Iron deficiency in pregnancy is very common as the requirements for iron progressively increase throughout the pregnancy in response to the expanding blood volume and the growing fetal demands. Maternal iron is responsible for fetal and early childhood stores up to 2 years of age, and iron deficiency in early childhood is linked to poor cognitive ability [4]. Several gastrointestinal disorders are associated with extreme iron deficiency: inflammatory disease, gastric bypass, and untreated celiac disease. These patients with prepregnancy depleted storages and impaired iron absorption respond poorly to oral supplementation and might require intravenous infusion.

In 2012, the IOM recommended a daily intake of 600 international units of 25-hydroxyvitamin D (25-OH-D) for pregnant women. Maternal deficiency is linked to disordered fetal bone homeostasis, to newborn fractures, and possibly to premature birth and preeclampsia [5]. Women living in the northern hemisphere are prone to vitamin D deficiency, and many might not compensate for the lack of exposure to sunlight with an adequate oral intake. This is particularly true for patients with gastrointestinal and liver diseases that have impaired absorption of fats and fat-soluble vitamins. Given the lack of data and guidelines, moderate sunlight exposure and vitamin D supplementation of 2,000 IU daily are reasonable recommendations in pregnancy. The target level of total vitamin D considered “normal” is a circulating level of 25-OH-D of 32 ng/ml.

Folic acid (folate) is responsible for fetal neurodevelopment, and 400 mg of folate is required daily during pregnancy.

In the United States, the decreased incidence of neural tube defects in newborns was achieved by adding folate to common food items and with an aggressive advertizing campaign promoting supplementation of folate in pregnancy. Folate is ubiquitous in fruits, vegetables, legumes, and grains. In addition, gut bacteria synthesize folate. Patients at risk for deficiency are patients with limited diet for personal and socioeconomic reasons, alcohol and substance abusers, and patients treated with chronic antibiotics or antifolate drugs.

Adequate amounts of folate are now added to all prenatal vitamins. Additional folate may be required in patients with a previously affected child with a neural tube defect and patients on antiepileptic drugs.

Omega-6 polyunsaturated fatty acid and omega-3 polyunsaturated fatty acid, most notably docosahexaenoic acid (DHA), are essential for neural, visual, and cognitive development and contribute to immune system functioning. The usual western diet is deficient in these nutrients that are found in seeds, nuts, and cold-water oily fishes. Moreover, expectant mothers might avoid eating fish because of concerns about their mercury intake. The evidence supporting the need for DHA supplementation in pregnancy emerged over the last decade as a result of studies linking children’s intellectual development to prenatal fatty acid intake of the mother. Current recommendations advise pregnant women to consume 500–600 mg of omega-3 fatty acid of which 200–300 mg of DHA daily [6]. It is important to stress that two servings weekly of low mercury content fish is safe in pregnancy and does not carry a risk of mercury toxicity. DHA is found in safe cold-water fish such as salmon and cod.

Calcium is required for fetal bone formation along with vitamin D, so consumption of 1,000 mg of calcium is recommended daily in pregnancy. Patients with chronic malabsorption, short gut, and small bowel disease are at particular risk for calcium deficiency in pregnancy. Moreover, pregnancy can further deplete calcium stores worsening preexisting premature osteoporosis.

Gestational vomiting that includes NVP and HG may result from various metabolic and endocrine factors, many of placental origin. The most implicated factor is human chorionic gonadotropin (hCG), which peaks in concentration around the peak time of symptoms. Several studies show that nausea and vomiting are worse in pregnant women with conditions associated with elevated hCG levels such as molar pregnancies, multiple gestations, and Down’s syndrome and that concentrations of hCG correlate positively with symptom severity in women with HG. Other factors, such as estrogen, progesterone, placental prostaglandin E2, and leptin, may also contribute to the pathogenesis of NVP and HG.

