotine involve multiple transmitter pathways and influence not only the immediate developmental events in fetal brain, but also the eventual programming of synaptic competence. Accordingly, defects may appear after a prolonged period of apparent normality, leading to cognitive and learning defects that appear in childhood or adolescence. Comparable alterations occur in peripheral autonomic pathways, leading to increased susceptibility to hypoxia-induced brain damage, perinatal mortality and Sudden Infant Death. Identifying the receptor-driven mechanisms that underlie the neurobehavioral damage caused by fetal nicotine exposure provides a rational basis for decisions about nicotine substitution therapy for smoking cessation in pregnancy. In contrast to the effects of nicotine, animal models of crack cocaine use in pregnancy indicate a more restricted spectrum of effects, a reflection of differences both in pharmacokinetics and pharmacodynamics of the two drugs. Notably, although cocaine, like nicotine, also targets cell replication, its effects are short-lived, permitting recovery to occur in between doses, so that the eventual consequences are much less severe. To some extent, the effects of cocaine on brain development resemble those of nicotine because the two share cardiovascular actions (vasoconstriction) that, under some circumstances, elicit fetal hypoxia-ischemia. In light of the fact that nearly all crack cocaine users smoke cigarettes, the identification of specific developmental effects of cocaine may prove difficult to detect. Although scientists and the public continue to pay far more attention to fetal cocaine effects than to those of nicotine or tobacco use, a change of focus to concentrate on tobacco could have a disproportionately larger impact on human health.

Fetal nicotine or cocaine exposure: which one is worse?

Background
A reduction in salt intake lowers blood pressure (BP) and, thereby, reduces cardiovascular risk. A recent meta-analysis by Graudal implied that salt reduction had adverse effects on hormones and lipids which might mitigate any benefit that occurs with BP reduction. However, Graudal's meta-analysis included a large number of very short-term trials with a large change in salt intake, and such studies are irrelevant to the public health recommendations for a longer-term modest reduction in salt intake. We have updated our Cochrane meta-analysis.  

Objectives
To assess (1) the effect of a longer-term modest reduction in salt intake (i.e. of public health relevance) on BP and whether there was a dose-response relationship; (2) the effect on BP by sex and ethnic group; (3) the effect on plasma renin activity, aldosterone, noradrenaline, adrenaline, cholesterol, low-density lipoprotein (LDL), high-density lipoprotein (HDL) and triglycerides.

Search methods
We searched MEDLINE, EMBASE, Cochrane Hypertension Group Specialised Register, Cochrane Central Register of Controlled Trials, and reference list of relevant articles.

Selection criteria
We included randomised trials with a modest reduction in salt intake and duration of at least 4 weeks.

Data collection and analysis
Data were extracted independently by two reviewers. Random effects meta-analyses, subgroup analyses and meta-regression were performed.

Main results
Thirty-four trials (3230 participants) were included. Meta-analysis showed that the mean change in urinary sodium (reduced salt vs usual salt) was -75 mmol/24-h (equivalent to a reduction of 4.4 g/d salt), the mean change in BP was -4.18 mmHg (95% CI: -5.18 to -3.18, I 2=75%) for systolic and -2.06 mmHg (95% CI: -2.67 to -1.45, I 2=68%) for diastolic BP. Meta-regression showed that age, ethnic group, BP status (hypertensive or normotensive) and the change in 24-h urinary sodium were all significantly associated with the fall in systolic BP, explaining 68% of the variance between studies. A 100 mmol reduction in 24 hour urinary sodium (6 g/day salt) was associated with a fall in systolic BP of 5.8 mmHg (95%CI: 2.5 to 9.2, P=0.001) after adjusting for age, ethnic group and BP status. For diastolic BP, age, ethnic group, BP status and the change in 24-h urinary sodium explained 41% of the variance between studies. Meta-analysis by subgroup showed that, in hypertensives, the mean effect was -5.39 mmHg (95% CI: -6.62 to -4.15, I 2=61%) for systolic and -2.82 mmHg (95% CI: -3.54 to -2.11, I 2=52%) for diastolic BP. In normotensives, the mean effect was -2.42 mmHg (95% CI: -3.56 to -1.29, I 2=66%) for systolic and -1.00 mmHg (95% CI: -1.85 to -0.15, I 2=66%) for diastolic BP. Further subgroup analysis showed that the decrease in systolic BP was significant in both whites and blacks, men and women. Meta-analysis of hormone and lipid data showed that the mean effect was 0.26 ng/ml/hr (95% CI: 0.17 to 0.36, I 2=70%) for plasma renin activity, 73.20 pmol/l (95% CI: 44.92 to 101.48, I 2=62%) for aldosterone, 31.67 pg/ml (95% CI: 6.57 to 56.77, I 2=5%) for noradrenaline, 6.70 pg/ml (95% CI: -0.25 to 13.64, I 2=12%) for adrenaline, 0.05 mmol/l (95% CI: -0.02 to 0.11, I 2=0%) for cholesterol, 0.05 mmol/l (95% CI: -0.01 to 0.12, I 2=0%) for LDL, -0.02 mmol/l (95% CI: -0.06 to 0.01, I 2=16%) for HDL, and 0.04 mmol/l (95% CI: -0.02 to 0.09, I 2=0%) for triglycerides.

