Pregnant for Nine Months, Postpartum for Life: Long-term Implications of Pregnancy Related Conditions

Abstract

Maternal mortality in the state of Missouri remains among the highest in the nation. Recognizing that the burden of making corrective actions does not rest solely with obstetric providers, it is time to consider how pregnancy affects our patients before, during, and after childbirth. Reviewing pregnancy history and pregnancy intention can be a chance to address modifiable risk factors to improve patient outcomes when providing medical care.

Introduction

Several medical conditions previously considered confined to pregnancy such as gestational hypertension, diabetes, preterm delivery, or fetal growth restriction actually require short- and long --term follow-up. In the United States (US) it is now estimated that nearly one in five pregnancies are affected by one or more adverse pregnancy outcomes.^1,2 Furthermore, these conditions are not spread equally across all pregnancies. Racial and ethnic minority groups are disproportionately affected due to social determinants of health (SDOH).³ Addressing these conditions are multifactorial and require a multidisciplinary approach (Figure 1). Understanding the long-term effects these conditions have on our patients can help bridge the gaps in care from a medical standpoint.

Figure 1.

Visual representation of how pregnancy-related conditions can affect multiple systems long-term.

Surveys of multiple specialties revealed that despite increased awareness of the ramifications of pregnancy-related conditions, clinicians neither performed routine screening, nor did they know what to do with the information they collected.^4,5 A recent study found that among adolescent and young adults seen in a rheumatology clinic, they overwhelmingly wanted sexual and reproductive health counseling from their rheumatologist (84%) rather than primary care (66%) or OB/GYN or adolescent medicine (58%).⁶

Major societies in both the US and Europe are now recommending using information from pregnancy histories to guide future care of patients.^7,8 To this extent, a patient’s pregnancy history and intention to become pregnant is a responsibility all physicians bear. Understanding a patient’s history of pregnancy-related conditions can help guide future screenings and management of chronic conditions. Equipping Missouri physicians with a better understanding of medical conditions during and after pregnancy from a systems-based perspective will help to address health disparities and improve health outcomes for the women of Missouri.

Cardiovascular

The diagnosis rate of hypertension (HTN) is on the rise due to the 2017 American College of Cardiology/American Heart Association guidelines redefining HTN starting at 130–139 mm Hg or 80–89 mm Hg.⁹ With the age of onset of cardiovascular disease (CVD) gradually lowering over time, more patients will enter pregnancy carrying a diagnosis of chronic HTN. In addition, patients with hypertensive disorders of pregnancy may have a period of blood pressure normalization after pregnancy but still benefit from early interventions due to an underlying higher risk of significant cardiovascular complications.

Hypertensive disorders of pregnancy (HDP) which include gestational hypertension, preeclampsia (preE), eclampsia and chronic HTN, affect between 13–15% of all pregnancies in the US.¹⁰ HDP and the complications resulting from it were the leading cause of mortality within the first year postpartum for Missouri women.¹¹ However, the risk for adverse events persists beyond the initial postpartum period and several studies have demonstrated the highest risk of cardiovascular complications are in the first 10 years with the average age being 38 years old.^12,13 Patients diagnosed with preE are at double the risk of stroke (both immediate and persisting), two to 12-fold times more likely to develop chronic HTN in the next 10 years, and have double the cardiovascular mortality risk.^12,14–16

Aside from hypertensive disorders which have more obvious cardiovascular implications, there are several other conditions during pregnancy that are important to be mindful of from a cardiovascular standpoint. Gestational diabetes (gDM), fetal growth restriction (FGR), and preterm delivery (PTD) all reveal an increased risk for CVD.

A history of gDM increases the risk of CVD in the first ten years after pregnancy, a risk independent from patients who develop type 2 diabetes mellitus (T2DM). In that initial decade, there is a 2.3-fold increase in cardiovascular events with a higher 30-year risk of atherosclerotic CVD.^1,17 The risk continues beyond that timeframe with a history of gDM imparting a less favorable cardiovascular metabolic panel during menopause than counterparts without gDM and increases a patient’s risk for CVD two-fold.^15,17 In a large, prospective cohort in the United Kingdom, patients who had “early menarche, early menopause, [younger] age at first birth, and a history of miscarriage, stillbirth, or hysterectomy were each associated with a higher risk of CVD later in life.” ¹⁸

Patients who had pregnancies with FGR can have direct cardiac remodeling changes persisting after pregnancy leading to early development of CVD.¹³ PTD incurred a two-fold risk for CVD, while recurrent pregnancy loss increased risk of ischemic heart disease.⁸

While not entirely understood, these conditions alter a patient’s cardiovascular risk factors especially for patients less than 50 years old. Whether these pregnancy conditions cause long-term cardiovascular damage or unmask damage at an earlier age is not yet determined. But the risk persists despite controlling for other variables such as obesity, smoking, and family history. No clear guidelines exist but considering the evidence for increasing diagnosis at a younger age, screening and tracking for these conditions can help identify patients for whom aggressive modification of risk factors could be important.

