Pregnancy and delivery involve dynamic alterations in many physiological systems. However, the physiological dynamics during pregnancy and after delivery have not been systematically analyzed at high temporal resolution in a large human population. Here, we present the dynamics of 76 lab tests based on a cross-sectional analysis of 44 million measurements from over 300,000 pregnancies. We analyzed each test at weekly intervals from 20 weeks preconception to 80 weeks postpartum, providing detailed temporal profiles. About half of the tests take 3 months to a year to return to baseline postpartum, highlighting the physiological load of childbirth. The precision of the data revealed effects of preconception supplements, overshoots after delivery and intricate temporal responses to changes in blood volume and renal filtration rate. Pregnancy complications—gestational diabetes, preeclampsia, and postpartum hemorrhage—showed distinct dynamical changes. These results provide a comprehensive dynamic portrait of the systems physiology of pregnancy.

Thyroid disorders are common and often require lifelong hormone replacement. Treating thyroid disorders involves a fascinating and troublesome delay, in which it takes many weeks for serum thyroid‐stimulating hormone (TSH) concentration to normalize after thyroid hormones return to normal. This delay challenges attempts to stabilize thyroid hormones in millions of patients. Despite its importance, the physiological mechanism for the delay is unclear. Here, we present data on hormone delays from Israeli medical records spanning 46 million life‐years and develop a mathematical model for dynamic compensation in the thyroid axis, which explains the delays. The delays are due to a feedback mechanism in which peripheral thyroid hormones and TSH control the growth of the thyroid and pituitary glands; enlarged or atrophied glands take many weeks to recover upon treatment due to the slow turnover of the tissues. The model explains why thyroid disorders such as Hashimoto's thyroiditis and Graves' disease have both subclinical and clinical states and explains the complex inverse relation between TSH and thyroid hormones. The present model may guide approaches to dynamically adjust the treatment of thyroid disorders.

High admission blood glucose (ABG) level has been associated with a poor short-term outcome among non-diabetic patients with heart failure (HF). We aimed to investigate the association between ABG levels and long-term (10 years) mortality in patients with or without pre-existing diabetes mellitus (DM) admitted with HF. We analyzed data on 1811 patients with DM and 2182 patients without pre-existing DM who were hospitalized with HF during a prospective national survey. The relationship between ABG and 10-year mortality was assessed using the Cox proportional hazard model adjusting for multiple variables. ABG was analyzed both as a categorical (200 mg/dL) and as a continuous variable. At 10 years of follow-up the cumulative probability of mortality was 85 and 78% among patients with DM and patients with no pre-existing DM (p < 0.001), respectively. Among patients with no pre-existing DM, glucose levels of 110–140, 140–200 and ≥200 mg/dL were associated with 9% (p = 0.140), 16% (p = 0.031) and 53% (p < 0.001) increased mortality risk compared to ABG < 110 mg/dL. Each 18-mg/dL (1-mmol/L) increase in glucose level was associated with a 5% increased risk of mortality (p < 0.001) among patients with no-pre-existing DM. In contrast, among patients with DM, only those with glucose levels >200 mg/dL had an increased mortality risk (>200 mg/dL versus 200 mg/dL is associated with increased mortality risk.

Anogenital distance (AGD) is a biomarker for the prenatal hormonal environment. Androgen excess is a key element in polycystic ovary syndrome (PCOS). The aim of this study was to assess the sonographic foetal AGD in a population of PCOS mothers in comparison to the general population. Foetal AGD was measured prospectively by 2D ultrasound in PCOS mothers and compared to prenatal AGD nomograms. The results were interpreted regarding maternal and foetal characteristics. The mean sonographic foetal AGD centile measurement in PCOS mothers was significantly longer in comparison to the general population (86.04% ± 18.22; p < 0.001). Estimated foetal weight and birthweight were appropriate for gestational age and did not correlate with AGD. Sonographic foetal AGD was significantly longer in PCOS diabetic mothers and in those who conceived following assisted reproduction treatments when compared to the general population (p < 0.001). Our results support the role of AGD as a biomarker of the prenatal hormonal environment and provide evidence for the hyperandrogenic effect in PCOS pregnancies on foetal androgenic status and genitalia development.

Background/Objectives: Studies have shown that chronobiological factors may adversely affect glycemic control in patients with type 2 diabetes mellitus. We assessed the association of chronobiological factors with glycemic control and neonatal birth weight in women with GDM. Methods: A prospective cohort study included 208 women aged 18–45 years with a singleton pregnancy who were randomly selected from among women undergoing follow-up for GDM at the Maternal-Fetal Medicine Unit of a tertiary medical center. Nutrition, sleep, and lifestyle patterns were assessed from onset of GDM until birth along with glycemic control and birth outcomes. Results: Multivariate analyses on a cohort of 208 women revealed that suboptimal glycemic control was associated with a late breakfast (RR = 2.26; 95% CI 1.09–4.67), increased carbohydrate intake in the evening (RR = 1.19; 95% CI 1.003–1.42), and poor sleep quality (RR = 2.14; 95% CI 1.04–4.41). The adjusted relative risk for neonatal birth weight above the 85th percentile was associated with increased carbohydrate intake in the morning (RR = 1.70; 95% CI 1.30–2.23) and increased carbohydrate intake in the evening (RR = 1.39; 95% CI 1.16–1.67). Conclusions: Chronobiological factors are associated with suboptimal glycemic control and birth weight above the 85th percentile in women with GDM. The study was registered under ClinicalTrials.gov.org, identifier: NCT02916667.

Objective: To evaluate the risk of progression to type 2 diabetes (T2D) following reactive hypoglycemia in 100 g oral glucose tolerance test (oGTT). Methods: A retrospective analysis of parturients with up to 5-year follow-up postpartum. Data were extracted from the computerized laboratory system of Meuhedet, an Israeli HMO and cross-linked with the Israeli National Registry of Diabetes. Included were parturients with no prior diabetesand available oGTT values during pregnancy. Reactive hypoglycemia was defined as glucose levels lower than 60 mg/dL in at least one of 3 post-glucose load values in oGTT. The cohort was divided into 3 groups: normal glucose status, reactive hypoglycemia, and GDM. Maternal characteristics, laboratory data, and progression to T2D over 5 years were compared. Univariate and survival analyses assessed the adjusted hazard ratio for T2D, stratified by obesity Results: Among 14,122 parturients, 16.8% had reactive hypoglycemia, 71% had normal glucose status, and 12.2% had GDM. Adjusted for age, obesity, and hypertension, Parturients with reactive hypoglycemia had similar T2D risk compared to normal glucose status and a lower risk compared to GDM patients, regardless of obesity status. Conclusions: Reactive hypoglycemia during oGTT does not increase the risk of progressing to T2D.