Phyiscal Activity and Pregnancy

First article looked at today concludes:

This meta-analysis suggests that higher leisure-time activity is associated with reduced risk of preterm birth. 

So, there is a possibility that a certain degree of physical activity reduces the chances that the mother will have  a preterm birth.  

What about gestational diabetes?  See here, abstract:

Physical activity has been inconsistently associated with risk of gestational diabetes mellitus in epidemiological studies, and questions remain about the strength and shape of the dose-response relationship between the two. We therefore conducted a systematic review and meta-analysis of cohort studies and randomized trials on physical activity and gestational diabetes mellitus. PubMed, Embase and Ovid databases were searched for cohort studies, and randomized controlled trials of physical activity and risk of gestational diabetes mellitus, up to August 5th 2015. Summary relative risks (RRs) were estimated using a random effects model. Twenty-five studies (26 publications) were included. For total physical activity the summary RR for high versus low activity was 0.62 (95 % CI 0.41-0.94, I2 = 0 %, n = 4) before pregnancy, and 0.66 (95 % CI 0.36-1.21, I2 = 0 %, n = 3) during pregnancy. For leisure-time physical activity the respective summary RRs for high versus low activity was 0.78 (95 % CI 0.61-1.00, I2 = 47 %, n = 8) before pregnancy, and it was 0.80 (95 % CI 0.64-1.00, I2 = 17 %, n = 17) during pregnancy. The summary RR for pre-pregnancy activity was 0.70 (95 % CI 0.49-1.01, I2 = 72.6 %, n = 3) per increment of 5 h/week and for activity during pregnancy was 0.98 (95 % CI 0.87-1.09, I2 = 0 %, n = 3) per 5 h/week. There was evidence of a nonlinear association between physical activity before pregnancy and the risk of gestational diabetes mellitus, pnonlinearity = 0.005, with a slightly steeper association at lower levels of activity although further reductions in risk were observed up to 10 h/week. There was also evidence of nonlinearity for physical activity in early pregnancy, pnonlinearity = 0.008, with no further reduction in risk above 8 h/week. There was some indication of inverse associations between walking (before and during pregnancy) and vigorous activity (before pregnancy) and the risk of gestational diabetes mellitus. This meta-analysis suggests that there is a significant inverse association between physical activity before pregnancy and in early pregnancy and the risk of gestational diabetes mellitus. Further studies are needed to clarify the association between specific types and intensities of activity and gestational diabetes mellitus.

So it seems physical activity can be helpful there as well. Of course, for both articles, this is for the general population; there may be individual cases where physical activity is restricted during pregnancy for health reasons.  

Maternal Smoke Exposure And Cell Signaling

It is know that maternal smoke exposure can possibly cause problems to the fetus.  Here is a mouse study demonstrating that offspring of smoke-exposed pregnant female mice were underweight with deceased lung volume, and that there were alterations in important cell signaling pathways that may have caused the negative effects on the fetal mice  Abstract:

The present study tested the hypothesis that maternal smoke exposure results in fetal lung growth retardation due to dysregulation in various signaling pathways, including the Wnt (wingless-related integration site)/β-catenin pathway. Pregnant female C57BL/6J mice were exposed to cigarette smoke (100-150 mg/m3) or room air, and offspring were humanely killed on 12.5, 14.5, 16.5, and 18.5 d post coitum (dpc). We assessed lung stereology with Cavalieri estimation; apoptosis with proliferating cell nuclear antigen, TUNEL, and caspase assays; and gene expression with quantitative PCR (qPCR) and RNA sequencing on lung epithelium and mesenchyme retrieved by laser capture microdissection. Results demonstrated a significant decrease in body weight and lung volume of smoke-exposed embryos. At 16.5 dpc, the reduction in lung volume was due to loss of lung mesenchymal tissue correlating with a decrease in cell proliferation (n = 10; air: 61.65% vs. smoke: 44.21%, P < 0.05). RNA sequence analysis demonstrated an alteration in the Wnt pathway, and qPCR confirmed an increased expression of secreted frizzled-related protein 1 (sFRP-1) [n = 12; relative quantification (RQ) 1 vs. 2.33, P < 0.05] and down-regulation of Cyclin D1 (n = 7; RQ 1 vs. 0.61, P < 0.05) in mesenchymal tissue. Furthermore, genome expression studies revealed a smoke-induced up-regulation of Rho-GTPase-dependent actin cytoskeletal signaling that can lead to loss of tissue integrity.-Unachukwu, U., Trischler, J., Goldklang, M., Xiao, R., D'Armiento, J. Maternal smoke exposure decreases mesenchymal proliferation and modulates Rho-GTPase-dependent actin cytoskeletal signaling in fetal lungs.