Due to cross-reactivity between hCG and the thyroid-stimulating hormone (TSH) receptor, thyroid dysfunction has also been implicated in the pathogenesis of NVP and HG. In fact, abnormal thyroid function tests (typically low TSH and slightly elevate FT4) are found in two-thirds of women with HG. Despite these laboratory abnormalities, women with HG are generally euthyroid with no history of prior thyroid diseases, absent goiter, and negative antithyroid antibodies [19].

Alterations in lower esophageal sphincter (LES) resting pressure and esophageal peristalsis have been linked to NVP. While these changes are more typically associated with heartburn in pregnancy, gastroesophageal reflux disease (GERD) may also produce nausea and contribute to the symptoms of HG.

Despite the popular use of the term “morning sickness,” NVP persists throughout the day in the majority of women and is limited to the morning in less than 2 % of women. It often begins within weeks of conceptions between 10 and 16 weeks and then resolves after 20 weeks. However, up to 10 % of women remain symptomatic beyond 22 weeks. While dehydration and orthostasis can occur in women with HG, most women with NVP have normal vital signs and a benign physical exam. The differential diagnosis for gestational vomiting includes gastroesophageal reflux disease, peptic ulcer disease (PUD), small bowel obstruction, acute cholecystitis, cholelithiasis, pancreatitis, as well as appendicitis, gastroenteritis, nephrolithiasis, pyelonephritis, and hepatitis.

NVP is associated with a favorable outcome for the fetus with a decreased risk of miscarriage and no consistent associations with perinatal mortality.

Despite its favorable effects on the fetus, NVP causes substantial psychosocial morbidity in the mother. NVP impairs employment, performance of household duties, and parenting [20]. It is also associated with feelings of depression, consideration of termination of pregnancy, and impaired relationships with partners.

Hyperemesis gravidarum (HG) is severe nausea and vomiting during pregnancy leading to fluid, electrolyte, and acid–base imbalance, nutritional deficiency, and weight loss. HG is commonly defined as the occurrence of greater than 3 episodes of vomiting per day accompanied by ketonuria and a weight loss of more than 3 kg or 5 % of body weight. HG is the most common reason for hospitalization in early pregnancy and second only to preterm labor throughout pregnancy. In the United States, more than 36,000 women are admitted to the hospital each year due to HG [21]. Unlike NVP, which is associated with favorable fetal outcomes, HG poses significant health risks to the mother and fetus.

HG presents in the first trimester of pregnancy, usually starting at 4–5 weeks of gestation. In addition to severe nausea and vomiting, 60 % of women with HG experience excess salivation. Patients may also complain of GER symptoms such as retrosternal discomfort and heartburn. A pregnancy-unique quantification of emesis and nausea (PUQE) score can be used to track the severity of symptoms (Table 5.8).

Patients may present with signs of dehydration, and severely affected patients may also have muscle wasting and weakness and/or mental status changes.

Laboratory abnormalities in women with HG are characteristic of severe dehydration. Prealbumin levels may be low, reflecting poor protein nutrition status in the mother and possibly predicting lower fetal birth weights. Vitamin and mineral deficiencies such as vitamin B1 (thiamine), iron, calcium, and folate are also possible [22].

Liver function tests are abnormal in up to 50 % of hospitalized patients with HG. Mild hyperbilirubinemia (bilirubin < 4 mg/dl) and/or a rise in alkaline phosphatase to twice the upper limit of normal may be seen. A moderate transaminitis is the most common liver test abnormality with alanine aminotransferase (ALT) levels generally greater than aspartate aminotransferase (AST) levels. The transaminase elevation is usually two to three times the upper limit of normal. Serum amylase and lipase elevations are seen in 10–15 % of women. The amylase elevation may be due to excessive salivary gland production. As in NVP, TSH levels may be low in HG due to cross-reaction between the alpha subunit of HCG with the TSH receptor. HG is a clinical diagnosis based on symptoms and the exclusion of other conditions. Like NVP, no specific testing is needed to diagnose HG, but they are necessary to monitor the metabolic disturbances and the nutritional status. Ultrasound of the abdomen and pelvis may be helpful in excluding other causes such as gallbladder disease and hydatidiform mole and in assessing for multiple gestation. The differential diagnosis includes NVP, acute thyroiditis, eating disorders, biliary tract disease, viral hepatitis, and GERD.