Endocrine

Traditionally, patients are only under the care of their obstetric provider for a limited time postpartum which means metabolic conditions that are diagnosed or develop during pregnancy may be lost to follow up. An awareness of the recommended surveillance for endocrine conditions after pregnancy is important.

Diabetes is recognized in 7% of US pregnancies with 86% of those representing gestational diabetes (gDM).¹⁹ Hyperglycemia is considered especially harmful during early fetal development and the American College of Obstetricians and Gynecologists (ACOG) has recognized that more patients are entering pregnancy with risk factors for T2DM. Screening patients for underlying T2DM or early gDM upon entry to prenatal care is now recommended.^19,20

Of patients who are diagnosed with gDM, up to one-third will be diagnosed with impaired glucose tolerance during the postpartum period, with between 15–70% progressing to T2DM later in life.¹⁹ After being released from obstetric care, the onus for knowing timing of screening often falls to the patient. In addition, they may lose access to healthcare coverage until their next pregnancy. For patients with a history of gDM, ACOG recommends screening for T2DM, insulin sensitivity, and insulin resistance between four and 12 weeks postpartum.^19,21 Recently ACOG released a practice update to consider screening in the immediate postpartum period prior to hospital discharge since less than half of patients undergo the recommended screening in the traditional four to 12 week timeframe.²¹ Both ACOG and the American Diabetes Association recommend screening every one to three years for patients with history of gDM. Given the lifelong increased risk for the development of T2DM, knowing a patient’s history allows for early screening and intervention.

Screening for a history of gDM is particularly important for patients who lack traditional or more obvious risk factors for T2DM like obesity or family history as these patients are much more likely to go without appropriate screening. Additionally, patients who would not typically be considered at increased risk for T2DM but do warrant increased surveillance based on pregnancy history include those with a history of PTD (both spontaneous or medically indicated). In one study, a history of PTD had a hazard ratio (HR) of T2DM 1.35 (95%, CI, 1.33–1.38) compared to delivery at term with even higher risk conferred at earlier gestational age at delivery.²²

There is overwhelming evidence that knowledge of a patient’s HDP would be important for our cardiovascular colleagues, but the process does not just have effects on the cardiovascular system. Patients with HDP had a hazard ratio (HR) of 1.72 for developing T2DM, even 30–46 years after delivery.²²

Optimizing the treatment of thyroid disorders prior to conception is critical as uncontrolled thyroid levels can lead to miscarriage, placental abruption, hypertensive disorders, growth restriction, neonatal goiter/hyperthyroidism, or congenital malformations.^23–25 For patients with hypothyroidism, levothyroxine supplementation will often require adjustments during each trimester beginning with an increased need at conception. Patients often return to prepregnancy doses shortly after delivery.²⁴ Counseling regarding pregnancy intention when treating hyperthyroidism is more often recognized given the association between treatment medications and birth defects. Graves’ disease can relapse or manifest for the first time during the postpartum period. Postpartum thyroiditis can affect 6–7% of patients with almost half progressing to permanent hypothyroidism. In patients that recover, the risk remains elevated for developing hypothyroidism and they should have annual screening.^23,24

Obesity is growing to be one of the most common risk factors affecting pregnancy. These patients carry elevated risks for developing adverse pregnancy outcomes most notably, HDP and gDM which then confer long term consequences.²⁶ Identifying a desire for pregnancy or contraceptive plan is an important component when counseling on weight loss.