The importance of pregnant women avoiding maternal smoke exposure is underlined with this study.

Insulin For Gestational Diabetes

This paper may be of interest for those who have gestational diabetes.  Abstract:

BACKGROUND:

Gestational diabetes mellitus (GDM) is associated with short- and long-term complications for the mother and her infant. Women who are unable to maintain their blood glucose concentration within pre-specified treatment targets with diet and lifestyle interventions will require anti-diabetic pharmacological therapies. This review explores the safety and effectiveness of insulin compared with oral anti-diabetic pharmacological therapies, non-pharmacological interventions and insulin regimens.

OBJECTIVES:

To evaluate the effects of insulin in treating women with gestational diabetes.

SEARCH METHODS:

We searched Pregnancy and Childbirth's Trials Register (1 May 2017), ClinicalTrials.gov, WHO International Clinical Trials Registry Platform (ICTRP) (1 May 2017) and reference lists of retrieved studies.

SELECTION CRITERIA:

We included randomised controlled trials (including those published in abstract form) comparing:a) insulin with an oral anti-diabetic pharmacological therapy;b) with a non-pharmacological intervention;c) different insulin analogues;d) different insulin regimens for treating women with diagnosed with GDM.We excluded quasi-randomised and trials including women with pre-existing type 1 or type 2 diabetes. Cross-over trials were not eligible for inclusion.

DATA COLLECTION AND ANALYSIS:

Two review authors independently assessed study eligibility, risk of bias, and extracted data. Data were checked for accuracy.

MAIN RESULTS:

We included 53 relevant studies (103 publications), reporting data for 7381 women. Forty-six of these studies reported data for 6435 infants but our analyses were based on fewer number of studies/participants.Overall, the risk of bias was unclear; 40 of the 53 included trials were not blinded. Overall, the quality of the evidence ranged from moderate to very low quality. The primary reasons for downgrading evidence were imprecision, risk of bias and inconsistency. We report the results for our maternal and infant GRADE outcomes for the main comparison. Insulin versus oral anti-diabetic pharmacological therapyFor the mother, insulin was associated with an increased risk for hypertensive disorders of pregnancy (not defined) compared to oral anti-diabetic pharmacological therapy (risk ratio (RR) 1.89, 95% confidence interval (CI) 1.14 to 3.12; four studies, 1214 women; moderate-quality evidence). There was no clear evidence of a difference between those who had been treated with insulin and those who had been treated with an oral anti-diabetic pharmacological therapy for the risk of pre-eclampsia (RR 1.14, 95% CI 0.86 to 1.52; 10 studies, 2060 women; moderate-quality evidence); the risk of birth by caesarean section (RR 1.03, 95% CI 0.93 to 1.14; 17 studies, 1988 women; moderate-quality evidence); or the risk of developing type 2 diabetes (metformin only) (RR 1.39, 95% CI 0.80 to 2.44; two studies, 754 women; moderate-quality evidence). The risk of undergoing induction of labour for those treated with insulin compared with oral anti-diabetic pharmacological therapy may possibly be increased, although the evidence was not clear (average RR 1.30, 95% CI 0.96 to 1.75; three studies, 348 women; I² = 32%; moderate-quality of evidence). There was no clear evidence of difference in postnatal weight retention between women treated with insulin and those treated with oral anti-diabetic pharmacological therapy (metformin) at six to eight weeks postpartum (MD -1.60 kg, 95% CI -6.34 to 3.14; one study, 167 women; low-quality evidence) or one year postpartum (MD -3.70, 95% CI -8.50 to 1.10; one study, 176 women; low-quality evidence). The outcomes of perineal trauma/tearing or postnatal depression were not reported in the included studies.For the infant, there was no evidence of a clear difference between those whose mothers had been treated with insulin and those treated with oral anti-diabetic pharmacological therapies for the risk of being born large-for-gestational age (average RR 1.01, 95% CI 0.76 to 1.35; 13 studies, 2352 infants; moderate-quality evidence); the risk of perinatal (fetal and neonatal death) mortality (RR 0.85; 95% CI 0.29 to 2.49; 10 studies, 1463 infants; low-quality evidence);, for the risk of death or serious morbidity composite (RR 1.03, 95% CI 0.84 to 1.26; two studies, 760 infants; moderate-quality evidence); the risk of neonatal hypoglycaemia (average RR 1.14, 95% CI 0.85 to 1.52; 24 studies, 3892 infants; low-quality evidence); neonatal adiposity at birth (% fat mass) (mean difference (MD) 1.6%, 95% CI -3.77 to 0.57; one study, 82 infants; moderate-quality evidence); neonatal adiposity at birth (skinfold sum/mm) (MD 0.8 mm, 95% CI -2.33 to 0.73; random-effects; one study, 82 infants; very low-quality evidence); or childhood adiposity (total percentage fat mass) (MD 0.5%; 95% CI -0.49 to 1.49; one study, 318 children; low-quality evidence). Low-quality evidence also found no clear differences between groups for rates of neurosensory disabilities in later childhood: hearing impairment (RR 0.31, 95% CI 0.01 to 7.49; one study, 93 children), visual impairment (RR 0.31, 95% CI 0.03 to 2.90; one study, 93 children), or any mild developmental delay (RR 1.07, 95% CI 0.33 to 3.44; one study, 93 children). Later infant mortality, and childhood diabetes were not reported as outcomes in the included studies.We also looked at comparisons for regular human insulin versus other insulin analogues, insulin versus diet/standard care, insulin versus exercise and comparisons of insulin regimens, however there was insufficient evidence to determine any differences for many of the key health outcomes. Please refer to the main results for more information about these comparisons.