Unlike NVP, HG is associated with both adverse maternal and fetal outcomes. In a study of over 150,000 singleton pregnancies, women with HG had increased rates of low pregnancy weight gain (<7 kg), low birth weight (LBW) babies, small for gestational age (SGA) babies, preterm birth, and poor 5-min Apgar scores [17].

Common maternal complications include weight loss, dehydration, micronutrient deficiency, and muscle weakness. More severe, albeit rare, complications include Mallory-Weiss tears, esophageal rupture, Wernicke’s encephalopathy with or without Korsakoff’s psychosis, central pontine myelinolysis due to rapid correction of severe hyponatremia, spontaneous pneumomediastinum, and vasospasm of the cerebral arteries. HG may also lead to psychological problems and result in termination of an otherwise wanted pregnancy and decreased likelihood to attempt a repeat pregnancy.

Various congenital malformations have been observed more in women with HG. Fetal coagulopathy and chondrodysplasia have also been reported from vitamin K deficiency with third trimester fetal intracranial hemorrhage [23].

Treatment modalities for NVP and HG range from simple dietary modifications to drug therapy and total parental nutrition (TPN). Severity of symptoms and maternal weight loss are useful in determining the aggressiveness of treatment.

Currently, studies demonstrate that management of NVP is suboptimal. One recent prospective study of 283 women with NVP during the first trimester found that only half were asked about the intensity and severity of their symptoms and less than a quarter were asked if their symptoms interfered with their daily tasks and work [24].

Affected women should avoid large meals and eat several small meals throughout the day. Meals that are bland and low in fat are preferred as fatty foods may further delay gastric emptying. Eating protein more than carbohydrates and taking in more liquids than solids may also help nausea by improving gastric dysrhythmias associated with NVP. Small volumes of salty liquids such as electrolyte replacement sport beverages are advised, and if the smell of hot foods is noxious, cold foods should be prepared.

Women with intractable symptoms unresponsive to dietary modification and pharmacologic treatment whom are unable to maintain weight require additional support. For these patients, intravenous fluid therapy, enteral nutrition, or parenteral nutrition should be used to prevent fetal intrauterine growth restriction, maternal dehydration, and malnutrition.

Women requiring multiple hospitalizations may be considered for in-home intravenous hydration.

Enteral tube feeding and total parenteral nutrition should be considered if intravenous therapy is not successful in reducing symptoms and there is still a caloric deficit. In addition to nasogastric tubes, percutaneous endoscopic gastrostomy (PEG) tubes [35] have been used successfully to maintain nutrition in women with HG. Both of these modes of feeding are limited however by the risk of increased nausea and vomiting caused by intragastric feeding. Post-pyloric feeding tubes, both nasojejunal, and percutaneous endoscopic gastrojejunostomy have been attempted to reduce this risk; however, dislodgement of the tubes [36] and gastric coiling are common complications. In addition, nasoenteric tubes, either nasogastric or nasojejunal, are often poorly tolerated due to aesthetics and physical discomfort. Recently, surgical jejunostomy has been described as an alternative mode of nutrition delivery to women with HG [37].

For women unable to tolerate enteral feeding, parenteral nutrition should be considered. This therapy, however, is costly and associated with significant maternal morbidity [38] and reported a 9 % complication rate for parenteral nutrition via peripherally inserted central catheters in pregnancy and a 50 % complication rate for centrally inserted catheters. Infection and thrombosis were the two most frequently occurring complications and were hypothesized to result from pregnancy-associated hypercoagulability and immunologic suppression [38, 39]. Patients on parenteral nutrition also had higher rates of neonatal complications including admission to the neonatal intensive care unit, SGA, termination of pregnancy from HG, and fetal loss compared with women treated with enteral feeds [40]. Thus, although it may be more tolerable to patients, parenteral nutrition should be reserved for selected patients with HG.