Authors' conclusions
A modest reduction in salt intake for 4 or more weeks causes significant and, from a population viewpoint, important falls in BP in both hypertensive and normotensive individuals, irrespective of sex and ethnic group. With salt reduction, there is a small physiological increase in plasma renin activity, aldosterone and noradrenaline. There is no significant change in lipid levels. These results provide further strong support for a reduction in population salt intake. This will likely lower population BP and, thereby, reduce cardiovascular disease. Additionally, our analysis demonstrates a significant association between the reduction in 24-h urinary sodium and the fall in systolic BP, indicating the greater the reduction in salt intake, the greater the fall in systolic BP. The current recommendations to reduce salt intake from 9-12 to 5-6 g/d will have a major effect on BP, but are not ideal. A further reduction to 3 g/d will have a greater effect and should become the long term target for population salt intake.

Effect of longer-term modest salt reduction on blood pressure.

A medical sensor may be adapted to account for factors that cause irregularities in pulse oximetry measurements or other spectrophotemetric measurements. Sensors are provided with surface features that reduce the amount of outside light or shunted light that impinge the detecting elements of the sensor. The sensor is adapted to reduce the effect of outside light or shunted light on pulse oximetry measurements.

Medical sensor and technique for using the same

Background
In spite of more than 100 years of investigations the question of whether a reduced sodium intake improves health is still unsolved.

Objectives
To estimate the effects of low sodium intake versus high sodium intake on systolic and diastolic blood pressure (SBP and DBP), plasma or serum levels of renin, aldosterone, catecholamines, cholesterol, high-density lipoprotein (HDL), low-density lipoprotein (LDL) and triglycerides.

Search methods
The Cochrane Hypertension Information Specialist searched the following databases for randomized controlled trials up to March 2016: the Cochrane Hypertension Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL) (2016, Issue 3), MEDLINE (from 1946), Embase (from 1974), the World Health Organization International Clinical Trials Registry Platform, and ClinicalTrials.gov. We also searched the reference lists of relevant articles.

Selection criteria
Studies randomising persons to low-sodium and high-sodium diets were included if they evaluated at least one of the above outcome parameters.

Data collection and analysis
Two review authors independently collected data, which were analysed with Review Manager 5.3.

Main results
A total of 185 studies were included. The average sodium intake was reduced from 201 mmol/day (corresponding to high usual level) to 66 mmol/day (corresponding to the recommended level).

The effect of sodium reduction on blood pressure (BP) was as follows: white people with normotension: SBP: mean difference (MD) -1.09 mmHg (95% confidence interval (CI): -1.63 to -0.56; P = 0.0001); 89 studies, 8569 participants; DBP: + 0.03 mmHg (MD 95% CI: -0.37 to 0.43; P = 0.89); 90 studies, 8833 participants. High-quality evidence.

Black people with normotension: SBP: MD -4.02 mmHg (95% CI:-7.37 to -0.68; P = 0.002); seven studies, 506 participants; DBP: MD -2.01 mmHg (95% CI:-4.37 to 0.35; P = 0.09); seven studies, 506 participants. Moderate-quality evidence.