AUTHORS' CONCLUSIONS:

The main comparison in this review is insulin versus oral anti-diabetic pharmacological therapies. Insulin and oral anti-diabetic pharmacological therapies have similar effects on key health outcomes. The quality of the evidence ranged from very low to moderate, with downgrading decisions due to imprecision, risk of bias and inconsistency.For the other comparisons of this review (insulin compared with non-pharmacological interventions, different insulin analogies or different insulin regimens), there is insufficient volume of high-quality evidence to determine differences for key health outcomes.Long-term maternal and neonatal outcomes were poorly reported for all comparisons.The evidence suggests that there are minimal harms associated with the effects of treatment with either insulin or oral anti-diabetic pharmacological therapies. The choice to use one or the other may be down to physician or maternal preference, availability or severity of GDM. Further research is needed to explore optimal insulin regimens. Further research could aim to report data for standardised GDM outcomes.

Chickens And Fetal Alcohol Syndrome

Mice are not the only animal model used to study human disorders. Avian embryos, in the case the chicken, can be used as model to investigate fetal alcohol syndrome, a devastating disorder that occurs wen pregnant women ignore the injunction against drinking alcohol.  These model organisms can be used to determine mechanisms by which alcohol does its damage, stressing cell signaling pathways, with the eventual hope of better dealing with the effects of this disorder.  Of course, the best therapy here, as with almost all disorders, is prevention.  Don't drink alcohol when pregnant.  Abstract:

Prenatal alcohol exposure (PAE) remains a leading preventable cause of structural birth defects and permanent neurodevelopmental disability. The chick (Gallus gallus domesticus) is a powerful embryological research model and was possibly the first (Fere, 1895) in which alcohol's teratogenicity was demonstrated. Pharmacologically relevant alcohol exposures in the range of 20-70 mM (20-80 mg/egg) disrupt chick embryo growth, morphogenesis, and behavior, and the resulting phenotypes strongly parallel those of mammalian models. The avian embryo's direct accessibility has enabled novel insights into alcohol's teratogenic mechanisms. These include the contribution of IGF1 signaling to growth suppression, the altered flow dynamics that reshape valvuloseptal morphogenesis and mediate its cardiac teratogenicity, and the suppression of Wnt and Shh signals to disrupt neural crest migration, expansion, and survival and underlie its characteristic craniofacial deficits. The genetic diversity within commercial avian strains enabled identification of unique loci, such as ribosome biogenesis, that modify vulnerability to alcohol. This venerable research model is equally relevant for the future, as the application of technological advances including CRISPR, optogenetics, and biophotonics to the embryo's ready accessibility creates a unique model in which investigators can manipulate and monitor the embryo in real-time to investigate alcohol's actions upon cell fate.

Aspirin Against Preeclampsia

By Nephron - Own work, CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=10874506

Preeclampsia is a disorder of pregnancy featuring high blood pressure and other physical manifestations, and which is linked to poor outcomes for mother and child.  Aspirin – a drug with an impressive array of health benefits (including cardiovascular and decreased risk of colorectal cancer, besides its typical use for pain, fever, and inflammation) now has shown to have preventive properties against preeclampsia.  Abstract:

Aspirin is currently the most widely prescribed treatment in the prevention of cardiovascular complications. The indications for the use of aspirin during pregnancy are, however, the subject of much controversy. Since the first evidence of the obstetric efficacy of aspirin in 1985, numerous studies have tried to determine the effect of low-dose aspirin on the incidence of preeclampsia, with very controversial results. Large meta-analyses including individual patient data have demonstrated that aspirin is effective in preventing preeclampsia in high-risk patients, mainly those with a history of preeclampsia. However, guidelines regarding the usage of aspirin to prevent preeclampsia differ considerably from one country to another. Screening modalities, target population, and aspirin dosage are still a matter of debate. In this review, we report the pharmacodynamics of aspirin, its main effects according to dosage and gestational age, and the evidence-based indications for primary and secondary prevention of preeclampsia.