Weight loss with the use of anti-obesity medications can lead to rapid return of fertility or alterations in contraception efficacy.^26,27 It remains unclear how much weight loss prior to pregnancy is beneficial and whether that benefit continues throughout pregnancy. With the pervasive prescribing of glucagon-like peptide-1 receptor agonists (GLP-1 RAs), understanding the potential effects in pregnancy is an increasingly important area of research.²⁸ One review demonstrated increased weight gain during pregnancy similar to weight regain for patients who did not use medications and no increase of congenital anomalies or fetal death with use of GLP-1 RA in early pregnancy.²⁸ A large comorbidity-controlled study showed improvement in adverse obstetric outcomes when a GLP-1 RA was used within two years of conception, with the most benefit in the groups with longer duration of use.²⁷

For our colleagues who are prescribing these medications, it is imperative to ask about pregnancy intention. The FDA recommends discontinuation of GLP-1 RAs or GLP-1 RA/Glucose-dependent insulinotropic peptide (GIP) receptor agonist based on half-life. For patients trying to conceive: liraglutide should be stopped 10–14 days, while semaglutide and tirzepatide should be stopped two months prior.^26,28–30 Especially important in tirzepatide counseling is an awareness of the decreased effectiveness of oral contraception.²⁶ When patients conceive while on anti-obesity medications, enrolling them in pregnancy exposure registries will help increase data in a population that is traditionally excluded from drug trials.

Renal

Renal conditions can either predate pregnancy or be discovered during routine laboratory work conducted during pregnancy. As more patients delay their first pregnancy, a larger proportion of patients have the potential to have underlying chronic conditions with renal complications that are either unrecognized or undermanaged. Renal conditions occurring during the reproductive years often have a delay in recognition, effective treatment, and referrals.³¹ Patients with underlying chronic kidney disease (CKD) can have advancement of their stage during pregnancy and shorten the time to renal replacement.³¹ Adequate counseling for patients with known CKD is essential for optimizing both pregnancy outcomes and long term care after pregnancy. However, a recent qualitative study demonstrated that many nephrologists felt unequipped to adequately counsel on contraception or risk of CKD during pregnancy. Patients were unaware of the potential interplay between CKD and pregnancy unless they had already experienced a pregnancy related complication. Patients were interested in discussing reproductive plans with their nephrologist but were unsure how to approach it. The authors identified that tools to accurately assess risk for patients are needed for nephrologists to have patient-centered discussions in addition to electronic medical record improvements to adequately screen for a patients’ reproductive intentions.³²

Clearly, hypertensive disorders both predating and during pregnancy have long term renal consequences. It is still unclear whether the renal injury is from the underlying pathology that leads to the HDP or the HTN itself that results in long term increased risk of renal disease.³³ The reduced glomerular filtration rate (GFR) that can be seen with preE can persist years after delivery or progress to end stage renal disease (ESRD). The proteinuria can persist even longer. If it persists beyond the first 12 weeks postpartum, patients should be seen by nephrology for further evaluation and all who have proteinuria during pregnancy should be screened annually for development of CKD or CVD.³⁴

Pregnancies with low-birth-weight or PTD are also at increased risk for ESRD.³⁵ A recent meta-analysis determined that PTD increased risk of CKD by 82% and ESRD by 122%.¹² The interplay between PTD and CKD/ESRD is not fully understood. More studies need to evaluate the relationship while controlling for the potential variables such as obesity, T2DM, and HTN which may separately increase risk for CKD/ESRD.

Gastro-Intestinal

Several acute and chronic conditions can be determined by learning a patient’s pregnancy history. Most conditions affecting the liver during pregnancy are limited to the pregnancy but some may benefit from follow up.

Patients are screened for chronic Hepatitis B and Hepatitis C to reduce the maternal-child transmission rates. Patients can experience a hepatitis flair both during and after pregnancy and monitoring for several months can identify patients who need acute intervention.^36,37 While data does not currently support treatment during pregnancy, patients with Hepatitis C should be referred for treatment postpartum and followed through sustained viral resistance.

In preE, one of the defining target organ abnormalities can be within the liver with severe complications consisting of hemolysis, elevated liver enzymes, and low platelet (HELLP) syndrome or subcapsular hematomas. The liver damage is typically self-limiting and liver enzymes typically normalize following delivery but may take weeks to months.³⁸ Similarly, elevated liver enzymes with intrahepatic cholestasis of pregnancy typically are self-limiting to the pregnancy time period.³⁷

Occasionally, elevated liver enzymes are discovered during pregnancy and not thought to be a result of preE but rather a component of metabolic dysfunction associated steatotic liver disease (MASLD). These patients need follow-up postpartum for disease management and discussion of future pregnancies. In a similar way that patients with mild CKD may not get adequate counseling about risk of progression during pregnancy, patients with known MASLD may not understand the increased risk for PTD (AOR 2.05), FGR (AOR 1.32), HDP (AOR 3.03), and overall maternal mortality (AOR 6.40) the disease has compared to matched controls.³⁹ This again highlights the importance of inquiring about reproductive intention by all clinicians.