Asian people with normotension: SBP: MD -0.72 mmHg (95% CI: -3.86 to 2.41; P = 0.65); DBP: MD -1.63 mmHg (95% CI:-3.35 to 0.08; P =0.06); three studies, 393 participants. Moderate-quality evidence.

White people with hypertension: SBP: MD -5.51 mmHg (95% CI: -6.45 to -4.57; P < 0.00001); 84 studies, 5925 participants; DBP: MD -2.88 mmHg (95% CI: -3.44 to -2.32; P < 0.00001); 85 studies, 6001 participants. High-quality evidence.

Black people with hypertension: SBP MD -6.64 mmHg (95% CI:-9.00 to -4.27; P = 0.00001); eight studies, 619 participants; DBP -2.91 mmHg (95% CI:-4.52, -1.30; P = 0.0004); eight studies, 619 participants. Moderate-quality evidence.

Asian people with hypertension: SBP: MD -7.75 mmHg (95% CI:-11,44 to -4.07; P < 0.0001) nine studies, 501 participants; DBP: MD -2.68 mmHg (95% CI: -4.21 to -1.15; P = 0.0006). Moderate-quality evidence.

In plasma or serum, there was a significant increase in renin (P < 0.00001), aldosterone (P < 0.00001), noradrenaline (P < 0.00001), adrenaline (P < 0.03), cholesterol (P < 0.0005) and triglyceride (P < 0.0006) with low sodium intake as compared with high sodium intake. All effects were stable in 125 study populations with a sodium intake below 250 mmol/day and a sodium reduction intervention of at least one week.

Authors' conclusions
Sodium reduction from an average high usual sodium intake level (201 mmol/day) to an average level of 66 mmol/day, which is below the recommended upper level of 100 mmol/day (5.8 g salt), resulted in a decrease in SBP/DBP of 1/0 mmHg in white participants with normotension and a decrease in SBP/DBP of 5.5/2.9 mmHg in white participants with hypertension. A few studies showed that these effects in black and Asian populations were greater. The effects on hormones and lipids were similar in people with normotension and hypertension. Renin increased 1.60 ng/mL/hour (55%); aldosterone increased 97.81 pg/mL (127%); adrenalin increased 7.55 pg/mL (14%); noradrenalin increased 63.56 pg/mL: (27%); cholesterol increased 5.59 mg/dL (2.9%); triglyceride increased 7.04 mg/dL (6.3%).

Effects of low sodium diet versus high sodium diet on blood pressure, renin, aldosterone, catecholamines, cholesterol, and triglyceride

Context.—One of the controversies in preventive medicine is whether a general
reduction in sodium intake can decrease the blood pressure of a population
and thereby reduce the number of strokes and myocardial infarctions. In recent
years the debate has been extended by studies indicating that reduced sodium
intake has adverse effects.Objective.—To estimate the effects of reduced sodium intake on systolic and diastolic
blood pressure (SBP and DBP), body weight, and plasma or serum levels of renin,
aldosterone, catecholamines, cholesterols, and triglyceride, and to evaluate
the stability of the blood pressure effect in relation to additional trials.Data Sources.—MEDLINE search from 1966 through December 1997 and reference lists of
relevant articles.Study Selection.—Studies randomizing persons to high-sodium and low-sodium diets were
included if they evaluated at least one of the effect parameters.Data Extraction.—Two authors independently recorded data.Data Synthesis.—In 58 trials of hypertensive persons, the effect of reduced sodium intake
as measured by urinary sodium excretion (mean, 118 mmol/24 h) on SBP was 3.9
mm Hg (95% confidence interval [CI], 3.0-4.8 mm Hg) (P<.001)
and on DBP was 1.9 mm Hg (95% CI, 1.3-2.5 mm Hg) (P<.001).
In 56 trials of normotensive persons, the effect of reduced sodium intake
(mean, 160 mmol/24 h) on SBP was 1.2 mm Hg (95% CI, 0.6-1.8 mm Hg) (P<.001) and on DBP was 0.26 mm Hg (95% CI, −0.3-0.9
mm Hg) (P=.12). The cumulative analysis showed that
this effect size has been stable since 1985. In plasma, the renin level increased
3.6-fold (P<.001), and the aldosterone level increased
3.2-fold (P<.001); the increases were proportional
to the degree of sodium reduction for both renin (r=0.66; P<.001) and aldosterone (r=0.64; P<.001). Body weight decreased significantly, and noradrenaline,
cholesterol, and low-density lipoprotein cholesterol levels increased. There
was no effect on adrenaline, triglyceride, and high-density lipoprotein cholesterol.Conclusion.—These results do not support a general recommendation to reduce sodium
intake. Reduced sodium intake may be used as a supplementary treatment in
hypertension. Further long-term studies of the effects of high reduction of
sodium intake on blood pressure and metabolic variables may clarify the disagreements
as to the role of reduced sodium intake, but ideally trials with hard end
points such as morbidity and survival should end the controversy.