Autism and maternal infections during pregnancy

There is epidemiological evidence that viral infections during pregnancy associate with higher frequency of autism in children. Recently, experimental data on this association were published in Science.

The phenomenon underlying the correlation is known as maternal immune activation. In experimental models (mice), the maternal immune activation increases the levels of a molecule, interleukin-17a, which affects the fetal brain development. Based upon these results, the authors of the study have proposed that targeting cells involved in the maternal immune response (i.e., the T helper 17 cells) may reduce the risk of having children with inflammation-associated autism.

Two years ago, another publication associated maternal infections during pregnancy not only with autism, but also with schizophrenia. In addition, the authors discussed clinical data that infections in pregnancy may increase the risk of epilepsy, cerebral palsy, Alzheimer and Parkinson diseases in the offspring.

What does this mean for pregnant women? Does it mean that it is better for future moms to not work, and limit their exposure to environments/settings where they can easily contract infectious diseases? This discussion is still missing from the publications. Another unanswered question is whether the increased rates of autism in the past years is due to the increased employment of women (see statistics in the graph below)

By Rcragun (Own work) [CC BY 3.0 (http://creativecommons.org/licenses/by/3.0)], via Wikimedia Commons

Many likely causes for the increased rates of autism have been discussed, such as the increased awareness of the condition (and therefore, its more frequent diagnosis), television, chemicals, vaccines, older age of the parents.  However, we need to consider additional factors, including the phenomenon of maternal immune activation and its effects on the fetal development of the central nervous system.
 
There are several historic phases, during which women have increased their representation in the workforce, and the fourth phase (from the late 70s to present days) coincides with the increased rates of diagnosed autism.  

Association/correlation does not mean causation; however, it might be prudent to protect pregnant women by offering  better work conditions – shorter workdays, days working from home, and a longer paid maternity leave that starts months before the due date.

Education, career, fun or baby

More and more frequently American women decide to have children later in life (beyond the age of 30). Higher education, building a career, the feeling of “not being ready” (emotionally or financially), or the desire to have fun are the likely reasons for late motherhood. 

The timing of becoming a parent is a very personal choice; however, I wish that the decision-makers had all the information before they decided…  I had my child in my mid-thirties; however, I would have had my baby earlier, if I had known all the risks of late pregnancy and late motherhood.

For the young women out there, here are some of the pros and cons of having a child in your twenties. 



Pros to having babies between 20 and 30:

• Pregnancy before age 22 decreases breast cancer risk (Schedin P. Nat Rev Cancer 6:281-91, 2006; Meier-Abt F, et al. Trends Mol Med 20:143-53, 2014; MacMahon B, et al., Bull World Health Organ 43:209-21, 1970; Polyak K. Cancer Cell 9:151-3, 2006.).

• Babies of younger mothers are healthier: with a lower chance of being premature, with low birth weight, or with genetic abnormalities.

• The women’s fertility is highest in the early 20s.

• At younger age, the risk of miscarriage is lower.

• Pregnancy is physically better tolerated by younger women.

• Younger women carry easier the physical demands of parenting.
  

Cons to having babies between 20 and 30: 

• The woman may need to postpone her education and/or career development

• Accumulation of debt: in their early 20s, recent college graduates still have college debt

• Frequently young mothers who go back to work earn less than their childless counterparts.

• Older mothers might be more emotionally mature for parenting.

• Pregnancies (especially at younger age) may increase the risk of ovarian and endometrial cancers (Hankinson SE, et al. Cancer 1995; 76:284–290; La Vecchia C, et al., Int J Cancer 1993; 53:215–219; Titus-Ernstoff L, et al. Br. J Cancer 2001; 84:714–721). 

*Paternal age also matters. The sperm of older men tends to have changes in single genes (e.g., fibroblast growth factor receptor 2 and 3, RET proto-oncogene; Jung A, et al., Andrologia 35(4):191-9. 2003). Children of older fathers (45 and older) are also at increased risk of autism, ADHD, psychosis, bipolar disorder, suicide attempts, substance use problems, failing a grade, and low educational attainment (D'Onofrio BM, et al., JAMA Psychiatry 71:432-8; 2014).