Neurology

Pregnancy and the postpartum period are times of increased risk of stroke. While the physiology of pregnancy increases this risk of stroke, concurrent hypertensive disorders are the leading cause.¹⁴ The overlapping cardiovascular and neurovascular effects of chronic HTN and preE are highlighted by the increased risk of stroke during and following a pregnancy. This risk increases when there is recurrence of preE in a subsequent pregnancy or when preE is diagnosed early.^14,40 Patients who had a history of preE had 1.55 fold higher odds of stroke than matched patients with similar cardiovascular risk factors.¹⁴ Patients with history of HDP should be counseled on the significantly increased lifetime risk of stroke.

Early treatment of HTN is also important for reducing the risk of seizures and lasting neurologic complications. For the rare number of patients who do experience eclampsia, establishing if there are any lasting sequelae is important. Seizures from eclampsia do not require long term antiepileptics or neurology follow up unless there is a delay in treatment and epilepsy, ischemic infarction, hemorrhage, cognitive disorder, visual abnormalities, or white brain matter lesions takes place.^41,42 In one study, 22.5% of hypertensive patients experiencing eclampsia had neuroimaging findings consistent with posterior reversible encephalopathy syndrome (PRES), a neurologic condition with headache, alterations in consciousness, visual disturbances and seizures.⁴² When identified and treated quickly, MRI detectable subcortical edema can be decreased and the sequela prevented.

Conclusion

Having an increased awareness of how pregnancy can impact overall health is not a reason to fear or discourage pregnancy in our patients. Approaching all patients with the attitude that pregnancy is inherently and universally dangerous is a harmful mentality. ACOG recommends discussions regarding pregnancy and contraception planning be tailored to the individual’s risk given the long history of inequity and inequality and the role SDOH have in contributing to pregnancy related morbidity in this country.^43,44 Pregnancy does not hold a universal risk or effect on long-term health for all patients (Table 1). Instead, looking at a patient’s pregnancy history can be seen as looking through a window into conditions that would otherwise be hidden until potentially devastating complications occur.² While examining a patient’s pregnancy history can highlight conditions that may occur earlier than anticipated, it remains important to also consider individual and systemic factors potentially contributing to underlying risks for developing chronic conditions.³

Table 1.

Summary of pregnancy-related conditions, their long-term impacts and care/screening suggestions by authors.

Pregnancy-related Condition	Long-Term Associated Risk	Management/Screening Consideration
Hypertensive Disorders of Pregnancy (preE, gestational hypertension, eclampsia)	2–12× risk of chronic HTN 2× risk of stroke 2× risk of CV mortality Increased risk of T2DM Increased risk of CKD	Risk factor modifications Annual screen for HTN T2DM screen q1–3yrs Annual screen for CKD/CVD if proteinuria present in pregnancy If proteinuria persists postpartum, consult Nephrology
Gestational Diabetes	2× risk for cardiovascular disease/events 15–70% risk of T2DM postpartum	Risk factor modifications T2DM screen q1–3yrs
Preterm Delivery	2× risk for CVD Increased risk for T2DM Increased risk of CKD/ESRD	Risk factor modifications T2DM screen q1–3yrs Annual screen for HTN Consider screening for CKD q1–3yrs, especially if other risk factors present
Fetal Growth Restriction	Increased risk for CVD	Annual screen for HTN Risk factor modifications
Postpartum Thyroiditis	>50% risk of permanent hypothyroidism	Annual screen for hypothyroidism

We recommend implementing universal screening for pregnancy intention as one method of opening the conversation. There are a multitude of tools available that clinics can adopt.⁴⁵ With the primary healthcare shortage, deferring counseling about pregnancy intention or contraception for patients with known comorbidities can be potentially dangerous.

Although pregnancy is a transient condition, it results in a permanent transformation as the patient is then postpartum for life, and complications experienced in the pregnancy likely impact their long-term health and well-being. No longer can the care that takes place during and around pregnancy be relegated to a subset of specialties in medicine. Reviewing pregnancy history and pregnancy potential are vital to all physicians. Informing patients that some conditions they thought were confined to pregnancy have long-term associations can help reinforce the importance of collaborative care, timely screening, and appropriate risk factor modification. Our goal with this article is to increase awareness across different disciplines of medicine of the role they may be able to play to positively impact long term health outcomes.