In general, infertility rates for men and women with IBD, which range from 5 to 14 %, are no higher than in the general population. Initial epidemiologic data suggested higher infertility rates and smaller family size in individuals with Crohn’s disease (CD); however, these studies predate the use of the more effective medical treatments used today [42]. They also did not account for higher voluntary childlessness rates in patients with IBD. Voluntary childlessness in IBD, although not fully understood, is likely the result of fears of IBD heritability, congenital abnormalities, and medication teratogenicity.

Notable subgroups of IBD patients do have compromised fertility, and patients should be aware that they may fall into this category. Women who have undergone ileal pouch-anal anastomosis (IPAA) comprise one of these subgroups. A recent systematic review found the infertility rate after IPAA to be about 30 % [43], likely due to adhesions and effect on tubal function.

Pregnancy does not significantly alter the course of preexisting IBD or increase the risk for future complications. In fact, some studies suggest that pregnancy may lower the risk for future disease relapse [44]. Based on data showing similar risks of exacerbation during pregnancy (32–34 %) versus the fertile years in women with UC and CD, in general, women with IBD can be counseled that their risk of flaring during pregnancy is the same as when they are not pregnant.

Disease remission at the time of conception is very important for maintaining inactive disease during pregnancy. Women with inactive disease at conception had the same rate of relapse as nonpregnant IBD women. In contrast, other studies have shown that if conception occurs when IBD is active, two-thirds of women will suffer from persistent activity and, of these, two-thirds will worsen [45]. Thus, women with IBD should be advised to be in disease remission prior to conception.

Women with IBD are at increased risk for certain adverse pregnancy outcomes. A recent meta-analysis combining 12 studies totaling 3907 patients with IBD found significantly increased risks for preterm birth [OR =1.87 (1.52, 2.31)], LBW [OR = 2.1 (1.38, 3.19)], and cesarean section OR =1.5 (1.26, 1.79)] [43] but not of congenital anomalies when controlled for medication use. Whether disease activity during pregnancy increases the risk of adverse outcome or simply having IBD increases risk is still controversial. Earlier studies suggested that disease activity at conception was a predictor for spontaneous abortion and preterm birth [46] and disease activity during pregnancy increased the risk for low birth weight (LBW) and preterm birth [47]. However, several recent studies have found the increased risk of adverse events in women with IBD to be independent of disease activity [48].

Treatment of flares in pregnancy follows the same guidelines as for nonpregnant patients with the added goal of inducing a rapid remission to maintain a healthy pregnancy. Corticosteroids, antibiotics, cyclosporine, and antitumor necrosis factor alpha (TNF-α) agents can be initiated, if needed, to control disease activity in pregnancy. Women with medically refractory disease, toxic megacolon, or a high-grade stricture may require surgical intervention despite the risk inherent to surgery in pregnancy of miscarriages and premature birth.

The mode of delivery in women with IBD is dictated by obstetric considerations. One exception, however, is women with active perianal disease in whom cesarean section is advised [42]. Vaginal delivery in these patients may further disrupt the perineum and injure the anal sphincter. Notably, healed perianal disease and presence of an ileoanal pouch are not contraindications to vaginal delivery, although some experts advocate for cesarean section in the setting of an ileoanal pouch in order to preserve sphincter function. Pregnant women with IBD should see their physicians regularly to allow for monitoring of disease activity, nutritional status, and medication adherence. A successful pregnancy requires team effort with regular communication among the treating obstetrician and/or perinatologist and gastroenterologist.

Breastfeeding is unlikely to influence disease activity and may in fact be protective for the future development of IBD. However, many women with IBD choose not to breastfeed [49]. Physician recommendations, the fear of medication transmission, and personal preferences are the most common reasons cited. Physicians must therefore be aware of the actual risks so they can educate their patients.

Most patients with IBD require pharmacologic therapy to maintain disease remission. Since controlled disease at conception is key to maintaining remission throughout pregnancy, medication discontinuation before attempting to conceive is not advised. With few exceptions, medications should be continued during the preconception period and pregnancy.