https://jamanetwork.com/journals/JAMA/articlepdf/187486/jma71026.pdf

Effects of Sodium Restriction on Blood Pressure, Renin, Aldosterone, Catecholamines, Cholesterols, and Triglyceride: A Meta-analysis

Arterial oxygen saturation in relation to metabolic acidosis in fetal lambs.

Neonatal complications in newborns with an umbilical artery pH <7.00

https://www.thelancet.com/pdfs/journals/lancet/PIIS0140-6736(00)02766-5.pdf

Fetal learning and memory

Background: Most laboratory parameters change during pregnancy. A serial study of a large number of routine haematological and biochemical blood parameters and biochemical urine parameters was conducted in a group of 66 healthy nulliparous pregnant women, who had an uncomplicated pregnancy. Methods: Blood samples and 24-h urine samples were obtained at four weeks intervals during pregnancy and at 1 (1P) and 6 (6P) weeks after delivery. Results: During pregnancy, haemoglobin concentration, haematocrit and erythrocyte count were lower, mean cell volume was not different, and mean cell haemoglobin and mean cell haemoglobin concentration were enhanced. The platelet count during pregnancy was not different from the level at 6P but increased 60% at 1P. Serum ferritin decreased 50% whereas plasma fibrinogen increased 100%. Serum creatinine (−28%), uric acid (−35%) and urea (−40%) concentrations were reduced during pregnancy. The serum concentrations of sodium (−4 mmol/1) and potassium (−0.2 mmol/1) were lower, but serum chloride was unaltered. Serum protein and albumen concentrations declined by 7.8 and 9.4 g/1 respectively. The serum concentrations of bilirubin, ALAT, ASAT and γ-GT remained unaltered. Serum LDH was 30% above normal non-pregnant values at 1P. The heat-stable alkaline phosphatase level increased in the third trimester. Heat-stable and heat-labile fractions were both elevated at 1P. The serum osmolality was 9 mosmol/kg lower and urine volume was about 25% higher during pregnancy. The creatinine excretion was unaltered but creatinine clearance increased by 25%. Conclusions: The concentrations of most components change during pregnancy. The interpretation of results of laboratory tests in pregnant women should be made with caution.

Haematological and biochemical profile of uncomplicated pregnancy in nulliparous women; A longitudinal study

The electrical conduction of the ECG from the fetal heart to the maternal abdomen has been modelled by using volume conductor models based on the measured actual geometry. The models have been verified by means of multi-lead recordings of the fetal ECG. The results show that early in pregnancy (less than 28 weeks) the conduction can successfully be described by an electrically homogeneous model. Based on this model, a description of the fetal ECG that is independent of the position of the fetus is derived. In late pregnancies, the conduction is dominated by the isolating effect of the vernix caseosa. As the distribution of the vernix over the fetal body is unknown, the shape of the fetal ECG is disturbed in an unintelligible way. As a consequence, caution has to be applied when using the shape of the fetal ECG for diagnostic means.

https://iopscience.iop.org/article/10.1088/0143-0815/10/4B/002/pdf

Henk W. Jongsma

Papers

Arterial oxygen saturation in relation to metabolic acidosis in fetal lambs.

Neonatal complications in newborns with an umbilical artery pH <7.00

Fetal learning and memory

Haematological and biochemical profile of uncomplicated pregnancy in nulliparous women; A longitudinal study

The effect of changes in the conductive medium on the fetal ECG throughout gestation.